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

Am J Physiol Endocrinol Metab. 2021 Jan 1;320(1):E7-E18. doi: 10.1152/ajpendo.00165.2020. Epub 2020 Oct 26.


Dietary carbohydrate restriction may improve the phenotype of Type 2 diabetes (T2D) patients. We aimed to investigate 6 wk of carbohydrate restriction on postprandial glucose metabolism, pancreatic α- and β-cell function, gut hormone secretion, and satiety in T2D patients. Methods In a crossover design, 28 T2D patients (mean HbA1c: 60 mmol/mol) were randomized to 6 wk of carbohydrate-reduced high-protein (CRHP) diet and 6 wk of conventional diabetes (CD) diet (energy-percentage carbohydrate/protein/fat: 30/30/40 vs. 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), β-cell sensitivity to glucose (Bup), glucagon, and gut hormones were measured. Gastric emptying was evaluated by postprandial paracetamol concentrations and satiety by visual analog scale ratings. A CRHP diet reduced postprandial glucose area under curve (net AUC) by 60% (P < 0.001), 24 h 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 min (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. A CRHP diet reduced glucose excursions and improved β-cell function, including proinsulin processing, and increased subjective satiety in patients with T2D.

Keywords: Type 2 diabetes mellitus; appetite regulatory hormones; incretin hormones; nutritional therapy; β-cell function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / diet therapy*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / psychology
  • Diet, Carbohydrate-Restricted* / adverse effects
  • Dietary Proteins
  • Female
  • Gastric Emptying
  • Gastrointestinal Hormones / metabolism*
  • Glucose / metabolism*
  • Humans
  • Hyperglycemia / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Male
  • Proinsulin / blood
  • Satiety Response*
  • Treatment Outcome


  • Blood Glucose
  • Dietary Proteins
  • Gastrointestinal Hormones
  • Proinsulin
  • Glucose