Effects of carbohydrate restriction on postprandial glucose metabolism, beta-cell function, gut hormone secretion, and satiety in patients with type 2 diabetes.

Background & Aims Dietary carbohydrate-restriction may improve the phenotype of type 2 diabetes (T2D) patients. We aimed to investigate 6 weeks of carbohydrate-restriction on postprandial glucose metabolism, pancreatic alpha- and beta-cell function, gut hormone secretion, and satiety in T2D patients. Methods In a cross-over design, 28 T2D patients (mean: HbA1c 60 mmol/mol) were randomized to 6 weeks of carbohydrate-reduced high-protein (CRHP) diet and 6 weeks of conventional diabetes (CD) diet (energy-percentage carbohydrate/protein/fat: 30/30/40 versus 50/17/33). Twenty-four-hour continuous glucose monitoring (CGM) and mixed meal tests were undertaken and fasting intact proinsulin (IP), 32,33 split proinsulin concentrations (SP), and postprandial insulin secretion rates (ISR), insulinogenic index (IGI), beta-cell sensitivity to glucose (Bup), glucagon and gut hormones were measured. Gastric emptying was evaluated by postprandial paracetamol concentrations and satiety by visual analogue scale ratings. Results A CRHP diet reduced: postprandial glucose area under curve (net AUC) by 60% (p<0.001), 24h glucose by 13% (p<0.001), fasting IP and SP concentrations (both absolute and relative to C-peptide, p<0.05), and postprandial ISR (24%, p=0.015), while IGI and Bup improved by 31% and 45% (both p<0.001). The CRHP diet increased postprandial glucagon net AUC by 235% (p<0.001), subjective satiety by 18% (p=0.03), delayed gastric emptying by 15 minutes (p<0.001), decreased gastric inhibitory polypeptide net AUC by 29% (p<0.001), but had no significant effect on glucagon-like-peptide-1, total peptide YY and cholecystokinin responses. Conclusions A CRHP diet reduced glucose excursions and improved beta-cell function, including proinsulin processing, and increased subjective satiety in patients with T2D.