Glucose regulation in Thoroughbred weanlings: Regulation by insulin, growth hormone and insulin-like growth factor-I

Diets rich in hydrolyzable carbohydrates induce a hyperglycemic/insulinemic response and may increase the incidence of metabolic disorders associated with some types of laminitis, exertional rhabdomyolysis and osteochondrosis in horses. This study applied the minimal model of glucose and insulin dynamics to determine the effect of diet on metabolites and hormones that regulate glucose metabolism in young horses. Twelve Thoroughbred foals were raised on pasture and supplemented twice daily with a feed high in either sugar and starch (SS) or fat and fiber (FF). As weanlings (age 199 ± 19 d, weight 274 ± 18 kg), the subjects underwent a modified frequent sampling intravenous glucose tolerance test during which they remained in stalls and had access to grass hay and water ad libitum. Samples were colleted at -60, -45, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 35, 40, 50, 60 , 70 , 80, 90, 100, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min with a glucose bolus of 300 mg/kg BW at 0 min and an insulin bolus of 1.5 mU/kg BW at 20 min. Plasma was analyzed for glucose, insulin, growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentrations. Insulin sensitivity, glucose effectiveness, acute insulin response to glucose and disposition index were derived using Minmod Millennium and WinSAAM software. Diet groups were compared using the non-parametric Kruskal-Wallis test or the sign test. Time interactions were compared using a mixed model with repeated effects. Rank-ordered linear regression was used for correlations. Basal glucose did not differ between groups (P = 0.75). There was nearly a trend towards higher basal (P = 0.11), and median insulin was higher in the sugar and starch foals at all 36 sample points (P = 0.030). The basal glucose:basal insulin ratio for the sugar and starch supplemented foals was lower than for fat and fiber foals (P = 0.025). Insulin sensitivity (SI) was lower in foals fed sugar and starch than foals fed fat and fiber (P = 0.007). Acute insulin response to glucose was directly correlated to weight (r = 0.78; P = 0.003) and inversely correlated with SI (r = -0.55; P = 0.067). The glucose:insulin ratio was directly correlated to SI (r = 0.92; P < 0.001). Growth hormone concentrations were increased from basal from 19 to 180 min after the glucose dose (P < 0.05). Basal IGF-I was higher (P = 0.006) in the SS group compared to the FF group. Concentrations of total IGF-I increased with time (P = 0.002) in the SS group. The change in IGF-I concentration from baseline to the end of the study was positively correlated (r = 0.72; P = 0.008) to the area under the insulin curve from 0 to 80 min. Basal IGF-I was inversely correlated to SI (r = 0.71; P = 0.015). These results show that the metabolic response to a diet high in hydrolyzable carbohydrates differs from the response to a fat and fiber meal resembling forage. Weanlings adapted to meals high in glucose equivalents have higher insulin and IGF-I secretion as compared to foals adapted to a fat and fiber feed, possibly contributing to lower insulin sensitivity observed in these foals. Such deviations may contribute to metabolic dysfunction and osteochondrosis in horses fed grain diets.