Effect Of Severe Maternal Hyperglycemia On Insulin Sensitivity In Rat Offspring

Background: Metabolic syndrome (MS) is a clustering of metabolicdisorders including obesity,2diabetes, hypertension and hyperlipaemia,with insulin resistance as the central feature of this syndrome. A globalincrease in the prevalence of MS has been found in the last decades due tothe worldwide epidemic of obesity. In recent years, the changes ofenvironment in early life had been considerd a key point in the progressionof IR. The epidemiological and clinical studies had strongly certified thatoffspring of women with diabetes in pregnancy were at increased risk of IR.Adverse maternal environments during gestation and lactation maypredispose the offspring to developing metabolic syndrome in adulthoods.However, the majority of investigations were employed to evaluate milddiabetic effects, and mostly in middle or later stages of pregnancy withhyperglycemia. In this study, we investigated maternal-fetal outcomes ofthe severe maternal hyperglycemia (>20mmol/L) during the whole periodsof pregnancy and lactation, and assessed the metabolic features in theiroffspring. Methods: Maternal hyperglycemia was induced by a40mg/kg singleinjection of streptozotocin (STZ) on the first day of gestation inSprague-Dawley rats. Control (CON) rats were injected with citrate buffer.Litters were adjusted to eight pups per dam and then weaned to standarddiet. Beginning with13-week-old, a subset of offspring from STZ andCON dams were switched to high-fat-diet (HFD) for another13weeks.Glucose and insulin tolerance tests (GTT and ITT) and insulin secretionassay were performed; serum levels of lipids and leptin were measured.Hepatic fat accumulation and islet area were evaluated throughhaematoxylin and eosin staining.Results: STZ offspring exhibited lower survival rate and lower birthweights; in addition, they showed impaired postnatal growth whichpersisted throughout the study. When maintained on standard chow diet,offspring from diabetic mothers exhibited relatively normal glucosetolerance as their counterparts from normal glycemic dams. However，STZoffspring fed with HFD showed more severe impairment in GTT, ITT andIRT. Furthermore, compared with CON-HFD rats, STZ-H animals hadsignificantly higher levels of TG and LDL, while significantly lower HDLlevel. And also, STZ-HFD rats exhibited more profound hepatic steatosis.Conclusions: Our studies indicate that offspring from diabetic damswould be prone to exhibit low birth weight and postnatal growth inhibition,but they could maintain normal glucose tolerance and insulin sensitivity. HFD accelerates the development of insulin resistance in the offspring ofdiabetic dams mainly via a compensatory response of islets.