Diabetes Support And Education Research Articles

Abstract 4144573: Cardiac biomarkers, intensive lifestyle intervention, and risk of heart failure subtypes in type 2 diabetes – a post-hoc analysis of the Look AHEAD trial

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) identify subclinical heart failure (HF) in type 2 diabetes (T2D). The contribution of changes in cardiac biomarkers to HF risk, particularly HF subtypes, is unclear. Whether HF risk associated with cardiac biomarkers is modifiable with an intensive lifestyle intervention (ILI) targeting weight loss is unknown. Methods: Adults with T2D and overweight/obesity in the Look Action for Health in Diabetes (AHEAD) trial without prevalent HF were included. NT-proBNP and hs-cTnT were measured at baseline, 1- and 4-years (Roche Diagnostics). Adjusted Cox models were created to evaluate the associations of baseline, 1- and 4-year change in NT-proBNP and hs-cTnT with risk of HF with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Interaction testing was performed to evaluate heterogeneous effects of the ILI vs diabetes support and education (DSE) across baseline cardiac biomarkers. Results: Of the 3,959 participants included, 212 had incident HF (108 HFpEF, 84 HFrEF) over 12 years. Higher baseline NT-proBNP and hs-cTnT were each significantly associated with higher risk of HFpEF and HFrEF ( Table) . Increases in NT-proBNP over 1- and 4-years were significantly associated with higher risk of HFpEF and HFrEF with a similar pattern of association for hs-cTnT and HF subtypes. After accounting for risk factor changes, the association of 1- and 4-year changes in NT-proBNP, but not hs-cTnT, with risk of HF subtypes remained significant. There was a significant interaction between NT-proBNP and ILI for risk of HFpEF but not HFrEF (p-int = 0.001). The ILI reduced HFpEF risk among participants with elevated (≥125 pg/mL) but not non-elevated NT-proBNP (<125 pg/mL) (ILI vs DSE HR [95% CI]: 0.48 [0.25-0.93] and 1.67 [0.94-2.94], respectively). No significant treatment group by hs-cTnT interactions were identified. Conclusions: In T2D, longitudinal changes in cardiac biomarkers, particularly NT-proBNP, are significantly associated with HF risk, independent of risk factor changes. In Look AHEAD, elevated NT-proBNP may identify individuals who are more likely to benefit from the ILI for HFpEF prevention.

Long-term sustained effects of the Look AHEAD lifestyle intervention on body composition among adults with type 2 diabetes.

The objective of the study was to test whether there are sustained effects of the Look AHEAD intensive lifestyle intervention (ILI), versus diabetes support and education (DSE), on weight and body composition 12 to 16 years after randomization. Participants were a subset of enrollees in the Look AHEAD dual-energy x-ray absorptiometry substudy who completed the final visit, composed of men (DSE = 99; ILI = 94) and women (DSE = 134; ILI = 135) with type 2 diabetes and mean (SD) age 57.2 (6.4) years and BMI 34.9 (5.1) kg/m2 at randomization. Dual-energy x-ray absorptiometry measured total and regional fat and lean masses at randomization, at Years 1, 4, and 8, and at the final visit. Linear mixed-effects regressions were applied with adjustment for group, clinic, sex, age, race/ethnicity, and baseline body composition. Weight and most body compartments were reduced by 2% to 8% (and BMI 4%) in ILI versus DSE in men but not women. ILI-induced loss of lean tissue did not show a lower percent lean mass versus DSE at 16 years after randomization. ILI-related changes in weight, fat, and lean mass were detectable 12 to 16 years after randomization in men but, for unknown reasons, not in women. There was no evidence that the intervention led to a disproportionate loss of lean mass by the end of the study.

Within and post-trial effects of an intensive lifestyle intervention on kidney disease in adults with overweight or obesity and type 2 diabetes mellitus: a secondary analysis of the Look AHEAD clinical trial

IntroductionThe Look AHEAD randomized clinical trial reported that an 8-year intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) in adults aged 45–76 years with type 2 diabetes...

Intensive lifestyle intervention in type 2 diabetes and risk of incident coronary artery disease for the common haptoglobin phenotypes: the Look AHEAD study

BackgroundIntensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown whether Hp phenotype modifies the effect of an intensive lifestyle intervention (ILI) on CAD in type 2 diabetes.MethodsHaptoglobin phenotype was measured in 4542 samples from the Action for Health in Diabetes (Look AHEAD) study. Cox regression models assessed the effect of ILI (focused on weight loss from caloric restriction and physical activity) versus diabetes support and education (DSE) on CAD events in each phenotype group, and within pre-specified subgroups including race/ethnicity, sex, history of cardiovascular disease, diabetes medication use, and diabetes duration.Results1590 (35%) participants had the Hp2-2 phenotype. The ILI did not lower glycated hemoglobin (%HbA1c) to < 6.5% in either phenotype, with a peak significant difference between treatment arms of 0.5% [non-Hp2-2] and 0.6% [Hp2-2]. The cumulative CAD incidence was 13.4% and 13.8% in the DSE arm and 12.2% and 13.6% in the ILI arm for non-Hp2-2 and Hp2-2 groups, respectively. Compared to DSE, the ILI was not associated with CAD among participants without (HR = 0.95, 95% CI 0.78–1.17) or with (0.89, 0.68–1.19) the Hp2-2 phenotype (p-interaction between Hp phenotype and ILI = 0.58). After Bonferroni correction, there were no significant results among any subgroups.ConclusionsHp phenotype did not modify the effect of the weight loss ILI on risk of CAD in Look AHEAD, potentially because it did not substantially impact glycemic control among participants with or without the Hp2-2 phenotype. Further research is needed to determine if these results are conclusive.

Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort.

Emerging evidence suggests that a number of factors can influence blood-based biomarker levels for Alzheimer's disease (AD) and Alzheimer's related dementias (ADRD). We examined the associations that demographic and clinical characteristics have with AD/ADRD blood-based biomarker levels in an observational continuation of a clinical trial cohort of older individuals with type 2 diabetes and overweight or obesity. Participants aged 45-76 years were randomized to a 10-year Intensive Lifestyle Intervention (ILI) or a diabetes support and education (DSE) condition. Stored baseline and end of intervention (8-13 years later) plasma samples were analyzed with the Quanterix Simoa HD-X Analyzer. Changes in Aβ42, Aβ40, Aβ42/Aβ40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic, and clinical characteristics. In a sample of 779 participants from the Look AHEAD cohort, we found significant associations between blood-based biomarkers for AD/ADRD and 15 of 18 demographic (age, gender, race and ethnicity, education) and clinical characteristics (APOE, depression, alcohol use, smoking, body mass index, HbA1c, diabetes duration, diabetes treatment, estimated glomerular filtration rate, hypertension, and history of cardiovascular disease) . Blood-based biomarkers of AD/ADRD are influenced by common demographic and clinical characteristics. These factors should be considered carefully when interpreting these AD/ADRD blood biomarker values for clinical or research purposes.

LONG-TERM IMPACT OF A LIFESTYLE INTERVENTION: THE ACTION FOR HEALTH IN DIABETES (LOOK AHEAD) TRIAL AND FOLLOW-UP

Abstract Mid-life weight loss and maintenance is often recommended as a means to improve health later in life, however its long-term benefits have not been rigorously established. The Look AHEAD randomized controlled trial compared an intensive lifestyle intervention (ILI) designed to induce and maintain a 7% weight loss through caloric restriction and increased physical activity with a control condition of diabetes support and education (DSE) in 5,145 individuals aged 45-76 years with type 2 diabetes and overweight/obesity over up to 11 years of follow-up beginning in 2001. Compared to DSE, ILI had greater initial improvements in cardiovascular disease risk factors; however, there were no overall differences in the incidence of the trial’s primary and secondary cardiovascular outcomes between the ILI and DSE groups. ILI did, though, have a positive impact on diabetes control and complications, depression, physical health–related quality of life, and health care use and costs. Subsequently, the Look AHEAD trial transitioned to an observational study in 2012 to assess the long-term benefits and potential harms of ILI, which continued for 10 years. This symposium will describe the design of the Look AHEAD trial and transition to the Look AHEAD Aging study, the most recent phone-only observational follow-up begun in 2022, and the long-term impact of the lifestyle intervention on sleep (Spira and colleagues), cognitive resilience (Espeland and colleagues), multi-morbidity and frailty assessed by the deficit accumulation model (Simpson and colleagues), and medical care utilization and costs (Davis and colleagues).

LONG-TERM ASSOCIATION OF AN INTENSIVE LIFESTYLE INTERVENTION ON GLOBAL COGNITIVE FUNCTION

Abstract The long-term effects of mid-life changes in lifestyle on later life cognitive function have not been rigorously assessed among individuals with type 2 diabetes. The Look AHEAD Aging study examined differences in standardized composite cognitive function scores in 1367 individuals, currently aged 64 to 95 years, who had enrolled an average of 20 years previously in a randomized controlled trial to compare a 10-year multidomain intensive lifestyle intervention (ILI) to a condition of diabetes support and education (DSE). The composite averaged standardized scores from the telephone administration of tests chosen to capture the individual cognitive domains of memory, attention/processing speed, executive function, and global cognitive function. At enrollment into the Look AHEAD Aging study there was no overall difference between intervention groups in cognitive test scores: mean [SE]: -0.01 [0.03] ILI versus 0.00 [0.04] DSE (p=0.76). However, among participants with overweight at Look AHEAD enrollment, those assigned to ILI had mean [95%CI] of 0.33 [0.08, 0.57] better global cognitive function scores than those assigned to DSE. For those initially with obesity, there was no relative intervention benefit: mean [95%CI] -0.08 [-0.18, 0.03] (interaction p=0.003). Benefits for those with overweight appeared to be strongest for tests of memory. ILI should be recommended to individuals with type 2 diabetes and overweight to provide long-term resilience against cognitive aging. The cognitive benefits we have reported earlier for individuals with overweight during intervention delivery endure for a decade following the cessation of the intervention.

Association of Lifestyle Intervention With Risk for Cardiovascular Events Differs by Level of Glycated Hemoglobin.

We reevaluated the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) to assess whether the effect of ILI on cardiovascular disease (CVD) prevention differed by baseline glycated hemoglobin (HbA1c). Look AHEAD randomized 5145 adults, aged 45 to 76 years with type 2 diabetes and overweight/obesity to ILI or a diabetes support and education (DSE) control group for a median of 9.6 years. ILI focused on achieving weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial's primary composite CVD outcome. We evaluated additive and multiplicative heterogeneity of the intervention on CVD risk by baseline HbA1c. Mean baseline HbA1c was 7.3% (SD 1.2) and ranged from 4.4% (quintile 1) to 14.5% (quintile 5). We observed additive and multiplicative heterogeneity of the association between ILI and CVD (all P < .001) by baseline HbA1c. Randomization to ILI was associated with lower CVD risk for HbA1c quintiles 1 [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.53, 0.88] and 2 (HR: 0.80, 95% CI: 0.66, 0.96) and associated with higher CVD risk for HbA1c quintile 5 (HR: 1.27, 95% CI: 1.02, 1.58), compared to DSE. Among adults with type 2 diabetes and overweight/obesity, randomization to a lifestyle intervention was differentially associated with CVD risk by baseline HbA1c such that it was associated with lower risk at lower HbA1c levels and higher risk at higher HbA1c levels. There is a critical need to develop and tailor lifestyle interventions to be successful for individuals with type 2 diabetes and high HbA1c.

Rationale, design, and cohort characteristics of the Action for Health in Diabetes Aging study.

Diabetes and overweight/obesity are described as accelerating aging processes, yet many individuals with these conditions maintain high levels of cognitive and physical function and independence late into life. The Look AHEAD Aging study is designed to identify 20-year trajectories of behaviors, risk factors, and medical history associated with resilience against geriatric syndromes and aging-related cognitive and physical functional deficits among individuals with these conditions. Look AHEAD Aging extends follow-up of the cohort of the former 10-year Look AHEAD trial. The original cohort (N = 5145) was enrolled in 2001 to 2004 when participants were aged 45 to 76 years and randomly assigned to a multidomain intensive lifestyle intervention (ILI) or a diabetes support and education (DSE) condition. The trial interventions ceased in 2012. Clinic-based follow-up continued through 2020. In 2021, the cohort was invited to enroll in Look AHEAD Aging, an additional 4-year telephone-based follow-up (every 6 months) enhanced with Medicare linkage. Standardized protocols assess multimorbidity, physical and cognitive function, health care utilization, and health-related quality of life. Of the original N = 5145 Look AHEAD participants, N = 1552 active survivors agreed to participate in Look AHEAD Aging. At consent, the cohort's mean age was 76 (range 63 to 94) years and participants had been followed for a mean of 20 years. Of the original Look AHEAD enrollees, those who were younger, female, or with no history of cardiovascular disease were more likely to be represented in the Look AHEAD Aging cohort. Intervention groups were comparable with respect to age, diabetes duration, body mass index, insulin use, hypertension, cardiovascular disease, and cognitive function. ILI participants had significantly lower deficit accumulation index scores. By continuing the long-term follow-up of an extensively characterized cohort of older individuals with type 2 diabetes, Look AHEAD Aging is well positioned to identify factors associated with resilience against aging-related conditions.

The association between Alzheimer’s disease blood‐based biomarkers and cognitive impairment and probable dementia in Look AHEAD MIND

AbstractBackgroundThe effect of an intensive lifestyle intervention (ILI) on Alzheimer’s disease (AD) blood‐based biomarker levels and cognitive outcomes among individuals with type 2 diabetes (T2D) is unknown. We examined AD biomarkers and cognitive outcomes in the Look AHEAD Study.MethodParticipants aged 45‐76 years were randomized at baseline to a 10‐year ILI or a diabetes support and education (DSE) condition. Cognitive assessments at years 8‐18 included measures of attention, executive function, global function, and memory. Mild cognitive impairment (MCI) and probable dementia were adjudicated by an expert panel. Stored baseline and end‐of‐intervention plasma samples were analyzed with the Quanterix Simoa HD‐X Analyzer. Changes in Aβ42/Aβ40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic characteristics, and cognitive outcomes. Cognitive scores and biomarker levels were converted to z‐scores. Cognitive trajectories were evaluated using mixed models to account for repeated measures; logistic regression was used for a composite outcome of MCI/dementia. Models were adjusted for baseline characteristics (age, sex, education, race/ethnicity, body mass index (BMI), CVD history, hypertension, diabetes duration, eGFR), APOE‐ε4, randomization arm, time from randomization, and time between blood draw and cognitive testing.ResultThe mean age of 779 participants was 61.4 years; 56% = female, 22.8% = APOE ε4+, mean BMI = 34.8, baseline diabetes duration &gt;5 years = 57%, 16.7% Black, 12.5% Hispanic, 66.2% White, and 4.7% other racial and ethnic groups. There were no associations between the intervention and biomarker levels at baseline or biomarker change over time. Increases in NfL levels significantly predicted lower memory (‐0.04 ±0.01; p = 0.002), global cognition scores (‐0.05 ±0.02; p = 0.011), executive function (‐0.04 ±0.01; p = 0.01), as well as increased risk of MCI/probable dementia (odds ratio [OR] 1.10, 95% CI 1.02‐1.19). Increases in GFAP predicted lower memory (‐0.10 ±0.03; p = 0.0001), global cognition (‐0.09 ±0.03; p = 0.009), executive function scores (‐0.12 ±0.03; p&lt;0.0001), and increased risk of MCI/probable dementia (OR 1.24, 95% CI 1.09‐1.41).ConclusionThere was no association between the intervention and changes in biomarker levels. Increasing levels of NfL and GFAP over the ∼10 year period were associated with reduced cognitive performance and increased risk of MCI/probable dementia.

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.

Abstract P153: Intensive Lifestyle Intervention in Type 2 Diabetes Mellitus Results in a More Favorable Sex Hormone Profile in Both Post-Menopausal Females and Older Males (The Look AHEAD Trial Sex Hormone Study)

Background: Prior studies showed an association between some adverse cardiometabolic outcomes and lower testosterone in males and higher estrogen in both males and post-menopausal females. However, few studies of sex hormones focused on people with type 2 diabetes (T2DM), assessed hormone changes over time or applied highly sensitive laboratory assays. Given the importance of lifestyle modification (i.e., diet, exercise and weight loss) in preventing cardiometabolic complications in people with T2DM, we examined the impact of an Intensive Lifestyle Intervention (ILI) on sex hormones over time and differences by sex. Methods: The Look AHEAD (Action for Health in Diabetes) Study was a randomized control trial of 5,145 individuals with BMI ≥25 and T2D to evaluate the effect of ILI compared to the Diabetes Support and Education (DSE) control group on incident cardiovascular events. We selected a sample of 472 males and 426 post-menopausal female participants (mean age 60 years [SD 6.3], 20.5% Black) to examine sex hormones (estradiol - E2, total testosterone - T) and sex hormone binding globulin (SHBG) at baseline and year 1. E2 and T were measured using mass spectrometry analysis and SHBG was measured using an immunoassay. Results: In males, ILI increased SHBG by 17.3% and T by 10.6% compared to the DSE group (Table). In postmenopausal females, ILI increased SHBG by 12.0% and decreased E2 by 23.4% compared to the DSE group (Table). The change in the sex hormone levels from baseline to 1-year follow up was attenuated when adjusted for change in BMI. Conclusion: ILI resulting in weight loss increased T in males and decreased E2 in postmenopausal females and increased SHBG in both sexes. We plan further analysis with a larger sample and longer follow-up to examine the role of weight loss either as a co-occurring metabolic process or as a mediator for the change in sex hormones to better understand the impact of lifestyle changes and sex diffrences.

Is the Long‐term Impact of a Multidomain Lifestyle Intervention on Cognitive Function Mediated by Changes in Leptin and Vascular Endothelial Growth Factor Concentrations?

AbstractBackgroundThe 10‐year intensive lifestyle intervention (ILI) of the Look AHEAD study resulted in a legacy of relative deficits in cognitive function among participants who entered the clinical trial with a history of cardiovascular disease or current obesity, as compared to participants assigned to the diabetes support and education (DSE) intervention. We hypothesized that levels of two weight‐sensitive proangiogenic cytokines, leptin and vascular endothelial growth factor (VEGF), which have been previously reported to be associated with cognitive function, may have been altered by the ILI and account for this concerning finding.MethodConcentrations of leptin and VEGF were determined using stored serum collected from 1,279 participants at Look AHEAD baseline, proximal to cessation of the intervention (Epoch 1), and an average of 4 years later (Epoch 2). Masked clinic staff conducted up to four standardized assessments of cognitive function at times ranging from 8 to 18 years after baseline. A composite score was derived from tests of attention, executive function, and memory. Mixed effects models were used to assess relative differences in leptin and VEGF concentrations between intervention groups and whether these accounted for changes in cognitive composite scores, overall and within subgroups defined by baseline history of cardiovascular disease or obesity.ResultIn both intervention groups, leptin concentrations increased from baseline to Epoch 1, and further between Epochs 1 and 2 (p&lt;0.001). VEGF concentrations decreased between enrollment and Epoch 2 in both groups, and decreased substantially more between Epoch 1 and 2 in ILI than in DSE (p = 0.04). Overall, there was little evidence that leptin and VEGF concentrations were related to cognitive functioning. ILI‐DSE differences in VEGF, but not leptin, concentrations varied depending on baseline history of cardiovascular disease and obesity, but neither leptin or VEGF concentrations accounted for the relative decrements in cognitive function evident during long‐term follow‐up in participants assigned to ILI.ConclusionAmong persons with type 2 diabetes and either a history of cardiovascular disease or obesity, long‐term relative deficits in cognitive function associated with intensive lifestyle intervention are not related to differences in two weight‐sensitive proangiogenic cytokines.

Racial/ethnic and socioeconomic disparities in weight outcomes, cardiovascular events, and mortality in the look AHEAD trial

BackgroundIntensive lifestyle interventions (ILI) for type 2 diabetes (T2D) improve health outcomes, but participants from different races/ethnicities or socioeconomic status may not benefit equally. MethodsWithin the Look AHEAD trial, we examined achievement of the 7% weight loss goal, as well as secondary weight, cardiovascular, and mortality outcomes, by race/ethnicity and educational attainment (EA). ResultsAmong 4,640 participants (31 % Black or Hispanic, 13 % with less than a high school degree), Black and Hispanic participants were less likely than White participants to achieve 7 % weight loss in both the ILI (45.8 % v. 60.7 %, p < 0.001 and 53.0 % v. 60.7 %, p = 0.01, respectively) and diabetes support and education (DSE) arms. Contrastingly, participants with less than a high school degree were more likely in the ILI but less likely in the DSE arm to achieve this goal, with a significant arm by EA interaction. Hispanic participants and those with lowest EA also experienced decreased mortality in the ILI versus the DSE arm. ConclusionsAll Look AHEAD participant subgroups achieved greater weight loss from ILI; however, Black and Hispanic participants lost less weight than White participants in both arms, while those with lowest EA benefited disproportionately from the ILI compared to participants with higher EA.

1199-P: Racial/Ethnic and Socioeconomic Disparities in the Look AHEAD Trial

Background: It is unknown whether the benefits of intensive lifestyle interventions (ILI) are equally distributed among participants with type 2 diabetes of different races/ethnicities or educational attainment. We hypothesized that individuals of White race/ethnicity and greater educational attainment (EA) would receive greater benefit from ILI within a clinical trial. Methods: Using data from the Look AHEAD trial which assigned adults with T2D to an ILI or diabetes support and education (DSE) , we examined weight outcomes (achievement of the 7% weight loss goal, percent weight change) , stratified by race/ethnicity and EA. Differences between groups are described using univariate analyses and multivariable linear and logistic regression adjusted for age, sex, treatment arm, and baseline insulin use. Results: Among 4,640 participants (mean age 59 years, 58% women) , 17% were non-Hispanic Black, 14% were Hispanic, and 13% did not have a high school degree. Black and Hispanic participants were less likely to achieve the weight loss goal in both the ILI (45.8% vs. 60.7%, p&amp;lt;0.0 and 53.0% vs. 60.7%, p=0.01, respectively) and DSE arms of the trial and achieved lesser percent weight loss in the ILI arm. By contrast, participants with lower EA (less than a high school degree) were more likely to achieve the weight loss goal in the ILI but numerically less likely to achieve it in the DSE arm, with evidence of an arm by education interaction (p for interaction 0.015) , suggesting greater benefit from the ILI in this subgroup. Participants with lower EA also achieved greater percent weight change than peers in the ILI at both 1 year and 4 years after randomization, with ongoing evidence of an arm by education interaction at 4 years. Conclusions: Black and Hispanic participants experienced less weight loss in both arms of the Look AHEAD trial, whereas those with lower EA experienced superior benefits in the ILI compared to other groups. Individuals with low EA may receive relatively greater benefits from ILIs, compared to those with higher EA. Disclosure S.Cromer: Other Relationship; Johnson &amp; Johnson Medical Devices Companies, Research Support; National Institute of Diabetes and Digestive and Kidney Diseases. J.B.Meigs: Consultant; Quest Diagnostics. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. Funding NIDDK F32DK127545

Weight Change During the Postintervention Follow-up of Look AHEAD.

Patients with type 2 diabetes are encouraged to lose weight, but excessive weight loss in older adults may be a marker of poor health and subsequent mortality. We examined weight change during the postintervention period of Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) with diabetes support and education (DSE) (control) in overweight/obese individuals with type 2 diabetes and sought to identify predictors of excessive postintervention weight loss and its association with mortality. These secondary analyses compared postintervention weight change (year 8 to final visit; median 16 years) in ILI and DSE in 3,999 Look AHEAD participants. Using empirically derived trajectory categories, we compared four subgroups: weight gainers (n = 307), weight stable (n = 1,561), steady losers (n = 1,731), and steep losers (n = 380), on postintervention mortality, demographic variables, and health status at randomization and year 8. Postintervention weight change averaged -3.7 ± 9.5%, with greater weight loss in the DSE than the ILI group. The steep weight loss trajectory subgroup lost on average 17.7 ± 6.6%; 30% of steep losers died during postintervention follow-up versus 10-18% in other trajectories (P < 0001). The following variables distinguished steep losers from weight stable: baseline, older, longer diabetes duration, higher BMI, and greater multimorbidity; intervention, randomization to control group and less weight loss in years 1-8; and year 8, higher prevalence of frailty, multimorbidity, and depressive symptoms and lower use of weight control strategies. Steep weight loss postintervention was associated with increased risk of mortality. Older individuals with longer duration of diabetes and multimorbidity should be monitored for excessive unintentional weight loss.

Effects of Intensive Lifestyle Intervention on All-Cause Mortality in Older Adults With Type 2 Diabetes and Overweight/Obesity: Results From the Look AHEAD Study.

Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) and diabetes support and education (DSE) (control) in 5,145 individuals with overweight/obesity and type 2 diabetes, found no significant differences in all-cause or cardiovascular mortality or morbidity during 9.6 (median) years of intervention. Participants in ILI who lost ≥10% at 1 year had lower risk of composite cardiovascular outcomes relative to DSE. Since effects of ILI may take many years to emerge, we conducted intent-to-treat analyses comparing mortality in ILI over 16.7 years (9.6 years of intervention and then observation) to DSE. In a secondary exploratory analysis, we compared mortality by magnitude of weight loss in ILI relative to DSE. Primary outcome was all-cause mortality from randomization to 16.7 years. Other outcomes included cause-specific mortality, interactions by subgroups (age, sex, race/ethnicity, and cardiovascular disease history), and an exploratory analysis by magnitude of weight loss in ILI versus DSE as reference. Analyses used proportional hazards regression and likelihood ratio. The incidence of all-cause mortality did not differ significantly in ILI and DSE (549 and 589 participants, respectively) (hazard ratio [HR] 0.91 [95% CI 0.81, 1.02]; P = 0.11). There were no significant differences between treatments in cause-specific mortality or within prespecified subgroups. ILI participants who lost ≥10% at 1 year had a 21% reduced risk of mortality (HR 0.79 [95% CI 0.67, 0.94]; P = 0.007) relative to DSE. ILI focused on weight loss did not significantly affect mortality risk. However, ILI participants who lost ≥10% had reduced mortality relative to DSE.

Abstract 009: Differential Effect Of An Intensive Lifestyle Intervention On Risk For Cardiovascular Events According To Baseline Level Of Glycated Hemoglobin

Introduction: A lack of effective interventions remains a major clinical gap in cardiovascular disease (CVD) prevention for individuals with type 2 diabetes (T2D) and high glycated hemoglobin (HbA1c). Our objective was to determine whether the effect of an intensive lifestyle intervention (ILI) on CVD prevention differed by baseline HbA1c among Action for Health in Diabetes (Look AHEAD) trial participants. Hypothesis: ILI will be associated with differential risk for CVD by HbA1c. Methods: Look AHEAD randomized 5145 adults, aged 45-76 years, with T2D and overweight/obesity, to ILI or a control of diabetes support and education (DSE) for a median of 9.6 years. ILI focused on weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial’s pre-specified primary CVD outcome. We assessed for additive (Poisson regression) and multiplicative (Cox proportional hazards) heterogeneity of intervention effects on CVD risk by HbA1c adjusting for stratified randomization and using intention to treat analysis. Results: Baseline HbA1c ranged from 4.4% to 14.5% (mean 7.3, SD 1.2). We observed additive and multiplicative heterogeneity of effects (all p&lt;0.001) between ILI and HbA1c on CVD risk (Figure). Compared to DSE, ILI was associated with lower risk for CVD for HbA1c quintiles 1 and 2. The “ILI-CVD” association changed direction at HbA1c=7.7%; ILI was associated with higher risk of CVD than DSE within HbA1c quintile 5 (and when continuous, HbA1c ≥8.7%). Conclusion: Among adults with T2D and overweight/obesity, the effect of a lifestyle intervention on CVD risk differed by HbA1c. There is a critical need to identify effective CVD prevention strategies for individuals with T2D and high HbA1c.

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.

Effects of a lifestyle intervention on daytime sleepiness and cognitive function

AbstractBackgroundDaytime sleepiness is common in older adults and may result from poor nighttime sleep due to sleep disordered breathing, fragmented sleep, or other sleep disorders. Daytime sleepiness may signify disruption of circadian rhythms and disorder in neural circuitry arising from neurodegenerative disease. We investigated the association between self‐reported daytime sleepiness and cognitive function in Look AHEAD, a randomized clinical trial of an intensive lifestyle intervention (ILI) in a cohort of adults with type 2 diabetes (T2D) and overweight or obesity at baseline.MethodParticipants (aged 45‐76 years) were randomized to ILI or diabetes support and education (DSE) conditions. After ∼10 years, the trial was stopped; observation continued to year 18. We included participants who reported levels of daytime sleepiness at baseline and year 18 (n=2,825). Change in daytime sleepiness was defined as increasing, stayed the same, or decreasing levels of daytime sleepiness. Cognitive assessments at years 13 and 18 included measures of global function, memory, executive function, and attention; a cognitive composite was derived from z‐score averages. The relationship between change in daytime sleepiness from baseline to year 18, and cognitive function at year 18 was examined using analysis of covariance, adjusting for year 13 cognitive performance, baseline age, gender, race/ethnicity, education, APOE ε4 carrier status, baseline CVD history, and baseline daytime sleepiness.ResultParticipants who reported increased daytime sleepiness from baseline to year 18 (n=402), performed significantly worse on the cognitive composite than those who reported no change (n=1089) or decreased levels of daytime sleepiness (n=948), (Least Squares Mean [standard error]) ‐0.50 (0.04); ‐0.40 (0.03), and ‐0.39 (0.03), respectively; p‐value=0.004. Significant interactions between treatment arm and daytime sleepiness were found in executive function (p&lt;0.10) and memory (p&lt;0.001) such that relationships were stronger among ILI compared with DSE participants including poorer scores among those with increasing daytime sleepiness in the executive function (34.3 (0.72); p&lt;0.02); and memory domains (6.5 (0.30); p&lt;0.05).ConclusionIncreasing daytime sleepiness over 18 years predicted poorer cognitive performance in older individuals at high risk for sleep disorders. ILI may exacerbate relationships between increasing daytime sleepiness and cognitive deficits in adults with T2D and overweight/obesity.