A “Spoonful of Sugar” and the Realities of Diabetes Prevention!

Given the remarkable progress made to date in regard to unraveling the pathophysiology and natural history of type 2 diabetes, identifying at-risk individuals, and evaluating effective clinical interventions for diabetes prevention, it would be very logical to think that assembling the required resources and implementing the “real-world” translation of findings to prevent type 2 diabetes would be only a matter of time. There is no debate on the need for widespread dissemination of effective interventions to delay onset of type 2 diabetes. First and foremost, there is an incredible amount of data defining the factors contributing to the development of diabetes (e.g., physical inactivity, dietary intake, and obesity). Second, we are all aware of the complications and the financial and emotional costs of the disease. Third, we recognize the global burden of the diabetes epidemic given the prevalence and incidence rates of obesity, prediabetes, and type 2 diabetes reported for each region of the world. And finally, it is no longer questioned that clinical interventions that consist of both lifestyle modification and metformin appear to be effective modalities in reducing the cumulative incidence of diabetes for at least 10 years (1–3). So, is there really any further debate needed regarding this topic? As outlined in this issue of the journal, the answer may not be so clear. Given the importance of this topic, our editorial team has featured articles focused on diabetes prevention in this issue of Diabetes Caredthe topics range from discussion of genetic risk and progression to diabetes to policy development (4–8). In this issue, Sullivan and colleagues, reporting on behalf of the Diabetes Prevention Program (DPP) Research Group, examined the utility of genetic risk scores (GRS) (as developed from a composite of single nucleotide polymorphisms at loci associated with type 2 diabetes) in predicting progression to diabetes and response to intervention in women with and without gestational diabetes mellitus (GDM) (4). Previously, the DPP Research Group reported that a prior analysis suggested that risk reduction for progression to diabetes in response to metformin was greater among women with GDM compared with women without GDM. Thus, the investigators hypothesized that genetic variability may be contributing to the observation and, if proven, would be an important finding. The data suggested the GRS predicted the presence of GDM, as it was higher in women with as opposed to without GDM. However, the GRS did not appear to be associated with progression to diabetes in high-risk women either with or without a GDM history in any of the study arms. The reasons for this observation are not precisely known, but the authors did state that the possible limitations of the study were small sample size and perhaps the long diabetes-free interval since the index pregnancy case, suggesting the DPP excluded women with GDM who had the highest risk for diabetes progression. Another topic featured in this issue and of importance to prevention of type 2 diabetes concerns pharmacologic therapies as a viable intervention. In both of the major prevention studies (DPP and the Finnish Diabetes Prevention Study [DPS]) and in subjects with type 2 diabetes, lifestyle intervention has been shown as the cornerstone of therapy. Unfortunately, after initial success, lifestyle intervention appears to be associated with weight regain over time (1–3,9). Thus, consideration of pharmacotherapies to delay progression to type 2 diabetes has been an area of great interest. A major question has been whether these therapies can be costeffective and whether the benefit outweighs the risk of therapy. We do have some information in this regard, at least for metformin, as in a prior report in Diabetes Care, the DPP Research Group provided a report on the long-term safety and tolerability and the longterm preventive effect of metformin (10). Importantly, the observations from that study demonstrated that weight loss was the major contributor and a strong predictor of diabetes