The cross-correlation coefficients of glycated albumin (GA) and hemoglobin (GHb) with the plasma glucose level in the preceding period were analyzed theoretically by introducing random fluctuation into daily plasma glucose variation. Computer simulation showed that GA and GHb adequately represented slow plasma glucose fluctuation in stable diabetic patients, but did not reflect rapid plasma glucose fluctuation in unstable diabetic patients. The cross correlation coefficients of GA and GHb with the previous plasma glucose level in stable diabetic patients were maximal for the plasma glucose levels 10-15 and 20-40 days before, respectively, whereas those in unstable diabetic patients showed a maximum for the plasma glucose level just a few days before. These results suggest that the cross-correlation coefficient depends strongly on plasma glucose stability in diabetic patients and that plasma glucose stability should be taken into consideration in analyzing cross-correlations between glycated proteins and the plasma glucose level in the preceding period.

View full abstract

We examined the preventive and therapeutic effects of nicotinamide and 3-aminobenzamide on diabetes in OLETF rats. Fifteen young (7 week-old pre-diabetic) and twenty-eight old (36-75week old diabetic) OLETF rats were each randomly divided into three groups, a nicotinamide group (0.05g/kg body wt·day, intraperitoneally), a 3-aminobenzamide group (0.05g/kg body wt·day, intraperitoneally), and a saline injected group (2ml/kg body wt). After 90 days, we evaluated the development of diabetes on the basis of the results of an OGTT. Nicotinamide-injected young OLEIT rats were prevented from developing diabetes, but all of the rats in the saline-injected group developed diabetes. Histopathologically, severe fibrosis and hypertrophy of the pancreatic islets were observed in the saline injected group but such findings in the nicotinamide-injected group were only slight. Moreover, in the old nicotinamide-injected OLETF rats the OGTT plasma glucose levels decreased and foci of islet-hyperplasia consisting of newly formed cells were observed. In the 3-aminobenzamide injected OLETF rats, on the other hand, no clear preventive or therapeutic effects were observed and some oncogenic effects were suggested.

View full abstract

To investigate the metabolic pathway of glycosylated (G-LDL) in macrophages (Mφ), we measured LDL accumulation and degradation in Mφ using¹²⁵ I labelled G LDL in both normal and streptozotosin-induced diabetic rats. We also conducted the same measurements for native LDL (N-LDL). The accumulation and degradation of G-LDL were significantly higher than those of N-LDL in both normal and diabetic rats. Regarding the comparison between the normal and diabetic rats, none measured values revealed significant differences in accumulation or degradation.
The accumulation of glycosylated albumin revealed no difference from that of native albumin in the Mφ of diabetic rats. In addition, the degradation of acetylated LDL (A-LDL) in the Mφ of diabetic rats was not affected by the existence of excess G-LDL.
All of these results suggest that G-LDL can be taken up and degraded by a metabolic pathway, other than that of specific high affinity receptors such as the scavenger for A LDL, in the Mφ of diabetic rats.

View full abstract

Diabetic patients have an increased risk of atherosclerotic disease relative to nondiabetic subjects. We measured the plasma concentrations of Lp (a) in 83 NIDDM patients not receiving lipid lowering drugs. Diabetic patients without complications (14.8±14.9mg/dl, n=22) had Lp (a) concentrations similar to the reported data of 99 nondiabetic controls. Lp (a) concentrations showed no relatioships with FBS and HbA₁c. In diabetic patients with retinopathy, proteinuria and/or ishcemic heart disease, Lp (a) concentrations were significantly higher than those of diabetic patients without complications. In multi-variate regression analysis, onlyproteinuria affected the Lp (a) level. In comparing the ApoB/ApoAl ratio and atherogenic index (A.I.), the plasma Lp (a) level showed a higher rate of abnormality, particularly in patients with ishcemic heart disease. Lp (a) may be a superior independent predictor of macrovascular complications of diabetes mellitus. In conclusion, Lp (a) is not elevated in diabetes mellitus without complications. Lp (a) showed a better association with proteinuria and macrovascular complications than did ApoB/ApoAl or A.I

View full abstract

This study included 509 patients (193 males, 316 females) with IDDM diagnosed before the age of 30, between 1963 and 1990, who had been treated at the Diabetes Center of Tokyo Women's Medical College for more than a year. Mortality was calculated by a direct method, starting from the first visit to the Diabetes Center up to the end of follow up. Out of the 509 patients, 435 (85.5%) were followed at the Diabetes Center unitil death or unitil July of 1992. A medical questionnaire was sent to the remaining 74 patients, resulting in an ascertainment of 95.9%(488/509) of all subjects. Of the 488, 11 patients were deceased, resulting in a standardized mortality ratio (SMR) of 2.8. Causes of death were diabetic nephropathy in 4, coronary artery disease in 2, diabetic ketoacidosis in 1 and unknown in 4. The mortality of our IDDM patients between 1963 and 1990 is lower than previous data from Japanese IDDM patients, based on a population based cohort reported by the Diabetes Epidemiology Research International Mortality Study Group.

View full abstract

Mortality from coronary heart disease (CHD) and cerebrovascular disease (CVD) and associated risk factors were examined. Among 1, 939 diabetic patients (NIDDM) studied, 503 deaths were observed during the follow-up period, among whom 62 were CHD deaths and 84 CVD deaths. The mortality rates of CHD (per 1, 000 person-years) were 3.95 for males and 2.57 for females, and those of CVD were 5.12 and 3.86, respectively, showing an increasing trend with age. The baseline factors associated with CHD mortality were age at entry, blood pressure, ischemic ECG changes, serum cholesterol level, diabetic retinopathy and albuminuria, while those associated with CVD were age at entry, hypertension, ischemic ECG changes, diabetic retinopathy, albuminuria and therapeutic regimen. These relationships were further analyzed by means of multiple logistic analysis. Furthermore, the baseline characteristics of the patients who died from CHD and CVD were compared with those of patients who died from other causes. Characteristics which differed significantly from those who died of other causes were obesity, ischemic ECG changes, serum cholesterol level and serum triglyceride level for CHD, and age at entry, age at death and hypertension for CVD.

View full abstract

We examined insulin sensitivity in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), using the euglycemic hyperinsulinemic glucose clamp technique. A 41-year-old woman was admitted to our hospital because of tonic clonic convulsion. She had been suffering from poorly controlled-diabetes mellitus for three years. She had high levels of plasma glucose and serum lactate as well as a mild hearing disturbance. A muscle biopsy showed ragged-red fibers. Islet cell antibody and insulin receptor antibody were negative. We identified an A to G transition at nucleotide 3243 in the tRNA^{Leu (UUR)} in mitochondrial DNA isolated from peripheral leucocytes. After correction of hyperglycemia with insulin treatment, the following studies were done. Responses of serum C-peptide immunoreactivity to oral administration of glucose were low, indicating insufficient insulin secretion from pancreatic B cells. The metabolic clearance rate of glucose (MCR), estimated using the euglycemic hyperinsulinemic glucose clamp technique, was lower in our patient (4.97, 5.58, and5.73 ml/kg/min) than in nondiabetic control subjects (9.37±0.92, n=5, mean±SD). Our findings suggest that glucose intolerance in a patient with MELAS may be due not only to insulin-secretion deficiency, but also to insulin resistance in peripheral tissues.

View full abstract

The first case was a 20-year-old women, who was admitted complaining of thirst and general fatigue. Her blood examinations showed remarkable elevations in blood glucose and ketones as well as metabolic acidosis. C-peptide (CPR) secretion was markedly reduced. Islet cell antibody (ICA) was positive. DR4 and DR2 haplotypes of human leucocyte antigens (HLA) were positive. Diagnosed as having diabetic ketoacidosis, she was treated with insulin. Shortey thereafter, she rejected treatment but she suffered no symptoms. At age 23 years, she visited our hospital again. Serum CPR responses to glucagon had recovered markedly and no medicine was required, though ICA was still positive.
The second case was a 48 year-old man, who visited our hospital complaining of thirst and general fatigue after common cold-like symptoms. Diagnosed as having diabetic ketoacidosis, he was treated with insulin. Two years later, he did not need insulin injections. However, abrupt elevations in blood glucose with ketonuria were sometimes observed after common cold like symptoms. Eventually, by age 54 years, constant insulin treatment was again needed.
Although these two cases represent similar remission-like periods, the mechanisms of their pancreatic islet-sell destruction must be different.

View full abstract