Glucose Infusion Research Articles

Rates of pyruvate carboxylase, glutamate and GABA neurotransmitter cycling, and glucose oxidation in multiple brain regions of the awake rat using a combination of [2-13C]/[1-13C]glucose infusion and 1H-[13C]NMR ex vivo

Anaplerosis occurs predominately in astroglia through the action of pyruvate carboxylase (PC). The rate of PC (Vpc) has been reported for cerebral cortex (or whole brain) of awake humans and anesthetized rodents, but regional brain rates remain largely unknown and, hence, were subjected to investigation in the current study. Awake male rats were infused with either [2-13C]glucose or [1-13C]glucose (n = 27/30) for 8, 15, 30, 60 or 120 min, followed by rapid euthanasia with focused-beam microwave irradiation to the brain. Blood plasma and extracts of cerebellum, hippocampus, striatum, and cerebral cortex were analyzed by 1H-[13C]-NMR to establish 13C-enrichment time courses for glutamate-C4,C3,C2, glutamine-C4,C3, GABA-C2,C3,C4 and aspartate-C2,C3. Metabolic rates were determined by fitting a three-compartment metabolic model (glutamatergic and GABAergic neurons and astroglia) to the eighteen time courses. Vpc varied by 44% across brain regions, being lowest in the cerebellum (0.087 ± 0.004 µmol/g/min) and highest in striatum (0.125 ± 0.009) with intermediate values in cerebral cortex (0.106 ± 0.005) and hippocampus (0.114 ± 0.005). Vpc constituted 13–19% of the oxidative glucose consumption rate. Combination of cerebral cortical data with literature values revealed a positive correlation between Vpc and the rates of glutamate/glutamine-cycling and oxidative glucose consumption, respectively, consistent with earlier observations.

Serotonin transporter is negatively associated with body mass index after glucose loading in humans.

Serotonin transporter (SERT) is a presynaptically localized membrane protein that regulates the serotonin transmission via its reuptake of released serotonin. We hypothesized that glucose loading may change SERT availability from brainstem in humans. An intravenous bolus injection of 18F-FP-CIT was administered after the infusion of glucose or placebo (normal saline), and the emission data were acquired over 90 mins in 33 healthy nonobese subjects. For a volume-of-interest-based analysis, an atlas involving midbrain, and pons was applied. SERT availability, binding potential (BPND), were measured via the simplified reference tissue method with a reference of cerebellum. For a voxel-based analysis, statistical parametric mapping 12 was used with parametric BPND images. BPNDs from midbrain (p=0.8937), and pons (p=0.1115) were not different between glucose and placebo loading. Both of BPNDs from midbrain after glucose, and placebo loading were negatively correlated with body mass index (BMI). BMI showed a trend of negative correlation with glucose-loaded BPND from pons, whereas, placebo-loaded BPNDs from pons did not show any significant association with BMI. In conclusion, SERT availability was negatively correlated with BMI after glucose loading in humans. SERT might have a role in eating behavior through the action of insulin. Further studies are needed to elucidate the underlying mechanism of this phenomenon.

Attitude, knowledge, and practices regarding blood glucose control: a survey of intensive care unit professionals

Background: Dysglycemia is a frequent and independent risk factor for poor outcomes in critically sick patients. Yet, in Saudi Arabian intensive care units (ICUs), blood glucose (BG) management hasn't gotten much attention. This study was done to assess attitudes, knowledge, and practices regarding BG control among ICU professionals in Saudi Arabia. Methods: A cross-sectional study was conducted among male and female ICU professionals (n = 150, between 25-55 years old) in Saudi Arabia. The study was performed using a self-administrated questionnaire. The questionnaire included years of professional experience and questions about their attitude, knowledge, and practices regarding BG control in the ICU. Results: A total of 150 questionnaires were enrolled in this study. The age of ICU professionals was 25-55 years old. In the study, when BG levels in non-diabetic individuals exceeded 6.1 mmol/l, 10 mmol/l, and 11.1 mmol/l, respectively, 78, 45, and 12 of the 15 respondents began using insulin. In addition, 78/150 (52.0%) respondents consistently administered a 40 ml 50% glucose solution to treat hypoglycemia, and 91/150 (60.7%) responders recognized BG values 15-30 minutes after glucose infusion. In addition, 58/150 (38.7%) respondents routinely detected BG levels every 1 hour in critically ill patients. Conclusion: In regards to BG control in ICU physicians, this study concluded the requirement for further training. In addition, according to continuing variation in practice, more clinical trials of BG control in critically ill patients are also needed.

Empagliflozin restores cardiac metabolic flexibility in diet-induced obese C57BL6/J mice.

Sodium-glucose co-transporter type 2 (SGLT2) inhibitor therapy to treat type 2 diabetes unexpectedly reduced all-cause mortality and hospitalization due to heart failure in several large-scale clinical trials, and has since been shown to produce similar cardiovascular disease-protective effects in patients without diabetes. How SGLT2 inhibitor therapy improves cardiovascular disease outcomes remains incompletely understood. Metabolic flexibility refers to the ability of a cell or organ to adjust its use of metabolic substrates, such as glucose or fatty acids, in response to physiological or pathophysiological conditions, and is a feature of a healthy heart that may be lost during diabetic cardiomyopathy and in the failing heart. We therefore undertook studies to determine the effects of SGLT2 inhibitor therapy on cardiac metabolic flexibility in vivo in obese, insulin resistant mice using a [U13C]-glucose infusion during fasting and hyperinsulinemic euglycemic clamp. Relative rates of cardiac glucose versus fatty acid use during fasting were unaffected by EMPA, whereas insulin-stimulated rates of glucose use were significantly increased by EMPA, alongside significant improvements in cardiac insulin signaling. These metabolic effects of EMPA were associated with reduced cardiac hypertrophy and protection from ischemia. These observations suggest that the cardiovascular disease-protective effects of SGLT2 inhibitors may in part be explained by beneficial effects on cardiac metabolic substrate selection.

Difficulties in managing hyperglycemia in extremely low birth weight infants – case report

Introduction. Studies have shown that 60-80% of ex­tremely low birth weight (ELBW) newborns develop hy­per­gly­ce­mia in the first two weeks of life. The cause is usually iatrogenic, through high rates of exogenous glu­cose infusion from total parenteral nutrition (TPN). Other mechanisms are represented by insulin resistance due to the immaturity of enzyme systems, increased he­pa­tic pro­duc­tion of glu­cose, the inability to inhibit glu­co­neo­ge­ne­sis, and by the ef­fect of stressors through the action of cate­cho­la­mines. Hy­per­gly­cemia generates multiple harmful effects, which can be reduced with the help of insulin therapy, op­ti­mizing growth and avoiding fluid overload. Materials and method. We present the case of three ELBW newborns with neonatal respiratory distress, who required surfactant and invasive mechanical ventilation, along with prolonged TPN. The newborns developed persistent hyperglycemia in the first weeks of life (plasma glucose above 180 mg/dl) de­spite the decrease in glucose concentration and infusion rate, requiring insulin infusion. Results. In all three cases, it was relatively difficult to control the plasma glucose le­vels. Weight gain was satisfactory, but the patients pre­sen­ted multiple severe complications. Conclusions. The ma­nage­ment of metabolic complications of ELBW new­borns is im­portant due to the major implications in their prognosis and survival. A special interest has recently been given to the concept of cellular modulation in critical pe­riods of de­velopment and the influence in the subsequent oc­cur­rence of some diseases. Extrauterine adaptation in ELBW newborns involves biochemical and metabolic ad­just­ments, with immediate and long-term impact.

Use of an ultrashort-acting selective β1-adrenergic receptor antagonist esmolol in ear, nose and throat surgery

Background / Aim: The concept of general balanced anaesthesia was devised in order to assure cardiovascular stability and fast post-anaesthesia recovery. This clinical trial was organised in order to investigate the parameters of cardiovascular function and emergence from anaesthesia in elective ear, nose and throat (ENT) surgery patients. Methods: A total of 40 ASA I and II patients of both sexes scheduled for elective ENT surgery were randomly divided into two equal groups. Both groups received a continuous IV infusion of glucose 5 % solution and in the esmolol group this infusion also contained esmolol. Esmolol infusion rate was 0.3 mg/kg/min during the first 5 min and thereafter 0.1 mg/kg/min. In critical phases of anaesthesia and operation (induction, intubation, first incision, surgical manipulations, wound suture, extubation), systolic and diastolic blood pressure were monitored. Recovery after anaesthesia was assessed based on times of eye opening on command, spontaneous eye opening and regaining of full orientation. Increases in cardiovascular parameters by 20 % of the baseline values or more were treated with IV boluses of fentanyl, alone or with droperidol and, if necessary, by adding isoflurane 0.5 % to the inhalational mixture. Consumption of drugs was recorded. Results: Esmolol assured stable values of cardiovascular parameters that were in most critical phases of anaesthesia and operation lower than in the control group. The duration of anaesthesia did not differ between the groups. In the esmolol group, lower consumption of fentanyl, droperidol and sevoflurane was registered. Patients in the esmolol group emerged from anaesthesia faster than patients in the control group. Conclusion: Continuous IV infusion of esmolol assures better cardiovascular stability, necessitates lower consumption of analgesics and anaesthetics and results in faster emergence from general anaesthesia in elective ENT surgery.

Novorođenče lečeno kontinuiranom terapijom zamene bubrežne funkcije za citrulinemiju-tip 1

Introduction: Hyperammonemia occurs as a result of the inability to convert ammonia, a metabolic toxin, into urea due to a block in the urea cycle, and there resulting neurotoxicity is responsible for the pathogenesis. Case Presentation: Our patient was 7 days old when followed up in an external center for 3 days with a preliminary diagnosis of neonatal sepsis. Lethargy, vomiting, tachypnea, and convulsions, which are frequently seen in the first neonatal forms of urea cycle disorders, were also present in our patient. He was referred to us as a result of high ammonia levels when he was examined in terms of congenital metabolic diseases. He was intubated due to the rapid development of respiratory failure. When he was admitted to our intensive care unit with hyperammonemia, light reflex could not be obtained, and widespread cutis marmaratus was developed. Continuous renal replacement therapy was started in our patient and administered intermittently for 120 hours. The glucose infusion rate was followed by high fluid. When it orally tolerated, it is supported with sodium benzoate and sodium stearyl fumarate to reduce ammonia. Nutrition was limited to protein with Basic P. Conclusion: After staying in the intensive care unit for 30 days, our patient was discharged with the recommendation of outpatient follow-up by the pediatric metabolism physician. When our patient came for his check up after two months,there was no nystagmus and no seizures.

Metformin improves skeletal muscle microvascular insulin resistance in metabolic syndrome.

Microvascular insulin resistance is present in metabolic syndrome and may contribute to increased cardiovascular disease risk and the impaired metabolic response to insulin observed. Metformin improves metabolic insulin resistance in humans. Its effects on macro and microvascular insulin resistance have not been defined. Eleven subjects with nondiabetic metabolic syndrome were studied four times (before and after 12 wk of treatment with placebo or metformin) using a crossover design, with an 8-wk washout interval between treatments. On each occasion, we measured three indices of large artery function [pulse wave velocity (PWV), radial pulse wave separation analysis (PWSA), brachial artery endothelial function (flow-mediated dilation-FMD)] as well as muscle microvascular perfusion [contrast-enhanced ultrasound (CEU)] before and at 120 min into a 150 min, 1 mU/min/kg euglycemic insulin clamp. Metformin decreased body mass index (BMI), fat weight, and % body fat (P < 0.05, each), however, placebo had no effect. Metformin (not placebo) improved metabolic insulin sensitivity, (clamp glucose infusion rate, P < 0.01), PWV, and FMD after insulin were unaffected by metformin treatment. PWSA improved with insulin only after metformin P < 0.01). Insulin decreased muscle microvascular blood volume measured by contrast ultrasound both before and after placebo and before metformin (P < 0.02 for each) but not after metformin. Short-term metformin treatment improves both metabolic and muscle microvascular response to insulin. Metformin's effect on microvascular insulin responsiveness may contribute to its beneficial metabolic effects. Metformin did not improve aortic stiffness or brachial artery endothelial function, but enhanced radial pulse wave properties consistent with relaxation of smaller arterioles.NEW & NOTEWORTHY Metformin, a first-line treatment for type 2 diabetes, is often used in patients with insulin resistance and metabolic syndrome. Here, we provide the first evidence for metformin improving muscle microvascular insulin sensitivity in insulin-resistant humans. Simultaneously, metformin improved muscle glucose disposal, supporting a close relationship between insulin's microvascular and its metabolic actions in muscle. Whether enhanced microvascular insulin sensitivity contributes to metformin's ability to decrease microvascular complications in diabetes remains to be resolved.

Implementation of an Intrapartum Glucose Management Protocol for Diabetes in Pregnancy

Achieving intrapartum euglycemia is recommended to reduce the risks of neonatal hypoglycemia. While institutions have best practices involving glucose infusion and insulin administration, published accounts are sparse. We sought to examine whether an insulin protocol for intrapartum glucose control among parturients with diabetes was associated with improved neonatal outcomes

Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats.

AimWe evaluated the efficacy of a novel brain permeable “metformin-like” AMP-activated protein kinase activator, R481, in regulating glucose homeostasis.Materials and MethodsWe used glucose sensing hypothalamic GT1-7 neuronal cells and pancreatic αTC1.9 α-cells to examine the effect of R481 on AMPK pathway activation and cellular metabolism. Glucose tolerance tests and hyperinsulinemic-euglycemic and hypoglycemic clamps were used in Sprague-Dawley rats to assess insulin sensitivity and hypoglycemia counterregulation, respectively.Results In vitro, we demonstrate that R481 increased AMPK phosphorylation in GT1-7 and αTC1.9 cells. In Sprague-Dawley rats, R481 increased peak glucose levels during a glucose tolerance test, without altering insulin levels or glucose clearance. The effect of R481 to raise peak glucose levels was attenuated by allosteric brain permeable AMPK inhibitor SBI-0206965. This effect was also completely abolished by blockade of the autonomic nervous system using hexamethonium. During hypoglycemic clamp studies, R481 treated animals had a significantly lower glucose infusion rate compared to vehicle treated controls. Peak plasma glucagon levels were significantly higher in R481 treated rats with no change to plasma adrenaline levels. In vitro, R481 did not alter glucagon release from αTC1.9 cells, but increased glycolysis. Non brain permeable AMPK activator R419 enhanced AMPK activity in vitro in neuronal cells but did not alter glucose excursion in vivo.ConclusionsThese data demonstrate that peripheral administration of the brain permeable “metformin-like” AMPK activator R481 increases blood glucose by activation of the autonomic nervous system and amplifies the glucagon response to hypoglycemia in rats. Taken together, our data suggest that R481 amplifies the counterregulatory response to hypoglycemia by a central rather than a direct effect on the pancreatic α-cell. These data provide proof-of-concept that central AMPK could be a target for future drug development for prevention of hypoglycemia in diabetes.

Hyperinsulinemic hypoglycemia in growth restricted convalescent preterm neonates: clinical characteristics and impediments to early diagnosis.

Describe clinical characteristics, course, and risk factors for hyper-insulinemic hypoglycemia (HIH) in preterm infants and identify impediments to early diagnosis. Electronic records of infant-mother dyads were used to describe clinical characteristics, lab parameters, and course of HIH. All eight patients (gestational ages 26w0d-29w3d) had intrauterine growth restriction (IUGR) due to placental insufficiency, (4/8) were small for gestational age. All maintained normal glucose levels with glucose infusion during the first 48h six of eight patients had cholestasis despite being on parenteral nutrition for short time (average 17days). Four of eight patients were treated with diazoxide (average 22days). Four of eight patients who recovered spontaneously (average 49days after diagnosis) responded to continuous feeds and hydrocortisone for other clinical indications. In IUGR preterms, HIH is asymptomatic, may be prolonged, requiring diazoxide treatment. Transient cholestasis is seen in majority of patients. Euglycemia should be demonstrated on bolus gavage feeds, off glucocorticoids before discontinuing blood glucose monitoring.

Role of the Gut in the Temporal Changes of β-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission.

The role of the gut in diabetes remission after Roux-en-Y gastric bypass (RYGB) is incompletely understood. We assessed the temporal change in insulin secretory capacity after RYGB, using oral and intravenous (IV) glucose, in individuals with type 2 diabetes. Longitudinal, prospective measures of β-cell function were assessed after oral glucose intake and graded glucose infusion in individuals with severe obesity and diabetes studied at 0, 3 (n = 29), 12 (n = 24), and 24 (n = 20) months after RYGB. Data were collected between 2015 and 2019 in an academic clinical research center. The decreases in body weight, fat mass, waist circumference, and insulin resistance after surgery (all P < 0.001 at 12 and 24 months) did not differ according to diabetes remission status. In contrast, both the magnitude and temporal changes in β-cell glucose sensitivity after oral glucose intake differed by remission status (P = 0.04): greater (6.5-fold; P < 0.01) and sustained in those in full remission, moderate and not sustained past 12 months in those with partial remission (3.3-fold; P < 0.001), and minimal in those not experiencing remission (2.7-fold; P = not significant). The improvement in β-cell function after IV glucose administration was not apparent until 12 months, significant only in those in full remission, and only ∼33% of that observed after oral glucose intake. Preintervention β-cell function and its change after surgery predicted remission; weight loss and insulin sensitivity did not. Our data show the time course of changes in β-cell function after RYGB. The improvement in β-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.

Effects of perioperative dextrose infusion on preventing postoperative nausea and vomiting in patients undergoing laparoscopic surgery: a meta-analysis of randomized controlled trials.

ObjectiveThe aim of this study was to systematically examine the literature and assess the effects of perioperative dextrose infusion on the prevention of postoperative nausea and vomiting (PONV) in patients following laparoscopic surgery under general anesthesia.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Studies were eligible for inclusion if they evaluated the prevention of PONV with perioperative intravenous dextrose. Studies listed in PUBMED, Web of Science, and EMBASE databases published up to December 2020 were identified. Data were extracted and analyzed independently using a fixed-effects or random-effects model according to the heterogeneity.ResultsSix RCTs involving 526 patients were included. Our results showed that perioperative dextrose infusion not only reduced the incidence of PONV (risk ratio [RR] = 0.61, 95% confidence interval [CI]: 0.39–0.95; I2 = 59%) but also decreased the requirement for antiemetics compared with the control (RR = 0.53, 95% CI: 0.42–0.66; I2 = 32%). Furthermore, perioperative glucose infusion did not increase blood glucose levels compared with the control (mean difference [95% CI] = 74.55 [−20.64 to 169.73] mg/dL; I2 = 100%).ConclusionOur study reveals that perioperative dextrose infusion may reduce the risk of PONV after laparoscopic surgery. However, additional population-based RCTs are needed to confirm this finding.

Effect of postharvest glucose infusion on exocarp colour of ‘Hass’ avocado (Persea americana Mill) during ripening

Effect of postharvest glucose infusion on exocarp colour of ‘Hass’ avocado (Persea americana Mill) during ripening

Pharmacokinetic and pharmacodynamic similarity between SAR341402 insulin aspart and Japan-approved NovoRapid in healthy Japanese subjects

This study compared the pharmacokinetic and glucodynamic profiles of biosimilar SAR341402 insulin aspart to Japan-approved insulin aspart (NovoRapid) in healthy Japanese males. In this single-center, randomized, double-blind, single-dose, two-period, crossover study, subjects received 0.3 U/kg of SAR341402 or NovoRapid before undergoing a 10 h euglycemic clamp procedure. Plasma insulin aspart concentrations and blood glucose levels were measured, and glucose infusion rates (GIRs) were assessed. Primary endpoints were maximum plasma insulin aspart concentration (INS-Cmax), area under the plasma insulin concentration–time curve to the last quantifiable concentration (INS-AUClast), area under the GIR–time curve during the clamp (GIR-AUC0–10 h), and maximum GIR (GIRmax). Forty subjects were randomized with 39 completing both treatment periods. Pharmacokinetic exposure showed a mean ratio between products of 1.00 (90% confidence interval [CI] 0.94–1.05) for INS-Cmax and 1.02 (90% CI 1.00–1.04) for INS-AUClast. Glucodynamic activity showed a mean ratio between products of 1.00 (95% CI 0.93–1.06) for GIR-AUC0–10 h and 1.01 (95% CI 0.95–1.08) for GIRmax. The 90% CIs for pairwise treatment ratios were within the predefined equivalence range of 0.80–1.25. Both treatments were well tolerated. We concluded that similar pharmacokinetic exposure and glucodynamic potency were shown for SAR341402 and NovoRapid in healthy Japanese males.

Disentangling the impact of alcohol use and hepatitis C on insulin action in Latino individuals.

Alcohol, insulin resistance (IR), and hepatitis C (HCV) are all significant contributors to adverse outcomes of chronic liver disease. Latinos are disproportionately affected by these risk factors. We investigated the relationship between alcohol use and insulin action in a prospective cohort of Latino individuals with and without HCV. One hundred fifty-three nondiabetic Latino individuals (60 HCV+, 93 HCV-) underwent clinical evaluation and metabolic testing; 56 had repeat testing over a median follow-up of 1.5years. Peripheral IR and hepatic IR were measured via steady-state plasma glucose (SSPG) and endogenous glucose production during a two-step, 240-min insulin suppression test. Insulin secretion (IS) was measured using the graded glucose infusion test. Alcohol use was categorized as none, moderate (≤1drink/day for women and ≤2drinks/day for men), and heavy (>moderate). Multivariable models including HCV status assessed associations of alcohol use with baseline SSPG, hepatic IR and IS, and changes in these parameters over time. Overall, the median age was 44years, 63.4% were male, 66.7% overweight/ obese, and 31.9% had heavy lifetime alcohol use while 60.4% had moderate lifetime alcohol use. SSPG and IS were similar by levels of alcohol use at baseline and alcohol use was not statistically significantly associated with change in these measures over time. However, lifetime daily heavy alcohol use (vs. not heavy, coef 2.4μU-mg/kg-min-ml, p=0.04) and HCV status (coef 4.4μU-mg/kg-min-ml, p=0.0003) were independently associated with higher baseline hepatic IR, and current heavy alcohol use was associated with greater change in hepatic IR in follow-up (coef 5.8μU-mg/kg-min-ml, p=0.03). In this cohort of Latino individuals, lifetime and current heavy alcohol use influenced hepatic IR and its change over time. Strategies to decrease rates of heavy alcohol use or increase abstinence along with lifestyle modification and anti-HCV therapy to reduce metabolic risk are critical to prevent adverse liver and metabolic outcomes in Latino individuals.

Comparison of Pharmacokinetics and Pharmacodynamics of Inhaled Technosphere Insulin and Subcutaneous Insulin Lispro in the Treatment of Type 1 Diabetes Mellitus.

BackgroundThis study was performed to satisfy a US Food and Drug Administration post-marketing requirement to compare the dose responses for Technosphere® Insulin (TI; MannKind Corporation, Westlake Village, CA, USA) and subcutaneous insulin lispro (LIS) across a wide range of doses.ObjectivesThis single-center, open-label, randomized, cross-over study defined the pharmacokinetic/pharmacodynamic curves for inhaled TI vs subcutaneous LIS in persons with type 1 diabetes mellitus.MethodsEach volunteer received six treatments while undergoing euglycemic clamps: three doses of TI (10, 30 and 120 U) and LIS (8, 30, and 90 U). Primary endpoint was area under the glucose infusion rate vs time curve from start of treatment administration to end of clamp. Key secondary endpoints included readouts of insulin exposure and timing of pharmacokinetic/pharmacodynamic profiles.ResultsInsulin exposure was more than dose proportional, increasing with dose1.08 for LIS and dose1.35 for TI. Time to reach 10% of the maximum glucose infusion rate was 7 to 15 min for TI vs 21 to 38 min for LIS. End of effect was dose dependent for both treatments, ranging from 2 to 6 h (TI) and 5 to 10 h (LIS). Glucose infusion rate exhibited saturation for both treatments. Technosphere Insulin produced a lesser total effect per unit insulin than LIS due to its faster absorption and correspondingly shorter duration of exposure. The difference was large enough to require significantly different doses to achieve the same total effect.ConclusionsTechnosphere Insulin has a considerably faster onset and shorter duration of action than LIS. Consequently, the overall effect of TI is smaller than that of LIS and unit-for-unit dose conversion is not appropriate.Clinical Trial RegistrationClinicalTrials.gov, NCT02470637; 12 June, 2015Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01084-0.

Congenital Hyperinsulinism and Maple Syrup Urine Disease: A Challenging Combination

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infancy. CHI is a challenging disease to diagnose and manage. Moreover, complicating the course of the disease with another metabolic disease, in this case maple syrup urine disease (MSUD), adds more challenges to the already complex management. We report a term neonate who developed symptomatic, non-ketotic hypoglycemia with a blood glucose (BG) level of 1.9 mmol/L at 21-hours of life. A critical sample at that time showed high serum insulin and C-peptide levels confirming the diagnosis of CHI. Tandem mass spectrometry done at the same time was suggestive of MSUD which was confirmed by high performance liquid chromatography. The diagnosis of both conditions was subsequently confirmed by molecular genetic testing. His hypoglycemia was managed with high glucose infusion with medical therapy for CHI and branched chain amino acids (BCAA) restricted medical formula. At the age of four months, a near-total pancreatectomy was done, due to the failure of conventional therapy. Throughout his complicated course, he required meticulous monitoring of his BG and modified plasma amino acid profile aiming to maintain the BG at ≥3.9 mmol/L and levels of the three BCAAs at the disease therapeutic targets for his age. The patient is currently 29 months old and has normal growth and development. This patient is perhaps the only known case of the co-occurrence of CHI with MSUD. Both hypoglycemia and leucine encephalopathy can result in death or permanent neurological damage. The management of CHI and MSUD in combination is very challenging.

The glucose infusion rate of parenteral nutrition in the first week of life in preterm infants: an observational study

BackgroundMost preterm infants require a continuous glucose infusion in the early postnatal period due to the interruption of the transplacental glucose supply after birth to promote better neurodevelopmental outcomes.AimsTo investigate the glucose infusion rate (GIR) on parenteral nutrition (PN) in the first week of life administered in preterm infants and its effect on neonatal morbidity and mortality.MethodsThis study included 97 infants aged < 37 gestational weeks and weighed < 2500 g at birth. Infants recruited in this study were classified into 3 groups based on the GIR usage in parenteral nutrition as follows: GIR usage of 5- < 7 g/kg/day (Group I), GIR usage of 7–13 g/kg/day (Group II), and GIR usage of > 13–15 g/kg/day (Group III). Univariate and multivariate logistic regression analyzes were carried out to investigate whether the GIR usage in the three groups was associated with selected neonatal morbidities and mortality. Neonatal morbidities analyzed included respiratory distress syndrome (RDS), necrotizing enterocolitis, sepsis, retinopathy of prematurity, pulmonary hypertension, hypoglycemia, and hyperglycemia.ResultOf 97 preterm infants included, 51.5% infants had a gestational age of 34- < 37 weeks, and 54.6% infants had a birth weight of 1500- < 2500 g. The multivariate logistic regression analysis showed that the GIR usage of 5- < 7 g/kg/day was an independent variable that significantly increased the risk of hypoglycemia (Adjusted Odds Ratio [AOR] = 4.000, 95% Confidence Interval [CI] = 1.384–11.565, P = 0.010) and reduced the risk of sepsis (AOR = 0.096, 95% CI = 0.012–0.757, P = 0.026). The GIR usage in all three groups did not increase the risk of mortality. For neonatal morbidity analyzed in this study, RDS (AOR = 5.404, 95%CI = 1.421–20.548, P = 0.013) was an independent risk factor of mortality.ConclusionThe GIR usage of < 7 g/kg/day in PN in the first week of life administered to preterm infants was an independent variable in increasing hypoglycemia, but in contrast, reducing the risk of sepsis.

A PID Control Algorithm for a Post-Prandial Hypoglycemic Clamp Study.

Post-prandial hypoglycemia occurs 2-5 hours after food intake, in not only insulin-treated patients with diabetes but also other metabolic disorders. For example, postprandial hypoglycemia is an increasingly recognized late metabolic complication of bariatric surgery (also known as PBH), particularly gastric bypass. Underlying mechanisms remain incompletely understood to date. Besides excessive insulin exposure, impaired counter-regulation may be a further pathophysiological feature. To test this hypothesis, we need standardized postprandial hypoglycemic clamp procedures in affected and unaffected individuals allowing to reach identical predefined postprandial hypoglycemic trajectories. Generally, in these experiments, clinical investigators manually adjust glucose infusion rate (GIR) to clamp blood glucose (BG) to a target hypoglycemic value. Nevertheless, reaching the desired target by manual adjustment may be challenging and possible glycemic undershoots when approaching hypoglycemia can be a safety concern for patients. In this study, we developed a PID algorithm to assist clinical investigators in adjusting GIR to reach the predefined trajectory and hypoglycemic target. The algorithm is developed in a manual mode to permit the clinical investigator to interfere. We test the controller in silico by simulating glucose-insulin dynamics in PBH and healthy nonsurgical individuals. Different scenarios are designed to test the robustness of the algorithm to different sources of variability and to errors, e.g. outliers in the BG measurements, sampling delays or missed measurements. The results prove that the PID algorithm is capable of accurately and safely reaching the target BG level, on both healthy and PBH subjects, with a median deviation from reference of 2.8% and 2.4% respectively.Clinical relevance- This control algorithm enables standardized, accurate and safe postprandial hypoglycemic clamps, as evidenced in silico in PBH patients and controls.