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Aim: To examine the determinants and metabolic impact of the reduction in fasting and postload insulin levels after a low n-6 to n-3 polyunsaturated fatty acid (PUFA) ratio diet in obese youth., Materials and Methods: Insulin secretion and clearance were assessed by measuring and modelling plasma insulin and C-peptide in 17 obese youth who underwent a nine-point, 180-minute oral glucose tolerance test (OGTT) before and after a 12-week, eucaloric low n-6:n-3 polyunsaturated fatty acid (PUFA) ratio diet. Hepatic fat content was assessed by repeated abdominal magnetic resonance imaging., Results: Insulin clearance at fasting and during the OGTT was significantly increased after the diet, while body weight, glucose levels, absolute and glucose-dependent insulin secretion, and model-derived variables of β-cell function were not affected. Dietary-induced changes in insulin clearance positively correlated with changes in whole-body insulin sensitivity and β-cell glucose sensitivity, but not with changes in hepatic fat. Subjects with greater increases in insulin clearance showed a worse metabolic profile at enrolment, characterized by impaired insulin clearance, β-cell glucose sensitivity, and glucose tolerance, and benefitted the most from the diet, achieving greater improvements in glucose-stimulated hyperinsulinaemia, insulin resistance, and β-cell function., Conclusions: We showed that a 12-week low n-6:n-3 PUFA ratio diet improves hyperinsulinaemia by increasing fasting and postload insulin clearance in obese youth, independently of weight loss, glucose concentrations, and insulin secretion., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: Multiple studies support the efficacy of combining a glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in people with type 2 diabetes inadequately controlled on dual/triple oral therapy. Fixed-ratio combinations of basal insulin + GLP-1RA represent a further advance to facilitate management. We assessed the impact of fixed-ratio combination basal insulin + GLP-1RA treatment on β-cell function., Materials and Methods: We analysed data from 351 participants in the LixiLan-G trial (NCT02787551) randomized to receive iGlarLixi (insulin glargine 100 U/ml + lixisenatide) or to continue daily/weekly GLP-1RA, both on top of metformin. Participants received a 2-h meal tolerance test before randomization and at study end (26 weeks), with timed plasma glucose and C-peptide determinations. β-cell function parameters were resolved using mathematical modelling., Results: In the GLP-1RA group (n = 162), both body weight and glycated haemoglobin decreased at week 26, yet none of the insulin secretion/β-cell function parameters changed significantly. In contrast, in the iGlarLixi group (n = 189), glycated haemoglobin decreased significantly more than in the GLP-1RA group (p < .0001) despite an increase in body weight (+1.7 ± 3.9 kg, p < .0001). Fasting and stimulated insulin secretion decreased at Week 26 (both p < .0001 vs. GLP-1RA), while β-cell glucose sensitivity increased by a median 35% (p = .0032 vs. GLP-1RA). The incremental meal tolerance test glucose area showed a larger reduction with iGlarLixi versus GLP-1RA (p < .0001)., Conclusions: In people with type 2 diabetes on metformin, 26-week treatment with iGlarLixi resulted in a marked improvement in β-cell function concomitant with sparing of endogenous insulin release and a reduction in meal absorption., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)