bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes and Severe Malaria—Clinical Profile and Outcome
Authors: THATOI PRAVAT K. 
Published: June 2018

Introduction: Diabetes mellitus is a global burden and India having second largest diabetics in the world. Malaria is a common vector borne disease in developing countries and so also in India. Diabetes mellitus may aggravate malaria infection like other infections.
Aim: To study the clinical profile and outcome of severe malaria in diabetes mellitus.
Methods: This was a descriptive analytical study where 200 adult patients of severe malaria according to WHO criteria admitted to our hospital (SCB Medical College and Hospital, Odisha, India) were studied for clinical profiles, associated comorbid conditions and outcome for a period of two years. We analysed patients with comorbid conditions like diabetes mellitus, hypertension and hypothyroid vs. no comorbid conditions. Only smear positive severe malaria patients were included and detailed clinical examination and laboratory investigations were done in all patients. Patients with other associated conditions like pregnancy, chronic kidney disease and immunocompromised states were excluded. The observed data was statistically analyzed.
Result: Out of 200 severe malaria patients 99 were males and 101 were females with mean age of 46.51± SD 3.67 years. Patients with established diabetes mellitus were 54 (male-27, female-27), hypertension were 36 (male-21, female-15), hypothyroid state were 36 (male-10, female-26) and no comorbidities were 74 (male-41, female-33). The mixed malarial infection of both Plasmodium falciparum and Plasmodium vivax was found more in diabetics vs. nondiabetics i.e., 22 (40.74%) vs. 23 (15.75%). There was more multi-organ involvement, shorter coma onset time and longer duration of coma observed on diabetics than nondiabetics. Nineteen (35.18%) patients died amongst 54 diabetics than 20 (13.69%) patients died amongst 146 nondiabetics.
Conclusion: There was more death and severity of malaria observed in diabetics than nondiabetics and then other comorbid conditions.

Disclosure
P.K. Thatoi: None.
Falls and Fall-Related Injuries among Adults aged =65 Years with Diabetes, United States, 2016
Authors: CHO PYONE , HORA ISRAEL A. 
Published: June 2018

Older adults are at increased risk of unintentional falls and fall-related injuries. Chronic diseases like diabetes are also common among older adults. Older diabetic adults are at increased risk for falls partly due to diabetes-related complications and medication side effects. We analyzed 2016 Behavioral Risk Factor Surveillance System survey data from 50 states, District of Columbia, and three U.S. territories to assess the risk of falling (percentage of older adults with self-reported falls and injurious falls) among 34,462 older adults aged ≥65 years with diabetes. We also examined the risk of falling by selected self-reported fall risk factors—sex, bodyweight, general health status, and comorbid conditions (history of stroke, visual impairment, arthritis, depression, difficulty walking or climbing stairs). Among older diabetic adults, 35.5% reported falling one or more times in the past 12 months; of those, 38.7% suffered injuries from falls. Compared to their counterparts without salient risk factors stated above, older diabetic adults with selected characteristics were significantly more likely to fall (all p values &lt; 0.001) (Table). Of eight risk factors under study, those with poor health, depression, and difficulty walking or climbing stairs had highest risk of falling. Understanding the role of potential risk factors is crucial for fall prevention in older adults with diabetes.Self-reported falls among older adults aged ≥65 years with diabetes by 3 selected risk factorsRisk FactorRisk FactorSample SizeSample SizePercent Who FellPercent Who FellComparisonComparisonCategoryClassificationTotalHistory of FallEstimate95% CIPercent Difference95% CI for DifferenceSexWomen19,1697,40037.836.2-39.44.62.4-6.8Men15,2925,45133.231.6-34.8Health statusPoor4,4462,44253.850.6-56.921.217.9-24.6Fair or better29,88210,35932.631.4-33.8Difficulty walking or Climbing stairsYes13,9577,11649.147.2-51.022.920.5-25.2No20,2865,64426.224.9-27.6

Disclosure
P. Cho: None. I.A. Hora: None.
Age and Gender-Related Variations in Comorbidities among Diabetes Patients—A Community-Based Cross-Sectional Study
Authors: UDDIN FAREED , ZAHEER SIDRA , SHAFIQUE KASHIF 
Published: June 2018

Background: Diabetes is a pandemic disease; co-existence of several chronic diseases with diabetes is an important challenge around the world. However, sociodemographic variations in diabetes with other comorbidities are poorly understood in our region. We sought to describe age and gender differences in prevalence and pattern of comorbidities among diabetes mellitus (DM) patients.
Methodology: A population based cross-sectional study was conducted among residents of Gulshan town, Karachi, Pakistan. Data of healthy individuals and those having diabetes with any chronic condition were recorded. All self-reported chronic conditions including DM were further assessed based on physical examinations, history of medicines use and on laboratory findings. For analysis, individuals were grouped into following categories (1) healthy individual (those who have No Disease) (2) DM patients (3) DM with one comorbidity (4) DM with two comorbidities (5) DM with three or more comorbidities.
Results: A total 2968 participants were recruited in this study. DM was present in 685 (23.1%) participants. The most commonly co-occurring chronic conditions with DM were Hypertension (14.8%), Obesity (7.9%) and Depression (6.5%). Women were 34% less likely to have diabetes with one-comorbidity (aOR 0.66, 95% CI 0.45-0.96) but more likely to have 3 or more comorbidities (aOR 2.32, 95% CI 1.61-3.33) than men. Older age was also significantly associated to DM with comorbidities, individuals who aged ≥60 years were significantly more likely to have DM with 3+ comorbidities (aOR 5.47, 95% CI 3.07-9.75) compared to younger age group of 30-39 years.
Conclusion: Risk factors like diabetes alone was considerably higher in 40-49 years old patients, diabetes +1 comorbidity in male gender and patients with moderate physical activity, diabetes +2 comorbidities in Pashtun ethnic while diabetes +3 comorbidities were found considerably higher among females gender.

Disclosure
F. Uddin: None. S. Zaheer: None. K. Shafique: None.
Whole Genome Sequence Association Analysis and Diabetes-centric Functional Annotation of Type 2 Diabetes
Authors: WESSEL JENNIFER , BRODY JENNIFER A. , MANNING ALISA ,   TOPMED DIABETES WORKING GROUP
Published: June 2018

Our understanding of the genetic basis of T2D has been significantly advanced by identification of T2D loci through analysis of common variation; however, evidence suggests a role for rare regulatory variation influencing T2D. We leveraged the largest available whole genome sequence (WGS) data from NHLBI’s Trans-Omics for Precision Medicine (TOPMed) initiative and diabetes-centric genomic function data to the interpretation of results. We performed single-variant pooled-ancestry association analyses with (&gt;30x deep sequence) WGS in 13,200 individuals (2,601 T2D and 10,599 controls) from 6 studies. The association analyses were performed in the Analysis Commons hosted on DNANexus. We demonstrated the utility of the OASIS (Omics Analysis, Search and Information System) platform and integrating diabetes-specific functional annotation in a recently discovered locus (GIP-IGF2BP1) to fine-map to the likely causal variants. Our results identified common (minor allele frequency [MAF] &gt; 0.05) variant associations (P &lt; 5 × 10-8) at a known locus with T2D: TCF7L2 (rs7903146, P = 3.8 × 10-12). We also identified a potentially novel association on Chr15q21 with 27 rare variants (MAF = 0.2%, P =1.3 × 10-8, r2=1) spanning a 7.5 MB region. In the Old Order Amish study, 53 individuals carry the haplotype tagged by these 27 variants; 17% of carriers are diagnosed with T2D compared to 3% of the non-carriers. Interrogation of the GIP-IGF2BP1 locus, utilizing diabetes-specific annotation and association evidence of both common and rare non-coding variants, within the OASIS browser implicated nearby genes in the region as being the likely biologic candidates.
In conclusion, preliminary results suggest WGS analysis can discover novel loci for complex traits. Work is ongoing to refine annotation for rare variant association tests and perform functional fine-mapping across the genome. We soon will extend our analysis into the next release of WGS data from TOPMed (N∼69,000 individuals).

Disclosure
J. Wessel: Employee; Spouse/Partner; Eli Lilly and Company. J.A. Brody: None. A. Manning: None.
Neighbourhood Deprivation and Quality of Life among People with Diabetes in England
Authors: ABUBAKARI ABDUL-RAZAK 
Published: June 2018

Background: Income levels and Socio-economic status at the individual level are known to be associated with adverse health outcomes including risk of diabetes and its complications. However it is unclear how neighbourhood deprivation levels influence perceived quality of life among people with diabetes. This study investigated the relationship between neighbourhood deprivation and quality of life among people with diabetes attending two hospital trusts in Liverpool, England.
Methods: eligible participants completed a set of study questionnaires including demographic characteristics and the Audit of Diabetes Dependent Quality of Life questionnaire. Postcode based neighbourhood deprivation data were obtained from the UK’s Department for Communities and Local Government website. Relevant statistical analyses were undertaken using SPSS version 22.
Results: a total of 123 people with type 1 and type 2 diabetes participated in the study. Majority of participants were type 2 diabetes patients (53%) and about half were men (51%). Overall 20% of participants reported poor quality of life. Compared to those with type 2 diabetes, a higher proportion of people with type 1 diabetes reported good quality of life (58% vs. 61%; p&lt;0.05). Poor neighbourhood deprivation was associated with poor quality of life, both in univariate and multivariate analysis (p&lt;0.05). However, there was no significant association between neighbourhood deprivation and patients’ perceptions of how diabetes affected their quality of life (p&gt;0.05).
Conclusion: Neighbourhood deprivation levels are significantly associated with quality of life among people with diabetes and could potentially be used to guide interventions aimed at promoting their health and well-being.

Disclosure
A. Abubakari: None.
Relationship between NK Cell Activity and Glucose Regulation in Type 2 Diabetes Patients
Authors: KIM JUNG HYE , PARK KAHUI , LEE SANG BAE , KIM MIN KYUNG , NAM JI SUN , KANG SHINAE , PARK JONG SUK , AHN CHUL WOO , KIM YU SIK 
Published: June 2018

Introduction: NK cells are cytotoxic lymphocytes critical to innate immunity. The purpose of this study is to find out the difference in NK cell activity between type 2 diabetes patients and controls, and to investigate the association between NK cell activity and glucose control.
Methods: 49 subjects were enrolled in this study, with 23 type 2 diabetes patients and 26 normal glucose tolerant controls. Anthropometric and biochemical parameters were assessed. Homeostatic model assessment (HOMA) was calculated for insulin resistance. NK cell activity was measured using a newly developed NK Vueⓡ Kit (ATgen, Seoul), which is a method of detecting and comparing interferon-gamma level from NK cells.
Results: NK cell activity was lower in type 2 diabetes patients compared to control subjects. There was a significant inverse linear relationship between NK cell activity and fasting plasma glucose after adjusting for age and gender (r = -0.346, P = 0.045). Postprandial glucose and HbA1c showed a similar tendency with NK cell activity (r = -0.313 and -0.241, and P = 0.072 and 0.17, respectively). Regression analysis showed HbA1c, fasting glucose and postprandial glucose to be independent predictors of NK cell activity (beta = -0.303, -0.360, -0.356, and P = 0.034, 0.011, 0.033). There was no relationship between NK cell activity and HOMA-IR.
Conclusions: NK cell activity was lower in type 2 diabetes compared to controls, and it was significantly related to degree of hyperglycemia. A further, larger population study is warranted to confirm the possible correlation.

Disclosure
J. Kim: None. K. Park: None. S. Lee: None. M. Kim: None. J. Nam: None. S. Kang: None. J. Park: None. C. Ahn: None. Y. Kim: None.
Innate Lymphoid Cells—A New Medium That Berberine Affect Glycolipid Metabolism
Authors: TONG XIAOLIN , GUO XIAOHUAN , ZHAO LINHUA , GAO ZEZHENG , FU LIUHUI , WANG XINMIAO , LI QINGWEI , ZHENG YUJIAO 
Published: June 2018

Diabetes mellitus (DM) is one of the most familiar chronic diseases threatening human health. Studies showed the occurrence and development of type 2 diabetes mellitus (T2DM) are closely related to obesity. Obesity gives rise to higher level expression of inflammatory cytokines, which activate the inflammatory signaling pathway and suppress the insulin signaling transduction, thus lead to insulin resistance. Management of obesity is beneficial for improving T2DM, and the innate lymphoid cells (ILCs) play an important role in obesity as well as T2DM. Group 2 innate lymphoid cells (ILC2s) could regulate fat metabolism, while Group 3 innate lymphoid cells (ILC3s) and their secreted IL-22 are capable for suppressing inflammation and reducing insulin resistance. The Berberine (BBR), an extractive of coptis chinensis, has been verified that had certain hypoglycemic effect. In this study, We used high fat diet (HFD)-induced diabetes model, and observed an effective weight control, reduced blood glucose and lower insulin level after mice were fed with exogenous BBR. Further studies showed that the proportion of ILC3s was increased and the expression of IL-22 was up-regulated in the small intestine. Meanwhile, the proportion of ILC2s and expression of IL-4, IL-5 and IL-13 was also increased in the adipose tissue. In short, the BBR might affect glycolipid metabolism through regulating the differentiation and function of ILCs in the fat or intestinal mucosa.

Disclosure
X. Tong: None. X. Guo: None. L. Zhao: None. Z. Gao: None. L. Fu: None. X. Wang: None. Q. Li: None. Y. Zheng: None.
Caveolin-1 Was Required for Glargine to Improve Insulin Sensitivity and Activate PI3K/AKT Pathway in Visceral Adipose Tissue of Type 2 Diabetic Mice
Authors: PENG HANGYA , LI HAICHENG , LIN SHUO , ZENG WEN , LIN CHUWEN , LIN KEYI , ZENG LONGYI 
Published: June 2018

Insulin treatment improves insulin sensitivity, but the underlying mechanism remains unknown. Caveolin-1(Cav-1) konckout mice present insulin resistance.Our aim is to investigate the effect of Cav-1 depletion on insulin sensitivity and PI3K/AKT activation in glargine treatment of type 2 diabetic mice. C57BL/6J mice were divided into five groups(n=5 for each group).We firstly used high-fat high-carbonhydrate diet with intraperitoneal injection of streptozotocin(40mg/kg for 3 days) to induce type 2 diabetic(T2DM group) mice. Next, glargine was started at a dose of 0.4u/day to T2DM mice for 3 weeks(Insulin group).Lastly, Cav-1 expression was silenced by lentiviral-vectored short hairpin RNA (shRNA) through tail vein injection in glargine treated T2DM mice(CAV1-shRNA group) with scramble virus injection as a negative control(Ctrl-shRNA group). As a result, improvement of insulin sensitivity and PI3K/AKT activation with upregulation of Cav-1 were observed in visceral adipose tissue of Insulin group compared with T2DM group (P&lt;0.05). In CAV1-shRNA group,impairment of insulin tolerance and PI3K/AKT activation couldn’t be improved by glargine compared with Ctrl-shRNA group (P&lt;0.05). Our findings suggest that Cav-1 is required for insulin to improve insulin sensitivity and PI3K/AKT activation. More studies are needed to elucidate the mechanism.

Disclosure
H. Peng: None. H. Li: None. S. Lin: None. W. Zeng: None. C. Lin: None. K. Lin: None. L. Zeng: None.
Dynamic Resting State Connectivity after a High-Sugar Meal—A Neural Signature of Feeding
Authors: SHEARRER GRACE E. , SADLER JENNIFER R. , BURGER KYLE 
Published: June 2018

The brain must integrate both external and internal feeding signals in an effort to maintain homeostasis and respond to the external food environment. Examination of the brain’s intrinsic connectivity, through resting state functional MRI (rsMRI), provides insight into how the brain integrates such signals. While this method has been used to identify differential connectivity associated with metabolic diseases (type 2 diabetes, obesity), fewer studies have tested differences in rsMRI following short-term manipulations, such as intake of a meal. Here, we studied the effect of a high-sugar meal using a within-subject design to test blood glucose and rsfMRI following: 1) an overnight fast and 2) a high-sugar breakfast (720 total kcals, 86g sugar) in 27 individuals (mean BMI 26.8). Independent component analysis resulted in 10 validated brain networks that were used to test within-network functional connectivity differences as a function of food intake. Fed vs. fasted resulted in an increase in blood glucose (p&lt;0.0001) and modulation of sensorimotor networks. Specifically, intake of a high sugar breakfast increased connectivity within the oral somatosensory (gustatory processing, i.e., mouth feel) and dorsolateral prefrontal (dlPFC; contextual stimuli control) cortices (voxels=13; coordinates (mm)=-50,8,24; FWEpcorrected =0.03). This result suggests that increased connectivity between state-based behavior control (dlPFC) and somatosensory areas may be a neural signature of a post-prandial state.

Disclosure
G.E. Shearrer: None. J.R. Sadler: None. K. Burger: None.
High-Fat Diet Induces Diabetogenic Alteration of Ventromedial Hypothalamus (VMH) Glucose Sensing Neurons That Is Reversed by Circadian-Timed Bromocriptine Treatment
Authors: STOELZEL CARL , DUVALLET EMILIE , ZHANG YAHONG , TSAI TSUNG-HUANG , EZROKHI MICHAEL , CINCOTTA ANTHONY 
Published: June 2018

The VMH is a glucose sensing center that elicits the counterregulatory response to local glucopenia. However, VMH sensing of local post-meal hyperglycemia can potentiate post-meal peripheral insulin action. The insulin resistant (IR) state is coupled to postprandial hyperglycemia and may derive from a shift in glucose sensing status in VMH. To test this postulate in vivo electrophysiological multi-unit responses (MURs) to local glucose (1-5 mM) or 2-deoxyglucose (2-DG, 1-15 mM) infusion at VMH were obtained and compared from rats (age 12 weeks, on 14 hour daily photoperiods) maintained for 5 weeks on either regular lab chow (RC, 18% of calories from fat) or high fat diet (HFD, 60% of calories from fat) (to induce the IR state) (N= 8 RD, 10 HFD). The impact of circadian-timed bromocriptine (BC) (10 mg/kg), a dopamine D2 receptor agonist and postprandial insulin sensitizer vs. vehicle (N=5-7/group), upon MURs in HFD rats was also examined. Relative to VMH MURs of RC rats, in HFD rats VMH MURs to local hyperglycemia were reduced 53% (P&lt;.05) and MURs to 2-DG-induced hypoglycemia were elevated 93% (P&lt;.05). Neuronal receiver operator characteristic analyses suggest these changes in MUR rates (VMH output activity) can significantly alter the brain’s ability to detect and respond appropriately to such changes in VMH physiological glucose levels. BC treatment of HFD rats at circadian time (CT) of daily waking, but not outside this CT window reduced VMH MUR to 2-DG and increased VMH MUR to hyperglycemia to levels observed in rats on RC diet (P&lt;.02-DG, p&lt;.001 glucose) accompanied by reduced blood glucose (12%, P&lt;.001) and hyperinsulinemia (66%, P&lt;.05). These findings indicate that the VMH glucose sensing apparatus is altered by HFD to facilitate hyperglycemia and inhibit post-meal insulin action at physiological glucose levels and that this perturbation of the HFD can be abrogated by circadian-timed bromocriptine administration.

Disclosure
C. Stoelzel: Employee; Self; VeroScience, LLC. E. Duvallet: Employee; Self; VeroScience, LLC. Y. Zhang: Employee; Self; VeroScience, LLC. T. Tsai: Employee; Self; VeroScience, LLC. M. Ezrokhi: Employee; Self; VeroScience, LLC. A. Cincotta: Employee; Self; VeroScience, LLC.. Stock/Shareholder; Self; VeroScience, LLC..
Inhibition of Transcriptional Regulator Taz (Wwtr1) by Antisense Oligonucleotide (ASO) Treatment Improves Obesity and Hepatic Steatosis in a Mouse Model of NASH
Authors: PERALTA RAECHEL , LOW AUDREY K. , SCHMIDT JOANNA , FERNG ANNIE , MURRAY SUE , GUO SHULING 
Published: June 2018

Nonalcoholic fatty liver disease (NAFLD) is a common disorder that affects millions of people around the world. People with fatty liver disease alone are usually asymptomatic until a second insult to the liver, such as oxidative stress, triggers more severe steatosis, inflammation and fibrosis resulting in nonalcoholic steatohepatitis (NASH). The additional stress and damage to the hepatocytes results in the release of signals, such as hedgehog (Hh), to induce the wound-healing response. Data from animal models and human NASH have demonstrated Hh pathway activation correlates with the severity of liver disease. (1). In addition, the transcriptional coactivator, Taz/Wwtr1, was shown to be increased in hepatocytes from human and mouse NASH livers. (2). Based on these findings we performed DGE and qRT-PCR analysis on mice fed a high fat, fructose, and cholesterol (AMLN) diet for 24 weeks and found elevated mRNA expression of Taz in the livers compared to the lean mice. We treated C57B/6 mice fed the AMLN diet for 24 weeks with ASOs targeting Taz RNA. After 12 weeks of Taz ASO treatment, we observed a 95% knockdown in Taz mRNA expression in the liver compared to the control ASO group. This was accompanied by a 38% loss in whole-body fat mass (EchoMRI) and a 69% decrease in epidydimal white adipose tissue weight. Plasma analysis demonstrated a significant decrease in glucose and cholesterol compared to the control ASO levels. In addition, we observed reductions in liver triglyceride content resulting in levels similar to a lean mouse. No improvements in liver fibrosis were observed with Taz ASO treatment. These positive effects on obesity, plasma cholesterol, and liver steatosis suggest that Taz is a potential therapeutic target for preventing the progression of NASH into a more dangerous and irreversible liver disease.

Disclosure
R. Peralta: None. A.K. Low: Employee; Self; Ionis Pharmaceuticals, Inc.. Other Relationship; Spouse/Partner; Abbott. J. Schmidt: Employee; Self; Ionis Pharmaceuticals, Inc.. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc.. A. Ferng: None. S. Murray: Employee; Self; Ionis Pharmaceuticals, Inc. S. Guo: Employee; Self; Ionis Pharmaceuticals, Inc..