GLP-1 Response to Oral Glucose Is Reduced in Prediabetes, Screen-Detected Type 2 Diabetes, and Obesity and Influenced by Sex: The ADDITION-PRO Study
GLP-1 Response to Oral Glucose Is Reduced in Prediabetes, Screen-Detected Type 2 Diabetes, and Obesity and Influenced by Sex: The ADDITION-PRO Study
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DOI：
10.2337/db14-1751
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发表时间：
2015-07-01
期刊：
影响因子：
7.7
通讯作者：
Jorgensen, Marit E.
中科院分区：
文献类型：
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作者：
Faerch, Kristine;Torekov, Signe S.;Jorgensen, Marit E.
葡萄糖刺激的GLP-1释放在肥胖和2型糖尿病发展中的作用尚不清楚。我们在一个大型研究人群中评估了GLP-1对口服葡萄糖的反应，这些人群包括正常和受损葡萄糖调节的瘦和肥胖男性和女性。在参加丹麦ADDITION-PRO研究（n = 1，462）的正常葡萄糖耐量（NGT）（n = 774）、前驱糖尿病（n = 525）或筛查检测到的2型糖尿病（n = 163）个体中分析口服葡萄糖耐量试验（OGTT）期间葡萄糖、胰岛素和GLP-1的循环浓度。与NGT患者相比，患有糖尿病前期或2型糖尿病的女性对OGTT的GLP-1反应低25%，患有糖尿病前期或2型糖尿病的男性和女性的120分钟GLP-1浓度均低16-21%，与年龄和肥胖无关。与正常体重个体相比，肥胖和超重个体对口服葡萄糖的GLP-1反应降低20%，与葡萄糖耐量状态无关。较高的GLP-1反应与较好的胰岛素敏感性和细胞功能、年龄较大和肥胖程度较轻相关。我们的研究结果表明，GLP-1对口服葡萄糖的反应降低发生在2型糖尿病和肥胖的发展之前，这可能对糖尿病的早期预防策略产生影响。
The role of glucose-stimulated release of GLP-1 in the development of obesity and type 2 diabetes is unclear. We assessed GLP-1 response to oral glucose in a large study population of lean and obese men and women with normal and impaired glucose regulation. Circulating concentrations of glucose, insulin, and GLP-1 during an oral glucose tolerance test (OGTT) were analyzed in individuals with normal glucose tolerance (NGT) (n = 774), prediabetes (n = 525), or screen-detected type 2 diabetes (n = 163) who attended the Danish ADDITION-PRO study (n = 1,462). Compared with individuals with NGT, women with prediabetes or type 2 diabetes had 25% lower GLP-1 response to an OGTT, and both men and women with prediabetes or type 2 diabetes had 16-21% lower 120-min GLP-1 concentrations independent of age and obesity. Obese and overweight individuals had up to 20% reduced GLP-1 response to oral glucose compared with normal weight individuals independent of glucose tolerance status. Higher GLP-1 responses were associated with better insulin sensitivity and -cell function, older age, and lesser degree of obesity. Our findings indicate that a reduction in GLP-1 response to oral glucose occurs prior to the development of type 2 diabetes and obesity, which can have consequences for early prevention strategies for diabetes.