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American Diabetes Journals 09/11/2019 17:39
OBJECTIVE. African Americans (AA) suffer disproportionately from diabetic nephropathy (DN). C-reactive protein (CRP) has been associated with prevalent DN, but its association with incident DN in AA is unknown. We examined hs-CRP and incident DN in AA. RESEARCH DESIGN AND METHODS. We conducted a longitudinal analysis of data from exams 1, 2, and 3 in 4,043 eligible Jackson Heart Study participants. Participants with DN or without hs-CRP at exam 1 were excluded. Incident DN was defined as urinary albumin-to-creatinine ratio (ACR) >30 mg/g or self-reported dialysis/transplantation and type 2 diabetes mellitus (DM) or HbA 1c >6.5% by exam 2 or 3 among participants free of DN at exam 1. Kaplan-Meier curves examined DN event-free survival probabil.
American Diabetes Journals 09/11/2019 17:39
OBJECTIVE. To study whether fibroblast growth factor 23 (FGF23) is associated with adverse outcomes in patients with type 2 diabetes and normal or mildly impaired kidney function. RESEARCH DESIGN AND METHODS. We analyzed COOH-terminal FGF23 levels in 310 patients with type 2 diabetes and estimated glomerular filtration rate ≥60 mL/min/1.73 m 2 .
American Diabetes Journals 08/30/2019 13:40
Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance and hyperglycemia. However, development of uncoupler-based therapy remains challenging due to its potentially lethal side effects. Here we identify pyruvate dehydrogenase (PDH) as a key modifier of the toxicity profile of dinitrophenol (DNP), a prototypical mitochondrial uncoupler. PDH activation by dichloroacetic acid (DCA) protects mice from DNP-induced hyperlactacidemia, hyperthermia and death while preserving the ability of DNP to promote fuel oxidation and improve insulin sensitivity in mice. Mechanistically, PDH activation switches on mitochondrial glucose oxidation to accommodate increased glycolytic flux, l.
American Diabetes Journals 08/26/2019 14:00
Deficiency of endothelial progenitor cells, including endothelial colony-forming cells (ECFC) and circulating angiogenic cells (CAC), plays an important role in retinal vascular degeneration in diabetic retinopathy (DR). Fenofibrate, an agonist of peroxisome proliferator-activated receptor-α (PPARα), has shown therapeutic effects on DR in both patients and diabetic animal models. However, the function of PPARα in ECFC/CAC has not been defined. In this study, we determined the regulation of ECFC/CAC by PPARα. As shown by flow cytometry and Seahorse analysis, ECFC/CAC numbers and mitochondrial function were decreased in the bone marrow, circulation and retina of db/db mice, correlating with PPARα down-regulation. Activation of PPARα by fenofi.
American Diabetes Journals 08/22/2019 17:43
Type 1 diabetes (T1D) imposes a significant health burden by its negative impact on tissue regeneration during wound healing. The adverse effect of diabetes is attributed to high levels of inflammation, but the cellular mechanisms responsible remain elusive. Here we show that intrinsic skeletal stem cells (SSCs) are essential for resolution of inflammation to occur during osseous healing by using genetic approaches to selectively ablate SSCs. T1D caused aberrant nuclear factor-kappaB (NF-B) activation in SSCs and substantially enhanced inflammation in vivo . Constitutive or tamoxifen-induced inhibition of NF-B in SSCs rescued the impact of diabetes on inflammation, SSC expansion, and tissue formation. In contrast, NF-kB inhibition in chondr.
American Diabetes Journals 08/22/2019 17:43
CCR2 has been proved to play an important role in diabetes. However, the role of CCR2 in diabetic cardiomyopathy has not been examined. In this study, we investigated the effects of cardiac CCR2 on diabetic cardiomyopathy. We created streptozotocin (STZ)-induced diabetic cardiomyopathy model. Expression of CCR2 were up-regulated in STZ-induced diabetic hearts. CCR2 knockout (CCR2 KO) significantly improved STZ-induced cardiac dysfunction and fibrosis. Moreover, deletion of CCR2 inhibited the STZ induced the apoptosis as well as the production of STZ-induced reactive oxygen species (ROS) in the heart. CCR2 knockout resulted in M2 polarization in heart from STZ treated-mice. Meantime, CCR2 inhibitor treatment also reversed hyperglycemia induc.
American Diabetes Journals 08/22/2019 17:43
Epithelial to mesenchymal transition (EMT) and wound vascularization are two critical inter-related processes that enable cutaneous wound healing. Zinc finger E-box binding homeobox 1 (ZEB1), primarily studied in the context of tumor biology, is a potent EMT-activator. ZEB1 is also known to contribute to endothelial cell survival as well as stimulate tumor angiogenesis. The role of ZEB1 in cutaneous wounds was assessed using Zeb1 +/- mice as Zeb1 -/- mice are not viable. Quantitative SILAC proteomics was utilized to elucidate the effect of elevated ZEB1, as noted during hyperglycemia. Under different glycemic conditions, ZEB1 binding to E-cadherin promoter was investigated using chromatin immunoprecipitation. Cutaneous wounding resulted in
American Diabetes Journals 08/22/2019 17:43
Type 2 diabetes mellitus (T2DM) patients have a considerably high risk of developing dementia, especially for those with mild cognitive impairment (MCI). The investigation of the microstructural change of white matter (WM) between T2DM with amnesic MCI (T2DM-aMCI) and T2DM with normal cognition (T2DM-NC) and their relationships to cognitive performances can help to understand the brain variations in T2DM-related amnesic cognitive impairment. In the present study, 36 T2DM-aMCI patients, 40 T2DM-NC patients and 40 healthy control (HC) individuals underwent diffusion tensor image and T1-weighted MRI scans and comprehensive cognition. All these cognitive functions exhibited intergroup ranking difference in patients. The T2DM-NC patients and HC
American Diabetes Journals 08/22/2019 17:43
Disruption of the adaptor protein SH2B1 is associated with severe obesity, insulin resistance and neurobehavioral abnormalities in mice and humans. Here we identify 15 SH2B1 mutations in severely obese children. Four obesity-associated human SH2B1 mutations lie in the Pleckstrin Homology (PH) domain, suggesting that the PH domain is essential for SH2B1’s function. We generated a mouse model of a human variant in this domain (P322S). P322S/P332S mice exhibited substantial prenatal lethality. Examination of the P322S/+ metabolic phenotype revealed late-onset glucose intolerance. To circumvent P322S/P322S lethality, mice containing a 2-amino acid deletion within the SH2B1 PH domain (P317, R318; PR) were studied. Mice homozygous for PR were bor.
American Diabetes Journals 08/20/2019 15:00
OBJECTIVE. Disturbed eating behavior (DEB) is prevalent in youth with type 1 diabetes and is accompanied by an increased risk for complications, morbidity, and mortality. Prospective studies on DEB in the challenging transition to adulthood are scarce. This longitudinal study examined DEB over a 1-year period and investigated the directionality of effects linking DEB to diabetes-specific functioning and depressive symptoms in adolescents and emerging adults. RESEARCH DESIGN AND METHODS. Three hundred youth (16–28 years old) with type 1 diabetes participated in a two-wave longitudinal study. Questionnaires measured DEB (Diabetes Eating Problem Survey-Revised [DEPS-R]), self-management, diabetes distress, and depressive symptoms. HbA 1c values
American Diabetes Journals 08/20/2019 15:00
OBJECTIVE. Microvascular complications are common among patients with diabetes mellitus (DM). The presence of heart failure (HF) is presumed to be due to macrovascular disease (typically HF with reduced ejection fraction [HFrEF] following myocardial infarction). We hypothesized that HF with preserved ejection fraction (HFpEF) in patients with DM may be a manifestation of microvascular disease compared with HFrEF. The objective of this study was to examine the prevalence and association with clinical outcome of microvascular complications in patients with HF and DM. RESEARCH DESIGN AND METHODS. We investigated the prevalence, association with clinical outcome, and cardiac structure and function of microvascular (neuropathy, nephropathy, and re.
American Diabetes Journals 08/20/2019 15:00
OBJECTIVE. HELP PD was a clinical trial of 301 adults with prediabetes. Participants were randomized to enhanced usual care (EUC) or to a lifestyle weight loss (LWL) intervention led by community health workers that consisted of a 6-month intensive phase (phase 1) and 18 months of maintenance (phase 2). At 24 months, participants were asked to enroll in phase 3 to assess whether continued group maintenance (GM) sessions would maintain improvements realized in phases 1 and 2 compared with self-directed maintenance (SM) or EUC. RESEARCH DESIGN AND METHODS. In phase 3, LWL participants were randomly assigned to GM or SM. EUC participants remained in the EUC arm and, along with participants in SM, received monthly newsletters. All participants re.
American Diabetes Journals 08/20/2019 15:00
Glycated hemoglobin targets have been given in guidelines for the last three decades, mostly without change at around 6.5–7.0% (47–53 mmol/mol). Personalization of such targets has also long been advocated, but often with little and inappropriate guidance. More recently some have suggested higher targets might be indicated, and more specifically lower targets avoided, even in those in whom they are easily attained without seeming burden or risk. Prospective data from randomized and observational studies, in people with type 2 diabetes and indeed those without diabetes, find cardiovascular and mortality risk are uniformly lowest at lower levels including into the normal range. In some studies with large populations, a high proportion of peop.
American Diabetes Journals 08/20/2019 15:00
The prevailing dogma is that thermogenic brown adipose tissue (BAT) contributes to improvements in glucose homeostasis in obesogenic animal models, though much of the evidence supporting this premise is from thermostressed rodents. Determination of whether modulation of the BAT morphology/function drives changes in glucoregulation at thermoneutrality requires further investigation. We used loss- and gain-of-function approaches including genetic manipulation of the lipolytic enzyme Pnpla2 , change in environmental temperature, and lifestyle interventions to comprehensively test the premise that a thermogenic-like BAT phenotype is coupled with enhanced glucose tolerance in female mice. In contrast to this hypothesis, we found that 1 ) compare.
American Diabetes Journals 08/20/2019 15:00
OBJECTIVE. Lifestyle interventions slow development of type 2 diabetes by half, but the impact of health payer reimbursement for delivery of intervention programs is not well known. We evaluated net commercial health payer expenditures when offering reimbursement for access to YMCA’s Diabetes Prevention Program (YDPP) in 42 states. RESEARCH DESIGN AND METHODS. We used a nonequivalent comparison group design to evaluate net health care expenditures for adults with prediabetes who attended one or more YDPP visit between 1 July 2009 and 31 May 2013 ("YDPP users"). Rolling, 1:1 nearest neighbor propensity score (PS) matching was used to identify a comparison group of nonusers. Administrative data provided measures of YDPP attendance, body weight
American Diabetes Journals 08/20/2019 15:00
OBJECTIVE. This trial compared the efficacy and safety of the first oral glucagon-like peptide 1 (GLP-1) receptor agonist, oral semaglutide, as monotherapy with placebo in patients with type 2 diabetes managed by diet and exercise alone. Two estimands addressed two efficacy-related questions: a treatment policy estimand (regardless of trial product discontinuation or rescue medication use) and a trial product estimand (on trial product without rescue medication use) in all randomized patients. RESEARCH DESIGN AND METHODS. This was a 26-week, phase 3a, randomized, double-blind, placebo-controlled, parallel-group trial conducted in 93 sites in nine countries. Adults with type 2 diabetes insufficiently controlled with diet and exercise were rand.

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