Groop L, Forsblom C, Lehtovirta M, Tuomi T, Karanko S, Nissén M, Ehrnström B O, Forsén B, Isomaa B, Snickars B, Taskinen M R
Department of Endocrinology, University of Lund, Malmö General Hospital, Sweden.
Diabetes. 1996 Nov;45(11):1585-93. doi: 10.2337/diab.45.11.1585.
Although a strong genetic susceptibility has been established for NIDDM and a maternal transmission of the disease predominates in some populations, a relationship between parental diabetes status and metabolic abnormalities in nondiabetic offspring has not been shown in humans. To address this question, we studied 2,152 first-degree relatives of patients with NIDDM (FH+) and 528 age- and weight-matched spouses without a family history of NIDDM (FH-) in Western Finland (the Botnia study). A subset of the subjects underwent a euglycemic insulin clamp combined with indirect calorimetry to measure insulin sensitivity and energy expenditure. Despite similar amounts of total body fat, persons with a family history of NIDDM had a greater waist-to-hip ratio (WHR) than spouses without a family history of diabetes (P < 0.003). They also had a decreased resting metabolic rate (P = 0.005), but this difference disappeared when adjusted for the difference in WHR. Insulin-stimulated glucose metabolism (P = 0.002), particularly nonoxidative glucose metabolism (P = 0.009), was reduced in FH+ compared with FH- subjects, and this difference remained after adjustment for WHR. A parental history of NIDDM influenced the insulin response to the oral glucose load, with male offspring of diabetic mothers showing the lowest insulin values (P = 0.011). Moreover, a parental effect was also observed on HDL and HDL2 cholesterol concentrations with female offspring of diabetic mothers showing lower values than female offspring of diabetic fathers (both P < 0.002). We conclude that abdominal obesity, insulin resistance, and decreased resting metabolic rate are characteristic features of first-degree relatives of patients with NIDDM and that the decrease in resting metabolic rate is partially related to the degree of abdominal obesity. A sex-specific paternal effect was observed on insulin and HDL cholesterol concentrations. Therefore, one has to consider the possibility of unprecedented maternal or paternal inheritance of different NIDDM phenotypes.
尽管已确定非胰岛素依赖型糖尿病（NIDDM）具有很强的遗传易感性，且在某些人群中该病以母系遗传为主，但在人类中，尚未证实父母的糖尿病状况与非糖尿病后代的代谢异常之间存在关联。为解决这一问题，我们在芬兰西部开展了一项研究（博特尼亚研究），对2152名NIDDM患者的一级亲属（FH +）和528名年龄及体重匹配、无NIDDM家族史的配偶（FH -）进行了研究。部分受试者接受了正常血糖胰岛素钳夹试验并结合间接测热法，以测量胰岛素敏感性和能量消耗。尽管总体脂肪量相似，但有NIDDM家族史的人的腰臀比（WHR）高于无糖尿病家族史的配偶（P < 0.003）。他们的静息代谢率也有所降低（P = 0.005），但在根据WHR差异进行调整后，这种差异消失了。与FH -受试者相比，FH +受试者的胰岛素刺激的葡萄糖代谢（P = 0.002），尤其是非氧化葡萄糖代谢（P = 0.009）降低，并且在根据WHR进行调整后，这种差异仍然存在。NIDDM的父母病史影响了对口服葡萄糖负荷的胰岛素反应，糖尿病母亲的男性后代胰岛素值最低（P = 0.011）。此外，在高密度脂蛋白（HDL）和HDL2胆固醇浓度方面也观察到了父母效应，糖尿病母亲的女性后代的值低于糖尿病父亲的女性后代（均P < 0.002）。我们得出结论，腹型肥胖、胰岛素抵抗和静息代谢率降低是NIDDM患者一级亲属的特征，静息代谢率的降低部分与腹型肥胖程度有关。在胰岛素和HDL胆固醇浓度方面观察到了性别特异性的父系效应。因此，必须考虑不同NIDDM表型前所未有的母系或父系遗传的可能性。
