Clinical Impact of Initiation of U-500 Insulin vs Continuation of U-100 Insulin in Subjects With Diabetes.

BACKGROUND: The prevalence of obesity and diabetes mellitus (DM) has each increased drastically according to the Centers for Disease Control and Prevention. Growth of severe insulinresistant DM is predicted. U-500 insulin is highly concentrated and can replace less concentrated formulations in patients that need high insulin dosages. The aim of this study was to compare clinical outcomes of U-500 and U-100 insulin regimens in veterans with obesity and insulin resistance. METHODS: A single-site retrospective chart analysis of adult subjects was conducted from July 2002 to June 2011. Data for repeated measures spanned a period from 3 months before the intervention (baseline) through 12 months afterward. The main outcome was the variation in hemoglobin A1c (HbA1c). Other outcomes included incidence of severe hypoglycemia, weight changes, cardiovascular events, and number of injections. RESULTS: A total of 142 subjects (68 taking U-500 and 74 taking U-100) were included. Baseline characteristics were similar between the groups, except for weight, which was higher among U-500 subjects. Mean HbA1c was reduced by 0.84% and 0.56% in U-500 and U-100, respectively (P = .003). Severe hypoglycemia occurred in 5 subjects in the U-500 group and 1 in the U-100 group (P = .08). No significant difference was noted in the number of cardiovascular events. The mean number of daily injections was 2 in the U-500 group, and 4 in the U-100 group (P < .001). CONCLUSIONS: U-500 insulin, when compared with U-100 insulin regimens, led to a statistically significant reduction in HbA1c and number of insulin injections. Additional research is necessary to assess the risk of severe hypoglycemia in U-500 users. Neither regimen was associated with increased cardiovascular risk.

Activation of protein kinase C-zeta by insulin and phosphatidylinositol-3,4,5-(PO4)3 is defective in muscle in type 2 diabetes and impaired glucose tolerance: amelioration by rosiglitazone and exercise.

Insulin resistance in type 2 diabetes is partly due to impaired glucose transport in skeletal muscle. Atypical protein kinase C (aPKC) and protein kinase B (PKB), operating downstream of phosphatidylinositol (PI) 3-kinase and its lipid product, PI-3,4,5-(PO(4))(3) (PIP(3)), apparently mediate insulin effects on glucose transport. We examined these signaling factors during hyperinsulinemic-euglycemic clamp studies in nondiabetic subjects, subjects with impaired glucose tolerance (IGT), and type 2 diabetic subjects. In nondiabetic control subjects, insulin provoked twofold increases in muscle aPKC activity. In both IGT and diabetes, aPKC activation was markedly (70-80%) diminished, most likely reflecting impaired activation of insulin receptor substrate (IRS)-1-dependent PI 3-kinase and decreased ability of PIP(3) to directly activate aPKCs; additionally, muscle PKC-zeta levels were diminished by 40%. PKB activation was diminished in patients with IGT but not significantly in diabetic patients. The insulin sensitizer rosiglitazone improved insulin-stimulated IRS-1-dependent PI 3-kinase and aPKC activation, as well as glucose disposal rates. Bicycle exercise, which activates aPKCs and stimulates glucose transport independently of PI 3-kinase, activated aPKCs comparably to insulin in nondiabetic subjects and better than insulin in diabetic patients. Defective aPKC activation contributes to skeletal muscle insulin resistance in IGT and type 2 diabetes, rosiglitazone improves insulin-stimulated aPKC activation, and exercise directly activates aPKCs in diabetic muscle.

Survival with serum sodium level of 180 mEq/L: permanent disorientation to place and time.

A 41-year-old woman who had undergone transfrontal craniotomy for a pituitary tumor 4 months before presentation was admitted with confusion and orientation only to self. She had a fever of 40 degrees C. Serum sodium and chloride levels on admission were 180 and 139 mEq/L, respectively. Measured serum osmolality was 380 mOsmol/L with a urine osmolality of 360 mOsmol/L. Magnetic resonance imaging revealed a 1.5-cm mass in the sella turcica, which was nonfunctioning on endocrine evaluation. The "bright spot" of a normal posterior pituitary was absent. Central diabetes insipidus was confirmed by a 300% increase in urine osmolality with desmopressin. The patient survived her severe hypernatremia, which has 70% mortality with a serum sodium level of 160 mEq/L or above. However, she developed permanent (6 months) disorientation to time and place even when hypernatremia was corrected, which has not been described previously.

Ensayo terapéutico con 1-25 dihidroxicolecalciferol en el hipoparatiroidismo posquirúrgico / Therapeutical assay with 1-25 dihydroxycholecalciferol in postsurgical hypoparathyroidism

Se presentan los resultados preliminares del empleo (no reportado) del 1-25 dihidroxicolecalciferol como coadyuvante en el tratamiento de hipoparatiroidismo posquirúrgico. En los seis pacientes estudiados se logró restaurar los niveles séricos de calcio (1,85 pre vs 2,25 nmol/L postratamiento) con disminución de la calciuria. Ningún caso mostró reacción adversa al medicamento, aunque en uno hubo manifestaciones clínicas de hipercalemia. Se sugiere emplear el medicamento en aquellos pacientes en los que la terapéutica convencional no sea eficaz

Ensayo terapéutico con 1-25 dihidroxicolecalciferol en el hipoparatiroidismo posquirúrgico / Therapeutical assay with 1-25 dihydroxycholecalciferol in postsurgical hypoparathyroidis

Se presentan los resultados preliminares del empleo (no reportado) del 1-25 dihidroxicolecalciferol como coadyuvante en el tratamiento de hipoparatiroidismo posquirúrgico. En los seis pacientes estudiados se logró restaurar los niveles séricos de calcio (1,85 pre vs 2,25 nmol/L postratamiento) con disminución de la calciuria. Ningún caso mostró reacción adversa al medicamento, aunque en uno hubo manifestaciones clínicas de hipercalemia. Se sugiere emplear el medicamento en aquellos pacientes en los que la terapéutica convencional no sea eficaz