Subcutaneous Adipose Tissue Glucose Research Articles

A prolonged run-in period of standard subcutaneous microdialysis ameliorates quality of interstitial glucose signal in patients after major cardiac surgery

We evaluated a standard subcutaneous microdialysis technique for glucose monitoring in two critically ill patient populations and tested whether a prolonged run-in period improves the quality of the interstitial glucose signal. 20 surgical patients after major cardiac surgery (APACHE II score: 10.1 ± 3.2) and 10 medical patients with severe sepsis (APACHE II score: 31.1 ± 4.3) were included in this investigation. A microdialysis catheter was inserted in the subcutaneous adipose tissue of the abdominal region. Interstitial fluid and arterial blood were sampled in hourly intervals to analyse glucose concentrations. Subcutaneous adipose tissue glucose was prospectively calibrated to reference arterial blood either at hour 1 or at hour 6. Median absolute relative difference of glucose (MARD), calibrated at hour 6 (6.2 (2.6; 12.4) %) versus hour 1 (9.9 (4.2; 17.9) %) after catheter insertion indicated a significant improvement in signal quality in patients after major cardiac surgery (p < 0.001). Prolonged run-in period revealed no significant improvement in patients with severe sepsis, but the number of extreme deviations from the blood plasma values could be reduced. Improved concurrence of glucose readings via a 6-hour run-in period could only be achieved in patients after major cardiac surgery.

The Pro12Ala polymorphism of the PPAR γ2 gene is associated with hepatic glucose uptake during hyperinsulinemia in subjects with type 2 diabetes mellitus

The Ala12 allele of the peroxisome proliferator–activated receptor γ gene ( PPARG2) has been associated with reduced risk of type 2 diabetes mellitus (T2DM) and increased whole-body and skeletal muscle insulin sensitivity in nondiabetic subjects. The effect of the Pro12Ala polymorphism on tissue specific insulin sensitivity in subjects with T2DM has not been previously investigated. We studied the effect of the Pro12Ala polymorphism on the rates of whole-body, skeletal muscle, and subcutaneous adipose tissue glucose uptake (GU) in T2DM subjects, and the rates of hepatic GU in nondiabetic and T2DM subjects during hyperinsulinemia. Our study included 105 T2DM subjects whose whole-body, skeletal muscle, subcutaneous adipose tissue, and hepatic GUs were measured using 18F-fluorodeoxyglucose and positron emission tomography during the hyperinsulinemic euglycemic clamp. Hepatic GU was also measured in 68 nondiabetic subjects. In obese (body mass index ≥27 kg/m 2) subjects with T2DM, the rate of hepatic GU was 28% lower in subjects with the Pro12Pro genotype than in carriers of the Ala12 allele ( P = .001); and a similar trend was observed in nondiabetic obese subjects ( P = .137). No effect of the Pro12Ala polymorphism on the rates of whole-body, skeletal muscle, or subcutaneous adipose tissue GU was observed in T2DM subjects. We conclude that the Ala12 allele of PPARG2 is associated with higher hepatic GU in obese subjects with T2DM.

Clinical Evaluation of Alternative-Site Glucose Measurements in Patients After Major Cardiac Surgery

Tight glycemic control improves outcome in critically ill patients but requires frequent glucose measurements. Subcutaneous adipose tissue (SAT) has been characterized as promising for glucose monitoring in diabetes, but it remains unknown whether it can also be used as an alternative site in critically ill patients. The present study was performed to clinically evaluate the relation of glucose in SAT compared with arterial blood in patients after major cardiac surgery. Forty critically ill patients were investigated at two clinical centers after major cardiac surgery. Arterial blood and SAT microdialysis samples were taken in hourly intervals for a period of up to 48 h. The glucose concentration in dialysate was calibrated using a two-step approach, first using the ionic reference technique to calculate the SAT glucose concentration (SATg) and second using a one-point calibration procedure to obtain a glucose profile comparable to SAT-derived blood glucose (BgSAT). Clinical validation of the data was performed by introducing data analysis based on an insulin titration algorithm. Correlation between dialysate glucose and blood glucose (median 0.80 [interquartile range 0.68-0.88]) was significantly improved using the ionic reference calibration technique (SATg vs.blood glucose 0.90 [0.83-0.94]; P < 0.001). Clinical evaluation of the data indicated that 96.1% of glucose readings from SAT would allow acceptable treatment according to a well-established insulin titration protocol. The results indicate good correlation between SATg and blood glucose in patients after major cardiac surgery. Clinical evaluation of the data suggests that with minor limitations, glucose from SAT can be used to establish tight glycemic control in this patient group.

Single Nucleotide Polymorphisms in the Peroxisome Proliferator–Activated Receptor δ Gene Are Associated With Skeletal Muscle Glucose Uptake

The peroxisome proliferator-activated receptors (PPARs) belong to a superfamily of nuclear receptors. It includes PPAR-delta, a key regulator of fatty acid oxidation and energy uncoupling, universally expressed in different tissues. The PPAR-delta gene (PPARD) maps to 6p21.2-p21.1 and has 11 exons and spans 35 kbp. We investigated the effects of single nucleotide polymorphisms (SNPs) of PPARD on whole-body, skeletal muscle, and subcutaneous adipose tissue glucose uptake in 129 healthy individuals using the hyperinsulinemic-euglycemic clamp technique combined with fluorine-18-labeled fluorodeoxyglucose ([18F]FDG) and positron emission tomography (PET). Three of six SNPs of PPARD and their haplogenotypes were significantly associated with whole-body insulin sensitivity. [18F]FDG-PET scanning indicated that SNPs of PPARD primarily affected insulin sensitivity by modifying glucose uptake in skeletal muscle but not in adipose tissue. Our results give evidence that SNPs of PPARD regulate insulin sensitivity particularly in skeletal muscle.

Rosiglitazone Treatment Increases Subcutaneous Adipose Tissue Glucose Uptake in Parallel with Perfusion in Patients with Type 2 Diabetes: A Double-Blind, Randomized Study with Metformin

We have shown that rosiglitazone increases whole-body and adipose tissue insulin sensitivity in humans. The aim of this study was to further examine whether possible changes in adipose perfusion could explain increased adipose tissue glucose uptake (GU). Thirty-seven patients with newly diagnosed type 2 diabetes were included. Patients were randomized into treatment with rosiglitazone, metformin, or placebo for 26 wk in a double-blinded trial. Femoral adipose flow and GU were measured with [15O]H2O, [18F]fluorodeoxyglucose and positron emission tomography during euglycemic hyperinsulinemia. Adipose masses were measured using magnetic resonance imaging. Metformin and rosiglitazone treatment improved glycemic control, but only rosiglitazone increased whole-body insulin sensitivity. Rosiglitazone treatment increased flow by 72% (P < 0.01) and GU by 23% (P < 0.05) and thereby decreased adipose tissue glucose extraction by 18% (P < 0.05); no changes were observed in the metformin or placebo-treated groups. When the adipose masses were taken into account, rosiglitazone treatment increased flow by 73% (P < 0.01) and GU by 24% (P < 0.05). During hyperinsulinemia, flow correlated with GU (r = 0.63; P < 0.01). In conclusion, s.c. GU is associated with flow in patients with type 2 diabetes. Rosiglitazone treatment enhances GU and flow but decreases glucose extraction, suggesting that perfusion may contribute to adipose tissue insulin sensitization by rosiglitazone.

Microdialysis measurement of glucose in subcutaneous adipose tissue up to three weeks in Type 1 diabetic patients

Background: Microdialysis of subcutaneous adipose tissue may provide an opportunity to monitor glucose continuously, when the device is connected to an extracorporal glucose sensor. We assessed whether our microdialysis probes are capable of measuring adipose tissue glucose over a prolonged period in Type 1 diabetic patients. Furthermore, the relationship between abdominal skinfold thickness and glucose recovery and the effect of spontaneous glucose excursions on its recovery were evaluated.Methods: Microdialysis probes were pairwise inserted subcutaneously into the abdominal fat and remained in situ for 3 weeks in eight Type 1 diabetic patients. At days 1, 3, 4, 8, 11, 16, and 18 of probe retention, glucose, as measured by microdialysis, was compared to capillary blood glucose concentrations during a 4 h period. The recovery of glucose obtained by microdialysis was expressed as a percentage of the capillary blood glucose concentration.Results: Eleven of the 16 inserted probes (69%) were evaluable during the complete study. Recovery of glucose was lower at day 1 and 3 (51±23% and 56±18%, respectively, mean±S.D.) compared to values found afterwards (67±19%, 72±13%, 76±14%, 71±16%, and 76±18%, for day 4, 8, 11, 16, and 18, respectively, for all P<0.05 vs. day 1 and 3). Skinfold thickness was inversely related to the overall 3 week glucose recovery (r=−0.76; P<0.03). Recovery was similar over a wide range of capillary blood glucose concentrations.Conclusions: Prolonged in vivo retention of microdialysis probes improves the recovery and lowers the variability of adipose tissue-sampled glucose in Type 1 diabetic patients. These findings show that microdialysis-based glucose measurements offer an opportunity for prolonged glucose monitoring.

Microdialysis of glucose in subcutaneous adipose tissue up to 3 weeks in healthy volunteers.

To measure possible changes in dialysate glucose concentrations over time, to validate the diffusional model for glucose transport from tissue to the probe, and to evaluate the actual glucose concentration in adipose tissue. Glucose concentrations in the subcutaneous adipose tissue of five healthy subjects (age 25 +/- 2.7 years, BMI 23.2 +/- 2.3 kg/m2 [mean +/- SD]) were measured by the microdialysis technique and compared with blood glucose. We applied microdialysis probes with hollow fibers of various membrane length (10-35 mm), used eight perfusion flow rates (0.5-20 microl/min), and perfused four glucose solutions (0.0, 2.8, 8.3, 11.1 mmol/l). After implantation, a substantial decrease in glucose recovery to the lowest value of 26 +/- 10% of the final plateau value was noted during the first few hours (n = 4). Recovery increased and stabilized after 5-9 days at 84.0 +/- 7.4% of capillary blood glucose when a flow rate of 0.5 microl/min was applied. According to the zero net-flux method, the glucose concentration in equilibrium, Cequi, with the surrounding tissue can be obtained. This concentration also decreases; however, 1 h after recovery, Cequi increases again over 1 or 2 days to a stable value that is not significantly different from the measured capillary blood glucose (P < 0.05). Using various perfusion flow rates and probes (membrane length 10-35 mm), it is shown that diffusion is the rate-limiting process for glucose transport through tissue. Insertion of the microdialysis probes causes damage to the adipose cells and the vascular bed around the probe. Glucose recovery decreases because of a lower blood supply. In 5-9 days, glucose recovery increases; apparently, this time is needed to repair the microstructure of tissue around the probe. After stabilization of the recovery, no loss of probe permeability, which is due to biocompatibility problems, was seen. The change during the 2 days in equilibrium concentration is probably caused by an inflammation reaction that consumes glucose around the probe. The individual increase in recovery during the 1st days after probe insertion until a stable plateau value is reached (flow rate >0 microl/min) is complicated for short-term clinical glucose measurements in adipose tissue. After stabilization, the mean equilibrium concentration of all subjects was equal to the mean capillary blood glucose concentration. Therefore, we conclude that capillary blood glucose concentration probably is the driving force for diffusion through the capillary wall into the probe and is not some interstitial concentration.

In vivo subcutaneous adipose tissue glucose kinetics after glucose ingestion in obesity and fasting

The kinetic pattern of subcutaneous adipose tissue extracellular glucose following glucose ingestion was investigated in vivo with a microdialysis technique in normal-weight (n=21) and obese subjects (n=18) before and after a 7-day fast (n = 9). A dialysis probe (4×0.5 mm) was implanted subcutaneously, and was continuously perfused (5 μl/min). The tissue dialysate glucose concentration was determined in 15-min samples before and during a period of 180 min after a 75-g oral glucose load. A comparison was made between the tissue dialysate concentrations and the venous blood glucose levels. In all study groups the increase in subcutaneous tissue dialysate glucose following glucose ingestion paralleled that in blood, with a time-lag of up to 15 min. In the normal-weight subjects the maximum relative increase in abdominal adipose tissue dialysate glucose was 25% higher (p <0.005) than the corresponding blood glucose level, and the total relative glucose level (area under curve, AUC) in abdominal fat was 20% (p<0.01) higher than in blood. In contrast, the kinetics of gluteal subcutaneous tissue dialysate and blood glucose levels were similar. In the obese patients before the fasting period the maximum relative glucose level in abdominal fat was almost twice as high as in blood (p<0.005), and the total glucose level (AUC) was 50% higher than the blood glucose AUC (p<0.005). After the fast, on the other hand, almost identical relative dynamics of abdominal subcutaneous tissue and blood glucose levels were found. It is concluded that ingested glucose is rapidly distributed to the interstitial compartment of subcutaneous adipose tissue. In normal-weight subjects the hexose is retained to some extent in the abdominal, but not in the gluteal, fat depot, which indicates regional differences in subcutaneous tissue glucose kinetics following glucose ingestion. In obesity the accumulation of glucose in abdominal fat is markedly increased, whereas after fasting the abdominal subcutaneous tissue glucose level closely resembles the venous blood glucose level. It remains to be elucidated whether the observed effects of obesity and fasting on the handling of glucose by adipose tissue following glucose ingestion are due to changes in subcutaneous tissue blood flow and/or tissue glucose utilization.

In vivo subcutaneous adipose tissue glucose kinetics after glucose ingestion in obesity and fasting

The kinetic pattern of subcutaneous adipose tissue extracellular glucose following glucose ingestion was investigated in vivo with a microdialysis technique in normal-weight (n = 21) and obese subjects (n = 18) before and after a 7-day fast (n = 9). A dialysis probe (4 x 0.5 mm) was implanted subcutaneously, and was continuously perfused (5 microliters/min). The tissue dialysate glucose concentration was determined in 15-min samples before and during a period of 180 min after a 75-g oral glucose load. A comparison was made between the tissue dialysate concentrations and the venous blood glucose levels. In all study groups the increase in subcutaneous tissue dialysate glucose following glucose ingestion paralleled that in blood, with a time-lag of up to 15 min. In the normal-weight subjects the maximum relative increase in abdominal adipose tissue dialysate glucose was 25% higher (p less than 0.005) than the corresponding blood glucose level, and the total relative glucose level (area under curve, AUC) in abdominal fat was 20% (p less than 0.01) higher than in blood. In contrast, the kinetics of gluteal subcutaneous tissue dialysate and blood glucose levels were similar. In the obese patients before the fasting period the maximum relative glucose level in abdominal fat was almost twice as high as in blood (p less than 0.005), and the total glucose level (AUC) was 50% higher than the blood glucose AUC (p less than 0.005). After the fast, on the other hand, almost identical relative dynamics of abdominal subcutaneous tissue and blood glucose levels were found.(ABSTRACT TRUNCATED AT 250 WORDS)

The half-life of triglycerides labeled from glucose in subcutaneous adipose tissue in human obesity. A preliminary report

The half-life of triglycerides labeled from glucose in subcutaneous adipose tissue in human obesity. A preliminary report