Relationship of calcium and magnesium intakes with the dietary approaches to stop hypertension score and blood pressure: the International Study of Macro/micronutrients and Blood Pressure.

OBJECTIVE: Research investigating calcium and magnesium intakes from the Dietary Approaches to Stop Hypertension (DASH) pattern and other sources in association with blood pressure is limited. We aimed to characterize sources/intake levels of calcium and magnesium in relation to overall diet quality (DASH-score) and determine modification effects with DASH score and blood pressure. METHODS: Cross-sectional United States data (average dietary and supplement intake from four 24 h recalls and eight blood pressure measurements) from two separate visits, 2195 men and women (40-59 years) in the International Study of Macro/Micronutrients and Blood Pressure were analysed. Food-based adherence to the DASH diet was estimated. Linear models tested associations between each 1-point DASH score with blood pressure. Participants were stratified by adherence to sex-specific recommended allowance for magnesium and calcium intakes. Effect-modification was tested across DASH-score quintiles and median of urinary sodium. RESULTS: DASH-score was inversely associated with SBP in fully adjusted models (-0.27; 95%CI: -0.38 to -0.15 mmHg). SBP was inversely associated with dietary calcium intake from DASH food groups: -1.54 (95% CI: -2.65 to -0.43) mmHg; calcium intake from other non-DASH food groups: -1.62 (95% CI: -2.94 to -0.29) mmHg. Dietary magnesium intake from DASH food groups (-1.59; 95% CI: -2.79, -0.40 mmHg) and from other non-DASH foods (-1.92; 95% CI: -3.31, -0.53 mmHg) was inversely associated with SBP. CONCLUSION: A higher DASH score showed a consistent association with lower BP suggesting a relationship between intakes of calcium and Mg with BP regardless of whether the source is part of the DASH diet or not, even when adjusted for supplement intakes.The INTERMAP is registered as NCT00005271 at www.clinicaltrials.gov .

Sun Exposure and Intima-Media Thickness in the Mexican Teachers' Cohort Study.

Objective: To determine whether long-term sun exposure has a protective role in subclinical cardiovascular disease in adult Mexican women. Materials and Methods: We conducted a cross-sectional analysis of a sample of women from the Mexican Teachers' Cohort (MTC) study. Sun exposure was assessed in the MTC 2008 baseline questionnaire, in which women were asked about their sun-related behavior. Vascular neurologists measured carotid intima-media thickness (IMT) using standard techniques. Multivariate linear regression models were used to estimate the difference in mean IMT and 95% confidence intervals (95% CIs), according to categories of sun exposure and multivariate logistic regression models were used to estimate the odds ratio (OR) and 95% CIs for carotid atherosclerosis. Results: The mean age of participants was 49.6 ± 5.5 years, the mean IMT was 0.678 ± 0.097 mm, and the mean accumulated hours of weekly sun exposure were 2.9 ± 1.9. Prevalence of carotid atherosclerosis was 20.9%. Compared with women in the lowest quartile of sun exposure, women in the highest quartile had lower mean IMT, but this was not significant in the multivariable adjusted analysis. (Adjusted mean % difference: -0.8; 95% CI: -2.3 to 0.8). The multivariate adjusted ORs of carotid atherosclerosis were 0.54 (95% CI: 0.24-1.18) for women who were exposed 9 hours. For women who denied regular sunscreen use, those in the higher exposure category (9 hours) had lower mean IMT compared with those in the lower category (multivariable-adjusted mean % difference = -2.67; 95% CI: -6.9 to -1.5). Conclusions: We observed that cumulative sun exposure was inversely associated with IMT and subclinical carotid atherosclerosis. If these findings are further replicated and seen for other cardiovascular outcomes, sun exposure could be an easy, affordable strategy to lower overall cardiovascular risk.

Blood pressure interactions with the DASH dietary pattern, sodium, and potassium: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP).

BACKGROUND: Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet enhances potassium intake and reduces sodium intake and blood pressure (BP), but the underlying metabolic pathways are unclear. OBJECTIVES: Among free-living populations, we delineated metabolic signatures associated with the DASH diet adherence, 24-hour urinary sodium and potassium excretions, and the potential metabolic pathways involved. METHODS: We used 24-hour urinary metabolic profiling by proton nuclear magnetic resonance spectroscopy to characterize the metabolic signatures associated with the DASH dietary pattern score (DASH score) and 24-hour excretion of sodium and potassium among participants in the United States (n = 2164) and United Kingdom (n = 496) enrolled in the International Study of Macro- and Micronutrients and Blood Pressure (INTERMAP). Multiple linear regression and cross-tabulation analyses were used to investigate the DASH-BP relation and its modulation by sodium and potassium. Potential pathways associated with DASH adherence, sodium and potassium excretion, and BP were identified using mediation analyses and metabolic reaction networks. RESULTS: Adherence to the DASH diet was associated with urinary potassium excretion (correlation coefficient, r = 0.42; P < 0.0001). In multivariable regression analyses, a 5-point higher DASH score (range, 7 to 35) was associated with a lower systolic BP by 1.35 mmHg (95% CI, -1.95 to -0.80 mmHg; P = 1.2 × 10-5); control of the model for potassium but not sodium attenuated the DASH-BP relation. Two common metabolites (hippurate and citrate) mediated the potassium-BP and DASH-BP relationships, while 5 metabolites (succinate, alanine, S-methyl cysteine sulfoxide, 4-hydroxyhippurate, and phenylacetylglutamine) were found to be specific to the DASH-BP relation. CONCLUSIONS: Greater adherence to the DASH diet is associated with lower BP and higher potassium intake across levels of sodium intake. The DASH diet recommends greater intake of fruits, vegetables, and other potassium-rich foods that may replace sodium-rich processed foods and thereby influence BP through overlapping metabolic pathways. Possible DASH-specific pathways are speculated but confirmation requires further study. INTERMAP is registered as NCT00005271 at www.clinicaltrials.gov.

Dairy consumption and subclinical atherosclerosis: A cross-sectional study among middle-aged Mexican women.

BACKGROUND AND AIMS: Many dietary guidelines encourage low-fat dairy products; however, recent studies have found null and inverse associations between high-fat dairy intake and cardiovascular disease (CVD) risk. We examined the association between the intake of total dairy and different types of dairy and carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, in Mexican women. METHODS AND RESULTS: Dairy consumption was assessed using a validated food-frequency questionnaire (FFQ) in 1759 women in the Mexican Teachers' Cohort (MTC) study who were free of CVD or cancer. We categorized participants according to total dairy intake and consumption of four mutually exclusive dairy groups: high-fat, low-fat, yogurt, and dairy with added sugars. IMT and atherosclerotic plaque were measured by B-mode ultrasonography. Subclinical atherosclerosis was defined as an IMT ≥0.8 mm and/or the presence of plaque. Multivariable linear regression and logistic regression models were used to respectively assess the mean percentage difference of mean IMT and odds ratios (OR) for subclinical atherosclerosis across quantiles of dairy consumption. Mean (±SD) age was 45.4 ± 5.0 years and the median (interquartile range: IQR) total dairy consumption was 11.0 (6.6, 17.1) servings/week. After adjusting for lifestyle, clinical, and dietary factors, comparing the highest category of consumption, to the lowest, total dairy was associated with increased IMT (2.6%, 95% confidence interval (CI): 0.6, 4.3; p-trend<0.01). Moreover, yogurt consumption was associated with lower odds of subclinical atherosclerosis (OR = 0.65, 95% CI: 0.47, 0.91; p-trend = 0.01). CONCLUSIONS: While total dairy consumption was associated with carotid wall thickening, yogurt consumption was related to lower subclinical atherosclerosis.

Association of recurrent common infections and subclinical cardiovascular disease in Mexican women.

BACKGROUND: Acute and agent-specific chronic infections have been associated with increased cardiovascular risk, however data on the burden of common recurrent infections on cardiovascular disease is limited. We hypothesized women with greater exposure to uncomplicated common infectious events had an increased risk of subclinical cardiovascular disease (sCVD). METHODS: In a cross-sectional study, we assessed the relation of recurrent infections and carotid artery intima-media thickness (IMT) in 1946 disease-free women from the Mexican Teachers' Cohort. Through 2012-2016, participants answered structured questions on respiratory, urinary and vaginal infections during the previous year and their IMT was measured using ultrasound by standardized neurologists. We defined sCVD as mean right and left IMT ≥0.8 mm or the presence of atheromatous plaque. Multivariable linear and logistic regression analyses were used to evaluate the association of infectious events with IMT and sCVD adjusting for age, sociodemographic, and cardiovascular risk factors. RESULTS: Among participants (50±5 years) 13% reported no infections, 20% one infection and 67% three or more episodes. Overall prevalence of sCVD was 12%(n = 240). Adjusted models for logistic regression showed that women with 2 or more infections had 91% higher odds of sCVD (OR 1.91; 95%CI 1.16, 3.13) compared to women without infections (p-trend:0.015). Sub-analyses by type of infection resulted not significant. Linear regression analysis did not show a significant association between mean IMT and recurrent infections. CONCLUSIONS: Recurrent infectious events in young adult women are associated with greater sCVD, which supports the hypothesis of low-grade chronic inflammation in the pathophysiology of cardiovascular disease.

Family Member Incarceration, Psychological Stress, and Subclinical Cardiovascular Disease in Mexican Women (2012-2016).

Objectives. To examine the association between family member incarceration, psychological stress, and subclinical cardiovascular disease (CVD).Methods. Between 2012 and 2016, 1849 CVD-free women from the Mexican Teachers' Cohort responded to questions on family incarceration from the Life Stressor Checklist. Perceived stress and hair cortisol levels were measured in a subset of participants. Carotid intima-media thickness was measured, and carotid atherosclerosis was determined in all participants. We used multivariable quantile, linear, and logistic regression models to evaluate the association between family member incarceration, stress, and subclinical CVD.Results. Among women with a mean age of 49.7 years (SD ±5.2), 15.3% reported family member incarceration. We found that both perceived stress and hair cortisol levels were significantly higher in women with an incarcerated family member relative to women without one. After multivariable adjustment, women who reported family member incarceration had 41% (95% confidence interval = 1.04, 2.00) higher odds of carotid atherosclerosis compared with those who did not.Conclusions. Family member incarceration was associated with robust markers of stress and cardiovascular risk. Mass incarceration may have a long-lasting impact on physical health of affected families.

The Association of Fasting Glucose, Insulin, and C-Peptide, with 19-Year Incidence of Coronary Heart Disease in Older Japanese-American Men; the Honolulu Heart Program.

The role of fasting glucose, insulin levels, and C-peptide in coronary heart disease (CHD) in non-diabetic individuals remains uncertain. We examined the association between fasting glucose, insulin and C-peptide with the long-term incidence of CHD in Japanese-American men. In 1980-1982, from a random sample of the Honolulu Heart Program men (n = 1378), aged 61-81 years, data on several CHD and metabolic risk factors were obtained to examine the relation of fasting glucose, insulin and C-peptide to 19-year CHD incidence. Age-adjusted incidence of CHD increased with increasing quintiles of glucose, insulin and C-peptide. Age-adjusted CHD rates in the glucose quintiles were 11.9, 11.6, 14.4, 18.1 and 24.1 per 1000 person-years (trend p < 0.001). In individual Cox models (lowest quintiles of glucose, insulin and C-peptide as reference) the relative risks (95% confidence interval) of CHD incidence for the glucose quintiles adjusting for age, smoking, hypertension, cholesterol, physical activity, and body mass index, were 0.9 (0.6-1.4), 1.2 (0.8-1.8), 1.4 (0.9-2.2), and 1.7 (1.1-2.6), respectively (trend p = 0.004). Insulin and C-peptide were not significantly associated with CHD on multivariate analysis. Fasting glucose remained the only significant predictor of increased CHD risk (p = 0.003) in a model combining all 3 metabolic variables. In this cohort, only fasting glucose independently predicts long-term incidence of CHD. Age-adjusted insulin and C-peptide levels were associated with CHD incidence, but after adjustment for other risk factors, do not independently predict CHD.

Effects of Walking on Coronary Heart Disease in Elderly Men with Diabetes.

Previous studies have shown that walking is associated with increased longevity and a reduced risk of cardiovascular and age-related diseases. Whether walking benefits individuals with diabetes who are at high risk of coronary heart disease (CHD) remains to be determined. The objective of this study is to examine the association between walking and risk of CHD among elderly men with and without diabetes. Walking data was assessed in 2732 men aged 71 to 93 years participating in the Honolulu Heart Program from 1991-1993. Study participants were initially without disabilities and free of prevalent CHD. Men were then followed for incident CHD for up to 7 years. For men with diabetes who walked <0.25 miles/day, the age-adjusted incidence of CHD was significantly higher than in men without diabetes (27.1 vs. 12.7/1000 person years, p = 0.026). In contrast when distance walked was >1.5 miles/day, incidence of CHD was similar in men with and without diabetes (12.2 vs. 9.1/1000 person-years, p = 0.46). While risk of CHD declined significantly with increasing walking distance in men with diabetes after age and risk factor adjustment (p = 0.043, p = 0.025), associations in those without diabetes were weaker (p = 0.070, p = 0.10). These findings suggest that among elderly men with diabetes who are capable of physical activity, walking reduces CHD risk to levels similar to when diabetes is absent. Walking is an easy, safe and accessible form of physical activity that may have marked health benefits for elderly men with diabetes.

International Comparison of Abdominal Fat Distribution Among Four Populations: The ERA-JUMP Study.

BACKGROUND: Abdominal fat distribution varies across groups with different races or environments. Whether environmental factors, apart from racial differences, affect abdominal fat distribution is unknown. METHODS: We compared the abdominal fat distribution of four groups; different races with similar environments (Caucasians vs. Japanese Americans), different environments with an identical race (Japanese Americans vs. Japanese), and similar races with similar environments (Japanese vs. Koreans). A population-based sample of 1212 men aged 40-49 were analyzed: 307 Caucasians and 300 Japanese Americans in the United States, 310 Japanese in Japan, and 295 Koreans in Korea. We compared the proportion of visceral adipose tissue area to total abdominal adipose tissue area (VAT%) and other factors that can affect abdominal fat distribution (smoking, alcohol use, physical activity levels, and metabolic factors). RESULTS: VAT% was significantly higher in Japanese and Koreans than in Japanese Americans and Caucasians (50.0, 48.5, 43.2, 41.0%, respectively, P < 0.001). Even after adjustment for possible confounders, the significant VAT% difference remained in comparing groups with identical race but different environments (i.e., Japanese vs. Japanese Americans). In contrast, comparing groups with different races but similar environments (i.e., Caucasians vs. Japanese Americans), VAT% was not significantly different. Comparing groups with similar races and similar environments (i.e., Japanese vs. Koreans), VAT% did not significantly differ. CONCLUSIONS: Environmental differences, apart from racial differences, affect the difference in abdominal fat distribution across different groups in middle-aged men.

Western and Modern Mexican dietary patterns are directly associated with incident hypertension in Mexican women: a prospective follow-up study.

BACKGROUND: Research has found that diet and dietary patterns are associated with blood pressure and hypertension. Limited research in this area has been conducted in a Mexican population. METHODS: We investigated the relation between dietary patterns (principal component analysis) and the incidence of self-reported treated hypertension in 62,913 women from the Mexican Teachers' Cohort, a large population-based cohort of female Mexican teachers, who were free of hypertension at baseline in 2006-2008 when diet was assessed using a food frequency questionnaire. Dietary patterns were categorized into quartiles and logistic regression models were fit. RESULTS: Participants were 42.1 ± 7.3 years old, had a BMI 27.0 ± 4.4 and a cumulative incidence of hypertension of 4.6%. Between baseline and first follow-up (2011-2014) we identified 2916 incident cases of hypertension. We identified three major components. The first was loaded heavily with vegetables, fruits and legumes; the second component was loaded heavily with processed meats, fast foods, and red meat; and finally the third component was loaded heavily with corn tortillas, hot peppers, and sodas. We named the components as Fruits & Vegetables (FV), Western (W), and Modern Mexican (MM). The multivariable-adjusted odds of hypertension in the highest quartile of the W pattern were 24% higher than the odds for individuals in the lowest quartile (95%CI = 1.10, 1.40; P-trend = 0.0004); women in the highest quartile of the MM pattern had 15% higher odds than women in the lowest quartile (95%CI = 1.02, 1.29; P-trend = 0.01). The FV pattern was not significantly associated with hypertension (OR for extreme quartiles = 0.94; 95%CI = 0.84, 1.05; P-trend = 0.19). CONCLUSION: The Western pattern and the Modern Mexican pattern, which showcases an undergoing nutrition transition, may affect the incidence of hypertension, whereas the FV pattern was not associated with hypertension. These findings are important in the prevention of hypertension and cardiovascular diseases in Mexico and possibly among Mexican people living in the US.

Serum cystatin C in youth with diabetes: The SEARCH for diabetes in youth study.

AIMS: We compared cystatin C in youth with versus without diabetes and determined factors associated with cystatin C in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D). METHODS: Youth (ages 12-19years) without diabetes (N=544) were ascertained from the NHANES Study 2000-2002 and those with T1D (N=977) and T2D (N=168) from the SEARCH for Diabetes in Youth Study. Adjusted means of cystatin C concentrations were compared amongst the 3 groups. Next, we performed multivariable analyses within the T1D and T2D SEARCH samples to determine the association between cystatin C and race, sex, age, diabetes duration, HbA1c, fasting glucose, and BMI. RESULTS: Adjusted cystatin C concentrations were statistically higher in NHANES (0.85mg/L) than in either the T1D (0.75mg/L) or T2D (0.70mg/L) SEARCH groups (P<0.0001). Fasting glucose was inversely related to cystatin C only in T1D (P<0.001) and BMI positively associated only in T2D (P<0.01) while HbA1c was inversely associated in both groups. CONCLUSIONS: Cystatin C concentrations are statistically higher in youth without diabetes compared to T1D or T2D, however the clinical relevance of this difference is quite small, especially in T1D. In youth with diabetes, cystatin C varies with BMI and acute and chronic glycemic control, however their effects may be different according to diabetes type.

The Associations of Atrial Fibrillation With the Risks of Incident Invasive Breast and Colorectal Cancer.

Atrial fibrillation (AF) is a common arrhythmia that poses a significant risk of stroke. Cross-sectional and case-control studies have shown evidence of associations between AF and breast or colorectal cancer, but there have been no longitudinal studies in which this has been assessed. We prospectively examined a cohort of 93,676 postmenopausal women enrolled in the Women's Health Initiative from 1994 to 1998 to determine whether there are relationships between baseline AF and the development of invasive breast or colorectal cancer. The prevalence of self-reported physician diagnosis of AF at baseline was 5.1%. Over approximately 15 years of follow-up, the incidence of invasive breast cancer was 5.7%, and the incidence of colorectal cancer was 1.6%. Adjusted hazard ratios and 95% confidence intervals were obtained using Cox proportional hazards models. We found no significant association between AF and incident colorectal cancer, but we did see a 19% excess risk of invasive breast cancer among those with AF (adjusted hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.03, 1.38). Additional adjustment for baseline use of cardiac glycosides attenuated the association between AF and invasive breast cancer (HR = 1.01, 95% CI: 0.85, 1.20). Cardiac glycoside use was strongly associated with incident invasive breast cancer (HR = 1.68, 95% CI: 1.33, 2.12) independent of AF and other confounders. Mechanisms of the associations among breast cancer, AF, and cardiac glycosides need further investigation.

Progression of coronary artery calcium in Japanese American men and white men in the ERA JUMP study.

BACKGROUND: Progression of coronary artery calcium (CAC) is associated with increased risk of coronary heart disease (CHD) and is reported to be greater in whites than blacks, Hispanics, and Chinese in the US. Our objective was to compare progression of CAC between Japanese Americans and whites. METHODS: Population-based sample of 303 Japanese American men and 310 white men aged 40-49years, free of clinical cardiovascular disease at baseline, were examined for CAC at baseline (2004-2007) and follow-up (2008-2013). Progression of CAC was defined as change in coronary calcium scores (CCS) in participants with baseline CCS>0 and incident CAC in participants with baseline CCS=0. Multiple linear regression and relative risk regression were used to compare change in CCS scores and incident CAC between the two races, respectively. RESULTS: Japanese American men had significantly greater annual change in CCS than white men (median [interquartile range]: 11.3 Agatston units [1.4, 24.9] vs 2.5 [-0.22, 14.5]) in the unadjusted analyses. After adjusting for cardiovascular risk factors and follow-up time, change in CCS (beta±CI) and incidence rate ratio of CAC was similar in Japanese American men and white men: -0.12 (-0.34, 0.15) and (0.87 [95% CI: 0.20, 3.9]), respectively. CONCLUSIONS: In contrast to previously reported greater progression of CAC in whites than other races, we found a similar progression of CAC in Japanese American men as white men. Our study identifies Japanese American men as a target group for prevention of CHD. Large prospective studies are warranted to confirm these findings.

Racial and ethnic differences in atrial fibrillation risk factors and predictors in women: Findings from the Women's Health Initiative.

BACKGROUND: The incidence of atrial fibrillation (AF) is higher in non-Hispanic whites (NHWs) compared with other race-ethnic groups, despite more favorable cardiovascular risk profiles. To explore reasons for this paradox, we compared the hazards of AF from traditional and other risk factors between 4 race-ethnic groups in a large cohort of postmenopausal women. METHODS: We included 114,083 NHWs, 11,876 African Americans, 5,174 Hispanics, and 3,803 Asians from the Women's Health Initiative free of AF at baseline. Women, averaging 63 years old, were followed up for incident AF using hospitalization records and diagnostic codes from Medicare claims. RESULTS: Over a mean of 13.7 years, 19,712 incident cases of AF were recorded. Despite a higher burden of hypertension, diabetes, and obesity, annual AF incidence was lower among nonwhites (0.7%, 0.4%, and 0.4% for African American, Hispanic, and Asian participants, respectively, compared with 1.2% for NHWs). The hazards of AF from hypertension, diabetes, obesity, heart failure, and coronary artery disease were similar across race-ethnic groups. Major risk factors, including hypertension, obesity, diabetes, smoking, peripheral arterial disease, coronary artery disease, and heart failure, accounted for an attributable risk of 50.3% in NHWs, 83.1% in African Americans, 65.6% in Hispanics, and 37.4% in Asians. Established AF prediction models performed comparably across race-ethnic groups. CONCLUSIONS: In this large study of postmenopausal women, traditional cardiovascular risk factors conferred a similar degree of individual risk of AF among 4 race-ethnic groups. However, major AF risk factors conferred a higher-attributable risk in African Americans and Hispanics compared with NHWs and Asians.

Significantly Greater Progression of Intima-Media Thickness of the Carotid Artery in Japanese American Men Than in White Men: The ERA JUMP Study.

BACKGROUND: Although a westernized lifestyle was associated with increased coronary heart disease (CHD), morbidity, and mortality in first- and second-generation Japanese Americans, CHD mortality was reported to be lower in this population than in whites. The risk profile of CHD for third- and fourth-generation Japanese Americans is not known. We compared the progression of carotid intima-media thickness (CIMT) between third- or fourth-generation Japanese Americans and whites. METHODS: Population-based samples of 473 men (Japanese Americans, 227; whites, 246) aged 40-49 years at baseline and free of clinical cardiovascular disease were examined for CIMT at baseline (2004-2007) and follow-up (2007-2013). CIMT was determined centrally at the University of Pittsburgh, Pittsburgh, Pennsylvania. Analysis of covariance was used to compare annualized progression of CIMT between Japanese Americans and whites, adjusting for cardiovascular risk factors and baseline CIMT. RESULTS: Progression of CIMT was significantly greater in Japanese Americans than in whites both before and after adjusting for covariates: mean, 14.4 µm/y; 95% confidence interval [CI],12.3-16.4 vs 9.8 µm/y; 95% CI, 7.8-11.7; P < 0.05 and 15.1 µm/y; 95% CI, 13.1-17.1 vs 9.1 µm/y; 95% CI, 7.2-11.0; P < 0.05, respectively. Age, total cholesterol/high-density lipoprotein cholesterol, and diabetes in Japanese Americans and age, hypertension, and lipid medication in whites were significantly associated with progression of CIMT. CONCLUSIONS: The significantly greater progression of CIMT in Japanese Americans than in whites might suggest a higher future burden of CHD in Japanese Americans than in whites. The current study identifies Japanese Americans as an important target group for prevention of CHD. Future research assessing carotid plaque in addition to CIMT is warranted.

Brachial-ankle pulse wave velocity is associated with coronary calcification among 1131 healthy middle-aged men.

BACKGROUND: Brachial-ankle pulse wave velocity (baPWV) is a simple and reproducible measure of arterial stiffness and is extensively used to assess cardiovascular disease (CVD) risk in eastern Asia. We examined whether baPWV is associated with coronary atherosclerosis in an international study of healthy middle-aged men. METHODS: A population-based sample of 1131 men aged 40-49 years was recruited - 257 Whites and 75 Blacks in Pittsburgh, US, 228 Japanese-Americans in Honolulu, US, 292 Japanese in Otsu, Japan, and 279 Koreans in Ansan, Korea. baPWV was measured with an automated waveform analyzer (VP2000, Omron) and atherosclerosis was examined as coronary artery calcification (CAC) by computed-tomography (GE-Imatron EBT scanner). Association of the presence of CAC (defined as ≥ 10 Agatston unit) was examined with continuous measure as well as with increasing quartiles of baPWV. RESULTS: As compared to the lowest quartile of baPWV, the multivariable-adjusted odds ratio (95% Confidence Interval [CI]) for the presence of CAC in the combined sample was 1.70 (0.98, 2.94) for 2nd quartile, 1.88 (1.08, 3.28) for 3rd quartile, and 2.16 (1.19, 3.94) for 4th quartile (p-trend = 0.01). The odds for CAC increased by 19% per 100 cm/s increase (p < 0.01), or by 36% per standard-deviation increase (p < 0.01) in baPWV. Similar effect-sizes were observed in individual races, and were significant among Whites, Blacks and Koreans. CONCLUSION: baPWV is cross-sectionally associated with CAC among healthy middle-aged men. The association was significant in Whites and Blacks in the US, and among Koreans. Longitudinal studies are needed to determine its CVD predictive ability.

The SEARCH for Diabetes in Youth study: rationale, findings, and future directions.

The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000, with funding from the Centers for Disease Control and Prevention and support from the National Institute of Diabetes and Digestive and Kidney Diseases, to address major knowledge gaps in the understanding of childhood diabetes. SEARCH is being conducted at five sites across the U.S. and represents the largest, most diverse study of diabetes among U.S. youth. An active registry of youth diagnosed with diabetes at age <20 years allows the assessment of prevalence (in 2001 and 2009), annual incidence (since 2002), and trends by age, race/ethnicity, sex, and diabetes type. Prevalence increased significantly from 2001 to 2009 for both type 1 and type 2 diabetes in most age, sex, and race/ethnic groups. SEARCH has also established a longitudinal cohort to assess the natural history and risk factors for acute and chronic diabetes-related complications as well as the quality of care and quality of life of persons with diabetes from diagnosis into young adulthood. Many youth with diabetes, particularly those from low-resourced racial/ethnic minority populations, are not meeting recommended guidelines for diabetes care. Markers of micro- and macrovascular complications are evident in youth with either diabetes type, highlighting the seriousness of diabetes in this contemporary cohort. This review summarizes the study methods, describes key registry and cohort findings and their clinical and public health implications, and discusses future directions.

Correlates of treatment patterns among youth with type 2 diabetes.

OBJECTIVE To describe treatment regimens in youth with type 2 diabetes and examine associations between regimens, demographic and clinical characteristics, and glycemic control. RESEARCH DESIGN AND METHODS This report includes 474 youth with a clinical diagnosis of type 2 diabetes who completed a SEARCH for Diabetes in Youth study visit. Diabetes treatment regimen was categorized as lifestyle alone, metformin monotherapy, any oral hypoglycemic agent (OHA) other than metformin or two or more OHAs, insulin monotherapy, and insulin plus any OHA(s). Association of treatment with demographic and clinical characteristics (fasting C-peptide [FCP], diabetes duration, and self-monitoring of blood glucose [SMBG]), and A1C was assessed by χ(2) and ANOVA. Multiple linear regression models were used to evaluate independent associations of treatment regimens and A1C, adjusting for demographics, diabetes duration, FCP, and SMBG. RESULTS Over 50% of participants reported treatment with metformin alone or lifestyle. Of the autoantibody-negative youth, 40% were on metformin alone, while 33% were on insulin-containing regimens. Participants on metformin alone had a lower A1C (7.0 ± 2.0%, 53 ± 22 mmol/mol) than those on insulin alone (9.2 ± 2.7%, 77 ± 30 mmol/mol) or insulin plus OHA (8.6 ± 2.6%, 70 ± 28 mmol/mol) (P < 0.001). These differences remained significant after adjustment (7.5 ± 0.3%, 58 ± 3 mmol/mol; 9.1 ± 0.4%, 76 ± 4 mmol/mol; and 8.6 ± 0.4%, 70 ± 4 mmol/mol) (P < 0.001) and were more striking in those with diabetes for ≥2 years (7.9 ± 2.8, 9.9 ± 2.8, and 9.8 ± 2.6%). Over one-half of those on insulin-containing therapies still experience treatment failure (A1C ≥8%, 64 mmol/mol). CONCLUSIONS Approximately half of youth with type 2 diabetes were managed with lifestyle or metformin alone and had better glycemic control than individuals using other therapies. Those with longer diabetes duration in particular commonly experienced treatment failures, and more effective management strategies are needed.

Peripheral neuropathy in adolescents and young adults with type 1 and type 2 diabetes from the SEARCH for Diabetes in Youth follow-up cohort: a pilot study.

OBJECTIVE: To estimate the prevalence of and risk factors for diabetic peripheral neuropathy (DPN) in a pilot study among youth participating in the SEARCH for Diabetes in Youth study. RESEARCH DESIGN AND METHODS: DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI) (examination for foot abnormalities, distal vibration perception, and ankle reflexes). An MNSI exam (MNSIE) score >2 is diagnostic for DPN. RESULTS: The MNSIE was completed in 399 subjects, including 329 youth with type 1 diabetes (mean age 15.7 ± 4.3 years, duration 6.2 ± 0.9 years) and 70 with type 2 diabetes (mean age 21.6 ± 4.1 years, duration 7.6 ± 1.8 years). Glycated hemoglobin (A1C) was similar in both groups (8.8 ± 1.8% for type 1 vs. 8.5 ± 2.9% for type 2). The prevalence of DPN was significantly higher in youth with type 2 compared with those with type 1 diabetes (25.7 vs. 8.2%; P < 0.0001). In unadjusted analyses, diabetes type, older age, longer duration of diabetes, increased waist circumference, elevated blood pressure, lower HDL cholesterol, and presence of microalbuminuria (urinary albumin-to-creatinine ratio >30 mg/g) were associated with DPN. The association between diabetes type and DPN remained significant after adjustment for age and sex (odds ratio 2.29 [95% CI 1.05-5.02], P = 0.03). CONCLUSIONS: DPN prevalence among youth with type 2 diabetes approached rates reported in adult populations with diabetes. Our findings suggest not only that youth with diabetes are at risk for DPN but also that many already show measurable signs of DPN.

Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth.

AIMS: Our study aims were to determine the frequency of MODY mutations (HNF1A, HNF4A, glucokinase) in a diverse population of youth with diabetes and to assess how well clinical features identify youth with maturity-onset diabetes of the young (MODY). METHODS: The SEARCH for Diabetes in Youth study is a US multicenter, population-based study of youth with diabetes diagnosed at age younger than 20 years. We sequenced genomic DNA for mutations in the HNF1A, HNF4A, and glucokinase genes in 586 participants enrolled in SEARCH between 2001 and 2006. Selection criteria included diabetes autoantibody negativity and fasting C-peptide levels of 0.8 ng/mL or greater. RESULTS: We identified a mutation in one of three MODY genes in 47 participants, or 8.0% of the tested sample, for a prevalence of at least 1.2% in the pediatric diabetes population. Of these, only 3 had a clinical diagnosis of MODY, and the majority was treated with insulin. Compared with the MODY-negative group, MODY-positive participants had lower FCP levels (2.2 ± 1.4 vs 3.2 ± 2.1 ng/mL, P < .01) and fewer type 2 diabetes-like metabolic features. Parental history of diabetes did not significantly differ between the 2 groups. CONCLUSIONS/INTERPRETATION: In this systematic study of MODY in a large pediatric US diabetes cohort, unselected by referral pattern or family history, MODY was usually misdiagnosed and incorrectly treated with insulin. Although many type 2 diabetes-like metabolic features were less common in the mutation-positive group, no single characteristic identified all patients with mutations. Clinicians should be alert to the possibility of MODY diagnosis, particularly in antibody-negative youth with diabetes.