Povezanost plazmatske koncentracije peptida 1 sličnog glukagonu i čimbenika rasta fibroblasta-21 s regulacijom glikemije, lipidemijom i mikrovaskularnim komplikacijama u bolesnika sa šećernom bolešću tipa 1 [The relationship of plasma concentrations of glucagone-like peptide 1 and fibroblast growth factor-21 with glucoregulation, lipidemia and microvascular complications in diabetes mellitus type 1 individuals]

Zibar, Karin (2015) Povezanost plazmatske koncentracije peptida 1 sličnog glukagonu i čimbenika rasta fibroblasta-21 s regulacijom glikemije, lipidemijom i mikrovaskularnim komplikacijama u bolesnika sa šećernom bolešću tipa 1 [The relationship of plasma concentrations of glucagone-like peptide 1 and fibroblast growth factor-21 with glucoregulation, lipidemia and microvascular complications in diabetes mellitus type 1 individuals]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Aim. To examine relationship of glucagon-like peptide 1 (GLP-1) and fibroblast growth factor- 21 (FGF-21) with glycemia, lipidemia and microvascular complications in type 1 diabetes mellitus (T1DM) patients. To analyze mutual relation between GLP-1 and FGF-21 and to examine relationship of GLP-1 and FGF-21 with insulin resistance (IR), metabolic syndrome (MS), glucagon and daily insulin dosage, respectively. To compare GLP-1 and FGF-21 concentrations between T1DM patients and healthy controls, respectively. ----- Materials and methods. In 30 T1DM patients and 10 healthy controls GLP-1 and FGF-21 concentrations were measured by ELISA. Data were analyzed by SPSS 15.0 with statistical significance at P<0.05. ----- Results. Higher GLP-1 was statistical significantly independently related to the lower fasting glycaemia and lower total cholesterol concentration, respectively. Higher GLP-1 was not related to the lower diabetic nephropaty or diabetic retinopathy prevalence, respectively, but it was related to the lower prevalence of diabetic neuropathy, at marginal significance level. Lower basal FGF-21 was statistical significantly independently associated with better glycaemia control. FGF-21 was not related to lipidaemia parameters. Lower FGF-21 was not associated with lower diabetic nephropathy or diabetic retinopathy, respectively. However, significant difference in FGF-21 was related to the different diabetic neuropathy stages and insulin sensitivity (IS), at the same time. Patients with higher IS and more severe diabetic neuropathy stage had higher FGF-21. GLP- 1 concentration was not related to FGF-21 concentration and the GLP-1 was not related to the glucagon concentration. Postprandial FGF-21 positively correlated with basal glucagon. Statistical significantly higher GLP-1 was found in patients with MS. Patients with higher FGF-21 concentrations had statistical significantly better IS. GLP-1 and FGF-21 concentrations did not corelate with daily insulin dosage, respectively. T1DM patients had statistical significantly lower basal GLP-1 and FGF-21 than healthy controls, respectively. ----- Conclusion. Higher GLP-1 concentration was independently related with lower fasting glycaemia and with lower total cholesterol concentration, respectively. Lower FGF-21 was associated with better glycaemia control, but not with better lipid profile. Significant deviation of basal GLP-1 and FGF-21 was found in T1DM patients in comparison with healthy controls. The results of the research support an important role of GLP-1 and FGF-21 in the pathogenesis of T1DM. Therefore, future therapy based on the hormones seems possible also in T1DM patients, along with insulin therapy.

Abstract in Croatian

Cilj. Ispitati povezanost koncentracija peptida 1 sličnog glukagonu (GLP-1) i čimbenika rasta fibroblasta-21 (FGF-21) s glikemijom, lipidemijom i mikrovaskularnim komplikacijama u osoba sa šećernom bolesti tipa 1 (ŠBT1). Analizirati međuodnos GLP-1 i FGF-21 te ispitati povezanost GLP-1 i FGF-21 s inzulinskom rezistencijom (IR), metaboličkim sindromom (MS), glukagonom i dnevnom dozom inzulina. Usporediti koncentracije GLP-1 i FGF-21 između osoba sa ŠBT1 i zdravih kontrolnih ispitanika. ----- Metode i ispitanici. U 30 osoba sa ŠBT1 te 10 zdravih ispitanika izmjerene su plazmatske koncentracije GLP-1 i FGF-21 postupkom ELISA. Podaci su analizirani pomoću statističkog programa SPSS 15.0, a značajnost je prihvaćena na razini P<0,05. ----- Rezultati. Viša koncentracija GLP-1 je bila statistički značajno neovisno povezana s nižom glikemijom natašte te s nižom koncentracijom ukupnog kolesterola. Viša koncentracija GLP-1 nije bila povezana s nižom prevalencijom dijabetičke nefropatije i dijabetičke retinopatije, a bila je povezana s nižom prevalencijom dijabetičke neuropatije. Niža koncentracija bazalnog FGF-21 je bila statistički značajno neovisno povezana s boljom regulacijom glikemije. Koncentracija FGF-21 nije bila povezana s parametrima lipidemije. Niža koncentracija FGF-21 nije bila povezana s nižom prevalencijom dijabetičke nefropatije i dijabetičke retinopatije, međutim, nađena je razlika u koncentraciji FGF-21 s obzirom na različite stupnjeve dijabetičke neuropatije, a istodobno ovisno i o inzulinskoj osjetljivosti (IO). U bolesnika s većom IO viši stupanj dijabetičke neuropatije bio je praćen većom koncentracijom FGF-21. Nije nađena povezanost GLP-1 s FGF-21 ni GLP-1 s glukagonom. Postprandijalni FGF-21 je pozitivno korelirao s bazalnom vrijednosti glukagona. Statistički značajno veći GLP-1 nađen je u osoba s MS. Osobe s većom koncentracijom FGF-21 imale su statistički značajno veću IO. Nije nađena povezanost GLP-1 i FGF-21 s dnevnom dozom inzulina. Osobe sa ŠBT1 su imale statistički značajno niže bazalne koncentracije GLP-1 i FGF-21 u odnosu na zdrave kontrolne ispitanike. ----- Zaključak. Veća koncentracija GLP-1 je bila neovisno povezana s nižom glikemijom natašte te s nižom koncentracijom ukupnog kolesterola. Niža koncentracija FGF-21 je bila povezana s boljom regulacijom glikemije, dok nije bila povezana s boljim lipidnim profilom. Nađena je devijacija bazalnih koncentracija GLP-1 i FGF-21 oboljelih od ŠBT1 u odnosu na zdrave ispitanike. Temeljem rezultata prikazanog istraživanja s velikom se vjerojatnošću može zaključiti da GLP-1 i FGF-21 imaju značajnu ulogu u patofiziologiji ŠBT1. Stoga je uz postojeću inzulinsku terapiju moguć na njima temeljen budući terapijski doprinos i u osoba sa ŠBT1.

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