Genetic analysis of the structure of predisposition to diabetes mellitus. IV. Population-genetics study of two types of diabetes mellitus with onset at age 20-40

It was found that age-specific morbidity risks of type I diabetes mellitus (DM I) increased from the age of 0-4 yrs (0.012-0.013%) to the age of 10-14 yrs (0.04-0.045%) and then slightly decreased to 0.02-0.03%, remaining at this level up to 40 yrs. The "cumulative" morbidity risk of DM I (population risk of development of DM I for each born individual, irrespective of family history) was found to be 0.2% for the age from 0-4 to 40 yrs. Assuming the age-specific morbidity risks of DM I after the age of 40 yrs to be the same as that at 40 yrs (0.02-0.03%), the "cumulative" morbidity risk for this type of DM from birth to 75 yrs old was estimated to be 0.36-0.44%. First incidences of DM II in the population were only observed in 20 yrs olds. The morbidity risk level for DM II at the age 20-24 yrs was found to be lower than that for DM I at this age. The risk was about the same level both for DM I and for DM II at the age 25-34 yrs, the morbidity risk levels for DM II after 35 yrs exceeding that for DM I. The "cumulative" risk of DM II by the age of 40 yrs was 0.1% for men and 0.15% for women. Analysis of familial data revealed statistically significant increase in recurrent morbidity risk in relatives only for the types of DM presented in probands.(ABSTRACT TRUNCATED AT 250 WORDS)     

Periodontal disease status of pregnant women with diabetes mellitus

The aim of the present study was to evaluate the association between type I diabetes mellitus (DM) and periodontal disease in pregnant women. Fifty-two pregnant women aged 27.9 +/- 6.9 years with type I DM participated in the present study. Forty-two non-pregnant type I female diabetics (mean age: 27.9 +/- 6.1 years) and 121 healthy non-pregnant women (mean age: 29.1 +/- 5.7 years) without diabetes formed the control group. All subjects were given a clinical periodontal examination including probing pocket depth (PPD), probing attachment level (PAL), assessment of plaque and gingivitis scores (SBI). Blood parameters included levels of hemoglobin, glycosylated hemoglobin, total cholesterol, triglyceride and leukocytes. The pregnant diabetic subjects showed despite a good metabolic control significantly higher values for the SBI compared to the controls. Pregnant diabetic subjects displayed a significant correlation between the dose of insulin per day and PPD (p < or = 0.05) as well as the PAL (p < or = 0.05). In conclusion, the results of the study indicate that pregnant diabetics demonstrate a higher degree of periodontal inflammation and destruction compared to non-pregnant diabetics and healthy non-pregnant patients.     

Three forms of DNA polymerase from Drosophila melanogaster embryos. Purification and properties.

DNA polymerase was purified from Drosophila melanogaster embryos by a combination of phosphocellulose adsorption, Sepharose 6B gel filtration, and DEAE-cellulose chromatography. Three enzyme forms, designated enzymes I, II, and III, were separated by differential elution from DEAE-cellulose and were further purified by glycerol gradient centrifugation. Purification was monitored with two synthetic primer-templates, poly(dA) . (dT)-16 and poly(rA) . (dT)-16. At the final step of purification, enzymes I, II, and III were purified approximately 1700-fold, 2000-fold and 1000-fold, respectively, on the basis of their activities with poly(dA) . (dT)-16. The DNA polymerase eluted heterogeneously as anomalously high-molecular-weight molecules from Sepharose 6B gel filtration columns. On DEAE-cellulose chromatography enzymes I and II eluted as distinct peaks and enzyme III eluted heterogeneously. On glycerol velocity gradients enzyme I sedimented at 5.5-7.3 S, enzyme II sedimented at 7.3-8.3 S, and enzyme III sedimented at 7.3-9.0 S. All enzymes were active with both synthetic primer-templates, except the 9.0 S component of enzyme III, which was inactive with poly(rA) . (dT)-16. Non-denaturing polyacrylamide gel electrophoresis did not separate poly(dA) . (dT)-16 activity from poly(rA) . (dT)-16 activity. The DNA polymerase preferred poly(dA) . (dT)-16 (with Mg2+) as a primer-template, although it was also active with poly(rA) . (dT)-16 (with Mn2+), and it preferred activated calf thymus DNA to native or heat-denatured calf thymus DNA. All three primer-template activities were inhibited by N-ethylmaleimide. Enzyme activity with activated DNA and poly(dA) . (dT)-16 was inhibited by K+ and activity with poly(rA) . (dT)-16 was stimulated by K+ and by spermidine. The optimum pH for enzyme activity with the synthetic primer-templates was 8.5. The DNA polymerases did not exhibit deoxyribonuclease or ATPase activities. The results of this study suggest that the forms of DNA polymerase from Drosophila embryos have physical properties similar to those of DNA polymerase-alpha and enzymatic properties similar to those of all three vertebrate DNA polymerases.     

Plasma free fatty acids, inhibitor of extrathyroidal conversion of T4 to T3 and thyroid hormone binding inhibitor in patients with various nonthyroidal illnesses.

In order to clarify the role of free fatty acid (FFA) in thyroid hormone abnormalities in patients with nonthyroidal illness, thyroid function, FFA, inhibitor of extrathyroidal conversion of T4 to T3 (IEC) and thyroid hormone binding inhibitor (THBI) were studied in 99 patients with various nonthyroidal illnesses including diabetes mellitus (DM) (n = 35), liver cirrhosis (LC) (n = 33), chronic obstructive pulmonary disease (COPD) (n = 17) and chronic heart failure (CHF) (n = 14). Patients were divided into three groups based on the level of serum T3: Group I (T3 < 50 ng/dl), Group II (50 < or = T3 < 80) and Group III (80 < or = T3). Serum T4, FT3 and the T3/T4 ratio decreased significantly in the order Group III, Group II and Group I (Group III > II > I). The plasma FFA level was 0.91 +/- 0.12 mmol/l in Group I (P < 0.05, vs. Group III), 0.65 +/- 0.06 in Group II and 0.54 +/- 0.04 in Group III, respectively. The incidence of positive IEC was 80.0% in Group I (P < 0.05, vs. Group III), 53.7% in Group II (P < 0.05, vs. Group III) and 34.2% in Group III. However, IEC was not correlated with the serum T3 concentration. The incidence of positive THBI was 80% in Group I (P < 0.05, vs. Group III), 68.3% in Group II and 47.4% in Group III, but THBI was not correlated with the serum T4 level. Positive correlations were observed among FFA, IEC and THBI (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Angiotensin converting enzyme (ACE) activity levels in insulin-independent diabetes mellitus and effect of ACE levels on diabetic patients with nephropathy

Involvement of complications is considered to be one of the major factors in the prognosis of diabetes mellitus (DM). Recent studies indicate that most diabetic complications such as nephropathy and hypertension are vascular-originated. Renin-angiotensin involvement, especially changes in ACE activity level, is considered to be a key factor since ACE converts angiotensin I to angiotensin II which is a potent vasoconstrictor and plays a vital role in the regulation of blood pressure. Our present study focused on ACE activity levels along with blood glucose and HbA(1c) levels in diabetic patients with (n=18) or without (n=25) nephropathy as compared to control subjects (n=25). Blood glucose levels were significantly higher in both diabetic groups compared to controls (p<0.001). On the other hand, compared to controls, blood HbA(1c) levels were slightly higher in DM patients without complications whereas they were significantly increased in nephropatic DM patients (p<0.001). There was a very strong increase (p<0.001) at the level of ACE activity in both of the diabetic groups (with nephropathy: 47.11+/-3.70 U l(-1); without complications: 43.72+/-2.93 U l(-1); controls: 25.15+/-2.30 U l(-1)). ACE activity levels were also significantly higher in diabetic patients with nephropathy than in type II DM patients without complication (p<0.01). Our results demonstrate that ACE activity levels are increased in diabetic patients. Additional significant increase in ACE activity levels in diabetic patients with complications such as nephropathy supports the hypothesis that ACE activity has an essential role in the development of complications in diabetes.     

Prevalence and determinants of diabetes mellitus among Iranian patients with chronic liver disease

BACKGROUND: Alterations in carbohydrate metabolism are frequently observed in cirrhosis. We conducted this study to define the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in Iranian patients with chronic liver disease (CLD), and explore the factors associated with DM in these patients. METHODS: One hundred and eighty-five patients with CLD were enrolled into the study. Fasting plasma glucose and two-hour plasma glucose were measured in patients' sera. DM and IGT were diagnosed according to the latest American Diabetes Association criteria. RESULTS: The subjects included 42 inactive HBV carriers with a mean age of 42.2 +/- 12.0 years, 102 patients with HBV or HCV chronic hepatitis with a mean age of 41.2 +/- 10.9 years, and 41 cirrhotic patients with a mean age of 52.1 +/- 11.4 years. DM and IGT were diagnosed in 40 (21.6%) and 21 (11.4%) patients, respectively. Univariate analysis showed that age (P = 0.000), CLD status (P = 0.000), history of hypertension (P = 0.007), family history of DM (P = 0.000), and body mass index (BMI) (P = 0.009) were associated with DM. Using Multivariate analysis, age (OR = 4.7, 95%CI: 1.8-12.2), family history of DM (OR = 6.6, 95%CI: 2.6-17.6), chronic hepatitis (OR = 11.6, 95%CI: 2.9-45.4), and cirrhosis (OR = 6.5, 95%CI: 2.4-17.4) remained as the factors independently associated with DM. When patients with cirrhosis and chronic hepatitis were analyzed separately, higher Child-Pugh's score in cirrhotic patients (OR = 9.6, 95%CI: 1.0-88.4) and older age (OR = 7.2, 95%CI: 1.0-49.1), higher fibrosis score (OR = 59.5, 95%CI: 2.9-1211.3/ OR = 11.9, 95%CI: 1.0-132.2), and higher BMI (OR = 30.3, 95%CI: 3.0-306.7) in patients with chronic hepatitis were found to be associated with higher prevalence of DM. CONCLUSIONS: Our findings indicate that patients with cirrhosis and chronic hepatitis are at the increased risk of DM occurrence. Older age, severe liver disease, and obesity were associated with DM in these patients.     

Impaired cerebral vasoreactivity in type 2 diabetes mellitus

The aim of our study was to assess cerebral vasoreactivity (CVR) in type 2 diabetes mellitus (DM2) and factors which may influence on it. According to previous studies, evaluating CVR in DM2 on the similar way, the results were dubious. For the evaluation CVR we used breath holding index (BHI) and transcranial Doppler ultrasound (TCD) in 50 patients with DM2 and 50 sex- and age-matched healthy controls. We observed epidemiologic and clinic data, other vascular risk factors and laboratory parameters. We found statistically significant difference in BHI between patients with DM2 (BHI = 0.69 +/- 0.31) and age- and sex-matched healthy controls (BHI = 1.33+/-0.28) (p < 0.05 ). Because of a significant correlation between BHI and age (p < 0.001) in healthy controls we made an adjustment of BHI for age before further analyses (BHIadj). In DM2 group we found a significant correlation between BHIadj and age (p = 0.0004), fasting glycemia (p = 0.04), and albuminuria (p = 0.04) (creatinine clearance in multivariate analysis (p = 0.007)). Our study has shown that CVR is impaired in DM2 patients and that it's severity was associated with age, fasting glycemia and renal function. Functional TCD is a very good screening method for detection and monitoring of cerebral microangiopathic changes in DM2 patients.     

Properties of multiple kinetic forms of soluble cyclic nucleotide phosphodiesterase activity of rat colonic mucosa

Soluble phosphodiesterase (EC 3.1.4.1) activity is 3-5-fold lower in superficial colonic epithelial cells compared to that in cells isolated from the lower colonic crypt. Higher phosphodiesterase activity in lower crypt cells is correlated with a 5-fold higher rate of incorporation of [3H]thymidine into DNA in these cells. DEAE-cellulose chromatography of the soluble fraction of superficial and proliferative colonic epithelial cells resulted in separation of three enzyme forms: (1) fraction I, an enzyme which hydrolyzes both cAMP and cGMP with high affinity (apparent Km cAMP = 5 +/- 1 microM, Km cGMP = 2.5 +/- 0.5 microM) and is stimulated 3-6-fold by Ca2+ plus calmodulin; (2) fraction II, a form which hydrolyzes both cAMP and cGMP with low affinity (S0.5 cAMP = 52 +/- 7 microM, S0.5 cGMP = 17 +/- 4 microM), exhibits positive copperativity with respect to substrate and shows cGMP stimulation of cAMP hydrolysis and (3) fraction III, a cAMP-specific form which exhibits biphasic kinetics, a low Km for cAMP (Km cAMP = 5 +/- 1 microM) and does not hydrolyze cGMP. The pattern of distribution of phosphodiesterase activities on DEAE-cellulose was similar in superficial and proliferative colonic epithelial cells. The higher specific activity in proliferative cells was reflected in higher activities of each of the three chromatographically distinct forms of the enzyme. In contrast to epithelial cells, the soluble fraction of homogenates of the submucosa and supporting cells exhibited phosphodiesterase forms I and II and was lacking in the form corresponding to fraction III of epithelial cells.     

Immunological and catalytic quantitation of splenic glucocerebrosidase from the three clinical forms of Gaucher disease.

The enzymatic activity of glucocerebrosidase in splenic extracts of the adult nonneurological form of Gaucher disease (type I) was 15% +/- 7% of normal, and the titer of enzyme cross-reacting material (ECRM) in these spleens was 54% +/- 9% of normal. The titer of ECRM in splenic extracts of tissues obtained from patients with the neurological forms of Gaucher disease (types II and III) was essentially the same as in type I Gaucher spleens (59% +/- 10% of normal), but the measurable catalytic activity of glucocerebrosidase in these spleens was substantially lower than that found in type I Gaucher spleens (2.3% +/- 0.6% of normal). Thus, the attentuated glucocerebrosidase activity in spleens from all three forms of Gaucher disease appears to stem from a structurally mutated enzyme that is altered in its catalytic efficiency and possibly in its antigenic expression.     

Association between monocyte Fcgamma subclass expression and acute coronary syndrome

BACKGROUND: Atherosclerosis lesions contain abundant immunoglobulins complexed with oxidized LDL (OxLDL) that are endocytosed by macrophages to form foam cells. While recent evidence supports a role for the macrophage scavenger receptor pathway in 75-90% of OxLDL uptake, in vitro evidence suggests another potential uptake pathway could involve autoantibody binding to IgG subclass-specific Fc receptors. OBJECTIVE AND METHODS: To address this mechanism from an in vivo standpoint, the objective of this study was to utilize flow cytometry to prospectively determine monocyte Fcgamma (FcR) I, II, and III receptor expression levels in patients with acute coronary syndrome (ACS, n = 48), diabetes mellitus (DM, n = 59), or neither (C, n = 88). RESULTS: Increased FcR I expression was found in the ACS versus DM groups [geometric mean, (95% CI) = 2.26 (2.07, 2.47) versus 1.83 (1.69, 1.98) (p < 0.001)] and versus C [1.90 (1.78, 2.03) (p = 0.005)]. Similar relationships were found with both the FcR II receptor [ACS mean = 4.57 (4.02, 5.19) versus DM 3.61 (3.22, 4.05) (p = 0.021) and versus C 3.86 (3.51, 4.24) (p = 0.09)] and FcR III receptor [ACS mean = 1.55 (1.44, 1.68) versus DM 1.36 (1.27, 1.46) (p = 0.038) and versus C 1.37 (1.30, 1.45) (p = 0.032)]. There was no difference between DM and C groups in FcR I, II or III expression. CONCLUSIONS: This in vivo data supports a possible second OxLDL-autoantibody macrophage uptake mechanism through an Fc receptor-mediated pathway and a potential relationship between atherosclerotic plaque macrophage FcR levels and ACS.     

Genetic analysis of the structure of the predisposition to diabetes mellitus. II. The prevalence, morbidity and heritability of diabetes mellitus

Prevalence of diabetes mellitus (D.M.) was estimated in several Moscow districts. The prevalence increases with the age from 0.073 in males and 0.085% in females at the age of 16-19 yrs to 4.9 in males and 6.2% in females at the age of 75 yrs and older. The overall prevalence of D.M. was 1.12%. The morbidity risks have the same patterns of increase: from 0.007 and 0.008% at the age of 0-4 yrs to 1.6 and 2.7% at the age of 75 yrs and older in males and females, respectively. The values of "cumulative" morbidity risk, for the population living long enough, derived from the estimates of age-specific morbidity risks were 6.57 for males and 11.93% for females. The estimate of correlation between first-degree relatives at onset-age of D.M. was 0.307. Accounted for the age-at-onset of the probands and for current ages of siblings, the estimates of recurrence risks, i.e. the probability to develop D.M. for siblings living long enough, were: 27.28 for sisters of the male-probands, 21.59 for sisters of the female-probands, 19.28 for brothers of male-probands and 9.62% for brothers of the female-probands. Thus, the family distribution of D.M., according to the sex of the probands and that of their relatives corresponds to the multifactorial model of inheritance for the diseases with sex-specific thresholds. The estimates of correlation in liability and that of heritability of D.M. calculated from the data on sibs, were 0.284 +/- 0.0351 and 0.568 +/- 0.0702, respectively. The data obtained show that hereditary factors play an essential role in the development of D.M. These results are of a practical interest for genetic counselling, as well as for establishing the preventive measures in the Public Health Service.     

Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus

Accelerated glycoxidation takes part in the development of diabetic complications. We determined advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP) in the sera of 52 patients with diabetes mellitus (DM) - 18 with DM Type 1 and 34 with DM Type 2 and examined their relationship to the compensation of the disease. AGEs were estimated spectrofluorimetrically (350 nm/440 nm) whereas AOPP were determined spectro-photometrically (340 nm). AGEs were elevated only in DM Type 2 (DM2 5.11+/-1.15 x 10(3) AU/g vs controls 4.08+/-0.71 x 10(3) AU/g, p<0.001, vs DM1 4.14+/-0.86 x 10(3) AU/g, p<0.005, DM1 vs controls were not significant). AOPP were elevated significantly in both types of DM with higher levels in DM Type 2 (DM2 157.50+/-75.15 micromol/l vs healthy subjects 79.80+/-23.72 micromol/l, p<0.001, vs DM1 97.50+/-30.91 micromol/l, p<0.005, DM1 vs controls p<0.05). There was a tight correlation between AGEs and AOPP in both types of DM (DM1 r=0.75, DM2 r=0.47 (p<0.05)) and both AGEs and AOPP correlated with triglycerides. In DM Type 1 only, AGEs correlated with HbA1c r=0.47 (p<0.05) and with blood glucose. Slight but not significant differences in AGEs and AOPP levels were observed in patients with or without diabetic complications. Oxidative stress is increased in both types of DM, more in Type 2 where it contributes to the formation of glycoxidation products.     

Polymorphisms of chemokine and chemokine receptor genes in Type 1 diabetes mellitus and its complications

Cytokines and chemokines have been implicated in the pathogenesis of Type 1 diabetes mellitus (T1DM) and its microvascular complications. Recently, genetic variants of monocyte chemotactic protein-1 (MCP-1), CC-chemokine receptor 2 (CCR2), CC-chemokine receptor 5 (CCR5) genes have been identified. The aim was to investigate whether genetic variants of the MCP-1 G(-2518)A, CCR2B 64I, CCR5 G(59029)A, and CCR5 Delta32 are associated with T1DM and its microvascular complications. Two hundred and sixty patients with T1DM with and without diabetic microvascular complications, and 104 normal controls were recruited for this study. Genotypes of the MCP-1 G(-2518)A, CCR2B 64I, CCR5 G(59029)A, and CCR5 delta32 were performed by polymerase chain reaction followed by digestion with appropriate restriction endonucleases. Frequencies of the MCP-1 A(-2518) allele (74.6% vs. 63.5%, p < 0.003) and A/A genotype (54.5% vs. 34.6%, p < 0.001, Pc = 0.002) were significantly higher in patients with T1DM compared with normal controls. CCR5 G(59029) was slightly increased in the patients with microvascular complications compared with the uncomplicated (21.4% vs. 10%, p < 0.03, Pc = ns). The frequency of haplotype G/G/W was slightly increased in the patients with diabetic complications compared to the uncomplicated (39.6% vs. 28.8%, p < 0.02, Pc = ns). These results suggest that polymorphisms of the MCP-1, CCR2 and CCR5 genes may be associated with T1DM and its complications.     

Increased renal TXA2 synthesis in diabetes mellitus: simultaneous determination of urinary TXB2 and 2,3-dinor-TXB2

The present study was designed to determine urinary excretion of kallikrein(KAL)-kinin as well as prostaglandin (PG) E2, TXB2 and 2,3-dinor-TXB2, a major urinary metabolite of TXA2 synthesized in platelets, by specific RIAs in patients with diabetes mellitus (DM). KAL or kinin excretion in 26 type II DM did not differ from control values obtained in 18 age-matched healthy subjects (C), although DM with HbA1 greater than 11% excreted less KAL. Urinary PGE2 excretion (7.6 +/- 2.8 ng/mg creatinine, mean +/- SE) was significantly lower in DM compared to C (17.5 +/- 3.9, p less than 0.05), while DM excreted more TXB2 (0.57 +/- 0.09, p less than 0.01) and 2,3-dinor-TXB2 (0.56 +/- 0.12, N.S.) than C (0.19 +/- 0.02 or 0.33 +/- 0.01). DM with or without mild proteinuria demonstrated lower PGE2, but higher TXB2 and 2,3-dinor-TXB2 excretion. A positive correlation of TXB2/2,3-dinor-TXB2 with proteinuria was observed in this group. However, in DM with massive proteinuria over 500 micrograms/mg creatinine, TXB2 and 2,3-dinor-TXB2 excretion decreased to levels almost identical to C. As a whole, a ratio of TXB2 to PGE2 or 2,3-dinor-TXB2 in DM was significantly higher than in C. The results suggest that a relative preponderance of TXB2 to 2,3-dinor-TXB2 may indicate an augmented renal, in addition to platelet, TXA2 synthesis. An excessive vasoconstrictive and proaggregatory TXA2 renal synthesis, concomitant with a decrease in vasodilatory and antiaggregatory PGE2, may have profound effects on renal functions such as protein excretion in DM.     

Contribution of nitric oxide to cutaneous microvascular dilation in individuals with type 2 diabetes mellitus

Microvascular pathophysiology associated with type 2 diabetes mellitus (T2DM) contributes to several aspects of the morbidity associated with the disease. We quantified the contribution of nitric oxide (NO) to the cutaneous vasodilator response to nonpainful local warming in subjects with T2DM (average duration of diabetes mellitus 7 +/- 1 yr) and in age-matched control subjects. We measured skin blood flow in conjunction with intradermal microdialysis of N(G)-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) or vehicle during 35 min of local warming to 42 degrees C. Microdialysis of sodium nitroprusside (SNP) was used for assessment of maximum cutaneous vascular conductance (CVC). Resting CVC was higher in T2DM subjects at vehicle sites (T2DM: 19 +/- 2 vs. control: 11 +/- 3%maxCVC; P < 0.05); this difference was abolished by l-NAME (T2DM: 10 +/- 1 vs. control: 8 +/- 1%maxCVC; P > 0.05). The relative contribution of NO to the vasodilator response to local warming was not different between groups (T2DM: 46 +/- 4 vs. control: 44 +/- 6%maxCVC; P > 0.05). However, absolute CVC during local warming was approximately 25% lower in T2DM subjects (T2DM: 1.79 +/- 0.15 AU/mmHg; controls: 2.42 +/- 0.20 AU/mmHg; P < 0.01), and absolute CVC during SNP was approximately 20% lower (T2DM: 1.91 +/- 0.12 vs. control: 2.38 +/- 0.13 AU/mmHg; P < 0.01). We conclude that the relative contribution of NO to vasodilation during local warming is similar between subjects with T2DM and control subjects, although T2DM was associated with a lower absolute maximum vasodilation.     

Association of CETP TaqI and APOE polymorphisms with type II diabetes mellitus in North Indians: a case control study

Background

Genetic variants of proteins involved in lipid metabolism may play an important role in determining the susceptibility for complications associated with type II diabetes mellitus (T2DM). Goal of the present study was to determine the association of cholesteryl ester transfer protein TaqI B, D442G, and APOE Hha I polymorphisms with T2DM and its complications.

Methods

Study subjects were 136 patients and 264 healthy controls. All polymorphisms were detected using PCR-RFLP and statistical analysis done with χ² test and ANOVA.

Results

Although CETP TaqI B polymorphism was not associated with the T2DM, yet B1B2 genotype was significantly (p = 0.028) associated with high risk of hypertension in diabetic patients (OR = 3.068, 95% CI 1.183–7.958). In North Indians D442G variation in CETP gene was found to be absent. Frequency of APOE HhaI polymorphism was also not different between patients and controls. In diabetic patients having neuropathy and retinopathy significantly different levels of total-cholesterol [(p = 0.001) and (p = 0.029) respectively] and LDL-cholesterol [(p = 0.001) and (p = 0.001) respectively] were observed when compared to patients with T2DM only. However, lipid levels did not show any correlation with the CETP TaqI B and APOE Hha I genetic polymorphisms.

Conclusion

CETP TaqI B and APOE HhaI polymorphism may not be associated with type II diabetes mellitus in North Indian population, however CETP TaqI B polymorphism may be associated with hypertension along with T2DM.     

N-acetyltransferase 2 polymorphism in patients with diabetes mellitus

The arylamine N-acetyltransferases (NATs) are a unique family of enzymes that catalyse the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of hydrazine and arylamine drugs and carcinogens. Human arylamine NATs are known to exist as two isoenzymes, NAT1 and NAT2. The objective of this study was to identify whether the genetic polymorphism of NAT2 plays a role in susceptibility to Diabetes Mellitus (DM). Ninety-seven patients with DM and 104 healthy controls were enrolled in the study. NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A polymorphisms were detected by using real time PCR with LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). According to our data, the NAT2*5A and NAT2*6A mutant genotypes and NAT2*14A heterozygous genotype were associated with an increased risk of development of DM (OR = 47.06; 95%CI: 10.55-209.77 for NAT 2*5A, OR = 18.48; 95%CI: 3.83-89.11 for NAT2*6A and OR = 18.22; 95%CI: 6.29-52.76 for NAT2*14A). However, the NAT2*7A/B gene polymorphism carried no increased risk for developing DM disease. After grouping according to phenotypes as either slow or fast acetylators, NAT2*6A slow acetylator was found to be a significant risk factor for DM (OR = 6.09; 95%CI: 1.99-18.6, p = 0.02). The results indicate that NAT2 slow acetylator genotypes may be an important genetic determinant for DM in the Turkish population.     

Cyclosporin A in insulin-dependent diabetes mellitus of recent onset: a pilot study in children

We report on the first pilot study in newly diabetic children treated with cyclosporin A (CsA), for 6 months. Three groups of children were recruited based on the desired CsA plasma level: group I (n = 13) aiming at 100 ng CsA/ml plasma; group II (n = 14) at 200 ng/ml, and group III (n = 13) aiming initially at 200 ng/ml and later on 100 ng/ml. These groups were compared to a control group (n = 12) receiving no CsA but the same insulin regimen. A significant reduction in insulin requirements was observed in the CsA-treated children, more marked in groups II and III (p less than 0.001 vs. control group). The rate of total remissions was 0 in the control group, and 30% in group I; it was 57 and 76% in groups II and III, respectively. CsA also induced an increase in C-peptide secretion after 6 months (p less than 0.01 in groups II and III vs. controls). Side effects of the drug were of minor clinical importance in group I. But in groups II and III, 48% of the children exhibited a reversible increase in blood pressure or plasma creatinine. This study demonstrates a dose-related effect of cyclosporin A (CsA) on the insulin requirements of newly diagnosed diabetic children (more frequent and prolonged remissions with the high CsA dosage). Nevertheless, the noticeable side effects, induced by this high dosage, are of concern for prolonged CsA administration in diabetic children.     

Elevated plasma levels of immunoreactive urotensin II and its increased urinary excretion in patients with Type 2 diabetes mellitus: association with progress of diabetic nephropathy

Urotensin II (UII) is the most potent vasoconstrictor peptide ever identified. In order to clarify the pathophysiological role of UII in diabetes mellitus, we examined plasma immunoreactive UII levels and urinary excretion of immunoreactive UII in 10 control subjects and 48 patients with Type 2 diabetes mellitus. The patients were divided into three groups according to the renal function: Group I with Ccr > or = 70 ml/min, group II with 30 < or = Ccr <70 ml/min and group III with Ccr <30 ml/min. Plasma immunoreactive UII levels were elevated in the three diabetic groups compared with normal controls (P <0.05). Group III patients had significantly higher plasma immunoreactive UII levels (15.9 +/- 2.2 fmol/ml, mean +/- S.E.M., n=6) by approximately 1.6-fold than did group I (10.9 +/- 0.9 fmol/ml, n=17) and group II (10.8 +/- 0.8 fmol/ml, n=25) (P <0.05). Urinary excretion of immunoreactive UII was significantly increased in group III patients (52.4 +/- 14.8 pmol/day) by more than 1.8-fold compared with control subjects, groups I and II (P <0.005). Fractional excretion of immunoreactive UII significantly increased as renal function decreased. Presence of diabetic retinopathy or neuropathy had negligible effects on plasma immunoreactive UII levels and urinary immunoreactive UII excretion. Reverse phase HPLC analyses showed three immunoreactive peaks in normal plasma extracts and multiple immunoreactive peaks in normal urine extracts. Thus, Type 2 diabetes mellitus itself is a factor to elevate plasma immunoreactive UII levels, and accompanying renal failure is another independent factor for the increased plasma immunoreactive UII levels in Type 2 diabetic patients. Increased urinary immunoreactive UII excretion in Type 2 diabetic patients with advanced diabetic nephropathy may be due not only to the elevated plasma immunoreactive UII levels but also to increased UII production and/or decreased UII degradation in the diseased kidney.     

Thyroid volume as measured by ultrasonography in patients With type 1 diabetes mellitus without thyroid dysfunction.

The aim of this cross-sectional study was to assess and compare thyroid volume and its derminants in a cohort of type 1 diabetes mellitus (DM1) and compare the results to a healthy control group. We studied 65 DM1 patients treated with an intensive insulin regimen and 65 matched controls. In all participants we evaluated weight, height, BMI, waist-hip ratio, body surface area and body composition variables determined by using a bioelectrical impedance analyser. Thyroid size was estimated by ultrasonography. We determined basal TSH, anti-thyroid antibodies and urinary iodine excretion. Body weight, height, BMI and body surface area were similar in DM1 patients and in controls. Fat-free mass was higher in both male and female DM1 patients than in controls (64.4 +/- 6.9 vs. 60.4 +/- 8.2 kg, p=0.03 and 48.3 +/- 5.7 vs. 45.4 +/- 6, p=0.04, respectively), and fat mass was lower in male DM1 patients than in controls (9.7 +/- 7 vs. 14.2 +/- 8.1 kg, p=0.01). Thyroid volume was greater in both male and female DM1 patients than in controls (11.12 +/- 2.87 vs. 9.63 +/- 2.27 ml, p=0.0001 and 9.5 +/- 2.3 vs. 7.7 +/- 2 ml, p=0.002, respectively). Urinary iodine excretion was similar in the two groups. In both DM1 patients and controls, thyroid volume correlated with weight, height, BMI, waist-hip ratio, body surface area, fat-free mass and the multivariate linear regression analysis with thyroid volume as the dependent variable showed that fat-free mass in either group was the only significant determinant of thyroid volume. We conclude that DM1 patients had larger thyroid volume compared with healthy controls with similar anthropometry; body composition is different in DM1 patients and that the anthropometric and body composition variables, especially fat-free mass and body surface area, predict thyroid volume either in DM1 patients or in healthy controls.