الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 236 |  |  |
| | | from | 236 | | |
Abstract
The present study was carried out in the Internal Medicine department, Minia university hospital along the period from January 2015 to November 2018.The subjects were collected from both Internal medicine and Diabetes outpatient clinics in Minia University Hospital.
The study aimed to:
1- Evaluate the clinical and biochemical risk factors of prediabetes and evaluate which of them favors the progression of prediabetes to T2DM.
2- Examine the frequency distribution of both TNF α 238 G/A gene polymorphism and TCF7L2 C/T rs 7903146 gene polymorphism in the Egyptian prediabetic subjects and patients with T2DM as compared with healthy volunteers.
3- Clarify the impact of these polymorphisms on different metabolic parameters of the study subjects.
4- Determine the impact of these polymorphisms on the susceptibility to prediabetes and on the progression of prediabetes to T2DM in the Egyptian population and if any of these polymorphisms had high risk of certain diabetic complication.
5- Estimate the role of serum level of TNF α in the occurrence of prediabetes and in its progression to T2DM.
Results:
When we compared the study groups as regard the anthropometric characteristics, we found that both of prediabetic and diabetic patients had higher values of BMI, waist circumference, hip circumference, and W/H ratio than the control group and this yielded a statistical significance.
As regard SBP, DBP and pulse they were higher in both prediabetics and diabetics than control and this yielded a statistical significance.
As regard clinical criteria of the study groups, we found that they were more frequent in diabetics than prediabetics; 5% of prediabetics Vs 52.5% of diabetics had hypertension. 10% of prediabetics Vs 12.5% of diabetics had neuropathy. 8.3% of prediabetics Vs 15% of diabetics had hepatomegaly, and this yielded a statistical significance.
As regard glycemic indices of the study groups, we found that FBG, 2HBG and HA1C were higher in diabetics than the other 2 groups and this had a statistical significance. As regard fasting insulin levels they were statistically higher in prediabetics as compared with diabetics and this had a statistical significance and they were higher in prediabetics and diabetics than control and this had a statistical significance also. Regarding HOMA B, it was higher in prediabetics than diabetics and this had a statistical significance, and it was lower in diabetics than control and this had a statistical significance also. As regard HOMA IR it was statistically higher in prediabetics as compared with diabetics and this had a statistical significance, and they were higher in prediabetics and diabetics than control and this had a statistical significance also. As regard serum TNF α it had statistically significant results, diabetic patients had the most higher values followed by the prediabetics and lastly control.
In our study we found that total cholesterol, LDL, TGs were higher in prediabetic subjects and in patients with diabetes than in the control group. And we found that HDL was higher in the control group than in both prediabetic subjects and patients with T2DM.
As regard A/C ratio, in prediabetics there were 4 patients had micro-albuminuria and only one patient had macro-albuminuria.
While in diabetics there were 7 patients with positive albuminuria; 3 patients had micro-albuminuria and 4 patients had macro-albuminuria, and the frequency of both micro-albuminuria and macro-albuminuria was statistically higher in diabetics than in prediabetics and this yielded a statistical significance and also, when we compared diabetics with control, but there was no statistical significance between prediabetics and control.
In respect to the frequency of fatty liver by ultrasound it was 30% in diabetics Vs 18.3% in prediabetics but this had no statistical significance, and when we compared prediabetics and diabetics Vs control the frequency of fatty liver was higher in both of them than control and this yielded a statistical significance. As regard fundus examination all subjects of prediabetes were normal and this yielded a statistical significance when they compared with diabetics. 12.5% of diabetics had non-proliferative retinopathy (NPR) and 5% of them had proliferative retinopathy (PR) and this yielded a statistical significance when they compared with control.
As regard ALT level we found that it was higher in diabetics than the other 2 groups and this had a statistical significance when each two groups were compared with each other. AST levels were statistically higher in diabetics as compared with prediabetics and control and this had a statistical significance, and they were higher in prediabetics than control but no statistical significance had been found. As regard urea it showed the similar finding being higher in diabetics than both prediabetics and control and this had a statistical significance. Serum creatinine was higher in prediabetics than control and also, higher in diabetics than control and this had a statistical significance. As regard CBC of the study groups, we found that RBCs levels were higher in prediabetics than the other 2 groups and this had a statistical significance when each two groups were compared with each other but they are still within the normal rang. WBCs levels were higher in prediabetics than the other 2 groups and this had a statistical significance when prediabetics were compared with diabetics but they are still within the normal rang. Platelets were significantly lower in prediabetics when compared with diabetics and lower in prediabetics when compared with control but they are still within the normal range.
In respect to the distribution of TNFα 238 G/A polymorphism genotypes: In prediabetics (group 1) the frequency of the genotypes was (GG genotype: 83.4% , AA genotype: 3.3% and GA genotype: 13.3 %). In patients with T2DM (group 2) it was (GG genotype: 75%, AA genotype 5%, and GA genotype: 20%). In control (group 3) it was (GG genotype: 90%, AA genotype: 2.5%, and GA genotype: 7.5%).
As regard the effect of TNFα 238 G/A polymorphism on the metabolic parameters of the prediabetics, we found that LDL level was higher in homozygous (AA) than wild type GG. As regard fasting insulin it was significantly higher in homozygous (AA) than both heterozygous (GA) genotype and wild type GG and it was also higher in heterozygous than wild type. As regard HOMA B it was higher in homozygous (AA) than both heterozygous (GA) genotype and wild type GG. As regard the effect of TNFα 238 G/A polymorphism on the metabolic parameters of the diabetics, no statistically significant difference could be detected among the 3 genotypes. We found that, there was no significant risk for the polymorphism and risk of occurrence of prediabetes.
In order to assess the ability of serum level of TNF α to predict prediabetes, the AUC of ROC curve was calculated, it was 0.75%. The diagnostic value of serum level of TNF α was assessed by calculating sensitivity, specificity, and accuracy of the best cut off value of it. They were 72.5%, 75% respectively, and cut off value of ≥30 had the best accuracy for prediction of prediabetes.
As regard the frequency of TCF7L2C/T genotypes in prediabetics it was (TT genotype 3.3%, CT genotype: 70% and CC genotype: 26.7%). In diabetics (TT genotype: 7.5%, CT genotype70%, and CC genotype: 22.5%). In control (TT genotype: 2.5%, CT genotype: 45%, and CC genotype: 52.5%).
When the laboratory data were compared according to the detected TCF7L2C/T genotypes in prediabetics, we found that fasting insulin levels were higher in both homozygous (TT) and heterozygous (CT) genotype than wild type and this had a statistical significance. Regarding HOMA B it shows the same finding being higher in both homozygous (TT) and heterozygous (CT) genotype than wild type and this had a statistical significance. HOMA IR was higher in heterozygous (CT) than wild type (CC) and this had a statistical significance.
Concerning the effect of TCF7L2 C/T polymorphism on the metabolic parameters of the diabetics, we found that total cholesterol was higher in heterozygous (CT) than both TT and CC genotype and we found that both TGs and LDL were higher in heterozygous (CT) than CC genotype. As regard fasting insulin levels and HOMA B both were statistically higher in wild type (CC) than heterozygous (CT). We found that in prediabetics the CT genotype had high risk of prediabetes (OR: 3.06, p=0.003), and T allele had high risk of prediabetes (OR: 1.8, p=0.03).
In our study, after 2 years of follow up 8 out of 60 subjects with prediabetes, had progressed to T2DM. As regard the demographic, anthropometric and clinical characteristics of them, they were 6 females and 2 males, their ages ranged from 37-55 years, 5 of them had positive family history of T2DM.
As regard the clinical characteristics of them, 3 of them were known hypertensive and on treatment, one of them had macro-albuminuria and fatty liver, 4 of them had neuropathy.
As regard the anthropometric characteristics of them, all had high values for BMI, waist circumference, hip circumference and W /H ratio. We found that they had statistically significant higher fasting insulin, higher HOMA B, higher TNFα .As regard the lipid profile they had high values of total cholesterol, TGs and LDL. As regard A/C ratio; 3 of them had micro -albuminuria and 1 patient had macro-albuminuria.
As regard TNFα 238G/A genotypes; 3 of the prediabetics who progressed to T2DM were heterozygous (GA) and 1 was homozygous (AA) and 4 were wild type GG. Concerning TCF7L2 C/Tgenotypes; 3 of the prediabetics who progressed to T2DM were heterozygous (CT), 2 were homozygous (TT) and 3 were wild type CC.
We found that BMI, fasting Insulin, WBCs, Hip C, DBP, weight, serum TNF, HOMA B, total cholesterol, and height respectively had higher risk for progression of prediabetes to T2DM. Also, we found that the TT genotype favored more progression having (OR: 10.6) (p=0.04).