A family history of type 2 diabetes increases risk factors associated with overfeeding

Aims/hypothesis  

The purpose of the study was to test prospectively whether healthy individuals with a family history of type 2 diabetes are more susceptible to adverse metabolic effects during experimental overfeeding.     

2型糖尿病家系青少年一级亲属心血管危险因素研究

目的探讨2型糖尿病（T2DM）家族史对青少年心血管危险因素的影响。方法秦皇岛地区12～18岁青少年4023人横断面调查。根据父母有无糖尿病分为糖尿病家族史阳性组（FH＋）和阴性组（FH-）。测量腰围（WC）、血压、FPG、血脂,计算BMI。结果（1）FH＋组腰围、FPG、TC和LDL-C均高于FH-组（P〈0.05）,超重/肥胖、高SBP、高FPG检出率高于FH-组（P〈0.05）。（2）校正年龄、性别后FH＋组SBP、FPG升高、超重/肥胖的危险性分别是FH-组的1.54、2.06、1.33倍,95%CI分别是（1.10～2.16）、（1.46～2.89）、（1.12～1.59）,具有2项以上心血管危险因素的危险性是FH-组的1.72倍。结论T2DM患者的青少年一级亲属已存在心血管危险因素增加和聚集。应重视对这一人群进行早期筛查和干预,以减少心血管病的发生。     

The impact of risk factors and more stringent diagnostic criteria of gestational diabetes on outcomes in central European women

OBJECTIVES: In the face of the ongoing discussion on the criteria for the diagnosis of gestational diabetes (GDM), we aimed to examine whether the criteria of the Fourth International Workshop Conference of GDM (WC) select women and children at risk better than the World Health Organization (WHO) criteria. DESIGN AND SETTING: This was a prospective longitudinal open study in five tertiary care centers in Austria. PATIENTS AND OUTCOME MEASURES: The impact of risk factors, different thresholds (WC vs. WHO), and numbers of abnormal glucose values (WC) during the 2-h, 75-g oral glucose tolerance test on fetal/neonatal complications and maternal postpartum glucose tolerance was studied in 1466 pregnant women. Women were treated if at least one value according to the WC (GDM-WC1) was met or exceeded. RESULTS: Forty-six percent of all women had GDM-WC1, whereas 29% had GDM-WHO, and 21% of all women had two or three abnormal values according to WC criteria (GDM-WC2). Eighty-five percent of the GDM-WHO were also identified by GDM-WC1. Previous GDM [odds ratio (OR) 2.9], glucosuria (OR 2.4), preconceptual overweight/obesity (OR 2.3), age 30 yr or older (OR 1.9), and large-for-gestational age (LGA) fetus (OR 1.8) were the best independent predictors of the occurrence of GDM. Previous GDM (OR 4.4) and overweight/obesity (OR 4.0) also independently predicted diabetes postpartum. GDM-WC1 had a higher rate of obstetrical complications (LGA neonates, neonatal hypoglycemia, cesarean sections; P < 0.001) and impaired postpartum glucose tolerance (P < 0.0001) than GDM-WHO. CONCLUSION: These results suggest the use of more stringent WC criteria for the diagnosis of GDM with the initiation of therapy in case of one fasting or stimulated abnormal glucose value because these criteria detected more LGA neonates with hypoglycemia and mothers with impaired postpartum glucose metabolism than the WHO criteria.     

The impact of maternal gestational weight gain on cardiometabolic risk factors in children

Aims/hypothesis

Accumulating evidence suggests an impact of gestational weight gain (GWG) on pregnancy outcomes; however, data on cardiometabolic risk factors later in life have not been comprehensively studied. This study aimed to evaluate the relationship between GWG and cardiometabolic risk in offspring aged 7 years.

Methods

We included a total of 905 mother–child pairs who enrolled in the follow-up visit of the multicentre Hyperglycemia and Adverse Pregnancy Outcome study, at the Hong Kong Centre. Women were classified as having gained weight below, within or exceeding the 2009 Institute of Medicine (IOM) guidelines. A standardised GWG according to pre-pregnancy BMI categories was calculated to explore for any quadratic relationship.

Results

Independent of pre-pregnancy BMI, gestational hyperglycaemia and other confounders, women who gained more weight than the IOM recommendations had offspring with a larger body size and increased odds of adiposity, hypertension and insulin resistance (range of p values of all the traits: 4.6?×?10^?9?<?p?<?0.0390) than women who were within the recommended range of weight gain during pregnancy. Meanwhile, women who gained less weight than outlined in the recommendations had offspring with increased risks of hypertension and insulin resistance, compared with those who gained weight within the recommended range (7.9?×?10^?3?<?p?<?0.0477). Quadratic relationships for diastolic blood pressure, AUC for insulin, pancreatic beta cell function and insulin sensitivity index were confirmed in the analysis of standardised GWG (1.4?×?10^?3?<?p_quadratic?<?0.0282). Further adjustment for current BMI noticeably attenuated the observed associations.

Conclusions/interpretation

Both excessive and inadequate GWG have independent and significant impacts on childhood adiposity, hypertension and insulin resistance. Our findings support the notion that adverse intrauterine exposures are associated with persistent cardiometabolic risk in the offspring.

     

Prevalence and risk factors for gestational diabetes assessed by universal screening

In order to evaluate the prevalence of gestational diabetes mellitus (GDM) and the presence of risk factors for GDM, we conducted a retrospective study of a cohort of Italian women. In addition, we compared universal versus selective screening to validate the ADA's recommendations in our population. From June 1st, 1995 to December 31st, 2001, universal screening for GDM was performed in 3950 women. The glucose challenge test (GCT) was positive (GCT+) in 1389 cases (35.2%). The 1-h glucose level after GCT enabled us to diagnose GDM directly in 24 pregnant women. Oral glucose tolerance test (OGTT) was performed in 1221 GCT+ women (144 cases with GCT+ dropped out) and GDM was diagnosed in 284 (23.2%) of them. OGTT was also performed in 391 randomly chosen, women from the GCT negative (GCT-) group. In this last group 25 (6.3%) women had GDM. Thus, the total number of subjects with GDM was 333 out of 3806 with a prevalence of 8.74% in the entire cohort. Assuming that the rate of GDM observed in the random sample of GCT- women is applicable to the whole group of 2561 GCT- women, then 161 GCT- patients could also have GDM. This will further increase the estimated prevalence for the whole cohort up to 12.3% (i.e. 469 out of 3806 pregnant women). There were 236 (5.6%) women with a low risk for GDM (normal weight, age less than 25 years and without a family history of diabetes). In this group we found 34 cases and five cases with positive screening test and GDM, respectively. Thus, if we excluded low risk women from the screening test, as suggested by ADA recommendations, only five women with GDM would have been missed. However, about 95% of our population were at medium or high risk for GDM and, therefore, would have been screened. The rate of GDM was significantly higher in women with a positive history of diabetes, increasing age, previous pregnancies, pre-pregnancy overweight and short stature. After logistic regression analysis, GDM diagnosis was significantly correlated with age (P<0.0001), pre-pregnancy BMI (P<0.0001), weight gain (P<0.0001) and family history of diabetes (P<0.01).     

The impact of family history of diabetes and lifestyle factors on abnormal glucose regulation in middle-aged Swedish men and women

Aims/hypothesis We investigated associations between abnormal glucose regulation and family history of diabetes, separately and in combination with lifestyle risk factors.Subjects and methods This cross-sectional study comprised 3,128 men and 4,821 women, aged 35–56 years, half with a family history of diabetes. Oral glucose tolerance testing identified subjects with previously undiagnosed prediabetes (IFG, IGT) and type 2 diabetes. Information on lifestyle factors was obtained by questionnaire. Biological interaction was measured with the synergy index.Results A family history of diabetes conferred a higher odds ratio (OR) for type 2 diabetes in men (OR=3.1, 95% CI 1.7–5.6) than in women (OR=1.7, 95% CI 1.0–3.0), and the synergy index was 2.8 (95% CI 0.9–9.0), suggesting interaction between a family history of diabetes and sex. For prediabetes and diabetes combined, the synergy index was 1.7 (1.0–2.8). Exposure to only one lifestyle risk factor (obesity, physical inactivity, smoking or low sense of coherence [a psychosocial index]) increased the risk to a similar extent in men and women. Combined exposure to a family history of diabetes and lifestyle-related risk factors had a greater effect on type 2 diabetes than any of these factors alone, especially in men. However, analysis of interaction between a family history of diabetes and the lifestyle factors did not indicate any interaction for diabetes, but did indicate interaction for a family history of diabetes and obesity in women with prediabetes.Conclusions/interpretation Our data suggest a more pronounced effect of a family history of diabetes on the risk of type 2 diabetes in men than in women. While both a family history of diabetes and lifestyle risk factors had effects on type 2 diabetes, irrespective of sex, these effects did not appear to interact.     

Waist circumference is the key risk factor for diabetes in Korean women with history of gestational diabetes

This study investigated relationships between various obesity indices and an onset of type 2 diabetes mellitus (TY2DM) in Korean women with history of gestational diabetes mellitus (GDM). A total of 909 women with history of GDM were enrolled from the four major hospitals, and the first postpartum follow-up examination was made at 6 weeks, and annually thereafter. During postpartum follow-up period, mean 2.13+/-1.75 years, we conducted 2h 75 g OGTT and measured glucose, insulin, c-peptide, lipid profiles, lifestyle and dietary evaluation. For obesity parameters, we measured body weight, body mass index (BMI), waist and hip circumference, subcutaneous fat thickness, body fat percent and weight using bioelectrical impedance tests. Diabetes incidence for 6 years was 12.8% and all the obesity indices were significantly higher in subjects with diabetes or glucose intolerance than those with normal glucose tolerance (p<0.001). When obesity indices were compared between <25th versus >75th percentile, the waist circumference presented with the strongest relationship (odds ratio=5.8, 95% CI 2.8-11.8). This relationship persisted, OR=3.86 (95% CI 1.8-8.2), even after adjusting for the potential confounders. This prospective study revealed that waist circumference is one of the key risk factors for the onset of diabetes in Korean women with history of GDM.     

妊娠糖尿病的危险因素

妊娠糖尿病是糖尿病分型中的一种独立类型.目前,妊娠糖尿病公认的危险因素包括年龄大于25岁、孕前体重指数大于25 kg/m2、非高加索白人、糖尿病家族史等.近年研究证实,妊娠糖尿病还与其他一些因素相关,如多囊卵巢综合征、身高偏矮、携带HBsAg、高血压等.及早的发现和干预这些高危因素,对于改善孕妇及子代的预后,减少人群中糖尿病的发病率有深远影响.     

Early manifestation of cardiovascular disease risk factors in offspring of mothers with previous history of gestational diabetes mellitus

This study investigated the long-term adverse effects of maternal gestational diabetes mellitus (GDM) on cardiovascular disease (CVD) risk factors in offspring. A total of 298 offspring (202 offspring of GDM mothers and 96 offspring of mothers with impaired glucose tolerance [IGT]) participated in the study. CVD risk factors included elevated body mass index (BMI), skinfold thickness, body fat, blood pressure, lipid profiles, and glucose values measured with a 2h oral glucose tolerance test. The BMI of offspring >or=5 years of age of GDM mothers was significantly higher than that of offspring of mothers with IGT when analysed according to age. In offspring of GDM mothers, CVD risk factors were positively correlated with age, except for lipid profiles. A significant negative relationship between age and BMI was observed in offspring of IGT mothers. The slope of the linear regression lines for BMI and fasting plasma insulin levels with age were significantly steeper for the offspring of GDM mothers than for those of IGT mothers. We conclude that childhood obesity, as well as altered glucose metabolism influenced by the maternal uterine environment, is more likely with advancing years in the offspring of GDM mothers than in the offspring of IGT mothers.     

Maternal age and family history are risk factors for ankylosing spondylitis

OBJECTIVE: To investigate prevalence and gender distribution in parents of children with ankylosing spondylitis (AS). METHODS: Family history of AS (parents, uncles, and aunts), maternal age at delivery, and consecutive pregnancy number were assessed in the relatives of 40 Mexican Mestizo patients with definite AS (New York Criteria). RESULTS: We evaluated the family history of AS in 34 families of 40 AS patients; 12 with none, 4 with a paternal history (4 healthy fathers with a brother with AS) (odds ratio, OR, 1.37, p = 0.75), 15 with a maternal history of AS, (15 healthy mothers with a brother with AS) (OR 1.4, p = 0.55), and 3 with both lines (OR 0.84, p = 0.92). In these families AS was more frequent in males (29%) than in females (10%), OR 3.40 (95% confidence interval, CI: 1.43-8.29, p = 0.003). Juvenile onset was more common in the offspring of mothers with family history (72%) (OR 13.0, 95% CI: 1.68-147.48, p = 0.009). The number of first-born children with AS (18%) was similar to the later-born children (23%) (OR 1.37, 95% CI: 0.38-5.31, p = 0.78). The frequency of AS increased when the maternal age at delivery was < or = 30 years (OR 0.20, 95% CI: 0.04-0.75, p = 0.01). CONCLUSION: In Mexican Mestizo patients, there is no correlation between the risk for AS and the gender of the affected parent. However we found an association between juvenile onset and maternal family history with an increased incidence in patients with younger mothers.     

The impact of nuts on diabetes and diabetes risk

Nuts have many nutritional benefits: they are high in monounsaturated and polyunsaturated fats, fiber, vitamin, minerals, and phytonutrients. Population studies indicate that individuals who regularly consume nuts have reduced risk for cardiovascular disease and diabetes. In clinical trials, nuts appear to have a neutral effect on glucose and insulin, and a beneficial effect on lipid profile. Thus, nuts can be a healthy dietary component for individuals with diabetes or those at risk for diabetes, providing overall caloric intake is regulated to maintain a healthy body weight.     

The relationship of family history and risk of type 2 diabetes differs by ancestry

AimType 2 diabetes (T2DM) in a first-degree relative is a risk factor for incident diabetes. Americans of African ancestry (AA) have higher rates of T2DM than Americans of European ancestry (EA). Thus, we aimed to determine whether the presence, number and kinship of affected relatives are associated with race-specific T2DM incidence in a prospective study of participants from the Genetic Study of Atherosclerosis Risk (GeneSTAR), who underwent baseline screening including a detailed family history.MethodsNondiabetic healthy siblings (n = 1405) of patients with early-onset coronary artery disease (18–59 years) were enrolled (861 EA and 544 AA) and followed for incident T2DM (mean 14 ± 6 years).ResultsBaseline age was 46.2 ± 7.3 years and 56% were female. T2DM occurred in 12.3% of EA and 19.1% of AA. Among EA, 32.6% had ≥ 1 affected first-degree relatives versus 53.1% in AA, P < 0.0001. In fully adjusted Cox proportional hazard analyses, any family history was related to incident T2DM in EA (HR = 2.53, 95% CI: 1.58–4.06) but not in AA (HR = 1.01, 0.67–1.53). The number of affected relatives conferred incremental risk of T2DM in EA with HR = 1.82 (1.08–3.06), 4.83 (2.15–10.85) and 8.46 (3.09–23.91) for 1, 2, and ≥ 3 affected, respectively. In AA only ≥ 3 affected increased risk (HR = 2.45, 1.44–4.19). Specific kinship patterns were associated with incident T2DM in EA but not in AA.ConclusionsThe presence of any first-degree relative with T2DM does not discriminate risk in AA given the high race-specific prevalence of diabetes. Accounting for the number of affected relatives may more appropriately estimate risk for incident diabetes in both races.     

The impact of ethnicity on glucose homeostasis after gestational diabetes mellitus

The objective of this study was to examine measures of insulin resistance and beta cell function in relation to ethnicity and the development of diabetes after gestational diabetes mellitus (GDM). Glucose homeostasis was assessed during a 75 g oral glucose tolerance test 1–2 years after delivery in 456 women with previous GDM (362 European, 94 non-European; including 41 Arab and 43 Asian women) and 133 control women. Insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). The insulinogenic index (I/G30) and the disposition index [(I/G30)/HOMA-IR] were used to quantify insulin secretion. Women developing diabetes after GDM were characterized by increased HOMA-IR [p = 0.010, adjusted for body mass index (BMI)], whereas the disposition index was decreased in all women with previous GDM irrespective of glucose tolerance, most pronounced in the presence of diabetes (BMI-adjusted p = 1 × 10^?5). Non-European origin was associated with increased HOMA-IR (p = 0.001 vs. European), strengthened by adjustment for BMI in Asian women (p = 0.046 vs. p = 0.016), but eradicated among Arab women (p = 0.004 vs. p = 0.65). Non-European women exhibited an increased frequency of diabetes after GDM (17 % vs. European 4 %, p = 2 × 10^?5). In addition to BMI, non-European and Asian origin was associated with the development of diabetes after GDM in a multivariate logistic regression analysis, whereas Arab origin was not. Our results highlight the importance of preventive measures to ensure a healthy lifestyle in women with GDM, particularly in high-risk ethnic groups.     

家族史与2型糖尿病发病风险关联性的研究进展

2型糖尿病(T2DM)的发病形势日趋严峻,被普遍认为是一种多因素导致的疾病,而糖尿病家族史是T2DM进展过程中的重要独立风险因素之一,可综合反映遗传易感性与共享环境因素对T2DM发病的影响,本文将针对遗传易感性和共享环境因素两方面阐述糖尿病家族史与T2DM发病风险的关联性。     

Comprehensive risk profiles of family history and lifestyle and metabolic risk factors in relation to diabetes: A prospective cohort study

BackgroundFamily history of diabetes, unhealthy lifestyles, and metabolic disorders are individually associated with higher risk of diabetes, but how different combinations of the three risk categories are associated with incident diabetes remains unclear. We aimed to estimate the associations of comprehensive risk profiles of family history and lifestyle and metabolic risk factors with diabetes risk.MethodsThis study included 5290 participants without diabetes at baseline with a mean follow‐up of 4.4 years. Five unhealthy lifestyles and five metabolic disorders were each allocated a score, resulting in an aggregated lifestyle and metabolic risk score ranging from 0 to 5. Eight risk profiles were constructed from combinations of three risk categories: family history of diabetes (yes, no), lifestyle risk (high, low), and metabolic risk (high, low).ResultsCompared with the profile without any risk category, other profiles exhibited incrementally higher risks of diabetes with increasing numbers of categories: the hazard ratio (HR, 95% confidence interval [CI]) for diabetes ranged from 1.34 (1.01–1.79) to 2.33 (1.60–3.39) for profiles with one risk category, ranged from 2.42 (1.45–4.04) to 4.18 (2.42–7.21) for profiles with two risk categories, and was 4.59 (2.85–7.39) for the profile with three risk categories. The associations between the numbers of risk categories and diabetes risk were more prominent in women (p _interaction = .025) and slightly more prominent in adults <55 years (p _interaction = .052).ConclusionsThis study delineated associations between comprehensive risk profiles with diabetes risk, with stronger associations observed in women and slightly stronger associations in adults younger than 55 years.     

有2型糖尿病家族史的非肥胖青少年血浆Ghrelin水平变化的影响因素

目的探讨有T2DM家族史且BMI正常的青少年空腹血浆中Ghrelin水平的变化及相关影响因素。方法80名13-15岁BMI正常青少年,根据有无糖尿病家族史分为糖尿病家族史阳性组（FHD＋）和糖尿病家族史阴性组（FHD-）。测量身高、体重及血压,检测FPG、血脂、空腹真胰岛素（FTI）及Ghrelin水平。结果FHD＋组BMI、FPG、FTI和胰岛素抵抗指数（HOMA-IR）高于FHD-组（P〈0．05）,空腹Ghrelin水平低于FHD-组（P〈0．01）。Ghrelin与FPG（r=-0．456,P〈0．01）,FTI（r=-0．183,P％0．05）和HOMA-IR（r=-0．237,P〈0．01）呈负相关。以Ghrelin为因变量,行多元线性回归显示,FPG（β=-354．435,P〈0．01）和FHD（β=-176．468,P〈0．01）为独立危险因素。结论有T2DM家族史的BMI正常的青少年已存在空腹Ghrelin水平的降低,FPG的升高和糖尿病家族史可能是Ghrelin水平降低的相关因素。     

Prediction of type 2 diabetes in women with a history of gestational diabetes using a genetic risk score

Aims/hypothesis

Women with a history of gestational diabetes mellitus (GDM) are at increased risk of future development of type 2 diabetes. Recently, over 65 genetic variants have been confirmed to be associated with diabetes. We investigated whether this genetic information could improve the prediction of future diabetes in women with GDM.

Methods

This was a prospective cohort study consisting of 395 women with GDM who were followed annually with an OGTT. A weighted genetic risk score (wGRS), consisting of 48 variants, was assessed for improving discrimination (C statistic) and risk reclassification (continuous net reclassification improvement [NRI] index) when added to clinical risk factors.

Results

Among the 395 women with GDM, 116 (29.4%) developed diabetes during a median follow-up period of 45 months. Women with GDM who went on to develop diabetes had a significantly higher wGRS than those who did not (9.36?±?0.92 vs 8.78?±?1.07; p?<?1.56?×?10^?7). In a complex clinical model adjusted for age, prepregnancy BMI, family history of diabetes, blood pressure, fasting glucose and fasting insulin concentration, the C statistic marginally improved from 0.741 without the wGRS to 0.775 with the wGRS (p?=?0.015). The addition of the wGRS to the clinical model resulted in a modest improvement in reclassification (continuous NRI 0.430 [95% CI 0.218, 0.642]; p?=?7.0?×?10^?5).

Conclusions/interpretation

In women with GDM, who are at high risk of diabetes, the wGRS was significantly associated with the future development of diabetes. Furthermore, it improved prediction over clinical risk factors.