Interstitial Glucose Concentrations Research Articles

A novel insulin combination of insulin degludec and insulin aspart achieves a more stable overnight glucose profile than insulin glargine: results from continuous glucose monitoring in a proof-of-concept trial.

Insulin degludec coformulated with insulin aspart (as IDegAsp) can cover 24 h basal insulin and postprandial insulin requirements after a main meal with one injection. We compared glycemic stability following IDegAsp or insulin glargine (IGlar) given before the evening meal in patients with type 2 diabetes. A subset of 112 insulin-naïve type 2 diabetes patients from a randomized, parallel-group trial (IDegAsp versus IGlar, each added to metformin) underwent 72 h continuous interstitial glucose (IG) monitoring after 16 weeks of treatment. End points included mean IG concentrations, 2 h postprandial IG increments and postprandial peak, IG fluctuation (summed area above and below mean IG), within-subject coefficient of variation (day-to-day variation) in mean nocturnal IG, and episodes of low (<3.5 mmol/liter) and high (>10 mmol/liter) IG. Values were derived for the entire 72 h, with the nocturnal interval (0001-0559 h) also assessed. The postdinner IG increment observed with IGlar did not occur with IDegAsp [IDegAsp - IGlar, -1.42 (-2.15, -0.70) mmol/liter]. Nocturnal IG fluctuation was 21% lower with IDegAsp [IDegAsp/IGlar, 0.79 (0.66, 0.96) mmol/liter], with 48% fewer nocturnal high IG episodes [ratio IDegAsp/IGlar, 0.52 (0.32, 0.87)]. IDegAsp given with the evening meal reduces postdinner glucose excursion and provides more stable nocturnal glycemia as compared with IGlar.

Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats

Hyperbaric oxygen therapy (HBOT) or intravenous hydroxocobalamin (OHCob) both abolish cyanide (CN)-induced surges in interstitial brain lactate and glucose concentrations. HBOT has been shown to induce a delayed increase in whole blood CN concentrations, whereas OHCob may act as an intravascular CN scavenger. Additionally, HBOT may prevent respiratory distress and restore blood pressure during CN intoxication, an effect not seen with OHCob administration. In this report, we evaluated the combined effects of HBOT and OHCob on interstitial lactate, glucose, and glycerol concentrations as well as lactate-to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 kPa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations, as well as in low lactate-to-pyruvate ratios compared with CN intoxicated controls. In rats receiving OHCob and HBOT, respiration improved and cyanosis disappeared, with subsequent stabilization of mean arterial blood pressure. The present findings indicate that a combined administration of OHCob and HBOT has a beneficial and persistent effect on the cerebral metabolism during CN intoxication.

Evaluation of a continuous glucose monitoring system compared with an in‐house standard laboratory assay and a handheld point‐of‐care glucometer in critically ill neonatal foals

To evaluate the applicability and accuracy of a continuous glucose monitoring system (CGMS) in critically ill foals by comparing the performance of the CGMS, a point-of-care (POC) glucometer, and an in-house standard laboratory assay (SLA). Prospective study. University teaching hospital. Seven critically ill neonatal foals requiring intensive care. Foals were instrumented with a CGMS that measured interstitial glucose concentration every 5minutes for the duration of 15-79 hours. Capillary and venous blood samples were taken every 4-6 hours for POC and SLA measurements, respectively. Bland-Altman analysis showed a mean bias (95% limits of agreement) of -0.1 (-3.9 to 3.5)mmol/L for comparison of CGMS versus SLA, 0.06 (-3.9 to 4.0)mmol/L for comparison of CGMS versus POC glucometer, and -0.16 (-1.8 to 1.5)mmol/L for comparison of POC glucometer versus SLA. Percent agreement and weighted kappa for classification in hypoglycemia, normoglycemia, and hyperglycemia were 68.4% and 0.296 for CGMS versus SLA, 72.4% and 0.442 for CGMS versus POC glucometer, and 80.7% and 0.568 for POC glucometer versus SLA. The CGMS may be helpful for monitoring a trend in interstitial glucose concentration in critically ill neonatal foals. However, considering the wide limits of agreement between methods, the CGMS should only be used as an adjunctive device to other, more accurate and readily available methods that are able to detect acute changes in glucose concentration. Its use is further limited by the relatively high costs of the sensors, the mandatory 2-hour initialization period, and the difficulties of keeping the transducer in place in an active foal. The POC glucometer used in this study is easy to use and proved to be sufficiently accurate for repeated, stall-sided glucose monitoring in neonatal foals.

Acute peripheral tissue effects of ghrelin on interstitial levels of glucose, glycerol, and lactate: a microdialysis study in healthy human subjects

Ghrelin is a gut-derived peptide and an endogenous ligand for the ghrelin receptor. Intravenous infusion of ghrelin induces insulin resistance and hyperglycemia and increases circulating levels of nonesterified free fatty acids. Our objective was to investigate whether the metabolic effects are mediated directly by ghrelin in skeletal muscle and adipose (peripheral and central) tissues. Ten healthy men (24.9 ± 1.3 yr) received 300 min of supraphysiological ghrelin administration by microdialysis catheters in skeletal muscle and adipose tissues in a randomized, single-blind, and placebo-controlled study. Microdialysis perfusates were analyzed every 30 min for glucose, glycerol, and lactate during both a basal period and a hyperinsulinemic euglycemic clamp. The primary outcome measures were interstitial concentrations of glucose, glycerol, and lactate in skeletal muscle and adipose tissues. Interstitial concentrations of glucose were similar in skeletal muscle, peripheral, and central adipose tissue in the basal period. During hyperinsulinemia, interstitial concentrations of glucose in skeletal muscle decreased in response to ghrelin exposure [2.84 ± 0.25 (ghrelin) vs. 3.06 ± 0.26 mmol/l (placebo), P = 0.04]. Ghrelin exposure did not impact on interstitial concentrations of glycerol and lactate. We conclude that ghrelin administration into skeletal muscle decreases interstitial concentrations of glucose during euglycemic hyperinsulinemia, which is indicative of increased insulin sensitivity without any effects on interstitial glycerol levels in either muscle or adipose tissue. These data contrast with the metabolic effects of ghrelin observed after systemic exposure and suggest the existence of a second messenger that remains to be identified.

Type 2 Diabetes Melittus–A Pathology on the Rise How do we Monitor it?

Type 2 diabetes is a chronic disease widespread in the world. Currently it is believed that there are over 500 million diabetics in the world and their number increases every year. This increase is primarily due to unhealthy eating habits, sedentary lifestyle, obesity and stress. In an OMS report stated that ‘’individuals live dangerously’’, this for failure to comply of the minimum precepts regarding lifestyle. Correct monitoring of the diabetic patient for preventing complications is an important aspect in the disease evolution. Methods that allow an accurate monitoring of diabetes include glycosylated hemoglobin, self-monitoring of blood glucose and continuous glucose monitoring with a system that measures interstitial glucose concentration. It is considered that the determination of glycosylated hemoglobin is the gold standard in monitoring diabetic patients, but the other two methods provide complementary information.

The Effect of Walking on Postprandial Glycemic Excursion in Patients With Type 1 Diabetes and Healthy People

OBJECTIVEPhysical activity (PA), even at low intensity, promotes health and improves hyperglycemia. However, the effect of low-intensity PA captured with accelerometery on glucose variability in healthy individuals and patients with type 1 diabetes has not been examined. Quantifying the effects of PA on glycemic variability would improve artificial endocrine pancreas (AEP) algorithms.RESEARCH DESIGN AND METHODSWe studied 12 healthy control subjects (five males, 37.7 ± 13.7 years of age) and 12 patients with type 1 diabetes (five males, 37.4 ± 14.2 years of age) for 88 h. Participants performed PA approximating a threefold increase over their basal metabolic rate. PA was captured using a PA-monitoring system, and interstitial fluid glucose concentrations were captured with continuous glucose monitors. In random order, one meal per day was followed by inactivity, and the other meals were followed by walking. Glucose and PA data for a total of 216 meals were analyzed from 30 min prior to meal ingestion to 270 min postmeal.RESULTSIn healthy subjects, the incremental glucose area under the curve was 4.5 mmol/L/270 min for meals followed by walking, whereas it was 9.6 mmol/L/270 min (P = 0.022) for meals followed by inactivity. The corresponding glucose excursions for those with type 1 diabetes were 7.5 mmol/L/270 min and 18.4 mmol/L/270 min, respectively (P < 0.001).CONCLUSIONSWalking significantly impacts postprandial glucose excursions in healthy populations and in those with type 1 diabetes. AEP algorithms incorporating PA may enhance tight glycemic control end points.

Hyperglycemia-induced stimulation of glucose transport in skeletal muscle measured by PET- [18F]6FDG and [18F]2FDG

A physiologically based model proposed by our group has been developed to assess glucose transport and phosphorylation in skeletal muscle. In this study, we investigated whether our model has the ability to detect a glucose-induced increase in glucose transport in skeletal muscle. In particular, we used small-animal positron emission tomography (PET) data obtained from [18F]6-fluoro-6-deoxy-D-glucose ([18F]6FDG). A 2 h PET scan was acquired following a bolus injection of [18F]6FDG in rats currently under euglycemic or hyperglycemic conditions, while somatostatin was infused during both conditions in order to prevent a rise in the endogenous plasma insulin concentration. We were thus able to assess the effect of hyperglycemia per se. For a comparison of radiopharmaceuticals, additional rats were studied under the same conditions, using [18F]2-fluoro-2-deoxy-D-glucose ([18F]2FDG). When [18F]6FDG was used, the time-activity curves (TACs) for skeletal muscle had distinctly different shapes during euglycemic and hyperglycemic conditions. This was not the case with [18F]2FDG. For both [18F]6FDG and [18F]2FDG, the model detects increases in both interstitial and intracellular glucose concentrations, increases in the maximal velocity of glucose transport and increases in the rate of glucose transport, all in response to hyperglycemia. In contrast, there was no increase in the maximum velocity of glucose phosphorylation or in the glucose phosphorylation rate. Our model-based analyses of the PET data, obtained with either [18F]6FDG or [18F]2FDG, detect physiological changes consistent with established behavior. Moreover, based on differences in the TAC shapes, [18F]6FDG appears to be superior to [18F]2FDG for evaluating the effect of hyperglycemia on glucose metabolism in skeletal muscle.

Effects of a high-carbohydrate versus high-protein meal on acute responses to hypoxia at rest and exercise

A carbohydrate (CHO) solution consumed before exposure to hypoxia has been reported to reduce arterial oxygen desaturation at rest. The purpose of this study was to determine whether this effect occurred during exercise and when the CHO load is part of a meal. Eleven male subjects (mean age 20.1 ± 1.8 years, BMI 24.3 ± 2.4 kg m(2)) consumed either a high-CHO (2,340 kJ, 70 % CHO, 12 % protein) or an isoenergetic high-protein (35 % CHO, 48 % protein) breakfast meal 60 min before being exposed to 15 min of hypoxia (F(I)O(2) = 13.5 %) followed by 30 min of exercise in hypoxia (60 % of VO₂max). Saturation of oxygen via a pulse oxymeter (SpO(2)), ventilatory parameters, substrate oxidation, interstitial glucose concentrations, and heart rate variability (HRV) were monitored continuously during the whole session. Results showed no effect from the type of meal on SpO(2) at rest but a 3.1 ± 0.4 % reduction of desaturation during exercise (P < 0.005) compared to the high-protein version. This was associated with higher levels of ventilation (P < 0.05) and CO(2) production (P < 0.01). Glucose oxidation was higher after the high-CHO than the high-protein breakfast over the whole session (+19.4 + 4.0 %, P < 0.0001), whereas the interstitial glucose levels were increased only at rest (P < 0.001). HRV indices were not different between conditions. In conclusion, a high-CHO meal consumed prior to moderate exercise in hypoxia condition reduced oxygen desaturation compared to a high-protein meal.

Evaluation of long-term glucose homeostasis in lean and obese cats by use of continuous glucose monitoring

To evaluate intraday and interday variations in glucose concentrations in cats and to test the utility of a continuous glucose monitoring system (CGMS). 6 lean and 8 long-term (> 5 years) obese cats. Blood glucose concentrations were measured during the course of 156 hours by use of a laboratory hexokinase-based reference method and a handheld glucometer. Interstitial glucose concentrations were evaluated with a CGMS. Paired measures of glucose concentrations obtained with the CGMS typically were marginally higher than concentrations for the reference method and less biased than concentrations obtained with the glucometer. This was partially confirmed by the concordance correlation coefficients of the concentration for the CGMS or glucometer versus the concentration for the reference method, although the correlation coefficients were not significantly different. Mean ± SD area under the curve for the glucose concentration (AUCG) did not differ significantly between lean (14.0 ± 0.5 g/dL•h) and obese (15.2 + 0.5 g/dL•h) cats during the 156-hour period, but one of the obese cats had a much higher AUCG. Within-day glucose variability was small in both lean and obese cats. Glucose homeostasis was maintained, even in long-term obese cats, and intraday glucose fluctuations were small. One obese cat might have been classified as prediabetic on the basis of the AUCG, which was approximately 25% higher than that of the other obese and lean cats. The CGMS can be useful in the evaluation of long-term effects of drugs or diet on glucose homeostasis in cats.

Accuracy of the Sof-Sensor Glucose Sensor with the iPro Calibration Algorithm

Performance characteristics of devices that measure interstitial fluid glucose concentrations continue to improve. The overall accuracy of continuous glucose monitoring (CGM) systems depends on the sensor, the reference blood glucose concentrations used for calibration, and the calibration algorithm. We examined the accuracy of the iPro calibration algorithm when applied retrospectively to data collected with Sof-sensor CGM sensors. A total of 768 sensors were worn by 71 adults (ages 19–72) and 61 children (ages 7–17) with type 1 diabetes. Sensor data from the first 3 days of wear, along with contemporaneous blood glucose (BG) concentrations measured by the Paradigm Link BG monitor, were supplied to the iPro algorithm to generate a data set of sensor glucose (SG) concentrations. The mean absolute relative difference (MARD) between SG and BG concentrations, the SG:BG agreement rate, and Clarke error grid analysis of paired SG and BG values were used to estimate the overall accuracy of the SG data. The MARD was 9.9% in adults and 10.1% in children, and were lowest in the 240–400 mg/dl range (6.8% in adults, 6.3% in children). The SG:BG agreement rate (i.e., the percentage of SG values within 20% of the reference BG value or the percentage within 20 mg/dl for reference values <80 mg/dl) was 89.1% for adults and 88.7% for children. The highest agreement rates were seen in the 240–400 mg/dl range (94.9% in adults, 95.2% in children). For values in the 40–80 mg/dl range, 88.7% of adult and 85.5% of pediatric SG values were within 20 mg/dl of the reference value, and for values in the 80–120 mg/dl range, 83.3% of adult and 81.2% of pediatric SG values were within 20% of the reference value. Clarke error grid analysis (Figure 1) showed that 99.0% (4849 of 4897) of adult and 98.4% (4116 of 4181) of pediatric-paired values were within zones A and B. Figure 1 Clarke error grid analysis of paired SG and BG values from adults and children. The iPro algorithm is at the heart of the iPro Professional CGM system, which is used by clinicians to gain insights that are not apparent with finger stick and hemoglobin A1c testing alone. A CGM sensor and an attached iPro recording device are worn by the patient for 3 days, and four BG values are measured each day. Data from the BG meter and recording device are then uploaded for report generation and analysis. Therapy adjustments based on retrospectively-generated glycemic profiles have been shown to reduce the duration of hypoglycemia compared with therapy adjustments guided by BG values alone.1 Retrospective CGM was found to be well tolerated and beneficial in children2 and has been used to demonstrate frequent hypoglycemia in adults with poor control.3 It may be especially useful for those with hypoglycemia unawareness, for those with postprandial hyperglycemia, or during therapy regimen adjustments.4 The iPro algorithm provides SG readings that are in good agreement with respect to home BG meter readings when used in conjunction with Sof-sensor CGM sensors. The accuracy is maintained in both adults and children for at least 3 days.

Continuous glucose monitoring system: Is it really accurate, safe and clinically useful?

The continuous glucose monitoring system (CGM) has been used for constant checking of glucose level by measuring interstitial glucose concentrations, since the early days of the 21st century. It can potentially improve diabetes care if used carefully with the understanding of the characteristics of this system. Although there is a time lag of approximately 5-15 min between blood and interstitial glucose levels, the system is considered the most suitable device for meticulous glucose control and prevention of hypoglycemia. A large number of studies have examined its accuracy, safety and clinical effectiveness. The continuous glucose-error grid analysis (CG-EGA), designed by WL Clarke, evaluates the clinical accuracy of CGM. It examines 'temporal' characteristics of the data, analyzing pairs of reference and sensor readings as a process in time represented by a 'bidimensional' time series and taking into account inherent physiological time lags. Investment in CG-EGA is clearly meaningful, even though there are other methodologies for evaluation. The use of each method complementarily is the most effective way to prove the accuracy of the device. The device has improved gradually, and real-time CGM, which allows real-time monitoring of blood glucose level, is already available commercially. The use of real-time CGM could potentially lead to over- or undertreatment with insulin. Patient education through proper and effective handling of the new device is essential to improve diabetes care. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00197.x, 2012).

Nutritional support and brain tissue glucose metabolism in poor-grade SAH: a retrospective observational study

IntroductionWe sought to determine the effect of nutritional support and insulin infusion therapy on serum and brain glucose levels and cerebral metabolic crisis after aneurysmal subarachnoid hemorrhage (SAH).MethodsWe used a retrospective observational cohort study of 50 mechanically ventilated poor-grade (Hunt-Hess 4 or 5) aneurysmal SAH patients who underwent brain microdialysis monitoring for an average of 109 hours. Enteral nutrition was started within 72 hours of admission whenever feasible. Intensive insulin therapy was used to maintain serum glucose levels between 5.5 and 7.8 mmol/l. Serum glucose, insulin and caloric intake from enteral tube feeds, dextrose and propofol were recorded hourly. Cerebral metabolic distress was defined as a lactate to pyruvate ratio (LPR) > 40. Time-series data were analyzed using a general linear model extended by generalized estimation equations (GEE).ResultsDaily mean caloric intake received was 13.8 ± 6.9 cal/kg and mean serum glucose was 7.9 ± 1 mmol/l. A total of 32% of hourly recordings indicated a state of metabolic distress and < 1% indicated a state of critical brain hypoglycemia (< 0.2 mmol/l). Calories received from enteral tube feeds were associated with higher serum glucose concentrations (Wald = 6.07, P = 0.048), more insulin administered (Wald = 108, P < 0.001), higher body mass index (Wald = 213.47, P < 0.001), and lower body temperature (Wald = 4.1, P = 0.043). Enteral feeding (Wald = 1.743, P = 0.418) was not related to brain glucose concentrations after accounting for serum glucose concentrations (Wald = 67.41, P < 0.001). In the presence of metabolic distress, increased insulin administration was associated with a relative reduction of interstitial brain glucose concentrations (Wald = 8.26, P = 0.017), independent of serum glucose levels.ConclusionsIn the presence of metabolic distress, insulin administration is associated with reductions in brain glucose concentration that are independent of serum glucose levels. Further study is needed to understand how nutritional support and insulin administration can be optimized to minimize secondary injury after subarachnoid hemorrhage.

Relation between brain interstitial and systemic glucose concentrations after subarachnoid hemorrhage

Relation between brain interstitial and systemic glucose concentrations after subarachnoid hemorrhage

Early Detection of Metabolic Changes Using Microdialysis During and After Experimental Kidney Transplantation in a Porcine Model

Microdialysis (MD) can detect organ-related metabolic changes before they become measurable in plasma through the biochemical parameters. This study aims to evaluate the early detection of metabolic changes during experimental kidney transplantation (KTx). During preparation of 8 donor kidneys, one MD catheter was inserted in the renal cortex and samples were collected. After a 6-hour cold ischemia time (CIT), kidneys were implanted in the 8 recipient pigs. Throughout the warm ischemia time (WIT) and after reperfusion, kidneys were monitored. The interstitial glucose, lactate, pyruvate, glutamate, and glycerol concentrations were evaluated. A significant decline in glucose level was observed at the end of CIT. The lactate level was reduced to the minimum point of 0.35 ± 0.08 mmol/L in CIT. After reperfusion, lactate values raised significantly. During the WIT, the pyruvate level increased, continued until the end of the WIT. For glutamate, a steady increase was noted during explantation, CIT, WIT, and early reperfusion phases. The increase of glycerol value continued in the early postreperfusion, which was then followed by a sharp decline. MD is a fast and simple minimally invasive method for measurement of metabolic substrates in renal parenchyma during KTx. MD offers the option of detecting minor changes of interstitial glucose, lactate, pyruvate, glutamate, and glycerol in every stage of KTx. Through the use of MD, metabolic changes can be continuously monitored during the entire procedure of KTx.

Rate of fall in blood glucose and recurrent hypoglycemia affect glucose dynamics and noradrenergic activation in the ventromedial hypothalamus

Noradrenergic activity in the ventromedial hypothalamus (VMH) is increased and activates a sympathoadrenal response during hypoglycemia. How the rate at which hypoglycemia develops affects local glucose concentrations and norepinephrine (NE) release was evaluated by placing microdialysis probes into the VMH of male Sprague-Dawley rats receiving insulin (20 mU·kg(-1)·min(-1)) and variable glucose infusions. During a first episode of hypoglycemia, interstitial glucose concentrations in the VMH generally declined at the same rate as plasma glucose; however, the faster hypoglycemia developed, the greater the magnitude of the initial NE release in the VMH (r(2) = 0.72, P < 0.001). Following recurrent episodes of hypoglycemia, VMH glucose decreased at a slower rate than plasma glucose, and the initial NE release was attenuated at the same rates of blood glucose decline. The plasma glucose threshold for the initial NE release in VMH was similar for all groups (∼3.23 mM); however, the VMH glucose threshold was stimulated and was lower when blood glucose declined more slowly (0.86 ± 0.06 vs. 1.06 ± 0.04 mmol/l, P < 0.01). The timing of the initial increase in NE release in VMH corresponded with an increase in plasma epinephrine during the first episode of hypoglycemia but not following recurrent hypoglycemia. Although a decrease in VMH glucose concentration is required for noradrenergic activation in VMH, there does not appear to be a set glucose threshold within the VMH for activation of this response.

A Hierarchical Whole-body Modeling Approach Elucidates the Link between in Vitro Insulin Signaling and in Vivo Glucose Homeostasis

Type 2 diabetes is a metabolic disease that profoundly affects energy homeostasis. The disease involves failure at several levels and subsystems and is characterized by insulin resistance in target cells and tissues (i.e. by impaired intracellular insulin signaling). We have previously used an iterative experimental-theoretical approach to unravel the early insulin signaling events in primary human adipocytes. That study, like most insulin signaling studies, is based on in vitro experimental examination of cells, and the in vivo relevance of such studies for human beings has not been systematically examined. Herein, we develop a hierarchical model of the adipose tissue, which links intracellular insulin control of glucose transport in human primary adipocytes with whole-body glucose homeostasis. An iterative approach between experiments and minimal modeling allowed us to conclude that it is not possible to scale up the experimentally determined glucose uptake by the isolated adipocytes to match the glucose uptake profile of the adipose tissue in vivo. However, a model that additionally includes insulin effects on blood flow in the adipose tissue and GLUT4 translocation due to cell handling can explain all data, but neither of these additions is sufficient independently. We also extend the minimal model to include hierarchical dynamic links to more detailed models (both to our own models and to those by others), which act as submodules that can be turned on or off. The resulting multilevel hierarchical model can merge detailed results on different subsystems into a coherent understanding of whole-body glucose homeostasis. This hierarchical modeling can potentially create bridges between other experimental model systems and the in vivo human situation and offers a framework for systematic evaluation of the physiological relevance of in vitro obtained molecular/cellular experimental data.

Using microdialysis for early detection of vascular thrombosis after kidney transplantation in an experimental porcine model

In kidney transplantation (KTx), vascular thrombosis has a major impact on morbidity and graft survival. The ischaemia, caused by thrombosis, can lead to interstitial metabolite changes. The aim of this experimental study was to create conditions in which the graft would be prone to vascular thrombosis following KTx and then to evaluate the role of microdialysis (MD) for its early detection. Sixteen randomized pigs in the control group received heparin and immunosuppressive drugs, while the case group received none. Based on histopathological evidence of vascular thrombosis, the case group was subdivided into mildly and severely congested subgroups. Using MD, we evaluated the interstitial concentrations of glucose, lactate to pyruvate ratio, glutamate and glycerol in the transplanted grafts during different phases of KTx. Following reperfusion, we noted considerable changes. The severely congested subgroup showed a low and decreasing level of glucose. Only in this group did the lactate to pyruvate ratio continue to increase until the end of monitoring. The glycerol level increased continuously in the entire case group and this increase was most significant in the severely congested subgroup. In all of the study groups, glutamate concentration remained in a low steady state until the end of monitoring. MD can be an appropriate method for early detection of vascular complications after KTx. Decreasing glucose levels, increased lactate to pyruvate ratio and increased glycerol levels are appropriate indicators for early detection of vascular thromboses following KTx. Particularly, the glycerol level could predict the necessity and urgency of intervention needed to ultimately save the transplanted kidney.

Current understanding of increased insulin sensitivity after exercise – emerging candidates

Exercise counteracts insulin resistance and improves glucose homeostasis in many ways. Apart from increasing muscle glucose uptake quickly, exercise also clearly increases muscle insulin sensitivity in the post-exercise period. This review will focus on the mechanisms responsible for this increased insulin sensitivity. It is believed that increased sarcolemmal content of the glucose transporter GLUT4 can explain the phenomenon to some extent. Surprisingly no improvement in the proximal insulin signalling pathway is observed at the level of the insulin receptor, IRS1, PI3K or Akt. Recently more distal signalling component in the insulin signalling pathway such as aPKC, Rac1, TBC1D4 and TBC1D1 have been described. These are all affected by both insulin and exercise which means that they are likely converging points in promoting GLUT4 translocation and therefore possible candidates for regulating insulin sensitivity after exercise. Whereas TBC1D1 does not appear to regulate insulin sensitivity after exercise, correlative evidence in contrast suggests TBC1D4 to be a relevant candidate. Little is known about aPKC and Rac1 in relation to insulin sensitivity after exercise. Besides mechanisms involved in signalling to GLUT4 translocation, factors influencing the trans-sarcolemmal glucose concentration gradient might also be important. With regard to the interstitial glucose concentration microvascular perfusion is particular relevant as correlative evidence supports a connection between insulin sensitivity and microvascular perfusion. Thus, there are new candidates at several levels which collectively might explain the phenomenon.

Relation between brain interstitial and systemic glucose concentrations after subarachnoid hemorrhage

The aim in the present investigation was to study the relation between brain interstitial and systemic blood glucose concentrations during the acute phase after subarachnoid hemorrhage (SAH). The authors also evaluated the effects of insulin administration on local brain energy metabolism. Nineteen patients with spontaneous SAH were prospectively monitored with intracerebral microdialysis (MD). The relation between plasma glucose and MD-measured interstitial brain glucose concentrations as well as the temporal pattern of MD glucose, lactate, pyruvate, glutamate, and glycerol was studied for 7 days after SAH. Using a target plasma glucose concentration of 5-10 mmol/L, the effect of insulin injection was also evaluated. The mean (± SD) correlation coefficient between plasma glucose and MD glucose was 0.27 ± 0.27 (p = 0.0005), with a high degree of individual variation. Microdialysis glucose, the MD/plasma glucose ratio, and MD glutamate concentrations decreased in parallel with a gradual increase in MD pyruvate and MD lactate concentrations. There were no significant changes in the MD L/P ratio or MD glycerol levels. Insulin administration induced a decrease in MD glucose and MD pyruvate. After SAH, there was a positive correlation between plasma and MD glucose concentrations with a high degree of individual variation. A gradual decline in MD glucose and the MD/plasma glucose ratio and an increase in MD pyruvate and MD lactate concentrations during the 1st week after SAH suggest a transition to a hyperglycolytic state with increased cerebral glucose consumption. The administration of insulin was related to a lowering of MD glucose and MD pyruvate, often to low levels even though plasma glucose values remained above 6 mmol/L. After SAH, the administration of insulin could impede the glucose supply of the brain.

Effect of Continuous Glucose Monitoring on Hypoglycemia in Type 1 Diabetes

OBJECTIVETo assess the impact of continuous glucose monitoring on hypoglycemia in people with type 1 diabetes.RESEARCH DESIGN AND METHODSIn this randomized, controlled, multicenter study, 120 children and adults on intensive therapy for type 1 diabetes and a screening level of glycated hemoglobin A1c (HbA1c) <7.5% were randomly assigned to a control group performing conventional home monitoring with a blood glucose meter and wearing a masked continuous glucose monitor every second week for five days or to a group with real-time continuous glucose monitoring. The primary outcome was the time spent in hypoglycemia (interstitial glucose concentration <63 mg/dL) over a period of 26 weeks. Analysis was by intention to treat for all randomized patients.RESULTSThe time per day spent in hypoglycemia was significantly shorter in the continuous monitoring group than in the control group (mean ± SD 0.48 ± 0.57 and 0.97 ± 1.55 h/day, respectively; ratio of means 0.49; 95% CI 0.26–0.76; P = 0.03). HbA1c at 26 weeks was lower in the continuous monitoring group than in the control group (difference −0.27%; 95% CI −0.47 to −0.07; P = 0.008). Time spent in 70 to 180 mg/dL normoglycemia was significantly longer in the continuous glucose monitoring group compared with the control group (mean hours per day, 17.6 vs. 16.0, P = 0.009).CONCLUSIONSContinuous glucose monitoring was associated with reduced time spent in hypoglycemia and a concomitant decrease in HbA1c in children and adults with type 1 diabetes.