Interstitial Glucose Concentrations Research Articles

A Tale of Two Compartments: Interstitial Versus Blood Glucose Monitoring

Self-monitoring of blood glucose was described as one of the most important advancements in diabetes management since the invention of insulin in 1920. Recent advances in glucose sensor technology for measuring interstitial glucose concentrations have challenged the dominance of glucose meters in diabetes management, while raising questions about the relationships between interstitial and blood glucose levels. This article will review the differences between interstitial and blood glucose and some of the challenges in measuring interstitial glucose levels accurately.

Glycemic Exposure Is Affected Favorably by Inhaled Human Insulin (Exubera) as Compared with Subcutaneous Insulin Glargine (Lantus) in Patients with Type 2 Diabetes

The objective was to compare the effects on glycemia of adding either inhaled human insulin (Exubera [EXU] [insulin human (recombinant DNA origin) inhalational powder]) or subcutaneous insulin glargine (GLA) to the treatment regimens of patients with type 2 diabetes uncontrolled with oral antidiabetic drugs. Forty patients were randomized to receive either EXU three times daily prior to meals or subcutaneous GLA once daily in a crossover design. Interstitial glucose concentrations were monitored using a continuous glucose monitoring system (CGMS) for the final 72-h period of 8 treatment days. Total insulin dosage on the last treatment day was approximately 40.1+/-18.1 units/day EXU compared with 16.4+/-4.8 units/day GLA. Serum insulin levels over the 72-h CGMS period were higher for EXU than for GLA (1,091+/-589 pmol/mL/h vs. 737+/-386 pmol/mL/h; ratio, 148; 95% confidence interval [CI], 130-169). The glucose exposure over this period was lower with EXU than with GLA (380+/-45 mmol/Lh vs. 426+/-89 mmol/Lh; ratio, 88.57; 95% CI, 84-93). The overall hypoglycemic event rate was 8.7 events per subject-month for EXU and 2.4 for GLA. Prandial insulin therapy with EXU, using a higher daily insulin dose, reduces total daily glucose exposure--in particular postmeal glycemia--more effectively than a basal insulin analog.

The Clinical Research Tool: A High-Performance Microdialysis-Based System for Reliably Measuring Interstitial Fluid Glucose Concentration

A novel microdialysis-based continuous glucose monitoring system, the so-called Clinical Research Tool (CRT), is presented. The CRT was designed exclusively for investigational use to offer high analytical accuracy and reliability. The CRT was built to avoid signal artifacts due to catheter clogging, flow obstruction by air bubbles, and flow variation caused by inconstant pumping. For differentiation between physiological events and system artifacts, the sensor current, counter electrode and polarization voltage, battery voltage, sensor temperature, and flow rate are recorded at a rate of 1 Hz. In vitro characterization with buffered glucose solutions (c(glucose) = 0 - 26 x 10(-3) mol liter(-1)) over 120 h yielded a mean absolute relative error (MARE) of 2.9 +/- 0.9% and a recorded mean flow rate of 330 +/- 48 nl/min with periodic flow rate variation amounting to 24 +/- 7%. The first 120 h in vivo testing was conducted with five type 1 diabetes subjects wearing two systems each. A mean flow rate of 350 +/- 59 nl/min and a periodic variation of 22 +/- 6% were recorded. Utilizing 3 blood glucose measurements per day and a physical lag time of 1980 s, retrospective calibration of the 10 in vivo experiments yielded a MARE value of 12.4 +/- 5.7. Clarke error grid analysis resulted in 81.0%, 16.6%, 0.8%, 1.6%, and 0% in regions A, B, C, D, and E, respectively. The CRT demonstrates exceptional reliability of system operation and very good measurement performance. The ability to differentiate between artifacts and physiological effects suggests the use of the CRT as a reference tool in clinical investigations.

Detection of Hypoglycemia with Continuous Interstitial and Traditional Blood Glucose Monitoring Using the FreeStyle Navigator Continuous Glucose Monitoring System

The objective of the analysis was to compare detection of hypoglycemic episodes (glucose <70 mg/dL lasting >15 min) with the FreeStyle Navigator Continuous Glucose Monitoring System (FSN-CGM) (Abbott Diabetes Care, Alameda, CA) alarms to detection with traditional finger stick testing at an average frequency of eight tests per day. The performance of FSN-CGM alarms was evaluated in a clinic setting using 58 subjects with type 1 diabetes mellitus (T1DM) monitoring interstitial glucose concentration over a 5-day period compared to reference YSI measurements (instrument manufactured by YSI, Yellow Springs, OH) at 15-min intervals. Finger stick glucose testing was evaluated in the home environment with 91 subjects with TIDM monitoring with the blood glucose meter integrated into the FreeStyle Navigator (FSN-BG) over a 20-day period. The reference was FSN-CGM with results masked from the subjects. Blood glucose values <=85 mg/dL were considered the optimal treatment level to avoid or reverse hypoglycemia. With a threshold alarm setting of 85 mg/dL, 90.6% of hypoglycemic episodes were detected within +/- 30 min by FSN-CGM in the clinic study. When the alarm was activated, YSI glucose was <= 85 mg/dL 77.2% of the time. In the home environment, the average FSN-BG testing frequency was 7.9 tests per day. Hypoglycemia was verified within +/- 30 min by FSN-BG measurements <= 85 mg/dL at a rate of 27.5%. Even with a high rate of FSN-BG testing, hypoglycemia detected by FSN-CGM was verified by patients with T1DM very infrequently. A high rate of hypoglycemia detection with a moderate rate of unnecessary alarms can be attained using FSN-CGM.

Low‐glycaemic index sweetener‐based beverages reduce 24‐h glucose profiles in healthy adults

Previous research has shown that substitution of high-glycaemic index (GI) bread for low-GI bread can favourably alter the 24-h glucose profile. Given the high beverage consumption in the UK, the present study aimed to evaluate the impact of consuming a beverage containing a low-GI, natural sweetener at mealtimes compared to a sucrose-based beverage, on the 24-h glucose profile. In a randomized crossover design, six subjects (aged 41 +/- 16 years; body mass index = 25.8 +/- 4.1 kg m(-2)) were provided with a diet including low-GI or control (sucrose) beverages on two nonconsecutive days. On each study day, subjects consumed the low-GI or control beverage at breakfast, lunch and dinner. Interstitial glucose concentrations were measured over 24 h using a continuous glucose monitoring system. Compared to the control beverage, the low-GI beverage significantly reduced mean glucose concentration over 24 h (P < 0.05). Similarly, 24-h and daytime incremental area under the curves for glucose were significantly lower (P = 0.001). The substitution of a sucrose-based beverage for a beverage containing a low-GI, natural sweetener at mealtimes is a simple dietary change that can significantly reduce 24-h glucose levels and may be beneficial for many individuals.

Diurnal correlation of ambulatory blood pressure and interstitial glucose in patients with normal glucose tolerance

Among the physiological variables whose diurnal profile is governed by circadian rhythmicity, plasma glucose concentrations, and arterial blood pressure constitute key elements of the physiological regulation of energy homeostasis. Evidence on their diurnal association derived from frequent measurements of both variables is, however, lacking in humans. We investigated the relationship between blood pressure levels recorded by an ambulatory device and interstitial glucose concentrations on an outpatient basis, in patients with normal glucose tolerance (N=20), either normotensive (group A; N=10), or newly diagnosed with essential hypertension (group B; N=10). In the population throughout the 24-h monitoring period, there was a significant positive correlation between interstitial glucose concentrations and systolic, diastolic, and mean 24-h blood pressure levels, which was retained in patients with hypertension compared with normotensive patients. In patients with newly diagnosed hypertension, interstitial glucose concentrations exhibit significant correlation to systolic blood pressure levels during the 24-h period, but no association with diastolic and mean blood pressure during the night, whereas the reverse is the case in patients with normal glucose tolerance and normal blood pressure. Diurnal variations of continuously monitored interstitial glucose concentrations significantly associate with blood pressure levels in both normotensive and hypertensive humans, indicating a common pathway of circadian autoregulation, probably stemming from both central mechanisms and peripheral inputs. Such a pathway might underlie similar pathophysiological aberration in disease states such as the metabolic syndrome.

Preclinical in vivo study of a fluorescence affinity sensor for short-term continuous glucose monitoring in a small and large animal model.

The performance of a fiber-coupled fluorescence affinity sensor (FAS) was studied in vivo in small and large animal models, in order to assess its feasibility and safety for short-term glucose monitoring in humans. Determination of interstitial glucose concentrations in skin tissue of hairless rats and small pigs was facilitated by measuring the fluorescence response of the implanted FAS over several hours and multiple days. Blood sugar changes in animals were induced by injections of insulin and dextrose. The Medtronic Minimed CGMS (Medtronic Diabetes, Northridge, CA) was used for comparison. The acute in vivo performance study of the fiber-coupled FAS showed that more than 96% of the paired FAS/venous blood glucose readings were in the clinically acceptable A and B regions of the Clarke Error Grid. Mean absolute relative difference (MARD) and root mean squared error (RMSE) values for small and large animal models were 18.5% and 19.8 mg/dL and 15.9% and 16.3 mg/dL, respectively. In comparison, MARD and RMSE for the Medtronic Minimed CGMS in small and large animal models were similar (in rats, 25.4% and 19.8 mg/dL, respectively; in pigs, 18.4% and 16.2 mg/dL, respectively). No instance of irritation or infection was observed at any implantation site. The in vivo performance of FAS over a 3-day period was successfully demonstrated in both animal models. Overall, the fiber-coupled FAS was safe, and its performance during 4-h and 3-day testing compared favorably to the commercially available Medtronic Minimed CGMS, indicating its potential value for diabetes management.

A double-blind, placebo-controlled test of 2 d of calorie deprivation: effects on cognition, activity, sleep, and interstitial glucose concentrations

BackgroundAnecdotal information and limited research suggest that short-term caloric deprivation adversely affects cognition. However, this issue has not been studied using double-blind, placebo-controlled procedures, because the formulation of a calorie-deficient feeding regimen identical to one with calories is impossible using ordinary foods. Therefore, test meals varying in caloric content, but indistinguishable in sensory characteristics, were formulated using hydrocolloid-based gels as the principal structural component. ObjectiveThe purpose of this study was to examine the effects of 2 d of near-total caloric deprivation on cognitive function, satiety, activity, sleep, and glucose concentrations in a controlled environment. DesignA double-blind, placebo-controlled crossover study of caloric deprivation was conduced in a controlled environment for 48 h. Cognitive function in 27 healthy young subjects was assessed repeatedly with standardized tests of vigilance, reaction time, learning, memory, logical reasoning, mood, and satiety. Wrist-worn monitors were used to assess ambulatory vigilance, activity, and sleep. Interstitial glucose concentrations were assessed continuously with a minimally invasive monitor. ResultsWhen the subjects received the near calorie-free diets, mean calorie consumption totaled 1311 kJ (313 kcal) over the testing period. During the fully fed treatment sessions, the subjects consumed a mean of 9612 kJ/d (2294 kcal/d), which matched their individual, daily energy requirements. Satiety and interstitial glucose concentrations were lower during the calorie-deprived diet (P < 0.001) than during the fully fed diet. There were no detectable effects of calorie deprivation on any aspect of cognitive performance, ambulatory vigilance, activity, or sleep. The mood states assessed, including fatigue, were not affected by calorie deprivation. ConclusionsCognitive performance, activity, sleep, and mood are not adversely affected in healthy humans by 2 d of calorie-deprivation when the subjects and investigators are unaware of the calorie content of the treatments.

Continuous Glucose Monitoring: Physiological and Technological Challenges

Over the past decade, several continuous glucose monitoring systems have been developed, representing remarkable technological achievements. Most of the systems monitor glucose invasively in the subcutaneous tissue. It is important to realize that there are discrepancies between blood and interstitial glucose concentration, which (1) may impact the quality of the system calibration and thereby the accuracy of the data, (2) may jeopardize the specificity and the sensitivity of hypoglycaemic alarms based on these systems and (3) must be considered in the design of closed-loop insulin delivery systems. The aim of this review is to make the point that the challenge of developing a continuous glucose monitoring system is not only technological, but must also take into account the physiology of glucose in alternate sites where it is sensed.

Optical Coherence Tomography-Based Continuous Noninvasive Glucose Monitoring in Patients with Diabetes

The objective of this feasibility study was to test an optical coherence tomography (OCT)-based system for noninvasive, accurate, and continuous monitoring of blood (as opposed to interstitial) glucose concentration in subjects with diabetes. OCT uses low coherence light with precise depth focusing ability to measure changes in the microvasculature structure for glucose detection. Thirty-three subjects with diabetes had blood glucose concentrations evaluated using simultaneous capillary and OCT-based device (Sentris-100, GlucoLight, Bethlehem, PA) measurements. Subjects received a 50-g carbohydrate load at the start of the study period. Two glucose values with 60 mg separation were used to calibrate the OCT system. Six subjects were excluded (two because of hardware and/or software failures at study initiation, two because of sensor connection problems, and two others because of problems with disposable device positioning on the skin). Of the 27 subjects who completed the study, 12 had type 1 diabetes, and 15 had type 2 diabetes. Statistical analysis included plotting of the Clarke error grid, comparison to International Organization for Standardization (ISO) standards for glucose monitoring systems, and calculation of the Pearson correlation coefficient. Based on a total of 236 matched points, Clarke error grid analysis indicated 83% in zone A, 16% in zone B, and <1% in zones C and D. ISO standards comparison showed 83% of OCT estimates were within 20% of the reference value for blood glucoses >75 mg/dL. No conclusions can be made about blood glucose estimates in the <75 mg/dL range since no low reference values occurred. The Pearson correlation coefficient comparing OCT versus capillary blood glucose was 0.85 (95% confidence interval 0.81-0.88, P < 0.0001). Mean relative absolute deviation was 11.5%, and median relative absolute deviation was 8.2%. This study demonstrated that the OCT system shows acceptable accuracy in the prediction of blood glucose levels in subjects with both type 1 and type 2 diabetes. Future efforts will evaluate the accuracy of the system in the hypoglycemic range.

Decreases in myocardial glucose and increases in pyruvate but not ischaemia are observed during porcine endotoxaemia

Myocardial dysfunction occurs commonly in septic shock. It is not known whether this is due to local ischaemia and metabolic disturbances. Our hypothesis was that endotoxaemic myocardial dysfunction may be associated with interstitial ischaemic and metabolic changes, measured using interstitial microdialysis (MD). Eighteen pigs were randomized to control (n=6) or endotoxin infusion (n=12). MD catheters were inserted into the myocardium for measurement of interstitial glucose, pyruvate and lactate concentrations. Plasma glucose and lactate concentrations and systemic haemodynamic parameters were measured simultaneously. Compared with the control group, the endotoxaemic animals had significantly decreased left ventricular stroke work and venous oxygen saturation (SvO2), and increased mean pulmonary artery pressure and plasma lactate. In the endotoxaemic group, decreases in interstitial glucose were observed, occurring simultaneously with increases in interstitial pruvate. Interstitial lactate: pyruvate ratios decreased with time in all animals. Despite severe systemic and pulmonary haemodynamic changes, interstitial MD measurements revealed no evidence of anaerobic metabolism in the myocardium of endotoxaemic pigs. There were, however, changes in glucose and pyruvate concentrations, suggesting local energy metabolic disturbances.

Interstitial glucose concentration in insulin-resistant human skeletal muscle: influence of one bout of exercise and of local perfusion with insulin or vanadate

The present study investigated the changes occurring in interstitial metabolite concentrations and blood flow in insulin-resistant human skeletal muscle during the post-exercise recovery period following a single 2-h bout of one-legged exercise. In addition, the effect of microdialysis perfusion with insulin or the insulin-mimetic trace element vanadate was explored. Eight microdialysis catheters, four in each leg, were inserted in the quadriceps femoris muscle of nine insulin-resistant obese male subjects 2 h following exercise. Two catheters in each leg were perfused at 0.2 microl/min for metabolite determinations and two at 1.33 microl/min for the determination of blood flow. Samples were collected until 9 h after the end of exercise had passed. The interstitial glucose concentration (mean +/- SD) was significantly lower in the exercised (2.8 +/- 1.3 mM) than in the rested leg (3.7 +/- 0.9 mM), P = 0.001, a difference that lasted at least 8 h after the exercise bout. On the other hand, blood flow was not different in the two legs. Microdialysis perfusion with insulin (14 mU/ml) or sodium metavanadate (100 mM) decreased the interstitial glucose concentration (P = 0.001) in both the exercised and rested leg. With vanadate, this decrease was similar in the exercised (-69%) and the rested leg (-71%), whereas insulin had a larger effect in the exercised leg (-29 vs. -6.9%), P = 0.05. This study shows that the interstitial glucose concentration in insulin-resistant skeletal muscle is markedly decreased for several hours following a single exercise session. This is in accordance with recent findings in healthy subjects. This change is accompanied by an increased insulin effect on the interstitial glucose concentration. The effect of vanadate was not decreased in insulin-resistant human skeletal muscle and was not augmented by exercise.

THE EFFECT OF ERYTHROPOIETIN ON ISCHEMIC DAMAGE IN THE CANINE KIDNEY

693 PREDICTING IRREPARABLE RENAL ISCHEMIC INJURY USING A REAL-TIME MARKER IN THE PORCINE MODEL Kyle J Weld*, Claudio Montiglio, Anneke C Bush, Patricia S Dixon, Harvey A Schwertner, Donna M Hensley, Jerry R Cowart, R Duane Cespedes. Lackland AFB, TX. INTRODUCTION AND OBJECTIVE: To determine the maximal renal tolerance of warm ischemia using renal cortical interstitial metabolic changes to identify a potential real-time marker of irreparable renal function. METHODS: Using a single kidney model, 15 pigs underwent 120, 150, and 180 minutes of warm ischemia. Microdialysis samples were collected before, during, and after the ischemia. Renal function assessments consisting of serum creatinine levels and GFR measurements were performed prior to ischemia and on post-ischemic days 1, 5, 9, 14, and 28. Kidneys exposed and not exposed to ischemia were collected for histologic study. RESULTS: Interstitial glucose and pyruvate concentrations declined while lactate concentrations increased to stable levels during ischemia. Glutamate spiked at 30 minutes of ischemia and subsequently tapered while glycerol increased throughout the warm ischemia time. By post-ischemic day 28, renal function at returned to baseline after 120 minutes of ischemia, but irreparable functional damage occurred after 150 and 180 minutes of ischemia. The functional data correlated with

Use of the Continuous Glucose Monitoring System in Goettingen Minipigs, With a Special Focus on the Evaluation of Insulin-Dependent Diabetes

Objectives Adult pig islet isolation has greatly improved in the past few years. Islet grafts may now be tested in large animals. Continuous Glucose Monitoring System (CGMS) was applied to diabetic Goettingen Minipigs (GMP) to improve the management of hyperglycemia and hypoglycemia and their welfare before transplantation. Methods GMP (25–35 kg) received a minipig diet once daily. Diabetes was induced by streptozotocin (STZ; 150 mg/kg intravenous [IV]; n = 5) or by surgical pancreatectomy (PGMP; n = 3). Interstitial glucose concentration (IGC) was monitored continuously with an implanted sensor; CGMS was calibrated using conventional blood glucose tests 3–4 times per day; CGMS data were fed into the monitor memory and analyzed using CGMS software. Results Glucose sensors were handled accurately. Diabetes occurred 2–3 days after STZ or immediately after pancreatectomy with basal C-peptide secretion of <0.4 ng/mL (measured using intravenous glucose tolerance test) and prompt loss of body weight. Insulin substitution was necessary to keep the GMP in good condition for up to 5–6 months, with stable body weight and normal behavior. Some GMP became hypoglycemic, which was only documented by CGMS, but not by conventional glucose assays. Tight glucose control and substitution of exocrine enzymes (Creon 25,000 E/d) reduced morbidity of the PGMP, which was then comparable with that of STZ-GMP. Conclusions The CGMS, developed for humans, is equally suitable for the 2 GMP diabetes models. Close-meshed glucose monitoring and insulin treatment improved the general condition of the diabetic GMP, ie, the islet graft recipients, and will thus greatly add to posttransplantation success.

Interstitial glucose profile associated with symptoms attributed to hypoglycemia by otherwise healthy women

Background:Reports of postprandial symptoms attributed to hypoglycemia by otherwise healthy individuals appear to be relatively common in UK women. Whether these symptoms are related to blood glucose is a contentious issue, which periodic ambulatory blood glucose measurement has failed to resolve. Objective:The authors investigated, using continuous glucose monitoring technology, whether postprandial symptoms are associated with interstitial glucose concentrations (IG) in the hypoglycemic range or with a previous fall in IG. Design:Thirty healthy nonobese women (age 20-48 y) who reported symptoms attributable to hypoglycemia and 20 nonsymptomatic controls wore a subcutaneous probe in abdominal fat for 4-7 d (median: 5 d) and kept a diet and activity diary during this time. Results:Twenty women reported postprandial symptoms; 41 episodes were recorded. When symptomatic, IG was ≤3.3 mmol/L in 5% of cases. A significant fall in IG over the preceding 60 min was observed before autonomic symptoms (P < 0.005). The proportion of total energy intake derived from dietary fat in the symptomatic group was higher than that in the controls (P < 0.05). The proportion of total sugars was similar between groups; however, the meal preceding symptoms had a higher percentage of energy derived from total sugars when compared with the individuals' diet over the study period (P < 0.05). Conclusions:Most symptoms attributable to hypoglycemia were not associated with an IG concentration in the hypoglycemic range. A previous fall in IG may be implicated in the etiology of autonomic symptoms, with the consumption of meals high in sugars potentially playing a role in symptom initiation.

Continuous Glucose Monitoring in Dogs and Cats

Use of continuous glucose monitoring in veterinary medicine is gaining popularity. Through use of a commercially available continuous glucose monitor system, insights into daily glucose changes in dogs and cats are achievable. The continuous glucose monitoring system measures glucose concentrations in the interstitial fluid of the subcutaneous space by use of a small, flexible probe. When placed in the subcutaneous tissue, the probe is connected to a recording device that is attached to the animal and records the interstitial fluid glucose concentration every 5 minutes (288 readings per 24 hours). Once attached and properly calibrated, the instrument can remain in place for several days, hospitalization of the patient is not necessary, and the normal daily routine of the animal can be maintained. The data from the recording device are then downloaded and a very detailed picture of the interstitial fluid glucose concentration over that time period can be obtained. Subcutaneous interstitial fluid glucose concentrations have a good correlation to blood glucose concentrations within a defined range. The continuous glucose monitoring system has distinct advantages over traditional blood glucose curves and is a valuable tool for managing diabetic dogs and cats. In addition, other clinical uses for continuous glucose monitoring are being developed. This review is designed to outline the technology behind the continuous glucose monitoring system, describe the clinical use of the instrument, provide clinical examples in which it may be useful, and discuss future directions for continuous glucose monitoring in dogs and cats.

Insulin, intracerebral glucose and bedside biochemical monitoring utilizing microdialysis

Following subarachnoid hemorrhage, hyperglycemia is strongly associated with complications and with impaired neurological recovery. Targeted insulin therapy for glycemic control might, on the contrary, have harmful effects by causing too low cerebral glucose levels. The study published by Schlenk and colleagues in the previous issue of Critical Care shows that insulin caused a significant decrease in the interstitial cerebral glucose concentration although the blood glucose level remained unaffected. Since several studies utilizing various analytical techniques have shown that cerebral blood flow and cerebral glucose uptake and metabolism are insulin-independent processes, the observation remains unexplained.

Continuous Glucose Profiles in Healthy Subjects under Everyday Life Conditions and after Different Meals

This study investigated continuous glucose profiles in nondiabetic subjects. Continuous interstitial glucose measurement was performed under everyday life conditions (2 days) and after ingestion of four meals with standardized carbohydrate content (50 grams), but with different types of carbohydrates and variable protein and fat content. Twenty-four healthy volunteers (12 female, 12 male, age 27.1 +/- 3.6 years) participated in the study. Each subject wore two microdialysis devices (SCGM1, Roche Diagnostics) simultaneously. The mean 24-hour interstitial glucose concentration under everyday life conditions was 89.3 +/- 6.2 mg/dl (mean +/- SD, n = 21), and mean interstitial glucose concentrations at daytime and during the night were 93.0 +/- 7.0 and 81.8 +/- 6.3 mg/dl, respectively. The highest postprandial glucose concentrations were observed after breakfast: 132.3 +/- 16.7 mg/dl (range 101-168 mg/dl); peak concentrations after lunch and dinner were 118.2 +/- 13.4 and 123.0 +/- 16.9 mg/dl, respectively. Mean time to peak glucose concentration was between 46 and 50 minutes. After ingestion of standardized meals with fast absorption characteristics, peak interstitial glucose concentrations were 133.2 +/- 14.4 and 137.2 +/- 21.1 mg/dl, respectively. Meals with a higher fiber, protein, and fat content induced a smaller increase and a slower decrease of postprandial glucose concentrations with peak values of 99.2 +/- 10.5 and 122.1 +/- 20.4 mg/dl, respectively. This study provided continuous glucose profiles in nondiabetic subjects and demonstrated that differences in meal composition are reflected in postprandial interstitial glucose concentrations. Regarding the increasing application of continuous glucose monitoring in diabetic patients, these data suggest that detailed information about the ingested meals is important for adequate interpretation of postprandial glucose profiles.

Metabolism in adipose tissue in response to citalopram and trimipramine treatment – An in situ microdialysis study

The intake of antidepressants is often accompanied by weight gain. Antidepressants may influence lipid and carbohydrate metabolism that can result in metabolic changes and obesity. We investigated the effect of citalopram and trimipramine on interstitial glycerol, glucose and lactate concentration and blood flow in subcutaneous adipose tissue of obese subjects by means of the microdialysis technique. In addition, the effect of stimulation with norepinephrine on metabolic response was investigated. Each subject was compared to a control subject matched for BMI and age. Each group comprised 10 subjects. Circulating plasma triglyceride concentrations were higher in drug-treated groups. In subcutaneous adipose tissue, microdialysis experiments revealed a higher and prolonged glycerol release in the presence of norepinephrine, but not under basal conditions. In citalopram treated subjects, basal glucose and lactate concentrations were higher compared with controls or with the trimipramine treated group. Local administration of norepinephrine induced a decrease in glucose levels and an increase in lactate levels, but without significant differences between groups. Local adipose tissue blood flow decreased in control groups following norepinephrine application, but remained constant in the antidepressant groups. In conclusion, citalopram and trimipramine affected glucose and lipid metabolism in adipose tissue and resulted in enhanced release of glycerol and free fatty acids into the circulation.

Fiber-coupled fluorescence affinity sensor for 3-day in vivo glucose sensing.

To evaluate the feasibility of an implantable fiber-coupled fluorescence affinity sensor (FAS) for glucose monitoring in humans, we studied the acute and chronic in vivo performance in hairless rats and pigs. The implantable fiber-coupled FAS was constructed by filling a dialysis chamber made of a regenerated cellulose membrane mounted to the distal tip of an optical fiber with fluorescent chemistry based on concanavalin A. Blood sugar changes in animals were induced by injections of insulin and dextrose. Determination of interstitial glucose concentrations in skin tissue was facilitated by measuring the fluorescence response of the FAS. The acute in vivo response of the fiber-coupled FAS exhibited good correlation coefficients (>0.77) with blood sugar changes and minimal lag times (2-10 min) after 2 hours of sensor implantation. Equilibrium of the sensor signal with interstitial fluid was required less than 60 min after implantation. For both rats and pigs, chronic response of the FAS to blood sugar modulations measured during the third day of implantation successfully demonstrated proof-of-concept for short-term glucose monitoring. A slight decrease in sensitivity after 3 days in the small animal model was assumed to be caused by excessive mechanical forces on the implanted device because of high animal motility. Overall, the chronic in vivo performance of the FAS in two different animal models over 3 days was clinically acceptable and comparable to other continuous glucose monitoring platforms. The major benefit of the FAS is the absence of "autodestructive" side products and any device-related warm-up time after sensor reconnection.