William C . Knowler

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BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the(More)
In 1997, an International Expert Committee was convened to reexamine the classification and diagnostic criteria of diabetes, which were based on the 1979 publication of the National Diabetes Data Group1 and subsequent WHO study group.2 As a result of its deliberations, the Committee recommended several changes to the diagnostic criteria for diabetes and for(More)
As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant(More)
BACKGROUND Common polymorphisms of the transcription factor 7-like 2 gene (TCF7L2) have recently been associated with type 2 diabetes. We examined whether the two most strongly associated variants (rs12255372 and rs7903146) predict the progression to diabetes in persons with impaired glucose tolerance who were enrolled in the Diabetes Prevention Program, in(More)
Adiponectin is a collagen-like circulating protein secreted by adipocytes that is proposed to mediate obesity-related resistance to insulin. In a case-control series, we assessed the role of adiponectin in later development of type 2 diabetes in 70 patients who later developed type 2 diabetes and 70 controls, matched for body-mass index, age, and sex. Cases(More)
BACKGROUND In the 2.8 years of the Diabetes Prevention Program (DPP) randomised clinical trial, diabetes incidence in high-risk adults was reduced by 58% with intensive lifestyle intervention and by 31% with metformin, compared with placebo. We investigated the persistence of these effects in the long term. METHODS All active DPP participants were(More)
contributes to both of these disease states. The hyperglycemic, hyperinsulinemic, insulin-resistant state is proinflammatory and is very different than the euglycemic, hyperinsulinemic state achieved with intensive insulin therapy. Insulin itself possesses anti-inflammatory properties (2). Intranuclear levels of nuclear factor , important in cancer(More)
Mapping by admixture linkage disequilibrium (MALD) is a potentially powerful technique for the mapping of complex genetic diseases. The practical requirements of this method include (a) a set of markers spanning the genome that have large allele-frequency differences between the parental ethnicities contributing to the admixed population and (b) an(More)
OBJECTIVE To examine the association between adiponectin, a known predictor of diabetes in Pima Indians, and markers of inflammation and endothelial function in nondiabetic subjects and to assess whether these markers predict later diabetes in a case-control study within a longitudinal health study in Pima Indians. RESEARCH DESIGN AND METHODS Participants(More)
OBJECTIVE The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes 1-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events. RESEARCH DESIGN AND METHODS This(More)