Division of Cardiovascular Medicine, Endocrinology and Metabolism, Tottori University, Tottori, Japan
Division of Cardiovascular Medicine, Endocrinology and Metabolism, Tottori University, Tottori, Japan.
BMJ Open Diabetes Res Care. 2022 Sep;10(5). doi: 10.1136/bmjdrc-2022-002908.
Pancreatic and duodenal homeobox factor-1 () is an imperative gene for insulin secretion in maturity-onset diabetes of the young 4. gene polymorphism was associated with lower first-phase insulin secretion in a genome-wide association study of intravenous glucose tolerance test. It was not associated with type 2 diabetes risk and insulin secretion in a genome-wide oral glucose tolerance test study. However, there have been no reports of overt type 2 diabetes and insulin resistance evaluation using a glucose clamp. We investigated polymorphism, insulin secretion, and insulin resistance in overt type 2 diabetes.
We performed a meal tolerance test (MTT) and hyperinsulinemic-euglycemic clamping on 63 Japanese subjects, 30 with type 2 diabetes and 33 non-diabetic. We analyzed the rs1124607 gene polymorphism and defined A/C and C/C as the high-risk group and A/A as the low-risk group.
HOMA-beta (homeostatic model assessment beta-cell function) was significantly lower in the high-risk group than in the low-risk group for all subjects (72.9±54.2% vs 107.0±63.5%, p<0.05). Glucose levels and glucose area under the curve (AUC) were not significantly different between both the risk groups. The insulin levels at 60 and 120 min and the insulin AUC after MTT were remarkably lower in the high-risk group than those in the low-risk group for all subjects (AUC 75.7±36.7 vs 112.7±59.5, p<0.05). High-risk subjects with type 2 diabetes had significantly lower insulin levels at 30 and 60 min and insulin AUC than low-risk subjects. Non-diabetic high-risk subjects depicted significantly lower insulin levels at 120 and 180 min. There were negligible differences in insulin resistance between the risk groups.
These results suggest that the genetic polymorphism is crucial for insulin secretion in Japanese patients with type 2 diabetes.
胰腺十二指肠同源盒因子-1() 是年轻起病的成年型糖尿病患者胰岛素分泌所必需的基因。4 基因多态性与静脉葡萄糖耐量试验的全基因组关联研究中第一时相胰岛素分泌降低相关。在全基因组口服葡萄糖耐量试验研究中，它与 2 型糖尿病风险和胰岛素分泌无关。然而，使用葡萄糖钳夹技术评估 2 型糖尿病和胰岛素抵抗的显性病例尚未有报道。我们研究了 rs1124607 基因多态性、胰岛素分泌和显性 2 型糖尿病的胰岛素抵抗。
我们对 63 名日本受试者进行了餐耐量试验（MTT）和高胰岛素-正葡萄糖钳夹试验，其中 30 名患有 2 型糖尿病，33 名非糖尿病患者。我们分析了 rs1124607 基因多态性，并将 A/C 和 C/C 定义为高风险组，A/A 定义为低风险组。
高风险组的 HOMA-β（稳态模型评估胰岛β细胞功能）明显低于低风险组（72.9±54.2% vs 107.0±63.5%，p<0.05）。两组的血糖水平和血糖曲线下面积（AUC）没有显著差异。高风险组的胰岛素水平在 MTT 后 60 分钟和 120 分钟以及胰岛素 AUC 显著低于低风险组（AUC 75.7±36.7 vs 112.7±59.5，p<0.05）。高风险组的 2 型糖尿病患者的胰岛素水平在 30 分钟和 60 分钟及胰岛素 AUC 明显低于低风险组。非糖尿病高风险组在 120 分钟和 180 分钟时的胰岛素水平明显较低。两组之间的胰岛素抵抗差异可忽略不计。
这些结果表明，在日本 2 型糖尿病患者中，基因多态性对胰岛素分泌至关重要。
