Determinants of initial insulin therapy for hospitalized patients with diabetes mellitus.

AIMS: Glycemic control immediately after hospital admission is difficult. This study aimed to develop an algorithm-based approach to initiate insulin therapy on admission. METHODS: Patients with history of diabetes mellitus admitted at UC Davis medical center, with any blood glucose (BG) value ≥ 180 mg/dL, or who received any insulin within the first 24 h of hospitalization were selected for a retrospective chart review. RESULTS: Total of 315 patient records were studied. Patients prescribed insulin prior to admission had higher 24-hour average BG and higher corrected total daily dose of insulin (CxTDD), compared with the patients who were not prescribed insulin prior to admission. For the patients not receiving home insulin and not given new glucocorticoids, first BG upon presentation correlated with the risk of first 24-hour average BG > 180 mg/dL. Factors associated with CxTDD were first BG, weight, oral intake, and glucocorticoid dose. Home insulin daily dose, opiate/intravenous pain medication and systemic inflammatory response syndrome were associated with CxTDD only in the patients receiving home insulin. CONCLUSIONS: A subgroup of patients can be given correction insulin as a sole initial treatment on admission. For patients requiring basal-bolus insulin, several factors associated with the initial insulin requirements are identified.

Meal Timing and Glycemic Control during Pregnancy-Is There a Link?

Hyperglycemia during pregnancy and gestational diabetes mellitus (GDM) constitute an important public health problem due to their prevalence and long-term health consequences both for the mother and offspring. Results from studies in rodents and some clinical investigations suggest that meal time manipulation may be a potential lifestyle approach against conditions involving perturbations in glucose homeostasis (e.g., hyperglycemia, insulin resistance, diabetes, etc.). The purpose of this review is to summarize and critically evaluate the current literature on the role of meal timing and daily nutrient distribution on glycemic control during pregnancy. Only a small number of mostly observational studies have assessed the role of meal timing in glucose homeostasis during pregnancy. Food consumption earlier in the day and short-term fasting with adequate nutrient intake may improve glycemic control during the second and third trimester of gestation. Considering that the field of chrononutrition is still in its infancy and many questions remain unanswered, future prospective and carefully designed studies are needed to better understand the role of meal timing in metabolic homeostasis and maternal and fetal health outcomes during pregnancy.

Relation between Retinopathy and Progression of Coronary Artery Calcium in Individuals with Versus Without Diabetes Mellitus (From the Multi-Ethnic Study of Atherosclerosis).

Retinopathy is a microvascular complication of diabetes mellitus (DM); however, it is also increasingly recognized in persons without DM. The microvascular diseases may play a prominent role in coronary heart disease (CHD) development in individuals with DM. We performed the study to evaluate the relation between non-DM retinopathy and CHD and also the association between baseline retinopathy and incidence and progression of CHD in individuals with and without DM. We included 5709 subjects with and without DM from the Multi-Ethnic Study of Atherosclerosis, who had retinal photos and coronary artery calcium score (CACS) available. We studied the association between baseline retinopathy and incidence and progression of coronary artery calcification (CAC) in subjects with and without DM. In DM group, the presence of retinopathy was significantly associated with an increased rate of CAC (RR 1.3 (95% CI [1.02, 1.66]) after adjusting for age, sex, race, follow-up time, and CHD risk factors. In non-DM group, the presence of retinopathy was not significantly associated with increased risk of CAC, however, the interaction between presence of retinopathy and DM status was not statistically significant. Within the DM group with CAC present at baseline, the presence of retinopathy was significantly associated with greater CAC progression (113 Agatson units (AU) greater, (95% CI [51-174]). In the non-DM group with present CAC at baseline; the presence of retinopathy was associated with 24 (95% CI [-0.69, 48.76]) AU higher CAC progression. All findings were adjusted for CHD risk factors. In conclusion, after adjustment for major CHD risk factors, retinopathy was associated with progression of CAC in both DM and non-DM individuals. However, the association was stronger in those with DM.

The IL-27 component EBI-3 and its receptor subunit IL-27Rα are essential for the cytoprotective action of humanin on male germ cells†.

Humanin (HN) is a mitochondrial-derived peptide that protects many cells/tissues from damage. We previously demonstrated that HN reduces stress-induced male germ cell apoptosis in rodents. HN action in neuronal cells is mediated through its binding to a trimeric cell membrane receptor composed of glycoprotein 130 (gp130), IL-27 receptor subunit (IL-27R, also known as WSX-1/TCCR), and ciliary neurotrophic factor receptor subunit (CNTFR). The mechanisms of HN action in testis remain unclear. We demonstrated in ex-vivo seminiferous tubules culture that HN prevented heat-induced germ cell apoptosis was blocked by specific anti-IL-27R, anti-gp130, and anti-EBI-3, but not by anti-CNTFR antibodies significantly. The cytoprotective action of HN was studied by using groups of il-27r-/- or ebi-3-/- mice administered the following treatment: (1) vehicle; (2) a single intraperitoneal (IP) injection of HN peptide; (3) testicular hyperthermia; and (4) testicular hyperthermia plus HN. We demonstrated that HN inhibited heat-induced germ cell apoptosis in wildtype but not in il-27r-/- or ebi-3-/- mice. HN restored heat-suppressed STAT3 phosphorylation in wildtype but not il-27r-/- or ebi-3-/- mice. Dot blot analyses showed the direct interaction of HN with IL-27R or EBI-3 peptide. Immunofluorescence staining showed the co-localization of IL-27R with HN and gp130 in Leydig cells and germ cells. We conclude that the anti-apoptotic effects of HN in mouse testes are mediated through interaction with EBI-3, IL-27R, and activation of gp130, whereas the role of CNTFR needs further studies. This suggests a multicomponent tissue-specific receptor for HN in the testis and links HN action with the IL-12/IL-27 family of cytokines.

Gynecomastia and hypertension in a patient treated with posaconazole.

Posaconazole therapy may lead to increased serum estradiol levels and development of gynecomastia. Early detection by endocrine hormone measurements may help preventing gynecomastia.

Intermittent fasting as a nutrition approach against obesity and metabolic disease.

PURPOSE OF REVIEW: Intermittent fasting has been proposed as a potential nutrition approach against obesity and metabolic disease. Although data from studies in rodents convincingly support the antiobesity and cardiometabolic benefits of intermittent fasting, its effects in human health are still debatable. RECENT FINDINGS: Recent studies have examined the effect of two intermittent fasting approaches, that is, alternate day fasting (ADF) and time-restricted eating (TRE), on weight loss and cardiometabolic risk factors. ADF seems to be an equally effective weight loss approach to caloric restriction, but adherence to ADF is more challenging. ADF improves cardiometabolic risk factors, whereas it may have superior metabolic benefits compared to caloric restriction in people with insulin resistance. TRE with ad libitum food intake is well tolerated and induces 2-4% weight loss in approximatively 3 months. Additionally, TRE may have metabolic benefits particularly in people with metabolically abnormal obesity even without weight loss. SUMMARY: Intermittent fasting is a promising nutritional approach against obesity and its related metabolic diseases. Further research is needed to: i) establish the long-term effectiveness of TRE in weight loss and metabolic health, ii) improve the long-term adherence to ADF and investigate its weight loss independent effects in metabolic health, and iii) determine the mechanisms underlying the potential cardiometabolic benefits of intermittent fasting in humans.

New Biomarkers to Evaluate Hyperandrogenemic Women and Hypogonadal Men.

Androgens can have variable effects on men and women. Women may be evaluated for androgen excess for several reasons. Typically, young premenopausal women present with clinical symptoms of hirsutism, alopecia, irregular menses, and/or infertility. The most common cause of these symptoms is polycystic ovary syndrome. After menopause, even though ovaries stop producing estrogen, they continue to produce androgen, and women can have new onset of hirsutism and alopecia. Laboratory evaluation involves measurement of the major ovarian and adrenal androgens. In women, age, phase of the menstrual cycle, menopausal status, obesity, metabolic health, and sex hormone-binding proteins significantly affect total-androgen levels and complicate interpretation. This review will summarize the clinically relevant evaluation of hyperandrogenemia at different life stages in women and highlight pitfalls associated with interpretation of commonly used hormone measurements. Hypogonadism in men is a clinical syndrome characterized by low testosterone and/or low sperm count. Symptoms of hypogonadism include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men. Hypogonadism is observed rarely in young boys and adolescent men. Based on the defects in testes, hypothalamus, and/or pituitary glands, hypogonadism can be broadly classified as primary, secondary, and mixed hypogonadism. Diagnosis of hypogonadism in men is based on symptoms and laboratory measurement. Biomarkers in use/development for hypogonadism are classified as hormonal, Leydig and Sertoli cell function, semen, genetic/RNA, metabolic, microbiome, and muscle mass-related. These biomarkers are useful for diagnosis of hypogonadism, determination of the type of hypogonadism, identification of the underlying causes, and therapeutic assessment. Measurement of serum testosterone is usually the most important single diagnostic test for male hypogonadism. Patients with primary hypogonadism have low testosterone and increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Patients with secondary hypogonadism have low testosterone and low or inappropriately normal LH and FSH. This review provides an overview of hypogonadism in men and a detailed discussion of biomarkers currently in use and in development for diagnosis thereof.

Lipid Lowering with Soluble Dietary Fiber.

Consumption of dietary soluble fibers has been associated with health benefits such as reduced lipid levels, lower blood pressure, improved blood glucose control, weight loss, improved immune function, and reduced inflammation. Many of these health benefits relate to a reduced risk of developing cardiovascular disease. In this paper, we have reviewed recent studies on the hypocholesterolemic effects of dietary soluble fibers as well as fiber-rich foods. Findings include the following: (a) consumption of water-soluble, viscous-forming fibers can reduce total and low-density lipoprotein cholesterol levels by about 5-10 %; (b) minimal changes of high-density lipoprotein cholesterol or triglyceride levels were observed; (c) cholesterol-lowering properties of soluble fibers depend on their physical and chemical properties; and (d) medium to high molecular weight fibers are more effective in reducing lipid levels. Hypocholesterolemic benefits were also observed with some fiber-rich foods, such as whole oats, whole barley, legumes, peas, beans, flax seeds, apples, and citrus foods.

Serum Testosterone (T) Level Variability in T Gel-Treated Older Hypogonadal Men: Treatment Monitoring Implications.

CONTEXT: The optimal frequency for on-treatment serum T measurement used for dose adjustment after transdermal T gel application is unknown, especially in older men with thinner skin and slower metabolic clearance. OBJECTIVES: The objectives of the study was to determine the variability of postgel application serum T concentrations and assess whether single levels are reflective of average serum T concentrations over 24 hours (Cavg0-24). DESIGN: This was a double-blinded, placebo-controlled randomized trial. SETTING: The study was conducted at five academic centers. PARTICIPANTS: Forty-seven symptomatic men 65 years old or older with an average of two morning T concentration less than 275 ng/dL participated in the study. INTERVENTION(S): Transdermal T or placebo gel was applied for 120 ± 14 days. Monthly dose adjustments were made if necessary to target serum T between 400 and 500 to 800 ng/dL. MAIN OUTCOME MEASURES: Variability of serum T 2 hours after the gel application on two outpatient visits and at multiple time points over 24 hours during the inpatient day was measured. RESULTS: On-treatment T levels varied substantially on the 2 ambulatory days and over 24 hours during the inpatient day. Ambulatory 2-hour postapplication T levels did not correlate significantly with either 2-hour postapplication serum T or Cavg0-24 measured during the inpatient day. Only 22.2% of men receiving T had a Cavg0-24 within the target range of 500-800 ng/dL; 81.5% had a Cavg0-24 within the broader 300-1000 ng/dL range. CONCLUSION: Large within-individual variations in serum T after T gel application render ambulatory 2-hour postapplication T level a poor indicator of average serum T on another day. Our data point out the limitations of dose adjustments based on a single postapplication serum T measurement.

Single, escalating dose pharmacokinetics, safety and food effects of a new oral androgen dimethandrolone undecanoate in man: a prototype oral male hormonal contraceptive.

The novel androgen, dimethandrolone (DMA) has both androgenic and progestational activities, properties that may maximize gonadotropin suppression. We assessed the pharmacokinetics of dimethandrolone undecanoate (DMAU), an orally bioavailable, longer acting ester of DMA, for male contraceptive development. Our objective was to examine the safety and pharmacokinetics of single, escalating doses of DMAU (powder in capsule formulation) administered orally with or without food in healthy men. We conducted a randomized, double-blind Phase 1 study. For each dose of DMAU (25-800 mg), 10 male volunteers received DMAU and two received placebo at two academic medical centres. DMAU was administered both fasting and after a high-fat meal (200-800 mg doses). Serial serum samples were collected over 24 h following each dose. DMAU was well tolerated without significant effects on vital signs, safety laboratory tests or electrocardiograms. When administered while fasting, serum DMA (active compound) was detectable in only 4/10 participants after the 800 mg dose. When administered with a 50% fat meal, serum DMA was detectable in all participants given 200 mg DMAU and showed a dose-incremental increase up to 800 mg, with peak levels 4-8 h after taking the dose. Serum gonadotropins and sex hormone concentrations were significantly suppressed 12 h after DMAU administration with food at doses above 200 mg. This first-in-man study demonstrated that a single, oral dose of DMAU up to 800 mg is safe. A high-fat meal markedly improved DMAU/DMA pharmacokinetics.

An update on male hypogonadism therapy.

INTRODUCTION: Men who have symptoms associated with persistently low serum total testosterone level should be assessed for testosterone replacement therapy. AREAS COVERED: Acute and chronic illnesses are associated with low serum testosterone and these should be recognized and treated. Once the diagnosis of male hypogonadism is made, the benefits of testosterone treatment usually outweigh the risks. Without contraindications, the patient should be offered testosterone replacement therapy. The options of testosterone delivery systems (injections, transdermal patches/gels, buccal tablets, capsules and implants) have increased in the last decade. Testosterone improves symptoms and signs of hypogonadism such as sexual function and energy, increases bone density and lean mass and decreases visceral adiposity. In men who desire fertility and who have secondary hypogonadism, testosterone can be withdrawn and the patients can be placed on gonadotropins. New modified designer androgens and selective androgen receptor modulators have been in preclinical and clinical trials for some time. None of these have been assessed for the treatment of male hypogonadism. EXPERT OPINION: Despite the lack of prospective long-term data from randomized, controlled clinical trials of testosterone treatment on prostate health and cardiovascular disease risk, the available evidence suggests that testosterone therapy should be offered to symptomatic hypogonadal men.

Hypogonadism in the aging male diagnosis, potential benefits, and risks of testosterone replacement therapy.

Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young male adults. There are a variety of testosterone formulations available for treatment of hypogonadism. Data from many small studies indicate that testosterone therapy offers several potential benefits to older hypogonadal men. A large multicenter NIH supported double blind, placebo controlled study is ongoing, and this study should greatly enhance the information available on efficacy and side effects of treatment. While safety data is available across many age groups, there are still unresolved concerns associated with testosterone therapy. We have reviewed the diagnostic methods as well as benefits and risks of testosterone replacement therapy for hypogonadism in aging men.

Time to recovery in diabetes and comorbidities following Hurricane Katrina.

BACKGROUND: The impact of a natural disaster on self-care and health care delivery has been well documented. The objective of the study was to document the recovery pattern from the impact of a natural disaster such as Hurricane Katrina on clinical and biochemical measures of diabetes and its comorbidities. METHODS: Patients were selected from Tulane University Hospital and Clinic, Southeast Louisiana Veterans Health Care System, and the Medical Center of Louisiana at New Orleans. Adults with diabetes and A(1c) measurement 6 months before (pre-K) Hurricane Katrina (February 28, 2005-August 27, 2005) and 6 to 16 months after (post-K) Katrina (March 1, 2006-December 31, 2006) were identified within the 3 facilities. Follow-up data (January 1, 2007-December 31, 2007) were 1 year after the first post-K visit. The outcome measures were hemoglobin A(1c) (HbA(1c)), systolic and diastolic blood pressure (BP), and lipids (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL], triglycerides). RESULTS: Averaged across the 3 facilities, the parameters significantly different in the follow-up period compared with pre- and post-K were HbA(1c) (P = .04), HDL, and systolic and diastolic BP (P < .0001). Parameters with significantly different patterns of change in the 3 facilities over time were HbA(1c), HDL, systolic and diastolic BP (P < .0001), and low-density lipoprotein (P < .01). CONCLUSIONS: Our results suggest that a variety of clinical and biochemical parameters related to diabetes and its comorbidities affected by natural disaster have varied the rate of recovery to predisaster levels.

Emerging concepts in the pathophysiology of type 2 diabetes mellitus.

Type 2 diabetes mellitus is a multifactorial metabolic disorder. It is characterized by chronic hyperglycemia, insulin resistance, and a relative insulin secretion defect. The prevalence of type 2 diabetes mellitus has risen worldwide in large part because of an increase in obesity and sedentary lifestyles. The underlying pathophysiology and complications of type 2 diabetes mellitus are still being elucidated. Recent advances in diabetes research have helped us to gain a better understanding about insulin resistance and insulin secretion defects. The evolving understanding about the influence of the incretin effect, insulin signal transduction, adipose tissue, intra-islet cell communication, and inflammation is changing the way in which we view type 2 diabetes mellitus. This new understanding will eventually provide us with new treatment approaches to help patients who have type 2 diabetes mellitus. This article gives a review of the current and emerging concepts of the pathophysiology of type 2 diabetes mellitus.