A Randomized Comparison of Postprandial Glucose Excursion Using Inhaled Insulin Versus Rapid-Acting Analog Insulin in Adults With Type 1 Diabetes Using Multiple Daily Injections of Insulin or Automated Insulin Delivery.

Objective: To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin.

Research Design And Methods: A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61).

Results: The primary outcome, the treatment group difference in area under the curve for glucose >180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference -12 mg/dL, 95% CI -22 to -2, P = 0.

Glycemic Control Predicts Severity of Hepatocyte Ballooning and Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease.

Background And Aims: Whether glycemic control, as opposed to diabetes status, is associated with the severity of NAFLD is open for study. We aimed to evaluate whether degree of glycemic control in the years preceding liver biopsy predicts the histological severity of NASH.

Approach And Results: Using the Duke NAFLD Clinical Database, we examined patients with biopsy-proven NAFLD/NASH (n = 713) and the association of liver injury with glycemic control as measured by hemoglobin A1c (HbA1c).

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect.

Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial.

Importance: Testosterone use in older men is increasing, but its long-term effects on progression of atherosclerosis are unknown.

Objective: To determine the effect of testosterone administration on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels.

Design, Setting, And Participants: Testosterone's Effects on Atherosclerosis Progression in Aging Men (TEAAM) was a placebo-controlled, double-blind, parallel-group randomized trial involving 308 men 60 years or older with low or low-normal testosterone levels (100-400 ng/dL; free testosterone <50 pg/mL), recruited at 3 US centers.

Rare coding variants and X-linked loci associated with age at menarche.

More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.

Practice Patterns in Screening for Metabolic Disease in Women with PCOS of Diverse Race-Ethnic Backgrounds.

Objectives: Women with polycystic ovary syndrome (PCOS) are at high risk for metabolic disorders, which prompted the American Association of Clinical Endocrinologists (AACE) to publish a 2005 position statement recommending screening for metabolic disease.The purposes of the present study were to 1) to examine changes in screening rates for obesity, type 2 diabetes (T2D), metabolic syndrome (MetS), hyperlipidemia (HL), nonalcoholic fatty liver disease (NAFLD), and hypertension (HTN) in women with PCOS after publication of the 2005 AACE position statement and 2) to determine if screening rates and metabolic disorders vary by race-ethnicity.

Methods: PCOS cases in 2006 (n = 547) and 2011 (n = 1,159) and metabolic disorders were identified by International Classification of Diseases, 9th revision (ICD9) code.

Association of sex hormones, aging, and atrial fibrillation in men: the Framingham Heart Study.

Background: Endogenous sex hormones have been related to cardiovascular outcomes and mortality. We hypothesized that sex hormones are related to atrial fibrillation (AF) in a community-based cohort of middle-aged to older men.

Methods And Results: We examined testosterone, estradiol, and dehydroepiandrosterone sulfate in relation to incident AF in men participating in the Framingham Heart Study.

Testosterone with dutasteride, but not anastrazole, improves insulin sensitivity in young obese men: a randomized controlled trial.

Introduction: Testosterone (T) administration to men increases T, estradiol (E2), dihydrotestosterone (DHT), and fat-free mass (FFM), and decreases fat mass (FM) but does not consistently improve insulin sensitivity (IS).

Aim: The aim of this study was to examine the effects of T administration in obese, nondiabetic men on body composition and IS, and to determine if inhibition (i) of metabolism of T to E2 with anastrazole or to DHT with dutasteride alters these effects.

Methods: This was a 98-day randomized, double-blind, parallel group, placebo-controlled trial of 57 men, 24-51 year, free T in the lower 25% of normal range (<0.

Circulating estrone levels are associated prospectively with diabetes risk in men of the Framingham Heart Study.

Objective: In postmenopausal women and preclinical murine models, estrogen administration reduces diabetes risk; however, the relationship of estradiol and estrone to diabetes in men is poorly understood. We determined the relationship between circulating estradiol and estrone levels and diabetes risk in community-dwelling men of the Framingham Heart Study (FHS).

Research Design And Methods: Cross-sectional relationships of estradiol and estrone levels with diabetes were assessed at examination 7 (1998-2001) in FHS generation 2 men (n = 1,458); prospective associations between hormone levels at examination 7 and incident diabetes were assessed 6.

A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.

Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies.

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)).

Genetic determinants of serum testosterone concentrations in men.

Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl.

Sex hormone-binding globulin, but not testosterone, is associated prospectively and independently with incident metabolic syndrome in men: the framingham heart study.

Objective: The association between total testosterone and metabolic syndrome has prompted speculation that low testosterone contributes to the pathophysiology of metabolic syndrome in men. We determined whether testosterone or sex hormone-binding globulin (SHBG) is independently associated with the risk of metabolic syndrome.

Research Design And Methods: Cross-sectional relationships of hormone levels with metabolic syndrome were assessed in a sample of men in generation 2 of the Framingham Heart Study (FHS) who did not receive testosterone or androgen-deprivation therapy (n = 1,625) and confirmed in a validation sample of men in FHS generation 3 (n = 1,912).

Cardiac natriuretic peptides, obesity, and insulin resistance: evidence from two community-based studies.

Background: The natriuretic peptides play an important role in salt homeostasis and blood pressure regulation. It has been suggested that obesity promotes a relative natriuretic peptide deficiency, but this has been a variable finding in prior studies and the cause is unknown.

Aim: The aim of this study was to examine the association between obesity and natriuretic peptide levels and evaluate the role of hyperinsulinemia and testosterone as mediators of this interaction.

Relation of visceral adiposity to circulating natriuretic peptides in ambulatory individuals.

Natriuretic peptides have important roles in the regulation of vasomotor tone, salt homeostasis, and ventricular remodeling. Lower natriuretic peptide levels observed in obese individuals may underlie the greater cardiovascular risk associated with obesity. Thus the aim of this study was to determine whether lower natriuretic peptide levels in obesity are attributable to differences in regional fat distribution.

Influence of sex and hormone status on circulating natriuretic peptides.

Objectives: The aim of this study was to assess the relationship between sex hormones and natriuretic peptide levels in community-based adults.

Background: Women have higher circulating natriuretic peptide concentrations than men, but the mechanisms for these sex-related differences and the impact of hormone therapy are unclear. Experimental studies suggest that androgens may suppress natriuretic peptide secretion.

Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation.

Context: Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation. Trial's Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm. The changes in muscle performance and physical function were evaluated in relation to participant's perception of change.

Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands--yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations.

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.

Adverse events associated with testosterone administration.

Background: Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied.

Methods: Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.

High prevalence of metabolic syndrome in first-degree male relatives of women with polycystic ovary syndrome is related to high rates of obesity.

Context: Women with polycystic ovary syndrome (PCOS) have twice the risk for metabolic syndrome (MetS) compared to women from the general population. Mothers and sisters of affected women also have an increased prevalence of MetS.

Objective: The aim of the study was to determine the prevalence of MetS in fathers and brothers of women with PCOS compared to men from the general population.

Metabolic phenotype in the brothers of women with polycystic ovary syndrome.

Objective: Hyperandrogenemia, insulin resistance, and dyslipidemia demonstrate familial aggregation in the female first-degree relatives of women with polycystic ovary syndrome (PCOS), suggesting that these defects are heritable. Hyperandrogenemia also appears to be the male reproductive phenotype. We performed this study to test the hypothesis that brothers of women with PCOS have metabolic defects similar to those of their proband sisters.