Action For Health In Diabetes Trial Research Articles

Association between longitudinal changes in body composition and the risk of kidney outcomes in participants with overweight/obesity and type 2 diabetes mellitus.

To assess the relationship of longitudinal changes in fat mass (FM), lean mass (LM) and waist circumference (WC) with incident kidney outcomes in people with overweight/obesity and type 2 diabetes mellitus (T2DM). A total of 3927 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 from the Look AHEAD (Action for Health in Diabetes) trial were included. The primary outcome was kidney outcomes, defined as a decrease in eGFR of at least 40% from baseline at follow-up visit, or end-stage kidney disease. During a median follow-up of 8.0 years, 450 kidney outcomes were documented after the first 1 year. In the intensive lifestyle intervention (ILI) group, reductions in FM (per 10% decrease, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69-0.94) and WC (per 10% decrease, adjusted HR 0.72, 95% CI 0.59-0.88) from baseline to 1-year follow-up were significantly associated with a lower risk of kidney outcomes. The change in LM was not significantly associated with risk of kidney outcomes (per 10% decrease, adjusted HR 0.78, 95% CI 0.58-1.06). In the diabetes support and education group (control group), no significant association was found between changes in body composition and kidney outcomes. Similar results were observed for the 4-year changes in body composition. In this post hoc analysis of the Look AHEAD trial, longitudinal declines in FM and WC were associated with a lower risk of kidney outcomes in the ILI group in participants with overweight/obesity and T2DM.

Association of Body Weight Time in Target Range With the Risk of Kidney Outcomes in Patients With Overweight/Obesity and Type 2 Diabetes Mellitus.

We assessed the relationship of body weight time in target range (TTR) with composite kidney outcome in people with overweight/obesity and type 2 diabetes mellitus (T2DM). Included in this study were 3,601 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 from the Look AHEAD (Action for Health in Diabetes) trial. Body weight TTR was defined as the proportion of time during the first 4 years that body weight was within the weight loss target (a weight loss of ≥7% from baseline). The primary outcome was composite kidney outcome, defined as eGFR decline ≥30% from baseline and to a level <60 mL/min/1.73 m2 at follow-up visit, or end-stage kidney disease. During a median follow-up of 8.0 years, 435 cases of composite kidney outcome were documented. Body weight TTR during the first 4 years was inversely associated with the subsequent risk of composite kidney outcome (per SD increment; adjusted hazard ratio [HR] 0.81; 95% CI 0.70-0.93). Accordingly, the adjusted HRs (95% CI) of composite kidney outcome were 1.00 (reference), 0.73 (0.54-1.00), 0.71 (0.52-0.99), and 0.54 (0.36-0.80) for participants with body weight TTR of 0%, >0% to <29.9%, 29.9% to <69.7%, and 69.7% to <100%, respectively. Similar results were found for a doubling of the urine albumin to creatinine ratio (secondary outcome). A higher body weight TTR, with a weight loss target of losing ≥7% of initial weight, was associated with a lower risk of kidney outcomes in participants with overweight/obesity and T2DM.

The Association of Total Knee Arthroplasty With Weight Loss in the Look AHEAD (Action for Health in Diabetes) Clinical Trial

BackgroundPatients who have obesity seldom lose weight after total knee arthroplasty (TKA). The Look AHEAD (Action for Health in Diabetes) trial randomized patients with type 2 diabetes who were overweight or had obesity to a 10-year intensive lifestyle intervention (ILI) or diabetes support and education (DSE). MethodsOf the total 5,145 participants enrolled who had a median 14-year follow-up, a subset of 4,624 met inclusion criteria. The ILI aimed at achieving and maintaining a 7% weight loss and included weekly counseling the first 6 months, with decreasing frequency thereafter. This secondary analysis was undertaken to determine what effects a TKA had on patients participating in a known successful weight loss program and specifically if there was a negative impact on weight loss or their Physical Component Score. ResultsThe analysis suggests that the ILI remained effective for maintaining or losing weight after TKA. Participants in ILI had significantly greater percent weight loss than those in DSE both before and after TKA (ILI-DSE before TKA: −3.6% (−5.0, −2.3); after TKA: −3.7% (−4.1, −3.3); both P < .0001). When comparing percent weight loss before to after TKA, there was no significant difference within either the DSE or ILI group (least square means ± standard error ILI: −0.36% ± 0.3, P = .21; DSE: −0.41% ± 0.29, P = .16). Physical Component Scores improved after TKA (P < .001), but no difference was found between TKA ILI and DSE groups before or after surgery. ConclusionParticipants who had a TKA did not have an altered ability to adhere to intervention goals to maintain weight loss or obtain further weight loss. The data suggest patients who have obesity can lose weight after TKA on a weight loss program.

Association of baseline and longitudinal changes in cardiometabolic health with risk of heart failure among adults with type 2 diabetes: an analysis from the Look AHEAD trial

Abstract Background Type 2 diabetes (T2D) is characterized by co-morbid cardiometabolic abnormalities and elevated heart failure (HF) risk. Purpose The purpose of this study was to evaluate the associations of baseline and longitudinal changes in cardiometabolic health with risk of HF among adults with T2D. Methods Adults with T2D enrolled in the Look AHEAD (Action for Health in Diabetes) trial without prevalent HF were included. Adjusted Cox models were used to create a cardiometabolic health score incorporating target levels of parameters weighted based on relative risk for HF. The associations of baseline, 1- and 4-year changes in the cardiometabolic health score with risk of overall HF, HF with preserved ejection fraction (HFpEF; EF≥50%), and HF with reduced EF (HFrEF; EF&amp;lt;50%) were assessed using adjusted Cox models. Results Of the 5,080 participants included, there were 257 incident HF events during 12.4-year follow-up. The cardiometabolic health score included 2-points each for target levels of waist circumference, glomerular filtration rate, urine albumin-to-creatinine ratio and 1-point each for blood pressure and hemoglobin A1c at target (Table 1). Higher baseline cardiometabolic health score was significantly associated with lower risk of overall HF (adjusted hazard ratio [aHR] per 1-unit higher score, 0.72 [95% CI, 0.66–0.79]) with similar associations observed for HFpEF and HFrEF (Table 2). Improvement in cardiometabolic health over 1- and 4-years was significantly associated with lower risk of overall HF (aHR per 1-unit increase in score at 1- and 4-years, 0.82 [95% CI, 0.73–0.92] and 0.80 [95% CI, 0.70–0.91], respectively). Conclusions Among adults with T2D, achieving target levels of more cardiometabolic health parameters at baseline and sustained improvements were associated with lower HF risk. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Diabetes and Digestive and Kidney Diseases

Eating breakfast is associated with weight loss during an intensive lifestyle intervention for overweight/obesity.

This study examined whether breakfast consumption frequency (BCF) is associated with weight-loss outcomes in the Look AHEAD (Action for Health in Diabetes) trial. Data from a subset of participants (n = 3,915) from Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) to diabetes support and education (DSE) in adults with overweight/obesity and type 2 diabetes, were analyzed. BCF was collected by yearly questionnaire. Multivariable linear regression models were used to estimate the association between average BCF and percentage weight change over 4 years, controlling for baseline sociodemographic, anthropometric, and diabetes-related variables. In separate models, adjustment for diet (n = 915) and physical activity level (n = 837) was performed in a subset of participants. Four-year average BCF was similar in DSE (n = 1,916) and ILI (n = 1,999) arms (p = 0.14). Each 1-day higher average BCF was associated with an additional 0.5% weight loss in the ILI arm (p < 0.0001) but not in the DSE arm (p = 0.58). This association in the ILI arm remained significant after adjustment for diet (p = 0.02) but not after adjustment for physical activity (p = 0.36). Breakfast consumption was associated with greater weight loss in the active treatment group of an ILI, which may be mediated by increased physical activity.

Racial/ethnic and socioeconomic disparities in the use of newer diabetes medications in the Look AHEAD study

SummaryBackgroundAmong patients with type 2 diabetes, minority racial/ethnic groups have a higher burden of cardiovascular disease, chronic kidney disease, and hypoglycaemia. These groups may especially benefit from newer diabetes medication classes, but high cost may limit access. We examined the association of race/ethnicity with the initiation of newer diabetes medications (GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors).MethodsWe conducted a secondary analysis of the Look AHEAD (Action for Health in Diabetes) trial including participants with at least one study visit after April 28, 2005. Cox proportional hazards models were used to estimate the association between race/ethnicity and socioeconomic factors with time to initiation of any newer diabetes medication from April 2005 to February 2020. Models were adjusted for demographic and clinical characteristics.FindingsAmong 4,892 participants, 63.6%, 15.7%, 12.6%, 5.2%, and 2.9% were White, Black, Hispanic, American Indian or Alaskan Native (AI/AN), or other race/ethnicity, respectively. During a median follow-up of 8.3 years, 2,180 (45.2%) participants were initiated on newer diabetes medications. Race/ethnicity was associated with newer diabetes medication initiation (p=.019). Specifically, initiation was lower among Black (HR 0.81, 95% CI 0.70 –0.94) and AI/AN participants (HR 0.51, 95% CI 0.26–0.99). Yearly family income was inversely associated with initiation of newer diabetes medications (HR 0.78, 95% CI 0.62–0.98) comparing the lowest and highest income groups. Findings were mostly driven by GLP-1 receptor agonists.InterpretationThese findings provide evidence of racial/ethnic disparities in the initiation of newer diabetes medications, independent of socioeconomic factors, which may contribute to worse health outcomes.

Evaluating a Mobile-Health-Enhanced Behavioral Lifestyle Intervention for Frailty in Diabetes: A Feasibility Study

Type 2 diabetes (T2D) and overweight are significant predictors of frailty in older adults. There are no widely accepted intervention strategies for frailty. The Look AHEAD (Action for Health in Diabetes) trial demonstrated the efficacy of behavioral lifestyle intervention on weight loss and glycemic control in overweight older adults with T2D. It is unknown whether this intervention can prevent/delay frailty in older adults. We designed a feasibility study examining the effect of a behavioral lifestyle intervention enhanced with mobile technology (Fitbit) for self-monitoring of diet and physical activity on frailty and T2D outcomes over 6 months in overweight older adults diagnosed with T2D. Forty older adults were randomized to receive either 10 group sessions vs. one condensed session plus monthly phone calls for 6 months. In this analysis, we are reporting on Fitbit wear adherence and weight changes on the 20 participants in the group session for the first 6 group sessions. The study sample was aged 72.3±6.4 years; 62% female; 52% Hispanic; BMI 33.7±5.9 kg/m2; hemoglobin A1c 7.2%; frailty score 1.1±1.0 kg/m2. Thirteen (65%) are pre-frail, 6 (30%) are non-frail, and 1 (5%) is frail (using Fried criteria). Their weight (lbs.) changed from session 1 (210.2±42.5) to session 6 (196.8±44.2). Ten participants wore Fitbit every day between sessions, averaged at 92±12%. The preliminary evaluation showed the feasibility of using Fitbit to promote self-monitoring adherence in a behavioral lifestyle intervention and a positive trend for weight loss. Evaluating intervention effect on frailty at 6 months will provide us further insights.

Abstract 15067: Association of Baseline and Longitudinal Changes in Body Composition Measures With Risk of Heart Failure and Myocardial Infarction in Type 2 Diabetes Mellitus - Findings From the Look Ahead Trial

Introduction: Intentional weight loss is associated with lower risk of heart failure (HF) and atherosclerotic cardiovascular disease among patients with type 2 diabetes mellitus (T2DM). However, the contribution of changes in body composition measures [lean mass (LM), fat mass (FM), waist circumference (WC)] to the risk of HF and myocardial infarction (MI) is not well-known. Methods: Adults with T2DM who had overweight or obesity enrolled in the Look AHEAD (Action for Health in Diabetes) trial without prevalent HF were included. LM and FM were predicted using validated equations and compared with DXA measurements. Adjusted Cox models were used to evaluate the associations of baseline and longitudinal changes in LM, FM, and WC over 1- (Y0 to Y1) and 4-year (Y0 to Y4) follow-up with risk of overall HF, HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF) and MI. Results: Among 5,103 participants, there were 257 incident HF events over 12.4 years of follow-up. Predicted and measured LM and FM were highly correlated (R 2 =0.87-0.92). LM and FM decreased with greater declines in the intensive lifestyle intervention arm (Figure 1A). In adjusted analyses, baseline measures of body composition were not significantly associated with risk of HF. Decline in FM, but not LM, over 1- and 4-year follow-up was significantly associated with lower risk of HF (Figure 1B). A significant association was observed between decline in WC and risk of overall HF and HFpEF but not HFrEF. Among adults without a history of CVD, changes in body composition were not associated with risk of MI. Conclusions: In adults with T2DM who had overweight or obesity, a lifestyle intervention is associated with significant loss of FM and LM. Decline in FM and WC, but not LM, were each significantly associated with lower risk of HF but not MI. Furthermore, decline in WC was significantly associated with lower risk of HFpEF but not HFrEF.

Parents lose less weight than nonparents in an intensive lifestyle intervention.

SummaryObjectiveUnderstand whether parents lose less weight than nonparents in behavioural weight interventions.MethodsThe Look AHEAD (Action for Health in Diabetes) trial randomized adults with Type 2 diabetes and overweight to an intensive lifestyle intervention (ILI) or control (diabetes support and education [DSE]). Participants who reported living with a child under age 18 were designated as ‘parents’ for this analysis. Intention to treat analysis was performed of the effect of the ILI on change in weight at 1 year by parental status. Adherence to attending intervention visits was compared between parents and nonparents. Subgroup analyses were done based on previous subgroup findings in the Look AHEAD study.ResultsAmong 4,547 participants, 15% were parents. Parents were younger and more likely to have self‐identified as African American or Hispanic/Latino. Comparing ILI with DSE, parents lost less weight than nonparents (−7.1% vs. −8.3%, p = 0.021). African American female parents lost 4% body weight compared with 7% in African American female nonparents (p = 0.01).ConclusionsIn a randomized trial, parents lost less weight than nonparents, and this difference was largest for African American women. These findings suggest parents face unique challenges achieving weight loss; more research is needed to understand and optimize interventions for parents.

Change in Cardiometabolic Risk Factors Associated With Magnitude of Weight Regain 3Years After a 1-Year Intensive Lifestyle Intervention in Type 2 Diabetes Mellitus: The Look AHEAD Trial.

BackgroundWeight regain after weight loss is common. The impact on cardiometabolic risk factors is not well established.Methods and ResultsPublicly available data were analyzed from participants of the Look AHEAD (Action for Health in Diabetes) trial with ≥3% initial weight loss (n=1561) during a 1‐year intensive lifestyle intervention and with year 4 follow‐up data. Participants who regained (regainers) or maintained (maintainers) weight loss were defined with 5 dichotomized cut points (0%, 25%, 50%, 75%, and 100%) of percentage weight loss regained (weight change from years 1–4 as percentage of first year weight loss). Change in cardiometabolic risk factors after initial weight loss was compared in maintainers and regainers, after controlling for demographics, medications, and baseline and year 1 change in body mass index. The effect was assessed separately in participants with <10% and ≥10% initial weight loss, and women and men. Maintainers exhibited significant improvements to the cardiometabolic risk factors assessed compared with regainers. No weight regain cut point maximized risk difference between maintainers and regainers across risk factors or sex/initial weight loss subgroups. For many risk factors, allowing more regain as part of maintenance (increasing cut point) diminished the cardiometabolic benefit among maintainers.ConclusionsMaintaining weight loss was better than regain for all risk factors. No single cut point maximized the risk difference between maintainers and regainers. Maintainers who kept off ≥75% of weight lost had the greatest benefit. These findings emphasize the importance of intervention programs focusing not only on weight loss but weight loss maintenance, given the adverse consequences of the latter.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00017953.

Islet autoantibody positivity in overweight and obese adults with type 2 diabetes

Islet autoantibodies are typically associated with type 1 diabetes, but have been found in patients diagnosed with type 2 diabetes in whom they are associated with lower adiposity. The significance of autoantibody positivity in overweight and obese patients is not well understood. The aim of this study was to determine the prevalence and clinical significance of islet autoantibodies in overweight/obese adults diagnosed with type 2 diabetes. This study includes 204 participants at one site of the multicenter Look AHEAD (Action for Health in Diabetes) trial (ClinicalTrials.gov identifier: NCT00017953) which randomized overweight/obese adults diagnosed with type 2 diabetes to an intensive lifestyle intervention or diabetes support and education. We measured antibodies to glutamic acid decarboxylase, insulinoma antigen-2, and zinc transporter 8. Participants with and without autoantibodies were compared with respect to baseline clinical features, and longitudinal changes in weight, hemoglobin A1c, and antihyperglycemic medications. We found that 13 participants (6.4%) were autoantibody positive, including six of 47 participants (12.8%) with BMI ≥40 kg/m2. At baseline, autoantibody positive participants had higher HDL cholesterol (1.27 vs. 1.09 mmol/L, p = .034) and lower fasting C-peptide (0.32 vs. 0.57 nmol/L, p = .049). Over four years, autoantibody positive participants lost 5.1 kg more weight than autoantibody negative participants (p = .056). Longitudinal changes in hemoglobin A1c did not differ by autoantibody status, though autoantibody positive participants were more likely to increase the number of antihyperglycemic medications or initiate insulin (p = .011). In conclusion, islet autoantibodies were present in 6.4% of overweight/obese adults with type 2 diabetes including those with severe obesity, and were associated with distinct clinical features. The effect of autoantibody positivity on weight loss interventions requires further study.

Cardiovascular Protection in People With Diabetes.

Cardiovascular Protection in People With Diabetes.

Pharmacologic Glycemic Management of Type 2 Diabetes in Adults.

Pharmacologic Glycemic Management of Type 2 Diabetes in Adults.

Abstract P249: Differential Response to a Lifestyle Intervention Between Parents and Non-parents

Background: Understanding and preventing cardiovascular disease among parents is important for reducing intergenerational transfer of cardiovascular disease. Prior research has not examined the effect of lifestyle interventions among parents compared to non-parents. We performed a retrospective analysis of the Look AHEAD (Action for Health in Diabetes) trial to assess outcome differences between participants with children younger than 18 years living in the home (referred to as parents) and those without (referred to as non-parents). Methods: Look AHEAD randomized adults aged 45-75 years with type 2 diabetes and BMI&gt;25kg/m 2 to an intensive lifestyle intervention aimed at weight loss, or to a diabetes support and education (control) arm. We examined effects of the intervention at 12 months on objectively measured change in weight (percent of baseline) and cardiovascular risk factors, and change in self-reported dietary intake. To determine whether parenting modified these outcomes, we used linear regression (continuous outcomes) or logistic regression (categorical outcomes) with a multiplicative interaction term for parenting status and treatment arm, adjusted for sociodemographic and clinical characteristics. Modeled results of the interaction are presented. Results: Among 4,547 participants at baseline, 699 (15%) were parents. Parents were younger than non-parents (54.1 vs 59.0 years, p&lt;0.001); more likely to be black (20.2% vs 15.4%) or Hispanic (19.3% vs 12.5%), p&lt;0.001; and more likely to have a professional degree (6.7% vs 5.0%) or no high school education (8.5% vs 5.7%), p&lt;0.001. Age-adjusted baseline prevalence of chronic disease was similar for parents and non-parents. In response to the intervention (treatment minus control arm), parents lost less weight than non-parents, (-7.1% vs -8.3%, p=0.019); and had less improvement in waist circumference (-5.6cm vs -7.2cm, p=0.008). There were trends towards parents having less improvement in triglycerides (-6.0mg/dl vs -17.7mg/dl, p=0.060) and servings of sweets/fats consumed per day (-0.4 vs -0.6, p=0.055). Conclusions: In a clinical trial of an intensive lifestyle intervention for patients with type 2 diabetes, participants with children living in the home had less favorable response to the intervention for change in weight and waist circumference. More research is needed to understand the association of parenthood with health behaviors to optimize cardiovascular risk reduction interventions for parents.

Changes in metformin use and other antihyperglycemic therapies after insulin initiation in patients with type 2 diabetes

AimsWhen patients with type 2 diabetes initiate insulin, metformin should be continued while continuation of other antihyperglycemics has unclear benefit. We aimed to identify practice patterns in antihyperglycemic therapy during the insulin transition, and determine factors associated with metformin continuation. MethodsWe performed a retrospective analysis of the Look AHEAD (Action for Health in Diabetes) trial which randomized overweight/obese adults under ambulatory care for type 2 diabetes to an intensive lifestyle intervention or diabetes support and education. Among the 931 participants who initiated insulin over ten years, we described longitudinal changes in antihyperglycemic medications during the insulin transition, and performed multivariable logistic regression to estimate the association between patient characteristics and metformin continuation. ResultsBefore insulin initiation, 81.0% of patients used multiple antihyperglycemics, the most common being metformin, sulfonylureas, and thiazolidinediones. After insulin initiation, metformin was continued in 80.3% of patients; other antihyperglycemics were continued less often, yet 58.0% of patients were treated with multiple non-insulin antihyperglycemics. Metformin continuation was inversely associated with age (fully adjusted (a) OR 0.60 per 10 years [0.42–0.86]), serum creatinine above safety thresholds (aOR 0.09 [0.02–0.36]), lower income (P = 0.025 for trend), taking more medications (aOR 0.92 per medication [0.86–0.98]), and initiating rapid, short, or premixed insulin (aOR 0.59 [0.39–0.89]). ConclusionsThe vast majority of patients with type 2 diabetes continue metformin after insulin initiation, consistent with guidelines. Other antihyperglycemics are frequently continued along with insulin, and further research is needed to determine which, if any, patients may benefit from this.

The Look AHEAD Trial: Translating Lessons Learned Into Clinical Practice and Further Study.

IN BRIEF Although the Look AHEAD (Action for Health in Diabetes) trial, which spanned more than 8 years, did not find significant differences in cardiovascular morbidity and mortality between study groups, it did demonstrate significant differences in weight loss and maintenance. Using lessons learned from the Look AHEAD protocol, clinicians can help people with type 2 diabetes lose weight, improve glucose management, increase physical activity, alter eating patterns, and support long-term positive health outcomes. It remains important, however, to avoid assigning a higher priority to weight loss goals than to improvements in glucose management, long-term health outcomes, and quality of life.

Changes in skeletal muscle and organ size after a weight-loss intervention in overweight and obese type 2 diabetic patients

Background: The effect of a weight-loss intervention on the masses of lean tissues and organs in humans is not well known.Objective: We studied the effects of a diet and exercise weight-loss intervention on skeletal muscle (SM) mass and selected organs over 2 y using MRI in overweight adults with type 2 diabetes.Design: Participants were 53 women and 39 men [mean ± SD: age 58 ± 7 y; body mass index (BMI; in kg/m2) 32 ± 3] enrolled in the Look AHEAD (Action for Health in Diabetes) trial and randomly assigned to an intensive lifestyle intervention (ILI) or diabetes support and education (DSE) on whom 2 y of data were collected. MRI-derived measurements of SM, heart, liver, kidney, spleen, and pancreas were acquired.Results: Adjusted for baseline weight, height, age, sex, and ethnicity, the ILI group weighed (mean ± SE) 6.6 ± 0.7 kg less after 1 y and 5.2 ± 0.7 kg less after 2 y, whereas the DSE group did not change significantly (−0.4 ± 0.6 and −1.0 ± 0.7 kg after 1 and 2 y, respectively; P-interaction < 0.001). Total SM decreased in both groups during year 1 (−1.4 ± 0.2 kg; P < 0.001) with appendicular SM regained during year 2. Liver and spleen masses decreased in the ILI group (−0.12 ± 0.02 and −0.006 ± 0.003 kg, respectively) but were unchanged in the DSE group (0.00 ± 0.02 and 0.004 ± 0.003 kg, respectively). Kidney mass decreased by 0.013 ± 0.003 kg (P < 0.001) over 2 y in both groups.Conclusions: Decreases in liver (in Caucasians but not African Americans) and spleen were detected after a 6.2-kg weight reduction compared with a control group. SM and kidney mass decreased in both groups. Appendicular SM was regained during the second year whereas trunk SM was not. No evidence of a disproportionate loss of high–metabolic rate organs (heart, liver, kidney, spleen) compared with SM was found.

Lifestyle Weight-Loss Intervention Outcomes in Overweight and Obese Adults with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

The majority of people with type 2 diabetes are overweight or obese, and weight loss is a recommended treatment strategy. A systematic review and meta-analysis was undertaken to answer the following primary question: In overweight or obese adults with type 2 diabetes, what are the outcomes on hemoglobin A1c (HbA1c) from lifestyle weight-loss interventions resulting in weight losses greater than or less than 5% at 12 months? Secondary questions are: What are the lipid (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides) and blood pressure (systolic and diastolic) outcomes from lifestyle weight-loss interventions resulting in weight losses greater than or less than 5% at 12 months? And, what are the weight and metabolic outcomes from differing amounts of macronutrients in weight-loss interventions? Inclusion criteria included randomized clinical trial implementing weight-loss interventions in overweight or obese adults with type 2 diabetes, minimum 12-month study duration, a 70% completion rate, and an HbA1c value reported at 12 months. Eleven trials (eight compared two weight-loss interventions and three compared a weight-loss intervention group with a usual care/control group) with 6,754 participants met study criteria. At 12 months, 17 study groups (8 categories of weight-loss intervention) reported weight loss <5% of initial weight (−3.2 kg [95% CI: −5.9, −0.6]). A meta-analysis of the weight-loss interventions reported nonsignificant beneficial effects on HbA1c, lipids, or blood pressure. Two study groups reported a weight loss of ≥5%: a Mediterranean-style diet implemented in newly diagnosed adults with type 2 diabetes and an intensive lifestyle intervention implemented in the Look AHEAD (Action for Health in Diabetes) trial. Both included regular physical activity and frequent contact with health professionals and reported significant beneficial effects on HbA1c, lipids, and blood pressure. Five trials (10 study groups) compared weight-loss interventions of differing amounts of macronutrients and reported nonsignificant differences in weight loss, HbA1c, lipids, and blood pressure. The majority of lifestyle weight-loss interventions in overweight or obese adults with type 2 diabetes resulted in weight loss <5% and did not result in beneficial metabolic outcomes. A weight loss of >5% appears necessary for beneficial effects on HbA1c, lipids, and blood pressure. Achieving this level of weight loss requires intense interventions, including energy restriction, regular physical activity, and frequent contact with health professionals. Weight loss for many overweight or obese individuals with type 2 diabetes might not be a realistic primary treatment strategy for improved glycemic control. Nutrition therapy for individuals with type 2 diabetes should encourage a healthful eating pattern, a reduced energy intake, regular physical activity, education, and support as primary treatment strategies.

Changes in Adipose Tissue Depots and Metabolic Markers Following a 1-Year Diet and Exercise Intervention in Overweight and Obese Patients With Type 2 Diabetes

OBJECTIVEWe aim to characterize the effects on total body fat and distribution of a 1-year intensive lifestyle intervention (ILI) for weight loss in overweight and obese adults with type 2 diabetes and to examine whether changes in adipose tissue (AT) depots were associated with changes in metabolic biomarkers.RESEARCH DESIGN AND METHODSParticipants were 54 females and 38 males (age 57.8 ± 6.7 years [mean ± SD]; BMI 31.7 ± 3.5 kg/m2) enrolled in the Look AHEAD (Action for Health in Diabetes) trial randomized to ILI or diabetes support and education (DSE) from whom baseline and 1-year MRI measures of total AT (TAT) and regional (arm, trunk, leg) AT, including subcutaneous AT (SAT), visceral AT (VAT), and intermuscular AT (IMAT), were acquired. We tested whether mean changes in ILI and DSE were equal and, within groups, whether changes were different from zero. Regression models tested whether changes in AT compartments were associated with metabolic variable changes.RESULTSBody weight changed −0.52 ± 3.62 kg (P = 0.31) in DSE and −7.24 ± 5.40 kg (P < 0.0001) in ILI. Mean ILI changes were different from DSE (P < 0.001 for TAT, SAT, and IMAT and P < 0.01 for VAT in females). Within ILI, SAT and VAT decreased in males and females (P < 0.0001), but IMAT was unchanged (0.00 ± 0.54 kg; P = 0.99). In DSE, SAT and VAT did not change, but IMAT increased by 0.46 ± 0.55 kg (P < 0.001). Controlling for weight loss, reduction of specific AT depots was associated with improvement in metabolic biomarkers.CONCLUSIONSWeight loss of 7–10% from an ILI over 1 year reduced SAT and VAT and prevented an increase in IMAT. Reductions in AT depots were associated with improvements in biomarkers.

Effect of a long-term behavioural weight loss intervention on nephropathy in overweight or obese adults with type 2 diabetes: a secondary analysis of the Look AHEAD randomised clinical trial

Long-term effects of behavioural weight loss interventions on diabetes complications are unknown. In a secondary analysis of the Look AHEAD (Action for Health in Diabetes) multicentre randomised clinical trial, we assessed whether an intensive lifestyle intervention (ILI) affects the development of nephropathy in people with type 2 diabetes. Overweight or obese people aged 45-76 years with type 2 diabetes were randomly assigned (1:1) to ILI or to a diabetes support and education (DSE) group by a central web-based data management system, stratified by clinical centre and blocked with random block sizes. The ILI was designed to achieve and maintain weight loss through reduced caloric consumption and increased physical activity. The interventions were terminated early because of absence of effect on the primary outcome of cardiovascular disease events in the main Look AHEAD trial. Albuminuria and estimated glomerular filtration rate were prespecified as two of many other outcomes and were assessed from baseline until the interventions ended. They were combined post hoc to define the main outcome for this report, very-high-risk chronic kidney disease (CKD), based on the 2013 Kidney Disease Improving Global Outcomes (KDIGO) classification. Outcomes assessors and laboratory staff were masked to treatment, but participants and interventionists were not masked. Time-to-event data were analysed by intention to treat by the Kaplan-Meier method and proportional hazards models. The Look AHEAD trial is registered with ClinicalTrials.gov, NCT00017953. Of the 5145 participants randomly assigned in the Look AHEAD trial (2570 to ILI and 2575 to DSE), analyses for very-high-risk CKD were done in 2423 (94%) of patients in the ILI group and 2408 (94%) of those in the DSE group. After a median of 8·0 years (IQR 7·9-9·9) of follow-up, the incidence of very-high-risk CKD was lower in the ILI group than in the DSE group, with incidence rates of 0·91 cases per 100 person-years in the DSE group and 0·63 per 100 person-years in the ILI group (difference 0·27 cases per 100 person-years, hazard ratio 0·69, 95% CI 0·55-0·87; p=0·0016). This effect was partly attributable to reductions in bodyweight, HbA1c, and systolic blood pressure. There were no safety concerns regarding kidney-related adverse events. Weight loss should be considered as an adjunct to medical treatments to prevent or delay progression of CKD in overweight or obese people with type 2 diabetes. National Institute of Diabetes and Digestive and Kidney Diseases.