Tip 2 Diabetes Mellitus gelişiminde insülin dışı hormonların olası rollerinin araştırılması

Insulin direnci Tip 2 Diabetes Mellitus etyopatogenezinde anahtar rol oynamaktadir.?nsulin disinda Glukagon ve Buyume Hormonunun da Tip 2 Diabetes Mellitusgelisiminde ve progresyonunda rol oynadigina dair kanitlar vardir.Bu calismadaki amacimiz tip 2 diyabet gelisiminde glukagon, buyume hormonu veIGF-1'in olasi rollerini arastirmak, tip 2 diyabetin yalniz bir beta hucredisfonksiyonu degil fakat ayni zamanda endokrin pankreasin genel bir bozuklugununsonucu oldugunu gostermek, BH ve glukagon salinimiyla iliskili saptanabilenpatolojilerin diyabetin gelisiminde olasi rolunu ortaya koymaktir.Calismaya alinan 100 vakaya oral glukoz tolerans testi yapildi ve 0, 60 ve 120.dakikalarda insulin, glukagon ve BH'nu bakilmis ve bazal IGF-1 olculmustur. OGTTsonucuna gore bozulmus glukoz toleransi, bozulmus aclik glukozu, diyabet vekontrol grubu olmak uzere 4 gruba ayrilmistir.HOMA skoru BGT grubunda 3,4 , BAG grubunda 4,1 , tip 2 DM grubunda 3,6 vekontrol grubunda 2,1 olarak hesaplandi. BGT, BAG ve tip 2 DM grubunun HOMAskoru kontrol grubuna gore anlamli yuksek bulundu (p<0,01).BGT grubunda IGF-1 duzeyi 103 ng/ml, BAG grubunda IGF-1 duzeyi 86 ng/ml vediyabet grubunda IGF-1 duzeyleri 107 ng/ml kontrol grubunda ise 182 ng/ml olaraksaptandi. Kontrol grubunun IGF-1 duzeyleri diger gruplara gore anlamli yuksekbulundu (p<0,05).?nsulin icin hesaplanan egri altinda kalan alan acisindan gruplar karsilastirildigindaBAG grubunda bu degerin diger gruplardan anlamli yuksek oldugu saptandi (p<0,05).BGT grubunda da egri altinda kalan alan kontrol grubundan anlamli yuksek bulundu(p<0,05). Diyabet grubu ile kontrol grubu arasinda fark saptanmadi.Glukagon icin hesaplanan egri altinda kalan alan acisindan gruplarkarsilastirildiginda BGT, BAG ve diyabet gruplarinda bu degerin kontrol grubundananlamli yuksek oldugu saptandi (p<0,05). BGT, BAG ve diyabet gruplari arasindaanlamli fark saptanmadi.Buyume Hormonu icin hesaplanan egri altinda kalan alan acisindan gruplarkarsilastirildiginda BAG grubunda bu deger diger gruplardan anlamli olarak yuksekbulundu (p<0,05). Kontrol grubu ile BGT ve diyabet grubu arasinda anlamli farkliliksaptanmadi.Sonuclarimiza gore insulin direnci ve bunun sonucunda gelisen hiperinsulinemininpreklinik donemde mutad bir bulgu oldugu, diyabetin insulin duzeylerinde dususesekonder gelistigi, insulin duzeylerindeki preklinik ve klinik diyabet donemlerindekifarkliliga karsin hiperglukagoneminin her uc donemde de gozlendigi ve dolayisiyladiyabete progresyonun belki de onemli bir nedeni oldugu soylenebilir. Ote yandanhem preklinik diyabet hem de diyabetik donemde IGF-1 duzeylerinin dusuksaptanmasi bu vakalarda daha once bildirilmis olan BH'nuna direncle uyum icindeolan bir sonuctur. BH'nu duzeylerinin yalniz bozulmus aclik glukozu grubundaanlamli olarak yuksek bulunmus olmasi, bu grubun diyabete gidis acisindan farkliozgun bir alt grubu olusturabilecegi ve bozulmus aclik glukozu grubunda aclikhiperglisemisinin onemli bir nedeninin de BH hipersekresyonunun oldugunudusundurtmektedir. AbstractInsulin resistance plays major role in etiopathogenesis of type 2 diabetes mellitus.Increasing evidence suggests that glucagon and growth hormone (GH) may play rolein development and progression of type 2 diabetes.The aim of our study is to evaluate the possible roles of glucagon, growth hormoneand IGF-1, to show that type 2 diabetes mellitus is not only a beta cell dysfunctionbut also develops as a result of failure of all endocrine pancreas and to identify whatthe roles of pathologic changes in growth hormone and glucagon secretion are in thedevelopment of diabetes.An oral glucose tolerance test (OGTT) was performed for all adults conducted forthis study. GH, Glucagon and insulin were measured at minutes of 0, 60, 120 andbasal IGF-1 was measured also. Participants divided into four groups according tothe result of OGTT. These groups were diabetes, impaired fasting glucose (IFG),impaired glucose tolerance (IGT) and control group.Insulin resistance which was calculated as HOMA-IR score was significiantly highercompared to participants with normal glucose tolerance (NGT) those with abnormalglucose tolerance.Plasma IGF-1 levels were significantly lower (p<0,05) in participants those withabnormal glucose toleranse compared to participants in control group.Area under curve calculated for insulin was significantly higher in subjects with IFG(p<0,05). There was significant difference between subjects with IGT and NGT,there was no difference between diabetic subjects and NGT. Area under curvecalculated for glucagon was significantly higher in participants with IGT, IFG anddiabetes compared to participants with NGT (p<0,05). There was no differencebetween IGT, IFG and diabetic group. Area under curve calculated for GH wassignificantly higher in participants with IGT compared to participants with IFG, DMand NGT (p<0,05).As a conclusion hyperinsulinemia is an absolute finding in subjects with prediabetesbut diabetes develops as a consequence of decreased insulin secretion. In spite of thedifferent levels of insulin in prediabetes and diabetes, hyperglucagonemia can beseen also in both diabetic and prediabetic subjects. Hyperglucagonemia may play animportant role in progression to diabetes. Low plasma concentrations of IGF-1 indiabetic and prediabetic subjects may be a result of GH resistance as shown inprevious studies. The significantly higher values of area under curve of GH insubjects with IFG may indicate that IFG can be an original subgroup and thehypersecretion of GH can be the cause of fasting hyperglycemia.