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.

Out-of-Pocket Costs among Commercially Insured Individuals with type 2 Diabetes and Obesity: Comparison between Ozempic and Sleeve Gastrectomy.

Objective: Determine out-of-pocket (OOP) costs two years after sleeve gastrectomy (SG) or initiating Ozempic for patients with type 2 diabetes (T2D) and obesity.

Summary Background Data: Individuals with obesity and T2D have a variety of treatment options. Risks and benefits of these treatment options are becoming more well documented; however, the real-world patient costs of these options are not known.

Call to action: Understanding the differences in the use of SGLT-2 inhibitors and GLP-1 receptor agonists.

Cardiovascular disease remains one of the most prominent global health problems and has been demonstrated to disproportionally affect certain communities. Despite an increasing collective effort to improve health inequalities, a multitude of disparities continue to affect cardiovascular outcomes. Among the most prominent disparities within cardiovascular disease prevention are with the use and distribution of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists.

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).

Surgical Menopause and Frailty Risk in Community-Dwelling Older Women: Study of Osteoporotic Fractures.

Objectives: To determine whether women with surgical menopause have a higher risk of frailty than naturally menopausal women.

Design: Prospective cohort study with up to 18 years of follow-up.

Setting: Four U.

Feasibility of 24-Hr Urine Collection for Measurement of Biomarkers in Community-Dwelling Older Adults.

Biologic markers are becoming a key part of gerontological research, including their measurement at multiple intervals to detect changes over time. This report examined the feasibility and quality of 24-hr urine collection to measure neuroendocrine biomarkers in a community-based sample of older caregivers and non-caregivers. At each interview, participants were instructed on the correct method to collect and store the sample.

Circulating Estrogen Levels and Self-Reported Health and Mobility Limitation in Community-Dwelling Men of the Framingham Heart Study.

Background: Self-rated health is a commonly used global indicator of health status. Few studies have examined the association of self-rated health and mobility with estrone and estradiol in men. Accordingly, we determined the cross-sectional, incident, and mediating relations between circulating estrone and estradiol levels with self-rated health, mobility limitation, and physical performance in community-dwelling men.

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.

Clinical update on screening, diagnosis and management of metabolic disorders and cardiovascular risk factors associated with polycystic ovary syndrome.

Purpose Of Review: Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in premenopausal women. This review discusses the screening, diagnosis and management of metabolic disorders and cardiovascular risk factors associated with PCOS, highlighting significant recent developments.

Recent Findings: PCOS is a complex genetic disorder with multiple susceptibility genes as well as environmental factors influencing the expression of various PCOS phenotypes.

Age trends in estradiol and estrone levels measured using liquid chromatography tandem mass spectrometry in community-dwelling men of the Framingham Heart Study.

Background: Age trends in estradiol and estrone levels in men and how lifestyle factors, comorbid conditions, testosterone, and sex hormone-binding globulin affect these age trends remain poorly understood, and were examined in men of the Framingham Heart Study.

Methods: Estrone and estradiol concentrations were measured in morning fasting samples using liquid chromatography tandem mass spectrometry in men of Framingham Offspring Generation. Free estradiol was calculated using a law of mass action equation.

Association of sex steroids, gonadotrophins, and their trajectories with clinical cardiovascular disease and all-cause mortality in elderly men from the Framingham Heart Study.

Background: Emerging data from longitudinal studies suggest that low sex steroid concentrations in men are associated with increased cardiovascular risk and mortality. The impact of longitudinal trajectory patterns from serial sex steroid and gonadotrophin measurements on the observed associations is unknown to date.

Methods: We prospectively evaluated 254 elderly men (mean age, 75·5 years) of the Framingham Heart Study with up to four serial measurements of serum total testosterone (TT), dehydroepiandrosterone sulphate (DHEAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and total estradiol (EST); and constructed age- and multivariable-adjusted Cox proportional hazard regression models relating baseline hormone concentrations and their mean, slope and variation over time (modelled as continuous and categorized into quartiles) to the incidence of clinical cardiovascular disease (CVD) and all-cause mortality at 5- and 10-year follow-up.

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.

Relation between sex hormone concentrations, peripheral arterial disease, and change in ankle-brachial index: findings from the Framingham Heart Study.

Objective: Our objective was to investigate cross-sectional and longitudinal associations of sex hormone concentrations with ankle-brachial index (ABI) and peripheral arterial disease (PAD).

Methods And Results: We used data from 3034 (1612 women) participants of the Framingham Heart Study. ABI was measured and PAD defined as ABI below 0.

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).