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Gender differences in non-glycemic responses to improved insulin sensitivity by pioglitazone treatment in patients with type 2 diabetes

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Abstract

Excess cortisol and GH induce insulin resistance, a central feature of type 2 diabetes (T2D). To study whether the insulin sensitizer pioglitazone affects basal cortisol levels and the GH–IGF-I axis in patients with T2D. Forty-eight patients with T2D (men/women = 28:20, age 61 ± 1 years, BMI 31 ± 0.6 kg/m2) were treated for 26 weeks with pioglitazone 30–45 mg daily in addition to their preexisting therapy. Insulin, proinsulin, HbA1c, IGF-I, IGFBP-1, and basal cortisol were analyzed before and after treatment. Pioglitazone decreased proinsulin/insulin ratio and HbA1c decreased (HbA1c from 7.8 ± 0.2 to 6.6 ± 0.2 % in men and from 7.6 ± 0.2 to 6.1 ± 0.2 % in women, p < 0.001 in both). There was a redistribution of fat but no change in waist circumference. IGF-I and adiponectin increased (p ≤ 0.001) in both genders. IGFBP-1 increased but significantly only for the whole group (p = 0.033). Triglycerides decreased significantly in women only (p = 0.015). Before treatment, women had lower basal cortisol (p = 0.045). Basal cortisol increased in women (from 390 ± 26 to 484 ± 32 nmol/L, p = 0.020) but not in men and did not differ between genders at week 26. ΔIGFBP-1 correlated with Δcortisol (r = 0.458; p = 0.049) and Δadiponectin (r = 0.600; p = 0.005) in women only. In addition to the known effect of improving insulin sensitivity, pioglitazone increased IGF-I regardless of gender and in women also increased basal cortisol. Increased IGF-I may contribute to improved insulin sensitivity after treatment. There seems to be gender differences in treatment responses to pioglitazone on lipid metabolism and basal cortisol, perhaps correcting different mechanisms of insulin resistance between genders.

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Acknowledgments

The authors gratefully thank Yvonne Strömberg, Elvi Sundberg, and Inga-Lena Wivall for expert performance of laboratory analyses. This study was funded by the Swedish Medical Research Council, the Family Erling Persson Foundation, and the Stockholm County Council (ALF).

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Author notes

  1. Mozhgan Dorkhan

    Present address: Division of Diabetes and Endocrinology, Department of Clinical Sciences, Malmö University Hospital, Lund University, Malmö, Sweden

Authors and Affiliations

  1. Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176, Stockholm, Sweden

    Lisa Arnetz, Michael Alvarsson, Kerstin Brismar & Neda Rajamand Ekberg

  2. Karolinska University Hospital, Stockholm, Sweden

    Lisa Arnetz, Michael Alvarsson, Kerstin Brismar & Neda Rajamand Ekberg

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  1. Lisa Arnetz
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  2. Mozhgan Dorkhan
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Correspondence to Lisa Arnetz.

Additional information

Communicated by Massimo Federici.

Lisa Arnetz and Mozhgan Dorkhan contributed equally to the study.

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Arnetz, L., Dorkhan, M., Alvarsson, M. et al. Gender differences in non-glycemic responses to improved insulin sensitivity by pioglitazone treatment in patients with type 2 diabetes. Acta Diabetol 51, 185–192 (2014). https://doi.org/10.1007/s00592-013-0457-y

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  • DOI: https://doi.org/10.1007/s00592-013-0457-y

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