Maintain Blood Glucose Concentrations Research Articles

Effects of the Maternal Thyroid Status on Embryo Physiology and Hatchability of Commercial Turkey Eggs

Fertile turkey eggs produced by commercial hens fed iodine or triiodothyronine were compared with those from hens fed a control diet to observe the effects of the maternal thyroid status on the energy budget of turkey eggs. Dietary iodine improved hatchability, decreased the number of dead pips, and maintained blood glucose concentrations during pipping and hatching with less reliance on hepatic gluconeogenesis (as assessed by glucose-6-phosphatase activity) compared with controls. Hatchability of eggs from hens fed triiodothyronine was not different from that of control hens but was less than those of iodine-fed hens. The data suggest that the maternal thyroid function of commercial breeder hens can influence hatchability of their eggs and that dietary iodine may be a means to improve hatchability of commercial turkey eggs.

Metabolic Consequences of Different Perioperative Fluid Therapies in the Neonatal Period

SANDSTROM, K.; NILSSON, K.; ANDREASSON, S.; NIKLASSON, A.; LARSSON, L. E. Author Information

The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus

Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.

Metabolic consequences of different perioperative fluid therapies in the neonatal period

Carbohydrate and fat metabolism during and after anaesthesia and surgery was studied in 14 neonates with major congenital non-cardiac anomalies. They were either given a glucose solution until surgery or starved for at least 4 h before surgery. Ringer-acetate alone or Ringer-acetate plus 10% glucose was used for the intraoperative fluid therapy. After anaesthesia all neonates were given a 10% glucose solution. Concentrations of glucose, free fatty acids, triglycerides, lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate were measured at predetermined intervals pre-, intra- and postoperatively. Blood glucose concentrations rose during surgery both in neonates given glucose before and during surgery (n = 6) and in neonates not given glucose before and during surgery (n = 6). Increased intraoperative levels of free fatty acids and 3-hydroxybutyrate were found in neonates not given glucose before and during surgery. The triglyceride levels were equal in both groups. In two neonates given glucose before surgery and Ringer-acetate during surgery increased levels of 3-hydroxybutyrate were found, particularly in one patient who became hypoglycaemic. In conclusion, starved neonates without intraoperative glucose supply mobilized fat and maintained blood glucose concentrations.

LOW SERUM GLUCOSE CONCENTRATIONS INDUCE GLUCAGON COUNTERREGULATION IN HEALTHY NEWBORNS

Before feeding regulatory mechanisms maintain blood glucose concentrations of the newborn to meet the demands of the central nervous system. The role of glucagon in this process has been investigated. Healthy, term babies without clinical signs of hypoglycemia were studied. A capillary blood sample was obtained at 3-15 hours (median 6 hours) of age, a second sample 24 hours later and serum concentrations of glucose, insulin and glucagon were measured. Glucose concentrations at the first sampling averaged 2.1 ± 0.5 mM (mean ± SD; n = 51) and were positively correlated with postnatal age. At the second sampling glucose concentrations had increased to 3.0 ± 0.5 mM. Glucagon concentrations were 541 ± 219 pg/ml at the first sampling and inversely correlated with glucose concentrations. At the second sampling glucagon concentrations had decreased to 406 ± 163 pg/ml. Insulin concentrations were 12.1 ± 2.4 and 10.6 ± 2.1 μU/ml, respectively, and did not correlate with glucose concentrations. In a multiple regression analysis glucose concentrations were inversely correlated with glucagon concentrations and positively correlated with birth weights but not correlated with insulin concentrations or other neonatal and maternal characteristics. The results suggest that glucagon is part of normal counterregulation against hypoglycemia and that neonatal energy stores, as indicated by birth weight, influence the ability to maintain normoglycemia.

Carbohydrate feeding during exercise.

During strenuous exercise (i.e. 70% maximal O2 consumption) there is a progressive shift from muscle glycogen to blood glucose oxidation with increasing duration of exercise. By maintaining blood glucose concentration and the rate of carbohydrate oxidation necessary to exercise strenuously, carbohydrate consumption throughout exercise delays fatigue by 30-60 min in endurance-trained subjects. This requires exogenous glucose supplementation at rates in excess of 1 gram/min (i.e., 16 mg/kg/min) as evidenced by the observation that intravenous glucose infusion at this rate is required to maintain blood glucose at 5 mM. Exogenous glucose must be infused at a rate of 2.6 gram/min (i.e., 37 mg/kg/min), which is similar to the total rate of carbohydrate oxidation, in order to maintain blood glucose at 10 mM after 2 h of exercise. However, carbohydrate supplementation during intense exercise does not spare muscle glycogen utilization in people. This suggests that over the course of 2-4 hours of exercise at 70% VO2max, muscle glycogen and blood glucose contribute equally to total carbohydrate oxidation. Furthermore, during the latter stages of prolonged exercise, exogenous blood glucose supplementation may be capable of supplying almost all of the carbohydrate requirements of exercise at intensities up to 70% VO2max.

Carbohydrate Supplementation during Exercise

Muscle glycogen and plasma glucose are oxidized by skeletal muscle to supply the carbohydrate energy needed to exercise strenuously for several hours (i.e., 70% maximal O2 consumption). With increasing exercise duration there is a progressive shift from muscle glycogen to blood glucose. Blood glucose concentration declines to hypoglycemic levels (i.e., 2.5 mmol/L) in well-trained cyclists after ∼3 h of exercise and this appears to cause muscle fatigue by reducing the contribution of blood glucose to oxidative metabolism. Carbohydrate feeding throughout exercise delays fatigue by 30–60 min, apparently by maintaining blood glucose concentration and the rate of carbohydrate oxidation necessary to exercise strenuously. Carbohydrate feedings do not spare muscle glycogen utilization. Very little muscle glycogen is used for energy during the 3–4-h period of prolonged exercise when fed carbohydrate, suggesting that blood glucose is the predominant carbohydrate source. At this time, exogenous glucose disposal exceeds 1 g/min (i.e., 16 mg · kg-1 · min-1) as evidenced by the observation that intravenous glucose infusion at this rate is required to maintain blood glucose at 5 mmol/L. However, at this time these cyclist cannot exercise more intensely than 74% of maximal O2 consumption, suggesting a limit to the rate at which blood glucose can be used for energy. It is important to realize that carbohydrate supplementation during exercise delays fatigue by 30–60 min, but does not prevent fatigue. In conclusion, fatigue during prolonged strenuous exercise is often due to inadequate carbohydrate oxidation. This is partly a result of hypoglycemia, which limits carbohydrate oxidation and causes muscle fatigue. Carbohydrate feedings during strenuous exercise maintain blood glucose oxidation and delay fatigue by 30–60 min, but do not prevent fatigue, which eventually results from other yet unknown factors.

Fresh human islet transplantation to replace pancreatic endocrine function in type 1 diabetic patients

The aim of this study was to evaluate the feasibility of islet allografts in patients with type 1 diabetes mellitus. Six patients received human islets from either one or two donors via the portal vein, after (n = 4) or simultaneously with (n = 2) a kidney graft. The patients with functioning kidney grafts (nos. 1-4) were already on triple immunosuppressive therapy (cyclosporine A, azathioprine, prednisone). Prednisone was increased to 60 mg/day for 15 days after the islet transplant in patient 1. Patients 2-4 and the patients who underwent a simultaneous kidney-islets graft (nos. 5, 6) also received antilymphocyte globulin. Intravenous insulin was given for the first 15 days to maintain blood glucose concentrations within the normal range. Patient 1 rejected the islets within 15 days of islet transplantation. In patient 2, a 25% reduction in insulin requirement was observed and 12 months after transplantation post-prandial serum C-peptide was 1.5 ng/ml. In patient 3, the insulin requirement decreased from 40 to 8 units/day with a post-prandial serum C-peptide of 4.1 ng/ml 12 months after islet transplantation. In patient 4 the post-prandial secretion of C-peptide increased to 6.4 ng/ml. Six months after the islet infusion, insulin therapy was discontinued and HbA1c, 24-h metabolic profile and oral glucose tolerance test remained within the normal range. He had remained off insulin for 5 months until recently, when foot gangrene paralleled a worsening of post-prandial glycaemic control. Twelve months after transplantation he is receiving 8 units insulin/day.(ABSTRACT TRUNCATED AT 250 WORDS)

1 Carbohydrate Ingestion During Prolonged Exercise

It is well recognized that energy from CHO oxidation is required to perform prolonged strenuous (greater than 60% VO2 max) exercise. During the past 25 years, the concept has developed that muscle glycogen is the predominant source of CHO energy for strenuous exercise; as a result, the potential energy contribution of blood glucose has been somewhat overlooked. Although during the first hour of exercise at 70-75% VO2max, most of the CHO energy is derived from muscle glycogen, it is clear that the contribution of muscle glycogen decreases over time as muscle glycogen stores become depleted, and that blood glucose uptake and oxidation increase progressively to maintain CHO oxidation (Fig. 1.7). We theorize that over the course of several hours of strenuous exercise (i.e., 3-4 h), blood glucose and muscle glycogen contribute equal amounts of CHO energy, making blood glucose at least as important as muscle glycogen as a CHO source. During the latter stages of exercise, blood glucose can potentially provide all of the CHO energy needed to support exercise at 70-75% VO2max if blood glucose availability is maintained. During prolonged exercise in the fasted state, however, blood glucose concentration often decreases owing to depletion of liver glycogen stores. This relative hypoglycemia, although only occasionally severe enough to result in fatigue from neuroglucopenia, causes fatigue by limiting blood glucose (and therefore total CHO) oxidation. The primary purpose of CHO ingestion during continuous strenuous exercise is to maintain blood glucose concentration and thus CHO oxidation and exercise tolerance during the latter stages of prolonged exercise. CHO feeding throughout continuous exercise does not alter muscle glycogen use. It appears that blood glucose must be supplemented at a rate of approximately 1 g/min late in exercise. Feeding sufficient amounts of CHO 30 minutes before fatigue is as effective as ingesting CHO throughout exercise in maintaining blood glucose availability and CHO oxidation late in exercise. Most persons should not wait, however, until they are fatigued before ingesting CHO, because it appears that glucose entry into the blood does not occur rapidly enough at this time. It also may be advantageous to ingest CHO throughout intermittent or low-intensity exercise rather than toward the end of exercise because of the potential for glycogen synthesis in resting muscle fibers. Finally, CHO ingestion during prolonged strenuous exercise delays by approximately 45 minutes but does not prevent fatigue, suggesting that factors other than CHO availability eventually cause fatigue.

Effects of Blood Glucose Concentration on Ratings of Perceived Exertion during Prolonged Low-Intensity Physical Exercise.

The purpose of this investigation was to determine the relationship between blood glucose concentration and perceived exertion during prolonged low-intensity exercise. After a 12-h overnight fast, seven young healthy males began bicycle exercise from 0800 h at 50% Vo2max. One hour after initiation of the exercise, 20% glucose was infused by means of an infusion pump, to maintain blood glucose concentration at a level of approximately 6.5 mM for 20 min. This was followed by 20 min of sham infusion (no glucose). This 40-min cycle was repeated until 220 min of exercise. During the first 120 min of exercise, the ratings of perceived exertion (RPE) increased gradually without any effects of the glucose infusion. Thereafter, RPE tended to decrease during glucose infusion, and finally showed a significant decrease from 180 (17 +/- 2) to 190 (16 +/- 2) min. This result showed that an increase in blood glucose concentration has a significant effect on perceived exertion, even if exercise time is prolonged. The different responses of RPE during the two phases of the exercise may be explained by the difference of glycogen concentration in muscle, because glucose infusion had no effect on RPE when muscle glycogen content was presumed to be at normal level, and was effective when glycogen in the exercising muscles was presumed to be depleted.

The effect of exogenous growth hormone on insulin requirements during closed loop insulin delivery in insulin-dependent diabetes mellitus.

The amount of insulin required to maintain similar blood glucose concentrations during an eight hour infusion of either saline or growth hormone (2 micrograms/kg/hr) was determined in five fed, insulin-dependent diabetic subjects during closed-loop insulin delivery. Elevations of serum growth hormone concentrations to levels previously observed in poorly controlled diabetic subjects were not accompanied by differences in the amount of insulin required to maintain blood glucose concentrations at levels comparable to those observed during the saline infusion. Specifically, no early insulin-like nor late anti-insulin effects of physiologic increases in serum growth hormone concentrations (10.27 +/- 0.23 mg/ml vs 5.69 +/- 1.5 mg/ml, P less than 0.05) on mean hourly blood glucose levels or mean hourly insulin requirements were observed. These studies suggest that serum growth hormone concentrations similar to those observed in poorly controlled diabetics do not affect the insulin requirements of well-insulinized diabetic subjects.

Role of Liver in Glucose Homeostasis

The liver has a unique role in regulation of blood glucose in the postabsorptive state, after ingestion of glucose-containing meals, and in circumstances of glucopenia. It is soley responsible for the delivery of glucose to the bloodstream in the fasted state, thereby maintaining blood glucose concentration for the ongoing needs of body tissues, particularly the brain. An equally important role is played by the liver in the maintenance of normal glucose tolerance in response to carbohydrate ingestion. The liver is the principal site of glucose deposition after glucose feeding, while muscle and adipose tissue represent relatively minor sites of disposal of ingested glucose. In addition, the rise in glucose and insulin caused by glucose ingestion inhibits endogenous hepatic glucose production, which serves to minimize postprandial elevations in blood glucose. When blood glucose is reduced by small increments in circulating insulin, a rebound increase in glucose output from the liver is the initial or principal mechanism counteracting the fall in blood glucose concentration. Studies in juvenile-onset diabetes indicate that the liver is capable of altering its release of glucose in response to changes in blood glucose concentration when small, physiologic doses of insulin are infused. These findings may provide an explanation for the efficacy of preprogrammed insulin delivery systems in the treatment of diabetes.

Effects of somatostatin (SRIF) infusion on glucose homeostasis in newborn lambs: evidence for a significant role of glucagon.

Summary: In order to investigate the significance and relative contribution of glucagon (IRG) and insulin (IRI) to neonatal glucose homeostasis, studies were conducted utilizing somatostatin (SRIF) in newborn fasting lambs aged 1–3 days. A priming dose followed by constant infusion of SRIF was maintained for 2 hr. During the first hour, SRIF alone was infused (period A); during the second hour, glucagon or insulin were additionally infused (period B); recovery was assessed 30 min after cessation of infusions (period C). During period A, a rapid and sustained suppression in the plasma concentrations of IRG and IRI occurred (P < 0.01), accompanied by a fall in plasma glucose significant at 60 min. Reinfusion of glucagon (5 ng/kg/min) during period B raised IRG by 342 ± 92 pg/ml (mean ± SEM, P < 0.01). Despite ongoing SRIF, plasma IRI also rose by 19.7 ± 7 μU/ml (P < 0.05) and was not accountable by contamination of the infused glucagon with insulin. Plasma glucose rose modestly, perhaps as a result of the antagonistic effects of glucagon and insulin. After cessation of SRIF and glucagon infusions (period C) plasma IRG fell, plasma IRI rose, and plasma glucose fell significantly (16.5 ± 4 mg/dl, P < 0.01). When insulin (0.1 units/kg/hr) was infused in period B, plasma IRI rose to approximately 70 μU/ml, plasma IRG remained suppressed and plasma glucose fell profoundly, recovering during period C as plasma IRI fell and plasma IRG rose. When, during period B, glucagon was infused at 10 times the original dose, plasma glucose concentration doubled despite a plasma IRI concentration of 100 μU/ml.These results demonstrate that: (1) SRIF effectively inhibits IRI and IRG secretion in newborn lambs; (2) glucose falls when both hormones are acutely suppressed, suggesting that glucagon is a major hormone for maintaining blood glucose concentration during short term fasting; a rise in glucose, as occurs in insulin-deficient diabetes, would be expected if insulin were the dominant hormone; (3) both insulin and glucagon and acute changes in the effective ratio of these hormones modulate glucose homeostasis; and (4) at physiologic concentrations glucagon can overcome the suppressive effects of SRIF on insulin secretion in newborn lambs.Speculation: In the lamb, insulin and glucagon are both important for neonatal glucose homeostasis. Acute changes in the ratio of these two hormones can effectively modulate plasma glucose concentration presumably through governing hepatic glucose output and/or peripheral glucose utilization. Extrapolation, made with due caution to human newborns, would suggest that the observed changes in glucagon and insulin in the immediate postnatal period have physiological significance in glucouse homeostasis.