Maria Inês Schmidt

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.

Health conditions and health-policy innovations in Brazil: the way forward.

Brazil is a large complex country that is undergoing rapid economic, social, and environmental change. In this Series of six articles, we have reported important improvements in health status and life expectancy, which can be ascribed largely to progress in social determinants of health and to implementation of a comprehensive national health system with strong social participation. Many challenges remain, however. Socioeconomic and regional disparities are still unacceptably large, reflecting the fact that much progress is still needed to improve basic living conditions for a large proportion of the population. New health problems arise as a result of urbanisation and social and environmental change, and some old health issues remain unabated. Administration of a complex, decentralised public-health system, in which a large share of services is contracted out to the private sector, together with many private insurance providers, inevitably causes conflict and contradiction. The challenge is ultimately political, and we conclude with a call for action that requires continuous engagement by Brazilian society as a whole in securing the right to health for all Brazilian people.

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.

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.

Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies.

BACKGROUND The WHO and American Diabetes Association criteria for diagnosing diabetes mellitus assume the presence of a glycaemic threshold with high sensitivity for identifying retinopathy. However, this assumption is based on data from three previous studies that had important limitations in detecting retinopathy. We aimed to provide updated data for the relation between fasting plasma glucose (FPG) and retinopathy, and to assess the diagnostic accuracy of current FPG thresholds in identifying both prevalent and incident retinopathy. METHODS We examined the data from three cross-sectional adult populations: those in the Blue Mountains Eye Study (BMES, Australia, n=3162), the Australian Diabetes, Obesity and Lifestyle Study (AusDiab, Australia, n=2182), and the Multi-Ethnic Study of Atherosclerosis (MESA, USA, n=6079). Retinopathy was diagnosed from multiple retinal photographs of each eye, and graded according to the modified Airlie House Classification system. Plasma glucose concentrations were measured from fasting venous blood samples. FINDINGS The overall prevalence of retinopathy was 11.5% in BMES (95% CI 10.4-12.6%), 9.6% in AusDiab (8.4-10.9), and 15.8% in MESA (14.9-16.7). However, we found inconsistent evidence of a uniform glycaemic threshold for prevalent and incident retinopathy, with analyses suggesting a continuous relation. The widely used diabetes FPG cutoff of 7.0 mmol/L or higher had sensitivity less than 40% (range 14.8-39.1) for detecting retinopathy, with specificity between 80.8% and 95.8%. The area under receiver operating characteristic curves for FPG and retinopathy was low and ranged from 0.56 to 0.61. INTERPRETATION We saw no evidence of a clear and consistent glycaemic threshold for the presence or incidence of retinopathy across different populations. The current FPG cutoff of 7.0 mmol/L used to diagnose diabetes did not accurately identify people with and without retinopathy. These findings suggest that the criteria for diagnosing diabetes could need reassessment.

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.

The Dawn Phenomenon, an Early Morning Glucose Rise: Implications for Diabetic Intraday Blood Glucose Variation

Eleven insulin-dependent (type I) diabetic subjects were studied during a 24-h period to assess intraday blood glucose (BG) variation and related free insulin (FI) levels. Ten patients exhibited the dawn phenomenon, a rise in early morning fasting blood glucose (123 ± 81.1 m/dl; mean ± SD). This increase was positively and significantly correlated with the morning postprandial BG peak (r = 0.723; P = 0.012). FI/BG ratios were highest during the night (0.717 and 0.666 at 2200 and 0400 h, respectively) and lowest during the early morning (0.294 at 0800 h) (P < 0.01). Three of the four observed hypoglycemic episodes occurred during the period when free insulin levels were high relative to BG. We conclude that the dawn phenomenon contributed directly and significantly to the BG maximum and indirectly, in some cases, to nocturnal hypoglycemia. It thus played an important role in the intraday blood glucose variation of such patients.