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Does diabetes prevention translate into reduced long-term vascular complications of diabetes?

ABSTRACT: The global epidemic of type 2 diabetes has prompted numerous studies and public health efforts to reduce its development. A variety of interventions, including lifestyle modifications and pharmacological agents directed at ameliorating the major risk factors for type 2 diabetes, are of proven efficacy in reducing the development of type 2 diabetes in people with impaired glucose tolerance. While prevention of the hyperglycaemia characteristic of diabetes is arguably an important, clinically relevant outcome, a more compelling outcome with greater clinical significance is the prevention or reduction of the relatively diabetes-specific microvascular and less-specific cardiovascular disease (CVD) complications associated with diabetes. These complications cause the majority of morbidity and excess mortality associated with diabetes. Any reduction in diabetes should, logically, also reduce the occurrence of its long-term complications; however, most diabetes prevention trials have not been of sufficient duration to allow such an evaluation. The limited long-term data, largely from the Da Qing Diabetes Prevention Study (DQDPS) and the Diabetes Prevention Program (DPP) and their respective follow-up studies (DQDPOS and DPPOS), suggest a reduction in microvascular complications and amelioration of CVD risk factors. Only the DQDPOS and Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) studies have shown a reduction in CVD events and only DQDPOS has demonstrated a decrease in CVD and overall mortality. While these limited data are promising, whether diabetes prevention directly reduces complication-related morbidity and mortality remains unclear. Longer follow-up of prevention studies is needed to supplement the limited current clinical trial data, to help differentiate the effects of diabetes prevention itself from the means used to reduce diabetes development and to understand the balance among benefits, risks and costs of prevention.

SUBMITTER: Nathan DM

PROVIDER: S-EPMC6818092 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Does diabetes prevention translate into reduced long-term vascular complications of diabetes?

Nathan David M DM Bennett Peter H PH Crandall Jill P JP Edelstein Sharon L SL Goldberg Ronald B RB Kahn Steven E SE Knowler William C WC Mather Kieren J KJ Mudaliar Sunder S Orchard Trevor J TJ Temprosa Marinella M White Neil H NH

Diabetologia 20190704 8

The global epidemic of type 2 diabetes has prompted numerous studies and public health efforts to reduce its development. A variety of interventions, including lifestyle modifications and pharmacological agents directed at ameliorating the major risk factors for type 2 diabetes, are of proven efficacy in reducing the development of type 2 diabetes in people with impaired glucose tolerance. While prevention of the hyperglycaemia characteristic of diabetes is arguably an important, clinically rele ...[more]

PMID: 31270584

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Project description:BackgroundThe prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood.MethodsWe previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated.ResultsAt the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up.ConclusionsAmong participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.).

Project description:AimsThe aim of the present study was to evaluate, by means of a meta-analysis approach, whether new available data, appeared on qualified literature, can support the effectiveness of an association of HbA1c variability with the risk of macro- and/or micro-vascular complications in type 2 diabetes mellitus (T2DM).MethodsThe meta-analysis was conducted according to PRISMA Statement guidelines and considered published studies on T2DM, presenting HbA1c variability as standard deviation (SD) or its derived coefficient of variation (CV). Literature search was performed on PubMed in the time range 2015-July 2022, with no restrictions of language.ResultsTwenty-three selected studies fulfilled the aims of the present investigation. Overall, the analysis of the risk as hazard ratios (HR) indicated a significant association between the HbA1c variability, expressed either as SD or CV, and the complications, except for neuropathy. Macro-vascular complications were all significantly associated with HbA1c variability, with HR 1.40 (95%CI 1.31-1.50, p < 0.0001) for stroke, 1.30 (95%CI 1.25-1.36, p < 0.0001) for transient ischaemic attack/coronary heart disease/myocardial infarction, and 1.32 (95%CI 1.13-1.56, p = 0.0007) for peripheral arterial disease. Micro-vascular complications yielded HR 1.29 (95%CI 1.22-1.36, p < 0.0001) for nephropathy, 1.03 (95%CI 0.99-1.08, p = 0.14) for neuropathy, and 1.15 (95%CI 1.08-1.24, p < 0.0001) for retinopathy. For all-cause mortality, HR was 1.33 (95%CI 1.27-1.39, p < 0.0001), and for cardiovascular mortality 1.25 (95%CI 1.17-1.34, p < 0.0001).ConclusionsOur meta-analysis on HbA1c variability performed on the most recent published data since 2015 indicates positive association between HbA1c variability and macro-/micro-vascular complications, as well as mortality events, in T2DM, suggesting that this long-term glycaemic parameter merits further attention as a predictive, independent risk factor for T2DM population.

Project description:BackgroundEffective prevention is needed to combat the worldwide epidemic of type 2 diabetes. We investigated the long-term extent of beneficial effects of lifestyle intervention and metformin on diabetes prevention, originally shown during the 3-year Diabetes Prevention Program (DPP), and assessed whether these interventions reduced diabetes-associated microvascular complications.MethodsThe DPP (1996-2001) was a randomised trial comparing an intensive lifestyle intervention or masked metformin with placebo in a cohort selected to be at very high risk of developing diabetes. All participants were offered lifestyle training at the end of the DPP. 2776 (88%) of the surviving DPP cohort were followed up in the DPP Outcomes Study (DPPOS, Sept 1, 2002, to Jan 2, 2014) and analysed by intention to treat on the basis of their original DPP assignment. During DPPOS, the original lifestyle intervention group was offered lifestyle reinforcement semi-annually and the metformin group received unmasked metformin. The primary outcomes were the development of diabetes and the prevalence of microvascular disease. For the assessment of microvascular disease, we used an aggregate microvascular outcome, composed of nephropathy, retinopathy, and neuropathy.FindingsDuring a mean follow-up of 15 years, diabetes incidence was reduced by 27% in the lifestyle intervention group (hazard ratio 0·73, 95% CI 0·65-0·83; p<0·0001) and by 18% in the metformin group (0·82, 0·72-0·93; p=0·001), compared with the placebo group, with declining between-group differences over time. At year 15, the cumulative incidences of diabetes were 55% in the lifestyle group, 56% in the metformin group, and 62% in the placebo group. The prevalences at the end of the study of the aggregate microvascular outcome were not significantly different between the treatment groups in the total cohort (placebo 12·4%, 95% CI 11·1-13·8; metformin 13·0%, 11·7-14·5; lifestyle intervention 11·3%, 10·1-12·7). However, in women (n=1887) the lifestyle intervention was associated with a lower prevalence (8·7%, 95% CI 7·4-10·2) than in the placebo (11·0%, 9·6-12·6) and metformin (11·2%, 9·7-12·9) groups, with reductions in the lifestyle intervention group of 21% (p=0·03) compared with placebo and 22% (p=0·02) compared with metformin. Compared with participants who developed diabetes, those who did not develop diabetes had a 28% lower prevalence of microvascular complications (relative risk 0·72, 95% CI 0·63-0·83; p<0·0001).InterpretationLifestyle intervention or metformin significantly reduced diabetes development over 15 years. There were no overall differences in the aggregate microvascular outcome between treatment groups; however, those who did not develop diabetes had a lower prevalence of microvascular complications than those who did develop diabetes. This result supports the importance of diabetes prevention.FundingNational Institute of Diabetes and Digestive and Kidney Diseases.

Project description:To investigate long-term metformin adherence in the Diabetes Prevention Program Outcomes Study (DPPOS) by examining: (1) predictors of long-term adherence to study metformin and (2) whether metformin adherence was associated with incident type 2 diabetes. DPPOS was an open-label continuation of the randomized clinical trial (Diabetes Prevention Program (DPP)) in which eligible participants randomized to the metformin group were offered study metformin and followed over 11 years. A brief structured adherence interview was administered semiannually. Metformin adherence was assessed by pill counts. Predictors of metformin adherence were examined in multivariate regression models. Incident diabetes associated with metformin adherence and other variables was assessed in Cox proportional hazards models. Of 868 participants eligible to continue taking study metformin, 664 (76%) took at least some metformin over 11 years, with 478 of them reporting problems with adherence. DPPOS cumulative adherence showed significant associations of higher adherence (≥80%) with early adherence at 3 months in DPP (p<0.001) and lower depression scores during DPPOS (p<0.001); significant differences were also seen by race/ethnicity (p<0.004). Predicting adherence by multivariate modeling showed odds of adherence significantly lower for Black participants and for participants reporting more than one barrier. Odds for adherence were significantly higher for those adherent early in DPP and those reporting at least one planned strategy to improve adherence. Higher metformin adherence was significantly associated with a lower diabetes risk (p=0.04), even after adjustment for demographic variables, depression, and anxiety scores. In this long-term diabetes prevention study, early metformin adherence and planned strategies to promote adherence improved long-term adherence over 11 years; higher adherence to metformin was related to lower diabetes incidence. Incorporating strategies to promote adherence when initially prescribing metformin and counseling to support adherence over time are warranted.

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Does diabetes prevention translate into reduced long-term vascular complications of diabetes?

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Does diabetes prevention translate into reduced long-term vascular complications of diabetes?

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