The CArdiovasCulAr Diabetes & Ethanol (CASCADE) Trial

the 2-year CArdiovaSCulAr Diabetes & Ethanol (CASCADE) randomized controlled intervention trial (NCT00784433) we randomized 224 type 2 diabetic patients (age=59years; HbA1C=6.9%) to one of three arms: Mediterranean diet + red wine, Mediterranean diet + white wine, or Mediterranean diet+ mineral water. Based on the DIRECT results, the Mediterranean diet, which was not calorie restricted, was chosen as the optimal diet for patients with type 2 diabetes. The intervention trial was conducted between June 2010 and May 2012. Retention was 94% after one year and 87% after two, without any apparent alcohol-related adverse events or changes in medication usage. CASCADE two-year results demonstrated that initiating moderate wine intake among patients with well-controlled T2D, as part of a healthy diet, is apparently safe and has the potential to modestly improve glucose control and lipids (Annals of Internal Medicine 2015). As opposed to our primary hypothesis, we found that red wine improved the lipid profile more than white wine. The significant interaction of wine with specific ADH polymorphisms further supports the causal interpretation and might assist in identifying T2D patients who may benefit from moderate wine consumption. This is, for our knowledge, the largest and longest RCT in this field and it follows our previous 3-month RCT pilot study (Diabetes Care 2007).
In the abdomen-MRI subgroup (with 44% abdominal visceral fat), we found at baseline that two abdominal subcutaneous adipose tissue (SAT) sub-depots—the superficial SAT(SSAT) and Deep SAT(DSAT)—were differently associated with cardio-metabolic parameters, suggesting that abdominal superficial subcutaneous fat is a putative distinct protective fat sub-depot in type 2 diabetes (Diabetes Care 2012). This finding opens multiple novel possibilities for adipose tissue re-distribution among different sub-depots during dietary intervention as a mechanism for the long-term outcome of such intervention. Moreover, the differential association exhibited between SSAT and DSAT and cardio-metabolic markers suggests that fat re-distribution may predict both the beneficial and possibly the detrimental effects of intervention. These findings are the basis for the CENTRAL trial