Hypogonadotrophic hypogonadism in type 2 diabetes.
Recent work shows a high prevalence of low testosterone and inappropriately low luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity in patients with type 2 diabetes. However, the duration of diabetes or HbA1c are not related to HH. Furthermore, recent data show that HH is not associated with type 1 diabetes. C-reactive protein concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and C- reactive protein concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is also relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations are also related to an increase in total and regional adiposity. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates insulin resistance and inflammation. In addition, low testosterone levels are associated with an increase in cardiovascular events. Testosterone therapy may therefore, reduce cardiovascular risk. This important aspect requires further investigation.
Dandona
P
P
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York, USA. pdandona@kaleidahealth.org
Dhindsa
S
S
Chaudhuri
A
A
Bhatia
V
V
Topiwala
S
S
D002097:C-Reactive Protein / Q000032:analysis; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D006801:Humans; D007006:Hypogonadism / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome; D009765:Obesity
D002097:C-Reactive Protein