Polymorphism in the angiotensin-converting enzyme [ACE] gene and ACE activity in type 2 diabetic patients

It has recently been shown that an insertion [I]/deletion [D] polymorphism exists in the angiotensin-converting enzyme [ACE] gene that can affect the serum ACE level. There are three genotypes: DD, DI, and II, with the ACE level being highest in DD, intermediate in DI, and lowest in II. The DD genotype has been reported as a genetic risk factor for diabetes mellitus. In the present investigation, 170 patients with type 2 diabetes mellitus [T2DM] and 144 control subjects were studied. The ACE I/D polymorphism was determined by polymerase chain reaction [PCR] utilizing specific primers. ACE activity was determined spectrophotometrically. Distribution of ACE gene [I/D] polymorphism and allele frequencies in patients with T2DM were significantly different from those in control [P < 0.001]; D allele frequency was 51% in T2DM vs. 48% in controls. The level of ACE activity was significantly higher in the DD genotype [91.1 +/- 23.18] than those in ID [60.6 +/- 22.8] and in II genotypes [36.8 +/- 6.9]. There was a significant difference in genotype distribution between the two groups [P < 0.001]. New normal ranges of serum ACE level were determined for each genotype. Moreover, we found test sensitivity to be 62.3%. Serum ACE activity was significantly associated with ACE [I/D] gene polymorphism

Myeloperoxidase deficiency in neutrophils of diabetic patients with and without infectious diseases

Myeloperoxidase [MPO], an iron-containing protein, is found in the azurophilic granules of neutrophils [PMNs], and catalyzes the conversion of hydrogen peroxide and chloride ions [Cl] into hypochlorous acid, which plays an important role in oxygen-dependent bacterial killing. The enzyme was first isolated in 1941, and deficiency of MPO was first described in 1954. Fewer than 5% of patients with MPO deficiency contract severe infections, which are usually fungal infections in diabetes mellitus [DM] patients. Besides the disorder in antifungal activity, diminished rate of bacterial [S. aureus] killing, and carcinogenesis, it seems that MPO deficiency is also related to atherosclerosis, degenerative neurologic diseases, as well as other disorders. In this study, we compared the levels of the MPO enzyme in the peripheral neutrophils of infected and non-infected DM patients at Imam Khomeini Hospital during 2005-2006. We compared these two groups the prevalence of MPO deficiency in each group, in order to then determine any correlations this may have with infection. In this case-control study, 50 patients were in the infected group [case group] and 50 were in the control group. Patients were chosen using simple sampling methods. Data was gathered from blood samples, using a qualitative test to determine MPO deficiency [Kaplow stain], laboratory results [BUN, Cr, PMN, HbA1c], interviews and completion of a questionnaires, as well as hospital records. Data were analyzed with SPSS software using T test and chi-square test, with a confidence index of 0.05. In spite of differences seen in stained slides, the MPO enzyme was positive in all of the patients, and no differences were seen between the two groups. The average patient age and the duration of DM in the case group were more than those of the control group. No statistical differences in the type of DM and glycosylated hemoglobin [HbA1c] levels were found between the two groups. Body mass indexes [BMI] and PMN counts were higher in the case group. The most prevalent infections were in the skin and soft tissue, bones and joints, as well as chronic respiratory infections [TB], pneumonia, urinary infections, CNS infections, gastrointestinal and intra-abdominal infections, mucormycosis, and sepsis. We found no correlation between MPO enzyme deficiency and age, sex, type or duration of DM, HbA1c levels and BMI

Lecithin cholesterol acyltransferase activity is decreased in type 2 diabetes mellitus

Lecithin cholesterol acyltransferase [LCAT] plays a major role in the removal of free cholesterol from tissues via assisting HDL-C maturation, and its activity has been proposed as the main indicator of HDL-C function. The aim of the study was to measure LCAT activity in type 2 diabetic patients and to elucidate whether LCAT is associated with metabolic control, and insulin resistance. A case-control study was conducted, recruiting 45 type 2 diabetes mellitus patients and 45 healthy subjects. Cases and controls were matched regarding gender, age and body mass index [BMI]. FBS, lipid profile, LCAT activity, HbA[IC], insulin were measured and insulin resistance [HOMA-IR] was calculated for both patients and controls. The studied variables were then compared between the two groups, and the association of LCAT activity with any of the variables was examined. Twenty-five subjects were female and 20 male both among patients and controls. Mean age of diabetics was 49.9 yrs and of controls 51.1 yrs. FBS, HbA[IC], HOMA-IR and TG in patients were significantly higher than controls, and HDL-C in controls was significantly higher than patients. LCAT activity of patients [73 +/- 9.1 nmol/L/h] was significantly lower than that in controls [88 +/- 4.5 |imol/L/h] [P < 0.001]. LCAT activity had significant inverse correlations with HbA[IC] and duration of diabetes. After multilinear regression analysis in patients, LCAT activity was only correlated with HbA[IC] level [B= -0.9, P < 0.001]. LCAT activity had no significant association with HDL-C and HOMA-IR in any of the groups. LCAT activity is significantly decreased in patients with type 2 diabetes compared with healthy controls, and has an inverse correlation with the magnitude of hyperglycemia

Association of angiotensin converting enzyme [ACE] gene polymorphism and diabetic nephropathy

Angiotensin I-converting Enzyme [ACE] gene polymorphism; genotype DD or D allele may be involved with an increased susceptibility to type 2 diabetes and diabetic nephropathy [DN]. We examined the frequency of ACE gene polymorphism in 170 patients [85 type 2 diabetes with nephropathy and 85 without it] in Tehran, Iran. DNA was extracted from the white blood cells and the I/D polymorphism of the ACE gene was detected by PCR. The frequency of DD, ID and II genotypes in type 2 diabetic patients were 20%, 61.2% and 18.8%, and in patients with nephropathy 30.6%, 55.3%, 14.1%, respectively. The DD genotype of the DN group was higher than that of the type 2 diabetes patients [30.6% vs 20%, P=0.157, RR=1.3] and the control group [30.6% vs 14.3%, P=0.006, RR=2.9]. The frequency of D allele in nephropathic patients was 58.2% as compared to the type 2 diabetic patients without nephropathy [50.5%] P=0.19, RR=1.16. The D allele frequency in the DN group was found slightly higher than of the type 2 diabetes [X2=0.684, OR=0.709, 95%CI: 0.313-1.606, P=0.408] which indicated the D allele was not associated with DN. It is suggested that DD genotype and D allele are not associated with diabetic nephropathy

Neutrophil alkaline phosphatese activity: a simple methods for monitoring long-term blood glucose control

Neutrophil alkaline phosphatase activity [NAP Score] increases in diabetes. We studied its correlation with glycosylated hemoglobin [GHb], FBS, serum electrolytes, age, sex, duration and acute or chronic complications of the disease. The study included eighty diabetic patients, 43 with IDDM, 37 with NIDDM, and forty healthy persons as a control group. For estimation of NAP activity a peripheral blood smear was stained by azodye method. One hundred neutrophils were scored zero to four according to the intensity of staining reaction in the cytoplasm. The NAP score was 71 in control group [normal score 10-100] and 132.2 in patients [p<0.01]. The mean level of GHb was 529.5 nmol/g.Hb in control group [normal 400-620] and 1005 in patients. Both parameters were increased significantly in IDDM compared to NIDDM [p < 0.05]. The regression analysis between NAP scores and GHb demonstrated a significant correlation [p < 0.004]. Neither had any correlation with other clinical or laboratory parameters except creatinine. Measurement of NAP activity may be a simple and objective method for assessing longterm blood glucose regulation in established diabetes

HLA-A, B, C and DR antigens in primary hypothyroidism

In a prospective study, HLA-ABC and DR antigens, anti-microsomal and anti-thyroglobulin antibodies were studied in 38 Iranian patients with primary idiopathic" hypothyroidism. Thirty-six out of 38 patients were female and the age range was 15-70 years. Fifty-eight percent were thyroprivic and the remaining were goitrous. The frequency of HLA-B5 was increased significantly in goitrous patients [p< 0.001] versus controls. Forty-seven percent of B5-positive goitrous patients were also positive for HLA-DR5. The anti-microsomal and anti-thyroglobulin antibody titers were significantly increased in half of the patients. There were no differences between thyroprivic and goitrous patients, with respect to antibody titers. We found no correlation among HLA-B5, HLA-DR5, anti-microsomal and anti-thyroglobulin antibodies. HLA-B5 and DR5 linkage may have a highly significant correlation with the development of goitrous hypothyroidism

study of 765 cases of clinically solitary cold thyroid nodules from iodine-deficient area

We studied the clinical, radioisotopic, and pathologic characteristics and the incidence of cancer in clinically solitary cold nodules of the thyroid in an iodine deficient area. The study included retrospective analysis of 765 patients who underwent thyroidectomy for a clinically single cold nodule in a ten-year period. We compared the pathological findings with clinical data. In pathological examination, 34% of glands were multinodular. The incidence of nodular colloid goiters were 81.7% and of thyroid cancer 10.2%. Thyroid malignancy increased significantly after age thirty [p<0.005]. The incidence of cancer was 8.3% in true solitary nodules versus 13.8% in clinically solitary nodules found to be pathologically multinodular [p<0.05]. Papillary carcinoma was the most frequent type [70.5%] and medullary carcinoma the least frequent type [2.6%]. Benign nodular lesions were the most common cause of cold nodules. There was no sex difference in the incidence of thyroid cancer. In the patients with thyroid carcinoma the percentage of multinodular glands was higher. Iodine deficiency may be a factor in changing certain characteristics of thyroid nodules