Testosterone treatment in obese hypogonadal men with type 2 diabetes
Effects of long-term testosterone therapy on patients with “diabesity”: Results of observational studies of pooled analyses in obese hypogonadal men with type 2 diabetes. Haider A, Yassin A, Doros G, et al. Int J Endocrinol 2014; Article ID: 683515.
Obesity is a chronic disease of increasing concern in developing and developed countries. It is associated with many comorbidities, including insulin resistance, type 2 diabetes mellitus (T2DM), and hypogonadism (testosterone deficiency [TD]).1 Patients who present with obesity and T2DM, termed “diabesity”,2 have an increased risk of cardiovascular disease (CVD). This summary discusses the key findings from a report1 using pooled data from two long-term, observational, prospective, cumulative registry studies to investigate the use of parenteral testosterone undecanoate (TU) 1,000 mg in obese hypogonadal men with T2DM.
What is known
In 2006, the prevalence of obesity and diabetes was reported to have increased by 7.8% and 7.3%, respectively, over the preceding decade.3 Increases in body weight and obesity are associated with an increased risk of insulin resistance and T2DM.4 Conversely, the risk of T2DM is decreased by 50–60% following a loss in body weight of 5–7%.5 Of clinical importance, patients with both obesity and T2DM exhibit higher risks of CVD6 and mortality.7,8 Thus, obesity and T2DM are associated with a number of comorbidities, and the combination of both diseases in a single patient represents a clinical therapeutic challenge.
The bidirectional relationship between TD, obesity, and T2DM is complex, and TD itself may be a risk factor for development of obesity and T2DM.1 Levels of testosterone are inversely related to obesity, and TD is associated with T2DM.9 Furthermore, TD was significantly associated with BMI and WC in a study of 355 men with T2DM.10 Testosterone is known to regulate many metabolic functions. Several studies have shown that testosterone therapy in men with T2DM improved parameters of both conditions, including body weight, WC, fasting blood glucose, and HbA1c.10-12
What this study adds
Findings from this 6-year study in obese, diabetic men with TD demonstrate that TU significantly improves a number of anthropometric parameters associated with obesity and T2DM. Improvements in weight loss and WC were independent of diet and exercise or behavioral counseling, and were sustained over 6 years. These results complement findings from a study in 20 hypogonadal men with metabolic syndrome, in which treatment with TU for 60 months significantly improved both WC (–9.6 ± 3.8 cm) and body weight (–15 ± 2.8 kg, both p<0.0001).13 These reductions in WC are important as this measure has previously been suggested as a risk factor of all-cause mortality,14 incident CVD, and diabetes.7 These findings suggest that TU may be an effective option in managing weight in obese, diabetic men with TD.
Despite poor control of T2DM at baseline (mean HbA1c, 8.08%), treatment with TU significantly reduced fasting blood glucose and HbA1c levels, and a large proportion of patients achieved target HbA1c levels (Figure). These findings support results from a study by Hackett et al., where adding TU to existing diabetic (and antihypertensive or lipid-lowering) therapy resulted in marked reductions in HbA1c of 0.41% within 6 weeks in poorly controlled patients (HbA1c >7.5) that were maintained at 30 weeks.15 This suggests that normalizing testosterone levels improves hyperglycemia and insulin resistance in obese, diabetic men with TD. Importantly, TU maintained improvements in glycemic control for 6 years,1 a target which is difficult to attain despite a modern generation of intensive diabetic treatments.16,17
Of equal importance, TU significantly reduced levels of CRP over the observation period in obese, diabetic men with TD, which may be linked to concurrent reductions in WC and blood pressure. Markers of liver function improved over 6 years, suggesting that TU reduces liver fat content and inflammation and, consequently, risks of cardiometabolic diseases are reduced. Significant benefits in lipid profile over 6 years were also observed; in particular, levels of LDL-C were significantly reduced and sustained over the observation period. Overall, these findings suggest that TU may improve cardiometabolic function and reduce CVD risk in obese, diabetic men with TD.
Whilst the findings of this study merit further exploration, there are some limitations to the study. Being a long-term, open-label, observational, and uncontrolled study some bias may have been introduced. Furthermore, improvements in weight and diabetic measures were not foreseen at study design. As a result, behavioral and lifestyle changes, duration of T2DM, and changes in co-medications were not assessed.