Increased proinsulin levels and decreased acute insulin response independently predict the incidence of type 2 diabetes in the Insulin Resistance Atherosclerosis Study
Increased proinsulin levels and decreased acute insulin response independently predict the incidence of type 2 diabetes in the Insulin Resistance Atherosclerosis Study
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DOI：
10.2337/diabetes.51.4.1263
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发表时间：
2002-04-01
期刊：
影响因子：
7.7
通讯作者：
Haffner, SM
中科院分区：
文献类型：
--
作者：
Hanley, AJG;D'Agostino, R;Haffner, SM
先前的研究表明，β细胞功能障碍可以预测糖尿病的发生，尽管尚不清楚联合使用胰岛素分泌措施是否可以进一步改善预测。胰岛素抵抗动脉粥样硬化研究是一项前瞻性、多中心、流行病学研究，研究胰岛素敏感性与糖尿病和心血管疾病风险之间的关系。在基线时，测量胰岛素、完整胰岛素原 (PI) 和分割 PI 的空腹浓度，并在频繁采样的静脉内葡萄糖耐量试验 (FSIGTT) 期间确定急性胰岛素反应 (AIR)。基线时没有糖尿病的受试者 (n = 903) 在 5 年随访后重新接受检查； 148 人患有糖尿病。在针对年龄、性别、诊所和种族进行调整的单独逻辑回归模型中，P 细胞功能障碍测量值的 1 SD 差异与糖尿病发病率相关（AIR：比值比 [OR] 0.37，95% CI 0.27-0.52；完整 PI：OR 1.90，95% CI 1.57-2.30；分割 PI：OR 1.94，95% CI 1.63-2.31）。对 BMI、糖耐量受损和胰岛素敏感性进行额外调整后，这些指标仍然与糖尿病风险显着相关（所有 P < 0.0001）。此外，在同时包含 PI 和 AIR 的模型中，每一个都是独立的预测因子，低 AIR 和高 PI 相结合的个体患糖尿病的风险最高。总之，低 AIR 和高 PI 可以独立预测特征明确的多种族人群中的糖尿病。尽管空腹 PI 更容易评估，但通过 FSIGTT 确定 AIR 可能会进一步改善预测。如果预防糖尿病的药物在正在进行的临床试验中被证明是有效的，那么进行 FSIGTT 可能会有益于识别最终需要终生药物治疗的更好（用于强化干预）的糖尿病前期受试者。
Previous studies have indicated that beta-cell dysfunction predicts the development of diabetes, although it is unknown whether the use of combinations of insulin secretory measures further improves prediction. The Insulin Resistance Atherosclerosis Study is a prospective, multicenter, epidemiological study of the relationship between insulin sensitivity and the risk of diabetes and cardiovascular disease. At baseline, fasting concentrations of insulin, intact proinsulin (PI), and split PI were measured, and acute insulin response (AIR) was determined during a frequently sampled intravenous glucose tolerance test (FSIGTT). Subjects who were nondiabetic at baseline (n = 903) were reexamined after 5 years of follow-up; 148 had developed diabetes. In separate logistic regression models adjusted for age, sex, clinic, and ethnicity, 1 SD differences in measures of P-cell dysfunction were associated with diabetes incidence (AIR: odds ratio [OR] 0.37, 95% CI 0.27-0.52; intact PI: OR 1.90, 95% CI 1.57-2.30; split PI: OR 1.94, 95% CI 1.63-2.31). After additional adjustment for BMI, impaired glucose tolerance, and insulin sensitivity, these measures continued to be significantly associated with risk of diabetes (all P < 0.0001). Furthermore, in models that included both PI and AIR, each was an independent predictor, and individuals who had combined low AIR and high PI experienced the highest diabetes risk. In conclusion, both low AIR and high PI independently predicted diabetes in a well-characterized multiethnic population. Although fasting PI is simpler to assess, determining AIR from an FSIGTT may further improve prediction. If pharmacological agents to prevent diabetes are proved to be efficacious in ongoing clinical trials, then it may be beneficial to perform FSIGTTs to identify better (for intensive intervention) prediabetic subjects who would ultimately require lifelong pharmacological therapy.