Haffner S M, Miettinen H, Mykkänen L, Stern M P
Department of Medicine, University of Texas Health Science Center at San Antonio, 78284-7873, USA.
Int J Obes Relat Metab Disord. 1998 Sep;22(9):899-905. doi: 10.1038/sj.ijo.0800679.
Leptin (the product of the human OB gene) is increased in obese individuals, suggesting resistance to its effect. However, there is considerable variability in leptin levels at each level of body mass index (BMI), suggesting that genetic and environmental factors may regulate leptin concentrations. Previous data have suggested that leptin levels are associated with insulin resistance and in a few reports with impaired insulin secretion. We examined whether non-diabetic subjects, with elevated specific insulin and proinsulin levels, had increased leptin levels.
We used a radioimmunoassay (RIA) to measure serum leptin levels in 197 non-diabetic Mexican Americans and non-Hispanic whites from the San Antonio Heart Study. We also evaluated whether leptin levels were associated with impaired insulin secretion or increased beta cell stress, as evaluated by the fasting proinsulin/insulin ratio. (Higher fasting proinsulin/insulin ratios are thought to reflect impaired insulin secretion.)
Leptin levels were significantly correlated with fasting specific insulin (r=0.55, P<0.001) and proinsulin (r=0.57, P<0.001) and inversely with the proinsulin/insulin ratio (r= -0.154, P=0.035) after adjustment for age, gender, ethnicity and 2 h glucose. These associations were similar in men and women and in Mexican Americans and in non-Hispanic whites. After further adjustment for BMI and waist-to-hip ratio (WHR), leptin levels remained significantly correlated with specific insulin (r=0.31, P<0.001) and proinsulin (r=0.24, P<0.001) although the magnitude of the associations were considerably attenuated.
We conclude that specific insulin and proinsulin are positively related to leptin levels and that these associations are to some degree independent of obesity and body fat distribution. Thus, subjects with increased insulin levels may be relatively resistant to the effects of leptin. However, leptin levels are associated with a decrease in the fasting proinsulin/insulin ratio suggesting that leptin levels are not associated with an impairment in insulin secretion.
瘦素（人类OB基因的产物）在肥胖个体中升高，提示对其作用存在抵抗。然而，在每个体重指数（BMI）水平上，瘦素水平存在相当大的变异性，这表明遗传和环境因素可能调节瘦素浓度。先前的数据表明，瘦素水平与胰岛素抵抗相关，并且在一些报告中与胰岛素分泌受损有关。我们研究了特定胰岛素和胰岛素原水平升高的非糖尿病受试者的瘦素水平是否升高。
我们使用放射免疫分析法（RIA）测量了来自圣安东尼奥心脏研究的197名非糖尿病墨西哥裔美国人和非西班牙裔白人的血清瘦素水平。我们还评估了瘦素水平是否与胰岛素分泌受损或β细胞应激增加相关，通过空腹胰岛素原/胰岛素比值进行评估。（较高的空腹胰岛素原/胰岛素比值被认为反映胰岛素分泌受损。）
在调整年龄、性别、种族和2小时血糖后，瘦素水平与空腹特定胰岛素（r = 0.55，P < 0.001）和胰岛素原（r = 0.57，P < 0.001）显著相关，与胰岛素原/胰岛素比值呈负相关（r = -0.154，P = 0.035）。这些关联在男性和女性以及墨西哥裔美国人和非西班牙裔白人中相似。在进一步调整BMI和腰臀比（WHR）后，瘦素水平仍与特定胰岛素（r = 0.31，P < 0.001）和胰岛素原（r = 0.24，P < 0.001）显著相关，尽管关联程度明显减弱。
我们得出结论，特定胰岛素和胰岛素原与瘦素水平呈正相关，并且这些关联在一定程度上独立于肥胖和体脂分布。因此，胰岛素水平升高的受试者可能对瘦素的作用相对抵抗。然而，瘦素水平与空腹胰岛素原/胰岛素比值降低相关，提示瘦素水平与胰岛素分泌受损无关。
