Category: Reproductive Endocrinology
Objective : We have previously shown that insulin resistant states of type 2 diabetes and obesity are associated with hypogonadotropic hypogonadism. Since fatty liver, NAFLD and NASH are also associated with insulin resistance, we hypothesized that these two conditions are also associated with an increased incidence of low testosterone concentrations.
Methods : To test this hypothesis, we analyzed the database of UBMD (n=250,000), the clinical arm of the University of Buffalo for the frequency of hypogonadism in patients with NAFLD and NASH.
Results : We identified 54 men who had testosterone concentrations available and had a diagnosis of NAFLD or NASH. About 60% of these patients had type 2 diabetes. Of these 54 men, 26 (48%) had subnormal total testosterone concentrations. Thirty four patients had their free testosterone concentrations measured. Twenty (59%) of them had subnormal free testosterone concentrations. NASH comprised of 33% of the patients with NAFLD. The prevalence of subnormal testosterone concentrations in men with and without NASH was 90% and 44% respectively (p=0.01 by Chi-Sq).
Discussion : Diabetes may have contributed to the presence of low testosterone concentrations in these patients. However, the prevalence of low testosterone concentrations in type 2 diabetes is around 33%. NAFLD, especially NASH appear to have a significantly greater prevalence of low testosterone concentrations than diabetes alone.
Conclusion : This initial observation needs further investigation and elucidation, especially since we have previously shown that testosterone replacement in type 2 diabetes with hypogonadism reduces adiposity and hepatic fat.
Husam Ghanim– ASSOCAITE PROFESSOR, State University of NY at Buffalo, Buffalo, New York
Manav Batra– Assistant Professor, University at Buffalo,SUNY, Williamsville, New York
Sandeep Dhindsa– Professor, Saint Louis University
Paresh Dandona– Chief of the Division of Endocrinology, Metabolism and Diabetes, State University of New York at Buffalo, Williamsville, New York
State University of NY at Buffalo
Buffalo, New York
Dr. Ghanim is a research Associate Professor in the division of Endocrinology, Diabetes and Metabolism at University at Buffalo
University at Buffalo,SUNY
Williamsville, New York
Saint Louis University
SANDEEP SINGH DHINDSA, M.D, F.A.C.E
Professor of Medicine
Chief, Division of Endocrinology and Metabolism, Saint Louis University
Chief of the Division of Endocrinology, Metabolism and Diabetes
State University of New York at Buffalo
Williamsville, New York
Dr. Dandona is a Distinguished Professor of Medicine and chief of the Division of Endocrinology, Diabetes and Metabolism, at the University at Buffalo, The State University of New York. He is also the founder and director of the Diabetes–Endocrinology Center of Western New York in Buffalo. Previously, he served as director of Diabetes and Metabolism at the Royal Free Hospital School of Medicine at the University of London, England, for 14 years. One of the world’s leading experts in the treatment of diabetes and vascular disease, Dr. Dandona is a Rhodes Scholar from India, trained at the University of Oxford and the University of London.
The Diabetes Endocrinology Center of Western New York probably has the finest standards of diabetic care anywhere: it is 21 years since the last chronic diabetic foot ulcer, gangrene or amputation was observed, while it is 16 years since the last patient had diabetic end stage renal failure. Dr Dandona received the Valor Award of the American Diabetes Association for his contributions to the standards of care in diabetes and the establishment of a network of diabetes care in Western New York.
He received the Pharmacia-Pfizer/Endocrine Society Award for the discovery of the anti-inflammatory effect of insulin. This discovery has been extended into potential cardio-protective and neuro-protective effects of insulin in acute myocardial infarction, stroke and Alzheimer’s disease. Trials are under way to translate these concepts into clinical practice. His work on obesity, oxidative stress and inflammation, and the pro-inflammatory effects of macronutrients (foods) is now recognized globally. His team is currently busy investigating potential anti-inflammatory foods. The third major discovery by his team is that of low testosterone concentrations in males with Type 2 Diabetes and obesity. His team has demonstrated that this is the most common cause of male hypogonadism and potentially infertility. He is currently leading pioneering trials on the benefits of testosterone replacement and other treatments in such patients. These studies show that hypogonadal patients are more insulin resistant and that testosterone treatment reverses this defect. His group also leads the world in adjunct treatments of type 1 diabetes.
Most recently, his group has taken global lead in the area of adjunct therapies in patients with type 1 diabetes. Thus, liraglutide and dapagliflozin, the two drugs licensed for use in type 2 diabetes, have both been shown to improve glycemic control in patients with type1 diabetes. As a result, Dapagliflozin is likely to be approved by the European Medicines Agency to approve the use of dapagliglozin in type 1 diabetes. He has recently been awarded with the largest grant ever from the Juvenile Diabetes research Foundation to investigate the effect of ‘triple therapy’ (insulin, semaglutide and dapagliflozin) in patients with type 1 diabetes. He has ben recognized internationally by the Fernando Medal of the Ceylon (Sri Lanka) College of Physicians; the Banting Award of the Endocrine Society of India; the Viswanathan Medal of the Research Society for Diabetes in India; the Ricardo Fernando Medal of the Diabetes Society of Philippines; and as Global Eminent Scholar of Kyung Hee University of South Korea.
Dr. Dandona has published more than 590 publications in peer-reviewed medical journals, and has presented keynote lectures on diabetes and insulin resistance at many national and international conferences. He is the founder editor of Metabolic Syndrome and Related Disorders, and is or has been on the editorial boards of the Journal of Clinical Endocrinology and Metabolism, Diabetes Care, Current Diabetes Reviews and Journal of Diabetes.