The link between metabolic features and TSH levels in polycystic ovary syndrome is modulated by the body weight: an euglycaemic–hyperinsulinaemic clamp study

Objective To evaluate the link among thyroid function, glucose/insulin metabolism and steroid hormones in women with polycystic ovary syndrome (PCOS), and to verify if the body mass index (BMI) might influence the interplay between PCOS features and subclinical hypothyroidism (SCH). Study design Case–control study conducted from January to December 2014. Methods One-hundred fifty-four young women with PCOS, according to Rotterdam criteria, and 88 controls were enrolled in an academic research environment. Anthropometric evaluation, hormonal and lipid assays, oral glucose tolerance test (OGTT) and euglycaemic–hyperinsulinaemic clamp were performed. Hirsutism was assessed with the Ferriman–Gallwey (FG) score. Main results SCH was found in 14% of PCOS subjects and in 1% of controls (P < 0.01). In PCOS women, TSH levels were directly correlated with fasting glycaemia, but not with other hormonal and metabolic parameters. When PCOS patients were classified on the basis of BMI, TSH levels significantly correlated with insulin secretion, insulin resistance, DHEAS and cortisol levels in obese PCOS women. Inverse correlations were found between TSH and both oestradiol and SHBG in the same group. In nonobese PCOS patients, only waist-to-hip ratio values were correlated with TSH. The prevalence of SCH was not different between nonobese and obese PCOS groups (14 and 15% respectively). However, SCH was associated with higher levels of insulin, DHEAS, cortisol and FG score only in the obese subgroup. Conclusions Our data confirm that the prevalence of SCH is increased in PCOS women. The presence of SCH is associated with endocrine and metabolic imbalances of PCOS, and the excessive body weight seems to promote this interplay.

Modern approach to the evaluation of the pharmacokinetics and pharmacodynamics of biosimilar recombinant human insulin and insulin analogues in I phase clinical study

The quality, pharmacokinetic and pharmacodynamic profiles, safety and immunogenicity must be compared to demonstrate the bio-similarities of recombinant human insulin and insulin analogues. To confirm these bio-similarities in clinical studies, it is necessary to adhere to a multi-phased approach, starting with the pharmacokinetics and pharmacodynamics of the study drugs. In this article, in accordance with modern approaches to drug research, evaluation of the pharmacokinetics and pharmacodynamics of recombinant human insulin and analogues of human insulin (biosimilar drugs) is performed in a double-blind, randomised crossover euglycaemic hyperinsulinaemic clamp study.This article describes the main approaches to the evaluation of the pharmacokinetic and pharmacodynamic parameters of recombinant human insulin preparations and insulin analogues during a euglycaemic hyperinsulinaemic clamp study. The inclusion criteria for the sample selection, design and conditions of the study, methods for the suppression of endogenous insulin, recommendations for doses of drugs, duration of the study and choice of primary and secondary pharmacokinetic and pharmacodynamic parameters for bio-similar insulin products (which depend on the duration of their effects) are described.

Effects on insulin sensitivity and body composition of combination therapy with GH and IGF1 in GH deficient adults with type 2 diabetes

Objective The aim of this trial was to evaluate the effect on insulin sensitivity and body composition of combination therapy with GH and IGF1 in adults with GH deficiency (GHD) and diabetes. Design, patients and methods A 6-month randomised placebo-controlled pilot study. Fourteen adults with GHD and type 2 diabetes were included. All received rhGH (0.15 mg/day for 1 month and 0.3 mg/day for 5 months) and were randomised to rhIGF1 (15 μg/kg per day for 1 month and 30 μg/kg per day for 5 months) or placebo. Insulin sensitivity was evaluated with euglycaemic hyperinsulinaemic clamp and body composition by computed tomography of abdominal and thigh fat, as well as bioimpedance. Results Twelve patients completed the study. They were overweight and obese; at baseline, insulin sensitivity (M-value) was low. IGF1 and IGF1 SDS increased in both groups, with the highest increase in the GH and IGF1 group. Positive changes in M-value by +1.4 mg/kg per min, in subcutaneous abdominal fat by −60.5 ml and in fat-free mass by +4.4% were seen in the GH and IGF1 group. Corresponding values in the GH and placebo-treated group were −1.5 mg/kg per min, +23 ml and −0.04% respectively (P=0.02, P=0.04 and P=0.03 for delta values between groups). No safety issues occurred. Conclusions Combined GH and IGF1 treatment resulted in positive, but rather small effects, and might be a treatment option in a few selected patients.