Aspirin is widely used by diabetic individuals as a prophylactic for atherosclerotic cardiovascular disease. Recently, the role of adhesion molecules on the development of atherosclerosis has been studied.However, the effects of aspirin on the expression of adhesion molecules in vivo has not been studied. In this study, 14 patients with type 2 diabetes and asymptomatic carotid atherosclerosis were given low-doses (81 mg/day) of aspirin for 12 weeks. HbA_1c, lipids, blood pressure, and soluble adhesion molecules were measured before and after treatment. Fourteen patients of comparable age, sex, and carotid atherosclerosis status assigned to a control group. Throughout the study period, the treatment modalities for diabetes, hypertension, and dyslipidemia were not altered in either group. In both groups, HbA_1c, lipids, and blood pressure did not change before and after treatment. Serum concentrations of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin did not change before and after treatment in the control group. In contrast, the serum concentrations of ICAM-1 decreased significantly after aspirin therapy (from 214.2ng/ml±16.1ng/ml to 193.0ng/ml±14.2ng/ml, p<0.05). Serum concentrations of VCAM-1 and E-selectin did not change significantly in aspirin-treated patients. Our results suggest that the anti-atherogenic effects of aspirin are explained, at least in part, by the reduced expression of ICAM-1.

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To elucidate the risk factors of hypertension, the incidence of hypertension in normotensive subjects was examined in 6305 Japanese subjects (2876 men and 3429 women) over a period of 9 years.
The incidence of hypertension was 1.41 times higher in obese subjects than in non-obese subjects (95% CI 1.25-1.60). Also, subjects with an impaired fasting glucose level had a 1.57 times higher (95% CI 1.13- 2.18) incidence of hypertension than normoglycemic subjects. Subjects with hypertriglyceridemia had a 1.25 times higher (95% CI 1.09-1.43) incidence of hypertension than normal subjects.
However, after adjustments for BMI, fasting glucose level and age were made, hypertriglyceridemia was not a risk factor for hypertension.
These findings suggest that abnormalities in glucose tolerance and obesity are independent risk factors of hypertension, while hypertriglyceridemia is a dependent factor.

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We studied the effect of Pioglitazone (Pio) on fibrinolytic and endothelial function in type 2 diabetes mellitus. Subjects were 56 patients with type 2 diabetes mellitus-12 men and 44 women aged 47-76 years (mean: 64.1 years)-Of these, 18 were treated with Pioglitazone alone (PI group), 12 with Gliclazide (Gli) alone (GL group), and 26 with Pioglitazone plus Gliclazide (PG group) for 12 weeks. Fasting blood samples were collected before and after administration to measure fasting plasma glucose (FPG), immunoreactive insulin (IRI), plasminogen activator inhibitor 1 (PAI-1), and von Willebrand factor (vWF) as a marker of endothelial dysfunction. In the PI and PG groups, PAI-1 and vWF were significantly decreased after treatment with Pio, with significant decr eases also seen in FPG and IRI. In the GL group, FPG decreased significantly and IRI increased significantly following administration of Gli, while PAI-1 and vWF were unchanged. These results suggest that Pio therapy for patients with type 2 diabetes mellitus is beneficial to the fibrinolytic system and vascular endothelial function, and controls hyperglycemia and ameliorating hyperinsulinemia.

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We measured the time constant (τ) of oxygen consumption (VO₂) and oxygen deficit during low-level constant work rate exercise using a bicycle ergometer in 28 patients with type 2 diabetes mellitus and compared their data to that for 25 age-and gender-matched controls and 21 patients with chronic heart failure (CHF). We also measured peak VO₂ and anaerobic threshold (AT) during graded exercise. Despite the lack of a significant difference in peak VO₂ and AT among the 3 groups, diabetic patients had a longer τ(38±13s) than controls (27±8s, p<0.005). The τ in diabetic patients was even somewhat longer, though not significantly so, than that in CHF (36±10s). Diabetic patients also had a 1.5-fold increase in oxygen deficit compared to controls (306±120vs. 227±103ml/kg, P<0.05), which was somewhat greater, though not significantly so, than that in CHF (281±93ml/kg). These results suggest notable abnormalities in the cardiopulmonary response at the onset of low-level exercise in patients with type 2 diabetes who have no cardiovascular complications. This data may reflect impairment in both oxygen delivery to skeletal muscles and in oxygen utilization by skeletal muscles, indicating that exercise training programs should begin with low-level exercise in untrained adults with type 2 diabetes mellitus even in the absence of cardiovascular complications.

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We studied changes of anti-islet autoantibody titers and clinical characterisics in 3 children with asymptomatic type 1 diabetes detected by urine glucose screening at school.
At screening, they did not require insulin treatment because glucose intolerance was relatively mild. They initially showed positive results in anti-islet antibodies, ICA, and-GAD antibody, and anti-IA-2 antibody. During follow-up of 4 to 14 months after diagnosis, and insulin serum C-peptide gradually deteriorated and insulin was eventually administered to all. Accompanied by the decline in endogenous insulin secretion, titers of anti-islet autoantibodies fluctuated, apparently reflecting the destruction of β-cells, the alteration of islet-antigens, and the progression of diabetes.
In a patient who started insulin treatment prior to reduced β-cell capacity early after diagnosis, the decline in antibody titers was slow, which may be associated with β-cell rest and antigen tolerance.

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[in Japanese]

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[in Japanese]

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