In experimental diabetes and after the administration of beta-hydroxybutyrate and non-esterified fatty acids (NEFA), an increase in circulating immunoreactive somatostatin (IRS) has been described. Both ketones and NEFA are raised in diabetic ketoacidosis. Therefore, we decided to investigate 10 patients in diabetic ketoacidosis by measuring, on admission and throughout the initial 24 hours of therapy, circulating levels of IRS, beta-hydroxybutyrate, acetoacetate, triglycerides, blood glucose, pH and NEFA. Fluids and insulin were administered IV following a previously established protocol. Nine patients showed abnormally high levels of circulating IRS. When compared with a group of controlled insulin-dependent diabetic patients, basal IRS was high (111 +/- 15 vs 28 +/- 3 pmol/l), and remained elevated for at least 24 h despite clear improvement of metabolic status. On admission we also found elevated levels of NEFA (1.04 +/- 0.2 mmol/l), triglycerides (4.7 +/- 1.1 mmol/l), beta-hydroxybutyrate (22.1 +/- 4mmol/l), and acetoacetate (4.8 +/- 1.1 mmol/l). A significant correlation was found initially between IRS and NEFA (p less than 0.01). We conclude that circulating IRS is high in most cases of diabetic ketoacidosis. The mechanism behind this hypersomatostatinaemia could be related to the abnormalities of lipid metabolism which occur in diabetic ketoacidosis.

One hundred and sixteen Latin American type 2 diabetic patients previously only on a diet were enrolled in this multicenter, multinational, nonrandomized, noncontrolled study. Only 109 completed the study. After 8 weeks of treatment with 120 mg of nateglinide, administered prior to each meal, the postprandial (2 h) glucose concentration decreased to 85.11 ± 5.65 mg/dl (p < 0.0001), and HbA_1c values decreased to 1.06 ± 0.10% (p < 0.0001). No response differences were detected in relation to age, gender, or ethnicity, but we did encounter a better response in recently diagnosed patients (≤1 year). No serious adverse events were observed. We can, therefore, conclude that nateglinide is a well-tolerated, safe, and effective insulinotropic agent.

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