Irisin is an adipokine/myokine which could be connected with insulin sensitivity. Polycystic ovary syndrome (PCOS) is characterized by oligo- or anovulation, polycystic ovary, hyperandrogenism and insulin resistance. The aim of the present study was to determine the relationship between serum irisin concentration and insulin sensitivity (Mffm) as well as the effect of insulin infusion on circulating irisin levels in PCOS women as compared with healthy controls. Seventy seven women were enrolled in the study - 57 with PCOS and 20 healthy controls matched for BMI and age. Hyperinsulinemic euglycemic clamps were performed in all of the study participants. The serum concentrations of irisin at baseline and after the clamp, as well as changes of serum irisin concentration in response to insulin supplied during the clamp (Δ irisin), were estimated. The mean serum concentrations of irisin at baseline and after hyperinsulinemia were higher in PCOS women in comparison to the control group (p=0.01; p=0.006, respectively). Insulin infusion resulted in a decrease of serum irisin concentration only in the PCOS group (p=0.007). In the control group, Δ irisin positively correlated with Mffm (r=0.56, p=0.009). In the entire group, multiple regression analysis showed that Δ irisin (β=0.70, p=0.0002), FFAs 60' during the clamp study (β=-0.22, p=0.01), SHBG (β=0.54, p<0.0001) and the interaction between Δ irisin and PCOS (β=-0.67, p=0.0004) were significantly associated with Mffm. The higher serum irisin concentrations at baseline and in response to insulin infusion might be secondary to insulin resistant conditions in PCOS women.

Summary Type B insulin resistance syndrome (TBIR) is characterised by the rapid onset of severe insulin resistance due to circulating anti-insulin receptor antibodies (AIRAs). Widespread acanthosis nigricans is normally seen, and co-occurrence with other autoimmune diseases is common. We report a 27-year-old Caucasian man with psoriasis and connective tissue disease who presented with unexplained rapid weight loss, severe acanthosis nigricans, and hyperglycaemia punctuated by fasting hypoglycaemia. Severe insulin resistance was confirmed by hyperinsulinaemic euglycaemic clamping, and immunoprecipitation assay demonstrated AIRAs, confirming TBIR. Treatment with corticosteroids, metformin and hydroxychloroquine allowed withdrawal of insulin therapy, with stabilisation of glycaemia and diminished signs of insulin resistance; however, morning fasting hypoglycaemic episodes persisted. Over three years of follow-up, metabolic control remained satisfactory on a regimen of metformin, hydroxychloroquine and methotrexate; however, psoriatic arthritis developed. This case illustrates TBIR as a rare but severe form of acquired insulin resistance and describes an effective multidisciplinary approach to treatment. Learning points: We describe an unusual case of type B insulin resistance syndrome (TBIR) in association with mixed connective tissue disease and psoriasis. Clinical evidence of severe insulin resistance was corroborated by euglycaemic hyperinsulinaemic clamp, and anti-insulin receptor autoantibodies were confirmed by immunoprecipitation assay. Treatment with metformin, hydroxychloroquine and methotrexate ameliorated extreme insulin resistance. Abstract Summary Type B insulin resistance syndrome (TBIR) is characterised by the rapid onset of severe insulin resistance due to circulating anti-insulin receptor antibodies (AIRAs). Widespread acanthosis nigricans is normally seen, and co-occurrence with other autoimmune diseases is common. We report a 27-year-old Caucasian man with psoriasis and connective tissue disease who presented with unexplained rapid weight loss, severe acanthosis nigricans, and hyperglycaemia punctuated by fasting hypoglycaemia. Severe insulin resistance was confirmed by hyperinsulinaemic euglycaemic clamping, and immunoprecipitation assay demonstrated AIRAs, confirming TBIR. Treatment with corticosteroids, metformin and hydroxychloroquine allowed withdrawal of insulin therapy, with stabilisation of glycaemia and diminished signs of insulin resistance; however, morning fasting hypoglycaemic episodes persisted. Over three years of follow-up, metabolic control remained satisfactory on a regimen of metformin, hydroxychloroquine and methotrexate; however, psoriatic arthritis developed. This case illustrates TBIR as a rare but severe form of acquired insulin resistance and describes an effective multidisciplinary approach to treatment. Learning points: We describe an unusual case of type B insulin resistance syndrome (TBIR) in association with mixed connective tissue disease and psoriasis. Clinical evidence of severe insulin resistance was corroborated by euglycaemic hyperinsulinaemic clamp, and anti-insulin receptor autoantibodies were confirmed by immunoprecipitation assay. Treatment with metformin, hydroxychloroquine and methotrexate ameliorated extreme insulin resistance.

Context Higher prevalence of polycystic ovary syndrome (PCOS) in women with type 1 diabetes (T1DM) is linked to exogenous insulin, especially when diabetes is diagnosed before puberty. Objective The study evaluates the impact of prepubertal onset of T1DM and insulin therapy on PCOS diagnosis and phenotypic characteristics in women with T1DM. Design, Setting, and Patients We studied 83 women with T1DM (age 26 ± 5 years, BMI 24 ± 3 kg/m²) 36 with premenarchal (PM) onset of T1DM [17 with PCOS diagnosed (PCOS+PM) and 19 without PCOS (noPCOS+PM)] and 47 women with postmenarchal onset of T1DM [24 with PCOS (PCOS-noPM) and 23 without PCOS (noPCOS-noPM)]. Outcome Measurements Clinical examination, assessment of serum sex hormones, glycated hemoglobin (HbA1c) and ultrasonographic evaluation of the ovaries were performed in all women. Results Applying Rotterdam criteria, 49% of women with T1DM were diagnosed with PCOS. There were no differences in hormonal profile and ovarian parameters between PCOS+PM and PCOS-noPM. Women with T1DM+PM had higher insulin dose/24 h and U/kg bw/24 h than T1DM-noPM (P-values = 0.014 and 0.001, respectively). Both PCOS+PM and noPCOS+PM groups had higher insulin dose U/kg bw/24 h in comparison to PCOS-noPM (P-values = 0.004 and = 0.006, respectively). In multivariable logistic regression analysis, age of menarche [odds ratio (OR): 0.672; 95% confidence interval (CI): 0.465-0.971] and HbA1c (OR: 0.569; 95% CI: 0.383-0.846) were associated with the diagnosis of PCOS. Conclusions There were no differences in the prevalence of PCOS between T1DM+PM and T1DM-noPM; however, earlier menarche might have an influence on PCOS diagnosis in women with T1DM.