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ImportanceA combination of diabetes, coronary heart disease (CHD), and stroke has multiplicative all-cause mortality risk compared with any individual morbidity in White populations, but there is a lack of studies in Black populations in the US.ObjectiveTo examine the association of cardiometabolic multimorbidity (diabetes, stroke, and CHD) individually and collectively with all-cause and CHD mortality.Design, Setting, and ParticipantsThis cohort study included Black adults in the Jackson Heart Study followed over a median of 15 years. Baseline examinations were performed between 2000 and 2004, with follow-up on all-cause and CHD mortality through May 31, 2018. Participants were categorized into mutually exclusive groups at baseline: (1) free of cardiometabolic morbidity, (2) diabetes, (3) CHD, (4) stroke, (5) diabetes and stroke, (6) CHD and stroke, (7) diabetes and CHD, and (8) diabetes, stroke, and CHD. Data were analyzed from 2019 to 2021.ExposureCardiometabolic disease alone or in combination.Main Outcomes and MeasuresThe main outcomes were all-cause mortality and CHD mortality. Cox models estimated hazard ratios (HRs) with 95% CIs adjusted for sociodemographic and cardiovascular risk factors.ResultsAmong 5064 participants (mean [SD] age, 55.4 [12.8] years; 3200 [63%] women) in the Jackson Heart Study, 897 (18%) had diabetes, 192 (4%) had CHD, and 104 (2%) had a history of stroke. Among participants with cardiometabolic morbidities, the crude all-cause mortality rates were lowest for diabetes alone (24.4 deaths per 1000 person-years) and highest for diabetes, CHD, and stroke combined (84.1 deaths per 1000 person-years). For people with only 1 cardiometabolic morbidity, risk for all-cause mortality was highest for people with stroke (HR, 1.74; 95% CI, 1.24-2.42), followed by CHD (HR, 1.59 (95% CI, 1.22-2.08) and diabetes (HR, 1.50; 95% CI, 1.22-1.85), compared with no cardiometabolic morbidities. There were also increased risks of mortality with combinations of diabetes and stroke (HR, 1.71; 95% CI, 1.09-2.68), CHD and stroke (HR, 2.23; 95% CI, 1.35-3.69), and diabetes and CHD (HR, 2.28; 95% CI, 1.65-3.15). The combination of diabetes, stroke, and CHD was associated with the highest all-cause mortality (HR, 3.68; 95% CI, 1.96-6.93). Findings were similar for CHD mortality, but with a larger magnitude of association (eg, diabetes, stroke, and CHD: HR, 13.52; 95% CI, 3.38-54.12).Conclusions and RelevanceIn this cohort study, an increasing number of cardiometabolic multimorbidities was associated with a multiplicative increase in risk of all-cause mortality among Black adults, with a greater magnitude of association for CHD mortality.

Key Clinical Points Glucose-Lowering Drugs to Reduce Cardiovascular Risk in Type 2 Diabetes The attainment of glycemic targets and comprehensive reduction in risk factors for cardiovascular disease...

The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits.

OBJECTIVE LDL cholesterol (LDLc)-lowering drugs modestly increase body weight and type 2 diabetes risk, but the extent to which the diabetogenic effect of lowering LDLc is mediated through increased BMI is unknown. RESEARCH DESIGN AND METHODS We conducted summary-level univariable and multivariable Mendelian randomization (MR) analyses in 921,908 participants to investigate the effect of lowering LDLc on type 2 diabetes risk and the proportion of this effect mediated through BMI. We used data from 92,532 participants from 14 observational studies to replicate findings in individual-level MR analyses. RESULTS A 1-SD decrease in genetically predicted LDLc was associated with increased type 2 diabetes odds (odds ratio [OR] 1.12 [95% CI 1.01, 1.24]) and BMI (β = 0.07 SD units [95% CI 0.02, 0.12]) in univariable MR analyses. The multivariable MR analysis showed evidence of an indirect effect of lowering LDLc on type 2 diabetes through BMI (OR 1.04 [95% CI 1.01, 1.08]) with a proportion mediated of 38% of the total effect (P = 0.03). Total and indirect effect estimates were similar across a number of sensitivity analyses. Individual-level MR analyses confirmed the indirect effect of lowering LDLc on type 2 diabetes through BMI with an estimated proportion mediated of 8% (P = 0.04). CONCLUSIONS These findings suggest that the diabetogenic effect attributed to lowering LDLc is partially mediated through increased BMI. Our results could help advance understanding of adipose tissue and lipids in type 2 diabetes pathophysiology and inform strategies to reduce diabetes risk among individuals taking LDLc-lowering medications.

Background The prognostic value of anthropometric, adipokine, and computed tomography measures of adiposity to predict diabetes in Black, specifically by normoglycemia versus prediabetes, remains incompletely understood. Methods and Results Among Black participants without diabetes in the JHS (Jackson Heart Study), waist circumference [WC], body mass index, adiponectin, leptin, and leptin:adiponectin ratio were standardized in sample 1 (2422 participants at baseline [2000–2004]) and WC, body mass index, visceral adipose tissue (VAT), subcutaneous adipose tissue, and liver attenuation in 1537 participants at examination 2 (2005–2008) (sample 2). Hazard ratios (HRs) for diabetes were estimated using interval‐censored Cox modeling adjusting for traditional risk factors and validated with the C index. Over 5 years, 300 and 122 incident diabetes cases occurred in sample 1 and sample 2, respectively. In sample 1 and sample 2, a 1‐SD higher log‐leptin:adiponectin ratio and VAT had the strongest associations (HR, 1.95 [95% CI, 1.67–2.27] and 1.76 [95% CI, 1.52–2.04]) and discriminatory power (C index 0.68 [95% CI, 0.64–0.71] and C index 0.67 [95% CI, 0.61–0.74]) with diabetes. The normoglycemic compared with the prediabetes group had a 1.3 to 1.9 times greater magnitude of associations with diabetes for WC, liver attenuation, and VAT ( P interaction 1c (HR, 0.74; 95% CI, 0.57–0.90) in normoglycemia, whereas HbA 1c was best in prediabetes (HR, 0.72; 95% CI, 0.66–0.78). Conclusions Overall, among Black adults, multiple measures of adiposity were associated with incident diabetes with modest predictive ability. In Black patients with normoglycemia, WC, liver attenuation, and VAT may appropriately identify those at high risk for diabetes, whereas HbA 1c was the best predictor in individuals with prediabetes.

OBJECTIVE Regression from prediabetes to normal glucose regulation (NGR) was associated with reduced incidence of diabetes by 56% over 10 years in participants in the Diabetes Prevention Program Outcomes Study (DPPOS). In an observational analysis, we examined whether regression to NGR also reduced risk for microvascular disease (MVD). RESEARCH DESIGN AND METHODS Generalized estimating equations were used to examine the prevalence of aggregate MVD at DPPOS year 11 in people who regressed to NGR at least once (vs. never) during the Diabetes Prevention Program (DPP). Logistic regression assessed the relationship of NGR with retinopathy, nephropathy, and neuropathy, individually. Generalized additive models fit smoothing splines to describe the relationship between average A1C during follow-up and MVD (and its subtypes) at the end of follow-up. RESULTS Regression to NGR was associated with lower prevalence of aggregate MVD in models adjusted for age, sex, race/ethnicity, baseline A1C, and treatment arm (odds ratio [OR] 0.78, 95% CI 0.65–0.78, P = 0.011). However, this association was lost in models that included average A1C during follow-up (OR 0.95, 95% CI 0.78–1.16, P = 0.63) or diabetes status at the end of follow-up (OR 0.92, 95% CI 0.75–1.12, P = 0.40). Similar results were observed in examination of the association between regression to NGR and prevalence of nephropathy and retinopathy, individually. Risk for aggregate MVD, nephropathy, and retinopathy increased across the A1C range. CONCLUSIONS Regression to NGR is associated with a lower prevalence of aggregate MVD, nephropathy, and retinopathy, primarily due to lower glycemic exposure over time. Differential risk for the MVD subtypes begins in the prediabetes A1C range.

ObjectiveTo develop clinical practice guidelines for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes mellitus (T2DM) in individuals at metabolic risk for developing these conditions.ConclusionsHealth care providers should incorporate regular screening and identification of individuals at metabolic risk (at higher risk for ASCVD and T2DM) with measurement of blood pressure, waist circumference, fasting lipid profile, and blood glucose. Individuals identified at metabolic risk should undergo 10-year global risk assessment for ASCVD or coronary heart disease to determine targets of therapy for reduction of apolipoprotein B–containing lipoproteins. Hypertension should be treated to targets outlined in this guideline. Individuals with prediabetes should be tested at least annually for progression to diabetes and referred to intensive diet and physical activity behavioral counseling programs. For the primary prevention of ASCVD and T2DM, the Writing Committee recommends lifestyle management be the first priority. Behavioral programs should include a heart-healthy dietary pattern and sodium restriction, as well as an active lifestyle with daily walking, limited sedentary time, and a structured program of physical activity, if appropriate. Individuals with excess weight should aim for loss of ≥5% of initial body weight in the first year. Behavior changes should be supported by a comprehensive program led by trained interventionists and reinforced by primary care providers. Pharmacological and medical therapy can be used in addition to lifestyle modification when recommended goals are not achieved.

Importance The net benefit of aspirin for prevention of cardiovascular disease (CVD), particularly primary prevention, remains debated in people with and without diabetes. Recent studies suggest that the benefits of preventive aspirin may be outweighed by the potential for harm in older adults; therefore, it is important to monitor current aspirin use in order to minimize risk for future harm in the oldest segment of the population. Objective To determine the prevalence of preventive aspirin use in older US adults with and without diabetes for both primary and secondary prevention by age, sex, and CVD risk category. Design, setting, and participants This cross-sectional analysis used nationally representative data from the National Health and Nutrition Examination Survey from 2011 to 2018. A total of 7103 individuals 60 years or older with and without diabetes completed a questionnaire on preventive aspirin use. Statistical analyses were performed from July 1, 2019, to April 1, 2021. Main outcomes and measures Preventive aspirin use was defined as participants' self-reported use of low-dose aspirin therapy based on their physician's advice or their own decision. Results A total of 7103 individuals (mean [SD] age, 69.6 [0.1] years; 45.2% men; 75.8% White participants) were evaluated. Overall, 61.7% of older US adults with diabetes vs 42.2% without diabetes used aspirin. Among people with diabetes, in multivariable logistic models adjusting for race, sex, education, CVD risk category, and body mass index, the likelihood of aspirin use in older vs younger age categories (reference: 60-69 years) did not differ. Among people without diabetes, aspirin use was significantly greater in older age categories vs the reference (model 3, 70-79 years, odds ratio [OR], 1.50; 95% CI, 1.23-1.83; model 3, ≥80 years, OR, 1.59; 95% CI, 1.24-2.04). An estimated 9.9 million US adults 70 years or older with or without diabetes reported taking aspirin for primary prevention. The likelihood of aspirin use for primary prevention in those at high vs low risk for CVD did not differ among older adults with diabetes (model 3, OR, 1.69; 95% CI, 0.65-4.39) but was significantly higher in those without diabetes (model 3, OR, 2.46; 95% CI, 1.63-3.71). Women vs men with diabetes were less likely to be using aspirin for primary prevention (model 3, OR, 0.63; 95% CI, 0.48-0.83). Conclusions and relevance This cross-sectional study found that preventive aspirin use was higher among older adults with diabetes than in those without diabetes. Results suggest that 9.9 million older US adults who previously took aspirin for primary prevention would not be recommended for its continued use, particularly among those with diabetes.

Importance Tens of millions of individuals in the United States have Type 2 diabetes, and most require treatment with glucose-lowering medications to manage the disease. Objective To examine trends in non-insulin drug treatment of Type 2 diabetes, including first-line and second-line therapies on top of metformin, from 2015 to 2019. Design, setting and participants We conducted a descriptive analysis of cross-sectional data using the IQVIA National Disease and Therapeutic Index (NDTI), a nationally representative audit of ambulatory physician practices in the United States. We focused on the use of non-insulin pharmacologic treatments for Type 2 diabetes among individuals age 35 years and older between January 1st 2015 and December 31st 2019. Main outcome and measures Type 2 diabetes visits where a prescription drug was used ("treatment visit"). Results Ambulatory diabetes visits decreased from 30.1 million (M) treatment visits in 2015 to 29.5 M treatment visits in 2019. Among treatment visits where a single drug was prescribed, use of metformin declined from 57.0% of monotherapy in 2015 to 46.0% of monotherapy in 2019, while during the same period the share of monotherapy accounted for by Glucagon-like peptide -1 (GLP-1) agonists increased from 4.3% to 8.5% and the share accounted for by sodium-glucose cotransporter-2 (SGLT-2) inhibitors increased from 7.3% to 19.5%. Among treatment visits where metformin plus another drug was prescribed, the share of second line therapy accounted for by dipeptidyl peptidase-4 (DPP-4) inhibitors decreased from 21.9% of treatment visits in 2015 to 20.8% of treatment visits in 2019; sulfonylurea use declined from 45.2% to 32.7%, use of SGLT-2 inhibitors increased from 14.5% to 21.2% and use of GLP-1 agonists increased from 9.8% to 18.2%. Conclusions and relevance Significant changes in the landscape of ambulatory care for diabetes have taken place during the past six years, including moderate declines in metformin monotherapy, moderate declines in second-line sulfonylurea use, and large increases in SGLT-2 use. These changes underscore the dynamic nature of drug utilization for diabetes in the United States, and reflect the effects of emerging evidence, evolving clinical guidelines and evolving regulatory and payment policies. This article is protected by copyright. All rights reserved.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Glycaemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycaemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated haemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.

To determine the prevalence and factors associated with depression and anxiety among people with and without diabetes during the coronavirus disease 2019 (COVID-19) outbreak.A cross-sectional questionnaire-based study collecting demographic and mental health data from 2166 participants living in the Arab Gulf region (568 with diabetes, 1598 without diabetes). Depression and anxiety were assessed using the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder scale, respectively.The prevalence of depression and anxiety symptoms were 61% and 45%, in people with diabetes (PWD) and 62% and 44%, respectively, in people without diabetes. PWD who have had their diabetes visit canceled by the clinic were more likely to report depression and anxiety symptoms than those without diabetes (odds ratio [95% confidence interval]: 1.37 [1.02, 1.84] and 1.37 [1.04, 1.80], for depression and anxiety; respectively). PWD who had no method of telecommunication with their health care providers (HCP) during the pandemic, PWD with A1C of ≥ 10%, women, employees (particularly HCPs), students, unmarried individuals, and those with lower income were more likely to report depression and/or anxiety symptoms (all P 0.01). Fear of acquiring the coronavirus infection; running out of diabetes medications; or requiring hospitalization for hypoglycemia, hyperglycemia, or diabetic ketoacidosis; and lack of telecommunication with HCPs were all associated with significantly higher odds of having depression and anxiety symptoms among PWD.The remarkably high prevalence of depression and anxiety symptoms during the COVID-19 pandemic, particularly among subgroups of PWD, calls for urgent public health policies to address mental health during the pandemic and reestablish health care access for PWD.目的: 明确2019年新型冠状病毒肺炎暴发期间糖尿病患者和非糖尿病者抑郁和焦虑的患病率及其相关因素。 方法: 这是一项基于横断面的问卷研究, 收集了居住在阿拉伯海湾地区的2166名受试者(568名糖尿病患者, 1598名非糖尿病者)的人口统计学和心理健康数据。抑郁和焦虑分别用9个条目的健康问卷和7个条目的广泛性焦虑量表进行评估。 结果: 糖尿病组抑郁和焦虑症状的发生率分别为61%和45%, 非糖尿病组分别为62%和44%。被门诊取消就诊的糖尿病患者比无糖尿病的患者更容易出现抑郁和焦虑症状(抑郁和焦虑的优势比[95%可信区间]分别为1.37[1.02, 1.84]和1.37[1.04, 1.80])。糖尿病患者中无法联系医疗服务提供者(HCP)的残疾人, A1C≥10%的残疾人, 女性, 从业人员(尤其是HCP), 学生, 未婚人士和低收入人群更易出现抑郁和/或焦虑症状(P0.0 1)。糖尿病患者中担心感染病毒; 糖尿病药物用完; 或因低血糖, 高血糖或糖尿病酮症酸中毒而需要住院; 缺乏与HCP的通讯, 这些都与出现抑郁和焦虑症状的几率显著增加有关。 结论: 新型冠状病毒肺炎大流行期间抑郁和焦虑症状的患病率非常高, 特别是在糖尿病患者亚群中, 迫切需要公共卫生政策来解决大流行期间的心理健康问题, 并重新建立糖尿病患者的卫生保健服务。.

Context Older adults have the greatest burden of diabetes; however, the contribution of age-related muscle loss to its development remains unclear. Objective We assessed the relationship of lean body mass with aging to incident diabetes in community-dwelling adults. Design and Setting We studied participants in the Baltimore Longitudinal Study of Aging with median follow-up of 7 years (range 1-16). Cox proportional hazard models with age as the time scale were used. Time-dependent lean body mass measures were updated at each follow-up visit available. Participants Participants included 871 men and 984 women without diabetes who had ≥ 1 assessment of body composition using dual x-ray absorptiometry. Main Outcomes Incident diabetes, defined as self-reported history and use of glucose-lowering medications; or fasting plasma glucose ≥ 126 mg/dL and 2-hour oral glucose tolerance test glucose ≥ 200 mg/dL either at the same visit or 2 consecutive visits. Results The baseline mean [standard deviation] age was 58.9 [17.3] years. Men and women with a higher percentage of total lean body mass had lower fasting and 2-hour glucose levels, and less prediabetes (all P Conclusions Relatively lower lean body mass with aging is associated with incident diabetes in men and partially related to anthropometrics, but not so in women.

ObjectiveThe optimal diet to improve glycemia in patients with type 2 diabetes remains unclear. Low carbohydrate, high fat (LCHF) diets can improve glycemic control, but have not been investigated in real-world settings.Research design and methodsWe investigated effects of the LCHF diet compared with usual care in a community-based cohort of patients with type 2 diabetes by performing a retrospective study of 49 patients who followed the LCHF diet for ≥3 months, and compared glycemic outcomes with age-matched and body mass index (BMI)-matched controls who received usual care (n=75). The primary outcome was change in A1C from baseline to the end of follow-up.ResultsCompared with the usual care group, the LCHF group showed a significantly greater reduction in A1C (−1.29% (95% CI −1.75 to −0.82; pConclusionsIn a community-based cohort of type 2 diabetes, the LCHF diet was associated with superior A1C reduction, greater weight loss and significantly more patients discontinuing or reducing antihyperglycemic therapies suggesting that the LCHF diet may be a metabolically favorable option in the dietary management of type 2 diabetes.

James L. Januzzi, Jr, MD, FACC, Chair Tariq Ahmad, MD, MPH, FACC Brendan Everett, MD, FACC William Hucker, MD, PHD Dharam J. Kumbhani, MD, SM, FACC Joseph E. Marine, MD, FACC Pamela B. Morris, MD, FACC Robert N. Piana, MD, FACC Sunil V. Rao, MD, FACC Marielle Scherrer-Crosbie, MD, PhD

Purpose of Review The purpose of this review is to summarize the current data for comparative effectiveness of glycemic control in older adults. Recent Findings In the last several years, professional societies have released guidelines for glycemic control in older adults, generally recommending individualized HbA1c goals. However, recent observational studies demonstrate that many older adults remain aggressively managed and are at increased risk of hypoglycemia. Large randomized trials of older adults with diabetes have failed to show convincing cardiovascular benefit from intensive glycemic control and suggest some microvascular benefit. Additionally, a few studies suggest that suboptimal glycemic control can increase the risk for geriatric syndromes. Emerging research suggests similar safety and efficacy of glucose-lowering therapies in older versus younger adults. Summary Overall, there is a paucity of data supporting the benefit of intensive glycemic control in older adults. More research is needed in this vulnerable population.

The American Diabetes Association (ADA) updates its Standards of Medical Care (SOMC) in Diabetes annually. These ADA standards make up a comprehensive document that serves as an excellent resource for clinical care. The current article comes from the ADA's Primary Care Advisory Group. This article highlights key aspects of the SOMC that are relevant to the day-to-day practice of osteopathic primary care physicians. It is not intended to replace the full SOMC but will refer to the master document for further explanation and evidence-based support.

Context The degree to which changes in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) relate to corresponding changes in plasma sex steroids is not known. Objective We examined whether changes in VAT and SAT areas assessed by computed tomography were associated with changes in sex hormones [dehydroepiandrosterone sulfate (DHEAS), testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG)] among Diabetes Prevention Program participants. Design Secondary analysis of a randomized trial. Participants Overweight and glucose-intolerant men (n = 246) and women (n = 309). Interventions Intensive lifestyle change with goals of weight reduction and 150 min/wk of moderate intensity exercise or metformin administered 850 mg twice a day or placebo. Main outcome measures Associations between changes in VAT, SAT, and sex hormone changes over 1 year. Results Among men, reductions in VAT and SAT were both independently associated with significant increases in total testosterone and SHBG in fully adjusted models. Among women, reductions in VAT and SAT were both independently associated with increases in SHBG and associations with estrone differed by menopausal status. Associations were similar by race/ethnicity and by randomization arm. No significant associations were observed between change in fat depot with change in estradiol or DHEAS. Conclusions Among overweight adults with impaired glucose intolerance, reductions in either VAT and SAT were associated with increased total testosterone in men and higher SHBG in men and women. Weight loss may affect sex hormone profiles via reductions in visceral and subcutaneous fat.

Diabetes in older adults is a growing public health burden. The unprecedented aging of the world's population is a major contributor to the diabetes epidemic, and older adults represent one of the fastest growing segments of the diabetes population. Of impending concern is that these numbers are projected to grow dramatically over the next few decades (1,2). Almost one-third of U.S. adults over the age of 65 years have diabetes. Approximately half of those are undiagnosed, and an additional one-third of older adults have prediabetes (3). Persons with diabetes today are living much longer compared with those in the past. We also recognize that management of older adults with diabetes is clearly more complicated given the observation that they commonly have multiple coexisting medical conditions that can impact clinical management. While rates of diabetes-related complications have declined overall in the general population, the incidence rates of macrovascular complications such as acute myocardial infarction and stroke continue to be the highest in older age-groups. These individuals also have the highest rate of diabetes-related end-stage renal disease (4). Heterogeneity in the health status of older adults (ranging from robust and otherwise healthy individuals to those with frailty and multiple comorbid conditions) and the paucity of evidence from clinical trials represent a challenge to making generalized treatment recommendations for older adults. Although many more individuals with type 1 diabetes are living longer (5), type 2 diabetes remains the most common type in older age-groups. Furthermore, older adults with diabetes may either have elderly onset disease (diagnosed at age 65 years or older) or long-standing diabetes with onset in middle age or earlier years (6), adding to the complexity of managing diabetes in older adults. Consequently, the American Diabetes Association (ADA) organized a Consensus Development Conference on Diabetes and Older Adults …

OBJECTIVE Hemoglobin A1c (HbA1c) level has been associated with increased mortality in middle-aged populations. The optimal intensity of glucose control in older adults with diabetes remains uncertain. We sought to estimate the risk of mortality by HbA1c levels among older adults with and without diabetes. RESEARCH DESIGN AND METHODS We analyzed data from adults aged ≥65 years (n = 7,333) from the Third National Health and Nutrition Examination Survey (NHANES III) (1998–1994) and Continuous NHANES (1999–2004) and their linked mortality data (through December 2011). Cox proportional hazards models were used to examine the relationship of HbA1c with the risk of all-cause and cause-specific (cardiovascular disease [CVD], cancer, and non-CVD/noncancer) mortality, separately for adults with diabetes and without diabetes. RESULTS Over a median follow-up of 8.9 years, 4,729 participants died (1,262 from CVD, 850 from cancer, and 2,617 from non-CVD/noncancer causes). Compared with those with diagnosed diabetes and an HbA1c 8.0%. HRs were 1.6 (95% CI 1.02, 2.6) and 1.8 (95% CI 1.3, 2.6) for HbA1c 8.0–8.9% and ≥9.0%, respectively (P for trend 6.5% had a 1.3 (95% CI 1.03, 1.8) times greater risk of all-cause mortality compared with participants without diabetes and HbA1c 5.0–5.6%. CONCLUSIONS An HbA1c >8.0% was associated with increased risk of all-cause and cause-specific mortality in older adults with diabetes. Our results support the idea that better glycemic control is important for reducing mortality; however, in light of the conflicting evidence base, there is also a need for individualized glycemic targets for older adults with diabetes depending on their demographics, duration of diabetes, and existing comorbidities.

IntroductionMitochondrial DNA copy number (mtDNA-CN) is a measure of mitochondrial dysfunction and is associated with diabetes in experimental models. To explore the temporality of mitochondrial dysfunction and diabetes, we estimated the prevalent and incident association of mtDNA-CN and diabetes.Research design and methodsWe assessed the associations of mtDNA-CN measured from buffy coat with prevalent and incident diabetes, stratified by race, in 8954 white and 2444 black participants in the Atherosclerosis Risk in Communities (ARIC) study, an observational cohort study. Follow-up for incident analyses was complete through visit 6, 2016.ResultsMean age at mtDNA-CN measurement was 57 years and 59% were female. Prevalence of diabetes at time of mtDNA-CN measurement was higher in blacks (563/2444, 23%) than whites (855/8954, 10%). The fully adjusted odds of prevalent diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.05 (95% CI 0.74 to 1.49) among black and 1.49 (95% CI 1.20 to 1.85) among white participants. Over a median follow-up time of 19 years (Q1, Q3: 11, 24 years), we observed 617 incident diabetes cases among 1744 black and 2121 cases among 7713 white participants free of diabetes at baseline. The fully adjusted hazard of incident diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.07 (95% CI 0.84 to 1.38) among black and 0.97 (95% CI 0.86 to 1.10) among white participants.ConclusionsLower mtDNA-CN in buffy coat was associated with prevalent diabetes in white but not black ARIC participants. Lower mtDNA-CN was not associated with incident diabetes over 20 years of follow-up in whites or blacks.

CKD is a common complication in people with diabetes ([1][1]) and contributes to approximately half of all incident cases of ESKD in the developed world ([2][2]). CKD occurs in approximately 40% of people with type 2 diabetes ([3][3]); given the health-related effects of CKD, there is great need for

People with diabetes are at a higher risk of atherosclerotic cardiovascular disease (ASCVD) compared with those without diabetes. Though aspirin has been shown to have an overall net clinical benefit when used for secondary prevention of ASCVD in people with and without diabetes, the evidence for primary prevention, especially in those with diabetes, remains inconsistent. In this article, we review the latest studies examining the risks and benefits of aspirin use for primary prevention of ASCVD in adults with diabetes, discuss key aspects in assessing the risk-benefit ratio of aspirin use for primary prevention of ASCVD, and summarize current guidelines from professional societies on aspirin use for primary prevention in adults with diabetes. In the general population, past studies have shown no difference in the beneficial effect of aspirin for primary cardiovascular disease prevention by diabetes status. However, several randomized controlled studies and meta-analyses in adults with diabetes have shown lack of net clinical benefit of aspirin use for primary prevention of ASCVD. The recent ASCEND trial documented cardiovascular benefit of aspirin for primary prevention in adults with diabetes but suggested that the increased risk of bleeding may outweigh the cardiovascular benefit. The decision to initiate aspirin for primary prevention of ASCVD must be considered carefully on an individual basis to balance the cardiovascular benefit and bleeding risk in all patients, especially those with diabetes. A multifactorial approach that focuses on managing ASCVD risk factors such as hypertension, dyslipidemia, dysglycemia, and smoking is recommended in all patients. More research is needed to identify subgroups of people with diabetes who are more likely to benefit from aspirin use for primary prevention of ASCVD and develop better antithrombotic strategies that shift the risk-benefit balance toward an overall net clinical benefit.

BACKGROUND: Identifying reliable predictors of long-term weight loss could lead to improved weight management. OBJECTIVE: To identify predictors. DESIGN: The Diabetes Prevention Program (DPP) was a randomized controlled trial that compared weight loss using placebo, intensive lifestyle intervention, or metformin, and its Outcomes Study (DPPOS) observed patients after the masked treatment phase ended. SETTING: 27 DPP/DPPOS clinics. PARTICIPANTS: Of the 3234 randomized participants, 1066 lost ≥ 5% of their baseline weight during the first year and have been followed for 15 years. MEASUREMENTS: Treatment assignment, personal characteristics, and weight. RESULTS: After 1 year, 289 (28.5%) metformin participants, 640 (62.6%) intensive lifestyle participants, and 137 (13.4%) placebo participants, achieved ≥ 5% weight loss. After the masked treatment phase ended, the mean (95% CI) amount of weight loss relative to baseline that was maintained between years 6 and 15 was 6.2% (5.2, 7.2) for metformin participants, 3.7% (3.1, 4.4) for intensive lifestyle participants, and 2.8% (1.3, 4.4) for placebo participants. Independent predictors of long-term weight loss included greater weight loss during the first year in all study groups, older age and continued use of metformin in the metformin group, older age and not having diabetes or a family history of diabetes in the intensive lifestyle group, and higher baseline fasting plasma glucose in the placebo group. LIMITATION: Post-hoc analysis. Nonrandomized subsets of randomized groups examined after year 1. CONCLUSION: Among those with ≥ 5% 1-year weight loss, the group originally randomized to metformin had the greatest success with weight loss during years 6–15. Older age and the amount of initial weight loss were the most consistent predictors for maintaining long-term weight loss. PRIMARY FUNDING SOURCE: National Institutes of Health. Trial Registration: ClinicalTrials.gov and .

CONTEXT: Despite sex differences in chronic kidney disease (CKD) onset and progression, it is unclear whether endogenous sex hormones are associated with kidney function in persons without CKD. DESIGN AND METHODS: We conducted a secondary analysis of the Diabetes Prevention Program (DPP) and its follow-up observational study, the DPP Outcomes Study, over 11 years. Participants included overweight and glucose-intolerant men (n = 889) and pre- and postmenopausal women (n = 1281) not using exogenous sex hormones and whose urine albumin-to-creatinine ratio (ACR) was

Background: Among African Americans (AAs), attaining higher levels of American Heart Association (AHA) ideal cardiovascular health (Life&rsquo, s Simple 7 [LS7]) is associated with lower risk of diabetes and cardiovascular disease (CVD). We previously showed that aldosterone is associated with higher risk of diabetes and CVD in AAs. Thus, we investigated the association of LS7 metrics with aldosterone in the Jackson Heart Study (JHS). Methods: Ideal metrics were defined by AHA 2020 goals for health behaviors (smoking, dietary intake, physical activity, and body mass index) and health factors (total cholesterol, blood pressure, and fasting glucose). The number of ideal LS7 metrics attained at baseline were summed into a continuous score (0&ndash, 7) and categorical groups (Poor: 0&ndash, 1, Intermediate: 2&ndash, 3, and Ideal: &ge, 4 ideal LS7 metrics). Multivariable linear regression was used. Results: Among 4,095 JHS participants (mean age 55 &plusmn, 13 years, 65% female), median serum aldosterone was 4.90, 4.30, and 3.70 ng/dL in the poor (n = 1132), intermediate (n = 2288) and ideal (n = 675) categories respectively. Aldosterone was 15% [0.85 (0.80, 0.90)] and 33% [0.67 (0.61, 0.75)] lower in the intermediate and ideal LS7 categories compared to the poor LS7 category. Each additional LS7 metric attained on continuous LS7 score (0&ndash, 7) was associated with an 11% [0.89 (0.86, 0.91)] lower aldosterone level with variation by sex with women having a 15% lower aldosterone vs. 5% in men. Conclusions: Higher attainment of ideal LS7 metrics was associated with lower serum aldosterone among AAs with a greater magnitude of association among women compared to men.

Background We investigated the associations of glycemic markers (HbA 1C [hemoglobin A 1C ], fasting plasma glucose, and insulin resistance—homeostasis model assessment of insulin resistance) with subclinical cardiovascular disease (CVD) among blacks. Methods We included 4303 community-dwelling blacks (64% women; mean age, 54.5 years) without prevalent CVD. Subclinical CVD was defined as ≥1 of the following: any coronary artery calcification (CAC), elevated carotid intima-media thickness (cIMT), left ventricular (LV) hypertrophy, LV ejection fraction 1C , and homeostasis model assessment of insulin resistance) with subclinical CVD measures were adjusted for traditional CVD risk factors. Results Each 1% increment in HbA 1C was associated with higher odds of CAC, abnormal cIMT, and subclinical CVD (all P 1C categories (all P P P P P Conclusions Among blacks, glycemic markers were differentially associated with various measures of subclinical CVD.

Context:Total pancreatectomy with islet auto transplantation (TPIAT) is a treatment for medically refractory chronic pancreatitis that can prevent postsurgical diabetes in some patients. Predictors of insulin independence are needed for appropriate patient selection and counseling.Objective:To explore glycemic predictors of insulin independence after TPIAT.Design:A prospective cohort of patients.Methods:We investigated 34 patients undergoing TPIAT from 2011-2016 at Johns Hopkins Hospital, all had a 75-g oral glucose tolerance test (OGTT) administered prior to their TPIAT. The primary outcome was insulin independence 1 year after TPIAT.Results:Ten of 34 (29%) patients were insulin independent 1 year after TPIAT. All patients with impaired fasting glucose and/or impaired glucose tolerance preoperatively were insulin dependent at 1 year. In age-adjusted regression analyses, fasting glucose ≤ 90 mg/dL [odds ratio (OR) = 6.56; 1.11 to 38.91; P = 0.04], 1-hour OGTT glucose ≤ 143 mg/dL (OR = 6.65; 1.11 to 39.91; P = 0.04), and 2-hour OGTT glucose ≤ 106 mg/dL (OR = 11.74; 1.46 to 94.14; P = 0.02) were significant predictors of insulin independence. In receiver operating characteristic analyses, homeostatic model assessment of β-cell function (HOMA-β) was the most robust predictor of insulin independence [area under the curve (AUC) = 0.88; 0.73 to 1.00].Conclusions:Normal preoperative glucose status and lower fasting and postchallenge OGTT glucose values are significant predictors of insulin independence after TPIAT. Higher islet function (HOMA-β) was the strongest predictor. OGTT testing may be a useful tool to aid in patient counseling prior to TPIAT and should be further investigated.

Background There is a need for continued surveillance of diabetes-related functional disability. In the present study, we examined associations between diabetes, hyperglycemia, and the burden of functional disability in a community-based population. Methods A cross-sectional analysis was conducted of 5035 participants who attended Visit 5 (2011–13) of the Atherosclerosis Risk in Communities study. Functional disability was dichotomously defined by any self-reported difficulty performing 12 tasks essential to independent living grouped into four functional domains. Associations of diagnosed diabetes (via self-report) and undiagnosed diabetes and prediabetes (via HbA1c) with functional disability were evaluated using Poisson regression. Results Participants had a mean age of 75 years, 42 % were male, 22 % were Black, and 31 % had diagnosed diabetes. Those with diagnosed diabetes had a significantly greater burden of functional disability than those without diabetes, even after adjustment for demographics, health behaviors, and comorbidities: prevalence ratios (95 % confidence intervals) were 1.24 (1.15, 1.34) for lower extremity mobility, 1.14 (1.07, 1.21) for general physical activities, 1.33 (1.16, 1.52) for instrumental activities of daily living (ADL), and 1.46 (1.24, 1.73) for ADL (all P 0.05). Conclusions Among older adults, the burden of functional disability associated with diabetes was not entirely explained by known risk factors, including comorbidities. Hyperglycemia below the threshold for the diagnosis of diabetes was not associated with disability. Research into effective strategies for the prevention of functional disability among older adults with diabetes is needed.

BackgroundCardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) in patients without cardiovascular or renal disease, a majority of newly diagnosed patients with type 2 diabetes often excluded from clinical trials on this association, is poorly understood. Thus, we investigate the risk of major adverse cardiovascular events (MACE) associated with DPP-4i in low-risk patients with diabetes.MethodsUsing a new-user retrospective cohort derived from IBM MarketScan Commercial Claims and Encounters (2010-2015), we identified patients aged 35-65 with type 2 diabetes, without cardiovascular or renal disease, initiating DPP-4i, sulfonylureas, or metformin. Primary composite outcome of time to first MACE was defined as the first of any of the following: myocardial infarction, cardiac arrest, coronary artery bypass graft, coronary angioplasty, heart failure, and stroke. Secondary outcomes were time to first heart failure, acute myocardial infarction, and stroke. We compared outcomes for DPP-4i versus sulfonylurea and DPP-4i versus metformin using propensity score weighted Cox proportional hazards, adjusting for demographics, baseline comorbidities, concomitant medications, and cumulative exposure.ResultsOf 445,701 individuals, 236,431 (53.0%) were male, median age was 51 (interquartile range: [44, 57]), 30,267 (6.79%) initiated DPP-4i, 52,138 (11.70%) initiated sulfonylureas, and 367,908 (82.55%) initiated metformin. After adjustment, DPP-4i was associated with lower risk of MACE than sulfonylurea (adjusted hazard ratio (aHR) = 0.87; 95% confidence interval (CI): 0.78-0.98), and similar risk to metformin (aHR = 1.07; 95% CI: 0.97-1.18). Risk for acute myocardial infarction (aHR = 0.70; 95% CI: 0.51-0.96), stroke (aHR = 0.57; 95% CI: 0.41-0.79), and heart failure (aHR = 0.57; 95% CI: 0.41-0.79) with DPP-4i was lower compared to sulfonylureas.ConclusionOur findings show that for this cohort of low-risk patients newly treated for type 2 diabetes, DPP-4i exhibited 13% lower risk for MACE compared to sulfonylureas and similar risk for MACE compared to metformin, suggesting DPP-4i is a low cardiovascular risk option for low-risk patients initiating antihyperglycemic treatment.

Aging is associated with changes in body composition, including both fat gain and muscle loss beginning in middle age, and is associated with increased risk of type 2 diabetes. Moreover, changes in fat distribution take place in adults as they age and may contribute to the increased risk of type 2 diabetes. Recent literature has shown differences in the age-related changes in body composition by diabetes status suggesting that some of these changes might not only be a risk factor of the development of diabetes but could also be a consequence of the disease. In this article, we review the current evidence on body composition changes that take place in adults after the diagnosis of type 2 diabetes and compare them to those observed in adults without diabetes as they age. We also review the effect of various lifestyle, pharmacological, and surgical treatments that lower blood glucose on body composition in adults with type 2 diabetes.

While there has been a growing utilization of total pancreatectomy with islet autotransplantation (TPIAT) for patients with medically refractory chronic pancreatitis over the past few decades, there remains a lack of consensus clinical guidelines to inform the counseling and management of patients undergoing TPIAT. In this article, we review the current clinical practice and published experience of several TPIAT centers, outline key aspects in managing patients undergoing TPIAT, and discuss the glycemic outcomes of this procedure. Aiming for lower inpatient glucose targets immediately after surgery (usually 100–120 mg/dl), maintaining all patients on subcutaneous insulin for at least 3 months to “rest” islets before an attempt is made to wean insulin, and close outpatient endocrinology follow-up after TPIAT particularly in the first year is common and related to better outcomes. Although TPIAT procedures and glycemic outcomes may differ across surgical centers, overall, approximately one third of patients are insulin independent at 1 year after TPIAT. Higher islet yield and lower preoperative glucose levels are among the strongest predictors of short-term post-operative insulin independence. Beyond 1 year post-operatively, the clinical management and long-term glycemic outcomes of patients after TPIAT are more variable. A multidisciplinary approach is essential in optimizing the preoperative, inpatient, and post-operative management and counseling of patients about the expected glycemic outcomes after surgery. Consensus guidelines for the clinical management of diabetes after TPIAT and harmonization of data collection protocols among TPIAT centers are needed to address the current knowledge gaps in clinical care and research and to optimize glycemic outcomes after TPIAT.

Background Serum cortisol levels have been associated with type 2 diabetes (T2D). However, the role of cortisol in glycemia and T2D is not fully elucidated among African Americans (AAs). We hypothesized that among AAs morning serum cortisol would be positively associated with glycemic measures and prevalent T2D. Methods We examined the cross-sectional association of baseline morning serum cortisol with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-β), and prevalent T2D in the Jackson Heart Study. Linear regression models were used to examine the association of log-transformed cortisol with glycemic traits, stratified by T2D status. Logistic regression was used to examine the association of log-transformed cortisol with prevalent T2D. Models were adjusted for age, sex, education, occupation, systolic blood pressure, waist circumference, physical activity, smoking, beta-blocker/hormone replacement medications and cortisol collection time. Results Among 4,206 AAs (mean age 55 ± 13 years, 64% female), 19% had prevalent T2D. A 100% increase in cortisol among participants without diabetes was associated with 2.7 mg/dL (95% CI: 2.0, 3.3) higher FPG and a 10.0% (95% CI: -14.0, -6.0) lower HOMA-β with no significant association with HbA1c or HOMA-IR. In participants with diabetes, a 100% increase in cortisol was associated with a 23.6 mg/dL (95% CI: 13.6, 33.7) higher FPG and a 0.6% (95% CI: 0.3, 0.9) higher HbA1c. Among all participants, quartile 4 vs. 1 of cortisol was associated with a 1.26-fold (95% CI: 1.75, 2.91) higher odds of prevalent T2D. Conclusion Higher morning serum cortisol was associated with higher FPG and lower β-cell function among participants without T2D and higher FPG and HbA1c in participants with diabetes. Among all participants, higher cortisol was associated with higher odds of T2D. These findings support a role for morning serum cortisol in glucose metabolism among AAs.

Whether endogenous sex hormones are associated with chronic kidney disease (CKD) is not known. We conducted a secondary analysis of longitudinal data from the DPPOS, the follow-up study of the Diabetes Prevention Program (DPP), a randomized trial of diabetes prevention that assigned participants to placebo, metformin, or lifestyle intervention. This analysis included overweight and glucose-intolerant men (n=889) and women (n=1281) not using exogenous sex hormones who had urine albumin-to-creatinine ratio [ACR] < 30 mg/g and normal estimated glomerular filtration ratio [eGFR] ≥ 60 ml/min/1.73 m2. Sex hormones (dehydroepiandrosterone [DHEAS], dihydrotestosterone, testosterone, estradiol, estrone, and sex hormone binding globulin [SHBG]) were measured at baseline. CKD was defined as incident low eGFR and/or albuminuria ACR ≥ 30 mg/g. eGFR and ACR were measured annually over 11 years of DPPOS follow-up. Multivariable Cox regression models adjusted for eGFR and log-ACR, age, race/ethnicity, body mass index, blood pressure, insulin resistance, high-density lipoprotein, C-reactive protein, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers at baseline. At baseline, the mean (SD) of eGFR was 94 (15) ml/min/1.73 m2, and the median (IQR) of ACR was 4.5 (3.3-7.6) mg/g. During the follow-up period, 187 men (24.6%) and 263 women (24.2%) had incident albuminuria and 136 men (17.9%) and 123 women (11.3%) had incident low eGFR. Fifty-four (7.1%) of men and 43 (3.9%) of women had both abnormalities. Among men, higher SHBG was associated with lower risk of low eGFR (pooled hazard ratio [HR] per SD, 95% confidence interval [CI]: 0.73 [0.57, 0.9], p=0.01) and lower risk for CKD (pooled HR per SD 95% CI: 0.78 [0.64, 0.95], p=0.01). No significant associations were observed among women. We conclude that among overweight glucose-intolerant men, higher SHBG was associated with reduced risk of CKD. Disclosure C. Kim: None. A. Ricardo: None. E.J. Boyko: None. C.A. Christophi: None. M. Temprosa: Other Relationship; Self; Merck KGaA. K. Watson: None. X. Pi-Sunyer: None. R. Rastogi Kalyani: None. D. Research Group: None.

Background: Immigration and the process of acculturation can lead to behavioral changes that exacerbate or reduce diabetes development. We investigated the association between acculturation strategies and cardiometabolic risk (CMR) factors among South Asian (SA) immigrants living in the U.S. Methods: Participants (n=849) in the Mediators of Atherosclerosis in SA Living in America (MASALA) study were categorized into 3 acculturation strategy classes based on self-reported questionnaire responses: separation (preference for SA culture), assimilation (preference for U.S. culture), and integration (similar preference for SA and U.S. cultures). Adjusted linear regression models examined associations of acculturation strategies with fasting and 2 hour glucose, lipids, blood pressure, waist circumference (WC), and body composition. Results: Overall, 22.4, 19.6, and 58% of men and 23.7, 26.2, and 50.1% of women were in separation, assimilation, and integration classes; respectively. Participants in the assimilation class had significantly lower levels of obesity, 2 hour glucose, insulin, HOMA-IR, triglycerides (TG), visceral fat, and higher HDL than those in the separation class (all p Conclusion: SA women who employed an assimilation strategy had a more favorable CMR profile compared to women using a separation strategy. Future research should investigate the behavioral pathways linking acculturation strategies with CMR and potential incorporation into prevention interventions. Disclosure M. Al-Sofiani: None. S.J. Langan: None. A.M. Kanaya: None. N.R. Kandula: None. B. Needham: None. C. Kim: None. D.M. Becker: None. D. Vaidya: None. S. Golden: None. C. Lee: None. R. Rastogi Kalyani: None.

Weight loss prevents progression to diabetes but long term effects on lean mass are unknown. We determined if intensive lifestyle modification (ILS), metformin (MET) or placebo (PLB) treatment in the Diabetes Prevention Program (DPP) had differential effects on appendicular lean mass (ALM) and sarcopenic-obesity (SO) ∼16 years after DPP randomization in the DPP Outcome Study (DPPOS). During DPP, 3234 participants at high risk for diabetes were randomized to ILS, MET or PLB; 2779 continued in DPPOS and were offered modified group ILS. During DPPOS, ILS was offered additional lifestyle reinforcement semi-annually and MET received unmasked metformin. This analysis includes 1374 DPPOS participants who had dual-energy X-ray absorptiometry scans at year 12 for ALM (sum of lean mass in arms and legs). Low ALM was defined as ALM/BMI 30. Prevalence of low ALM and SO was compared across the 3 groups using Pearson’s chi-squared test. Logistic regression models determined the associations between treatment and low ALM or SO and between weight loss and low ALM or SO. Mean age at Y12 was 66.5 (±9.5) years. Mean time since DPP baseline was 15.6 (±0.7) years. Weight loss (DPP baseline to DPPOS Y12) did not differ by group (-4.4 kg ILS; -3.5 kg MET; -3.1 kg PLB; p=0.114). Prevalence of low ALM differed by group in men (35.7% ILS, 28.3% MET, 22.5% PLB; p=0.049) but not women (20.9% ILS, 24.8% MET, 24.1% PLB; p=0.482). In men, low ALM prevalence was higher in ILS compared with PLB (P=0.024) but not in MET vs. PLB. Prevalence of SO did not differ across groups in men (23.1% ISL, 22.0% MET, 14.1% PLB; p=0.112) or women (17.3% ILS, 20.9% MET, 20.3% PLB; p=0.492). SO prevalence was not different in ILS vs. PLB or in MET vs. PLB in men or women. More weight loss was associated with higher risk of low ALM and SO in women and men (p Disclosure A.V. Schwartz: None. Q. Pan: None. H.P. Hazuda: None. E. Horton: Advisory Panel; Self; PTS Diagnostics, Merck & Co., Inc., Theracos, Inc.. M.A. Hoskin: None. R. Rastogi Kalyani: None. W.C. Knowler: None. A. Kriska: None. M. Schlögl: None. H. Florez: Advisory Panel; Self; Sanofi. D. Research Group: None.

CONTEXT: Previous studies have suggested less cardioprotective benefit of aspirin in adults with diabetes, raising concerns about “aspirin resistance” and potentially reduced effectiveness for prevention of cardiovascular disease (CVD). OBJECTIVE: To examine differences in platelet response to aspirin by diabetes status. DESIGN, SETTING, PARTICIPANTS: We examined platelet response before and after aspirin (81 mg/day for 14 days) in 2113 adults (175 with diabetes, 1,938 without diabetes), in the Genetic Study of Aspirin Responsiveness cohort, who had family history of early-onset CVD. MAIN OUTCOME MEASURES: In vivo platelet activation (urinary thromboxane B2), in vitro platelet aggregation to agonists (arachidonic acid, adenosine diphosphate, collagen), and platelet function analyzer-100 closure time. RESULTS: Although adults with diabetes had higher in vivo platelet activation before aspirin, the reduction in in vivo platelet activation after aspirin was similar in those with vs without diabetes. Likewise, the reduction in multiple in vitro platelet measures was similar after aspirin by diabetes status. In regression analyses adjusted for age, sex, race, BMI, smoking, platelet counts, and fibrinogen levels, in vivo platelet activation remained higher in adults with vs without diabetes after aspirin (P = 0.04), but this difference was attenuated after additional adjustment for preaspirin levels (P = 0.10). No differences by diabetes status were noted for any of the in vitro platelet measures after aspirin in fully adjusted models that also accounted for preaspirin levels. CONCLUSIONS: In vitro platelet response to aspirin does not differ by diabetes status, suggesting no intrinsic differences in platelet response to aspirin. Instead, factors extrinsic to platelet function should be investigated to give further insights into aspirin use for primary prevention in diabetes.

Diabetes is more common in older adults, has a high prevalence in long-term care (LTC) facilities, and is associated with significant disease burden and higher cost. The heterogeneity of this population with regard to comorbidities and overall health status is critical to establishing personalized goals and treatments for diabetes. The risk of hypoglycemia is the most important factor in determining glycemic goals due to the catastrophic consequences in this population. Simplified treatment regimens are preferred, and the sole use of sliding scale insulin (SSI) should be avoided. This position statement provides a classification system for older adults in LTC settings, describes how diabetes goals and management should be tailored based on comorbidities, delineates key issues to consider when using glucose-lowering agents in this population, and provides recommendations on how to replace SSI in LTC facilities. As these patients transition from one setting to another, or from one provider to another, their risk for adverse events increases. Strategies are presented to reduce these risks and ensure safe transitions. This article addresses diabetes management at end of life and in those receiving palliative and hospice care. The integration of diabetes management into LTC facilities is important and requires an interprofessional team approach. To facilitate this approach, acceptance by administrative personnel is needed, as are protocols and possibly system changes. It is important for clinicians to understand the characteristics, challenges, and barriers related to the older population living in LTC facilities as well as the proper functioning of the facilities themselves. Once these challenges are identified, individualized approaches can be designed to improve diabetes management while lowering the risk of hypoglycemia and ultimately improving quality of life.

Objective. Previous observational studies suggest higher rates of vestibular dysfunction among patients with type 2 diabetes mellitus (DM) compared with those without diabetes. This study aims to functionally localize vestibular dysfunction in adults with type 2 DM. Study Design. Prospective cohort study. Setting. Tertiary academic medical center. Subjects and Methods. Adults 50 years of age and older with 10-year history of type 2 DM were recruited (December 2011–February 2013, n = 25). Vestibular function was assessed by cervical and ocular vestibular-evoked myogenic potentials (VEMPs), testing the saccule and utricle, respectively. Head thrust dynamic visual acuity testing assessed semicircular canal (SCC) function in all canal planes. Results were compared with nondiabetic age-matched controls (n = 25). Results. Subjects were 64.7 6 7.6 years old, were 40% female, and had a mean hemoglobin A1c of 8.3% 6 1.7%. SCC dysfunction was more common than otoconial organ dysfunction, with 70% of subjects with DM demonstrating impaired performance of at least 1 SCC (DlogMAR 0.18) and 50% demonstrating otoconial organ impairment (absent ocular VEMP and/or cervical VEMP). Adults with type 2 DM had poorer lateral and superior SCC performance (P \.05) but similar posterior SCC performance compared with controls (P = .16). Both cervical VEMP peak-to-peak amplitude and ocular VEMP n1 amplitude were also decreased with diabetes (P \.01). Conclusion. Adults with type 2 DM have poorer performance on tests of vestibular function related to both SCC and otoconial organ function compared with nondiabetic agematched adults. Future studies are needed to better understand the relationship between vestibular function and functional disability in persons with diabetes.

Whether individuals with insulin resistance (IR) but without criteria for diabetes exhibit reduced mitochondrial oxidative capacity is unclear; addressing this question could guide research for new therapeutics. We investigated 248 participants without diabetes from the Baltimore Longitudinal Study of Aging (BLSA) to determine whether impaired mitochondrial capacity is associated with prediabetes, IR, and duration and severity of hyperglycemia exposure. Mitochondrial capacity was assessed as the postexercise phosphocreatine recovery time constant (τPCr) by 31P-magnetic resonance spectroscopy, with higher τPCr values reflecting reduced capacity. Prediabetes was defined using the American Diabetes Association criteria from fasting and 2-h glucose measurements. IR and sensitivity were calculated using HOMA-IR and Matsuda indices. The duration and severity of hyperglycemia exposure were estimated as the number of years from prediabetes onset and the average oral glucose tolerance test (OGTT) 2-h glucose measurement over previous BLSA visits. Covariates included age, sex, body composition, physical activity, and other confounders. Higher likelihood of prediabetes, higher HOMA-IR, and lower Matsuda index were associated with longer τPCr. Among 205 participants with previous OGTT data, greater severity and longer duration of hyperglycemia were independently associated with longer τPC. In conclusion, in individuals without diabetes a more impaired mitochondrial capacity is associated with greater IR and a higher likelihood of prediabetes.

Type 2 diabetes (T2DM) in a first-degree relative is a risk factor for incident diabetes. Americans of African ancestry (AA) have higher rates of T2DM than Americans of European ancestry (EA). Thus, we aimed to determine whether the presence, number and kinship of affected relatives are associated with race-specific T2DM incidence in a prospective study of participants from the Genetic Study of Atherosclerosis Risk (GeneSTAR), who underwent baseline screening including a detailed family history.Nondiabetic healthy siblings (n=1405) of patients with early-onset coronary artery disease (18-59 years) were enrolled (861 EA and 544 AA) and followed for incident T2DM (mean 14±6 years).Baseline age was 46.2±7.3 years and 56% were female. T2DM occurred in 12.3% of EA and 19.1% of AA. Among EA, 32.6% had ≥1 affected first-degree relatives versus 53.1% in AA, P0.0001. In fully adjusted Cox proportional hazard analyses, any family history was related to incident T2DM in EA (HR=2.53, 95% CI: 1.58-4.06) but not in AA (HR=1.01, 0.67-1.53). The number of affected relatives conferred incremental risk of T2DM in EA with HR=1.82 (1.08-3.06), 4.83 (2.15-10.85) and 8.46 (3.09-23.91) for 1, 2, and ≥3 affected, respectively. In AA only ≥3 affected increased risk (HR=2.45, 1.44-4.19). Specific kinship patterns were associated with incident T2DM in EA but not in AA.The presence of any first-degree relative with T2DM does not discriminate risk in AA given the high race-specific prevalence of diabetes. Accounting for the number of affected relatives may more appropriately estimate risk for incident diabetes in both races.

Obesity, particularly central adiposity, is a well-established risk factor for cardiovascular disease (CVD). Waist circumference (WC) is measured in numerous epidemiologic studies as a relatively simple indicator of central adiposity. However, recently, investigators have considered a measure that takes height into consideration, waist-to-height ratio (WHtR) as a more sensitive predictor of CVD. A limited number of studies have examined the association between various measures of central adiposity and obesity with CVD, but there is a dearth of information on this topic focused specifically on African American adults. Given the high rates of cardiovascular disease and metabolic risk factors in this population, it is important to develop validated, easy-to-measure indicators of CVD risk for clinical use. Data from 4758 African American adults participating in the baseline visit of the Jackson Heart Study with available risk factor data were examined, with three measures of body habitus (body mass index (BMI), WC, and WHtR) and five CVD risk factors (HDL and LDL cholesterol, triglycerides, diabetes, and hypertension), the latter also categorized into multiple (2+) risk factors present. C-statistics for waist circumference (WC), BMI, and WHtR were computed and compared for each model to assess their discriminant abilities. WHtR was a stronger correlate of HDL cholesterol, triglycerides, diabetes, hypertension, and multiple risk factors compared to BMI, and was a stronger correlate of HDL cholesterol when compared to WC. These data indicate that, for African American adults, WHtR may be more appropriate measure to identify those at elevated risk for CVD.

Diabetes increases mortality by two- to fourfold from atherosclerosis-related causes, including coronary artery disease, stroke, and peripheral artery disease (1). There is a paucity of population-based data on subclinical atherosclerotic disease in arterial beds other than the coronary arteries in persons with diabetes (2). In the Jackson Heart Study (JHS), we examined the association of diabetes with abdominal aortic calcification (AAC) among African Americans. Among included individuals ( n = 1,664), the mean age was 57 (± 11) years, 69% were female, and 18.3% had diabetes (based on fasting blood glucose [FBG], HbA1c, use of glucose-lowering medications, or physician diagnosis). The median AAC and coronary artery calcification (CAC) scores were 904.15 (interquartile range 0–1093.10) and 0 (0–96.19), respectively. The prevalence of any AAC or CAC was 69% and 49%, respectively. Individuals with diabetes were older, had higher BMI, had higher systolic blood pressure and prevalence of hypertension, had lower …

Description: The American Diabetes Association (ADA) annually updates the Standards of Medical Care in Diabetes to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of patients with diabetes. Methods: For the 2017 Standards, the ADA Professional Practice Committee updated previous MEDLINE searches performed from 1 January 2016 to November 2016 to add, clarify, or revise recommendations based on new evidence. The committee rates the recommendations as A, B, or C, depending on the quality of evidence, or E for expert consensus or clinical experience. The Standards were reviewed and approved by the Executive Committee of the ADA Board of Directors, which includes health care professionals, scientists, and laypersons. Feedback from the larger clinical community informed revisions. Recommendations: This synopsis focuses on recommendations from the 2017 Standards about pharmacologic approaches to glycemic treatment of type 2 diabetes.

Background Studies exploring the association between insulin resistance ( IR ) and cardiovascular disease in blacks have not been conclusive, especially for coronary heart disease ( CHD ). The McAuley index and homeostasis model assessment of IR ( HOMA ‐ IR ) perform differently in predicting cardiovascular disease. We investigated this association in the Jackson Heart Study, a large longitudinal cohort of blacks. Methods and Results IR was estimated for 3565 participants without diabetes mellitus and cardiovascular disease at baseline using the McAuley index and HOMA ‐ IR , and their associations with incident CHD and stroke (composite outcome) were compared. A lower McAuley index and higher HOMA ‐ IR are indicative of IR . Cox regression analysis was used to estimate adjusted hazard ratios for incident CHD and/or stroke. There were 158 events (89 CHD ‐only, 58 stroke‐only, and 11 CHD /stroke) over a median follow‐up of 8.4 years. After adjustment for demographic factors, the risk of the composite outcome decreased with each SD increase in the McAuley index (hazard ratio 0.80; 95% CI : 0.67–0.96), with no attenuation after further accounting for CHD and stroke risk factors. When considered individually, McAuley index and HOMA ‐ IR were associated with CHD (hazard ratio 0.71, 95% CI : 0.55–0.92 and hazard ratio 1.33, 95% CI : 1.03–1.72, respectively), but not stroke risk. The log HOMA ‐ IR and CHD association was present in men, but not in women ( P interaction =0.01). Conclusions Both HOMA‐IR and the McAuley index demonstrate strong associations with CHD but not stroke risk in blacks. The log HOMA ‐ IR and CHD association was present in men, but not in women.

OBJECTIVE Persons with diabetes have accelerated muscle loss compared with their counterparts. The relationship of hyperglycemia per se to declines in muscle function has not been explored yet has implications for developing appropriate intervention strategies to prevent muscle loss. RESEARCH DESIGN AND METHODS We examined 984 participants aged 25–96 years in the Baltimore Longitudinal Study of Aging (2003–2011) with HbA1c, knee extensor strength (isokinetic dynamometer), and lean body mass (DEXA) measured at baseline. Participants had repeated measurements up to 7.5 years later. Muscle quality was defined as knee extensor strength/leg lean mass. Participants were categorized by HbA1c quartile ( RESULTS Muscle strength and quality were significantly lower across HbA1c quartiles (both P < 0.001), without differences in muscle mass at baseline. Comparing highest versus lowest HbA1c quartiles and adjusting for age, race, sex, weight, and height, strength was significantly lower (−4.70 ± 2.30 N · m; P value trend = 0.02) and results were unchanged after adjustment for physical activity (P value trend = 0.045) but of borderline significance after additional adjustment for peripheral neuropathy (P value trend = 0.05). Adjusting for demographics, muscle quality was significantly lower (−0.32 ± 0.15 N · m/kg; P value trend = 0.02) in the highest versus lowest HbA1c quartiles, but differences were attenuated after adjusting for weight and height (−0.25 ± 0.15 N · m/kg; P value trend = 0.07). Muscle mass measures were similar across HbA1c quartiles. CONCLUSIONS Hyperglycemia is associated with persistently lower muscle strength with aging, but this effect may be mediated, at least in part, by peripheral neuropathy. Future studies should explore if better glycemic control can preserve muscle function in diabetes.

Summary The term sarcopenia refers to the loss of muscle mass that occurs with ageing. On the basis of study results showing that muscle mass is only moderately related to functional outcomes, international working groups have proposed that loss of muscle strength or physical function should also be included in the definition. Irrespective of how sarcopenia is defined, both low muscle mass and poor muscle strength are clearly highly prevalent and important risk factors for disability and potentially mortality in individuals as they age. Many chronic diseases, in addition to ageing, could also accelerate decrease of muscle mass and strength, and this effect could be a main underlying mechanism by which chronic diseases cause physical disability. In this Review, we address both age-related and disease-related muscle loss, with a focus on diabetes and obesity but including other disease states, and potential common mechanisms and treatments. Development of treatments for age-related and disease-related muscle loss might improve active life expectancy in older people, and lead to substantial health-care savings and improved quality of life.

OBJECTIVE Controversy exists about the coronary artery disease (CAD) risk conveyed by diabetes in young and middle-aged women. We investigated sex differences in CAD by diabetes status among healthy individuals with different underlying risks of heart disease. RESEARCH DESIGN AND METHODS We examined subjects aged RESULTS In the absence of diabetes, CAD rates were lower among women in GeneSTAR, MESA, and NHANES (4.27, 1.66, and 0.40/1,000 person-years, respectively) versus men (11.22, 5.64, and 0.88/1,000 person-years); log-rank P < 0.001 (GeneSTAR/MESA) and P = 0.07 (NHANES). In the presence of diabetes, CAD event rates were similar among women (17.65, 7.34, and 2.37/1,000 person-years) versus men (12.86, 9.71, and 1.83/1,000 person-years); all log-rank P values > 0.05. Adjusting for demographics, diabetes was associated with a significant four- to fivefold higher CAD rate among women in each cohort, without differences in men. In meta-analyses of three cohorts, additionally adjusted for BMI, smoking, hypertension, HDL, and non-HDL cholesterol, antihypertensive and cholesterol-lowering medication use, the hazard ratio of CAD in men versus women among nondiabetes was 2.43 (1.76–3.35) and diabetes was 0.89 (0.43–1.83); P = 0.013 interaction by diabetes status. CONCLUSIONS Though young and middle-aged women are less likely to develop CAD in the absence of diabetes, the presence of diabetes equalizes the risk by sex. Our findings support aggressive CAD prevention strategies in women with diabetes and at similar levels to those that exist in men.