Infant feeding, early weight gain, and risk of type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group

OBJECTIVE: To evaluate whether the increased risk of type 1 diabetes conferred by an early introduction of cow's milk supplements can be mediated by accelerated growth in formula-fed infants. RESEARCH DESIGN AND METHODS: All children < or = 14 years of age who were diagnosed with type 1 diabetes from September 1986 to April 1989 were invited to participate in the study. Birth date- and sex-matched control children were randomly selected from the Finnish Population Registry. At least three weight measurements from the first year of life were obtained for 435 full-term diabetic subjects and 386 control subjects from well-baby clinics and school health care units. RESULTS: Increase in body weight was greater in the diabetic girls than in the control girls, and the difference increased from 111 g (95% CI 0-218, P = 0.04) at 1 month of age to 286 g (95% CI 123-450, P = 0.0006) at 7 months. For boys, the difference in weight between the diabetic subjects and the control subjects remained stable during infancy (difference 95 g, 95% CI-2-205, P = 0.09). Increased weight was associated on average with a 1.5-fold risk of type 1 diabetes. Early introduction of formula feeding (< 3 vs. > or = 3 months) was also associated with an increased risk of type 1 diabetes after adjustment for the individual weight gain curve (adjusted odds ratio 1.53, 95% CI 1.1-2.2). No evidence for interaction was observed. CONCLUSIONS: These observations indicate that an early exposure to cow's milk formula-feeding and rapid growth in infancy are independent risk factors of childhood type 1 diabetes.     

Self-reported diabetes and health behaviors in remote indigenous communities in northern queensland,australia

OBJECTIVE: This study examines associations between self-reported diabetes and self-reported smoking, alcohol consumption, fruit consumption, and participation in adequate exercise in remote indigenous communities, using data from the Well Persons' Health Check (WPHC). RESEARCH DESIGN AND METHODS: The WPHC was a cross-sectional survey of 2,862 indigenous individuals (1,602 Aborigines, 1,074 Torres Strait Islanders, and 186 persons of joint descent) aged > or =15 years. The study was conducted in 26 remote communities in northern Queensland, Australia, between March 1998 and October 2000. RESULTS: A total of 32% of individuals with self-reported diabetes and 25% of other individuals reported eating enough fruit, according to National Health and Medical Research Council criteria: odds ratio (OR) 1.407 (95% CI 1.108-1.786), P = 0.006. After adjustment for age, sex, and ethnicity, no significant difference could be observed: adjusted OR 1.22 (0.944-1.574), P = 0.128. A total of 58% of participants who reported diabetes and 51% of others reported adequate exercise: OR 0.761 (0.609-0.952), P = 0.018. This difference was not significant after adjustment for age, sex, and ethnicity: adjusted OR 0.896 (0.705-1.14), P = 0.370. A total of 43% of individuals who reported diabetes and 72% of others reported consuming alcohol: OR 0.295 (0.235-0.369), P < 0.001. After adjustment for age, sex, and ethnicity, this difference was still significant: adjusted OR 0.550 (0.428-0.709), P < 0.001. Diabetic drinkers consumed alcohol at harmful levels similar to those of nondiabetic drinkers (P = 0.691). A total of 40% of individuals who reported diabetes and 63% of other persons were tobacco smokers: OR 0.403 (0.322-0.505), P < 0.001. Although this crude difference was attenuated by adjustment for age, sex, and ethnicity, persons with self-reported diabetes were still significantly less likely to smoke tobacco than other participants: adjusted OR 0.666 (0.521-0.852), P = 0.001. Smoking prevalence among the diabetic indigenous participants was more than double that in nondiabetic nonindigenous Australians. CONCLUSIONS: This study suggests that indigenous individuals with diabetes living in rural and remote communities are not adopting lifestyle changes required for optimal self-management of the disease. This contributes to the large excess of mortality and morbidity experienced by this population.     

Prospective associations of fasting insulin, body fat distribution, and diabetes with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

OBJECTIVE: We tested the hypothesis that diabetes, body fat distribution, and (in nondiabetic subjects) fasting insulin levels are positively associated with ischemic stroke incidence in the general population. RESEARCH DESIGN AND METHODS: As part of the Atherosclerosis Risk in Communities (ARIC) Study, we measured diabetes by using fasting glucose criteria, waist and hip circumferences, and fasting insulin levels with a radioimmunoassay in > 12,000 adults aged 45-64 years who had no cardiovascular disease at baseline. We followed them for 6-8 years for ischemic stroke occurrence (n = 191). RESULTS: After adjustment for age, sex, race, ARIC community, smoking, and education level, the relative risk of ischemic stroke was 3.70 (95% CI 2.7-5.1) for diabetes, 1.74 (1.4-2.2) for a 0.11 increment of waist-to-hip ratio, and 1.19 (1.1-1.3) for a 50-pmol/l increment of fasting insulin among nondiabetic subjects. Ischemic stroke incidence was not statistically significantly associated with BMI (comparably adjusted relative risk = 1.15, 95% CI 0.97-1.36). With adjustment for other stroke risk factors (some of which may mediate the effects of diabetes, fat distribution, and hyperinsulinemia), the relative risks for diabetes, waist-to-hip ratio, and fasting insulin level were 2.22 (95% CI 1.5-3.2), 1.08 (0.8-1.4), and 1.14 (1.01-1.3), respectively. CONCLUSIONS: Diabetes is a strong risk factor for ischemic stroke. Aspects of insulin resistance, as reflected by elevated waist-to-hip ratios and elevated fasting insulin levels, may also contribute to a greater risk of ischemic stroke.     

Racial differences in diabetic nephropathy,cardiovascular disease,and mortality in a national population of veterans

OBJECTIVE: To determine racial differences in the prevalence of diabetic nephropathy, cardiovascular disease (CVD), and risk of mortality in a national health care system. RESEARCH DESIGN AND METHODS: A longitudinal cohort study was conducted in 429,918 veterans with diabetes. Racial minority groups were analyzed for baseline differences in prevalence of early diabetic nephropathy, diabetic end-stage renal disease (ESRD) and CVD, and longitudinal risk of mortality compared with Caucasians. RESULTS: The 429,918 patients identified with diabetes were of the following racial groups: Caucasian (56.2%), African American (15.3%), Asian (0.5%), Native American (0.4%), and unknown race (21.4%). Minority individuals were, on average, younger and less likely to have CVD but were more likely to have renal disease than Caucasians. After adjustment for age, sex, and economic status, African Americans (adjusted odds ratio [OR] = 1.3, 95% CI 1.2-1.4) and Native Americans (1.5, 1.1-2.1) were more likely to have early diabetic nephropathy than Caucasians. Diabetic ESRD was more likely to be present in African Americans (1.9, 1.9-2.0), Hispanics (1.4, 1.3-1.4), Asians (1.8, 1.5-2.1), and Native Americans (1.9, 1.5-2.3) than Caucasians. Concurrently, the adjusted OR of CVD in racial minority groups was 27-49% less than in Caucasians, whereas the 18-month risk of mortality among people from most racial minority groups was 7-12% lower than in Caucasians. CONCLUSIONS: We conclude that when access to care is comparable, microvascular complications, macrovascular disease, and subsequent death occur with different frequencies among various racial groups.     

Role of systolic blood pressure and plasma triglycerides in diabetic peripheral arterial disease. The Edinburgh Artery Study

OBJECTIVE: To determine the risk factors for peripheral arterial disease (PAD) in a diabetic population and to examine whether different levels of these risk factors might explain why diabetic subjects have an increased risk of PAD compared with normal glucose tolerance subjects. RESEARCH DESIGN AND METHODS: There were 1,592 men and women aged 55-74 years selected at random from the age-sex registers of 11 general practices in Edinburgh, Scotland. Subjects underwent a comprehensive medical examination, including assessment for PAD (intermittent claudication on World Health Organization questionnaire or major asymptomatic disease on noninvasive testing) and a glucose tolerance test. RESULTS: Of the subjects, 288 (18.7%) were found to have diabetes or impaired glucose tolerance (IGT). The prevalence of PAD was greater in those with diabetes/IGT (20.6%) compared with those with normal glucose tolerance (12.5%) (odds ratio [OR] 1.64, 95% CI 1.17-2.31). Among the diabetes/IGT group, mean levels of smoking, systolic blood pressure, and triglycerides were higher in subjects with PAD than in those without PAD (P < or = 0.05). Mean levels of systolic blood pressure and plasma triglycerides were also higher in diabetic subjects than in nondiabetic subjects with PAD (P < or = 0.05). In multivariate analysis, those with diabetes/IGT no longer had a significantly higher risk of PAD after adjusting separately for systolic blood pressure (OR 1.22, 95% CI 0.85-1.73) and plasma triglycerides (OR 1.26, 95% CI 0.89-1.79). Simultaneous adjustment for both systolic blood pressure and triglycerides reduced the risk of PAD among diabetic subjects to 1.11 (95% CI 0.78-1.58). CONCLUSIONS: Increased mean levels of triglycerides and systolic blood pressure may help to explain the higher prevalence of PAD in diabetic subjects compared with that in normal glucose tolerance subjects.     

Triptan Exposure During Pregnancy and the Risk of Major Congenital Malformations and Adverse Pregnancy Outcomes: Results From The Norwegian Mother and Child Cohort Study

(Headache 2010;50:563‐575) Objective.— To evaluate the safety of triptan therapy during pregnancy. Background.— Information on the safety of triptan therapy during pregnancy is scarce and only available for sumatriptan, naratriptan, and rizatriptan. No associations with congenital malformations have been detected so far, but one study found a significant association between sumatriptan exposure during pregnancy and prematurity. Methods.— The study population consisted of 69,929 pregnant women and their newborn children for whom data on drug exposure and pregnancy outcome were available. Information on triptan therapy and potential socio‐demographic and medical confounding factors was obtained from the Norwegian Mother and Child Cohort Study. Information on congenital malformations and other adverse pregnancy outcomes was obtained from the Norwegian Medical Birth Registry. The datasets were linked via the women's personal identification number. Pearson's χ² tests and logistic regression analyses were used to identify associations between triptan therapy and pregnancy outcome. Results.— No significant associations between triptan therapy during the first trimester and major congenital malformations (unadjusted OR: 1.0; 95% CI 0.8‐1.3, adjusted OR: 1.0; 95% CI 0.7‐1.2) or other adverse pregnancy outcomes were found. Triptan therapy during the second and/or third trimesters was significantly associated with atonic uterus (unadjusted OR: 1.5; 95% CI 1.1‐1.9, adjusted OR: 1.4; 95% CI 1.1‐1.8), and blood loss >500 mL during labor (unadjusted OR: 1.3; 95% CI 1.1‐1.5, adjusted OR: 1.3; 95% CI 1.1‐1.5). Conclusions.— Triptan therapy during pregnancy was not associated with an overall increased risk of congenital malformations. It cannot, however, be excluded that a difference in the risk between triptan use and individual or rare congenital malformations may exist. A slight increase in the risk of atonic uterus and hemorrhage was associated with triptan use during the second and/or third trimesters. Although the present findings are reassuring, confirmation in independent studies is warranted.     

Older women with diabetes have a higher risk of falls: a prospective study

OBJECTIVE: To determine whether older women with diabetes have an increased risk of falls and whether known risk factors for falls account for any increased risk. RESEARCH DESIGN AND METHODS: This prospective cohort study included 9,249 women > or =67 years of age enrolled in the Study of Osteoporotic Fractures. Diabetes was determined by questionnaire at baseline. Physical performance was measured at the second examination. Subsequently, falls were ascertained every 4 months by postcard. RESULTS: A total of 629 (6.8%) women had diabetes, including 99 who used insulin. During an average of 7.2 years, 1,640 women (18%) fell more than once a year. Diabetes, stratified by insulin use, was associated with an increased risk of falling more than once a year (age-adjusted odds ratio [OR] 1.68 [95% CI 1.37-2.07] for non-insulin-treated diabetes; age-adjusted OR 2.78 [1.82-4.24] for insulin-treated diabetes). In the first 2 years of follow-up, women with diabetes were not more likely to fall than women without diabetes (44 vs. 42%; P = 0.26), but they had more falls (3.1 vs. 2.4; P < 0.01). Women with diabetes were more likely to have other risk factors for falls, which appeared to account for the increased risk of falls associated with non-insulin-treated diabetes (adjusted OR 1.18 [0.87-1.60]) but not insulin-treated diabetes (adjusted OR 2.76 [1.52-5.01]). CONCLUSIONS: Older women with diabetes have an increased risk of falling, partly because of the increased rates of known fall risk factors, and may benefit from interventions to prevent falls. Further research is needed to determine whether diabetes treatment reduces fall risk.     

Urinary cadmium,impaired fasting glucose,and diabetes in the NHANES III

OBJECTIVE: Increasing rates of type 2 diabetes worldwide suggest that diabetes may be caused by environmental toxins. Cadmium is a widespread environmental pollutant that accumulates in the pancreas and exerts diabetogenic effects in animals. To test the hypothesis that exposure to cadmium is associated with impaired fasting glucose and type 2 diabetes, we examined the associations between urinary cadmium and the prevalence of impaired fasting glucose (prediabetes) and diabetes in the Third National Health and Nutrition Examination Survey (NHANES III). RESEARCH DESIGN AND METHODS: We analyzed data on 8,722 adults > or =40 years of age from the NHANES III (1988-1994), a cross-sectional health survey of a nationally representative sample of the noninstitutionalized civilian U.S. population. We studied urinary levels of cadmium (adjusted for urine creatinine) in relation to the prevalence of impaired fasting glucose and diabetes, using the criteria of the American Diabetes Association. RESULTS: After adjustment for age, ethnicity, sex, and BMI, the odds of impaired fasting glucose and diabetes increased dose-dependently with elevations in urinary cadmium from 0-0.99 to 1.00-1.99 and > or =2 micro g/g creatinine (impaired fasting glucose, odds ratio [OR] 1.48, 95% CI 1.21-1.82 and OR 2.05, 95% CI 1.42-2.95; diabetes, OR 1.24, 95% CI 1.06-1.45 and OR 1.45, 95% CI 1.07-1.97). CONCLUSIONS: In this large cross-sectional study, urinary cadmium levels are significantly and dose-dependently associated with both impaired fasting glucose and diabetes. These findings, which require confirmation in prospective studies, suggest that cadmium may cause prediabetes and diabetes in humans.     

Risk factors associated with difficult venous access in adult ED patients

Objective

The objective was to determine risk factors associated with difficult venous access (DVA) in the emergency department (ED).

Methods

This was a prospective, observational study conducted in the ED of an urban tertiary care hospital. Adult patients undergoing intravenous (IV) placement were consecutively enrolled during periods of block enrollment. The primary outcome was DVA, defined as 3 or more IV attempts or use of a method of rescue vascular access to establish IV access. Univariate and multivariate analyses for factors predicting DVA were performed using logistic regression.

Results

A total of 743 patients were enrolled, of which 88 (11.8%) met the criteria for DVA. In the adjusted analysis, only 3 medical conditions were significantly associated with DVA: diabetes (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.1-2.8), sickle cell disease (OR 3.8, 95% CI 1.5-9.5), and history of IV drug abuse (OR 2.5, 95% CI 1.1-5.7). Notably, age, body mass index, and dialysis were not. Of patients who reported a history of requiring multiple IV attempts in the past for IV access, 14% met criteria for DVA on this visit (OR 7.7 95% CI 3-18). Of the patients who reported a history of IV insertion into the external jugular, ultrasound-guided IV placement, or a central venous catheter for IV access, 26% had DVA on this visit (OR 16.7, 95% CI 6.8-41).

Conclusions

Nearly 1 of every 9 to 10 adults in an urban ED had DVA. Diabetes, IV drug abuse, and sickle cell disease were found to be significantly associated with DVA.     

Infant feeding in Finnish children less than 7 yr of age with newly diagnosed IDDM. Childhood Diabetes in Finland Study Group

OBJECTIVE: We studied associations between the type of feeding in infancy and the incidence of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: We studied 103 newly diagnosed diabetic children less than 7 yr of age and 103 age- and sex-matched population-based control children in a countrywide study. Results: The risk of IDDM was decreased (P less than 0.05) among children breast-fed for at least 7 mo (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.24-0.85) or exclusively breast-fed for at least 3 (OR 0.33, 95% CI 0.13-0.84) or 4 (OR 0.43, 95% CI 0.22-0.84) mo. Also, children who were greater than or equal to 4 mo old at the time of introduction of supplementary milk feeding had a lower risk of diabetes (OR 0.48, 95% CI 0.26-0.91). CONCLUSIONS: The protective effects of a long duration of breast-feeding and a late introduction of dairy products on the risk of IDDM remained significant after adjusting for the mother's education.     

Statin Use and Risk of Community-Acquired Staphylococcus aureus Bacteremia: A Population-Based Case-Control Study

Objective

To ascertain whether persons treated with statins experience a decreased risk of community-acquired Staphylococcus aureus bacteremia (CA-SAB) as compared with nonusers.

Changes in the epidemiology of pneumococcal bacteremia in a Swiss university hospital during a 15-year period, 1986-2000

OBJECTIVE: To evaluate changes in epidemiological characteristics and outcome of patients with pneumococcal bacteremia during a 15-year period in a Swiss university hospital. PATIENTS AND METHODS: We reviewed the medical records of all hospitalized adults at the University Hospital Basel, Basel, Switzerland, whose blood culture yielded Streptococcus pneumoniae from January 1, 1986, through December 31, 2000. RESULTS: We analyzed 405 episodes of pneumococcal bacteremia in 394 patients. The mean annual incidence of 1.78 episodes per 1000 hospital admissions was inversely related to the mean atmospheric temperature of the area. During the study period, penicillin nonsusceptibility increased from 0% to 17%. The overall case-fatality rate was 25%, which decreased from 33% to 17% between the first and the second half of the study period (P<.001). The proportion of women with pneumococcal bacteremia increased from 37% to 52%. Independent risk factors for fatal outcome were coronary artery disease (P<.001; relative risk [RR], 4.3; 95% confidence interval [CI], 3.4-5.1), neutropenia (P=.001; RR, 3.2; 95% CI, 1.9-4.8), and age 65 years or older (P=.001; RR, 2.9; 95% CI, 1.8-4.2), whereas prior respiratory tract infection (P=.03; RR, 0.3; 95% CI, 0.1-0.5) and the occurrence of pneumococcal bacteremia in the second half of the study period (P=.01; RR, 0.4; 95% CI, 0.2-0.6) were independent predictors of survival. The case-fatality rate in human immunodeficiency virus (HIV)-infected patients was significantly lower than in patients not infected with HIV or in those with unknown HIV status (9% vs 27%; P=.006), which correlated with the younger mean +/- SD age of HIV-infected patients (33.2+/-6.6 years) compared with patients not infected with HIV (63.1+/-18.1 years) (P<.001). CONCLUSIONS: The case-fatality rate of patients with pneumococcal bacteremia decreased significantly between the first and second half of the study period, despite the increased prevalence of penicillin-nonsusceptible isolates. Independent risk factors for fatal outcome were coronary artery disease, neutropenia, and age 65 years or older, whereas prior respiratory tract infection and the occurrence of pneumococcal bacteremia in the second half of the study period were independent predictors of survival. HIV infection was a predisposing factor for pneumococcal bacteremia but was not a risk factor for fatal outcome.     

Risk factors for infective endocarditis and outcome of patients with Staphylococcus aureus bacteremia

OBJECTIVE: To investigate the risk factors for Staphylococcus aureus infective endocarditis (SAIE) and 6-month mortality in patients with S aureus bacteremia (SAB). PATIENTS AND METHODS: This study consisted of patients who were diagnosed as having nosocomial or community-acquired SAB or SAIE between June 1, 2000, and December 31, 2005. Clinical characteristics of patients with SAB were compared with those of patients with SAIE, and predictors of mortality in patients with SAB were analyzed. RESULTS: The median age of the 132 randomly selected patients with SAB and the 66 patients with SAIE was 66 and 68 years, respectively. Univariable analysis showed that unknown origin of SAB, a valvular prosthesis, a pacemaker, persistent fever, and persistent bacteremia were significantly associated with SAIE. In multivariable analysis, unknown origin of SAB (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.9-9.3; P=.001), a valvular prosthesis (OR, 9.2; 95% CI, 3.2-26.2; P<.001), persistent fever (OR, 3.1; 95% CI, 1.0-9.0; P=.04), and persistent bacteremia (OR, 6.8; 95% CI, 2.3-20.2- P=.001) were independently associated with SAIE. Six- month mortality was 8% in patients with SAB vs 35% in patients with SAIE (OR, 6.5; 95% CI, 2.9- 14.8; P<.001). In univariable analysis, methicillin- resistant S aureus (OR, 7.2; 95% CI, 1.7 - 29.4; P=.005) was significantly associated with 6-month mortality in patients with SAB. CONCLUSION: Unknown origin of SAB, a valvular prosthesis, persistent fever, and persistent bacteremia were independently associated with SAIE in patients with SAB. In univariable analysis, methicillin-resistant S aureus was associated with 6-month mortality in patients with SAB. S aureus infective endocarditis had a significantly higher mortality than SAB. The optimal management of SAB and SAIE deserves further study.     

The effect of diabetes combined with stroke on disability,self-rated health,and mortality in older Mexican Americans: results from the Hispanic EPESE

OBJECTIVE: To examine how diabetes in combination with stroke affects functional activities of daily living (ADLs) and instrumental activities of daily living (IADLs), self-rated health, and 5-year mortality in elderly Mexican Americans with or without other comorbid conditions. DESIGN: Longitudinal study. SETTING: Five southwestern states. PARTICIPANTS: A total of 3050 subjects of age 65 years or older, of whom 23% had diabetes and 6% had a stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: ADL and IADL disabilities, self-rated health, and 5-year mortality. RESULTS: Subjects with both diabetes and stroke but without other comorbid conditions had almost 18 times higher risk of having any ADL disability (odds ratio [OR]=18.8; 95% confidence interval [CI], 3.3-105.2) and 10 times higher risk of having any IADL disability (OR=10.6; 95% CI, 1.1-101.5), compared with subjects without either of the 2 conditions. The risk of disability was further increased if the subject had a comorbid condition (hypertension, heart attack, cancer, hip fracture, arthritis). The risk of fair or poor self-rated health was 3.5 (95% CI, 1.4-8.6) and the hazard ratio for 5-year mortality was 2.4 (95% CI, 1.7-3.4) in people with both diseases. CONCLUSIONS: Diabetes and stroke in combination is strongly associated with a higher risk of disabilities, poor self-rated health, and 5-year mortality in elderly Mexican Americans. The effect on outcomes appears to follow an additive model. Information on disability risk and morbidity and mortality should be useful to rehabilitation professionals in discharge planning and allocation of therapy resources.     

Impact of diabetes mellitus on other cardiovascular risk factors in patients with stenosis of the internal carotid artery

AIM: To examine cardiovascular risk factors, clinical features and their impact on the results of carotid endarterectomy in diabetic patients with stenosis of the internal carotid artery. MATERIAL AND METHODS: We analysed data on 100 diabetic and 607 nondiabetic patients who underwent carotid endarterectomy in Vilnius University Emergency hospital from 1995 through 2005. RESULTS: Diabetic patients with carotid artery stenosis were younger (p < 0.05), they smoked less often (p < 0.001) and were more often obese (p < 0.001) than nondiabetic patients. 93% of diabetic patients had arterial hypertension or hypercholesterolemia or even more cardiovascular risk factors. Diabetic were more likely to have nonspecific symptoms and severe bilateral carotid stenosis (p < 0.01). Perioperative stroke and mortality rate was 12% for diabetic and 3.4% for nondiabetic patients (p < 0.001), but no perioperative myocardial infarction was identified in diabetic patients. Four clinical factors increased the odds of complications: age 75 > (odds ratio--OR 2.2; 95% confidence interval--CI 1-4.9), smoking (OR 2.7, 95% CI 1.8-4.2), obesity (OR 6.1; 95% CI 3.9-9.5) and severe bilateral carotid stenosis (OR 2.1; 95% CI 1.3-3.6). CONCLUSION: Diabetes mellitus in patients with severe carotid artery stenosis changes conventional risk factors, clinical picture of the disease and increases the risk of carotid endarterectomy.     

Association of adiponectin gene variations with risk of incident myocardial infarction and ischemic stroke: a nested case-control study

BACKGROUND: Adiponectin (ADIPOQ) gene variations are associated with risk of cardiovascular disease in patients with diabetes. No prospective data are available, however, on the risk of atherothrombotic disorders in persons with ADIPOQ variations who do not have diabetes. METHODS: From a group of DNA samples collected at baseline in a prospective cohort of 14 916 initially healthy American men, we assessed the presence of 5 ADIPOQ genetic variants (rs266729, rs182052, rs822396, rs2241766, and rs1501299) in samples from 600 Caucasian men who subsequently suffered an atherothrombotic event (incident myocardial infarction or ischemic stroke) and from 600 age- and smoking-matched Caucasian men who remained free of reported vascular disease during follow-up (controls). RESULTS: Genotype distributions for the variations tested were in Hardy-Weinberg equilibrium. Marker-by-marker conditional logistic regression analysis, adjusted for potential risk factors, showed an association of rs266729 [recessive: odds ratio (OR), 0.26; 95% confidence interval (CI), 0.10-0.64; P=0.004] and rs182052 (recessive: OR, 0.40; 95% CI, 0.21-0.76; P=0.006) with decreased risk of ischemic stroke. These findings remained significant after Bonferroni correction. Haplotype-based (constituted by rs266729, rs182052, and rs822396) conditional logistic regression analysis, adjusted for the same potential risk factors, showed an association of haplotype G-A-G (OR, 0.28; 95% CI, 0.09-0.87; P=0.03) with decreased risk of ischemic stroke. Prespecified analysis limited to participants without baseline diabetes showed similar significant findings. CONCLUSIONS: The present prospective investigation provides further evidence for a protective role of adiponectin gene variation in the risk of ischemic stroke that was independent of the presence of diabetes.