Glucose sensing by means of silicon photonics

Diabetes is a fast growing metabolic disease, where the patients suffer from disordered glucose blood levels. Monitoring the blood glucose values in combination with extra insulin injection is currently the only therapy to keep the glucose concentration in diabetic patients under control, minimizing the long- term effects of elevated glucose concentrations and improving quality of life of the diabetic patients. Implantable sensors allow continuous glucose monitoring, offering the most reliable data to control the glucose levels. Infrared absorption spectrometers offer a non-chemical measurement method to determine the small glucose concentrations in blood serum. In this work, a spectrometer platform based on silicon photonics is presented, allowing the realization of very small glucose sensors suitable for building implantable sensors. A proof-of-concept of a spectrometer with integrated evanescent sample interface is presented, and the route towards a fully implantable spectrometer is discussed

Measuring Blood Glucose Concentrations in Photometric Glucometers Requiring Very Small Sample Volumes

Glucometers present an important self-monitoring tool for diabetes patients and therefore must exhibit high accu- racy as well as good usability features. Based on an invasive, photometric measurement principle that drastically reduces the volume of the blood sample needed from the patient, we present a framework that is capable of dealing with small blood samples, while maintaining the required accuracy. The framework consists of two major parts: 1) image segmentation; and 2) convergence detection. Step 1) is based on iterative mode-seeking methods to estimate the intensity value of the region of interest. We present several variations of these methods and give theoretical proofs of their convergence. Our approach is able to deal with changes in the number and position of clusters without any prior knowledge. Furthermore, we propose a method based on sparse approximation to decrease the computational load, while maintaining accuracy. Step 2) is achieved by employing temporal tracking and prediction, herewith decreasing the measurement time, and, thus, improving usability. Our framework is validated on several real data sets with different characteristics. We show that we are able to estimate the underlying glucose concentration from much smaller blood samples than is currently state-of-the- art with sufficient accuracy according to the most recent ISO standards and reduce measurement time significantly compared to state-of-the-art methods

Associations between paternally transmitted fetal IGF2 variants and maternal circulating glucose concentrations in pregnancy.

OBJECTIVE: To test the hypothesis that polymorphic variation in the paternally transmitted fetal IGF2 gene is associated with maternal glucose concentrations in the third trimester of pregnancy. RESEARCH DESIGN AND METHODS: A total of 17 haplotype tag single nucleotide polymorphisms in the IGF2 gene region were genotyped in 1,160 mother/partner/offspring trios from the prospective Cambridge Baby Growth Study (n = 845 trios) and the retrospective Cambridge Wellbeing Study (n = 315 trios) (3,480 samples in total). Associations were tested between inferred parent-of-origin fetal alleles, z scores of maternal glucose concentrations 60 min. after an oral glucose load performed at week 28 of pregnancy, and offspring birth weights. RESULTS: Using the minimum P value test, paternally transmitted fetal IGF2 polymorphisms were associated with maternal glucose concentrations; specifically, paternally transmitted fetal rs6578987 (P = 0.006), rs680 (P = 0.01), rs10770125 (P = 0.0002), and rs7924316 (P = 0.01) alleles were associated with increased maternal glucose concentrations in the third trimester of pregnancy and placental IGF-II contents at birth (P = 0.03). In contrast, there were no associations between maternal glucose concentrations and maternal or maternally transmitted fetal IGF2 genotypes. CONCLUSIONS: Polymorphic variation in paternally transmitted fetal IGF2 is associated with increased maternal glucose concentrations in pregnancy and could potentially alter the risk of gestational diabetes in the mother. The association may be at least partially mediated by changes in placental IGF2 expression

What factors determine placental glucose transfer kinetics?

Introduction: transfer of glucose across the human placenta is directly proportional to maternal glucose concentrations even when these are well above the physiological range. This study investigates the relationship between maternal and fetal glucose concentrations and transfer across the placenta.Methods: transfer of d-glucose, 3H-3-o-methyl-d-glucose (3H-3MG) and 14C-l-glucose across the isolated perfused human placental cotyledon was determined for maternal and fetal arterial d-glucose concentrations between 0 and 20 mmol/l.Results: clearance of 3H-3MG or 14C-l-glucose was not affected by maternal or fetal d-glucose concentrations in either circulation.Discussion: based on the arterial glucose concentrations and the reported KM for GLUT1, the transfer of d-glucose and 3H-3MG would be expected to show signs of saturation as d-glucose concentrations increased but this did not occur. One explanation for this is that incomplete mixing of maternal blood and the rate of diffusion across unstirred layers may lower the effective concentration of glucose at the microvillous membrane and subsequently at the basal membrane. Uncertainties about the affinity of GLUT1 for glucose, both outside and inside the cell, may also contribute to the difference between the predicted and observed kinetics.Conclusion: these factors may therefore help explain why the observed and predicted kinetics differ and they emphasise the importance of understanding the function of transport proteins in their physiological context. The development of a computational model of glucose transfer may improve our understanding of how the determinants of placental glucose transfer interact and function as a syste

Evaluation of the relationship between capillary and venous plasma glucose concentrations obtained by the HemoCue Glucose 201+ system during an oral glucose tolerance test

Abstract In 55 women with previous gestational diabetes mellitus, simultaneous capillary and venous plasma glucose concentrations were measured at 0, 30 and 120 min during a 75 g oral glucose tolerance test (OGTT). The aims of the study were to examine the relationship between capillary and venous glucose measurements, and to establish equations for the conversion of capillary and venous glucose concentrations using the HemoCue Glucose 201+ system. Additionally, the correlation between the capillary and venous glucose concentrations with the diagnostic cut-off limits proposed by the World Health Organization (WHO) in 1999 was evaluated. Capillary glucose concentrations were consistently higher than venous glucose concentrations at all time points of the OGTT (p < 0.001), and the correlations between the measurements were statistically highly significant (p < 0.001). The differences between the samples were greatest in the non-fasting state as revealed by the 95% prediction intervals (mmol/L) in Bland-Altman plots; ? 0.54 at 0 min, ? 2.01 at 30 min, and ? 1.35 at 120 min. Equivalence values for capillary plasma glucose concentrations derived from this study tended to be higher than those proposed by the WHO as diagnostic cut-off limits. Stratifying subjects by glucose tolerance status according to the WHO criteria revealed disagreements related to glucose values close to the diagnostic cut-off points. The study findings highlight the uncertainty associated with derived equivalence values. However, capillary plasma glucose measurements could be suitable for diagnostic purposes in epidemiological studies and when translating results on a group basis

Which variables are associated with blood glucose levels outside the target range in surgical critically ill patients? A retrospective observational study

<p>Abstract</p> <p>Background</p> <p>The aim of the present study is to determine the variables affecting blood glucose concentrations outside the target range of 80 and 150 mg/dl in critically ill surgical patients.</p> <p>Methods</p> <p>All critically ill surgical patients admitted to a university ICU, from 01/2007 to 12/2008, were surveyed daily using computer assistance with respect to minimal and maximal daily blood glucose concentrations, application of insulin and demographic/clinical variables. Multiple logistic regression for clustered data with backward elimination was performed to identify variables strongly associated with blood glucose concentrations < 80 mg/dl or ≥ 150 mg/dl in 804 patients with an ICU stay > 72 hours.</p> <p>Results</p> <p>Application of insulin (odds ratio (OR) 2.1, with corresponding 95% confidence interval (CI) 1.7; 2.6), noradrenaline (OR 1.4, 95% CI 1.2 - 1.8) or steroids (1.3, 1.003 - 1.7), and age (per year) (1.02, 1.01 - 1.03) were associated with an increased risk of blood glucose concentrations < 80 mg/dl. In analogy, application of insulin (OR 2.4, 95% CI 2.0 - 2.7), noradrenaline (1.4, 1.2 - 1.6) or steroids (1.4, 1.2 - 1.7), severe sepsis (1.2, 1.1 - 1.4), neurosurgery (OR 1.0) compared to abdominal, vascular and trauma surgery, and age (per year) (1.01, 1.01 - 1.02), were associated with an increased risk of blood glucose concentrations ≥ 150 mg/dl.</p> <p>Conclusions</p> <p>Critically ill surgical patients are at an increased risk for fluctuating blood glucose concentrations ranging < 80 mg/dl or ≥ 150 mg/dl in particular if they are of advanced age and require administration of insulin, noradrenaline, and/or steroids. Patients who underwent neurosurgery and/or presented with severe sepsis/shock are those in particular at risk for blood glucose concentrations ≥ 150 mg/dl.</p

Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease

Trajectories of cardiometabolic risk factors before diagnosis of three subtypes of type 2 diabetes: a post-hoc analysis of the longitudinal Whitehall II cohort study

SummaryBackgroundMost clinicians acknowledge that type 2 diabetes is multifactorial and has heterogeneous characteristics, but neither prevention nor treatment is systematically stratified. To address the heterogeneity of the disease, we examined whether patients diagnosed on the basis of fasting glucose concentrations, those diagnosed on the basis of 2 h concentrations, and those diagnosed on the basis of both criteria differed in terms of pathogenesis or cardiovascular risks.MethodsRetrospectively, we analysed trajectories of cardiometabolic risk factors and 10 year cardiovascular risks in the prospective Whitehall II study cohort by use of multilevel longitudinal modelling. Participants were diagnosed by 75 g oral glucose-tolerance tests. We classified those diagnosed with type 2 diabetes into three subgroups: diagnosed on the basis of fasting glucose concentrations, diagnosed on the basis of 2 h glucose concentrations, and diagnosed on the basis of both concentrations. We also developed a classification tree for identification of individuals who are likely to have high fasting and 2 h glucose concentrations, but for whom only fasting concentrations are available.ResultsMedian follow-up was 14·2 years with 15 826 person-examinations (1991–2009). Of 10 308 individuals, 6843 were included and 6569 remained diabetes free. 274 cases of type 2 diabetes were identified: 55 had high fasting glucose concentrations only, 148 had high 2 h concentrations only, and 71 had high fasting and 2 h concentrations. At diagnosis, participants with high fasting and 2 h glucose concentrations had higher mean body-mass indices (30·9 kg/m2 [SD 5·7]) than did those with high fasting concentrations (28·4 kg/m2 [4·4]; p=0·0009) or 2 h concentrations (27·9 kg/m2 [4·9]; <0·0001). Mean glycated haemoglobin A1c concentrations were also higher in the fasting and 2 h subgroup (7·4% [1·6]) than in the fasting (5·9% [0·5]; <0·0001) or 2 h (5·9% [0·6]; <0·0001) sugroups. Additionally, the fasting and 2 h subgroup had a higher proportion of individuals with moderate or high risk of cardiovascular disease than did the fasting subgroup (p=0·02). A classic pattern of β-cell decompensation before diagnosis was noted only in the fasting and 2 h subgroup. Additionally, glucose concentrations and insulin resistance accelerated more substantially before diagnosis in the fasting and 2 h subgroup than in the fasting subgroup or the 2 h subgroup.InterpretationPatients with type 2 diabetes diagnosed on the basis of increased fasting glucose concentrations or 2 h glucose concentrations, or both, have distinct cardiometabolic risk development before diagnosis.FundingUK Medical Research Council, UK Economic and Social Research Council, British Heart Foundation, UK Health and Safety Executive, UK Department of Health, US National Heart Lung and Blood Institute, US National Institute on Aging, US Agency for Health Care Policy Research, and John D and Catherine T MacArthur Foundation

Effect of Insulin and Fasting Regimen on Blood Glucose Concentrations of Diabetic Dogs During Phacoemulsification

This study aimed to compare four protocols for preanesthetic insulin administration and fasting time with respect to the variation of intraoperative blood glucose (BG) concentrations versus preanesthetic values (baseline). The patient records of dogs undergoing cataract surgery were included. Data on anesthetic protocols, comorbidities, and intraoperative complications (hyper- and hypoglycemia, hypotension, hypothermia, and bradycardia) were analyzed. The insulin/fasting protocols included (A) 12 hr fasting and half insulin dose, (B) 6 hr fasting and half insulin dose, (C) 12 hr fasting and full insulin dose, and (D) 12 hr fasting and no insulin. Forty-eight dogs were included (14 in A, 10 in B, 13 in C, and 11 in D). Protocol D resulted in a significant increase of intraoperative BG concentrations compared with baseline (P = .001), whereas in the remaining groups, the baseline BG did not differ from intraoperative values. There were no statistically significant associations between the treatment group and the occurrence of intraoperative complications or the presence of diagnosed comorbidities. In conclusion, different insulin and fasting regimen protocols may be used for diabetic patients with no apparent benefit or risk from one protocol versus another. The use of insulin before surgery results in lesser increase of BG intraoperatively as compared with preanesthetic values. However, whether this should be interpreted as better perioperative control of glycemia remains debatable