The role and place of androgenotherapy in multifactoral management of diabetes mellitus type 2
AbstractIntroduction: the relevance of combing diabetes mellitus type 2 (DM2) and the problem of androgenodeficiency (testosterone deficiency) in men depend on the high risk of developing cardiovascular complications. Cardiovascular diseases are the main cause of high mortality rate in patients with DM2 and this tendency is seen in all countries of the world.
Testosterone is a hormone which plays the leading part in the metabolism of fats, proteins and carbohydrates. Androgenodeficiency is associated with increasing visceral fat depots, decreasing insulin sensitivity, hypertriglyceridemia, hypercholesterinemia and reduced level of low density lipoproteins (LDL). As a result the testosterone deficiency affects the cardiovascular system hastening cardiovascular complications of DM2. Therefore replacement androgenotherapy in patients with DM2 can contribute to improving not only the fat and muscular mass ratio but also metabolic indices such as elimination of hyperglycemia, dyslipidaemia and blood pressure normalization.
Objective – to estimate the role and place of androgenotherapy in managing DM2 under conditions of glucosetoxicity and lipotoxicity.
Materials and methods. 40 patients (men) aged 49–70 with DM2 resulting from visceral obesity with laboratory confirmed androgenodeficiency were investigated. After randomization procedure by using random numbers method the patients were divided into two groups (basic and control) according to the age, body mass index (BMI), level of glycated hemoglobin (HbA1с), dyslipidaemia parameters and testosterone level. At inclusion into the research all the patients received combined glucose decreasing therapy «DPP-4 inhibitor + metformin» (50/1000 twice a day). The basic group additionally received androgenotherapy with transdermal 1% testosterone gel (50 mg of testosterone daily) for 12 weeks. All the patients were taught at the DM2 School and got recommendations on changing diet and increasing physical activity. The dynamics of fasting glycemia (FG), HbA1с, lipid spectrum indices (total cholesterol (TC), LDL, triglycerides (TG)) as well as total testosterone (T) and globulin binding sex hormones (GBSH) was estimated. The evaluation of the body composition was performed by impedancometric method using the body composition monitor Omron BF508. The exclusion criterion was the level of total prostate specific antigen (PCA) >2,5 ng/ml. Statistic data processing was carried out using the program SPSS for Windows 10.0 (SPSS Inc.).
Results. Positive dynamics of the metabolic indices was noted in both groups 12 weeks later, it was more marked (and reliably significant) in the group of the patients who received replacement androgenotherapy. In the basic group FG decreased by 2,1 mmol/l (p<0,05), HbA1с – by 1,0% (p<0,05), TC – by 1,2 mmol/l (p<0,05), TG – by 0,4 mmol/l (p<0,05). In the control group there was a tendency toward improving these indices with FG decreasing by 1,3 mmol/l (p=0,12), HbA1с – by 0,4% (p=0,07), TC – by 0,4 mmol/l (p=0,17), TG – by 0,1 mmol/l (p=0,22). At the same time T increased by 4,1 and by 0,2, and GBSH decreased by 1,2 and by 0,1 in the basic and control groups respectively. It is important to mention that in the basic group there was a reliable decrease of the body mass ( by 3,2 kg, p<0,05), BMI (by 1,2 kg/m2, p<0,05) and visceral fat level (by 0,6 U, p<0,05). The patients in the basic group were able to have more active life style, improved sexual activity and asked to continue androgenotherapy after the investigation.
Conclusions. The combination of the novel glucose reducing therapy with DPP-4 inhibitors medications and metformin as well as replacement androgenotherapy in patients with DM2 resulting from visceral obesity and androgenodeficiency makes it possible to bring reliably significant improvement of metabolic and anthropometric indices and reduce the risk of developing cardiovascular complications in DM2. This approach of simultaneous correcting several risk factors – hyperglycemia, dyslipidaemia and androgenodeficiency – should be introduced into medical practice to manage DM2 not only in patients already having glucose- and lipotoxicity but also for administration of starting glucose reducing therapy.
Keywords:diabetes mellitus type 2, testosterone deficiency, androgenotherapy