Perturbation of blood glucose control related to the menstrual cycle has been reported in women with insulin-dependent diabetes mellitus (IDDM). We examined insulin sensitivity using the euglycemic-hyperinsulinemic clamp technique by measuring body weight, C-peptide, estradio1, progesterone, and tumor necrosis factor-α(TNF) levels, during thefollicular and luteal phase of the menstrual cycle in 8 female patients with IDDM who had regular menstrual cycles. Four patients (50%) needed an extra dose of insulin in the luteal phase, because of worsened glycemic conditions.
The glucose infusion rates (GIR) of all 8 patients were3.79±0.66 (mean±SD) mg/kg/min in the luteal phase, and 4.93±1.44mg/kg.per minute in the follicular phase, which showed no statistically significant difference (P=0.08). Three of 8 patients showed an increase of more than 20% in GIR, and 5 patients showed anincrease of 20% or less in the follicular phase during which estradiol and progesterone significantly decreased. Two of 4 who needed the extra insulin dose in the luteal phase showed a GIR increase in the follicular phase. TheTNF-α levels during both cycles in all 8 patients remained within the normal range and showed no difference between the cycles. In conclusion, changes in insulin sensitivity related to the menstrual cycle demonstrated individual variations anddid not correspond to changes in GIR.

View full abstract

We conducted multicenter trials to assess the reproducibility of nerve conduction studies for use in future drug development for treatment of diabetic polyneuropathy (DPN).
All measurements were repeated twice at intervals of 1 to 4 weeks in 132 healthy subjects (63 men) and 172 patients (99 men) with DPN.Using a standardized method, 32 centers participated in the control study, and 65 in the DPN study.Motor nerve conduction studies consisted of stimulating the left median and tibial nerves and measuring amplitude, terminal latency (TL), and minimal F-wave latency (FWL).For sensory nerve assessment, amplitude was recorded antidromically after distal stimulation of the left median and sural nerves.We also calculated motor conduction velocity (MCV), F-wave conduction velocity (FCV) and sensory conduction velocity (SCV).
The range of relative inter-trial variation (RRIV) and intraclass correlation coefficient (ICC) were used as an index of reproducibility.Of all the measurements, FWL yielded the highest ICC with the smallest RRIV for both median and tibial nerves in healthy subjects as well as in DPN.We conclude that median and tibial FWL provide the most reproducible measure ments for sequential nerve conduction studies in multicenter trials of diabetic polyneuropathies.

View full abstract

We studied the characteristics of HLA-associated genetic factors in a Japanese population with childhood-onset IDDM. HLA-DRB 1, DQA 1 and DQB 1 genotypes in 90 diabetics patients were examined by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP). HLAA, B, C phenotypes in 55 diabetic patients were also examined by the lymphocyte cytotoxicity test (LCT). Compared with healthy controls, patients showed significant increases of DRB 1*0405, 0901; DQA 1*0301=2; DQB 1*0302, 0303 and A24; B54, B61; C1, C3. However, DRB 1*0403, 0803, 1401, 1405, 1501, 1502; DQA 1*0101=4, 0102, 0103, 0401; DQB 1*0301, 0502, 0503, 0601, 0602=3 and All, A31; C9, C10, C11 were obgerved less frequently in patients than in controls. The significant increases of B54, B61, C1, C3 in patients were due to a strong linkage disequilibrium with A24, and the association of A24 with IDDM was independent of DRB 1*0405 and *0901. Therefore, A24 confers an additional susceptibility to DRB 1. With regard to age distribution at clinical onset and the interval from clinical onset to initiation of insulin therapy, A24 was associated with IDDM in the younger age-group (0-10 years) and in the acute clinical-onset type. These findings suggest that specific HLA-class I antigens are associated with clinical heterogeneity such as age-at-onset and clinical onset forms of IDDM in this Japanese population.

View full abstract

Endocrine and metabolic effects of glucagon as a premedication in endoscopic examinations of the upper gastrointestinal tract of diabetic patients were investigated. We measured the levels of blood glucose, immunoreactive insulin, growth hormone and adrenocorticotropic hormone after intramuscular injection of glucagon in the diabetic patients (n=7) and in non-diabetic subjects (n=10) before upper gastrointestinal endoscopy. Scopolamine butylbromide was used in a control study to evaluate and compare the effects of glucagon.
The maximal increase in the levels of blood glucose after intramuscular injection was about 96 mg/dl from basal in the diabetic patients and 55mg/dl from basal in the non-diabetic subjects, and the increase after 120 minutes was 39.0mg/dl in diabetic patients and -2.1mg/dl in the nondiabetic subjects. However, there was no change in blood glucose levels after intramuscular injection of scopolamine butylbromide in both diabetic patients and non-diabetic subjects. Serum levels of immunoreactive insulin changed in parallel with the levels of blood glucose. There was a significant difference in the serum levels of growth hormone between glucagon and scopolamine butylbromide injections. There was no statistical difference in serum levels of adrenocorticotropic hormone between glucagon and scopolamine butylbromide injections.
In one of ten non-diabetic subjects injected with glucagon, mild asymptomatic reactive hypoglycemia (41mg/dl) was observed but no therapy was required. No other untoward effects of glucagon were noted in either diabetic patients or non-diabetic subjects.
Thus, glucagon can be safely used in diabetic patients as a premedicative drug for an endoscopic examination, especially in cases in which anticholinergic drugs are contraindicated.

View full abstract

Only a few studies have investigated the range of fasting plasma glucose (FPG) in which insulin resistance as measured by homeostasis model assessment (HOMA) and by euglycemic clamping might highly correlate. To determine this range, we attempted to determine whether the correlation coefficient between the HOMA-estimate of insulin resistance (HOMA-IR) and the reciprocal of glucose infusion rate (GIR) during euglycemic clamping changes with an increase in FPG in patients with obese and non-obese type 2 diabetes mellitus (DM). We measured HOMA-IR (fasting glucose [mg/dl]×fasting insulin [μU/m/]/405) and GIR (mg/kg/min) during 90-minute euglycemic (80mg/dl) and hyperinsulinemic (63±18μU/ml) clamping studies in 42 patients with type 2 DM. Patients were 27 men and 15 women, 57.3±12 years of age, and either obese (body mass index [BMI]≥25kg/m², 17 patients) or non-obese (BMI≤25kg/m², 25 patients). Their average FPG was 140±38mg/dl. In 15 patients (FPG<170mg/dl, BMI≥25kg/m²), HOMA-IR and 1/GIR were highly correlated (r=0.82, p<0.01). In this range of FPG, fasting insulin was significantly correlated with both 1/GIR and HOMA-IR, however, BMI, TG and TCho were not correlated with either 1/GIR or HOMA-IR. Age, sex and oral hypoglycemic agent also had no association with 1/GIR and HOMA-IR.
In conclusion, these results suggest that HOMA-IR is a useful index for determining insulin resistance at the FPG range of 80-170 mg/dl in patients with obese type 2 DM.

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

We report the case of a pregnant woman who developed diabetic ketoacidosis (DKA) at 27 weeks of gestation as first presentation of diabetes mellitus (DM). The patient was a 37-year-old woman without past or family histories of diabetic mellitus. Previous routine urinalysis had been negative for urine sugar. She was admitted to our hospital at 27 weeks of gestation with a 5-day history of polydipsia. On admission, she was orientated, but heavy ketonuria and glycosuria were present, random plasma glucose was769mg/dl, arterial blood was pH 7.271, and base excess was -13.9 mEq/l, confirming metabolic acidosis. She was diagnosed as having DKA. Routine therapy for DKA was commenced, and subsequently, she was treated with intensive insulin therapy. She was able to deliver a 3, 665g infant at 40 weeks of gestation. The infant had no complications or malformations. Tests for islet-cell antibodies (ICA), antiglutamic acid decaboxylase antibodies (GAD-Ab) and various antivirus antibodies were negative. Laboratory determination of HLA type revealed B 54-DR 4 haplotype. Insulin-dependent diabetes mellitus (IDDM) was suggested because endogenous insulin secretion was severely reduced urinary CPR was 10.3, 14.4μ/day and ΔCPR6' during intravenous 1mg glucagon load was 0.2ng/ml. A daily dose of 29 units of insulin was needed to maintain a normal glucose level. This case is noteworthy as a report in Japan of successful treatment and delivery of a patient with DM and DKA in pregnancy.

View full abstract

Thyrotoxic crisis in a 42-year-old woman with mitochondrial diabetes mellitus is reported. She was diagnosed with juvenile diabetes mellitus during the first pregnancy at the age of 24, and has since been treated with insulin therapy. Her mother also had diabetes mellitus. The patient noticed a swelling in her anterior neck in November 1996. She visited our hospital due to slight fever, frequent vomiting and body weight loss on May 1, 1997. She had short stature, hearing loss, tachycardia, and somnolence without exophthalmos or tremor. Serum thyroid hormone levels were markedly increased, where as serum thyroid stimulating hormone (TSH) was suppressed. Antimicrosomal antibody and TSH binding inhibitory immunoglobulin were strongly positive. Thecefore, thyrotoxic crisis was diagnosed, and dexamethasone and propranolol were administered. Serum Cpeptide was undetectable, but antibodies for glutamic acid decarboxylase and islet-cell antibody were both negative. Mitochondrial DNA analysis revealed a point mutation of A 3243 G. The present case suggests that thyrotoxic crisis could develop even though mitochondrial function is suppressed due to mitochondrial gene mutation.

View full abstract

[in Japanese]

View full abstract