Showing papers in "Diabetes Care in 2021"

Social Determinants of Health and Diabetes: A Scientific Review.

Abstract: Decades of research have demonstrated that diabetes affects racial and ethnic minority and low-income adult populations in the U.S. disproportionately, with relatively intractable patterns seen in these populations’ higher risk of diabetes and rates of diabetes complications and mortality (1). With a health care shift toward greater emphasis on population health outcomes and value-based care, social determinants of health (SDOH) have risen to the forefront as essential intervention targets to achieve health equity (2–4). Most recently, the COVID-19 pandemic has highlighted unequal vulnerabilities borne by racial and ethnic minority groups and by disadvantaged communities. In the wake of concurrent pandemic and racial injustice events in the U.S., the American College of Physicians, American Academy of Pediatrics, Society of General Internal Medicine, National Academy of Medicine, and other professional organizations have published statements on SDOH (5–8), and calls to action focus on amelioration of these determinants at individual, organizational, and policy levels (9–11). In diabetes, understanding and mitigating the impact of SDOH are priorities due to disease prevalence, economic costs, and disproportionate population burden (12–14). In 2013, the American Diabetes Association (ADA) published a scientific statement on socioecological determinants of prediabetes and type 2 diabetes (15). Toward the goal ofunderstanding and advancing opportunities for health improvement among the population with diabetes through addressing SDOH, ADA convened the current SDOH and diabetes writing committee, prepandemic, to review the literature on 1 ) associations of SDOH with diabetes risk and outcomes and 2 ) impact of interventions targeting amelioration of SDOH on diabetes outcomes. This article begins with an overview of key definitions and SDOH frameworks. The literature review focuses primarily on U.S.-based studies of adults with diabetes and on five SDOH: socioeconomic status (education, income, occupation); neighborhood and physical environment (housing, built environment, toxic environmental …

COVID-19 Severity Is Tripled in the Diabetes Community: A Prospective Analysis of the Pandemic's Impact in Type 1 and Type 2 Diabetes.

Abstract: OBJECTIVE To quantify and contextualize the risk for coronavirus disease 2019 (COVID-19)–related hospitalization and illness severity in type 1 diabetes. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study to identify case subjects with COVID-19 across a regional health care network of 137 service locations. Using an electronic health record query, chart review, and patient contact, we identified clinical factors influencing illness severity. RESULTS We identified COVID-19 in 6,138, 40, and 273 patients without diabetes and with type 1 and type 2 diabetes, respectively. Compared with not having diabetes, people with type 1 diabetes had adjusted odds ratios of 3.90 (95% CI 1.75–8.69) for hospitalization and 3.35 (95% CI 1.53–7.33) for greater illness severity, which was similar to risk in type 2 diabetes. Among patients with type 1 diabetes, glycosylated hemoglobin (HbA1c), hypertension, race, recent diabetic ketoacidosis, health insurance status, and less diabetes technology use were significantly associated with illness severity. CONCLUSIONS Diabetes status, both type 1 and type 2, independently increases the adverse impacts of COVID-19. Potentially modifiable factors (e.g., HbA1c) had significant but modest impact compared with comparatively static factors (e.g., race and insurance) in type 1 diabetes, indicating an urgent and continued need to mitigate severe acute respiratory syndrome coronavirus 2 infection risk in this community.

The Management of Type 1 Diabetes in Adults. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

Abstract: The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycemia, behavioral considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management, and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that health care professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors.

Type 2 Diabetes and COVID-19-Related Mortality in the Critical Care Setting: A National Cohort Study in England, March-July 2020.

Abstract: OBJECTIVE: To describe the relationship between type 2 diabetes and all-cause mortality among adults with coronavirus disease 2019 (COVID-19) in the critical care setting. RESEARCH DESIGN AND METHODS: This was a nationwide retrospective cohort study in people admitted to hospital in England with COVID-19 requiring admission to a high dependency unit (HDU) or intensive care unit (ICU) between 1 March 2020 and 27 July 2020. Cox proportional hazards models were used to estimate 30-day in-hospital all-cause mortality associated with type 2 diabetes, with adjustment for age, sex, ethnicity, obesity, and other major comorbidities (chronic respiratory disease, asthma, chronic heart disease, hypertension, immunosuppression, chronic neurological disease, chronic renal disease, and chronic liver disease). RESULTS: A total of 19,256 COVID-19-related HDU and ICU admissions were included in the primary analysis, including 13,809 HDU (mean age 70 years) and 5,447 ICU (mean age 58 years) admissions. Of those admitted, 3,524 (18.3%) had type 2 diabetes and 5,077 (26.4%) died during the study period. Patients with type 2 diabetes were at increased risk of death (adjusted hazard ratio [aHR] 1.23 [95% CI 1.14, 1.32]), and this result was consistent in HDU and ICU subsets. The relative mortality risk associated with type 2 diabetes decreased with higher age (age 18-49 years aHR 1.50 [95% CI 1.05, 2.15], age 50-64 years 1.29 [1.10, 1.51], and age ≥65 years 1.18 [1.09, 1.29], P value for age-type 2 diabetes interaction = 0.002). CONCLUSIONS: Type 2 diabetes may be an independent prognostic factor for survival in people with severe COVID-19 requiring critical care treatment, and in this setting the risk increase associated with type 2 diabetes is greatest in younger people.

COVID-19, Hyperglycemia, and New-Onset Diabetes.

Abstract: Certain chronic comorbidities, including diabetes, are highly prevalent in people with coronavirus disease 2019 (COVID-19) and are associated with an increased risk of severe COVID-19 and mortality. Mild glucose elevations are also common in COVID-19 patients and associated with worse outcomes even in people without diabetes. Several studies have recently reported new-onset diabetes associated with COVID-19. The phenomenon of new-onset diabetes following admission to the hospital has been observed previously with other viral infections and acute illnesses. The precise mechanisms for new-onset diabetes in people with COVID-19 are not known, but it is likely that a number of complex interrelated processes are involved, including previously undiagnosed diabetes, stress hyperglycemia, steroid-induced hyperglycemia, and direct or indirect effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the β-cell. There is an urgent need for research to help guide management pathways for these patients. In view of increased mortality in people with new-onset diabetes, hospital protocols should include efforts to recognize and manage acute hyperglycemia, including diabetic ketoacidosis, in people admitted to the hospital. Whether new-onset diabetes is likely to remain permanent is not known, as the long-term follow-up of these patients is limited. Prospective studies of metabolism in the setting of postacute COVID-19 will be required to understand the etiology, prognosis, and treatment opportunities.

A Decade of Disparities in Diabetes Technology Use and HbA1c in Pediatric Type 1 Diabetes: A Transatlantic Comparison

Abstract: OBJECTIVE As diabetes technology use in youth increases worldwide, inequalities in access may exacerbate disparities in hemoglobin A1c (HbA1c). We hypothesized that an increasing gap in diabetes technology use by socioeconomic status (SES) would be associated with increased HbA1c disparities. RESEARCH DESIGN AND METHODS Participants aged RESULTS HbA1c was higher in participants with lower SES (in 2010–2012 and 2016–2018, respectively: 8.0% and 7.8% in Q1 and 7.6% and 7.5% in Q5 for DPV; 9.0% and 9.3% in Q1 and 7.8% and 8.0% in Q5 for T1DX). For DPV, the association between SES and HbA1c did not change between the two time periods, whereas for T1DX, disparities in HbA1c by SES increased significantly (P CONCLUSIONS Although causal conclusions cannot be drawn, diabetes technology use is lowest and HbA1c is highest in those of the lowest SES quintile in the T1DX, and this difference for HbA1c broadened in the past decade. Associations of SES with technology use and HbA1c were weaker in the DPV registry.

Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening.

Abstract: OBJECTIVE Assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS A total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m2; and HbA1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis. RESULTS The prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3–4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI). CONCLUSIONS Moderate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.

Improved Glycemic Outcomes With Medtronic MiniMed Advanced Hybrid Closed-Loop Delivery: Results From a Randomized Crossover Trial Comparing Automated Insulin Delivery With Predictive Low Glucose Suspend in People With Type 1 Diabetes.

Abstract: OBJECTIVE To study the MiniMed Advanced Hybrid Closed-Loop (AHCL) system, which includes an algorithm with individualized basal target set points, automated correction bolus function, and improved Auto Mode stability. RESEARCH DESIGN AND METHODS This dual-center, randomized, open-label, two-sequence crossover study in automated-insulin-delivery–naive participants with type 1 diabetes (aged 7–80 years) compared AHCL to sensor-augmented pump therapy with predictive low glucose management (SAP + PLGM). Each study phase was 4 weeks, preceded by a 2- to 4-week run-in and separated by a 2-week washout. RESULTS The study was completed by 59 of 60 people (mean age 23.3 ± 14.4 years). Time in target range (TIR) 3.9–10 mmol/L (70–180 mg/dL) favored AHCL over SAP + PLGM (70.4 ± 8.1% vs. 57.9 ± 11.7%) by 12.5 ± 8.5% (P 22 years]) demonstrated improvement, with adolescents showing the largest improvement (14.4 ± 8.4%). Mean sensor glucose (SG) at run-in was 9.3 ± 0.9 mmol/L (167 ± 16.2 mg/dL) and improved with AHCL (8.5 ± 0.7 mmol/L [153 ± 12.6 mg/dL], P CONCLUSIONS AHCL with automated correction bolus demonstrated significant improvement in glucose control compared with SAP + PLGM. A lower algorithm SG set point during AHCL resulted in greater TIR, with no increase in hypoglycemia.

Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study.

Abstract: OBJECTIVE Cotadutide, a dual GLP-1 and glucagon receptor agonist, is under development for nonalcoholic steatohepatitis (NASH) and chronic kidney disease with type 2 diabetes. The effects of cotadutide on hepatic and metabolic parameters were evaluated in participants with overweight/obesity and type 2 diabetes. RESEARCH DESIGN AND METHODS In this phase 2b study, 834 adults with BMI ≥25 kg/m2 and type 2 diabetes inadequately controlled with metformin (glycated hemoglobin A1c [HbA1c] of 7.0%–10.5% [53–91 mmol/mol]) were randomized to double-blind cotadutide 100 μg (n = 100), 200 μg (n = 256), or 300 μg (n = 256); placebo (n = 110); or open-label liraglutide 1.8 mg (n = 110)—all administered subcutaneously. Coprimary end points were changes in HbA1c and body weight at week 14. The originally randomized interventions were continued to week 54. Liver damage biomarkers and liver fibrosis algorithms were assessed. RESULTS Cotadutide significantly decreased HbA1c and body weight at weeks 14 and 54 versus placebo (all P CONCLUSIONS Cotadutide treatment for 54 weeks improved glycemic control and weight loss in participants with overweight/obesity and type 2 diabetes. Ad hoc analyses demonstrated improvements in hepatic parameters and support further evaluation of cotadutide in NASH.

Time in Range in Relation to All-Cause and Cardiovascular Mortality in Patients With Type 2 Diabetes: A Prospective Cohort Study.

Abstract: OBJECTIVE There is growing evidence linking time in range (TIR), an emerging metric for assessing glycemic control, to diabetes-related outcomes. We aimed to investigate the association between TIR and mortality in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 6,225 adult patients with type 2 diabetes were included from January 2005 to December 2015 from a single center in Shanghai, China. TIR was measured with continuous glucose monitoring at baseline, and the participants were stratified into four groups by TIR: >85%, 71–85%, 51–70%, and ≤50%. Cox proportional hazards regression models were used to estimate the association between different levels of TIR and the risks of all-cause and cardiovascular disease (CVD) mortality. RESULTS The mean age of the participants was 61.7 years at baseline. During a median follow-up of 6.9 years, 838 deaths were identified, 287 of which were due to CVD. The multivariable-adjusted hazard ratios associated with different levels of TIR (>85% [reference group], 71–85%, 51–70%, and ≤50%) were 1.00, 1.23 (95% CI 0.98–1.55), 1.30 (95% CI 1.04–1.63), and 1.83 (95% CI 1.48–2.28) for all-cause mortality (P for trend CONCLUSIONS The current study indicated an association of lower TIR with an increased risk of all-cause and CVD mortality among patients with type 2 diabetes, supporting the validity of TIR as a surrogate marker of long-term adverse clinical outcomes.

Worldwide Epidemiology of Diabetes-Related End-Stage Renal Disease, 2000-2015.

Abstract: OBJECTIVE The annual risk among patients with diabetes of reaching end-stage renal disease (ESRD) is largely unknown worldwide. This study aimed to compare the incidence of diabetes-related ESRD by creating a global atlas during 2000–2015. RESEARCH DESIGN AND METHODS The annual incidence of ESRD among patients with diabetes was calculated as the quotient of the number of incident ESRD patients with diabetes divided by the total number of patients with diabetes after subtraction of the number with existing ESRD. The estimated ESRD prevalence and annual incidence were validated with use of the data provided by Fresenius Medical Care, Germany, and previously reported data, respectively. RESULTS Data were obtained from 142 countries, covering 97.3% of the world population. The global percentage of the prevalent ESRD patients with diabetes increased from 19.0% in 2000 to 29.7% in 2015 worldwide, while the percentage of incident ESRD patients due to diabetes increased from 22.1% to 31.3%. The global annual incidence of ESRD among patients with diabetes increased from 375.8 to 1,016.0/million with diabetes during 2000–2015. The highest average rates were observed in the Western Pacific Region. Comparatively, the rates of incident ESRD among European patients with diabetes ranged from one-half (309.2 vs. 544.6) to one-third (419.4 vs. 1,245.2) of the rates of the Western Pacific population during 2000–2015. CONCLUSIONS Great and nonrandom geographic variation in the annual rates among patients with diabetes of reaching ESRD suggests that distinct health care, environmental, and/or genetic factors contribute to the progression of diabetic kidney disease. Measures to prevent and treat diabetes-related ESRD require better patient susceptibility stratification.

Multicenter Trial of a Tubeless, On-Body Automated Insulin Delivery System With Customizable Glycemic Targets in Pediatric and Adult Participants With Type 1 Diabetes

Abstract: OBJECTIVE Advances in diabetes technology have transformed the treatment paradigm for type 1 diabetes, yet the burden of disease is significant. We report on a pivotal safety study of the first tubeless, on-body automated insulin delivery system with customizable glycemic targets. RESEARCH DESIGN AND METHODS This single-arm, multicenter, prospective study enrolled 112 children (age 6–13.9 years) and 129 adults (age 14–70 years). A 2-week standard therapy phase (usual insulin regimen) was followed by 3 months of automated insulin delivery. Primary safety outcomes were incidence of severe hypoglycemia and diabetic ketoacidosis. Primary effectiveness outcomes were change in HbA1c and percent time in sensor glucose range 70–180 mg/dL (“time in range”). RESULTS A total of 235 participants (98% of enrolled, including 111 children and 124 adults) completed the study. HbA1c was significantly reduced in children by 0.71% (7.8 mmol/mol) (mean ± SD: 7.67 ± 0.95% to 6.99 ± 0.63% [60 ± 10.4 mmol/mol to 53 ± 6.9 mmol/mol], P CONCLUSIONS This tubeless automated insulin delivery system was safe and allowed participants to significantly improve HbA1c levels and time in target glucose range with a very low occurrence of hypoglycemia.

High Prevalence of Advanced Liver Fibrosis Assessed by Transient Elastography Among U.S. Adults With Type 2 Diabetes.

Abstract: OBJECTIVE Type 2 diabetes mellitus (T2DM) is an important risk factor for the progression of metabolic liver disease to advanced fibrosis. Here, we provide an estimate of the prevalence of steatosis and fibrosis in U.S. adults with T2DM on the basis of transient elastography (TE) and identify factors associated with these conditions. RESEARCH DESIGN AND METHODS This is a cross-sectional study of U.S. adults with T2DM participating in the 2017–2018 cycle of the National Health and Nutrition Examination Survey who were evaluated by TE. Hepatic steatosis and fibrosis were diagnosed by the median value of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. RESULTS Among the 825 patients with reliable TE examination results, 484 (53.7%) were assessed using the M probe and 341 (46.3%) using the XL probe. Liver steatosis (CAP ≥274 dB/m), advanced fibrosis (LSM ≥9.7 kPa), and cirrhosis (LSM ≥13.6 kPa) were present in 73.8% (95% CI 68.5%–78.5%), 15.4% (95% CI 12.2%–19.0%), and 7.7% (95% CI 4.8%–11.9%) of patients, respectively. The mean ± SE age of patients with advanced fibrosis and cirrhosis was 63.7 ± 2.2 years and 57.8 ± 1.6 years, respectively. In the multivariable logistic regression model, BMI, non-Black race, and ALT levels were independent predictors of steatosis; and BMI, non-Black race, and AST and γ-glutamyltranspeptidase levels were independent predictors of advanced fibrosis. CONCLUSIONS Prevalence of both liver steatosis and fibrosis is high in patients with T2DM from the United States and obesity is a major risk factor. Our results support the screening of these conditions among patients with diabetes.

Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes.

Abstract: Improvement of glucose levels into the normal range can occur in some people living with diabetes, either spontaneously or after medical interventions, and in some cases can persist after withdrawal of glucose-lowering pharmacotherapy. Such sustained improvement may now be occurring more often due to newer forms of treatment. However, terminology for describing this process and objective measures for defining it are not well established, and the long-term risks versus benefits of its attainment are not well understood. To update prior discussions of this issue, an international expert group was convened by the American Diabetes Association to propose nomenclature and principles for data collection and analysis, with the goal of establishing a base of information to support future clinical guidance. This group proposed "remission" as the most appropriate descriptive term, and HbA1c <6.5% (48 mmol/mol) measured at least 3 months after cessation of glucose-lowering pharmacotherapy as the usual diagnostic criterion. The group also made suggestions for active observation of individuals experiencing a remission and discussed further questions and unmet needs regarding predictors and outcomes of remission.

Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11).

Abstract: OBJECTIVE To compare efficacy and safety of dulaglutide at doses of 3.0 and 4.5 mg versus 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin. RESEARCH DESIGN AND METHODS Patients were randomly assigned to once-weekly dulaglutide 1.5 mg, 3.0 mg, or 4.5 mg for 52 weeks. The primary objective was determining superiority of dulaglutide 3.0 mg and/or 4.5 mg over 1.5 mg in HbA1c reduction at 36 weeks. Secondary superiority objectives included change in body weight. Two estimands addressed efficacy objectives: treatment regimen (regardless of treatment discontinuation or rescue medication) and efficacy (on treatment without rescue medication) in all randomly assigned patients. RESULTS Mean baseline HbA1c and BMI in randomly assigned patients (N = 1,842) was 8.6% (70 mmol/mol) and 34.2 kg/m2, respectively. At 36 weeks, dulaglutide 4.5 mg provided superior HbA1c reductions compared with 1.5 mg (treatment-regimen estimand: −1.77 vs. −1.54% [−19.4 vs. −16.8 mmol/mol], estimated treatment difference [ETD] −0.24% (−2.6 mmol/mol), P CONCLUSIONS In patients with type 2 diabetes inadequately controlled by metformin, escalation from dulaglutide 1.5 mg to 3.0 mg or 4.5 mg provided clinically relevant, dose-related reductions in HbA1c and body weight with a similar safety profile.

Natriuretic effect of two weeks of dapagliflozin treatment in patients with type 2 diabetes and preserved kidney function during standardized sodium intake: Results of the dapasalt trial

Abstract: OBJECTIVE Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk for heart failure hospitalization potentially by inducing sodium excretion, osmotic diuresis, and plasma volume contraction. Few studies have investigated this hypothesis, but none have assessed cumulative sodium excretion with SGLT2 inhibition during standardized sodium intake in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS The DAPASALT trial was a mechanistic, nonrandomized, open-label study in patients with type 2 diabetes with preserved kidney function on a controlled standardized sodium diet (150 mmol/day). It evaluated the effects of dapagliflozin on sodium excretion, 24-h blood pressure, and extracellular, intracellular, and plasma volumes at the start of treatment (ST) (days 2–4), end of treatment (ET) (days 12–14), and follow-up (FU) (days 15–18). RESULTS Fourteen patients were included in the efficacy analysis. Mean (SD) baseline sodium excretion (150 [32] mmol/24-h) did not significantly change during treatment (change at ST: −7.0 mmol/24-h [95% CI −22.4, 8.4]; change at ET: 2.1 mmol/24-h [−28.8, 33.0]). Mean baseline 24-h systolic blood pressure was 128 (10) mmHg and significantly reduced at ST (−6.1 mmHg [−9.1, −3.1]; P CONCLUSIONS During standardized sodium intake, dapagliflozin reduced blood pressure without clear changes in urinary sodium excretion, suggesting that factors other than natriuresis and volume changes may contribute to the blood pressure–lowering effects.

Interpretable Machine Learning Framework Reveals Robust Gut Microbiome Features Associated With Type 2 Diabetes

Abstract: OBJECTIVE To identify the core gut microbial features associated with type 2 diabetes risk and potential demographic, adiposity, and dietary factors associated with these features. RESEARCH DESIGN AND METHODS We used an interpretable machine learning framework to identify the type 2 diabetes–related gut microbiome features in the cross-sectional analyses of three Chinese cohorts: one discovery cohort (n = 1,832, 270 cases of type 2 diabetes) and two validation cohorts (cohort 1: n = 203, 48 cases; cohort 2: n = 7,009, 608 cases). We constructed a microbiome risk score (MRS) with the identified features. We examined the prospective association of the MRS with glucose increment in 249 participants without type 2 diabetes and assessed the correlation between the MRS and host blood metabolites (n = 1,016). We transferred human fecal samples with different MRS levels to germ-free mice to confirm the MRS–type 2 diabetes relationship. We then examined the prospective association of demographic, adiposity, and dietary factors with the MRS (n = 1,832). RESULTS The MRS (including 14 microbial features) consistently associated with type 2 diabetes, with risk ratio for per 1-unit change in MRS 1.28 (95% CI 1.23–1.33), 1.23 (1.13–1.34), and 1.12 (1.06–1.18) across three cohorts. The MRS was positively associated with future glucose increment (P CONCLUSIONS Our results reveal a core set of gut microbiome features associated with type 2 diabetes risk and future glucose increment.

Continuous Glucose Monitoring in the Intensive Care Unit During the COVID-19 Pandemic.

Abstract: OBJECTIVE Real-time continuous glucose monitoring (rtCGM) in critically ill hospitalized patients holds promise; however, real-world data are needed. RESEARCH DESIGN AND METHODS We placed Dexcom G6 CGM on intensive care unit (ICU) patients at Montefiore Medical Center with confirmed coronavirus disease 2019 (COVID-19) infection and glycemic variability. We analyzed inpatient CGM accuracy using point-of-care (POC) glucose-CGM matched pairs and included patients for analysis regardless of clinical status. RESULTS We included 11 patients with CGM: 8 on continuous insulin infusion (CII), 8 on vasopressors, 8 intubated, 4 on high-dose glucocorticoids, 6 on renal replacement therapy, and 2 with anasarca. Accuracy was 12.58% for mean and 6.3% for median absolute relative difference. CGM reduced POC testing by ∼60% for patients on CII. CONCLUSIONS In this real-world preliminary analysis of rtCGM during critical illness, we demonstrate early feasibility, considerable accuracy, and meaningful reduction in the frequency of POC glucose testing.

Metabolic Syndrome and COVID-19 Mortality Among Adult Black Patients in New Orleans

Abstract: OBJECTIVE Coronavirus disease 2019 (COVID-19) mortality is high in patients with hypertension, obesity, and diabetes. We examined the association between hypertension, obesity, and diabetes, individually and clustered as metabolic syndrome (MetS), and COVID-19 outcomes in patients hospitalized in New Orleans during the peak of the outbreak. RESEARCH DESIGN AND METHODS Data were collected from 287 consecutive patients with COVID-19 hospitalized at two hospitals in New Orleans, LA from 30 March to 5 April 2020. MetS was identified per World Health Organization criteria. RESULTS Among 287 patients (mean age 61.5 years; female, 56.8%; non-Hispanic black, 85.4%), MetS was present in 188 (66%). MetS was significantly associated with mortality (adjusted odds ratio [aOR] 3.42 [95% CI 1.52–7.69]), intensive care unit (ICU) (aOR 4.59 [CI 2.53–8.32]), invasive mechanical ventilation (IMV) (aOR 4.71 [CI 2.50–8.87]), and acute respiratory distress syndrome (ARDS) (aOR 4.70 [CI 2.25–9.82]) compared with non-MetS. Multivariable analyses of hypertension, obesity, and diabetes individually showed no association with mortality. Obesity was associated with ICU (aOR 2.18 [CI, 1.25–3.81]), ARDS (aOR 2.44 [CI 1.28–4.65]), and IMV (aOR 2.36 [CI 1.33–4.21]). Diabetes was associated with ICU (aOR 2.22 [CI 1.24–3.98]) and IMV (aOR 2.12 [CI 1.16–3.89]). Hypertension was not significantly associated with any outcome. Inflammatory biomarkers associated with MetS, CRP, and lactate dehydrogenase (LDH) were associated with mortality (CRP [aOR 3.66] [CI 1.22–10.97] and LDH [aOR 3.49] [CI 1.78–6.83]). CONCLUSIONS In predominantly black patients hospitalized for COVID-19, the clustering of hypertension, obesity, and diabetes as MetS increased the odds of mortality compared with these comorbidities individually.

Association Between Achieving Inpatient Glycemic Control and Clinical Outcomes in Hospitalized Patients With COVID-19: A Multicenter, Retrospective Hospital-Based Analysis.

Abstract: OBJECTIVE Diabetes and hyperglycemia are important risk factors for poor outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). We hypothesized that achieving glycemic control soon after admission, in both intensive care unit (ICU) and non-ICU settings, could affect outcomes in patients with COVID-19. RESEARCH DESIGN AND METHODS We analyzed pooled data from the Glytec national database including 1,544 patients with COVID-19 from 91 hospitals in 12 states. Patients were stratified according to achieved mean glucose category in mg/dL (≤7.77, 7.83–10, 10.1–13.88, and >13.88 mmol/L; ≤140, 141–180, 181–250, and >250 mg/dL) during days 2–3 in non-ICU patients or on day 2 in ICU patients. We conducted a survival analysis to determine the association between glucose category and hospital mortality. RESULTS Overall, 18.1% (279/1,544) of patients died in the hospital. In non-ICU patients, severe hyperglycemia (blood glucose [BG] >13.88 mmol/L [250 mg/dL]) on days 2–3 was independently associated with high mortality (adjusted hazard ratio [HR] 7.17; 95% CI 2.62–19.62) compared with patients with BG CONCLUSIONS Both hyperglycemia and hypoglycemia were associated with poor outcomes in patients with COVID-19. Admission glucose was a strong predictor of death among patients directly admitted to the ICU. Severe hyperglycemia after admission was a strong predictor of death among non-ICU patients.

Diagnosis of Neuropathy and Risk Factors for Corneal Nerve Loss in Type 1 and Type 2 Diabetes: A Corneal Confocal Microscopy Study

Abstract: OBJECTIVE To assess the diagnostic utility of corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for corneal nerve loss. RESEARCH DESIGN AND METHODS A total of 490 participants, including 72 healthy control subjects, 149 with type 1 diabetes, and 269 with type 2 diabetes, underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors. RESULTS Corneal nerve fiber density (CNFD) (P CONCLUSIONS CCM identifies more severe corneal nerve loss in patients with type 1 diabetes compared with type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in corneal nerve fiber length differ between type 1 and type 2 diabetes.

Diabetes and Overweight/Obesity Are Independent, Nonadditive Risk Factors for In-Hospital Severity of COVID-19: An International, Multicenter Retrospective Meta-analysis.

Abstract: OBJECTIVE Obesity is an established risk factor for severe coronavirus disease 2019 (COVID-19), but the contribution of overweight and/or diabetes remains unclear. In a multicenter, international study, we investigated if overweight, obesity, and diabetes were independently associated with COVID-19 severity and whether the BMI-associated risk was increased among those with diabetes. RESEARCH DESIGN AND METHODS We retrospectively extracted data from health care records and regional databases of hospitalized adult patients with COVID-19 from 18 sites in 11 countries. We used standardized definitions and analyses to generate site-specific estimates, modeling the odds of each outcome (supplemental oxygen/noninvasive ventilatory support, invasive mechanical ventilatory support, and in-hospital mortality) by BMI category (reference, overweight, obese), adjusting for age, sex, and prespecified comorbidities. Subgroup analysis was performed on patients with preexisting diabetes. Site-specific estimates were combined in a meta-analysis. RESULTS Among 7,244 patients (65.6% overweight/obese), those with overweight were more likely to require oxygen/noninvasive ventilatory support (random effects adjusted odds ratio [aOR], 1.44; 95% CI 1.15–1.80) and invasive mechanical ventilatory support (aOR, 1.22; 95% CI 1.03–1.46). There was no association between overweight and in-hospital mortality (aOR, 0.88; 95% CI 0.74–1.04). Similar effects were observed in patients with obesity or diabetes. In the subgroup analysis, the aOR for any outcome was not additionally increased in those with diabetes and overweight or obesity. CONCLUSIONS In adults hospitalized with COVID-19, overweight, obesity, and diabetes were associated with increased odds of requiring respiratory support but were not associated with death. In patients with diabetes, the odds of severe COVID-19 were not increased above the BMI-associated risk.

Glycemic Outcome Associated With Insulin Pump and Glucose Sensor Use in Children and Adolescents With Type 1 Diabetes. Data From the International Pediatric Registry SWEET

Abstract: OBJECTIVE Insulin delivery methods, glucose-monitoring modalities, and related outcomes were examined in a large, international, diverse cohort of children and adolescents with type 1 diabetes from the Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) -Registry. RESEARCH DESIGN AND METHODS Participants with type 1 diabetes of ≥1 year, aged ≤18 years, and who had documented pump or sensor usage during the period August 2017–July 2019 were stratified into four categories: injections–no sensor (referent); injections + sensor; pump–no sensor; and pump + sensor. HbA1c and proportion of patients with diabetic ketoacidosis (DKA) or severe hypoglycemia (SH) were analyzed; linear and logistic regression models adjusted for demographics, region, and gross domestic product per capita were applied. RESULTS Data of 25,654 participants were analyzed. The proportions of participants (adjusted HbA1c data) by study group were as follows: injections–no sensor group, 37.44% (8.72; 95% CI 8.68–8.75); injections + sensor group, 14.98% (8.30; 95% CI 8.25–8.35); pump–no sensor group, 17.22% (8.07; 95% CI 8.03–8.12); and pump + sensor group, 30.35% (7.81; 95% CI 7.77–7.84). HbA1c was lower in all categories of participants who used a pump and/or sensor compared with the injections–no sensor treatment method (P CONCLUSIONS Lower HbA1c and fewer DKA episodes were observed in participants using either a pump or continuous glucose monitoring (CGM) or both. Pump use was associated with a lower rate of SH. Across SWEET centers, use of pumps and CGM is increasing. The concomitant use of pump and CGM was associated with an additive benefit.

Multicenter, Head-to-Head, Real-World Validation Study of Seven Automated Artificial Intelligence Diabetic Retinopathy Screening Systems.

Abstract: OBJECTIVE With rising global prevalence of diabetic retinopathy (DR), automated DR screening is needed for primary care settings. Two automated artificial intelligence (AI)–based DR screening algorithms have U.S. Food and Drug Administration (FDA) approval. Several others are under consideration while in clinical use in other countries, but their real-world performance has not been evaluated systematically. We compared the performance of seven automated AI-based DR screening algorithms (including one FDA-approved algorithm) against human graders when analyzing real-world retinal imaging data. RESEARCH DESIGN AND METHODS This was a multicenter, noninterventional device validation study evaluating a total of 311,604 retinal images from 23,724 veterans who presented for teleretinal DR screening at the Veterans Affairs (VA) Puget Sound Health Care System (HCS) or Atlanta VA HCS from 2006 to 2018. Five companies provided seven algorithms, including one with FDA approval, that independently analyzed all scans, regardless of image quality. The sensitivity/specificity of each algorithm when classifying images as referable DR or not were compared with original VA teleretinal grades and a regraded arbitrated data set. Value per encounter was estimated. RESULTS Although high negative predictive values (82.72–93.69%) were observed, sensitivities varied widely (50.98–85.90%). Most algorithms performed no better than humans against the arbitrated data set, but two achieved higher sensitivities, and one yielded comparable sensitivity (80.47%, P = 0.441) and specificity (81.28%, P = 0.195). Notably, one had lower sensitivity (74.42%) for proliferative DR (P = 9.77 × 10−4) than the VA teleretinal graders. Value per encounter varied at $15.14–$18.06 for ophthalmologists and $7.74–$9.24 for optometrists. CONCLUSIONS The DR screening algorithms showed significant performance differences. These results argue for rigorous testing of all such algorithms on real-world data before clinical implementation.

Association of Serum 25-Hydroxyvitamin D Concentrations With All-Cause and Cause-Specific Mortality Among Individuals With Diabetes

Abstract: OBJECTIVE The evidence regarding vitamin D status and mortality among diabetes is scarce. This study aimed to examine the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among adults with diabetes. RESEARCH DESIGN AND METHODS This study included 6,329 adults with diabetes from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2001–2014. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2015. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% CIs for mortality from all causes, cardiovascular disease (CVD), and cancer. RESULTS The weighted mean (95% CI) level of serum 25(OH)D was 57.7 (56.6, 58.8) nmol/L, and 46.6% had deficient vitamin D ( 75 nmol/L were 0.59 (0.43, 0.83) for all-cause mortality (Ptrend = 0.003), 0.50 (0.29, 0.86) for CVD mortality (Ptrend = 0.02), and 0.49 (0.23, 1.04) for cancer mortality (Ptrend = 0.12). CONCLUSIONS Higher serum 25(OH)D levels were significantly associated with lower all-cause and CVD mortality. These findings suggest that maintaining adequate vitamin D status may lower mortality risk in individuals with diabetes.

Racial and Ethnic Disparities in Rates of Continuous Glucose Monitor Initiation and Continued Use in Children With Type 1 Diabetes.

Abstract: OBJECTIVE Racial/ethnic disparities in continuous glucose monitor (CGM) use exist among children with type 1 diabetes. It is not known whether differential rates of device initiation or sustained use are the cause of this disparity. Our objective was to compare CGM initiation rates and continued use among non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic children. RESEARCH DESIGN AND METHODS We conducted a retrospective review including children with type 1 diabetes attending the Children’s Hospital of Philadelphia between 1 January 15 and 31 December 18. RESULTS Of 1,509 eligible children, 726 (48%) started CGM during the study period. More NHW (54%) than NHB (31%) and Hispanic (33%) children started CGM (P CONCLUSIONS Lower CGM use in NHB children was due to lower rates of device initiation and higher rates of discontinuation. Interventions to address both of these barriers are needed to reduce disparities in CGM use.

Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.

Abstract: OBJECTIVE Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS We identified 11 genomic regions associated with plasma vitamin C (P CONCLUSIONS These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.

Important Drop in Rate of Acute Diabetes Complications in People With Type 1 or Type 2 Diabetes After Initiation of Flash Glucose Monitoring in France: The RELIEF Study.

Abstract: OBJECTIVE The RELIEF study assessed rates of hospitalization for acute diabetes complications in France before and after initiation of the FreeStyle Libre system. RESEARCH DESIGN AND METHODS A total of 74,011 patients with type 1 diabetes or type 2 diabetes who initiated the FreeStyle Libre system were identified from the French national claims database with use of ICD-10 codes, from hospitalizations with diabetes as a contributing diagnosis, or the prescription of insulin. Patients were subclassified based on self-monitoring of blood glucose (SMBG) strip acquisition prior to starting FreeStyle Libre. Hospitalizations for diabetic ketoacidosis (DKA), severe hypoglycemia, diabetes-related coma, and hyperglycemia were recorded for the 12 months before and after initiation. RESULTS Hospitalizations for acute diabetes complications fell in type 1 diabetes (−49.0%) and in type 2 diabetes (−39.4%) following FreeStyle Libre initiation. DKA fell in type 1 diabetes (−56.2%) and in type 2 diabetes (−52.1%), as did diabetes-related comas in type 1 diabetes (−39.6%) and in type 2 diabetes (−31.9%). Hospitalizations for hypoglycemia and hyperglycemia decreased in type 2 diabetes (−10.8% and −26.5%, respectively). Before initiation, hospitalizations were most marked for people noncompliant with SMBG and for those with highest acquisition of SMBG, which fell by 54.0% and 51.2%, respectively, following FreeStyle Libre initiation. Persistence with FreeStyle Libre at 12 months was at 98.1%. CONCLUSIONS This large retrospective study on hospitalizations for acute diabetes complications shows that a significantly lower incidence of admissions for DKA and for diabetes-related coma is associated with use of flash glucose monitoring. This study has significant implications for patient-centered diabetes care and potentially for long-term health economic outcomes.

Social Determinants of Health and Structural Inequities-Root Causes of Diabetes Disparities

Abstract: Diabetes is the seventh leading cause of death in the U.S. and remains a significant cause of disability and decreased quality of life (1,2). In 2018, over 34 million people in the U.S. had diabetes (1). Historically marginalized groups such as racial and ethnic minorities, as well as those with lower socioeconomic status, bear a disproportionate burden of diabetes and its associated complications: blindness, neuropathy, limb amputations, chronic kidney disease, cardiovascular disease, and death (1,3). Additionally, the economic burden of diabetes amounts to approximately $237 billion in direct medical costs and $90 billion in lost productivity (4). Diabetes is a public health crisis that must be addressed by acknowledging and intervening on contextual factors outside of traditional medical care if we are to truly make an impact on improving outcomes, particularly for our most marginalized communities. While contributors to diabetes outcomes are unequivocally multifactorial, cumulative evidence suggests that certain factors play a larger role than others (5). For example, medical care plays a relatively small part (approximately 10–15%) in shaping individual and population-level health outcomes (5,6). In contrast, social and environmental factors, collectively known as the social determinants of health (SDOH), combined account for 50% to 60% of health outcomes and are a key contributor to health and health care disparities (5,6). The World Health Organization’s definition of SDOH also notes that these social and environmental factors are “shaped by the distribution of money, power and resources at global, national and local levels” and are largely responsible for inequities in health outcomes (7). To achieve health equity, we must address SDOH, and do so at …

Effects of Vitamin C Supplementation on Glycemic Control and Cardiovascular Risk Factors in People With Type 2 Diabetes: A GRADE-Assessed Systematic Review and Meta-analysis of Randomized Controlled Trials.

Abstract: BACKGROUND: Evidence suggests that vitamin C supplementation could be a potential therapy in type 2 diabetes. However, its effectiveness and evidence quality require further evaluation. PURPOSE: To investigate the efficacy of oral vitamin C supplementation in improving glycemic control, cardiovascular risk factors, and oxidative stress in people with type 2 diabetes. DATA SOURCES: Databases (PubMed, Embase, Scopus, Cochrane Library) and clinical trial registries were searched for randomized controlled trials up to 8 September 2020. STUDY SELECTION: Trials in adults with type 2 diabetes were included. Trials were excluded if supplements were not exclusive to vitamin C and if <2 weeks in duration. DATA EXTRACTION: Primary outcomes were HbA1c, glucose, cholesterol, triglycerides, and blood pressure (BP). Data were extracted for changes in outcomes between vitamin C and control groups. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation methods. DATA SYNTHESIS: Twenty-eight studies (N = 1,574 participants) were included in the review. Outcomes that changed to a statistically and clinically significant extent with vitamin C were systolic BP (mean difference -6.27 [95% CI -9.60, -2.96] mmHg; P = 0.0002), with moderate evidence certainty, and HbA1c (-0.54% [-0.90, -0.17]; P = 0.004) and diastolic BP (-3.77 [-6.13, -1.42] mmHg; P = 0.002) with very low evidence certainty. LIMITATIONS: Studies were predominantly short term (<6 months) with a small number of participants (n < 100). CONCLUSIONS: While evidence from short-term studies suggests that vitamin C supplementation may improve glycemic control and BP in people with type 2 diabetes, vitamin C supplementation cannot currently be recommended as a therapy until larger, long-term, and high-quality trials confirm these findings.