Velasquez-Mieyer P A, Cowan P A, Arheart K L, Buffington C K, Spencer K A, Connelly B E, Cowan G W, Lustig R H
Department of Pediatrics, University of Tennessee Health Science Center, Memphis, USA.
Int J Obes Relat Metab Disord. 2003 Feb;27(2):219-26. doi: 10.1038/sj.ijo.802227.
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.
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.
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.
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.
高胰岛素血症是许多肥胖综合征的常见特征。我们研究了在不进行饮食或运动干预的情况下，抑制胰岛素分泌是否能促进肥胖成年人的体重减轻，并改变其食物摄入量和偏好。
44名严重肥胖成年人（89%为女性，39%为少数族裔）接受了为期24周的长效奥曲肽40mg肌肉注射，每28天一次，以抑制胰岛素分泌。在治疗前后进行口服葡萄糖耐量试验，计算β细胞活性指标（CIRgp）、胰岛素敏感性指标（CISI）和清除率指标（CP/I AUC），并获取瘦素水平、3天食物记录和碳水化合物渴望测量值。在一个可评估的亚组中进行了治疗前后的双能X线吸收法评估。
对于整个队列，在显著抑制胰岛素分泌的同时，胰岛素敏感性、体重减轻和体重指数（BMI）均得到改善。瘦素、脂肪量、总热量摄入和对碳水化合物的渴望均显著降低。按BMI反应分组时，高反应者（HR；DeltaBMI<-3kg/m²）和低反应者（LR；DeltaBMI在-3至-0.5之间）对CIRgp和IAUC的抑制作用高于无反应者（NR；DeltaBMI>-0.5）。仅在HR和LR中，CISI得到改善，瘦素和脂肪量显著下降。相反，NR中的瘦素和脂肪量均增加。仅HR中的碳水化合物摄入量受到显著抑制，而HR和LR中的碳水化合物渴望评分均降低。对于整个队列，DeltaBMI与DeltaCISI、Delta脂肪量和Delta瘦素相关。Delta脂肪量也与DeltaIAUC和DeltaCISI相关。
在一组肥胖成年人亚组中，胰岛素分泌的抑制与体重和脂肪量的减少以及热量摄入和常量营养素偏好的相应调节有关。
