Effects of metformin and intensive lifestyle interventions on the incidence of kidney disease in adults in the DPP/DPPOS.

AIMS: We analyzed the incidence of kidney disease in the Diabetes Prevention Program Outcomes Study (DPPOS) by originally randomized treatment group assignment: Intensive Lifestyle (ILS), Metformin (MET) or Placebo (PLB). METHODS: The current analyses used a time-to-event approach in which the primary outcome was kidney disease, ascertained as urine albumin-to-creatinine ratio (ACR) ≥ 3.39 mg/mmol (30 mg/g) or eGFR <45 mL/min/1.73m2, with confirmation required at the next visit, or adjudicated end-stage kidney disease (ESKD). RESULTS: At a median of 21 years following randomization in DPP, diabetes development was reduced in both the ILS (HR 0.73 [95%CI = 0.62, 0.85]) and MET groups (HR 0.85 [0.73, 0.99]) compared to the PLB group. Although risk for developing the primary kidney disease outcome was higher among those with incident diabetes compared to those without (HR 1.81 [1.43, 2.30]), it did not differ by intervention groups (ILS vs. PLB 1.02 (0.81, 1.29); MET vs. PLB 1.08 (0.86, 1.35). There was a non-significant metformin by age interaction (p = 0.057), with metformin being beneficial for kidney disease in the younger but potentially harmful in the older participants. CONCLUSIONS: Development of kidney disease was increased in participants who developed diabetes but did not differ by original treatment group assignment. CLINICAL TRIAL REGISTRATIONS: Diabetes Prevention Program (DPP) Clinical trial reg. no. NCT00004992 DPP Outcomes Study (DPPOS) Clinical trial reg. no. NCT0038727.

National Trends in the Achievement of Recommended Strategies for Stroke Prevention in U.S. Adults With Type 2 Diabetes, 2001-2018.

OBJECTIVE: To assess the national prevalence of and trends in achieving current guideline-recommended treatment goals and pharmacotherapies for primary and secondary prevention of stroke among U.S. adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We performed serial cross-sectional analyses in 4,834 adults aged ≥45 years with T2D who participated in the 2001-2018 National Health and Nutrition Examination Survey. With stratification by stroke history, we estimated the proportion of adults with T2D who achieved current guideline-recommended strategies for stroke prevention. Preventive strategies for stroke were benchmarked against diabetes care and cardiovascular risk reduction guidelines. RESULTS: Overall in 2001-2018, among those without stroke history, the proportion who achieved primary stroke prevention strategies ranged from 8.4% (95% CI 6.8-10.1) for aspirin/clopidogrel treatment in those with a higher cardiovascular disease risk to 80.5% (78.8-82.2) for nonsmoking. Among those with stroke history, the proportion who achieved secondary stroke prevention strategies ranged from 11.8% (8.7-14.8) for weight control to 80.0% (74.9-84.9) for glycemic control. From 2001 to 2018, among those without stroke history, there was a significant increase in statin therapy (Ptrend < 0.0001), smoking abstinence (Ptrend = 0.01), and ACE inhibitor/angiotensin receptor blocker treatment for hypertension (Ptrend = 0.04) but a substantial decline in weight control (Ptrend < 0.001). Among those with stroke history, only statin therapy (Ptrend = 0.01) increased significantly over time. CONCLUSIONS: During 2001-2018, the achievement of some current guideline-recommended strategies for stroke prevention among U.S. adults with T2D improved but remains a challenge overall. Efforts are needed to improve implementation of strategies for stroke prevention in this population.

Per- and polyfluoroalkyl substances and incident diabetes in midlife women: the Study of Women's Health Across the Nation (SWAN).

AIMS/HYPOTHESIS: Diabetogenic effects of per- and polyfluoroalkyl substances (PFAS) have been suggested. However, evidence based on prospective cohort studies is limited. We examined the association between serum PFAS concentrations and incident diabetes in the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS). METHODS: We included 1237 diabetes-free women aged 45-56 years at baseline (1999-2000) who were followed up to 2017. At each follow-up visit, women with incident diabetes were identified by the presence of one or more of the following conditions: (1) use of a glucose-lowering medication at any visit; (2) fasting glucose ≥7 mmol/l on two consecutive visits while not on steroids; and (3) any two visits with self-reported diabetes and at least one visit with fasting blood glucose ≥7 mmol/l. Serum concentrations of 11 PFAS were quantified by online solid-phase extraction-HPLC-isotope dilution-tandem MS. Seven PFAS with high detection rates (>96%) (n-perfluorooctanoic acid [n-PFOA], perfluorononanoic acid [PFNA], perfluorohexane sulfonic acid [PFHxS], n-perfluorooctane sulfonic acid [n-PFOS], sum of perfluoromethylheptane sulfonic acid isomers [Sm-PFOS], 2-[N-methyl-perfluorooctane sulfonamido] acetic acid [MeFOSAA] and 2-[N-ethyl-perfluorooctane sulfonamido] acetic acid) were included in data analysis. Cox proportional hazards models were used to compute HRs and 95% CIs. Quantile-based g-computation was used to evaluate the joint effects of PFAS mixtures. RESULTS: After adjustment for race/ethnicity, site, education, smoking status, alcohol consumption, total energy intake, physical activity, menopausal status and BMI, the HR (95% CI) comparing the lowest with the highest tertile was 1.67 (1.21, 2.31) for n-PFOA (ptrend = 0.001), 1.58 (1.13, 2.21) for PFHxS (ptrend = 0.003), 1.36 (0.97, 1.90) for Sm-PFOS (ptrend = 0.05), 1.85 (1.28, 2.67) for MeFOSAA (ptrend = 0.0004) and 1.64 (1.17, 2.31) for the sum of four common PFAS (n-PFOA, PFNA, PFHxS and total PFOS) (ptrend = 0.002). Exposure to seven PFAS as mixtures was associated with an HR of 2.62 (95% CI 1.12, 6.20), comparing the top with the bottom tertiles for all seven PFAS. CONCLUSIONS/INTERPRETATION: This study suggests that PFAS may increase diabetes risk in midlife women. Reduced exposure to these 'forever and everywhere chemicals' may be an important preventative approach to lowering population-wide diabetes risk.

Development of clinical prediction models for renal and cardiovascular outcomes and mortality in patients with type 2 diabetes and chronic kidney disease using time-varying predictors.

AIMS: To develop a set of prediction models for end-stage kidney disease (ESKD), cardiovascular outcomes, and mortality in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) using commonly measured clinical variables. METHODS: We studied 1432 participants with T2D and CKD enrolled in the Chronic Renal Insufficiency Cohort, followed for a median period of 7 years. We used Cox proportional-hazards models to model the six outcomes (ESKD, stroke, myocardial infarction (MI), congestive heart failure (CHF), death before ESKD, and all-cause mortality). We internally evaluated these models using concordance and calibration measures. RESULTS: The newly developed six prediction models included 15 predictors: age at diabetes diagnosis, sex, blood pressure, body mass index, hemoglobin A1c, high density lipoprotein cholesterol, urine protein-to-creatinine ratio, estimated glomerular filtration rate, smoking status, and history of stroke, MI, CHF, ESKD, and amputation. The resulting models demonstrated good/strong discrimination (cross-validation C-index range: 0.70 to 0.90) and calibration. CONCLUSIONS: This study provided an internally validated and useful tool for predicting individual adverse outcomes and mortality in patients with T2D and CKD. These models may inform optimal use of targeted health interventions.

Type 1 diabetes and oral health: Findings from the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

OBJECTIVE: To describe long-term oral health outcomes and examine associations between sociodemographic factors, clinical characteristics, and markers of diabetes control on tooth loss in participants with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. RESEARCH DESIGN AND METHODS: Oral health outcomes related to tooth loss were reported at annual visits during EDIC years 22-26 (2015-2019). Generalized estimating equation models were used to assess the association of individual risk factors and tooth loss, over repeated time points. RESULTS: A total of 165 (17%) participants with type 1 diabetes reported 221 oral health outcomes related to tooth loss over a five-year period. After controlling for age and current tobacco use, the presence of diabetic peripheral neuropathy was significantly associated with an increased odds of tooth loss (OR = 1.88, 95% CI 1.24, 2.87) while higher mean HDL/LDL cholesterol ratio was significantly associated with a decreased odds of tooth loss (OR = 0.87, 95% CI = 0.79, 0.97). CONCLUSIONS: These findings suggest that diabetes-related complications, either resulting from or independent of poor glycemia, may be directly associated with oral health conditions, and support the need for individuals with type 1 diabetes and providers to implement lifestyle and medical interventions to reduce oral health risks.

Integrating hypertension and diabetes management in primary health care settings: HEARTS as a tool / Integración del manejo de la hipertensión y la diabetes en entornos de atención primaria de salud: HEARTS como herramienta / Integrando o manejo da hipertensão e do diabetes na atenção primária à saúde: uso do HEARTS como instrumento

ABSTRACT Hypertension and diabetes are modifiable cardiovascular disease (CVD) risk factors that contribute to nearly one-third of all deaths in the Americas Region each year (2.3 million deaths). Despite advances in the detection and clinical management of hypertension and diabetes, there are substantial gaps in their implementation globally and in the Region. The considerable overlap in risk factors, prognosis, and treatment of hypertension and diabetes creates a unique opportunity for a unified implementation model for management at the population level. This report highlights one such high-profile effort, the Pan American Health Organization's "HEARTS in the Americas" program, based on the World Health Organization's HEARTS Technical Package for Cardiovascular Disease Management in Primary Health Care. The HEARTS program aims to improve the implementation of preventive CVD care in primary health systems using six evidence-based, pragmatic components: Healthy-lifestyle counseling, Evidence-based protocols, Access to essential medicines and technology, Risk-based CVD management, Team-based care, and Systems for monitoring. To date, HEARTS implementation projects have focused primarily on hypertension given that it is the leading modifiable CVD risk factor and can be treated cost-effectively. The objective of this report is to describe opportunities for integration of diabetes clinical care and policy within the HEARTS hypertension framework. A substantial global burden of disease could be averted with integrated primary care management of these conditions. Thus, there is an urgency in applying lessons from HEARTS to close these implementation gaps and improve the integrated detection, treatment, and control of diabetes and hypertension.

RESUMEN La hipertensión y la diabetes son los factores de riesgo modificables de las enfermedades cardiovasculares asociados a casi un tercio de todas las muertes en la Región de las Américas cada año (2,3 millones). A pesar de los avances en la detección y el manejo clínico de la hipertensión y la diabetes, existen brechas sustanciales en la implementación a nivel regional y mundial. El considerable solapamiento en los factores de riesgo, el pronóstico y el tratamiento de la hipertensión y la diabetes crea una oportunidad única para un modelo unificado de implementación para el manejo a nivel poblacional. En este informe se pone de relieve una iniciativa importante de este tipo, el programa HEARTS en las Américas de la Organización Panamericana de la Salud, basado en el paquete técnico HEARTS para el manejo de las enfermedades cardiovasculares en la atención primaria de salud. El programa HEARTS tiene como objetivo mejorar la implementación de la atención preventiva de las enfermedades cardiovasculares en los sistemas de atención primaria de salud mediante seis componentes pragmáticos basados en la evidencia: Hábitos y estilos de vida saludables: asesoramiento para los pacientes; Evidencia: protocolos basados en la evidencia; Acceso a medicamentos y tecnologías esenciales; Riesgo cardiovascular: manejo de las enfermedades cardiovasculares basado en el riesgo; Trabajo en equipos; y Sistemas de monitoreo. Hasta la fecha, los proyectos de implementación de HEARTS se han centrado principalmente en la hipertensión, dado que es el principal factor de riesgo modificable de las enfermedades cardiovasculares y puede tratarse de una manera costo-eficaz. El objetivo de este informe es describir las oportunidades para la integración de la política y la atención clínica en el marco HEARTS para la hipertensión. Se podría evitar una significativa carga mundial de enfermedad con un manejo integrado de la atención primaria de estos problemas de salud. Por lo tanto, existe una urgencia en la aplicación de las enseñanzas de HEARTS para salvar estas brechas en la implementación y mejorar la detección, el tratamiento y el control integrados de la diabetes y la hipertensión.

RESUMO Hipertensão e diabetes são fatores de risco modificáveis para doenças cardiovasculares (DCV) que contribuem para quase um terço de todas as mortes na Região das Américas a cada ano (2,3 milhões de mortes). Apesar dos avanços na detecção e no manejo clínico da hipertensão e do diabetes, existem lacunas importantes em sua implementação mundialmente e na região. A sobreposição considerável de fatores de risco, prognóstico e tratamento da hipertensão e do diabetes cria uma oportunidade única para um modelo de implementação unificado para o manejo dessas doenças em nível populacional. Este relatório destaca um desses esforços de alto nível, o programa "HEARTS nas Américas" da Organização Pan-Americana da Saúde, baseado no Pacote Técnico HEARTS da Organização Mundial da Saúde para o manejo de DCV na atenção primária à saúde. O programa HEARTS visa melhorar a implementação de cuidados preventivos de DCV nos sistemas de atenção primária utilizando seis componentes pragmáticos e baseados em evidências: Hábitos saudáveis (aconselhamento a pacientes), protocolos baseados em Evidências, Acesso a medicamentos e tecnologias essenciais, manejo das DCV baseado em Risco, Trabalho de equipe como base para a atenção e Sistemas de monitoramento. Até hoje, os projetos de implementação do HEARTS têm se concentrado principalmente na hipertensão, considerando que é o principal fator de risco modificável de DCV e pode ser tratada de forma custo-efetiva. O objetivo deste relatório é descrever as oportunidades de integração do manejo clínico e de políticas para o diabetes dentro da estrutura HEARTS de manejo da hipertensão. Uma importante carga global de doença poderia ser evitada com o manejo integrado dessas duas afecções na atenção primária. Assim, há uma urgência na aplicação das lições de HEARTS para fechar estas lacunas de implementação e melhorar a detecção, o tratamento e o controle integrados do diabetes e da hipertensão.

Associations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) and PFAS mixtures with adipokines in midlife women.

BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure have been associated with obesity and related comorbidities, possibly through disrupting signaling pathways of adipokines. Both leptin and adiponectin can modulate metabolic processes. However, the effects of PFAS on adipokines are not well understood. OBJECTIVE: We determined if serum PFAS concentrations were associated with adipokine profiles in midlife women. METHODS: We examined 1245 women aged 45-56 years from the Study of Women's Health Across the Nation. Concentrations of 11 PFAS were quantified in baseline serum samples collected in 1999-2000. Linear and branched perfluorooctane sulfonic acid isomers (n-PFOS and Sm-PFOS) and their sum (PFOS), linear perfluorooctanoic acid (n-PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA), and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (EtFOSAA) with detection frequencies >60% were included in the analysis. Adipokines including leptin, soluble leptin receptor (sOB-R), free leptin index (FLI, the ratio of leptin to sOB-R), total and high molecular weight (HMW) adiponectin were assessed in 2002-2003. We utilized multivariable linear regressions and Bayesian kernel machine regression (BKMR) to assess individual and overall joint effects of PFAS on adipokines with adjustment for age, race/ethnicity, study site, education, smoking status, physical activity, menopausal status, and waist circumference. RESULTS: A doubling of PFAS concentrations was associated with 7.8% (95% CI: 2.5%, 13.4%) higher FLI for PFOS, 9.4% (95% CI: 3.7%, 15.3%) for n-PFOA, 5.5% (95% CI: 2.2%, 9.0%) for EtFOSAA and 7.4% (95% CI: 2.8%, 12.2%) for MeFOSAA. Similar associations were found for leptin. Only EtFOSAA was associated with lower sOB-R concentrations (-1.4%, 95% CI: -2.7%, -0.1%). Results remained in women with overweight or obesity but not those with normal weight or underweight. No statistically significant associations were observed with total or HMW adiponectin, except for PFNA with total and HMW adiponectin observed in women with normal weight or underweight. In BKMR analysis, women with PFAS concentrations at the median and the 90th percentile had 30.9% (95% CI: 15.6%, 48.3%) and 52.1% (95% CI: 27.9%, 81.0%) higher FLI, respectively, compared with those with concentrations fixed at the 10th percentile. CONCLUSION: Some PFAS may alter circulating levels of leptin. Understanding associations between PFAS and adipokines may help elucidate whether PFAS can influence obesity and metabolic disease.

Risk factors for orgasmic and concomitant erectile dysfunction in men with type 1 diabetes: a cross-sectional study.

In this study, we sought to determine the burden and characteristics of orgasmic dysfunction (OD) and concomitant erectile dysfunction (ED) in men with type 1 diabetes (T1D) enrolled in the Epidemiology of Diabetes Interventions and Complications (EDIC) study. In 2010, we assessed orgasmic and erectile function using the International Index of Erectile Function (IIEF). Sociodemographic, clinical, and diabetes characteristics were compared by OD status (OD only, OD and ED, no ED or OD). Age-adjusted associations between risk factors and OD status were examined. OD and ED information was available from 563 men. Eighty-three men (14.7%) reported OD of whom 21 reported OD only and 62 reported OD and ED. Age-adjusted odds ratios demonstrated that men who reported OD only had higher odds of depression, low sexual desire, and decreased alcohol use compared with men reporting no dysfunction. Men with OD concomitant with ED had greater odds of elevated hemoglobin A1C, peripheral and autonomic neuropathy, and nephropathy. Men reporting both dysfunctions were also more likely to report smoking, lower urinary tract symptoms, and had greater odds of androgen deficiency than men with no sexual dysfunction. Men with longstanding T1D suffer from an increased burden of OD. Psychogenic factors predominate in men reporting OD only while men who present with concomitant ED report increased burden of diabetes severity, characteristics previously observed with incident ED. ED may be the central impediment to sexual function in men with OD and ED. Longitudinal studies to characterize OD and ED experience over time are warranted.

Severe obesity and the impact of medical weight loss on estimated glomerular filtration rate.

OBJECTIVE: To assess the impact of obesity, glucose tolerance, and weight loss on renal function, we measured serum creatinine and cystatin C and estimated glomerular filtration rate (GFR) indexed to 1.73m2 body surface area (BSA) and GFR indexed to actual BSA in subjects with normal and abnormal glucose tolerance before and up to 2 years after medical weight loss. METHODS: We studied 146 subjects at baseline and 3-to-6 months after 18% reduction in weight; 43 were also studied at 2-years. GFR was estimated using the MDRD, CKD-EPICr, CKD-EPICysCr, and the CKD-EPICys equations. RESULTS: eGFR was consistently lower when creatinine-based rather than cystatin C-based estimating equations were used. eGFR was lower when creatinine-based or cystatin C-based equations were indexed to 1.73m2 BSA than when they were indexed to actual BSA. eGFR indexed to actual BSA was more likely to demonstrate hyperfiltration (eGFR ≥135 ml/min) than eGFR indexed to 1.73m2 BSA and decreased into the normal range with weight loss. eGFR was highest in subjects with impaired fasting glucose but there was little difference in the patterns of change in eGFR across groups by glucose tolerance status. CONCLUSIONS: With severe obesity, high fat-free mass and BSA result in low estimates of eGFR indexed to 1.73m2 BSA, especially when creatinine-based estimating equations are used. GFR indexed to actual BSA is approximately 50% higher. When eGFR is indexed to actual BSA, many subjects display evidence of renal hyperfiltration which improves with weight loss. In subjects with severe obesity undergoing medical weight loss, estimating equations that use cystatin C and are indexed to actual BSA may provide a more accurate assessment of renal function.

The association between perceived discrimination in midlife and peripheral neuropathy in a population-based cohort of women: the Study of Women's Health Across the Nation.

PURPOSE: Peripheral neuropathy (PN) is a highly prevalent condition with serious sequelae. Many studies of the condition have been restricted to populations with diabetes, limiting evidence of potential contributing risk factors including salient psychosocial risk factors such as discrimination. METHODS: The longitudinal Study of Women's Health Across the Nation was used to assess the relationship between perceived discrimination and prevalent PN in 1718 ethnically diverse midlife women. We used multivariable logistic regression to determine the association between perceived discrimination (Detroit Area Study Everyday Discrimination Scale) and PN (symptom questionnaire and monofilament testing) and conducted an assessment of the mediating effects of body mass index (BMI). RESULTS: The prevalence of PN was 26.1% in the total sample and 40.9% among women with diabetes. Women who reported perceived discrimination had 29% higher odds of PN compared with women who did not report perceived discrimination (95% confidence interval, 1.01-1.66). Approximately 30% of the total effect of discrimination on PN was mediated indirectly by BMI. CONCLUSIONS: More research is needed to determine the contributing factors to nondiabetic PN. Our findings reaffirm the impact of financial strain, BMI, and diabetes as significant correlates of PN and highlight discrimination as an important risk factor.

Blood pressure, antihypertensive medication use, and risk of erectile dysfunction in men with type I diabetes.

OBJECTIVE: To gain insight into the effect of blood pressure on the pathophysiology of diabetic erectile dysfunction, we determined the onset, severity and treatment of hypertension and risk of incident erectile dysfunction in men with type I diabetes. METHODS: This prospective cohort study included 692 men without prevalent erectile dysfunction in the Epidemiology of Diabetes Interventions and Complications study. Erectile dysfunction was assessed yearly for 16 years with a single question querying presence of impotence. Multivariable cox proportional hazards models examined associations of hypertension variables with risk for incident erectile dysfunction. RESULTS: Over 7762 person-years of follow-up, 337 of 692 men reported incident erectile dysfunction representing an unadjusted rate of 43.4 cases per 1000 person-years. Risk of erectile dysfunction significantly increased with each 10 mmHg of SBP elevation for those not taking antihypertensive medications, after adjustment for age, cigarette smoking and HbA1c levels [relative risk (RR) = 1.21, 95% CI = 1.04-1.41]. This relationship disappeared among those reporting antihypertensive medication use (RR = 0.96, 95% CI = 0.84-1.10) and the interaction between SBP and medication use was statistically significant (P = 0.02). Antihypertensive medication did not confer any reduction of erectile dysfunction risk, with similar rates across all measures of blood pressure and hypertension. CONCLUSION: Among men with type 1 diabetes not using antihypertensive medications, higher SBP is associated with increased risk of developing erectile dysfunction. These findings provide evidence to support further investigation into the potential benefit of early blood pressure control on risk of erectile dysfunction in men with diabetes regardless of age, blood pressure level, or glycemic control.

Changes in Screening Practices for Prediabetes and Diabetes Since the Recommendation for Hemoglobin A1c Testing.

OBJECTIVE: Screening involves the presumptive identification of asymptomatic individuals at increased risk for unrecognized disease. We examined changes in screening practices for prediabetes and diabetes since January 2010, when HbA1c was first recommended as an option for screening and diagnosis. RESEARCH DESIGN AND METHODS: We studied members without diabetes of an HMO ≥45 years of age continuously enrolled for ≥3 years and assigned to primary care clinicians affiliated with a large academic health system. We defined screening as the first oral glucose tolerance test, HbA1c, or glucose test performed between 2010 and 2014. RESULTS: Of 12,772 eligible patients, 9,941 (78%) were screened at least once over 3 years. HbA1c was the initial screening test 14% of the time and glucose 86% of the time. Of those screened with HbA1c, 63% had abnormal results defined as HbA1c ≥5.7% (≥39 mmol/mol). Of those tested with glucose, 30% had abnormal results defined as glucose ≥100 mg/dL, and 5% had abnormal results defined as glucose ≥126 mg/dL. Patients with abnormal HbA1c levels and those with glucose levels ≥126 mg/dL were equally likely to be scheduled for follow-up appointments (41% vs. 39%), but those with abnormal HbA1c levels were more likely to be diagnosed with prediabetes or diabetes (36% vs. 26%). CONCLUSIONS: As we observed in 2004, rates of screening are high. HbA1c is still used less frequently than glucose for screening but is more likely to result in a clinical diagnosis. Evidence to support guidelines to define the role of random glucose screening, including definition of appropriate cut points and follow-up, is needed.

The Effect of Attrition on Reported Diabetes Remission Rates Following Roux-en-Y Gastric Bypass: a Sensitivity Analysis.

OBJECTIVE: Attrition, or loss to follow-up, is a common problem in studies of type 2 diabetes remission following roux-en-Y gastric bypass (RYGB) and is often correlated with weight loss. Thus, reported rates of remission may be inflated by attrition bias. We investigate the effect of attrition bias on reported diabetes remission rates following RYGB. METHODS: Using sensitivity analyses, we identified sets of attrition and remission rates that produced simulated outcomes within 95% confidence intervals of the reported outcomes from five studies of diabetes remission following RYGB. RESULTS: Potential attrition bias varied greatly, yielding possible remission rates of diabetes ranging from 20 to 40% at 1 year. For studies with the attrition greater than ~ 20%, estimates that ignored attrition overestimated diabetes remission rates. Kaplan-Meier estimates were less affected by attrition. Potential for bias was most evident in the study with the largest sample size. CONCLUSION: Researchers, clinicians, and policymakers can measure potential attrition bias in clinical studies. In the case of remission of diabetes following RYGB, the potential bias in reported remission rates is generally less than 10%, varies considerably among studies, and is primarily driven by attrition rate and study size. Studies with very large sample sizes may provide a narrow confidence interval around a biased estimate.

Treatment of Type 1 Diabetes: Synopsis of the 2017 American Diabetes Association Standards of Medical Care in Diabetes.

DESCRIPTION: The American Diabetes Association (ADA) annually updates 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 of Care, the ADA Professional Practice Committee did MEDLINE searches from 1 January 2016 to November 2016 to add, clarify, or revise recommendations on the basis of new evidence. The committee rated the recommendations as A, B, or C, depending on the quality of evidence, or E for expert consensus or clinical experience. The Standards of Care 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. RECOMMENDATION: This synopsis focuses on recommendations from the 2017 Standards of Care about monitoring and pharmacologic approaches to glycemic management for type 1 diabetes.

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: a Joint Statement by International Diabetes Organizations.

BACKGROUND: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. AIM: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. METHODS: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005-30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28-30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee. RESULTS: Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI ≥40 kg/m2) and in those with class II obesity (BMI 35.0-39.9 kg/m2) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0-34.9 kg/m2 if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m2 for Asian patients. CONCLUSIONS: Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.

Incidence and Risk Factors for Developing Diabetic Retinopathy among Youths with Type 1 or Type 2 Diabetes throughout the United States.

PURPOSE: Despite the increasing prevalence of type 2 diabetes mellitus (T2DM) among children and adolescents, little is known about their risk of developing diabetic retinopathy (DR). We sought to identify risk factors for DR in youths with diabetes mellitus, to compare DR rates for youths with type 1 diabetes mellitus (T1DM) and those with T2DM, and to assess whether adherence to DR screening guidelines promoted by the American Academy of Ophthalmology, American Academy of Pediatrics, and American Diabetes Association adequately capture youths with DR. DESIGN: Retrospective observational longitudinal cohort study. PARTICIPANTS: Youths aged ≤21 years with newly diagnosed T1DM or T2DM who were enrolled in a large US managed-care network. METHODS: In this study of youths aged ≤21 years with newly diagnosed T1DM or T2DM who were under ophthalmic surveillance, we identified the incidence and timing of DR onset. Kaplan-Meier survival curves assessed the timing of initial diagnosis of DR for participants. Multivariable Cox proportional hazard regression modeling identified factors associated with the hazard of developing DR. Model predictors were age and calendar year at initial diabetes mellitus diagnosis, sex, race/ethnicity, net worth, and glycated hemoglobin A1c fraction (HbA1c). MAIN OUTCOME MEASURES: Hazard ratios (HRs) with 95% confidence intervals (CIs) for developing DR. RESULTS: Among the 2240 youths with T1DM and 1768 youths with T2DM, 20.1% and 7.2% developed DR over a median follow-up time of 3.2 and 3.1 years, respectively. Survival curves demonstrated that youths with T1DM developed DR faster than youths with T2DM (P < 0.0001). For every 1-point increase in HbA1c, the hazard for DR increased by 20% (HR = 1.20; 95% CI 1.06-1.35) and 30% (HR = 1.30; 95% CI 1.08-1.56) among youths with T1DM and T2DM, respectively. Current guidelines suggest that ophthalmic screening begin 3 to 5 years after initial diabetes mellitus diagnosis, at which point in our study, >18% of youths with T1DM had already received ≥1 DR diagnosis. CONCLUSIONS: Youths with T1DM or T2DM exhibit a considerable risk for DR and should undergo regular screenings by eye-care professionals to ensure timely DR diagnosis and limit progression to vision-threatening disease.

Reconciliation of Type 2 Diabetes Remission Rates in Studies of Roux-en-Y Gastric Bypass.

OBJECTIVE: Bariatric surgery may induce remission of type 2 diabetes in obese patients. However, estimates of remission rates reported in the literature range from 25 to 81%, contributing to the uncertainty patients and physicians both face as they assess treatment options. This analysis attempts to reconcile the seemingly disparate rates of diabetes remission reported in studies of Roux-en-Y gastric bypass (RYGB) surgery. It examines variation in the methodologies used to derive the estimates and proposes outcomes that should be reported by all studies. RESEARCH DESIGN AND METHODS: A literature review yielded 10 large (n > 100), recent (index surgery since 2000) studies of diabetes remission after RYGB. These studies differed in definitions of remission (partial vs. complete), lengths of follow-up (1 year vs. ≥3 years), reported outcomes (cumulative vs. prevalent remission), and risks of attrition bias. RESULTS: Reported rates of partial remission were 10-30 percentage points higher than rates of complete remission. Study duration explained 69% of the variability in cumulative remission rates, plateauing at 3 years. Adjustment for attrition increased the explained variability to 87%. Attrition-adjusted, 3-year cumulative, complete remission rates ranged from 63 to 65%; however, this does not account for relapse. Attrition-adjusted, 3-year prevalent complete remission rates that accounted for relapse were 23%. CONCLUSIONS: Variations in reported rates of diabetes remission after RYGB are primarily related to definitions and study duration. Future studies should report both cumulative and prevalent remission to aid decision making and more easily compare studies.

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations.

BACKGROUND: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. AIM: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. METHODS: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005-30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28-30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee. RESULTS: Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI≥40 kg/m(2)) and in those with class II obesity (BMI 35.0-39.9 kg/m(2)) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0-34.9 kg/m(2) if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m(2) for Asian patients. CONCLUSIONS: Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations.

BACKGROUND: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. AIM: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. METHODS: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005-30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28-30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee. RESULTS: Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI ≥40 kg/m(2)) and in those with class II obesity (BMI 35.0-39.9 kg/m(2)) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0-34.9 kg/m(2) if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m(2) for Asian patients. CONCLUSIONS: Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.