Comparison of insulin sensitivity between healthy neonatal foals and horses using minimal model analysis

Abstract

The equine neonate is considered to have impaired glucose tolerance due to delayed maturation of the pancreatic endocrine system. Few studies have investigated insulin sensitivity in newborn foals using dynamic testing methods. The objective of this study was to assess insulin sensitivity by comparing the insulin-modified frequently sampled intravenous glucose tolerance test (I-FSIGTT) between neonatal foals and adult horses. This study was performed on healthy neonatal foals (n = 12), 24 to 60 hours of age, and horses (n = 8), 3 to 14 years of age using dextrose (300 mg/kg IV) and insulin (0.02 IU/kg IV). Insulin sensitivity (SI), acute insulin response to glucose (AIRg), glucose effectiveness (Sg), and disposition index (DI) were calculated using minimal model analysis. Proxy measurements were calculated using fasting insulin and glucose concentrations. Nonparametric statistical methods were used for analysis and reported as median and interquartile range (IQR). SI was significantly higher in foals (18.3 L·min-1· μIU-1 [13.4–28.4]) compared to horses (0.9 L·min-1· μIU-1 [0.5–1.1]); (p < 0.0001). DI was higher in foals (12 × 103 [8 × 103−14 × 103]) compared to horses (4 × 102 [2 × 102−7 × 102]); (p < 0.0001). AIRg and Sg were not different between foals and horses. The modified insulin to glucose ratio (MIRG) was lower in foals (1.72 μIUinsulin2/10·L·mgglucose [1.43–2.68]) compared to horses (3.91 μIU insulin2/10·L·mgglucose [2.57–7.89]); (p = 0.009). The homeostasis model assessment of beta cell function (HOMA-BC%) was higher in horses (78.4% [43–116]) compared to foals (23.2% [17.8–42.2]); (p = 0.0096). Our results suggest that healthy neonatal foals are insulin sensitive in the first days of life, which contradicts current literature regarding the equine neonate. Newborn foals may be more insulin sensitive immediately after birth as an evolutionary adaptation to conserve energy during the transition to extrauterine life.

Energy endocrine physiology, pathophysiology, and nutrition of the foal

“…22 It has been proposed that foals are born in an insulin-resistant state due to peripartum increases in cortisol concentrations 16,21,23 ; however, this effect may be short-lived based on recent work from our lab, showing that low doses of insulin (0.02 IU/kg, IV) have hypoglycemic effects in 1-to 3-day-old foals. 24 Insulin also resulted in hypoglycemia in 2-to 4-dayold foals born to mares that experienced illness during pregnancy. 25 In contrast, another study 26 noted minimal insulin response to hyperglycemia in 2-hourold foals, suggesting that other endocrine factors peaking around this time (within hours of birth), such as cortisol and epinephrine, interfere with insulin secretion.…”

“…Clinicians must be careful with insulin administration to sick newborn foals because most are insulin sensitive and may develop hypoglycemia. 24 It is better to use continuous rate infusions (CRI) over intravenous or subcutaneous administration, except in those with severe hyperglycemia. The recommended starting CRI for regular insulin is 0.0025 to 0.01 IU/kg/h with steady increases every 2 to 4 h to 0.2 IU/kg/h, with even higher rates until normoglycemia is restored.…”

“…When defining hyperglycemia, it is important to note that glucose concentrations of 200 to 250 mg/dL in healthy foals after nursing are normal. 24,31 However, these glucose values are abnormal in foals receiving parenteral dextrose or parenteral nutrition. In these animals, hyperglycemia results from endocrine dysregulation or organ dysfunction or is iatrogenic.…”