Fluctuations In Blood Glucose Concentrations Research Articles

Red blood cells as glucose carriers to the human brain: Modulation of cerebral activity by erythrocyte exchange transfusion in Glut1 deficiency (G1D)

Red blood cells circulating through the brain are briefly but closely apposed to the capillary endothelium. We hypothesized that this contact provides a nearly direct pathway for metabolic substrate transfer to neural cells that complements the better characterized plasma to endothelium transfer. While brain function is considered independent of normal fluctuations in blood glucose concentration, this is not borne out by persons with glucose transporter I (GLUT1) deficiency (G1D). In them, encephalopathy is often ameliorated by meal or carbohydrate administration, and this enabled us to test our hypothesis: Since red blood cells contain glucose, and since the red cells of G1D individuals are also deficient in GLUT1, replacing them with normal donor cells via exchange transfusion could augment erythrocyte to neural cell glucose transport via mass action in the setting of unaltered erythrocyte count or plasma glucose abundance. This motivated us to perform red blood cell exchange in 3 G1D persons. There were rapid, favorable and unprecedented changes in cognitive, electroencephalographic and quality-of-life measures. The hypothesized transfer mechanism was further substantiated by in vitro measurement of direct erythrocyte to endothelial cell glucose flux. The results also indicate that the adult intellect is capable of significant enhancement without deliberate practice. ClinicalTrials.gov registration: NCT04137692 https://clinicaltrials.gov/ct2/show/NCT04137692

An Aldehyde Responsive, Cleavable Linker for Glucose Responsive Insulins.

A glucose responsive insulin (GRI) that responds to changes in blood glucose concentrations has remained an elusive goal. Here we describe the development of glucose cleavable linkers based on hydrazone and thiazolidine structures. We developed linkers with low levels of spontaneous hydrolysis but increased level of hydrolysis with rising concentrations of glucose, which demonstrated their glucose responsiveness in vitro. Lipidated hydrazones and thiazolidines were conjugated to the LysB29 side-chain of HI by pH-controlled acylations providing GRIs with glucose responsiveness confirmed in vitro for thiazolidines. Clamp studies showed increased glucose infusion at hyperglycemic conditions for one GRI indicative of a true glucose response. The glucose responsive cleavable linker in these GRIs allow changes in glucose levels to drive the release of active insulin from a circulating depot. We have demonstrated an unprecedented, chemically responsive linker concept for biopharmaceuticals.

1103-P: Glucose-Responsive Insulin: An Unprecedented Cleavable Linker Concept

Achieving the optimal combination of multiple glucose measurements and insulin injections provides a complex daily situation for most insulin-dependent diabetes patients with currently available insulin products. To date, several fast-acting and long-acting insulins have been developed. However, while the pharmacokinetic profiles have been optimized, it has remained an elusive goal for decades to develop a Glucose Responsive Insulin (GRI), which can be responsive to the fluctuations in blood glucose concentrations during the day. Here we present an unprecedented GRI concept. The concept is based on the hydrolysis of a cleavable linker that is covalently bound to insulin. The chemical nature of this central linker is designed to rapidly release active insulin when glucose rises above euglycemia (5 mM), and this release of active insulin will increase with increasing blood glucose concentration. The second element of the concept is an albumin-mediated inactivation of the GRI by lipidation. After injection, the GRI will bind to albumin and circulate as a depot, resulting in a slow release of insulin like seen with other basal insulins such as insulin Detemir. At the linker level, we have tested three concentrations of glucose, and glucose responsiveness was demonstrated by a decrease in reaction time with increasing glucose concentration. Moreover, fully conjugated GRI molecules were tested in 90% pancreatectomized rats, a model of type 1 diabetes, demonstrating significant and long-lasting glucose lowering effect as compared to control. Overall, we have demonstrated the feasibility of providing a GRI approach, which combines the properties of a basal insulin with that of a bolus insulin. With the circulating depot approach the concept also holds a promise for liver preference. Ultimately our approach could provide a safe insulin for the treatment of insulin-dependent diabetes with very low risk of side effects. Disclosure K. Mannerstedt: Employee; Self; Gubra. E. Engholm: Employee; Self; Gubra. N.K. Mishra: Employee; Self; Gubra. M. Lundh: Employee; Self; Gubra. N. Buch-Månson: None. L.N. Fink: Employee; Self; Gubra. Stock/Shareholder; Self; Novo Nordisk A/S. S.L. Pedersen: None. P.J. Pedersen: Employee; Self; Gubra. P. Le-Huu: Employee; Self; Gubra, Novo Nordisk A/S. Employee; Spouse/Partner; Novo Nordisk A/S. J. Lai: Employee; Self; Gubra. K.J. Jensen: Consultant; Self; Gubra. Stock/Shareholder; Self; Gubra. K. Fosgerau: Stock/Shareholder; Self; Gubra.

Glycemic Variability and Hemoglobin A1c and Their Associations with Blood Pressure Among Overweight Adults with Prediabetes or Type 2 Diabetes (P12-008-19)

ObjectivesHemoglobin A1c (HbA1c) is associated with hypertension in prediabetes (PD) and type 2 diabetes (T2D), both of which are associated with increased cardiovascular disease (CVD) risk. Traditionally, HbA1c is the standard approach to assessing glycemic status, however, glycemic variability (GV)—the daily fluctuations in blood glucose concentrations—may be more predictive of CVD. Little is known regarding the relationship between GV and blood pressure (BP). Therefore, we examined GV and HbA1c and their associations with BP in overweight adults with PD and early stage T2D enrolled in a weight loss study. MethodsParticipants had a history of PD or T2D treated with lifestyle alone or lifestyle and metformin. Data for this report were obtained at baseline and included sociodemographics, height, weight, BP, and HbA1c. Up to two weeks of continuous glucose monitoring data were collected using the Abbott Freestyle Libre Pro, and mean amplitude of glycemic excursions (MAGE) was computed using EasyGV. Linear mixed models were used to test the associations of MAGE and HbA1c with BP, with adjustment for sociodemographic characteristics, as well as to compare MAGE on weekdays versus weekends. Repeated measures ANOVA was used to investigate the within-subject and between-subject variation of MAGE. All analyses were performed using R software. ResultsStudy participants (n = 35) were mostly female (66%) and non-Hispanic white (69%), with a mean (SD) age of 57 (11) years, BMI of 33.0 (4.0) kg/m2, HbA1c of 5.6 (0.5) %, and systolic and diastolic BP (SBP, DBP) of 124 (14) and 71 (8) mmHg, respectively. MAGE differed significantly between participants (P < 0.001), however within person was fairly stable (P = 0.14). There were no significant differences in MAGE on weekdays versus weekends (P = 0.27). MAGE, but not HbA1c, was positively associated with SBP (P = 0.02 vs P = 0.44), while adjusting for age, gender, race and BMI. When HbA1c was added to the model, the association of MAGE with SBP remained significant (P = 0.03). ConclusionsAmong overweight adults with PD and early-stage T2D, MAGE was found to be associated with SBP. This suggests that a measure of daily GV may be a good alternative measure of metabolic health outcomes in this population. Funding SourcesThis work was funded by the American Heart Association.

Glucose concentrations after insulin-induced hypoglycemia and glycemic variability in healthy and diabetic cats.

BackgroundLittle information is available about posthypoglycemic hyperglycemia (PHH) in diabetic cats, and a causal link between hypoglycemia and subsequent hyperglycemia is not clear. Fluctuations in blood glucose concentrations might only represent high glycemic variability.HypothesisInsulin induces PHH in healthy cats, and PHH is associated with poorly regulated diabetes and increased glycemic variability in diabetic cats.AnimalsSix healthy cats, 133 diabetic cats.MethodsInsulin (protamine‐zinc and degludec; 0.1‐0.3 IU/kg) administered to healthy cats. Blood glucose curves were generated with portable glucose meter to determine the percentage of curves with PHH. Data from insulin‐treated diabetic cats with blood glucose curves showing hypoglycemia included data of cats with and without PHH. Post‐hypoglycemic hyperglycemia was defined as blood glucose concentrations <4 mmol/L followed by blood glucose concentrations >15 mmol/L within 12 hours. Glycemic variability was calculated as the standard deviation of the blood glucose concentrations.ResultsIn healthy cats, all insulin doses caused hypoglycemia but PHH was not observed; glycemic variability did not differ between insulin preparations. Among diabetic cats with hypoglycemia, 33 (25%) had PHH. Compared with cats without PHH, their daily insulin dose was higher (1.09 ± 0.55 versus 0.65 ± 0.56 IU/kg; P < .001), serum fructosamine concentration was higher (565 ± 113 versus 430 ± 112 µmol/L; P < .001), remission was less frequent (10% versus 56%; P < .001), and glycemic variability was larger (8.1 ± 2.4 mmol/L versus 2.9 ± 2.2 mmol/L; P < .001).Conclusions and Clinical ImportanceInsulin‐induced hypoglycemia did not cause PHH in healthy cats but it occurred in 25% of diabetic cats with hypoglycemia, particularly when diabetes was poorly controlled. Glycemic variability was increased in cats with PHH.

Conventional insulin pump therapy in two neonatal diabetes patients harboring the homozygous PTF1A enhancer mutation: Need for a novel approach for the management of neonatal diabetes

Kurnaz E, Aycan Z, Yıldırım N, Çetinkaya S. Conventional insulin pump therapy in two neonatal diabetes patients harboring the homozygous PTF1A enhancer mutation: Need for a novel approach for the management of neonatal diabetes. Turk J Pediatr 2017; 59: 458-462. The enhancer of PTF1A mutation causes developmental defects of the pancreas. This condition can result in insulin-requiring diabetes and exocrine pancreatic insufficiency. We report two patients with diabetes mellitus harboring the homozygous PTF1A enhancer mutation. The patients had hyperglycemia in the first month of life and were started with subcutaneous insulin injections with NPH insulin. When blood glucose (BG) exceeded 250 mg/dl, a conservative dose of rapid-acting insulin was administered to restore BG to the target range. In cases with documented poor control (persistent hypoglycemia and rebound hyperglycemia), it was decided that the baby would benefit from a continuous subcutaneous insulin infusion pump. But our experience shows that wide fluctuations in BG concentrations despite the strict follow-up was probably due to the absence of circulating glucagon. Further treatment options would overcome this problem, especially for children with pancreas agenesis. We could say theoretically that using diluted insulin, a sensor-augmented insulin pump system and single-hormone (insulin alone) and dual-hormone (insulin and glucagon) artificial pancreas systems may mitigate the severity of hypogylcemia.

The effects of differing proportions of dietary macronutrients on the digestibility and post-prandial endocrine responses in domestic cats (Felis catus)

SummaryThe aim of this study was to compare the effects of feeding two diets with different macronutrient proportions (high protein, low carbohydrate and low protein, high carbohydrate) on the digestibility and post-prandial endocrine responses of cats fed at maintenance levels, and to evaluate the effectiveness of the marginal ear vein prick technique for the measurement of blood glucose levels in feline studies. Two diets were fed to 16 adult domestic short-haired cats for a period of three weeks (eight cats per diet). Following a seven-day dietary adaptation period, the apparent macronutrient digestibility of the two diets was determined (days 8-19) using the total faecal collection method. The faeces were freeze dried, ground and analysed for dry matter, crude protein, crude fat and gross energy and then apparent digestibility was calculated. On days 20 and 21, the post-prandial glucose responses of the cats fed a single meal of one of the two diets were measured in serial blood samples collected using the marginal ear vein prick technique.Results showed that the high protein, low carbohydrate diet had higher (p &lt; 0.05) apparent digestibility of dry matter, crude protein, crude fat and energy, lower (p &lt; 0.01) daily faecal output and smaller fluctuations in blood glucose concentrations. Despite the two groups of cats having similar calorific intakes, the cats fed the high protein diet lost weight over the study period, whereas those fed the high carbohydrate, low protein diet gained weight. The marginal ear vein prick technique proved to be an effective alternative to catheterisation for blood glucose determination. The high protein diet tested in the current study, in addition to being more aligned to the cat's natural carnivorous diet, may be beneficial for weight management and blood glucose control in cats.

The strong relation between post-hemodialysis blood methylglyoxal levels and post-hemodialysis blood glucose concentration rise.

Hemodialysis is known to decrease blood glucose concentration (BGC), insulin, and methylglyoxal levels. However, the effects of decreases in these factors on the increase in post-hemodialysis BGC remain unknown. This study identifies the effects of hemodialysis-induced changes in concentrations of these elements on post-hemodialysis BGC. Study subjects included seventeen insulin-treated diabetes patients receiving hemodialysis. The fluctuations in BGC on hemodialysis-treatment days and non-hemodialysis-treatment days were evaluated using a continuous glucose monitoring system. BGC was evaluated before breakfast, before starting hemodialysis, at the end of hemodialysis, 1 h post-hemodialysis (lunch), and 6 h post-hemodialysis (dinner). BGC, insulin, and methylglyoxal levels were measured at the start and end of hemodialysis. This study also evaluated the changes in the concentrations of glucose and insulin in the arterial line and the venous line during hemodialysis. Hemodialysis decreases BGC, insulin, and methylglyoxal levels. Concentrations of glucose and insulin in the arterial line gradually decreased during dialysis, while concentrations in the venous line approached their original concentrations in the dialysis solution. BGC rose sharply after eating lunch 1 h post-hemodialysis. The blood glucose, insulin, and methylglyoxal concentrations at the end of hemodialysis were associated with the M values and the mean amplitude of glycemic excursion values between before lunch and dinner. In particular, methylglyoxal concentration at the end of hemodialysis was strongly related to the post-hemodialysis increase in BGC. Hemodialysis-induced decreases in methylglyoxal concentrations and methylglyoxal concentration at the end of hemodialysis influence post-hemodialysis fluctuations in BGC.

Mitochondrial function and insulin secretion

In the endocrine fraction of the pancreas, the β-cell rapidly reacts to fluctuations in blood glucose concentrations by adjusting the rate of insulin secretion. Glucose-sensing coupled to insulin exocytosis depends on transduction of metabolic signals into intracellular messengers recognized by the secretory machinery. Mitochondria play a central role in this process by connecting glucose metabolism to insulin release. Mitochondrial activity is primarily regulated by metabolic fluxes, but also by dynamic morphology changes and free Ca2+ concentrations. Recent advances of mitochondrial Ca2+ homeostasis are discussed; in particular the roles of the newly-identified mitochondrial Ca2+ uniporter MCU and its regulatory partner MICU1, as well as the mitochondrial Na+–Ca2+ exchanger. This review describes how mitochondria function both as sensors and generators of metabolic signals; such as NADPH, long chain acyl-CoA, glutamate. The coupling factors are additive to the Ca2+ signal and participate to the amplifying pathway of glucose-stimulated insulin secretion.

Continuous Glucose Monitoring during Critical Care

Continuous Glucose Monitoring during Critical Care

Glucose fluctuation on the progression of diabetic macroangiopathy—New findings from monocyte adhesion to endothelial cells

The aim of this study was to elucidate the effect of repetitive fluctuations in blood glucose concentrations on monocyte adhesion to the aortic endothelium. Streptozotocin induced diabetes rats were fed twice daily to induce repetitive postprandial glucose spikes. Then, we compared the number of monocytes adherent to the endothelium of thoracic aorta in these rats with that in rats fed ad libitum. In addition, we evaluated the effect of N-acetyl- l cystein and probucol which are known as antioxidants on the monocyte adhesion to endothelial cells. Streptozotocin induced diabetes rats fed twice daily showed remarkably lower HbA 1c than the rats fed ad libitum. However, the former group showed markedly higher number of monocytes adherent to the endothelium than the latter. Both N-acetyl- l cystein and probucol could not reduce the number of adherent monocytes in streptozotocin induced diabetes rats fed twice daily. Our data demonstrated that repetitive postprandial fluctuation in glucose concentration evokes monocyte adhesion to endothelial cells that was worse than that induced by stable hyperglycemia in vivo.

An endocrinologist's view on the practical use of insulin

The use of sliding-scale SC insulin for glycemic control in hospitalized patients with diabetes mellitus can produce clinically important fluctuations in blood glucose concentrations over time. Although the plasma concentration of insulin peaks after ∼2 hours, the stimulation of glucose utilization by insulin does not peak until 3 to 4 hours after SC administration. Thus, the repeated administration of sliding-scale SC insulin every 4 hours can create a large cumulative effect on glucose utilization and a precipitous decline in blood glucose concentration in a relatively short period of time. Even rapid-acting insulin analogues reach their peak effects on glucose utilization after ∼2 hours. At the University of Washington Medical Center in Seattle, Washington, a hospital-wide protocol has been developed for the use of IV insulin for hospitalized diabetic patients who are not eating or eating very little. An initial IV insulin dose is selected on the basis of the patient's insulin sensitivity, and subsequent doses are adjusted in response to changes in blood glucose values over time. The use of IV insulin reduces the likelihood that patients will develop hypoglycemia or hyperglycemia in both critical and noncritical care settings. Standardized methods, which are valuable for patient care and for educating clinicians about insulin use, have also been developed to transition patients to SC insulin.

Assessment of the relationship between glucose and A1c using kinetic modeling

Treatment goals for diabetic patients are directed towards lowering A1c values by controlling blood glucose concentrations (BGC), making it important to understand the relationship between the two parameters. Because findings from clinical trials about the relationship between BGC and A1c values show a profound variability around the obtained regression lines, they are difficult to apply to individual patients. Therefore, a model was developed and applied based on the kinetics of HbA1c formation and removal. It takes the instability of A1c and loss of hemoglobin into consideration. Data from clinical studies and hypothetical scenarios were used to test the model and to describe the relationship between A1c and BGC. A close agreement between experimental and calculated data was obtained in steady-state and non-steady-state conditions. Aside the erythrocyte life span, the chemical instability of A1c appears to affect A1c levels markedly and their changes due to therapy. A threefold increase in BGC over 30 days prior to A1c measurement can cause an increase in A1c value of about 120% as compared with 4% when it occurs 4 months prior to A1c measurement. Profound daily fluctuations in BGC result in minor changes in A1c. In conclusion, A1c provides information about a patient's glycemia, mainly over the past 2 months, and may not reflect well daily blood glucose fluctuations. This model might be suitable to identify individual differences in glycation rates.

Repetitive Fluctuations in Blood Glucose Enhance Monocyte Adhesion to the Endothelium of Rat Thoracic Aorta

The aim of this study was to elucidate the effect of repetitive fluctuations in blood glucose concentrations on monocyte adhesion to the aortic endothelium. Nonobese type 2 diabetes, Goto-Kakizaki (GK) rats were fed twice daily to induce repetitive postprandial glucose spikes. Then, we compared the number of monocytes adherent to the endothelium of thoracic aorta in these rats with that in rats fed ad libitum. To suppress the glucose spikes, rats were injected with an inhibitor of sodium-glucose transporter, phloridzin, just before each meal for 12 weeks. GK rats fed twice daily showed significantly lower HbA1c than GK rats fed ad libitum. However, the former group showed markedly higher number of monocytes adherent to the endothelium than the latter, together with increased arterial intimal thickening. Phloridzin significantly reduced the number of adherent monocytes in GK rats fed twice daily. Our data demonstrated that repetitive postprandial fluctuation in glucose concentration evokes monocyte adhesion to endothelial cells that was worse than that induced by stable hyperglycemia in vivo. Suppression of such fluctuations efficiently suppressed monocyte adhesion to the aortic endothelium.

Apical GLUT2

Understanding the mechanisms that determine postprandial fluctuations in blood glucose concentration is central for effective glycemic control in the management of diabetes. Intestinal sugar absorption is one such mechanism, and studies on its increase in experimental diabetes led us to propose a new model of sugar absorption. In the apical GLUT2 model, the glucose transported by the Na(+)/glucose cotransporter SGLT1 promotes insertion of GLUT2 into the apical membrane within minutes, so that the mechanism operates during assimilation of a meal containing high-glycemic index carbohydrate to provide a facilitated component of absorption up to three times greater than by SGLT1. Here we review the evidence for the apical GLUT2 model and describe how apical GLUT2 is a target for multiple short-term nutrient-sensing mechanisms by dietary sugars, local and endocrine hormones, cellular energy status, stress, and diabetes. These mechanisms suggest that apical GLUT2 is a potential therapeutic target for novel dietary or pharmacological approaches to control intestinal sugar delivery and thereby improve glycemic control.

Evidence that glucokinase regulatory protein is expressed and interacts with glucokinase in rat brain.

Our previous description of functional glucokinase isoforms in the rat brain has opened new questions concerning the presence of glucokinase regulatory protein in the brain and the functional role of its interactions with glucokinase. In this study, we found glucokinase regulatory protein mRNA in rat brain, pancreatic islets and liver. In addition, we found two other variant splicing isoforms, both identified in hypothalamus, pancreatic islets and liver. In situ hybridization studies revealed the presence of glucokinase regulatory protein mRNA, the highest number of positive cells being found in the paraventricular nucleus of the hypothalamus. Glucokinase regulatory protein gene expression gave rise to a protein of 69 kDa mainly in nuclear and soluble cell fractions. Glutathione S-transferase protein fused either to rat liver or human pancreatic islet glucokinase were able to precipitate glucokinase regulatory protein from liver or hypothalamic extracts in the presence of fructose-6-phosphate, the amount of protein co-precipitated being decreased with fructose-1-phosphate. These findings suggest that the presence of glucokinase and glucokinase regulatory protein in the rat brain would facilitate the adaptation of this organ to fluctuations in blood glucose concentrations, and both proteins may participate in glucose-sensing and metabolic regulation in the central nervous system.

Functional glucokinase isoforms are expressed in rat brain.

Recently, the description of glucokinase mRNA in certain neuroendocrine cells has opened new ways to characterize this enzyme in the rat brain. In this study, we found glucokinase mRNA and a similar RNA splicing pattern of the glucokinase gene product in rat hypothalamus and pancreatic islets; the mRNA that codes for B1 isoform was the most abundant, with minor amounts of those coding for the B2, P1, P2, P1/B2, and P2/B2 isoforms. Glucokinase gene expression in rat brain gave rise to a protein of 52 kDa with a high apparent Km for glucose and no product inhibition by glucose 6-phosphate, with a contribution to the total glucose phosphorylating activity of between 40 and 14%; the hypothalamus and cerebral cortex were the regions of maximal activity. Low and high Km hexokinases were characterized by several criteria. Also, using RT-PCR analysis we found a glucokinase regulatory protein mRNA similar to that previously reported in liver. These findings indicate that the glucokinase present in rat brain should facilitate the adaptation of this organ to fluctuations in blood glucose concentrations, and the expression of glucokinase and GLUT-2 in the same hypothalamic neurons suggests a role in glucose sensing.

Blood glucose dependence of visual flicker threshold.

Published research indicated that fluctuations in blood glucose concentration (BGC) change the biochemical balance of the retina and may alter the sensitivity of retinal cells. Low-contrast flicker was used in this research to measure the changes in sensitivity of the retina accompanying shifts in BGC. In five subjects without diabetes and four subjects with diabetes, simultaneous measurements of flicker thresholds, using a two-alternative, forced choice psychometric test, and BGC, were made every 15 to 30 minutes for several hours, while BGC was allowed to fluctuate spontaneously. Flicker thresholds were found to rise and fall, generally tracking BGC in each subject. First-day flicker threshold measurements were used to "calibrate" the method for each subject, and subsequent days' measurements were used to infer blood glucose. The resulting inferred blood glucose values correlated with BGC measured from blood samples in the range of 70 mg/dL to 500 mg/dL with a maximum error of +/-33% in 97% of the measurements. The feasibility of using flicker sensitivity for monitoring blood glucose levels noninvasively is discussed. Improvements in the testing method can potentially reach +/-18% error margin with 1-minute measurements, according to computer simulations. Devices using a visual test would be inexpensive to manufacture and would need no disposable supplies. Planned research will assess the long-term stability of flicker threshold measurements and will determine the applicability of the technique in diabetic retinopathy, in hypoglycemia and in the presence of fatigue and inattention.

Noninvasive Prediction of Glucose by Near-Infrared Diffuse Reflectance Spectroscopy

Self-monitoring of blood glucose by diabetics is crucial in the reduction of complications related to diabetes. Current monitoring techniques are invasive and painful, and discourage regular use. The aim of this study was to demonstrate the use of near-infrared (NIR) diffuse reflectance over the 1050-2450 nm wavelength range for noninvasive monitoring of blood glucose. Two approaches were used to develop calibration models for predicting the concentration of blood glucose. In the first approach, seven diabetic subjects were studied over a 35-day period with random collection of NIR spectra. Corresponding blood samples were collected for analyte analysis during the collection of each NIR spectrum. The second approach involved three nondiabetic subjects and the use of oral glucose tolerance tests (OGTTs) over multiple days to cause fluctuations in blood glucose concentrations. Twenty NIR spectra were collected over the 3.5-h test, with 16 corresponding blood specimens taken for analyte analysis. Statistically valid calibration models were developed on three of the seven diabetic subjects. The mean standard error of prediction through cross-validation was 1.41 mmol/L (25 mg/dL). The results from the OGTT testing of three nondiabetic subjects yielded a mean standard error of calibration of 1.1 mmol/L (20 mg/dL). Validation of the calibration model with an independent test set produced a mean standard error of prediction equivalent to 1.03 mmol/L (19 mg/dL). These data provide preliminary evidence and allow cautious optimism that NIR diffuse reflectance spectroscopy using the 1050-2450 nm wavelength range can be used to predict blood glucose concentrations noninvasively. Substantial research is still required to validate whether this technology is a viable tool for long-term home diagnostic use by diabetics.

Determination of glucose by capillary electrophoresis/laser-induced fluorescence in transdermally collected samples.

Capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection has been used for the determination of glucose in samples collected by noninvasive means. The method uses an enzymatic reaction scheme that provides for the determination of small quantities of glucose with detection limits of 80 nM. This approach is used to evaluate passive transdermal diffusion as a noninvasive means to sample glucose in vivo. A simple sampling cell design is presented. Sample collection was performed on volunteer human subjects. Our experiments show that fluctuations in blood glucose concentration are reflected in the samples obtained by passive transdermal diffusion after glucose intake. The results indicate that glucose from the subcutaneous fluid can be accessed by passive diffusion.