Altered glucagon and GIP responses in South Asian versus Nordic women after gestational diabetes mellitus

Abstract Aims/hypothesis We aimed to compare ethnic differences in levels of glucagon, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) following a pregnancy complicated by gestational diabetes mellitus (GDM), and to assess whether the higher insulin levels observed in South Asian compared with Nordic women could be explained by differences in the hormone secretory responses. Methods We measured glucagon, GIP and GLP-1 in 178 South Asian and 107 Nordic women during an OGTT, and stratified participants by glycaemic status. Glucagon and total GLP-1 and GIP responses when fasting and post-OGTT were assessed by linear mixed models. Ethnic differences in incretin and glucagon levels were evaluated by linear regression analyses. Pre-hepatic insulin levels were estimated using deconvolution of C-peptide kinetics. Results Ethnic differences in glucagon and incretin levels varied by glycaemic status. In the normoglycaemic South Asian group, early (0–15 min) glucagon suppression post-OGTT was significantly attenuated compared with the Nordic group ( p =0.002). Fasting glucagon levels did not differ ( p =0.139), but total glucagon exposure (including fasting levels) was higher in South Asian women ( p =0.013). No differences in GIP and GLP responses to the OGTT were observed ( p =0.490 and p =0.802). In women with prediabetes or diabetes, fasting glucagon was higher in the South Asian group ( p =0.010), but there were no significant differences in early glucagon suppression post-OGTT ( p =0.986). GIP responses to the OGTT were lower among South Asian women ( p <0.001), despite higher insulin responses compared with the Nordic women. GLP-1 responses did not differ between the ethnic groups ( p =0.661). The higher pre-hepatic insulin levels in South Asian vs Nordic normoglycaemic women were not associated with differences in incretin levels, but were associated with lower insulin sensitivity in the regression analyses ( p <0.001). Conclusions/interpretation When examined 1–3 years post-GDM, normoglycaemic South Asian women had less early glucagon suppression and higher total glucagon exposure post-OGTT compared with Nordic women. The higher pre-hepatic insulin levels were not associated with higher incretin levels, but were associated with lower insulin sensitivity.