Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults

Abstract

Purpose: Hyperinsulinemia is a common feature of many obesity syndromes. We investigated whether suppression of insulin secretion, without dietary or exercise intervention, could promote weight loss and alter food intake and preference in obese adults.

Methods: Suppression of insulin secretion was achieved using octreotide-LAR 40 mg IM q28d for 24 weeks in 44 severely obese adults (89% female, 39% minority). Oral glucose tolerance testing was performed before and after treatment, indices of beta-cell activity (CIRgp), insulin sensitivity (CISI), and clearance (CP/I AUC) were computed, and leptin levels, 3-day food records and carbohydrate-craving measurements were obtained. DEXA evaluations were performed pre- and post-therapy in an evaluable subgroup.

Results: For the entire cohort, significant insulin suppression was achieved with simultaneous improvements in insulin sensitivity, weight loss, and body mass index (BMI). Leptin, fat mass, total caloric intake, and carbohydrate craving significantly decreased. When grouped by BMI response, high responders (HR; DeltaBMI<-3 kg/m(2)) and low responders (LR; DeltaBMI between -3 and -0.5) exhibited higher suppression of CIRgp and IAUC than nonresponders (NR; DeltaBMI-0.5). CISI improved and significant declines in leptin and fat mass occurred only in HR and LR. Conversely, both leptin and fat mass increased in NR. Carbohydrate intake was markedly suppressed in HR only, while carbohydrate-craving scores decreased in HR and LR. For the entire cohort, DeltaBMI correlated with DeltaCISI, Deltafat mass, and Deltaleptin. DeltaFat mass also correlated with DeltaIAUC and DeltaCISI.

Conclusions: In a subcohort of obese adults, suppression of insulin secretion was associated with loss of body weight and fat mass and with concomitant modulation of caloric intake and macronutrient preference.

Figures

Figure 1

Excursions of insulin (a–c) during oral glucose tolerance testing in 44 subjects with obesity, stratified by BMI response to insulin suppression. Curves for HR (a; white squares), LR (b; gray circles), and NR (c; black squares) are plotted both at Week 0 (solid lines) and at Week 24 (dashed lines). Error bars denote s.e.m. ANOVA with repeated measures document significant differences between the insulin curves at week 0 and 24 for HR (P = 0.001) and LR (P < 0.001), while NR did not have significant differences in insulin excursion following treatment with octreotide.

Figure 2

Alterations in macronutrient intake in 44 subjects with obesity, stratified by BMI response to insulin suppression (HR, white squares; LR, gray circles; NR, black squares). (a) Although carbohydrate intake decreased in all subjects (P < 0.001), the suppression of carbohydrate intake was greatest in HR, and was less pronounced in LR and NR. (b) As a percent of daily ingested calories as carbohydrate, only HR demonstrated a decrease from 47% to 35% (P = 0.017). (c) Fat intake decreased in all groups (P < 0.001), but the decrease was indistinguishable among response strata. (d) Protein intake also decreased in all groups (P < 0.001), but the decrease was indistinguishable among response strata.