Whether a missense mutation in the β3AR gene predisposes Japanese to develop diabetes mellitus (DM), obesity (OB), hypertension (HT) and visceral fat syndrome was investigated. We determined the frequency of a mutation in β3AR by the polymerase chain reaction (PCR), amplifying genamic DNA from leucocytes, and by restriction-fragment-length-polyrnorphism after digesting the PCR products with Bst01, in 153 patients and 120 healthy volunteers. Seven of the 273 individuals demonstrated Trp64Arg homozygotes and the 64Arg allelic frequency was 0.19. The frequency of Trp64Arg homozygotes in diabetic patients (3.9%) was higher than that in healthy volunteers (1.7%), but the difference Was not statistically significant (P=0.18). The allelic frequency of mutation (Trp64Arg) was not significantly higher in the patients with HT or OB. No significant difference in the missense mutation rate among the average body mass indices in each genotype was observed. Abdominal computed tomography in 5 diabetics homozygous for the Arg/Arg mutation demonstrated that 3 of the 5 (all 3 were males, and only 1 was obese) were of the visceral fat type. This study thus indicates that a missense mutation in the β3AR, gene was not associated directly with DM, OB or HT but might possibly contribute to visceral fat syndrome.

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We evaluated diabetic neuropathy by measuring the current perception threshold (CPT). For measurement we used the Neurometer (Neurotron Inc., Baltimore, Md., USA), a device which measures CPT at 2k Hz, 250 Hz and 5 Hz, and also characterizes the nerve condition as hyperesthetic or hypesthetic. fihe CPT grade may be obtained by comparison with healthy control subjects at the same anatomie site. Forty-seven normal eontrols (C) and 73 patients with diabetes mellitus (DM) were studied. The diabetics included 15 without neuropathy (D), 43 with neuropathy (DN), and 15 With a histary of diabetic foot (DF). VVe compared the CPT at the right great toe with data from conventional neurophysiologic testing and clinical characteristics. Significant correlations were seen between conventional tests and CPT (r=0.33-0.65, p<0.01).No correlation existed between CPT and plasma glucose or HbA1c, The CPTs of DF patients were significantly higher than those of C, D, or DN subjects at all frequencies tested (p<0.01), and the CPT grades provided good discrimination between the three diabetic groups (p<0.05).CPT abnormalities most often were hyperesthesia in D (40.0%) and hypesthesia in DF (75.6%). We concluded that the CPT is reliable in clinical peripheral nerve evaluation and shouid be useful for assessing hyperesthesia in diabetic neuropathy.

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We investigated the family environment of senile non-insulin dependent diabetic patients and compared their glycated hemoglobin (HbA_1c) levels according to factars mentianed belaw. Ninety-four senile diabetics out of 304 outpatient diabetics were interviewed regarding their family environment: marital state, number of generatians of family living together, the person who cooks patient's food, etc. We classified and compared the patients' HbA_1c levels according to several environmental factors. The mean (±SD) HbA_1c levels were 7.1±1.2% in the patients of a onegenerationfamily, 7.2±1.2% in those of a two-generation family, and 6.5±1.1% in those of a three-generation family (one-generation vs. three-generation; P=0.04). HbA_1c levels were 7.1±1.2% in the patients whose daily meals were cooked by themselves, 7.1±1.1% by their spouses, and 6.6±1.2% by others (such as their daughters or daughters-in-law)(patients vs. others; P=0.09). There were no si, gnif icant differences in marital state (single vs. married=6. 8±1.2% vs. 7.1±1.2%; P=0.35) or gender (male vs. female=6.9±1.1% vs. 7.1±1.3%; P=0.41). These findings suggest that the family environmental, factors especially the number of generations living together, have an infiuence an the metabolic control in senile diabetic patients.

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In a prolonged hyperglycemic state, there is increased production of activated oxygen through the Maillard reaction by glycation of proteins and autooxidation of glucose. In this study, we used electron spin resonace (ESR) to measure total serum superoxide dismutase activity (T-SOD) and Cu, Zn-SOD activity. We also studied the correlation between glycated albumin (GA) and glycohemoglobin (HbA1c) values. The subjects were 66 randomly selected outpatients with diabetes and 54 age-and sex-matched healthy controls. The T-SOD activity was 3.2±0.8 U/ml (mean±SD) in the control group and was significantly elevated at 4.8±1.8 U/ml in the diabetic group. When stratified according to glycemic control, the activity was significantly higher in the poorly controlled group (HbA_1c≥7.0%, 40 subjects) at 5.2±1.9 U/ml compared to the well-controlled group (HbA1c<7.0%, 26 subjects) at 4.3±1.6 U/ml. The Cu, Zn-SOD activity was 1.2±0.5 U/ml in the control group versus 1.4±1.1 U/ ml in the diabetic group, indicating no significant difference between the two groups, but it was significantly higher in the poorly controlled group at 1.7±1.2 U/ml. There was a significant positive correlation between T-SOD activity and GA (r=0.257) and HbA1c (r=0.450) and between Cu, Zn-SOD activity and HbA_1c (r=0.587).

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The influence of hepatitis C virus (HCV) infection on diabetic retinopathy in 415 patients with NIDDM was studied. They were examined for anti-HCV antibody (HCV Ab) and divided into 2 groups, a positive HCV Ab group (n=45) and a negative HCV Ab group (n=370). The incidence of retinopathy in the positive HCV Ab group (46.7%) was significantly higher than that in the negative group (27.8%)(p<0.05), [nevertheless the equivalent diabetes controls in two groups]. Also, the patients in the positive HCV Ab group with diabetes of less 20 years' duration had a higher incidence of retinopathy. Quantitative evaluation of HCV infection revealed that the incidence of retinopathy in 16 patients with HCV-RNA≥5.0 Meq/ml (81.3%) was significantly higher than that in 20 patients with HCV-RNA<5.0 Meq/ml (30%)(p<0.05). In the measurement of intrinsic interferon-α-producing capacity, no significant difference was observed between patients with and without retinopathy. These results suggest that the amount of HCV-RNA would increase the incidence of retinopathy in NIDDM patients with chroni hepatitis C.

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A 76-year-old man was admitted to our hospital because of general fatigue and anorexia. Because he was losing weight progressively, total parenteral nutrition (TPN) was started with additional oral intake. Two weeks after the beginning of TPN, he developed recurrent hypoglycemic attacks 3-4 hours after meals. The hypoglycemic attacks disappeared after discontinuation of TPN. Impaired glucose tolerance with delayed insulin response was diagnosed by 75 g OGTT. The meal tolerance test during TPN revealed an excess of and delayed insulin secretion followed by postprandial hypoglycemia. Furthermore, the glucagon response to insulin-induced hypoglycemia was impaired. Chronic infusion of glucose by TPN stimulated the pancreatic B cell and potentiated the insulin response to a meal. The hypersecretion of insulin subsequently induced hypoglycemia probably by the addrtive effect of delayed insulin secretion and impaired glucagon response. Both excess insulin secretion and postprandial hypoglycemia disappeared after discontinuation of TPN. In conclusion, food intake during TPN treatment in patients with impaired glucose tolerance should be carefully monitored for blood glucose level to detect possible postprandial hypoglycemia.

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A 74-year-old man with slowly progressive insulin-dependent diabetes mellitus (IDDM) was admitted to our hospital. He suffered from gastric cancer and was treated by total gastrectomy one year earlier. Since then, postprandial hyperglycemia followed by preprandial hypoglycemic attacks impaired the control of blood glucose levels, which was not corrected by intensive insulin therapy with food intake divided into 6 times per day. Introduction of an α-glucosidase inhibitor (α-GI, voglibose, 0.6 mg per day) in combination with the intensive insulin therapy resulted in well controlled plasma glucose levels, and the hypoglycemic attacks subsided. Oral administration of 75 g of sucrose after treatment with regular insulin (7 IU, sc) with or without voglibose (0.2 mg, po) administration revealed that voglibose corrected the hyperglycemia at 90 min, with no hypoglycemia at 180 min. Hemoglobin Alc levels improved from 9.6% to 7.8%. These findings suggest that α-GI is a useful supplement for the control of plasma glucose by intensive insulin therapy in a totally gastrectomized patient with IDDM.

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[in Japanese]

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We have studied the effect of troglitazone on ATP-sensitive K⁺ (KATP) channels. Pancreatic β-cell type and cardiac type KATP channels were reconstituted in COS1 cells by heterologously expressing SUR1 plus Kir 6.2 and SUR2 plus Kir 6.2, respectively. Troglitazone inhibited ⁸⁶Rb⁺ efflux through both KATP channels in the presence of metabolic inhibitors. This suggests that troglitazone might modify various cellular functions regulated by KATP channels including insulin secretion and cytoprotection in cardiac ischemia by inhibiting the channels.

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