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.     

New-onset diabetes and risk of all-cause and cardiovascular mortality: the Cardiovascular Health Study

OBJECTIVE: Cardiovascular risk associated with new-onset diabetes is not well characterized. We hypothesized that risk of all-cause and cardiovascular mortality would be similar among participants with and without new-onset diabetes in the first years of follow-up and rise over time for new-onset diabetes. RESEARCH DESIGN AND METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of cardiovascular risk factors in adults aged > or =65 years. We used CHS participants to define a cohort (n = 282) with new-onset diabetes during 11 years of follow-up. New-onset diabetes was defined by initiation of antidiabetes medication or by fasting plasma glucose >125 mg/dl among CHS participants without diabetes at study entry. Three CHS participants without diabetes were matched for age, sex, and race to each participant with new-onset diabetes at the time of diabetes identification (n = 837). Survival analysis provided adjusted hazard ratios (HRs) for all-cause and cardiovascular mortality. RESULTS: During a median of 5.9 years of follow-up, there were 352 deaths, of which 41% were cardiovascular. In adjusted analyses, new-onset diabetes was associated with an HR of 1.9 (95% CI 1.4-2.5) for all-cause and 2.2 (1.4-3.4) for cardiovascular mortality compared with no diabetes. Mortality risks were elevated within 2 years of onset, especially cardiovascular risk (4.3 [95% CI 1.7-10.8]), and did not increase over time. CONCLUSIONS: Our findings indicate that there may be a mortality differential soon after diabetes onset in older adults and suggest that long-term macrovascular damage from atherosclerosis may not be primarily responsible for increased risk.     

Periodontal disease and mortality in type 2 diabetes

OBJECTIVE: Periodontal disease may contribute to the increased mortality associated with diabetes. RESEARCH DESIGN AND METHODS: In a prospective longitudinal study of 628 subjects aged > or =35 years, we examined the effect of periodontal disease on overall and cardiovascular disease mortality in Pima Indians with type 2 diabetes. Periodontal abnormality was classified as no or mild, moderate, and severe, based on panoramic radiographs and clinical dental examinations. RESULTS: During a median follow-up of 11 years (range 0.3-16), 204 subjects died. The age- and sex-adjusted death rates for all natural causes expressed as the number of deaths per 1,000 person-years of follow-up were 3.7 (95% CI 0.7-6.6) for no or mild periodontal disease, 19.6 (10.7-28.5) for moderate periodontal disease, and 28.4 (22.3-34.6) for severe periodontal disease. Periodontal disease predicted deaths from ischemic heart disease (IHD) (P trend = 0.04) and diabetic nephropathy (P trend < 0.01). Death rates from other causes were not associated with periodontal disease. After adjustment for age, sex, duration of diabetes, HbA1c, macroalbuminuria, BMI, serum cholesterol concentration, hypertension, electrocardiographic abnormalities, and current smoking in a proportional hazards model, subjects with severe periodontal disease had 3.2 times the risk (95% CI 1.1-9.3) of cardiorenal mortality (IHD and diabetic nephropathy combined) compared with the reference group (no or mild periodontal disease and moderate periodontal disease combined). CONCLUSIONS: Periodontal disease is a strong predictor of mortality from IHD and diabetic nephropathy in Pima Indians with type 2 diabetes. The effect of periodontal disease is in addition to the effects of traditional risk factors for these diseases.     

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.     

Metabolic syndrome as a predictor of all-cause and cardiovascular mortality in type 2 diabetes: the Casale Monferrato Study

OBJECTIVE: The aim of this study was to assess in an 11-year survival follow-up of a population-based cohort of type 2 diabetes the predictive role of World Health Organization-defined metabolic syndrome, independent of conventional cardiovascular risk factors. RESEARCH DESIGN AND METHODS: During the follow-up (1991-2001), 1,565 patients were regularly examined with centralized measurements of HbA(1c). The independent role of the metabolic syndrome as a predictor of all-cause and cardiovascular mortality was assessed with multivariate Cox proportional hazards modeling. RESULTS: At baseline, the prevalence of the metabolic syndrome was 75.6% (95% CI 73.6-77.9). Results are based on 685 deaths (520 with the metabolic syndrome and 165 without it) in 10,890.2 person-years of observations. With respect to subjects without the metabolic syndrome, those with the metabolic syndrome had a similar hazard ratio (HR) of cardiovascular mortality after adjustment for age, sex, smoking, total cholesterol level, and coronary heart disease. In contrast, relative to subjects with diabetes only, the HR of subjects with only one component of the syndrome was 2.92 (1.16-7.33), independent of other risk factors. CONCLUSIONS: We found that 1) the prevalence of the metabolic syndrome in a population-based cohort of type 2 diabetes is high (75.6%); 2) the metabolic syndrome is not a predictor of 11-year all-cause and cardiovascular mortality; and 3) more than twofold higher cardiovascular risk, independent of conventional risk factors, is evident in diabetic subjects with only one component of the syndrome compared with those with diabetes only. Categorizing type 2 diabetic subjects as having or not having the metabolic syndrome does not provide further prediction compared with the knowledge of its single components.     

Silent myocardial ischemia in patients with diabetes: who to screen.

OBJECTIVE: Silent myocardial ischemia (SMI) is more common in diabetic patients than in the general population. However, the exact prevalence of SMI is not known, and routine screening is costly. The purpose of this 1-year study was to estimate the prevalence of SMI and define a high-risk diabetic population by systematically testing patients with no symptoms of coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: The criteria for inclusion in this study were age (between 25 and 75 years), duration of diabetes (>15 years for type 1 diabetes, 10 years for type 2 diabetes with no cardiovascular risk factors, and 5 years for type 2 diabetes with at least one cardiovascular risk factor), and absence of clinical or electrocardiogram (ECG) symptoms of CAD. For 1 year, 203 patients were screened, including 28 women and 45 men with type 1 diabetes (aged 41.5+/-10.9 years, mean duration of diabetes 20.9+/-7.7 years [mean +/- SD]) and 61 women and 69 men with type 2 diabetes (aged 60.7+/-8.7 years, duration of diabetes 16.5+/-7.1 years). Exercise ECG was the first choice for screening method. If exercise ECG was not possible or inconclusive, thallium myocardial scintigraphy (TMS) with exercise testing and/or dipyridamole injection was performed. If any one of these tests was positive, coronary angiography was carried out and was considered to be positive with a stenosis of > or =50%. RESULTS: Positive screening results were obtained in 32 patients (15.7%). Coronary angiography demonstrated significant lesions in 19 patients (9.3%) and nonsignificant lesions in 7 patients (1 false-positive result for exercise ECG and 6 false-positive results for TMS). Coronary angiography was not performed in six patients. All but 3 of the 19 patients (15 men and 4 women) in whom silent coronary lesions were detected presented with type 2 diabetes. The main differences between the 16 type 2 diabetic patients presenting with coronary lesions and the type 2 diabetic patients without SMI were a higher prevalence of peripheral macroangiopathy (56.2 vs. 15.1%, respectively, P < 0.01) and a higher prevalence of retinopathy (P < 0.05). No correlation was found between SMI and duration of diabetes, HbA1c level, renal status, or cardiovascular risk factors except for family history of CAD. CONCLUSIONS: The results of this study allowed us to determine a high-risk group for SMI in the diabetic population. SMI with significant lesions occurs in 20.9% of type 2 diabetic male patients who are totally asymptomatic for CAD. Based on these findings, we recommend routine screening for male patients in whom the duration of type 2 diabetes is >10 years or even less when more than one cardiovascular risk factor is present.     

Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study.

OBJECTIVE: This population-based study, carried out in the framework of the Verona Diabetes Study, investigated mortality from specific causes in known type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A cohort of 7,148 known type 2 diabetic patients (3,366 men and 3,782 women) was identified on 31 December 1986 and followed up for 5 years (1987-1991). Underlying causes of death were obtained from death certificates and were coded according to the International Classification of Diseases, Ninth Revision. Cause-specific death rates of diabetic subjects were compared with those of the inhabitants of Verona. By 31 December 1991, 1,550 diabetic subjects (744 men and 806 women) had died. RESULTS: The standardized mortality ratio (SMR) for all causes of death was 1.42 (95% CI 1.35-1.50). The highest SMRs were for the following specific causes: diabetes (SMR 4.47 [3.91-5.10]), gastrointestinal diseases (1.83 [1.50-2.21])--particularly liver cirrhosis (2.52 [1.96-3.20])--and cardiovascular diseases (1.34 [1.23-1.44]), particularly cerebrovascular (1.48 [1.25-1.73]) and ischemic heart diseases (1.41 [1.24-1.62]). A significantly higher than expected risk of mortality for cardiovascular causes was already present in the first 5 years after diagnosis and decreased with age. Type 2 diabetic patients treated with insulin had a higher risk of dying than those treated orally or by diet. CONCLUSIONS: The highest SMRs in the diabetic cohort were for diabetes and liver cirrhosis. The mortality risk for cardiovascular diseases, although significantly higher than expected, was much lower in Italian type 2 diabetic patients than that reported for American patients. The evidence of an early effect on mortality suggests that prevention, early diagnosis, and treatment should be improved.     

Microalbuminuria: a genetic link between diabetes and cardiovascular disease?

Non-insulin-dependent diabetes is associated with a 2-3 fold increased risk of cardiovascular disease. The poor relationship between this risk and either glycaemic control or diabetes duration suggests that some other aspect of the diabetic state, and not hyperglycaemia per se, mediates this risk. This other aspect of diabetes does not comprise alterations in recognized cardiovascular risk factors such as blood pressure or lipids, as the major component of the excess risk is in those diabetics with low levels of the other risk factors. It thus appears that there may be some factors that predispose both to diabetes and to cardiovascular disease. In insulin-dependent diabetics most of the excess risk of cardiovascular disease occurs in subjects with proteinuria, and microalbuminuria or proteinuria in non-insulin-dependent diabetics also substantially increases cardiovascular risk. Although changes in recognized risk factors in diabetics with nephropathy may partly explain these observations, we and others have shown that microalbuminuric non-diabetics also have a markedly increased prevalence of cardiovascular disease and substantially increased cardiovascular mortality. The observations that in insulin-dependent diabetics nephropathy shows family clustering and that these patients have elevated sodium lithium counter-transport rate, a possible genetic marker for the vascular complications of hypertension, have led to the suggestion that microalbuminuria may be a marker of a genetic predisposition to vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aortic distensibility is reduced in subjects with type 2 diabetes and cardiac autonomic neuropathy

BACKGROUND: Reduced aortic distensibility predicts cardiovascular mortality in patients with type 2 diabetes and impaired glucose tolerance. Cardiac autonomic neuropathy is common in subjects with diabetes. However, the relationship between the elastic properties of the aorta and autonomic neuropathy has not been studied to date in subjects with type 2 diabetes. MATERIALS AND METHODS: In this cross-sectional study, a total of 87 subjects with type 2 diabetes (27 with and 60 without cardiac autonomic neuropathy) as well as 60 healthy individuals, matched for age and sex with the diabetic subjects, were examined. Cardiac autonomic neuropathy was diagnosed on the basis of the battery of the classic cardiovascular autonomic function tests. Aortic distensibility was assessed by high-resolution ultrasonography. RESULTS: Diabetic patients had reduced aortic distensibility in comparison with the control subjects: 1.81 +/- 0.58 vs. 2.53 +/- 0.34 10-6 cm2 dyn-1, respectively (P < 0.0001). In addition, diabetic individuals with cardiac autonomic neuropathy had reduced aortic distensibility as compared with patients without this complication: 1.60 +/- 0.72 vs. 1.90 +/- 0.48 10-6 cm2 dyn-1, respectively (P = 0.02). Multivariate linear regression analysis in the diabetic group, after controlling for a number of confounding factors such as age, systolic and diastolic blood pressure, duration of diabetes and presence as well as severity of cardiac autonomic neuropathy, demonstrated a significant and independent association between duration of diabetes [B = -0.02, SE(B) = 0.01, P = 0.01] and presence of cardiac autonomic neuropathy [B = -0.29, SE(B) = 0.14, P = 0.03] with aortic distensibility. CONCLUSION: Type 2 diabetes is associated with a significant reduction in the elastic properties of the aorta. In addition, known duration of diabetes and presence of cardiac autonomic neuropathy are the main predictors of aortic distensibility in subjects with type 2 diabetes.     

Elevated plasma asymmetric dimethylarginine as a marker of cardiovascular morbidity in early diabetic nephropathy in type 1 diabetes

OBJECTIVE: Increased plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, has been associated with endothelial dysfunction, insulin resistance, and atherosclerosis in nondiabetic populations. In end-stage renal failure, circulating ADMA is elevated and a strong predictor of cardiovascular outcome. This study investigated the relation between ADMA and diabetic micro- and macrovascular complications in a large cohort of type 1 diabetic patients with and without early diabetic nephropathy. RESEARCH DESIGN AND METHODS: ADMA concentrations in plasma were determined by a high-performance liquid chromatography method in 408 type 1 diabetic patients with overt diabetic nephropathy (252 men; mean age 42.7 years [SD 11.0], mean duration of diabetes 28 years [SD 9], median serum creatinine level 102 micromol/l [range 52-684]). A group of 192 patients with longstanding type 1 diabetes and persistent normoalbuminuria served as control subjects (118 men; mean age 42.6 years [SD 10.2], mean duration of diabetes 27 years [SD 9]). RESULTS: In patients with diabetic nephropathy, mean +/- SD plasma ADMA concentration was elevated 0.46 +/- 0.08 vs. 0.40 +/- 0.08 micromol/l in normoalbuminuric patients (P<0.001). An increase in plasma ADMA of 0.1 micromol/l increased the odds ratio of nephropathy to 2.77 (95% CI 1.89-4.05) (P<0.001). Circulating ADMA increased in nephropathy patients with declining kidney function, as indicated by elevated values in the lower quartiles of glomerular filtration rate (<76 ml.min(-1).1.73 m(-2)) (P<0.001 ANOVA). Mean ADMA levels were similar in patients with or without diabetic retinopathy (P>0.2). However, in 44 patients with nephropathy and history of myocardial infarction and/or stroke, ADMA was significantly elevated at 0.48 +/- 0.08 micromol/l compared with 0.46 +/- 0.08 micromol/l in patients without major cardiovascular events (P=0.05). CONCLUSIONS: Elevated circulating ADMA may contribute to the excess cardiovascular morbidity and mortality in early diabetic nephropathy.     

Control to goal of cardiometabolic risk factors among Nigerians living with type 2 diabetes mellitus

BACKGROUND : Cardiovascular risk factors contribute to morbidity and mortality among diabetic patients. National and international guidelines on management of diabetes therefore emphasize control to goals of blood glucose, blood pressure, dyslipidemia, and obesity so as to minimize the development of complications and enhance the patients' quality of life. OBJECTIVE : To evaluate the status of control to goals of cardiometabolic risk factors among the diabetic patients attending the Diabetes clinic of University of Nigeria Teaching Hospital, Enugu. MATERIALS AND METHODS : A survey of 233 type 2 diabetic patients recruited from the Diabetes clinic of our hospital was carried out. Standard procedures as described in the WHO STEP instrument were used to determine the waist circumference, weight, height, and systolic and diastolic blood pressure. Fasting blood glucose and lipid profiles were also assessed. Therapeutic goals used to define risk or poor control were values adopted by expert groups such as American diabetes association (ADA), National cholesterol education program (NCEP), American association of clinical endocrinologist (AACE) and International diabetes federation (IDF). RESULTS : There were 98 males and 135 females with mean (SD) duration of diabetes mellitus (DM) of 6.7 (6.3) years. Suboptimal glycemic, blood pressure control and dyslipidemia were observed in 65.7%, 51.9%, 97.1% of the subjects respectively while 60.1% of the subjects were found to be overweight/obese. Comparing the mean indices of risk factors with the recommended therapeutic goals, status of control was optimal for HDL-cholesterol, waist circumference and triglycerides. All the other risk factors were suboptimal. CONCLUSION : Control to goals of cardiovascular risk factors is poor among the patients. There is the need to identify and tackle the possible contributing factors so as to reduce the morbidity and mortality in these patients.     

Natural history and prognostic factors of diabetic nephropathy in type 2 diabetes

BACKGROUND: The causes and mechanisms of increased mortality of patients with diabetic nephropathy are unclear, and its natural history is poorly understood. Aim: To evaluate risk factors for mortality in type 2 diabetic patients with nephropathy. DESIGN: Retrospective study of clinical and biochemical parameters in diabetic nephropathic patients and controls sampled from a secondary care register. METHODS: We studied 170 type 2 diabetic patients (from 1987 to 1995) with nephropathy (proteinuria >0.5 g/24 h) and 170 non-nephropathic patients. Follow-up was until death or December 1997. Details of demographics, clinical and treatment history were obtained from medical records. RESULTS: Mean follow-up was 5.3 years. Of the patients with nephropathy at baseline, 63 (37%) died compared with 14 (8%) non-nephropathic patients (chi(2)=53.8, p<0.0001). Age- and sex-adjusted all-cause mortality rates were 8.1 (6.4, 9.8) and 1.4 (0.5, 2.2) deaths per 100 person-years, respectively (rate ratio 5.8). Forty-four patients (57%) died from cardiovascular causes (rate ratio 5.4). Mortality was directly proportional to degree of proteinuria: 0.5-2 g/24 h, 4.6 (2.9-7.1); >2 g/24 h, 9.9 (7.3-13.5) per 100 patient-years. A 36% (5-78%) excess risk of mortality was observed for each log unit increase in proteinuria. Multivariate Cox regression analyses confirmed a five-fold excess risk for all-cause and cardiovascular mortality in patients with nephropathy compared with those without. This was independent of other risk factors including baseline age [5% (1-8%)/year], creatinine [2.5 (1.12-5.6)/10 micromol/l] and glycaemic control (HbA(1c)) [15% (1-31%) per 1% rise]. CONCLUSIONS: Proteinuria is a potentially preventable and reversible risk factor associated with high mortality in type 2 diabetic patients. Prevention of the development of overt nephropathy and improvement in diabetes control may reduce mortality in these patients.     

Relationship between diabetes and mortality: a population study using record linkage

OBJECTIVE: To determine patterns and causes of mortality for patients with diabetes in a district health authority RESEARCH DESIGN AND METHODS: The study used cross-sectional record linkage, combining an electronic death register with a diabetic patient register constructed from a variety of routine health data sources collected from 1991 to 1997. The study was conducted in Cardiff and the Vale of Glamorgan, Wales, U.K., and included all diabetic deaths between 1993 and 1996. RESULTS: Of 1,694 deaths in patients with known diabetes, only 674 (39.8%) had diabetes recorded as an immediate or antecedent cause of death. Mortality rates were 41.8 per 1,000 for the diabetic population and 10.1 per 1,000 for the nondiabetic population. The standard mean ratio for the diabetic population was 1.24 (95% CI 1.12-1.35), with the risk of mortality relative to the nondiabetic population decreasing with age. Males with diabetes lost an average of 7.0 years from the year of diagnosis, and females with diabetes lost an average of 7.5 years. The most common cause of death was cardiovascular disease, which accounted for 49.1% of deaths in the diabetic population. CONCLUSIONS: Diabetes is recorded as a cause of death on a minority of death certificates for patients with diabetes. Using death certificates in isolation, therefore, is a poor method of estimating diabetic mortality, but results can be improved with the use of record linkage techniques. Patients with diabetes have an excess risk of mortality compared with the nondiabetic population. Life-years lost for patients with diabetes is strongly related to age at diagnosis and is a means of expressing mortality without relying on accurate prevalence data.     

The significant effect of diabetes duration on coronary heart disease mortality: the Framingham Heart Study

OBJECTIVE: The risk of coronary heart disease (CHD) in type 2 diabetes is two- to threefold higher than in the general population, but the effect of diabetes duration on CHD risk has not been well characterized. We hypothesized that duration of diabetes is an important predictor of incident CHD among people with diabetes. RESEARCH DESIGN AND METHODS: The duration of diabetes (fasting glucose > or =126 mg/dl, random glucose > or =200 mg/dl, or use of an oral hypoglycemic agent or insulin) was assessed in participants with diabetes in the original and offspring cohorts of the Framingham Heart Study. Only subjects with diabetes diagnosed between the ages of 30 and 74 years, without a history of ketoacidosis, and free of cardiovascular disease at the baseline evaluation were included. Cox proportional hazards models were used to estimate the hazard ratio of incident CHD events and mortality over a 12-year follow-up period; models were adjusted for known CHD risk factors. RESULTS: Among 588 person-exams with diabetes (mean age 58 +/- 9 years, 56% men), there were 86 CHD events, including 36 deaths. After adjustment for age, sex, and CHD risk factors, the risk of CHD was 1.38 times higher for each 10-year increase in duration of diabetes (95% CI 0.99-1.92), and the risk for CHD death was 1.86 times higher (1.17-2.93) for the same increase in duration of diabetes. CONCLUSIONS: Duration of diabetes increases the risk of CHD death independent of coexisting risk factors. Further research is necessary to understand the pathophysiology of this increased risk.     

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.     

Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease: the Hoorn Study

OBJECTIVE: Measures of baroreflex sensitivity, heart rate variability (HRV), and the classical Ewing test parameters are currently used for the diagnosis of diabetic autonomic neuropathy and for mortality risk stratification after myocardial infarction. However, the strengths of the associations of these measures of autonomic function with risk of mortality have never been compared in one study population. Furthermore, no evidence is available on the possible effect of glucose tolerance on these associations. RESEARCH DESIGN AND METHODS: The study population (n = 605) consisted of a glucose tolerance-stratified sample from a general population (50-75 years of age). Cardiac cycle duration and continuous finger arterial pressure were measured under two conditions: at rest and on metronome breathing. From these readings, seven parameters of autonomic function were assessed (one Ewing, five HRV, and one baroreflex sensitivity). RESULTS: During 9 years of follow-up, 101 individuals died, 43 from cardiovascular causes. Subjects with diabetes and low levels of the autonomic function parameters, indicating impaired autonomic function, had an approximately doubled risk of mortality. This association was consistent, though not statistically significant, for all parameters. The elevated risk was not observed in subjects without diabetes, hypertension, or prevalent cardiovascular disease. CONCLUSIONS: Impaired autonomic function is associated with all-cause and cardiovascular mortality. Moreover, the results of the present study suggest that cardiac autonomic dysfunction in patients already at risk (diabetes, hypertension, or history of cardiovascular disease) may be especially hazardous.     

All-cause mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population

OBJECTIVE: To establish all-cause death rates and life expectancies of and risk factors for mortality in insulin-treated diabetic individuals living in Canterbury, New Zealand. RESEARCH DESIGN AND METHODS: Insulin-treated diabetic subjects (n = 1,008) on the Canterbury Diabetes Registry were tracked over 9 years, and their vital status was determined. Death rates were standardized using direct and indirect methods. Cox proportional hazard regression was used to model the effects of demographic and clinical covariates on survival time. RESULTS: At study entry, age ranged from 2.9 to 92.7 years, with mean 48.7 +/- 20.4 years; age at diagnosis was 0.2-88.9 years, mean 34.5 +/- 20.0 years; and duration of diabetes was 0.1-58.5 years, mean 14.0 +/- 10.6 years. There were 303 deaths in 7,372 person-years of follow-up with a standardized mortality ratio (SMR) of 2.6 (95% CI 2.4-3.0). Relative mortality was greatest for those aged 30-39 years (SMR 9.2 [4.8-16.2]). The death rate for the diabetic cohort standardized against the Segi world standard population was 16.2 per 1,000. Attained age, sex, and clinical subtype were significant predictors of mortality The SMR for subjects with type 1 diabetes and age at onset <30 years was 3.7 (CI 2.7-5.0), 2.2 (1.8-2.6) for those with onset > or =30 years, and 3.1 (2.5-3.7) for subjects suspected of having latent autoimmune diabetes in adulthood or insulin-treated type 2 diabetes. Life expectancy was reduced for both sexes at all ages. CONCLUSIONS: Mortality rates for insulin-treated diabetic individuals remain high, resulting in shortened life spans relative to the general population. Marked differences in mortality exist between clinical groups of subjects. Further research is needed to improve diabetes classification and to clarify differences in health outcomes.     

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.     

Peak expiratory flow rate: relationship to risk variables and mortality: the Wisconsin Epidemiologic Study of diabetic retinopathy.

OBJECTIVE: To examine correlates of peak expiratory flow rate in people with type 1 diabetes and to evaluate the relationship of peak expiratory flow rate to mortality. RESEARCH DESIGN AND METHODS: A cohort study that was originally designed to determine the prevalence, incidence, and severity of diabetic retinopathy also provided the opportunity to measure peak expiratory flow rate. This was first measured at a 10-year follow-up and was evaluated in regard to risk factors for microvascular complications of diabetes. Mortality during 6 years of follow-up after the measurement was also ascertained. RESULTS: In multivariable analysis, peak expiratory flow rate was associated with sex, age, height, BMI, history of cardiovascular disease, pulse rate, duration of diabetes, glycosylated hemoglobin, and end-stage renal disease. Peak expiratory flow rate was significantly associated with survival in categorical analyses. Even after considering age, sex, renal disease, history of cardiovascular disease, respiratory symptoms, duration of diabetes, cigarette smoking, and hypertension, peak expiratory flow rate was still significantly related to survival (hazard ratio 0.61 [95% CI 0.46-0.82]). CONCLUSIONS: These data indicate that peak expiratory flow rate is associated with risk factors for other complications of diabetes. In addition, peak expiratory flow rate is a significant predictor of survival over even a relatively short period of time (6 years) in patients with younger-onset diabetes.     

A prospective cohort study of predictive value of homocysteine in patients with type 2 diabetes and coronary artery disease

BACKGROUND: Little evidence exists on the role of homocysteine as a predictor of mortality in patients with type 2 diabetes. The aim of this study was to investigate whether elevated plasma homocysteine levels are independently associated with all-cause or cardiovascular mortality in patients with type 2 diabetes and coronary artery disease. METHODS: This is a prospective cohort study that included 507 patients with type 2 diabetes and angiographically proven coronary artery disease. Patients were divided into 2 groups according to homocysteine level above or below median value (12.4 micromol/L): the high homocysteine group (255 patients) and the low homocysteine group (252 patients). The primary end-point of the study was all-cause mortality. RESULTS: There were 103 deaths during a 4-year follow-up: 62 deaths in the high homocysteine group and 41 deaths in the low homocysteine group (Kaplan-Meier estimates of mortality 25.6% and 17.4%, respectively (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.03-2.27, P=0.031). Sixty-two of 103 deaths (60.2%) were of cardiovascular origin: 37 deaths (14.5%) occurred in the high homocysteine group and 25 deaths (9.9%) occurred in the low homocysteine group (P=0.115). Cox proportional hazards model showed that plasma homocysteine was not an independent correlate of all-cause (adjusted hazard ratio [HR] 1.10, 95% CI 0.89-1.33; P=0.397 for 5 micromol/L increase in concentration) or cardiovascular (adjusted HR 1.04, 95% CI 0.80-1.36, P=0.753, for 5 micromol/L increase in concentration) mortality. CONCLUSION: In patients with type 2 diabetes and coronary artery disease, elevated level of homocysteine is an associate of increased cardiovascular risk but not an independent predictor of cardiovascular mortality.