Management of cardiovascular risk factors in type 2 diabetes mellitus

Cardiovascular disease is by far the major cause of morbidity and mortality in subjects with diabetes mellitus type 2. The risk of cardiovascular disease in persons with type 2 diabetes is greater for any given risk factor, alone or in combination, than it is in persons without diabetes. Independent risk factors for cardiovascular disease in type 2 diabetes are hyperglycemia, hypertension, dyslipidemia and smoking. Subjects with diabetes mellitus type 2 benefit from cardiovascular risk factor modification, either as a primary or secondary intervention, as much as or more than those without diabetes. Risk factor modification includes behavioral modification to affect regular physical activity, healthy diet, weight loss, and smoking cessation. In addition, an optimal glycemic control with HbA1c < 7% is crucial and, aggressive management of hypertension (< 130/80 mmHg) and dyslipidemia are particularly important. Finally, aspirin (100 mg/d) is standard in secondary prophylaxis of cardiovascular events and should strongly be considered in primary prophylaxis if subjects have more than 1 concomitant cardiovascular risk factors.     

Non-invasive cardiovascular risk assessment in women with type 2 diabetes.

This study assessed and compared carotid intima-media thickness (IMT) in postmenopausal women with type 2 diabetes with that in postmenopausal women without type 2 diabetes and compared risk factors that contribute to increased carotid IMT in these groups of women. Carotid IMT, a non-invasive assessment of cardiovascular risk, was measured using high-resolution ultrasound in 20 postmenopausal women with type 2 diabetes and 20 postmenopausal women without type 2 diabetes who had no known coronary heart disease. Risk factors (age, race, family history, diabetes, hypertension, high cholesterol, years past menopause, use of hormone replacement therapy, perceived level of physical activity, and body mass index) known to contribute to coronary heart disease were also assessed. Mean carotid IMT was .88 mm for women with type 2 diabetes compared with .74 mm for women without type 2 diabetes. There were no differences between groups in age, race, cholesterol, and perceived level of physical activity. Women with type 2 diabetes, however, reported more hypertension ( P = .004), greater body mass index ( P = .026), and less use of hormone replacement therapy ( P = .027). Of concern is that 10% of the women with diabetes had stenosis that required surgical intervention. Findings suggest that carotid IMT is a valid way to screen for cardiovascular risk, particularly in postmenopausal women who are at high risk for coronary heart disease. It may also be a feasible, non-invasive method for the detection and prevention of the macrovascular complications of diabetes.     

Increased risk of cardiovascular disease in young women following gestational diabetes mellitus

OBJECTIVE—To determine whether women with gestational diabetes mellitus (GDM) have an increased risk of cardiovascular disease (CVD) following pregnancy.RESEARCH DESIGN AND METHODS—All women aged 20–49 years with live births between April 1994 and March 1997 in Ontario, Canada, were identified. Women with GDM were matched with 10 women without GDM and were followed for CVD.RESULTS—The matched cohorts included 8,191 women with GDM and 81,262 women without GDM. Mean age at entry was 31 years, and median follow-up was 11.5 years. The hazard ratio for CVD events was 1.71 (95% CI 1.08–2.69). After adjustment for subsequent type 2 diabetes, the hazard ratio was attenuated (1.13 [95% CI 0.67–1.89]).CONCLUSIONS—Young women with GDM had a substantially increased risk for CVD compared with women without GDM. Much of this increased risk was attributable to subsequent development of type 2 diabetes.Gestational diabetes mellitus (GDM) is a common condition affecting 2–4% of pregnant women (1) and is associated with adverse outcomes for both the fetus and the mother. Previous GDM is a major risk factor for type 2 diabetes, which occurs in 20–60% of affected women within 5 years of the pregnancy (2). Women with a history of GDM are also at increased risk of other cardiovascular risk factors, such as obesity, hypertension, dyslipidemia, and the metabolic syndrome (3–5), as well as subclinical atherosclerosis (6). Taken together, these findings suggest that GDM identifies a population of young women at increased risk for cardiovascular disease (CVD). We used population-based administrative data to determine whether women with GDM have a heightened risk for CVD compared with women without GDM and whether any increase in risk is independent of subsequent type 2 diabetes.     

Physical activity and metabolic risk in individuals with a family history of type 2 diabetes

OBJECTIVE: We sought to examine the independent associations between different dimensions of physical activity with intermediary and clustered metabolic risk factors in overweight individuals with an increased risk of type 2 diabetes to inform future preventive action. RESEARCH DESIGN AND METHODS: We measured total body movement and five other subcomponents of physical activity by accelerometry in 258 adults (aged 30-50 years) with a family history of type 2 diabetes. We estimated aerobic fitness from an incremental treadmill exercise test. We measured body composition by bioimpedance and waist circumference, blood pressure, fasting triglycerides, HDL cholesterol, glucose, and insulin with standard methods. We constructed a standardized continuously distributed variable for clustered risk. RESULTS: Total body movement (counts . day(-1)) was significantly and independently associated with three of six risk factors (fasting triglycerides, insulin, and HDL) and with clustered metabolic risk (P = 0.004) after adjustment for age, sex, and obesity. Time spent at moderate- and vigorous-intensity physical activity (MPVA) was independently associated with clustered metabolic risk (P = 0.03). Five- and 10-min bouts of MVPA, time spent sedentary, time spent at light-intensity activity, and aerobic fitness were not significantly related with clustered risk after adjustment for confounding factors. CONCLUSIONS: Total body movement is associated with intermediary phenotypic risk factors for cardiovascular disease and metabolic disease and with clustered metabolic risk independent of aerobic fitness and obesity. Increasing the total amount of physical activity in sedentary and overweight individuals may have beneficial effects on metabolic risk factors.     

The presence of family history and the development of type 2 diabetes mellitus risk factors in rural children.

Type 2 diabetes mellitus is reaching epidemic proportions among children and adolescents. School health fairs offer an opportunity to identify children with risk factors for the development of type 2 diabetes mellitus. This study identified selected risk factors (i.e., high-risk racial/ethnic group, obesity, elevated blood pressure, elevated casual blood glucose, elevated total cholesterol, and the presence of acanthosis nigricans) for development of type 2 diabetes mellitus in rural children with or without a family history of diabetes during annual school health fairs. Of the children screened, 40% (673) presented with two or more of the identified risk factors for type 2 diabetes mellitus. The presence of multiple risk factors in participants reporting a positive family history of diabetes mellitus versus those with no family history was not statistically significant. Based on the study results, factors other than family history may be more predictive for the development of type 2 diabetes mellitus in rural school children.     

Estrogen therapy and risk of cardiovascular events among women with type 2 diabetes

OBJECTIVE: To evaluate the association between estrogen therapy and cardiovascular disease risk among women with type 2 diabetes. RESEARCH DESIGN AND METHODS: A retrospective, case-cohort study was conducted among 6017 women aged 45-80 years with type 2 diabetes from 1 January 1986 to 31 December 1992 at the Group Health Cooperative in Washington state. Cardiovascular outcomes, including nonfatal myocardial infarction (n = 215), coronary revascularization (n = 253), and cardiovascular deaths (n = 229), were ascertained through 31 December 1998. Use of estrogen and progestin was derived from automated pharmacy records and modeled as a time-dependent variable. Median follow-up was 6.8 years. Multivariable-adjusted relative risk (RR) and 95% CI were calculated using Cox proportional hazard models for case-cohort analyses. RESULTS: Current use of estrogen with (RR 0.43, 95% CI 0.22-0.85) or without (0.48, 0.30-0.78) progestin was associated with a decreased risk of cardiovascular events compared with never having used estrogen. Risk of cardiovascular events associated with a first episode of estrogen use (with or without progestin) of <25 months' duration (1.12, 0.49-2.54), first episode of use >or=25 months' duration (0.32, 0.06-1.70), and current use that was not the first episode of use (0.42, 0.42-0.67) indicated that recent initiation was not associated with an increase or decrease in risk. CONCLUSIONS: These results show an association of estrogen therapy, with or without progestin, with decreased risk of cardiovascular events among women with type 2 diabetes. This association should be further investigated in large randomized, controlled trials.     

2型糖尿病家族史风险通路识别及功能分析

目的: 探讨2型糖尿病家族史与胰岛素抵抗间的关系,采用信息学方法对从基因表达库（Gene Expression Omnibus, GEO）获取的具有2型糖尿病家族史但自身血糖正常的研究对象进行相关基因表达谱分析,识别2型糖尿病疾病风险通路,并对关键基因产物进行功能分析。方法: 对美国国立生物技术信息中心（National Center for Biotechnology Information,NCBI）的综合性基因表达与杂交阵列数据库中26名有2型糖尿病家族史但自身血糖正常的研究对象和15名无糖尿病家族史的血糖正常的人群进行数据分析（GSE25462）,运用Bergman微小模型技术结合静脉糖耐量试验评估胰岛素敏感指数,并对骨骼肌细胞基因表达谱芯片采用生物信息学方法（基因功能富集分析方法、风险通路识别方法等）进行数据分析,进而在分子层面进行2型糖尿病致病机制研究。结果: 有2型糖尿病家族史但自身血糖正常的研究对象其胰岛素敏感性下降41%（P<0.05）。通过差异表达分析,共发现202个基因表达在家族史阳性组与家族史阴性组间的差异有统计学意义,同时鉴定了富集差异显著的5条通路,分别是多能干细胞的造血功能、万能干细胞的造血功能、JAK1/3在c-细胞活素信号通路的作用、TOB在T细胞信号通路中的抗增殖作用、B细胞的发育。结论: 有2型糖尿病家族史但自身血糖正常的研究对象存在胰岛素抵抗,2型糖尿病的致病机制与造血干细胞功能及免疫状态有重要联系。     

Hyperglycemia as a risk factor for cardiovascular disease in type 2 diabetes.

According to several prospective population-based studies, glycemic control influences the risk for cardiovascular disease, including coronary heart disease, independently of conventional risk factors in patients with type 2 diabetes. Recent clinical trials, particularly the United Kingdom Prospective Diabetes Study, have shown that microvascular complications and macrovascular complications, although to a lesser extent, can be prevented in patients with type 2 diabetes with correction of glycemic control. However, in the treatment and prevention of cardiovascular disease in type 2 diabetes, all known cardiovascular risk factors should be attacked simultaneously.     

Cardiovascular risk in women with type 2 diabetes

Type 2 DM appears to eliminate the relative survival advantage experienced by premenopausal nondiabetic women compared with men with regard to CVD. The role of traditional cardiovascular risk factors, while important, cannot fully account for the disparate increase in CVD among women with type 2 DM compared with nondiabetic women. The interplay between type 2 DM and female hormones may prove important. Other less traditional risk factors such as endothelial dysfunction and impaired fibrinolysis may also play a role. Impairments in cardiovascular exercise performance in women with type 2 DM may provide insight in the future as representative of a pre-CVD state. Future research should focus on the specific causes of CVD in women with DM. In the meantime, it is important to aggressively treat modifiable risk factors in this population (Table 1). The impact of this health problem will continue to increase in our aging society, because a steadily increasing proportion of the population will be women; furthermore, an increasing percentage of these women will have diabetes if current trends continue.     

2型糖尿病合并冠心病患者糖化血红蛋白与心血管危险因素分析

在目前全球糖尿病(DM)流行的大环境下,我国的DM发病率也呈快速增长趋势。预计到2025年,我国DM患者将超过5000万,我国将成为世界上DM患者最多的国家。随着DM发病率增高,由此引发的心脑血管疾病发病率也居高不下[1～3]。2001年公布的美国胆固醇教育项目专家组关于成人高胆固醇血症筛选、评估、治疗的第三次报告(ATPⅢ)提出,DM是冠心病的等危症(CHD risk equivalents)[4]。     

Consequences of a family history of type 1 and type 2 diabetes on the phenotype of patients with type 2 diabetes

OBJECTIVE: To investigate the impact of a family history of type 1 and type 2 diabetes on the phenotype of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a population-based study, we compared the phenotype in 3 groups of patients with type 2 diabetes. The first group had no family history of diabetes (FH-, n = 148); the second group had a family history of type 2 diabetes only (FH+(TYPE2), n = 1,211); and the third group had a family history of both type 1 and type 2 diabetes (FH+(MIXED), n = 240). Furthermore, we studied the frequency of GAD antibodies (GADabs), HLA-DQB1 risk genotypes, and the presence of coronary heart disease (CHD) according to family history in unrelated patients with type 2 diabetes from 787 families (148 FH-, 546 FH+(TYPE2) and 93 FH+(MIXED)). RESULTS: Patients with no family history of diabetes were older at the onset of the disease, had a better beta-cell function (P = 0.004), and had higher HDL cholesterol concentrations (P = 0.006) than patients with a family history of diabetes. Patients with a family history of only type 2 diabetes had higher BMI and fasting C-peptide concentrations (P = 0.031) but lower frequency of GADab (11 vs. 23%, P = 0.001) and DQB1 risk genotypes (37 vs. 54%, P = 0.003) compared with patients with a family history of both type 1 and type 2 diabetes. In addition, hypertension (P = 0.05) and CHD (P = 0.031) were more common in FH+(TYPE2) than in FH+(MIXED) patients. In patients <60 years old, a family history of type 1 diabetes was associated with a reduced risk of CHD independent of age, hypertension, and HDL cholesterol concentrations. The results were similar when the GADab+ patients were excluded from the analysis. CONCLUSIONS: A family history of both type 1 and type 2 diabetes had a profound influence on the phenotype of patients with type 2 diabetes, which suggests a genetic interaction between type 1 and type 2 diabetes.     

Sex differences in cardiovascular disease risk and exercise in type 2 diabetes

Diabetes currently affects approximately 14% of the US population, and cardiovascular disease (CVD) is a leading cause of morbidity and mortality in those with diabetes. Although in the general population women are at lower risk than men for CVD, women have a disproportionately greater increase in risk for CVD than do men in the context of diabetes. Physical activity is considered a cornerstone in the prevention and treatment of CVD and its risk factors, but greater barriers to physical activity may exist for women with diabetes compared to their male counterparts. In this article, we review sex differences in CVD incidence and risk among diabetics, sex differences in physical activity behaviors, cardiovascular abnormalities and impaired exercise capacity in women living with diabetes, and the effects of exercise on prevention and treatment of CVD in diabetic women. Finally, we discuss future research needed to clarify potential sex differences in the cardiovascular effects of diabetes and to establish ways to reduce the barriers to exercise in women with diabetes.     

Long-acting injectable progestin contraception and risk of type 2 diabetes in Latino women with prior gestational diabetes mellitus

OBJECTIVE: To investigate the impact of a long-acting injectable progestin, depo-medroxyprogesterone acetate (DMPA), compared with combination oral contraceptives (COCs) on the risk of diabetes in Latino women with prior gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: An observational cohort study of 526 Hispanic women with prior GDM who were not diabetic in their postpartum visit during January 1987 to October 1997 and who elected DMPA (n = 96) or COCs (n = 430) as initial contraception were followed for a maximum of 9.2 years with a median follow-up of approximately 12 months. Oral glucose tolerance tests were performed and choice of contraception method was recorded at each visit as part of routine clinical care. RESULTS: Annual diabetes incidence rates were 19% in the DMPA group and 12% in the COC group, with an unadjusted hazard ratio (HR) of 1.58 (95% CI 1.00-2.50; P = 0.05) for DMPA compared with COCs. Adjustment for baseline imbalances reduced the HR to 1.18 (0.67-2.28; P = 0.57). Additional adjustment for weight gain during follow-up, which was on average 1.8 kg higher in the DMPA group (P < 0.0001), reduced the HR to 1.07. DMPA interacted with baseline serum triglyceride levels and, separately, with breast-feeding to increase the diabetes risk. CONCLUSIONS: DMPA use was associated with an increased risk of diabetes that appeared to be explained by three factors: 1) use in women with increased baseline diabetes risk, 2) weight gain during use, and 3) use with high baseline triglycerides and/or during breast-feeding.     

妊娠期糖尿病妇女产后2型糖尿病发生及预防的研究进展

随着糖尿病(diabetes mellitus,DM)发病率及相关病死率在全球范围内的不断上升,严重威胁人类健康,DM预防已成为世界各国共同关注的健康问题。同时,文献显示妊娠期