A cross-sectional analysis of the association between testosterone and biopsy-proven non-alcoholic fatty liver disease in men with obesity.

PURPOSE: To study the association between testosterone and non-alcoholic fatty liver disease (NAFLD) since prior studies have reported inconsistent results. METHODS: A retrospective analysis was performed including obese men who underwent a liver biopsy and a metabolic and hepatological work-up. Free testosterone (CFT) was calculated by the Vermeulen equation. The association between total testosterone (total T) and CFT on the one hand and NAFLD and fibrosis on the other hand was investigated and corrected for biasing factors such as metabolic parameters. RESULTS: In total, 134 men (mean age 45 ± 12 years, median BMI 39.6 (25.0-64.9) kg/m²) were included. The level of total T and CFT did not significantly differ between NAFL and NASH and the stages of steatosis and ballooning. CFT was significantly lower in a higher stage of fibrosis (p = 0.013), not seen for total T and not persisting after controlling for the influence of BMI, HDL cholesterol and HOMA-IR. A higher stage of lobular inflammation was associated with a lower level of total T (p = 0.033), not seen for CFT and not persisting after controlling for the influence of visceral adipose tissue surface and HOMA-IR. CONCLUSIONS: This is the second largest study investigating the association between testosterone and biopsy-proven NAFLD. No significant association between testosterone levels and NAFLD, and the different histological subgroups or fibrosis was seen. The lower level of CFT in a higher stage of fibrosis and the association between total T and lobular inflammation was driven by poor metabolic parameters.

Effects of treatment for diabetes mellitus on testosterone concentrations: A systematic review.

BACKGROUND: Low testosterone levels are frequently present in men with obesity and insulin resistance. Currently available treatment options (testosterone replacement therapy or lifestyle changes) hold possible risks or are insufficient. Since low testosterone levels are closely related to obesity and type 2 diabetes, treatment modalities for these conditions could result into improvement of testosterone levels. OBJECTIVES: To summarize the available evidence on the effects of traditional and recent treatment modalities for diabetes mellitus on testosterone levels and androgen-deficiency-related signs and symptoms. MATERIALS AND METHODS: PubMed was searched from the year 2000 till present using MESH terms: "hypogonadism," "testosterone," "testosterone deficiency," "functional hypogonadism," and the different classes of medications. Studies with observational and experimental designs on humans that evaluated the effect of antidiabetic medications on gonadotropins and testosterone were eligible for inclusion. RESULTS: Current available data show no or only limited improvement on testosterone levels with the classic antidiabetic drugs. Studies with GLP1-receptor analogues show beneficial effects on both body weight and testosterone levels in men with low testosterone levels and obesity with or without type 2 diabetes. However, data are limited to small and heterogeneous study groups and only few studies report data about impact on androgen-deficiency-related signs and symptoms. DISCUSSION AND CONCLUSION: With the recent advances in the knowledge of the pathophysiological pathways in obesity, there is an enormous progress in the development of medications for obesity and type 2 diabetes. Newer incretin-based agents have a great potential for the treatment of functional hypogonadism due to obesity since they show promising weight reducing results. However, before the use of GLP1-receptor analogues can be suggested to treat functional hypogonadism, further studies are needed.

Rapid-acting insulin analogues: Theory and best clinical practice in type 1 and type 2 diabetes.

Since the discovery of insulin 100 years ago, insulin preparations have improved significantly. Starting from purified animal insulins, evolving to human insulins produced by genetically modified organisms, and ultimately to insulin analogues, all in an attempt to mimic physiological insulin action profiles seen in individuals without diabetes. Achieving strict glucose control without hypoglycaemia and preventing chronic complications of diabetes while preserving quality of life remains a challenging goal, but the advent of newer ultra-rapid-acting insulin analogues may enable intensive insulin therapy without being too disruptive to daily life. Ultra-rapid-acting insulin analogues can be administered shortly before meals and give better coverage of mealtime-induced glucose excursions than conventional insulin preparations. They also increase convenience with timing of bolus dosing. In this review, we focus on the progress that has been made in rapid-acting insulins. We summarize pharmacokinetic and pharmacodynamic data, clinical trial data supporting the use of these new formulations as part of a basal-bolus regimen and continuous subcutaneous insulin infusion, and provide a clinical perspective to help guide healthcare professionals when and for whom to use ultra-fast-acting insulins.

Prevalence of and risk factors for sexual dysfunctions in adults with type 1 or type 2 diabetes: Results from Diabetes MILES - Flanders.

BACKGROUND AND AIMS: The prevalence of sexual dysfunctions in people with diabetes is still debated and understudied in women. This study examines the prevalence of sexual dysfunction in men and women with type 1 or type 2 diabetes (T1D or T2D) and the associations with clinical and psychological variables. METHODS: Adults with diabetes (n = 756) completed an online survey including questions on sexual functioning (adapted Short Sexual Functional Scale), general emotional well-being (WHO-5), symptoms of anxiety (GAD-7) and diabetes distress (PAID-20). RESULTS: One third of participants reported a sexual dysfunction. Men reported erectile dysfunction (T1D: 20%; T2D: 33%), and orgasmic dysfunction (T1D: 22%; T2D: 27%). In men, sexual dysfunction was independently associated with, older age (OR = 1.05, p = 0.022), higher waist circumference (OR = 1.04; p < 0.001) and longer duration of diabetes (OR = 1.04; p = 0.007). More men with sexual dysfunction reported diabetes distress (20% vs. 12%, p = 0.026). Women reported decreased desire (T1D: 22%; T2D: 15%) and decreased arousal (T1D: 9%; T2D: 11%). More women with sexual dysfunction reported diabetes distress (36% vs. 21%, p = 0.003), impaired emotional well-being (36% vs. 25%, p = 0.036) and anxiety symptoms (20% vs. 11%, p = 0.026). CONCLUSION: Sexual dysfunctions are common in both men and women with diabetes. In men, sexual dysfunctions were associated with clinical factors. More women with sexual dysfunction reported low emotional well-being and anxiety symptoms compared to women without sexual dysfunction. For both men and women, sexual dysfunctions were associated with diabetes distress.

Nonmosaic Isodicentric Y Chromosome: A Rare Cause of Azoospermia- From Genetics to Clinical Practice.

Azoospermia is diagnosed when no spermatozoa can be detected after centrifugation of seminal fluid on at least two separate occasions. A number of genetic disorders can be related to nonobstructive azoospermia, and in up to 15% of azoospermic males, a genetic disorder is diagnosed. A 36-year-old male with nonobstructive azoospermia was referred to our department of diabetes and endocrinology due to an aberrant testicular biopsy. The biopsy showed a disrupted spermatogenesis with a maturation arrest at the spermatocyte level in most tubuli seminiferi while others showed a Sertoli cell-only syndrome. Screening for Y chromosome microdeletions on peripheral blood using molecular analysis detected a terminal deletion of AZFbc. The result of karyotyping and fluorescence in situ hybridization (FISH) described an isodicentric Y chromosome with karyotype 46,X,idic(Y)(q11.22). Based on this case and the current available literature, we conclude that performing a testicular biopsy in patients with a nonmosaic idic(Y)(q) is not meaningful and that the prognosis on infertility is poor. Biological fatherhood is extremely unlikely in these patients, and proper counselling should be provided.

Prenatal exposure to environmental contaminants and body composition at age 7-9 years.

The study aim was to investigate the association between prenatal exposure to endocrine disrupting chemicals (EDCs) and the body composition of 7 to 9 year old Flemish children. The subjects were 114 Flemish children (50% boys) that took part in the first Flemish Environment and Health Study (2002-2006). Cadmium, PCBs, dioxins, p,p'-DDE and HCB were analysed in cord blood/plasma. When the child reached 7-9 years, height, weight, waist circumference and skinfolds were measured. Significant associations between prenatal exposure to EDCs and indicators of body composition were only found in girls. After adjustment for confounders and covariates, a significant negative association was found in girls between prenatal cadmium exposure and weight, BMI and waist circumference (indicator of abdominal fat) and the sum of four skinfolds (indicator of subcutaneous fat). In contrast, a significant positive association (after adjustment for confounders/covariates) was found between prenatal p,p'-DDE exposure and waist circumference as well as waist/height ratio in girls (indicators of abdominal fat). No significant associations were found for prenatal PCBs, dioxins and HCB exposure after adjustment for confounders/covariates. This study suggests a positive association between prenatal p,p'-DDE exposure and indicators of abdominal fat and a negative association between prenatal cadmium exposure and indicators of both abdominal as well as subcutaneous fat in girls between 7 and 9 years old.

Validity of parentally reported versus measured weight, length and waist in 7- to 9-year-old children for use in follow-up studies.

UNLABELLED: The aim of this prospective cohort study was to assess the validity of parentally reported anthropometric data compared to measured data in 7- to 9-year-old Flemish children especially for use in follow-up studies. The subjects were 116 Flemish children of a birth cohort recruited in the first Flemish Environment and Health Study (2002-2003). Data about anthropometric measures (waist circumference (WC), weight and length) were obtained by a postal parentally reported questionnaire and during a home visit. Our study showed that parents tend to overreport their child's WC and underreport the BMI, especially in children with large WC and high BMI. The median difference between measured and parentally reported WC was 1.6% of the median measured WC; for BMI, the median difference was 2.8% of the median measured BMI. Both for WC and BMI, we observed a good agreement between parentally reported values and measured values to classify children in the highest 10 and 20% of the study population. When classifying the children in 'overweight' and 'not overweight', there were less misclassifications when parentally reported WC was used compared to parentally reported BMI. CONCLUSIONS: Although there is a high agreement between parentally reported and measured WC, the parentally reported data must be used with reserve. Moreover, this study is the first to suggest that WC is a better indicator compared to BMI when parentally reported values are used to classify children.