Hyperglycaemic preterm neonates exhibit insulin resistance and low insulin production.

OBJECTIVES: To explore and compare the relationships between postmenstrual age (PMA), insulin, C-peptide and blood glucose concentrations (BGC) in hyperglycaemic and euglycaemic preterm neonates (PMA <30 weeks). DESIGN: Observational. SETTING: Dunedin Hospital Neonatal Intensive Care Unit, New Zealand. PATIENTS: Preterm neonates were recruited and included nine insulin-treated hyperglycaemic and 20 euglycaemic neonates. Samples for euglycaemic neonates were obtained from leftover blood, and for insulin-treated neonates, additional blood was collected at the same time as the patients' routine 4 hourly blood glucose test over a 24-hour period (six samples). MAIN OUTCOME MEASURES: Blood samples were collected, plasma was analysed for insulin and C-peptide and was measured in temporal association with BGC. RESULTS: The euglycaemic neonates had a mean PMA (SD) of 28 (1.4) weeks and the insulin-treated neonates had 25.5 (1.8) weeks. C-peptide plasma concentrations were significantly lower (p<0.01) in the insulin-treated hyperglycaemic neonates (51.7 (100) pmol/L; 200(208) pmol/L) indicating lower insulin production. Insulin plasma concentrations (r=-0.38), BGC (r=-0.38), C-peptide plasma concentrations (r=0.36) and insulin/C-peptide ratios (r=-0.49) were all significantly affected by PMA (p<0.01). As expected, insulin plasma concentrations were higher in the insulin-treated hyperglycaemic neonates (156 (161) pmol/L; 93.2 (63.1) pmol/L, p<0.01) confirming that intravenous exogenous insulin reached these neonates. CONCLUSIONS: This study demonstrates that preterm neonates exhibit insulin resistance, hyperglycaemic neonates have lower insulin production than euglycaemic neonates and treatment with exogenous insulin did not appear to suppress insulin production in these neonates.

Herbal Medicines: challenges in the modern world. Part 5. status and current directions of complementary and alternative herbal medicine worldwide.

INTRODUCTION: Herbal medicine (HM) use is growing worldwide. Single herb preparations, ethnic and modern HM formulations are widely used as adjunct therapies or to improve consumer wellbeing. Areas covered: This final part in the publication series summarizes common tendencies in HM use as adjunct or alternative medicine, education of healthcare professionals and consumers, current and proposed guidelines regulating of production. We discuss potential HM-HM and HM-drug interactions that could lead to severe adverse events in situations where HMs are taken without proper medical professional oversight. Expert commentary: A number of serious problems have arisen with the steady global increase in HM use. HM interaction with conventional drugs (CD) may result in inadequate dosing of CD or adverse reactions; HM-HM interaction within herbal supplements could lead to toxicity of formulations. Inadequate education of clinicians and patients regarding medicinal properties of HMs must be addressed regionally and globally to ensure consumer safety.

Insulin resistance, glucagon-like peptide-1 and factors influencing glucose homeostasis in neonates.

OBJECTIVES: To explore the relationships between postmenstrual age (PMA), insulin, C-peptide, glucagon and blood glucose concentrations (BGCs) in preterm and term neonates. To compare glucagon-like peptide-1 (GLP-1) concentrations in fed versus never-fed neonates. DESIGN: Observational. SETTING: Dunedin Hospital Neonatal Intensive Care Unit, New Zealand. PATIENTS: Term or preterm euglycaemic neonates (102) receiving routine blood tests (343 samples). INTERVENTIONS: None: plasma was obtained from surplus samples from routine clinical care. MAIN OUTCOME MEASURES: Insulin, C-peptide, GLP-1 and glucagon concentrations were measured in temporal association with BGC. RESULTS: Insulin and C-peptide concentrations were elevated in very preterm infants (PMA≤32 weeks) and decreased to term; this relationship persisted when BGCs were accounted for. Generalised linear mixed models showed that insulin:C-peptide ratio and insulin:BGC ratio decreased significantly with increasing PMA (p<0.001). GLP-1 increased following initial oral feeds regardless of PMA (p<0.001). CONCLUSION: Preterm neonates exhibit insulin resistance in the absence of hyperglycaemia. Enteral feeds result in an increase in GLP-1. These factors are likely to contribute to the increased risk of hyperglycaemia in premature neonates (PMA<32 weeks).

Haematocrit influences insulin concentration measurements in dried blood spots.

INTRODUCTION: A major barrier to conducting pharmacokinetic studies in neonates is the relatively large blood volume required by most assays. The use of dried blood spots (DBS) has potential to enable the use of smaller volumes and simplify sample processing and handling. AIM: The aim of this study is to determine the effect of haematocrit on insulin concentrations from DBS. METHODS: DBS of varying haematocrit (0.25-0.65) were prepared at three insulin plasma concentrations (10, 25, and 50 mU/L). DBS were analysed for insulin using the method developed by Butter et al. (2001). DBS and paired plasma samples were obtained from neonates at Dunedin Hospital NICU. RESULTS: Insulin chemiluminescence responses were significantly lower at higher haematocrit values (p < 0.05). All results showed high variability (CV% = 9-61%). Calculated whole blood concentrations were plotted against chemiluminescence and an exponential function [Formula: see text] fitted. Plasma insulin concentrations from neonatal DBS were typically higher than paired plasma samples. CONCLUSIONS: Haematocrit has a significant effect on insulin measurement by chemiluminescence when using DBS. Plasma insulin concentration could be determined when haematocrit was known. DBS insulin concentrations higher than plasma indicate that insulin may be present in red blood cells. However, measuring plasma insulin concentrations with DBS in neonates is not ideal due to high variability.

Effect of gestational age and blood glucose on C-peptide excretion rate and clearance in neonates.

AIMS: The aim of this study was to measure urinary C-peptide concentrations, and then calculate C-peptide clearance (Cl), and excretion rate (UER) in neonates. In addition, the effect of gestational age (GA) and blood glucose levels (BGL) on C-peptide UER were investigated. METHODS: Insulin concentrations in plasma and C-peptide concentrations were measured in plasma and urine, in 20 neonates. Chemiluminescent immunoassays were used for insulin and C-peptide measurements, with urine diluted to 40% with bovine serum albumin 1% in phosphate buffered saline. Urine volume and time of collection were recorded and used to calculate UER and Cl. RESULTS: The mean Cl of C-peptide was 0.309 ± 0.329 mL/min/kg, and UER was 0.0329 ± 0.0342 pmol/min/kg. Correlations between Cl or UER and GA were not significant (P > 0.05). No significant correlation was shown between Cl or UER and BGL (P > 0.05). CONCLUSIONS: Both Cl and UER were highly variable in neonates, but were not correlated with GA. Additionally, BGL did not appear to affect C-peptide UER and Cl. As GA and BGL did not appear to affect Cl and UER, urinary C-peptide may provide a non-invasive method of measuring insulin production in neonates.