Gastaldelli Amalia, Miyazaki Yoshinori, Pettiti Maura, Matsuda Masafumi, Mahankali Srihanth, Santini Eleonora, DeFronzo Ralph A, Ferrannini Ele
Metabolism Unit, Department of Internal Medicine, University of Pisa, Via Savi, I-56100 Pisa, Italy.
J Clin Endocrinol Metab. 2002 Nov;87(11):5098-103. doi: 10.1210/jc.2002-020696.
Visceral fat (VF) excess has been associated with decreased peripheral insulin sensitivity and has been suggested to contribute to hepatic insulin resistance. However, the mechanisms by which VF impacts on hepatic glucose metabolism and the quantitative role of VF in glycemic control have not been investigated. In the present study 63 type 2 diabetic subjects (age, 55 +/- 1 yr; fasting plasma glucose, 5.5-14.4 mmol/liter; hemoglobin A(1c), 6.1-11.7%) underwent measurement of 1) fat-free mass ((3)H(2)O technique), 2) sc and visceral abdominal fat area (magnetic resonance imaging), 3) insulin sensitivity (euglycemic insulin clamp), 4) endogenous glucose output ([(3)H]glucose infusion technique), and 5) gluconeogenesis ((2)H(2)O method). After adjustment for sex, age, body mass index, diabetes duration, ethnicity, and sc fat area, VF area was positively related to fasting hyperglycemia (partial r = 0.46; P = 0.001) as well as to hemoglobin A(1c) (partial r = 0.50; P = 0.0003). Insulin sensitivity was reciprocally related to VF independently of body mass index (partial r = 0.33; P = 0.01). In contrast, the relation of basal endogenous glucose output to VF was not statistically significant. This lack of association was explained by the fact that VF was positively associated with gluconeogenesis flux (confounder-adjusted, partial r = 0.45; P = 0.003), but was reciprocally associated with glycogenolysis (partial r = 0.31; P < 0.05). We conclude that in patients with established type 2 diabetes, VF accumulation has a significant negative impact on glycemic control through a decrease in peripheral insulin sensitivity and an enhancement of gluconeogenesis.
内脏脂肪（VF）过多与外周胰岛素敏感性降低有关，并被认为会导致肝脏胰岛素抵抗。然而，VF影响肝脏葡萄糖代谢的机制以及VF在血糖控制中的定量作用尚未得到研究。在本研究中，63名2型糖尿病患者（年龄55±1岁；空腹血糖5.5 - 14.4 mmol/升；糖化血红蛋白6.1 - 11.7%）接受了以下测量：1）去脂体重（（3）H（2）O技术），2）皮下和内脏腹部脂肪面积（磁共振成像），3）胰岛素敏感性（正常血糖胰岛素钳夹），4）内源性葡萄糖生成（（3）H葡萄糖输注技术），以及5）糖异生（（2）H（2）O方法）。在对性别、年龄、体重指数、糖尿病病程、种族和皮下脂肪面积进行调整后，VF面积与空腹高血糖呈正相关（偏相关系数r = 0.46；P = 0.001），与糖化血红蛋白也呈正相关（偏相关系数r = 0.50；P = 0.0003）。胰岛素敏感性与VF呈负相关，且独立于体重指数（偏相关系数r = 0.33；P = 0.01）。相比之下，基础内源性葡萄糖生成与VF的关系无统计学意义。这种缺乏关联的情况可以通过以下事实来解释：VF与糖异生通量呈正相关（经混杂因素调整后，偏相关系数r = 0.45；P = 0.003），但与糖原分解呈负相关（偏相关系数r = 0.31；P < 0.05）。我们得出结论，在已确诊的2型糖尿病患者中，VF堆积通过降低外周胰岛素敏感性和增强糖异生对血糖控制产生显著负面影响。
