Keep the muscles, lose the fat: Combined lifestyle intervention in older adults with obesity and type 2 diabetes

This thesis focusses on the role of nutrition and exercise during lifestyle intervention in older adults with obesity and type 2 diabetes. The main question was whether extra dietary protein, delivered via a whey protein drink with leucine and vitamin D, would benefit the preservation of muscle mass during weight loss, and glucose control. The substantial loss of muscle mass during intentional weight loss is often taken for granted. However, this is disadvantageous for older adults with obesity and type 2 diabetes. First, diet-induced loss of muscle mass increases the risk of weight cycling and the risk of sarcopenic obesity in the longer term. Second, the loss of muscle mass reduces the capacity for glucose uptake from the circulation. Previous work showed that lean mass, of which muscle tissue is a major component, can be preserved during weight loss in older adults with obesity who received the protein drink in combination with resistance exercise. In the current thesis, we evaluated the effectiveness of the protein drink on the preservation of lean mass during weight loss and improvement in glucose control in the metabolically more compromised population of older adults with obesity and type 2 diabetes. A 3-month combined lifestyle intervention was developed and contained the following key elements: 1) moderate caloric restriction with dietary counselling using alternate weekly individual and group sessions guided by a dietician, 2) progressive resistance exercise and high-intensity interval training 3 times per week in 1h group sessions supervised by personal trainers, and 3) coaching on lifestyle using various behaviour change techniques. We used a randomized controlled trial design to evaluate the effect of the protein drink. This drink contained 21 g of protein and was prescribed during breakfast (7x/week) and after training (3x/week). Consumption of the protein drink led to an increased protein intake (from 0.85 to 1.15 g/kg body weight per day), increased lean mass during weight loss, and improved insulin sensitivity, compared to an isocaloric control drink. Glucose control, muscle strength, and physical performance showed clinically meaningful improvements, irrespective of the use of the protein drink. Evaluation at six months after completion of the lifestyle intervention showed that participants still had preserved their lean mass, and had maintained their loss of total and visceral fat mass and their improved physical performance, irrespective of the use of the protein drink during intervention. Analysis according to diabetes subtype suggested that participants with predominant muscle insulin resistance benefitted the most from the protein drink, in terms of lean mass gain and improvement in insulin sensitivity. This may be related to an increased peripheral insulin sensitivity in this subtype upon lifestyle intervention. Protein supplementation did not reduce circulating levels of pro- or anti-inflammatory biomarkers. Neither level nor change in chronic low-grade inflammation was related to the preservation of lean mass. In conclusion, we accomplished preservation of lean mass during weight loss in older adults with obesity and type 2 diabetes, with lasting effect on fat loss and physical performance. The combination of resistance type exercise and additional protein intake is key to achieve preservation of lean mass during weight loss. With availability of a new generation of anti-obesity medications based on incretin-mimetic action, large weight loss can be expected in the treatment of obesity and type 2 diabetes. With this, also large losses of muscle mass can be anticipated which may be a threat to older adults, risking the development of sarcopenic obesity. Future research needs to optimise our intensive lifestyle approach in the reality of effective weight loss medication.