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Bruce B Duncan

Publications and source records attributed to Bruce B Duncan.

32 records · Page 2Linked to original sources

Adiponectin and the development of type 2 diabetes: the atherosclerosis risk in communities study.

Adipocyte-derived secretory proteins have been increasingly linked to diabetes. To investigate whether adiponectin, a major adipocyte secretory protein, predicts diabetes, we conducted a case-cohort study representing the approximately 9-year experience of the 10,275 middle-aged, U.S. African-American and white participants of the Atherosclerosis Risk in Communities (ARIC) study. Adiponectin was measured on stored plasma of 581 incident diabetes case subjects and 572 noncase subjects. Overall hazard ratios (95% CIs) for developing diabetes, for those in the second, third, and fourth (versus the first) quartile of adiponectin were 0.57 (0.41-0.78), 0.39 (0.27-0.56), and 0.18 (0.11-0.27), respectively, after adjustment for age, sex, ethnicity, study center, parental history of diabetes, and hypertension and 0.72 (0.48-1.09), 0.67 (0.43-1.04), and 0.58 (0.34-0.99), respectively, after additional adjustment for BMI, waist-to-hip ratio, fasting glucose, insulin, and a score composed of six inflammation markers. The association was of similar magnitude in men and women and in whites and African Americans, but was absent in smokers and in those with a greater inflammation score (interaction P < 0.01 for each). In conclusion, in this community-based sample of U.S. adults, higher adiponectin levels were associated with a lower incidence of diabetes.

Adiponectin↗

Fasting plasma free fatty acids and risk of type 2 diabetes: the atherosclerosis risk in communities study.

OBJECTIVE: To evaluate whether plasma levels of free fatty acids (FFAs) are independently associated with incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS: A case-cohort design was used to randomly select 580 incident cases of diabetes and 566 noncases from 10,275 African-American and white men and women in the Atherosclerosis Risk in Communities study, aged 45-64 years and without prevalent diabetes at the baseline exam. Incident diabetes was ascertained at three exams over 9 years of follow-up. FFA levels were measured in plasma samples collected at the baseline exam. RESULTS: At baseline, FFA level was inversely associated with height and positively associated with female sex, BMI, waist circumference, waist-to-hip ratio, heart rate, plasma triglycerides, and an inflammation score quantifying levels of six systemic inflammation markers. Relative risks for incident diabetes (fourth vs. first quartile of FFAs) were increased in a basic model adjusted for age, sex, race, and center (hazard ratio 1.68, 95% CI 1.20-2.34) and in a model further adjusted for baseline fasting glucose, insulin, BMI, waist circumference, triglycerides, and the inflammation score (1.63, 1.04-2.57). Relative risks associated with a greater FFA level were lowest among those of normal weight and highest among the obese, but a formal test of interaction between FFAs and BMI was not statistically significant. CONCLUSIONS: Individuals with higher fasting levels of plasma FFAs were at modestly higher risk of type 2 diabetes in this cohort of middle-aged adults.

Blood Glucose↗

Risk factors for progression to incident hyperinsulinemia: the Atherosclerosis Risk in Communities Study, 1987-1998.

Hyperinsulinemia is a marker of insulin resistance, a correlate of the metabolic syndrome, and an established precursor of type 2 diabetes. This US study investigated the role of risk factors associated with hyperinsulinemia in cross-sectional studies in progression to incident hyperinsulinemia. Nondiabetic participants from the Atherosclerosis Risk in Communities Study (n = 9,020) were followed from 1987 to 1998 for the development of hyperinsulinemia (fasting serum insulin > or = 90th percentile, 19.1 micro U/ml). After adjustment for demographic characteristics, all risk factors simultaneously, and baseline insulin value, the risk of progressing to hyperinsulinemia increased per standard deviation increase in baseline uric acid (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.2, 1.4; per 1.4 mg/dl) and waist/hip ratio (OR = 1.4, 95% CI: 1.2, 1.5; per 0.08) and was inversely associated with high density lipoprotein cholesterol (OR = 0.8, 95% CI: 0.7, 0.9; per 0.4 mmol/liter). Starting to smoke (OR = 1.5, 95% CI: 1.2, 2.0) and becoming obese (OR = 2.4, 95% CI: 1.8, 3.1) during the study were also associated with increased risk. The associations were similar across race and gender groups. These data suggest that, in addition to weight gain, hyperuricemia, dyslipidemia, and smoking can be detected prior to development of hyperinsulinemia.

Arteriosclerosis↗

Racial differences in the prevalence of hypertensive retinopathy.

Few population-based data support the hypothesis that hypertensive retinopathy is more common in African Americans than in whites. We examined racial differences in the prevalence of and risk factors for hypertensive retinopathy in a population-based sample of 1860 African Americans and 7874 white persons, aged 49 to 73 years, without diabetes. Retinal photographs were taken of one randomly selected eye and evaluated for the presence of retinopathy (flame and blot-shaped retinal hemorrhages, microaneurysms, and soft exudates) according to standardized protocols by graders masked to participant characteristics. The prevalence of retinopathy was 2 times higher in African Americans than in whites (7.7% versus 4.1%, age- and gender-adjusted odds ratio [OR] 2.03, 95% confidence intervals [CI] 1.65, 2.49). After controlling for 6-year mean arterial blood pressure, use of antihypertensive medications and left ventricular hypertrophy by ECG criteria, the excess prevalence of retinopathy in African Americans was reduced by 40% (adjusted OR 1.61, 95% CI 1.26, 2.06). Further adjustment for other vascular risk factors, common carotid artery intima-media thickness, and serum creatinine levels reduced the excess prevalence in African Americans by another 13% (adjusted OR 1.48, 95% CI 1.08, 2.03). We conclude that hypertensive retinopathy is twice as frequent in African Americans compared with whites without diabetes and that the excess prevalence of retinopathy in African Americans is associated with blood pressure and severity of hypertension.

Aged↗

Inflammation markers predict increased weight gain in smoking quitters.

OBJECTIVE: Undesirable weight gain often follows smoking cessation. We investigated whether weight gain after smoking cessation is greater in those with higher levels of inflammatory markers. RESEARCH METHODS AND PROCEDURES: We studied weight gain and risk of a large gain (> or = 90th percentile) over 3 years in a cohort study of 11,687 U.S. men and women, 45 to 64 years old, with focus on the 2664 who continued and the 493 who quit smoking. RESULTS: Among new quitters, adjusted weight gain for those in the highest (vs. lowest) quartile of leukocytes was 0.56 kg/yr more (95% confidence interval, 0.17 to 0.95); for those in the highest (vs. lowest) quartile of fibrinogen, 0.60 kg/yr more (95% confidence interval, 0.27 to 0.92; p = 0.02 and 0.001 for adjusted smoking status by leukocyte and smoking status by fibrinogen interaction terms, respectively). In adjusted analyses, the odds ratio for a large gain associated with quitting (vs. continuing) was 6.2 for those in the highest quartile of leukocytes vs. 2.2 for those in the lowest leukocyte quartile (p = 0.03 for smoking status by inflammatory marker interaction). Similarly, the odds ratio for a large gain associated with quitting was 4.5 in the highest fibrinogen quartile vs. 2.5 in the lowest (p = 0. 09 for the interaction term). DISCUSSION: Weight gain after smoking cessation is increased in those with higher baseline levels of leukocytes and fibrinogen. These findings suggest a close relationship between inflammatory mediators and regulators of energy balance that may have important clinical implications.

Biomarkers↗

Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study.

To examine the association of low-grade systemic inflammation with diabetes, as well as its heterogeneity across subgroups, we designed a case-cohort study representing the approximately 9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants. Analytes were measured on stored plasma of 581 incident cases of diabetes and 572 noncases. Statistically significant hazard ratios of developing diabetes for those in the fourth (versus first) quartile of inflammation markers, adjusted for age, sex, ethnicity, study center, parental history of diabetes, and hypertension, ranged from 1.9 to 2.8 for sialic acid, orosomucoid, interleukin-6, and C-reactive protein. After additional adjustment for BMI, waist-to-hip ratio, and fasting glucose and insulin, only the interleukin-6 association remained statistically significant (HR = 1.6, 1.01-2.7). Exclusion of GAD antibody-positive individuals changed associations minimally. An overall inflammation score based on these four markers plus white cell count and fibrinogen predicted diabetes in whites but not African Americans (interaction P = 0.005) and in nonsmokers but not smokers (interaction P = 0.13). The fully adjusted hazard ratio comparing white nonsmokers with score extremes was 3.7 (P for linear trend = 0.008). In conclusion, a low-grade inflammation predicts incident type 2 diabetes. The association is absent in smokers and African-Americans.

Black People↗

Prediction of coronary heart disease in middle-aged adults with diabetes.

OBJECTIVE: To determine the 10-year probability of coronary heart disease (CHD) in diabetic adults and how well basic and novel risk factors predict CHD risk. RESEARCH DESIGN AND METHODS: We measured risk factors in 14054 participants (1500 with diabetes) initially free of CHD in the Atherosclerosis Risk in Communities study from 1987 to 1989 and followed them prospectively for CHD incidence through 1998. We used proportional hazards regression models and receiver operating characteristic (ROC) curves for CHD risk prediction. RESULTS: Based on our model using basic risk factors (age, race, total and HDL cholesterol, systolic blood pressure, antihypertensives, and smoking status), approximately 61% of diabetic women and 86% of diabetic men had a predicted 10-year CHD probability >or=10%. This CHD risk-prediction model had an area under the ROC curve of 0.72 in diabetic women and 0.67 in diabetic men. Novel risk factors or subclinical disease markers individually added only modest predictivity, but the addition of multiple markers (BMI, waist-to-hip ratio, Keys dietary score, serum albumin and creatinine, factor VIII, white blood cell count, left ventricular hypertrophy determined by electrocardiogram, and carotid intima-media thickness) increased the area under the curve by approximately 10%. CONCLUSIONS: Although all diabetic adults are at high risk for CHD, their variation in CHD risk can be predicted moderately well by basic risk factors. No single novel risk marker greatly enhanced absolute CHD risk assessment, but a battery of novel markers did. Our model can provide estimates of CHD risk for the primary prevention of this disease in people with type 2 diabetes.

Coronary Disease↗

Detection of undiagnosed diabetes and other hyperglycemia states: the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To evaluate screening strategies based on fasting plasma glucose (FPG), clinical information, and the oral glucose tolerance test (OGTT) for detection of diabetes or other hyperglycemic states-impaired fasting glucose (IFG) and impaired glucose tolerance-meriting clinical intervention. RESEARCH DESIGN AND METHODS: We studied 8,286 African-American and white men and women without known diabetes, aged 53-75 years, who received an OGTT during the fourth exam of the Atherosclerosis Risk in Communities Study. Using a split sample technique, we estimated the diagnostic properties of various clinical detection rules derived from logistic regression modeling. Screening strategies utilizing FPG, these detection rules, and/or the OGTT were then compared in terms of both the fraction of hyperglycemia cases detected and the sample fraction receiving different screening tests and identified as screen positive. RESULTS: Screening based on the IFG cut point (> or =6.1 mmol/l), followed by a clinical detection rule for those below this value, detected 86.3% of diabetic case subjects and 66.0% of all hyperglycemia cases, identifying 42% of the sample as screen positive. Applying an OGTT for those positive by the rule provides diagnostic labeling and reduces the fraction that is screen positive to 29%. Another strategy, to apply an OGTT to those with an FPG cut point between 5.6 and 6.1 mmol/l, also identifies 29% of the sample as screen positive, although it detects slightly fewer hyperglycemia cases. CONCLUSIONS: Screening strategies based on FPG, complemented by clinical detection rules and/or an OGTT, are effective and practical in the detection of hyperglycemic states meriting clinical intervention.

Aged↗

Retinal arteriolar narrowing and risk of diabetes mellitus in middle-aged persons.

CONTEXT: Microvascular processes have been hypothesized to play a role in the pathogenesis of type 2 diabetes mellitus, but prospective clinical data regarding this hypothesis are unavailable. OBJECTIVE: To examine the relation of retinal arteriolar narrowing, a marker of microvascular damage from aging, hypertension, and inflammation, to incident diabetes in healthy middle-aged persons. DESIGN, SETTING, AND PARTICIPANTS: The Atherosclerosis Risk in Communities Study, an ongoing population-based, prospective cohort study in 4 US communities that began in 1987-1989. Included in this analysis were 7993 persons aged 49 to 73 years without diabetes, of whom retinal photographs were taken during the third examination (1993-1995). MAIN OUTCOME MEASURES: Incident diabetes (defined as fasting glucose levels of > or =126 mg/dL [7.0 mmol/L], casual levels of > or =200 mg/dL [11.1 mmol/L], diabetic medications use, or physician diagnosis of diabetes at the fourth examination) by quartile of retinal arteriole-to-venule ratio (AVR). RESULTS: After a median follow-up of 3.5 years, 291 persons (3.6%) had incident diabetes. The incidence of diabetes was higher in persons with lower AVR at baseline (2.4%, 3.1%, 4.0%, and 5.2%, from highest to lowest AVR quartile; P for trend < .001). After controlling for fasting glucose and insulin levels, family history of diabetes, adiposity, physical activity, blood pressure, and other factors, persons in the lowest quartile of AVR were 71% more likely to develop diabetes than those in the highest quartile (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.13-2.57; P for trend =.002). This association persisted with different diagnostic criteria (OR, 1.92; 95% CI, 1.10-3.36; P for trend =.01, using a fasting glucose level of > or =141 mg/dL [7.8 mmol/L] as a cutoff), and was seen even in people at lower risk of diabetes, including those without a family history of diabetes, without impaired fasting glucose, and with lower measures of adiposity. CONCLUSIONS: Retinal arteriolar narrowing is independently associated with risk of diabetes, supporting a microvascular role in the development of clinical diabetes.

Aged↗

Retinal arteriolar narrowing and risk of coronary heart disease in men and women. The Atherosclerosis Risk in Communities Study.

CONTEXT: Microvascular processes have been hypothesized to play a greater role in the development of coronary heart disease (CHD) in women than in men; however, prospective clinical data are limited. OBJECTIVE: To examine the association between retinal arteriolar narrowing, a marker of microvascular damage from hypertension and inflammation, and incident CHD in healthy middle-aged women and men. DESIGN, SETTING, AND PARTICIPANTS: The Atherosclerosis Risk in Communities Study, an ongoing prospective, population-based cohort study in 4 US communities initiated in 1987-1989. Retinal photographs were taken in 9648 women and men aged 51 to 72 years without CHD at the third examination (1993-1995). To quantify retinal arteriolar narrowing, the photographs were digitized, individual arteriolar and venular diameters were measured, and a summary arteriole-to-venule ratio (AVR) was calculated. MAIN OUTCOME MEASURE: Risk of CHD associated with retinal arteriolar narrowing. RESULTS: During an average 3.5 years of follow-up, 84 women and 187 men experienced incident CHD events. In women, after controlling for mean arterial blood pressure averaged over the previous 6 years, diabetes, cigarette smoking, plasma lipid levels, and other risk factors, each SD decrease in the AVR was associated with an increased risk of any incident CHD (relative risk [RR], 1.37; 95% confidence interval [CI], 1.08-1.72) and of acute myocardial infarction (RR, 1.50; 95% CI, 1.10-2.04). In contrast, AVR was unrelated to any incident CHD in men (RR, 1.00; 95% CI, 0.84-1.18) or to acute myocardial infarction (RR, 1.08; 95% CI, 0.85-1.38). CONCLUSION: Retinal arteriolar narrowing is related to risk of CHD in women but not in men, supporting a more prominent microvascular role in the development of CHD in women than in men. Future work is needed to confirm these findings.

Aged↗

B-mode ultrasound-detected carotid artery lesions with and without acoustic shadowing and their association with markers of inflammation and endothelial activation: the atherosclerosis risk in communities study.

In a cross-sectional study of 8695 men and women free of clinical CVD, aged 45-64 years at the 1987-1989 baseline Atherosclerosis Risk in Communities (ARIC) study exam, we examined the relationship between carotid artery lesions (CALs), with and without acoustic shadowing (AS) as an index of plaque mineralization, to systemic markers of inflammation and markers of endothelial function, including endothelial adhesion molecules. A three-level variable, based on the presence of extracranial CALs and AS, identified by B-mode ultrasound of six 1 cm arterial segments, defined the outcome. Among subjects without evidence of AS, after controlling for age, gender, ethnicity, study site, body mass index, hypertension, diabetes, and smoking status, CALs were associated with systemic markers of inflammation, including higher levels of fibrinogen [OR=1.24 (95% CI: 1.09, 1.40)] and white blood cell count [OR=1.37 (95% CI: 1.21, 1.56)]. Among subjects with a CAL, after controlling for the above risk factors as well as mean far wall intima-media thickness, AS was associated with higher levels of von Willebrand factor [OR=1.38 (95% CI: 1.10, 1.74)], a marker of endothelial activation. Associations with endothelial adhesion molecules were inconsistent. Further studies aimed at elucidating the mechanisms of arterial mineralization are warranted.

Arteriosclerosis↗

Red wine with the noon meal lowers post-meal blood pressure: a randomized trial in centrally obese, hypertensive patients.

OBJECTIVE: Despite being recognized as a cause of hypertension at higher doses, consumption of lesser amounts of alcohol appears to protect against cardiovascular disease and acutely reduces blood pressure. We tested the hypothesis that two glasses of red wine, taken together with the noon meal, would cause postprandial reduction in blood pressure in hypertensive individuals. METHOD: Thirteen (8 female) middle-aged, centrally obese, hypertensive and otherwise healthy participants received, in an open randomized crossover experiment, red wine (250 ml to approximately 23 g of ethanol) and a placebo equivalent, together with a standardized lunch. Blood pressure was measured with 24-hour ambulatory monitoring. RESULTS: Wine with the meal produced a mean (SD) reduction of 5.3 (7.66) mmHg in postprandial blood pressure (p = .03), which persisted for most of the remaining daytime interval. The maximal blood pressure reduction was 8.5 (11.84) mmHg, occurring 3 hours after intervention (p = .02). In addition, nocturnal dipping in systolic blood pressure was lessened during the wine intervention period (5.3 [10.19] vs 11.1 [8.08] mmHg; p = .03). CONCLUSIONS: Ingestion of 250 ml of red wine, together with the noon meal, resulted in reduction of the postprandial blood pressure of centrally obese, hypertensive subjects. The effect lasted throughout most of the remaining daytime interval and appeared to modify the usual blood pressure variation pattern.

Adult↗

Total sialic acid and associated elements of the metabolic syndrome in women with and without previous gestational diabetes.

OBJECTIVE: Inflammatory markers predict type 2 diabetes and relate to the metabolic syndrome. Gestational diabetes mellitus (GDM) predicts type 2 diabetes and may be part of this syndrome. To examine the association of inflammatory markers with GDM, we investigated total sialic acid (TSA) in women with and without previous GDM. RESEARCH DESIGN AND METHODS: All women with GDM and a random sample of women from one center of the Brazilian Study of Gestational Diabetes were invited to return 7 years after their index pregnancy. After an interview, an oral glucose tolerance test and anthropometry were performed. A total of 46 women with and 50 women without previous GDM completed the protocol. RESULTS: Mean TSA was significantly higher in women with (71.8 +/- 11.1 mg/dl) than without (67.5 +/- 9.8 mg/dl) previous GDM (P < 0.05). In a linear regression model, TSA was 4 mg/dl (P < 0.05) higher in women with previous GDM, after adjustment for BMI, fasting insulin sensitivity, and number of years spent in school. In a similar model, current 2-h plasma glucose levels were associated with higher TSA levels after adjustment for waist-to-hip ratio and the log of triglycerides. TSA was strongly correlated with individual components and aggregates (r = 0.55, P < 0.001) of the metabolic syndrome. CONCLUSIONS: Increased TSA levels are associated with previous GDM and are strongly linked to the metabolic syndrome. These findings in young women suggest that a chronic mild systemic inflammatory response is an early feature of the metabolic syndrome and that GDM may be a window for its investigation.

Biomarkers↗

Similarities in mortality patterns from influenza in the first half of the 20th century and the rise and fall of ischemic heart disease in the United States: a new hypothesis concerning the coronary heart disease epidemic.

The classic risk factors for developing coronary heart disease (CHD) explain less than 50% of the decrease in mortality observed since 1950. The transition currently under way, from the degenerative to the infectious-inflammatory paradigm, requires a new causal interpretation of temporal trends. The following is an ecological study based on data from the United States showing that in men and women an association between the age distribution of mortality due to influenza and pneumonia (I&P) associated with the influenza pandemic in 1918-1919 in the 10-49-year age bracket and the distribution of CHD mortality from 1920 to 1985 in survivors from the corresponding birth cohorts. It further shows a significant negative correlation (r = -0.68, p = 0.042) between excess mortality from I&P accumulated in epidemics from 1931 to 1940 (used as indicator for persistent circulation of H1N1 virus combined with vulnerability to infection) and the order of the beginning in the decline in CHD mortality in nine geographic divisions in the United States. In light of current biological knowledge, the data suggest that the 1918 influenza pandemic and the subsequent epidemics up to 1957 might have played a determinant role in the epidemic of CHD mortality registered in the 20th century.

Cohort Studies↗