Time-dependent impact of diabetes on mortality in patients after major lower extremity amputation: survival in a population-based 5-year cohort in Germany

OBJECTIVE

To estimate the impact of diabetes on mortality in patients after first major lower extremity amputation (LEA).

RESEARCH DESIGN AND METHODS

Using claims data of a nationwide statutory health insurance, we assessed all deaths in a cohort of all 444 patients with a first major LEA since 2005 (71.8% male; mean age 69.1 years; 58.3% diabetic; 43% with amputation above the knee) up to 2009. Using Cox regression, we estimated the time-dependent hazard ratios to compare patients with and without diabetes.

RESULTS

The cumulative 5-year mortality was 68% in diabetic and 59% in nondiabetic individuals. In the first course, mortality was lower in diabetic compared with nondiabetic patients. Later, the diabetes risk increased yielding crossed survival curves after 2 to 3 years (time dependency of diabetes; P = 0.003). Age- and sex-adjusted hazard ratios for diabetes were as follows: 0–30 days: 0.50 [95% CI 0.31–0.84]; 31–60 days: 0.60 [0.25–1.41]; 61 days to 6 months: 0.75 [0.38–1.48]; >6–12 months: 1.27 [0.63–2.53]; >12–24 months: 1.65 [0.88–3.08]; >24–36 months: 2.02 [0.80–5.09]; and >36–60 months: 1.91 [0.70–5.21]. The pattern was similar in both sexes. In the full model, significant risk factors for mortality were age (1.05; 1.03–1.06), amputation above the knee (1.50; 1.16–1.94), and quartile category 3 or 4 of the number of prescribed medications (1.64; 1.12–2.40 and 1.76; 1.20–2.59). Further adjustment for comorbidity did not alter the results.

CONCLUSIONS

In this population-based study, we found a time-dependent mortality risk of diabetes following first major LEA, which may be in part a result of a healthier lifestyle in diabetic patients or the access to specific treatment structures in diabetic individuals.Lower extremity complications, particularly ulceration and amputation, are significant sources of morbidity in the diabetic population. Although the reduction of lower extremity amputation (LEA) in diabetes has frequently been cited as a primary objective by health systems and organizations (1,2), diabetic individuals still have a largely increased LEA risk compared with nondiabetic patients (3,4). Avoidance of amputation should not only be targeted because of the associated economic consequences (high costs because of repeated hospitalizations, rehabilitation, home care, and social-service support) but also because of quality-of-life issues. Alternative treatment options might seem costly in the short term, but most cost-effectiveness analyses that also considered the long-term perspective have concluded that treatment alternatives in which the limb is saved are most cost effective (see Supplementary Ref. 1). Furthermore, diabetes has been considered to be associated with an excess mortality in patients after LEA, in particular in the perioperative period and during the first year (5,6). Some studies found contrasting results, with similar or reduced mortality in diabetic compared with nondiabetic patients (7–11; and Supplementary Refs. 2–4). However, several studies are not population based but use data from specialized diabetes centers or had short follow-up periods. Thus results remain controversial.Hence, the aim of our study was to evaluate the mortality risk in diabetic and nondiabetic individuals after a first major LEA since 2005 up to 2009 in Germany, using claim data of a nationwide statutory health insurance.     

Mortality in diabetic and nondiabetic patients after amputations performed from 1990 to 1995: a 5-year follow-up study

OBJECTIVE: To compare survival rates after first amputation between patients with and without diabetes. RESEARCH DESIGN AAND METHODS: We performed a retrospective study of all nontraumatic amputations performed at our center in the years 1990-1995 in patients with (n = 100) and without (n = 151) diabetes. Survival status was assessed from the first amputation until 31 December 2001. RESULTS: Altogether, 61% of the patients with and 54.3% of those without diabetes died 5.2 (4.5-5.8) and 5.3 (4.7-5.9) [mean (95% CI)] years after the first amputation, respectively (P = 0.80). Survival was not different between patients with and without diabetes after controlling for the level (major versus minor) (P = 0.67) or the cause (ischemia versus infection) of amputation (P = 0.72). No sex differences were found for survival in either study group. Independent predictors of mortality in the diabetic group were duration of diabetes (P = 0.05), history of stroke (P = 0.02), and serum creatinine level (P < 0.0001), while in the nondiabetic group independent predictors were history of stroke (P = 0.04), serum creatinine level (P = 0.005), and higher white blood cell count (P = 0.02). The peak incidence of amputations was observed in the decade of 67-76 years of age in both groups. Major amputations were more common among nondiabetic patients in all age-groups. Median hospital stay and postoperative complications were comparable between the two groups. CONCLUSIONS: All-cause mortality is high after an amputation in both diabetic and nondiabetic patients. Mortality rates, hospital stay, and postoperative complications are not different between diabetic and nondiabetic amputees. No modifiable factors, with the exception of nephropathy, were found to improve survival in amputees. Peripheral vascular disease and neuropathy are the main cause of amputations; prevention, therefore, of these complications is warranted to prevent amputations and the subsequent high mortality.     

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.     

Does diabetes mellitus explain the higher hospital mortality of women with acute myocardial infarction? Results from the Berlin Myocardial Infarction Registry.

BACKGROUND: Women with acute myocardial infarction (AMI) exhibit greater hospital mortality than do men. In general, diabetes mellitus is one of the major factors influencing the outcome of patients with AMI. The aim of this study was to analyze the interaction between diabetes and gender, specifically with regard to the higher hospital mortality of female AMI patients aged < or = 75 years. METHODS: We prospectively collected data from 3,715 patients aged < or = 75 (2,794 men, 921 women) with acute myocardial infarction who were treated in 25 hospitals in Berlin, Germany, from 1999 to 2002. In a multivariate analysis, we specifically studied the interaction between the factors diabetes mellitus and gender in their effects on hospital mortality. RESULTS: After adjustment in multivariate analysis, the interaction between gender and diabetes was statistically significant, and the estimated odds ratios were as follows: female diabetic patients compared with male diabetic patients, odds ratio (OR) = 2.28 (95% confidence interval [CI] 1.42-3.68); female diabetic patients compared with male nondiabetic patients, OR = 2.90 (95% CI 1.90-4.42); and female diabetic patients compared with female nondiabetic patients, OR = 2.92 (95% CI 1.75-4.87). There was no statistically significant difference between the risk of dying for female nondiabetic patients or for male diabetic patients when compared with male nondiabetic patients. CONCLUSIONS: In AMI patients aged < or = 75 years, female gender alone is not an independent predictor of hospital mortality. Detailed, multivariate analysis reveals that specifically diabetic women demonstrate higher hospital mortality than do men. Special attention should be provided to these female diabetic patients.     

Diagnosis of type 2 diabetes at an older age: effect on mortality in men and women

OBJECTIVE: To compare the mortality of people who were diagnosed with type 2 diabetes over 65 years of age with that of nondiabetic individuals. RESEARCH DESIGN AND METHODS: Using a population-based diabetes information system for an observational cohort study in Tayside, Scotland, people who were diagnosed with type 2 diabetes over the age of 65 years between 1993 and 2002 were identified. Nondiabetic comparators, matched for age and sex, were identified from the nondiabetic population. The two cohorts were followed up for mortality and cardiovascular mortality according to death certification records. RESULTS: There were 3,594 people with type 2 diabetes (48% male) and 7,188 matched comparators identified in the study. Over a mean follow-up period of 4.6 +/- 2.9 years for 3,594 people with type 2 diabetes and 7,188 comparators, 909 (25.3%) patients in the diabetic cohort and 1,651 (23.0%) in the nondiabetic cohort died. The adjusted relative risk for mortality in the diabetic cohort compared with the nondiabetic cohort was 1.06 (95% CI 0.94-1.19) for men and 1.29 (1.15-1.45) for women. Cardiovascular deaths accounted for 49.4% of the deaths in people with and 45.2% in those without diabetes (adjusted relative risk 1.01 [0.93-1.10]). CONCLUSIONS: Men diagnosed with type 2 diabetes over the age of 65 years have no excess mortality compared with their nondiabetic counterparts, a finding that was not replicated for women.     

Elevated remnant-like particle cholesterol and triglyceride levels in diabetic men and women in the Framingham Offspring Study

OBJECTIVE: Remnants of triglyceride-rich lipoproteins are thought to be atherogenic. A new antibody-based assay allows for the isolation of remnant-like particles (RLPs) from plasma or serum, and the subsequent measurement of RLP cholesterol (RLPC) and triglycerides (RLPTGs). We hypothesized that diabetic patients would have higher remnant levels than nondiabetic patients. DESIGN AND METHODS: We compared RLPC and RLPTG levels of diabetic subjects (68 women, 121 men) participating in the Framingham Heart Study with those of nondiabetic subjects (1,499 women, 1,357 men). RESULTS: Mean RLPC values for diabetic women were 106% higher than those for nondiabetic women (0.367 +/- 0.546 mmol/l [14.2 +/- 21.1 mg/dl] vs. 0.179 +/- 0.109 mmol/l [6.9 +/- 4.2 mg/dl]; P < 0.0001), and RLPTG values for diabetic women were 385% higher than those for nondiabetic women (1.089 +/- 2.775 mmol/l [93.1 +/- 245.6 mg/dl] vs. 0.217 +/- 0.235 mmol/l [19.2 +/- 20.8 mg/dl]; P < 0.0001). Similar but less striking differences were observed in diabetic men, who had mean RLPC values 28% higher than those seen in nondiabetic men (0.285 +/- 0.261 mmol/l [11.0 +/- 10.1 mg/dl] vs. 0.223 +/- 0.163 mmol/l [8.6 +/- 6.3 mg/dl]; P < 0.001) and mean RLPTG values 70% higher than those seen in nondiabetic men (0.606 +/- 1.019 mmol/l [53.6 +/- 90.2 mg/dl] vs. 0.357 +/- 0.546 mmol/l [31.6 +/- 48.3 mg/dl]; P < 0.001). Moreover, diabetic men and women had significantly higher total triglycerides and lower HDL cholesterol levels than nondiabetic subjects. CONCLUSIONS: The data indicate that RLP particles are elevated in diabetic subjects. To achieve optimal reduction of risk for cardiovascular disease, treatment of elevated RLP values, along with the control of LDL cholesterol levels, should be considered.     

Diabetes is an independent risk factor for in-hospital mortality from acute spontaneous intracerebral hemorrhage

OBJECTIVE: We tested the hypothesis that diabetes is an independent determinant of outcome after intracerebral hemorrhage (ICH). RESEARCH DESIGN AND METHODS: This was a hospital-based prospective study The setting was an acute care 350-bed hospital in the city of Barcelona, Spain. Spontaneous ICH was diagnosed in 229 (11%) of 2,000 consecutive stroke patients included in a prospective stroke registry during a 10-year period. Main outcome measures were frequency of demographic variables, risk factors, clinical events, neuroimaging data, and outcome in ICH patients with and without diabetes. Variables related to vital status at discharge (alive or dead) in the univariate analysis plus age were studied in 4 logistical regression models. RESULTS: A total of 35 patients (15.3%) had diabetes. The overall in-hospital mortality rate was 54.3% in the diabetic group and 26.3% in the nondiabetic group (P < 0.001). Previous cerebral infarction, altered consciousness, sensory symptoms, cranial nerve palsy, multiple topography of the hematoma, intraventricular hemorrhage, and infectious complications were significantly more frequent in diabetic patients than in nondiabetic patients. The presence of diabetes was a significant predictive variable in the model based on demographic variables and cardiovascular risk factors (odds ratio 2.98 [95% CI 1.37-6.46]) and in the models based on these variables plus clinical variables (5.76 [2.01-16.51]), neuroimaging variables (5.59 [1.87-16.691), and outcome data (6.10 [2.04-18.291). CONCLUSIONS: Diabetes is an independent determinant of death after ICH. ICH in diabetic individuals presents some different clinical features compared with ICH in nondiabetic patients.     

Effect of diabetes on the mortality risk of cardiogenic shock in a community-based population

OBJECTIVE: To examine the mortality of diabetic vs nondiabetic patients with anterior myocardial infarction (AMI) among the subsets of this population who did and did not develop cardiogenic shock. PATIENTS AND METHODS: The study population consisted of a consecutive series of 1263 Olmsted County, Minnesota, patients admitted to the coronary care unit at the Mayo Clinic in Rochester, Minn, between January 1, 1988, and July 31, 2000. Of these patients, 73 met the criteria for cardiogenic shock during their hospitalization. In-hospital and postadmission mortality were compared between diabetic and nondiabetic patients within the cardiogenic shock and nonshock patient groups, respectively. RESULTS: In patients with AMI and cardiogenic shock, diabetes was associated with a trend for increased in-hospital mortality (odds ratio, 2.82; 95% confidence interval [CI], 0.90-9.92; P = .08). In 73 patients with cardiogenic shock, estimated survival at 1, 3, and 5 years was 25%, 17%, and 17%, respectively, for diabetic patients, and 50%, 44%, and 36%, respectively, for nondiabetic patients (P = .046). The association between diabetic patients and increased long-term mortality was stronger in patients with cardiogenic shock than in patients without cardiogenic shock (adjusted relative risk, 2.08; 95% CI, 1.11-3.90; P = .02). In diabetic patients without cardiogenic shock, estimated survival at 1, 3, and 5 years was low, at 75%, 61%, and 45%, respectively, compared with 83%, 76%, and 69%, respectively, for nondiabetic patients (adjusted relative risk, 1.29; 95% CI, 1.02-1.62; P = .03). CONCLUSION: The presence of diabetes as a comorbidity in patients with AMI appears to be associated with increased mortality compared with nondiabetic patients, and this relationship may be potentially magnified in patients who develop cardiogenic shock.     

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.     

Prevalence and mortality of acute myocardial infarction in patients with diabetes

The purpose of this study was to investigate if insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) predispose to the development of acute myocardial infarction (AMI) and modify the prognosis. The study includes 832 AMI patients consecutively hospitalized over a 3-yr period. The prevalence of diabetes mellitus among the AMI patients was 9.7% and is significantly higher than in an age-matched population, where it is 6.1% (P less than 0.001). The prevalence of diabetes was higher for women than for men (14.9% versus 7.6%). The risk of AMI was found to be twice as high among IDDM than among nondiabetic patients (P less than 0.001). Men with NIDDM were not found to have a significantly higher risk of AMI (P greater than 0.1), but the risk of AMI in women with NIDDM was approximately doubled (P less than 0.01). During the first month following AMI the mortality rate for nondiabetic patients was 20.2% compared with 42.0% for diabetic patients (P less than 0.001). Insulin treatment in NIDDM was associated with a reduced mortality rate compared with treatment with oral agents (P less than 0.05). The mortality rate was significantly higher in patients with poor metabolic control compared with patients in good control, whether before AMI or at the time of hospitalization. Diabetic patients had a higher risk of developing cardiogenic shock and conduction disorders than nondiabetic patients. We conclude that diabetes mellitus disposes to AMI and that the mortality rate of AMI is significantly increased among diabetic patients. Poor metabolic regulation of the diabetes may aggravate the prognosis for AMI.     

High risk of cardiovascular disease in patients with type 1 diabetes in the U.K.: a cohort study using the general practice research database

OBJECTIVE: To estimate the absolute and relative risk of cardiovascular disease (CVD) in patients with type 1 diabetes in the U.K. RESEARCH DESIGN AND METHODS: Subjects with type 1 diabetes (n = 7,479) and five age- and sex-matched subjects without diabetes (n = 38,116) and free of CVD at baseline were selected from the General Practice Research Database (GPRD), a large primary care database representative of the U.K. population. Incident major CVD events, comprising myocardial infarction, acute coronary heart disease death, coronary revascularizations, or stroke, were captured for the period 1992-1999. RESULTS: The hazard ratio (HR) for major CVD was 3.6 (95% CI 2.9-4.5) in type 1 diabetic men compared with those without diabetes and 7.7 (5.5-10.7) in women. Increased HRs were found for acute coronary events (3.0 and 7.6 in type 1 diabetic men and women, respectively, versus nondiabetic subjects), coronary revascularizations (5.0 in men, 16.8 in women), and for stroke (3.7 in men, 4.8 in women). Type 1 diabetic men aged 45-55 years had an absolute CVD risk similar to that of men in the general population 10-15 years older, with an even greater difference in women. CONCLUSIONS: Despite advances in care, these data show that absolute and relative risks of CVD remain extremely high in patients with type 1 diabetes. Women with type 1 diabetes continue to experience greater relative risks of CVD than men compared with those without diabetes.     

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.     

Treatment disparities in the care of patients with and without diabetes presenting with non-ST-segment elevation acute coronary syndromes

OBJECTIVE: The objective of this study was to characterize treatment patterns among patients with diabetes presenting with non-ST-segment elevation (NSTE) acute coronary syndromes (ACSs). RESEARCH DESIGN AND METHODS: We compared adherence to treatment recommendations from the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for NSTE ACS among 46,410 patients from 413 U.S. hospitals that were included in the Can Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) quality improvement initiative. Patients were stratified as nondiabetic, non-insulin-dependent diabetic (type 2 diabetic), and insulin-treated diabetic. RESULTS: Insulin-treated diabetic patients were less likely than nondiabetic patients to receive aspirin (adjusted odds ratio 0.83 [95% CI 0.74-0.93]), beta-blockers (0.89 [0.83-0.96]), heparin (0.90 [0.83-0.98]), and glycoprotein IIb/IIIa inhibitors (0.86 [0.79-0.93]). Type 2 diabetic patients were treated similarly to nondiabetic patients. After adjustment for differences in clinical characteristics, insulin-treated diabetic patients were significantly less likely than nondiabetic patients to receive cardiac catheterization within 48 h of presentation (0.80 [0.74-0.86]) or percutaneous coronary intervention (0.87 [0.82-0.94]). Compared with nondiabetic patients, insulin-treated diabetic and type 2 diabetic patients were more likely to undergo coronary artery bypass grafting (1.34 [1.21-1.49] and 1.35 [1.26-1.44]). In-hospital mortality rates were higher in insulin-treated diabetic (6.8%) and type 2 diabetic (5.4%) than in nondiabetic (4.4%) patients. CONCLUSIONS: Diabetic patients have a higher risk of mortality than nondiabetic patients, yet physicians adhere to the ACC/AHA NSTE ACS guidelines less often when treating diabetic patients, particularly insulin-treated diabetic patients. Increased use of guideline-recommended therapies and early invasive management strategies in diabetic patients may improve their outcomes.     

Mortality and causes of death in a national sample of diabetic patients in Taiwan

OBJECTIVE: To determine the mortality rate, causes of death, and standardized mortality ratio (SMR) in Taiwanese diabetic patients. RESEARCH DESIGN AND METHODS: A cohort of 256036 diabetic patients (118855 men and 137181 women, aged 61.2 +/- 15.2 years) using the National Health Insurance were assembled during the years 1995-1998 and followed up to the end of 2001. Deaths were verified by indexing to the National Register of Deaths. Underlying causes of death were determined from death certificates coded according to the ninth revision of the International Classification of Diseases. The general population of Taiwan was used as reference for SMR calculation. RESULTS: With a total of 1124348.4 person-years of follow-up, 43888 patients died and the crude mortality rate was 39.0/1000 person-years. Mortality rates increased with age, and diabetic men had a significantly higher risk of death than women. However, mortality rate ratio for men versus women attenuated with increasing age. The overall SMR was 1.63 (1.62-1.65), and SMRs also attenuated in the elderly. Causes of death ascribed to diabetes; cancer; cardiopulmonary disease; stroke; disease of arteries, arterioles, and capillaries; nephropathy; infection; digestive diseases; accidents; and suicide were 28.8, 18.5, 9.0, 10.5, 0.3, 4.8, 6.4, 7.9, 3.2, and 0.8%, respectively. CONCLUSIONS: Approximately 71.2% of the diabetes-related deaths would not be ascribed to diabetes on death certificates in Taiwan. The diabetic men have higher risk of dying than women, and diabetic patients have excess mortality when compared with the general population. For underlying causes of death not listed as diabetes, total cardiovascular death, including cardiopulmonary disease, stroke, and disease of arteries, arterioles, and capillaries, is the most common cause of death, followed by cancer.     

Age-related macular degeneration in newly diagnosed type 2 diabetic patients and control subjects: a 10-year follow-up on evolution, risk factors, and prognostic significance

OBJECTIVE: To investigate the evolution of visual acuity, age-related macular degeneration (AMD), and its relation to 10-year cardiovascular mortality and risk factors in patients with newly diagnosed type 2 diabetes and control subjects. RESEARCH DESIGN AND METHODS: A 10-year prospective study consisting of a representative group of 133 (70 men, 63 women) newly diagnosed type 2 diabetic patients diagnosed at health centers between 1979 and 1981 and 144 (62 men, 82 women) nondiabetic control subjects recruited from the population register was performed. The frequency of AMD was determined by grading of 45 degrees stereoscopic fundus photographs. The subjects were studied at baseline and after 5 and 10 years. RESULTS: By the 10-year follow-up, visual acuity had declined more markedly in the diabetic patients than in the control subjects. Although the frequency of AMD was nearly the same in both groups (11-19%), it decreased visual acuity earlier in the diabetic patients than in the control group. AMD at baseline predicted 10-year cardiovascular mortality independently of adjustment for other risk factors in the diabetic patients (odds ratio [95% CI] 4.7 [1.1-19.3], P = 0.033). CONCLUSIONS: Visual acuity deteriorated earlier in newly diagnosed type 2 diabetic patients than in the control group although the cross-sectional frequency of AMD was nearly the same in both groups. Interestingly, AMD was an independent risk factor for cardiovascular mortality in type 2 diabetic patients, but the background mechanism(s) behind this association is unknown.     

Recent trends in cardiovascular complications among men and women with and without diabetes

OBJECTIVE: To compare recent trends in cardiovascular disease (CVD) outcomes among men and women with diabetes with those in the nondiabetic population. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using provincial health claims data to identify adults with (n = 670,602) and without (n = 9,190,721) diabetes living in Ontario, Canada, between 1 April 1992 and 31 March 2000. We compared changes in the annual age-/sex-adjusted rates and numbers of subjects admitted for acute myocardial infarction (AMI) and stroke and of deaths from AMI, stroke, and all causes between those with and without diabetes. RESULTS: Over the 8-year period, the rate of patients admitted for AMI and stroke fell to a greater extent in the diabetic than the nondiabetic population (AMI: -15.1 vs. -9.1%, P < 0.0001; stroke: -24.2 vs. 19.4%, P < 0.0001). Diabetic patients experienced similar reductions in case-fatality rates related to AMI and stroke than those without diabetes (-44.1 vs. -33.2%, P = 0.1; -17.1 vs. -16.6%, P = 0.9, respectively). Declines in all-cause mortality were also comparable in the two populations. Over the same period, the number of diabetes cases increased from 405,471 to 670,602. Thus, while CVD rates fell, the number of events occurring in this population rose substantially (AMI: +44.6%, stroke: +26.1%, AMI deaths: +17.2%, and stroke deaths: +13.2%). CONCLUSIONS: Our findings demonstrate a significant reduction in the rate of people affected by CVD within the diabetic population. However, as the number of people with diabetes rises, so may the absolute burden of CVD in our society.     

Awareness and treatment of dyslipidemia in young adults with type 1 diabetes

OBJECTIVE: Dyslipidemia is a preventable major risk factor for coronary heart disease (CHD). Despite an increased risk of CHD in type 1 diabetes, little is known concerning awareness and adequacy of dyslipidemia treatment in this population. In this report, we describe the prevalence of dyslipidemia and adequacy of pharmacological treatment in patients with type 1 diabetes and comparable nondiabetic subjects. RESEARCH DESIGN AND METHODS: From 2000 to 2002, the Coronary Artery Calcification in Type 1 Diabetes study obtained fasting lipid profiles in 1,416 individuals aged 19-56 years with no history of CHD: 652 type 1 diabetic patients (46% men, mean age 37 +/- 9 years) and 764 nondiabetic control subjects (50% men, mean age 39 +/- 9 years). These data combined with patient questionnaire results were used to determine prevalence of dyslipidemia and adequacy of pharmacological treatment. For all subjects, dyslipidemia was defined using National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: Type 1 diabetic subjects had significantly less dyslipidemia than nondiabetic control subjects (47 vs. 58%, P < 0.001), and a higher percentage of those with abnormal lipids were aware of (52 vs. 34%, P < 0.0001), on medication for (36 vs. 9%, P < 0.0001), and in control of their lipid levels (15 vs. 1.4%, P < 0.001). Of those on treatment, control was achieved in 41% of type 1 diabetic subjects and 15% of nondiabetic participants (P < 0.01). CONCLUSIONS: Dyslipidemia, a major risk factor for CHD, remains largely undiagnosed and undertreated in high-risk populations, such as patients with type 1 diabetes.     

Diabetes and cause-specific mortality in a prospective cohort of one million u.s. Adults

OBJECTIVE Diabetes is a major predictor of death from heart disease and stroke; its impact on nonvascular mortality, including specific cancers, is less understood. We examined the association of diabetes with cause-specific mortality, including deaths from specific cancers. RESEARCH DESIGN AND METHODS A prospective cohort of 1,053,831 U.S. adults, without cancer at baseline, enrolled in the Cancer Prevention Study-II in 1982 and was followed for mortality until December 2008. At baseline, participants completed a self-administered questionnaire that included information on diabetes, smoking, physical activity, height, and weight. Multivariable-adjusted relative risks (RRs) (95% CI) were estimated using Cox proportional hazards regression. RESULTS During 26 years of follow-up, 243,051 men and 222,109 women died. In multivariable models that controlled for age, BMI, and other variables, diabetes was associated with higher risk of all-cause mortality (women RR 1.90 [95% CI 1.87-1.93]; men 1.73 [1.70-1.75]). Among women, diabetes was associated with higher risk of death from cancers of the liver (1.40 [1.05-1.86]), pancreas (1.31 [1.14-1.51]), endometrium (1.33 [1.08-1.65]), colon (1.18 [1.04-1.33]), and breast (1.16 [1.03-1.29]). Among men, diabetes was associated with risk of death from cancers of the breast (4.20 [2.20-8.04]), liver (2.26 [1.89-2.70]), oral cavity and pharynx (1.44 [1.07-1.94]), pancreas (1.40 [1.23-1.59]), bladder (1.22 [1.01-1.47]), colon (1.15 [1.03-1.29]), and (inversely) prostate (0.88 [0.79-0.97]). Diabetes was also associated with higher risks of death involving the circulatory system, respiratory system, digestive system, genitourinary system, and external causes/accidental deaths. CONCLUSIONS Diabetes is associated with higher risk of death for many diseases, including several specific forms of cancer.     

Sex differences in the prognostic importance of diabetes in patients with ischemic heart disease undergoing coronary angiography

OBJECTIVE: Women with ischemic heart disease have poorer outcomes than men and are suggested to have greater risk associated with diabetes. We evaluated the prognosis associated with diabetes, in analyses stratified by sex, to determine whether similar differences are seen in a large unselected cohort of patients. RESEARCH DESIGN AND METHODS: Using the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), a clinical data collection and follow-up initiative capturing all patients undergoing cardiac catheterization in Alberta, Canada, the relative significance of diabetes on long-term survival in 13152 men and 4249 women was evaluated in patients presenting with or without myocardial infarction and according to first treatment received. RESULTS: The 1-year mortality rates were 4.7% and 6.8% in men and women (P < 0.001), 4.1% and 7.4% in nondiabetic and diabetic men (P < 0.001), and 5.8% and 9.6% in nondiabetic and diabetic women, respectively (P < 0.001). The risk-adjusted Cox proportional hazard ratios associated with diabetes in myocardial infarction were 1.03 in men and 1.20 in women. The diabetes hazard ratios for percutaneous coronary intervention were 1.28 in men and 1.40 in women, 1.23 in men and 1.32 in women for bypass surgery, and 1.26 in men and 1.31 in women for medical therapy (P = NS for all diabetes hazard ratio comparisons between men and women). CONCLUSIONS: Hazard ratios quantifying the adverse prognosis associated with diabetes in patients undergoing angiography are consistently higher among women than men, but the differences across sexes are not statistically significant. These slight sex differences noted in the APPROACH registry are similar to previously reported findings and may be clinically important.