Naslov (srp)

Analiza uticaja insulinske rezistencije i metaboličkih determinanti na kognitivnu disfunkciju u blagom kognitivnom poremećaju i Alchajmerovoj bolesti : doktorska disertacija

Autor

Maćešić, Marija, 1978-

Doprinosi

Lalić, Nebojša M., 1958-
Kostić, Vladimir S., 1953-
Jotić, Aleksandra, 1966-
Stefanova, Elka, 1959-
Zamaklar, Miroslava, 1946-

Opis (srp)

Uvod: Prethodne studije su ukazale na moguću ulogu snižene insulinske senzitivnosti i sekrecije u patogenezi Alchajmerove bolesti (AB) i blagog kognitivnog poremećaja (BKP), prelaznog stanja između normalnog procesa starenja i AB. Međutim, složeni mehanizmi kojima poremećaji insulinske senzitivnosti mogu ostvarivati svoj uticaj u nastanku kognitivne disfunkcije još uvek nisu do kraja proučeni. Cilj:Cilj rada je ispitivanje povezanosti insulinske rezistencije (IR) i metaboličkih parametara i ispoljavanja kognitivne disfunkcije u BKP i AB. Metode: U ispitivanje je uključeno 62 ispitanika sa AB (grupa A), 41 ispitanika sa BKP (grupa B) i 40 zdravih ispitanika (grupa C). U svakog bolesnika je evaluirano stanje insulinske senzitivnosti metodom hiperinsulinemijskog euglikemijskog klampa i metodom modela homeostaze, kapacitet rane faze insulinske sekrecije metodom intravenskog testa tolerancije glukoze (FPIR i AIR), nivo insulina u serumu RIA metodom, adiponektina ELISA metodom, lipidni parametri, ukupni holesterol (h), HDL-h, LDL-h, trigliceridi metodom hromatografije, apolipoproteini ApoAI, ApoAII, ApoB, Lp(a), ApoE metodom nefelometrije. Rezultati: Evaluacijom stanja insulinske senzitivnosti primenom obe metode je pokazan značajno viši nivo insulinske rezistencije (IR) u grupi A u odnosu na grupu B i C, (M vrednost: A:6.22+/-0.31; B: 7.70+/-0.42; C:8.25+/-0.24 mg/min/kg, p<0.001); (HOMA-IR: A:4.59+/-0.28; B:3.35+/-0.27; C:1.49+/-0.15, p<0.001). Istovremeno, oba parametra kapaciteta rane faze insulinske sekrecije, AIR i FPIR su bila značajno niža u grupi A u odnosu na grupu B i C (AIR: A:26.49+/-2.02; B:49.54+/-6.26; C:72.05+/-3.68 mU/l); (FPIR: A:68.90+/-3.53; B:112.51+/-7.36; C:147.43+/-8.86 mU/l, p<0.001). Bazalna insulinemija je bila značajno viša u grupi A u odnosu na grupe B i C (A:18.08+/-1.54; B:13.77+/-1.08; C:7.18+/-0.68 mU/l, p<0.01). Nivo adiponektina u serumu je bio niži u grupu A vs B vs C (A:14.91+/-0.42; B:16.99+/-0.91; C:18.63+/-0.58 ng/m, A vs B and A vs C p<0.01, B vs C p< 0.05), dok je nivo ukupnog h, LDL-h, ApoB and Lp(a) bio značajno niži, a HDL-h I ApoAI unačajno niži u grupi A i B vs C. Nivo triglicerida i ApoAII se nije značajno razlikovao među grupama. Binarnom logističkom regresijom je uočena značajan uticaj M vrednosti, insulinemije našte i FPIR sa ispoljavanjem BKP i AD (p=0.006, p=0.06, p=0.01, respektivno). Zaključak: Naši rezultati ukazuju da u bolesnika sa AB i BKP, IR sa sniženim kapacitetom insulinske sekrecije ostvaruje snažan uticaj na ispoljavanje AB i BKP, sa manjim uticajem sniženog nivoa adiponektina i aterogenim lipidnim profilom.

Opis (srp)

medicina - endokrinologija / medicine- endocrinology Datum odbrane: 19.09.2016.

Opis (eng)

Introduction: Previous studies have shown that impairment in insulin sensitivity and insulin secretion can be the essential in pathogenesis of Alzheimer's disease (AD) and mild cognitive impairment (MCI), intermediate state between normal aging and dementia. However, the precise pathogenic mechanisms of influence of decreased insulin sensitivity and insulin secretion capacity on developing cognitive dysfunction has not yet been clarified. Aim: The aim of this study was to evaluate correlation of possible changes in insulin sensitivity and metabolic parameters on the occurrence of cognitive impairment in patients with MCI and AD. Methods: The study included 62 patients with AD (group A), 41 patients with MCI (group B) and 25 healthy controls (group C). Insulin sensitivity was estimated using euglycemic hyperinsulinemic clamp method and homeostasis model assessment. Insulin secretion capacity was analyzed using intravenous glucose tolerance test (FPIR and AIR). Plasma insulin (PI) levels were evaluated using RIA method and adiponectin by ELISA, total cholesterol (Ch), HDL-Ch, LDL-Ch and triglycerides by enzymatic methods, apolipoproteins (Apo) ApoAI, ApoAII, Lp(a), ApoB and ApoE were determined by using nephelometry method. Results: Insulin resistance (IR) were significantly higher in group A compared to groups B and C, (M value: A:6.22+/-0.31; B:7.70+/-0.42; C:8.25+/-0.24mg/min/kg, p<0.001); (HOMA-IR: A:4.59+/-0.28; B: 3.35+/-0.27; C:1.49+/-0.15, p<0.001). Both parameters of insulin secretion capacity were significantly lower in group A compared to groups B and C, (AIR: A: 26.49+/-2.02; B:49.54+/-6.26; C:72.05+/-3.68 mU/l); (FPIR: A:68.90+/-3.53; B:112.51+/-7.36; C: 147.43+/-8.86mU/l, p<0.001). PI levels were higher in group A compared to groups B and C (A:18.08+/-1.54; B:13.77+/-1.08; C:7.18+/-0.68 mU/l, p<0.01).Plasma adiponectin levels were lower and in group A vs B vs C (A:14.91+/-0.42; B:16.99+/-0.91; C:18.63+/-0.58 ng/m, A vs B and A vs C p<0.01, B vs C p< 0.05), while the levels of Ch, LDL-Ch, ApoB and Lp(a) were significantly higher and HDL-Ch and ApoAI levels being lower in group A and B vs C. The triglycerides and ApoAII levels did not differ between the groups. Binary logistic regression analysis identified only M value, FPIR and plasma insulin as independent predictors for AD and MCI (p=0.006, p=0.06, p=0.01, respectively). Conclusion: These results imply that in AD and MCI, IR with increased plasma insulin and decreased FPIR strongly facilitate the development of AD and MCI, with milder influence of low adiponectin levels and atherogenic lipid profile.

Jezik

srpski

Datum

2016

Licenca

Creative Commons licenca
Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 2.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 2.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/2.0/at/legalcode

Predmet

OSNO - Opšta sistematizacija naučnih oblasti, Endokrini sistem

insulin resistance, mild cognitive impairment, Alcheimer’s disease

OSNO - Opšta sistematizacija naučnih oblasti, Endokrini sistem

insulinska rezistencija, blagi kognitivni poremećaj, Alchajmerova bolest

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