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We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese Japanese patients. Participants were divided into groups for normal glucose tolerance, prediabetes, and type 2 diabetes based on the oral glucose tolerance test (OGTT). Activities of prohormone convertase (PC) 1/3 and PC2 in fasting states were estimated. Multiple regression analysis was undertaken to ascertain if alteration of the activities of these enzymes contributes to the development of impaired glucose tolerance by comparison with HOMA-β and the oral disposition index (DI(O)). Overall, 452 subjects were included. PC1/3 activity tended to decrease in type 2 diabetes compared with normal glucose tolerance. PC2 activity showed no difference among the three groups. Decreased estimated PC1/3 activity was significantly associated with type 2 diabetes after adjustment for sex, age, creatinine, triglycerides, HOMA-β and DI(O). Odds ratios (95% CI) of PC1/3, HOMA-β, and DI(O) were 2.16 (1.12-4.19), 3.44 (1.82-6.52) and 14.60 (7.87-27.11), respectively. Furthermore, decreased PC1/3(≤1.7) combined with decreased HOMA-β (≤30) had a sensitivity of 73% and specificity of 62%. Decreased PC1/3 activity may be a useful measurement of beta-cell function alongside decreased HOMA-β or DI(O). A combined decrease in estimated fasting PC1/3 activity and HOMA-β measurement led to suspicion of type 2 diabetes in the non-obese Japanese population studied.

Congenital adrenocortical unresponsiveness to ACTH is characterized by hyperpigmentation, muscular weakness, and episodes of hypoglycemia, with lethargy or coma and convulsion, and without signs or symptoms of salt wasting. Endocrinological evaluation reveals low levels of serum and urinary glucocorticoids, elevated levels of plasma ACTH and unresponsiveness to exogenous ACTH. On the other hand, aldosterone secretion or excretion is normal and is elevated during a low sodium diet. We reported on two patients with this syndrome. Case A, a 4 year-old-girl, showed skin hyperpigmentation, hypoglycemia, convulsion and coma. She was tall wlth a marked advance of bone age. Case B, a 4 year-old-boy, showed skin hyperpigmentation, fatigability and muscular weakness. Both of them revealed low urinary excretion of THE, THF, cortolone, and beta-cortolone and low levels of plasma cortisol. The levels of urinary glucocorticoids and plasma cortisol did not respond to ACTH administration. During a low sodium diet, urinary aldosterone excretion was elevated, urinary sodium excretion ws decreased, and the patients were able to conserve sodium normally. We also summerized other reported cases and discussed the etiology of this syndrome.