Arnold, J.F.H. (Jarinke) (2012) Pro-enkefaline A en de relatie met mortaliteit en kwaliteit van leven bij patiënten met type 2 diabetes mellitus. thesis, Medicine.
Full text available on request.Abstract
Title: Proenkephalin A and the relationship with mortality and health related quality of life in patients with type 2 diabetes mellitus BACKGROUND: The precursor hormone proenkephalin A (PENK-A) and the derived enkephalin peptides have been found in the pancreatic islets and have been suggested to be involved in the glucose metabolism. They also influence a variety of cardiovascular functions e.g. blood pressure. In addition, enkephalins have been implicated in the pathofysiology of dementia disorders such as Alzheimer disease, which affect the health related quality of life (HRQOL). We aimed to investigate whether the serum concentration PENK-A was related to all-cause and cardiovascular mortality and with HRQOL in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 1689 primary care patients with T2DM participated in this prospective observational study, as part of the ZODIAC project. EDTA plasma was stored at -80°C, until assessment of PENK-A by sandwich immunoassay. HRQOL was measured with the RAND-36 questionnaire. Cox proportional hazards models were used to investigate the relationship between the serum concentration PENK-A and mortality with adjustment for the selected confounders. Three models were chosen: model 1 included only PENK-A, model 2 included age and gender as confounders and model 3 included 9 cardiovascular risk factors as additional potential confounders (diabetes duration, smoking, macrovascular complications, BMI, systolic blood pressure, HbA1c, serum creatinine, cholesterol-HDL ratio and albuminuria). Harrell’s C statistic was used to investigate the capability of each model to predict mortality. We used linear regression analyses to investigate whether there was a relationship between PENK-A and HRQOL. RESULTS: PENK-A was assessed in baseline serum samples of 1204 patients (71.3%) with a median [interquartile range] concentration of 112.0 [91.2-143.0] pmol/l. During a median follow-up period of 5.5 [3.1-10.1] years, 361 (30.0%) patients had died of which 153 (42.4%) were attributed to cardiovascular causes. The results of the Cox regression showed increased hazard ratios for all-cause and cardiovascular mortality for the crude model, and after adjustment for age and gender. In model 1 the hazard for mortality increased with 278% and 451% respectively, for every increase of 1 pmol Log PENK-A. However, in model 3, the association of log PENK-A with mortality lost its significance. According to the Harrell’s C statistic, model 3 was the best model to predict mortality. The results of the univariate linear regression showed a negative relationship between the serum concentration PENK-A and HRQOL. CONCLUSION: Higher levels PENK-A were associated with an increased all-cause and cardiovascular mortality in patients with T2DM, even after adjusting for age and gender. However, after adjustment for several cardiovascular risk factors this significant association was no longer observed. The serum concentration PENK-A was not independently associated with HRQOL.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Facultaire begeleider: and H.J.G. Bilo, prof. dr. internist |
| Supervisor name: | Directe begeleider: and Hateren, drs. K.J.J. van AIOS huisartsgeneeskunde en arts-on and Locatie: Diabetes kenniscentrum Isala klinieken, Zwolle |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:41 |
| Last Modified: | 25 Jun 2020 10:41 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/285 |
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