Maintain Blood Glucose Concentrations Research Articles

Modelling Insulin Clearance and Degradation in Very Premature Infants

Inability to maintain blood glucose concentrations (BG) to a normal range is a common complication of prematurity and stress in neonatal intensive care units (NICUs). STAR (Stochastic TARgeted) glycaemic control uses physiological models to capture and predict patient glycaemic behaviour, and thus dose insulin safely and effectively for tight glycaemic control. STAR in the NICU has in past been based on a simple NICU model. In this study, clinical data is used to identify and validate insulin kinetic parameters of the more physiologically descriptive NICING (Neonatal Intensive Care Insulin-Nutrition-Glucose) model. C-peptide, plasma insulin and BG from a cohort of 41 extremely pre-term (median age 27.2 [26.2 - 28.7] weeks) and very low birth-weight infants (median birth weight 839 [735 - 1000] g) was used alongside C-peptide kinetic models to identify model parameters associated with insulin kinetics in the NICING model. These kinetic parameters in the NICING model were validated by fitting the model to a cohort of 160 glucose, insulin, and nutrition data records from extremely premature infants from two different NICUs. The model fits data and predicts changes in BG in a manner similar to the previous NICU model, indicating that it will perform safely and effectively in the clinical setting. However, the NICING model is more physiologically descriptive, capturing more insulin kinetics and allowing consistency with existing adult ICU glycaemic control protocols and other diabetes models.

One center in Brussels has consistently had the lowest HbA1c values in the 4 studies (1994-2009) by the Hvidoere International Study Group on Childhood Diabetes: What are the "recipes"?

The principal aims of therapeutic management of the child, adolescent and adult with type 1 diabetes are to allow good quality of life and to avoid long-term complications (retinopathy, neuropathy, nephropathy, cardiovascular disease, etc.) by maintaining blood glucose concentrations close to normal level. Glycated hemoglobin levels (HbA1c) provide a good criterion of overall glycemic control. The Hvidoere Study Group (HSG) on Childhood Diabetes, founded in 1994, is an international group representing about twenty highly experienced pediatric centers from Europe, North America, Japan and Australia. Four international comparisons of metabolic control (1995, 1998, 2005, 2009) have been performed. The one center that has consistently had the lowest HbA1c values (approximate 7.3% or 56.3 mmol/mol) is my center in Brussels. This is more often obtained with a twice-daily free-mixed regimen with additional supplemental fast insulins ad hoc. The so-called "Dorchy's recipes" are summarized. The conclusion is that the number of daily insulin injections, 2 or ≥ 4, or the use of pumps, by itself does not necessarily give better results. Intensified therapy should not depend upon the number of insulin doses per day, by syringe, pen or pump but rather should be redefined as to intent-to-treat ascertainment (i.e., goals). When there are no mutually agreed upon goals for BG and/or HbA1c, when there is insufficient education and psychosocial support by the medical team or at home, there is likely to be poor outcomes, as shown by the HSG. One of our recipes is not to systematically replace rapid-acting human insulins by fast-acting analogues. Because the multicenter studies of the HSG, performed in developed countries without financial restriction, show that treatment of childhood diabetes is inadequate in general and that levels of HbA1c are very different, diabetes treatment teams should individually explore the reasons for failure, without any prejudice or bias. Any dogmatism must be avoided. Treatment cost vs results must also be taken into account.

Intensive intravenous infusion of insulin in diabetic cats.

BackgroundRemission occurs in 10–50% of cats with diabetes mellitus (DM). It is assumed that intensive treatment improves β‐cell function and increases remission rates.HypothesisInitial intravenous infusion of insulin that achieves tight glycemic control decreases subsequent insulin requirements and increases remission rate in diabetic cats.AnimalsThirty cats with newly diagnosed DM.MethodsProspective study. Cats were randomly assigned to one of 2 groups. Cats in group 1 (n = 15) received intravenous infusion of insulin with the goal of maintaining blood glucose concentrations at 90–180 mg/dL, for 6 days. Cats in group 2 (n = 15) received subcutaneous injections of insulin glargine (cats ≤4 kg: 0.5–1.0 IU, q12h; >4 kg 1.5–2.0 IU, q12h), for 6 days. Thereafter, all cats were treated with subcutaneous injections of insulin glargine and followed up for 6 months. Cats were considered in remission when euglycemia occurred for ≥4 weeks without the administration of insulin. Nonparametric tests were used for statistical analysis.ResultsIn groups 1 and 2, remission was achieved in 10/15 and in 7/14 cats (P = .46), and good metabolic control was achieved in 3/5 and in 1/7 cats (P = .22), respectively. Overall, good metabolic control or remission occurred in 13/15 cats of group 1 and in 8/14 cats of group 2. In group 1, the median insulin dosage given during the 6‐month follow‐up was significantly lower than in group 2 (group 1: 0.32 IU/kg/day, group 2: 0.51 IU/kg/day; P = .013).Conclusions and Clinical ImportanceInitial intravenous infusion of insulin for tight glycemic control in cats with DM decreases insulin requirements during the subsequent 6 months.

Hypoglycaemia and neonatal brain injury

The transition from fetal to neonatal life requires metabolic adaptation to ensure energy supply to vital organs and systems after separation from the placental circulation. Under normal conditions this is achieved through the mobilisation and use of alternative cerebral fuels (fatty acids, ketone bodies and lactate) when blood glucose concentration falls. The level of blood glucose (BG) concentration that leads to cerebral injury in newborns and adverse neurodevelopmental outcome is unknown: low BG is often observed during postnatal adaptation of healthy term infants without apparent adverse consequence, and the capacity to mobilise and use alternative cerebral fuels when BG is low varies between patient groups. Severe hypoxic-ischaemic encephalopathy (HIE) is associated with impaired metabolic adaptation, and animal and human data suggest that levels of hypoglycaemia that are tolerated under normal conditions may be harmful in association with hypoxia-ischaemia. The spectrum of cerebral injury associated with hypoglycaemia is wide and includes: white matter injury including parenchymal haemorrhage and ischaemic stroke, cortical neuronal injury, and sometimes signal change in the basal ganglia (mainly the globus pallidus) and thalami. Vulnerability of the white matter and cortex of the posterior parietal and occipital lobes has been well reported in human imaging studies, but the site of injury is more widespread in pathological and experimental studies of neonatal hypoglycaemia. In the largest series of infants with isolated neonatal hypoglycaemia and acute neurological dysfunction, there was an association with a predominantly posterior pattern of injury in one third of the cohort, and a more extensive distribution of lesions was common. Safe clinical management relies on the identification of infants at risk of neurological sequelae from hypoglycaemia, adequate energy provision after birth, monitoring of blood glucose, and prompt intervention to raise the BG at specified thresholds, with the caveat that acute neurological dysfunction in association with low BG at any level should prompt urgent investigation and treatment. The optimal target blood glucose level for ensuring adequate energy provision in health and in HIE remains unknown. However, recent data support guidance to maintain blood glucose concentration ≥2.5mmol/L in neonates with signs of acute neurological dysfunction, which includes those with HIE, and is higher than the accepted threshold of ≥2mmol/L in infants without abnormal signs or hyperinsulinism.

Intraoperative hyperglycemia during liver resection: predictors and association with the extent of hepatocytes injury.

BackgroundPatients undergoing liver resection are at risk for intraoperative hyperglycemia and acute hyperglycemia is known to induce hepatocytes injury. Thus, we aimed to evaluate whether intraoperative hyperglycemia during liver resection is associated with the extent of hepatic injury.MethodsThis 1 year retrospective observation consecutively enrolled 85 patients undergoing liver resection for hepatocellular carcinoma. Blood glucose concentrations were measured at predetermined time points including every start/end of intermittent hepatic inflow occlusion (IHIO) via arterial blood analysis. Postoperative transaminase concentrations were used as surrogate parameters indicating the extent of surgery-related acute hepatocytes injury.ResultsThirty (35.5%) patients developed hyperglycemia (blood glucose > 180 mg/dl) during surgery. Prolonged (≥ 3 rounds) IHIO (odds ratio [OR] 7.34, P = 0.004) was determined as a risk factors for hyperglycemia as well as cirrhosis (OR 4.07, P = 0.022), lower prothrombin time (OR 0.01, P = 0.025), and greater total cholesterol level (OR 1.04, P = 0.003). Hyperglycemia was independently associated with perioperative increase in transaminase concentrations (aspartate transaminase, β 105.1, standard error 41.7, P = 0.014; alanine transaminase, β 81.6, standard error 38.1, P = 0.035). Of note, blood glucose > 160 or 140 mg/dl was not associated with postoperative transaminase concentrations.ConclusionsHyperglycemia during liver resection might be associated with the extent of hepatocytes injury. It would be rational to maintain blood glucose concentration < 180 mg/dl throughout the surgery in consideration of parenchymal disease, coagulation status, lipid profile, and the cumulative hepatic ischemia in patients undergoing liver resection for hepatocellular carcinoma.

HPMC/PAA hybrid nanogels via aqueous-phase synthesis for controlled delivery of insulin.

A facile controlled-release delivery system has been developed with hydroxypropylmethylcellulose/poly(acrylic acid) (HPMC/PAA) hybrid nanogels by surfactant-free polymerization in aqueous solution. The effect of temperature, reaction time, and amount of cross-linker on the size and morphology of the nanogels has been studied. The results showed that when the reaction temperature is higher than the lower critical solution temperature, the particle size increases with increasing temperature. And in a certain range, the particle size decreases with increasing reaction time and amount of cross-linker, the prepared nanogel under each condition being spherical. Thus, the HPMC/PAA hybrid nanogels were prepared at 41 °C for 4 h, and possessed a size ranging from 250 nm to 615 nm. Then, insulin was loaded into the nanogel, and the pH and temperature sensitivity of the nanogel was studied, the results indicating that the release behavior of the nanogel can be regulated by pH and temperature. Finally, in streptozotocin-induced diabetic mice, insulin-loaded HPMC/PAA complex was able to maintain blood glucose concentration at a low level for the first week compared to a control group. Therefore, the nanogels have potential biological application as a long-term, sustained insulin delivery system.

Carbohydrate ingestion before and during soccer match play and blood glucose and lactate concentrations.

The ingestion of carbohydrate (CHO) before and during exercise and at halftime is commonly recommended to soccer players for maintaining blood glucose concentrations throughout match play. However, an exercise-induced rebound glycemic response has been observed in the early stages of the second half of simulated soccer-specific exercise when CHO-electrolyte beverages were consumed regularly. Therefore, the metabolic effects of CHO beverage consumption throughout soccer match play remain unclear. To investigate the blood glucose and blood lactate responses to CHOs ingested before and during soccer match play. Crossover study. Applied research study. Ten male outfield academy soccer players (age = 15.6 ± 0.2 years, height = 1.74 ± 0.02 m, mass = 65.3 ± 1.9 kg, estimated maximal oxygen consumption = 58.4 ± 0.8 mL·kg(-1)·min(-1)). Players received a 6% CHO-electrolyte solution or an electrolyte (placebo) solution 2 hours before kickoff, before each half (within 10 minutes), and every 15 minutes throughout exercise. Blood samples were obtained at rest, every 15 minutes during the match (first half: 0-15, 15-30, and 30-45 minutes; second half: 45-60, 60-75, and 75-90 minutes) and 10 minutes into the halftime break. Metabolic responses (blood glucose and blood lactate concentrations) and markers of exercise intensity (heart rate) were recorded. Supplementation influenced the blood glucose response to exercise (time × treatment interaction effect: P ≤ .05), such that glucose concentrations were higher at 30 to 45 minutes in the CHO than in the placebo condition. However, in the second half, blood glucose concentrations were similar between conditions because of transient reductions from peak values occurring in both trials at halftime. Blood lactate concentrations were elevated above those at rest in the first 15 minutes of exercise (time-of-sample effect: P < .001) and remained elevated throughout exercise. Supplementation did not influence the pattern of response (time × treatment interaction effect: P = .49). Ingestion of a 6% CHO-electrolyte beverage before and during soccer match play did not benefit blood glucose concentrations throughout the second half of exercise.

MAGiC DRAGONS: A Protocol for Accurate Glycaemic Control in General Wards

Accurate glycaemic control (AGC) has been shown to be beneficial to the outcomes of critically ill patients. These benefits may also extend to patients in less acute wards, particularly those with existing diabetes. However, the clinical demands of an intensive care glycaemic control protocol are not appropriate for the general wards where the nurse-to-patient ratio is much lower and patients do not typically have an intravenous line available for insulin delivery. Thus, there is a need for a safe, effective glycemic control protocol tailored to the needs of general wards to enable appropriate care for diabetic patients and further testing of the benefits of glycaemic control for this cohort. This paper presents the development and testing of such a protocol for glycaemic control in the general wards.The DRAGONS protocol (Dynamic Regulation for Accurate Glycaemic-control Optimising iNsulin Subcutaneously) was designed to use subcutaneous insulin and only require blood glucose (BG) measurements every four hours, while maintaining BG concentrations within the range 4.4-8.0 mmol/L. Virtual trial simulation indicated an expected time in the target band of 73.0%, with < 2% risk of BG < 4.0 mmol/L. In the first patient recruited to the pilot trial, the DRAGONS protocol achieved 46% time in band and no severe hypoglycaemic episodes. This trial has also highlighted the need for careful selection of the insulin injection site to prevent excessively rapid transport to plasma.

Neonatal Hypoglycemia

Glucose is essential for cerebral metabolism. Unsurprisingly therefore, hypoglycemia may result in encephalopathy. Knowledge of the homeostatic mechanisms that maintain blood glucose concentrations within a tight range is the key for diagnosis and appropriate management of hypoglycemia. Neonatal hypoglycemia can be transient and is commonly observed in at-risk infants. A wide range of rare endocrine and metabolic disorders can present with neonatal hypoglycemia, of which congenital hyperinsulinism is responsible for the most severe form of hypoglycemia. Collection of appropriate blood samples for hormones and intermediary metabolites during an episode of hypoglycemia is critical for diagnosis and appropriate management. Prompt diagnosis with aggressive early intervention remains the mainstay of treatment to avert irreversible brain damage.

Mechanism-based antioxidant therapies promise to prevent diabetic complications?

Intensive blood glucose control can prevent the initiation and progression of diabetic complications. However, the impacts of intensive therapy against diabetic complications might be limited, because of difficulty in maintaining blood glucose concentrations close to the normal range or other unknown reasons. Thus, another approach based on the elucidation of mechanisms of diabetic complications might be required to prevent the progression of the complications.

Evaluation of insulin secretion and action in New World camelids

To measure and compare insulin secretion and sensitivity in healthy alpacas and llamas via glucose clamping techniques. 8 llamas and 8 alpacas. Hyperinsulinemic euglycemic clamping (HEC) and hyperglycemic clamping (HGC) were performed on each camelid in a crossover design with a minimum 48-hour washout period between clamping procedures. The HEC technique was performed to measure insulin sensitivity. Insulin was infused IV at 6 mU/min/kg for 4 hours, and an IV infusion of glucose was adjusted to maintain blood glucose concentration at 150 mg/dL. Concentrations of blood glucose and plasma insulin were determined throughout. The HGC technique was performed to assess insulin secretion in response to exogenous glucose infusion. An IV infusion of glucose was administered to maintain blood glucose concentration at 320 mg/dL for 3 hours, and concentrations of blood glucose and plasma insulin were determined throughout. Alpacas and llamas were not significantly different with respect to whole-body insulin sensitivity during HEC or in pancreatic β-cell response during HGC. Alpacas and llamas had markedly lower insulin sensitivity during HEC and markedly lower pancreatic β-cell response during HGC, in comparison with many other species. New World camelids had lower glucose-induced insulin secretion and marked insulin resistance in comparison with other species. This likely contributes to the disorders of fat and glucose metabolism that are common to camelids.

Neonatal Hyperglycaemia Increases Mortality and Morbidity in Preterm Lambs

Background: Hyperglycaemic preterm babies suffer increased mortality and morbidity, but it is not known if these associations are causal or if treatment with insulin improves outcome. Objectives: We aimed to investigate the effect of neonatal hyperglycaemia, and its treatment with insulin, on mortality and morbidity in preterm lambs. Methods: Preterm lambs (137 days’ gestation; term = 148 days) were randomised to a 12-day intravenous infusion of saline (PremC; n = 39), 50% dextrose (HYPER; n = 47), or 50% dextrose + insulin (INS; n = 21). Term controls (TermC; n = 19) received saline. Dextrose and insulin infusions were titrated to maintain blood glucose concentrations (BGC) at 10–12 mmol·l^–1 (HYPER) or 4–6 mmol·l^–1 (INS). Results: HYPER lambs had higher BGC (mean (SEM); TermC: 5.6 (0.1), PremC: 5.5 (0.1), HYPER: 10.8 (0.6), INS: 6.2 (0.3) mmol·l^–1; p < 0.0001), higher mortality (n (%); TermC: 0, PremC: 2 (5), HYPER: 11 (23), INS: 0; p < 0.001), higher incidence of fever (n (%); TermC: 3 (16), PremC: 13 (33), HYPER: 26 (55), INS: 6 (29); p = 0.01) and lower weight gain (mean (SEM); TermC: 45.9 (2.9), PremC: 44.2 (2.1), HYPER: 28.4 (1.9), INS: 28.7 (2.8) g·kg^–1·day^–1; p < 0.0001). Conclusions: Neonatal hyperglycaemia in preterm lambs causes increased mortality and morbidity, and decreases growth. Insulin treatment to restore euglycaemia attenuated the increased mortality and morbidity, but not the decreased growth.

Sympathetic inhibition attenuates hypoxia induced insulin resistance in healthy adult humans

Acute exposure to hypoxia decreases insulin sensitivity in healthy adult humans; the mechanism is unclear, but increased activation of the sympathetic nervous system may be involved. We have investigated the hypothesis that short-term sympathetic inhibition attenuates hypoxia induced insulin resistance. Insulin sensitivity (via the hyperinsulinaemic euglycaemic clamp) was determined in 10 healthy men (age 23 ± 1 years, body mass index 24.2 ± 0.8 kg m⁻² (means ± SEM)), in a random order, during normoxia (FIO₂ =0.21), hypoxia (FIO₂ =0.11), normoxia and sympathetic inhibition (via 48 h transdermal administration of the centrally acting α2-adrenergic receptor agonist, clonidine), and hypoxia and sympathetic inhibition.Oxyhaemoglobin saturation (pulse oximetry) was decreased (P<0.001) with hypoxia (63 ± 2%) compared with normoxia (96 ± 0%), and was unaffected by sympathetic inhibition (P>0.25). The area under the noradrenaline curve (relative to the normoxia response) was increased with hypoxia (137 ± 13%; P =0.02); clonidine prevented the hypoxia induced increase (94 ± 14%; P =0.43). The glucose infusion rate (adjusted for fat free mass and circulating insulin concentration) required to maintain blood glucose concentration at 5 mmol l⁻¹ during administration of insulin was decreased in hypoxia compared with normoxia (225 ± 23 vs. 128 ± 30 nmol (kg fat free mass)⁻¹ pmol l⁻¹ min⁻¹; P =0.03), and unchanged during normoxia and sympathetic inhibition (219 ± 19; P =0.86) and hypoxia and sympathetic inhibition (169 ± 23; P =0.23). We conclude that short-term sympathetic inhibition attenuates hypoxia induced insulin resistance.

Impacto de diferentes fuentes proteicas en la respuesta glucémica e insulinémica

Objective: The maintenance of normal blood glucose concentrations is a crucial factor to the achievement of a good health status throughout life. However, the occurrence of abnormalities in this parameter has become increasingly common, which can result in several non-transmissible diseases, such as type 2 diabetes and cardiovascular diseases. Therefore, the purpose of this study was to discuss the role of protein sources in the glycemic and insulin responses. Methods: In this review paper, we critically analyzed recently published studies that discussed the role of different protein sources in the glycemic and insulin responses in healthy individuals and in those who have cardiovascular diseases or type 2 diabetes. Results: The results of some of these studies suggest that the daily ingestion of at least one high protein meal containing low to moderate amounts of carbohydrate increases insulin secretion and glucose uptake, improving insulin sensitivity. Furthermore, the results indicate that these effects are particularly associated with the consumption of animal protein (p.e. hydrolyzed whey protein), which has a high content of branched-chain amino acids such as leucine, valine and others such as arginine, which leads to improvements in insulin secretion and uptake glucose, since it increases insulin sensitivity. However, there is still no consensus in the literature about the quantity and quality of protein capable of reducing or maintaining blood-glucose concentrations at the desirable range, without causing adverse effects. The difference in the results of the studies may be associated to methodological problems presented by these studies. Conclusions: Well designed studies should be conducted to identify the quantity and quality of protein that can lead to the improvement on blood glucose concentrations, without negative effects to health. These studies should also identify the mechanisms and the magnitude by which protein may affect glycemic response.

Impact of different protein sources in the glycemic and insulinemic responses.

The maintenance of normal blood glucose concentrations is a crucial factor to the achievement of a good health status throughout life. However, the occurrence of abnormalities in this parameter has become increasingly common, which can result in several non-transmissible diseases, such as type 2 diabetes and cardiovascular diseases. Therefore, the purpose of this study was to discuss the role of protein sources in the glycemic and insulinemic responses. In this review paper, we critically analyzed recently published studies that discussed the role of different protein sources in the glycemic and insulinemic responses in healthy individuals and in those who have cardiovascular diseases or type 2 diabetes. The results of some of these studies suggest that the daily ingestion of at least one high protein meal containing low to moderate amounts of carbohydrate increases insulin secretion and glucose uptake, improving insulin sensitivity. Furthermore, the results indicate that these effects are particularly associated with the consumption of animal protein (p.e. hydrolyzed whey protein), which has a high content of branched-chain amino acids such as leucine, valine and others such as arginine, which leads to improvements in insulin secretion and uptake glucose, since it increases insulin sensitivity. However, there is still no consensus in the literature about the quantity and quality of protein capable of reducing or maintaining blood-glucose concentrations at the desirable range, without causing adverse effects. The difference in the results of the studies may be associated to methodological problems presented by these studies. Well designed studies should be conducted to identify the quantity and quality of protein that can lead to the improvement on blood glucose concentrations, without negative effects to health. These studies should also identify the mechanisms and the magnitude by which protein may affect glycemic response.

Blood Glucose Regulation during Prolonged, Submaximal, Continuous Exercise: A Guide for Clinicians

Management of many chronic diseases now includes regular exercise as part of a viable treatment plan. Exercise in the form of prolonged, submaximal, continuous exercise (SUBEX; i.e., approximately 30 min to 1 h, approximately 40-70% of maximal oxygen uptake) is often prescribed due to its relatively low risk, the willingness of patients to undertake, its efficacy, its affordability, and its ease of prescription. Specifically, patients who are insulin resistant or that have type 2 diabetes mellitus may benefit from regular exercise of this type. During this type of exercise, muscles dramatically increase glucose uptake as the liver increases both glycogenolysis and gluco-neogenesis. While a redundancy of mechanisms is at work to maintain blood glucose concentration ([glucose]) during this type of exercise, the major regulator of blood glucose is the insulin/glucagon response. At exercise onset, blood [glucose] transiently rises before beginning to decline after approximately 30 min, causing a subsequent decline in blood [insulin] and rise in blood glucagon. This leads to many downstream effects, including an increase in glucose output from the liver to maintain adequate glucose in the blood to fuel both the muscles and the brain. Finally, when analyzing blood [glucose], consideration should be given to nutritional status (postabsorptive versus postprandial) as well as both what the analyzer measures and the type of sample used (plasma versus whole blood). In view of both prescribing exercise to patients as well as designing studies that perturb glucose homeostasis, it is imperative that clinicians and researchers alike understand the controls of blood glucose homeostasis during SUBEX.

The influence of maternal glycaemia and dietary glycaemic index on pregnancy outcome in healthy mothers

Infant birth weight has increased in Ireland in recent years along with levels of childhood overweight and obesity. The present article reviews the current literature on maternal glycaemia and the role of the dietary glycaemic index (GI) and its impact on pregnancy outcomes. It is known that maternal weight and weight gain significantly influence infant birth weight. Fetal macrosomia (birth weight >4000 g) is associated with an increased risk of perinatal trauma to both mother and infant. Furthermore, macrosomic infants have greater risk of being obese in childhood, adolescence and adulthood compared to normal-sized infants. There is evidence that there is a direct relationship between maternal blood glucose levels during pregnancy and fetal growth and size at birth, even when maternal blood glucose levels are within their normal range. Thus, maintaining blood glucose concentrations within normal parameters during pregnancy may reduce the incidence of fetal macrosomia. Maternal diet, and particularly its carbohydrate (CHO) type and content, influences maternal blood glucose concentrations. However, different CHO foods produce different glycaemic responses. The GI was conceived by Jenkins in 1981 as a method for assessing the glycaemic responses of different CHO. Data from clinical studies in healthy pregnant women have documented that consuming a low-GI diet during pregnancy reduces peaks in postprandial glucose levels and normalises infant birth weight. Pregnancy is a physiological condition where the GI may be of particular relevance as glucose is the primary fuel for fetal growth.

Inhibition of Cytokine-Induced .BETA. Cell Apoptosis via Laccase and Its Therapeutic Advantages for Insulin-Dependent Diabetes Mellitus, Type 1 Diabetes

In pancreatic islets, free radical formation produced upon exposure to proinflammatory cytokines mediates β cell destruction, which ultimately leads to type 1 diabetes (T1D). In this study, we examined whether laccase, a family of the blue copper protein, can be successfully used to prevent β cells from cytokine-mediated apoptosis. Non-obese diabetic (NOD) mice were used for these experiments. In parallel, the RINm5f β cell line was employed as a model system for in vitro experiments. The results demonstrated that laccase effectively scavenged peroxinitrite, which can be formed by nitric oxide, and upregulated the expression of antioxidant enzymes, such as manganese superoxide dismutase (MnSOD) and catalase. Interestingly, laccase balanced pro- (Bax) and anti-apoptotic (Bcl-2) proteins in terms of both the mRNA and protein levels with a downregulation of cytochrome c protein in RINm5f cells. In addition, laccase maintained blood glucose concentrations at a normal level with a simultaneous increase in plasma insulin levels during the spontaneous induction of diabetes in NOD mice. In conclusion, the antioxidant potentials of laccase in scavenging free radicals and upregulation of antioxidant enzymes may exert its pro-survival effect by counteracting the increased intracellular oxidative stress, and, consequently, by inhibiting apoptosis induced by cytokine-mediated activation during the course of T1D.

What Is a NICE-SUGAR for Patients in the Intensive Care Unit?

What Is a NICE-SUGAR for Patients in the Intensive Care Unit?

The Role of Insulin‐like Signaling for the Central and Peripheral Regulation of Nutrient Homeostasis and Life Span

It is incontrovertible that insulin‐like signaling is critical for development and growth of metazoans: Animals cannot survive without insulin‐like signaling, as it regulates nutrient storage and utilization throughout life. Regardless, the life‐span of lower metazoans‐C. elegans and Drosophila‐benefits from reduced insulin secretion or attenuation of the insulin‐like signaling cascades. One of the most important effects of insulin in higher animals and humans is to maintain blood glucose concentration within a narrow physiologic range. While glucose homeostasis is important, insulin‐like signaling can have detrimental effects upon life span. In higher animals and humans, reduced insulin secretion or resistance to the action of insulin causes glucose intolerance that can progress to life‐threatening diabetes. During insulin resistance, compensatory hyperinsulinemia is essential to prevent the fatal effects of hyperglycemia owing to insulin resistance. However, increased circulating insulin might have damaging effects upon peripheral tissues and the brain that can promote age‐related disease and reduce life span. By manipulating the expression of the insulin receptor substrates (Irs1, Irs2 and Irs4) in mice, we reveal the role of insulin‐like signaling upon peripheral and central nutrient homeostasis, and suggest that the brain is a site where reduced insulin‐like signaling can have a consistent effect to extend mammalian lifespan‐just as reduced insulin‐like signaling extends the life span of worms and flies.