Mitochondrial gene mutations in the tRNA(Leu(UUR)) region and diabetes: prevalence and clinical phenotypes in Japan.

BACKGROUND: Mitochondrial gene mutations play a role in the development of diabetes mellitus. We have assessed the frequency of the A3243G and other mitochondrial mutations in Japan and in the relationship to clinical features of diabetes. METHODS: DNA was obtained from peripheral leukocytes of 240 patients with diabetes mellitus (39 with type 1; 188 with type 2; 13 with gestational diabetes) and 125 control subjects. We used PCR-restriction fragment length polymorphism analysis (ApaI) for A3243G and PCR-single-strand conformation polymorphism analysis to determine the mutations in the mitochondrial gene including nucleotide position 3243. RESULTS: The A3243G mutation was found in seven patients, and an inverse relationship was observed between the degree of heteroplasmy and the age at onset of diabetes. A3156G, G3357A, C3375A, and T3394C were detected in addition. Those who shared the same mutation showed similar clinical characteristics, thus representing a putative clinical subtype. The patients with A3156G had a sudden onset of hyperglycemia and showed a rapid progression to an insulin-dependent state with positive anti-glutamic acid decarboxylase antibody. Those with T3394C showed a mild defect in glucose-stimulated insulin secretion, and hyperglycemia appeared after adding such factors as aging or obesity. CONCLUSIONS: The identification of mitochondrial gene mutations allows preclinical diagnosis of diabetes and prediction of the age at onset by evaluating the degree of heteroplasmy in cases with A3243G. Mutation detection may also be important for patient management and identification of affected family members.

One-day survey of albuminuria in diabetic outpatients in Fukuoka Prefecture, Japan. Fukuoka Diabetic Clinic Group.

The prevalences and risk factors of micro- and macroalbuminuria were surveyed in all 927 patients with diabetes mellitus who visited outpatient clinics in 27 hospitals in the Fukuoka prefecture on a designated day. The urinary albumin-creatinine ratio (UAI; mg/g Cr) of spot urine was determined in all patients except those with persistent macroproteinuria. The results were as follows: (1) The prevalences of microalbuminuria (UAI 30-299) and macroalbuminuria (UAI greater than or equal to 300) were 26% and 15%, respectively. (2) Hyperglycemia and high blood pressure synergistically increased the prevalences. (3) The independent risk factors of microalbuminuria were severities of retinopathy and neuropathy, duration of diabetes, blood pressure, and HbA1c, as determined by logistic regression analysis, although the explanation rate was low.

Lack of association between blood pressure and insulin in patients with insulinoma.

To investigate the hypothesis that insulin affects the regulation of blood pressure, blood pressure and fasting insulin and glucose levels were measured in seven patients with insulinoma both before and after resection of the insulinoma. The diagnosis of all insulinoma cases was confirmed during surgery. Before surgery, systolic and diastolic blood pressures were 127 +/- 15 and 74 +/- 9 mmHg, respectively, and did not correlate with the fasting insulin levels. At least 3 weeks after the surgery, significant decreases in fasting insulin levels (from 568 +/- 571 to 74 +/- 43 pmol/l, P less than 0.005) and body weight (-9.8 +/- 7.1%, P less than 0.05) were observed along with a significant increase in fasting glucose levels (98.2 +/- 43.2%, P less than 0.001). However, both systolic (-4.7 +/- 9.9%) and diastolic (-0.2 +/- 6.3%) blood pressures remained unchanged. The changes in fasting insulin levels were not linearly correlated with those in systolic and diastolic blood pressures. Even after the changes in both body weight and fasting glucose levels were taken into consideration using partial correlations, the changes in fasting insulin levels did not correlate with those in systolic and diastolic blood pressures. It was concluded that blood pressure, both systolic and diastolic, was not at hypertensive levels in the patients with insulinoma and showed no decrease after resection of the insulinoma. Therefore, insulin may not affect the regulation of blood pressure in patients with insulinoma.