Blood Glucose Levels In Range Research Articles

Glucose-Induced Cellular Morphological Changes Across Mammalian Species

All organisms encounter environmental fluctuations and must contend with these changes to maintain homeostasis. Some mammals tolerate a wide range of intracellular conditions while others do not. Altered glucose levels are an example of a physiological challenge that can be encountered by cells. We studied responses of dermal fibroblasts obtained from skin biopsies to altered glucose treatments in culture using a comparative approach. Specifically, we investigated responses of mammals known to tolerate a range of blood glucose levels (fruit-eating geladas and Egyptian rousettes) as well as a hibernator (ground squirrel), which exhibits a marked winter decrease in glucose metabolism. As a comparison, we investigated species that maintain fairly stable blood glucose (human and rat). Fibroblasts were cultured at baseline (8mM glucose), then subjected to hypoglycemic (2.5mM) and hyperglycemic (30mM) treatment over 24h. We assayed glycolytic rate in human and rat fibroblasts using a Seahorse XFp analyzer, and found no significance between oxygen consumption or glycolysis across glucose treatments (all p>0.05). To investigate underlying cell phenotypes, we used Cell Painting, employing fluorescent stains to mark organelles. Hoechst 34580 stained DNA, to quantify number and size of nuclei, offering insights into proliferation. MitoTracker Deep Red visualized mitochondria, providing information about energy generation. Alexa Fluor 488 Concanavalin A conjugate marked endoplasmic reticulum. F-actin was stained with Alexa Fluor 555 Phalloidin conjugate, detecting cytoskeletal organization and overall cell structure. Images were analyzed with CellProfiler software, which extracts ~1400 morphological cell features, including area, compactness, fluorescence intensity, and cell connectivity to quantify subtle changes in phenotype. Each extracted feature will be compared across treatments and within a comparative context. We predict that fibroblasts exposed to hyperglycemia exhibit mitochondrial fragmentation and redistribution (MitoTracker) and increased production of reactive oxygen species (assessed with MitoSOX), which is linked to the opening of mitochondrial permeability transition pores. Cell Profiler analysis will identify structural changes that could indicate negative outcomes, such as mitophagy. Hyperglycemia may also induce endoplasmic stress, increasing lipid droplets and altering shape and size of the endoplasmic reticulum. In contrast, hypoglycemia will cause mitochondrial degradation. In both hyper- and hypoglycemia, proliferation rates are predicted to decrease, resulting in fewer nuclei and reduced cell connectivity. Phenotypic differences across species, evaluated in the context of their organismal phenotype, will help explain the mechanisms of cell function in mammals under environmental stress. Funding by NSF #2022046. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Glycemic Control in Critically Ill COVID-19 Patients: Systematic Review and Meta-Analysis.

Background: Given the mortality risk in COVID-19 patients, it is necessary to estimate the impact of glycemic control on mortality rates among inpatients by designing and implementing evidence-based blood glucose (BG) control methods. There is evidence to suggest that COVID-19 patients with hyperglycemia are at risk of mortality, and glycemic control may improve outcomes. However, the optimal target range of blood glucose levels in critically ill COVID-19 patients remains unclear, and further research is needed to establish the most effective glycemic control strategies in this population. Methods: The investigation was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data sources were drawn from Google Scholar, ResearchGate, PubMed (MEDLINE), Cochrane Library, and Embase databases. Randomized controlled trials, non-randomized controlled trials, retrospective cohort studies, and observational studies with comparison groups specific to tight glycemic control in COVID-19 patients with and without diabetes. Results: Eleven observational studies (26,953 patients hospitalized for COVID-19) were included. The incidence of death was significantly higher among COVID-19 patients diagnosed with diabetes than those without diabetes (OR = 2.70 [2.11, 3.45] at a 95% confidence interval). Incidences of death (OR of 3.76 (3.00, 4.72) at a 95% confidence interval) and complications (OR of 0.88 [0.76, 1.02] at a 95% confidence interval) were also significantly higher for COVID-19 patients with poor glycemic control. Conclusion: These findings suggest that poor glycemic control in critically ill patients leads to an increased mortality rate, infection rate, mechanical ventilation, and prolonged hospitalization.

Reduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study

Objective: The aim of the study was to investigate the different extent of inhibition of endogenous insulin secretion by the reduction of C-peptide levels in an euglycemic clamp study and its effects on the evaluation of pharmacokinetics, pharmacodynamics of insulin preparations, and quality of clamp study to determine the best reduction range of C-peptide levels. Methods: Healthy Chinese male volunteers were enrolled and underwent a single-dose euglycemic clamp test. Participants were subcutaneously injected with long-acting insulin glargine (0.4 IU/kg). Blood samples were collected pretest and up to 24 h post-test to assess pharmacokinetics (PK), pharmacodynamics (PD), and C-peptide levels. Results: We divided the 39 volunteers enrolled in the study into three groups according to the reduction of C-peptide levels: group A (ratio of C-peptide reduction <30%, n = 13), group B (ratio of C-peptide reduction between ≥ 30% and <50%, n = 15), and group C (ratio of C-peptide reduction ≥50%, n = 11); there were significant differences in the three groups (p = 0.000). The upper and lower limits of blood glucose oscillation in group C was statistically lower than the other groups, the range of oscillating glucose levels in group C was −17.0 ± 6.6% to −1.1 ± 6.7%. The AUC0–24 h in groups A, B, and C were 9.7 ± 2.2, 11.0 ± 2.9, and 11.9 ± 2.1 ng/ml × min, respectively, which indicated an increasing trend in the three groups (P trend = 0.041). For quality assessment, the average glucose (p = 0.000) and MEFTG (p = 0.001) levels in three groups were significantly different. Conclusion: The different extent of inhibition of endogenous insulin will influence the PK/PD of insulin preparations and the quality of the euglycemic clamp. Furthermore, the ratio of C-peptide reduction should be above 50% to free from the interference of endogenous insulin, and the range of blood glucose levels should be consistently maintained at −10% to 0 in the euglycemic clamp.

A Pilot Trial to Evaluate the Accuracy of a Novel Non-Invasive Glucose Meter.

The non-invasive self-monitoring of blood glucose (SMBG) has been the subject of intense investigation over recent decades. We conducted a pilot study designed to examine a novel non-invasive glucometer, the HGR GWave, utilizing radiofrequency (RF) sensing. Blood glucose levels assessed by this HGR prototype were compared to measurements performed by a hexokinase core laboratory assay during an oral glucose tolerance test (oGTT) for 5 subjects with type 2 diabetes. The HGR glucose meter readings were also compared to two Abbot Freestyle® glucose meters, which were also used for calibration. The accuracy of the results was evaluated through the calculation of relative absolute difference (RAD), specified percentage differences between 43 reference glucose measurements, and using comparator measurements. The median RAD was −4.787. We detected 79.04%, 92.99% and 97.64% of HGR readings within ±10%, ±15% and ±20% of the reference glucose measurements. The HGR readings had a high correlation with reference lab glucose measurements with R2 = 0.924 (95% CI 0.929–0.979; p < 0.0001). When compared to the Freestyle® glucose meters 94.3% and 100% of the readings were within ±5% and ±10%, with R2 = 0.975 (0.975–0.994; p < 0.0001). The HGR prototype glucose meter was found to be accurate in detecting real-time blood glucose during an oGTT in this small pilot study. A study with a broader range of blood glucose levels is needed to further assess its accuracy and its suitability for clinical use.

Learning Carbohydrate Digestion and Insulin Absorption Curves Using Blood Glucose Level Prediction and Deep Learning Models.

Type 1 diabetes is a chronic disease caused by the inability of the pancreas to produce insulin. Patients suffering type 1 diabetes depend on the appropriate estimation of the units of insulin they have to use in order to keep blood glucose levels in range (considering the calories taken and the physical exercise carried out). In recent years, machine learning models have been developed in order to help type 1 diabetes patients with their blood glucose control. These models tend to receive the insulin units used and the carbohydrate taken as inputs and generate optimal estimations for future blood glucose levels over a prediction horizon. The body glucose kinetics is a complex user-dependent process, and learning patient-specific blood glucose patterns from insulin units and carbohydrate content is a difficult task even for deep learning-based models. This paper proposes a novel mechanism to increase the accuracy of blood glucose predictions from deep learning models based on the estimation of carbohydrate digestion and insulin absorption curves for a particular patient. This manuscript proposes a method to estimate absorption curves by using a simplified model with two parameters which are fitted to each patient by using a genetic algorithm. Using simulated data, the results show the ability of the proposed model to estimate absorption curves with mean absolute errors below 0.1 for normalized fast insulin curves having a maximum value of 1 unit.

Study of blood glucose and insulin infusion rate in real-time in diabetic rats using an artificial pancreas system.

Artificial pancreas system (APS) is an emerging new treatment for type 1 diabetes mellitus. The aim of this study was to develop a rat APS as a research tool and demonstrate its application. We established a rat APS using Medtronic Minimed Pump 722, Medtronic Enlite sensor, and the open artificial pancreas system as a controller. We tested different dilutions of Humalog (100 units/ml) in saline ranged from 1:3 to 1:20 and determined that 1:7 dilution works well for rats with ~500g bodyweight. Blood glucose levels (BGL) of diabetic rats fed with chow diet (58% carbohydrate) whose BGL was managed by the closed-loop APS for the total duration of 207h were in euglycemic range (70-180 mg/dl) for 94.5% of the time with 2.1% and 3.4% for hyperglycemia (>180mg/dl) and hypoglycemia (<70 mg/dl), respectively. Diabetic rats fed with Sucrose pellets (94.8% carbohydrate) for the experimental duration of 175h were in euglycemic range for 61% of the time with 35% and 4% for hyperglycemia and hypoglycemia, respectively. Heathy rats fed with chow diet showed almost a straight line of BGL ~ 95 mg/dl (average 94.8 mg/dl) during the entire experimental period (281h), which was minimally altered by food intake. In the healthy rats, feeding sucrose pellets caused greater range of BGL in high and low levels but still within euglycemic range (99.9%). Next, to study how healthy and diabetic rats handle supra-physiological concentrations of glucose, we intraperitoneally injected various amounts of 50% dextrose (2, 3, 4g/kg) and monitored BGL. Duration of hyperglycemia after injection of 50% dextrose at all three different concentrations was significantly greater for healthy rats than diabetic rats, suggesting that insulin infusion by APS was superior in reducing BGL as compared to natural insulin released from pancreatic β-cells. Ex vivo studies showed that islets isolated from diabetic rats were almost completely devoid of pancreatic β-cells but with intact α-cells as expected. Lipid droplet deposition in the liver of diabetic rats was significantly lower with higher levels of triacylglyceride in the blood as compared to those of healthy rats, suggesting lipid metabolism was altered in diabetic rats. However, glycogen storage in the liver determined by Periodic acid-Schiff staining was not altered in diabetic rats as compared to healthy rats. A rat APS may be used as a powerful tool not only to study alterations of glucose and insulin homeostasis in real-time caused by diet, exercise, hormones, or antidiabetic agents, but also to test mathematical and engineering models of blood glucose prediction or new algorithms for closed-loop APS.

Maintaining Blood Glucose Levels in Range (70-150 mg/dL) is Difficult in COVID-19 Compared to Non-COVID-19 ICU Patients-A Retrospective Analysis.

Beta cell dysfunction is suggested in patients with COVID-19 infections. Poor glycemic control in ICU is associated with poor patient outcomes. This is a single center, retrospective analysis of 562 patients in an intensive care unit from 1 March to 30 April 2020. We review the time in range (70–150 mg/dL) spent by critically ill COVID-19 patients and non-COVID-19 patients, along with the daily insulin use. Ninety-three in the COVID-19 cohort and 469 in the non-COVID-19 cohort were compared for percentage of blood glucose TIR (70–150 mg/dL) and average daily insulin use. The COVID-19 cohort spent significantly less TIR (70–150 mg/dL) compared to the non-COVID-19 cohort (44.4% vs. 68.5%). Daily average insulin use in the COVID-19 cohort was higher (8.37 units versus 6.17 units). ICU COVID-19 patients spent less time in range (70–150 mg/dL) and required higher daily insulin dose. A higher requirement for ventilator and days on ventilator was associated with a lower TIR. Mortality was lower for COVID-19 patients who achieved a higher TIR.

Lifetime overproduction of circulating angiotensin-(1-7) in rats attenuates the increase in skeletal muscle damage biomarkers after exhaustive exercise.

Angiotensin-(1-7) (Ang-[1-7]) can modulate glucose metabolism and protect against muscular damage. The aim of this study was to investigate the influence of lifetime increase of circulating levels of Ang-(1-7) at exhaustive swimming exercise (ESE). Sprague-Dawley (SD) and transgenic rats TGR(A1-7)3292 (TR) which overproduce Ang-(1-7) (2.5-fold increase) were submitted to ESE. The data showed no differences in time to exhaustion (SD: 4.90 ± 1.37 h vs. TR: 5.15 ± 1.15 h), creatine kinase, and transforming growth factor beta (TGF-β). Lactate dehydrogenase (SD: 219.9 ± 12.04 U/L vs. TR: 143.9 ± 35.21 U/L) and α-actinin (SD: 336.7 ± 104.5 U/L vs. TR: 224.6 ± 82.45 U/L) values were significantly lower in TR. There was a significant decrease in the range of blood glucose levels (SD: -41.4 ± 28.32 mg/dl vs. TR: -13.08 ± 39.63 mg/dl) in SD rats. Muscle (SD: 0.06 ± 0.02 mg/g vs. TR: 0.13 ± 0.01 mg/g) and hepatic glycogen (SD: 0.66 ± 0.36 mg/g vs. TG: 2.24 ± 1.85 mg/g) in TR were higher. The TR presented attenuation of the increase in skeletal muscle damage biomarkers and of the changes in glucose metabolism after ESE.

Blood glucose levels in healthy, term, appropriate for gestational age, exclusively breastfed infants

Objective This study aimed to determine blood glucose levels ofhealthy, term, appropriate for gestational age (AGA), exclusivelybreastfed infants at the age of 6, 12, 24, 48, and 72 hours of life,and to investigate the incidence of hypoglycemia in those infants.Methods All healthy, term, AGA infants born in CiptoMangunkusumo General Hospital, Jakarta, who were exclusivelybreastfed during the recruitment period of December 2003 untilFebruary 2004, were included in this study. These infants weresubjected to blood glucose level determination at the age of 6, 12,24, 48, or 72 hours of life, and the clinical signs of hypoglycemiawere monitored.Results Two hundred and fifteen blood samples taken from 137newborns were studied. There was no incidence of hypoglycemiaobserved, whether symptomatic or asymptomatic. The range ofblood glucose levels was between 41 mg/dl and 115 mg/dl. Themeans and the standard deviations (SD) of the blood glucose lev-els of the 6-, 12-, 24-, 48- and 72-hour old infants were 59.7 (11.98)mg/dl, 64.1 (13.51) mg/dl, 65.9 (14.42) mg/dl, 67.0 (14.95) mg/dl,and 78.6 (16.51) mg/dl, respectively.Conclusions The current concern for hypoglycemia in the popu-lation of healthy, term, AGA, exclusively breastfed infants duringthe first few days of life was not proven to exist. Therefore, there isno reason to resort to prelacteal feeding in such infants

Association of Random Plasma Glucose Levels With the Risk for Cardiovascular Disease Among Chinese Adults Without Known Diabetes.

Diabetes is a known risk factor for cardiovascular disease (CVD). Substantial uncertainty remains, however, about the relevance to CVD risk for blood glucose levels below the diabetes threshold. To examine the association of random plasma glucose (RPG) levels with the risk for major CVD in Chinese adults without known diabetes. This prospective cohort study included 467 508 men and women aged 30 to 79 years with no history of diabetes, ischemic heart disease (IHD), stroke, or transient ischemic attack. Participants were recruited from 5 urban and 5 rural diverse locations across China from June 25, 2004, to July 15, 2008, and followed up to January 1, 2014. Baseline and usual (longer-term average) RPG level. Cardiovascular deaths, major coronary events (MCE) (including fatal IHD and nonfatal myocardial infarction), ischemic stroke (IS), major occlusive vascular disease (MOVD) (including MCE or IS), and intracerebral hemorrhage. Preliminary validation of stroke and IHD events demonstrated positive predictive values of approximately 90% and 85%, respectively. Cox regression yielded adjusted hazard ratios (aHRs) for CVD associated with RPG levels. Among the 467 508 participants (41.0% men; 59.0% women; mean [SD] age, 51 [11] years), a significant positive association of baseline RPG levels with CVD risks continued to 4.0 mmol/L (72 mg/dL). After adjusting for regression dilution bias, each 1-mmol/L (18-mg/dL) higher usual RPG level above 5.9 mmol/L (106 mg/dL) was associated with an 11% higher risk for cardiovascular death (6645 deaths; aHR, 1.11; 95% CI, 1.10-1.13). Similarly strong positive associations were seen for MCE (3270 events; aHR, 1.10; 95% CI, 1.08-1.13), IS (19 153 events; aHR, 1.08; 95% CI, 1.07-1.09), and MOVD (22 023 events; aHR, 1.08; 95% CI, 1.07-1.09). For intracerebral hemorrhage, the association was weaker, but also significant (4326 events; aHR, 1.05; 95% CI, 1.02-1.07). These associations persisted after excluding participants who developed diabetes during follow-up. Among adult Chinese without diabetes, lower RPG levels are associated with lower risks for major CVDs, even within a normal range of blood glucose levels.

Glucose levels in newborns with special reference to hypoglycemia: a study from rural India.

Hypoglycemia is one of the common metabolic problems in neonatal medicine. There is association between blood glucose levels and neurological development. The study involved 100 mothers and neonates blood glucose levels were measured using a standard glucometer in mother delivering babies within half an hour of delivery and in newborns at 0, 3, 6, 12, 24 h of life. Blood glucose levels were low at 0th and 6th h and maximum at 24th h. Neonates born to mothers with high maternal blood glucose levels were hypoglycemic showing a negative correlation. The mean blood glucose levels were low in pre-term and post-term compared with term babies and range of blood glucose levels were wide in preterm and post term babies.

Toward CMOS image sensor based glucose monitoring

Complementary metal oxide semiconductor (CMOS) image sensor is a powerful tool for biosensing applications. In this present study, CMOS image sensor has been exploited for detecting glucose levels by simple photon count variation with high sensitivity. Various concentrations of glucose (100 mg dL(-1) to 1000 mg dL(-1)) were added onto a simple poly-dimethylsiloxane (PDMS) chip and the oxidation of glucose was catalyzed with the aid of an enzymatic reaction. Oxidized glucose produces a brown color with the help of chromogen during enzymatic reaction and the color density varies with the glucose concentration. Photons pass through the PDMS chip with varying color density and hit the sensor surface. Photon count was recognized by CMOS image sensor depending on the color density with respect to the glucose concentration and it was converted into digital form. By correlating the obtained digital results with glucose concentration it is possible to measure a wide range of blood glucose levels with great linearity based on CMOS image sensor and therefore this technique will promote a convenient point-of-care diagnosis.

Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: A cross-sectional study

The goal of the study was to determine the association between diabetes and inflammation in clinically diagnosed diabetes patients. We hypothesized that low-grade inflammation in diabetes is associated with the level of glucose control. Using a cross-sectional design we compared pro- and anti-inflammatory cytokines in a community-recruited cohort of 367 Mexican Americans with type 2-diabetes having a wide range of blood glucose levels. Cytokines (IL-6, TNF-α, IL-1β, IL-8) and adipokines (adiponectin, resistin and leptin) were measured using multiplex ELISA. Our data indicated that diabetes as whole was strongly associated with elevated levels of IL-6, leptin, CRP and TNF-α, whereas worsening of glucose control was positively and linearly associated with high levels of IL-6, and leptin. The associations remained statistically significant even after controlling for BMI and age (p=0.01). The association between TNF-α, however, was attenuated when comparisons were performed based on glucose control. Strong interaction effects between age and diabetes and BMI and diabetes were observed for IL-8, resistin and CRP. The cytokine/adipokine profiles of Mexican Americans with diabetes suggest an association between low-grade inflammation and quality of glucose control. Unique to in our population is that the chronic inflammation is accompanied by lower levels of leptin.

Stable refraction and visual acuity in diabetic patients with variable glucose levels under routine care

To investigate how refraction and visual acuity may vary in patients with diabetes under routine care. Fifty-three eyes of 53 patients with various degrees of diabetic retinopathy were examined prospectively on four different occasions within a month. Refraction, best-corrected visual acuity (expressed as logMAR score) and blood glucose were measured on each occasion. Intraindividual variability was calculated as the range between the highest and lowest measurements. Associations between blood glucose levels and each of the other variables were tested by linear regression analysis for each patient. Refraction was completely stable in 43 patients and changed only slightly in 10, in whom the mean intraindividual variability of the spherical equivalent was 0.4 dioptres. Visual acuity test results were also highly reproducible. Mean intraindividual variability in visual acuity was 0.08 logMAR. Mean haemoglobin A1c (HbA1c) was 7.3 ± 1.5% but individual blood glucose levels ranged from 2.8 to > 22.2 mmol/l. Intraindividual variability ranged from 0.5 to 18.1 mmol/l, with a median of 6.0 mmol/l for the entire group. There were no associations between refraction or visual acuity and blood glucose levels or inter- or intraindividual glucose variations. Refraction and visual acuity test results were highly reproducible and stable in patients with reasonably well controlled diabetes but variable blood glucose levels under routine care.

Engineering periplasmic ligand binding proteins as glucose nanosensors

Diabetes affects over 100 million people worldwide. Better methods for monitoring blood glucose levels are needed for improving disease management. Several labs have previously made glucose nanosensors by modifying members of the periplasmic ligand binding protein superfamily. This minireview summarizes recent developments in constructing new versions of these proteins that are responsive within the physiological range of blood glucose levels, employ new reporter groups, and/or are more robust. These experiments are important steps in the development of novel proteins that have the characteristics needed for an implantable glucose nanosensor for diabetes management: specificity for glucose, rapid response, sensitivity within the physiological range of glucose concentrations, reproducibility, and robustness.

Effect of popular takeaway foods on blood glucose levels in type 1 diabetes mellitus patients on intensive insulin therapy

Intensive insulin therapy (IIT) is the preferred treatment for patients with type 1 diabetes, which requires them to calculate the total number of grams of carbohydrate eaten, but little research has been performed on the effect of mixed meals on blood sugar. We examined the effects of popular takeaway foods on glycaemic response in people with type 1 diabetes. Nine participants on IIT each consumed a pasta, Thai, hamburger and sandwich (cheese sandwich and an apple) meal on four different occasions, at least 3 days apart. The meals had the same amount of carbohydrate but different macronutrient quantities and different glycaemic indices (GI). Participants' normal basal insulin was given, but the mealtime bolus insulin was withheld to measure blood glucose level (BGL), every half hour for 3 h postprandially. The glycaemic response as measured by 2-h BGL, the area under the BGL curve and BGL range (maximum-minimum over 3 h) were consistently lower after ingesting a low-GI high-fat pasta meal in relation to the other meals. There was no difference between the sandwich, Thai and hamburger meals. BGLs rose between 3.91 and 8.44 mmol/l at the conclusion of 3 h, which shows that a single CHO portion (15 g) can raise BGLs by 1-2 mmol/l, depending on the GI of the food. People with type 1 diabetes on IIT who are concerned about postprandial glycaemic variability should consider not only overall carbohydrate content but also glycaemic index and fat content when adjusting insulin dosages.

Survey of the management of neonatal hyperglycaemia in Australasia

Hyperglycaemia is a common problem in very low birthweight (VLBW) preterm neonates and has been associated with an increase in intraventricular haemorrhage and mortality. There are few data to guide clinicians on the best range of blood glucose levels to aim for when treating hyperglycaemic preterm babies with insulin. The aim of this study was to survey all Australasian tertiary neonatal intensive care units for their current practice in the definition and management of neonatal hyperglycaemia to aid in the design of a randomised controlled trial of the effect of tight glycaemic control on long-term outcome in VLBW babies. An online survey was sent to the 27 tertiary neonatal units in Australasia asking the respondents for details of their unit's definition and management of hyperglycaemia in VLBW infants. Twenty-three tertiary neonatal units responded to the questionnaire. There were six different definitions of hyperglycaemia, with most units defining neonatal hyperglycaemia as a blood glucose level greater than 10 mM. There were large variations in the criteria for commencing insulin (blood glucose level 8-15 mM +/- glycosuria) and target blood glucose ranges for babies on insulin (ranging from 2.5-8 mM to 8-15 mM). There is a wide variation in the management of neonatal hyperglycaemia between tertiary neonatal units in Australasia. This reflects the paucity of data available in this area. Further research on the management of neonatal hyperglycaemia is needed.

Failure to achieve glycemic control despite intensive insulin therapy in a medical ICU: incidence and influence on ICU mortality

Intensive insulin therapy reduces mortality in subgroups of intensive care unit (ICU) patients, and awareness of the importance of blood glucose level (BGL) control has increased among ICU physicians and nurses. The impact of insulin treatment strategies on mortality may be influenced by their efficacy in achieving the target BGL range. We assessed the efficacy of an insulin treatment strategy in maintaining BGL within the target range, and we compared ICU mortality in patients who did and did not reach the BGL target. Prospective cohort study. 12-bed medical ICU in a tertiary teaching hospital. Adults consecutively admitted over a 9-month period to an ICU where standard care included an insulin treatment strategy aimed at maintaining BGL<or=7 mmol/l. 105 patients were included. Median SAPS II was 45 (31-54). Failure to control BGL (mean capillary BGL >7 mmol/l after initial hyperglycemia correction) occurred in 32 patients (31.1%) and was associated with a significant increase in ICU mortality (56.2 vs. 23.3% in patients with successful BGL control). In the multivariate analysis, failure to control BGL independently predicted death in the ICU (OR 5.9, 2.1-16.6, p<0.001). Failure to control BGL despite intensive insulin therapy was common and independently associated with ICU mortality. Failure to control BGL may considerably affect the overall impact of insulin treatment strategies on mortality.

Continuous Glucose Monitoring in Normal Mice and Mice with Prediabetes and Diabetes

It is well established that the key to minimizing diabetes-associated complications, in both type 1 and type 2 diabetes, is tight regulation of blood glucose levels. Currently the major approach to regulating blood glucose levels in patients with diabetes relies on external blood glucose monitors. However, poor patient compliance usually results in limited insights into the dynamic range of blood glucose levels (i.e., hyperglycemia vs. hypoglycemia), and inadequate prediction and control of blood glucose levels in these patients. Implantable glucose sensors hold promise for controlling blood glucose levels, but currently these sensors have only limited in vivo life span. Recently we have developed an extremely robust murine model for implantable glucose sensors. In the present study, we have extended this model by developing a complete system for real-time continuous glucose monitoring in normal mice and mice with prediabetes and diabetes (type 1). These studies demonstrated that (1) glucose sensors can be implanted and maintained subcutaneously in the mice; (2) continuous glucose sensor data can be obtained for at least 5 days; and (3) subcutaneous blood glucose sensing paralleled blood glucose levels in normal mice and mice with prediabetes and diabetes. Subcutaneous blood glucose sensing also successfully tracked changes in blood glucose levels induced in the mice with diabetes by administration of oral glucose or insulin. These results mirror the results for subcutaneous blood glucose sensing seen in both normal subjects and patients with diabetes, and therefore validate both our continuous glucose monitoring system in the mouse, and the use of the mouse as a model for implantable glucose sensing in vivo.

Is Nondiabetic Hyperglycemia a Risk Factor for Cardiovascular Disease?

Although hyperglycemia increases the risk of cardiovascular disease (CVD) in diabetic patients, the risk associated with blood glucose levels in the nondiabetic range remains unsettled. We identified 38 reports in which CVD incidence or mortality was an end point, blood glucose levels were measured prospectively, and the relative risk (RR) and information necessary to calculate the variance were reported comparing groups of nondiabetic people. These reports were prospective studies, published in English-language journals. First author, publication year, participant age and sex, study duration, CVD end points, glucose assessment methods, control for confounding, range of blood glucose levels, RR, and confidence intervals (CIs) or P values were extracted. Using a random effects model, we calculated pooled RRs and 95% CIs. The group with the highest postchallenge blood glucose level (midpoint range, 150-194 mg/dL [8.3-10.8 mmol/L]) had a 27% greater risk for CVD compared with the group with the lowest level (midpoint range, 69-107 mg/dL [3.8-5.9 mmol/L]) (RR, 1.27 [95% CI, 1.09-1.48]). The results were similar when combining studies regardless of type of blood glucose assessment (RR, 1.36 [95% CI, 1.23-1.52]) and when using strict criteria for exclusion of diabetic subjects (RR, 1.26 [95% CI, 1.11-1.43]). Adjustment for CVD risk factors attenuated but did not abolish this relationship (RR, 1.19 [95% CI, 1.07-1.32]). The RR was greater in cohorts including women than in cohorts of men (RR, 1.56 vs 1.24 [P = .03]). Blood glucose level is a risk marker for CVD among apparently healthy individuals without diabetes.