To investigate changes in tissue hydration and structural changes in diabetic patients using an MRI scanner (SIGNA 1.5-Tesla) with an extremity coil, spin-lattice relaxation time (T₁ value), cross-sectional area, and coefficient of variation (CV value) of signal intensities of the sural nerve, respectively, were determined as indexes of nerve edema, nerve swelling or shrinkage and structural change, and were calculated in normal subjects (normal group, n=7) and diabetic patients (diabetic group, n=33). T₁ value of the sural nerve, but not muscle or adipose tissue, was significantly prolonged in diabetic group (1000±273 vs 702±324 msec, P<0.01), indicating the prescnce of nerve edema in the diabetic group. There were no differences in cross-sectional area. CV values were significantly higher in the diabetic group (P<0.05). T₁ values were positively correlated with glycemic control (fasting plasma glucose; r=40, HbA₁c; r=0.35)(P<0.05) and negatively correlated with motor nerve conduction velocity (r=-0.42, P<0.01). These findings indicate that MRI is of value in the objective evaluation of structural changes in diabetic neuropathy.

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Since aerobic exercise is anappropriate physical exercise for diabetic patients, we measured anaerobic threshold (AT) in 576 subjects, 384 males and 192 females, with non-insulin-dependent diabetes mellitus (NIDDM). We examined relationships between AT and sex, age, diabetic therapy, and blood glucose. As a control group, we also measured AT in 47 healthy males and 49 healthy females with normal glucose tolerance. The oxygen intake (ml/min/kg) and work rate (watt) of the NIDDM patients at the AT decreased with age and tended to remain lower than in the healthy controls. The heart rate at the AT was significantly negatively correlated with age in both males and females, corresponding to 63% of the presumed maximum heart rate for the male patients and 65% for the female patients. Systolic blood pressure at the AT tends to rise with age. For most patients, the intensity of exercise was in the range of “fairly light” (level 11) to “somewhat hard” (level 13) accoring to the index “rating of perceived exertion” (RPE), We found no specific relationship between AT, and diabetic therapy or blood glucose. In conclusion, AT is considered to be an effective index of the aerobic intensity level.

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In order to evaluate risk factors, other than hypertension, for the development of established nephropathy in non-insulin-dependent diabetes, thirty-eight patients with overt proteinuria were evaluated retrospectively for a consecutive three-year period. All subjects were under 70 years of age and had serum creatinine (Cr) levels within the normal range and serum albumin (Alb) levels over 3.0g/dl at the start of the study. Subjects with non-diabetic renal disease or urinary tract infection were excluded. Mean hemoglobin A₁ (HbA₁), serum total cholesterol (T-CHO) and Alb values over the 3-year period were calculated from measurements of these variables every month for each subject. The patients were divided into two groups, matched for clinical variables, according to average change in 1/Cr (Δ1/Cr). A significant (p<0.01) decrease in 1/Cr was found in the group below the mean Δ1/Cr value (group II), but no significant change was found in the other group (group I). No significant differences in systolic or diastolic blood pressure were detected either between groups or within groups. In group II, Δ1/Cr was invertedly correlated with HbA₁ (r=-0.49, p<0.05) and T-CHO (r=-0.52, p<0.05), and positively correlated with Alb (r=0.77, p<0.01). Moreover, principal component analysis obtained from HbA₁, T-CHO and Alb on changes in Δ1/Cr showed that HbA₁ and Alb were predominant in the first component, and that T-CHO was predominant in the second component.
These findings suggest that hyperglycemia and hypoalbuminemia may be the major contributory factors, followed by hypercholesterolemia, in the development of established diabetic nephropathy.

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Many studies have indicated that Lp (a) may be an independent risk factor for ischemic heart disease (IHD). Although elevation of Lp (a) in diabetes, especially in subjects with nephropathy, has also been reported, the significance of Lp (a) as a risk factor for diabetic angiopathy is still unclear. In the present study, we determined Lp (a) concentrations in 596 NIDDM patients, and assessed the clinical implications of Lp (a) in subjects with arteriosclerosis obliterans (ASO). ASO was found in 78 patients (prevalence=13%). The patients with ASO tended to be older, to have longstanding DM, lower BMI, reduced HDL-C and ApoAl, and increased Lp (a) levels. ASO was also frequently associated with hypertension, IHD, and nephropathy. Most of the patients with ASO were treated with insulin. Since nephropathy is associated with elevated Lp (a) levels, when adjusted for nephropathy plasma Lp (a) levels were not correlated with ASO. Discriminant analysis demonstrated that aging, nephropathy, and hypertension, but not Lp (a), may be independent risk factors for ASO in NIDDM.

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A follow-ups tudy with a mean observation period of 15 years was performed to examine the natural history of diabetic patients in Japan. The subjects were 1, 939 non-insulin-dependent diabetic (NIDDM) patients registered in our institution during 1960-1979, of whom 1, 000 (51.5%) were alive, 880 (45.4%) deceased and 59 (3.0%) untraceable at the end of 1993. Mortality per 1, 000 person-years among these subjects increased from 28.94 in 1960-1984 to 35.74 in 1985-1993, but the O/E ratio (ratio of observed over expected number of deaths) decreased from 1.77 to 1.52 for the corresponding periods, suggesting an improvement in the prognosis of diabetic patients, except for the group with age at entry≥65 year, in which the O/E ratio increased. Changes in O/E ratio by cause of death were examined. Among patients with age at entry<65 years, a decrease in O/E ratio for all causes, malignant neoplasms, cerebrocardiovascular and renal disease was observed, but no significant change was found for ischemic heart disease. By contrast, among patients aged≥65years, the O/E ratios for all causes, malignant neoplasms, cerebrocardiovascular and renal disease increased, and among these an increase in ischemic heart disease and cerebrovascular disease was noted. The O/E ratio for renal disease tended to decrease regardless of age at entry. These findings considered as a whole imply changes in the structure of the cause of death in diabetic patients in Japan.

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We report a case of dorsal pancreatic hypoplasia complicated by common bile duct dilatation and insulin-dependent diabetes mellitus in a 25-year-old woman. The patient was admitted to our hospital because of thirst and fatigue. She was alert at admission, but laboratory findings revealed a fasting blood glucose level of 332mg/dl, ketosis and liver dysfunction (GOT 61u/l, GPT 68u/l, ALP 654u/l, LAP 582u/l). Abdominal ultrasonography revealed common bile duct dilatation and endoscopic retrograde cholangiopancreatography showed congenital hypoplasia of the dorsal pancreas with common bile duct dilatation. As endogenous insulin secretion was severely decreased based on the results of urinary c-peptide secretion and glucagon loading test, intensive insulin therapy was prescribed for glycemic control. Congenital hypoplasia of the dorsal pancreas associated with diabetes mellitus has been reported in 19 cases throughout the world. According to our knowledge, this report is the first of type I diabetes with congenital hypoplasia of the dorsal pancreas and common bile duct dilatation describing histopathological evidence of islet hypoplasia without insulitis.

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We report a 72-year-old woman with diabetes mellitus who complained of dizziness. She was treated with oral hypoglycemic agents initially at 60 years and later with insulin at 71 years. Her HbA₁c level was 6.5%, and urinary CPR excretion was 24.5-56.2μg/day. There was no micro-or macro-angiopathy. The patient had severe macrocytic hyperchromic amemia, and her serum LDH levels, predominantly I type isozyme, were elevated. Bone marrow showed megaloblastic change with Howell-jolly dodies. The serum vitamin B₁₂ concentration was low, but serum iron, ferritin, folic acid and UIBC levels were within the normal range. Intrinsic factor antibody, parietal cell antibody, and islet cell antibody and glutamic acid decarboxylase were positive, but other autoantibodies were negative. B54 (22) and DR4 haplotypes were positive. Dizziness and anemia were improved by administration of vitamin B₁₂. These findings indicated a diagnosis of diabetes mellitus with pernicious anemia, which might be causally related to autoimmunity. Reports of patiemts with both diseases have been rare in Japan, and most of the cases were in middle-age or elderly women who had no deficiency of insulin secretion, the same, as in our case.

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A 30-year-old woman, in whom diabetes mellitus was diagnosed at 24 years of age, was initially managed with diet alone. The need for insulin to control diabetes was noted at age 27. She became pregnant at age 29 years and delivered at age 30. Five months after delivery, she suffered a speech disturbance which resolved rapidly without treatment. Four months later, blepharoptosis developed in her right eye, and a diagnosis of myasthenia gravis was made based on the presence of anti-acetylcholine-receptor antibody, the waning phenomenon upon stimulation of the right orbicularis oculi muscle, a positive Tensilon test and identification of a thymoma on chest CT. Her diabetes was of the slowly progressive IDDM type, because her disease developed at an early age and was not associated with obesity or a family history of diabetes. Progressive decreases in insulin secretion and GAD65 antibodies were observed.
This woman manifested slowly progressive IDDM, after a five years disease duration, associated with myasthenia gravis. Diabetic patients with myasthenia gravis are relatively rare. Eleven cases have been reported since 1979 in Japan. Of the total 12 cases, including our case, seven had IDDM and two had NIDDM. HLA-DR4 was observed in three cases. The association between diabetes and myasthenia gravis remains to be clarified, but the preliminary data from these 12 cases suggest that myasthenia gravis is more often associated with IDDM than with NIDDM. This implies an immunological association between diabetes and myashenia gravis.

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