**1. Introduction**

The incidence of type 2 diabetes mellitus continues to rise worldwide and it is now estimated that diabetes affects more than 382 million people worldwide [1]). In the United States, the prevalence of diabetes ranges from 5.8 to 12.9 percent [2], but one of the most bothersome finding is the continuous increase in its prevalence; both community-based Framingham Heart Study and the National Health and Nutrition Examination Survey (NHANES) reported nearly doubling in the incidence of type 2 diabetes over the past decades [3] [4]

Obesity is one of the most important clinical risk factor for diabetes. In Nurses' Health Study, there was an approximately 100-fold increased risk of incident diabetes over 14 years in individuals whose baseline BMI was >35 kg/m2 compared with those with BMI <22 [5]. While the relationship between BMI and the risk of type 2 diabetes seems to be curvilinear, there is also an additional risk brought by the weight gain. In the same study, a weight gain of 8.0 to 10.9 kg after 18 years was associated with a relative risk for diabetes of 8.0 to 10.9 kg compared with those with minimal weight gain [5].

Sustained weight loss, on the other hand, can substantially improve glycemic control in patients with type 2 diabetes, by providing a partial correction of the two major metabolic abnormalities in type 2 diabetes: insulin resistance and impaired insulin secretion. A weight reduction of only 5 to 10 percent of initial body weight in overweight individuals can have a lasting beneficial impact on serum glucose, dyslipidemia, and hypertension [6]. However, the amount of weight loss required to achieve an ideal glycemic response may depend on the initial glucose level, as shown by the UKPDS study, with higher goals needed for those with non-controlled diabetes [7].

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While the benefits of weight loss for obese patients with diabetes are indubitable, there are several strategies for achieving weight loss, with physical activity and intensive lifestyle modification being important components of almost all programs. The Look AHEAD Study, the largest and longest randomized controlled trial of a behavioral intervention for weight loss in patients with diabetes, showed a mean body weight reduction of 8.5% at year one; over the next four years, a gradual regaining of weight was observed, followed by the maintenance of losses of approximately 4-5% in subsequent years [8]. This quite poor maintenance of weight loss, associated with the trial's negative finding with regard to its cardiovascular endpoints [9] sustains the need, at least in some diabetic patients, for more aggressive approaches in order to obtain substantial and durable weight loss.
