(5)妊娠時のインスリン抵抗性の機序と肥満・妊娠糖尿病との関連(<特集>第58回シンポジウム1「妊娠と栄養・代謝-妊娠中の適切な栄養管理をめざして-」)

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Recently, Japan has experienced an enormous increase of type 2 diabetes with a corresponding increase in registered automobiles and fat intake attributed mainly so-called westernization. It has also been suggested that both insulin secretion and insulin sensitivity are reduced compared to those of Caucasians. The objective of this study was to investigate the effects of obesity on carbohydrate profiles such as insulin sensitivity and insulin secretion during pregnancy and to assess differences in carbohydrate profile between a normal carbohydrate tolerant group and a gestational diabetes mellitus (GDM) group in Japan. GDM is defined as any degree of glucose intolerance with onset or recognition during pregnancy. Therefore, it includes undiagnosed diabetes mellitus. We examined the issue of whether the incidence of obstetric or perinatal complications in GDM, considered to represent undiagnosed diabetes mellitus, is higher than that in other types of GDM. Furthermore, to investigate the mechanism of insulin resistance in pregnancy, we compared serum adipokine levels in pregnant women with or without GDM. The diagnosis of GDM was performed in our center using a 75g oral glucose tolerance test (OGTT) between 24 and 28 weeks of pregnancy. The subjects were 328 pregnant women who visited to our hospitals during 2000〜2004. Of the 328 subjects, 55 were diagnosed as having GDM and, among these, 30 were obese. Of the 273 normal carbohydrate group, 30 women were obese. It has been reported that the homeostasis model assessment insulin resistance (HOMA-IR) calculated from fasting blood glucose (FBG) and fasting blood insulin (FBI) useful indices for evaluating insulin resistance not only in a normal, obese subjects, and diabetes in non-pregnancy but also in pregnant women. The insulinpgenic index (I. I.) has been useful to evaluate the ability of insulin secretion in obese normal carbohydrate and glucose intolerant subjects. Therefore, we compared these parameters for insulin resistance with β-cell function in non-obese or obese normal glucose tolerance (NGT) and obese and non-obese gestational diabetes mellitus (GDM). Secondly, GDM cases from 1991〜2004 at our center were classified as either GDM-A or GDM-B. GDM-A comprised undiagnosed diabetes mellitus (DM), including patients who displayed diabetic retinopathy, required insulin therapy for a long time after delivery, or were evaluated as having a DM pattern following a 75g OGTT after delivery. Complications during pregnancy, and obstetric and perinatal outcomes were compared between two groups. Thirdly, we compared serum levels of adipokines such as adiponectin, TNF-α, resistin, and leptin in pregnant women with or without obesity to investigate the mechanisms of insulin resistance in pregnancy. Serum levels of adipokines were measured by ELISA. In the GDM group, FBG and FBI showed significantly high levels compared to those in the NGT group, HOMA-R was highest in these groups. The obese and non-obese GDM group showed significantly low levels compared to that in the NGT group. In the 3^<rd> trimester in the NGT group, the levels of adiponectin were significantly lower than those in the 1st and 2^<nd> trimester. By contrast, resistin levels were increased in the 3^<rd> trimester in the NGT group. In GDM-A (n=17), 7 patients were reclassified with diabetes mellitus following a 75g OGTT after delivery, and 8 required insulin therapy for more than 3 months after delivery. Compared to GDM-B, GDM-A patients displayed a higher incidence of preeclampsia and cesarean section. Also, the incidences of congenital malformations, heavy-for-date births, hypoglycemia, and hyperbilirubinemia in the GDM-A group were higher than those in the GDM-B. These results suggest that the non-obese GDM group is mainly due to the β-cell defect and the obese GDM group is involved in both insulin resistance and β-cell defect. Therefore, β-cell function is a key factor for the onset of GDM during pregnancy in Japan. Also, the decrease of adiponectin and the increase of resistin levels in the serum may be involved in insulin resistance in the late pregnancy. In Japan, undiagnosed DM represents a high risk group in GDM. Screening for GDM in early pregnancy is therefore recommended, and in obese women, screening for diabetes mellitus before pregnancy may be more important. Finally, an experiment using mice demonstrated that oxidative stress is involved in congenital malformations caused by diabetic mothers, suggesting that antioxidant agents may become effective tools in reducing congenital malformations in the future.
社団法人日本産科婦人科学会の論文
2006-09-01

(5)妊娠時のインスリン抵抗性の機序と肥満・妊娠糖尿病との関連(<特集>第58回シンポジウム1「妊娠と栄養・代謝-妊娠中の適切な栄養管理をめざして-」)

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