A low n-6 to n-3 polyunsaturated fatty acid ratio diet improves hyperinsulinaemia by restoring insulin clearance in obese youth

Abstract

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.

Keywords: adolescents; dietary lipids; fatty liver disease; glucose metabolism; insulin clearance; insulin metabolism; insulin resistance; insulin secretion; liver; obesity; β-cell function.

FIGURE 1

A, Plasma insulin, B, Glucose, and C, C‐peptide concentrations; D, Insulin secretion rate (ISR); E, Area under the 180‐minute curve (AUC_{0−180 min}) of ISR; F, ISR relative to plasma glucose; G, β‐cell glucose sensitivity (β‐GS); H, ISR at a fixed fasting plasma glucose of 5 mmol/L (ISR@5); I, β‐cell rate sensitivity (β‐RS); potentiation factor ratio at J, 120 minutes, and K, 180 minutes; insulin clearance at L, Fasting, M, During the oral glucose tolerance test (OGTT), and N, Percentage reduction from fasting to OGTT; and O, Oral glucose insulin sensitivity (OGIS) index at baseline (week 0) and after the low n‐6:n‐3 polyunsaturated fatty acid ratio diet (week 12) in obese youth. Lines and columns indicate means. Error bars and shaded areas indicate SEM. Panels A and B are modified with permission from. Group differences were tested using paired Wilcoxon signed‐rank test. P values less than .10 are reported

FIGURE 2

A, Correlation between changes in oral glucose insulin sensitivity (OGIS) index and changes in insulin clearance during the oral glucose tolerance test (OGTT); correlation between changes in hepatic fat fraction (HFF%), and B, Changes in insulin clearance during the OGTT, or C, Changes in OGIS index; and D, Correlation between changes in β‐cell glucose sensitivity and changes in insulin clearance during the OGTT. Changes were calculated as the difference between values measured after and before the 12‐week low n‐6:n‐3 polyunsaturated fatty acid ratio diet. Correlations were tested using Pearson's correlation. Areas between dotted lines indicate 95% confidence intervals of the best‐fit line

FIGURE 3

A, Plasma insulin, and B, Glucose concentrations in response to a 75‐g oral glucose tolerance test at baseline (week 0) and after the low n‐6:n‐3 polyunsaturated fatty acid ratio diet (week 12) in participants with marked increase (> 25% from baseline) or minor change (± 25%) in postload insulin clearance. Data are reported as mean ± SEM