The comparative efficacy of lifestyle intervention and metformin by educational attainment in the Diabetes Prevention Program.
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ABSTRACT:
SUBMITTER: O'Brien MJ
PROVIDER: S-EPMC4490008 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
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The comparative efficacy of lifestyle intervention and metformin by educational attainment in the Diabetes Prevention Program.
O'Brien Matthew J MJ Whitaker Robert C RC Yu Daohai D Ackermann Ronald T RT
Preventive medicine 20150527
<h4>Objective</h4>Educational attainment is inversely associated with type 2 diabetes risk, but it is unknown whether education impacts individuals' diabetes prevention efforts. We examined the comparative efficacy of intensive lifestyle intervention and metformin by educational attainment among participants in the Diabetes Prevention Program (DPP), an ongoing U.S. multi-site trial beginning in 1996.<h4>Methods</h4>We studied 2,910 DPP participants randomized to receive lifestyle intervention, m ...[more]
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Project description:ObjectiveWe examined the association of the Diabetes Prevention Program (DPP) intervention arms (lifestyle intervention, metformin, and placebo) with cognition in the Diabetes Prevention Program Outcomes Study (DPPOS). We also examined metformin use, incident type 2 diabetes, and glycemia as exposures.Research design and methodsThe DPP lasted 2.8 years, followed by a 13-month bridge to DPPOS. Cognition was assessed in DPPOS years 8 and 10 (12 and 14 years after randomization) with the Spanish English Verbal Learning Test (SEVLT), letter fluency and animal fluency tests, Digit Symbol Substitution Test (DSST), and a composite cognitive score.ResultsA total of 2,280 participants (749 lifestyle, 776 metformin, and 755 placebo) aged 63.1 ± 10.7 years underwent cognitive assessments; 67.7% women, 54.6% non-Hispanic white, 20.7% non-Hispanic black, 14.6% Hispanic, 5.5% American Indian, and 4.6% Asian; 26.6% were homozygous or heterozygous for APOE-ε4. At the time of cognitive assessment, type 2 diabetes was higher in the placebo group (57.9%; P < 0.001) compared with lifestyle (47.0%) and metformin (50.4%). Metformin exposure was higher in the metformin group (8.72 years; P < 0.001) compared with placebo (1.43 years) and lifestyle (0.96 years). There were no differences in cognition across intervention arms. Type 2 diabetes was not related to cognition, but higher glycated hemoglobin at year 8 was related to worse cognition after confounder adjustment. Cumulative metformin exposure was not related to cognition.ConclusionsExposure to intensive lifestyle intervention or metformin was not related to cognition among DPPOS participants. Higher glycemia was related to worse cognitive performance. Metformin seemed cognitively safe among DPPOS participants.
| S-EPMC5481986 | biostudies-literature
Project description:BackgroundIdentifying reliable predictors of long-term weight loss (LTWL) could lead to improved weight management.ObjectiveTo identify some predictors of LTWL.DesignThe DPP (Diabetes Prevention Program) was a randomized controlled trial that compared weight loss with metformin, intensive lifestyle intervention (ILS), or placebo. Its Outcomes Study (DPPOS) observed patients after the masked treatment phase ended. (ClinicalTrials.gov: NCT00004992 and NCT00038727).Setting27 DPP and DPPOS clinics.ParticipantsOf the 3234 randomly assigned participants, 1066 lost at least 5% of baseline weight in the first year and were followed for 15 years.MeasurementsTreatment assignment, personal characteristics, and weight.ResultsAfter 1 year, 289 (28.5%) participants in the metformin group, 640 (62.6%) in the ILS group, and 137 (13.4%) in the placebo group had lost at least 5% of their weight. After the masked treatment phase ended, the mean weight loss relative to baseline that was maintained between years 6 and 15 was 6.2% (95% CI, 5.2% to 7.2%) in the metformin group, 3.7% (CI, 3.1% to 4.4%) in the ILS group, and 2.8% (CI, 1.3% to 4.4%) in the placebo group. Independent predictors of LTWL included greater weight loss in the first year in all groups, older age and continued metformin use in the metformin group, older age and absence of either diabetes or a family history of diabetes in the ILS group, and higher fasting plasma glucose levels at baseline in the placebo group.LimitationPost hoc analysis; examination of nonrandomized subsets of randomized groups after year 1.ConclusionAmong persons with weight loss of at least 5% after 1 year, those originally randomly assigned to metformin had the greatest loss during years 6 to 15. Older age and the amount of weight initially lost were the most consistent predictors of LTWL maintenance.Primary funding sourceNational Institutes of Health.
| S-EPMC6829283 | biostudies-literature
Project description:Aims/hypothesisWe compared the associations of circulating biomarkers of inflammation, endothelial and adipocyte dysfunction and coagulation with incident diabetes in the placebo, lifestyle and metformin intervention arms of the Diabetes Prevention Program, a randomised clinical trial, to determine whether reported associations in general populations are reproduced in individuals with impaired glucose tolerance, and whether these associations are independent of traditional diabetes risk factors. We further investigated whether biomarker-incident diabetes associations are influenced by interventions that alter pathophysiology, biomarker concentrations and rates of incident diabetes.MethodsThe Diabetes Prevention Program randomised 3234 individuals with impaired glucose tolerance into placebo, metformin (850 mg twice daily) and intensive lifestyle groups and showed that metformin and lifestyle reduced incident diabetes by 31% and 58%, respectively compared with placebo over an average follow-up period of 3.2 years. For this study, we measured adiponectin, leptin, tissue plasminogen activator (as a surrogate for plasminogen activator inhibitor 1), high-sensitivity C-reactive protein, IL-6, monocyte chemotactic protein 1, fibrinogen, E-selectin and intercellular adhesion molecule 1 at baseline and at 1 year by specific immunoassays. Traditional diabetes risk factors were defined as family history, HDL-cholesterol, triacylglycerol, BMI, fasting and 2 h glucose, HbA1c, systolic blood pressure, inverse of fasting insulin and insulinogenic index. Cox proportional hazard models were used to assess the effects of each biomarker on the development of diabetes assessed semi-annually and the effects of covariates on these.ResultsE-selectin, (HR 1.19 [95% CI 1.06, 1.34]), adiponectin (0.84 [0.71, 0.99]) and tissue plasminogen activator (1.13 [1.03, 1.24]) were associated with incident diabetes in the placebo group, independent of diabetes risk factors. Only the association between adiponectin and diabetes was maintained in the lifestyle (0.69 [0.52, 0.92]) and metformin groups (0.79 [0.66, 0.94]). E-selectin was not related to diabetes development in either lifestyle or metformin groups. A novel association appeared for change in IL-6 in the metformin group (1.09 [1.021, 1.173]) and for baseline leptin in the lifestyle groups (1.31 [1.06, 1.63]).Conclusions/interpretationThese findings clarify associations between an extensive group of biomarkers and incident diabetes in a multi-ethnic cohort with impaired glucose tolerance, the effects of diabetes risk factors on these, and demonstrate differential modification of associations by interventions. They strengthen evidence linking adiponectin to diabetes development, and argue against a central role for endothelial dysfunction. The findings have implications for the pathophysiology of diabetes development and its prevention.
| S-EPMC6456055 | biostudies-literature
Project description:ObjectiveTo determine whether metformin or lifestyle modification can lower rates of all-cause and cause-specific mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.Research design and methodsFrom 1996 to 1999, 3,234 adults at high risk for type 2 diabetes were randomized to an intensive lifestyle intervention, masked metformin, or placebo. Placebo and lifestyle interventions stopped in 2001, and a modified lifestyle program was offered to everyone, but unmasked study metformin continued in those originally randomized. Causes of deaths through 31 December 2018 were adjudicated by blinded reviews. All-cause and cause-specific mortality hazard ratios (HRs) were estimated from Cox proportional hazards regression models and Fine-Gray models, respectively.ResultsOver a median of 21 years (interquartile range 20-21), 453 participants died. Cancer was the leading cause of death (n = 170), followed by cardiovascular disease (n = 131). Compared with placebo, metformin did not influence mortality from all causes (HR 0.99 [95% CI 0.79, 1.25]), cancer (HR 1.04 [95% CI 0.72, 1.52]), or cardiovascular disease (HR 1.08 [95% CI 0.70, 1.66]). Similarly, lifestyle modification did not impact all-cause (HR 1.02 [95% CI 0.81, 1.28]), cancer (HR 1.07 [95% CI 0.74, 1.55]), or cardiovascular disease (HR 1.18 [95% CI 0.77, 1.81]) mortality. Analyses adjusted for diabetes status and duration, BMI, cumulative glycemic exposure, and cardiovascular risks yielded results similar to those for all-cause mortality.ConclusionsCancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.
| S-EPMC8669534 | biostudies-literature
Project description:BackgroundAdults at high risk for diabetes may have reduced health-related quality of life (HRQoL).ObjectiveTo assess changes in HRQoL after interventions aimed at diabetes risk reduction.Design, setting, and participantsA randomized clinical trial, the Diabetes Prevention Program, was conducted in 27 centers in the United States, in 3,234 non-diabetic persons with elevated fasting and post-load plasma glucose, mean age 51 years, mean BMI 34 Kg/m(2); 68 % women, and 45 % members of minority groups.InterventionsIntensive lifestyle (ILS) program with the goals of at least 7 % weight loss and 150 min of physical activity per week, metformin (MET) 850 mg twice daily, or placebo (PLB).MeasurementsHRQoL using the 36-Item Short-Form (SF-36) health survey to evaluate health utility index (SF-6D), physical component summaries (PCS) and mental component summaries (MCS). A minimally important difference (MID) was met when the mean of HRQoL scores between groups differed by at least 3 %.ResultsAfter a mean follow-up of 3.2 years, there were significant improvements in the SF-6D (+0.008, p=0.04) and PCS (+1.57, p<0.0001) scores in ILS but not in MET participants (+0.002 and +0.15, respectively, p=0.6) compared to the PLB group. ILS participants showed improvements in general health (+3.2, p<0.001), physical function (+3.6, p<0.001), bodily pain (+1.9, p=0.01), and vitality (+2.1, p=0.01) domain scores. Treatment effects remained significant after adjusting sequentially for baseline demographic factors, and for medical and psychological comorbidities. Increased physical activity and weight reduction mediated these ILS treatment effects. Participants who experienced weight gain had significant worsening on the same HRQoL specific domains when compared to those that had treatment-related (ILS or MET) weight loss. No benefits with ILS or MET were observed in the MCS score.ConclusionOverweight/obese adults at high risk for diabetes show small improvement in most physical HRQoL and vitality scores through the weight loss and increased physical activity achieved with an ILS intervention.
| S-EPMC3509296 | biostudies-literature
Project description:Genome-wide association studies have begun to elucidate the genetic architecture of type 2 diabetes. We examined whether single nucleotide polymorphisms (SNPs) identified through targeted complementary approaches affect diabetes incidence in the at-risk population of the Diabetes Prevention Program (DPP) and whether they influence a response to preventive interventions.We selected SNPs identified by prior genome-wide association studies for type 2 diabetes and related traits, or capturing common variation in 40 candidate genes previously associated with type 2 diabetes, implicated in monogenic diabetes, encoding type 2 diabetes drug targets or drug-metabolizing/transporting enzymes, or involved in relevant physiological processes. We analyzed 1,590 SNPs for association with incident diabetes and their interaction with response to metformin or lifestyle interventions in 2,994 DPP participants. We controlled for multiple hypothesis testing by assessing false discovery rates.We replicated the association of variants in the metformin transporter gene SLC47A1 with metformin response and detected nominal interactions in the AMP kinase (AMPK) gene STK11, the AMPK subunit genes PRKAA1 and PRKAA2, and a missense SNP in SLC22A1, which encodes another metformin transporter. The most significant association with diabetes incidence occurred in the AMPK subunit gene PRKAG2 (hazard ratio 1.24, 95% CI 1.09-1.40, P = 7 × 10(-4)). Overall, there were nominal associations with diabetes incidence at 85 SNPs and nominal interactions with the metformin and lifestyle interventions at 91 and 69 mostly nonoverlapping SNPs, respectively. The lowest P values were consistent with experiment-wide 33% false discovery rates.We have identified potential genetic determinants of metformin response. These results merit confirmation in independent samples.
| S-EPMC3279522 | biostudies-literature
Project description:IntroductionDiabetes and obesity pose a significant burden for the U.S. military beneficiary population, creating a great need to provide evidence-based diabetes and obesity prevention services for military personnel, retirees, and their dependents. Despite increasing dissemination of the Diabetes Prevention Program (DPP) lifestyle intervention nationwide, formal evaluation of implementation of this highly successful program is limited in the military setting. The purpose of this study is to prospectively evaluate delivery of a direct adaptation of a 1-year DPP lifestyle intervention at a U.S. Air Force medical facility, Wright-Patterson Medical Center (WPMC), to determine the feasibility of delivery of the program in a group of at-risk active duty military, retirees, and family members, as well as assess effectiveness in improving weight and other risk factors for type 2 diabetes.Materials and methodsA pre/post study design was utilized to evaluate feasibility and effectiveness of the DPP Group Lifestyle Balance (GLB), an up-to-date, 22-session direct adaptation of the DPP curriculum, at WPMC. Participants chose to complete the 1-year program either in coach-led face-to-face groups or via DVD with weekly telephonic coach contact. The study was approved by the University of Pittsburgh and WPMC Institutional Review Boards.ResultsA total of 99 individuals enrolled in the study, with 83 (84%) and 77 (78%) completing 6- and 12-month follow-up assessments, respectively. The mean age of participants at baseline was 57 (range 20-85 years), with 63% being female. The group was comprised of individuals who were non-Hispanic White (73.7%), non-Hispanic Black (18.2%), and other race or Hispanic ethnicity (8.1%). Within this group, there were 10 active duty military, 37 retirees, and 52 family members. The DPP-GLB program was shown to be feasible to implement in this military healthcare setting as demonstrated by the high engagement over the course of the year-long program. Significant improvements were shown in the two main behavioral goals: mean weight (-12.8 lbs, -6.3%, P < .001) and mean physical activity (PA) (+18.9 Met-hrs/wk, P < .001). In addition, significant improvements in other diabetes and cardiovascular risk factors including low-density lipoprotein cholesterol, fasting insulin, diastolic blood pressure, and waist circumference were noted, as well as improvement in health-related quality of life.ConclusionsThese results demonstrate that the DPP-GLB program delivered via face-to-face groups or DVD was feasible and effective in improving weight, PA levels, and diabetes and cardiovascular risk factors in this group of active and retired military personnel and their family members. The program was well received by the program participants as well as the WPMC team. These findings offer a model for provision of the DPP-GLB program throughout the Military Health System.
| S-EPMC10187478 | biostudies-literature
Project description:Although intensive lifestyle change (ILS) and metformin reduce diabetes incidence in subjects with impaired glucose tolerance (IGT), their effects on lipoprotein subfractions have not been studied.The objective of the study was to characterize the effects of ILS and metformin vs placebo interventions on lipoprotein subfractions in the Diabetes Prevention Program.This was a randomized clinical trial, testing the effects of ILS, metformin, and placebo on diabetes development in subjects with IGT.Selected individuals with IGT randomized in the Diabetes Prevention Program participated in the study.Interventions included randomization to metformin 850 mg or placebo twice daily or ILS aimed at a 7% weight loss using a low-fat diet with increased physical activity.Lipoprotein subfraction size, density, and concentration measured by magnetic resonance and density gradient ultracentrifugation at baseline and 1 year were measured.ILS decreased large and buoyant very low-density lipoprotein, small and dense low-density lipoprotein (LDL), and small high-density lipoprotein (HDL) and raised large HDL. Metformin modestly reduced small and dense LDL and raised small and large HDL. Change in insulin resistance largely accounted for the intervention-associated decreases in large very low-density lipoprotein, whereas changes in body mass index (BMI) and adiponectin were strongly associated with changes in LDL. Baseline and a change in adiponectin were related to change in large HDL, and BMI change associated with small HDL change. The effect of metformin to increase small HDL was independent of adiponectin, BMI, and insulin resistance.ILS and metformin treatment have favorable effects on lipoprotein subfractions that are primarily mediated by intervention-related changes in insulin resistance, BMI, and adiponectin. Interventions that slow the development of diabetes may also retard the progression of atherosclerosis.
| S-EPMC3790618 | biostudies-literature
Project description:The largest and longest clinical trial of metformin for the prevention of diabetes is the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP/DPPOS). In this review, we summarise data from the DPP/DPPOS, focusing on metformin for diabetes prevention, as well as its long-term glycaemic and cardiometabolic effects and safety in people at high-risk of developing diabetes. The DPP (1996-2001) was a RCT of 3234 adults who, at baseline, were at high-risk of developing diabetes. Participants were assigned to masked placebo (n = 1082) or metformin (n = 1073) 850 mg twice daily, or intensive lifestyle intervention (n = 1079). The masked metformin/placebo intervention phase ended approximately 1 year ahead of schedule because of demonstrated efficacy. Primary outcome was reported at 2.8 years. At the end of the DPP, all participants were offered lifestyle education and 88% (n = 2776) of the surviving DPP cohort continued follow-up in the DPPOS. Participants originally assigned to metformin continued to receive metformin, unmasked. The DPP/DPPOS cohort has now been followed for over 15 years with prospective assessment of glycaemic, cardiometabolic, health economic and safety outcomes. After an average follow-up of 2.8 years, metformin reduced the incidence of diabetes by 31% compared with placebo, with a greater effect in those who were more obese, had a higher fasting glucose or a history of gestational diabetes. The DPPOS addressed the longer-term effects of metformin, showing a risk reduction of 18% over 10 and 15 years post-randomisation. Metformin treatment for diabetes prevention was estimated to be cost-saving. At 15 years, lack of progression to diabetes was associated with a 28% lower risk of microvascular complications across treatment arms, a reduction that was no different among treatment groups. Recent findings suggest metformin may reduce atherosclerosis development in men. Originally used for the treatment of type 2 diabetes, metformin, now proven to prevent or delay diabetes, may serve as an important tool in battling the growing diabetes epidemic. Long-term follow-up, currently underway in the DPP/DPPOS, is now evaluating metformin's potential role, when started early in the spectrum of dysglycaemia, on later-stage comorbidities, including cardiovascular disease and cancer.Trial registrationClinicalTrials.gov NCT00038727 and NCT00004992.
| S-EPMC5709233 | biostudies-literature
Project description:IntroductionLifestyle interventions promoting weight loss and physical activity are important elements of prevention efforts with the evaluation of program impact typically limited to weight loss. Unfortunately, diabetes/cardiovascular disease risk factors and activity are infrequently reported and inconsistent in findings when examined. This inconsistency may partially be due to a lack of consideration for ceiling effects because of broad risk profile inclusion criteria in community translation efforts. To demonstrate this, change in each individual cardiometabolic risk factor limited to those who, at baseline, had a clinically defined abnormal value for that risk factor was examined in 2 cohorts using identical community translations of the Diabetes Prevention Program lifestyle intervention.MethodsFor both studies (2010-2014, 2014-2019), adults with prediabetes and/or metabolic syndrome were recruited through community centers. Outcome measures collected at baseline and 6 months included BMI, activity, blood pressure, lipids, and fasting glucose. Data analyses examined pre-post change in each variable after 6 months of intervention and change within randomized groups at 6 months.ResultsChange results were examined for the entire cohort and separately for participants with baseline values outside the recommended range for that risk factor. Whether assessing the pre-post intervention change or change within the randomized groups at 6 months, often the risk factor-specific approach demonstrated a greater effect size for that variable and sometimes newly reached statistical significance.ConclusionsWhen examining the effectiveness of community translation efforts, consideration of the individual's baseline profile with risk factor-specific analysis is suggested to understand the full extent of the impact of the intervention.
| S-EPMC9059238 | biostudies-literature