NIDDM patients who are positive for GAD antibody are at risk of developing IDDM in the future. Therefore, we measured GAD antibodies and HLA in NIDDM patients, and investigated the clinical significance of GAD antibody. We measured GAD antibodies by RIA and class II HLA by DNA typing in 901 NIDDM patients. GAD antibody-positive (>5U/ml) patients accounted for 2.8% in the diet group: D (n=317); 3.9% in the SU group (n=413); and 7.6% in the insulin therapy group: Ins (n=161). After 10-12 months, when we reexamined GAD antibody-positive patients, all 9 patients in the D group, 10 of 16 patients in the SU group, and 7 of 12 patients in the Ins group were negative for GAD antibody. Concerning groups D and SU, the fasting serum CPR level was significantly low and the levels of fasting blood glucose and HbA1c were significantly high in patients who remained positive for GAD antibodies compared with those in patients who became negative for GAD antibody. Moreover, serum CPR levels were markedly decreased in 3 patients who remained positive for GAD antibodies and were continuously treated with SU. HLA, DR and DQ haplotypes of GAD antibody-positive NIDDM patients were different from those with acute onset IDDM and slowly progressive IDDM. These findings suggest that determination of the time course of GAD antibody development is useful for determining the onset of IDDM and the selection of treatment.

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Long-term prognoses were compared in individuals with and without glucose intolerance in the general population of two rural Japanese communities, Tanno and Sobetsu. A prospective cohort study of 1, 996 men and women between the ages of 40 and 64 years at the baseline examination was conducted over an 18-year period, from 1977 to 1995. During this follow-up study, 177 people dropped out, leaving 1, 819 cases available for statistical analysis. In the first year of the study, 885 cases were diagnosed as normal glucose tolerant (NGT), 798 cases as borderline diabetic (BDM), and 113 cases as diabetic (DM). Of the 1, 819 subjects, 256 died during the 18-year period. The main cause of death in glucose intolerant (BDM&DM) subjects was malignant neoplasms, followed by cardiovascular disease, and cerebrovascular disease. The survival curve for subjects with glucose intolerance was lower than for those without glucose intolerance. Cox's hazard regression model revealed a significant association between glucose intolerance and fatal events (relative risk 1.43: 95% CI 1.02-2.00) only in men. The survival curve for the end point of cardiovascular mortality in subjects with glucose intolerance was lower thant that in those without glucose intolerance (p<0.05).

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The clinical significance of measuring serum thrombomodulin (TM) in diabetic mellitus was assessed on the basis of the results of a 5-year follow-up study. The quality of glycemic control strongly affected the trend of TM levels in the group of patients who had high TM levels at the beginning of this study. This finding suggested that patients with severe damage to endothelial cells are considerably affected by the quality of glycemic control. In the high-TM group, a high percentage of patients had diabetic nephropathy or retinopathy throughout the study, and when glycemic control was unimproved, severe complications were frequently observed. Among the cases with coronary risk factors, such as hyperlipidemia and/or hypertension, abnormal findings were significantly more frequent in the high-TM group, as shown by dipyridamole-loaded ²⁰¹T1 myocar dialscintigraphy, and the same finding was also obtained in the cases without chest pain or ischemic findings, as shown by electrocardiograms when the patients were in stable condition. Thus, serum TM seemed to be a useful warnign marker not only for microangiopathy, but for myocardial ischemia, especially silent myocardial ischemia, in diabetic patients.

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[in Japanese]

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A 66-year-old man with an 8-year history of poorly controlled non-insulin-dependent diabetes mellitus complicated by peripheral sensory neuropathy, retinopathy, and nephropathy, was hospital izedfor control of his diabetes. Marked painless swelling of the right knee gradually developed over a period of five years. A radiograph of the right knee showed findings consistent with a diagnosis of Charcot's neuroarthropathy. On admission, metabolic bone markers of bone resorption were increased and markers of bone formation were decreased. The patient became well after glycemic control and treatment with bisphosphonates and aldose reductase inhibitor for 9 months, and the bone marker values after treatment were significantly improved compared with their levels on admission. These observations suggested that measurements of metabolic bone markers are of value in monitoring the control of diabetic bone complications.

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To evaluate the efficacy of acarbose (A) and glibenclamide (G) in NIDDM, we examined the effect of A and G on visceral fat accumulation and insulin resistance in NIDDM patients. We divided 41 NIDDM patients who had not received any diabetic medication into two groups. The 14 mild cases were treated with A (150-300mg/day), and the others were treated with G (1.25-7.5mg/day) and followed for 24 weeks. We evaluated visceral fat area (VF), subcutaneous fat area (SF), and the VF/SF ratio by abdominal CT at the level of the umbilicus. Insulin resistance was evaluated by the oral glucose tolerance test. Body mass index (BMI) after treatment in the A group had decreased significantly (p<0.05) compared to before treatment, but did not change significantly in the G group. The VA (139.4±67.0cm²) and the VA/SA ratio (1.000±0.428) after treatment in the G group were significantly (p<0.05) increased compared with the VA (102.4±52.3cm²) and the VA/SA ratio (0.770±0.444) before treatment. They were also decreased in the A group, but not significantly. An oral glucose tolerance test after treatment showed a significant decrease in plasma glucose levels (PG) in both groups and a significant increase in plasma insulin level (PI) after glucose load in the G group, but a decrease in PI in the A group compared with before treatment. In conclusion, gliben-clamide treatment resulted in significant worsening of visceral fat accumulation and hyperinsulinemia in NIDDM patients, whereas acarbose treatment resulted in significant improvement.

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We report a case of severe troglitazone (TG)-induced liver injury in an NIDDM patient without diabetic complications. The patient was a 48-yr-old woman. She was orally administered 400mg of TG per day without other medication. Three months after the administration, she had increased serum levels of GOT (301IU/l) and GPT (571IU/l) without symptoms. Two weeks later, general fatigue developed with a further increase in serum GOT (471IU/l) and GPT (826IU/l) with normal serum bilirubin levels. Viral markers and autoantibodies were negative. The increased variables gradually decreased and were normalized 30 days after the treatment was stopped. This indicates that liver injury may gradually occur as a toxic effect of TG on hepatic cells. We should check the liver function at least once a month during the adminstration to prevent fulminant hepatitis. If liver injury develops, the treatment should be immediately stopped.

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The Glycohemoglobin (GHb) Standardization Committee conducted the fifth external quality assessment to evaluate the interlaboratory variation of GHb values measured by various methods including HPLC, various kinds of immunoassay (IMA) and affinity chromatographic methods in 1, 901 institutes throughout the country using four samples {2 concentrated whole blood (M·A·P, Nisseki) and 2 lyophilized hemolysate}.
We got the following results,
1) The CVs as indices of the interlaboratory variation ranged from 4.5 to 5.7% when all data were combined. It was different depending on an analytical method used:HPLC, 3.1-4.8%; IMA, 5.2-6.4%; Affinity, 5.2-6.0%.
2) The means of the measured values were different depending on a method used. The value measured by the affinity chromatographic method was significantly higher than the others.
The CVs of all values except for those measured by the affinity chromatographic method ranged from 4.4 to 5.4%, which were good enough from a clinical point of view.
3) The CVs of the GHb values corrected with the assigned values of a new calibrator candidate were much smaller than those without correction, except for that obtained by the affinity chromato graphicmethod. The new calibrator candidate appeared not to be suitable for correction of the values measured by the affinity method.
4) Percent distributions of participants classified by the upper value of their reference interval for GHb were as follows:≤5.8%, 77.6%; 5.9-6.0%, 14.7% and ≥6.1%, 7.7%.
In conclusion, the interlaboratory difference in GHb measurement was reduced to a clinically permissible level.

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