A low-glycemic index diet combined with exercise reduces insulin resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese, prediabetic humans

Abstract

Background: The optimal lifestyle intervention that reverses diabetes risk factors is not known.

Objective: We examined the effect of a low-glycemic index (GI) diet and exercise intervention on glucose metabolism and insulin secretion in obese, prediabetic individuals.

Design: Twenty-two participants [mean ± SEM age: 66 ± 1 y; body mass index (in kg/m(2)): 34.4 ± 0.8] underwent a 12-wk exercise-training intervention (1 h/d for 5 d/wk at ≈ 85% of maximum heart rate) while randomly assigned to receive either a low-GI diet (LoGIX; 40 ± 0.3 units) or a high-GI diet (HiGIX; 80 ± 0.6 units). Body composition (measured by using dual-energy X-ray absorptiometry and computed tomography), insulin sensitivity (measured with a hyperinsulinemic euglycemic clamp with [6,6-(2)H(2)]-glucose), and oral glucose-induced insulin and incretin hormone secretion were examined.

Results: Both groups lost equal amounts of body weight (-8.8 ± 0.9%) and adiposity and showed similar improvements in peripheral tissue (+76.2 ± 14.9%) and hepatic insulin sensitivity (+27.1 ± 7.1%) (all P < 0.05). However, oral glucose-induced insulin secretion was reduced only in the LoGIX group (6.59 ± 0.86 nmol in the prestudy compared with 4.70 ± 0.67 nmol in the poststudy, P < 0.05), which was a change related to the suppressed postprandial response of glucose-dependent insulinotropic polypeptide. When corrected for changes in β cell glucose exposure, changes in insulin secretion were attenuated in the LoGIX group but became significantly elevated in the HiGIX group.

Conclusions: Although lifestyle-induced weight loss improves insulin resistance in prediabetic individuals, postprandial hyperinsulinemia is reduced only when a low-GI diet is consumed. In contrast, a high-GI diet impairs pancreatic β cell and intestinal K cell function despite significant weight loss. These findings highlight the important role of the gut in mediating the effects of a low-GI diet on type 2 diabetes risk reduction.

Figures

FIGURE 1.

Study flowchart. A total of 413 men and women responded to the study advertisements. After review of our inclusion and exclusion criteria, 313 individuals were ineligible to partake in the study. After a full medical screening, a further 78 potential subjects were excluded from further participation. Twenty-four individuals were randomly assigned to the 12-wk exercise-training program combined with either a low–glycemic index diet (LoGIX; n = 12) or a high–glycemic index diet (HiGIX; n = 12). Two subjects were excluded from the LoGIX intervention (one subject failed to comply with the intervention, and the second subject declined to complete the postintervention testing). No adverse events were associated with our testing procedures or the intervention. Final statistical analyses were performed in 22 participants (LoGIX, n = 10; HiGIX, n = 12).

FIGURE 2.

Mean (±SEM) study-diet glycemic responses. A subgroup of individuals (n = 8) were selected to undergo two 1-d diet tests in which they consumed meals (solid black arrows) representative of our low–glycemic index diet (LoGIX) and high–glycemic index diet (HiGIX) study groups in a counterbalanced crossover design. A: Plasma glucose concentrations were measured every 10 min for 10 h. B: The incremental area under the glucose-response curve (iAUC) was calculated over the 10-h diet test. *The HiGIX (black bar) meals elicited a greater glycemic response than did the LoGIX (gray bar), P < 0.05 (paired t test).

FIGURE 3.

Mean (±SEM) insulin sensitivity (n = 22). After 12 wk of aerobic exercise combined with either a low–glycemic index diet (LoGIX; gray bars) or a high–glycemic index diet (HiGIX; black bars), changes in glucose kinetics were measured during 40 mU · m−2 · min−1 hyperinsulinemic euglycemic clamps. Values represent poststudy minus prestudy changes (Δ) in glucose kinetics. Basal rates of glucose appearance (Ra) decreased significantly (A) [basal Ra of hepatic glucose production (Basal Ra HGP); main effect of time, P < 0.05 (2-factor ANOVA)], whereas insulin-suppression of HGP (Insulin-Suppressed Ra HGP) increased after the intervention (B) (P < 0.05). Rates of glucose disappearance during hyperinsulinemia (Insulin-Stimulated Rd) increased significantly (C) (P < 0.05). No significant differences between LoGIX and HiGIX groups were observed (P = NS).

FIGURE 4.

Mean (±SEM) oral glucose–induced metabolic responses (n = 22). After the 12-wk intervention, changes in the glucose [A(i) and A(ii) (low–glycemic index diet [LoGIX] and high–glycemic index diet [HiGIX], respectively)], insulin [B(i) and B(ii)], C-peptide [C(i) and C(ii)], and glucose-dependent insulinotropic polypeptide (GIP) [D(i) and D(ii)] secretory responses to oral glucose were assessed. Each panel represents the metabolic response after glucose ingestion (oral-glucose-tolerance test) at t = 0 min. Solid lines represent prestudy values; dotted lines represent poststudy values. Glucose, insulin, C-peptide, and GIP responses to oral glucose ingestion were attenuated in the LoGIX group only after the intervention. *Significant prestudy compared with poststudy differences, P < 0.05 (2-factor ANOVA). The black bar is positioned above prestudy and poststudy time points that were significantly different. #Significant differences between groups (LoGIX compared with HiGIX) with regard to the pre- to postintervention changes at specific time points, P < 0.05.

FIGURE 5.

Mean (±SEM) oral glucose–induced insulin secretion (n = 22). After 12 wk of aerobic exercise combined with either a low–glycemic index diet (LoGIX; gray bars) or a high–glycemic index diet (HiGIX; black bars), changes in oral glucose–induced insulin secretion were assessed via peripheral blood C-peptide deconvolution. Values represent poststudy minus prestudy changes (Δ). A: The oral glucose–induced insulin secretion rate area under the curve (ISR AUC) was significantly reduced only in the LoGIX group (#LoGIX compared with HiGIX: P < 0.05, 2-factor ANOVA). B: Insulin resistance (IR; defined as the reciprocal of the glucose rate of disappearance divided by the steady state plasma insulin concentration) was equally reduced in both groups (LoGIX compared with HiGIX, P = NS). C: Oral glucose–induced insulin secretion corrected for changes in insulin resistance [the insulin secretory response to an oral-glucose-tolerance test corrected for changes in IR (ISR/G ÷ IR)] was unchanged in the LoGIX group but increased in the HiGIX group (#LoGIX compared with HiGIX, P < 0.05). *Significant prestudy compared with poststudy differences, P < 0.05. a.u., arbitrary units.