Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Association of cumulative social risk and gestational diabetes mellitus in the US, 2007-2018.

AIMS: Little is known regarding the association of multiple social risk factors and gestational diabetes mellitus (GDM). METHODS: We analyzed the 2007-2018 National Health and Nutrition Examination Surveys including 10,439 women aged ≥20 years (8 % with history of GDM). We created a cumulative social risk score (CSR) by adding scores assigned to each of the following: race/ethnicity, citizenship status and country of birth, education, and family income (score of 0 used as reference group). Using logistic regression, we assessed the associations of individual social risk factors (education, income, race/ethnicity and citizenship status) and CSR score with GDM, adjusting for age, parity, insurance status, care access, smoking, diet, physical activity, and body mass index. RESULTS: Among individual social risk factors, being a non-U.S. citizen (OR:1.51, 95% CI: 1.06-2.15) or belonging to a minority racial/ethnic group (OR:1.30, 95% CI: 1.04-1.59) was significantly associated with a greater odds of GDM. When examining the combined effects of social risk factors, a CSR score ≥3 was associated with an increased odds of GDM (OR:1.64, 95% CI: 1.22-2.1). CONCLUSIONS: Women with a greater burden of social risk factors are more likely to have GDM, thus should be the focus of interventions to prevent and treat GDM.

Ideal Cardiovascular Health and Adipokine Levels: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: To evaluate the association between ideal cardiovascular health (CVH) and adipokine levels. Adipokines are hormones implicated in obesity and its cardiometabolic consequences. The concept of ideal CVH was introduced to promote 7 key health factors and behaviors in the general population. Previous studies have found strong associations between obesity and ideal CVH. However, existing literature on the link between CVH and adipokines is scarce. METHODS: We studied 1842 Multi-Ethnic Study of Atherosclerosis participants free of cardiovascular disease who had 7 CVH metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) measured at baseline and serum adipokine levels measured at a median of 2.4 years later. Each CVH metric was assigned a score of 0 (poor), 1 (intermediate), or 2 (ideal), and all scores were summed for a total CVH score (0-14). The total CVH scores of 0 to 8, 9 to 10, and 11 to 14 were considered inadequate, average, and optimal, respectively. We used multivariable linear regression models to assess the nonconcurrent associations between the CVH score and log-transformed adipokine levels. RESULTS: The mean age was 62.1 ± 9.8 years; 50.2% of participants were men. After adjusting for sociodemographic factors, a 1-unit higher CVH score was significantly associated with 4% higher adiponectin and 15% and 1% lower leptin and resistin levels. Individuals with optimal CVH scores had 27% higher adiponectin and 56% lower leptin levels than those with inadequate CVH scores. Similar trends were observed for those with average versus inadequate CVH scores. CONCLUSION: In a multi-ethnic cohort free of cardiovascular disease at baseline, individuals with average and optimal CVH scores had a more favorable adipokine profile than those with inadequate CVH scores.

The role of aldosterone and ideal cardiovascular health in incident diabetes: The Jackson Heart Study.

Background: Greater attainment of ideal cardiovascular health (ICH) and lower serum aldosterone are associated with lower diabetes risk. Higher levels of ICH are associated with lower aldosterone. The mediational role of aldosterone in the association of ICH with incident diabetes remains unexplored. Thus, we examined the mediational role of aldosterone in the association of 5 ICH components (smoking, diet, physical activity, body mass index [BMI], and cholesterol) with incident diabetes. Additionally, we investigated the mediational role of glucose and blood pressure (BP) in the association of aldosterone with incident diabetes in an African American (AA) cohort. Methods: We conducted a prospective cohort analysis among AA adults, aged 21-94 years, in the Jackson Heart Study. Data on ICH, aldosterone, and cardiometabolic risk factors were collected at exam 1 (2000-2004). Diabetes (fasting glucose ≥ 126 mg/dL, physician diagnosis, use of diabetes drugs, or glycated hemoglobin ≥ 6.5%) was assessed at exams 1 through 3 (2009-2012). ICH metrics were defined by American Heart Association 2020 goals for smoking, dietary intake, physical activity, BMI, total cholesterol, BP and glucose. The number of ICH metrics attained at exam 1, excluding BP and fasting glucose, were summed (0-2, vs. 3+). R Package Mediation was used to examine: 1) The mediational role of aldosterone in the association of ICH with incident diabetes; and 2) the mediational role of BP and glucose in the association of aldosterone with incident diabetes. Results: Among 2,791 participants (mean age: 53±12, 65% female) over a median of 7.5 years, there were 497 incident diabetes cases. Risk of incident diabetes was 37% (HR: 0.63, 95%CI: 0.47, 0.84) lower in 3+ ICH category compared to 0-2 ICH category. Aldosterone mediated 6.98% (95% CI: 1.8%, 18.0%) of the direct effect of ICH on incident diabetes. A 1-unit increase in log-aldosterone was associated with a 44% higher risk of diabetes (HR 1.44, 95%CI 1.25-1.64). BP and glucose mediated 16.3% (95% CI: 7.0%, 31.0%) and 19.7% (95% CI: 6.5%, 34.0%) of the association of aldosterone with incident diabetes, respectively. Conclusion: Aldosterone is a mediator of the association of ICH with incident diabetes, whereas BP and glucose are mediators of the association of aldosterone with incident diabetes, emphasizing the importance of the renin-angiotensin-aldosterone system and ICH in lowering risk of diabetes in AA populations.

The need for screening, early diagnosis, and prediction of chronic kidney disease in people with diabetes in low- and middle-income countries-a review of the current literature.

Chronic kidney disease (CKD) in people with diabetes is becoming an increasing major public health concern, disproportionately burdening low- and middle-income countries (LMICs). This rising burden is due to various factors, including the lack of disease awareness that results in late referral and the cost of screening and consequent treatment of the comorbid conditions, as well as other factors endemic to LMICs relating to inadequate management of risk factors. We critically assessed the extant literature, by performing searches of Medline via PubMed, EBSCOhost, Scopus, and Web of Science, for studies pertaining to screening, diagnosis, and prediction of CKD amongst adults with diabetes in LMICs, using relevant key terms. The relevant studies were summarized through key themes derived from the Wilson and Jungner criteria. We found that screening for CKD in people with diabetes is generally infrequent in LMICs. Also, LMICs are ill-equipped to appropriately manage diabetes-associated CKD, especially its late stages, in which supportive care and kidney replacement therapy (KRT) might be required. There are acceptable and relatively simple tools that can aid diabetes-associated CKD screening in these countries; however, these tools come with limitations. Thus, effective implementation of diabetes-associated CKD screening in LMICs remains a challenge, and the cost-effectiveness of such an undertaking largely remains to be explored. In conclusion, for many compelling reasons, screening for CKD in people with diabetes should be a high policy priority in LMICs, as the huge cost associated with higher mortality and morbidity in this group and the cost of KRT offers a compelling economic incentive for improving early detection of diabetes in CKD.

Quality of Care Among Patients with Diabetes and Cerebrovascular Disease. Insights from The Diabetes Collaborative Registry.

BACKGROUND: Although secondary cardiovascular prevention is a focus among patients with type 2 diabetes (T2D) and coronary artery disease (CAD) or peripheral artery disease (PAD), the application of guideline-recommended therapy in T2D patients and isolated cerebrovascular disease (CeVD) remains unknown. METHODS: In a US outpatient registry, T2D patients with established cardiovascular disease from 2014-2018 were categorized as: isolated CeVD, CeVD plus CAD or PAD, or isolated CAD/PAD. In each group, we determined the proportion with optimal secondary prevention (hemoglobin [Hb]A1C <8%, blood pressure <130/80 mm Hg, use of antithrombotics, use of statins, non-smoking/cessation counseling, and use of glucose-lowering medications with cardioprotective effects (sodium-glucose cotransporter [SGLT]-2 inhibitors, glucagon-like peptide [GLP]-1 receptor agonists, thiazolidinediones [TZDs]). Hierarchical Poisson regression was used to estimate relative rate of achieving each target across groups, adjusted for age and chronic kidney disease (where relevant). RESULTS: Our study included 727,467 T2D outpatients with cardiovascular disease (isolated CeVD [n = 99,777], CeVD plus CAD/PAD [n = 158,361], isolated CAD/PAD [n = 469,329]). Compared with isolated CAD/PAD patients, isolated CeVD patients more often had an HbA1c <8% (adjusted relative risk [aRR] 1.10; 95% confidence interval [CI], 1.08-1.11) but less often had a blood pressure of ≤130/80 mm Hg (aRR 0.93; 95% CI, 0.92-0.94) or were prescribed antithrombotics (0.84; 95% CI, 0.83-0.85), statins (0.86; 95% CI, 0.85-0.87), GLP-1 agonists (0.75; 95% CI, 0.73-0.78), SGLT2 inhibitors (0.73; 95% CI, 0.71-0.76), and TZDs (aRR 0.76; 95% CI, 0.73-0.78). CONCLUSION: Among T2D patients, those with isolated CeVD had the lowest rates of secondary cardiovascular prevention goals attainment. More focus is needed on secondary prevention in patients with CeVD.

Correlates of cardiorespiratory fitness among overweight or obese individuals with type 2 diabetes.

INTRODUCTION: Mechanistic studies suggest that type 2 diabetes is independently associated with low cardiorespiratory fitness (CRF). Little is known about the CRF profile in type 2 diabetes; we assessed the correlates of low CRF among overweight/obese adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 4215 participants with type 2 diabetes and without cardiovascular disease underwent maximal exercise testing in the Look AHEAD (Action for Health in Diabetes) study. Low CRF was defined based on the Aerobics Center Longitudinal Study reference standards. Calorie intake and physical activity were assessed using questionnaires. Body fat composition was assessed using dual-energy X-ray absorptiometry. RESULTS: Waist circumference, systolic blood pressure, glycemic measures, whole body fat, caloric intake, and fat-free mass were inversely associated with fitness across sex (all p<0.001). Comparing with moderate or high CRF groups, the low CRF group was associated with higher adjusted odds of obesity (OR 3.19 (95% CI 1.95 to 5.20) in men, 3.86 (95% CI 2.55 to 5.84)) in women), abdominal obesity (OR 3.99 (95% CI 2.00 to 7.96) in men, 2.28 (95% CI 1.08 to 4.79) in women), hypertension (OR 1.74 (95% CI 1.09 to 2.77) in men, 1.44 (95% CI 1.02 to 2.05) in women), metabolic syndrome (OR 5.52 (95% CI 2.51 to 12.14) in men, 2.25 (95% CI 1.35 to 3.76) in women), use of beta-blocker (1.22 (95% CI 0.86 to 1.73) in men, 1.33 (95% CI 1.03 to 1.73) in women), and ACE inhibitor/angiotensin-receptor blocker (1.86 (95% CI 1.39 to 2.50) in men, 1.07 (95% CI 0.86 to 1.32) in women). Women with low CRF had higher odds of current smoking (2.02 (95% CI 1.25 to 3.28)). CONCLUSIONS: Low CRF was associated with increased odds of cardiometabolic correlates in a large cohort of adults with type 2 diabetes.

Screening for Diabetes and Prediabetes.

Overt type 2 diabetes mellitus (T2DM) is preceded by prediabetes and latent diabetes (lasts 9-12 years). Key dysglycemia screening tests are fasting plasma glucose and hemoglobin A1C. Screen-detected T2DM benefits from multifactorial management of cardiovascular risk beyond glycemia. Prediabetes is best addressed by lifestyle modification, with the goal of preventing T2DM. Although there is no trial evidence of prediabetes/T2DM screening effectiveness, simulations suggest that clinic-based opportunistic screening of high-risk individuals is cost-effective. The most rigorous extant recommendations are those of the American Diabetes Association and US Preventive Services Task Force, which advise opportunistic 3-yearly screening.

The association of cortisol curve features with incident diabetes among whites and African Americans: The CARDIA study.

INTRODUCTION: A flatter diurnal cortisol curve has been associated with incident diabetes among older white adults. However, this relationship has not been examined among middle-aged individuals or African Americans [AA]. We analyzed the longitudinal association of baseline diurnal cortisol curve features with incident diabetes over a 10 year period in a cohort of AA and white participants who were, on average, 40 years old. METHODS: Salivary cortisol was collected immediately post-awakening, then subsequently 45 min, 2.5 h, 8 h, and 12 h later, as well as at bedtime. Cortisol curve features included wake-up cortisol; cortisol awakening response (CAR); early, late, and overall decline slopes; bedtime cortisol; and 16 -h area under the curve (AUC). Salivary cortisol (nmol/L) was log-transformed due to positively skewed distributions. Diabetes was defined as fasting plasma glucose ≥ 126 mg/dL or taking diabetes medication. Logistic regression models were used to investigate the association of log-transformed cortisol curve features with incident diabetes. The analysis was stratified by race and adjusted for age, sex, education, depressive symptoms, smoking status, beta-blocker and steroid medication use and BMI. RESULTS: Among 376 AA and 333 white participants (mean age 40 years), 67 incident diabetes cases occurred over 10 years. After full adjustment for additional covariates, a 1-unit log increase in CAR was associated with a 53 % lower odds of incident diabetes among whites (Odds Ratio [OR] 0.47, 95 % CI: 0.24, 0.90). A 1-SD increase in late decline slope was associated with a 416 % higher odds of incident diabetes among whites (OR 5.16, 95 % CI: 1.32, 20.20). There were no significant associations in AAs. CONCLUSION: A robust CAR and flatter late decline slope are associated with lower and higher odds of incident diabetes, respectively, among younger to middle-aged whites and may provide a future target for diabetes prevention in this population.

Clinical and Public Health Implications of 2019 Endocrine Society Guidelines for Diagnosis of Diabetes in Older Adults.

OBJECTIVE: Screening for diabetes is typically done using hemoglobin A1c (HbA1c) or fasting plasma glucose (FPG). The 2019 Endocrine Society guidelines recommend further testing using an oral glucose tolerance test (OGTT) in older adults with prediabetic HbA1c or FPG. We evaluated the impact of this recommendation on diabetes prevalence, eligibility for glucose-lowering treatment, and estimated cost of implementation in a nationally representative sample. RESEARCH DESIGN AND METHODS: We included 2,236 adults aged ≥65 years without known diabetes from the 2005-2016 National Health and Nutrition Examination Survey. Diabetes was defined using: 1) the Endocrine Society approach (HbA1c ≥6.5%, FPG ≥126 mg/dL, or 2-h plasma glucose ≥200 mg/dL among those with HbA1c 5.7-6.4% or FPG 100-125 mg/dL); and 2) a standard approach (HbA1c ≥6.5% or FPG ≥126 mg/dL). Treatment eligibility was defined using HbA1c cut points (≥7% to ≥9%). OGTT screening costs were estimated using Medicare fee schedules. RESULTS: Diabetes prevalence was 15.7% (∼5.0 million) using the Endocrine Society's approach and 7.3% (∼2.3 million) using the standard approach. Treatment eligibility ranged from 5.4% to 0.06% and 11.8% to 1.3% for diabetes cases identified through the Endocrine Society or standard approach, respectively. By definition, diabetes identified exclusively through the Endocrine Society approach had HbA11c <6.5% and would not be recommended for glucose-lowering treatment. Screening all older adults with prediabetic HbA1c/FPG (∼18.3 million) with OGTT could cost between $737 million and $1.7 billion. CONCLUSIONS: Adopting the 2019 Endocrine Society guidelines would substantially increase the number of older adults classified as having diabetes, require significant financial resources, but likely offer limited benefits.

National Trends in Cessation Counseling, Prescription Medication Use, and Associated Costs Among US Adult Cigarette Smokers.

Importance: Cigarette smoking is the leading cause of preventable disease and death in the United States. When used separately or in combination, smoking cessation counseling and cessation medications have been associated with increased cessation rates. Objectives: To present trends in self-reported receipt of physician advice to quit smoking and in use of prescription smoking cessation medication along with their associated expenditures among a nationally representative sample of active adult smokers in the United States. Design, Setting, and Participants: This repeated cross-sectional study of US adults aged 18 years or older was conducted from July 5, 2018, through August 15, 2018. Data were collected between January 1, 2006, and December 31, 2015, from the Medical Expenditure Panel Survey, an annual US survey of individuals and families, health care personnel, and employers. Participants (n = 29 106) were noninstitutionalized civilians who were randomly drawn from the respondents of the previous year's National Health Interview Survey. Multivariable logistic regression models were used to examine the associations between sociodemographic factors and receipt of physician cessation advice and use of cessation prescription medication. A 2-part econometric model was used to assess health care expenditures. Main Outcomes and Measures: Trends in self-reported receipt of physician advice to quit and uptake of prescription smoking cessation medications with associated total and out-of-pocket expenditures. Results: The study sample consisted of 29 106 participants, with a mean (SD) age of 57 (10) years and a composition of 13 670 women (47.0%). The results were weighted to provide estimates for 31.2 million active adult cigarette smokers. The proportion of smokers who reported receiving physician advice to quit increased from 60.2% (95% CI, 58.5%-62.0%) in 2006 to 2007 to 64.9% (95% CI, 62.8%-66.9%) in 2014 to 2015, with a P for trend = .001. The odds of receiving physician cessation advice was statistically significantly higher in women (odds ratio [OR], 1.50; 95% CI, 1.39-1.59) and lower among uninsured participants (OR, 0.58; 95% CI, 0.52-0.65). Overall, prescription smoking cessation medication use decreased with a corresponding reduction in total expenditures from $146 million (out-of-pocket cost, $46 million) in 2006 to 2007 to $73 million (out-of-pocket cost, $9 million) in 2014 to 2015. Male (odds ratio [OR], 0.78; 95% CI, 0.66-0.91), uninsured (OR, 0.58; 95% CI, 0.41-0.83), and racial/ethnic minority (African American: OR, 0.51 [95% CI, 0.38-0.69]; Asian: OR, 0.31 [95% CI, 0.10-0.93]; Hispanic: OR, 0.53 [95% CI, 0.36-0.78]) participants were less likely to use prescription smoking cessation medications. Conclusions and Relevance: The lower rates of delivery of physician advice to quit smoking and the lower uptake of known prescription smoking cessation medications among men, younger adults, uninsured individuals, racial/ethnic minority groups, and those without smoking-associated comorbidities may be associated with the higher smoking rates among these subgroups despite an all-time low prevalence of smoking in the United States; this finding calls for a more targeted implementation of smoking cessation guidelines.

The Association of Life's Simple 7 with Aldosterone among African Americans in the Jackson Heart Study.

BACKGROUND: Among African Americans (AAs), attaining higher levels of American Heart Association (AHA) ideal cardiovascular health (Life's Simple 7 [LS7]) is associated with lower risk of diabetes and cardiovascular disease (CVD). We previously showed that aldosterone is associated with higher risk of diabetes and CVD in AAs. Thus, we investigated the association of LS7 metrics with aldosterone in the Jackson Heart Study (JHS). METHODS: Ideal metrics were defined by AHA 2020 goals for health behaviors (smoking, dietary intake, physical activity, and body mass index) and health factors (total cholesterol, blood pressure, and fasting glucose). The number of ideal LS7 metrics attained at baseline were summed into a continuous score (0-7) and categorical groups (Poor: 0-1, Intermediate: 2-3, and Ideal: ≥4 ideal LS7 metrics). Multivariable linear regression was used. RESULTS: Among 4,095 JHS participants (mean age 55 ± 13 years, 65% female), median serum aldosterone was 4.90, 4.30, and 3.70 ng/dL in the poor (n = 1132), intermediate (n = 2288) and ideal (n = 675) categories respectively. Aldosterone was 15% [0.85 (0.80, 0.90)] and 33% [0.67 (0.61, 0.75)] lower in the intermediate and ideal LS7 categories compared to the poor LS7 category. Each additional LS7 metric attained on continuous LS7 score (0-7) was associated with an 11% [0.89 (0.86, 0.91)] lower aldosterone level with variation by sex with women having a 15% lower aldosterone vs. 5% in men. CONCLUSIONS: Higher attainment of ideal LS7 metrics was associated with lower serum aldosterone among AAs with a greater magnitude of association among women compared to men.

Cardiac Dysfunction Among People Living With HIV: A Systematic Review and Meta-Analysis.

OBJECTIVE: To synthesize existing epidemiological data on cardiac dysfunction in HIV. BACKGROUND: Data on the burden and risk of human immunodeficiency virus (HIV) infection-associated cardiac dysfunction have not been adequately synthesized. We performed meta-analyses of extant literature on the frequency of several subtypes of cardiac dysfunction among people living with HIV. METHODS: We searched electronic databases and reference lists of review articles and combined the study-specific estimates using random-effects model meta-analyses. Heterogeneity was explored using subgroup analyses and meta-regressions. RESULTS: We included 63 reports from 54 studies comprising up to 125,382 adults with HIV infection and 12,655 cases of various cardiac dysfunctions. The pooled prevalence (95% confidence interval) was 12.3% (6.4% to 19.7%; 26 studies) for left ventricular systolic dysfunction (LVSD); 12.0% (7.6% to 17.2%; 17 studies) for dilated cardiomyopathy; 29.3% (22.6% to 36.5%; 20 studies) for grades I to III diastolic dysfunction; and 11.7% (8.5% to 15.3%; 11 studies) for grades II to III diastolic dysfunction. The pooled incidence and prevalence of clinical heart failure were 0.9 per 100 person-years (0.4 to 2.1 per 100 person-years; 4 studies) and 6.5% (4.4% to 9.6%; 8 studies), respectively. The combined prevalence of pulmonary hypertension and right ventricular dysfunction were 11.5% (5.5% to 19.2%; 14 studies) and 8.0% (5.2% to 11.2%; 10 studies), respectively. Significant heterogeneity was observed across studies for all the outcomes analyzed (I2 > 70%, p < 0.01), only partly explained by available study level characteristics. There was a trend for lower prevalence of LVSD in studies reporting higher antiretroviral therapy use or lower proportion of acquired immune deficiency syndrome. The prevalence of LVSD was higher in the African region. After taking into account the effect of regional variation, there was evidence of lower prevalence of LVSD in studies published more recently. CONCLUSIONS: Cardiac dysfunction is frequent in people living with HIV. Additional prospective studies are needed to better understand the burden and risk of various forms of cardiac dysfunction related to HIV and the associated mechanisms. (Cardiac dysfunction in people living with HIV-a systematic review and meta-analysis; CRD42018095374).

Ideal cardiovascular health, glycaemic status and incident type 2 diabetes mellitus: the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

AIMS/HYPOTHESIS: Ideal cardiovascular health (CVH) is associated with lower diabetes risk. However, it is unclear whether this association is similar across glycaemic levels (normal [<5.6 mmol/l] vs impaired fasting glucose [IFG] [5.6-6.9 mmol/l]). METHODS: A secondary data analysis was performed in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Incident diabetes was assessed among 7758 participants without diabetes at baseline (2003-2007) followed over 9.5 years. Baseline cholesterol, blood pressure, diet, smoking, physical activity and BMI were used to categorise participants based on the number (0-1, 2-3 and ≥4) of ideal CVH components. Risk ratios (RRs) were calculated using modified Poisson regression, adjusting for cardiovascular risk factors. RESULTS: Among participants (mean age 63.0 [SD 8.4] years, 56% female, 73% white, 27% African-American), there were 891 incident diabetes cases. Participants with ≥4 vs 0-1 ideal CVH components with normal fasting glucose (n = 6004) had 80% lower risk (RR 0.20; 95% CI 0.10, 0.37), while participants with baseline IFG (n = 1754) had 13% lower risk (RR 0.87; 95% CI 0.58, 1.30) (p for interaction by baseline glucose status <0.0001). Additionally, the magnitude of the association of ideal CVH components with lower diabetes risk was stronger among white than African-American participants (p for interaction = 0.0338). CONCLUSIONS/INTERPRETATION: A higher number of ideal CVH components was associated with a dose-dependent lower risk of diabetes for participants with normal fasting glucose but not IFG. Tailored efforts that take into account observed differences by race and glycaemic level are needed for the primordial prevention of diabetes.

The association of morning serum cortisol with glucose metabolism and diabetes: The Jackson Heart Study.

BACKGROUND: Serum cortisol levels have been associated with type 2 diabetes (T2D). However, the role of cortisol in glycemia and T2D is not fully elucidated among African Americans (AAs). We hypothesized that among AAs morning serum cortisol would be positively associated with glycemic measures and prevalent T2D. METHODS: We examined the cross-sectional association of baseline morning serum cortisol with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), ß-cell function (HOMA-ß), and prevalent T2D in the Jackson Heart Study. Linear regression models were used to examine the association of log-transformed cortisol with glycemic traits, stratified by T2D status. Logistic regression was used to examine the association of log-transformed cortisol with prevalent T2D. Models were adjusted for age, sex, education, occupation, systolic blood pressure, waist circumference, physical activity, smoking, beta-blocker/hormone replacement medications and cortisol collection time. RESULTS: Among 4,206 AAs (mean age 55 ± 13 years, 64% female), 19% had prevalent T2D. A 100% increase in cortisol among participants without diabetes was associated with 2.7 mg/dL (95% CI: 2.0, 3.3) higher FPG and a 10.0% (95% CI: -14.0, -6.0) lower HOMA-ß with no significant association with HbA1c or HOMA-IR. In participants with diabetes, a 100% increase in cortisol was associated with a 23.6 mg/dL (95% CI: 13.6, 33.7) higher FPG and a 0.6% (95% CI: 0.3, 0.9) higher HbA1c. Among all participants, quartile 4 vs. 1 of cortisol was associated with a 1.26-fold (95% CI: 1.75, 2.91) higher odds of prevalent T2D. CONCLUSION: Higher morning serum cortisol was associated with higher FPG and lower ß-cell function among participants without T2D and higher FPG and HbA1c in participants with diabetes. Among all participants, higher cortisol was associated with higher odds of T2D. These findings support a role for morning serum cortisol in glucose metabolism among AAs.

Bariatric Surgery and Hepatocellular Carcinoma: a Propensity Score-Matched Analysis.

BACKGROUND: The association between obesity and rising incidence of hepatocellular carcinoma (HCC) in the USA has been documented; however, the role of bariatric surgery remains less clear. AIM: To evaluate the cross-sectional association of prior-bariatric surgery and HCC. METHODS: The United States Nationwide Inpatient Sample (NIS) database was queried from 2004 to 2014 for discharges with a diagnosis of morbid obesity. Primary outcomes of interest were HCC and in-hospital mortality rate. Secondary outcomes were length of stay and cost. Baseline characteristics were balanced using propensity score matching (PSM). Using Poisson and logistic regressions, adjusted HCC prevalence ratio (PR) and mortality odds ratio (OR) were derived in patients with prior-bariatric surgery compared to those without bariatric surgery. RESULTS: Of the 2,881,414 patients included in our study, 267,082 (9.3%) underwent bariatric surgery. From 2004 to 2014, there was a threefold increase in age-adjusted prevalence of HCC from 27 per 100,000 to 72 per 100,000 (PTrend < 0.001). After PSM, 230,956 patients with prior-bariatric surgery were matched with 230,956 patients without bariatric surgery. Prior-bariatric surgery was associated with lower prevalence of HCC (PR 0.11; 95% CI, 0.03-0.48; P < 0.001). In-hospital mortality was also lower for patients with surgery (OR 0.22; 95% CI, 0.20-0.26; P < 0.001). The occurrence of HCC added $18,840 extra cost, increased mean length of stay by 2 (95% CI; 1-3) days, and increased risk of death by 65% (aOR 1.65; 95% CI 1.18-2.29). CONCLUSION: In this nationwide study of morbidly obese patients, prior-bariatric surgery was associated with a lower prevalence of HCC and lower in-patient mortality.

The double burden of malnutrition among adolescents: analysis of data from the Global School-Based Student Health and Health Behavior in School-Aged Children surveys in 57 low- and middle-income countries.

Background: Adults and young children in countries experiencing the nutrition transition are known to be affected simultaneously by undernutrition and overnutrition. Adolescence is a critical period for growth and development. Yet, it is unknown to what extent this double burden of malnutrition affects adolescents in low- and middle-income countries (LMICs) and the macrolevel contextual factors associated with the double burden of malnutrition. Objective: The aim was to quantify the magnitude of the double burden of malnutrition among adolescents and to examine the potential sources of heterogeneity in prevalence estimates across LMICs. Design: We used individual-participant data from the Global School-Based Student Health and Health Behavior in School-Aged Children surveys conducted in 57 LMICs between 2003 and 2013, comprising 129,276 adolescents aged 12-15 y. Pooled estimates of stunting, thinness, or both; overweight or obesity; and concurrent stunting and overweight or obesity were calculated overall, by regions, and stratified by sex, with random-effects meta-analysis. Guided by UNICEF's conceptual framework for child malnutrition, we used ecological linear regression models to examine the association between macrolevel contextual factors (internal conflict, lack of democracy, gross domestic product, food insecurity, urbanization, and survey year) and stunting, thinness, and overweight and obesity prevalence, respectively. Results: The prevalence of stunting was 10.2% (95% CI: 8.3%, 12.2%) and of thinness was 5.5% (95% CI: 4.3%, 6.9%). The prevalence of overweight or obesity was 21.4% (95% CI: 18.6%, 24.2%). Between 38.4% and 58.7% of the variance in adolescent malnutrition was explained by macrolevel contextual factors. The prevalence of concurrent stunting and overweight or obesity was 2.0% (95% CI: 1.7%, 2.5%). Conclusions: The double burden of malnutrition among adolescents in LMICs is common. Context-sensitive implementation and scale-up of interventions and policies for the double burden of malnutrition are needed to achieve the Sustainable Development Goal to end malnutrition in all of its forms by 2030. This trial was registered at clinicaltrials.gov as NCT03346473.