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Natural Compounds and Biopolymers-Based Hydrogels Join Forces to Promote Wound Healing.

Rapid and complete wound healing is a clinical emergency, mainly in pathological conditions such as Type 2 Diabetes mellitus. Many therapeutic tools are not resolutive, and the research for a more efficient remedial remains a challenge. Wound dressings play an essential role in diabetic wound healing. In particular, biocompatible hydrogels represent the most attractive wound dressings due to their ability to retain moisture as well as ability to act as a barrier against bacteria. In the last years, different functionalized hydrogels have been proposed as wound dressing materials, showing encouraging outcomes with great benefits in the healing of the diabetic wounds. Specifically, because of their excellent biocompatibility and biodegradability, natural bioactive compounds, as well as biomacromolecules such as polysaccharides and protein, are usually employed in the biomedical field. In this review, readers can find the main discoveries regarding the employment of naturally occurring compounds and biopolymers as wound healing promoters with antibacterial activity. The emerging approaches and engineered devices for effective wound care in diabetic patients are reported and deeply investigated.

Prevalence of Diabetes and Its Association with Atherosclerotic Cardiovascular Disease Risk in Patients with Familial Hypercholesterolemia An Analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH).

Familial hypercholesterolemia (FH) and type 2 diabetes mellitus (T2DM) are both associated with a high risk of atherosclerotic cardiovascular disease (ASCVD). Little is known about the prevalence of T2DM and its association with ASCVD risk in FH patients. This was a cross-sectional analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH) including adults with FH (n 1719, mean age 51.3 ± 14.6 years). Of FH patients, 7.2% had a diagnosis of T2DM. The prevalence of ASCVD, coronary artery disease (CAD), and stroke was higher among subjects with T2DM compared with those without (55.3% vs. 23.3%, 48.8% vs. 20.7%, 8.3% vs. 2.7%, respectively,

Combinatory Effect and Modes of Action of Chrysin and Bone Marrow-Derived Mesenchymal Stem Cells on StreptozotocinNicotinamide-Induced Diabetic Rats.

The purpose of this study was to see how chrysin andor bone marrow-derived mesenchymal stem cells (BM-MSCs) affected streptozotocin (STZ)nicotinamide (NA)-induced diabetic rats as an animal model of type 2 diabetes mellitus (T2DM). Male Wistar rats were given a single intraperitoneal (i.p.) injection of 60 mg STZkg bodyweight (bw) 15 min after an i.p. injection of NA (120 mgkg bw) to induce T2DM. The diabetic rats were given chrysin orally at a dose of 100 mgkg bw every other day, BM-MSCs intravenously at a dose of 1 × 10

Glucose Uptake Is Increased by Estradiol Dipropionate in L6 Skeletal Muscle Cells.

GLUT4 is an important glucose transporter, which is closely related to insulin resistance and type 2 diabetes. In this study, we investigated the mechanism of Estradiol Dipropionate (EDP) on uptake of glucose in L6 skeletal muscle cells. In our study, we confirmed that EDP promoted uptake of glucose in L6 skeletal muscle cells in both normal and insulin resistant models. Western blot indicated that EDP accelerated GLUT4 expression and significantly activated AMPK and PKC phosphorylation the expression of GLUT4 was significantly inhibited by AMPK inhibitor compound C and PKC inhibitor Gö6983, but not by Wortmannin (Akt inhibitor). Meanwhile, EDP boosted GLUT4 expression, and also increased intracellular Ca

Chemical and Biological Investigations of

This study was designed to investigate the impact of different extraction solvent systems on the chemical composition and biological activities of

Should Carbohydrate Intake Be More Liberal during Oral and Enteral Nutrition in Type 2 Diabetic Patients

Carbohydrate (CHO) intake in oral and enteral nutrition is regularly reduced in nutritional support of older patients due to the high prevalence of diabetes (usually type 2-T2DM) in this age group. However, CHO shortage can lead to the lack of building blocks necessary for tissue regeneration and other anabolic processes. Moreover, low CHO intake decreases CHO oxidation and can increase insulin resistance. The aim of our current study was to determine the extent to which an increased intake of a rapidly digestible carbohydrate-maltodextrin-affects blood glucose levels monitored continuously for one week in patients with and without T2DM. Twenty-one patients (14 T2DM and seven without diabetes) were studied for two weeks. During the first week, patients with T2DM received standard diabetic nutrition (250 g CHO per day) and patients without diabetes received a standard diet (350 g of CHO per day). During the second week, the daily CHO intake was increased to 400 in T2DM and 500 g in nondiabetic patients by addition of 150 g maltodextrin divided into three equal doses of 50 g and given immediately after the main meal. Plasma glucose level was monitored continually with the help of a subcutaneous sensor during both weeks. The increased CHO intake led to transient postprandial increase of glucose levels in T2DM patients. This rise was more manifest during the first three days of CHO intake, and then the postprandial peak hyperglycemia was blunted. During the nights fasting period, the glucose levels were not influenced by maltodextrin. Supplementation of additional CHO did not influence the percentual range of high glucose level and decreased a risk of hypoglycaemia. No change in T2DM treatment was indicated. The results confirm our assumption that increased CHO intake as an alternative to CHO restriction in type 2 diabetic patients during oral and enteral nutritional support is safe.

Selective Daily Mobility Bias in the Community Food Environment Case Study of Greater Hartford, Connecticut.

The community food environment has potential influences on community members dietary health outcomes, such as obesity and Type II diabetes. However, most existing studies evaluating such health effects neglect human mobility. In food patrons daily travels, certain locations may be preferred and patronized more frequently than others. This behavioral uncertainty, known as the selective daily mobility bias (SDMB), is less explored in community-food-environment research. In this paper, we aim to confirm the existence of the SDMB by systematically exploring the large-scale GPS-based restaurant-visit patterns in the Greater Harford region, Connecticut. Next, we explore the restaurant and neighborhood characteristics that are associated with the restaurant-visit patterns. Our primary results demonstrate that (1) most restaurant customers originate from areas outside of the census tract where the restaurant is located, and (2) restaurants located in socially vulnerable areas attract more customers in total, more customers from local areas, and more customers from other socially vulnerable areas. These results confirm the relevance of the SDMB to the community food environment, and suggest ways that the SDMB can be moderated by an uneven socio-economic landscape. The findings demonstrate the necessity of incorporating human-mobility data into the study of the community food environment.

Increased Intake of Omega-3 Polyunsaturated Fatty Acids Is Associated with Reduced Odds of Low Hand Grip Strength in Korean Adults.

Nutritional status is thought to be one of the modifiable risk factors for muscle health. This study investigates the association between dietary omega-3 polyunsaturated fatty acids (PUFA) intake and hand grip strength (HGS) in Korean adults. The cross-sectional analysis was performed on 18,278 participants aged ≥19 years enrolled in the Korea National Health and Nutrition Examination Survey from 2016-2019. Omega-3 PUFA consumption was positively linked to the dietary intake of nuts, fish, and shellfish in Korean adults. After adjusting for potential confounders, the results showed that increased omega-3 PUFA intake was associated with a decreased risk of low HGS (odds ratio (OR) for upper quartile (Q4) compared to Q1, men OR 1.42 (95% CI 1.17-1.72), women OR 1.61 (1.37-1.89)). This inverse association was reported in people who did no resistance exercise or had an insufficient protein intake. In contrast, this association was not evident in adults who did resistance exercise or had sufficient protein intake. Furthermore, participants with hypertension or type 2 diabetes showed stronger associations between dietary omega-3 PUFA intake and HGS compared with other subgroups. These results suggest that dietary omega-3 PUFA intake positively related with HGS in Korean adults.

Gut Microbial-Derived Short Chain Fatty Acids Impact on Adipose Tissue Physiology.

Obesity is a global public health issue and major risk factor for pathological conditions, including type 2 diabetes, dyslipidemia, coronary artery disease, hepatic steatosis, and certain types of cancer. These metabolic complications result from a combination of genetics and environmental influences, thus contributing to impact whole-body homeostasis. Mechanistic animal and human studies have indicated that an altered gut microbiota can mediate the development of obesity, leading to inflammation beyond the intestine. Moreover, prior research suggests an interaction between gut microbiota and peripheral organs such as adipose tissue via different signaling pathways yet, to what degree and in exactly what ways this inter-organ crosstalk modulates obesity remains elusive. This review emphasizes the influence of circulating gut-derived short chain fatty acids (SCFAs) i.e., acetate, propionate, and butyrate, on adipose tissue metabolism in the scope of obesity, with an emphasis on adipocyte physiology in vitro and in vivo. Furthermore, we discuss some of the well-established mechanisms via which microbial SCFAs exert a role as a prominent host energy source, hence regulating overall energy balance and health. Collectively, exploring the mechanisms via which SCFAs impact adipose tissue metabolism appears to be a promising avenue to improve metabolic conditions related to obesity.

GLP-1R Signaling and Functional Molecules in Incretin Therapy.

Glucagon-like peptide-1 receptor (GLP-1R) is a critical therapeutic target for type 2 diabetes mellitus (T2DM). The GLP-1R cellular signaling mechanism relevant to insulin secretion and blood glucose regulation has been extensively studied. Numerous drugs targeting GLP-1R have entered clinical treatment. However, novel functional molecules with reduced side effects and enhanced therapeutic efficacy are still in high demand. In this review, we summarize the basis of GLP-1R cellular signaling, and how it is involved in the treatment of T2DM. We review the functional molecules of incretin therapy in various stages of clinical trials. We also outline the current strategies and emerging techniques that are furthering the development of novel therapeutic drugs for T2DM and other metabolic diseases.

Lipidomic Analysis to Assess the Correlation between Ceramides, Stress Hyperglycemia, and HbA1c in Acute Myocardial Infarction.

Ceramides have been associated with cardiometabolic disease (e.g., acute myocardial infarction (AMI) and type 2 diabetes (T2D)) and adverse outcomes. Acute admission hyperglycemia (AH) is a transient glucose alteration in response to stress. As glycated hemoglobin (HbA1c) reflects the glycemia over a longer period of time, its use may be helpful in distinguishing between the AH and hyperglycemia associated with T2D in the AMI setting. The aim was to assess the correlation of ceramides with both AH (defined as an admission glucose level ≥140 mgdL in the absence of T2D) and HbA1c-T2D and other demographic, clinical, and inflammatory-related biomarkers in AMI. High-performance liquid chromatography-tandem mass spectrometry was used to identify nine ceramide species, and their three ratios, in 140 AMI patients (FTGM coronary unit, Massa, Italy). The ceramides did not correlate with stress hyperglycemia, but specific species were elevated in T2D-AMI. Moreover, some ceramides were associated with other cardiometabolic risk factors. Ceramides assessment may be helpful in better understanding the pathogenic molecular mechanisms underlying myocardial acute events and cardiometabolic risk, as a basis for the future evaluation of their role as prognostic predictors and therapeutic targets in T2D-AMI patients.

Structural Characterization and Hypoglycemic Function of Polysaccharides from

The polysaccharides isolated and purified from different parts of the medicinal fungus

Isorhamnetin Reduces Glucose Level, Inflammation, and Oxidative Stress in High-Fat DietStreptozotocin Diabetic Mice Model.

Isorhamnetin is a flavonoid that is found in medical plants. Several studies showed that isorhamnetin has anti-inflammatory and anti-obesity effects. This study aims to investigate the anti-diabetic effects of isorhamnetin in a high-fat diet and Streptozotocin-(HFDSTZ)-induced mice model of type 2 diabetes. Mice were fed with HFD followed by two consecutive low doses of STZ (40 mgkg). HFDSTZ diabetic mice were treated orally with isorhamnetin (10 mgkg) or (200 mgkg) metformin for 10 days before sacrificing the mice and collecting plasma and soleus muscle for further analysis. Isorhamnetin reduced the elevated levels of serum glucose compared to the vehicle control group ( Isorhamnetin ameliorates insulin resistance, oxidative stress, and inflammation. Isorhamnetin could represent a promising therapeutic agent to treat T2D.

Several Metabolite Families Display Inflexibility during Glucose Challenge in Patients with Type 2 Diabetes An Untargeted Metabolomics Study.

Metabolic inflexibility is a hallmark of insulin resistance and can be extensively explored with high-throughput metabolomics techniques. However, the dynamic regulation of the metabolome during an oral glucose tolerance test (OGTT) in subjects with type 2 diabetes (T2D) is largely unknown. We aimed to identify alterations in metabolite responses to OGTT in subjects with T2D using untargeted metabolomics of both plasma and subcutaneous adipose tissue (SAT) samples. Twenty subjects with T2D and twenty healthy controls matched for sex, age, and body mass index (BMI) were profiled with untargeted metabolomics both in plasma (755 metabolites) and in the SAT (588) during an OGTT. We assessed metabolite concentration changes 90 min after the glucose load, and those responses were compared between patients with T2D and controls. Post-hoc analyses were performed to explore the associations between glucose-induced metabolite responses and markers of obesity and glucose metabolism, sex, and age. During the OGTT, T2D subjects had an impaired reduction in plasma levels of several metabolite families, including acylcarnitines, amino acids, acyl ethanolamines, and fatty acid derivates (

Appraising the Effects of Metabolic Traits on the Risk of Glaucoma A Mendelian Randomization Study.

Metabolic traits are associated with the risk of developing glaucoma in observational studies. To assess whether theses associations reflect causality, we conducted a Mendelian randomization (MR) study. Our study included up to 20,906 glaucoma cases and 438,188 controls. Genetic instruments associated with the concerned 11 exposures at the genome-wide significance level were selected from corresponding genome-wide association studies. Summary-level data for glaucoma were obtained from the UK Biobank, the GERA study, and the FinnGen consortium. Univariable and multivariable MR analyses were conducted separately in two populations. Our results showed that higher genetic liability to type 2 diabetes (T2D) was causally and independently associated with an increased risk of glaucoma (odds ratio OR, 1.11 95% confidence interval CI, 1.06-1.16

Single Point Insulin Sensitivity Estimator (SPISE) As a Prognostic Marker for Emerging Dysglycemia in Children with Overweight or Obesity.

The single point insulin sensitivity estimator (SPISE) is a recently developed fasting index for insulin sensitivity based on triglycerides, high density lipoprotein cholesterol, and body mass index. SPISE has been validated in juveniles and adults still, its role during childhood remains unclear. To evaluate the age- and sex-specific distribution of SPISE, its correlation with established fasting indexes and its application as a prognostic marker for future dysglycemia during childhood and adolescence were assessed. We performed linear modeling and correlation analyses on a cross-sectional cohort of 2107 children and adolescents (age 5 to 18.4 years) with overweight or obesity. Furthermore, survival analyses were conducted upon a longitudinal cohort of 591 children with overweightobesity (1712 observations) with a maximum follow-up time of nearly 20 years, targeting prediabetesdysglycemia as the end point. The SPISE index decreased significantly with age (-0.34 units per year,

Simultaneous Quantification of Serum Lipids and Their Association with Type 2 Diabetes Mellitus-Positive Hepatocellular Cancer.

Type 2 diabetes mellitus (T2DM) has been recognized as one of the most important and independent risk factors for hepatocellular cancer (HCC). However, there is still a lack of ideal tumor markers for HCC detection in the T2DM population. Serum lipids have been revealed as potential tumor markers for HCC. In this study, our objective was to develop a novel liquid chromatography-tandem mass spectrometry (LC-MSMS) method to detect several lipids including 8,15-dihydroxy-5,9,11,13-eicosatetraenoic acid (8,15-DiHETE), hexadecanedioic acid (HDA), 15-keto-13,14-dihydroprostaglandin A2 (DHK-PGA2), ricinoleic acid (RCL), octadecanedioic acid (OA) and 16-hydroxy hexadecanoic acid (16OHHA) in serum and explore their diagnostic potential for T2DM-positive T2DM() HCC. A robust LC-MSMS method was established for the measurement of 8,15-DiHETE, HDA, DHK-PGA2, RCL, OA, and 16OHHA. The methodology validation was conducted, and the results suggested the reliability of this LC-MSMS method for targeted lipids. Several serum lipids, including 8,15-DiHETE, HDA, DHK-PGA2, and OA were increased in T2DM() HCC patients. A biomarker signature that incorporated HDA, DHK-PGA2, and AFP was established and showed good diagnostic potential for T2DM() HCC, and the area under the ROC curve (AUC) was 0.87 for diagnosing T2DM() HCC from T2DM individuals. Additionally, the biomarker signature diagnosed small-size (AUC 0.88) and early-stage (AUC 0.79) tumors with high efficacy. Moreover, the biomarker signature could differentiate T2DM() HCC from other T2DM() tumors, including pancreatic, gastric and colorectal cancer (AUC 0.88) as well. In

Links between Metabolic Syndrome and Hypertension The Relationship with the Current Antidiabetic Drugs.

Hypertension poses a significant burden in the general population, being responsible for increasing cardiovascular morbidity and mortality, leading to adverse outcomes. Moreover, the association of hypertension with dyslipidaemia, obesity, and insulin resistance, also known as metabolic syndrome, further increases the overall cardiovascular risk of an individual. The complex pathophysiological overlap between the components of the metabolic syndrome may in part explain how novel antidiabetic drugs express pleiotropic effects. Taking into consideration that a significant proportion of patients do not achieve target blood pressure values or glucose levels, more efforts need to be undertaken to increase awareness among patients and physicians. Novel drugs, such as incretin-based therapies and renal glucose reuptake inhibitors, show promising results in decreasing cardiovascular events in patients with metabolic syndrome. The effects of sodium-glucose co-transporter-2 inhibitors are expressed at different levels, including renoprotection through glucosuria, natriuresis and decreased intraglomerular pressure, metabolic effects such as enhanced insulin sensitivity, cardiac protection through decreased myocardial oxidative stress and, to a lesser extent, decreased blood pressure values. These pleiotropic effects are also observed after treatment with glucagon-like peptide-1 receptor agonists, positively influencing the cardiovascular outcomes of patients with metabolic syndrome. The initial combination of the two classes may be the best choice in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors because of their complementary mechanisms of action. In addition, the novel mineralocorticoid receptor antagonists show significant cardio-renal benefits, as well as anti-inflammatory and anti-fibrotic effects. Overall, the key to better control of hypertension in patients with metabolic syndrome is to consider targeting multiple pathogenic mechanisms, using a combination of the different therapeutic agents, as well as drastic lifestyle changes. This article will briefly summarize the association of hypertension with metabolic syndrome, as well as take into account the influence of antidiabetic drugs on blood pressure control.

The Role of Advanced Glycation End Products on Dyslipidemia.

Disorders of lipoprotein metabolism and glucose homeostasis are common consequences of insulin resistance and usually co-segregate in patients with metabolic syndrome and type 2 diabetes mellitus (DM). Insulin-resistant subjects are characterized by atherogenic dyslipidemia, a specific lipid pattern which includes hypertriglyceridemia, reduced high-density lipoprotein cholesterol level, and increased proportion of small, dense low-density lipoprotein (LDL). Chronic hyperglycemia favors the processes of non-enzymatic glycation, leading to the increased production of advanced glycation end products (AGEs). Apart from direct harmful effects, AGEs are also potent inducers of oxidative stress and inflammation. In addition, increased AGEs production may induce further qualitative modifications of small, dense LDL particles, converting them to glycated LDLs. These particles are even more atherogenic and may confer an increased cardiovascular risk. In this narrative review, we summarize the available evidence of the pathophysiological role and clinical importance of circulating AGEs and glycated LDLs in patients with dyslipidemia, particularly those with DM and related complications. In addition, we discuss recent advances and the issues that should be improved regarding laboratory assessment of AGEs and glycated LDLs, as well as the possibilities for their therapeutic modulation.

Obstructive Sleep Apnea, Circadian Clock Disruption, and Metabolic Consequences.

Obstructive sleep apnea (OSA) is a chronic disorder characterized by recurrent episodes of apnea and hypopnea during sleep. It is associated with various cardiovascular and metabolic complications, including type 2 diabetes mellitus (T2DM) and obesity. Many pathways can be responsible for T2DM development in OSA patients, e.g., those related to HIF-1 and SIRT1 expression. Moreover, epigenetic mechanisms, such as

Associations between Periodontitis, COVID-19, and Cardiometabolic Complications Molecular Mechanisms and Clinical Evidence.

Periodontitis is a microbially driven, host-mediated disease that leads to loss of periodontal attachment and resorption of bone. It is associated with the elevation of systemic inflammatory markers and with the presence of systemic comorbidities. Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients have mild symptoms, others experience important complications that can lead to death. After the spread of the COVID-19 pandemic, several investigations demonstrating the possible relationship between periodontitis and COVID-19 have been reported. In addition, both periodontal disease and COVID-19 seem to provoke andor impair several cardiometabolic complications such as cardiovascular disease, type 2 diabetes, metabolic syndrome, dyslipidemia, insulin resistance, obesity, non-alcoholic fatty liver disease, and neurological and neuropsychiatric complications. Therefore, due to the increasing number of investigations focusing on the periodontitis-COVID-19 relationship and considering the severe complications that such an association might cause, this review aims to summarize all existing emerging evidence regarding the link between the periodontitis-COVID-19 axis and consequent cardiometabolic impairments.

HIIT Ameliorates Inflammation and Lipid Metabolism by Regulating Macrophage Polarization and Mitochondrial Dynamics in the Liver of Type 2 Diabetes Mellitus Mice.

High-intensity interval training (HIIT), a new type of exercise, can effectively prevent the progression of metabolic diseases. The aim of this study was to investigate the effects of HIIT on liver inflammation and metabolic disorders in type 2 diabetes mellitus (T2DM) mice induced by a high-fat diet (HFD) combined with streptozotocin (STZ) and to explore the possible mechanisms of macrophage polarization and mitochondrial dynamics. Our results showed that HIIT can increase fatty acid oxidation-related gene (PPARα, CPT1α, and ACOX1) mRNA levels and decrease adipogenesis-related gene (PPARγ) mRNA levels to improve liver metabolism in T2DM mice. The improvement of lipid metabolism disorder may occur through increasing liver mitochondrial biosynthesis-related genes (PGC-1α and TFAM) and restoring mitochondrial dynamics-related gene (MFN2 and DRP1) mRNA levels. HIIT can also reduce the mRNA levels of liver inflammatory factors (TNF-α, IL-6, and MCP-1) in T2DM mice. The reduction in liver inflammation may occur through reducing the expression of total macrophage marker (F480) and M1 macrophage marker (CD86) mRNA and protein and increasing the expression of M2 macrophage marker (CD163, CD206, and Arg1) mRNA and protein in the liver. HIIT can also increase the expression of insulin signaling pathway (IRS1, PI3K, and AKT) mRNA and protein in the liver of T2DM mice, which may be related to the improvements in liver inflammation and lipid metabolism. In conclusion, these results suggested that 8 weeks of HIIT can improve inflammation and lipid metabolism disorders in the liver of type 2 diabetes mellitus mice, macrophage M1M2 polarization, and mitochondrial dynamics may be involved in this process.

Clinical Inertia in the Management of Type 2 Diabetes Mellitus A Systematic Review.

This review seeks to establish, through the recent available literature, the prevalence of therapeutic intensification delay and its sequences in poorly controlled Type 2 Diabetes Mellitus (T2DM) patients. The strategy identified studies exploring the clinical inertia and its associated factors in the treatment of patients with T2DM. A total of 25 studies meeting the pre-established quality criteria were included in this review. These studies were conducted between 2004 and 2021 and represented 575,067 patients diagnosed with T2DM. Trusted electronic bibliographic databases, including Medline, Embase, and the Cochrane Central Register of Controlled Trials, were used to collect studies by utilizing a comprehensive set of search terms to identify Medical Subject Headings (MeSH) terms. Most o the studies included in this review showed clinical inertia rates over 50% of T2DM patients. In the USA, clinical inertia ranged from 35.4% to 85.8%. In the UK, clinical inertia ranged from 22.1% to 69.1%. In Spain, clinical inertia ranged from 18.1% to 60%. In Canada, Brazil, and Thailand, clinical inertia was reported as 65.8%, 68%, and 68.4%, respectively. The highest clinical inertia was reported in the USA (85.8%). A significant number of patients with T2DM suffered from poor glycemic control for quite a long time before treatment intensification with oral antidiabetic drugs (OADs) or insulin. Barriers to treatment intensification exist at the provider, patient, and system levels. There are deficiencies pointed out by this review at specialized centers in terms of clinical inertia in the management of T2DM including in developed countries. This review shows that the earlier intensification in the T2DM treatment is appropriate to address issues around therapeutic inertia.

A Nonrandomized Phase 2 Trial of EG-Mirotin, a Novel, First-in-Class, Subcutaneously Deliverable Peptide Drug for Nonproliferative Diabetic Retinopathy.

The

A Systematic Review and Meta-Analysis of Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Injections in Type-2 Diabetes.

Diabetes mellitus (DM) has a growing prevalence worldwide, even in developing countries. Many antidiabetic agents are used to improve glycemic control however, in cases of an insufficient outcome, insulin is administered. Yet, the timing of proper insulin administration is still a subject of intense research. To date, there have been no recommendations or guidelines for the use of continuous subcutaneous insulin infusion (CSII) in Type 2 Diabetes Mellitus (T2DM). In the present study, we have performed a meta-analysis to evaluate the use of CSII in patients with T2DM. An extensive literature search was conducted through the electronic databases Pubmed, Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) from October 2019-May 2022, for interventional studies related to T2DMI and CSII versus multiple daily injections (MDI). We included articles published in the English language only, yielding a total of thirteen studies. We found better outcomes in patients receiving CSII, in regard to glycated hemoglobin (HbA1c) and total insulin dose. In contrast, fasting plasma glucose and body weight did not show statistically significant differences between the two groups. Our analyses showed that CSII could be beneficial in patients with T2DM in order to achieve their glucose targets.

Medium- and Long-Term Effects of Dapagliflozin on Serum Uric Acid Level in Patients with Type 2 Diabetes A Real-World Study.

We aimed to explore the medium- and long-term (≥12 weeks) effects of dapagliflozin on serum uric acid (SUA) level in patients with type 2 diabetes mellitus (T2DM) in the real world study and to explore the influencing factors of dapagliflozin on reducing SUA level. This observational, prospective cohort study was based on the real world. There were 77 patients included in this study. They were divided into two groups. Patients in treatment group (

Association of Advanced Lipoprotein Subpopulation Profiles with Insulin Resistance and Inflammation in Patients with Type 2 Diabetes Mellitus.

Plasma lipoproteins exist as several subpopulations with distinct particle number and size that are not fully reflected in the conventional lipid panel. In this study, we sought to quantify lipoprotein subpopulations in patients with type 2 diabetes mellitus (T2DM) to determine whether specific lipoprotein subpopulations are associated with insulin resistance and inflammation markers. The study included 57 patients with T2DM (age, 61.14 ± 9.99 years HbA1c, 8.66 ± 1.60% mean body mass index, 35.15 ± 6.65 kgm

Identification of FGF13 as a Potential Biomarker and Target for Diagnosis of Impaired Glucose Tolerance.

Early identification of pre-diabetes provides an opportunity for intervention and treatment to delay its progression to type 2 diabetes mellitus (T2DM). We aimed to identify the biomarkers of impaired glucose tolerance (IGT) through bioinformatics analysis. The GSE76896 dataset, including non-diabetic (ND), IGT, and T2DM clinical samples, was deeply analyzed to identify 309 Co-DEGs for IGT and T2DM. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that inflammatory responses and the PI3K-AKT signaling pathway are important patho-physiological features of IGT and T2DM. Protein-protein interaction (PPI) network analysis and cytoHubba technolgy identified seven hub genes namely, CCL2, CXCL1, CXCL8, EDN1, FGF13, MMP1, and NGF. The expression and ROC curves of these hub genes were validated using the GSE38642 dataset. Through an immunofluorescence assay, we found that the expression of FGF13 in islets of mice in the HFD and T2DM groups was significantly lower than in the control group. Similarly, the level of FGF13 in the sera of IGT and T2DM patients was lower than that in the healthy group. Together, these results suggest that FGF13 can be treated as a novel biomarker of IGT, which may provide new targets for the diagnosis and treatment of pre-diabetes and T2DM.

Role of Impaired Glycolysis in Perturbations of Amino Acid Metabolism in Diabetes Mellitus.

The most frequent alterations in plasma amino acid concentrations in type 1 and type 2 diabetes are decreased L-serine and increased branched-chain amino acid (BCAA valine, leucine, and isoleucine) levels. The likely cause of L-serine deficiency is decreased synthesis of 3-phosphoglycerate, the main endogenous precursor of L-serine, due to impaired glycolysis. The BCAA levels increase due to decreased supply of pyruvate and oxaloacetate from glycolysis, enhanced supply of NADH H

GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease Current Evidence and Future Perspectives.

To date, non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease, affecting up to 70% of patients with diabetes. Currently, there are no specific drugs available for its treatment. Beyond their anti-hyperglycemic effect and the surprising role of cardio- and nephroprotection, GLP-1 receptor agonists (GLP-1 RAs) have shown a significant impact on body weight and clinical, biochemical and histological markers of fatty liver and fibrosis in patients with NAFLD. Therefore, GLP-1 RAs could be a weapon for the treatment of both diabetes mellitus and NAFLD. The aim of this review is to summarize the evidence currently available on the role of GLP-1 RAs in the treatment of NAFLD and to hypothesize potential future scenarios.

Exogenous H

Obesity, along with type 2 diabetes mellitus (T2DM), is a major contributor to hypertension. The renin-angiotensin-aldosterone system is involved in the occurrence of diabetes and hypertension. However, the mechanism by which obesity is related to T2DM induced hypertension is unclear. In this study, we observed that blood pressure and serum renin content were increased in patients with diabetes and hypertension. Hydrogen sulfide (H

Recent Pharmacological Options in Type 2 Diabetes and Synergic Mechanism in Cardiovascular Disease.

Diabetes Mellitus is a multifactorial disease with a critical impact worldwide. During prediabetes, the presence of various inflammatory cytokines and oxidative stress will lead to the pathogenesis of type 2 diabetes. Furthermore, insulin resistance and chronic hyperglycemia will lead to micro- and macrovascular complications (cardiovascular disease, heart failure, hypertension, chronic kidney disease, and atherosclerosis). The development through the years of pharmacological options allowed us to reduce the persistence of chronic hyperglycemia and reduce diabetic complications. This review aims to highlight the specific mechanisms with which the new treatments for type 2 diabetes reduce oxidative stress and insulin resistance and improve cardiovascular outcomes.

Gender Differences and Cardiometabolic Risk The Importance of the Risk Factors.

Metabolic syndrome (Mets) is a clinical condition characterized by a cluster of major risk factors for cardiovascular disease (CVD) and type 2 diabetes proatherogenic dyslipidemia, elevated blood pressure, dysglycemia, and abdominal obesity. Each risk factor has an independent effect, but, when aggregated, they become synergistic, doubling the risk of developing cardiovascular diseases and causing a 1.5-fold increase in all-cause mortality. We will highlight gender differences in the epidemiology, etiology, pathophysiology, and clinical expression of the aforementioned Mets components. Moreover, we will discuss gender differences in new biochemical markers of metabolic syndrome and cardiovascular risk.

Dapagliflozin Treatment Augments Bioactive Phosphatidylethanolamine Concentrations in Kidney Cortex Membrane Fractions of Hypertensive Diabetic dbdb Mice and Alters the Density of Lipid Rafts in Mouse Proximal Tubule Cells.

In addition to inhibiting renal glucose reabsorption and allowing for glucose excretion, the sodiumglucose cotransporter 2 (SGLT2) inhibitor dapagliflozin may be efficacious in treating various comorbidities associated with type 2 diabetes mellitus (T2DM). The molecular mechanisms by which dapagliflozin exerts its beneficial effects are largely unknown. We hypothesized dapagliflozin treatment in the diabetic kidney alters plasma membrane lipid composition, suppresses extracellular vesicle (EV) release from kidney cells, and disrupts lipid rafts in proximal tubule cells. In order to test this hypothesis, we treated diabetic dbdb mice with dapagliflozin (N 8) or vehicle (N 8) and performed mass spectrometry-based lipidomics to investigate changes in the concentrations of membrane lipids in the kidney cortex. In addition, we isolated urinary EVs (uEVs) from urine samples collected during the active phase and the inactive phase of the mice and then probed for changes in membrane proteins enriched in the EVs. Multiple triacylglycerols (TAGs) were enriched in the kidney cortex membrane fractions of vehicle-treated diabetic dbdb mice, while the levels of multiple phosphatidylethanolamines were significantly higher in similar mice treated with dapagliflozin. EV concentration and size were lesser in the urine samples collected during the inactive phase of dapagliflozin-treated diabetic mice. In cultured mouse proximal tubule cells treated with dapagliflozin, the lipid raft protein caveolin-1 shifted from less dense fractions to more dense sucrose density gradient fractions. Taken together, these results suggest dapagliflozin may regulate lipid-mediated signal transduction in the diabetic kidney.

Dysregulated UPR and ER Stress Related to a Mutation in the

The Cohen Diabetic rat is a model of type 2 diabetes mellitus that consists of the susceptible (CDsy) and resistant (CDry) strains. Diabetes develops in CDsy provided diabetogenic diet (DD) but not when fed regular diet (RD) nor in CDry given either diet. We recently identified in CDsy a deletion in

Anti-IL17A Halts the Onset of Diabetic Retinopathy in Type I and II Diabetic Mice.

There are 463 million diabetics worldwide, and more than half have diabetic retinopathy. Yet, treatments are still lacking for non-proliferative diabetic retinopathy. We and others previously provided evidence that Interleukin-17A (IL-17A) plays a pivotal role in non-proliferative diabetic retinopathy. However, all murine studies used Type I diabetes models. Hence, it was the aim of this study to determine if IL-17A induces non-proliferative diabetic retinopathy in Type II diabetic mice, as identified for Type I diabetes. While examining the efficacy of anti-IL-17A as a potential therapeutic in a short-term Type I and a long-term Type II diabetes model using different routes of administration of anti-IL-17A treatments. Retinal inflammation was significantly decreased (

The Predictive Role of Extracellular NAPRT for the Detection of Advanced Fibrosis in Biopsy-Proven Non-Alcoholic Fatty Liver Disease.

Intrahepatic oxidative stress is a key driver of inflammation and fibrogenesis in non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the role of extracellular Nicotinamide phosphoribosyltransferase (eNAMPT) and extracellular nicotinic acid phosphoribosyltransferase (eNAPRT) for the detection of advanced fibrosis. eNAMPT and eNAPRT were tested in 180 consecutive biopsy-proven NAFLD patients and compared with liver stiffness (LS) and the FIB-4 score. eNAMPT was similarly distributed across fibrosis stages, whereas eNAPRT was increased in patients with advanced fibrosis (

miR-24-3p and Body Mass Index as Type 2 Diabetes Risk Factors in Spanish Women 15 Years after Gestational Diabetes Mellitus Diagnosis.

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance that is diagnosed for the first time during pregnancy. The objective of this study is to know the glucose tolerance status after 15 years of pregnancy in patients diagnosed with gestational diabetes and to assess the long-term effect of GDM on the circulating miRNA profile of these women. To answer these, 30 randomly selected women diagnosed with GDM during 2005-2006 were included in the study, and glucose tolerance was measured using the National Diabetes Data Group criteria. Additionally, four miRNAs (hsa-miR-1-3p, hsa-miR-24-3p, hsa-miR-329-3p, hsa-miR-543) were selected for their analysis in the plasma of women 15 years after the diagnosis of GDM. In our study we discovered that, fifteen years after the diagnosis of GDM, 50% of women have some degree of glucose intolerance directly related to body weight and body mass index during pregnancy. Dysglycemic women also showed a significantly increased level of circulating hsa-miR-24-3p. Thus, we can conclude that initial weight and BMI, together with circulating expression levels of hsa-miR-24-3p, could be good predictors of the future development of dysglycemia in women with a previous diagnosis of GDM.

Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy.

The main cause of morbidity and mortality in diabetes mellitus (DM) is cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here, we compared these two models for their effects on cardiac structure, function and transcriptome. Different doses of STZ and diet chows were used to generate T1DM and T2DM in C57BL6J mice. Normal euglycemic and nonobese sex- and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR and RNA-seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM affected left ventricular function and myocardial performance differently. T1DM displayed exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis, along with increased cardiac oxidative stress, CM DNA damage and senescence, when compared to T2DM in mice. T1DM and T2DM affected the whole cardiac transcriptome differently. In conclusion, the STZ-induced T1DM and T2DM mouse models showed significant differences in cardiac remodeling, function and the whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.

PLVAP as an Early Marker of Glomerular Endothelial Damage in Mice with Diabetic Kidney Disease.

Plasmalemma vesicle-associated protein (PLVAP) is the main component of endothelial diaphragms in fenestrae, caveolae, and transendothelial channels. PLVAP is expressed in the adult kidney glomerulus upon injury. Glomerular endothelial injury is associated with progressive loss of kidney function in diabetic kidney disease (DKD). This study aimed to investigate whether PLVAP could serve as a marker for glomerular endothelial damage in DKD. Glomerular PLVAP expression was analyzed in different mouse models of DKD and their respective healthy control animals using automatic digital quantification of histological whole kidney sections. Transgenic mice expressing a dominant-negative GIP receptor (GIPR

Integrating Common Risk Factors with Polygenic Scores Improves the Prediction of Type 2 Diabetes.

We tested associations between 13 established genetic variants and type 2 diabetes (T2D) in 1371 study participants from the Volga-Ural region of the Eurasian continent, and evaluated the predictive ability of the model containing polygenic scores for the variants associated with T2D in our dataset, alone and in combination with other risk factors such as age and sex. Using logistic regression analysis, we found associations with T2D for the

Vitamin D, Gut Microbiota, and Cardiometabolic Diseases-A Possible Three-Way Axis.

Metabolic syndrome (MetSyn) is a precursor for several cardiometabolic diseases such as obesity, type-2 diabetes mellitus (T2DM), and cardiovascular diseases. Emerging evidence suggests that vitamin D deficiency links to cardiometabolic diseases through microbiota. A combination of poor vitamin D status and dysbiosis may contribute to the progression of cardiometabolic diseases. Therefore, in this review, we present the relationship among vitamin D, microbiota, and cardiometabolic diseases with a focus on MetSyn. We searched major databases for reports on vitamin D, microbiota, and MetSyn until June 2022. We reviewed 13 reports on the relation between vitamin D and MetSyn (6 randomized controlled and 7 cross-sectional studies) and 6 reports on the effect of vitamin D on the gut microbiome. Adequate vitamin D status has a beneficial effect on gut microbiota, therefore preventing the progression of MetSyn. Further, well-controlled studies are needed for a better understanding of the mechanisms of action involving vitamin D and microbiota in the pathogenesis of cardiometabolic diseases.

The Synergistic Action of Metformin and

Metformin, an antidiabetic drug, and

Factors Associated with Medication Adherence among Patients with Type 2 Diabetes Mellitus A Hospital-Based Cross-Sectional Study in Nepal.

As diabetes increases globally, high mortality increases due to complications of uncontrolled sugar. Medication adherence is important to control blood sugar and prevent its complications. Objective of the study was to identify factors associated with medication adherence among type 2 diabetes patients. A cross-sectional study was conducted among 343 patients visiting Dhulikhel Hospital, Nepal, for their fasting blood sugar test from September to December 2016. Inclusion criteria patients with type 2 diabetes, under diabetes medication for past three months (minimum), age ≥ 18 years. The outcome of the study was medication adherence measured using the eight-item Morisky medication adherence scale (MMAS-8) (© 2006 Donald E. Morisky). Multivariate logistic regression was used for the analysis. Results showed that 61% of respondents had high medication adherence adherence was positively associated with formal education AOR 2.43 (95% CI 1.34, 4.39) and attendance at diabetes counseling AOR 1.76 (95% CI 1.02, 3.04) after adjusting for age, occupation, medicine intake duration and diabetes medicine types. The study concluded that formal education and attendance at diabetes counseling positively affected patients adherence to medicine. We encourage healthcare institutions to provide counseling services to all the patients with type 2 diabetes and focus more on those who are less educated.

Glutathione S-Transferase P1 Genetic Variants Influence on the HbA1c Level in Type Two Diabetic Patients.

GST (glutathione S-transferases) are capable of influencing glucose homeostasis, probably through regulation of the response to oxidant stress. The aim of our study was to investigate the relationship between GSTP1 gene polymorphism and glycated hemoglobin (HbA1c) levels in type two diabetic (T2D) patients. A total of 307 T2D patients were included. Analysis of the GSTP1 gene polymorphism (rs1695) was conducted using the TaqMan qPCR method endpoint genotyping. HbA1c was determined using a COBAS 6000 autoanalyzer. A univariable linear regression and multivariable linear regression model were used to investigate the association between mean HbA1c level and GSTP1 gene polymorphism, age at T2D diagnosis, T2D duration, therapy with insulin, gender, BMI, smoking status. GSTP1 ValVal genotype, age at T2D diagnosis, T2D duration and therapy with insulin were statistically significant contributors to HbA1c levels (

From Zero to Hero Type 2 Diabetes Mellitus Patients Hike on the Way of St. James-A Feasibility Study with Analyses of Patients Quality of Life, Diabetes Distress and Glucose Profile.

This study investigates the feasibility of an accompanied 5-day hiking tour (Way of St. James) for type 2 diabetes mellitus (T2DM) patients and its impact on their quality of lifewell-being, diabetes distress and glucose profile. Twenty-three T2DM patients (with and without insulin therapy) participated in the study. The 120 km pilgrimage (from Ferrol to Santiago de Compostela, Spain) was accompanied by three physicians, two diabetes counselors and one sports scientist. Quality of lifewell-being was assessed by the World Health Organizations (WHO)-5 questionnaire, and diabetes distress was evaluated based on the Problem Areas in Diabetes (PAID) scale. The glucose levels of six insulin-treated patients were measured using continuous glucose monitoring (CGM) devices, considering that insulin-treated patients can be at increased risk of exercise-induced hypoglycemia. A significant improvement in quality of lifewell-being was reported (

Impact of Patient-Centered and Self-Care Education on Diabetes Control in a Family Practice Setting in Saudi Arabia.

Diabetes mellitus is a chronic and complex medical disease that leads to significant morbidity and mortality. Patient-centered diabetes education that emphasizes active patient involvement, self, and shared care constitutes a substantial and essential component of the comprehensive diabetes management approach. To assess the impact of patient-centered diabetes education sessions on the prescribed treatment plan in controlling diabetes and other related cardiovascular risk factors. In a pre-experimental pretest-posttest one group study design, all referred patients with type 2 diabetes (T2DM) to the diabetes educator clinic ( This study showed a considerable positive impact of diabetes education and patient-centered care on optimizing glycemic and other cardiovascular risk control. The needs of certain patients with T2DM should be addressed individually to achieve the best possible outcomes. Further research is needed to explore the long-term benefits of this intervention.

Association between METS-IR and Prediabetes or Type 2 Diabetes Mellitus among Elderly Subjects in China A Large-Scale Population-Based Study.

The metabolic score for insulin resistance (METS-IR) was recently proposed as a non-insulin-based, novel index for assessing insulin resistance (IR) in the Western population. However, evidence for the link between METS-IR and prediabetes or type 2 diabetes mellitus (T2DM) among the elderly Chinese population was still limited. We aimed to investigate the associations between METS-IR and prediabetes or T2DM based on large-scale, cross-sectional, routine physical examination data. In a total of 18,112 primary care service users, an increased METS-IR was independently associated with a higher prevalence of prediabetes (adjusted odds ratio aOR 1.457, 95% confidence interval CI 1.343 to 1.581,

This article reports the results of

The Association between Non-Alcoholic Fatty Liver Disease and Dynapenia in Men Diagnosed with Type 2 Diabetes Mellitus.

Konjac Glucomannan An Emerging Specialty Medical Food to Aid in the Treatment of Type 2 Diabetes Mellitus.

There are many factors causing T2DM thus, it is difficult to prevent and cure it with conventional treatment. In order to realize the continuous intervention of T2DM, the treatment strategy of combining diet therapy and traditional medication came into being. As a natural product with the concept of being healthy, konjac flour and its derivatives are popular with the public. Its main component, Konjac glucomannan (KGM), can not only be applied as a food additive, which greatly improves the taste and flavor of food and extends the shelf life of food but also occupies an important role in T2DM. KGM can extend gastric emptying time, increase satiety, and promote liver glycogen synthesis, and also has the potential to improve intestinal flora and the metabolic system through a variety of molecular pathways in order to positively regulate oxidative stress and immune inflammation, and protect the liver and kidneys. In order to establish the theoretical justification for the adjunctive treatment of T2DM, we have outlined the physicochemical features of KGM in this article, emphasizing the advantages of KGM as a meal for special medical purposes of T2DM.

Gestational diabetes mellitus (GDM) is a metabolic disorder in pregnant women leading to various complications. Consequently, factors predisposing its development are being sought. Previous studies have shown that the pathogenesis of GDM is similar to that of type 2 diabetes, and it is therefore thought that the two diseases may have a common genetic basis. The aim of this study was to examine the associations between thyroid adenoma-associated (

The Role of Pancreatic Fatty Acid Synthesis in Islet Morphology and Function after Caloric Restriction or Roux-En-Y Gastric Bypass Surgery in Mice.

Both caloric restriction (CR) and Roux-en-Y gastric bypass (RYGB) are practical interventions for type 2 diabetes mellitus (T2DM), while the molecular mechanisms of CR and RYGB regarding glycemic control are still poorly understood. Here, we explore the effects and underlying mechanisms of CR and RYGB on β-cell area and function. Average islet size was measured by histological analysis. The pancreatic lipid content was detected by using a commercial lipid assay kit. The expression levels of lipogenic transcription factors and enzymes in mouse pancreas were determined by quantitative PCR, Western blot, and immunofluorescence. CR decreased the mean size of islets and pancreatic insulin production in both regular diet-fed and high-fat diet-fed mice. Increased β-cell apoptosis was detected in the calorie-restricted mice. Interestingly, the lipogenic transcription factors and enzymes such as SREBP1c, PPARγ, FASN and ACC were upregulated in the pancreas after CR. In contrast to CR, RYGB decreased the apoptosis of β-cells and the expression of fatty acid synthase. Pancreatic fatty acid synthesis is critical to the β-cell function after CR and RYGB.

Impact of COVID-19 on the Microbiome and Inflammatory Status of Type 2 Diabetes Patients.

The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic has advanced our understanding of the host-microbiome-virus interplay. Several studies in various geographical regions report that SARS-CoV-2 infection disrupts the intestinal microbiota, allowing pathogenic bacteria such as

Type 2 Diabetes Related Mitochondrial Defects in Peripheral Mononucleated Blood Cells from Overweight Postmenopausal Women.

Type 2 diabetes (T2D) is a multisystem disease that is the subject of many studies, but the earliest cause of the disease has yet to be elucidated. Mitochondrial impairment has been associated with diabetes in several tissues. To extend the association between T2D and mitochondrial impairment to blood cells, we investigated T2D-related changes in peripheral mononucleated blood cells (PBMCs) mitochondrial function in two groups of women (CTRL vs. T2D mean age 54.1 ± 3.8 vs. 60.9 ± 4.8 mean BMI 25.6 ± 5.2 vs. 30.0 ± 5), together with a panel of blood biomarkers, anthropometric measurements and physiological parameters (VO

Multimodal Comparison of Diabetic Neuropathy in Aged Streptozotocin-Treated Sprague-Dawley and Zucker Diabetic Fatty Rats.

The development and progression of diabetic polyneuropathy (DPN) are due to multiple mechanisms. The creation of reliable animal models of DPN has been challenging and this issue has not yet been solved. However, despite some recognized differences from humans, most of the current knowledge on the pathogenesis of DPN relies on results achieved using rodent animal models. The simplest experimental DPN model reproduces type 1 diabetes, induced by massive chemical destruction of pancreatic beta cells with streptozotocin (STZ). Spontaneoustransgenic models of diabetes are less frequently used, mostly because they are less predictable in clinical course, more expensive, and require a variable time to achieve homogeneous metabolic conditions. Among them, Zucker diabetic fatty (ZDF) rats represent a typical type 2 diabetes model. Both STZ-induced and ZDF rats have been extensively used, but only very few studies have compared the long-term similarities and differences existing between these two models. Moreover, inconsistencies have been reported regarding several aspects of short-term in vivo studies using these models. In this study, we compared the long-term course of DPN in STZ-treated Sprague-Dawley and ZDF rats with a multimodal set of readout measures.

Fecal Microbiota Transplantation in Patients Co-Infected with SARS-CoV2 and

The COVID-19 pandemic has challenged the treatment of To achieve this goal, we performed a comparative, retrospective, single-center study on 86 patients (admitted between January 2020 and March 2022). We based our approach on specific inclusion criteria 1. The study group included 46 co-infected patients (COVID-19 and CD) receiving antibiotics and FMT 2. In the control group, 40 co-infected patients received antibiotics only. Our results showed no significant group differences in terms of gender, age, risk factors such as cardiovascular and neurological diseases, type 2 diabetes, and obesity ( Our study provides new data to support the multiple benefits of FMT in the case of COVID-19 and CD co-infection by improving patients quality of life and inflammatory syndrome.

The Landscape of HNF1B Deficiency A Syndrome Not Yet Fully Explored.

The hepatocyte nuclear factor 1β (HNF1B) gene is involved in the development of specialized epithelia of several organs during the early and late phases of embryogenesis, performing its function mainly by regulating the cell cycle and apoptosis pathways. The first pathogenic variant of HNF1B (namely, R177X) was reported in 1997 and is associated with the maturity-onset diabetes of the young. Since then, more than 230 different HNF1B variants have been reported, revealing a multifaceted syndrome with complex and heterogenous genetic, pathologic, and clinical profiles, mainly affecting the pediatric population. The pancreas and kidneys are the most frequently affected organs, resulting in diabetes, renal cysts, and a decrease in renal function, leading, in 2001, to the definition of HNF1B deficiency syndrome, including renal cysts and diabetes. However, several other organs and systems have since emerged as being affected by HNF1B defect, while diabetes and renal cysts are not always present. Especially, liver involvement has generally been overlooked but recently emerged as particularly relevant (mostly showing chronically elevated liver enzymes) and with a putative relation with tumor development, thus requiring a more granular analysis. Nowadays, HNF1B-associated disease has been recognized as a clinical entity with a broader and more variable multisystem phenotype, but the reasons for the phenotypic heterogeneity are still poorly understood. In this review, we aimed to describe the multifaceted nature of HNF1B deficiency in the pediatric and adult populations we analyzed the genetic, phenotypic, and clinical features of this complex and misdiagnosed syndrome, covering the most frequent, unusual, and recently identified traits.

New Treatment for Type 2 Diabetes Mellitus Using a Novel Bipyrazole Compound.

2,3,3,5-Tetramethyl-4-nitro-2H-1,3-bipyrazole (TMNB) is a novel bipyrazole compound with unknown therapeutic potential in diabetes mellitus. This study aims to investigate the anti-diabetic effects of TMNB in a high-fat diet and streptozotocin-(HFDSTZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mgkg). HFDSTZ diabetic rats were treated orally with TMNB (10 mgkg) or (200 mgkg) metformin for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. TMNB reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (

Altered Functional Connectivity Density in Type 2 Diabetes Mellitus with and without Mild Cognitive Impairment.

Although disturbed functional connectivity is known to be a factor influencing cognitive impairment, the neuropathological mechanisms underlying the cognitive impairment caused by type 2 diabetes mellitus (T2DM) remain unclear. To characterize the neural mechanisms underlying T2DM-related brain damage, we explored the altered functional architecture patterns in different cognitive states in T2DM patients. Thirty-seven T2DM patients with normal cognitive function (DMCN), 40 T2DM patients with mild cognitive impairment (MCI) (DMCI), and 40 healthy controls underwent neuropsychological assessments and resting-state functional MRI examinations. Functional connectivity density (FCD) analysis was performed, and the relationship between abnormal FCD and clinicalcognitive variables was assessed. The regions showing abnormal FCD in T2DM patients were mainly located in the temporal lobe and cerebellum, but the abnormal functional architecture was more extensive in DMCI patients. Moreover, in comparison with the DMCN group, DMCI patients showed reduced long-range FCD in the left superior temporal gyrus (STG), which was correlated with the Rey auditory verbal learning test score in all T2DM patients. Thus, DMCI patients show functional architecture abnormalities in more brain regions involved in higher-level cognitive function (executive function and auditory memory function), and the left STG may be involved in the neuropathology of auditory memory in T2DM patients. These findings provide some new insights into understanding the neural mechanisms underlying T2DM-related cognitive impairment.

Peptidomics Profile, Bioactive Peptides Identification and Biological Activities of Six Different Cheese Varieties.

Several recent published studies reported that cheese consumption may protect against the onset of cardiovascular diseases and type-2 diabetes due to the presence of bioactive peptides. In the present work, six cheese varieties (the Egyptian traditional cheeses Karish, Domiati and Ras as well as Feta-type, Gouda and Edam cheeses) were characterized for their peptidomics profiles with high-resolution mass spectrometry, biological activities and content in bioactive peptides. The highest ACE-inhibitory and DPP-IV-inhibitory activities were found in Gouda cheese, which also displayed the highest antioxidant activity. A total of 809 peptides originating from the major milk proteins were identified, and 82 of them were bioactive. Most of them showed ACE-inhibitory, antioxidant and DPP-IV-inhibitory activities. The highest amount of the in vivo anti-hypertensive tripeptides VPP and IPP was found in Gouda cheese (39.19 ± 1.26 and 17.72 ± 0.89 mg100 g of cheese, respectively), whereas the highest amount of APFPE was detected in Edam cheese (509.13 ± 20.44 mg100 g of cheese). These results suggest that the intake of Edam, Domiati and, especially, Gouda cheeses may result in a possible anti-hypertensive effect in hypertensive subjects.

Type 2 Diabetes and Alzheimers Disease The Emerging Role of Cellular Lipotoxicity.

Type 2 diabetes (T2D) and Alzheimers diseases (AD) represent major health issues that have reached alarming levels in the last decades. Although growing evidence demonstrates that AD is a significant comorbidity of T2D, and there is a 1.4-2-fold increase in the risk of developing AD among T2D patients, the involvement of possible common triggers in the pathogenesis of these two diseases remains largely unknown. Of note, recent mechanistic insights suggest that lipotoxicity could represent the missing ring in the pathogenetic mechanisms linking T2D to AD. Indeed, obesity, which represents the main cause of lipotoxicity, has been recognized as a major risk factor for both pathological conditions. Lipotoxicity can lead to inflammation, insulin resistance, oxidative stress, ceramide and amyloid accumulation, endoplasmic reticulum stress, ferroptosis, and autophagy, which are shared biological events in the pathogenesis of T2D and AD. In the current review, we try to provide a critical and comprehensive view of the common molecular pathways activated by lipotoxicity in T2D and AD, attempting to summarize how these mechanisms can drive future research and open the way to new therapeutic perspectives.

Bavachin and Corylifol A Improve Muscle Atrophy by Enhancing Mitochondria Quality Control in Type 2 Diabetic Mice.

Type 2 diabetes reduces muscle mass and function. Chronic inflammation and mitochondrial dysfunction play critical roles in muscle atrophy pathogenesis. Here, we investigated the effects of bavachin and corylifol A from

Cranberry Proanthocyanidins as a Therapeutic Strategy to Curb Metabolic Syndrome and Fatty Liver-Associated Disorders.

While the prevalence of metabolic syndrome (MetS) is steadily increasing worldwide, no optimal pharmacotherapy is readily available to address its multifaceted risk factors and halt its complications. This growing challenge mandates the development of other future curative directions. The purpose of the present study is to investigate the efficacy of cranberry proanthocyanidins (PACs) in improving MetS pathological conditions and liver complications C57BL6J mice were fed either a standard chow or a high fathigh sucrose (HFHS) diet with and without PACs (200 mgkg), delivered by daily gavage for 12 weeks. Our results show that PACs lowered HFHS-induced obesity, insulin resistance, and hyperlipidemia. In conjunction, PACs lessened circulatory markers of oxidative stress (OxS) and inflammation. Similarly, the anti-oxidative and anti-inflammatory capacities of PACs were noted in the liver in association with improved hepatic steatosis. Inhibition of lipogenesis and stimulation of beta-oxidation could account for PACs-mediated decline of fatty liver as evidenced not only by the expression of rate-limiting enzymes but also by the status of AMPKα (the key sensor of cellular energy) and the powerful transcription factors (PPARα, PGC1α, SREBP1c, ChREBP). Likewise, treatment with PACs resulted in the downregulation of critical enzymes of liver gluconeogenesis, a process contributing to increased rates of glucose production in type 2 diabetes. Our findings demonstrate that PACs prevented obesity and improved insulin resistance likely via suppression of OxS and inflammation while diminishing hyperlipidemia and fatty liver disease, as clear evidence for their strength of fighting the cluster of MetS abnormalities.

Association of Serum Antioxidant Minerals and Type 2 Diabetes Mellitus in Chinese Urban Residents.

Antioxidant minerals including zinc, copper and selenium play critical roles in the maintenance of the redox balance in the body. However, their influences on type 2 diabetes mellitus (T2DM) are still inconclusive in Chinese populations. To elucidate the relationship between antioxidant minerals and T2DM, serum zinc, copper and selenium concentrations were measured in 1443 Chinese urban residents using a 12 matched case-control study. Conditional logistic regression models (CLR) were used to obtain the odds ratios (ORs) and 95% confidence intervals (CIs), and restricted cubic splines (RCS) were used to examine their dose-response associations. Serum zinc (OR 0.52 0.35, 0.77) and copper concentrations (OR 0.25 0.17, 0.37) were negatively associated with T2DM in a fully adjusted model. An L-shaped zinc-T2DM association (

A Comparative Study on Improving Streptozotocin-Induced Type 2 Diabetes in Rats by Hydrosol, Extract and Nanoemulsion Prepared from Cinnamon Leaves.

Verapamil-loaded supramolecular hydrogel patch attenuates metabolic dysfunction-associated fatty liver disease via restoration of autophagic clearance of aggregated proteins and inhibition of NLRP3.

Obesity, a serious threat to public health, is linked to chronic metabolic complications including insulin resistance, type-2 diabetes, and metabolic dysfunction-associated fatty liver disease (MAFLD). Current obesity medications are challenged by poor effectiveness, poor patient compliance, and potential side effects. Verapamil is an inhibitor of L-type calcium channels, FDA-approved for the treatment of hypertension. We previously investigated the effect of verapamil on modulating autophagy to treat obesity-associated lipotoxicity. This study aims to develop a verapamil transdermal patch and to evaluate its anti-obesity effects. Verapamil is loaded in biomimetic vascular bundle-like carboxymethyl pullulan-based supramolecular hydrogel patches cross-linked with citric acid and glycerol linkages (CLCMP). The investigation was then carried out to determine the therapeutic effect of verapamil-loaded CLCMP (VeraCLCMP) on diet-induced obese mice. VeraCLCMP hydrogel patches with hierarchically organized and anisotropic pore structures not only improved verapamil bioavailability without modifying its chemical structure but also enhanced verapamil release through the stratum corneum barrier. VeraCLCMP patches exhibit low toxicity and high effectiveness at delivering verapamil into the systemic circulation through the dermis in a sustained manner. Specifically, transdermal administration of this patch into diet-induced obese mice drastically improved glucose tolerance and insulin sensitivity and alleviated metabolic derangements associated with MAFLD. Furthermore, we uncovered a distinct molecular mechanism underlying the anti-obesity effects associated with the hepatic NLR family pyrin domain-containing 3 (NLRP3) inflammasome and autophagic clearance by the veraCLCMP hydrogel patches. The current study provides promising drug delivery platforms for long-term family treatment of chronic diseases, including obesity and metabolic dysfunctions.

Dietary pattern scores in relation to pre-diabetes regression to normal glycemia or progression to type 2 diabetes a 9-year follow-up.

We aimed to assess potential associations of habitual dietary pattern scores in relation to the risk of pre-diabetes (Pre-DM) progression to type 2 diabetes mellitus (T2DM) or the chance of returning to normal glycemia. This cohort study included 334 Pre-DM individuals (mean age of 49.4 years, and 51.5% men) who participated in the third phase of the Tehran Lipid and Glucose Study (2006-2008) and followed up for a median of 9 years. A validated food frequency questionnaire at baseline assessed usual intakes of the participants. Major dietary patterns were identified using principal component analysis. The DASH score and Mediterranean diet score (MDS) were also calculated. Multinomial logistic regression analysis was used to estimate the odds ratios (95% confidence intervals (CIs)) of developing T2DM and returning to normal glycemia in relation to dietary pattern scores. During the study follow-up, 39.8% progressed to T2DM, and 39.8% returned to normal glycemia. Three following major dietary patterns, including Western-style (with a higher load of red meats, hydrogenated fats, sodium, and total fat intakes), healthy pattern (with a higher load of whole grains, vegetables, and dairy products), and processed-foods pattern (with a higher load of processed-meats, fast-foods, salty snakes, and sweets and candies) were identified. The Western-style dietary pattern increased the risk of progressing to T2DM by 38% (OR 1.38 95% CI 1.00 to 1.89, P 0.050). Other dietary pattern scores were not related to regression or progression from Pre-DM. The Western-style dietary pattern (characterized by higher load of red meats, hydrogenated fats, sodium intake, and high-GI foods) may accelerate the progression of Pre-DM to T2DM.

A qualitative exploration of the experiences of peer leaders in an intervention to improve diabetes medication adherence in African Americans.

African Americans chronically managing their diabetes benefit from receiving support from peers with shared experiences. Peer support is known to improve the well-being of individuals receiving support, however, there is limited literature on the experiences of those providing the support. The Peers Supporting Health Literacy, Self-efficacy, Self-Advocacy, and Adherence (Peers LEAD) program pairs Peer Ambassadors who are adherent to their diabetes medication, with Peer Buddies who need support with their medication adherence. Peer Ambassadors engage with Peer Buddies as they receive diabetes information, develop the skills and motivation to address identified psychosocialsociocultural issues to enhance their diabetes medication adherence. This study qualitatively explores the experiences of African Americans who provided peer support in the Peers LEAD medication adherence intervention. Two focus groups were conducted with twelve Peer Ambassadors to explore their experiences of providing peer support in the Peers LEAD medication adherence intervention. Qualitative content analysis was conducted using an inductive open coding approach. Emergent themes provided insight into Peer Ambassador rationale for providing peer support and the benefits and challenges they experienced in their roles. Themes regarding their rationale included their desire to receive support for their diabetes self-management as well as to contribute to their communities in reducing the stigma associated with diabetes. The perceived benefits they gained centered on creating interpersonal connections, experiencing personal growth as they adapted to their roles, and experiencing opportunities to contribute to an intervention regardless of professional training. Peer Ambassadors reflected on the challenges which included difficulties on coming to terms with their role as Peer Ambassadors, seeing African Americans experience complications associated with diabetes, and navigating supporting Peer Buddies who are also burdened with the challenges their family members are experiencing with managing their diabetes. This study provides unique insight to what motivates individuals to provide peer support and what they gain from these experiences despite the challenges. Understanding the experiences of peers participating in such interventions may help inform the structure and content of programs that use peer support to focus on the benefits of and the motivation for participating in the program.

Handgrip strength is inversely associated with augmentation index in patients with type 2 diabetes.

Handgrip strength (HGS) is a measure of overall skeletal muscle strength and is used to identify risks for cardiovascular disease and mortality. Furthermore, HGS is an indicator of arterial stiffness that leads to atherosclerotic cardiovascular disease. This study aimed to examine the relationship between HGS and augmentation index (AIx) in patients with type 2 diabetes. A cross-sectional study was conducted to examine patients with type 2 diabetes whose HGS and AIx were measured in our hospital. AIx was measured noninvasively using an applanation tonometer, and multiple regression analyses were conducted to assess the independent relationship between HGS and AIx. This study included 404 patients. After adjusting for age, gender, body mass index, duration of diabetes, smoking and exercise habit, biochemical parameters, and physiological parameters related to arterial stiffness, HGS was found to be independently and inversely associated with AIx (β - 0.270, p 0.006). HGS was independently and inversely associated with AIx in patients with type 2 diabetes. Patients with diminished HGS should be subjected to intensive exercise therapy for reducing the risk of arterial stiffness and cardiovascular disease.Trial registration UMIN000023010.

Biomedical consequences of elevated cholesterol-containing lipoproteins and apolipoproteins on cardiovascular and non-cardiovascular outcomes.

Higher concentrations of cholesterol-containing low-density lipoprotein (LDL-C) increase the risk of cardiovascular disease (CVD). The association of LDL-C with non-CVD traits remains unclear, as are the possible independent contributions of other cholesterol-containing lipoproteins and apolipoproteins. Nuclear magnetic resonance spectroscopy was used to measure the cholesterol content of high density (HDL-C), very low-density (VLDL-C), intermediate-density (IDL-C), as well as low-density lipoprotein fractions, the apolipoproteins Apo-A1 and Apo-B, as well as total triglycerides (TG), remnant-cholesterol (Rem-Chol) and total cholesterol (TC). The causal effects of these exposures were assessed against 33 outcomes using univariable and multivariable Mendelian randomization (MR). The majority of cholesterol containing lipoproteins and apolipoproteins affect coronary heart disease (CHD), carotid intima-media thickness, carotid plaque, C-reactive protein (CRP) and blood pressure. Multivariable MR indicated that many of these effects act independently of HDL-C, LDL-C and TG, the most frequently measured lipid fractions. Higher concentrations of TG, VLDL-C, Rem-Chol and Apo-B increased heart failure (HF) risk often independently of LDL-C, HDL-C or TG. Finally, a subset of these exposures associated with non-CVD traits such as Alzheimers disease (AD HDL-C, LDL-C, IDL-C, Apo-B), type 2 diabetes (T2DM VLDL-C, IDL-C, LDL-C), and inflammatory bowel disease (IBD LDL-C, IDL-C). The cholesterol content of a wide range of lipoprotein and apolipoproteins associate with measures of atherosclerosis, blood pressure, CRP, and CHD, with a subset affecting HF, T2DM, AD and IBD risk. Many of the observed effects appear to act independently of LDL-C, HDL-C, and TG, supporting the targeting of lipid fractions beyond LDL-C for disease prevention. It is known that increases in the amount of certain fats and proteins in the blood can lead to heart attacks. These increases are also found in people with other diseases. Here, we looked at inherited differences in some fats and proteins in blood to explore whether these could be associated with various diseases. We found that some fats and proteins in blood were associated with heart disease (including heart failure), blood pressure, blockages in blood vessels, and to a lesser extent with diabetes, Alzheimer’s disease, and inflammatory bowel disease. These findings suggest that changes to lipids and proteins in the blood might lead to various diseases, including some that are not normally associated with changes in the blood. Monitoring these changes could improve diagnosis and treatment of these diseases.

Feasibility study of automated cardiac motion quantification to assess left ventricular function in type 2 diabetes.

The global incidence of diabetes and related complications is gradually increasing, with cardiovascular complications being the leading cause of death in the diabetic population. The purpose of this study was to examine left ventricular function in individuals with type 2 diabetes mellitus (T2D) and conduct a feasibility analysis using automated cardiac motion quantification (aCMQ) approach. A total of 150 T2D patients with a history of diabetes mellitus dating back more than 10 years were chosen, and we treated 87 patients with T2D that had been present for less than 15 years as group I, 63 patients with T2D that had been present for more than 15 years as group II, and 50 healthy volunteers as the control group. From the three groups, clinical information, conventional ultrasonography parameters, and mitral annular plane systolic excursion (MAPSE) parameters were gathered. aCMQ technique was used to collect longitudinal strain and circumferential strain in the left ventricle. Tissue motion mitral annular displacement technique (TMAD) in aCMQ was used to collect parameters related to TMAD, and cardiac motion quantification (CMQ) was used to collect two-dimensional global longitudinal strain (2D-GLS) to compare the degree of difference between the aforementioned three groups. The differences between longitudinal strain groups in aCMQ were all statistically significant and gradually decreased with increasing disease duration. Most TMAD parameters were lower in groups I and II than in the control group, and TMAD parameters gradually decreased with increasing disease duration. The results of the LV global longitudinal strain and 2D-GLS using Bland-Altman analyses showed high agreement between and within groups, Pearson correlation analysis showed a significant positive correlation (r 0.18, P < 0.05), and the AUC of ROC curves predicting the value of left ventricular function in patients with T2D was 0.723 and 0.628, respectively. With significant positive correlations between MAPSE, s, and the majority of the TAMD parameters (P < 0.05), TAMD, MAPSE, and s demonstrated high inter- and intra-group agreement using Bland-Altman analyses, and the three had predictive value in assessing left ventricular function in T2D patients by ROC curve. Reduced longitudinal strain and reduced mitral annular displacement were seen in patients with different disease stages of T2D, so the application of aCMQ and TAMD was effective in detecting altered left ventricular function in patients with T2D. aCMQ had higher value in predicting left ventricular function in patients with T2D compared to CMQ for overall longitudinal strain, and the software performed the depiction automatically, reducing manual errors. MAPSE parameters and s can replace the TMAD technique for assessing mitral annular motion and was simpler to perform, saving operational time.

Major adverse cardiovascular events among patients with type-2 diabetes, a nationwide cohort study comparing primary metabolic and bariatric surgery to GLP-1 receptor agonist treatment.

Glucagon-like Peptide-1 receptor agonists (GLP-1 RA) and metabolic and bariatric surgery (MBS) both improve cardiovascular outcomes in patients with severe obesity and type-2 diabetes (T2D). The aim of the present study was to assess the impact of MBS on major cardiovascular adverse events (MACE) in patients with severe obesity and T2D compared to patients with T2D treated with GLP-1 RA. In this propensity score matched cohort study on nationwide data, patients with T2D and severe obesity who underwent MBS in Sweden from 2007 until 2019 were identified from the Scandinavian Obesity Surgery Registry and matched to a non-surgical group with T2D treated with GLP-1 RA (81.7% liraglutide, 9.0% dulaglutide, 6.0% exenatide, 1.6% lixisenatide and 0.8% semaglutide) from the general population using generalized linear model. Major outcome was MACE (hospitalization for acute coronary syndrome or cerebrovascular event or all-cause death), evaluated with multivariable Cox regression. In total 2161 patients (obesity class I (10.2%), class II (40.3%), class III (49.5%)) were matched to 2161 non-surgical patients (mean age 51.1 ± 9.29 vs 51.5 ± 8.92 years, 64.8% vs. 64.4% women, with mean number of diabetes drugs of 2.5 ± 0.89 vs 2.6 ± 0.87, a mean duration of diabetes of 6.0 ± 4.15 vs 6.0 ± 4.51 years with 44.2% vs. 42.8% being treated with insulin at baseline). During the study period, 113 patients (8-year cumulative incidence 9.3%) compared to 130 non-surgical patients (8-year cumulative incidence 11.3%) suffered from MACE or all-cause mortality (HR 0.76, 95%CI 0.59-0.98), and 69 patients (8-year cumulative incidence 5.1%) compared to 92 non-surgical patients (8-year cumulative incidence 7.6%) suffered from a non-fatal MACE (HR 0.68, 95%CI 0.49-0.93). In this matched cohort study, MBS was associated with lower risk for MACE compared to treatment with early GLP-1 RA in patients with T2D.

Pilot study of optical coherence tomography angiography-derived microvascular metrics in hands and feet of healthy and diabetic people.

Optical coherence tomography angiography (OCTA) is a non-invasive, high-resolution imaging modality with growing application in dermatology and microvascular assessment. Accepted reference values for OCTA-derived microvascular parameters in skin do not yet exist but need to be established to drive OCTA into the clinic. In this pilot study, we assess a range of OCTA microvascular metrics at rest and after post-occlusive reactive hyperaemia (PORH) in the hands and feet of 52 healthy people and 11 people with well-controlled type 2 diabetes mellitus (T2DM). We calculate each metric, measure test-retest repeatability, and evaluate correlation with demographic risk factors. Our study delivers extremity-specific, age-dependent reference values and coefficients of repeatability of nine microvascular metrics at baseline and at the maximum of PORH. Significant differences are not seen for age-dependent microvascular metrics in hand, but they are present for several metrics in the foot. Significant differences are observed between hand and foot, both at baseline and maximum PORH, for most of the microvascular metrics with generally higher values in the hand. Despite a large variability over a range of individuals, as is expected based on heterogeneous ageing phenotypes of the population, the test-retest repeatability is 3.5% to 18% of the mean value for all metrics, which highlights the opportunities for OCTA-based studies in larger cohorts, for longitudinal monitoring, and for assessing the efficacy of interventions. Additionally, branchpoint density in the hand and foot and changes in vessel diameter in response to PORH stood out as good discriminators between healthy and T2DM groups, which indicates their potential value as biomarkers. This study, building on our previous work, represents a further step towards standardised OCTA in clinical practice and research.

Cohort Profile CArdiovascular Risk in patients with DIAbetes in NAvarra (CARDIANA cohort).

The CArdiovascular Risk in patients with DIAbetes in Navarra (CARDIANA cohort) cohort was established to assess the effects of sociodemographic and clinical variables on the risk of cardiovascular events in patients with type 1 (T1D) or type 2 (T2D) diabetes, with a special focus on socioeconomic factors, and to validate and develop cardiovascular risk models for these patients. The CARDIANA cohort included all patients with T1D and T2D diabetes registered in the Public Health Service of Navarra with prevalent disease on 1 January 2012. It consisted of 1067 patients with T1D (ages 2-88 years) and 33842 patients with T2D (ages 20-105 years), whose data were retrospectively extracted from the Health and Administrative System Databases. The follow-up period for wave 1 was from 1 January 2012 to 31 December 2016. During these 5 years, 9 patients (0.8% 95% CI (0.4% to 1.6%)) in the T1D cohort developed a cardiovascular disease event, whereas for the T2D cohort, 2602 (7.7% 95% CI (7.4% to 8.0%)) had an event. For the T2D cohort, physical activity was associated with a reduced risk of cardiovascular events, with adjusted estimated ORs equal to 0.84 (95% CI 0.66 to 1.07) for the partially active group and 0.71 (95% CI 0.56 to 0.91) for the active group, compared with patients in the non-active group. The CARDIANA cohort is currently being used to assess the effect of sociodemographic risk factors on CV risk at 5 years and to externally validate cardiovascular predictive models. A second wave is being conducted in late 2022 and early 2023, to extend the follow-up other 5 years, from 1 January 2016 to 31 December 2021. Periodic data extractions are planned every 5 years.

Intermittent protein restriction improves glucose homeostasis in Zucker diabetic fatty rats and single-cell sequencing reveals distinct changes in β cells.

Diabetes is caused by the interplay between genetic and environmental factors, therefore changes of lifestyle and dietary patterns are the most common practices for diabetes intervention. Protein restriction and caloric restriction have been shown to improve diabetic hyperglycemia in both animal models and humans. We report here the effectiveness of intermittent protein restriction (IPR) for the intervention of diabetes in Zucker diabetic fatty (ZDF) rats. Administration of IPR significantly reduced hyperglycemia and decreased glucose production in the liver. IPR protected pancreatic islets from diabetes-mediated damages as well as elevated the number and the proliferation activity of β cells. Single-cell RNA sequencing performed with isolated islets from the ZDF rats revealed that IPR was able to reverse the diabetes-associated β cell dedifferentiation. In addition, diabetic β cells in ZDF rats were associated with increased expressions of islet amyloid polypeptide, chromogranin and genes involved in endoplasmic reticulum stress. A β cell dedifferentiation marker Cd81 was also increased in the β cells of diabetic rats. In contrast, the expressions of D-box binding PAR bZIP transcription factor Dbp and immediate-early response genes were reduced in the diabetic β cells. In conclusion, these results indicated that IPR is effective in glycemic control and β cell protection in a diabetic rat model. In addition, diabetes in ZDF rats is associated with changes in the expression of genes involved in many facets of β cell functions.

Baseline and longitudinal trajectories of body-mass index and all-cause mortality among patients with type 2 diabetes.

To investigate the associations of baseline body mass index (BMI) and longitudinal BMI trajectories with all-cause mortality among patients with type 2 diabetes mellitus (T2DM). We used data from the diabetes surveillance system of Yinzhou Health Information System with T2DM patients registered from 2010 to 2015. Participants aged ≥ 40 years were included and were followed up until September 30, 2021. The latent class growth mixture model was used to identify different changing patterns in BMI for 5 years from registration. Cox proportional hazards models were used to examine the associations of baseline BMI and 5-year BMI trajectories with all-cause mortality. We observed a nonlinear association between baseline BMI and all-cause mortality (P for nonlinearity < 0.001), with an increased risk of death for low but not high BMI. However, compared with participants with medium-stable BMI for 5 years from baseline, individuals with increasing BMI had higher mortality, with adjusted hazard ratios (95% confidence intervals) 1.21 (1.021.43) for early-increasing and 1.47 (1.191.80) for late-sharp increasing groups. These findings suggest that while obesity itself may not be associated with an increased risk for mortality, weight gain, and in particular rapid weight gain, is a risk factor for mortality among patients with T2DM.

Emerging roles of oxyntomodulin-based glucagon-like peptide-1glucagon co-agonist analogs in diabetes and obesity.

Oxyntomodulin (OXM) is an endogenous peptide hormone secreted from the intestines following nutrient ingestion that activates both glucagon-like peptide-1 (GLP-1) and glucagon receptors. OXM is known to exert various effects, including improvement in glucose tolerance, promotion of energy expenditure, acceleration of liver lipolysis, inhibition of food intake, delay of gastric emptying, neuroprotection, and pain relief. The antidiabetic and antiobesity properties have led to the development of biologically active and enzymatically stable OXM-based analogs with proposed therapeutic promise for metabolic diseases. Structural modification of OXM was ongoing to enhance its potency and prolong half-life, and several GLP-1glucagon dual receptor agonist-based therapies are being explored in clinical trials for the treatment of type 2 diabetes mellitus and its complications. In the present article, we provide a brief overview of the physiology of OXM, focusing on its structural-activity relationship and ongoing clinical development.

Combined effect of SDF-1 peptide and angiogenic cues in co-axial PLGAgelatin fibers for cutaneous wound healing in diabetic rats.

Skin regeneration is hindered by poor vascularization, prolonged inflammation, and excessive scar tissue formation, which necessitate newer strategies to simultaneously induce blood vessel regeneration, resolve inflammation, and induce host cell recruitment. Concurrent deployment of multiple biological cues to realize synergistic reparative effects may be an enticing avenue for wound healing. Herein, we simultaneously deployed SDF (stromal cell-derived factor)- 1α, VEGF (vascular endothelial growth factor)-binding peptide (BP), and GLP (glucagon like peptide)- 1 analog, liraglutide (LG) in coreshell poly(L-lactide-co-glycolide)gelatin fibers to harness their synergistic effects for skin repair in healthy as well as diabetic wound models in rats. Microscopic techniques, such as SEM and TEM revealed fibrous and coreshell type morphology of membranes. Boyden chamber assay and scratch-wound assay displayed significant migration of HUVECs (human umbilical vein endothelial cells) in SDF-1α containing fibers. Subcutaneous implantation of membranes revealed higher cellular infiltration in SDF-1α loaded fibers, especially, those which were co-loaded with LG or BP. Implantation of membranes in an excisional wound model in healthy rats further showed significant and rapid wound closure in dual cues loaded groups as compared to control or single cue loaded groups. Similarly, the implantation of dressings in type 2 diabetes rat model revealed fast healing, skin appendages regeneration, and blood vessel regeneration in dual cues loaded fibers (SDF-1αLG, SDF-1αBP). Taken together, coreshell type fibers containing bioactive peptides significantly promoted wound repair in healthy as well as diabetic wound models in rats.

Rapid and non-invasive diagnosis of type 2 diabetes through sniffing urinary acetone by a proton transfer reaction mass spectrometry.

Urinary acetone in urine is produced from fat metabolism in human body, which can be accelerated in diabetic patients because of insufficient utilization and storage of glucose. In this study, we tried to develop a novel diagnosis method of type 2 diabetes (T2D) through sniffing urinary acetone by a proton transfer reaction mass spectrometry (PTR-MS). A total of 180 T2D patients and 180 healthy volunteers were recruited from three hospitals for multicenter study. Urine samples were collected in the morning when donators were fasting and stored in glass bottles. Acetone in the headspace of these bottles was qualitatively and quantitatively detected by the PTR-MS in 8 h. Using a threshold of 690.1 ppbv, a diagnostic model was established using urinary acetone with an accuracy of 81.3% (sensitivity 73.3%, specificity 89.3%) in hospital Ⅰ. In the verification studies, the accuracies were 92.5% (sensitivity 88.7%, specificity 96.2%) in hospital Ⅱ and 83.7% (sensitivity 76.9%, specificity 90.4%) in hospital Ⅲ, respectively. The accuracy is comparable to that of clinically used diagnosis methods, fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), and glycosylated hemoglobin A1c (HbA1c) test. The sensitivity for 35 newly diagnosed patients was 85.7%. The newly developed technology is completely non-invasive and much more rapid than clinical FPG, OGTT, and HbA1c tests. It has a promising prospect in clinical use. But the applicability in different human races still need more validations.

The nature and characteristics of hypertriglyceridemia in a large cohort with type 2 diabetes.

To determine the prevalence of mild, moderate and severe hypertriglyceridemia (HTG) in a large, diverse healthcare system cohort with type 2 diabetes (T2D) and to study associations between triglyceride levels and demographic factors, glycemic control, body weight and to investigate whether triglyceride levels associate with markers of fatty liver and renal disease. 19,086 individuals with T2D were studied between 2015 and 2020. We compared groups with normotriglyceridemia (<150 mgdl <1.7 mmoll), mild (150-199 mgdl 1.7-2.25 mmoll), moderate (200-499 mgdl 2.26-5.64 mmoll) or severe HTG (>499 mgdl >5.64 mmoll). We also performed univariate and multivariate correlational analyses with triglyceride level as a continuous variable. 39 % had triglyceride levels ≥150 mgdl (<1.7 mmoll), 19 % had moderate and 2 % had severe HTG. There was a lower proportion of Blacks in all HTG categories compared to Whites. There was no overall gender difference in prevalence except that severe HTG was more common in men and as HTG severity worsened mean age fell. Triglycerides correlated with HbA1c and associated with BMI, LDL-C, diastolic BP, transaminases and urine albumincreatinine ratio, independent of HbA1c. This study fills gaps in our knowledge of the distribution and clinical associations of HTG in T2D and characterizes the features of the small but important group with severe HTG. We demonstrate the influence of age, sex and race, confirm the moderate effects of glycemic control and obesity on triglyceride level, and provide evidence that triglyceride levels may be a marker for fatty liver and nephropathy independent of glycemic control.

A Guide for Selection of Genetic Instruments in Mendelian Randomization Studies of Type 2 Diabetes and HbA1c Toward an Integrated Approach.

In this study we examine the instrument selection strategies currently used throughout the type 2 diabetes and HbA1c Mendelian randomization (MR) literature. We then argue for a more integrated and thorough approach, providing a framework to do this in the context of HbA1c and diabetes. We conducted a literature search for MR studies that have instrumented diabetes andor HbA1c. We also used data from the UK Biobank (UKB) (N 349,326) to calculate instrument strength metrics that are key in MR studies (the F statistic for average strength and R2 for total strength) with two different methods (individual-level data regression and Cragg-Donald formula). We used a 157-single nucleotide polymorphism (SNP) instrument for diabetes and a 51-SNP instrument (with partition into glycemic and erythrocytic as well) for HbA1c. Our literature search yielded 48 studies for diabetes and 22 for HbA1c. Our UKB empirical examples showed that irrespective of the method used to calculate metrics of strength and whether the instrument was the main one or included partition by function, the HbA1c genetic instrument is strong in terms of both average and total strength. For diabetes, a 157-SNP instrument was shown to have good average strength and total strength, but these were both substantially lesser than those of the HbA1c instrument. We provide a careful set of five recommendations to researchers who wish to genetically instrument type 2 diabetes andor HbA1c. In MR studies of glycemia, investigators should take a more integrated approach when selecting genetic instruments, and we give specific guidance on how to do this.

Bacille Calmette Guerin (BCG) and prevention of types 1 and 2 diabetes Results of two observational studies.

Diabetes is a common disease marked by high blood sugars. An earlier clinical trial in type 1 diabetic subjects (T1Ds) found that repeat BCG vaccinations succeeded in lowering HbA1c values over a multi-year course. Here we seek to determine whether BCG therapy for bladder cancer may improve blood sugar levels in patients with comorbid T1D and type 2 diabetes (T2D). We also investigate whether BCG exposure may reduce onset of T1D and T2D by examining country-by-country impact of BCG childhood vaccination policies in relation to disease incidence. We first analyzed three large US patient datasets (Optum Labs data N 45 million, Massachusetts General Brigham N 6.5 million, and Quest Diagnostics N 263 million adults), by sorting out subjects with documented T1D (N 19) or T2D (N 106) undergoing BCG therapy for bladder cancer, and then by retrospectively assessing BCGs subsequent year-by-year impact on blood sugar trends. Additionally, we performed an ecological analysis of global data to assess the country-by-country associations between mandatory neonatal BCG vaccination programs and T1D and T2D incidence. Multi-dose BCG therapy in adults with comorbid diabetes and bladder cancer was associated with multi-year and stable lowering of HbA1c in T1Ds, but not in T2Ds. The lack of a similar benefit in T2D may be due to concurrent administration of the diabetes drug metformin, which inhibits BCGs beneficial effect on glycolysis pathways. Countries with mandatory neonatal BCG vaccination policies had a lower incidence of T1D in two international databases and a lower incidence of T2D in one of the databases. The epidemiological evidence analyzed here suggests that BCG may play a role in the prevention of T1D. It does not support prevention of T2D, most likely because of interference by metformin. Our ecological analysis of global data suggests a role for neonatal BCG in the prevention of T1D and, to a lesser extent, T2D. Randomized clinical trials are needed to confirm these findings.

Temporal trends in, and associations of, early-career general practitioner prescriptions of second-line Type 2 Diabetes medications, 2010-2018.

Second-line pharmacotherapy for Type 2 Diabetes Mellitus (diabetes) is necessary for optimal glycaemic control and preventing longer-term complications. We aimed to describe temporal trends in, and associations of, Australian general practitioner (GP) registrars prescription, and initiation, of new second-line oral agents (dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists) compared to sulphonylureas. A longitudinal analysis (2010-2018) of data from the Registrar Clinical Encounters in Training project. Analysis included any diabetes problemdiagnosis that involved prescription of sulphonylureas or new oral agents. Simple and multiple logistic regression models were fitted within the generalised estimating equations framework. 2333 registrars recorded 6064 diabetes problemsdiagnoses (1.4%). 835 problemsdiagnoses involved sulphonylurea or new medication prescription. Of these, 61.0% 95% CI57.4-64.4 involved new medication prescription. 230 problemsdiagnoses involved sulphonylurea or new medication initiation, with 77% 95%CI70.8-82.1 involving a new medication. There was a significant 52% per year increase in prescribing (OR 1.5295% CI1.38-1.68,p<0.001), and a 77% per (two-to-three-year) time-interval increase in initiation (OR 1.77,95% CI1.30-2.43,p <0.001) of new medications compared to sulphonylureas. New medications were prescribed less for non-English-speaking patients. There was some regional variation in prescribing. Registrar uptake of new oral agents compared to sulphonylureas has increased rapidly.

Longitudinal HbA1c trajectory modelling reveals the association of HbA1c and risk of hospitalization for heart failure for patients with type 2 diabetes mellitus.

Inconsistent conclusions in past studies on the association between poor glycaemic control and the risk of hospitalization for heart failure (HHF) have been reported largely due to the analysis of non-trajectory-based HbA1c values. Trajectory analysis can incorporate the effects of HbA1c variability across time, which may better elucidate its association with macrovascular complications. Furthermore, studies analysing the relationship between HbA1c trajectories from diabetes diagnosis and the occurrence of HHF are scarce. This is a prospective cohort study of the SingHealth Diabetes Registry (SDR). 17,389 patients diagnosed with type 2 diabetes mellitus (T2DM) from 2013 to 2016 with clinical records extending to the end of 2019 were included in the latent class growth analysis to extract longitudinal HbA1c trajectories. Association between HbA1c trajectories and risk of first known HHF is quantified with the Cox Proportional Hazards (PH) model. 5 distinct HbA1c trajectories were identified as 1. low stable (36.1%), 2. elevated stable (40.4%), 3. high decreasing (3.5%), 4. high with a sharp decline (10.8%), and 5. moderate decreasing (9.2%) over the study period of 7 years. Poorly controlled HbA1c trajectories (Classes 3, 4, and 5) are associated with a higher risk of HHF. Using the diabetes diagnosis time instead of a commonly used pre-defined study start time or time from recruitment has an impact on HbA1c clustering results. Findings suggest that tracking the evolution of HbA1c with time has its importance in assessing the HHF risk of T2DM patients, and T2DM diagnosis time as a baseline is strongly recommended in HbA1c trajectory modelling. To the authors knowledge, this is the first study to identify an association between HbA1c trajectories and HHF occurrence from diabetes diagnosis time.

Evaluation of pharmacist consults within a collaborative enhanced primary care team model to improve diabetes care.

An enhanced primary care team model was implemented to provide proactive, longitudinal care to patients with diabetes, grounded in close partnership between primary care providers (PCPs), nurses, and Medication Management Services (MMS) pharmacists. The purpose of this study is to evaluate the impact of the MMS pharmacist involvement in the enhanced primary care model for patients with diabetes. This retrospective cohort study compared the quality of diabetes care between patients referred to a pharmacist and propensity score matched controls who were not. Eligible patients were adults (age 18 to 75 years) enrolled in the enhanced primary care team process who did not meet at least one of four diabetes quality indicators at 13 Mayo Clinic Rochester primary care practice locations. The intervention examined was asynchronous e-consults by pharmacists affiliated with the primary care practice. The primary outcome was change in the proportion of patients meeting the composite of four diabetes treatment goals (D4), including hemoglobin A1c (HbA1c) control, blood pressure control, aspirin use, and statin use at six months from enrollment among patients who received pharmacist intervention compared to matched patients who did not. Secondary outcomes were each of the D4 goal individually. The proportion of patients meeting the D4 increased with pharmacist e-consults (N 85) compared to matched controls with no review (N 170) (27% vs 7.0%, p<0.001). The change in patients meeting treatment goals of HbA1c (12.9% vs 4.1%, p 0.020), blood pressure (9.4% vs 2.4%, p 0.023), aspirin use (10.6% vs 2.9%, p 0.018), and statin use (17.6% vs -1.2%, p<0.001) all increased with pharmacist e-consults. Pharmacist engagement in the enhanced primary care team improved diabetes management. This supports the inclusion and utilization of pharmacists in multidisciplinary efforts to improve diabetes care.

Reduced expression level of protein phosphatase, PPM1E, serves to maintain insulin secretion in type 2 diabetes.

Reversible phosphorylation is an important regulatory mechanism. Regulation of protein phosphorylation in β-cells has been extensively investigated, but less is known about protein dephosphorylation. To understand the role of protein dephosphorylation in β-cells and type 2 diabetes (T2D), we first examined mRNA expression of type 2C family (PP2C) of protein phosphatases in islets from T2D donors. Phosphatase expression overall was changed in T2D, and that of PPM1E was most markedly downregulated. PPM1E expression correlated inversely with HbA1c. Silencing of PPM1E increased glucose-stimulated insulin secretion (GSIS) in INS-1 83213 cells andor islets from T2D patients while PPM1E overexpression decreased GSIS. Increased GSIS following PPM1E silencing was associated with decreased oxidative stress, elevated cytosolic Ca2 levels and ATPADP ratio, increased hyperpolarization of the inner mitochondrial membrane and phosphorylation of CaMKII, AMPK and acetyl-coA carboxylase. Silencing of PPM1E, however, did not change insulin content. Increased GSIS, cell viability, and activation of AMPK upon metformin treatment in β-cells were observed upon PPM1E silencing. Thus, protein dephosphorylation via PPM1E abrogates GSIS. Consequently, reduced PPM1E expression in T2D may be a compensatory response of β-cells to uphold insulin secretion under metabolic duress. Targeting PPM1E in β-cells may thus represent a novel therapeutic strategy for treatment of T2D.

Efficacy of Dapagliflozin by Baseline Diabetes Medications A Prespecified Analysis From the DAPA-CKD Study.

To determine whether the benefits of dapagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD) in the Dapagliflozin And Prevention of Adverse Outcomes in CKD trial (DAPA-CKD) varied by background glucose-lowering therapy (GLT). We randomized 4,304 adults (including 2,906 with type 2 diabetes) with a baseline estimated glomerular filtration rate (eGFR) 25-75 mLmin1.73 m2 and urinary albumin-to-creatinine ratio of 200-5,000 mgg to dapagliflozin 10 mg or placebo once daily (NCT03036150). The primary end point was a composite of ≥50% eGFR decline, end-stage kidney disease, and kidney or cardiovascular cause of death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. In this prespecified analysis, we investigated the effects of dapagliflozin on these and other outcomes according to baseline GLT class or number of GLTs. The effects of dapagliflozin on the primary composite outcome were consistent across GLT classes and according to the number of GLTs (all interaction P > 0.08). Similarly, we found consistent benefit of dapagliflozin compared with placebo on the secondary end points regardless of background GLT class or number of GLTs. The same applied to the rate of decline in the eGFR rate and safety end points. Dapagliflozin reduced the initiation of insulin therapy during follow-up compared with placebo (hazard ratio 0.72 95% CI 0.54-0.96 P 0.025). Dapagliflozin reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD across baseline GLT class or classes in combination.

Perspectives on Promoting Physical Activity Using eHealth in Primary Care by Health Care Professionals and Individuals With Prediabetes and Type 2 Diabetes Qualitative Study.

The trend of an exponential increase in prediabetes and type 2 diabetes (T2D) is projected to continue rising worldwide. Physical activity could help prevent T2D and the progression and complications of the disease. Therefore, we need to create opportunities for individuals to acquire the necessary knowledge and skills to self-manage their chronic condition through physical activity. eHealth is a potential resource that could facilitate self-management and thus improve population health. However, there is limited research on users perception of eHealth in promoting physical activity in primary care settings. This study aims to explore the perspectives of health care professionals and individuals with prediabetes and T2D on eHealth to promote physical activity in primary care. A qualitative approach was applied using focus group discussions among individuals with prediabetes or T2D (14 participants in four groups) and health care professionals (10 participants in two groups). The discussions were audio-recorded and transcribed verbatim. Qualitative content analysis was used inductively to code the data. Three main categories emerged utility, adoption process, and accountability. The utility of eHealth was described as a motivational, entertaining, and stimulating tool. Registration of daily medical measurements and lifestyle parameters in a cohesive digital platform was recognized as a potential resource for strengthening self-management skills. The adoption process includes eHealth to increase the accessibility of care and personalize the support of physical activity. However, participants stated that digital technology might only suit some and could increase health care providers administrative burden. Accountability refers to the knowledge and skills to optimize eHealth and ensure data integrity and security. People with prediabetes and T2D and health care professionals positively viewed an integration of eHealth technology in primary care to promote physical activity. A cohesive platform using personal metrics, goal-setting, and social support to promote physical activity was suggested. This study identified eHealth illiteracy, inequality, privacy, confidentiality, and an increased workload on health care professionals as factors of concern when integrating eHealth into primary care. Continuous development of eHealth competence was reported as necessary to optimize the implementation of eHealth technology in primary care.

Long non-coding RNAs TUG1 and MEG3 in patients with type 2 diabetes and their association with endoplasmic reticulum stress markers.

Long non-coding RNAs (lncRNAs), including taurine upregulated gene 1 (TUG1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed 3 (MEG3) play a regulatory role in endoplasmic reticulum (ER) stress. The present study aimed to investigate the expression of these lncRNAs in patients with type 2 diabetes and their association with biochemical and ER stress parameters. Participants included 57 patients with diabetes and 32 healthy individuals. Real-time PCR was performed to assess MALAT1, TUG1, MEG3, ATF4, and CHOP gene expression in peripheral blood mononuclear cells. Plasma GRP78, advanced glycation end products (AGEs), and insulin were measured using enzyme-linked immunosorbent assay (ELISA), and insulin resistance (IR) was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR). The expression of TUG1, MEG3, ATF4, and CHOP genes was significantly increased in the patients with diabetes compared to healthy individuals. MALAT1 gene expression was also higher in patients group although it did not reach significant levels. TUG1 and MEG3 expression revealed significant positive correlations with the indices of glycemic control, including FBS, HbA1c, HOMA-IR, and AGEs, as well as markers of ER stress. MALAT1 expression was also positively correlated with ATF4 and AGEs. The expression levels of TUG1 and MEG3 lncRNAs were increased in patients with diabetes and were associated with glycemic control and components of ER stress. Thus, these lncRNAs might be considered appropriate markers to identify ER stress due to hyperglycemia.

Evaluating Objective Metrics of habit strength for taking medications.

Habit strength for taking medication is associated with medication adherence. However, habit strength is typically measured via self-reports, which have limitations. Objective sensors may provide advantages to self-reports. To evaluate whether habit-strength metrics derived from objective sensor data (MEMS® Caps AARDEX Group) are associated with self-reported habit strength and adherence (objective and self-reported) and whether objective and self-reported habit strength are independently associated with adherence. Patients (N 79) on oral medications for type 2 diabetes completed self-reports of habit strength and medication adherence and used MEMS® Caps to take their prescribed medication for one month. MEMS® Caps data were used to create five objective metrics of habit strength (e.g., individual-level variance in pill timing) and quantify medication adherence (% days correct dosing). Consistency in behavior from week to week (versus across each day) had the greatest association with self-reported habit strength (r(78) 0.29, p 0.01), self-reported adherence (r(78) 0.32, p 0.005), and objective adherence (r(78) 0.61, p < 0.001). Objective and self-reported habit strength were independently associated with adherence. Weekly pill-timing consistency may be more useful than daily pill-timing consistency for predicting adherence and understanding patients medication-taking habits. Self-reports and objective metrics of habit strength may be measuring different constructs, warranting further research.

Purification and characterization of the dipeptidyl peptidase-IV inhibitory peptides from eel (Anguilla rostrata) scraps enzymatic hydrolysate for the treatment of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a serious threat to human health. Owing to the action of dipeptidyl peptidase-IV (DPP-IV), the half-life of entero-insulin hormone after secretion is extremely short, causing insufficient insulin secretion in diabetic patients. Dipeptidyl peptidase-IV inhibitors can be used as a new treatment for T2DM. In this study, the proteins of eel (Anguilla rostrata) scraps hydrolyzed using Protamex protease (EPHs) were found to have strong DPP-IV inhibitory activity. The study also provided research ideas for the development and utilization of A. rostrata scraps. The median inhibition concentration (IC The protein hydrolysates isolated from eel scraps are potential functional food ingredients for the treatment of T2DM. © 2023 Society of Chemical Industry.

Association of Netrin 1 with hsCRP in Subjects with Obesity and Recent Diagnosis of Type 2 Diabetes.

Netrin 1 (Ntn1) is a cell migration protein with an anti-inflammatory effect, which may play a key role in the pathological development of type 2 diabetes (T2D). In this study, we evaluate the relationships between the serum concentrations of Ntn1, glucose, and high-sensitivity C-reactive Protein (hsCRP). We carried out a cross-sectional study including 90 individuals divided into three groups (

Professional continuous glucose monitoring in patients with diabetes mellitus A systematic review and meta-analysis.

To evaluate the effect on glucose control of professional continuous glucose monitoring (p-CGM)-based care as compared with standard care in the management of patients with type 1 and type 2 diabetes. The PubMed database was searched comprehensively to identify prospective or retrospective studies evaluating p-CGM as a diagnostic tool for subsequent implementation of lifestyle andor medication changes and reporting glycated haemoglobin (HbA1c) as an outcome measure. We found 872 articles, 22 of which were included in the meta-analysis. Overall, the use of p-CGM was associated with greater HbA1c reduction from baseline (-0.28%, 95% confidence interval CI -0.36% to -0.21%, I In patients with type 1 and type 2 diabetes, p-CGM-driven care is superior to usual care in improving glucose control without increasing hypoglycaemia.

Clinical validation of the nursing diagnosis decreased diversional activity engagement in patients with diabetes.

Diagnostic accuracy studies are important to identify the best set of defining characteristics for a given nursing diagnosis. The reliability of nursing inferences can be increased by using clinical indicators with high prediction capacity helping nurses to be more accurate in their clinical practice. To clinically validate the nursing diagnosis Decreased diversional activity engagement in adult patients with diabetes. A diagnostic accuracy study with a cross-sectional design was carried out patients with type 2 diabetes. A latent class model with random effects was used to measure the sensitivity and specificity. The diagnosis of Decreased diversional activity engagement was present in 62.2% of the patients. The defining characteristics with high sensitivity (good indicators for confirmation) were discontent with situation, physical deconditioning, and altertion in mood. Boredom, flat affect, discontent with situation, and frequent naps were the defining characteristics with the highest specificity values. These factors are considered good integrating components of the diagnosis under investigation in patients with diabetes. The nursing diagnosis decreased diversional activity engagement is frequent in patients with diabetes, and discontent with situation can be considered a good predictor of its occurrence due to its high values of specificity and sensitivity. The use of accurate clinical indicators in the diagnostic reasoning of nurses contributes to the achievement of outcomes centered on the patients human responses.

Triterpenoid CDDO-EA inhibits lipopolysaccharide-induced inflammatory responses in skeletal muscle cells through suppression of NF-κB.

Chronic inflammation is a major contributor to the development of obesity-induced insulin resistance, which then can lead to the development of type 2 diabetes (T2D). Skeletal muscle plays a pivotal role in insulin-stimulated whole-body glucose disposal. Therefore, dysregulation of glucose metabolism by inflammation in skeletal muscle can adversely affect skeletal muscle insulin sensitivity and contribute to the pathogenesis of T2D. The mechanism underlying insulin resistance is not well known however, macrophages are important initiators in the development of the chronic inflammatory state leading to insulin resistance. Skeletal muscle consists of resident macrophages which can be activated by lipopolysaccharide (LPS). These activated macrophages affect myocytes via a paracrine action of pro-inflammatory mediators resulting in secretion of myokines that contribute to inflammation and ultimately skeletal muscle insulin resistance. Therefore, knowing that synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acids (CDDOs) can attenuate macrophage pro-inflammatory responses in chronic disorders, such as cancer and obesity, and that macrophage pro-inflammatory responses can modulate skeletal muscle inflammation, we first examined whether CDDO-ethyl amide (CDDO-EA) inhibited chemokine and cytokine production in macrophages since this had not been reported for CDDO-EA. CDDO-EA blocked LPS-induced tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukine-1beta (IL-1β), and interleukine-6 (IL-6) production in RAW 264.7 mouse and THP-1 human macrophages. Although many studies show that CDDOs have anti-inflammatory properties in several tissues and cells, little is known about the anti-inflammatory effects of CDDOs on skeletal muscle. We hypothesized that CDDO-EA protects skeletal muscle from LPS-induced inflammation by blocking nuclear factor kappa B (NF-κB) signaling. Our studies demonstrate that CDDO-EA prevented LPS-induced TNF-α and MCP-1 gene expression by inhibiting the NF-κB signaling pathway in L6-GLUT4myc rat myotubes. Our findings suggest that CDDO-EA suppresses LPS-induced inflammation in macrophages and myocytes and that CDDO-EA is a promising compound as a therapeutic agent for protecting skeletal muscle from inflammation.

Glucose-Responsive Microparticle-Loaded Dissolving Microneedles for Selective Delivery of Metformin A Proof-of-Concept Study.

Diabetes mellitus (DM) is a metabolic disorder that is one of the most common health problems in the world, primarily type 2 DM (T2DM). Metformin (MTF), as the first-line treatment of DMT2, is effective in lowering glucose levels, but its oral administration causes problems, including gastrointestinal side effects, low bioavailability, and the risk of hypoglycemia. In this study, we formulated MTF into microparticles incorporating a glucose-responsive polymer (MP-MTF-GR), which could potentially increase the bioavailability and extend and control the release of MTF according to glucose levels. This system was delivered by dissolving microneedles (MP-MTF-GR-DMN), applied through the skin, thereby preventing gastrointestinal side effects of orally administered MTF. MP-MTF-GR was formulated using various concentrations of gelatin as a polymer combined with phenylboronic acid (PBA) as a glucose-responsive material. MP-MTF-GR was encapsulated in DMN using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as DMN polymers. The physicochemical evaluation of MP-MTF-GR showed that MTF could be completely entrapped in MP with the percentage of MTF trapped increasing with increasing gelatin concentration without changing the chemical structure of MTF and producing stable MP. In addition, the results of the physicochemical evaluation of MP-MTF-GR-DMN showed that DMN had adequate mechanical strength properties and penetration ability and was stable to environmental changes. The results of the in vitro release and ex vivo permeation study on media with various concentrations of glucose showed that the release and permeation of MTF from the formula increased with increasing glucose levels in the media. The MP-MTF-GR-DMN formula successfully delivered MTF through the skin at 11.30 ± 0.29, 23.31 ± 1.64, 36.12 ± 3.77, and 53.09 ± 3.01 μg from PBS, PBS glucose 1%, PBS glucose 2%, and PBS glucose 4%, respectively, at 24 h, which indicates glucose-responsive permeation and release behavior. The formula developed was also proven to be nontoxic based on hemolysis tests. Importantly, the in vivo study on the rat model showed that this combination approach could provide a better glucose reduction compared to other routes, reducing the blood glucose level to normal levels after 3 h and maintaining this level for 8 h. Furthermore, this approach did not change the skin moisture of the rats. This MP-MTF-GR-DMN is a promising alternative to MTF delivery to overcome MTF problems and increase the effectiveness of T2DM therapy.

The Diabetes Tune-Up Group A Multidisciplinary Approach to Improve Diabetes Distress and A1C Among Adults With Type 1 and Type 2 Diabetes.

The purpose of this study was to assess the feasibility of delivering the Diabetes Tune-Up Group (DTU), a cognitive-behavioral-therapy-based (CBT) multidisciplinary intervention for adults with diabetes distress and elevated A1C using a group in-person delivery format. The DTU intervention consisted of 6 weekly group sessions (90 minutes in duration per session). The groups were cofacilitated by a diabetes care and education specialist (DCES) and a masters-level clinical psychology trainee. The intervention integrated CBT with patient-centered diabetes education. Using a prepost study design, participants completed assessments at baseline, post-intervention, and 3 months following the intervention. The sample consisted of 29 adults with type 1 diabetes (N 8) or type 2 diabetes (N 21) who were predominantly female (79%), White (59%), and educated (56% with a college degree or greater). Participants attended 131 total sessions out of 174 possible sessions, for an overall attendance rate of 75.3%. At 3-month follow-up, significant improvements were observed in A1C values (mean decrease 0.39%). Diabetes distress improved significantly from baseline (mean 3.44, SD 0.68) to post-intervention (mean 2.94, SD 0.68), and 3-month follow-up (mean 2.55, SD 0.75). Significant improvements were also observed in diabetes self-efficacy from baseline to post-intervention and at 3-month follow-up. This group-based, multidisciplinary intervention resulted in improvements in A1C, diabetes distress, and patient self-efficacy in caring for diabetes. Future studies to validate this intervention approach across settings and delivery platforms are needed.

Increased methylglyoxal formation in plasma and tissues during a glucose tolerance test is derived from exogenous glucose.

The dicarbonyl compound methylglyoxal (MGO) is a major precursor in the formation of advanced glycation endproducts (AGEs). MGO and AGEs are increased in subjects with diabetes and are associated with fatal and non-fatal cardiovascular disease. Previously we have shown that plasma MGO concentrations rapidly increase in the postprandial phase, with a higher increase in individuals with type 2 diabetes. In current study, we investigated whether postprandial MGO formation in plasma and tissues originates from exogenous glucose and whether the increased plasma MGO concentration leads to a fast formation of MGO-derived AGEs. We performed a stable isotope labelled oral glucose tolerance test (OGTT) in 12 healthy males with universally labelled D()13C glucose. Analysis of plasma labelled 13C3 MGO and glucose levels at eleven time-points during the OGTT revealed that the newly formed MGO during OGTT is completely derived from exogenous glucose. Moreover, a fast formation of protein-bound MGO-derived AGEs during the OGTT was observed. In accordance, ex vivo incubation of MGO with plasma or albumin showed a rapid decrease of MGO and a fast increase of MGO-derived AGEs. In an intraperitoneal glucose tolerance test in C57BL6J mice, we confirmed that the formation of postprandial MGO is derived from exogenous glucose in plasma and also showed in tissues that MGO is increased and this is also from exogenous glucose. Collectively, increased formation of MGO during a glucose tolerance test arises from exogenous glucose both in plasma and in tissues, and this leads to a fast formation of MGO-derived AGEs.