The DAPA-DIET study: Metabolic response to Dapagliflozin combined with dietary carbohydrate restriction in patients with Type 2 Diabetes Mellitus and Obesity-A longitudinal cohort study.

OBJECTIVE: The cardio-renal benefits of sodium glucose-like transporter 2 inhibitor (SGLT2i) therapies have been demonstrated in patients with and without type 2 diabetes. However, no studies have explored the long-term metabolic effects of SGLT2i, combined with dietary carbohydrate restriction. Our primary objective was to describe long-term changes in weight, energy expenditure, appetite and body composition after 12 months of Dapagliflozin therapy, with carbohydrate restriction, in people with type 2 diabetes and obesity. Our secondary objective was to assess changes in adiponectin and leptin. METHOD: This was a 12-month cohort study in a secondary care setting. Participants (n = 18) with type 2 diabetes (T2D) and class 3 obesity underwent baseline indirect calorimetry for determination of 24-h energy expenditure, body composition, fasting serum leptin and adiponectin levels, and appetitive assessments. Following initiation of Dapagliflozin (and dietary carbohydrate restriction), measurements were repeated at monthly intervals up to 12 months. RESULTS: Mean starting weight of participants was 129.4 kg (SD 25.9), mean BMI 46.1 kg/m2 (SD 8.3) and mean HbA1c 53.9 mmol/mol (14.1). Seventeen participants completed the study; after 12 months of Dapagliflozin and dietary carbohydrate restriction, mean weight loss was 8.1 kg (SD 11.3 kg; p = .009). This was mediated by reduced fat mass (mean loss, 9.9 kg; SD 10.4 kg; p = .002) associated with reduced serum leptin at 12 months (mean reduction 11,254 pg/ml; SD 16,075; p = .011). There were no significant changes in self-reported appetite, 24-h energy expenditure or serum adiponectin during follow-up. CONCLUSION: In this study, combined Dapagliflozin therapy and carbohydrate restriction in patients with T2D and obesity resulted in a significant reduction of body weight and fat mass at 12 months without any discernible changes in energy expenditure or appetite. These results offer a scientific and clinical rationale to conduct an exploratory trial investigating the effects of a low carbohydrate diet combined with SGLT2 inhibitors in patients with T2D.

Elevated concentrations of retinol-binding protein-4 (RBP-4) in gestational diabetes mellitus: negative correlation with soluble vascular cell adhesion molecule-1 (sVCAM-1).

BACKGROUND: Retinol-binding protein-4 (RBP-4) may increase insulin resistance (IR) in animals, with elevated levels reported in humans with obesity and type 2 diabetes. There are, however, few data on concentrations of RBP-4 in gestational diabetes mellitus (GDM). METHODS: We measured fasting serum levels of RBP-4, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in 50 women at 28 weeks of gestation, divided according to the results of a 50 g glucose challenge test (GCT) and a 75 g oral glucose tolerance test (OGTT): (1) controls (n = 20), normal responses to both GCT and OGTT; (2) intermediate group (IG) (n = 15): false positive GCT, but normal OGTT; and (3) GDM group (n = 15), both GCT and OGTT abnormal. IR was assessed by homeostasis model assessment (HOMA-IR) and by insulin resistance index (IRI) based on glycemia and insulinemia during OGTT. RESULTS: All groups were matched for age and body mass index (BMI). RBP-4 levels (microg/ml, mean+/-standard deviation) were higher in women with GDM vs. controls (53.9 +/- 17.9 vs. 29.7 +/- 13.9, p < or = 0.001), with a trend towards higher RBP-4 in GDM compared with IG (38.0 +/- 19.3, p = 0.07). There was no significant correlation between RBP-4 and age, BMI, insulin, IRI or HOMA-IR, but there was a moderate, significant negative correlation between RBP-4 and sVCAM-1 (r(2) = 0.20, p = 0.001). CONCLUSIONS: RBP-4 levels are elevated in women with GDM, but do not correlate with IR indices and correlate negatively with sVCAM-1. The physiological significance of RBP-4 rise in women with GDM remains to be elucidated.