bluuebunny/crossref_metadata_2025 huggingface dataset:
LGR4 and Its Extracellular Domain as Novel Regulators of ß-Cell Survival and Proliferation
Authors: Filipowska Joanna K , Kondegowda Nagesha G , Vasavada Rupangi C
Published: May 2021

Our lab has shown that RANK (Receptor activator of the NF-κB) by interacting with its ligand, RANKL, inhibits ß-cell proliferation and survival; which can be reversed by Osteoprotegerin (OPG). Recently, the G protein-coupled receptor LGR4 (leucine-rich repeat-containing G protein-coupled receptor 4), which binds R-spondin (RSPO), was identified as a novel receptor for RANKL in osteoclast precursor cells. Thus, RANKL can bind two distinct receptors, RANK and LGR4 in osteoclasts, leading to opposite effects on osteoclastogenesis. LGR4 is expressed in rodent and human ß-cells, but the role of this receptor in ß-cells remains unknown. We postulated that LGR4 through its interaction with RANKL is involved in regulating ß-cell survival and proliferation. Our data indicate expression of specific LGR4 family members, Lgr4, Rank, Rankl, is modulated by stressors, such as cytokines, ER stress, diabetes and aging, in INS1 cells, rodent and human islets. Knocking down Lgr4 in INS1 cells or rodent islets has no significant effect on ß-cell proliferation but is detrimental for ß-cell survival in basal and cytokine-stimulated conditions. We also propose that the soluble extracellular domain of LGR4 (LGR4-ECD), which binds to its ligands (RSPO/RANKL), holds therapeutic potential like OPG, by inhibiting the interaction between RANKL/RANK. At 200ng/ml LGR4-ECD significantly enhances young adult (8-12-week-old) and aged (1.y.o.) rodent ß-cell proliferation, as well as human ß-cell proliferation, in islets from not only control subjects (45±17 y.o.), but also with Type 2 diabetes (48±7 y.o.). Additionally, LGR4-ECD significantly promotes mouse and human ß-cell survival against cytokine-induced cell death. Future studies will determine the physiological role of LGR4 and the therapeutic potential of LGR4-ECD on the beta cell in vivo in basal conditions and in the setting of diabetes.

Acknowledgements: Funding: JDRF postdoctoral fellowship # 3-PDF-2020-936-A-N to JF; Human Islets: IIDP
Racial Disparities Among Clinical Trials for Inherited Forms of Lipodystrophy
Authors: Abel Brent S , Cochran Elaine K , Startzell Megan S , Brown Rebecca J
Published: May 2021

Background: There has been renewed interest in understanding how medical research serves minority communities disproportionally affected by disease. A recent study in a predominantly white population identified 12 subjects with partial lipodystrophy by genetics without clinical diagnosis of lipodystrophy (Gonzaga-Jauregui et al., 2020). Partial lipodystrophies are rare monogenic disorders leading to diabetes that can be challenging to diagnosis due to their similarity with common obesity-associated metabolic syndrome. We hypothesize minority populations may be underdiagnosed with lipodystrophy, and thus underrepresented in clinical trials.

Methods: We compared racial demographics of lipodystrophic subjects participating in clinical trials to subjects with predicted loss-of-function (pLOF) mutations in 4 genes associated with lipodystrophy in the GnomAD dataset (>140K exome sequences): LMNA & PPARG (causing dominantly inherited partial lipodystrophy), and AGPAT2 & BSCL2 (causing recessively inherited generalized lipodystrophy, which is more phenotypically apparent, as an internal control for the study design). We also compared rates of synonymous mutations in these 4 genes among races to test if subjects of different ethnicities may be more genetically predisposed to developing inherited forms of lipodystrophy. Comparisons were done using chi-square analysis.

Results: We identified 322 subjects with pLOF mutations in genes associated with lipodystrophy in the GnomAD dataset. The racial composition of GnomAD subjects with pLOF mutations in each gene was different than GnomAD subjects without pLOF mutations (p<0.001). 144 lipodystrophic subjects with known pathogenic variants in these genes participated in clinical trials. The racial composition of GnomAD and clinical trial subjects with LMNA mutations were significantly different (p=0.024) with the clinical trial cohort being more enriched for white patients (78 vs 21%) and less enriched for Latino patients (7 vs. 21%). There were no differences for other genes. The rates of synonymous mutations were different among patients of different ethnicities, p<0.001 for all genes.

Discussion: Partial lipodystrophy due to LMNA mutations may be underdiagnosed in Latinos, leading to reduced participation in clinical trials. The lack of differences in other genes suggests there is no overall cohort bias. Different rates of synonymous mutations suggest there may be evolutionary drivers to racial differences in inherited forms of lipodystrophy, such as founder mutations or heterozygote advantage. Future work will determine prevalence of pLOF variants in lipodystrophy-associated genes in other genetic data sets enriched for minority subjects.
The Role of Inositol Phosphate Multikinase (IPMK) in Time Restricted Feeding in Animal Model
Authors: Jung Ik-Rak , Tu-Sekine Becky , Anokye-Danso Frederick , Ahima Rexford S , Kim Sangwon
Published: May 2021

Obesity is a major public health problem of the U.S. and is associated with diabetes, cardiovascular diseases and other diseases. Most research studies focus on excessive food consumption as the main cause of obesity. However, emerging data indicate that the timing of feeding can have significant effects on body weight and metabolism. Numerous studies in animals and small clinical studies in humans have shown that eating erratically over the 24 hour period or out of phase with the circadian rhythm predisposes toward weight gain, steatosis, dyslipidemia, insulin resistance and diabetes. Furthermore, studies indicate that restricting food intake to the active period synchronizes the circadian rhythm and metabolism, enhances weight loss and improves metabolic outcomes. Time restricted feeding (TRF) increases the amplitudes of clock gene expression and pathways mediating nutrient sensing and hepatic metabolism. However, the mechanisms mediating the effects of TRF are not fully understood. Here we characterized mice (10 week-old) fed a high-fat diet ad libitum (ALF) or from 7 pm to 7 am (TRF) for 2 weeks. The basal glucose production rate was similar between the two groups. Under hyperinsulinemic-euglycemic clamp, the glucose infusion rate (GIR) was significantly greater in TRF group compared to ALF group indicating an increase in insulin sensitivity. Using radioisotopic tracers, we demonstrated that the hepatic glucose production (HGP) was significantly reduced and the glucose disappearance rate was increased in TRF group compared to ALF group. Moreover, a biochemical analyses of liver tissues revealed that Inositol phosphate multikinase (IPMK) act as a key enzyme for inositol polyphosphate biosynthesis and play a role in insulin-, nutrient-, and energy-mediated metabolic signaling, was increased during TRF. Moreover, deletion of IPMK in hepatocytes decreased insulin stimulated AKT phosphorylation while increased lipid accumulation and gluconeogenesis. Importantly, hepatic deletion of IPMK attenuated the beneficial effects of TRF suggesting that IPMK in the liver may contributes to beneficial effects of TRF. Our findings provide the potential mechanism by which TRF confers the beneficial effects and may provide a novel therapeutic strategy for treating diabetes.
Clinical Trials Evaluating Turmeric Dietary Supplement Treatment of Obesity-Associated Disorders of Glucose Metabolism or Bone
Authors: Panknin Timothy M , Bucchireddigari Bhanu , Howe Carol , Hauer Megan , Rossi Anthony M , Funk Janet L
Published: May 2021

Curcumin-enriched turmeric dietary supplements (DS) are one of the top selling botanicals in the United States. Recent observational studies by our research group have documented turmeric DS use by almost a quarter of breast cancer survivors concurrent with anti-estrogen therapy and a third of those with rheumatoid arthritis. However, some recent reviews have suggested that there is no evidence of any biological effect of curcumin in humans, albeit without rigorous review of published reports. A scoping review of the literature was therefore undertaken to identify clinical trials testing oral curcumin-containing turmeric dietary supplements in humans. Using a defined search strategy, eight databases were reviewed (thru 05/29/2019), identifying 4767 potential English language reports for inclusion, from which all but n = 315 were excluded after review by three independent observers. The majority of studies reported significant effects of turmeric DS on clinical endpoints. Obesity-associated disorders of glucose and lipid metabolism (n =69, including type 2 diabetes mellitus [T2DM], metabolic syndrome and/or hyperlipidemia) or musculoskeletal disorders (n = 46), of which half related to osteoarthritis, were among the most commonly studied diseases in turmeric DS clinical trials, with reported benefits related to inhibition of inflammation, amelioration of hyperlipidemia, increases in adiponectin, and improved glucose control. As is common for botanical clinical trials, the quality of the studies were variable due to lack of clarity about product content as well as study design (e.g. only 60% of T2DM trials and 74% of osteoarthritis trials were randomized, placebo-controlled and double-blinded). However, particularly with respect to treatment of osteoarthritis and metabolic consequences of insulin resistance, the preponderance of the data were suggestive of beneficial physiologic effects. Given the current widespread use of turmeric DS by Americans and existing evidence of possible clinical benefits, further evaluation of turmeric DS efficacy and safety may be warranted.
Comparison Between Glycemic Variability Values Calculated From Professional-CGM and Glycemic Variability Values Calculated From Personal-CGM
Authors: Takeishi Soichi , Inoue Tatsuo
Published: May 2021

It is important whether the differences between glycemic variability (GV) values calculated from professional CGM and GV values calculated from personal CGM are acceptable when using professional CGM data and personal CGM data together in studies. This is a prospective study. 41 inpatients with type 2 diabetes wore professional CGM (iPro2) and personal CGM (GUARDIAN CONNECT) in parallel for 6 days (CGM attachment: day 1). Each CGM were calibrated 22 times from day 2 to day 5, on the same timing in all patients (n of calibration = 902). Four 24 h GV from day 2 to day 5 per patient were evaluated (n of 24 h GV = 164) on each CGM. There were no significant differences between the standard deviation on professional CGM and that on personal CGM (32.2 mg/dL vs 32.8 mg/dL, p = 0.21). For time in range (70–180 mg/dL) [TIR 70–180], mean glucose levels and coefficient of variation (CV), the values were numerically almost equal between GV on professional CGM and that on personal CGM. However, for TIR 70–180 and CV, the GV on professional CGM was statistically significantly lower than that on personal CGM (70.8 % vs 72.5 %, p = 0.002, 20.6 % vs 21.3 %, p = 0.04); and for mean glucose levels, the GV on professional CGM was statistically significantly higher than that on personal CGM (157.7 mg/dL vs 155.2 mg/dL, p < 0.001). For mean absolute glucose (MAG) and glycemic variability percentage (GVP), the GV on professional CGM was significantly lower than that on personal CGM (25.3 mg/dL/h vs 41.0 mg/dL/h, p < 0.001, 14.4 % vs 31.1 %, p < 0.001). The calibrations, whose blood glucose levels (BG) were higher than ‘sensor glucose levels just before the BG’ (SGjb), were more than those, whose BG were lower than SGjb (482 times vs 420 times). The mean absolute relative differences on professional CGM were significantly lower than those on personal CGM (5.0 % vs 6.3 %, p < 0.001). The study patients correlated to distributions of ‘ratio of CV on personal CGM to CV on professional CGM on the same day’ (correlation ratio: η 2 = 0.48, p < 0.001). The results of TIR 70–180 and mean glucose levels may have been caused by the fact that the calibration BG were high dissociated from SGjb and algorithm of professional CGM is easier to allow the dissociation than that of personal CGM. The results of CV may have been caused by the individual differences in sensor accuracy between professional CGM and personal CGM. The results of MAG and GVP may have been caused by the fact that personal CGM can reveal detailed glycemic variability which cannot be revealed by professional CGM, due to real time calibration. According to purpose of studies, it should be determined whether using professional CGM data and personal CGM data together is acceptable.
Efficacy and Safety of Ertugliflozin in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease Using Insulin
Authors: Lingvay Ildiko , Greenberg Michelle D , Gallo Silvina , Shi Harry , Liu Jie , Gantz Ira
Published: May 2021

Introduction: Ertugliflozin (ERTU), a sodium-glucose cotransporter 2 inhibitor, is approved as an adjunct to diet and exercise to improve glycemic control in patients (pts) with type 2 diabetes mellitus (T2DM). Aim: As part of the VERTIS CV trial (NCT01986881), the efficacy and safety of ERTU were assessed in pts with T2DM and established atherosclerotic cardiovascular disease (ASCVD) inadequately controlled by insulin. Methods: Pts were randomly assigned to placebo (PBO), ERTU 5 mg or 15 mg once daily. A pre-specified sub-study was conducted in pts on a stable dose of insulin ≥20 units/day (± metformin). The primary endpoint was HbA1c change from baseline at 18 weeks. Key secondary endpoints included proportion of patients achieving HbA1c <7%, fasting plasma glucose (FPG), body weight (BW), and systolic blood pressure (SBP). Changes from baseline at Week 18 for continuous efficacy endpoints were assessed using a constrained longitudinal data analysis model. HbA1c reduction was also assessed in subgroups based on baseline HbA1c, age, sex, race, ethnicity, and use of metformin. Results: Of 8246 pts randomized in VERTIS CV, 1065 pts (ERTU 5 mg: 348; ERTU 15 mg: 370; PBO: 347) with T2DM and ASCVD were included in the sub-study. Mean baseline characteristics were similar across treatment groups; age 64.8 years, T2DM duration 16.7 years, HbA1c 8.4%, and eGFR 73.7 mL/min/1.73 m2. At baseline, 40.6% of pts were on insulin alone, 59.4% were receiving insulin + metformin; median (range) insulin dose was 58.0 (20–350) units/day. At Week 18, least squares mean change (95% confidence interval) from baseline in HbA1c was significantly greater with ERTU 5 mg and 15 mg vs PBO. PBO-adjusted differences were −0.6% (−0.7, −0.4) and −0.7% (−0.8, −0.5), for ERTU 5 mg and 15 mg, respectively (P<0.001 for both). HbA1c reductions were greater with ERTU vs PBO for all subgroups including by use of metformin. At Week 18, 10.7%, 20.7%, and 21.1% of pts with PBO, ERTU 5 mg and 15 mg, respectively, achieved HbA1c <7.0%. ERTU 5 mg and 15 mg significantly reduced FPG, BW, SBP, and ERTU 15 mg led to a small reduction in total daily insulin dose. The overall incidence of adverse events and serious adverse events was similar across treatment groups. In women, the incidences of genital mycotic infections was higher with ERTU 5 mg (3.4%; P=0.05) and ERTU 15 mg (3.6%; P=0.04) vs PBO (0.0%). The incidences of urinary tract infections (3.2–4.1%), symptomatic hypoglycemia (26.4–28.5%), and severe hypoglycemia (3.5–5.1%) were similar across treatment groups. The incidences of hypovolemia were low (1.4–2.4%) and similar across treatment groups. Conclusion: ERTU added to insulin (± metformin) led to greater reductions from baseline in HbA1c, FPG, BW, and SBP, and a higher proportion of pts achieving HbA1c <7.0%, vs PBO at 18 weeks in pts with T2DM and ASCVD, without increasing the risk of hypoglycemia.
Improving Glycemic Control of Diabetic Patients in an Outpatient Practice
Authors: Gibbs Otto T , Otuonye Gene C , Sammour Ahmed H , Aguasvivasbello Marnie , Williams Karlene D
Published: May 2021

Diabetes Mellitus (DM) is a devastating condition with premature mortality, poor quality of life, & vast economic cost contributing to substantial societal burden. More resources are allocated to DM than any other condition, & with an estimated worldwide prevalence of 350 million people by 2025, it remains an urgent epidemic. Providing standardized, high quality care (HQC) to improve DM control is a matter of utmost importance. Our residents receive primary care training in a federal funded healthcare system, with yearly reports from Medicare addressing compliance with current accepted standards, including but not limited to DM management. In this Quality Improvement (QI) project, we sought to directly address deficiencies in their management.

A retrospective chart review was conducted over 1 year. Patients with uncontrolled (UC) DM were identified & a root cause analysis conducted. It was noted that over 40% of diabetics were UC, with a hemoglobin A1c (HbA1c) >8%; 60% of whom did not have appropriate escalation of management (AEOM) in further encounters. A QI intervention was developed aiming to improve AEOM in patients. Plan-Do-Study-Act cycles focused on the creation of a standardized documentation system (SDS) for UC DM encounters, a tracking system & a designated “DM manager”, who ensured electronic prescription delivery & early follow-up (F/U) appointments. Clear metrics of AEOM were established & clinicians underwent small group educational sessions emphasizing each intervention, with review of updated ADA guidelines. Although prospective biweekly chart review is ongoing, Fisher’s exact test was used for statistical analysis of initial post interventional data.

A total of 33 UC DM patient encounters were analyzed thus far. In January 2020, 31% of all encounters used the newly created SDS; of which 69% had AEOM. In February 2020, 57% of all encounters used the SDS; 71% of providers had AEOM. Of the encounters using the SDS, 83% had AEOM compared to 67% in those without (p:0.42). Average F/U time per patient was 6 weeks.

Delivering standardized & HQC in DM patients presents a challenge dependent on a variety of system & patient factors. This becomes more apparent in rural & low-income populations as in our clinic. Although HbA1c is a well-established method of monitoring glycemic control, we propose that other uniform performance measures be used to dynamically assess overall DM management. Our metrics include standardized, replicable documentation, early F/U time & defined AEOM parameters such as timely addition of new medication, dose adjustments, & utilization of resources such as DM educators. Thus far, there appears to be a non-statistically significant trend towards improved standardization of provider documentation, F/U visits & AEOM. Further data is needed. We hope to see these measures translate into overall improved glycemic control.
A Case Series of Hyperglycemic Hyperosmolar State During the Global COVID-19 Pandemic
Authors: Hoag Benjamin Donald , Knoll Michelle , Paprocki Emily
Published: May 2021

Hyperglycemic hyperosmolar state (HHS) is rare in pediatrics, particularly in patients with antibody positive diabetes mellitus (DM). Recent literature has implicated COVID-19 in the reported increase in new-onset DM cases, as well as mixed diabetic ketoacidosis (DKA) and HHS cases, however a rise in HHS cases alone has not been well reported [1,2]. We noted an anecdotal increase in the frequency of HHS cases in our pediatric tertiary care center following the onset of the global COVID-19 pandemic. To investigate further, a retrospective chart review evaluating all patients with DM admitted in the first 6 months of 2019 and the first 6 months of 2020 was conducted. A diagnosis of HHS was defined as a blood glucose over 600 mg/dL with a serum osmolality (calculated or measured) greater than 320 mOsm/kg on initial laboratory evaluation. Patients with DKA, defined as a serum bicarbonate level less than 16 mmol/L with evidence of significant ketosis (serum ketones greater than 3 mmol/L), were excluded from the study. During the first 6 months of 2019, 1 patient met inclusion criteria. However, the diagnosis of HHS was complicated by a concurrent diagnosis of diabetes insipidus, which may have contributed to the hyperosmolar state, and a nonketotic lactic acidosis. Five HHS cases were noted in the first 6 months of 2020, 4 of which occurred in May and June. For the 2020 HHS cohort, the average patient age ± SD was 12 ± 3.34 years. The mean ± SD laboratory values included bicarbonate 18.2 ± 1.64 mmol/L, serum blood glucose 776.8 ± 30.75 mg/dL, calculated serum osmolality 328 ± 4.18 mOsm/kg, and HgA1C 12.72 ± 1.16%. All 5 patients in the 2020 cohort had new-onset DM, with 4 of the 5 patients having at least 1 positive DM antibody (GAD antibodies were positive in 3, ICA/IA-2 antibodies in 2, and Zinc Transporter 8 antibodies in 1). No patients displayed COVID-19 symptoms, and only 1 patient was tested for COVID-19 by PCR, which returned negative. However, SARS-CoV2 antibody testing was not available, and it is unknown if these patients had prior COVID-19 illness. In conclusion, we noted an increased incidence of HHS at our hospital, particularly among new-onset, antibody positive DM patients during the initial months of the COVID-19 pandemic. Further study and investigation are needed to determine the cause of this increased local incidence, and if infectious, social, or economic influences related to the COVID-19 pandemic contributed. References: [1] Chan, K.H., et al., Clinical characteristics and outcome in patients with combined diabetic ketoacidosis and hyperosmolar hyperglycemic state associated with COVID-19: A retrospective, hospital-based observational case series. Diabetes Res Clin Pract, 2020. 166: p. 108279. [2] Unsworth, R., et al., New-Onset Type 1 Diabetes in Children During COVID-19: Multicenter Regional Findings in the U.K. Diabetes Care, 2020.
An Observational Study on Glycemic Outcomes, Lifestyle and Psychosocial Health of Patients With Diabetes During Covid-19 Lockdown From Bangalore
Authors: Selvarajan Raja , Jaganmohan Balaji , Vijayaraghavan Radhika
Published: May 2021

Background and Aims:

Lockdown during the COVID-19 pandemic imposed many restrictions on the public. Loss of continuum of care along with improper lifestyle was expected to worsen glycemic control in people with type 2 diabetes (T2D). We aimed to identify the effects of lockdown on their glycemic status, lifestyle changes and psychosocial health.

Methods:

The pre- and post-lockdown data of 110 adults with T2D who were under regular follow up was collected by direct interview during their visit to the diabetes clinic. The variables analyzed included demographic data, HbA1c, body weight, lifestyle changes, psychosocial factors and use of technology.

Result:

The overall physical activity had dipped significantly accounting to lockdown restrictions and fear. Dietary adherence was better with participants exhibiting increased consumption of vegetables (80.9%), fruits (42.7%), and decreased unhealthy snacking (63%). 90% of them had access to medications during lockdown. There was significant change noted in the mean HbA1c (0.9- 1.45%) and body weight (1–3.5kgs) before and after lockdown. There was a great increase in Screen time attributing to Work from home and restrictions to move out. 63.6% of them spent time with their family members. Those with prior mental stress,poor sleep and unhealthy dietary habits had worsening glycemic control as seen in those with less physical activity and an unhealthy diet. An increasing trend of utilisation of health related mobile internet technology apps were noted.

Conclusion:

Lockdown did cause a major change in the overall glycemic control. Measures to promote healthy lifestyle practices along with ways to reduce psychosocial stress must be implemented for better T2D management during such restricted times. Telemedicine paved a greater way and scope of continuum of Diabetes care.
How Did Elderly T2D Patients Cope With the Quebec Covid-19 Lockdown
Authors: Elstein Jack , Gilfix Reisa , Elstein Eleanor
Published: May 2021

The Canadian city most affected by the first wave of the Covid-19 (CV19) pandemic was Montreal. Montreal was in lockdown (LD) from Mar 13- Jun 15, 2020. The elderly, diabetics, and the economically disadvantaged are among the groups most at risk of CV19 and the psychosocial effects of LD. We sought to ascertain the effect of the LD on the wellbeing of lower income elderly T2D pts. As we felt it unethical to do non-essential testing during a pandemic we relied on clinically available HbA1c’s as surrogates for metabolic wellbeing. Most HbA1c‘s used reflect a high (r=0.91) correlation with 3 month values for the time periods of interest. The study group was composed of 38 mostly elderly T2D pts. All pts lived alone or with similarly aged spouses in non-institutional settings in a lower middle class neighborhood of Montreal. None had organized domestic help from family or the community. None had documented acute medical episodes or medication changes between Jan and Sept 2020. None have conditions known to render HbA1c non reliable. Pts were interviewed by telephone to assess their overall coping with the LD. In particular they were questioned about medical issues, difficulties obtaining medications +/- groceries and psychological or social stress. HbA1c values between Jan 1 - Mar 15, 2020 and after Aug 25, 2020 (non LD values) and between Apr 20 - Aug 15, 2020 (LD values) were recorded. Differences in the recorded non LD and LD HbA1c’s were compared and analyzed for the group as a whole, by gender, and by insulin use. There were 38 pts, 22 M 56–77 yrs (mean 72.1) and 16 F 41–90 yrs (mean 75.2), 89.5% (34/38) were > 65 yrs. Ten M and 9 F were on insulin. No pt reported severe hypoglycemia or weight fluctuations. All claimed to be following public health guidelines. There were no significant differences (d) between the mean HbA1c’s non LD compared to LD neither for the entire group (d= 0.2), M (d=0.2), F (d=0.2), insulin treated pts (d=0.3) nor those not treated with insulin (d=0.0). There were no overt medical decompensations. No pt reported having been unable to access medications or groceries. No pt reported significant psychological distress or feelings of isolation. None had been diagnosed with CV19. This largely geriatric T2D cohort did not report any overt deleterious effects from the LD. There were no significant differences in HbA1c non LD compared to LD. It is not possible to determine how effective the LD was in protecting these pts from CV19 other than to note that none had been diagnosed as having contracted the disease. As the 2nd wave of CV19 evolves, health care professionals will have the opportunity to study the effect of public health interventions, not only on controlling the spread of CV19, but also on the general wellbeing of different pt populations.
Hyperglycemia Is Associated With Increased Mortality in Critically Ill Patients With COVID-19
Authors: Bass* Ilana R , Mazori* Alon , Chan Lili , Mathews Kusum , Altman Deena , Saha Aparna , Soh Howard , Wen Huei Hsun , Bose Sonali , Leven Emily , Wang Jing Gennie , Mosoyan Gohar , Pattharanitima Pattharawin , Greco Giampolo , Gallagher Emily Jane
Published: May 2021

Objective: To explore the relationship between diabetes mellitus (DM), hyperglycemia, and adverse outcomes in critically ill patients with coronavirus disease 2019 (COVID-19).

Research Design and Methods: The study population comprised 133 patients with COVID-19 admitted to an intensive care unit (ICU) at an academic, urban, quaternary-care center between March 10th and April 8th, 2020. Patients were categorized based on the presence of DM and early-onset hyperglycemia (EHG), defined as a blood glucose >180 mg/dL during the first two days of ICU admission. The primary outcome was 14-day in-hospital mortality; also examined were 60-day in-hospital mortality and the levels of C-reactive protein (CRP), interleukin 6, procalcitonin, and lactate. Results: Compared to non-DM patients without EHG, non-DM patients with EHG exhibited higher adjusted hazard ratios (HR) for in-hospital mortality at 14 days (HR 5.76, p=0.008) and 60 days (HR 7.28, p=0.004). Non-DM patients with EHG also featured higher levels of mean CRP (322.3±177.7 mg/L, p=0.036), procalcitonin (34.75±69.33 ng/mL, p=0.028), and lactate (2.7±2.1 mmol/L, p=0.023). Conclusions: In patients with critical illness from COVID-19, those without DM with EHG were at greatest risk of 14-day and 60-day in-hospital mortality. The limitations of our study include its retrospective design, and relatively small cohort. However, our results raise the possibility that the combination of elevated glucose and lactate may identify a specific cohort of individuals at high mortality risk from COVID-19, and suggest that glucose testing and control are important in individuals with COVID-19, even in those without pre-existing diabetes.
Impact of Covid19 Lockdown on Glycemic Control
Authors: Rodriguez Giovanna , Bahtiyar Mert , Kirupakaran Johnathan , Kubbar Alaa , Singh Shikha , Karnik Suruchi , Hashmi Syed Salman , Bahtiyar Gul
Published: May 2021

Evidence shows that people with poor glycemic control are at greater risk of mortality due to Covid19. It is important to achieve and maintain good glycemic control to prevent negative outcomes during this pandemic (1). To study the effect of lockdown on glucose control we conducted an observational, retrospective cohort study involving 98 patients followed at endocrine clinic at an inner city, community hospital in Brooklyn, NY in the period February to May 2020. Of the cohort, 60% were women, mean age was 54.1 + 15.3 years, 70% was Hispanic, 24% was African American with a predominance of type 2 diabetes (86%). Mean HbA1c of prelockdown and lockdown phase was 9.77 ± 2.26% and 9.49 ± 2.17 % respectively and the difference was statistically significant (p < 0.001) both in patients with Type 1 and Type 2 diabetes. Mean BMI of prelockdown and lockdown phase was 30.5 ± 6.8% and 30.1 ± 6.05% respectively and the difference was not statistically significant (p = 0.33). Despite no significant change in BMI, the factors responsible for improvement in HbA1c might be a result of refined eating patterns (increased consumption of homemade food), increased adherence to medication and time to cope with the daily challenges of diabetes management (1). Reference: Maddaloni E, Coraggio L, Pieralice S, Carlone A, Pozzilli P, Buzzetti R. Effects of COVID-19 Lockdown on Glucose Control: Continuous Glucose Monitoring Data From People With Diabetes on Intensive Insulin Therapy. Diabetes Care Aug 2020, 43 (8) e86-e87; DOI: 10.2337/dc20-0954
Implementation of a Continuous Glucose Monitoring Program at a Safety Net Hospital During Covid 19 Pandemic
Authors: Finn Erin E , Schlichting Lindsay , Pereira Rocio Ines
Published: May 2021

Background: COVID 19 disproportionately impacts individuals with diabetes leading to increased morbidity and mortality. Hyperglycemia is common in hospitalized patients with COVID requiring intensive monitoring and management. Close monitoring of glucoses requires increased use of personal protective equipment (PPE), which has been in limited supply since the beginning of the pandemic. The FDA granted conditional allowance for use of continuous glucose monitors (CGM) in hospital settings during the COVID pandemic to allow for preservation of PPE. We present the process of implementing a continuous glucose monitoring program in an urban safety net hospital.

Methods: The program was implemented at a county urban safety net hospital. Patients were eligible to be started on Dexcom G6 CGM if they had hyperglycemia requiring multiple insulin injections daily, were in contact isolation, and were located in 1 of 3 units of the hospital (medical intensive care unit [MICU], surgical intensive care unit, COVID 19 floor unit). Initial program was started in the MICU and subsequently expanded. Nurses and staff underwent training using videos, in-person demonstrations, and written guides. Informational Technology modified the electronic medical system to allow for ordering and documentation of CGM values by nurses. Supplies were stored both on unit and in central supply allowing for primary team to initiate monitoring independent of diabetes team. Records of patients participating in program were maintained by the diabetes team. Amount of PPE saved was estimated to be 10 instances/day while on insulin drip and 3/day when using subcutaneous insulin.

Results: A total of 69 patients used a CGM during their hospital course. Average age was 56 years old, 69 % were male, average BMI 31, and 84% had known diabetes prior to admission. The majority of patients were critically ill with 68% intubated, 48% on vasopressors, 6% requiring dialysis, 38% on insulin drip, 46% were on tube feeds, and 74% received steroids. The racial demographics of the patients were 72% White, 3% Black, 4% Native American, 4% Asian, and 14% other. For ethnicity, 73% identified as Hispanic and half spoke Spanish as their primary language. An estimated 2600 instances of PPE were saved. Challenges that were faced in implementing the program included consistent training of large numbers of staff, maintaining supplies in stock, troubleshooting discordant values, and restricting use of CGM to patients who met qualifications.

Conclusion: Overall, the implementation of CGM was successful and received a positive response. Staff in the primary units quickly became comfortable with the application of the technology. Potential challenges in the future include ongoing training, improving troubleshooting of technology, validating the accuracy of the devices, and developing funding for CGM equipment and interpretation.
Incidence of Diabetic Ketoacidosis in Hospitalized COVID19 Patients With Type 2 Diabetes
Authors: Almistehi Wael Mohammad , Alturki Abdulrahman Mohammed , Bukhari Bashear Adnan
Published: May 2021

Introduction: Diabetes is a disease of persistent hyperglycemia with a devastating complication and even death if left untreated. Morbidity and mortality often increased for any condition among patients with diabetes. Diabetic ketoacidosis (DKA) is an acute and life-threatening complication of diabetes. It can occur to type 2 diabetes (T2DM) under severe stress. Since the pandemic of Coronavirus disease 2019 (COVID19), that caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, Hubei China, in December 2019, more than 47 million infected cases reported leading to more than 1.2 million deaths reported worldwide. The presence of diabetes in COVID19 patients had a higher odd of severity and mortality of the COVID19 compared to patients without diabetes. Our study aims to identify the incidence rate of DKA in T2DM admitted with COVID19 in a tertiary care center. Evidence showed those populations at considerable risk for morbidity and mortality and no available data in Saudi Arabia. Method: A retrospective cohort of adult patients admitted for COVID19, with a diagnosis of T2DM or clinical evidence of DKA in a tertiary care center named King Fahad Medical City located in Riyadh in Saudi Arabia. The study involved a chart review. Data collected from the beginning of March 2020 till the end of June 2020. Results: Of 244 patients with T2DM admitted for COVID19, 190 patients were male, and 55 patients were female. The mean age was 59-year-old. out of 244 patients collected, 20 had developed DKA. The incidence rate of DKA was 8%. Number and percentage of male was 15 (71.4%) and female 6 (28.6%). Out of 20 patients admitted with DKA and COVID-19, two patients were not known to have diabetes prior to the presentation. Mortality resulted in 5 out of 20 during admission stay, represent 25% of all patients with DKA. Discussion: Here we report the first study in S.A. about DKA incidence in T2DM with COVID19 pneumonia. In the present study, an alarming observation of a higher incidence of DKA in a patient with type 2 diabetes and COVID19 infection as incidence reaches 8% over a short period of time while incidence worldwide area range was less than 2 per 1000 person-year for DKA in type 2 diabetes without COVID19. A study reported 20 % of patients who have diabetes and COVID19 presented ketosis developed DKA. We report the incidence of DKA in selected group. The mortality rate was not far from different evidence in the world. The mortality rate was 25% in the present study. In the USA, it reaches 30% of inpatient with hyperglycemia at presentation. Conclusion: DKA is a life-threatening complication, and it became worse when it is related to COVID19. The incidence of DKA and mortality related to COVID19 increased when DKA occurs for T2DM subjects. A more prospective study is warranted and a longer duration of the study to establish the accurate incidence and mortality rate.
Outpatient Diabetic Outcome During the Covid-19 Pandemic: A Retrospective Single Center Analysis
Authors: Krahmer Robert , Thongprayoon Charat , Ruanpeng Darin
Published: May 2021

Background: Previous studies have shown that telemedicine is an effective alternative method for health care delivery. The COVID-19 pandemic has acutely stimulated expansion of telemedicine across the country. This study aimed to determine characteristics of telehealth visit and short term HbA1c outcome in patients with diabetes mellitus in endocrinology clinic during the COVID-19 pandemic. Methods: A single center retrospective chart review was conducted in all patients seen in endocrinology clinic for diabetes mellitus between 5/27/2020–7/20/2020. Data were extracted from electronic medical record. The primary research question is percentage of patients who achieved HbA1C ≤ 8% at 3 month follow up. Secondary research questions are characteristic of patients and clinic visits, diabetic technology usage, 3 month follow up mean HbA1c and HbA1c change. This project was approved by the institutional review boards. Results: Two hundred and six diabetic patients were seen: 72 (35%) in person, 49 (24%) phone visit, and 85 (41%) VDO visit. Mean age for patients adopted in person visit was 57 (SD 15) years, phone visit was 68 (SD 13) years and VDO visit was 54 (SD 18) years, p <0.001. Male percentage for in person, phone and VDO visit was 44%, 59% and 61% respectively, p 0.09. New consult visit percentage for in person, phone and VDO visit was 7%, 2% and 5% respectively, p 0.46. Percentage of patients using insulin pump or continuous glucose monitoring for in person, phone and VDO visit was 33%, 43% and 54%, respectively, p 0.03. Baseline HbA1c was done in 89% (64/72) in person, 45% (22/49) phone and 52% (44/85) VDO visit. Among patients who had baseline HbA1c, average HbA1c was 8.6% (SD 1.8) for in person visit, 8.0% (SD 1.1) for phone visit and 8.1% (SD 1.8) for VDO visit, p 0.25. At 3 months, HbA1c was done in 38% of patients who had in person visit, 36% phone visit, and 43% VDO visit. Among patients who had 3 month follow up HbA1c, HbA1c ≤ 8% was achieved in 50%, 61% and 69% for in person, phone and VDO respectively, p 0.56. Mean 3 month follow up HbA1c was 8.1% (SD 1.3), 7.7% (SD 0.9) and 7.8% (SD 1.6) for in-person, phone and VDO visit respectively, p 0.47. Comparing mean HbA1c in patients who had both baseline and 3 month follow up HbA1c, changes were significant for in person visit 9.1% to 8.1% (p 0.01) and VDO visit 8.7% to 7.6% (p 0.01). No significant change in 3 month follow up HbA1c was observed in phone visit, 7.7% to 7.6% (p 0.88). Conclusions: This retrospective study showed that during the COVID-19 pandemic, no differences in short term HbA1c outcome (3 month follow up mean HbA1c and percentage of patients who achieved HbA1c ≤ 8%) were observed among patients who adopted in-person and telehealth visit. Patients who adopted phone visit appeared to be older; and there was more diabetic technology usage (insulin pump or continuous glucose monitoring) among patients who adopted telehealth (phone and VDO) compared to in person visit.
17q12 Deletion Syndrome. A Rare Association Between Diabetes and Renal/Urogenital Abnormalities
Authors: Perdomo Laura Sofia , Perdomo Rodriguez Juan Pablo
Published: May 2021

Introduction: Maturity onset diabetes of the young type 5 (MODY 5) is an autosomal dominant, non-autoimmune form of diabetes mellitus caused by HNF1b gene mutations/deletions. Because of a high prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in MODY 5 patients, understanding the extra-pancreatic manifestations of MODY 5 can target genetic testing to provide an earlier diagnosis.

Case Description: A 26-year-old male was referred for consultation after his primary care physician found an HbA1c of 11.4% and prescribed metformin 500mg/day. He reported weight loss during the previous weeks and a history of Attention Deficit Hyperactivity Disorder (ADHD). He denied urinary tract infections or renal disease. Family history included diabetes (24-year-old brother (also with ADHD) and both parents). His BMI was 17.07 kg/m2 and labs showed a normal lipid profile, including HDL-C 74 mg/dL; urine albumin 0.8 mg/dL; “inappropriately normal” insulin and c-peptide; and negative GAD65, IA-2, and ZNT8 antibodies. Glimepiride 1mg/day at breakfast was added, with referral to a geneticist to rule out MODY. A follow-up HbA1c was 7.1%; Januvia 100 mg/day was added. Glimepiride was later switched to glipizide 7.5 mg at breakfast and 2.5 mg at supper due to overnight hypoglycemia. Genetic testing revealed a male pathogenic 1.39 Mb deletion of 17q12 containing 20 genes, including HNF1b, consistent with MODY 5. Renal ultrasound showed mild hydronephrosis, increased echogenicity of both kidneys, and bilateral non-obstructing nephrolithiasis. Subsequently, his mother (previously diagnosed with diabetes, fatty liver disease, dyslipidemia, and multiple scattered non-obstructing calculi and cysts in both kidneys) was found to have the same genetic defect. His brother’s diabetes is currently well controlled with glargine 0.3 u/kg and aspart 0.05–0.15 u/kg/meal. Unlike the proband, he has obesity (BMI 30 kg/m2), dyslipidemia, and CKD (GFR 57 ml/min); further workup is pending at this time.

Discussion: Because patients with MODY 5 are at high risk for CKD3-4/ESRD, MODY 5 should be considered in young adults with diabetes who have negative islet autoantibodies and extra-pancreatic manifestations including elevated liver enzymes, renal cysts and nephrolithiasis; ADHD and learning difficulties; and pancreatic and hepatic morphological abnormalities. HNF1b-targeted genetic testing should be considered in patients with this clinical presentation.
A Bizarre Case of Recurrent Hypoglycemia
Authors: Pant Nicole , Steinberg Helmut O
Published: May 2021

Introduction: Severe hypoglycemia is extremely rare in non-diabetic subjects and requires thorough evaluation due to its life threatening consequences. Any injuries resulting from medication use, including physical harm, mental harm, or loss of function is defined as adverse drug events (ADEs). Medication errors can occur due to the inappropriate use of medicine in any prescription stage. We hereby present an intriguing case of recurrent hypoglycemia in relation to it. Case presentation: A 65 year-old white male with surgically induced panhypopituitarism on replacement hydrocortisone, levothyroxine and testosterone was transferred to our hospital with recurrent serious hypoglycemic episodes. He was in his usual state of health until about 2 weeks prior to presentation when he became increasingly fatigued. He was found to have severe hypoglycemia with a blood sugar of 20 mg/dl. He was treated for hypoglycemia and was discharged home 2 days later with an increased dose of hydrocortisone and the provisional diagnosis of adrenal crisis. At home, his symptoms of hypoglycemia recurred. He was then referred to our facility where the Endocrinology service was consulted. At admission, his blood sugar was 69 mg/dl, but it rapidly dropped down to 39 mg/dl with confirmatory serum glucose level of 24 mg/dl. He was started on Dextrose 10%. On further inquiry his daughter told us that she had discovered two different medications in one prescription bottle which had been refilled about 2 weeks prior to this hospitalization, coinciding with the onset of symptoms. The bottle in question was supposed to be for hydrocortisone 10 mg tablets, but it contained 2 different tablets with inscription GXL10 and P10. An online search identified tablets as Glucotrol-XL 10 mg and hydrocortisone 10 mg. Urine drug screen (UDS) for sulfonylureas and glinide was positive for Glipizide (203 ng/ml, normal level 0). His blood sugar stabilized with Dextrose and he was safely discharged home. So it was concluded that recurrent hypoglycemia was secondary to inadvertent administration of hypoglycemic agents, Glucotrol-XL 10 mg, likely aggravated by missing doses of hydrocortisone. Discussion: The first report of medication errors was published in 1940. ADEs comprise the largest single category of adverse events experienced by hospitalized patients,accounting for about 19 percent of all injuries. ADEs are associated with increased morbidity and mortality, prolonged hospitalizations, and higher costs of care. Four medications or medication classes were implicated in 67% of hospitalizations: warfarin, insulins, oral antiplatelet agents, and oral hypoglycemic agents. ADEs in the outpatient setting are an important cause of emergency department visits and hospital admissions. This case emphasized the importance of taking a thorough history and focusing on patient safety and quality care in healthcare.