Effect of Isocaloric, Time-Restricted Eating on Body Weight in Adults With Obesity : A Randomized Controlled Trial.

BACKGROUND: Time-restricted eating (TRE) lowers body weight in many studies. Whether TRE induces weight loss independent of reductions in calorie intake, as seen in rodent studies, is unknown. OBJECTIVE: To determine the effect of TRE versus a usual eating pattern (UEP) on body weight in the setting of stable caloric intake. DESIGN: Randomized, isocaloric feeding study. (ClinicalTrials.gov: NCT03527368). SETTING: Clinical research unit. PARTICIPANTS: Adults with obesity and prediabetes or diet-controlled diabetes. INTERVENTION: Participants were randomly assigned 1:1 to TRE (10-hour eating window, 80% of calories before 1 p.m.) or UEP (≤16-hour window, ≥50% of calories after 5 p.m.) for 12 weeks. Both groups had the same nutrient content and were isocaloric with total calories determined at baseline. MEASUREMENTS: Primary outcome was change in body weight at 12 weeks. Secondary outcomes were fasting glucose, homeostatic model assessment for insulin resistance (HOMA-IR), glucose area under the curve by oral glucose tolerance test, and glycated albumin. We used linear mixed models to evaluate the effect of interventions on outcomes. RESULTS: All 41 randomly assigned participants (mean age, 59 years; 93% women; 93% Black race; mean BMI, 36 kg/m2) completed the intervention. Baseline weight was 95.6 kg (95% CI, 89.6 to 101.6 kg) in the TRE group and 103.7 kg (CI, 95.3 to 112.0 kg) in the UEP group. At 12 weeks, weight decreased by 2.3 kg (CI, 1.0 to 3.5 kg) in the TRE group and by 2.6 kg (CI, 1.5 to 3.7 kg) in the UEP group (average difference TRE vs. UEP, 0.3 kg [CI, -1.2 to 1.9 kg]). Change in glycemic measures did not differ between groups. LIMITATION: Small, single-site study; baseline differences in weight by group. CONCLUSION: In the setting of isocaloric eating, TRE did not decrease weight or improve glucose homeostasis relative to a UEP, suggesting that any effects of TRE on weight in prior studies may be due to reductions in caloric intake. PRIMARY FUNDING SOURCE: American Heart Association.

Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study.

AIMS/HYPOTHESIS: We examined the association of attainment of diabetes remission in the context of a 12 year intensive lifestyle intervention with subsequent incidence of chronic kidney disease (CKD) and CVD. METHODS: The Look AHEAD study was a multi-centre RCT comparing the effect of a 12 year intensive lifestyle intervention with that of diabetes support and education on CVD and other long-term health conditions. We compared the incidence of CVD and CKD among 4402 and 4132 participants, respectively, based on achievement and duration of diabetes remission. Participants were 58% female, and had a mean age of 59 years, a duration of diabetes of 6 year and BMI of 35.8 kg/m2. We applied an epidemiological definition of remission: taking no diabetes medications and having HbA1c <48 mmol/mol (6.5%) at a single point in time. We defined high-risk or very high-risk CKD based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, and CVD incidence as any occurrence of non-fatal acute myocardial infarction, stroke, admission for angina or CVD death. RESULTS: Participants with evidence of any remission during follow-up had a 33% lower rate of CKD (HR 0.67; 95% CI 0.52, 0.87) and a 40% lower rate of the composite CVD measure (HR 0.60; 95% CI 0.47, 0.79) in multivariate analyses adjusting for HbA1c, BP, lipid levels, CVD history, diabetes duration and intervention arm, compared with participants without remission. The magnitude of risk reduction was greatest for participants with evidence of longer-term remission. CONCLUSIONS/INTERPRETATION: Participants with type 2 diabetes with evidence of remission had a substantially lower incidence of CKD and CVD, respectively, compared with participants who did not achieve remission. This association may be affected by post-baseline improvements in weight, fitness, HbA1c and LDL-cholesterol. TRIAL REGISTRATION: ClinicalTrials.gov NCT00017953 DATA AVAILABILITY: https://repository.niddk.nih.gov/studies/look-ahead/.

Engaging Payors and Primary Care Physicians Together in Improving Diabetes Prevention.

BACKGROUND: Type 2 diabetes can be prevented through lifestyle programs like the Diabetes Prevention Programs (DPP), but few people with prediabetes participate in them, in part because their insurance does not reliably cover DPPs. Prior studies have not focused on payor-level barriers. OBJECTIVE: To understand barriers to DPP uptake that exist and intersect at different levels (patients, PCPs, and payors) to inform strategies to improve diabetes prevention in primary care settings through interviews with PCPs and payors. DESIGN: From May 2020 to October 2021, we conducted remote, semi-structured interviews with PCPs and payors. PARTICIPANTS: PCPs were from primary care practices affiliated with one mid-Atlantic academic system. Payor leaders were from regional commercial, Medicare, and Medicaid plans. APPROACH: Using a standardized interview guide focused on barriers, facilitators, and potential intervention components, interviews were audio-recorded using Zoom and professionally transcribed. Two reviewers double-coded transcripts using the framework analytic approach. KEY RESULTS: We interviewed 16 PCPs from 13 primary care clinics and 7 payor leaders representing 6 insurance plans. Two themes emerged from PCP reports of patient-level barriers: (1) lack of programs and insurance coverage of resources to address nutrition and exercise and (2) inadequate resources to address social determinants of health that impact diabetes prevention. Among barriers PCPs faced, we identified two themes: (1) low PCP knowledge about DPPs and misperceptions of insurance coverage of DPPs and (2) inadequate clinical staff to address diabetes prevention. Barriers common to PCPs and payors included (1) absence of prediabetes quality measures and (2) inadequate engagement of PCPs and patients with payors. CONCLUSIONS: Discussions with PCPs and payors revealed systemic barriers that suggest important priorities to improve prediabetes clinical care, including universal coverage of DPPs, clarity about coverage benefits, data reporting and outreach by payors to PCPs, and adoption of appropriate prediabetes quality measures.

A Qualitative Study of Perspectives of Older Adults on Deintensifying Diabetes Medications.

BACKGROUND: While many older adults with type 2 diabetes have tight glycemic control beyond guideline-recommended targets, deintensifying (stopping or dose-reducing) diabetes medications rarely occurs. OBJECTIVE: To explore the perspectives of older adults with type 2 diabetes around deintensifying diabetes medications. DESIGN: This qualitative study used individual semi-structured interviews, which included three clinical scenarios where deintensification may be indicated. PARTICIPANTS: Twenty-four adults aged ≥65 years with medication-treated type 2 diabetes and hemoglobin A1c <7.5% were included (to thematic saturation) using a maximal variation sampling strategy for diabetes treatment and physician specialty. APPROACH: Interviews were independently coded by two investigators and analyzed using a grounded theory approach. We identified major themes and subthemes and coded responses to the clinical scenarios as positive (in favor of deintensification), negative, or ambiguous. KEY RESULTS: Participants' mean age was 74 years, half were women, and 58% used a sulfonylurea or insulin. The first of four major themes was fear of losing control of diabetes, which participants weighed against the benefits of taking less medication (Theme 2). Few participants viewed glycemic control below target as a reason for deintensification and a majority would restart the medication if their home glucose increased. Some participants were anchored to their current diabetes treatment (Theme 3) driven by unrealistic views of medication benefits. A trusting patient-provider relationship (Theme 4) was a positive influence. In clinical scenarios, 8%, 4%, and 75% of participants viewed deintensification positively in the setting of poor health, limited life expectancy, and high hypoglycemia risk, respectively. CONCLUSIONS: Optimizing deintensification requires patient education that describes both individualized glycemic targets and how they will change over the lifespan. Deintensification is an opportunity for shared decision-making, but providers must understand patients' beliefs about their medications and address misconceptions. Hypoglycemia prevention may be a helpful framing for discussing deintensification.

A National Survey of Physicians' Views on the Importance and Implementation of Deintensifying Diabetes Medications.

BACKGROUND: Guidelines recommend deintensifying hypoglycemia-causing medications for older adults with diabetes whose hemoglobin A1c is below their individualized target, but this rarely occurs in practice. OBJECTIVE: To understand physicians' decision-making around deintensifying diabetes treatment. DESIGN: National physician survey. PARTICIPANTS: US physicians in general medicine, geriatrics, or endocrinology providing outpatient diabetes care. MAIN MEASURES: Physicians rated the importance of deintensifying diabetes medications for older adults with type 2 diabetes, and of switching medication classes, on 5-point Likert scales. They reported the frequency of these actions for their patients, and listed important barriers and facilitators. We evaluated the independent association between physicians' professional and practice characteristics and the importance of deintensifying and switching diabetes medications using multivariable ordered logistic regression models. KEY RESULTS: There were 445 eligible respondents (response rate 37.5%). The majority of physicians viewed deintensifying (80%) and switching (92%) diabetes medications as important or very important to the care of older adults. Despite this, one-third of physicians reported deintensifying diabetes medications rarely or never. While most physicians recognized multiple reasons to deintensify, two-thirds of physicians reported barriers of short-term hyperglycemia and patient reluctance to change medications or allow higher glucose levels. In multivariable models, geriatricians rated deintensification as more important compared to other specialties (p=0.027), and endocrinologists rated switching as more important compared to other specialties (p<0.006). Physicians with fewer years in practice rated higher importance of deintensification (p<0.001) and switching (p=0.003). CONCLUSIONS: While most US physicians viewed deintensifying and switching diabetes medications as important for the care of older adults, they deintensified infrequently. Physicians had ambivalence about the relative benefits and harms of deintensification and viewed it as a potential source of conflict with their patients. These factors likely contribute to clinical inertia, and studies focused on improving shared decision-making around deintensifying diabetes medications are needed.

Cooking behaviours after Diabetes Prevention Program (DPP) participation among DPP participants in Baltimore, MD.

OBJECTIVE: The Diabetes Prevention Program (DPP) is a widely implemented 12-month behavioural weight loss programme for individuals with prediabetes. The DPP covers nutrition but does not explicitly incorporate cooking skills education. The objective of the current study is to describe food and cooking skills (FACS) and strategies of recent DPP participants. DESIGN: Photo-elicitation in-depth interviews were conducted from June to August, 2021. SETTING: Baltimore, MD, USA. PARTICIPANTS: Thirteen Black women who participated in DPP. RESULTS: The DPP curriculum influenced participants' healthy cooking practices. Many participants reported shifting from frying foods to air-frying and baking foods to promote healthier cooking and more efficient meal preparation. Participants also reported that their participation in DPP made them more mindful of consuming fruits and vegetables and avoiding foods high in carbohydrates, fats, sugars and Na. With respect to food skills, participants reported that they were more attentive to reading labels and packaging on foods and assessing the quality of ingredients when grocery shopping. CONCLUSIONS: Overall, participants reported changing their food preferences, shopping practices and cooking strategies to promote healthier eating after completing the DPP. Incorporating hands-on cooking skills and practices into the DPP curriculum may support sustained behaviour change to manage prediabetes and prevent development of type 2 diabetes among participants.

Predictors of Follow-Up Appointment No-Shows Before and During COVID Among Adults with Type 2 Diabetes.

Background: The coronavirus disease 2019 (COVID-19) pandemic has rapidly transformed health care delivery into telehealth visits. Attending regular medical appointments are critical to prevent or delay diabetes-related complications. Although telehealth visits have addressed some barriers to in-person visits, appointment no-shows are still noted in the telehealth setting. It is not completely clear how the predictors of appointment no-shows differ between in-person and telehealth visits in diabetes care. Objective: This retrospective study examined if predictors of appointment no-shows differ (1) between pre-COVID (January 1, 2019-March 22, 2020) and COVID (March 23, 2020-December 31, 2020) periods and (2) by health care delivery modes (in-person or telehealth visits) during COVID among adults with type 2 diabetes mellitus (T2DM). Methods: We used electronic health records between January 1, 2019 and December 31, 2020 across four diabetes clinics in a tertiary academic hospital in Baltimore, Maryland. Appointments marked as completed or no-show by established adults with T2DM were included in the analyses. Results: Among 7,276 appointments made by 2,235 patients, overall appointment no-show was 14.99%. Being older and White were protective against appointment no-shows in both unadjusted and adjusted models during both time periods. The interaction terms of COVID periods (i.e., pre-COVID vs. COVID) were significant for when glycated hemoglobin drawn before this visit and for missing body mass index. Telehealth visits during COVID decreased more half of the odds of appointment no-shows. Conclusions: In the context of diabetes care, the implementation of telehealth reduced appointment no-shows. Future studies are needed to address social determinants of health, including access to internet access, to further reduce health disparities among adults with T2DM.

Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycaemia in type 2 diabetes in adults, published since 2006 and last updated in 2019. The target audience is the full spectrum of the professional healthcare team providing diabetes care in the USA and Europe. A systematic examination of publications since 2018 informed new recommendations. These include additional focus on social determinants of health, the healthcare system and physical activity behaviours including sleep. There is a greater emphasis on weight management as part of the holistic approach to diabetes management. The results of cardiovascular and kidney outcomes trials involving sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, including assessment of subgroups, inform broader recommendations for cardiorenal protection in people with diabetes at high risk of cardiorenal disease. After a summary listing of consensus recommendations, practical tips for implementation are provided.

A behavioral weight-loss intervention, but not metformin, decreases a marker of gut barrier permeability: results from the SPIRIT randomized trial.

BACKGROUND/OBJECTIVES: Lipopolysaccharide-binding protein (LBP), a biomarker of gut barrier permeability to lipopolysaccharides, is higher in adults with obesity and type 2 diabetes. Behavioral weight loss and metformin have distinct effects on the gut microbiome, but their impact on gut permeability to lipopolysaccharides is unknown. This study's objective was to determine the effects of a behavioral weight-loss intervention or metformin treatment on plasma LBP. SUBJECTS/METHODS: SPIRIT was a randomized trial of adults with overweight or obesity. Participants were randomized to one of three arms: metformin treatment, coach-directed behavioral weight loss on a DASH diet, or self-directed care (control). Of 121 participants, a random subset (n = 88) was selected to have LBP measured at baseline, 6 months, and 12 months post intervention. Intervention effects on LBP over time were assessed using generalized estimating equations (GEE). We also examined whether the intervention effects were modified by change in diet and weight. RESULTS: Arms were balanced by sex (83% female), race (51% white), and age (mean 60 years), with no differences in baseline LBP (median 4.23 µg/mL). At 1 year, mean weight change was -3.00% in the metformin arm, -3.02% in the coach-directed behavioral weight-loss arm, and +0.33% in the self-directed (control) arm. The corresponding change in LBP was +1.03, -0.98, +1.03 µg/mL. The behavioral weight-loss intervention reduced LBP compared to self-directed care (ß = -0.17, 95% CI: -0.33 to -0.01); no other between-arm comparisons were significant. Behavioral weight-loss participants who reduced dietary fat showed the greatest reductions in 6-month LBP (ß = -2.84, 95% CI: -5.17 to -0.50). CONCLUSIONS: Despite similar weight loss in the behavioral weight loss arm and the metformin arm, only the behavioral weight-loss intervention reduced LBP compared to control. Lifestyle weight-loss interventions that promote a DASH diet may be effective at reducing gut barrier permeability to lipopolysaccharides. CLINICAL TRIALS REGISTRATION NUMBER: NCT02431676, https://clinicaltrials.gov.

Clinical Care Among Individuals with Prediabetes in Primary Care: a Retrospective Cohort Study.

BACKGROUND: The incidence of diabetes in the general US population (6.7 per 1000 adults in 2018) has not changed significantly since 2000, suggesting that individuals with prediabetes are not connecting to evidence-based interventions. OBJECTIVE: We sought to describe the clinical care of individuals with prediabetes, determine patient factors associated with this care, and evaluate risk for diabetes development. DESIGN: Retrospective cohort study using linked claims and electronic health record data. PARTICIPANTS: We created a cohort of adults with prediabetes based on laboratory measures. We excluded patients with a prior history of diabetes, pregnancy in prior 6 months, or recent steroid use. MAIN MEASURES: We measured ordering and completion of clinical services targeting prediabetes management and diabetes incidence within 12 months following cohort entry. We tested the strength of the association between individuals' characteristics and outcomes of interest using bivariate and multiple logistic regression. RESULTS: Our cohort included 3888 patients with a laboratory diagnosis of prediabetes (incident or prevalent prediabetes). Within 12 months, 63.4% had repeat glycemic testing, yet only 10.4% had coded diagnoses of prediabetes, 1.0% were referred for nutrition services, and 5.4% were prescribed metformin. Most patients completed labs and nutrition visits when referred and filled metformin when prescribed. Individuals with a higher glycemic level or BMI were more likely to receive prediabetes clinical care. Six percent of individuals developed diabetes within 12 months of cohort entry and had higher glycemic levels and BMI ≥ 30 kg/m2. In the adjusted model, Black individuals had 1.4 times higher odds of developing diabetes than White individuals. CONCLUSIONS: Rates of prediabetes clinical care activities are low and have not improved. Strategies are urgently needed to improve prediabetes care delivery thereby preventing or delaying incident diabetes.

The Longer-Term Benefits and Harms of Glucagon-Like Peptide-1 Receptor Agonists: a Systematic Review and Meta-Analysis.

BACKGROUND: Previous meta-analyses of the benefits and harms of glucagon-like peptide-1 receptor agonists (GLP1RAs) have been limited to specific outcomes and comparisons and often included short-term results. We aimed to estimate the longer-term effects of GLP1RAs on cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events in patients with type 2 diabetes, compared to placebo and other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov (inception-July 2019) for randomized controlled trials ≥ 52 weeks' duration that compared a GLP1RA to placebo or other anti-hyperglycemic medication and included at least one outcome of interest. Outcomes included cardiovascular risk factors, microvascular and macrovascular complications, all-cause mortality, and treatment-related adverse events. We performed random effects meta-analyses to give summary estimates using weighted mean differences (MD) and pooled relative risks (RR). Risk of bias was assessed using the Cochrane Collaboration risk of bias in randomized trials tool. Quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Forty-five trials with a mean duration of 1.7 years comprising 71,517 patients were included. Compared to placebo, GLP1RAs reduced cardiovascular risk factors, microvascular complications (including renal events, RR 0.85, 0.80-0.90), macrovascular complications (including stroke, RR 0.86, 0.78-0.95), and mortality (RR 0.89, 0.84-0.94). Compared to other anti-hyperglycemic medications, GLP1RAs only reduced cardiovascular risk factors. Increased gastrointestinal events causing treatment discontinuation were observed in both comparisons. DISCUSSION: GLP1RAs reduced cardiovascular risk factors and increased gastrointestinal events compared to placebo and other anti-hyperglycemic medications. GLP1RAs also reduced MACE, stroke, renal events, and mortality in comparisons with placebo; however, analyses were inconclusive for comparisons with other anti-hyperglycemic medications. Given the high costs of GLP1RAs, the lack of long-term evidence comparing GLP1RAs to other anti-hyperglycemic medications has significant policy and clinical practice implications.

Longer-term Benefits and Risks of Sodium-Glucose Cotransporter-2 Inhibitors in Type 2 Diabetes: a Systematic Review and Meta-analysis.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a recent class of medication approved for the treatment of type 2 diabetes (T2D). Previous meta-analyses have quantified the benefits and harms of SGLT2Is; however, these analyses have been limited to specific outcomes and comparisons and included trials of short duration. We comprehensively reviewed the longer-term benefits and harms of SGLT2Is compared to placebo or other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov from inception to July 2019 for randomized controlled trials of minimum 52 weeks' duration that enrolled adults with T2D, compared an SGLT2I to either placebo or other anti-hyperglycemic medications, and reported at least one outcome of interest including cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events. We conducted random effects meta-analyses to provide summary estimates using weighted mean differences (MD) and pooled relative risks (RR). The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Fifty articles describing 39 trials (vs. placebo, n = 28; vs. other anti-hyperglycemic medication, n = 12; vs. both, n = 1) and 112,128 patients were included in our analyses. Compared to placebo, SGLT2Is reduced cardiovascular risk factors (e.g., hemoglobin A1c, MD - 0.55%, 95% CI - 0.62, - 0.49), macrovascular outcomes (e.g., hospitalization for heart failure, RR 0.70, 95% CI 0.62, 0.78), and mortality (RR 0.87, 95% CI 0.80, 0.94). Compared to other anti-hyperglycemic medications, SGLT2Is reduced cardiovascular risk factors, but insufficient data existed for other outcomes. About a fourfold increased risk of genital yeast infections for both genders was observed for comparisons vs. placebo and other anti-hyperglycemic medications. DISCUSSION: We found that SGLT2Is led to durable reductions in cardiovascular risk factors compared to both placebo and other anti-hyperglycemic medications. Reductions in macrovascular complications and mortality were only observed in comparisons with placebo, although trials comparing SGLT2Is vs. other anti-hyperglycemic medications were not designed to assess longer-term outcomes.

Hypoglycemia Communication in Primary Care Visits for Patients with Diabetes.

BACKGROUND: Hypoglycemia is a common and serious adverse effect of diabetes treatment, especially for patients using insulin or insulin secretagogues. Guidelines recommend that these patients be assessed for interval hypoglycemic events at each clinical encounter and be provided anticipatory guidance for hypoglycemia prevention. OBJECTIVE: To determine the frequency and content of hypoglycemia communication in primary care visits. DESIGN: Qualitative study PARTICIPANTS: We examined 83 primary care visits from one urban health practice representing 8 clinicians and 33 patients using insulin or insulin secretagogues. APPROACH: Using a directed content analysis approach, we analyzed audio-recorded primary care visits collected as part of the Achieving Blood Pressure Control Together study, a randomized trial of behavioral interventions for hypertension. The coding framework included communication about interval hypoglycemia, defined as discussion of hypoglycemic events or symptoms; the components of hypoglycemia anticipatory guidance in diabetes guidelines; and hypoglycemia unawareness. Hypoglycemia documentation in visit notes was compared to visit transcripts. KEY RESULTS: Communication about interval hypoglycemia occurred in 24% of visits, and hypoglycemic events were reported in 16%. Despite patients voicing fear of hypoglycemia, clinicians rarely assessed hypoglycemia frequency, severity, or its impact on quality of life. Hypoglycemia anticipatory guidance was provided in 21% of visits which focused on diet and behavior change; clinicians rarely counseled on hypoglycemia treatment or avoidance of driving. Limited discussions of hypoglycemia unawareness occurred in 8% of visits. Documentation in visit notes had low sensitivity but high specificity for ascertaining interval hypoglycemia communication or hypoglycemic events, compared to visit transcripts. CONCLUSIONS: In this high hypoglycemia risk population, communication about interval hypoglycemia and counseling for hypoglycemia prevention occurred in a minority of visits. There is a need to support clinicians to more regularly assess their patients' hypoglycemia burden and enhance counseling practices in order to optimize hypoglycemia prevention in primary care.

Interaction of diabetes genetic risk and successful lifestyle modification in the Diabetes Prevention Programme.

AIM: To test whether diabetes genetic risk modifies the association of successful lifestyle changes with incident diabetes. MATERIALS AND METHODS: We studied 823 individuals randomized to the intensive lifestyle intervention (ILS) arm of the Diabetes Prevention Programme who were diabetes-free 1 year after enrolment. We tested additive and multiplicative interactions of a 67-variant diabetes genetic risk score (GRS) with achievement of three ILS goals at 1 year (≥7% weight loss, ≥150 min/wk of moderate leisure-time physical activity, and/or a goal for self-reported total fat intake) on the primary outcome of incident diabetes over 3 years of follow-up. RESULTS: A lower GRS and achieving each or all three ILS goals were each associated with lower incidence of diabetes (all P < 0.05). Additive interactions were significant between the GRS and achievement of the weight loss goal (P < 0.001), physical activity goal (P = 0.02), and all three ILS goals (P < 0.001) for diabetes risk. Achievement of all three ILS goals was associated with 1.8 (95% CI 0.3, 3.4), 3.1 (95% CI 1.5, 4.7), and 3.9 (95% CI 1.6, 6.2) fewer diabetes cases/100-person-years in the first, second and third GRS tertiles (P < 0.001 for trend). Multiplicative interactions between the GRS and ILS goal achievement were significant for the diet goal (P < 0.001), but not for weight loss (P = 0.18) or physical activity (P = 0.62) goals. CONCLUSIONS: Genetic risk may identify high-risk subgroups for whom successful lifestyle modification is associated with greater absolute reduction in the risk of incident diabetes.

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.

National Survey of Primary Care Physicians' Knowledge, Practices, and Perceptions of Prediabetes.

BACKGROUND: Despite strong evidence and national policy supporting type 2 diabetes prevention, little is known about type 2 diabetes prevention in the primary care setting. OBJECTIVE: Our objective was to assess primary care physicians' knowledge and practice regarding perceived barriers and potential interventions to improving management of prediabetes. DESIGN: Cross-sectional mailed survey. PARTICIPANTS: Nationally representative random sample of US primary care physicians (PCPs) identified from the American Medical Association Physician Masterfile. MAIN MEASURES: We assessed PCP knowledge, practice behaviors, and perceptions related to prediabetes. We performed chi-square and Fisher's exact tests to evaluate the association between PCP characteristics and the main survey outcomes. KEY RESULTS: In total, 298 (33%) eligible participants returned the survey. PCPs had limited knowledge of risk factors for prediabetes screening, laboratory diagnostic criteria for prediabetes, and management recommendations for patients with prediabetes. Only 36% of PCPs refer patients to a diabetes prevention lifestyle change program as their initial management approach, while 43% discuss starting metformin for prediabetes. PCPs believed that barriers to type 2 diabetes prevention are both at the individual level (e.g., patients' lack of motivation) and at the system level (e.g., lack of weight loss resources). PCPs reported that increased access to and insurance coverage of type 2 diabetes prevention programs and coordination of referral of patients to these resources would facilitate type 2 diabetes preventive efforts. CONCLUSIONS: Addressing gaps in PCP knowledge may improve the identification and management of people with prediabetes, but system-level changes are necessary to support type 2 diabetes prevention in the primary care setting.

Approaches to Risk Assessment Among Older Patients With Diabetes.

PURPOSE OF REVIEW: A patient's prognosis and risk of adverse drug effects are important considerations for individualizing care of older patients with diabetes. This review summarizes the evidence for risk assessment and proposes approaches for clinicians in the context of current clinical guidelines. RECENT FINDINGS: Diabetes guidelines vary in their recommendations for how life expectancy should be estimated and used to inform the selection of glycemic targets. Readily available prognostic tools may improve estimation of life expectancy but require validation among patients with diabetes. Treatment decisions based on prognosis are difficult for clinicians to communicate and for patients to understand. Determining hypoglycemia risk involves assessing major risk factors; models to synthesize these factors have been developed. Applying risk assessment to individualize diabetes care is complex and currently relies heavily on clinician judgment. More research is need to validate structured approaches to risk assessment and determine how to incorporate them into patient-centered diabetes care.

A Systematic Review of Community Health Center Based Interventions for People with Diabetes.

Community health centers (CHCs) focus on serving socioeconomically disadvantaged populations with heightened chronic disease burden, making CHCs an ideal setting for implementing diabetes care programs that target vulnerable populations. We aimed to synthesize evidence concerning the effects of CHC interventions in people with diabetes. To do this, four electronic databases were searched, including PubMed, EMBASE, CINAHL, and Scopus, and hand searches of reference collections were undertaken to identify intervention trials published in English. We screened 892 unique titles and abstracts. Two reviewers then independently evaluated 221 full-text articles. We discovered 29 articles met our eligibility criteria for inclusion. We found 27 unique studies with two companion articles. Seventeen studies were randomized controlled trials and the majority had a higher proportion of female and racial/ethnic minorities in the study sample. CHC interventions often involved either one-on-one or group education sessions supplemented by a phone follow-up that were delivered by health providers, nutritionists, or community health workers. CHC interventions using education sessions combined with follow up via phone generally resulted in significant improvements in hemoglobin A1C, while sole telephone-based education studies showed no significant improvements. CHC interventions had no significant effects on physical activity in all six studies that examined the outcome. Overall, we found that CHC interventions were in general effective in improving glucose control when using face-to-face interactions in low-income, underserved, and racial and ethnic minority patients with diabetes. Evidence was limited, however, in regards to other outcomes which suggests the need for continued evaluations of CHC intervention models.

Predictors of Insulin Initiation in Patients with Type 2 Diabetes: An Analysis of the Look AHEAD Randomized Trial.

BACKGROUND: The decision to initiate insulin in patients with type 2 diabetes is a challenging escalation of care that requires an individualized approach. However, the sociodemographic and clinical factors affecting insulin initiation are not well understood. OBJECTIVE: We sought to identify patient factors that were independent predictors of insulin initiation among participants in the Look AHEAD (Action for Health in Diabetes) clinical trial. DESIGN: Retrospective analysis of a randomized clinical trial. PARTICIPANTS: Beginning in 2001, Look AHEAD enrolled ambulatory U.S. adults with type 2 diabetes who were overweight or obese and had a primary healthcare provider. Participants were randomized (1:1) to an intensive lifestyle intervention, or diabetes support and education. This study examined 3913 participants across the two trial arms who were not using insulin at baseline. MAIN MEASURES: We used Cox proportional hazards models to estimate the association between participant characteristics and time to insulin initiation. We performed time-varying adjustment for HbA1c measured eight times over the 10-year study period, as well as for multiple clinical and socioeconomic factors. KEY RESULTS: A total of 1087 participants (27.8%) initiated insulin during a median follow-up of 8.0 years. Age was inversely associated with insulin initiation (adjusted hazard ratio [aHR] 0.88 per 10 years, P = 0.025). The risk of insulin initiation was greater with a higher number of diabetes complications (P < 0.001 for trend); chronic kidney disease and cardiovascular disease were independently associated with insulin initiation. There was a lower risk of insulin initiation in black (aHR 0.77, P = 0.008) and Hispanic participants (aHR 0.66, P < 0.001) relative to white participants. Socioeconomic factors were not associated with insulin initiation. CONCLUSIONS: Patient age, race/ethnicity, and diabetes complications may influence insulin initiation in type 2 diabetes, independent of glycemic control. Future work is needed to understand the drivers of racial differences in antihyperglycemic treatment, and to identify patients who benefit most from insulin.