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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]