Relation Of Ghrelin And Cardio-cerebrovascular Complications In Type 2 Diabetes Mellitus

BACKGROUND AND OBJECTIVEGhrelin as the endogenous ligand of the growth hormone secretagogue receptor was found to play a role in the regulation of energy balance and glucose homeostasis,it had been connected to type 2 diabetes mellitus (T2DM) intimately. To date,it had been reported that ghrelin acted as a vasodilator and showed to improve endothelial dysfunction and anti-inflammatory actions.Moreover.Low plasma ghrelin levels had been reported to be associated with obesity,iusulin resistance,hyperinsulinemia and elevated blood pressure,all of which were risk factors of cardio-cerebrovascular diseases.How does the levels of plasma ghrelin in T2DM with cardio-cerebrovascular complications patients change?Could the change of plasma ghrelin levels reflect T2DM cardio-cerebrovascular complications? This study aims to investigate the effect of glucagon on ghrelin secretion in T2DM with cardio-cerebrovascular complications patients through administration of exogenous glucagon.To approach the relation of ghrelin and T2DM cardio-cerebrovascular complications.MATERIALS AND METHODSSubjects were healthy and diabetic volunteers who visited to the first affiliated hospital of Shantou University Medical colleage within 2006-5～2007-5. 30 healthy controls including 15 males and 15 females, with mean age 51±12 yr. 58 diabetic patients without acute or chronic diabetic complications as T2DM group(DM group)including 30 males and 28 females, with mean age 53±9 yr. T2DM with cardio-cerebrovascular complications group(DC group) including 13 males and 11 females, with mean age 56±9 yr. All subjects were admitted to investigation after an over 8-hour overnight fast and took a measurement for height, weight, WC, SBP and DBP first. Venous blood was sampled at fasting and 6min after intravenous injection of 1mg of glucagon for measurement of glucose, C-peptide, ghrelin, GHbA1c, TG, TC, HDLc, LDLc, AST, ALT and UA. Plasma ghrelin was measured by ELISA and C-peptide was measured by RIA. The data acquired was calculated and analysed by software HOMA2 Calculator V2.2,Curve Expert 1.3 and SPSS11.0. RESULTS(1)There was no significant difference in constituent ratio of sex, age, TG, TC, HDLc, LDLc, AST, ALT and UA among three groups(P>0.05). (2) Waist Circumference,BMI,SBP,DBP, GHbA1c and HOMA2 IR in DM group and DC group were significantly higher than those in NC group(P<0.01) . Waist Circumference,BMI,SBP and DBP in DC group were significantly higher than those in DM group(P<0.05). There was no significant difference in GHbA1c and HOMA2 IR between DM group and DC group (P>0.05). (3) Fasting glucose and fasting C-peptide in DM group and DC group were significantly higher than those in NC group(P<0.05), there was no significant difference between DC group and DM group(P>0.05). Fasting ghrelin in DC group were significantly lower than in DM group and NC group(P<0.01), there was no significant difference between DM group and NC group(P>0.05). Paired-sample T test showed that after injection of glucagon, glucose and C-peptide were significantly increased in every group (P=0.000), and ghrelin was significantly decreased in NC group(P=0.000),but ghrelin levels in DM group and DC group had no significant change (P>0.05). (4) Correlate and regressive analysis: Fasting ghrelin level was significantly negative correlated with Waist Circumference (R=-0.380, P=0.000) ,BMI(R=-0.290,P=0.006), SBP(R=-0.449,P=0.000),DBP(R=-0.366,P=0.000), GHbA1c(R=-0.267,P=0.005)and HOMA2 IR(R=-0.203,P=0.033),was significantly positive correlated with HOMA2 %S(R=0.192,P=0.045)in Pearson correlations. Percentage change of plasma ghrelin level was significantly positive correlated with Waist Circumferenc(eR=0.255,P=0.009),SBP(R=0.189,P=0.047), TC(R=0.212,P=0.026)and HDLc(R=0.02,P=0.034)in Pearson correlations. In multivariates regression modle, percentage change of C-peptide and TC were preditors of percentage change of ghrelin level,and Waist Circumference was preditor of fasting ghrelin level.CONCLUSIONS(1)Lower fasting plasma ghrelin levels in T2DM with cardio-cerebrovascular complications patients was associated with central obesity ,iusulin resistance,elevated GHbA1c and blood pressure.(2)Ghrelin was a cardiovascular-protective factor.Lower fasting plasma ghrelin levels in T2DM with cardio-cerebrovascular complications patients would be concerned with consumption of endogenous ghrelin. It needs to be researched advancely whether a low ghrelin concentration may be a risk factor or a marker for T2DM cardio-cerebrovascular complications.(3)The effect of ghrelin suppression by glucagon was weaken in T2DM with cardio-cerebrovascular complications patients. The weaken efficiency may be associated with impaired islet function; First-phase insulin secretion defects in T2DM with cardio-cerebrovascular complications patients would mediate this weaken efficiency.