Neonatal hypoglycaemia in Nepal 2. Availability of alternative fuels.
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AIMS: To study early neonatal metabolic adaptation in a hospital population of neonates in Nepal. METHODS: A cross sectional study was made of 578 neonates, 0 to 48 hours after birth, in the main maternity hospital in Kathmandu. The following clinical and nutritional variables were assessed: concentrations and age profiles of blood glucose, hydroxybutyrate, lactate, pyruvate, free fatty acids (FFA) and glycerol; associations between alternative fuel levels and hypoglycaemia; and regression of possible risk factors for ketone availability. RESULTS: Risk factors for impaired metabolic adaptation were common, especially low birthweight (32%), feeding delays, and cold stress. Blood glucose and ketones rose with age, but important age effects were also found for risk factors like hypothermia, thyroid hormone activities, and feeding practices. Alternative fuel concentrations, except FFA, were significantly reduced in infants with moderate hypoglycaemia during the first 48 hours after birth. Unlike earlier studies, small for gestational age (SGA) infants had significantly higher hydroxybutyrate:glucose ratios which suggested counter regulatory ketogenesis. Hypoglycaemic infants were not hyperinsulinaemic. Regression analysis showed risk factors for impaired counter regulation which included male and large infants, hypothermia, and poorer infant thyroid function. SGA infants and those whose mothers had received no antenatal care had increased counter regulation. CONCLUSIONS: Alternative fuels are important in the metabolic assessment of neonates, and they might provide effective cerebral metabolism even during moderate hypoglycaemia. Hypoglycaemic infants generally had lower concentrations of alternative fuels through either reduced availability or increased consumption. SGA and post term infants increased counter regulatory ketogenesis with early neonatal hypoglycaemia, but hypothermia, male gender, and low infant T4 were associated with impaired counter regulation after birth. (+info)
High- or low-salt diet from weaning to adulthood: effect on insulin sensitivity in Wistar rats.
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Because of conflicting results in the literature, further studies are needed to confirm an association between the degree of salt consumption and insulin sensitivity. The aim of this study was to measure insulin sensitivity in rats fed from weaning to adulthood with a low (LSD), normal (NSD), or high (HSD) salt diet. Body weight, carcass lipid content, blood glucose, nonesterified fatty acids, plasma insulin, plasma renin activity, and a glucose transporter (GLUT4) were measured. A euglycemic hyperinsulinemic clamp was used in 52 anesthetized rats. Body weight was higher in rats on LSD than in those on NSD (P<0.05) or HSD (P<0.001). Percentage fat carcass content was higher (P<0.05) in rats on LSD than in those on NSD. Basal plasma insulin and glucose levels were not altered (P>0.05) by salt consumption. Nonesterified fatty acids were lower in rats on HSD than in those on LSD (P<0.05) or NSD (P<0.01). Glucose uptake was lower in rats on LSD than in those on NSD (P<0.05) or HSD (P<0. 001). When a euglycemic hyperinsulinemic clamp was used on pair-weight rats, similar results were obtained, which suggests that the effect of LSD on insulin sensitivity was not due to higher body weight. GLUT4 in insulin-sensitive tissues was increased in rats on HSD except in the cardiac muscle. Captopril treatment partially reversed low insulin sensitivity in LSD rats, whereas losartan did not change it, which indicates that the effect of LSD on insulin sensitivity is angiotensin independent. In conclusion, the present results demonstrate that chronic dietary salt restriction induces a decrease in insulin sensitivity not associated with renin-angiotensin system activity or body weight changes. (+info)
Insulin action is associated with endothelial function in hypertension and type 2 diabetes.
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A primary defect in the vascular action of insulin may be a key intermediate mechanism that links endothelial dysfunction with reduced insulin-mediated cellular glucose uptake in metabolic and cardiovascular disorders. The present study was designed to characterize more fully the relations between insulin action and endothelial function in male patients with essential hypertension (H, n=9) or type 2 diabetes (D, n=9) along with healthy control subjects (C) matched for age, body mass index, and lipid profile. They attended for measurement of whole-body insulin sensitivity (MCR) by the hyperinsulinemic clamp technique (day 1) and forearm vasoreactivity in response to intra-arterial infusions of insulin/glucose (day 2) and N(G)-monomethyl-L-arginine (L-NMMA) and norepinephrine (day 3) by bilateral venous-occlusion plethysmography. Results expressed as mean+/-SE MCR (mL/kg per minute) were 7.22+/-0. 99 (C), 6.32+/-0.78 (H), and 5.06+/-0.53 (D). Insulin/glucose-mediated vasodilation (IGMV) was 17.1+/-5.6% (C), 17. 2+/-5.5% (H), and 12.3+/-6.4% (D). L-NMMA vasoconstriction (LNV) was 37.9+/-5.1% (C), 37.5+/-2.3% (H), and 33.6+/-2.8% (D). There were no significant differences among groups for these parameters. Pooled correlation analyses revealed associations between MCR and IGMV (r=0. 46, P<0.05), MCR and LNV (r=0.44, P<0.05), and IGMV and LNV (r=0.52, P<0.01). This study supports functional coupling between insulin action (both metabolic and vascular) and basal endothelial nitric oxide production in humans. (+info)
Acute hyperinsulinemia and very-low-density and low-density lipoprotein subfractions in obese subjects.
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BACKGROUND: The influence of hyperinsulinemia on concentrations of lipoprotein subfractions in obese, nondiabetic persons has not been clarified. OBJECTIVE: We analyzed VLDL and LDL subfractions before and after a euglycemic, hyperinsulinemic clamp. DESIGN: Lipoprotein subfractions were isolated from plasma samples obtained in the basal state and after a 4-h clamp from obese patients, obese patients with type 2 diabetes, and nonobese control subjects. RESULTS: Hyperinsulinemia tended to reduce concentrations (&xmacr;: 20%) of large, triacylglycerol-rich VLDL(1) in obese patients but had a minor effect on VLDL(2) and VLDL(3). Placing obese patients into insulin-sensitive and insulin-resistant subgroups revealed distinct effects of the degree of insulin sensitivity on VLDL. VLDL(1) concentrations decreased by a mean of 38% (P < 0.05) in insulin-sensitive patients after the clamp, similar to but less marked than the decrease observed in control subjects (&xmacr;: 62%; P < 0.01). VLDL(1) concentrations did not change significantly after the clamp in insulin-resistant patients (and patients with type 2 diabetes), whereas VLDL(3) concentrations decreased in both groups, in contrast with the changes seen in the insulin-sensitive patients and control subjects. Acute hyperinsulinemia modified the LDL subfraction profile toward a greater prevalence of small, dense LDLs in insulin-resistant patients and patients with type 2 diabetes. CONCLUSIONS: Insulin resistance appears to be the primary determinant of the modifications to VLDL subfraction concentrations. Our results suggest a continuum of impaired insulin action on VLDL, ranging from that in healthy persons to that in patients with type 2 diabetes, in which obese patients occupy a transition state. Insulin resistance may also play a role in detrimental modifications to the LDL profile by allowing the development of hypertriglyceridemia. (+info)
A switch in the direction of the effect of insulin on the partitioning of hepatic fatty acids for the formation of secreted triacylglycerol occurs in vivo, as predicted from studies with perfused livers.
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The direct effects of insulin on hepatic triacylglycerol secretion are important because they may determine the degree of postprandial hyperlipidaemia, a known risk factor for the development of atherosclerotic lesions. Previous work from this laboratory, conducted on isolated perfused rat livers [Zammit, V.A., Lankester, D.J., Brown, A.M. & Park, B.S. (1999) Eur. J. Biochem. 263, 859-864], has indicated that the effect of insulin on hepatic triacylglycerol secretion is dependent on the prior physiological state of the donor animals. In this paper, we demonstrate that a switch in the direction of insulin action on hepatic partitioning of fatty acyl moieties towards triacylglycerol secretion also occurs in vivo between the fed, normoinsulinaemic state and the fasted or severely insulin-deficient states. The partitioning of fatty acids in the liver of awake, unstressed rats was studied using selective labelling of hepatic fatty acids during hyperinsulinaemic-euglycaemic clamps achieved through the use of hepatocyte-targeted liposome-encapsulated insulin preparations. The data show that, whereas in the fed, normoinsulinaemic state, insulinization of the liver raises the proportion of fatty acids directed towards secreted triacylglycerol, in the fasted or insulin-deficient states, insulin inhibits the partitioning of acyl moieties into secreted triacylglycerol. These data show that observations on the direction of insulin action on hepatic triacylglycerol secretion obtained using isolated perfused rat livers are reflected in the effects of the hormone on hepatic fatty acid partitioning in vivo. They offer an explanation for the positive relationship between chronic hyperinsulinaemia, hepatic VLDL-triacylglycerol secretion and hypertriglyceridaemia observed previously in insulin-resistant states. (+info)
Genetics of neonatal hyperinsulinism.
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Congenital hyperinsulinism (HI) is a clinically and genetically heterogeneous entity. The clinical heterogeneity is manifested by severity ranging from extremely severe, life threatening disease to very mild clinical symptoms, which may even be difficult to identify. Furthermore, clinical responsiveness to medical and surgical management is extremely variable. Recent discoveries have begun to clarify the molecular aetiology of this disease and thus the mechanisms responsible for this clinical heterogeneity are becoming more clear. Mutations in 4 different genes have been identified in patients with this clinical syndrome. Most cases are caused by mutations in either of the 2 subunits of the beta cell ATP sensitive K(+) channel (K(ATP)), whereas others are caused by mutations in the beta cell enzymes glucokinase and glutamate dehydrogenase. However, for as many as 50% of the cases, no genetic aetiology has yet been determined. The study of the genetics of this disease has provided important new information about beta cell physiology. Although the clinical ramifications of these findings are still limited, in some situations genetic studies might greatly aid in patient management. (+info)
Hyperinsulinism of infancy: towards an understanding of unregulated insulin release. European Network for Research into Hyperinsulinism in Infancy.
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Insulin is synthesised, stored, and secreted from pancreatic beta cells. These are located within the islets of Langerhans, which are distributed throughout the pancreas. Less than 2% of the total pancreas is devoted to an endocrine function. When the mechanisms that control insulin release are compromised, potentially lethal diseases such as diabetes and neonatal hypoglycaemia are manifest. This article reviews the physiology of insulin release and illustrates how defects in these processes will result in the pathophysiology of hyperinsulinism of infancy. (+info)
Practical management of hyperinsulinism in infancy.
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Hyperinsulinism in infancy is one of the most difficult problems to manage in contemporary paediatric endocrinology. Although the diagnosis can usually be achieved without difficulty, it presents the paediatrician with formidable day to day management problems. Despite recent advances in understanding the pathophysiology of hyperinsulinism, the neurological outcome remains poor, and there is often a choice of unsatisfactory treatments, with life long sequelae for the child and his or her family. This paper presents a state of the art overview on management derived from a consensus workshop held by the European network for research into hyperinsulinism (ENRHI). The consensus is presented as an educational aid for paediatricians and children's nurses. It offers a practical guide to management based on the most up to date knowledge. It presents a proposed management cascade and focuses on the clinical recognition of the disease, the immediate steps that should be taken to stabilise the infant during diagnostic investigations, and the principles of definitive treatment. (+info)