Frequent samplings of WGTT and Bergman's minimal model analysis were performed in 12 patients with Cushing's syndrome, 6 with acromegaly, 6 with pheochromocytoma, and 33 with type 2 diabetes to elucidate the mechanisms underlying glucose intolerance. Nineteen healthy young volunteers served as controls. Insulin sensitivity (S_I) was low in patients with Cushing's syndrome, acromegaly, and type 2 diabetes but normal in patients with pheochromocytoma. The acute insulin response to glucose (AIR) was lower than normal in patients with acromegaly, pheochromocytoma and type 2 diabetes. A compensatory increase in the AIR, which might be expected, was absent in patients with Cushing's syndrome. Glucose effectiveness (S_G) was normal in all endocrine disorders but impaired in type 2 diabetes. We concluded that insulin resistance and the failure of the β-cell compensatory mechanism contribute to glucose intolerance in Cushing's syndrome and acromegaly, while deficient insulin secretion plays a major role in pheochromocytoma. The coexistence of insulin resistance, β-cell failure and impaired S_G are characteristic of type 2 diabetes.

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A previous retrospective study (first report) on the urinary albumin-creatinine ratio (A/C) was conducted on 107 type 2 diabetes patients over a 9-year-period (1986-1995) based on longitudinally measured data. In the present study we investigated the clinical background of the patients that influenced the in progress with respect to the presence of diabetic retinopathy (DR), comparing it with the clinical background of the patients with diabetic nephropathy (DN).
The subjects were classified into4groups in the first year (1986); an NDR group (N), an SDR group (S), a PPDR group (PP), and a PDR group (P). The results of 9 years of follow-up showed that there were no changes in 59.4% of Group N or 65.0% of Group S, 20.0% of whom improved and were re-classified into Group N. There were no improved patients in Group P. Progression to Group PP or more was seen in 8.7% of Group N and35.0% of Group S, while, 87.5% of Group PP progressed to be Group P.
In the final year of the study (1995), patients were categorized into 3 groups with respect to the changes in DR; Group I (N→N, S→N, S), Group II (N→S), and Group III (progression to Group PP or more). The average HbA₁c level rose significantly (p<0.05) with progression of DR, and the increase was significantly greater than the increase in of DN. None of the cases with good blood glucose control (HbA₁<8.0%)c, showed progression of DR. The prevalence rate of poor blood glucose control (HbA₁c>8.0%) was more significantly correlated with Groups II and III than Group I in the first6of the9years (p<0.05).
Serumlipid values, syotolic and diastolic blood pressure had no significantly relation to progression of DR (whereas they related to it of DN).
These results suggest that hyperglycemia and duration of diabetes were the determinant factors for progression in DR. Hypertension, hyperglycemia, and hyperlipidemia were significantly correlated with progression in DN. The point of no return of DR was the SDR stage.

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A 34-year-old man experiencing thirst had been consistently drinking 2-3l of sugar-containing soft drinks per day since October 1998. On January 26, 1999, he experienced severe thirst, abdominal pain and vomiting. He was admitted to a local hospital on January27. Laboratory examination revealed hyperglycemia (756mg/dl), metabolic acidosis (pH 7.129, HCO₃^- 4.5mmol/l) and an increased concentration of ketone bodies in the urine, indicating diabetic ketoacidosis (DKA). The laboratory findings also revealed a severe hyperlipidemia: triglyceride (TG) 8, 220mg/dl level and a cholesterol count of978mg/dl. His DKA and hyperlipidemia improved with fluid replacement and continuous insulin infusion. On the following day, however, the patient's abdominal pain began to worsen. Abdominal computed tomography revealed a swollen pancreas with edema in the surrounding areas. He was transferred to our hospital with a diagnosis of acute pancreatitis on January 28. The logical sequence of events occurring in our patient was DKA resulting in a marked elevation of his TG level leading to acute pancreatitis. The patient was successfully treated using fluid and insulin infusion, plasma exchange, and the administration of a protease inhibitor. This report describes a rare case of DKA in a young, obese man with severe hyperlipidemia and acute pancreatitis.

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The mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) plays the major role in acetaldehyde detoxification after alcohol ingestion. To determine the gene effect on the glycemic state, we investigated the ALDH 2 genotype in 163 male type-2 diabetes patients randomly screened in our out-patient clinic. Female patients were excluded because few were in the habit of consuming alcohol. The results showed that in the group of alcohol drinkers the HbA₁c level in the inactive ALDH 2 group (8.1±1.3n=38) was higher than in the active ALDH 2 group (7.5±0.9n=70) (p=0.017, student's t test), suggesting the deleterious effect of ALDH 2 mutation on glycemic control in diabetes.
We speculate that, acetaldehyde accumulation in patients with inactive ALDH 2 worsens hyperglycemia, because acetaldehyde reduces glucose-induced insulin secretion by β-cell and inhibits insulin action.

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[in Japanese]

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