Programming of glucose-insulin homoeostasis: long-term consequences of pre-natal versus early post-natal nutrition insults. Evidence from a sheep model.

Aim Exposure to adverse intra-uterine conditions can predispose for metabolic disorders later in life. By using a sheep model, we studied (i) how programming of glucose-insulin homoeostasis during late gestation is manifested later in life depending on the early post-natal dietary exposure and (ii) whether dietary alteration in obese individuals can prevent adverse outcomes of early life programming. Methods During late gestation, twin-pregnant sheep were fed 100% ( NORM) or 50% ( LOW) of energy and protein requirements. After birth, offspring were exposed to a moderate ( CONV) or high-carbohydrate-high-fat ( HCHF) diet until around puberty. Offspring remaining thereafter (exclusively females) were fed a moderate diet until young adulthood. Results LOW lambs had increased insulin secretory responses during intravenous glucose tolerance tests indicative of reduced insulin sensitivity. HCHF lambs were hypertriglyceridaemic, 75% had mild pancreatic collagen infiltration, and their acute insulin secretory response and insulin clearance during intravenous glucose and insulin tolerance tests, respectively, were reduced. However, NORM- HCHF in contrast to LOW- HCHF lambs had normal glucose tolerance, indicating that later health outcomes are highly influenced by pre-natal nutrition. Dietary alteration normalized glucose-insulin homoeostasis in adult HCHF females, whereas late-gestation undernutrition ( LOW) permanently depressed insulin sensitivity. Conclusion Maintenance of glucose tolerance in sheep exposed to pre-natal undernutrition relied on pancreatic hypersecretion of insulin to compensate for reduced insulin sensitivity. A mismatching high-fat diet in early post-natal life interfered with this pancreatic hypersecretion resulting in reduced glucose tolerance. Early post-natal, but not late pre-natal, impacts on glucose-insulin homoeostasis could be reversed by dietary correction later in life. [ABSTRACT FROM AUTHOR]