A High Protein Diet Is More Effective in Improving Insulin Resistance and Glycemic Variability Compared to a Mediterranean Diet-A Cross-Over Controlled Inpatient Dietary Study

Abstract

The optimal dietary pattern to improve metabolic function remains elusive. In a 21-day randomized controlled inpatient crossover feeding trial of 20 insulin-resistant obese women, we assessed the extent to which two isocaloric dietary interventions-Mediterranean (M) and high protein (HP)-improved metabolic parameters. Obese women were assigned to one of the following dietary sequences: M-HP or HP-M. Cardiometabolic parameters, body weight, glucose monitoring and gut microbiome composition were assessed. Sixteen women completed the study. Compared to the M diet, the HP diet was more effective in (i) reducing insulin resistance (insulin: Beta (95% CI) = -6.98 (-12.30, -1.65) µIU/mL, p = 0.01; HOMA-IR: -1.78 (95% CI: -3.03, -0.52), p = 9 × 10^-3); and (ii) improving glycemic variability (-3.13 (-4.60, -1.67) mg/dL, p = 4 × 10^-4), a risk factor for T2D development. We then identified a panel of 10 microbial genera predictive of the difference in glycemic variability between the two diets. These include the genera Coprococcus and Lachnoclostridium, previously associated with glucose homeostasis and insulin resistance. Our results suggest that morbidly obese women with insulin resistance can achieve better control of insulin resistance and glycemic variability on a high HP diet compared to an M diet.

Keywords: Mediterranean diet; dietary intervention; glycemic variability; gut microbiome; high protein diet; insulin resistance; obesity.

Figure 1

Study flowchart.

Figure 2

(A) Effect of diet on the mean change from baseline of insulin, HOMA-IR and glucose. Mean differences between high protein and Mediterranean diet in change from baseline of considered variables along with related standardized effect size and p-values are shown. Estimates were calculated using a mixed effect regression model, after adjusting for dietary sequence and treatment period. (B) Summary sensor glucose profiles for 24 h during (i) Mediterranean) and (ii) high protein diet. The solid blue line represents the median, the dark-blue shaded areas the interquartile range, while the light-blue shaded areas the 5th–95th percentile range. Green lines represent the normal range of glucose concentration, 70–180 mg/dL. (C) Effect of diet on glucose-related outcomes. Mean difference in glucose-related indices between high protein and Mediterranean diets along with related standardized effect size and p-values are shown. Estimates were calculated using a mixed effect regression model, after adjusting for dietary sequence and treatment period. HP: high protein diet, M: Mediterranean diet; HOMA-IR: homeostasis model assessment of insulin resistance CI: confidence interval; SD: standard deviation; MAGE: mean amplitude of glycemic excursions; MODD: mean of daily differences; (N = 16).

Figure 3

Microbial genera associated with the difference in glucose standard deviation between diets. Association between baseline microbial composition and mean difference of glucose index between HP and M diets was evaluated using zero sum constraint regression model. Results are reported in terms of beta regression coefficients, where the increase in the relative abundance of the selected genus at baseline is associated with an increased difference (red bars) or a decreased difference (blue bars) in SD of glucose concentration between HP and M diets. OTUs at baseline were first agglomerated to genus level. Relative abundances were filtered for sparsity and log transformed before the analysis. SD: standard deviation; (N = 16).