Department of Clinical Sciences, Malmö, Lund University, Clinical Research Centre, Building 60 Floor 13, Skåne University Hospital, Malmö, Entrance 72, Malmö SE-205 02, Sweden.
J Clin Endocrinol Metab. 2012 May;97(5):E810-8. doi: 10.1210/jc.2011-2444. Epub 2012 Mar 7.
A common genetic variant (rs10423928, A-allele) in the glucose-dependent insulinotropic polypeptide receptor gene (GIPR) is associated with decreased insulin secretion. Glucose-dependent insulinotropic polypeptide is secreted after food consumption and gipr knockout mice fed a high-fat diet are protected against obesity and disturbances in glucose homeostasis.
Our objective was to examine the interactions between rs10423928 and macronutrients and fiber intakes on body mass index and type 2 diabetes risk.
DESIGN, SETTING, AND PARTICIPANTS: Among nondiabetic subjects in the Swedish population-based Malmö Diet and Cancer cohort (n = 24,840; 45-74 yr), 1541 diabetes cases were identified during 12 yr of follow-up. Dietary intakes were assessed using a diet history method.
Incident type 2 diabetes was identified through registers.
There was no indication that dietary intakes significantly modify the association between GIPR genotype and body mass index (P interaction >0.08). We observed significant interactions between GIPR genotype and quintiles of carbohydrate (P = 0.0005) and fat intake (P = 0.0006) on incident type 2 diabetes. The TT-genotype carriers within the highest compared with the lowest carbohydrate quintile were at 23% (95% confidence interval = 5-39%) decreased type 2 diabetes risk. In contrast, AA-genotype carriers in the highest compared with the lowest fat quintile were at 69% (95% confidence interval = 29-86%) decreased risk.
Our prospective, observational study indicates that the type 2 diabetes risk by dietary intake of carbohydrate and fat may be dependent on GIPR genotype. In line with results in gipr knockout mice, AA-genotype carriers consuming high-fat low-carbohydrate diets had reduced type 2 diabetes risk, whereas high-carbohydrate low-fat diets benefitted the two thirds of population homozygous for the T-allele.
葡萄糖依赖性胰岛素释放多肽受体基因（GIPR）中的一个常见遗传变异（rs10423928，A 等位基因）与胰岛素分泌减少有关。进食后会分泌葡萄糖依赖性胰岛素释放多肽，高脂肪饮食喂养的 GIPR 基因敲除小鼠可预防肥胖和葡萄糖稳态紊乱。
我们旨在研究 rs10423928 与宏量营养素和膳食纤维摄入量之间的相互作用对体重指数和 2 型糖尿病风险的影响。
设计、地点和参与者：在非糖尿病的瑞典人群基础马尔默饮食与癌症队列（n=24840；45-74 岁）中，1541 例糖尿病病例在 12 年的随访中被确诊。采用饮食史法评估膳食摄入量。
通过登记确定 2 型糖尿病的发病情况。
没有迹象表明膳食摄入量显著改变 GIPR 基因型与体重指数之间的关联（P 交互作用>0.08）。我们观察到 GIPR 基因型与碳水化合物摄入量五分位数（P=0.0005）和脂肪摄入量五分位数（P=0.0006）之间存在显著的交互作用。与最低碳水化合物五分位组相比，GIPR 基因型 TT 携带者发生 2 型糖尿病的风险降低了 23%（95%置信区间=5-39%）。相反，与最低脂肪五分位组相比，GIPR 基因型 AA 携带者的风险降低了 69%（95%置信区间=29-86%）。
我们的前瞻性观察性研究表明，碳水化合物和脂肪的饮食摄入与 2 型糖尿病风险之间可能存在 GIPR 基因型的依赖性。与 GIPR 基因敲除小鼠的结果一致，AA 基因型携带者摄入高脂肪低碳水化合物饮食可降低 2 型糖尿病风险，而三分之二的人群携带 T 等位基因，食用高碳水化合物低脂肪饮食可获益。
