Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study.

Background: Identifying reliable predictors of long-term weight loss (LTWL) could lead to improved weight management. Objective: To identify some predictors of LTWL. Design: The DPP (Diabetes Prevention Program) was a randomized controlled trial that compared weight loss with metformin, intensive lifestyle intervention (ILS), or placebo. Its Outcomes Study (DPPOS) observed patients after the masked treatment phase ended. (ClinicalTrials.gov: NCT00004992 and NCT00038727). Setting: 27 DPP and DPPOS clinics. Participants: Of the 3234 randomly assigned participants, 1066 lost at least 5% of baseline weight in the first year and were followed for 15 years. Measurements: Treatment assignment, personal characteristics, and weight. Results: After 1 year, 289 (28.5%) participants in the metformin group, 640 (62.6%) in the ILS group, and 137 (13.4%) in the placebo group had lost at least 5% of their weight. After the masked treatment phase ended, the mean weight loss relative to baseline that was maintained between years 6 and 15 was 6.2% (95% CI, 5.2% to 7.2%) in the metformin group, 3.7% (CI, 3.1% to 4.4%) in the ILS group, and 2.8% (CI, 1.3% to 4.4%) in the placebo group. Independent predictors of LTWL included greater weight loss in the first year in all groups, older age and continued metformin use in the metformin group, older age and absence of either diabetes or a family history of diabetes in the ILS group, and higher fasting plasma glucose levels at baseline in the placebo group. Limitation: Post hoc analysis; examination of nonrandomized subsets of randomized groups after year 1. Conclusion: Among persons with weight loss of at least 5% after 1 year, those originally randomly assigned to metformin had the greatest loss during years 6 to 15. Older age and the amount of weight initially lost were the most consistent predictors of LTWL maintenance. Primary Funding Source: National Institutes of Health.

Reflection Magnitude, a Measure of Arterial Stiffness, Predicts Incident Heart Failure in Men But Not Women: Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Arterial stiffness is a risk factor for heart failure (HF) and is higher in women. Our objective was to investigate sex differences between arterial stiffness and incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA) population. METHODS AND RESULTS: Applanation tonometry from 5959 participants (52.8% women) was used to calculate augmentation index (AIx), pulse pressure amplification (PPA), and reflection magnitude (RM). Sex-specific risk of HF was assessed with the use of a competing-risk regression model. Women had higher AIx (P < .00001), higher RM (P = .023), and lower PPA (P < .00001) indicating greater arterial stiffness in women. However, increasing RM quartile independently predicted HF in men (adjusted hazard ratios and 95% confidence intervals: Q2: 2.05 [1.06-3.96; P = .033]; Q3: 2.49 [1.30-4.73; P = .006]; Q4: 3.26 [1.75-6.08; P = .0002]) but not in women (Q2: 1.04 [0.54-1.98; P = .91]; Q3: 1.30 [0.71-2.37; P = .4]; Q4: 0.79 [0.4-1.55; P = .49]). CONCLUSION: Women demonstrate greater arterial stiffness than men. Despite this, arterial stiffness, as measured by RM, predicts incident HF in men but not in women. RM represents a novel risk factor for HF in men but not in women. Further investigation of risk factors for HF in women is warranted. CONCLUSION: Arterial stiffness, measured by RM, predicts incident HF in men but not in women in this MESA cohort.

Abdominal aortic calcium, coronary artery calcium, and cardiovascular morbidity and mortality in the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: To evaluate the predictive value of abdominal aortic calcium (AAC) for incident cardiovascular disease (CVD) independent of coronary artery calcium (CAC). APPROACH AND RESULTS: We evaluated the association of AAC with CVD in 1974 men and women aged 45 to 84 years randomly selected from the Multi-Ethnic Study of Atherosclerosis participants who had complete AAC and CAC data from computed tomographic scans. AAC and CAC were each divided into following 3 percentile categories: 0 to 50th, 51st to 75th, and 76th to 100th. During a mean of 5.5 years of follow-up, there were 50 hard coronary heart disease events, 83 hard CVD events, 30 fatal CVD events, and 105 total deaths. In multivariable-adjusted Cox models including both AAC and CAC, comparing the fourth quartile with the ≤ 50th percentile, AAC and CAC were each significantly and independently predictive of hard coronary heart disease and hard CVD, with hazard ratios ranging from 2.4 to 4.4. For CVD mortality, the hazard ratio was highly significant for the fourth quartile of AAC, 5.9 (P=0.01), whereas the association for the fourth quartile of CAC (hazard ratio, 2.1) was not significant. For total mortality, the fourth quartile hazard ratio for AAC was 2.7 (P=0.001), and for CAC, it was 1.9, P=0.04. Area under the receiver operating characteristic curve analyses showed improvement for both AAC and CAC separately, although improvement was greater with CAC for hard coronary heart disease and hard CVD, and greater with AAC for CVD mortality and total mortality. Sensitivity analyses defining AAC and CAC as continuous variables mirrored these results. CONCLUSIONS: AAC and CAC predicted hard coronary heart disease and hard CVD events independent of one another. Only AAC was independently related to CVD mortality, and AAC showed a stronger association than CAC with total mortality.

Associations Between Visceral Fat, Abdominal Muscle, and Coronary Artery Calcification: A Cross-Sectional Analysis of the Multi-Ethnic Study of Atherosclerosis.

The associations of body composition components, including muscle and adipose tissue, and markers of subclinical coronary artery disease are unclear. We examined the relation between abdominal computed tomography (CT)-derived measures of the area and density of fat and muscle with coronary artery calcification (CAC), using data from the Multi-Ethnic Study of Atherosclerosis (MESA). A total of 1,974 randomly selected MESA participants free of coronary heart disease underwent abdominal CT scans at examinations 2 or 3, with the resulting images interrogated for abdominal body composition. Using 6 cross-sectional slices spanning L2 to L5, the Medical Imaging Processing Analysis and Visualization software was used to determine abdominal muscle and fat composition using appropriate Hounsfield units ranges. CT chest scans were used to obtain CAC scores, calculated using the Agatston method and spatially weighted calcium score. Multivariable linear and logistic regression analyses were performed to assess the relation between abdominal visceral fat and muscle area and density to prevalent CAC. A total of 1,089 participants had a CAC >0, with an average CAC score of 310. In the fully adjusted model, for every 10-cm2 increase in visceral fat area, the likelihood of having a CAC greater than 0 increased by 0.60% (p <0.001). In the minimally adjusted model, abdominal muscle area was significantly associated with CAC >0, which became nonsignificant in the fully adjusted model. For the density of visceral fat, every 1-Hounsfield unit increase (less lipid-dense fat tissue), the likelihood of having a CAC score >0 decreased by 0.29% (p <0.05). No significant relation was observed between density of abdominal muscle and CAC >0. A greater area and higher lipid density of abdominal visceral fat were associated with an increased likelihood of having CAC, whereas there was no significant relation between abdominal muscle area or density and CAC. The quantity and the quality of fat have associations, with an important marker of subclinical atherosclerosis, CAC, and their significance with respect to cardiovascular outcomes, require further evaluation.

The association of insulin responses and insulin sensitivity with cognition in adults with pre-diabetes: The Diabetes Prevention Program Outcomes Study.

OBJECTIVE: Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant(s) of dysglycemia, impaired insulin sensitivity (ISens) or the islet ß-cell's response (IResp), contribute to poorer cognitive function, independent of dysglycemia is not established. Among 1052 adults with pre-diabetes from the Diabetes Prevention Program Outcomes Study (DPPOS), we investigated the relationship between IResp, ISens and cognitive function. RESEARCH DESIGN AND METHODS: IResp was estimated by the insulinogenic index (IGI; pmol/mmol) and ISens as 1/fasting insulin from repeated annual oral glucose tolerance tests. The mean IResp and mean ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and executive function (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Linear regression models were run for each cognitive outcome and were adjusted for dysglycemia and other factors. RESULTS: Higher IResp was associated with poorer performance on the DSST (-0.69 points per 100 unit increase in IGI, 95 % CI: -1.37, -0.01). ISens was not associated with DSST, nor were IResp or ISens associated with performance on the SEVLT. CONCLUSIONS: These results suggest that a greater ß-cell response in people at high risk for type 2 diabetes is associated with poorer executive function, independent of dysglycemia and ISens.

Association Between Measures of Body Composition and Coronary Calcium: Findings From the Multi-Ethnic Study of Atherosclerosis.

Background Obesity, as measured by body mass index, is widely recognized as a risk factor for the development of cardiovascular disease. However, the role of body composition components such as fat and lean mass is not well studied. Methods and Results A total of 3129 patients who underwent computed tomography scans for quantification of coronary artery calcification and had bioelectrical impedance analysis of body composition (fat mass and fat-free mass) during exam 5 of MESA (Multi-Ethnic Study of Atherosclerosis) were included in this cross-sectional analysis. Multivariable adjusted linear regression analysis was performed to assess the relationship between both fat mass and fat-free mass to prevalent coronary artery calcification, a marker of subclinical coronary artery disease quantified by both the coronary artery calcification (CAC) Agatston score and the spatially weighted calcium score. CAC and spatially weighted calcium score were natural log-transformed for analysis as continuous variables. Fat-free mass, but not fat mass, was independently associated with CAC. There was a 7.6% prevalence risk difference for CAC>0 per 10 kg. Fat-free mass was also significantly associated with natural log of CAC (coefficient=0.272, P<0.001). Both fat-free mass and fat mass were positively associated with natural log of spatially weighted calcium score, with risk difference coefficients of 0.729 and 0.359, respectively (P<0.001). Conclusions In this cross-sectional study, higher lean mass by bioelectrical impedance analysis and, to a lesser extent, higher fat mass by bioelectrical impedance analysis were significantly associated with higher coronary calcium, a marker of subclinical cardiovascular disease. Further exploration of the relationship between components of body composition and the development of cardiovascular disease is warranted.

Urinary cortisol and cardiovascular events in women vs. men: The multi-ethnic study of atherosclerosis.

Research suggests that women experience greater cardiovascular ischemic effects from stress than men. Visceral adiposity is an endocrine tissue that differs by sex and interacts with stress hormones. We hypothesized that urinary cortisol would be associated with increased cardiovascular events and change in coronary artery calcium score (CAC) in women, and these relationships would vary by central obesity. In the Multi-Ethnic Study of Atherosclerosis Stress Ancillary study, cortisol was quantified by 12-h overnight urine collection. Central obesity was estimated by waist-hip ratio (WHR). Multivariable Cox models estimated the relationship between cortisol and cardiovascular events and assessed for moderation by WHR. The relationship between cortisol and change in CAC Agatston score was assessed by Tobit regression models. 918 patients were analyzed with median follow up of 11 years. There was no association between urinary cortisol and cardiovascular events in the cohort. However, in individuals with below median WHR, higher urinary cortisol levels (upper tertile) were associated with higher cardiovascular event rates in the full cohort, women, and men, but not in groups with above median WHR. There was significant moderation by WHR in women, but not men, whereby the association between elevated cortisol and increased cardiovascular events diminished as WHR increased. Urinary cortisol was associated with increased change in CAC in women (P = 0.003) but not men, without moderation by WHR. Our study highlights associations between cortisol and subclinical atherosclerosis in women, and moderation of the relationship between cortisol and cardiovascular events by central obesity in both genders.

Effects of metformin and intensive lifestyle interventions on the incidence of kidney disease in adults in the DPP/DPPOS.

AIMS: We analyzed the incidence of kidney disease in the Diabetes Prevention Program Outcomes Study (DPPOS) by originally randomized treatment group assignment: Intensive Lifestyle (ILS), Metformin (MET) or Placebo (PLB). METHODS: The current analyses used a time-to-event approach in which the primary outcome was kidney disease, ascertained as urine albumin-to-creatinine ratio (ACR) ≥ 3.39 mg/mmol (30 mg/g) or eGFR <45 mL/min/1.73m2, with confirmation required at the next visit, or adjudicated end-stage kidney disease (ESKD). RESULTS: At a median of 21 years following randomization in DPP, diabetes development was reduced in both the ILS (HR 0.73 [95%CI = 0.62, 0.85]) and MET groups (HR 0.85 [0.73, 0.99]) compared to the PLB group. Although risk for developing the primary kidney disease outcome was higher among those with incident diabetes compared to those without (HR 1.81 [1.43, 2.30]), it did not differ by intervention groups (ILS vs. PLB 1.02 (0.81, 1.29); MET vs. PLB 1.08 (0.86, 1.35). There was a non-significant metformin by age interaction (p = 0.057), with metformin being beneficial for kidney disease in the younger but potentially harmful in the older participants. CONCLUSIONS: Development of kidney disease was increased in participants who developed diabetes but did not differ by original treatment group assignment. CLINICAL TRIAL REGISTRATIONS: Diabetes Prevention Program (DPP) Clinical trial reg. no. NCT00004992 DPP Outcomes Study (DPPOS) Clinical trial reg. no. NCT0038727.

Sympathetic innervation of the supraclavicular brown adipose tissue: A detailed anatomical study.

BACKGROUND: The supraclavicular fossa is the dominant location for human brown adipose tissue (BAT). Activation of BAT promotes non-shivering thermogenesis by utilization of glucose and free fatty acids and has been the focus of pharmacological and non-pharmacological approaches for modulation in order to improve body weight and glucose homeostasis. Sympathetic neural control of supraclavicular BAT has received much attention, but its innervation has not been extensively investigated in humans. METHODS: Dissection of the cervical region in human cadavers was performed to find the distribution of sympathetic nerve branches to supraclavicular fat pad. Furthermore, proximal segments of the 4th cervical nerve were evaluated histologically to assess its sympathetic components. RESULTS: Nerve branches terminating in supraclavicular fat pad were identified in all dissections, including those from the 3rd and 4th cervical nerves and from the cervical sympathetic plexus. Histology of the proximal segments of the 4th cervical nerves confirmed tyrosine hydroxylase positive thin nerve fibers in all fascicles with either a scattered or clustered distribution pattern. The scattered pattern was more predominant than the clustered pattern (80% vs. 20%) across cadavers. These sympathetic nerve fibers occupied only 2.48% of the nerve cross sectional area on average. CONCLUSIONS: Human sympathetic nerves use multiple pathways to innervate the supraclavicular fat pad. The present finding serves as a framework for future clinical approaches to activate human BAT in the supraclavicular region.

Longitudinal associations of insulin resistance with change in bone mineral density in midlife women.

BACKGROUNDThe effects of insulin resistance on bone mineral density (BMD) are unclear.METHODSIn Study of Women's Health Across the Nation (SWAN) participants, we used multivariable regression to test average insulin resistance (homeostatic model assessment of insulin resistance, HOMA-IR) and rate of change in insulin resistance as predictors of rate of change in lumbar spine (LS) and femoral neck (FN) BMD in 3 stages: premenopause (n = 861), menopause transition (MT) (n = 571), and postmenopause (n = 693). Models controlled for age, average BW, change in BW, cigarette use, race and ethnicity, and study site.RESULTSThe relation between HOMA-IR and BMD decline was biphasic. When average log2HOMA-IR was less than 1.5, greater HOMA-IR was associated with slower BMD decline; i.e., each doubling of average HOMA-IR in premenopause was associated with a 0.0032 (P = 0.01, LS) and 0.0041 (P = 0.004, FN) g/cm2 per year slower BMD loss. When greater than or equal to 1.5, average log2HOMA-IR was not associated with BMD change. In women in whom HOMA-IR decreased in premenopause, the association between the HOMA-IR change rate and BMD change rate was positive; i.e, slower HOMA-IR decline was associated with slower BMD loss. In women in whom insulin resistance increased in premenopause, the association was negative; i.e, faster HOMA-IR rise was associated with faster BMD decline. Associations of average HOMA-IR and HOMA-IR change rate with BMD change rate were similar in postmenopause, but weaker during the MT.CONCLUSIONWhen it decreases, insulin resistance is associated with BMD preservation; when it increases, insulin resistance is associated with BMD loss.FUNDINGThe SWAN has grant support from the NIH of the Department of Health and Human Services (DHHS) through the NIH National Institute on Aging (NIA), National Institute of Nursing Research (NINR), and Office of Research on Women's Health (ORWH) (grants U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, and U19AG063720).

Sex Differences in the Association of Body Composition and Cardiovascular Mortality.

Background To determine whether differences in body composition contribute to sex differences in cardiovascular disease (CVD) mortality, we investigated the relationship between components of body composition and CVD mortality in healthy men and women. Methods and Results Dual energy x-ray absorptiometry body composition data from the National Health and Nutrition Examination Survey 1999-2004 and CVD mortality data from the National Health and Nutrition Examination Survey 1999-2014 were evaluated in 11 463 individuals 20 years of age and older. Individuals were divided into 4 body composition groups (low muscle mass-low fat mass-the referent; low muscle-high fat; high muscle-low fat, and high muscle-high fat), and adjusted competing risks analyses were performed for CVD versus non-CVD mortality. In women, high muscle/high fat mass was associated with a significantly lower adjusted CVD mortality rate (hazard ratio [HR], 0.58; 95% CI, 0.39-0.86; P=0.01), but high muscle/low fat mass was not. In men, both high muscle-high fat (HR, 0.74; 95% CI, 0.53-1.04; P=0.08) and high muscle-low fat mass (HR, 0.40; 95% CI, 0.21-0.77; P=0.01) were associated with lower CVD. Further, in adjusted competing risks analyses stratified by sex, the CVD rate in women tends to significantly decrease as normalized total fat increase (total fat fourth quartile: HR, 0.56; 95% CI, 0.34-0.94; P<0.03), whereas this is not noted in men. Conclusions Higher muscle mass is associated with lower CVD and mortality in men and women. However, in women, high fat, regardless of muscle mass level, appears to be associated with lower CVD mortality risk. This finding highlights the importance of muscle mass in healthy men and women for CVD risk prevention, while suggesting sexual dimorphism with respect to the CVD risk associated with fat mass.

An obesity paradox in acute heart failure: analysis of body mass index and inhospital mortality for 108,927 patients in the Acute Decompensated Heart Failure National Registry.

BACKGROUND: Prior studies on chronic systolic heart failure (HF) have demonstrated that body mass index (BMI) is inversely associated with mortality, the so-called obesity paradox. The aim of this study was to determine whether BMI influences the mortality risk in acute decompensated HF, a subject not previously studied. METHODS: The Acute Decompensated Heart Failure National Registry was analyzed for acute HF hospitalizations in 263 hospitals in the United States from October 2001 through December 2004. Patients with documented height and weight were divided into BMI (measured in kilograms per square meter) quartiles. Inhospital mortality by BMI quartile for all the patients and for those with reduced (n = 43,255) and preserved (n = 37,901) systolic function was assessed. RESULTS: Body mass index quartiles in the 108,927 hospitalizations were QI (16.0-23.6 kg/m2), QII (23.7-27.7 kg/m2), QIII (27.8-33.3 kg/m2), and QIV (33.4-60.0 kg/m2). Patients in the higher BMI quartiles were younger, had more diabetes, and had a higher left ventricular ejection fraction. Inhospital mortality rates decreased in a near-linear fashion across successively higher BMI quartiles. After adjustments for age, sex, blood urea nitrogen, blood pressure, creatinine, sodium, heart rate, and dyspnea at rest, BMI quartile still predicted mortality risk. For every 5-U increase in BMI, the odds of risk-adjusted mortality was 10% lower (95% CI 0.88-0.93, P < .0001). CONCLUSIONS: In this cohort of hospitalized patients with HF, higher BMI was associated with lower inhospital mortality risk. The relationship between BMI and adverse outcomes in HF appears to be complex and deserving of further study.

Relation of Stress Hormones (Urinary Catecholamines/Cortisol) to Coronary Artery Calcium in Men Versus Women (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

The relation between high levels of psychosocial stress and the development of coronary artery disease (CAD) has been increasingly recognized, especially in women. We hypothesized that simple biomarkers of stress, urinary catecholamines/cortisol levels, are associated with more coronary artery calcium (CAC), an indicator of CAD, and that this relation is stronger in women compared with men. Using data from the Multi-Ethnic Study of Atherosclerosis Stress study, we examined the relation between urinary catecholamines/cortisol and CAC. The study cohort (n = 654) was 53% women, and 56.4% of the cohort had detectable CAC. Multivariable regression analyses assessed the relation between urinary catecholamines/cortisol and CAC (odds CAC >0 through logistic and ln CAC through Tobit model). There was an association between increased cortisol and increased CAC and an inverse association between dopamine and CAC. These relations were seen in men and women, with no difference between the genders. In conclusion, higher cortisol and lower dopamine levels are independently associated with higher CAC to a similar degree in men and women. These simple urinary biomarkers contribute to our understanding of the role of stress in the pathogenesis of CAD and may be incorporated into future strategies to prevent and treat CAD.

Diabetic cardiomyopathy.

This article focuses on advances in the understanding of the pathogenesis and treatment of diabetic cardiomyopathy. Patients with diabetes are at an elevated risk for heart failure, and comorbid heart failure confers an increased risk of morbidity and mortality. Diabetic cardiomyopathy and to apply proven lifesaving therapies in all heart failure patients, including those with diabetes, in the absence of contraindications or intolerance.

Polycystic ovarian syndrome: the next cardiovascular dilemma in women?

All known risks for cardiovascular disease are increased in women with polycystic ovary syndrome, which features amenorrhea, hirsutism, and obesity. Epidemiologic studies in these patients and their families have revealed a familial predisposition not only to polycystic ovary syndrome, but also diabetes, hypertension, and cardiovascular disease. The heterogeneity of phenotypes (clinically and biochemically) leads to difficulty in achieving a precise diagnosis, defining a single underlying pathogenesis, and selecting a homogeneous population for much needed prospective studies. The authors believe that while insulin resistance plays and important role in some cases of polycystic ovarian syndrome, it is the overall milieu created by the co-existence of several cardiovascular risk factors in polycystic ovarian syndrome patients which could be an important target for preventative strategies and therapy.

Relation of Muscle Mass and Fat Mass to Cardiovascular Disease Mortality.

We evaluated the relation between components of body composition and mortality in patients with cardiovascular disease (CVD). Dual x-ray absorptiometry body composition data from the National Health and Nutrition Examination Survey 1999 to 2004 was linked to total and CVD mortality data 1999 to 2006 in 6,451 patients with CVD. Kaplan-Meier survival analysis for the end points of total and CVD mortality was plotted by quartiles of muscle mass, fat mass, and categories of body mass index (BMI). Subjects were stratified into 4 groups (low muscle/low fat mass, low muscle/high fat mass, high muscle/low fat mass, and high muscle/high fat mass). Adjusted Cox proportional hazards regression determined hazard ratios for total and CVD mortality. Rates of cardiovascular/total mortality were lower in higher quartiles of muscle mass, fat mass, and higher categories of BMI (p <0.001). The high muscle/low fat mass group had a lower risk of CVD and total mortality (risk-adjusted hazard ratios of 0.32, 95% confidence interval 0.14 to 0.73 and 0.38, 95% confidence interval 0.22 to 0.68, for CVD and total mortality, respectively). Thus, increasing fat mass, muscle mass, and BMI were all correlated with improved survival. The specific subgroup of high muscle and low fat mass had the lowest mortality risk compared with other body composition subtypes. This suggests the importance of body composition assessment in the prediction of cardiovascular and total mortality in patients with CVD.

Association of menopause age and N-terminal pro brain natriuretic peptide: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: Menopause age can affect the risk of developing cardiovascular disease (CVD). The purpose of this study was to investigate the associations of early menopause (menopause occurring before age 45 y) and menopause age with N-terminal pro brain natriuretic peptide (NT-proBNP), a potential risk marker of CVD and heart failure. METHODS: Our cross-sectional study included 2,275 postmenopausal women, aged 45 to 85 years and without clinical CVD (2000-2002), from the Multi-Ethnic Study of Atherosclerosis. Participants were classified as having or not having early menopause. NT-proBNP was log-transformed. Multivariable linear regression was used for analysis. RESULTS: Five hundred sixty-one women had early menopause. The median (25th-75th percentiles) NT-proBNP value was 79.0 (41.1-151.6) pg/mL for all participants, 83.4 (41.4-164.9) pg/mL for women with early menopause, and 78.0 (40.8-148.3) pg/mL for women without early menopause. The mean (SD) age was 65 (10.1) and 65 (8.9) years for women with and without early menopause, respectively. No significant interactions between menopause age and ethnicity were observed. In multivariable analysis, early menopause was associated with a 10.7% increase in NT-proBNP levels, whereas each 1-year increase in menopause age was associated with a 0.7% decrease in NT-proBNP levels. CONCLUSIONS: Early menopause is associated with greater NT-proBNP levels, whereas each 1-year increase in menopause age is associated with lower NT-proBNP levels, in postmenopausal women.

Preventing heart failure in patients with diabetes.

Diabetic cardiomyopathy is characterized by a prominent interstitial fibrosis. Postulated etiologies include microangiopathy, autonomic neuropathy, and metabolic factors. A common root of these pathologies is hyperglycemia or hyperinsulinemia, both of which are prominent in type 2 diabetes mellitus, which has the highest incidence of cardiovascular morbidity and mortality. The relative importance of each factor is a matter of debate; it is likely that both of these factors in addition to the concomitant risk factors seen in diabetics (dyslipidemias, hypertension, obesity, coagulation abnormalities) contribute to the spectrum of myocardial disease in diabetes. A discussion of these contributive pathologies and the hyperglycemia and hyperinsulinemia that underlie them is the subject of this review. Treatment methodologies to control the development of such pathology also are discussed.

Muscle mass index as a predictor of longevity in older adults.

OBJECTIVE: Obesity (as defined by body mass index) has not been associated consistently with higher mortality in older adults. However, total body mass includes fat and muscle, which have different metabolic effects. This study was designed to test the hypothesis that greater muscle mass in older adults is associated with lower all-cause mortality. METHODS: All-cause mortality was analyzed by the year 2004 in 3659 participants from the National Health and Nutrition Examination Survey III who were aged 55 years or more (65 years if women) at the time of the survey (1988-1994). Individuals who were underweight or died in the first 2 years of follow-up were excluded to remove frail elders from the sample. Skeletal muscle mass was measured using bioelectrical impedance, and muscle mass index was defined as muscle mass divided by height squared. Modified Poisson regression and proportional hazards regression were used to examine the relationship of muscle mass index with all-cause mortality risk and rate, respectively, adjusted for central obesity (waist hip ratio) and other significant covariates. RESULTS: In adjusted analyses, total mortality was significantly lower in the fourth quartile of muscle mass index compared with the first quartile: adjusted risk ratio 0.81 (95% confidence interval, 0.71-0.91) and adjusted hazard ratio 0.80 (95% confidence interval, 0.66-0.97). CONCLUSIONS: This study demonstrates the survival predication ability of relative muscle mass and highlights the need to look beyond total body mass in assessing the health of older adults.

Insulin resistance and bone strength: findings from the study of midlife in the United States.

Although several studies have noted increased fracture risk in individuals with type 2 diabetes mellitus (T2DM), the pathophysiologic mechanisms underlying this association are not known. We hypothesize that insulin resistance (the key pathology in T2DM) negatively influences bone remodeling and leads to reduced bone strength. Data for this study came from 717 participants in the Biomarker Project of the Midlife in the United States Study (MIDUS II). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting morning blood glucose and insulin levels. Projected 2D (areal) bone mineral density (BMD) was measured in the lumbar spine and left hip using dual-energy X-ray absorptiometry (DXA). Femoral neck axis length and width were measured from the hip DXA scans, and combined with BMD and body weight and height to create composite indices of femoral neck strength relative to load in three different failure modes: compression, bending, and impact. We used multiple linear regressions to examine the relationship between HOMA-IR and bone strength, adjusted for age, gender, race/ethnicity, menopausal transition stage (in women), and study site. Greater HOMA-IR was associated with lower values of all three composite indices of femoral neck strength relative to load, but was not associated with BMD in the femoral neck. Every doubling of HOMA-IR was associated with a 0.34 to 0.40 SD decrement in the strength indices (p<0.001). On their own, higher levels of fasting insulin (but not of glucose) were independently associated with lower bone strength. Our study confirms that greater insulin resistance is related to lower femoral neck strength relative to load. Further, we note that hyperinsulinemia, rather than hyperglycemia, underlies this relationship. Although cross-sectional associations do not prove causality, our findings do suggest that insulin resistance and in particular, hyperinsulinemia, may negatively affect bone strength relative to load.