Commentary: Of hopes and DREAMS: The quest to prevent type 2 diabetes

University of Washington Seattle, Seattle, Washington, United States
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 01/2007; 91(12):4762-3. DOI: 10.1210/jc.2006-2164
Source: PubMed


The old adage that "prevention is better than cure" holds particularly well for a chronic disease like type 2 diabetes, withitsepidemicscaleandmultiplecripplingcomplications. Clearly, any intervention that can halt this epidemic safely and effectively will have huge public health implications. Several clinical trials have therefore attempted to address the question of preventing diabetes. Among these, the Dia- betes Prevention Program clearly demonstrated that inten- sive lifestyle change was effective not only in decreasing the progression of impaired glucose tolerance to diabetes, but was also associated with significant improvement in other cardiovascular risk factors (1). The Finnish Diabetes Preven- tion Study reported similar findings (2). One would think that therein lies the simple answer to diabetes prevention. Unfortunately,translationoftheseresultstothegeneralpub- lic has been difficult. Large, randomized trials have also assessed the potential of the medications metformin (Dia- betes Prevention Program) and acarbose (STOP-NIDDM) to slow the progression to diabetes, and these have both dem- onstrated some benefit (1, 3). When one compares the results in the Diabetes Prevention Program, metformin was only abouthalfaseffectiveaswasintensivelifestylechange.Acar- bose, although not compared head-to-head with intensive lifestyle,appearstobenobetterthanmetformin.Atthistime, neither of these drugs is currently approved for diabetes prevention. Whether they ever will be approved is another question. With the availability of other classes of agents with different mechanisms of action, many pharmaceutical com- panies and clinical trialists continue to investigate the effect of pharmacological therapy to prevent diabetes. The most recent large clinical trial to address the preven- tion of diabetes has been the Diabetes Reduction Assessment with Ramipril and Rosiglitazone (DREAM) trial (4, 5), for which there was a good rationale. First, post hoc analyses of a variety of studies have shown that blockade of the renin- angiotensinsystemdecreasesincidentdiabetes.Inparticular, the HOPE study demonstrated a significant reduction in new-onset diabetes in people with increased cardiovascular risks (6). Second, rosiglitazone is a thiazolidinedione insulin- sensitizer, and a previous drug in this class, which is no longer available, had been shown to prevent diabetes in a small single-center study in Hispanic women with a history of gestational diabetes (7); the same was suggested in a discontinued arm in the Diabetes Prevention Program (8). The DREAM trial was an international effort performed in 5269 individuals (59% women) of whom 44% had a history of hypertension, 44% were current or former smokers, and 36% had dyslipidemia. The results of the study were mixed (4, 5), which for the most part was not unexpected. The effect of ramipril (titrated to 15 mg/d) on glucose metabolism was small. Although the study demonstrated a modest glucose- lowering effect, the drug did not slow the rate of develop- ment of diabetes. In contrast, rosiglitazone (titrated to 8 mg/d) very significantly reduced the development of dia- betes by some 60% in this relatively healthy population with impaired fasting glucose or impaired glucose tolerance.

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    ABSTRACT: To review the pathophysiology, diagnosis, and management of cystic fibrosis-related diabetes mellitus (CFRD). We performed a MEDLINE search of the literature, using the search terms "cystic fibrosis-related diabetes, "CFRD," and "cystic fibrosis and diabetes," to identify pertinent articles available in English. In patients with cystic fibrosis (CF), CFRD is a major cause for an accelerated decline in health. It is the result of multiple pathophysiologic mechanisms, including destruction of pancreatic islet cells, impaired hepatic response to the antigluconeogenic effects of insulin, and impaired insulin sensitivity. Nutritional management and adequate caloric intake are paramount to successful management of CF. Although insulin remains the standard of care for treating CFRD in conjunction with fasting hyperglycemia, a small but growing body of literature supports the use of oral therapies. In this article, we discuss the benefits of and possible adverse reactions to the various classes of oral and injectable agents used in the treatment of diabetes mellitus, with special attention to the population of patients with CF. Orally administered agents can have a role in the treatment of CFRD. Further study is needed to determine the optimal combination of therapeutic modalities for CFRD.
    Endocrine Practice 01/2009; 14(9):1169-79. DOI:10.4158/EP.14.9.1169 · 2.81 Impact Factor


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