We compared the insulin sensitivity index (SI) measured by euglycemic clamping with the glucose infusion rate (GIR) and fasting insulin concentration. Euglycemic clamping was conducted at 2 insulin infusion rates (1.12 mU/kg/min and 2.24 mU/kg/min) in 45 patients with type 2 diabetes mellitus treated with diet or oral hypoglycemic drugs. Patients were 29 men and 16 women, 58±11 years of age, and either obese (body mass index [BMI] 25 kg/m², 17 patients) or nonobese (BMI<25 kg/m², 28 patients).
In obese patients, greater peripheral insulin concentrations (68±18 μU/ml, 133±43 μU/ml) than those of nonobese patients (55±13 μU/ml, 98±27 μU/ml) were required to maintain a quantitatively equivalent GIR (3.8±1.4 mg/kg/min, 7.1±2.1 mg/kg/min) to those of nonobese patients (4.1±1.8 mg/kg/min, 6.7±2.1 mg/kg/min). SI of obese patients (0.94±0.73±10^-3 dl /kgμmin/μU/ml) did not differ from that of nonobese patients (0.92±0.57±10^-3dl /kgμmin/μU/ml).
SI and GIR/IRI correlated (r=0.52, p<0.05) in obese patients, but not in nonobese patients. Obese patients had much higher fasting insulin (8.9±3.2 μU/ml) than that of nonobese patients (6.9±2.4 μU/ml) and fasting insulin concentration correlated with the reciprocal of SI (r=0.52, p<0.05) or reciprocal of GIR (r=0.69, p<0.01) at a fasting plasma glucose of<170 mg/dl.
In conclusion, we showed that a while GIR or SI of obese type 2 DM subjects did not differ from that of nonobese DM subjects, insulin resistance was increased more in obese patients than in nonobese patients. Peripheral insulin concentration must therefore be cousidered during clamping for evaluating SI, b) Fasting insulin concentration is useful as a surrogate for GIR or SI in obese type 2 DM subjects when insulin-glucose feedback is operative.

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This prospective study was conducted to investigate the approriate cutoff titer of GAD antibody (GADA) to predict insulin-requirement in diabetic patients with non-insulin-dependent diabetes mellitus. Fifty-four diabetic patients with non-insulin-dependent diabetes mellitus were registered and followed up for a mean of 4 years. All the patients were assessed for positivity of autoantibodies, HLA-DR type, serum C-peptide concentration, and body mass index (BMI) at the time of registration. Patients who required insulin showed lower serum C-peptide concentrations, lower BMI, a higher frequency of the HLA-DR 4 allele and higher titers of GADA. Autoantibodies other than GADA (insulin autoantibody and IA-2 antibody) were detected only in the patients who required insulin. The ROC plot for GADA revealed that 10 U is the most appropriate cutoff titer to predict insulin-requirement (accuracy 88%); the serum C-peptide concentrations and BMI showed only about 60% accuracy at the maximum for such prediction. Logistic regression analysis showed that positivity for the DR 4 allele could also be a useful marker for eventual insulin-requirement (p = 0.07), in addition to high GADA titers. In conclusion, the most appropriate cutoff titer of GADA to predict insulinrequirement in diabetic patients with non-insulin-dependent diabetes mellitus among Japanese is suggested to be 10 U (Cosmic).

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We studied the relationship between the degree of intima-medial thickness (IMT) of carotid arteries, antibody against glycated and oxidized low density lipoprotein (Ab-g1cLDL or Ab-oxLDL) and other risk factors for atherosclerosis and microangiopathy in patients with type 2 diabetes, 43 climacteric patients were compared to 20 control subjects. As an index of atherosclerosis, we measured the average thickness of 6 portions of the carotid artery wall. Ab-g1cLDL and Ab-oxLDL were evaluated by ELISA. Mean IMT, HbAic, total cholesterol, triglyceride, LDL-cholesterol, apolipoprotein B, lipoprotein (a), Ab-g1cLDL, urinary albumin excretion rate (AER), and systolic blood pressure (SBP) were significantly higher in diabetics than those in controls. Logistic regression analysis indicated that glycemic controls and duration of diabetes contributed to the degree of IMT in diabetics with retinopathy. AER was a significantly related to SBP and BMI in diabetics. Ab-oxLDL was lower in diabetics than in controls. Although no evidence of a concurrent increase in Ab-g1cLDL and Ab-oxLDL was found, we assume that hyperglycemia accerelated changes in LDL and contributed to macro- and microangiopathy in type 2 diabetes.

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We studied factors contributing to troglitazone and metformin efficacy in type 2 diabetes mellitus. Troglitazone and metformin administration for 24 weeks similarly decreased fasting plasma glucose (FPG) and HbA_1c. In simple linear regression analysis, the reduction in FPG correlated significantly with the insulin resistance index of homeostasis model assessment (HOMA-R), fasting plasma insulin (IRI), age, body mass index, and FPG in troglitazone and with FPG, HbAic, HOMA-R, duration of diabetes, and age in metformin. Stepwise multiple regression analysis showed that pretreatment HOMA-R and FPG contributed most strongly to FPG reduction in troglitazone and metformin. In the troglitazone group, subgroups with higher pretreatment IRI had greater FPG reduction, whereas subgroups with 160 mg/dl or above pretreatment FPG showed no additional improvement. These results suggest that troglitazone and metformin are equally beneficial in glycemic control in diabetes mellitus and that more potent hypoglycemic action can be expected in patients with higher HOMA-R accompanied by higher IRI in troglitazone and with higher FPG in metformin.

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A 20-year-old woman visited the dermatology clinic April 1997 with a 2-month history of reddish papules, reticular erythema and pigmentation on the trunk. She had lost 12 kg before the visit. Serum 3-hydroxy-butyric acid was elevated (3 OHBA, 3, 450 urmol/l) and prurigo pigmentosa was diagnosed. Although skin eruptions ameliorated due to the minocycline, polydipsia, polyuria, and body weight loss progressed. Diabetic ketoacidosis (DKA) was diagnosed in October based on hyperglycemia (450 mg/dl) and further elevated 3 OHBA (8, 670 μmol/l). Since fasting serum C-peptide was 0.8 ng/ml and anti-GAD Ab was 117 U/l, she was thought to have type 1 diabetes, and insulin therapy was started. This is, to our knowledge, the first case of prurigo pigmentosa developing in association with DKA to be treated successfully by minocycline. This effect of minocycline suggests that prurigo pigmentosa is pathogenetically dependent on ketosis.

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A 63-year-old man was admitted to our hospital with general malaise. He had had diabetes mellitus since the age of 45 and was treated using insulin therapy. He had hypokalemia, metabolic acidosis without ketosis, and hypothyroidism. Further laboratory studies showed distal renal tubular acidosis and Fanconi syndrome. Autoantibodies to the thyroid were positive, but, autoantibodies to glutamic acid decarboxylase and islet cells were negative. His insulin secretion was very disturbed. He was suspected of having slowly progressive insulin-dependent diabetes mellitus. Diabetes mellitus with chronic thyroiditis, distal renal tubular acidosis, and Fanconi syndrome is very rare. It is of interest that this man had diabetes mellitus and rare autoimmune syndromes.

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A 45 year-old Japanese female with newly diagnosed diabetes mellitus complicated by Fournier's gangrene is described. Minor trauma a few days before led to the development of cellulitis of the left foot and perineal necrotizing fasciitis. The patient presented with diabetic ketoacidosis. The post-prandial plasma glucose and HbA1c levels were 742 mg/dl (41.2 mmol/l) and 12.4%, respectively. Peripheral neuropathy, background retinopathy as well as microalbuminuria were noted. The urinary C-peptide excretion level was 3.3 μg/day even after glycemic control was achieved by vigorous insulin administration. The peak serum C-peptide level following glucagon provocation was 0.8 ng/ml. Tests for both anti-porcine glutamic acid decarboxylase antibody and anti-islet cell antibody were negative. Anti-IA 2 antibody was not detected either. Hearing loss was not present and there was no history of diabetes mellitus in the mother. Cultures of the perineal necrotic tissue revealed S. faecalis, S. epidermidis, K pneumoniae, C. albicans and C. glabrata, while S. aureus was grown from the pus obtained from the foot wound. Antibiotic therapy and thorough debridement combined with reconstructive procedures brought about a favorable outcome. This is an unusual case of Fournier's gangrene from three aspects: 1) simultaneous infections of different sites caused by different microorganisms, 2) the diagnosis in a female diabetic, and 3) requirement of long-term insulin therapy to achieve near normoglycemia.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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