HNF1α defect influences post-prandial lipid regulationReport as inadecuate

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Hepatocyte nuclear factor 1 alpha HNF1α defects cause Mature Onset Diabetes of the Young type 3 MODY3, characterized by defects in beta-cell insulin secretion. However, HNF1α is involved in many other metabolic pathways with relevance for monogenic or polygenic type 2 diabetes. We aimed to investigate gut hormones, lipids, and insulin regulation in response to a meal test in HNF1α defect carriers MODY3 compared to non-diabetic subjects controls and type 2 diabetes T2D.


We administered a standardized liquid meal to each participant. Over 6 hours, we measured post-meal responses of insulin regulation blood glucose, c-peptide, insulin, gut hormones ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and lipids non-esterified fatty acids NEFA and triglycerides.


We found that MODY3 participants had lower insulin secretion indices than controls and T2D participants, showing the expected β-cell defect. MODY3 had similar glycated hemoglobin levels HbA1c median IQR: 6.5 5.6–7.6% compared to T2D median: 6.6 6.2–6.9%; P<0.05. MODY3 had greater insulin sensitivity Matsuda index: 71.9 29.6; 125.5 than T2D 3.2 4.0; 6.0; P<0.05. MODY3 experienced a larger decrease in the ratio of NEFA to insulin NEFA 30–0 - insulin 30–0: -39 -78; -30 x104 in the early post-prandial period 0–30 minutes compared to controls and to T2D -2.0 -0.6; -6.4 x104; P<0.05. MODY3 had lower fasting 0.66 0.46; 1.2 mM and post-meal triglycerides levels compared to T2D fasting: 2.3 1.7; 2.7 mM; P<0.05. We did not detect significant post-meal differences in ghrelin and incretins between MODY3 and other groups.


In response to a standard meal test, MODY3 showed greater early post-prandial NEFA diminution in response to relatively low early insulin secretion, and they maintained very low post-prandial triglycerides levels.

Author: Matthieu St-Jean, François Boudreau, André C. Carpentier, Marie-France Hivert



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