Testosterone and glucose metabolism in men: current concepts and controversies

A wealth of observational studies show that low testosterone is associated with insulin resistance and with an increased risk of diabetes and the metabolic syndrome. Experimental studies have identified potential mechanisms by which low testosterone may lead to insulin resistance. Visceral adipose tissue is an important intermediate in this relationship. Actions of testosterone or its metabolite oestradiol on other tissues such as muscle, liver, bone or the brain, and body composition-independent effects may also play a role. However, definitive evidence from randomised controlled trials (RCTs) to clarify whether the association of low testosterone with disordered glucose metabolism is causative is currently lacking. It therefore remains possible that this association is due to reverse causation, or simply originates by association with common health and lifestyle factors. RCTs of testosterone therapy in men with or without diabetes consistently show modest metabolically favourable changes in body composition. Despite this, testosterone effects on glucose metabolism have been inconsistent. Recent evidence suggests that the hypothalamic–pituitary–testicular axis suppression in the majority of obese men with metabolic disorders is functional, and may be, at least in part, reversible with weight loss. Until further evidence is available, lifestyle measures with emphasis on weight reduction, treatment of comorbidities and optimisation of diabetic control should remain the first-line treatment in these men. Such measures, if successful, may be sufficient to normalise testosterone levels in men with metabolic disorders, who typically have only modest reductions in circulating testosterone levels.

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Brain Glucose Metabolism in Health, Obesity, and Cognitive Decline—Does Insulin Have Anything to Do with It? A Narrative Review

Journal of Clinical Medicine ◽

10.3390/jcm10071532 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1532

Author(s):

Eleni Rebelos ◽

Juha O. Rinne ◽

Pirjo Nuutila ◽

Laura L. Ekblad

Keyword(s):

Insulin Resistance ◽

Glucose Metabolism ◽

Cognitive Decline ◽

Fdg Pet ◽

Metabolic Disorders ◽

Brain Glucose ◽

Brain Glucose Metabolism ◽

Systemic Insulin Resistance ◽

Increased Risk ◽

18F Fdg

Imaging brain glucose metabolism with fluorine-labelled fluorodeoxyglucose ([18F]-FDG) positron emission tomography (PET) has long been utilized to aid the diagnosis of memory disorders, in particular in differentiating Alzheimer’s disease (AD) from other neurological conditions causing cognitive decline. The interest for studying brain glucose metabolism in the context of metabolic disorders has arisen more recently. Obesity and type 2 diabetes—two diseases characterized by systemic insulin resistance—are associated with an increased risk for AD. Along with the well-defined patterns of fasting [18F]-FDG-PET changes that occur in AD, recent evidence has shown alterations in fasting and insulin-stimulated brain glucose metabolism also in obesity and systemic insulin resistance. Thus, it is important to clarify whether changes in brain glucose metabolism are just an epiphenomenon of the pathophysiology of the metabolic and neurologic disorders, or a crucial determinant of their pathophysiologic cascade. In this review, we discuss the current knowledge regarding alterations in brain glucose metabolism, studied with [18F]-FDG-PET from metabolic disorders to AD, with a special focus on how manipulation of insulin levels affects brain glucose metabolism in health and in systemic insulin resistance. A better understanding of alterations in brain glucose metabolism in health, obesity, and neurodegeneration, and the relationships between insulin resistance and central nervous system glucose metabolism may be an important step for the battle against metabolic and cognitive disorders.

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Low testosterone levels are predictive for incident atrial fibrillation and ischaemic stroke in men, but protective in women – results from the FINRISK study

European Journal of Preventive Cardiology ◽

10.1177/2047487318778346 ◽

2018 ◽

Vol 25 (11) ◽

pp. 1133-1139 ◽

Cited By ~ 16

Author(s):

Tanja Zeller ◽

Renate B Schnabel ◽

Sebastian Appelbaum ◽

Francisco Ojeda ◽

Filip Berisha ◽

...

Keyword(s):

Atrial Fibrillation ◽

Confidence Interval ◽

Ischaemic Stroke ◽

Cox Regression ◽

Experimental Studies ◽

Hazard Ratio ◽

Total Testosterone ◽

Testosterone Levels ◽

Increased Risk ◽

Low Testosterone

Background Atrial fibrillation is the most common serious abnormal heart rhythm, and a frequent cause of ischaemic stroke. Recent experimental studies, mainly in orchiectomised rats, report a relationship between sex hormones and atrial electrophysiology and electroanatomy. We aimed to evaluate whether low testosterone levels are predictive for atrial fibrillation and/or ischaemic stroke in men and women. Design and methods The serum total testosterone levels were measured at baseline in a population cohort of 7892 subjects (3876 male, 4016 female), aged 25–74 years, using a commercially available immunoassay. The main outcome measure was atrial fibrillation or ischaemic stroke, whichever came first. Results During a median follow-up of 13.8 years, a total of 629 subjects (8.0%) suffered from incident atrial fibrillation ( n = 426) and/or ischemic stroke ( n = 276). Cox regression analyses, adjusted for age (used as time-scale), geographical region, total cholesterol (log), high-density lipoprotein-cholesterol (log), hypertension medication, known diabetes, smoking status, waist-hip-ratio, and time of blood drawn, documented differential predictive value of low sex-specific testosterone levels for atrial fibrillation and/or ischaemic stroke, in men and in women: Increasing levels were associated with lower risk in men (hazard ratio per one nmol/l increase 0.98 (95% confidence interval 0.93–1.00); p = 0.049). On the other hand, increasing testosterone levels were associated with higher risk in women (hazard ratio per one nmol/l increase 1.17 (95% confidence interval 1.02–1.36); p = 0.031). Conclusion Our study indicates that low testosterone levels are associated with increased risk of future atrial fibrillation and/or ischaemic stroke in men, while they are protective in women.

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Metabolic Syndrome During Menopause

Current Vascular Pharmacology ◽

10.2174/1570161116666180904094149 ◽

2019 ◽

Vol 17 (6) ◽

pp. 595-603 ◽

Cited By ~ 4

Author(s):

Sezcan Mumusoglu ◽

Bulent Okan Yildiz

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Central Obesity ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Natural Menopause ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Aging Women

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.

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Emerging roles of C1Q tumor necrosis factor-related proteins in metabolic diseases

Translational Medicine Communications ◽

10.1186/s41231-021-00083-4 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Manjunath Ramanjaneya ◽

Jayakumar Jerobin ◽

Ilham Bettahi ◽

Kodappully Sivaraman Siveen ◽

Abdul-Badi Abou-Samra

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Metabolic Disorders ◽

Pharmacological Intervention ◽

Alcoholic Fatty Liver ◽

The Metabolic Syndrome ◽

Related Proteins ◽

Necrosis Factor

AbstractObesity and insulin resistance are key elements of the metabolic syndrome, which includes type 2 diabetes (T2D), dyslipidemia, systemic inflammation, hypertension, elevated risk for cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). C1Q Tumor necrosis factor-related proteins (CTRPs) have recently emerged as important regulators of metabolism as a core component in the interrelationship between insulin resistance, adiposity and inflammation. To date 15 CTRP members have been identified and most of the CTRPs are dysregulated in obesity, T2D, coronary artery disease and NAFLD. Pharmacological intervention and lifestyle modification alter expression of CTRPs in circulation and in metabolically active tissues. CTRPs enhance metabolism mainly through activation of AMPK/AKT dependent pathways and possess insulin sensitizing properties. Thus dysregulated expression of CTRPs in metabolic disorders could contribute to the pathogenesis of the disease. For these reasons CTRPs appear to be promising targets for early detection, prevention and treatment of metabolic disorders. This review article aims at exploring the role of CTRPs in metabolic syndrome.

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Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-2373 ◽

2013 ◽

Vol 98 (12) ◽

pp. 4899-4907 ◽

Cited By ~ 235

Author(s):

Kyung Hee Park ◽

Lesya Zaichenko ◽

Mary Brinkoetter ◽

Bindiya Thakkar ◽

Ayse Sahin-Efe ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Body Mass Index ◽

Body Mass ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Cvd Risk ◽

Baseline Serum ◽

The Metabolic Syndrome ◽

Increased Risk

Context: Irisin, a recently identified hormone, has been proposed to regulate energy homeostasis and obesity in mice. Whether irisin levels are associated with risk of the metabolic syndrome (MetS), cardiometabolic variables, and cardiovascular disease (CVD) risk in humans remains unknown. Objective: Our objective was to assess the associations between baseline serum irisin levels and MetS, cardiometabolic variables, and CVD risk. Design, Setting, and Subjects: We conducted a comparative cross-sectional evaluation of baseline circulating levels of the novel hormone irisin and the established adipokine adiponectin with MetS, cardiometabolic variables, and CVD risk in a sample of 151 subjects. Results: Baseline irisin levels were significantly higher in subjects with MetS than in subjects without MetS. Irisin was associated negatively with adiponectin (r = −0.4, P < .001) and positively with body mass index (r = 0.22, P = .008), systolic (r = 0.17, P = .04) and diastolic (r = 0.27, P = .001) blood pressure, fasting glucose (r = 0.25, P = .002), triglycerides (r = 0.25, P = .003), and homeostasis model assessment for insulin resistance (r = 0.33, P < .001). After adjustment for potential confounders, including body mass index, subjects in the highest tertile of irisin levels were more likely to have MetS (odds ratio [OR] = 9.44, 95% confidence interval [CI] = 2.66–33.44), elevated fasting blood glucose (OR = 5.80, 95% CI = 1.72–19.60), high triglycerides (OR = 3.89, 95% CI = 1.16–13.03), and low high-density lipoprotein cholesterol (OR = 3.30, 95% CI = 1.18–9.20). Irisin was independently associated with homeostasis model assessment for insulin resistance and general Framingham risk profile in multiple linear regression analyses after adjustment for confounders. Adiponectin demonstrated the expected associations with outcomes. Conclusions: Irisin is associated with increased risk of MetS, cardiometabolic variables, and CVD in humans, indicating either increased secretion by adipose/muscle tissue and/or a compensatory increase of irisin to overcome an underlying irisin resistance in these subjects.

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Insulin resistance induced by long-term sleep deprivation in rhesus macaques can be attenuated by Bifidobacterium

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00329.2021 ◽

2021 ◽

Author(s):

Ying Zhao ◽

Yan Shu ◽

Ning Zhao ◽

Zili Zhou ◽

Xiong Jia ◽

...

Keyword(s):

Insulin Resistance ◽

Circadian Rhythm ◽

Blood Glucose ◽

Glucose Metabolism ◽

Sleep Deprivation ◽

Rhesus Macaques ◽

Intravenous Glucose ◽

Increased Risk ◽

The Impact

Long-term sleep deprivation (SD) is a bad lifestyle habit, especially among specific occupational practitioners, characterized by circadian rhythm misalignment and abnormal sleep/wake cycles. SD is closely associated with an increased risk of metabolic disturbance, particularly obesity and insulin resistance. The incretin hormone, glucagon-like peptide-1 (GLP-1), is a critical insulin release determinant secreted by the intestinal L-cell upon food intake. Besides, the gut microbiota participates in metabolic homeostasis and regulates GLP-1 release in a circadian rhythm manner. As a commonly recognized intestinal probiotic, Bifidobacterium has various clinical indications regarding its curative effect. However, few studies have investigated the effect of Bifidobacterium supplementation on sleep disorders. In the present study, we explored the impact of long-term SD on the endocrine metabolism of rhesus monkeys and determined the effect of Bifidobacterium supplementation on the SD-induced metabolic status. Lipids concentrations, body weight, fast blood glucose, and insulin levels increased after SD. Furthermore, after two months of long-term SD, the intravenous glucose tolerance test (iVGTT) showed that the glucose metabolism was impaired and the insulin sensitivity decreased. Moreover, one month of Bifidobacterium oral administration significantly reduced blood glucose and attenuated insulin resistance in rhesus macaques. Overall, our results suggested that Bifidobacterium might be used to alleviate SD-induced aberrant glucose metabolism and improve insulin resistance. Also, it might help in better understanding the mechanisms governing the beneficial effects of Bifidobacterium.

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Female offspring born to obese and insulin-resistant dams are not at increased risk for obesity and metabolic dysfunction during early development

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0371 ◽

2018 ◽

Vol 96 (1) ◽

pp. 97-102 ◽

Cited By ~ 1

Author(s):

Hanin Aburasayn ◽

Rami Al Batran ◽

Keshav Gopal ◽

Malak Almutairi ◽

Amina Eshreif ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Female Offspring ◽

Metabolic Dysfunction ◽

Insulin Resistant ◽

The Metabolic Syndrome ◽

Rate Versus ◽

Increased Risk ◽

Study Completion ◽

Reduced Rate

The percentage of women who are obese at the time of conception or during pregnancy is increasing, with animal and human studies demonstrating that offspring born to obese dams or mothers are at increased risk for obesity and the metabolic syndrome. Our goal was to confirm in an experimental model of metabolic syndrome in the dam, whether the offspring would be at increased risk of obesity. Conversely, we observed that male offspring born to dams with metabolic syndrome had no alterations in their body mass profiles, whereas female offspring born to dams with metabolic syndrome were heavier at weaning, but exhibited no perturbations in energy metabolism. Moreover, they gained weight at a reduced rate versus female offspring born to healthy dams, and thus weighed less at study completion. Hence, our findings suggest that factors other than increased adiposity and insulin resistance during pregnancy are responsible for the increased risk of obesity in children born to obese mothers.

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Metabolic syndrome risk factors are associated with white rice intake in Korean adolescent girls and boys

British Journal Of Nutrition ◽

10.1017/s0007114514003845 ◽

2015 ◽

Vol 113 (3) ◽

pp. 479-487 ◽

Cited By ~ 13

Author(s):

SuJin Song ◽

Hee Young Paik ◽

Won O. Song ◽

YoonJu Song

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Dietary Intake ◽

Carbohydrate Intake ◽

Multivariate Linear Regression Analysis ◽

Total Carbohydrate ◽

White Rice ◽

The Metabolic Syndrome ◽

Increased Risk

In the present study, we examined the associations of total carbohydrate intake, dietary glycaemic load (DGL) and white rice intake with metabolic syndrome risk factors by sex in Korean adolescents. For the present cross-sectional study, data from the Fourth Korea National Health and Nutrition Examination Survey (2007–9) were used. A total of 2209 adolescents (n 1164 boys and n 1045 girls) aged 10–18 years with complete anthropometric, biochemical and dietary intake data were included in the study. Dietary intake data were obtained using the 24 h recall method, and total carbohydrate intake, DGL and white rice intake were divided into quartiles by sex. The metabolic syndrome and its risk factors were defined using the International Diabetes Federation criteria for children and adolescents. Fasting insulin levels and insulin resistance were included as the metabolic syndrome risk factors. All statistical analyses considered the complex sampling design effect and appropriate sampling weights. Multivariate linear regression analysis was used to estimate means with their standard errors of the mean for the metabolic syndrome risk factors across the quartiles of total carbohydrate intake, DGL and white rice intake. While high DGL was significantly associated with increased fasting glucose levels in boys, high total carbohydrate intake, DGL and white rice intake were consistently associated with reduced HDL-cholesterol levels in girls. High white rice intake was significantly associated with an increased risk of insulin resistance and the metabolic syndrome in girls but not in boys. Optimising dietary carbohydrate intake with respect to the source or amount is fundamental to preventing and managing metabolic diseases in Asian adolescents.

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World endocrinology news

Obesity and metabolism ◽

10.14341/omet2008245-54 ◽

2008 ◽

Vol 5 (2) ◽

pp. 45-54

Author(s):

M A Berkovskaya

Keyword(s):

Insulin Resistance ◽

Cardiovascular Disease ◽

Metabolic Syndrome ◽

Vitamin D ◽

Glucose Metabolism ◽

Oral Cancer ◽

Fat Distribution ◽

Lower Prevalence ◽

The Metabolic Syndrome

The role of interleukin-6 in insulin resistance, body fat distribution and energy balance Disorders of glucose metabolism and risk of oral cancer. Duration of lactation is associated with lower prevalence of the metabolic syndrome in midlife--SWAN, the study of women's health across the nation. Vitamin D deficiency and risk of cardiovascular disease. Adypocyte prolactin: regulation of release and putative functions.

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Metabolic syndrome and insulin resistance in obese adolescents

Revista Paulista de Pediatria ◽

10.1590/s0103-05822014000100010 ◽

2014 ◽

Vol 32 (1) ◽

pp. 55-59 ◽

Cited By ~ 26

Author(s):

Amanda Oliva Gobato ◽

Ana Carolina J. Vasques ◽

Mariana Porto Zambon ◽

Antonio de Azevedo Barros Filho ◽

Gabriel Hessel

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Body Composition ◽

Subcutaneous Fat ◽

Hdl Cholesterol ◽

Cutoff Point ◽

Abdominal Circumference ◽

Model Assessment ◽

Obese Adolescents ◽

The Metabolic Syndrome

Objective: To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. Methods: A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI), body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. Results: The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032) and with metabolic syndrome (p=0.006). All body composition indicators were correlated with insulin resistance (p<0.01). In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. Conclusions: All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance.

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