Metabolic syndrome is not associated with markers of subclinical atherosclerosis, serum adiponectin and endogenous androgen concentrations in Japanese men with Type 2 diabetes.

AIMS: Metabolic syndrome is characterized by its association with certain cardiovascular disease risk factors. The aim of this study was to investigate the relationships between metabolic syndrome and markers of subclinical atherosclerosis, serum adiponectin and endogenous androgen concentrations in Japanese men with Type 2 diabetes. METHODS: Using the 2005 International Diabetes Federation (IDF) definition, we assessed the prevalence of the metabolic syndrome in 424 consecutive men with Type 2 diabetes aged 40-75 years in a cross-sectional study. We compared characteristics including ultrasonographic carotid atherosclerosis markers, pulse-wave velocity (PWV), and serum adiponectin, free testosterone, and dehydroepiandrosterone sulphate (DHEA-S) concentrations in diabetic patients with and without the metabolic syndrome. RESULTS: The prevalence of the metabolic syndrome in Japanese men with Type 2 diabetes was 46.9%. Men with the metabolic syndrome had higher urinary albumin excretion rate than those without. Carotid intima-media thickness (0.97 +/- 0.26 vs. 0.91 +/- 0.18 mm), plaque score [3.3 (1.5-8.1) vs. 3.8 (1.3-6.2)], PWV (1818 +/- 331 vs. 1749 +/- 331 cm/s) and ankle-brachial index (1.10 +/- 0.14 vs. 1.08 +/- 0.16) did not differ significantly between patients with and without the metabolic syndrome. Similarly, serum adiponectin [3.70 (2.06-6.09) vs. 4.65 (3.09-7.02) microg/ml], free testosterone (36.4 +/- 10.7 vs. 34.7 +/- 11.1 pmol/l), and DHEA-S concentrations (3.29 +/- 1.83 vs. 3.17 +/- 1.63 micromol/l) did not differ significantly between groups, CONCLUSIONS: The metabolic syndrome, as defined by the IDF, is not significantly associated with subclinical atherosclerosis markers, serum adiponectin, or endogenous androgen concentrations in Japanese men with Type 2 diabetes.

The association between end-stage diabetic nephropathy and methylenetetrahydrofolate reductase genotype with macroangiopathy in type 2 diabetes mellitus.

The T/T genotype of the methylenetetrahydrofolate reductase C677 T gene polymorphism is associated with elevated homocysteine levels and presumably with increased atherosclerotic risk. We evaluated the interaction between this gene polymorphism and end-stage diabetic nephropathy on the observed prevalence of macroangiopathy in type 2 diabetes mellitus. The methylenetetrahydrofolate reductase 677 C/T genotypes were determined in 174 type 2 diabetic patients: 80 with and 94 without renal failure due to diabetic nephropathy. In the patients with renal failure, the T/T genotype and T allele were significantly associated with macroangiopathy (T/T; 31 % vs. 2 %, P = 0.0001 T allele; 59 % vs. 29 %, P = 0.00014), whereas the associations were not significant in the patients without renal failure. In the multiple logistic regression analysis, age (10 years OR 4.05 [1.79 - 9.31], P < 0.0005) and 677 T allele (6.84 [2.12 - 22.05], P = 0.0013) were significantly associated with macroangiopathy in the patients with renal failure. In conclusion, this study demonstrated that the 677 T/T genotype and T allele of MTHFR were significantly associated with macroangiopathy in type 2 diabetic patients with renal failure. The MTHFR 677 T allele, together with renal dysfunction due to diabetic nephropathy, could be a strong risk factor for atherosclerotic disease.

Intercellular adhesion molecule-1 (ICAM-1) polymorphism is associated with diabetic retinopathy in Type 2 diabetes mellitus.

AIMS: Leucocyte adhesion to the diabetic retinal vasculature has been implicated in the pathogenesis of diabetic retinopathy. We evaluated the relationship between genetic polymorphisms in leucocyte and endothelial cell adhesion molecules and diabetic retinopathy in Type 2 diabetes mellitus. METHODS: We determined ICAM-1, platelet endothelial cell adhesion molecule-1 (PECAM-1), and leucocyte endothelial adhesion molecule-1 (LECAM-1) genotypes in 81 patients with and 50 without diabetic retinopathy. RESULTS: The frequency of ICAM-1 469KK genotype and K allele were significantly higher in the patients with diabetic retinopathy than in those without retinopathy (genotype 42% vs. 20%, chi2 = 6.70, P = 0.035; allele 66% vs. 50%, chi2 = 6.49, P = 0.011). With regard to the PECAM-1 V125L and LECAM-1 P213S polymorphisms, there were no significant associations between the distribution of genotypes or allele frequencies and the presence of diabetic retinopathy. Independent of other risk factors, the ICAM-1 469KK genotype was associated with a 3.51-fold increased risk for retinopathy. CONCLUSIONS: These data suggest that the ICAM-1 469KK genotype could be a genetic risk factor for retinopathy in Type 2 diabetes mellitus.

Interleukin-6 polymorphism (-634C/G) in the promotor region and the progression of diabetic nephropathy in type 2 diabetes.

AIMS: Interleukin-6 (IL-6) is a multifunctional cytokine produced by many different cell types, including glomerular mesangial cells. Recently, a novel C/G polymorphism at position -634 in the promotor region of the IL-6 gene has been reported. The aim of this study was to investigate whether the -634C/G polymorphism is associated with an increased risk for progression to diabetic nephropathy as well as elevated levels of IL-6 secretion by peripheral blood mononuclear cells. METHODS: The frequency of the -634C/G polymorphism was determined in Japanese patients with Type 2 diabetes and either normoalbuminuria (n = 162), microalbuminuria (n = 138), or macroalbuminuria (n = 154) by polymerase chain reaction-restriction fragment length polymorphism analysis. The level of IL-6 secretion in relation to genotype was assessed in lipopolysaccharide or advanced glycation end products-stimulated IL-6 secretion by peripheral mononuclear cells. RESULTS: The frequency of the -634G/G genotype and -634*G allele was significantly increased in the patients with macroalbuminuria compared with patients with normoalbuminuria (genotype: chi2 = 6.787, Pc = 0.0368; allele: chi2 = 9.080, Pc = 0.0104). Stepwise multiple regression analysis in these patients showed that hypertension (F = 40.48) and IL-6-634 gene polymorphism (F = 5.48) were the relevant variables for the progression of Type 2 diabetic nephropathy. Analysis of the IL-6 secretion data revealed that individuals carrying the -634*G allele had a higher IL-6 secretion capacity than those without the *G allele (P < 0.05). CONCLUSIONS: These results suggest that the IL-6-634C/G polymorphism may be a possible genetic susceptibility factor for the progression of diabetic nephropathy.

Tumor necrosis factor microsatellite polymorphism influences the development of insulin dependency in adult-onset diabetes patients with the DRB1*1502-DQB1*0601 allele and anti-glutamic acid decarboxylase antibodies.

Recently, several studies have demonstrated that tumor necrosis factor microsatellite polymorphism (TNFalpha) contributes to the susceptibility of type 1 diabetes. This study investigates the influence of TNFalpha on the predisposition to insulin dependency in adult-onset diabetic patients with type 1 diabetes-protective human leukocyte antigen haplotypes. The TNFalpha of three groups of DRB1*1502DQB1*0601-positive diabetic patients who had initially been nonketotic and noninsulin dependent for more than 1 yr was analyzed. Group A included 11 antibodies to glutamic acid decarboxylase (GADab)-positive patients who developed insulin dependency within 4 yr of diabetes onset. Group B included 11 GADab-positive patients who remained noninsulin dependent for more than 12 yr. Group C included 12 GADab-negative type 2 diabetes, and a control group included 18 nondiabetic subjects. In the group C and control subjects, DRB1*1502-DQB1*0601 was strongly associated with the TNFalpha13 allele. DRB1*1502-DQB1*0601 was strongly associated with the TNFalpha12 allele among the group A patients, but not among the group B patients. Interestingly, sera from all patients with non-TNFalpha12 and non-TNFalpha13 in group B reacted with GAD65 protein by Western blot. These results suggest that TNFalpha is associated with a predisposition to progression to insulin dependency in GADab/DRB1*1502DQB1*0601-positive diabetic patients initially diagnosed with type 2 diabetes and that determination of these patients' TNFalpha genotype may allow for better prediction of their clinical course.

[A case of systemic lupus erythematosus complicated with marked intestinal edema and paralytic ileus].

A 43-years-old female was admitted to our hospital because of facial erythema and photosensitivity in 1983 and was diagnosed as systemic lupus erythematosus (SLE). She was treated with betamethazone 2.5 mg/day as an outpatient. Abdominal pain and diarrhea were developed in September, 1995. So she was admitted to our hospital and diagnosed as having paralytic ileus. Ultrasonography showed marked intestinal edema. Forbidden oral intake and given antibiotics, she was satisfactorily improved in a few days, but the symptoms got worse soon. We forbid oral intake again. We performed a pulse therapy with 1 g of methylprednisolone and increased a dose of betamethasone 2.5 to 4.0 mg/day, but the symptoms were not improved. Since October 6th, serum creatinine level (s-CRE) increased to 8.1 mg/dl at October, 20th. We suspected the worsening of SLE nephropathy or drug-induced nephropathy, so we stopped a medication of pravastatin and used 50 mg/day of azathioprine. Moreover, we did a pulse therapy of methylprednisolone and a plasmapheresis. By these treatments, s-CRE level returned to normal range and paralytic ileus was completely improved. The cause of hypercreatininemia was suspected to be rhabdomyolysis due to pravastatin. The main cause of paralytic ileus with intestinal edema was suspected to be vascular disturbance of superior mesenteric arteries. We consider that pulse therapy and plasmapheresis are useful for a patient of SLE with marked intestinal edema and paralytic ileus.