2048-P: The Physiological Effects of VLCD in Overweight Nondiabetics

Abstract

Background: Very Low-Calorie Diets (VLCD) are being increasingly used as a treatment for obesity and diabetes, yet concerns persist regarding reductions in muscle mass (as a crucial locomotory and insulin sensitive organ), while many physiological effects of VLCD are ill-defined. We thus explored the effects of VLCD on body composition, insulin sensitivity and vascular function in the overweight. Methods: Eight overweight men (47±7y; 103±14kg; BMI 32±4, mean±SD) were placed on a VLCD, of <800kcal/day for 6-weeks via meal replacements. Before/after VLCD, we conducted: OGTT, DXA to quantity fat and lean body mass, ultrasound (U.S.) to determine flow-mediated dilatation (FMD), and echocardiogram (ECHO) for left ventricular function (LVF). Insulin sensitivity was assessed via: i) HOMA-IR ii) area under the curve (AUC) for insulin and glucose iii) QUICKI iv) Matsuda Index. Results: VLCD reduced body weight (∆ -10.5±3 kg), fat mass (∆ -6.8±2 kg) and lean body mass (∆ -4.1±2 kg); all p<0.001. Significant improvements occurred in insulin sensitivity (HOMA-IR ∆ -0.6 ±0.6; AUC insulin ∆ -2147±2153 miliU/L*minute; QUICKI ∆ +0.05±0.03, and Matsuda Index ∆ 5.4±3.5); all P<0.05). No significant differences were observed in FMD (∆ 0.5±1.7%, P=0.5), LVF (∆ 1.4 ±6.9%, P=0.6), or AUC glucose (∆ -23.3±167.2 mmol/L*minute, P=0.7). No correlation was evident between degree of insulin sensitivity biomarkers and body weight or fat loss (e.g., Pearson -0.1<r<0.1, P>0.8). Conclusion: VLCD predictably induced marked weight loss and improved insulin sensitivity during just 6-weeks of VLCD, and this was associated with body fat loss and muscle wasting. Nonetheless, the poor correlation between total weight or body fat loss and improved indices of insulin action points to metabolic reprogramming of insulin sensitive tissues in response to energy restriction, rather than fat loss per se, in driving some of the health benefits of VLCD. Developing means to mitigate muscle atrophy with VLCD is crucial to maximizing therapeutic benefits, especially in aging. Disclosure M. Abdul Aziz: None. B.E. Phillips: None. I. Ramzan: None. J. Cegielski: None. K. Smith: None. I.R. Idris: None. P.J. Atherton: None. Funding Medical Research Council UK