Abstract
One of the complications from chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men is the high prevalence of hypogonadotropic hypogonadism (HH). Both T2DM and hypogonadism are associated with impaired bone health and increased fracture risk but whether the combination results in even worse bone disease than either one alone is not well-studied. It is possible that having both conditions predisposes men to an even greater risk for fracture than either one alone. Given the common occurrence of HH or hypogonadism in general in T2DM, a significant number of men could be at risk. To date, there is very little information on the bone health men with both hypogonadism and T2DM. Insulin resistance, which is the primary defect in T2DM, is associated with low testosterone (T) levels in men and may play a role in the bidirectional relationship between these two conditions, which together may portend a worse outcome for bone. The present manuscript aims to review the available evidences on the effect of the combination of hypogonadism and T2DM on bone health and metabolic profile, highlights the possible metabolic role of the skeleton, and examines the pathways involved in the interplay between bone, insulin resistance, and gonadal steroids.
Highlights
The frequent association between hypogonadism and metabolic disorders, such as obesity, insulin resistance, metabolic syndrome (MetS), and type 2 diabetes mellitus (T2DM), is well-known and has been described in multiple studies [1,2,3,4,5,6,7]
We examine the impact of the combination of hypogonadism and T2DM on bone health, and discuss the pathways involved in the interplay between insulin resistance and hyperglycemia, with gonadal hormones and bone metabolism
The impact of T2DM on the hypothalamic-pituitary-gonadal axis is manifested by a type of hypogonadism that is characterized by reduced or normal gonadotropins resulting in the so-called hypogonadotropic hypogonadism (HH)
Summary
The frequent association between hypogonadism and metabolic disorders, such as obesity, insulin resistance, metabolic syndrome (MetS), and type 2 diabetes mellitus (T2DM), is well-known and has been described in multiple studies [1,2,3,4,5,6,7]. Regardless of the etiology of low T, the coexistence of hypogonadism and T2DM could be detrimental to bone as each is associated with increased fracture risk. Low T levels is a risk factor for age-related decline in bone mass and increase in fragility fractures in men, making androgen deficiency an important risk factor for osteoporosis [15, 16]. Substantial epidemiological evidence show that people with T2DM have an increased risk of fractures compared to those without diabetes despite a normal or high normal bone mineral density (BMD) [17,18,19,20,21]. We examine the impact of the combination of hypogonadism and T2DM on bone health, and discuss the pathways involved in the interplay between insulin resistance and hyperglycemia, with gonadal hormones and bone metabolism
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