Bruce Bartholow Duncan

Smoking, Smoking Cessation, and Risk for Type 2 Diabetes Mellitus: A Cohort Study

BACKGROUND Cigarette smoking is an established predictor of incident type 2 diabetes mellitus, but the effects of smoking cessation on diabetes risk are unknown. OBJECTIVE To test the hypothesis that smoking cessation increases diabetes risk in the short term, possibly owing to cessation-related weight gain. DESIGN Prospective cohort study. SETTING The ARIC (Atherosclerosis Risk in Communities) Study. PATIENTS 10,892 middle-aged adults who initially did not have diabetes in 1987 to 1989. MEASUREMENTS Smoking was assessed by interview at baseline and at subsequent follow-up. Incident diabetes was ascertained by fasting glucose assays through 1998 and self-report of physician diagnosis or use of diabetes medications through 2004. RESULTS During 9 years of follow-up, 1254 adults developed type 2 diabetes. Compared with adults who never smoked, the adjusted hazard ratio of incident diabetes in the highest tertile of pack-years was 1.42 (95% CI, 1.20 to 1.67). In the first 3 years of follow-up, 380 adults quit smoking. After adjustment for age, race, sex, education, adiposity, physical activity, lipid levels, blood pressure, and ARIC Study center, compared with adults who never smoked, the hazard ratios of diabetes among former smokers, new quitters, and continuing smokers were 1.22 (CI, 0.99 to 1.50), 1.73 (CI, 1.19 to 2.53), and 1.31 (CI, 1.04 to 1.65), respectively. Further adjustment for weight change and leukocyte count attenuated these risks substantially. In an analysis of long-term risk after quitting, the highest risk occurred in the first 3 years (hazard ratio, 1.91 [CI, 1.19 to 3.05]), then gradually decreased to 0 at 12 years. LIMITATION Residual confounding is possible even with meticulous adjustment for established diabetes risk factors. CONCLUSION Cigarette smoking predicts incident type 2 diabetes, but smoking cessation leads to higher short-term risk. For smokers at risk for diabetes, smoking cessation should be coupled with strategies for diabetes prevention and early detection.

Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study

BACKGROUND Type 2 diabetes mellitus and atherosclerotic cardiovascular disease have common antecedents. Since markers of inflammation predict coronary heart disease and are raised in patients with type 2 diabetes, we investigated whether they predict whether people will develop type 2 diabetes. METHODS 12,330 men and women, aged 45-64 years, were followed up for a mean of 7 years. We analysed the association between different markers of acute inflammation and subsequent diagnosis of diabetes. In a subgroup of 610 individuals selected originally for an unrelated atherosclerosis case-control study, we also investigated diabetes associations with total sialic acid and orosomucoid, haptoglobin, and alpha1-antitrypsin. FINDINGS 1335 individuals had a new diagnosis of diabetes. Adjusted odds ratios for developing diabetes for quartile extremes were 1.9 (95% CI 1.6-2.3) for raised white-cell count, 1.3 (1.0-1.5) for low serum albumin, and 1.2 (1.0-1.5) for raised fibrinogen. In the subgroup analysis, individuals with concentrations of orosomucoid and sialic acid of more than the median had odds ratios of 7.9 (2.6-23.7) and 3.7 (1.4-9.8), respectively. Adjustment for body-mass index and waist-to-hip ratio lessened the associations; those for white-cell count (1.5 [1.3-1.8]), orosomucoid (7.1 [2.1-23.7]), and sialic acid (2.8 [1.0-8.1]) remained significant. INTERPRETATION Markers of inflammation are associated with the development of diabetes in middle-aged adults. Although autoimmunity may partly explain these associations, they probably reflect the pathogenesis of type 2 diabetes.

Chronic non-communicable diseases in Brazil: burden and current challenges

Non-communicable diseases (NCDs) have become a major health priority in Brazil--72% of all deaths were attributable to NCDs in 2007. They are also the main source of disease burden, with neuropsychiatric disorders being the single largest contributor. Morbidity and mortality due to NCDs are greatest in the poor population. Although the crude NCD mortality increased 5% between 1996 and 2007, age-standardised mortality declined by 20%. Declines were primarily for cardiovascular and chronic respiratory diseases, in association with the successful implementation of health policies that lead to decreases in smoking and the expansion of access to primary health care. Of note, however, the prevalence of diabetes and hypertension is rising in parallel with that of excess weight; these increases are associated with unfavourable changes of diet and physical activity. Brazil has implemented major policies for the prevention of NCDs, and its age-adjusted NCD mortality is falling by 1·8% per year. However, the unfavourable trends for most major risk factors pose an enormous challenge and call for additional and timely action and policies, especially those of a legislative and regulatory nature and those providing cost-effective chronic care for individuals affected by NCDs.

Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): Objectives and Design

Although low- and middle-income countries still bear the burden of major infectious diseases, chronic noncommunicable diseases are becoming increasingly common due to rapid demographic, epidemiologic, and nutritional transitions. However, information is generally scant in these countries regarding chronic disease incidence, social determinants, and risk factors. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) aims to contribute relevant information with respect to the development and progression of clinical and subclinical chronic diseases, particularly cardiovascular diseases and diabetes. In this report, the authors delineate the studys objectives, principal methodological features, and timeline. At baseline, ELSA-Brasil enrolled 15,105 civil servants from 5 universities and 1 research institute. The baseline examination (2008-2010) included detailed interviews, clinical and anthropometric examinations, an oral glucose tolerance test, overnight urine collection, a 12-lead resting electrocardiogram, measurement of carotid intima-media thickness, echocardiography, measurement of pulse wave velocity, hepatic ultrasonography, retinal fundus photography, and an analysis of heart rate variability. Long-term biologic sample storage will allow investigation of biomarkers that may predict cardiovascular diseases and diabetes. Annual telephone surveillance, initiated in 2009, will continue for the duration of the study. A follow-up examination is scheduled for 2012-2013.

Retinal arteriolar diameter and risk for hypertension.

Context Does narrowing of small arterioles lead to or result from hypertension? Contribution This large prospective study measured diameters of small retinal vessels using digitized photographs in people without preexisting hypertension. After 3 years, more people with narrowed arterioles at baseline had hypertension than did people without any arteriolar narrowing. Implications Smaller arteriolar diameters are independently associated with development of hypertension. Cautions Rather than leading to hypertension, reduced arteriolar diameters at baseline might have reflected elevated blood pressure in persons who did not yet meet diagnostic criteria for hypertension. The Editors Hypertension affects up to 50 million people in the United States and is the single most important modifiable risk factor for stroke (1). Despite extensive research, much remains to be elucidated about the risk factors and pathogenesis of hypertension. A key characteristic of hypertension is the presence of narrowing and vasoconstriction of the small arteries and arterioles in the peripheral circulation (2-4). However, it is uncertain whether reduced arteriolar caliber, by increasing peripheral vascular resistance, contributes to the subsequent development of hypertension (5-7). Prospective clinical data demonstrating a link between smaller arteriolar caliber and risk for hypertension are unavailable, largely because the microcirculation is difficult to evaluate outside of experimental settings (5-7). As a result, the value of specific antihypertensive treatment targeted at the peripheral microcirculation remains questionable (7). The retinal arterioles offer a unique opportunity to noninvasively investigate the relation of arteriolar characteristics to the development of cardiovascular disease (8). We recently developed a method to quantify retinal arteriolar diameters from digitized retinal photographs (9). In this study, we examine whether retinal arteriolar narrowing is related to incident hypertension in a cohort of middle-aged normotensive persons. Methods Study Sample The Atherosclerosis Risk in Communities (ARIC) study is a population-based cohort study with 4 examinations (10). The ARIC study examined 15792 participants 45 to 64 years of age at baseline from 1987 to 1989 (10). The study sample was selected by probability sampling from 4 U.S. communities: Forsyth County, North Carolina; Jackson, Mississippi; suburbs of Minneapolis, Minnesota; and Washington County, Maryland. The Jackson sample included African-American persons only; in the other field centers, samples were representative of the populations in these communities (that is, mostly white persons in the suburbs of Minneapolis and Washington County and about 15% African-American persons in Forsyth County). Initial participation rates were 46% in Jackson and approximately 65% in the other communities. Participants were examined every 3 years; the second examination was done between 1990 and 1992 (n = 14348 [93% of 15440 survivors]), the third examination was done between 1993 and 1995 (n = 12887 [86% of 14944 survivors]), and the fourth examination was done between 1996 and 1998 (n = 11656 [81% of 14485 survivors]). Retinal photographs were taken at the third examination. Of the 12887 persons who returned for this examination, we excluded 38 whose race was neither African American nor white and 42 nonwhite residents in the suburbs of Minneapolis and Washington County, 1009 with no photographs or ungradable photographs, and 1434 who did not participate in the fourth examination. We further excluded 4464 persons with prevalent hypertension diagnosed at the first, second, or third examination and 272 persons with missing hypertension data. The remaining cohort consisted of 5628 normotensive persons at the third examination (Figure 1). Excluded participants (n = 7259) were older and more likely to be African American; had higher systolic and diastolic blood pressures, body mass indexes, waist-to-hip ratios, and fasting glucose and triglyceride levels; had lower high-density lipoprotein cholesterol levels; and were more likely to currently smoke and drink alcohol compared with participants included in the study (data not shown). Figure 1. Study design and population. Institutional review boards at each study site and at the Fundus Photograph Reading Center at the University of Wisconsin, Madison, Wisconsin, approved the study. Informed consent was obtained from all participants. Measurement of Retinal Arteriolar Diameters The retinal photography procedure has been reported in detail (9). Briefly, photographs of the retina of one randomly selected eye were taken after 5 minutes of dark adaptation. To estimate a generalized reduction in arteriolar diameters (referred to as generalized retinal arteriolar narrowing in this paper), the photographs were digitized, and the diameters of all arterioles and venules coursing through a specified area surrounding the optic disc were measured on the computer by graders who were blinded to participant identity. The individual arteriolar and venular diameters were combined into summary measures (in m) and combined as an arteriole-to-venule ratio on the basis of formulas described elsewhere (9). The arteriole-to-venule ratio accounts for magnification differences among photographs and is distributed normally. An arteriole-to-venule ratio of 1.0 indicates that retinal arteriolar diameters were, on average, the same as venular diameters, whereas a smaller ratio represents narrower arterioles, because venular diameters vary little (9). Figure 2 shows examples of retinas with low and high arteriole-to-venule ratios. The intra- and intergrader reliability coefficients for the arteriole-to-venule ratio were 0.84 and 0.79, respectively (9). Figure 2. Retinal photographs with arteriole-to-venule ratios. Top. Bottom. Trained graders who were blinded to retinal vessel measurements also evaluated photographs for the presence of localized areas of arteriolar constriction (referred to as focal retinal arteriolar narrowing) as well as other retinal microvascular characteristics (arteriovenous nicking, microaneurysms, and retinal hemorrhages) by using a standard protocol. Intra- and intergrader statistics ranged from 0.61 to 1.00 (9). Definition of Incident Hypertension Trained technicians performed a standard evaluation of blood pressure at each examination (11). Blood pressure was taken with a random-zero sphygmomanometer, and the mean of the last 2 measurements was used. Hypertension was defined as systolic blood pressure of 140 mm Hg or higher, diastolic blood pressure of 90 mm Hg or higher, or use of antihypertensive medication during the previous 2 weeks (11). Persons without preexisting hypertension at the first, second, or third examination who met these criteria at the fourth examination were defined as having incident hypertension. To examine the effect of current and previous blood pressure on these associations, we defined a persons 6-year average systolic and diastolic blood pressures as the mean of the blood pressure measurements taken at the first, second, and third examinations. The 6-year average systolic and diastolic blood pressures were then included as covariates in the assessment of the independence of retinal arteriolar narrowing with incident hypertension. We categorized a person as having normal blood pressure for systolic values averaging less than 130 mm Hg and diastolic values averaging less than 85 mm Hg and as having high normal blood pressure for systolic values averaging 130 to 139 mm Hg or diastolic values of 85 to 90 mm Hg, according to the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification (12). Definition of Other Variables Height and weight were measured with participants dressed in scrub suits. Body mass index, defined as weight/height2, was then computed. We calculated waist-to-hip ratio as the circumference of the waist (umbilical level) divided by the circumference of the hips (maximum circumference of the buttocks). We characterized physical activity by using a sports index; scores ranged from 1 (low) to 5 (high) (13). Diabetes mellitus was defined as a fasting glucose level of 7.0 mmol/L (126 mg/dL) or higher, a nonfasting glucose level of 11.1 mmol/L (200 mg/dL) or higher, or a history of physician-diagnosed diabetes or treatment for diabetes. Blood collection and processing for total and high-density lipoprotein cholesterol levels, triglyceride level, and fasting glucose level are described elsewhere (14). All variables were based on data from the third examination. Statistical Analysis For analysis of generalized retinal arteriolar narrowing, the arteriole-to-venule ratio was categorized into quintiles (with the first quintile indicating the largest arteriolar diameters and the fifth representing the smallest diameters). We also analyzed the ratio as a continuous variable (per SD reduction). Focal retinal arteriolar narrowing and other lesions were defined as binary variables. We used analysis of covariance to compare the arteriole-to-venule ratio and its components (summary measures of retinal arteriolar and venular diameters) between persons who did and did not subsequently develop hypertension. We used multiple logistic regression to calculate the odds ratio of incident hypertension by comparing a given arteriole-to-venule ratio quintile with the first quintile and the presence versus the absence of focal narrowing and other lesions. In these models, we adjusted for age, sex, race, field center, 6-year average systolic and diastolic blood pressures (mm Hg), body mass index (kg/m2), waist-to-hip ratio, sports activity index (1 to 5), diabetes (yes or no), cigarette smoking and alcohol consumption (current, former, or never), total cholesterol level, high-density lipoprotein cholesterol and triglyceride levels (mmol/L), and fasting glucose

Gestational diabetes and pregnancy outcomes - a systematic review of the World Health Organization (WHO) and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) diagnostic criteria

BackgroundTwo criteria based on a 2 h 75 g OGTT are being used for the diagnosis of gestational diabetes (GDM), those recommended over the years by the World Health Organization (WHO), and those recently recommended by the International Association for Diabetes in Pregnancy Study Group (IADPSG), the latter generated in the HAPO study and based on pregnancy outcomes. Our aim is to systematically review the evidence for the associations between GDM (according to these criteria) and adverse outcomes.MethodsWe searched relevant studies in MEDLINE, EMBASE, LILACS, the Cochrane Library, CINHAL, WHO-Afro library, IMSEAR, EMCAT, IMEMR and WPRIM. We included cohort studies permitting the evaluation of GDM diagnosed by WHO and or IADPSG criteria against adverse maternal and perinatal outcomes in untreated women. Only studies with universal application of a 75 g OGTT were included. Relative risks (RRs) and their 95% confidence intervals (CI) were obtained for each study. We combined study results using a random-effects model. Inconsistency across studies was defined by an inconsistency index (I2) > 50%.ResultsData were extracted from eight studies, totaling 44,829 women. Greater risk of adverse outcomes was observed for both diagnostic criteria. When using the WHO criteria, consistent associations were seen for macrosomia (RR = 1.81; 95%CI 1.47-2.22; p < 0.001); large for gestational age (RR = 1.53; 95%CI 1.39-1.69; p < 0.001); perinatal mortality (RR = 1.55; 95% CI 0.88-2.73; p = 0.13); preeclampsia (RR = 1.69; 95%CI 1.31-2.18; p < 0.001); and cesarean delivery (RR = 1.37;95%CI 1.24-1.51; p < 0.001). Less data were available for the IADPSG criteria, and associations were inconsistent across studies (I2 ≥ 73%). Magnitudes of RRs and their 95%CIs were 1.73 (1.28-2.35; p = 0.001) for large for gestational age; 1.71 (1.38-2.13; p < 0.001) for preeclampsia; and 1.23 (1.01-1.51; p = 0.04) for cesarean delivery. Excluding either the HAPO or the EBDG studies minimally altered these associations, but the RRs seen for the IADPSG criteria were reduced after excluding HAPO.ConclusionsThe WHO and the IADPSG criteria for GDM identified women at a small increased risk for adverse pregnancy outcomes. Associations were of similar magnitude for both criteria. However, high inconsistency was seen for those with the IADPSG criteria. Full evaluation of the latter in settings other than HAPO requires additional studies.

Clustering of dyslipidemia, hyperuricemia, diabetes, and hypertension and its association with fasting insulin and central and overall obesity in a general population

Clustering of elevated triglycerides, decreased high-density lipoprotein cholesterol (HDL-C), hyperuricemia, diabetes, and hypertension has been related to insulin resistance/high insulin levels and central and/or overall obesity. The extent to which these abnormalities cluster and whether hyperinsulinemia, central adiposity, and overall obesity each independently associate with this clustering were evaluated in 14,481 US whites and African-Americans 45 to 64 years of age. With the exception of hypertension, abnormalities rarely existed in isolated form. Clustering greatly exceeded chance association (P < .001). Although this clustering was greater in relative terms (ratio of observed to expected cluster frequency) in the lean and less centrally obese, it was greater in absolute terms (observed minus expected cluster frequency as a percent of total population) in the more centrally and more generally obese. The greatest excesses were found for clusters that included both hypertriglyceridemia and low HDL-C. Multiple logistic regression models showed strong and independent graded relationships of clusters with quintiles of fasting insulin (fifth quintile odds ratio, 10 to 54, P < .001) and to a lesser degree with quintiles of the waist to hip ratio (2.2 to 5.4, P < .001 for most) and of body mass index (1.6 to 4.5, P < .05 for most). In conclusion, all abnormalities cluster in excess of that predicted by chance, with clusters showing remarkable and graded independent associations with fasting hyperinsulinemia and to a lesser extent with central and overall obesity. Thus, a metabolic syndrome occurs in both lean and obese middle-aged US adults.

B-mode-detected carotid artery plaque in a general population. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

There is little information on the distribution of atherosclerotic lesions of the extracranial carotid artery wall in free-living populations. The purpose of the present study was to describe the prevalence from 1987 through 1989 of extracranial carotid artery plaque and plaque with acoustic attenuation (shadowing) lesions in a general population of white and black adults from four US communities. Methods B-mode ultrasound was used to characterize wall lesions in the common and internal carotid arteries and at the carotid artery bifurcation in 14 046 men and women 45 to 64 years old who participated in the Atherosclerosis Risk in Communities Study baseline survey. Results Thirty-four percent of participants had plaque and 6.4% had plaque with acoustic shadowing. The prevalence of plaque with acoustic shadowing increased steadily with age from 2.5% at ages 45 to 49 to 12.4% at ages 60 to 64. Overall, whites had more plaque with acoustic shadowing lesions than blacks (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.02 to 1.46), and men had more than women (OR, 1.42; 95% CI, 1.22 to 1.63). However, plaque lesions in the common carotid artery were less common among whites than among blacks, and no racial difference was observed in the prevalence of plaque with acoustic shadowing at this segment. Conclusions Although these prevalence rates are likely to be underestimated because of the emphasis on arterial boundary visualization of the scanning protocol, they show a large, mostly asymptomatic burden of atherosclerosis in these populations, especially among older individuals. Site-specific frequency rates of plaque varied between blacks and whites. Among those with plaque, however, whites had more lesions with acoustic shadowing attenuation.

Cohort Profile: Longitudinal Study of Adult Health (ELSA-Brasil)

Chronic diseases are a global problem, yet information on their determinants is generally scant in low- and middle-income countries. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) aims to contribute relevant information regarding the development and progression of clinical and subclinical chronic diseases, particularly cardiovascular diseases and diabetes, in one such setting. At Visit 1, we enrolled 15 105 civil servants from predefined universities or research institutes. Baseline assessment (2008–10) included detailed interviews and measurements to assess social and biological determinants of health, as well as various clinical and subclinical conditions related to diabetes, cardiovascular diseases and mental health. A second visit of interviews and examinations is under way (2012–14) to enrich the assessment of cohort exposures and to detect initial incident events. Annual surveillance has been conducted since 2009 for the ascertainment of incident events. Biological samples (sera, plasma, urine and DNA) obtained at both visits have been placed in long-term storage. Baseline data are available for analyses, and collaboration via specific research proposals directed to study investigators is welcome.

Cross-Sectional and Prospective Study of Lung Function in Adults With Type 2 Diabetes The Atherosclerosis Risk in Communities (ARIC) Study

OBJECTIVE—The aim of this study was to test the hypothesis that diabetes is independently associated with reduced lung function, both cross-sectionally and longitudinally. RESEARCH DESIGN AND METHODS—We conducted cross-sectional and prospective analyses of diabetes status and lung function decline using baseline and 3-year follow-up data on 1,100 diabetic and 10,162 nondiabetic middle-aged adults from the Atherosclerosis Risk in Communities (ARIC) Study. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured at baseline and at the 3-year follow-up using standard spirometry. RESULTS—At baseline, adults with diabetes had significantly lower predicted FVC (96 vs. 103%, P < 0.001) and predicted FEV1 (92 vs. 96%, P < 0.001) than those without diabetes. These differences remained significant after adjustment for demographic characteristics, adiposity, smoking, physical activity index, education, and ARIC field center. Graded, inverse associations were observed between hyperglycemia, diabetes severity (i.e., duration of diabetes and types of antidiabetes medications), and FVC and FEV1 (all Ptrend < 0.001). In prospective analyses, FVC declined faster in diabetic adults than in their nondiabetic counterparts (64 vs. 58 ml/year, P = 0.01). Diabetes severity as indicated by intensity of antidiabetic treatment also showed graded relationships with the rate of FVC decline (P < 0.01). CONCLUSIONS—These data support the notion that the lung is a target organ for diabetic injury. Additional research is required to identify pathophysiologic mechanisms and to determine clinical significance.