Boering, M. (2014) The effects of intraperitoneal and subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus. thesis, Medicine.
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Abstract
Introduction In adults with type 1 diabetes mellitus (T1DM) elevated concentrations of sex hormone-binding globulin (SHBG) have been reported. SHBG is produced in the liver and secreted into the (portal) circulation where it binds and transports androgens and oestrogens inactively, thus regulating their availability for target tissues and cells. These elevated SHBG concentrations may be due to low portal insulin concentrations and a subsequent impaired hepatic SHBG synthesis. With continuous intraperitoneal infusion (CIPII) higher portal levels of insulin can be achieved as compared to subcutaneous (SC) insulin therapy. The aim of this study was to analyse the effect of the route of insulin administration, CIPII versus SC, on SHBG-concentrations in T1DM patients. Research design and methods Post-hoc analysis of SHBG in samples derived from an open-labelled cross-over trial where patients with T1DM were randomized into receiving CIPII through an implantable pump (MIP2007C, Medtronic) followed by SC insulin therapy or vice versa. Both treatment phases were 6 months in duration with a cross-over phase of 4 weeks in between to minimize the carry-over effects of CIPII. Measurements were performed at baseline and at the start, halfway, and end of both treatment phases. In order to gain information on steroid and gonadotropin function; testosterone, estradiol, LH- and FSH-concentrations were also measured and the free-androgen index (FAI) was calculated. To calculate the mean difference between the two therapies with a 95% confidence interval (CI), the linear mixed models analysis which takes treatment order into account was used according to the Hills-Armitage principle. This accounts for any period effect. Results Twenty patients with a mean (±standard deviation (SD)) age of 43 (±13) years, diabetes duration of 23 (±11) years and HbA1C 72 (±12) mmol/mol were analysed. The estimated mean change in SHBG was -10.3 nmol/L (95% confidence interval (CI) -17.4, -3.2 nmol/L; p = 0.007) during the CIPII phase and -3.7 nmol/L (95% CI -12.0, 4.6 nmol/L; p = 0.359) during the SC phase. When taking the effect of treatment order into account, the estimated mean difference between the CIPII treatment phase and the SC treatment phase was -6.6 nmol/L (95% CI -17.5, 4.3 nmol/L; p = 0.219). Furthermore, the estimated mean change in testosterone was -3.2 nmol/L (95% CI -5.5, -0.8 nmol/L; p = 0.0123) during the CIPII treatment phase and -1.2 nmol/L (95% CI -3.7, 1.3 nmol/L; p = 0.325) during the SC treatment phase. The difference in change during the CIPII and SC treatment phase and the estimated mean change between the CIPII treatment phase and the SC treatment phase was non-significant for estradiol, LH, FSH and FAI. Conclusions In patients with T1DM, SHBG and testosterone concentrations decreased significantly during CIPII therapy while there were no changes during SC insulin therapy. Nevertheless, the difference in change between the two routes of insulin administration was not significant; possibly due to a small sample size. The results of this study support the hypothesis that portal insulin concentration have an effect on circulating SHBG concentrations. This finding could lead to further research on the effects of CIPII insulin on SHBG, steroids and associated pathology in T1DM.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Bilo, Professor H. J.G. |
| Supervisor name: | Dijk, P.R. van and Logtenberg, S.J.J. and Groenier, K.H. and Isala, Zwolle |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:45 |
| Last Modified: | 25 Jun 2020 10:45 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/685 |
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