Increased parathyroid hormone and decreased calcitriol during neonatal extracorporeal membrane oxygenation.

OBJECTIVE: We noted that age-related normal calcium doses in neonates on venoarterial extracorporeal membrane oxygenation result in hypercalcemia. To avoid hypercalcemia and its potential consequences these infants are given one-half the normal calcium dose. We studied the pathogenesis of hypercalcemia and hypomagnesemia by evaluating calcitriol, intact parathyroid hormone, and calcitonin status during extracorporeal membrane oxygenation. DESIGN AND SETTING: Prospective, observational study in the intensive care unit of a 225-bed tertiary care pediatric hospital. PATIENTS AND PARTICIPANTS: Twelve neonates under 7 days old with severe pulmonary disease requiring extracorporeal membrane oxygenation. MEASUREMENTS AND RESULTS: Blood was obtained for intact parathyroid hormone and calcitriol concentrations before cannulation, during (extracorporeal membrane oxygenation days 2, 4, and predecannulation in those on >6 days), and after decannulation on days 1 and 3. Calcitonin concentrations were measured before cannulation, during, and after decannulation in the last seven patients. Prior to cannulation parathyroid hormone was normal (1.4-5.7 pmol/l) and on day 2 increased to 7.8+/-8.4 pmol/l. Before cannulation calcitriol was 14.5+/-8.21 pmol/l (normal 41-143 pmol/l), and concentrations remained low until after decannulation. In three of the seven infants calcitonin concentrations (normal <73 ng/l) were above the upper limit of the assay (>1150 ng/l) prior to cannulation and during extracorporeal membrane oxygenation. CONCLUSIONS: Regulation of the vitamin D-endocrine system during neonatal venoarterial extracorporeal membrane oxygenation appears to be aberrant compared to normal vitamin D-endocrine system regulation. The pathogenesis of this abnormality remains unclear and requires further study.

New drugs for management of diabetes: insulin analogues, inhaled insulin, pramlintide, and novel peptides.

Diabetes mellitus has reached epidemic proportions and contributes to considerable morbidity and mortality in the form of metabolic, microvascular, and macrovascular complications. Although there is no cure, large controlled studies demonstrate the importance of strict glycemic control in reducing progression of microvascular disease and associated morbidity. Insulin replacement is necessary for all patients with type 1 diabetes. In treatment of type 2 diabetes, more timely addition of insulin as patients fail to attain glycemic targets on combinations of oral agents has become widely accepted. Pharmacokinetic properties of human insulins limit their ability to mimic physiologic insulin secretion. Analog insulins (prandial and basal) are designed with improved physiologic pharmacokinetic characteristics to enable more simplified insulin dosage adjustments and a reduced risk for hypoglycemia. Inhaled administration has emerged as a promising route for noninvasive prandial insulin. Clinical trials are under way to further characterize safety and efficacy of inhaled insulin preparations. Despite numerous pharmacologic advancements, the majority of diabetic patients continue to have inadequate glycemic control. New information regarding biochemistry and pathophysiology of the disease is providing exciting opportunities for drug development. Promising new therapeutic classes include the synthetic analog of amylin (pramlintide), glucagon-like peptide (GLP-1) derivatives, and dipeptidyl peptidase IV inhibitors. Intriguingly, GLP-1 hormones may have important biologic actions aside from stimulating insulin release, including inhibition of gastric motility and acid secretion, suppression of glucagon secretion, and islet cell proliferation. Although additional studies are needed, perhaps these emerging agents will have greater efficacy and safety because of a higher degree of selectivity for their molecular targets.