Variation In Blood Glucose Concentration Research Articles

Transient Neonatal Diabetes Mellitus with the Rare Association of Nonsuppurative Sialadenitis and Genetic Defects in 6q24

Background Transient neonatal diabetes mellitus (TNDM) is the most common cause of diabetes in the first week of life, with an overall incidence of 1 in 90,000 to 160,000 live births. TNDM occurs soon after birth and undergoes spontaneous remission during infancy; however, it may relapse to a permanent form of diabetes mellitus in childhood or adolescence. We report a case of TNDM due to hypomethylation on chromosome 6q24, associated with a rare clinical finding of nonsuppurative submandibular sialadenitis managed by subcutaneous insulin, and who underwent remission by three months of age. Case Presentation. We report a male neonate of Arab ancestry delivered by caesarean section at 37 weeks of gestation. He had intrauterine growth retardation with a birth weight of 2.099 kg. He presented with hyperglycemia on the first day of life, which was managed with parenteral insulin infusion. Blood glucose control was initially difficult to achieve due to difficulties in preparing such small doses of insulin and the significant variations in blood glucose concentrations, without ketosis. Blood tests revealed low serum insulin and C-peptide levels. Genetic analysis revealed multiple loci hypomethylation of the PLAGL1/HYMAI-DMR in the TNDM region in chromosome 6q24 and two pathogenic heterozygous variants in the ZFP57 gene. Segregation analysis showed that both parents were heterozygous carriers of familial ZFP57 variants. The clinical course was associated with bilateral nonsuppurative sialadenitis, which is extremely rare among newborns. Conclusion Sialadenitis is a well-known phenomenon that is rarely diagnosed in neonates. To the best of our knowledge, this is the first case report to describe the exceedingly rare association of nonsuppurative submandibular sialadenitis in a neonate with TNDM due to multiple loci hypomethylation of the PLAGL1/HYMAI-DMR in the TNDM region in 6q24 and heterozygous pathogenic variants in the ZFP57 gene.

Construction of flexible enzymatic electrode based on gradient hollow fiber membrane and multi-wall carbon tubes meshes

In this study, we developed a convenient way to construct a flexible enzymatic electrode with excellent stability and electrochemical performance for implanted glucose monitoring. The electrode was constructed through the co-immobilization of the glucose oxidase micro-particles (GOD MPs) and multi-wall carbon nanotubes (CNT) on the inner surface of a gradient-structured hollow fiber membrane (GHM), where CNT improved the electron transport efficiency and GHM controlled the transfer of substances and interferences. GOD MPs showed higher stability under various operation conditions than the free enzymes due to the MnCO3 template method, which enabled the biosensor to remain relative sensitivity at >86% over 9 days. The GOD MPs biosensor also showed high selectivity, reproducibility, and linear sensing range from 0 mM to 24 mM (R2 = 0.9993) with a current sensitivity of 25 nA/mM. The combination of porous-structured membrane and the flexible CNT meshes ensures the electrical connections and sensing accuracy of the biosensor under the deformation status. In-vivo experiments showed reliable current responses to variations in blood glucose concentrations that were consistent with tail blood test results. This co-immobilization of enzyme micro-particles in the 3D porous structure method developed a bio-composite platform technology towards the applications in flexible sensing and implantable medical devices.

Physiological condition of nestling great tits (Parus major) declines with the date of brood initiation: a long term study of first clutches

In seasonal environments, a temporal decline in breeding performance (e.g. clutch size, nestling condition, and fledging success) of altricial bird species is a well-known phenomenon. In this study, we present the effect of laying phenology on the physiological condition of nestling great tits (Parus major) in 14 consecutive breeding seasons. We used blood haemoglobin and baseline glucose concentrations as indicators of nestling physiological condition. Nestling blood haemoglobin reflects food base quality and availability during the breeding period. Blood glucose concentration can be used as a supplementary reverse index of condition, since it is negatively related to environmental quality. It might be indicative of the stress caused by unfavourable extrinsic factors, though, due to potential confounding factors such as adverse weather conditions, low food quality, or feeding interruptions, glucose levels should be used in this ecological context with caution. Great tit nestlings from earlier broods were characterised by higher mean haemoglobin concentrations, indicating a seasonal decline in food quality and availability. The blood glucose concentration displayed an opposite pattern, with nestlings from earlier broods being characterised by lower mean concentrations than those from later broods. However, very little of the variation in blood glucose concentration can be explained by the variation in laying date, which suggests that blood glucose concentration is of little importance in the context of breeding phenology. Our results show that the physiological condition of nestlings of this species decreases as the breeding season progresses, most probably due to environmental factors.

Continuous Blood Glucose Monitoring Reveals Enormous Circadian Variations in Pregnant Diabetic Rats.

Diabetes in pregnancy is a major burden with acute and long-term consequences. Its treatment requires adequate diagnosis and monitoring of therapy. Many experimental research on diabetes during pregnancy has been performed in rats. Recently, continuous blood glucose monitoring of non-pregnant diabetic rats revealed an increased circadian variability of blood glucose that made a single blood glucose measurement per day inappropriate to reflect glycemic status. Continuous blood glucose measurement has never been performed in pregnant rats. We wanted to perform continuous blood glucose monitoring in pregnant rats to decipher the influence of pregnancy on blood glucose in diabetic and normoglycemic status. We used the transgenic Tet29 diabetes rat model with an inducible knock down of the insulin receptor via RNA interference upon application of doxycycline (DOX) leading to insulin resistant type II diabetes. All Tet29 rats received a HD-XG telemetry implant (Data Sciences International, USA) that measured blood glucose and activity continuously. Rats were divided into four groups and blood glucose was monitored until end of pregnancy or the corresponding period: Tet29 + DOX (diabetic) non-pregnant, Tet29 + DOX (diabetic) pregnant, Tet29 (normoglycemic) non-pregnant, Tet29 (normoglycemic) pregnant. All analyzed rats displayed a circadian variation in blood glucose concentration. Circadian variability was much more pronounced in pregnant diabetic rats than in normoglycemic pregnant rats. Pregnancy ameliorated variation in blood glucose in diabetic situation. Pregnancy continuously decreased blood glucose during normoglycemic pregnancy. Diabetic rats were less active than normoglycemic rats. We performed a calculation showing that application of continuous blood glucose measurement reduces animal numbers needed to detect a given effect in experimental setting by decreasing variability and SD. Continuous blood glucose monitoring via a telemetry device in pregnant rats provides a more informative picture of the glycemic situation in comparison to single measurements. This could improve diagnosis and therapy of diabetes, decrease animal numbers within experimental settings, and add another physiological parameter (activity) to the analysis that could be helpful in testing therapeutic concepts targeting blood glucose levels and peripheral muscle function. We propose continuous glucose monitoring as a new tool for the evaluation of pregnant diabetic rats.

Development of Cu nanoflowers modified the flexible needle-type microelectrode and its application in continuous monitoring glucose in vivo

A minimally invasive glucose microbiosensor based the flexibly integrated electrode for continuous monitoring glucose in vivo has been developed in this study. This was achieved by coating needle-type microelectrode with Cu nanoflowers, nafion, glucose oxidase (GOD) and polyurethane (PU) membranes, successfully prepared with layer-by-layer deposition. The Cu nanomaterials provided a large specific surface area and electrocatalytic activity for glucose detection. The PU layers as mass-transport limiting membranes significantly enhanced the linearity and stability of sensors. The resulting biosensor exhibited a wide linear range of 0–20 mM, with a good sensitivity of 42.38 nA mM−1 (correlation coefficient r2 was 0.99) and a fast response time of less than 15 s. In vivo implantable experiments using anesthetized rats showed excellent real-time response to the variation of blood glucose concentration. And the variation tendency of sensor output was consistent with that using the glucose meter. Overall, the results supported the suitability of this microsensor for measuring rapid changes of glucose in vivo. This work offers a promising approach in implantable device applications related to diabetes management as well as other medical diagnosis.

Current status and issues of the artificial pancreas: abridged English translation of a special issue in Japanese.

Surgical stress induces hyperglycemia and gives rise to glucose toxicity, which causes infectious diseases, resulting in unfavorable surgical outcomes. Intensive insulin treatment can control short- and long-term complications in patients with not only diabetes mellitus, but also surgical diabetes; however, it is associated with an increased risk of hypoglycemia. The wearable artificial pancreas was originally developed to control glucose levels in patients with type 1 diabetes, progressing to a device with enhanced stability and safety for these patients. Its usability has further progressed to include patients with type 2 diabetes. The bedside artificial pancreas is the only closed-loop-type artificial pancreas which can maintain stable glycemic control in accordance with a target blood glucose range, based on the patient's actual blood glucose levels. Moreover, this stable glycemic control with a low variation in blood glucose concentration within the target range is produced without any hypoglycemia. Significant advances of this device will now occur due to the approval of treatment for perioperative glycemic control by the Japanese Health Care Insurance System in 2016. Along with an increase in the number of mainly elderly patients with low glucose tolerance, it is expected that the role of the artificial pancreas will increase in the future. Considering the current state and expense of regenerative and transplant medicine, along with donor shortages, further development of the artificial pancreas and associated glycemic control can be expected.

Investigations on Multisensor-Based Noninvasive Blood Glucose Measurement System

Noninvasive blood glucose (NIBG) measurement technique has been explored for the last three decades to facilitate diabetes management. Photoplethysmogram (PPG) signal may be used to measure the variations in blood glucose concentration. However, the literature reveals that physiological perturbations such as temperature, skin moisture, and sweat lead to less accurate NIBG measurements. The task of minimizing the effect of these perturbations for accurate measurements is an important research area. Therefore, in the present work, galvanic skin response (GSR) and temperature measurements along with PPG were used to measure blood glucose noninvasively. The data extracted from the sensors were used to estimate blood glucose concentration with the help of two machine learning (ML) techniques, i.e., multiple linear regression (MLR) and artificial neural network (ANN). The accuracy of proposed multisensor system was evaluated by pairing and comparing noninvasive measurements with invasively measured readings. The study was performed on 50 nondiabetic subjects with body mass index (BMI) 27.3 ± 3 kg/m2. The results revealed that multisensor NIBG measurement system significantly improves mean absolute prediction error and correlation coefficient in comparison to the techniques reported in the literature.

Noninvasive monitoring of blood glucose concentration in diabetic patients with optical coherence tomography

Optical coherence tomography (OCT) has been used to noninvasively monitor the blood glucose concentration (BGC) in healthy subjects with good accuracy and acceptable specificity. Based on this, the paper further considered the possibility of OCT in noninvasive monitoring BGC in diabetic patients. The OCT signal slope (OCTSS) changed with variation of BGC. The correlation coefficient R between BGC and OCTSS in diabetic patients was 0.91; while the correlation coefficient R in healthy volunteers was 0.78. Thus, a better linear dependence of OCTSS on BGC in diabetic patients was presented in the experiment. The results showed that the capability and accuracy of OCT in noninvasive monitoring BGC of diabetic patients, and the noninvasive monitoring BGC in diabetic patients may be better than the monitoring in the healthy subjects.

PVDF-Nafion nanomembranes coated microneedles for in vivo transcutaneous implantable glucose sensing.

We demonstrate that microporous PVDF membranes sandwiched between multiple layers of nanomaterials can be used for continuous monitoring of glucose level in vivo. This is achieved by coating needle electrodes with Polyaniline nanofiber, Platinum nanoparticles, glucose oxidase enzyme and porous layers, successfully fabricated with layer-by-layer deposition. Nanoparticles incorporated into conductive Polyaniline nanofibers resulted in high surface to volume ratio and electrocatalytic activity for glucose enzyme. A composite coating membrane of porous PVDF and nano-sphere Nafion limited the glucose transportation and increased the lifetime of in vivo measurements. The glucose biosensor exhibited a sub-microamperometric output current, fast response time of less than 30s and a sensitivity of 0.23 μA/mM. The linear sensing range in terms of glucose concentration was from 0 to 20mM. Implantable experiments using mice models showed excellent response to the variation of blood glucose concentration while maintaining biocompatibility with the surrounding tissues. The sensitivity was shown to remain within 10% close to initial sensitivity within the 7 days of continuous monitoring, and maintain at 70% of the initial sensitivity within 21 days.

Comparative Study of Variations in Blood Glucose Concentration in Different Phases of Menstrual Cycle in Young Healthy Women Aged 18-22 Years.

Comparative Study of Variations in Blood Glucose Concentration in Different Phases of Menstrual Cycle in Young Healthy Women Aged 18-22 Years.

Perioperative glycemic control using an artificial endocrine pancreas in patients undergoing total pancreatectomy: Tight glycemic control may be justified in order to avoid brittle diabetes

I dedicate this paper to the late Prof. Yukihiko Nosé with all my heart. In 2001, under the direction of Prof. Nosé and Prof. Brunicardi at Baylor College of Medicine, we published a review article entitled "Artificial endocrine pancreas" in JACS. Subsequently, we reported that perioperative tight glycemic control (TGC) using an artificial pancreas (AP) with a closed-loop system could stably maintain near-normoglycemia in total-pancreatectomized dogs. Based on this experimental study in Houston, since 2006, we have introduced perioperative TGC using an AP into clinical use in Kochi. As of 2011, this novel TGC method has provided safe and stable blood glucose levels in more than 400 surgical patients. In this paper, we report new clinical findings regarding perioperative TGC using an AP in total-pancreatectomized patients. TGC using an AP enables us to achieve stable glycemic control not only without hypoglycemia and hyperglycemia but also with less variation in blood glucose concentration from the target blood glucose range, even in patients with the most serious form of diabetes, so-called "brittle diabetes", undergoing total pancreatectomy. To the best of our knowledge, this is the first clinical report of TGC using an AP in patients undergoing total pancreatic resection.

Noninvasive blood glucose monitoring during oral intake of different sugars with optical coherence tomography in human subjects

The potential of OCT applied to noninvasive blood glucose monitoring has attracted significant efforts. In this work we investigated the feasibility of OCT in monitoring blood glucose during oral intake of different sugars in humans. Five groups of experiments were performed, in which different sugars were used. The OCT signal slope (OCTSS) changed with variation of blood glucose concentration (BGC). A good correlation between OCTSS and BGC was observed in these experiments. The averaged correlation coefficients R between OCTSS and BGC are 0.900, 0.836, 0.895 and 0.884, corresponding to oral administration of glucose, fructose, sucrose and mixed sugar, respectively. Our studies demonstrated the capability and accuracy of the OCT system in monitoring BGC noninvasively and it could become a powerful tool in daily blood glucose monitoring for patients.

Pancreatic β‐cell: the beauty of being plastic

Pancreatic β‐cell: the beauty of being plastic

Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?

Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P < 0.0001) of patients in the control group. If appropriately applied, such protocols should decrease both the mean blood glucose concentration and its variability (variation of blood glucose concentration). Thus, it is logically possible that the benefit of intensive insulin therapy in the first Leuven trial was due to a decrease in mean glucose levels, a decrease in their variability, or both. Several recent studies have confirmed significant associations between variability of blood glucose levels and patient outcomes. Decreasing the variability of blood glucose levels might be an important dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.

Serum glycated albumin: Potential use as an index of glycemic control in diabetic dogs

Measurements of serum fructosamine, glycated hemoglobin, and glycated albumin (GA) complement serum glucose concentration for better management of diabetes mellitus (DM). Especially, the serum fructosamine test has long been used for diagnosing and monitoring the effect of treatment of DM in dogs. However, fructosamine tests are currently not performed in veterinary medicine in Japan. GA and fructoasmine levels have been shown to strongly correlate. However, the clinical implications of using GA remain to be elucidated. Therefore, the purpose of the current study was threefold: 1) Determine whether GA% is altered by acute hyperglycemia in normal dogs, simulating stress induced hyperglycemia; 2) Demonstrate that GA% does not dynamically change with diurnal variation of blood glucose concentration in diabetic dogs; and 3) Investigate whether GA% is capable of providing an index of glycemic control for 1-3 weeks in diabetic dogs as is the case with diabetic human patients. Our study demonstrated that serum GA% remains very stable and unaltered under acute hyperglycemic conditions (intravenous glucose injection) and in spite of diurnal variation of blood glucose concentration. Furthermore, serum GA% can reflect long-term changes (almost 1-3 weeks) in blood glucose concentration and the effect of injected insulin in diabetic dogs.

Glucose control in critical illness using a web-based insulin dose calculator

Objective We describe a modified version of a web-based insulin calculator for the control of blood glucose in critical care. Design We modified a previously described calculator by incorporating bolus doses of insulin to be given. The calculator is now also able to store blood glucose concentrations, insulin rates, bed number and the date and time of calculation. We modified our feeding protocol to restrict the target enteral feed from 1800 to 1500 kcal per day and removed the night time rest period. Setting A 16-bedded intensive care unit. Patients and participants All patients admitted to the ICU between June 2005 and May 2006. Measurements and results Six hundred and sixty-one patients admitted (mean APACHE II score 16 [S.D. 7]), mean age 51 years [S.D. 17]. One hundred and forty-six patients died prior to ICU discharge. Total of 5573 patient days with 13,029 recorded calculation data points. Mean blood glucose concentration was 6.7 mmol (95CI 3.7–12.1). There were 34 episodes of treated hypoglycaemia of which 11 were on an insulin infusion. There were two troughs in the time of data entry that corresponded with staff handover. There was no evidence of diurnal variation in blood glucose concentration. The mean value of the insulin infusion rate was 4.3 units/h (S.D. 3.7). Conclusions The web-based insulin calculator facilitates the dosing of insulin in critical care. The lack of diurnal blood glucose concentrations suggests that once daily estimation of blood glucose may be an acceptable method of monitoring blood glucose concentrations in critical care.

Pharmacodynamics And Stability of Subcutaneously Infused Glucagon in A Type 1 Diabetic Swine Model In Vivo

The objective of this study was to determine the in vivo pharmacodynamics of glucagon and to test its glycemic effect over days by assessing its time course of activity and potency in a type 1 diabetic swine model. Individual experiments were conducted in different pigs using glucagon preparations that were reconstituted on different days and stored at room temperature or near body temperature before usage. All experiments involved a subcutaneous bolus of glucagon to counter impending hypoglycemia induced by an earlier bolus of fast-acting insulin. Frequent blood-glucose measurements, using a standard in vitro hand-held meter, were taken during each experiment to track variations in blood-glucose concentration. Significant glucagon action was observed as early as 5 min after administration, as evidenced by an effective halt to declining blood glucose and a subsequent twofold rise in blood glucose after approximately 20 min. Results also indicate that the consumption of glucagon from the subcutaneous depot is substantially faster than that of fast-acting insulin. Furthermore, no significant depreciation was observed in glucagon efficacy across aging preparations as old as 7 days. These results suggest profound utility of subcutaneous glucagon in a closed-loop glucose control system, especially since glucagon would provide an effective safeguarding measure to stave off impending hypoglycemia, an application where the rapid effect of subcutaneous glucagon is both serendipitous and essential. Despite the notion that the stability of glucagon in solution at room temperature is inferior to that of fast-acting insulin, its subcutaneous administration has promising prospects for long-term closed-loop ambulatory care.

In vivo study of glucose-induced changes in skin properties assessed with optical coherence tomography

Recently, our in vivo studies demonstrated a strong correlation between blood glucose concentration and the slope of the optical coherence tomography (OCT) signal when the probing beam was scanned over a straight line. To improve the sensitivity of OCT for blood glucose monitoring, two-dimensional (2D) lateral scanning of the OCT probing beam was proposed. Depth-dependent changes in pig skin properties with variation of blood glucose concentration were revealed due to significant suppression of speckle noise and motion artefacts in 2D scanning mode. The correlation coefficient of the OCT signal slope with blood glucose concentration varied periodically in the range from −0.9 to +0.9 depending on depth. The period of variation of the correlation coefficient was 100–150 µm that corresponded to the distance between neighbour collagen bundles. We also observed a decrease of skin thickness by 10 ± 7.5 µm with an increase of blood glucose concentration by 277 ± 56 mg dl−1. Mechanisms of glucose-induced changes in skin properties owing to tissue layer shift caused by dehydration associated with the glucose osmotic effect were considered.

Gastrointestinal motility and glycemic control in diabetes: the chicken and the egg revisited?

Upper gastrointestinal dysfunction occurs frequently in diabetes and potentially contributes to both abdominal symptoms and impaired glycemic control; conversely, variations in blood glucose concentration reversibly affect gut motility in humans. In this issue of the JCI, Anitha et al. report apoptosis of rodent enteric neurons under hyperglycemic conditions, both in vitro and in vivo, associated with impaired PI3K activity and preventable by glial cell line-derived neurotrophic factor. These observations add to recent insights gained from animal models regarding the etiology of diabetic gastrointestinal dysfunction, but investigators must strive to translate animal data to human diabetes.

247 Infusion Rate of Glucose is The Major Predictor of Hyperglycemia in Very Premature Infants Receiving Total Parenteral Nutrition

Background: Hyperglycemia occurs frequently in very premature infants receiving total parenteral nutrition (TPN). Commonly, the glucose infusion rates in TPN exceed the patient's glucose needs. In adult intensive care patients, accompanying hyperglycemia was associated with increased mortality. Since premature infants also represent a high-risk population, preventing hyperglycemia while providing sufficient energy intake may likewise reduce the risk of an adverse outcome.Objective: To determine whether hyperglycemia in infants receiving standard TPN is primarily due to differences in their ability to suppress hepatic glucose production when presented with a high rate of exogenous glucose or to failure of the infant's disposal rate to match the intake.Design/Methods: 11 clinically stable infants (962±49 g; 26.7±0.4 wks) were studied on day 4±1 of life while receiving TPN as ordered by the attending physician. Glucose production rate (GPR) was measured during an 8 h period of stable blood glucose using isotope dilution of [6,6–2H2]glucose. Multiple regression analysis was used to determine the effects of infusion rate of glucose, lipids and amino acids, residual GPR, gestational age and birth weight on blood glucose concentration.Results: Range and median (within parenthesis) for each parameter: Blood glucose 5.3–12.6 (7.1) mM; Total glucose appearance rate (Ra) 8.9–13.1 (10.9) mg/kg min of which glucose infusion was 7.3–11.3 (9.5) mg/kg min and residual GPR 0.1–1.5 (1.4) mg/kg min; Infusion rate of lipids was 0.6–2.7 (2.1) mg/kg min and of amino acids 1.6–2.2 (2.0) mg/kg min. Glucose Ra explained 58% of the variation in blood glucose concentration (p<0.007), of which the glucose infusion rate accounted for the major part, 49% (p<0.02) and GPR for only 9% (p<0.05); gestational age explained 9% while infusion rates of amino acids and lipids, and birth weight did not affect blood glucose concentration. GPR was suppressed by 80% (assuming a normal glucose turnover rate of 6 mg/kg min).Conclusion: In premature infants receiving TPN, the infusion rate of glucose is the strongest predictor of hyperglycemia, while residual GPR and gestational age have marginal impact. A potential clinical implication of these results is that a reduction of the glucose infusion rate while maintaining adequate supply of lipids and amino acids will reduce the incidence of hyperglycemia without compromising energy and protein balance. Grants: NIHRO1-HD37957–05; GCRCNIHHO1-RR-001888.