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Diabetes mellitus and thyroid disorders are common endocrinopathies, which often occur parallel. Dyslipidemia is very common in both of these conditions. The development of hypothyroidism is well-known in type 1 diabetics, but it was not distinctly understood in type 2 diabetics. Thus we tried to examine the association between type II deiodinase (D2 or DIO2) Thr92Ala single nucleotide gene polymorphism and thyroid function among type 2 diabetes mellitus patients. A total of 130 type 2 diabetics were screened and genotyped for DIO2 Thr92Ala polymorphism. Fasting plasma glucose, Glycosylated haemoglobin, lipid and thyroid profiles, malondialdehyde (MDA) and paraoxonase were estimated according to standard procedures. A significant altered level of thyroid hormones (TH's) was found in Ala/Ala genotype when compared with Thr/Thr or Thr/Ala genotype. DIO2 and T 3 :T 4 ratio significantly decreased, whereas total T 4 and thyroid stimulating hormone levels significantly elevated among Ala/Ala genotype (131 ± 30 ng/ml; 0.12 ± 0.05; 7.17 ± 2.05 lg/dl; 4.77 ± 3.1 lIU/ml, respectively) when compared with Thr/Thr ? Thr/Ala genotypes (176 ± 33 ng/ml; 0.21 ± 0.05; 5.21 ± 1.1 lg/dl; 2.59 ± 1.61 lIU/ml respectively). Moreover, D2 levels were significantly negatively correlated with TH's levels except total T 4 among Ala/Ala genotypes. All the patients were having a poor glycemic control, and their glycemic status was positively correlating with MDA levels. On the other hand, serum paraoxonase activity decreased among Ala/Ala genotype (104 ± 21 vs. 118 ± 18 nmol/min/ml). In conclusion, DIO2 Ala92 homozygous variant found to be associated with altered levels of DIO2, Thyroid profile and paraoxonase. Hence, we recommend to do detail study of genetic factors related to thyroid function and prevent additional diabetic complications.

The inverse relationship between serum levels of High Density Lipoprotein (HDL) and the development of Cardio Vascular Disease (CVD) risk among diabetic patients was known for several decades. Besides the decreasing quantity of HDL, the qualitative functions of HDL are adversely affected during uncompensated oxidative stress among diabetics and leads to implication of several complications such as dyslipidemia, lipid peroxidation, endothelial dysfunction and atherosclerosis. Therefore we have undertaken this study to determine anti-atherogenic property of HDL by measuring it's one of the associated enzymes; paraoxonase (PON) among type 2 diabetes patients, along with the serum activity of superoxide dismutase (SOD) as an index of antioxidant status and lipid peroxidation end product, i.e malondialdehyde (MDA) as a marker for oxidative stress. This study included a total of 56 untreated type 2 diabetic patients and 29 healthy volunteers as controls. FBS, PPBS, HbA 1C and fasting lipid profile were measured in both the study groups. Activity of basal PON, SOD and plasma MDA levels was determined in both the study groups according to standard clinical laboratory procedures. All the diabetic patients were under poor glycemic control. Serum levels of HDL between the two study groups are not significantly differed. But, serum basal PON and SOD activity were significantly decreased, whereas MDA levels were highly elevated (284±59 nM/mL/min, 111± 35 μmol/L, 10.38±4.17 IU/mL respectively) when compared with healthy controls (371±46 nM/mL/min, 63±12 μmol/L, 16.91±2.89 IU/mL respectively). Although there is no significant reduction in concentrations of HDL in diabetics when compared with controls, but there was a significant decrease in anti-atherogenic property i.e. activity of paraoxonase enzyme. Moreover the serum activity of paraoxonase was significant and negatively correlated with MDA levels (r =-0.53, P<0.001) as well as with FBS (r=-0.30, P<0.05). Therefore the qualitative functions of HDL are significantly affected by hyperglycemia induced oxidative stress. Hence, we concluded that the quality of HDL is most important in order to determine oxidative stress related complications in diabetes mellitus than its concentration.

BACKGROUND Paraoxonase 1, an arylesterase, is associated with high-density lipoprotein and it prevents LDL from peroxidation by hydrolysing lipid peroxides and thereby providing protection against atherosclerosis. A polymorphism of paraoxonase 1 gene provoking a glutamine-to-arginine (A-allele or Q allele to B-allele or R allele) interchange at aminoacid-192 has been reported to determine differences in arylesterase activity towards LDL's oxidised aryl esters, hydrolysed at a higher rate by Q-alloenzyme than Ralloenzyme. AIM We carried out this study to determine the association of paraoxonase 1 gene Q192R polymorphism (R-allele) with coronary atherosclerosis and to find out if the low arylesterase activity caused by the paraoxonase 1 gene Q192R polymorphism (Rallele) is associated with atherosclerosis. STUDY DESIGN Case control study. METHODS Genotype analysis was done on 181 angiographically proven coronary atherosclerosis patients and 177 healthy controls by polymerase chain reaction followed by restriction digestion. Paraoxonase 1 arylesterase activity was estimated with phenyl acetate as substrate. RESULTS Cases had significantly higher frequency of R+ genotype (RR and QR) than control subjects (0.78 versus 0.49; P=.001). Significantly, lower plasma paraoxonase 1 activity was observed in coronary atherosclerosis patients as compared to healthy controls (71.3 kIU/mL versus 84.74 kIU/mL, P <0.05). Risk stratification is possible based on paraoxonase 1 activity-<65 kIU/mL-high risk, 65-80 kIU/mL = moderate risk, >80 kIU/mL-low risk for atherosclerosis. The mean paraoxonase 1 activity among R+ genotypic individuals is 63.52 kIU/mL whereas the mean paraoxonase 1 activity among R-genotype is 103.26, p value is 0.004. On univariate analysis, the odds ratio for R+ genotype is 3.6 (p=0.00). On multivariate analysis, the odds ratio for R+ genotype is 2.5 (p=0.00). CONCLUSION The low plasma Paraoxonase 1 activity and the R genotype maybe independent risk factors for coronary atherosclerosis.

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