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/.

Advancing type 2 diabetes therapy with iGlarLixi in older people: Pooled analysis of four randomized controlled trials.

AIM: To assess the efficacy and safety of iGlarLixi in older people (≥65 years) with type 2 diabetes (T2D) advancing or switching from oral agents, a glucagon-like peptide-1 receptor agonist (GLP-1RA), or basal insulin. MATERIALS AND METHODS: The data of participants aged <65 years and ≥65 years from four LixiLan trials (LixiLan-O, LixiLan-G, LixiLan-L, SoliMix) were evaluated over 26 or 30 weeks. RESULTS: Participants aged <65/≥65 years (n = 1039/n = 497) had a mean baseline body mass index of 31.4 and 30.7 kg/m2 and glycated haemoglobin (HbA1c) concentration of 66 mmol/mol (8.2%) and 65 mmol/mol (8.1%), respectively. Least squares mean HbA1c change from baseline to end of treatment (EOT) was -14.32 mmol/mol (-1.31%) (95% confidence interval [CI] -14.97, -13.77 [-1.37%, -1.26%]) for those aged <65 years and -13.66 mmol/mol (-1.25%) (95% CI -14.54, -12.79 [-1.33%, -1.17%]) for those aged ≥65 years. At EOT, achievement of HbA1c targets was similar between the group aged <65 years and the group aged ≥65 years: <53 mmol/mol (<7%) (59.0% and 56.5%, respectively), <59 mmol/mol (<7.5%) (75.5% and 73.0%, respectively) and <64 mmol/mol (<8%) (83.8% and 84.1%, respectively). The incidence and event rate of American Diabetes Association Level 1 hypoglycaemia during the studies were also comparable between the two groups: 26.7% and 28.2% and 1.7 and 2.1 events per patient-year for the group aged <65 years and the group aged ≥65 years, respectively. A clinically relevant reduction in HbA1c (>1% from baseline for HbA1c ≥64 mmol/mol [≥8%] or ≥0.5% from baseline for HbA1c <64 mmol/mol [<8%]) without hypoglycaemia was attained by 50.0% and 47.6% of participants aged <65 years and ≥65 years, respectively. Adverse events were similar between the two age groups. CONCLUSIONS: iGlarLixi is a simple, well-tolerated, once-daily alternative for treatment advancement in older people with T2D that provides significant improvements in glycaemic control without increasing hypoglycaemia risk, thus reducing the treatment burden.

Comparative safety and cardiovascular effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in nursing homes.

AIM: Studies examining the safety and effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus glucagon-like peptide-1 receptor agonists (GLP-1RAs) among community-dwelling adults may not generalize to nursing home (NH) residents, who are typically older and more multimorbid. We compared the safety and cardiovascular effectiveness of SGLT2is and GLP-1RAs among US NH residents. MATERIALS AND METHODS: Eligible individuals were aged ≥66 years with type 2 diabetes mellitus and initiated an SGLT2i or GLP-1RA in an NH between 2013 and 2018. Safety outcomes included fall-related injuries, hypoglycaemia, diabetic ketoacidosis (DKA), urinary tract infection or genital infection, and acute kidney injury in the year following treatment initiation. Cardiovascular effectiveness outcomes included death, major adverse cardiovascular events and hospitalization for heart failure. Per-protocol adjusted hazard ratios (HR) were calculated using stabilized inverse probability of treatment and censoring weighted cause-specific hazard regression models accounting for 127 covariates. RESULTS: The study population included 7710 residents (31.08% SGLT2i, 68.92% GLP-1RA). Compared with GLP-1RA initiators, SGLT2i initiators had higher rates of DKA (HR 1.95, 95% confidence limits 1.27, 2.99) and death (HR 1.18, 95% confidence limits 1.02, 1.36). Rates of urinary tract infection or genital infection, acute kidney injury, major adverse cardiovascular events, and heart failure were also elevated, while rates of fall-related injuries and hypoglycaemia were reduced, but all estimates were imprecise and highly compatible with no difference. CONCLUSIONS: SGLT2is do not have superior, and may have inferior, effectiveness compared with GLP-1RAs for cardiovascular and mortality outcomes in NH residents. Residents initiating SGLT2is should be monitored closely for DKA.

Use of Telemedicine in Adults with Type 1 Diabetes: Do Age and Use of Diabetes-Related Technology Matter?

Objective: Older adults are generally less proficient in technology use compared with younger adults. Data on telemedicine use during the COVID-19 pandemic in older persons with type 1 diabetes (T1D) and the association of telemedicine with the use of diabetes-related technology are limited. We evaluated care delivery to older adults compared with younger adults with T1D in a prepandemic and pandemic period. Methods: Data from electronic health records were evaluated for visit types (in-person, phone, and video) from two sequential 12-month intervals: prepandemic (April 2019-March 2020) and pandemic (April 2020-March 2021). Results: Data from 2,832 unique adults with T1D were evaluated in two age cohorts: younger (40-64 years) and older (≥65 years). Half of each group used continuous glucose monitoring (CGM), whereas 54% of the younger and 37% of the older cohort used pump therapy (p < 0.001). During the pandemic compared with the prepandemic period, visit frequency increased in both the younger (0.65 vs. 0.76 visits/patient/quarter; p < 0.01) and older (0.72 vs. 0.80 visits/patient/quarter; p < 0.01) cohorts. During the pandemic, older adults used more phone visits compared with younger adults (48% vs. 32%; p = 0.001). Patients using either pump therapy or CGM were more likely to use video visits compared with phone visits in both younger (41% vs. 24%; p < 0.001) and older cohorts (53% vs. 42%; p < 0.001). Conclusions: Adults using diabetes-related technologies, independent of age, accessed more video visits than those not using devices. Telemedicine visits appeared to maintain continuity of care for younger and older adults with T1D, supporting the future of a hybrid-care model.

Effects of dipeptidyl peptidase-4 inhibitors and sulphonylureas on cognitive and physical function in nursing home residents.

AIMS: Dipeptidyl peptidase-4 inhibitors (DPP4Is) may mitigate hypoglycaemia-mediated declines in cognitive and physical functioning compared with sulphonylureas (SUs), yet comparative studies are unavailable among older adults, particularly nursing home (NH) residents. We evaluated the effects of DPP4Is versus SUs on cognitive and physical functioning among NH residents. MATERIALS AND METHODS: This new-user cohort study included long-stay NH residents aged ≥65 years from the 2007-2010 national US Minimum Data Set (MDS) clinical assessments and linked Medicare claims. We measured cognitive decline from the validated 6-point MDS Cognitive Performance Scale, functional decline from the validated 28-point MDS Activities of Daily Living scale, and hospitalizations or emergency department visits for altered mental status from Medicare claims. We compared 180-day outcomes in residents who initiated a DPP4I versus SU after 1:1 propensity score matching using Cox regression models. RESULTS: The matched cohort (N = 1784) had a mean ± SD age of 80 ± 8 years and 73% were women. Approximately 46% had no or mild cognitive impairment and 35% had no or mild functional impairment before treatment initiation. Compared with SU users, DPP4I users had lower 180-day rates of cognitive decline [hazard ratio (HR) = 0.61, 95% confidence interval (CI) 0.31-1.19], altered mental status events (HR = 0.71, 95% CI 0.39-1.27), and functional decline (HR = 0.89, 95% CI 0.51-1.56), but estimates were imprecise. CONCLUSIONS: Rates of cognitive and functional decline may be reduced among older NH residents using DPP4Is compared with SUs, but larger studies with greater statistical power should resolve the remaining uncertainty by providing more precise effect estimates.

INSULIN GLARGINE 300 U/ML IS ASSOCIATED WITH LESS WEIGHT GAIN WHILE MAINTAINING GLYCEMIC CONTROL AND LOW RISK OF HYPOGLYCEMIA COMPARED WITH INSULIN GLARGINE 100 U/ML IN AN AGING POPULATION WITH TYPE 2 DIABETES.

OBJECTIVE: Assess efficacy, hypoglycemia, and weight gain in patients with type 2 diabetes (T2D) treated with insulin glargine 300 U/mL (Gla-300) or 100 U/mL (Gla-100) across different age groups. METHODS: Pooled data were generated for patients randomized to Gla-300 or Gla-100 in the EDITION 2 (NCT01499095) and 3 (NCT01676220) studies. In 4 age groups (<55, ≥55 to <60, ≥60 to <65, ≥65 years), glycated hemoglobin A1C (A1C), percentage of patients reaching A1C <7.5% (58 mmol/mol), weight change, confirmed hypoglycemia (blood glucose ≤70 mg/dL), and/or severe hypoglycemia (events requiring third-party assistance) were analyzed with descriptive statistics and logistic, binomial, and analysis of covariance regression modeling. RESULTS: A1C reductions from baseline and proportions of patients at target were similar for Gla-300 and Gla-100 across all age groups at 6 and 12 months, but hypoglycemia incidence and event rate were lower with Gla-300 at 6 (both P<.001) and 12 months ( P<.001 and P = .005, respectively). Patients on Gla-300 gained less weight than those on Gla-100 at 6 ( P = .027) and 12 months ( P = .021). Changes in weight and daily weight-adjusted insulin dose decreased with increasing age at 6 ( P<.001 and P = .017, respectively) and 12 months ( P<.001 and P = .011, respectively). CONCLUSION: Older patients with T2D may benefit from treatment with Gla-300, which is associated with a lower hypoglycemia rate and less weight gain with similar efficacy compared with Gla-100. ABBREVIATIONS: A1C = glycated hemoglobin A1C BMI = body mass index Gla-100 = insulin glargine 100 U/mL Gla-300 = insulin glargine 300 U/mL OAD = oral antidiabetes drug T2D = type 2 diabetes.

Diabetes Management in the Elderly.

IN BRIEF Older adults with diabetes present unique challenges and require considerations that are not traditionally associated with diabetes management. In this review, we focus on issues that are unique to the older population and provide practical guidance for clincians who care for them.

Diabetes in long-term care facilities.

With the aging of the population and longer life expectancies, the prevalence of population with multiple chronic medical conditions has increased. Difficulty managing these conditions as people age (because of changes in physical, functional, or cognitive abilities and the complexity of many treatment regimens), has led to more individuals with multiple medical conditions admitted to the long-term care facilities. Older adults with diabetes residing in the long-term facilities represent the most vulnerable of this cohort. Studies that specifically target diabetes management in older population are lacking and those that target diabetes management in the long-term care facilities are even fewer. The lack of knowledge regarding the care of the elderly residing in long-term care with diabetes may lead to treatment failure and higher risk of hyperglycemia, as well as hypoglycemia. In aging populations, hypoglycemia has the potential for catastrophic consequences. To avoid this, the management of older population with diabetes and other medical comorbidities residing in long-term care facilities requires a more holistic approach compared with focusing on individual chronic disease goal achievement.

Dynamical glucometry: use of multiscale entropy analysis in diabetes.

Diabetes mellitus (DM) is one of the world's most prevalent medical conditions. Contemporary management focuses on lowering mean blood glucose values toward a normal range, but largely ignores the dynamics of glucose fluctuations. We probed analyte time series obtained from continuous glucose monitor (CGM) sensors. We show that the fluctuations in CGM values sampled every 5 min are not uncorrelated noise. Next, using multiscale entropy analysis, we quantified the complexity of the temporal structure of the CGM time series from a group of elderly subjects with type 2 DM and age-matched controls. We further probed the structure of these CGM time series using detrended fluctuation analysis. Our findings indicate that the dynamics of glucose fluctuations from control subjects are more complex than those of subjects with type 2 DM over time scales ranging from about 5 min to 5 h. These findings support consideration of a new framework, dynamical glucometry, to guide mechanistic research and to help assess and compare therapeutic interventions, which should enhance complexity of glucose fluctuations and not just lower mean and variance of blood glucose levels.

Glucose Targets Using Continuous Glucose Monitoring Metrics in Older Adults With Diabetes: Are We There Yet?

The older population is increasing worldwide and up to 30% of older adults have diabetes. Older adults with diabetes are at risk of glucose-related acute and chronic complications. Recently, mostly in type 1 diabetes (T1D), continuous glucose monitoring (CGM) devices have proven beneficial in improving time in range (TIR glucose, 70-180 mg/dL or glucose 3.9-10 mmol/L), glycated hemoglobin (HbA1c), and in lowering hypoglycemia (time below range [TBR] glucose <70 mg/dL or glucose <3.9 mmol/L). The international consensus group formulated CGM glycemic targets relating to older adults with diabetes based on very limited data. Their recommendations, based on expert opinion, were aimed at mitigating hypoglycemia in all older adults. However, older adults with diabetes are a heterogeneous group, ranging from healthy to very complex frail individuals based on chronological, biological, and functional aging. Recent clinical trial and real-world data, mostly from healthy older adults with T1D, demonstrated that older adults often achieve CGM targets, including TIR recommended for non-vulnerable groups, but less often meet the recommended TBR <1%. Existing data also support that hypoglycemia avoidance may be more strongly related to minimization of glucose variability (coefficient of variation [CV]) rather than lower TIR. Very limited data are available for glucose goals in older adults adjusted for the complexity of their health status. Herein, we review the bidirectional associations between glucose and health status in older adults with diabetes; use of diabetes technologies, and their impact on glucose control; discuss current guidelines; and propose a new set of CGM targets for older adults with insulin-treated diabetes that are individualized for health and living status.

Impact of a tubeless, disposable insulin pump on emergency department visits and inpatient admissions among a Medicare population.

BACKGROUND: A tubeless, disposable insulin pump (Omnipod DASH Insulin Management System, Insulet Corporation) has demonstrated improved glycemic outcomes for people with diabetes who require insulin. The impact of the system on downstream health care events has not been studied. OBJECTIVE: To assess health care resource utilization for a Medicare population before and after starting tubeless, disposable insulin pump therapy. METHODS: This retrospective, observational analysis used data from the Centers for Medicare & Medicaid Services 100% Research Identifiable Files. Study outcomes included change in event rates for diabetes-related emergency department (DRED) visits, all-cause emergency department (ACED) visits, diabetes-related inpatient (DRIP) admissions, and all-cause inpatient (ACIP) admissions among Medicare beneficiaries who started the tubeless, disposable insulin pump in 2020 (postpump observation period) as compared with the same duration and calendar period in 2019 (prepump observation period) with no pump use. Subgroup analyses were performed based on Medicare entitlement reason, diabetes type, and diagnosis status for depressive disorder. RESULTS: A total of 811 users met the criteria for analysis: 46.2% had type 2 diabetes, a majority (59.2%) were aged 65 years or older, and 37.0% had a diagnosis for depressive disorder. Significant reductions were observed for DRED of -46.9% (95% CI = -63% to -23%); ACED of -29.0% (95% CI = -37% to -20%); ACIP of -19.9% (95% CI = -32% to -6%). DRIP rates declined notably (-36.6%; 95% CI = -61% to 4%). Event rates observed across subgroups demonstrated consistent downward trends; however, not all were statistically significant. CONCLUSIONS: These findings demonstrate that use of the tubeless, disposable insulin pump was associated with reductions in DRED, ACED, and ACIP. Our results provide real-world evidence to support the use of the tubeless, disposable insulin pump among Medicare beneficiaries who require insulin, regardless of diabetes type or Medicare entitlement reason. Additional studies are recommended to further evaluate the effect of insulin pumps on health care utilization among the Medicare population and other insurance populations.

Continuous Glucose Monitoring Use in Older Adults for Optimal Diabetes Management.

More than one third of U.S. adults age ≥65 years have diabetes. According to early studies, 61% of all diabetes-related costs in the United States were for individuals age ≥65 years, and more than half of these costs attributable to treating diabetes-related complications. Numerous studies have shown that use of continuous glucose monitoring (CGM) has been shown to improve glycemic control and reduce the incidence and severity of hypoglycemia in younger adults with type 1 diabetes and insulin-treated type 2 diabetes (T2D), and there is growing evidence demonstrating the same benefits in older T2D populations. However, because older adults with diabetes are a heterogeneous group with variable clinical, functional, and psychosocial milieu, clinicians must consider whether each patient can use CGM and, if so, the type of CGM device best addresses each patient's needs and capabilities. This article reviews the evidence supporting CGM in the older population, discusses the barriers and benefits of CGM use in older adults with diabetes, and provides recommendations for how different types of CGM systems can be used strategically to improve glycemic control, reduce hypoglycemia, decrease the burden of diabetes, and improve quality of life.

Geriatric Syndromes in Older Adults with Diabetes.

Over one-quarter of adults ≥65 years old have diabetes in the United States. Guidelines recommend individualization of glycemic targets in older adults with diabetes as well as implementing treatment strategies that minimize risk for hypoglycemia. Patient-centered management decisions should be informed by comorbidities, the individual's capacity for self-care, and the presence of key geriatric syndromes that may impact self-management and patient safety. Key geriatric syndromes include cognitive impairment, depression, functional impairments (eg, vision, hearing, and mobility challenges), falls and fractures, polypharmacy, and urinary incontinence. Screening for geriatric syndromes in older adults is recommended to inform treatment strategies and optimize outcomes.

Adoption of sodium-glucose cotransporter-2 inhibitors among prescribers caring for nursing home residents.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitor (SGLT2I) use has increased among community-dwelling populations, but little is known about how clinicians have prescribed them for US nursing home (NH) residents. We described the adoption of SGLT2Is by prescribers caring for long-stay NH residents by clinician specialty and over time, compared with sulfonylureas, an older diabetes medication class. METHODS: We conducted a retrospective cohort study of prescribers of SGLT2Is and sulfonylureas for all long-stay US NH residents aged 65 years or older (2017-2019). Using 100% of Medicare Part D claims linked to prescriber characteristics data, we identified all dispensings of SGLT2Is and sulfonylureas for long-stay NH residents and their associated prescribers. We described the distribution of prescriber specialties for each drug class over time as well as the number of NH residents prescribed SGLT2s versus sulfonylureas. We estimated the proportions of prescribers who prescribed both drug classes versus only sulfonylureas or only SGLT2Is. RESULTS: We identified 36,427 unique prescribers (SGLT2I: N = 5811; sulfonylureas: N = 35,443) for 117,667 NH residents between 2017 and 2019. For both classes, family medicine and internal medicine physicians accounted for most prescriptions (75%-81%). Most clinicians (87%) prescribed only sulfonylureas, 2% prescribed SGLT2Is only, and 11% prescribed both. Geriatricians were least likely to prescribe only SGLT2Is. We observed an increase in the number of residents with SGLT2I use from n = 2344 in 2017 to n = 5748 in 2019. CONCLUSIONS: Among NH residents, most clinicians have not incorporated SGLT2Is into their prescribing for diabetes, but the extent of use is increasing. Family medicine and internal medicine physicians prescribed the majority of diabetes medications for NH residents, and geriatricians were the least likely to prescribe only SGLT2Is. Future research should explore provider concerns regarding SGLT2I prescribing, particularly adverse events.

Comparative safety of sulfonylureas among U.S. nursing home residents.

BACKGROUND: The comparative safety of sulfonylureas (SUs) in nursing home (NH) residents remains understudied despite widespread use. We compared the effects of three SU medications and initial SU doses on adverse glycemic and cardiovascular events among NH residents. METHODS: This national retrospective cohort study linked Medicare claims with Minimum Data Set 2.0 assessments for long-stay NH residents aged ≥65 years between January 2008 and September 2010. Exposures were the SU medication initiated (glimepiride, glipizide, or glyburide) and doses (standard or reduced). One-year outcomes were hospitalizations or emergency department visits for severe hypoglycemia, heart failure (HF), stroke, and acute myocardial infarction (AMI). After the inverse probability of treatment and inverse probability of censoring by death weighting, we estimated hazard ratios (HR) using Cox regression models with robust 95% confidence intervals (CI). RESULTS: The cohort (N = 6821) included 3698 new glipizide, 1754 glimepiride, and 1369 glyburide users. Overall, the mean (standard deviation) age was 81.4 (8.2) years, 4816 (70.6%) were female, and 5164 (75.7%) were White non-Hispanic residents. The rates of severe hypoglycemia were 30.3 (95% CI 22.3-40.1), 49.0 (95% CI 34.5-67.5), and 35.9 (95% CI 22.2-54.9) events per 1000 person-years among new glipizide, glimepiride, and glyburide users, respectively (glimepiride versus glipizide HR 1.6, 95% CI 1.0-2.4, p = 0.04; glyburide versus glipizide HR 1.2, 95% CI 0.7-1.9, p = 0.59). The rates of severe hypoglycemia were 27.1 (95% CI 18.6-38.0) and 42.8 (95% CI 33.6-53.8) events per 1000 person-years among new users of reduced and standard SU doses, respectively (HR 2.2, 95% CI 1.4-3.5, p < 0.01). Rates of HF, stroke, and AMI were similar between medications and doses. CONCLUSIONS: Among long-stay NH residents, new use of glimepiride and standard SU doses resulted in higher rates of severe hypoglycemic events. Cardiovascular outcomes may not be affected by the choice of SU medication or dose.

An Examination of Whether Diabetes Control and Treatments Are Associated With Change in Frailty Index Across 8 Years: An Ancillary Exploratory Study From the Action for Health in Diabetes (Look AHEAD) Trial.

OBJECTIVE: The aim of this study was to describe cross-sectional and longitudinal associations between glycated hemoglobin (HbA1c) levels and strategies to control type 2 diabetes with baseline levels and 8-year changes in a deficit accumulation frailty index (FI), a commonly used marker of biological aging. RESEARCH DESIGN AND METHODS: We conducted exploratory analyses from 4,169 participants, aged 45-76 years, who were followed in the Action for Health in Diabetes (Look AHEAD) randomized controlled clinical trial, pooling data across intervention groups. We related baseline and 8-year levels of HbA1c with FI scores using analyses of variance and covariance. Associations between 8-year changes in FI and the use of diabetes medication classes and weight changes were assessed with control for HbA1c levels. Inverse probability weighting was used to assess bias associated with differential follow-up. RESULTS: Baseline and average HbA1c levels over time of <7%, as compared with ≥8%, were associated with less increase in FI scores over 8 years (both P ≤ 0.002). After adjustment for HbA1c, use of metformin and weight loss >5% were independently associated with slower increases in frailty. CONCLUSIONS: Lower HbA1c levels among individuals with diabetes are associated with slower biological aging as captured by a deficit accumulation FI. Strategies to control diabetes through weight loss or metformin use may also slow aging.

Association of Type 2 Diabetes Subgroups With Cognitive Status Without Modification From Lifestyle Intervention.

CONTEXT: Type 2 diabetes is a risk factor for incident dementia but whether risk and treatment/prevention strategies differ by diabetes subgroup is unknown. OBJECTIVE: We assessed (1) whether specific type 2 diabetes (T2D) subgroups are associated with mild cognitive impairment (MCI) or probable dementia (PD), and (2) whether T2D subgroups modified the association of the Action for Health in Diabetes (Look AHEAD) multidomain intensive lifestyle intervention (ILI) with MCI/PD. METHODS: We included 3760 Look AHEAD participants with T2D and overweight or obesity randomly assigned to 10 years of ILI or diabetes support and education. We used k-means clustering techniques with data on age of diabetes diagnosis, body mass index, waist circumference, and glycated hemoglobin (HbA1c) to characterize diabetes subgroups at randomization. Prevalent MCI/PD were centrally adjudicated based on standardized cognitive tests and other health information 10 to 13 years after randomization. We estimated marginal probabilities for prevalent MCI/PD among T2D subgroups with adjustment for potential confounders and attrition and examined whether ILI modified any associations. RESULTS: Four distinct T2D subgroups were identified, characterized by older age at diabetes onset (43% of sample), high HbA1c (13%), severe obesity (23%), and younger age at onset (22%). Unadjusted prevalence of MCI/PD (314 cases, 8.4%) differed across T2D subgroup (older onset = 10.5%, severe obesity = 9.0%, high HbA1c = 7.9%, and younger onset = 4.0%). Adjusted probability for MCI/PD within T2D subgroup was highest for the severe obesity subgroup and lowest for the younger onset subgroup but did not differ by ILI arm (interaction P value = 0.84). CONCLUSIONS: Among individuals with T2D and overweight or obesity, probability of MCI/PD differed by T2D subgroup. Probability of MCI/PD was highest for a subgroup characterized by severe obesity. CLINICALTRIALS.GOV IDENTIFIER: NCT00017953.