妊娠期糖尿病治疗对其后代儿童期肥胖症的影响

目的评估妊娠期糖尿病的治疗对其后代儿童时期肥胖症发病情况的影响。方法选取入院生产的137名患有妊娠期糖尿病的妇女,对接受治疗与未接受治疗的孕妇后代进行追踪研究,研究指标包括身高、体质量、血压、腰围、空腹血糖、空腹胰岛素、甘油三酯含量和高密度脂蛋白及胆固醇的含量。结果治疗组与未治疗组的后代体质量指数>P95（肥胖）的例数分别占总人数的8.8%和9.5%（P=0.79）,体质量指数>P85（超重）的例数占总人数的16.8%和19.7%（P=0.65）。其中治疗组与未治疗组的体质量指数、空腹血糖值、甘油三酯含量、高密度脂蛋白含量、血压值、胰岛素抵抗值之间差异并无统计学意义（P>0.05）。但治疗组与未治疗组女性后代的空腹血糖和胰岛素抵抗值之间的差异有统计学意义（P=0.002,0.02）。结论尽管妊娠期糖尿病的治疗可以降低其女性后代的空腹血糖值,但总体而言并未降低儿童时期肥胖症的发生率。     

脂肪因子Omentin-1与妊娠期糖尿病相关性研究

目的观察妊娠期糖尿病(GDM)患者血清脂肪因子Omentin-1水平变化,并探讨其临床意义。方法采用酶联免疫吸附测定(ELISA)法定量85例GDM及匹配设置的85例糖耐量正常孕妇(NGT)血清Omentin-1水平,同时检测两组糖脂生化指标、炎性指标、空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR)。结果 GDM组孕前体质量指数(BMI)、超敏-C反应蛋白(hs-CRP)、血脂、血糖、FINS及HOMA-IR均明显高于NGT组,血清Omentin-1明显低于NGT组,差异有统计学意义(P0.05)。产前肥胖和/或HOMA-IR≥2时,血清Omentin-1水平明显降低。血清Omentin-1与高密度脂蛋白(HDL)呈正相关,而与孕前BMI、产前BMI、FPG、FINS及HOMA-IR呈负相关。多元逐步回归分析孕前BMI、三酰甘油(TG)、空腹血糖(FPG)、FINS是GDM血清Omentin-1的独立影响因素。结论血清Omentin-1与GDM关系密切,反映孕妇糖、脂代谢紊乱和胰岛素抵抗程度,可能直接参与了GDM疾病的发生和发展。     

Sex-Specific Associations of Gestational Glucose Tolerance With Childhood Body Composition

OBJECTIVE

To examine the associations of maternal gestational glucose tolerance with offspring body composition in late childhood.

RESEARCH DESIGN AND METHODS

Among 958 women in the prebirth cohort Project Viva, glucose tolerance was assessed in the second trimester by nonfasting 50-g 1-h glucose challenge test (GCT), followed if abnormal by fasting 100-g 3-h oral glucose tolerance test (OGTT). We categorized women as normoglycemic (83.3%) if GCT was ≤140 mg/dL, isolated hyperglycemia (9.1%) if GCT was abnormal but OGTT normal, intermediate glucose intolerance (IGI) (3.3%) if there was one abnormal value on OGTT, or gestational diabetes mellitus (GDM) (4.5%) if there were two or more abnormal OGTT values. Using multivariable linear regression, we examined adjusted associations of glucose tolerance with offspring overall (N = 958) and central (N = 760) adiposity and body composition using dual X-ray absorptiometry (DXA) measured at the school-age visit (95 ± 10 months).

RESULTS

Compared with that in the male offspring of normoglycemic mothers, DXA fat mass was higher in male offspring of GDM mothers (1.89 kg [95% CI 0.33–3.45]) but not in male offspring of mothers with IGI (0.06 kg [−1.45 to 1.57]). DXA trunk-to-peripheral fat mass, a measure of central adiposity, was also somewhat higher in male offspring of GDM mothers (0.04 [−0.01 to 0.09]). In girls, DXA fat mass was higher in offspring of mothers with IGI (2.23 kg [0.12–4.34]) but not GDM (−1.25 kg [−3.13 to 0.63]). We showed no association of gestational glucose tolerance with DXA lean mass.

CONCLUSIONS

In this study, only male offspring of GDM mothers manifested increased adiposity, whereas only female offspring of mothers with IGI did so. Sex differences in glycemic sensitivity may explain these findings.The prevalence of gestational diabetes mellitus (GDM) has increased during the past 20 years, alongside obesity and type 2 diabetes (1). Heavier mothers are more likely to exhibit hyperglycemia during pregnancy than are normal-weight mothers. Because GDM is associated with both higher birth weight and increased fetal adiposity (2) and because birth weight is directly associated with later obesity, it has been postulated that hyperglycemic intrauterine environment may program the fetus via metabolic changes in the child (3,4).Two recent meta-analyses concluded that the evidence for an association between preexisting diabetes or GDM and offspring overweight and obesity in childhood is inconsistent (5,6). One reason is that many studies did not adjust for maternal prepregnancy adiposity, which itself is a major determinant of both GDM and offspring adiposity. In their review, Philipps et al. (5) reported that in offspring of mothers with diabetes (all types of diabetes combined vs. no diabetes), the unadjusted mean BMI z score was 0.28 higher (95% CI 0.09–0.47) but that the z score was only 0.07 higher (−0.15 to 0.28) after adjustment for maternal prepregnancy BMI.Another reason for inconsistency is that many studies used BMI or other weight and height measures for the childhood outcome instead of more direct and accurate measures of adiposity or fat distribution. Indeed, we previously reported that 3-year-old children of mothers with GDM had greater adiposity than normoglycemic mothers when it was assessed by the sum of skinfold thicknesses but not by BMI (7). Two studies reported results of the association of GDM exposure with body composition measured by dual X-ray absorptiometry (DXA) or magnetic resonance imaging in school-aged children. Chandler-Laney et al. (8) showed that maternal glucose concentration during pregnancy was positively associated with both fat and lean mass as measured by DXA in children aged 5–10 years (8). However, these results were not adjusted for maternal BMI. Crume et al. (9) reported that exposure to maternal GDM was associated with more subcutaneous abdominal fat (+ 34.7 cm², P = 0.01) as measured by magnetic resonance imaging in children aged 6–13 years, but adjustment for maternal prepregnancy BMI substantially attenuated the association (+ 22.4 cm², P = 0.10).Another important consideration is that the association of GDM exposure with offspring adiposity or weight seems to be transient (10,11). For example, Silverman et al. (12) showed that offspring of mothers with diabetes were larger than a reference population at birth and again at school age but not as toddlers. Discrepancies in the literature could to some extent be explained by differences in the age at which the outcome was measured.Finally, while an increasing number of studies suggest that intrauterine programming may differ by sex (13), few studies have explored sex differences in the associations of GDM with offspring adiposity in childhood (14,15).Our aim was to fill these research gaps by examining associations of maternal gestational glucose tolerance with several measures of childhood adiposity at the school-age visit, before and after adjustment for maternal prepregnancy BMI, and according to sex of the child.     

Prevalence and Predictors of Overweight and Insulin Resistance in Offspring of Mothers With Gestational Diabetes Mellitus

OBJECTIVE

Gestational diabetes mellitus (GDM) is associated with high birth weight in the offspring. This may lead to overweight and insulin resistance during childhood. The aim of the study was to assess the impact of GDM on overweight risk and insulin resistance in offspring.

RESEARCH DESIGN AND METHODS

BMI measurements were collected at age 2, 8, and 11 years from 232 offspring of mothers with GDM (OGDM) and compared with those from 757 offspring of mothers with type 1 diabetes (OT1D) and 431 offspring of nondiabetic mothers (ONDM) born between 1989 and 2000. Insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) was determined at age 8 and 11 years in 751 children (74 OGDM). Overweight was defined as BMI percentile ≥90; insulin resistance was defined by HOMA-IR.

RESULTS

Overweight prevalence was increased in OGDM compared with OT1D and to ONDM throughout childhood (age 11 years 31.1, 15.8, and 15.5%; P = 0.005). Maternal obesity was an important predictor of overweight risk in children (age 11 years odds ratio 7.0 [95% CI 1.8–27.7]; P = 0.006); birth size and maternal smoking during pregnancy were inconsistently associated with and treatment of GDM during pregnancy did not affect overweight risk. HOMA-IR was increased in OGDM compared with offspring of ONDM mothers (P = 0.01, adjusted for sex and age) and was associated with the child''s BMI (P = 0.004).

CONCLUSIONS

Overweight and insulin resistance in children is increased in OGDM compared with OT1D or ONDM. The finding that overweight risk is associated mainly with maternal obesity suggests that familial predisposition contributes to childhood growth in these offspring.The increasing prevalence of obesity in children is a major burden not only for affected individuals but also for the health economy. To develop preventive strategies, it is useful to identify subjects at high risk and factors that predict overweight risk. It is widely accepted that gestational and perinatal factors influence weight development in childhood, and several studies indicated that intrauterine exposure to maternal diabetes conveys high risk for obesity and type 2 diabetes in offspring of mothers with diabetes regardless of maternal diabetes type (1–3). Furthermore, an association between increasing hyperglycemia in pregnancy and increasing risk of childhood obesity has been reported (4). The findings have led to the hypothesis that fetal overnutrition leads to increased risk of obesity and insulin resistance later in life (5).Not all studies, however, show a direct relationship between childhood obesity and diabetes. Our own studies show that maternal type 1 diabetes is unlikely to be a primary association with obesity in offspring, but that factors such as high birth size predispose offspring of mothers with type 1 diabetes (OT1D) to overweight during childhood (6). In addition, others report that maternal pregravid BMI is the strongest predictor of childhood obesity independent of maternal glucose status or birth weight (7). The aim of our study was to determine whether maternal diabetes per se is a risk factor for childhood obesity and insulin resistance by comparing outcome in offspring of mothers with gestational diabetes mellitus (OGDM) and OT1D. Because a previous study reported age-dependent associations of gestational diabetes mellitus (GDM) with higher child weight status (1), a secondary objective was to examine whether associations between offspring weight and peri- or postnatal factors are consistent over time.     

Determinants of insulin resistance in infants at age 1 year: impact of gestational diabetes mellitus

OBJECTIVE

The offspring of women with gestational diabetes mellitus (GDM) display a propensity for the early accrual of cardiometabolic risk factors, including insulin resistance, in childhood and adolescence. Thus, we sought to identify early life determinants of insulin resistance in infants of women with and without GDM.

RESEARCH DESIGN AND METHODS

In total, 104 full-term, singleton infants born to women with (n = 36) and without (n = 68) GDM were evaluated at age 1 year, with insulin resistance assessed by homeostasis model (HOMA-IR).

RESULTS

HOMA-IR at 1 year did not differ between infants born to mothers with and without GDM (P = 0.74). The sole independent predictor of infant HOMA-IR in the non-GDM group was birth weight (t = 3.33, P = 0.002). In contrast, weight gain in the 1st year was the only independent predictor of HOMA-IR in infants of women with GDM (t = 2.19, P = 0.039).

CONCLUSIONS

In the 1st year of life, weight gain in infants born to women with GDM is associated with insulin resistance, unlike in their peers.The offspring of women with gestational diabetes mellitus (GDM) exhibit a propensity for the early accrual of cardiometabolic risk factors in childhood and adolescence (1). Indeed, compared with their peers, offspring exposed to GDM in utero are more likely to develop insulin resistance in childhood and by as early as age 5 years (2,3). However, little is known about perinatal and early life risk factors associated with infant insulin resistance after exposure to maternal GDM. Thus, we sought to evaluate insulin resistance and its determinants in the offspring of women with and without GDM at age 1 year.     

Untreated Mild Hyperglycemia During Pregnancy and Anthropometric Measures of Obesity in Offspring at Age 5–7 Years

OBJECTIVE

Obesity in the offspring of women with hyperglycemia during pregnancy has been reported, but the results are conflicting. This study examined the association of hyperglycemia during pregnancy and anthropometry in 5- to 7-year-old offspring whose mothers participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study at the Belfast Centre.

RESEARCH DESIGN AND METHODS

Women in the HAPO study underwent a 75-g oral glucose tolerance test (OGTT) at approximately 28 weeks of gestation. Mothers and caregivers remained blinded to the results unless the fasting plasma glucose (FPG) concentration was >5.8 mmol/L or the 2-h plasma glucose (2hPG) concentration was >11.1 mmol/L. Offspring weight, height, and skinfold thicknesses (triceps, subscapular, and suprailiac) were measured at age 5–7 years. Overweight, obesity, and extreme obesity were defined as a BMI z score ≥85th, ≥95th, and ≥99th percentile, respectively, based on the 1990 British Growth Standard.

RESULTS

Belfast HAPO offspring (n = 1,320, 82%) aged 5–7 years attended for follow-up. With use of multiple regression, maternal FPG, 1h PG, and 2hPG did not show any relation to offspring BMI z score or offspring skinfold sum independent of maternal BMI at OGTT and offspring birth weight z score. This lack of association with maternal glycemia persisted with the offspring BMI z score expressed as ≥85th, ≥95th, or 99th percentile and the sum of skinfolds expressed as ≥90th percentile specific for sex. The initially significant relation between FPG and all offspring adiposity measures was explained by maternal BMI at the OGTT.

CONCLUSIONS

After adjustment for maternal BMI at the OGTT, higher maternal FPG concentration during pregnancy (short of diabetes) is no longer a risk factor for obesity, as reflected by BMI and the sum of skinfolds in offspring aged 5–7 years.     

Bile acid metabolism is altered in those with insulin resistance after gestational diabetes mellitus

BackgroundBile acids (BAs) are known mediators of glucose metabolism that are altered in type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM). We hypothesised that post-prandial BA fractions are changed in women with Insulin resistance (IR) after recovery from GDM using homeostatic model assessment (HOMA-IR).Methods45 women median age 44(31–47) with previous GDM, including 20 with HOMA-IR >2.8 and 25 age-matched controls with HOMA-IR ≤ 2.8 were studied. After an overnight fast, all underwent an oral glucose tolerance test. Blood samples were collected at baseline and every 30 min for 120 min and analysed for glucose on automated platform and for total BAs, their conjugates and fractions using liquid-chromatography tandem mass-spectrometry. Baseline samples were analysed for insulin on automated platform. Delta (Δ) change (difference between baseline and maximal post-prandial response) were calculated. Data is presented as median (IQR).ResultsFasting primary and unconjugated BAs were higher in women with HOMA-IR >2.8 vs. those with HOMA-IR ≤ 2.8 [0.24 (0.16–0.33) vs 0.06(0.04–0.22) μmol/L and 0.91(0.56–1.84) μmol/L vs. 0.69(0.32–0.89) μmol/L respectively. ∆ taurine-conjugated BAs was higher in women with HOMA-IR ≤ 2.8 than those with HOMA-IR > 2.8 [0.33(0.20–0.54) vs 0.23(0.13–0.34) μmol/L]. Fasting glucose and non-12α-hydroxylated BAs were negatively correlated in women with HOMA-IR >2.8 (all p < 0.05).ConclusionsFollowing GDM, individuals with HOMA-IR >2.8 have altered conjugated and non-12α-hydroxylated fractions of BAs. It remains to be elucidated if the altered BA metabolism is a contributing factor to the pathogenesis or a consequence of GDM.     

α2-HS糖蛋白与妊娠期糖尿病关系的研究

目的观察不同程度糖代谢异常孕妇血清α2-HS糖蛋白(AHSG)浓度的变化并探讨其与血糖、血脂代谢及胰岛素抵抗的关系。方法根据75 g口服葡萄糖耐量(OGTT)结果将135名孕周为36～41周的孕妇分为3组:妊娠期糖尿病(GDM)组(45例)、糖耐量异常(GIGT)组(45例)、正常糖耐量(NGT)组(45例)。检测各组血清AHSG、空腹血糖(FPG)、空腹胰岛素(FINS)、空腹血脂([总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]水平并计算体重指数(BMI)、胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)。结果 GDM组、GIGT组、NGT组的AHSG浓度分别为150.2±20.0、131.9±16.0(、124.0±15.0)μg/L,3组之间差异均有统计学意义(P<0.05)。GDM组FPG、TG、LDL-C、FINS水平均高于NGT组(P<0.05、P<0.01),HDL-C水平低于NGT组(P<0.05);GDM组TG、FINS水平高于GIGT组(P均<0.05、P<0.01);GIGT组TG、LDL-C、FINS高于NGT组(P<0.05、P<0.01);3组之间TC水平差异无统计学意义(P>0.05)。NGT组、GIGT组、GDM组HOMA-IR逐渐升高、HOMA-β逐渐下降3,组之间差异均有统计学意义(P<0.05)。AHSG浓度与BMI、TG、FINS、HOMA-IR呈正相关[相关系数(r)分别为0.406、0.503、0.533、0.612,P均<0.05],与HDL-C、HOMA-β呈负相关(r分别为-0.321、-0.589,P均<0.05),与FPG、TC无相关性(r分别为0.0580、.095,P均>0.05)。结论 AHSG在GDM患者的血糖、血脂代谢中发挥重要作用。AHSG参与了胰岛素抵抗、加重了β细胞损害,与GDM的发病关系密切。     

NGAL联合HOMA-IR指数对高危孕妇妊娠期糖尿病的预测价值研究

目的 探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)联合胰岛素抵抗指数(HOMA-IR)对高危孕妇妊娠期糖尿病(gestational diabetes mellitus,GDM)的预测价值及妊娠结局.方法 筛选124例具有GDM危险因素的孕妇,将其中60例GDM孕妇纳入GDM组,余64例纳入GDM高危组.比较两组...     

Association of Maternal Folate and Vitamin B12 in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study

OBJECTIVETo investigate the association of folate and vitamin B₁₂ in early pregnancy with gestational diabetes mellitus (GDM) risk.RESEARCH DESIGN AND METHODSThe data of this study were from a subcohort within the Shanghai Preconception Cohort Study. We included pregnancies with red blood cell (RBC) folate and vitamin B₁₂ measurements at recruitment (between 9 and 13 gestational weeks) and those with three samples available for glucose measurements under an oral glucose tolerance test. GDM was diagnosed between 24 and 28 weeks’ gestation. Odds ratio (OR) and 95% CI of having GDM was used to quantify the association.RESULTSA total of 1,058 pregnant women were included, and GDM occurred in 180 (17.01%). RBC folate and vitamin B₁₂ were significantly higher in pregnancies with GDM than those without GDM (P values were 0.045 and 0.002, respectively) and positively correlated with 1-h and 2-h serum glucose. Daily folic acid supplementation in early pregnancy increases the risk of GDM; OR (95% CI) was 1.73 (1.19–2.53) (P = 0.004). Compared with RBC folate <400 ng/mL, pregnancies with RBC folate ≥600 ng/mL were associated with ∼1.60-fold higher odds of GDM; the adjusted OR (95% CI) was 1.58 (1.03–2.41) (P = 0.033). A significant trend of risk effect on GDM risk across categories of RBC folate was observed (P_trend = 0.021). Vitamin B₁₂ was significantly associated with GDM risk (OR 1.14 per 100 pg/mL; P = 0.002). No significant association of serum folate and percentile ratio of RBC folate/vitamin B₁₂ with GDM was observed.CONCLUSIONSHigher maternal RBC folate and vitamin B₁₂ levels in early pregnancy are significantly associated with GDM risk, while the balance of folate/vitamin B₁₂ is not significantly associated with GDM.     

血清网膜素1与妊娠期糖尿病的相关性

目的探讨血清网膜素1(omentin 1)与妊娠期糖尿病(GDM)的关系。方法酶联免疫法定量85例孕前肥胖GDM,85例孕前正常GDM及匹配设置的85例糖耐量正常（NGT）孕妇血清网膜素1水平,同时检测3组血清空腹血糖（FPG）、空腹胰岛素（FINS)水平,计算胰岛素抵抗指数（HOMA IR)。结果①GDM组FPG、FINS及HOMA IR均明显高于NGT组,且后二者还表现为：肥胖GDM＞非肥胖GDM＞NGT组(P＜0.05);②GDM组血清网膜素1明显低于NGT组,表现为：肥胖GDM＜非肥胖GDM＜NGT组(P＜0.05);③相关性分析：血清网膜素1与BMI、FPG、FINS 及HOMA IR明显负相关(P＜0.05);④多元回归分析：孕前肥胖GDM组：网膜素 1=484.126 5.015BMI 7.016FPG 13.224FINS;孕前正常GDM组：网膜素 1=497.008 4.092BMI 6.079FPG 11.258FINS。结论血清网膜素1与GDM关系密切,能反映孕妇糖、脂代谢紊乱和胰岛素抵抗程度,可能参与了GDM疾病的发生和发展。     

Genetic Risk Score for Type 2 Diabetes and Traits Related to Glucose-Insulin Homeostasis in Youth: The Exploring Perinatal Outcomes Among Children (EPOCH) Study

OBJECTIVEThe metabolic phenotype of youth-onset type 2 diabetes (T2D) differs from that of adult-onset T2D, but little is known about genetic contributions. We aimed to evaluate the association between a T2D genetic risk score (GRS) and traits related to glucose-insulin homeostasis among healthy youth.RESEARCH DESIGN AND METHODSWe used data from 356 youth (mean age 16.7 years; 50% female) in the Exploring Perinatal Outcomes Among Children (EPOCH) cohort to calculate a standardized weighted GRS based on 271 single nucleotide polymorphisms associated with T2D in adults. We used linear regression to assess associations of the GRS with log-transformed fasting glucose, 2-h glucose, HOMA of insulin resistance (HOMA-IR), oral disposition index, and insulinogenic index adjusted for age, sex, BMI z score, in utero exposure to maternal diabetes, and genetic principal components. We also evaluated effect modification by BMI z score, in utero exposure to maternal diabetes, and ethnicity.RESULTSHigher weighted GRS was associated with lower oral disposition index (β = −0.11; 95% CI −0.19, −0.02) and insulinogenic index (β = −0.08; 95% CI −0.17, −0.001), but not with fasting glucose (β = 0.01; 95% CI −0.01, 0.02), 2-h glucose (β = 0.03; 95% CI −0.0004, 0.06), or HOMA-IR (β = 0.02; 95% CI −0.04, 0.07). BMI z score and in utero exposure to maternal diabetes increased the effect of the GRS on glucose levels.CONCLUSIONSOur results suggest that T2D genetic risk factors established in adults are relevant to glucose-insulin homeostasis in youth and that maintaining a healthy weight may be particularly important for youth with high genetic risk of T2D.     

Epigenome-Wide Association Study Reveals Methylation Loci Associated With Offspring Gestational Diabetes Mellitus Exposure and Maternal Methylome

OBJECTIVEGestational diabetes mellitus (GDM) is associated with an increased risk of obesity and insulin resistance in offspring later in life, which might be explained by epigenetic changes in response to maternal hyperglycemic exposure.RESEARCH DESIGN AND METHODSWe explored the association between GDM exposure and maternal blood and newborn cord blood methylation in 536 mother-offspring pairs from the prospective FinnGeDi cohort using Illumina MethylationEPIC 850K BeadChip arrays. We assessed two hypotheses. First, we tested for shared maternal and offspring epigenetic effects resulting from GDM exposure. Second, we tested whether GDM exposure and maternal methylation had an epigenetic effect on the offspring.RESULTSWe did not find any epigenetic marks (differentially methylated CpG probes) with shared and consistent effects between mothers and offspring. After including maternal methylation in the model, we identified a single significant (false discovery rate 1.38 × 10⁻²) CpG at the cg22790973 probe (TFCP2) associated with GDM. We identified seven additional FDR-significant interactions of maternal methylation and GDM status, with the strongest association at the same cg22790973 probe (TFCP2), as well as cg03456133, cg24440941 (H3C6), cg20002843 (LOC127841), cg19107264, and cg11493553 located within the UBE3C gene and cg17065901 in FAM13A, both susceptibility genes for type 2 diabetes and BMI, and cg23355087 within the DLGAP2 gene, known to be involved in insulin resistance during pregnancy.CONCLUSIONSOur study reveals the potential complexity of the epigenetic transmission between mothers with GDM and their offspring, likely determined by not only GDM exposure but also other factors indicated by maternal epigenetic status, such as maternal metabolic history.     

Association Between Insulin Resistance and Cardiovascular Disease Risk Varies According to Glucose Tolerance Status: A Nationwide Prospective Cohort Study

OBJECTIVETo investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status.RESEARCH DESIGN AND METHODSWe analyzed a nationwide sample of 111,576 adults without CVD at baseline, using data from the China Cardiometabolic Disease and Cancer Cohort Study. Insulin resistance was estimated by sex-specific HOMA of insulin resistance (HOMA-IR) quartiles for participants with normal glucose tolerance, prediabetes, or diabetes, separately, and by 1 SD of HOMA-IR for the overall study participants. We used Cox proportional hazards models to examine the association between insulin resistance and incident CVD according to glucose tolerance status and evaluate the CVD risk associated with the combined categories of insulin resistance and obesity in prediabetes and diabetes, as compared with normal glucose tolerance. Models were adjusted for age, sex, education attainment, alcohol drinking, smoking, physical activity, and diet quality.RESULTSIn participants with normal glucose tolerance, prediabetes, and diabetes defined by three glucose parameters, multivariable-adjusted hazard ratios (95% CIs) for incident CVD associated with the highest versus the lowest quartile of HOMA-IR were 1.03 (0.82–1.30), 1.23 (1.07–1.42), and 1.61 (1.30–2.00), respectively; the corresponding values for CVD per 1-SD increase in HOMA-IR were 1.04 (0.92–1.18), 1.12 (1.06–1.18), and 1.15 (1.09–1.21), respectively (P for interaction = 0.011). Compared with participants with normal glucose tolerance, in participants with prediabetes, the combination of the highest HOMA-IR quartile and obesity showed 17% (95% CI 2–34%) higher risk of CVD, while the combination of the lowest two HOMA-IR quartiles and nonobesity showed 15–17% lower risk of CVD. In participants with diabetes, the upper two HOMA-IR quartiles exhibited 44–77% higher risk of CVD, regardless of obesity status. Consistent findings were observed for glucose tolerance status defined by different combinations of glycemic parameters.CONCLUSIONSGlucose intolerance status exacerbated the association between insulin resistance and CVD risk. Compared with adults with normal glucose tolerance, adults with prediabetes who were both insulin resistant and obese exhibited higher risks of CVD, while in adults with diabetes, the CVD risk related to insulin resistance remained, regardless of obesity.     

食欲素A水平与妊娠期糖尿病糖脂代谢指标及新生儿体重的相关性研究

目的 探讨妊娠期糖尿病(GDM)患者血清、脐血食欲素A(orexin-A,OXA)水平与糖脂代谢指标及新生儿体重的相关性.方法 收集90例GDM孕妇(GDM组)和50例正常孕妇(对照组),检测并比较两组孕妇分娩前总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、三酰甘油(TG)、空腹血糖(FPG)、糖化...     

Impact of different stereoisomers of inositol on insulin sensitivity of gestational diabetes mellitus patients

BACKGROUNDInositol is a hexa-carbon polyol, a naturally soluble vitamin, often found in various foods.AIMTo discuss the impact of different stereoisomers of inositol on insulin sensitivity of gestational diabetes mellitus (GDM) patients.METHODSEighty GDM pregnant women were divided into four groups according to their treatment received: A group (placebo folic acid 400 μg/d), B group [myo-inositol (MI) 1500 mg, twice a day], C group [D-chiro-inositol (DCI) 250 mg, twice a day], and D group (inositol MI and inositol DCI 1500 mg/250 mg, twice a day). Each patient routinely used dietary guidance adjustments and did some safe and effective aerobic exercise in addition to receiving placebo or inositol from GDM diagnosis to delivery. Triglyceride, total cholesterol, fasting plasma glucose, oral glucose tolerance test postprandial glucose (2 h postprandial blood glucose), fasting insulin, fasting plasma glucose, and glycosylated hemoglobin levels and Homeostasis Model Assessment-insulin resistance (HOMA-IR) and Homeostasis Model Assessment-insulin sensitivity index (HOMA-ISI) scores were determined before treatment and 8 wk after treatment onset. Adverse maternal and infant outcomes, including hypoglycemia, excessive amniotic fluid, premature infants, macrosomia, fetal distress etc., were also recorded. RESULTSThere was no statistical difference in the baseline data of each group. The levels of 2 h blood glucose, glycosylated hemoglobin, fasting insulin, total cholesterol, and triglyceride in the B, C, and D groups were significantly lower than those in the control group (A group) after treatment (P < 0.05). Moreover, compared with the B group, the level of the above indexes in the C and D groups decreased more significantly, and the differences were statistically significant (P < 0.05). The HOMA-IR of B, C, and D groups decreased significantly, and the HOMA-ISI increased significantly compared with the A group, and the differences were statistically significant (P < 0.05), among which the decrease of HOMA-IR and the increase of HOMA-ISI were more significant in the C and D group compared with the B group (P < 0.05). The occurrence rate of adverse maternal and infant outcomes in the C and D group was significantly lower than that in the control group (A group), and the differences were statistically significant (P < 0.05). CONCLUSIONTreatment with different inositol stereoisomers (inositol MI and inositol DCI) can improve insulin sensitivity and reduce insulin resistance in diabetic patients, and inositol DCI has a better curative effect than inositol MI.     

The relationship between homeostasis model assessment and cardiovascular risk factors in Iranian subjects with normal fasting glucose and normal glucose tolerance

BACKGROUND: Insulin resistance is a complex problem which may not always correlate with all its cardiovascular risk factors in various populations. We investigated the relationship between homeostasis model assessment of insulin resistance (HOMA-IR) with cardiovascular risk factors in Iranian subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT). METHODS: Of the 605 subjects aged 25-79 y enrolled in this study, after the oral glucose tolerance test, 366 subjects aged 25-50 y and 135 aged >50 y were classified as NFG and NGT. Insulin resistance was estimated by the HOMA-IR. RESULTS: Women had higher values of body mass index (BMI), insulin and HOMA-IR than men in both age groups. The prevalence of insulin resistance, general and abdominal obesity, low HDL-C and physical inactivity was higher in women than men in the 2 age groups. Men had a higher prevalence of hypertension and hypertriglyceridemia in the group with age 25-50 y. The Pearson correlation controlled for age, BMI, waist circumference and physical activity showed that HOMA-IR had significant correlation with triglyceride and inversely associated with HDL-C in both sexes. In addition, the results of HOMA-IR quartiles demonstrated that the prevalence of hypertension, obesity, and low HDL-C was particular high in women with HOMA-IR >2.39. Multiple regression indicated that log HOMA-IR was independently predicted by BMI, triglyceride and HDL-C in men and BMI, HDL-C and waist-to-hip (WHR) ratio in women. CONCLUSIONS: HOMA-IR is associated with the features of metabolic syndrome with a sex difference in the degree and predictors of HOMA-IR and the frequency of cardiovascular risk factors.     

Determinants of body fat in infants of women with gestational diabetes mellitus differ with fetal sex

OBJECTIVE

Neonatal adiposity is a well-recognized complication of gestational diabetes mellitus (GDM). This study aimed to identify factors influencing adiposity in male and female infants of women treated for GDM.

RESEARCH DESIGN AND METHODS

This was a prospective study of 84 women with GDM. Daily blood glucose levels (BGLs) were retrieved from glucose meters, and overall mean fasting and mean 2-h postprandial BGLs were calculated for each woman. Infant body composition was measured at birth, and regression analysis was used to identify significant predictors of infant body fat separately in male and female infants.

RESULTS

Maternal fasting BGL was the major predictor of adiposity in male infants but had little relationship to adiposity in female infants. In male infants, percent fat was increased by 0.44% for each 0.1 mmol/L increase in mean maternal fasting BGL. Maternal BMI was the primary predictor in female infants but had little effect in males. In female infants, percent fat was increased by 0.11% for each 1 kg/m² increase in maternal prepregnancy BMI.

CONCLUSIONS

Fetal sex may influence the impact that treatment strategies for GDM have on infant adiposity.The maternal metabolic disturbance of gestational diabetes mellitus (GDM) affects fetal development and alters birth weight, BMI, and percent body fat at birth (1,2). Current treatment of GDM achieves normalization of birth weight and reduces neonatal complications (3). However, the effects of GDM on the offspring extend well beyond the fetal period and, thus, offspring of women with GDM also have an increased risk of unfavorable long-term outcomes such as obesity and diabetes, well above that explained by genetics alone (4), even after treatment.To date, studies designed to inform optimal treatment of GDM have focused on normalization of birth weight, but neonatal adiposity may be a more sensitive marker of disturbed in utero metabolism, risk of obesity, and poor long-term health than birth weight alone (1). Body fat at birth is elevated in infants born to women with GDM even when birth weight is normal (1). In a group of 6- to 12-year-old children born to women with GDM, percent body fat in childhood was significantly correlated to body fat at birth, but there was no relationship between birth weight and weight at the time of study (5). Even though treatment of mild GDM does reduce the incidence of macrosomia, it does not reduce the incidence of obesity in the offspring at 4–5 years (6).To interrupt the obesity cycle and reduce the risk of future poor adult health, it may be necessary to normalize neonatal adiposity as well as birth weight. To do this, it is essential to understand the factors that determine adiposity in infants of women with GDM.While genetic factors may be the primary determinant of lean body mass, fetal fat mass may be more strongly influenced by the in utero environment (7). A range of maternal factors have been identified as determinants of neonatal size and body fat, including maternal BMI, parity, maternal glucose concentration, and insulin sensitivity (8–10). Higher gestational weight gain is associated with increased infant birth weight in lean and moderately overweight women (11) and in women with normal glucose tolerance (9) but not in obese women (11) or women with GDM (9). However, the factors influencing fetal fat accretion remain poorly understood.Both body weight and body composition at birth are different in male and female infants (12), and sex of the infant has been reported as a significant determinant of each (9). We hypothesized that the determinants of fetal body composition may also differ with fetal sex. The aim of this study was to identify factors that influence adiposity in male and female infants born to women treated for GDM.     

Early postpartum metabolic assessment in women with prior gestational diabetes.

OBJECTIVE: To present the results of early postpartum metabolic assessment in women with gestational diabetes mellitus (GDM), to determine predictive factors for subsequent diabetes, and to investigate the association of postpartum glucose tolerance with other components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 788 women were evaluated 3-6 months after a GDM pregnancy. A 75-g oral glucose tolerance test (OGTT) was performed. Cholesterol, HDL cholesterol, triglycerides, blood pressure, BMI, and body fat distribution were assessed. Clinical and obstetric history, baseline variables at the diagnosis of GDM, metabolic control during pregnancy, and index pregnancy outcome were compared in women with diabetes and women without diabetes (American Diabetes Association [ADA] criteria) after pregnancy. Multivariate logistic regression analysis was used to ascertain independent predictors of subsequent diabetes. Correlation coefficients were assessed between postpartum glucose tolerance and lipid levels, blood pressure, BMI, and body fat distribution. RESULTS: According to ADA criteria, 588 (74.6%) women were normal, 46 (5.8%) had impaired fasting glucose, 82 (10.4%) had impaired glucose tolerance, 29 (3.7%) had both impaired fasting glucose and impaired glucose tolerance, and 43 (5.4%) had diabetes. Prepregnancy obesity, recurrence of GDM, gestational age at diagnosis of GDM, glucose values in the 100-g OGTT, number of abnormal values in the 100-g OGTT, fasting C-peptide levels in pregnancy, C-peptide/glucose score in pregnancy, insulin requirement in pregnancy, 3rd trimester HbA1c levels, and macrosomia differed significantly in women with subsequent diabetes. Independent predictors of postpartum diabetes were prepregnancy obesity, C-peptide/glucose score during pregnancy, and the number of abnormal values in the 100-g diagnostic OGTT. The area under the postpartum glucose curve was positively associated with BMI, waist circumference, waist-to-hip ratio, triglycerides, and systolic and diastolic blood pressures. CONCLUSIONS: Low C-peptide/glucose score during pregnancy together with prepregnancy obesity and severity of GDM (number of abnormal values in the 100-g diagnostic OGTT) are independent predictors of subsequent diabetes. Our data suggest that regardless of obesity and severity of GDM, a beta-cell defect increases the risk of postpartum diabetes. The association of postpartum glucose tolerance with triglyceride levels, blood pressure, obesity, and regional distribution of body fat suggests that postpartum glucose intolerance anticipates a high-risk cardiovascular profile that comprises other risk factors besides diabetes.     

Determinants of mild gestational hyperglycemia and gestational diabetes mellitus in a large dutch multiethnic cohort.

OBJECTIVE: The purpose of this study was to identify independent determinants of mild gestational hyperglycemia (MGH) and gestational diabetes mellitus (GDM) and to assess the correlation between fasting glucose and C-peptide levels among control, MGH, and GDM women. RESEARCH DESIGN AND METHODS: A total of 1,022 consecutive women were evaluated with a 1-h 50-g glucose challenge test (GCT) at between 16 and 33 weeks of gestation. Women with a capillary whole-blood glucose > or =7.8 mmol/l in the GCT underwent a 3-h 100-g oral glucose tolerance test (OGTT). On the basis of a positive GCT, the women with a positive OGTT were classified as GDM, whereas the women with a negative OGTT were classified as MGH. The following data were collected for all women: age, prepregnancy BMI, ethnicity, clinical and obstetric history, pregnancy outcome, and C-peptide level. RESULTS: A total of 813 women (79.6%) were normal, 138 (13.5%) had MGH, and 71 (6.9%) had GDM. There was a stepwise significant increase in mean fasting glucose (3.6 +/- 0.4, 3.9 +/- 0.4, and 4.7 +/- 0.7 mmol/l, respectively) and C-peptide level (0.60 [0.1-2.4], 0.86 [0.3-2.0], and 1.00 [0.5-1.6] nmol/l, respectively) among the three diagnostic groups. Maternal age, non-Caucasian ethnicity, and prepregnancy BMI were associated with GDM, whereas only maternal age and prepregnancy BMI were associated with MGH. A positive correlation between levels of fasting glucose and C-peptide was found in control women (r = 0.39 [95% CI 0.31-0.46]). A similar result was seen in MGH women (r = 0.38 [95% CI 0.23-0.52]), whereas the correlation between fasting glucose and C-peptide was nearly lost in GDM women (r = 0.14 [CI -0.09 to 0.36]). The fasting C-peptide-to-glucose ratio was reduced by 60% in GDM patients versus control subjects and MGH patients (0.41 +/- 0.25 vs. 0.70 +/- 0.20 and 0.73 +/- 0.23, P < 0.001). CONCLUSIONS: Of the well-known independent determinants of GDM, only maternal age and prepregnancy BMI were associated with MGH. It appears that additional factors promoting loss of beta-cell function distinguish MGH from GDM. One of these factors appears to be ethnicity.