Retinopathy predicts cardiovascular mortality in type 2 diabetic men and women

OBJECTIVE: To investigate the association of retinopathy with the risk of all-cause, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality in type 2 diabetic subjects in a population-based 18-year follow-up study with particular emphasis on sex differences. RESEARCH DESIGN AND METHODS: Our study cohort comprised 425 Finnish type 2 diabetic men and 399 type 2 diabetic women who were free of CVD at baseline. The findings were classified based on standardized clinical ophthalmoscopy to categories of no retinopathy, background retinopathy, and proliferative retinopathy. The study end points were all-cause, CVD, and CHD mortality. RESULTS: Adjusted Cox model hazard ratios (95% CIs) of all-cause, CVD, and CHD mortality in men were 1.34 (0.98-1.83), 1.30 (0.86-1.96), and 1.18 (0.74-1.89), respectively, for background retinopathy and 3.05 (1.70-5.45), 3.32 (1.61-6.78), and 2.54 (1.07-6.04), respectively, for proliferative retinopathy and in women 1.61 (1.17-2.22), 1.71 (1.17-2.51), and 1.79 (1.13-2.85), respectively, for background retinopathy and 2.92 (1.41-6.06), 3.17 (1.38-7.30), and 4.98 (2.06-12.06), respectively, for proliferative retinopathy. CONCLUSIONS: Proliferative retinopathy in both sexes and background retinopathy in women predicted all-cause, CVD, and CHD death. These associations were independent of current smoking, hypertension, total cholesterol, HDL cholesterol, glycemic control of diabetes, duration of diabetes, and proteinuria. This suggests the presence of common background pathways for diabetic microvascular and macrovascular disease other than those included in the conventional risk assessment of CVD. The sex difference observed in the association of background retinopathy with macrovascular disease warrants closer examination.     

All-cause and cardiovascular mortality among diabetic participants in the San Antonio Heart Study: evidence against the "Hispanic Paradox"

OBJECTIVE: The observation that Hispanics have lower all-cause and cardiovascular mortality, despite increased diabetes and obesity, lower socioeconomic status (SES), and barriers to health care, has been termed the "Hispanic Paradox." We examined the relationship between ethnicity and all-cause and cardiovascular mortality in Mexican Americans (MAs) and non-Hispanic whites (NHWs) with diabetes. RESEARCH DESIGN AND METHODS: In the San Antonio Heart Study, a prospective cohort, we compared the mortality in 554 U.S.-born MAs, 95 Mexico-born MAs, and 178 NHW participants with diabetes aged 25-72 years. Over an average of 10.4 years, 188 deaths occurred: 115 from cardiovascular disease (CVD) [death certificate ICD-9 codes 401-414 or 420-447 (excluding 427.5)]. Because of potential differences between migrants and nonmigrants, hazard ratios (HRs) were calculated comparing U.S.-born MAs and Mexico-born MAs with NHWs. RESULTS: The age- and sex-adjusted HR for all-cause mortality comparing U.S.-born MAs with NHWs was 1.66 (95% CI 1.15-2.40), while comparing Mexico-born MAs with NHWs was 1.14 (95% CI 0.63-2.06). Cardiovascular mortality HRs were 1.66 (95% CI 1.04-2.65) and 0.89 (95% CI 0.40-2.01), respectively. After adjusting for possible confounders, such as fasting glucose and diabetes duration, the hazard of all-cause and cardiovascular mortality (although not statistically significant) appeared higher in U.S.-born MAs than in the other two groups. CONCLUSIONS: We found it important to differentiate MAs by birthplace. Among diabetic participants, contrary to the prediction of the "Hispanic Paradox," compared with NHWs, U.S.-born MAs were at greater risk of all-cause and cardiovascular mortality, while Mexico-born MAs appeared to be at similar risk.     

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.     

Heart rate recovery following maximal exercise testing as a predictor of cardiovascular disease and all-cause mortality in men with diabetes

OBJECTIVE: Heart rate recovery (HRR) is an independent prognostic indicator for cardiovascular disease (CVD) and all-cause mortality in healthy men. We examined the association of HRR to CVD-related and all-cause mortality in men with diabetes. RESEARCH DESIGN AND METHODS: In this cohort study we examined 2,333 men with documented diabetes (mean age 49.4 years) that had baseline 5-min HRR measurement following maximal exercise (heart rate(peak) - heart rate(5 min of recovery)) at The Cooper Clinic, Dallas, TX. We identified HRR quartiles as quartile 1 <55, quartile 2 55-66, quartile 3 67-75, and quartile 4 >75 bpm. Hazard ratios (HRs) for cardiovascular and all-cause death were adjusted for age, cardiorespiratory fitness, resting heart rate, fasting blood glucose, BMI, smoking habit, alcohol consumption, total cholesterol, triglyceride, and history of CVD at baseline. RESULTS: During a median of 14.9 years follow-up, there were 142 deaths that were considered CVD related and 287 total deaths. Compared with men in the highest quartile of HRR, adjusted HRs in the first, second, and third quartiles were 2.0 (95% CI 1.1-3.8), 1.5 (0.8-2.7), and 1.5 (0.9-2.8), respectively, for cardiovascular death (P for trend < 0.001). Similarly, for all-cause death, adjusted HRs in the first, second, and third quartiles were 2.0 (1.3-3.2), 1.5 (1.0-2.3), and 1.5 (1.1-2.3) (P for trend < 0.001). CONCLUSIONS: Among men with diabetes, a decreased HRR, even measured as long as 5 min after recovery, was independently predictive of cardiovascular and all-cause death.     

Proinsulin concentration is an independent predictor of all-cause and cardiovascular mortality: an 11-year follow-up of the Hoorn Study

OBJECTIVE: High proinsulin concentration may be a better predictor for cardiovascular disease (CVD) mortality than insulin concentration. Previous observations may have been confounded by glucose tolerance status or lack of precision because of high intraindividual variability. We investigated the longitudinal relation of means of duplicate measurements of insulin and proinsulin with all-cause and CVD mortality in a population-based cohort taking glucose tolerance status into account. RESEARCH DESIGN AND METHODS: Fasting and post-75-g glucose-load (2-h) glucose, insulin, and proinsulin values were determined in duplicate on separate days in 277 participants with normal glucose metabolism, 208 participants with impaired glucose metabolism, and 119 newly detected patients with type 2 diabetes of the Hoorn Study. Insulin resistance and beta-cell function were estimated by homeostasis model assessment (HOMA-IR and HOMA-B, respectively), and the fasting proinsulin-to-insulin ratio was calculated. Subjects were followed with respect to mortality until January 2003. RESULTS: Fasting proinsulin levels were significantly associated with all-cause and CVD mortality. The hazard ratios (HRs) per increase in interquartile range adjusted for age and sex were 1.21 (95% CI 1.04-1.42) for all-cause mortality and 1.33 (1.06-1.66) for CVD mortality. Adjustment for glucose tolerance status and HOMA-IR did not substantially change the associations. CONCLUSIONS: Fasting proinsulin was associated with all-cause and CVD mortality, independent of glucose tolerance status and insulin resistance and largely independent of other CVD risk factors. Proinsulin might play a role in the relationship between insulin resistance and CVD.     

Postchallenge hyperglycemia and mortality in a national sample of U.S. adults

OBJECTIVE: Although postchallenge hyperglycemia is a well-established feature of type 2 diabetes, its association with risk of mortality is uncertain. Therefore, the aim of this study was to assess the independent association of fasting and 2-h glucose levels with all-cause and cardiovascular disease (CVD) mortality. RESEARCH DESIGN AND METHODS: We analyzed data from the Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study, a prospective cohort study of U.S. adults examined in the NHANES II, and focused on the 3,092 adults aged 30-74 years who underwent an oral glucose tolerance test at baseline (1976-1980). Deaths were identified from U.S. national mortality files from 1976 to 1992. To account for the complex survey design, we used SUDAAN statistical software for weighted analysis. RESULTS: Compared with their normoglycemic counterparts (fasting glucose [FG] < 7.0 and 2-h glucose < 7.8 mmol/l), adults with fasting and postchallenge hyperglycemia (FG > or =7.0 and 2-h glucose > or =11.1 mmol/l) had a twofold higher risk of death after 16 years of follow-up (age- and sex-adjusted relative hazard [RH] 2.1, 95% CI 1.4-3.2). However, adults with isolated postchallenge hyperglycemia (FG < 7.0 and 2-h glucose > or =11.1 mmol/l) were also at higher risk of death (1.6, 1.0-2.6). In proportional hazards analysis, FG (fully adjusted RH 1.10 per 1 SD; 95% CI 1.01, 1.22) and 2-h glucose (1.14, 1.00-1.29) showed nearly identical predictive value for mortality. Similar trends were observed for CVD mortality. CONCLUSIONS: These results suggest that postchallenge hyperglycemia is associated with increased risk of all-cause and CVD mortality independently of other CVD risk factors.     

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.     

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.     

Cardiovascular effects of dipeptidyl peptidase-4 inhibitor in diabetic patients with and without established cardiovascular disease: a meta-analysis and systematic review

Objectives: We aim to conduct a meta-analysis, by stratifying diabetic patients with or without clinical cardiovascular diseases (CVD), to explore whether there are different cardiovascular effects of dipeptidyl peptidase-4 inhibitors (DPP-4is) on these two different classes of diabetic patients.

Methods: We searchedMedline,Embase, theCochrane Libraryand ClinicalTrials.gov for relevant randomized controlled trials (RCTs). The included trials are divided into CVD (+) trials (subjects with established CVD), and CVD (-) trials (subjects with no CVD). We use all-cause mortality and cardiovascular outcomes as primary endpoints.

Results: (1) Three CVD (+) trials were included and 36,895 subjects were enrolled with a mean follow-up duration of 127.1 weeks. The pooled results showed that DPP-4is treatment, compared with the placebo, did not significantly affect all-cause mortality (RR, 1.03; 95% CI, 0.95 to 1.11), cardiovascular death (1.01, 0.91 to 1.12), myocardial infarction (0.98, 0.88 to 1.08) or stroke (1.02, 0.88 to 1.18) in diabetic patients with coexisting CVD history; however, it significantly increased the risk of heart failure (1.14, 1.01 to 1.27) in this population. 2) Thirty-five CVD (-) trials were included, and 29,600 patients were enrolled with a mean follow-up duration of 77.8 weeks. The analysis comparing DPP-4is with the placebo control showed that DPP-4is treatment did not significantly affect the risk of all-cause mortality or cardiovascular outcomes in diabetic patients free of CVD history. However, when compared with the active control, the pooling data showed that DPP-4is had a significant reduction on the risk of stroke (0.58, 0.34 to 0.99) but did not significantly affect the risk of all-cause mortality and other cardiovascular outcomes.

Conclusion: DPP-4is may have no cardiovascular protective effects in diabetic patients with coexisting CVD, while there is a lack of definitive evidence supporting the cardiovascular benefits of DPP-4is treatment among diabetic patients free of CVD history.     

Associations of Type 2 Diabetes Onset Age With Cardiovascular Disease and Mortality: The Kailuan Study

OBJECTIVEWe aimed to explore the associations between type 2 diabetes onset age and cardiovascular disease (CVD) and all-cause mortality in the Chinese population.RESEARCH DESIGN AND METHODSThis study included 101,080 participants free of prevalent diabetes and CVD at baseline from the Kailuan Study. All participants were monitored biennially until 31 December 2017. During follow-up, 11,384 participants were diagnosed as having type 2 diabetes. For each case subject, one control subject was randomly selected, matched for age (± 1 years) and sex. The final analysis comprised 10,777 case-control pairs. Weighted Cox regression models were used to evaluate the average hazard ratios (AHRs) and 95% CIs of incident CVD and all-cause mortality among patients with new-onset type 2 diabetes versus control subjects across age-groups.ResultsDuring a median follow-up of 5.57 years, 1,794 incident events (907 CVD events, of which there were 725 strokes and 887 deaths) occurred. After adjustment for potential confounders, participants with type 2 diabetes diagnosed at age <45 years had the highest relative risks of CVD and all-cause mortality relative to the matched control subjects, with AHRs of 3.21 (95% CI 1.18–8.72) for CVD, 2.99 (95% CI 1.01–9.17) for stroke, and 4.79 (95% CI 1.95–11.76) for all-cause mortality. The risks gradually attenuated with each decade increase in type 2 diabetes onset age.CONCLUSIONSThe relative risks of CVD and all-cause mortality differed across type 2 diabetes onset age-groups, and the associations were more evident in younger-onset type 2 diabetes.     

Plant-Based Diets and All-cause and Cardiovascular Mortality in a Nationwide Cohort in Spain: The ENRICA Study

ObjectiveTo investigate the associations of a healthful plant-based diet index (hPDI) and an unhealthful plant-based diet index (uPDI) with all-cause and cardiovascular disease (CVD) mortality in Spanish adults.Patients and MethodsWe analyzed data from 11,825 individuals 18 years of age or older, representative of the Spanish population, recruited between 2008 and 2010 and followed-up to 2020. Food consumption was collected at baseline using a validated dietary history, which served to calculate two plant-based diet indices based on 18 major food groups (range, 18-90 points). For (1) hPDI only the consumption of healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea/coffee) received positive scores; whereas for (2) uPDI, only the consumption of less healthy plant foods (fruit juices, sugar-sweetened beverages, refined grains, potatoes, and sweets/desserts) received positive scores. Multivariable-adjusted Cox models were used to estimate HRs and their 95% CIs.ResultsAfter a median follow-up of 10.9 and 9.8 years, 699 all-cause and 157 CVD deaths were ascertained, respectively. Each 10-point increase in hPDI was associated with 14% lower risk of all-cause death (HR, 0.86; 95% CI, 0.74 to 0.99), and 37% lower risk of CVD death (HR, 0.63; 95% CI, 0.46 to 0.85). No significant associations were found for uPDI.ConclusionHigher adherence to an hPDI diet, but not to a uPDI, was associated with lower all-cause and CVD mortality. This suggests that the quality of the plant food consumed is paramount to achieve diet-related benefits in mortality.Trial registrationclinicaltrials.gov Identifier: NCT02804672     

Association of Combined Healthy Lifestyles With Cardiovascular Disease and Mortality of Patients With Diabetes: An International Multicohort Study

ObjectiveTo prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes.Patients and MethodsPatients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health–AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non–current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020.ResultsA total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses.ConclusionThe international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.     

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.     

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.     

Ethnicity, race, and baseline retinopathy correlates in the veterans affairs diabetes trial

OBJECTIVE: The Veterans Affairs Diabetes Trial (VADT) cohort is enriched with approximately 20% Hispanics and 20% African Americans, affording a unique opportunity to study ethnic differences in retinopathy. RESEARCH DESIGN AND METHODS: Cross-sectional analyses on the baseline seven-field stereo fundus photos of 1,283 patients are reported here. Diabetic retinopathy scores are grouped into four classes of increasing severity: none (10-14), minimal nonproliferative diabetic retinopathy (NPDR) (15-39), moderate to severe NPDR (40-59), and proliferative diabetic retinopathy (60+). These four groups have also been dichotomized to none or minimal (10-39) and moderate to severe diabetic retinopathy (40+). RESULTS: The prevalence of diabetic retinopathy scores >40 was higher for Hispanics (36%) and African Americans (29%) than for non-Hispanic whites (22%). The difference between Hispanics and non-Hispanic whites was significant (P < 0.05). Similarly, the prevalence of diabetic retinopathy scores >40 was significantly higher in African Americans than in non-Hispanic whites (P < 0.05). These differences could not be accounted for by an imbalance in traditional risk factors such as age, duration of diagnosed diabetes, HbA(1c) (A1C), and blood pressure. Diabetic retinopathy severity scores were also significantly associated with increasing years of disease duration, A1C, systolic and diastolic blood pressure, the degree of microalbuminuria, fibrinogen, and the percentage of patients with amputations. There was no relationship between retinopathy severity and the percentage of people who had strokes or cardiac revascularization procedures. There was an inverse relationship between retinopathy severity and total cholesterol, triglycerides, and plasminogen activator inhibitor-1 as well as with smoking history. Diabetic retinopathy scores were not associated with age. CONCLUSIONS: In addition to many well-known associations with retinopathy, a higher frequency of severe diabetic retinopathy was found in the Hispanic and African-American patients at entry into the VADT that is not accounted for by traditional risk factors for diabetic retinopathy, and these substantial ethnic differences remain to be explained.     

Plasma insulin and all-cause, cardiovascular, and noncardiovascular mortality: the 22-year follow-up results of the Helsinki Policemen Study

OBJECTIVE: To investigate the association of plasma insulin with all-cause, cardiovascular, and noncardiovascular mortality. RESEARCH DESIGN AND METHODS: We studied 22-year mortality data from the Helsinki Policemen Study The study population comprised 970 men, 34-64 years of age, who were free of coronary heart disease, other cardiovascular disease, and diabetes. Area under the insulin response curve (AUC insulin) during an oral glucose tolerance test was used to reflect plasma insulin levels. RESULTS: During the follow-up period, 276 men died: 130 from cardiovascular and 146 from noncardiovascular causes. The hazard ratio (HR) for hyperinsulinemia (highest AUC insulin quintile vs. combined lower quintiles) with regard to all-cause mortality adjusting for age, was 1.94 (95% CI 1.20-3.13) during the first 10 years of the follow-up period and 1.51 (1.15-1.97) during the entire 22 years; adjusting for other risk factors, the HR was 1.88 (1.08-3.30) and 1.37 (1.00-1.87) during 10 and 22 years, respectively The corresponding HRs for cardiovascular mortality during 10 and 22 years were 2.67 (1.35-5.29) and 1.73 (1.19-2.53), respectively, for age-adjusted and 2.30 (1.03-5.12) and 1.39 (0.90-2.15), respectively, for multiple-adjusted HRs. A U-shaped association was observed between insulin and noncardiovascular mortality, multiple-adjusted HRs for lowest and highest versus middle AUC insulin quintiles were 1.85 (1.20-2.86) and 1.43 (0.91-2.24), respectively CONCLUSIONS: Hyperinsulinemia was associated with increased all-cause and cardiovascular mortality in Helsinki policemen independent of other risk factors, although these associations weakened with the lengthening of the follow-up period. The association of insulin with noncardiovascular mortality was U-shaped.     

PAI-1 4G/5G insertion/deletion promoter polymorphism and microvascular complications in type 2 diabetes mellitus

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the regulation of fibrinolysis and extracellular matrix turnover. PAI-1 4G/5G insertion/deletion polymorphism in the PAI-1 promoter region has been shown to modulate PAI-1 plasma levels. We investigated the relationship between this polymorphism and the prevalence of diabetic nephropathy and retinopathy in patients with type 2 diabetes in the Austrian population. PATIENTS AND METHODS: 147 consecutive patients with type 2 diabetes mellitus (96 men, 51 women; median age, 65 years; IQR, 59-71) were analyzed for the PAI-1 4G/5G genotype. RESULTS: The genotype distribution in the individuals tested was as follows: 17% (n = 25) 5G/5G, 54% (n = 80) 4G/5G, and 29% (n = 42) 4G/4G. Patients homozygous for allele 4G had a significantly higher risk of diabetic proliferative retinopathy than patients without signs of diabetic retinopathy or nonproliferative retinopathy (OR, 7.3; 95% CI, 1.4-38.8; P = 0.02). No significant associations were observed between the PAI-1 genotype and the presence of albuminuria. CONCLUSION: According to our results, diabetic proliferative retinopathy might be associated with the prevalence of PAI-1 genotype 4G/4G.     

Oxygen uptake at aerobic threshold is inversely associated with fatal cardiovascular and all-cause mortality events

Purpose: We aimed to assess the associations of oxygen uptake at aerobic threshold (VO₂ at AT) with cardiovascular and all-cause mortality.

Design: VO₂ at AT was assessed in 1663 middle-aged men in a cohort study. Hazard ratios (HRs) were calculated for sudden cardiac death (SCD), fatal coronary heart disease (CHD) and cardiovascular disease (CVD) and all-cause mortality.

Results: During a median follow-up of 25.6 years, 138 SCDs, 209 fatal CHDs, 333 fatal CVDs and 719 all-cause mortality events occurred. On adjustment for established risk factors, the HRs (95% CIs) for SCD, fatal CHD, fatal CVD and all-cause mortality were 0.48 (0.28–0.82), 0.48 (0.31–0.74), 0.57 (0.41–0.79) and 0.66 (0.53–0.82), respectively comparing extreme quartiles of VO₂ at AT. On further adjustment for peak VO₂, the HRs were 0.87 (0.48–1.56), 0.83 (0.52–1.34), 0.91 (0.63–1.30) and 0.88 (0.69–1.12), respectively. Addition of VO₂ at AT to a standard CVD mortality risk prediction model was associated with a C-index change of 0.0085 (95% CI: ?0.0002–0.0172; p?=?.05) at 25 years.

Conclusions: VO₂ at AT is inversely associated with cardiovascular and all-cause mortality events, but the associations are partly dependent on peak VO₂. VO₂ at AT may improve the prediction of the long-term risk for CVD mortality.

• KEY MESSAGES

• Oxygen uptake at aerobic threshold (VO₂ at AT), a cardiopulmonary exercise testing parameter, may be a useful prognostic tool for adverse clinical outcomes in the general population.

• In a population-based prospective cohort study of men, VO₂ at AT was inversely associated with cardiovascular and all-cause mortality events and improved the prediction of cardiovascular mortality.

• In populations who cannot achieve maximal VO₂, VO₂ at AT may serve as a useful prognostic tool; however, further studies are warranted.

     

Impact of diabetes duration and cardiovascular risk factors on mortality in type 2 diabetes: the Hoorn Study

BACKGROUND: Several studies have reported differences in the mortality risk between diabetic subjects detected by screening and known diabetic patients. We studied mortality in relation to diabetes duration, and the contribution of other cardiovascular risk factors to the elevated risk. MATERIALS AND METHODS: Participants were type 2 diabetic subjects (n = 174) of a population-based cohort study. Of these, 95 were diagnosed by screening. Known diabetic subjects were grouped into two categories of diabetes duration, with a median duration of 2.4 and 11.2 years, respectively. We assessed the contribution of classical cardiovascular risk factors (dyslipidaemia, hypertension, and prior myocardial infarction), and of new cardiovascular risk factors (microalbuminuria, von Willebrand factor, sVCAM-1 and C-reactive protein) to the mortality risk during nearly 10 years of follow up. Cox's proportional hazards model was used to study the association of diabetes duration and mortality. RESULTS: The age- and sex-adjusted relative risks of mortality were 2.06 (95% C.I. 1.04-4.10) and 3.19 (1.64-6.20) for the patients with short- and long-term diabetes compared with the screening-detected diabetic subjects, respectively. Adjustment for cardiovascular risk factors resulted in a reduction of mortality risk in both groups: 1.13 (0.51-2.50) and 2.39 (1.18-4.83), respectively. Mortality risk significantly increased with increasing diabetes duration, even after multiple adjustment (P-value for trend ranged from < 0.001-0.018). CONCLUSIONS: Mortality risk increased with increasing diabetes duration. In subjects with short diabetes duration the mortality risk could largely be attributed to other risk factors. In subjects with a longer diabetes duration, however, the elevated mortality risk was independent of these cardiovascular risk factors.     

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.