Diabetic retinopathy is associated with mortality and cardiovascular disease incidence: the EURODIAB prospective complications study

OBJECTIVE: To study the relationship of nonproliferative and proliferative retinopathy with all-cause mortality and cardiovascular disease (CVD) incidence in type 1 diabetic patients and, additionally, the role of cardiovascular risk factors in these associations. RESEARCH DESIGN AND METHODS: This prospective study included 2,237 type 1 diabetic patients from 31 centers in 16 European countries at baseline, aged 15-60 years, who were examined for retinopathy by taking two-field 45 degrees fundus photographs, which were centrally graded. Mortality and cardiovascular morbidity follow-up was assessed 6-8 years after baseline examination according to a standardized protocol. RESULTS: After 7.9 years of follow-up, 64 patients had died and 128 patients had incident CVD. The age- and sex-adjusted hazard ratios (HRs) of all-cause mortality were 1.45 (95% CI 0.71-2.96) and 4.16 (1.96-8.84) in patients with nonproliferative and proliferative retinopathy at baseline, respectively. Adjustments for cardiovascular risk factors completely obliterated the association with nonproliferative retinopathy, whereas the association with proliferative retinopathy remained twofold increased, although nonsignificant. The age- and sex-adjusted HRs of incident CVD were 1.73 (1.15-2.60) and 2.05 (1.22-3.45) in patients with nonproliferative and proliferative retinopathy, respectively. After adjustments for cardiovascular risk factors, both associations were attenuated and lost statistical significance. CONCLUSIONS: This study shows that type 1 diabetic patients with nonproliferative or proliferative retinopathy have an increased risk for all-cause mortality and incident CVD. The presence of cardiovascular risk factors explained the associations to a large extent, except for the associations with proliferative retinopathy, which suggests that other shared mechanisms may be involved.     

Relationship between plasma sialic acid concentration and microvascular and macrovascular complications in type 1 diabetes: the EURODIAB Complications Study

OBJECTIVE: To test the hypothesis that an increased plasma concentration of sialic acid, a marker of the acute-phase response, is related to the presence of diabetic micro- and macrovascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: We investigated the relationship between plasma sialic acid concentration and nephropathy, retinopathy, neuropathy, and coronary heart disease (CHD) in a cross-sectional survey of 1,369 people with type 1 diabetes. Subjects were participants in the EURODIAB IDDM Complications Study, which involved 31 centers in 16 European countries. RESULTS: There was a significantly increasing trend of plasma sialic acid with severity of retinopathy (P < 0.001 in men) and with degree of urinary albumin excretion (P < 0.001 men, P < 0.01 women). Plasma sialic acid correlated with increasing plasma creatinine concentration (P < 0.009 men, P < 0.0002 women), and men with neuropathy had a higher plasma sialic acid concentration than those without (P < 0.006). There was no significant correlation between plasma sialic acid and CHD in either sex. Elevated plasma sialic acid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration, HbA1c, plasma triglyceride and cholesterol concentrations, waist-to-hip ratio, hypertension and smoking (in men), and low physical exercise (in women). In multiple logistic regression analysis, plasma sialic acid was independently related to proliferative retinopathy and urinary albumin excretion rate in men. CONCLUSIONS: We conclude that an elevated plasma sialic concentration is strongly related to the presence of microvascular complications in type 1 diabetes, especially retinopathy and nephropathy. Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.     

Usefulness of home blood pressure measurement in the morning in type 2 diabetic patients

OBJECTIVE: Recently, repeated home blood pressure (HBP) measurements in the morning for a long period have been shown to have a stronger predictive power for mortality in patients with hypertension than occasional casual/clinic blood pressure (CBP) measurements. We studied whether HBP in the morning in type 2 diabetic patients is useful for prediction of diabetic complications. RESEARCH DESIGN AND METHODS: The occurrence of diabetic complications (nephropathy, retinopathy, coronary heart disease [CHD], and cerebrovascular disease [CVD]) were examined in relation to morning HBP as well as to CBP in 170 type 2 diabetic patients treated with antidiabetic and antihypertensive drugs. Blood pressure was measured at the clinic during the day and at home after awakening in the morning. Clinic hypertension (CH) and morning hypertension (MH) were defined as systolic blood pressure (SBP) > or =130 mmHg and/or diastolic blood pressure (DBP) > or =85 mmHg. The relation of CH and MH to the prevalence of these events was examined. RESULTS: There were no significant differences in the prevalence of nephropathy, retinopathy, CHD, and CVD between the two groups with (n = 131) and without CH (n = 39), whereas the prevalences of these events in the patients with MH (n = 97) were significantly higher (P < 0.05) than in those without MH (n = 73). The prevalence of nephropathy was highly associated with systolic MH. CONCLUSIONS: Elevations of HBP in the morning in diabetic patients are strongly related to microvascular and macrovascular complications, especially nephropathy. It is concluded that the control of MH may prevent vascular complications in type 2 diabetic patients.     

Cardiometabolic risk in impaired fasting glucose and impaired glucose tolerance: the Atherosclerosis Risk in Communities Study

OBJECTIVE: We compared and contrasted cardiovascular disease (CVD) risk factors, subclinical manifestations of CVD, incident coronary heart disease (CHD), and all-cause mortality by categories of impaired glucose regulation in nondiabetic individuals. RESEARCH DESIGN AND METHODS: The study included 6,888 participants aged 52-75 years who had no history of diabetes or CVD. All-cause mortality and incident CHD were ascertained over a median of 6.3 years of follow-up. RESULTS: Agreement between fasting and postchallenge glucose impairment was poor: 3,048 subjects (44%) had neither impaired fasting glucose (IFG) nor impaired glucose tolerance (IGT), 1,690 (25%) had isolated IFG, 1,000 (14%) had isolated IGT, and 1,149 (17%) had both IFG and IGT. After adjustment for age, sex, race, and center, subjects with isolated IFG were more likely to smoke, consume alcohol, and had higher mean BMI, waist circumference, LDL cholesterol, and fasting insulin and lower HDL cholesterol than those with isolated IGT, while subjects with isolated IGT had higher mean triglycerides, systolic blood pressure, and white cell counts. Measures of subclinical CVD and rates of all-cause mortality and incident CHD were similar in isolated IFG and isolated IGT. CONCLUSIONS: Neither isolated IFG nor isolated IGT was associated with a more adverse CVD risk profile.     

Urinary albumin excretion is correlated to fibrinogen levels and protein S activity in patients with type 1 diabetes mellitus without overt diabetic nephropathy

The aim of the study was to test the hypothesis that in diabetic patients without overt nephropathy there may be a correlation between the activity of natural anticoagulant proteins and glomerular dysfunction. Assays for functional activity of proteins S and C, measurements of urinary albumin excretion, lipid parameters and haemoglobin A1c were performed in 91 patients with type 1 diabetes mellitus and 85 patients with type 2. Patients with type 1 diabetes and microalbuminuria had significantly higher mean age (44.1 +/- 10.9 vs. 37.9 +/- 12.7 years; p<0.05), fibrinogen level (3.75 +/- 1.0 vs. 3.21 +/- 0.8 g/l; p<0.01), protein S activity (92.3 +/- 17.6 vs. 84.5 +/- 15.5%; p<0.05) and higher prevalence of retinopathy (p<0.01) and macrovascular disease (p<0.01) than those with normoalbuminuria. Albumin excretion was significantly correlated to age (r=0.25, p<0.05), fibrinogen level (r=0.39, p<0.01), protein S activity (r=0.27; p<0.05), total cholesterol (r=0.23; p<0.05), apoprotein B (r=0.22; p<0.05), retinopathy (r=0.33; p<0.01) and macrovascular disease (r=0.33; p<0.01). Patients with type 2 diabetes mellitus and microalbuminuria had significantly higher apoprotein B levels (1.17 +/- 0.3 vs. 1.06 +/- 1.2 mg/dl; p<0.05) than those with normoalbuminuria, and apoprotein B was significantly correlated to albumin excretion (r=0.22; p<0.05). In a multivariate model of type 1 diabetes mellitus with fibrinogen, protein S and C activity, cholesterol, triglycerides, haemoglobin A1c, retinopathy, and macrovascular disease as independent parameters (r=0.53; p<0.003), there was significant independent correlation of fibrinogen (beta=0.28; p<0.01), protein S activity (beta=0.27; p<0.05) and retinopathy (beta=0.21; p<0.01) with albumin excretion. We conclude that in type 1 diabetes, relative elevation of fibrinogen level and protein S activity appear in the early stages of development of diabetic nephropathy, and may be related to the pathogenesis of diabetic kidney disease.     

Predictive properties of impaired glucose tolerance for cardiovascular risk are not explained by the development of overt diabetes during follow-up

OBJECTIVE: To evaluate the relationship of impaired glucose tolerance (IGT) at baseline to coronary heart disease (CHD) incidence, and cardiovascular disease (CVD) and total mortality at follow-up, and to analyze whether the relationship is independent of the subsequent development of diabetes during follow-up. RESEARCH DESIGN AND METHODS: A baseline screening survey for diabetes was performed in 1987 using a 2-h 75-g oral glucose tolerance test. A total of 1234 men and 1386 women aged 45-64 years, who were free of diabetes at baseline, were followed up for 10 years. During the follow-up, 153 subjects had an incident CHD event, 224 died, and 100 deaths were due to cardiovascular causes. Multivariate adjusted (adjusted for age, sex, waist-to-hip ratio, systolic blood pressure, cholesterol, HDL cholesterol, and smoking) hazard ratio (HR) was estimated using Cox regression analysis. RESULTS: In subjects who had IGT at baseline and who did not progress to diabetes during the follow-up, the multivariate adjusted HR (95% CI) was 1.49 (0.95-2.34) for CHD incidence, 2.34 (1.42-3.85) for CVD mortality, and 1.65 (1.13-2.40) for all-cause mortality. CONCLUSIONS: Baseline IGT was an independent risk predictor for cardiovascular morbidity and mortality and for total mortality, which was not confounded by the subsequent development of overt diabetes.     

Complications and cardiovascular risk factors in South Asians and Europeans with early-onset type 2 diabetes

BACKGROUND: Type 2 diabetes is a major cardiovascular risk factor, and early-onset (<40 years) type 2 diabetes is becoming more common. AIM: To determine the prevalence of complications, and cardiovascular risk factors at diagnosis, in early-onset type 2 diabetes, and to compare these between South Asians and Europeans. DESIGN: Prospective study of newly-diagnosed type 2 diabetes patients aged <40 years, attending hospital and primary care clinics 1999-2001. METHODS: Patients were assessed for signs of macrovascular disease, retinopathy, neuropathy and nephropathy. Cardiovascular risk factors were also determined. RESULTS: Overall, 292 patients were enrolled (165 South Asians). Macrovascular disease was more prevalent in South Asians (15.7% vs. 9.4%, p<0.001), as was microvascular disease (27.3% vs. 16.5%, p<0.001), including retinopathy (17.5% vs. 7.9%, p<0.001), and nephropathy (18.1% vs. 7.8%, p<0.001). South Asians had trends towards greater waist:hip ratio (0.95 vs. 0.90), and higher blood pressure (127/80 vs. 123/76 mmHg). HDL cholesterol was lower (1.0 vs. 1.3 mmol/l, p<0.001) and fasting triglycerides higher (1.9 vs. 1.5 mmol/l, p<0.001) in South Asians. Absolute CHD risk was significantly higher in South Asians (16.9% vs. 13.7%, p<0.001). DISCUSSION: Complications were common at diagnosis, with a quarter of all patients having evidence of at least one diabetic complication. South Asians had a higher prevalence of established macrovascular and microvascular disease, compared to Europeans, and a higher risk of CHD, predominantly because of lower HDL cholesterol and higher blood pressure.     

Type 2 diabetes as a "coronary heart disease equivalent": an 18-year prospective population-based study in Finnish subjects

OBJECTIVE: The purpose of this study was to investigate the hypothesis that coronary heart disease (CHD) mortality in diabetic subjects without prior evidence of CHD is equal to that in nondiabetic subjects with prior myocardial infarction or any prior evidence of CHD. RESEARCH DESIGN AND METHODS: During an 18-year follow-up total, cardiovascular disease (CVD) and CHD deaths were registered in a Finnish population-based study of 1,373 nondiabetic and 1,059 diabetic subjects. RESULTS: Adjusted multivariate Cox hazard models indicated that diabetic subjects without prior myocardial infarction, compared with nondiabetic subjects with prior myocardial infarction, had a hazard ratio (HR) of 0.9 (95% CI 0.6-1.5) for the risk of CHD death. The corresponding HR was 0.9 (0.5-1.4) in men and 1.9 (0.6 -6.1) in women. Diabetic subjects without any prior evidence of CHD (myocardial infarction or ischemic electrocardiogram [ECG] changes or angina pectoris), compared with nondiabetic subjects with prior evidence of CHD, had an HR of 1.9 (1.4-2.6) for CHD death (men 1.5 [1.0-2.2]; women 3.5 [1.8-6.8]). The results for CVD and total mortality were quite similar to those for CHD mortality. CONCLUSIONS: Diabetes without prior myocardial infarction and prior myocardial infarction without diabetes indicate similar risk for CHD death in men and women. However, diabetes without any prior evidence of CHD (myocardial infarction or angina pectoris or ischemic ECG changes) indicates a higher risk than prior evidence of CHD in nondiabetic subjects, especially in women.     

Associations of mortality and diabetes complications in patients with type 1 and type 2 diabetes: early treatment diabetic retinopathy study report no. 27

OBJECTIVE: Diabetes is a leading cause of morbidity and mortality. The purpose of this study is to assess the associations between diabetes complications and mortality in the Early Treatment Diabetic Retinopathy Study (ETDRS). RESEARCH DESIGN AND METHODS: We examined demographic, clinical, and laboratory characteristics of the 3,711 subjects enrolled in the ETDRS, a randomized controlled clinical trial designed to evaluate the role of laser photocoagulation and aspirin therapy for diabetic retinopathy. The outcome assessed was all-cause mortality. Multivariable Cox proportional hazards regression was used to assess associations between diabetes complications and mortality for type 1 and type 2 diabetes separately. RESULTS: The 5-year estimates of all-cause mortality were 5.5 and 18.9% for patients with type 1 and type 2 diabetes, respectively. In patients with type 1 diabetes, amputation (hazard ratio [HR] 5.08 [95% CI 2.06-12.54]) and poor visual acuity (1.74 [1.10-2.75]) remained significantly associated with mortality, after adjusting for other diabetes complications and baseline characteristics. In patients with type 2 diabetes, macrovascular disease and worsening levels of nephropathy, neuropathy, retinopathy, and visual acuity are associated with progressively increasing risks of mortality, after controlling for other baseline risk factors. CONCLUSIONS: Amputation is the strongest predictor for mortality in patients with type 1 diabetes. All complications independently predict mortality in patients with type 2 diabetes. There is an increased risk for mortality as the degree of each complication worsens. Additional studies are needed to investigate the effectiveness of tertiary prevention to decrease mortality in these patients.     

Glomerular filtration rate, cardiorenal end points, and all-cause mortality in type 2 diabetic patients

OBJECTIVE: Chronic kidney disease (CKD) predicts cardiovascular disease (CVD) in the general population. We investigated the effects of stages of renal function using the estimated glomerular filtration rate (eGFR) on all-cause mortality and cardiovascular end points in a prospective cohort of Chinese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Between 1995 and 2000, 4,421 patients without macrovascular disease or end-stage renal disease were recruited. Renal function was assessed by eGFR, as calculated by the abbreviated Modification of Diet in Renal Disease Study Group formula. Clinical end points included all-cause mortality, cardiovascular end point (cardiovascular death, new admissions due to angina, myocardial infarction, stroke, revascularization, or heart failure), and renal end point (reduction in eGFR by >50%, progression of eGFR to stage 5, or dialysis or renal death). RESULTS: After a median follow-up period of 39.4 months (interquartile range 20.3-55), all-cause mortality rate increased from 1.2% (95% CI 0.8-1.7) to 18.3% (9.1-27.5) (P for trend <0.001) as renal function deteriorated from stage 1 (eGFR > or =90 ml/min per 1.73 m(2)) to stage 4 (15-29 ml/min per 1.73 m(2)). The respective rate of new cardiovascular end points also increased from 2.6% (2.0-3.3) to 25.3% (15.0-35.7) (P for trend <0.001). After adjustment for covariates (age, sex, albuminuria, use of renin-angiotensin-aldosterone system [RAAS] inhibitors, lipids, blood pressure, and glycemic control), hazard ratios across different stages of eGFR (> or =90, 60-89, 30-59, and 15-29 ml/min per 1.73 m(2)) for all-cause mortality were 1.00, 1.27, 2.34, and 9.82 (P for trend <0.001), for cardiovascular end points were 1.00, 1.04, 1.05, and 3.23 (P for trend <0.001), and for renal end points were 1.00, 1.36, 3.34, and 27.3 (P for trend <0.001), respectively. CONCLUSIONS: Chinese type 2 diabetic patients with reduced eGFR were at high risk of developing cardiovascular end points and all-cause mortality, independent of albuminuria and metabolic control.     

Relation of lower-extremity amputation to all-cause and cardiovascular disease mortality in American Indians: the Strong Heart Study

OBJECTIVE: To compare risk of all-cause and cardiovascular disease (CVD) mortality in people with a lower-extremity amputation (LEA) attributable to diabetes and people without an LEA. RESEARCH DESIGN AND METHODS: The Strong Heart Study is a study of CVD and its risk factors in 13 American-Indian communities. LEA was ascertained at baseline by direct examination of the legs and feet. Mortality surveillance is complete through 2000. RESULTS: Of 2,108 participants with diabetes at baseline, 134 participants (6.4%) had an LEA. Abnormal ankle-brachial index (53%), albuminuria (87%), and long diabetes duration (mean 19.8 years) were common among diabetic subjects with LEA. Mean diabetes duration among diabetic participants without LEA and in those with toe and below-the-knee amputations was 11.9, 18.6, and 21.1 years, respectively. During 8.7 (+/-2.9) years of follow-up, 102 of the participants with LEA (76%) died from all causes and 35 (26%) died from CVD. Of the 1,974 diabetic participants without LEA at baseline, 604 (31%) died from all causes and 206 (10%) died from CVD. The unadjusted hazard ratios (HRs) for all-cause and CVD mortality in diabetic participants with LEA compared with those without were 4.0 and 4.1, respectively. Adjusting for known and suspected confounders, LEA persisted as a predictor of all-cause (HR 2.2, 95% CI 1.7-2.9) and CVD mortality (HR 1.9, 95% CI 1.3-2.9). We observed a significant interaction between baseline LEA and sex on CVD mortality, with female sex conferring added risk of CVD mortality. CONCLUSIONS: LEA is a potent predictor of all-cause and CVD mortality in diabetic American Indians. The combination of female sex and LEA is associated with greater risk of CVD mortality than either factor alone.     

Normotensive women with type 2 diabetes and microalbuminuria are at high risk for macrovascular disease

OBJECTIVE: The excess risk of macrovascular disease and death associated with diabetes seems higher in women than in men. The pathogenesis for this risk difference has not been fully elucidated. We investigated whether female sex was associated with macrovascular disease and death, independently of known risk factors related to type 2 diabetes, nephropathy, or retinopathy in normotensive patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS: We conducted a prospective, prolonged follow-up study of a subgroup of 67 diabetic patients (46 men and 21 women) without established cardiovascular disease who participated in a larger clinical trial. Data were collected on current and past health, medication use, blood pressure, renal function, and HbA(1c) during the follow-up period of 4.7 +/- 0.8 (means +/- SE) years. The end point was a composite of death, cardiovascular disease, cerebrovascular events, and peripheral artery disease. RESULTS: Of the women, eight (38.1%) met the end point compared with six (13.4%) of the men (P = 0.02 for difference in event-free survival). The hazard ratio of women relative to men was 3.19 (95% CI 1.11-9.21), which further increased after adjusting for age, systolic blood pressure, BMI, smoking, total-to-HDL cholesterol ratio, urinary albumin excretion, and retinopathy. CONCLUSIONS: In our study population of normotensive patients with type 2 diabetes and microalbuminuria, female sex was associated with increased risk of fatal and nonfatal cardiovascular disease, independent of the classical cardiovascular risk factors, the severity of nephropathy or presence of retinopathy, or health care utilization.     

Prospective study of high-sensitivity C-reactive protein as a determinant of mortality: results from the MONICA/KORA Augsburg Cohort Study, 1984-1998

BACKGROUND: C-reactive protein (CRP), an exquisitely sensitive systemic marker of inflammation, has emerged as an independent predictor of cardiovascular diseases (CVD). Because other chronic diseases are also associated with an inflammatory response, we sought to assess the association of high-sensitivity CRP (hsCRP) with total and cause-specific mortality in a large cohort of middle-aged men. METHODS: We measured hsCRP at baseline in 3620 middle-aged men, randomly drawn from 3 samples of the general population in the Augsburg area (Southern 0Germany) in 1984-85, 1989-90, and 1994-95. Outcome was defined as all deaths, fatal CVD, fatal coronary heart disease (CHD) including sudden cardiac deaths, and cancer deaths. RESULTS: During an average follow-up of 7.1 years, 408 deaths occurred (CVD 196, CHD 129, cancer 127). In multivariable Cox regression analysis, subjects with hsCRP >3 mg/L at baseline showed an almost 2-fold increased risk to die vs those with hsCRP <1 mg/L [hazard ratio (HR) 1.88, 95% CI 1.41-2.52]. HRs were 2.15 (95% CI 1.39-3.34) for fatal CVD, 1.74 (1.04-2.92) for fatal CHD, and 1.65 (1.01-2.68) for cancer mortality. In contrast, neither total nor HDL cholesterol significantly predicted all-cause or cancer mortality, and cholesterol had only modest effects on CVD mortality. CONCLUSIONS: Our results suggest that increased circulating hsCRP concentrations are associated with an increased risk of death from several widespread chronic diseases. Persistently increased hsCRP is a sensitive and valuable nonspecific indicator of an ongoing disease process that deserves serious and careful medical attention.     

Risk factors for coronary heart disease in type 1 diabetic patients in Europe: the EURODIAB Prospective Complications Study

OBJECTIVE: The goal of the study was to examine risk factors in the prediction of coronary heart disease (CHD) and differences in men and women in the EURODIAB Prospective Complications Study. RESEARCH DESIGN AND METHODS: Baseline risk factors and CHD at follow-up were assessed in 2,329 type 1 diabetic patients without prior CHD. CHD was defined as physician-diagnosed myocardial infarction, angina pectoris, coronary artery bypass graft surgery, and/or Minnesota-coded ischemic electrocardiograms or fatal CHD. RESULTS: There were 151 patients who developed CHD, and the 7-year incidence rate was 8.0 (per 1,000 person-years) in men and 10.2 in women. After adjustment for age and/or duration of diabetes, the following risk factors were related to CHD in men: age, GHb, waist-to-hip ratio (WHR), HDL cholesterol, smoking, albumin excretion rate (AER), and autonomic neuropathy. The following risk factors were related to CHD in women: age, systolic blood pressure (BP), fasting triglycerides, AER, and retinopathy. Multivariate standardized Cox proportional hazards models showed that age (hazard ratio 1.5), AER (1.3 in men and 1.6 in women), WHR (1.3 in men), smoking (1.5 in men), fasting triglycerides (1.3 in women) or HDL cholesterol (0.74 in women), and systolic BP (1.3 in women) were predictors of CHD. CONCLUSIONS: This study supports the evidence for a strong predictive role of baseline albuminuria in the pathogenesis of CHD in type 1 diabetes. Furthermore, sex-specific risk factors such as systolic BP, fasting triglycerides (or HDL cholesterol), and WHR were found to be important in the development of CHD.     

成人隐匿性自身免疫糖尿病与2型糖尿病的血管并发症比较

目的 探讨成人隐匿性自身免疫糖尿病(LADA)与2型糖尿病(T2DM)血管并发症(包括微血管病变及相关大血管疾病)的差异.方法 比较203例LADA患者与年龄、性别、糖尿病病程及糖尿病家族史匹配的T2DM患者24 h尿白蛋白、眼底检查或荧光造影、心电图、肌电图、血压、血脂、体质指数、空腹血糖、餐后2h血糖、糖化血红蛋白、C肽等方面的差异.结果 ①微血管病变:LADA患者较T2DM患者糖尿病肾病的患病率高(39.9%vs.28.6%,P＜0.05),而2组间视网膜病变和周围神经病变的患病率差异无统计学意义(P＞0.05).②大血管病变:LADA患者较T2DM患者高血压、代谢综合征的患病率低(38.9%vs.55.7%,P＜0.01;33.0%vs.45.3%,P＜0.01),2组间冠心病及脑梗死的患病率差异无统计学意义(均P＞0.05).结论LADA患者与T2DM患者血管并发症存在差异:LADA患者糖尿病肾病患病率较高,而高血压和代谢综合征的患病率较低.     

Gender difference in the impact of type 2 diabetes on coronary heart disease risk

OBJECTIVE: To explain the stronger effect of type 2 diabetes on the risk of coronary heart disease (CHD) in women compared with men. RESEARCH DESIGN AND METHODS: The study population consisted of 1,296 nondiabetic subjects and 835 type 2 diabetic subjects aged 45-64 years without cardiovascular disease. The end points were CHD death and a major CHD event (CHD death or nonfatal myocardial infarction). The follow-up time was 13 years. RESULTS: Major CHD event rate per 1,000 person-years was 11.6 in nondiabetic men, 1.8 in nondiabetic women, 36.3 in diabetic men, and 31.6 in diabetic women. The diabetes-related hazard ratio for a major CHD event from the Cox model, adjusted for age and area of residence, was 2.9 (95% CI 2.2-3.9) in men and 14.4 (8.4-24.5) in women, and after further adjustment for cardiovascular risk factors, 2.8 (2.0-3.7) and 9.5 (5.5-16.9), respectively. The burden of conventional risk factors in the presence of diabetes was greater in women than in men at baseline. Prospectively, elevated blood pressure, low HDL cholesterol, and high triglycerides contributed to diabetes-related CHD risk more in women than in men. However, after adjusting for conventional risk factors, a substantial proportion of diabetes-related CHD risk remained unexplained in both genders. CONCLUSIONS: The stronger effect of type 2 diabetes on the risk of CHD in women compared with men was in part explained by a heavier risk factor burden and a greater effect of blood pressure and atherogenic dyslipidemia in diabetic women.     

Sex Differences in Coronary Artery Calcium and Mortality From Coronary Heart Disease,Cardiovascular Disease,and All Causes in Adults With Diabetes: The Coronary Calcium Consortium

OBJECTIVEWhile diabetes has been previously noted to be a stronger risk factor for cardiovascular disease (CVD) in women compared with men, whether this is still the case is not clear. Coronary artery calcium (CAC) predicts coronary heart disease (CHD) and CVD in people with diabetes; however, its sex-specific impact is less defined. We compared the relation of CAC in women versus men with diabetes for total, CVD, and CHD mortality.RESEARCH DESIGN AND METHODSWe studied adults with diabetes from a large registry of patients with CAC scanning with mortality follow-up over 11.5 years. Cox regression examined the relation of CAC with mortality end points.RESULTSAmong 4,503 adults with diabetes (32.5% women) aged 21–93 years, 61.2% of women and 80.4% of men had CAC >0. Total, CVD, and CHD mortality rates were directly related to CAC; women had higher total and CVD death rates than men when CAC >100. Age- and risk factor–adjusted hazard ratios (HRs) per log unit CAC were higher among women versus men for total mortality (1.28 vs. 1.18) (interaction P = 0.01) and CVD mortality (1.47 vs. 1.27) (interaction P = 0.04) but were similar for CHD mortality (1.48 and 1.48). For CVD mortality, HRs with CAC scores of 101–400 and >400 were 3.67 and 6.27, respectively, for women and 1.63 and 3.48, respectively, for men (interaction P = 0.04). For total mortality, HRs were 2.56 and 4.05 for women, respectively, and 1.88 and 2.66 for men, respectively (interaction P = 0.01).CONCLUSIONSCAC predicts CHD, CVD, and all-cause mortality in patients with diabetes; however, greater CAC predicts CVD and total mortality more strongly in women.     

Similar 9-year mortality risks and reproducibility for the World Health Organization and American Diabetes Association glucose tolerance categories: the Hoorn Study

OBJECTIVE: To compare the risks of all-cause and cardiovascular disease (CVD) mortality in the American Diabetes Association (ADA) and World Health Organization (WHO) glucose tolerance categories after 9 years of follow-up in the Hoorn Study and to study the test-retest reproducibility of those categories. RESEARCH DESIGN AND METHODS: In this population-based cohort study of 2,468 elderly men and women, subjects were classified according to both the WHO and the ADA criteria. Causes of death were extracted from the medical records. Age- and sex-adjusted relative risks were estimated by Cox's proportional hazards model. Reproducibility of the diagnostic criteria was assessed in a sample of 1,109 subjects with duplicate oral glucose tolerance tests. RESULTS: Subjects with known diabetes had a four to five times higher risk of all-cause and CVD mortality compared with normal subjects (P<0.05). The relative risks of all-cause mortality were 1.67 (95% CI 1.09-2.57) and 1.56 (1.00-2.43) for newly diagnosed diabetic subjects according to the WHO and ADA criteria, respectively. The WHO and ADA criteria had similar levels of reproducibility The overall K was 0.59 (0.54-0.64) for WHO criteria and 0.61 (0.56-0.66) for ADA criteria. For the category of newly diagnosed diabetes according to WHO or ADA, the percentages of agreement for the second test compared with the first test were 77% (85/110) and 74% (74/100), respectively. CONCLUSIONS: Both sets of diagnostic criteria identify criteria-specific diabetic subjects with an increased mortality risk compared with normal subjects, and the reproducibility of both criteria is similar.     

Metabolic syndrome: risk factor distribution and 18-year mortality in the multiple risk factor intervention trial

OBJECTIVE: To examine the long-term association of metabolic syndrome with mortality among those at high risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: A total of 10,950 Multiple Risk Factor Intervention Trial (MRFIT) survivors were followed for mortality an additional median 18.4 years (1980-1999). Proportional hazards models examined multivariate-adjusted risks associated with Adult Treatment Panel III-defined metabolic syndrome conditions, with BMI substituted for waist circumference. RESULTS: At MRFIT annual visit 6, 4,588 (41.9%) men, mean age (+/-SD) 53.0 +/- 5.9 years, had metabolic syndrome and 6,362 did not. Comparing men with metabolic syndrome to men without, adjusted hazard ratios (HRs) were 1.21 (95% CI 1.13-1.29), 1.49 (1.35-1.64), and 1.51 (1.34-1.70) for 18-year total, CVD, and coronary heart disease mortality, respectively. Among men with metabolic syndrome, elevated glucose (1.54 [1.34-1.78]) and low HDL cholesterol (1.45 [1.17-1.54]) were most predictive of CVD mortality, followed by elevated BMI (1.34 [1.17-1.54]), elevated blood pressure (1.25 [0.98-1.58]), and elevated triglycerides (1.06 [0.86-1.30]). In contrast, for men without metabolic syndrome, the HR for low HDL cholesterol was 1.02 (0.86-1.22). Among metabolic syndrome men with no nonfatal CVD event, smokers with elevated LDL cholesterol showed higher CVD mortality (1.79 [1.22-2.63]) compared with nonsmokers without elevated LDL cholesterol; this additional risk was even greater for metabolic syndrome men with a nonfatal CVD event (2.11 [1.32-3.38]). CONCLUSIONS: Metabolic syndrome is associated with an increased risk of mortality. Among those with metabolic syndrome, risk is further increased by having more metabolic syndrome conditions, by cigarette smoking, and by elevated LDL cholesterol. Primary prevention of each metabolic syndrome condition should be emphasized, and presence of each condition should be treated in accordance with current guidelines.     

Cholesterol reduction yields clinical benefits: meta-analysis including recent trials

BACKGROUND: Previous meta-analyses reported by Gould et al found significant decreases of 15% in the risk for coronary heart disease (CHD)-related mortality and 11 % in risk for all-cause mortality per decrease of 10% in total cholesterol (TC) level. OBJECTIVE: To evaluate the effects of reducing cholesterol on clinical events after including data from recent clinical trials. METHODS: Using a literature search (MeSH key terms, including: bezafibrate, coronary disease, efficacy, gemfibrozil, hydroxymethylglutaryl-CoA reductase inhibitors, hypercholesterolemia, niacin [nicotinic acids], randomized controlled trials, and treatment outcome; years: 1999-2005), we identified trials published in English that assessed the effects of lipid-modifying therapies on CHD end points, including CHD-related death, myocardial infarction, and angina pectoris. We also included all studies from the previously published meta-analysis. Using the same analytic approach as previously, we determined the effects of net absolute reductions (1 mmol/L [38.7 mg/dL]) in TC and low-density lipoprotein cholesterol (LDL-C) on the relative risks (RRs) for all-cause mortality, CHD-related mortality, any CHD event (mortality or nonfatal myocardial infarction), and non-CHD-related mortality. RESULTS: We included 62 studies involving 216,616 patients, including 126,474 from 24 randomized controlled trials the findings of which were published since the previous meta-analysis (1998). Among all patients, for every 1-mmol/L decrease in TC, there was a 17.5 reduction in RR for all-cause mortality; 24.5 %, for CHD-related mortality; and 29.5% for any CHD event. Corresponding reductions for every 1-mmol/L decrease in LDL-C were 15.6%, 28.0%, and 26.6%, respectively. Similar relationships were observed in patients without CHD. No significant relationship was found between lipid reduction and non-CHD-related mortality risk. CONCLUSIONS: The results from the present analysis support conclusions from previous meta-analyses that cholesterol lowering is clinically beneficial in patients with CHD or at elevated CHD risk. These results also support the previous finding that non-CHD-related mortality is unrelated to lipid reductions.