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

Published on Aug 1, 2019in Diabetologia7.113
· DOI :10.1007/s00125-019-4928-8
David M. Nathan107
Estimated H-index: 107
(Harvard University),
Peter H. Bennett89
Estimated H-index: 89
(NIH: National Institutes of Health)
+ 9 AuthorsNeil H. White51
Estimated H-index: 51
(WashU: Washington University in St. Louis)
Sources
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.
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References46
Newest
#1Qiuhong Gong (Academy of Medical Sciences, United Kingdom)H-Index: 1
#2Ping Zhang (CDC: Centers for Disease Control and Prevention)H-Index: 38
Last. Gojka RoglicH-Index: 22
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Summary Background Lifestyle interventions can delay the onset of type 2 diabetes in people with impaired glucose tolerance, but whether this leads subsequently to fewer complications or to increased longevity is uncertain. We aimed to assess the long-term effects of lifestyle interventions in people with impaired glucose tolerance on the incidence of diabetes, its complications, and mortality. Methods The original study was a cluster randomised trial, started in 1986, in which 33 clinics in Da ...
10 CitationsSource
#1Ronald B. Goldberg (UM: University of Miami)H-Index: 46
#2George A. Bray (LSU: Louisiana State University)H-Index: 117
Last. Marinella Temprosa (GW: George Washington University)H-Index: 20
view all 7 authors...
Aims/hypothesis We 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...
3 CitationsSource
Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subje...
25 CitationsSource
#1Rury R. Holman (University of Oxford)H-Index: 99
#2Ruth L. Coleman (University of Oxford)H-Index: 13
Last. Jialun ChenH-Index: 1
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Summary Background The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced. Methods The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, ...
62 CitationsSource
#1Leigh Perreault (CU: University of Colorado Boulder)H-Index: 27
#2Qing Pan (GW: George Washington University)H-Index: 13
Last. W. C. Knowler (NIH: National Institutes of Health)H-Index: 49
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Aim Approximately half of the participants in the Diabetes Prevention Outcomes Study (DPPOS) had diabetes after 15 years of follow-up, whereas nearly all the others remained with pre-diabetes. We examined whether formerly unexplored factors in the DPPOS coexisted with known risk factors that posed additional risk for, or protection from, diabetes as well as microvascular disease. Methods Cox proportional hazard models were used to examine predictors of diabetes. Sequential modelling procedures c...
5 CitationsSource
#1Ronald B. Goldberg (UM: University of Miami)H-Index: 46
#2Vanita R. Aroda (MedStar Health)H-Index: 20
Last. Marinella Temprosa (GW: George Washington University)H-Index: 20
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Background —Despite the reduced incidence of coronary heart disease (CHD) with intensive risk factor management, people with diabetes and prediabetes remain at increased CHD risk. Diabetes prevention interventions may be needed to reduce CHD risk. This approach was examined in the Diabetes Prevention Program (DPP) and its Outcome Study (DPPOS), a long-term intervention study in 3234 subjects with prediabetes (mean [±SD] age 64±10 yrs) which showed reduced diabetes risk with lifestyle and metform...
30 CitationsSource
#1Qiuhong Gong (Academy of Medical Sciences, United Kingdom)H-Index: 2
#2Ping Zhang (CDC: Centers for Disease Control and Prevention)H-Index: 38
Last. Guangwei Li (Academy of Medical Sciences, United Kingdom)H-Index: 11
view all 15 authors...
OBJECTIVE People with impaired glucose tolerance (IGT) have increased risk of mortality and a high risk of progression to diabetes, but the extent that the excess mortality is associated with IGT per se or is the result of subsequent diabetes is unclear. RESEARCH DESIGN AND METHODS We compared mortality before and after the development of diabetes among 542 persons with IGT initially who participated in a 6-year lifestyle diabetes prevention trial and were followed-up from 1986 to 2009. RESULTS ...
10 CitationsSource
#4David M. Nathan (GW: George Washington University)H-Index: 107
#5Ionut Bebu (University of Pittsburgh)H-Index: 14
Last. John M. LachinH-Index: 78
view all 8 authors...
Risk factors for CVD are well-established in type 2 but not type 1 diabetes (T1DM). We assessed risk factors in the long-term (mean 27 years) follow-up of the Diabetes Control and Complications Trial (DCCT) T1DM cohort. Cox proportional hazards multivariate models assessed the association of traditional and novel risk factors, including HbA1c, with major atherosclerotic cardiovascular events (MACE: fatal or non-fatal myocardial infarction or stroke) and any-CVD (MACE plus confirmed angina, silen...
47 CitationsSource
Background The worldwide epidemic of type 2 diabetes requires effective prevention. We determined the long-term extent of beneficial effects of lifestyle intervention and metformin on diabetes prevention, originally demonstrated during the 3-year Diabetes Prevention Program (DPP), and whether diabetes-associated microvascular complications are reduced.
223 CitationsSource
#1Ronald B. Goldberg (UM: University of Miami)H-Index: 46
#2Marinella Temprosa (GW: George Washington University)H-Index: 20
Last. Karol E. Watson (UCLA: University of California, Los Angeles)H-Index: 43
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OBJECTIVE We evaluate whether lifestyle and metformin interventions used to prevent diabetes have durable effects on markers of inflammation and coagulation and whether the effects are influenced by the development of diabetes. RESEARCH DESIGN AND METHODS The Diabetes Prevention Program was a controlled clinical trial of 3,234 subjects at high risk for diabetes who were randomized to lifestyle, metformin, or placebo interventions for 3.4 years. Diabetes was diagnosed semiannually by fasting gluc...
19 CitationsSource
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#1William C. Knowler (NIH: National Institutes of Health)H-Index: 90
#2Jill P. Crandall (Albert Einstein College of Medicine)H-Index: 37
Purpose of Review There have been many randomized clinical trials testing lifestyle and drug interventions to prevent the development of type 2 diabetes in nondiabetic adults at high risk of the disease. We review the major trials using pharmacologic interventions with the primary outcome of preventing diabetes. The trials are grouped according to the main mechanism by which the drugs were thought to have the potential for preventing diabetes.
Source
#1Tzu-Ho Tsai (NYMU: National Yang-Ming University)
#2Nicole Huang (NYMU: National Yang-Ming University)H-Index: 23
Last. Yiing-Jenq Chou (NYMU: National Yang-Ming University)H-Index: 24
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#1Matti UusitupaH-Index: 38
#1Matti UusitupaH-Index: 84
Last. John L. SievenpiperH-Index: 44
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Prevention of type 2 diabetes (T2D) is a great challenge worldwide. The aim of this evidence synthesis was to summarize the available evidence in order to update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy. We conducted a systematic review and, where appropriate, meta-analyses of randomized controlled trials (RCTs) carried out in people with impaired glucose tolerance (IGT) (six studies) or dysmetabolism (one study) to answer the f...
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#1Silvio E. Inzucchi (Yale University)H-Index: 75
#2Catherine M. Viscoli (Yale University)H-Index: 32
Last. Walter N. Kernan (Yale University)H-Index: 32
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#1Hao Li (CQMU: Chongqing Medical University)H-Index: 2
#2Shen Tian (CQMU: Chongqing Medical University)
Last. Ling-quan Kong (CQMU: Chongqing Medical University)H-Index: 5
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Source