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American Diabetes Journals 03/20/2020 14:50
OBJECTIVE. Most individuals with two or more islet autoantibodies progress to clinical type 1 diabetes. However, in some individuals, autoantibodies are subsequently lost. Here, our objectives were to determine the frequency of autoantibody loss (reversion) in multiple-autoantibody–positive individuals and to determine the association between reversion and progression to clinical disease. RESEARCH DESIGN AND METHODS. We analyzed multiple-autoantibody–positive individuals participating in TrialNet’s Pathway to Prevention Study for reversion and determined the effect of reversion on progression to clinical disease using a Cox regression analysis. RESULTS. Of 3,284 multiple-autoantibody–positive subjects, reversion occurred in 134 (4.1%) and was
American Diabetes Journals 03/20/2020 14:50
OBJECTIVE. Self-management education and support are essential for improved diabetes control. A 1-year randomized telephonic diabetes self-management intervention (Bronx A1C) among a predominantly Latino and African American population in New York City was found effective in improving blood glucose control. To further those findings, this current study assessed the intervention’s impact in reducing health care utilization and costs over 4 years. RESEARCH DESIGN AND METHODS. We measured inpatient ( n = 816) health care utilization for Bronx A1C participants using an administrative data set containing all hospital discharges for New York State from 2006 to 2014. Multilevel mixed modeling was used to assess changes in health care utilization and.
American Diabetes Journals 03/20/2020 14:50
OBJECTIVE. To investigate the role of epigenetics in statins’ diabetogenic effect comparing DNA methylation (DNAm) between statin users and nonusers in an epigenome-wide association study in blood. RESEARCH DESIGN AND METHODS. Five cohort studies’ participants ( n = 8,270) were classified as statin users when they were on statin therapy at the time of DNAm assessment with Illumina 450K or EPIC array or noncurrent users otherwise.
American Diabetes Journals 03/20/2020 14:50
OBJECTIVE. Insulin dosing in type 1 diabetes (T1D) is oftentimes complicated by fluctuating insulin requirements driven by metabolic and psychobehavioral factors impacting individuals’ insulin sensitivity (IS). In this context, smart bolus calculators that automatically tailor prandial insulin dosing to the metabolic state of a person can improve glucose management in T1D. RESEARCH DESIGN AND METHODS. Fifteen adults with T1D using continuous glucose monitors (CGMs) and insulin pumps completed two 24-h admissions in a hotel setting. During the admissions, participants engaged in an early afternoon 45-min aerobic exercise session, after which they received a standardized dinner meal. The dinner bolus was computed using a standard bolus calculat.
American Diabetes Journals 03/20/2020 14:50
Reduced storage of dietary fatty acids (DFAs) in abdominal adipose tissues with enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and prediabetes. We measured DFA metabolism and organ partitioning using positron emission tomography with oral and intravenous long-chain fatty acid and glucose tracers during a standard liquid meal in 12 obese subjects with T2D before and 8–12 days after bariatric surgery (sleeve gastrectomy or sleeve gastrectomy and biliopancreatic diversion with duodenal switch). Bariatric surgery reduced cardiac DFA uptake from a median (standard uptake value [SUV]) 1.75 (interquartile range 1.39–2.57) before to 1.09 (1.04–1.53) after surgery ( P = 0.01) and systemic DFA spillover from 56.7
American Diabetes Journals 03/20/2020 14:50
OBJECTIVE. Coronary artery disease (CAD) is a major challenge in patients with type 2 diabetes (T2D). Coronary computed tomography angiography (CCTA) provides a detailed anatomic map of the coronary circulation. Proteomics are increasingly used to improve diagnostic and therapeutic algorithms. We hypothesized that the protein panel is differentially associated with T2D and CAD. RESEARCH DESIGN AND METHODS. In CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation—a cohort of 528 individuals with no previous cardiovascular event undergoing CCTA), participants were grouped into CAD – (clean coronaries) and CAD + (diffuse lumen narrowing or plaques). Plasma proteins were screened by aptamer
American Diabetes Journals 03/20/2020 14:50
OBJECTIVE. Bariatric surgery is an effective treatment for obesity, but it is unknown if outcomes differ between adults with early- versus adult-onset obesity. We investigated how obesity status at 20 years of age affects outcomes after bariatric surgery later in life. RESEARCH DESIGN AND METHODS. The Swedish Obese Subjects study is a prospective matched study performed at 25 surgical departments and 480 primary health care centers. Participants aged 37–60 years with BMI ≥34 kg/m 2 (men) or ≥38 kg/m 2 (women) were recruited between 1987 and 2001; 2,007 participants received bariatric surgery and 2,040 usual care. Self-reported body weight at 20 years of age was used to stratify patients into subgroups with normal BMI ( <25 kg/m 2 ), overweigh.
American Diabetes Journals 03/20/2020 14:50
Approximately 10% of patients with type 2 diabetes suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model mimicking the characteristics of patients with LADA. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT-PCR and quantitative real-time PCR of laser microdissected islets for gene expression of proinflammatory cytokines, the proliferation marker proliferating cell nuclear antigen (PCNA), the anti-inflammatory cytokine interleukin (IL) 10, and the apoptosis markers caspase 3 and TUNEL as well as insulin. Human and r.
American Diabetes Journals 03/20/2020 14:50
The signal peptide of preproinsulin is a major source for HLA class I autoantigen epitopes implicated in CD8 T cell (CTL)–mediated β-cell destruction in type 1 diabetes (T1D). Among them, the 10-mer epitope located at the C-terminal end of the signal peptide was found to be the most prevalent in patients with recent-onset T1D. While the combined action of signal peptide peptidase and endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) is required for processing of the signal peptide, the mechanisms controlling signal peptide trimming and the contribution of the T1D inflammatory milieu on these mechanisms are unknown. Here, we show in human β-cells that ER stress regulates ERAP1 gene expression at posttranscriptional level via the IRE1α/miR-
American Diabetes Journals 03/20/2020 14:50
OBJECTIVE. To analyze the differences in health care costs according to glycemic control in people with type 2 diabetes. RESEARCH DESIGN AND METHODS. Data on health care resource utilization from 100,391 people with type 2 diabetes were extracted from the electronic database used at the Catalan Health Institute.
American Diabetes Journals 03/20/2020 14:50
BACKGROUND. Identifying patients at high risk of diabetic kidney disease (DKD) helps improve clinical outcome. PURPOSE. To establish a model for predicting DKD. DATA SOURCES. The derivation cohort was from a meta-analysis. The validation cohort was from a Chinese cohort. STUDY SELECTION. Cohort studies that reported risk factors of DKD with their corresponding risk ratios (RRs) in patients with type 2 diabetes were selected. All patients had estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 and urinary albumin-to-creatinine ratio (UACR) <30 mg/g at baseline. DATA EXTRACTION. Risk factors and their corresponding RRs were extracted. Only risk factors with statistical significance were included in our DKD risk prediction model. DATA S.
American Diabetes Journals 03/20/2020 14:50
Secretion of glucagon from the pancreatic α-cells is conventionally seen as the first and most important defense against hypoglycemia. Recent findings, however, show that α-cell signals stimulate insulin secretion from the neighboring β-cell. This article focuses on these seemingly counterintuitive local actions of α-cells and describes how they impact islet biology and glucose metabolism. It is mostly based on studies published in the last decade on the physiology of α-cells in human islets and incorporates results from rodents where appropriate. As this and the accompanying articles show, the emerging picture of α-cell function is one of increased complexity that needs to be considered when developing new therapies aimed at promoting isle.
American Diabetes Journals 03/20/2020 14:50
A single bout of exercise enhances insulin action in the exercised muscle. However, not all human studies find that this translates into increased whole-body insulin action, suggesting that insulin action in rested muscle or other organs may be decreased by exercise. To investigate this, eight healthy men underwent a euglycemic-hyperinsulinemic clamp on 2 separate days: one day with prior one-legged knee-extensor exercise to local exhaustion (~2.5 h) and another day without exercise. Whole-body glucose disposal was ~18% lower on the exercise day as compared with the resting day due to decreased (~37%) insulin-stimulated glucose uptake in the nonexercised muscle. Insulin signaling at the level of Akt2 was impaired in the nonexercised muscle
American Diabetes Journals 03/20/2020 14:50
OBJECTIVE. Excessive iron intake has been linked to diabetes risk. However, the evidence is inconsistent. This study examined the association between dietary heme and nonheme iron intake and diabetes risk in the Chinese population. RESEARCH DESIGN AND METHODS. We included 17,026 adults (8,346 men and 8,680 women) who were part of the China Health and Nutrition Survey (1991–2015) prospective cohort. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. Diabetes cases were identified through a questionnaire. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS. A total of 547 men and 577 women developed diabetes during 202,138 person-years of foll.
American Diabetes Journals 03/20/2020 14:50
OBJECTIVE. To assess whether initiation of insulin glargine (glargine), compared with initiation of NPH or insulin detemir (detemir), was associated with an increased risk of breast cancer in women with diabetes. RESEARCH DESIGN AND METHODS. This was a retrospective new-user cohort study of female Medicare beneficiaries aged ≥65 years initiating glargine (203,159), detemir (67,012), or NPH (47,388) from September 2006 to September 2015, with follow-up through May 2017.
American Diabetes Journals 03/20/2020 14:50
Glucagon is historically described as the counterregulatory hormone to insulin, induced by fasting/hypoglycemia to raise blood glucose through action mediated in the liver. However, it is becoming clear that the biology of glucagon is much more complex and extends beyond hepatic actions to exert control on glucose metabolism. We discuss the inconsistencies with the canonical view that glucagon is primarily a hyperglycemic agent driven by fasting/hypoglycemia and highlight the recent advances that have reshaped the metabolic role of glucagon. These concepts are placed within the context of both normal physiology and the pathophysiology of disease and then extended to discuss emerging strategies that incorporate glucagon agonism in the pharma.
American Diabetes Journals 03/20/2020 14:50
OBJECTIVE. To construct and internally validate prediction models to estimate the risk of long-term end-organ complications and mortality in patients with type 2 diabetes and obesity that can be used to inform treatment decisions for patients and practitioners who are considering metabolic surgery. RESEARCH DESIGN AND METHODS. A total of 2,287 patients with type 2 diabetes who underwent metabolic surgery between 1998 and 2017 in the Cleveland Clinic Health System were propensity-matched 1:5 to 11,435 nonsurgical patients with BMI ≥30 kg/m 2 and type 2 diabetes who received usual care with follow-up through December 2018.

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