Impaired beta cell glucose sensitivity and whole-body insulin sensitivity as predictors of hyperglycaemia in non-diabetic subjects
Impaired beta cell glucose sensitivity and whole-body insulin sensitivity as predictors of hyperglycaemia in non-diabetic subjects
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DOI：
10.1007/s00125-005-0004-7
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发表时间：
2005-12-01
期刊：
影响因子：
8.2
通讯作者：
Ferrannini, E
中科院分区：
文献类型：
--
作者：
Walker, M;Mari, A;Ferrannini, E
目的/假设：这项前瞻性研究的目的是调查具有英国血统的受试者糖耐量恶化的预测因素。方法：共156名非糖尿病受试者(86名有2型糖尿病家族史的受试者)在基线和5年后接受了75g OGTT和人体测量评估。采用模型评估法研究大鼠胰岛β细胞功能和全身胰岛素敏感性。如果在随访期内糖耐量从正常、空腹血糖受损、糖耐量受损和糖尿病转移了一步或多步，受试者被归类为进展者。结果：基线时，进展者(n=22)的肥胖增加，家族性糖尿病和糖耐量异常的比例高于非进展者。进展期患者的基线胰岛β细胞对血糖变化的敏感性(p<；0.02)和全身胰岛素敏感性(p<；0.0001)降低。Logistic回归分析显示，基线和随访时β细胞葡萄糖敏感性和胰岛素敏感性的变化，而不是传统的临床预测因素(肥胖、家族性糖尿病和血糖水平)是进展的关键独立预测因素(解释进展的50%以上)。结论/解释：胰岛β细胞葡萄糖感觉受损和全身胰岛素敏感性受损预测进展为高血糖。值得注意的是，这些病理生理变化忽略了临床危险因素的重要性，并突出了预防策略的潜在代谢目标。
Aims/hypothesis: The aim of this prospective study was to investigate predictors of deteriorating glucose tolerance in subjects of British extraction. Methods: A total of 156 non-diabetic subjects (86 with a family history of type 2 diabetes) underwent a 75-g OGTT and anthropometric assessment at baseline and 5 years later. Pancreatic beta cell function and whole-body insulin sensitivity were studied by model assessment. Subjects were classified as progressors if glucose tolerance moved one or more steps from normal, impaired fasting glucose, impaired glucose tolerance and diabetes over the follow-up period. Results: At baseline, the progressors (n=22) had increased adiposity and a higher proportion of familial diabetes and abnormal glucose tolerance than non-progressors. Baseline pancreatic beta cell sensitivity to changes in glucose (p < 0.02) and whole-body insulin sensitivity (p < 0.0001) were decreased in the progressors. Logistic regression revealed that baseline and follow-up changes in beta cell glucose sensitivity and insulin sensitivity, rather than the classical clinical predictors (adiposity, familial diabetes and glucose levels), were the key independent predictors of progression (explaining over 50% of the progression). Conclusions/interpretation: Impaired pancreatic beta cell glucose sensing and whole-body insulin sensitivity predict progression to hyperglycaemia. Strikingly, these pathophysiological changes override the importance of the clinical risk factors and highlight potential metabolic targets for prevention strategies.