Trends in HbA1c levels and implications for diabetes screening in tuberculosis cases undergoing treatment in India.

SETTING: The optimal timing of screening for diabetes mellitus (DM) among tuberculosis (TB) cases is unclear due to the possibility of stress hyperglycemia. DESIGN: We evaluated adult (18 years) pulmonary TB cases at treatment initiation as well as at 3 months, 6 months and 12 months. DM was identified by self-report (known DM) or glycated hemoglobin (HbA1c)  6.5% (new DM). Trends in HbA1c levels during treatment were assessed using non-parametric tests. RESULTS: Of the 392 participants enrolled, 75 (19%) had DM, 30 (40%) of whom had new DM. Of the 45 participants with known DM, respectively 37 (82%) and 40 (89%) received medication to lower glucose levels at treatment initiation and completion; one participant with new DM initiated glucose-lowering medication during follow-up. The median HbA1c level in participants with known, new and no DM was respectively 10.1% (interquartile range [IQR] 8.3-11.6), 8.5% (IQR 6.7-11.5) and 5.6% (IQR 5.3-5.9) at treatment initiation, and 8.7% (IQR 6.8-11.3), 7.1% (IQR 5.8-9.5) and 5.3% (IQR 5.1-5.6) at treatment completion (P < 0.001). Overall, 5 (12%) with known and 13 (43%) with new DM at treatment initiation had reverted to HbA1c < 6.5% by treatment completion (P = 0.003); the majority of reversions occurred during the first 3 months, with no significant reversions beyond 6 months. CONCLUSION: HbA1c levels declined with anti-tuberculosis treatment. Repeat HbA1c testing at treatment completion could reduce the risk of misdiagnosis of DM.

Prevalence and correlates of depressive symptoms in older adults across the glycaemic spectrum: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS: To document the prevalence of current depressive symptoms and history of depression across the glycaemic spectrum in older adults, and examine if measures of health status and healthcare satisfaction, access and utilization explain differences in the prevalence of current depressive symptoms by diabetes status. METHODS: We conducted a cross-sectional study of 6226 participants aged 67-90 years who attended the 2011-2013 visit of the Atherosclerosis Risk in Communities (ARIC) study. Diabetes was based on self-report, medication use and HbA1c . Current depressive symptoms were defined using the Center for Epidemiologic Studies Depression 11-item questionnaire, and history of depression was assessed via self-report. We examined obesity, history of cardiovascular disease, hypertension, kidney disease, cognitive function, and self-reported health compared with others. Prevalence and prevalence ratios were estimated using age-, race-, and sex-adjusted Poisson regression. RESULTS: The prevalence of current depressive symptoms was 5.4% in people without diabetes and 11.0% in people with diabetes (prevalence ratio 2.04, 95% CI 1.60, 2.48); the prevalence of history of depression was 11% in people without diabetes and 17.7% in people with diabetes (prevalence ratio 1.61, 95% CI 1.28,1.95). Strong correlates of current depressive symptoms were history of depression (prevalence ratio 3.86, 95% CI 3.05, 4.90) and reporting poor health compared with others (prevalence ratio 3.88, 95% CI 2.93, 5.15). No variables had significantly different associations with depressive symptoms across glycaemic categories (P for interaction >0.10). CONCLUSIONS: In older adults, current depressive symptoms were twice as prevalent in people with diabetes compared with those without. Measures of health status and healthcare did not explain differences in depressive symptoms between people with and without diabetes.

Effects of dietary carbohydrate on 1,5-anhydroglucitol in a population without diabetes: results from the OmniCarb trial.

AIMS: To determine the effects of dietary changes in amount and type of carbohydrate on 1,5-anhydroglucitol levels. METHODS: We conducted an ancillary study to a completed, randomized clinical trial in overweight and obese adults without diabetes (N=159). Using a crossover design, participants were fed each one of four diets in turn for 5 weeks, with 2-week washout periods inbetween. The four diets were: high glycaemic index (≥65) with high proportion of carbohydrate (58% kcal) (GC); low glycaemic index (GI≤45) with low proportion of carbohydrate (40% kcal) (gc); low glycaemic index with high proportion of carbohydrate (gC); and high glycaemic index with low proportion of carbohydrate (Gc). Plasma 1,5-anhydroglucitol levels were measured at baseline and after each feeding period. RESULTS: At baseline, participants had a mean age of 53 years (53% women, 52% non-Hispanic black, 50% obese). Their mean fasting glucose and 1,5-anhydroglucitol levels were 97 mg/dl (5.4 mmol/l) and 18.6 µg/mL (113.3 µmol/l), respectively. Compared with baseline, each of the four diets reduced 1,5-anhydroglucitol by a range of -2.4 to -3.7 µg/mL (-14.6 to -22.5 µmol/l); all P <0.001). Reducing either glycaemic index or proportion of carbohydrate lowered 1,5-anhydroglucitol levels. These effects were additive, such that reducing both glycaemic index and proportion of carbohydrates decreased 1,5-anhydroglucitol by -1.31 µg/mL [95% CI: -1.63, -0.99; P<0.001 or -8.0 (-9.9, -6.0) µmol/l]. Furthermore, these effects were confirmed in a subgroup of participants with 12-h glucose monitoring and no documented hyperglycaemia (fasting glucose <160 mg/dl or 8.9 mmol/l). CONCLUSIONS: Both type and amount of dietary carbohydrate affect 1,5-anhydroglucitol plasma concentrations in adults without diabetes. This finding contradicts the long-standing notion that 1,5-anhydroglucitol remains at constant concentrations in the blood in the absence of hyperglycaemic excursions. (Clinical trials registry number: NCT00051350).

Prevalence of dysglycemia and clinical presentation of pulmonary tuberculosis in Western India.

SETTING: Pune, India. OBJECTIVES: To estimate the prevalence and risk factors of pre-diabetes mellitus (DM) and DM, and its associations with the clinical presentation of tuberculosis (TB). DESIGN: Screening for DM was conducted among adults (age  18 years) with confirmed TB between December 2013 and January 2017. We used multinomial regression to evaluate the risk factors for pre-DM (glycated hemoglobin [HbA1c]  5.7-6.5% or fasting glucose 100-125 mg/dl) and DM (HbA1c  6.5% or fasting glucose  126 mg/dl or random blood glucose > 200 mg/dl or self-reported DM history/treatment) and the association of dysglycemia with the severity of TB disease. RESULTS: Among 1793 participants screened, 890 (50%) had microbiologically confirmed TB. Of these, 33% had pre-DM and 18% had DM; 41% were newly diagnosed. The median HbA1c level among newly diagnosed DM was 7.0% vs. 10.3% among known DM (P < 0.001). DM (adjusted OR [aOR] 4.94, 95%CI 2.33-10.48) and each per cent increase in HbA1c (aOR 1.42, 95%CI 1.01-2.01) was associated with >1+ smear grade or 9 days to TB detection. CONCLUSION: Over half of newly diagnosed TB patients had DM or pre-DM. DM and increasing dysglycemia was associated with higher bacterial burden at TB diagnosis, potentially indicating a higher risk of TB transmission to close contacts.

Pre-diabetes and serum sex steroid hormones among US men.

Several studies demonstrate a link between diabetes and sex steroid hormones, but the link with pre-diabetes remains elusive. In this study, we hypothesize that pre-diabetes, which is characterised by having impaired fasting glucose and/or impaired glucose tolerance and/or impaired HbA1C, may influence circulating sex steroid hormone concentrations in men. Thus, we investigated whether serum sex steroid hormone concentrations differ between men with and without pre-diabetes. We analyzed data for 1139 men who were aged 20+ years when they participated in the Third National Health and Nutrition Examination Survey. We calculated adjusted geometric mean serum concentrations of total and estimated free testosterone, androstanediol glucuronide, total and estimated free estradiol, and sex hormone-binding globulin (SHBG) in men with and without pre-diabetes. Logistic regression was used to calculate adjusted odds ratios (OR) of lower concentrations of androgens and SHBG, and higher concentrations of estradiol by prediabetes status. Adjusting for age and race/ethnicity, total testosterone concentration was lower among men with (geometric mean: 4.68 ng/mL) than without (5.36 ng/mL, p = 0.01) pre-diabetes. SHBG concentration was also lower in men with (31.67 nmol/L) than without (36.16 nmol/L; p = 0.01) pre-diabetes. Concentrations of the other hormones did not differ between men with and without pre-diabetes. After adjusting for demographic and lifestyle factors, pre-diabetic men had a higher odds of lower testosterone (OR: 2.58; 95% CI: 1.54-4.29), higher free estradiol level (OR: 1.59; 95% CI: 1.14-2.22), and lower SHBG level (OR: 2.27; 95% CI: 1.32-3.92) compared to men without pre-diabetes. These associations were attenuated after adjusting for adiposity (testosterone OR: 1.76; 95% CI 0.95-3.27, free estradiol OR: 1.29, 95% CI: 0.88-1.88, SHBG OR: 1.71; 95% CI 0.88-3.30). Our findings suggest that men with pre-diabetes have lower circulating total testosterone and SHBG and higher free estradiol levels.

Risk prediction of major complications in individuals with diabetes: the Atherosclerosis Risk in Communities Study.

AIMS: To develop a prediction equation for 10-year risk of a combined endpoint (incident coronary heart disease, stroke, heart failure, chronic kidney disease, lower extremity hospitalizations) in people with diabetes, using demographic and clinical information, and a panel of traditional and non-traditional biomarkers. METHODS: We included in the study 654 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, with diagnosed diabetes (visit 2; 1990-1992). Models included self-reported variables (Model 1), clinical measurements (Model 2), and glycated haemoglobin (Model 3). Model 4 tested the addition of 12 blood-based biomarkers. We compared models using prediction and discrimination statistics. RESULTS: Successive stages of model development improved risk prediction. The C-statistics (95% confidence intervals) of models 1, 2, and 3 were 0.667 (0.64, 0.70), 0.683 (0.65, 0.71), and 0.694 (0.66, 0.72), respectively (p < 0.05 for differences). The addition of three traditional and non-traditional biomarkers [ß-2 microglobulin, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C-based eGFR] to Model 3 significantly improved discrimination (C-statistic = 0.716; p = 0.003) and accuracy of 10-year risk prediction for major complications in people with diabetes (midpoint percentiles of lowest and highest deciles of predicted risk changed from 18-68% to 12-87%). CONCLUSIONS: These biomarkers, particularly those of kidney filtration, may help distinguish between people at low versus high risk of long-term major complications.

Parathyroid hormone is associated with incident diabetes in white, but not black adults: The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: Accumulating evidence has linked elevated parathyroid hormone (PTH) with insulin resistance, beta cell dysfunction and dysglycaemia, however, its role in the development of diabetes is largely unclear, particularly among non-whites. We sought to examine the association of PTH with the incidence of diabetes. METHODS: We studied 8066 white and 2034 black adults aged 46-70 years at baseline (1990-92) from the ARIC Study with follow-up for incident diabetes ascertained during study visits conducted in 1993-95 and 1996-98. Hazard ratios (HR) and their 95% CIs for diabetes adjusted for demographics, lifestyle, and 25-hydroxyvitamin D were estimated according to PTH measured at baseline. RESULTS: PTH was higher among blacks than whites (median [IQR], 43.8 [35.0-55.8] vs. 37.9 [30.4-47.3] pg/mL; P<0.001). During a median follow-up of 6 years, 498 white and 167 black participants developed diabetes. The association of PTH with diabetes varied significantly by race (P-interaction 0.02). PTH was not associated with risk for diabetes among black adults. Among whites, HRs according to quintiles of PTH were 1 (referent), 0.95 (0.71, 1.29), 0.95 (0.70, 1.28), 1.12 (0.84, 1.51), and 1.31 (0.98, 1.76) (P-trend 0.03). When a clinical cut-point for PTH was applied (≥65pg/mL; 5.7% of whites), the HR for diabetes among whites was 1.38 (1.01, 1.88). Results were similar when restricted to participants with normal baseline kidney function. CONCLUSION: In this large, population-based study, elevated PTH was independently associated with risk for diabetes among white, but not black adults. Further studies are needed to elucidate the mechanisms that may underlie this differential association of PTH with diabetes across race groups.

Vitamin D, vitamin D binding protein gene polymorphisms, race and risk of incident stroke: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: Low vitamin D levels, measured by serum 25-hydroxyvitamin D [25(OH)D], are associated with increased stroke risk. Less is known about whether this association differs by race or D binding protein (DBP) single nucleotide polymorphism (SNP) status. Our objective was to characterize the associations of and interactions between 25(OH)D levels and DBP SNPs with incident stroke. It was hypothesized that associations of low 25(OH)D with stroke risk would be stronger amongst persons with genotypes associated with higher DBP levels. METHODS: 25(OH)D was measured by mass spectroscopy in 12 158 participants in the Atherosclerosis Risk in Communities (ARIC) study (baseline 1990-1992, mean age 57 years, 57% female, 23% black) and they were followed through 2011 for adjudicated stroke events. Two DBP SNPs (rs7041, rs4588) were genotyped. Cox models were adjusted for demographic/behavioral/socioeconomic factors. RESULTS: During a median of 20 years follow-up, 804 incident strokes occurred. The lowest quintile of 25(OH)D (<17.2 ng/ml) was associated with higher stroke risk [hazard ratio (HR) 1.34 (1.06-1.71) versus highest quintile]; this association was similar by race (P interaction 0.60). There was weak evidence of increased risk of stroke amongst those with 25(OH)D < 17.2 ng/ml and either rs7041 TG/GG [HR = 1.29 (1.00-1.67)] versus TT genotype [HR = 1.19 (0.94-1.52)] (P interaction 0.28) or rs4588 CA/AA [HR = 1.37 (1.07-1.74)] versus CC genotype [HR = 1.14 (0.91-1.41)] (P interaction 0.11). CONCLUSIONS: Low 25(OH)D is a risk factor for stroke. Persons with low 25(OH)D who are genetically predisposed to high DBP (rs7041 G, rs4588 A alleles), who therefore have lower predicted bioavailable 25(OH)D, may be at greater risk for stroke, although our results were not conclusive and should be interpreted as hypothesis generating.

Racial variation in sex steroid hormone concentration in black and white men: a meta-analysis.

Sex steroid hormones are associated with chronic diseases and mortality with risk associations that differ between racial and ethnic groups. However, it is currently unclear whether sex steroid hormone levels differ between black and white men. The aim of this study was to assess racial variation in circulating testosterone, free testosterone, sex hormone-binding globulin (SHBG) and estradiol levels in men. We searched PubMed for articles comparing circulating hormones in black and white men. A meta-analysis was performed using weighted mean differences (WMD) to compare hormones levels between black and white men. Fifteen eligible studies were identified; three did not report adjusted means. After age adjustment, free testosterone levels were significantly higher in black than in white men (WMD = 4.07 pg/mL, 95% CI 1.26, 6.88). Depending on the free testosterone concentration in white men, this WMD translates into a racial difference ranging from 2.5 to 4.9%. Total testosterone (WMD = 0.10 ng/mL, 95% CI -0.02, 0.22), estradiol (WMD = 0.67 pg/mL, 95% CI -0.04, 1.38) and SHBG (WMD = -0.45 nmol/L, 95% CI -1.75, 0.85) concentrations did not differ comparing blacks with whites. After adjustment for age, black men have a modestly but significantly 2.5 to 4.9% higher free testosterone level than white men. Based on previous studies on effects of sex steroid hormones on risk of chronic diseases or mortality, this modest difference is unlikely to explain racial differences in disease risk.

Association between endogenous sex steroid hormones and inflammatory biomarkers in US men.

Sex steroid hormones and inflammatory biomarkers are both associated with the development and progression of chronic diseases, but their interrelationship is relatively uncharacterized. We examined the association of sex hormones and sex hormone-binding globulin (SHBG) with biomarkers of inflammation, C-reactive protein (CRP) and white blood cell (WBC) count. The study included data from 809 adult men in the National Health and Nutrition Examination Survey 1999-2004. Geometric means and 95% confidence intervals were estimated separately for CRP and WBC concentrations by sex steroid hormones and SHBG using weighted linear regression models. Higher concentrations of total (slope per one quintile in concentration, -0.18; p-trend, 0.001) and calculated free (slope, -0.13; p-trend, 0.03) testosterone were statistically significantly associated with lower concentrations of CRP, but not with WBC count. Men in the bottom quintile of total testosterone (≤3.3 ng/mL), who might be considered to have clinically low testosterone, were more likely to have elevated CRP (≥3 mg/L) compared with men in the top four quintiles (OR, 1.61; 95% CI, 1.00-2.61). Total and calculated free estradiol (E2) were positively associated with both CRP (Total E2: slope, 0.14; p-trend, <0.001; Free E2: slope, 0.15; p-trend, <0.001) and WBC (Total E2: slope, 0.02; p-trend, 0.08; Free E2: slope, 0.02; p-trend, 0.02) concentrations. SHBG concentrations were inversely associated with WBC count (slope, -0.03; p-trend, 0.04), but not with CRP. These cross-sectional findings are consistent with the hypothesis that higher androgen and lower oestrogen concentrations may have an anti-inflammatory effect in men.

Liver enzymes, race, gender and diabetes risk: the Atherosclerosis Risk in Communities (ARIC) Study.

AIMS: To examine the associations of the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase(AST), and gamma-glutamyl transferase (GGT) with diabetes risk and to determine whether associations differ by race and/or gender. We hypothesized that all liver enzymes would be associated with diabetes risk and that associations would differ by race and gender. METHODS: Prospective cohort of 7495 white and 1842 black participants without diabetes in the Atherosclerosis Risk in Communities Study. Poisson and Cox models adjusted for demographic, socio-behavioural, and metabolic and health-related factors were used. RESULTS: During a median of 12 years of follow-up, 2182 incident cases of diabetes occurred. Higher liver enzyme levels were independently associated with diabetes risk: adjusted hazard ratios (95% confidence intervals) were 1.68 (1.49-1.89), 1.16 (1.02-1.31) and 1.95 (1.70-2.24) comparing the highest with the lowest quartiles of ALT, AST, and GGT, respectively. Gamma-Glutamyl transferase was most strongly related to diabetes risk, even at levels considered within the normal range (≤ 60 U/l) in clinical practice. Adjusted incidence rates by quartiles of liver enzymes were similar by gender but higher in black versus white participants. Nonetheless, relative associations of ALT, AST, and GGT with diabetes were similar by race (P for interactions > 0.05). CONCLUSIONS: Compared with ALT and AST, GGT was more strongly associated with diabetes risk. Our findings suggest that abnormalities in liver enzymes precede the diagnosis of diabetes by many years and that individuals with elevated liver enzymes, even within the normal range as defined in clinical practice, are at high risk for diabetes.

Age at menarche and risk of type 2 diabetes among African-American and white women in the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: We examined race differences in the association between age at menarche and type 2 diabetes before and after adjustment for adiposity. METHODS: We analysed baseline and 9-year follow-up data from 8,491 women (n = 2,505 African-American, mean age 53.3 years; n = 5,986 white, mean age 54.0 years) in the Atherosclerosis Risk in Communities (ARIC) study. Stratifying by race, we used logistic regression to estimate the OR for prevalent diabetes at baseline, and Cox proportional hazard models to estimate the HR for incident diabetes over follow-up according to age at menarche category (8-11, 12, 13, 14 and 15-18 years). RESULTS: Adjusting for age and centre, we found that early age at menarche (8-11 vs 13 years) was associated with diabetes for white, but not African-American women in both the prevalent (white OR 1.72, 95% CI 1.32, 2.25; African-American OR 1.13, 95% CI 0.84, 1.51; interaction p = 0.043) and incident models (white HR 1.43, 95% CI 1.08, 1.89; African-American HR 1.20, 95% CI 0.87, 1.67; interaction p = 0.527). Adjustment for adiposity and lifestyle confounders attenuated associations for prevalent (white OR 1.41, 95% CI 1.05, 1.89; African-American OR 0.94, 95% CI 0.68, 1.30; interaction p = 0.093) and incident diabetes (white HR 1.22, 95% CI 0.92, 1.63; African-American HR 1.11, 95% CI 0.80, 1.56; interaction p = 0.554). CONCLUSIONS/INTERPRETATION: Early menarche was associated with type 2 diabetes in white women, and adulthood adiposity attenuated the relationship. We did not find a similar association in African-American women. Our findings suggest that there may be race/ethnic differences in the influence of developmental factors in the aetiology of type 2 diabetes, which merit further investigation.

Risk factors for lacune subtypes in the Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: Lacunar infarctions are mainly due to 2 microvascular pathologies: lipohyalinosis and microatheroma. Little is known about risk factor differences for these subtypes. We hypothesized that diabetes and glycated hemoglobin (HbA(1)c) would be related preferentially to the lipohyalinotic subtype. METHODS: We performed a cross-section analysis of the brain MRI data from 1,827 participants in the Atherosclerosis Risk in Communities study. We divided subcortical lesions ≤ 20 mm in diameter into those ≤ 7 mm (of probable lipohyalinotic etiology) and 8-20 mm (probably due to microatheroma) and used Poisson regression to investigate associations with the number of each type of lesion. Unlike previous studies, we also fitted a model involving lesions <3 mm. RESULTS: Age (prevalence ratio [PR] 1.11 per year; 95% confidence interval [CI] 1.08-1.14), black ethnicity (vs white, PR 1.66; 95% CI 1.27-2.16), hypertension (PR 2.12; 95% CI 1.61-2.79), diabetes (PR 1.42; 95% CI 1.08-1.87), and ever-smoking (PR 1.34; 95% CI 1.04-1.74) were significantly associated with lesions ≤ 7 mm. Findings were similar for lesions <3 mm. HbA(1)c, substituted for diabetes, was also associated with smaller lesions. Significantly associated with 8-20 mm lesions were age (PR 1.14; 95% CI 1.09-1.20), hypertension (PR 1.79; 95% CI 1.14-2.83), ever-smoking (PR 2.66; 95% CI 1.63-4.34), and low-density lipoprotein (LDL) cholesterol (PR 1.27 per SD; 95% CI 1.06-1.52). When we analyzed only participants with lesions, history of smoking (PR 1.99; 95% CI 1.23-3.20) and LDL (PR 1.33 per SD; 95% CI 1.08-1.65) were associated with lesions 8-20 mm. CONCLUSIONS: Smaller lacunes (even those <3 mm) were associated with diabetes and HbA(1)c, and larger lacunes associated with LDL cholesterol, differences which support long-held theories relating to their underlying pathology. The findings may contribute to broader understanding of cerebral microvascular disease.

Glycated haemoglobin and cognitive decline: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: This study aimed to examine the association between diabetes and hyperglycaemia-assessed by HbA(1c)-and change in cognitive function in persons with and without diabetes. METHODS: This was a prospective cohort study of 8,442 non-diabetic and 516 diabetic participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined the association of baseline categories of HbA(1c) with 6 year change in three measures of cognition: the digit symbol substitution test (DSST); the delayed word recall test (DWRT); and the word fluency test (WFT). Our primary outcomes were the quintiles with the greatest annual cognitive decline for each test. Logistic regression models were adjusted for demographic (age, sex, race, field centre, education, income), lifestyle (smoking, drinking) and metabolic (adiposity, blood pressure, cholesterol) factors. RESULTS: The mean age was 56 years. Women accounted for 56% of the study population and 21% of the study population were black. The mean HbA(1c) was 5.7% overall: 8.5% in persons with and 5.5% in persons without diabetes. In adjusted logistic regression models, diagnosed diabetes was associated with cognitive decline on the DSST (OR 1.42, 95% CI 1.14-1.75, p = 0.002), but HbA(1c) was not a significant independent predictor of cognitive decline when stratifying by diabetes diagnosis (diabetes, p trend = 0.320; no diabetes, p trend = 0.566). Trends were not significant for the DWRT or WFT in either the presence or the absence of diabetes. CONCLUSIONS/INTERPRETATION: Hyperglycaemia, as measured by HbA(1c), did not add predictive power beyond diabetes status for 6 year cognitive decline in this middle-aged population. Additional work is needed to identify the non-glycaemic factors by which diabetes may contribute to cognitive decline.

Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies.

BACKGROUND: Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances. METHODS: We undertook a meta-analysis of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from studies in the Emerging Risk Factors Collaboration. We combined within-study regressions that were adjusted for age, sex, smoking, systolic blood pressure, and body-mass index to calculate hazard ratios (HRs) for vascular disease. FINDINGS: Analyses included data for 698 782 people (52 765 non-fatal or fatal vascular outcomes; 8.49 million person-years at risk) from 102 prospective studies. Adjusted HRs with diabetes were: 2.00 (95% CI 1.83-2.19) for coronary heart disease; 2.27 (1.95-2.65) for ischaemic stroke; 1.56 (1.19-2.05) for haemorrhagic stroke; 1.84 (1.59-2.13) for unclassified stroke; and 1.73 (1.51-1.98) for the aggregate of other vascular deaths. HRs did not change appreciably after further adjustment for lipid, inflammatory, or renal markers. HRs for coronary heart disease were higher in women than in men, at 40-59 years than at 70 years and older, and with fatal than with non-fatal disease. At an adult population-wide prevalence of 10%, diabetes was estimated to account for 11% (10-12%) of vascular deaths. Fasting blood glucose concentration was non-linearly related to vascular risk, with no significant associations between 3.90 mmol/L and 5.59 mmol/L. Compared with fasting blood glucose concentrations of 3.90-5.59 mmol/L, HRs for coronary heart disease were: 1.07 (0.97-1.18) for lower than 3.90 mmol/L; 1.11 (1.04-1.18) for 5.60-6.09 mmol/L; and 1.17 (1.08-1.26) for 6.10-6.99 mmol/L. In people without a history of diabetes, information about fasting blood glucose concentration or impaired fasting glucose status did not significantly improve metrics of vascular disease prediction when added to information about several conventional risk factors. INTERPRETATION: Diabetes confers about a two-fold excess risk for a wide range of vascular diseases, independently from other conventional risk factors. In people without diabetes, fasting blood glucose concentration is modestly and non-linearly associated with risk of vascular disease. FUNDING: British Heart Foundation, UK Medical Research Council, and Pfizer.

HbA 1c as a risk factor for heart failure in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: Heart failure (HF) incidence in diabetes in both the presence and absence of CHD is rising. Prospective population-based studies can help describe the relationship between HbA(1c), a measure of glycaemia control, and HF risk. METHODS: We studied the incidence of HF hospitalisation or death among 1,827 participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes and no evidence of HF at baseline. Cox proportional hazard models included age, sex, race, education, health insurance status, alcohol consumption, BMI and WHR, and major CHD risk factors (BP level and medications, LDL- and HDL-cholesterol levels, and smoking). RESULTS: In this population of persons with diabetes, crude HF incidence rates per 1,000 person-years were lower in the absence of CHD (incidence rate 15.5 for CHD-negative vs 56.4 for CHD-positive, p<0.001). The adjusted HR of HF for each 1% higher HbA(1c) was 1.17 (95% CI 1.11-1.25) for the non-CHD group and 1.20 (95% CI 1.04-1.40) for the CHD group. When the analysis was limited to HF cases which occurred in the absence of prevalent or incident CHD (during follow-up) the adjusted HR remained 1.20 (95% CI 1.11-1.29). CONCLUSIONS/INTERPRETATIONS: These data suggest HbA(1c) is an independent risk factor for incident HF in persons with diabetes with and without CHD. Long-term clinical trials of tight glycaemic control should quantify the impact of different treatment regimens on HF risk reduction.

Stability of haemoglobin A1c (HbA1c) measurements from frozen whole blood samples stored for over a decade.

OBJECTIVE: Haemoglobin A1c (HbA1c), a measure of long-term glycaemic control, is at the centre of the clinical management of diabetes mellitus. However, the reproducibility of HbA1c measurements from whole blood samples which have been in long-term storage is unknown. We undertook this study to assess the reproducibility of HbA1c measurements from whole blood samples that had been in storage at -70 degrees C for over a decade. RESEARCH DESIGN AND METHODS: Three hundred and thirty-six samples of frozen whole blood from the Atherosclerosis Risk in Communities (ARIC) Study, stored at -70 degrees C for 11-14 years assayed for HbA1c using a dedicated ion-exchange HPLC assay (Tosoh A1c 2.2 Plus HPLC) were compared with measurements on these same samples conducted prior to storage (in 1990-92) using a Diamat (Bio-Rad) HPLC instrument. RESULTS: HbA1c measurements from long-term stored samples were strongly correlated with values obtained prior to long-term storage (r=0.97). The difference between HbA1c from long- and short-term stored samples had a mean of 0.35% HbA1c (sd=0.35) and a CV of 5.8%, which was approximately three times that of duplicate assays (CV 1.3 to 2.5%). CONCLUSIONS: These data demonstrate that highly correlated but more variable and slightly higher HbA1c results were obtained from frozen whole blood samples that have been in storage for more than a decade. This highly reproducible assay performance would lead to comparable ranking of individuals and unbiased estimates of relative risks and odds ratios in epidemiological studies (case-control and cohort designs), but results should be realigned when the absolute value is of interest. These results have important implications for epidemiological studies and clinical trials which have stored whole blood specimens.

Serum dehydroepiandrosterone and dehydroepiandrosterone sulfate and risk of melanoma or squamous cell carcinoma of the skin.

BACKGROUND: Dehydroepiandrosterone (DHEA) and its analogs have potent chemoprotective actions in mouse skin tumorigenesis models. To assess this association in humans, we investigated the relationship of prediagnostic serum concentrations of DHEA and dehydroepiandrosterone sulfate (DHEAS) to the subsequent risk of developing malignant melanoma and squamous cell carcinoma of the skin in residents of Washington County, Maryland, USA. PATIENTS AND METHODS: In a nested case-control study, serum that had been stored in 1974 was thawed and assayed for DHEA and DHEAS for 23 cases of malignant melanoma and 28 cases of squamous cell carcinoma and 1-2 matched controls per case. RESULTS: The mean serum concentrations of DHEA or DHEAS were similar in cases and controls. There were no statistically significant trends in the risk of developing malignant melanoma or squamous cell skin cancer by concentration of either steroid (all p-for-trends >0.30). CONCLUSION: The results of this study do not support the hypothesis that physiological concentrations of DHEA or DHEAS protect against skin cancer in humans.

Licensing telemedicine: the need for a national system.

The expansion of information technology has shattered geographic boundaries, allowing for extraordinarily increased access to health information and expanded opportunities for telemedicine practice across state boundaries. But despite its recent growth, telemedicine technology remains embedded in a state-based licensure system that places severe limits on its expansion. The current system of medical licensure is based primarily on statutes written at the turn of the 20th century. This system is inadequate to address the emerging medical practices and future uses of medical technology in the telecommunications age. To respond to the changes offered by the telecommunications revolution, we need to design a new regulatory structure for the 21st century. The purpose of this article is to propose a policy of national telemedicine licensure. The primary goal here is not to simply develop a policy proposal, but to discuss the rationale for national licensure and place it on the policy agenda. A national licensure system will expand the market for telemedicine, promote both the use and development of new technologies, and simultaneously eliminate many of the legal and regulatory ambiguities that plague and constrain the present system.