Millions Of Diabetic Patients Research Articles

Synthesis of a highly thermostable insulin by phenylalanine conjugation at B29 Lysine

Globally, millions of diabetic patients require daily life-saving insulin injections. Insulin heat-lability and fibrillation pose significant challenges, especially in parts of the world without ready access to uninterrupted refrigeration. Here, we have synthesized four human insulin analogs by conjugating ε-amine of B29 lysine of insulin with acetic acid, phenylacetic acid, alanine, and phenylalanine residues. Of these, phenylalanine-conjugated insulin, termed FHI, was the most stable under high temperature (65 °C), elevated salt stress (25 mM NaCl), and varying pH levels (ranging from highly acidic pH 1.6 to physiological pH 7.4). It resists fibrillation for a significantly longer duration with sustained biological activity in in vitro, ex vivo, and in vivo and displays prolonged stability over its native counterpart. We further unravel the critical interactions, such as additional aromatic π-π interactions and hydrogen bonding in FHI, that are notably absent in native insulin. These interactions confer enhanced structural stability of FHI and offer a promising solution to the challenges associated with insulin heat sensitivity.

Optimizing the Performance of AI Model for Non-Invasive Continuous Glucose Monitoring: Hyperparameter Tuning and Random Oversampling Approach

Diabetes Mellitus (DM) as a non-communicable disease (NCD) continues to increase every year. Continuous glucose monitoring (CGM) is essential for effective DM management. However, existing disposable glucose monitoring methods still rely on invasive techniques, cause pain, and lack continuous monitoring capabilities. On the other hand, non-invasive techniques are not feasible for CGM due to the biometric data's complexity and the classification system's inadequate performance. This study aims to develop a non-invasive technology to improve the performance of a non-invasive blood glucose classification system using Artificial Intelligence (AI), specifically Convolutional Neural Network (CNN) and an oversampling technique. The oversampling technique could improve data quantity by balancing the amount of data for each class. This study recruited twenty-three participants in the age range of 20 to 22 years comprising seven females and fifteen males. During data recording sessions, blood glucose levels were simultaneously assessed using a gold-standard glucometer and a non-invasive CGM prototype. The proposed CNN model successfully improved the classification accuracy of non-invasive blood glucose monitoring significantly. With the implementation of oversampling for augmenting the data, the accuracy of the proposed model increased to more than 88%. This study concludes that non-invasive approaches combined with AI technology have the potential to provide a convenient and pain-free alternative to traditional monitoring methods, significantly improving diabetes management and enhancing the overall quality of life for those affected by this condition. These findings could revolutionize the field of diabetes management, offering a more comfortable and accurate monitoring solution that could potentially transform the lives of millions of diabetes patients.

Endurance Exercise Training Mitigates Diastolic Dysfunction in Diabetic Mice Independent of Phosphorylation of Ulk1 at S555.

Millions of diabetic patients suffer from cardiovascular complications. One of the earliest signs of diabetic complications in the heart is diastolic dysfunction. Regular exercise is a highly effective preventive/therapeutic intervention against diastolic dysfunction in diabetes, but the underlying mechanism(s) remain poorly understood. Studies have shown that the accumulation of damaged or dysfunctional mitochondria in the myocardium is at the center of this pathology. Here, we employed a mouse model of diabetes to test the hypothesis that endurance exercise training mitigates diastolic dysfunction by promoting cardiac mitophagy (the clearance of mitochondria via autophagy) via S555 phosphorylation of Ulk1. High-fat diet (HFD) feeding and streptozotocin (STZ) injection in mice led to reduced endurance capacity, impaired diastolic function, increased myocardial oxidative stress, and compromised mitochondrial structure and function, which were all ameliorated by 6 weeks of voluntary wheel running. Using CRISPR/Cas9-mediated gene editing, we generated non-phosphorylatable Ulk1 (S555A) mutant mice and showed the requirement of p-Ulk1at S555 for exercise-induced mitophagy in the myocardium. However, diabetic Ulk1 (S555A) mice retained the benefits of exercise intervention. We conclude that endurance exercise training mitigates diabetes-induced diastolic dysfunction independent of Ulk1 phosphorylation at S555.

Wearable filamentary continuous sensor for interstitial glucose detection in diabetes management

The development of novel diabetes monitoring sensors is important for the diabetes management of millions of diabetic patients. This work reports a flexible filamentary continuous glucose monitoring (CGM) sensor. A multilayer CGM sensor has been constructed on titanium filament with low cost and ease of use. The sensor, made of flexible material, offers better adaptability and comfort than traditional rigid filament CGM sensors, allowing continuous monitoring of subcutaneous blood glucose levels to provide patients with treatment strategies. The performance and reliability of the sensor were verified through rat experiments. The trend of the increase and decrease of the detected current was generally consistent with the actual blood glucose, and the detected values were located in regions A and B of the Clarke error grid. The results show that the sensor has the advantages of high sensitivity, high accuracy and fast response speed, which is suitable for monitoring the blood glucose level for a long time and has a broad application prospect in diabetes monitoring, exercise monitoring, health management and clinical application.

A REVIEW OF HERBAL DRUGS AND PROSPECTIVE STUDIES FOR MANAGEMENT OF DIABETES MELLITUS

Diabetes mellitus (DM) is a metabolic disorder, occur when the pancreas does not make sufficient amount of insulin. Hyperglycaemia leads to severe injure especially the nerves and blood vessels (retinopathy, neuropathy, and nephropathy). According to World Health Organization the diabetic people is expected to increase up to 300 million or more by the year 2025. We searched the scientific database using various original research articles, clinical trials, meta analysis, patent reports, validation study, observational study, review articles published in PubMed, Scopus, Science direct and Google by using the keyword. After an initial search, 528 articles were identified, out of which 50 articles had required criteria for the comparative study and meta-analysis of related topics. Herbal plants were extremely venerated source of medicine in Ayurveda and now they have become a growing part of modern, high-tech medicine. It also reveals the information about the most recent innovation in the treatment of Type-I and Type II Diabetes mellitus. These reviews have proven that the herbal drugs were used for the treatment of Type II Diabetes mellitus worldwide. It also reveals that new approaches of nanotechnology were good choice for the management of Diabetes mellitus now a days. Hopefully, these new kind of treatment may help in making the everyday lives of millions of diabetes patients more comfortable.

A Conductive Hydrogel Microneedle-Based Assay Integrating PEDOT:PSS and Ag-Pt Nanoparticles for Real-Time, Enzyme-Less, and Electrochemical Sensing of Glucose.

Continuous glucose meters (CGMs) have tremendously boosted diabetes care by emancipating millions of diabetic patients' need for repeated self-testing by pricking their fingers every few hours. However, CGMs still suffer from major deficiencies regarding accuracy, precision, and stability. This is mainly due to their dependency on an enzymatic detection mechanism. Here a low-cost hydrogel microneedle (HMN)-CGM assay fabricated using swellable dopamine (DA)-hyaluronic acid (HA) hydrogel for glucose interrogation in dermal interstitial fluid (ISF) is introduced. Platinum and silver nanoparticles are synthesized within the 3D porous hydrogel scaffolds for nonenzymatic electrochemical sensing of the glucose. Incorporation of a highly water dispersible conductive polymer, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) enhances the electrical properties of HMN array, making the patch suitable as the working electrode of the sensor. The in vitro and ex vivo characterization of this newly developed HMN patch is fully studied. The performance of the HMN-CGM for real-time measurement of glucose is also shown using a rat model of type 1 diabetes. The device introduces the first HMN-based assay for tracking important disease biomarkers and expect to pave the way for next generation of polymeric-based sensors.

Insulin Analogues with Altered Insulin Receptor Isoform Binding Specificities and Enhanced Aggregation Stabilities.

Insulin is a lifesaver for millions of diabetic patients. There is a need for new insulin analogues with more physiological profiles and analogues that will be thermally more stable than human insulin. Here, we describe the chemical engineering of 48 insulin analogues that were designed to have changed binding specificities toward isoforms A and B of the insulin receptor (IR-A and IR-B). We systematically modified insulin at the C-terminus of the B-chain, at the N-terminus of the A-chain, and at A14 and A18 positions. We discovered an insulin analogue that has Cα-carboxyamidated Glu at B31 and Ala at B29 and that has a more than 3-fold-enhanced binding specificity in favor of the "metabolic" IR-B isoform. The analogue is more resistant to the formation of insulin fibrils at 37 °C and is also more efficient in mice than human insulin. Therefore, [AlaB29,GluB31,amideB31]-insulin may be interesting for further clinical evaluation.

Neonatal Fc receptor-targeted lignin-encapsulated porous silicon nanoparticles for enhanced cellular interactions and insulin permeation across the intestinal epithelium

Oral insulin delivery could change the life of millions of diabetic patients as an effective, safe, easy-to-use, and affordable alternative to insulin injections, known by an inherently thwarted patient compliance. Here, we designed a multistage nanoparticle (NP) system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration. The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix, and surface-functionalized with the Fc fragment of immunoglobulin G, which acts as a targeting ligand for the neonatal Fc receptor (FcRn). The developed NPs presented small size (211 ± 1 nm) and narrow size distribution. The NPs remained intact in stomach and intestinal pH conditions, releasing the drug exclusively at pH 7.4, which mimics blood circulation. This formulation showed to be highly cytocompatible, and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells, which express FcRn, as demonstrated by Western blot. Ultimately, in vitro permeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model, showing apparent permeability coefficients (Papp) of 2.37 × 10−6 cm/s, over the 1.66 × 10−6 cm/s observed for their non-functionalized counterparts. Overall, these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.

(Plenary) Electrochemical/Optical Sensors in Medicine: Meeting Needs for the 21st Century

Over the past 40 years, miniaturized potentiometric and amperometric sensors for ions (K+, Ca++, Na+, Mg++, Cl-, H+), gases (O2 and CO2), and nutrients/metabolites (glucose, lactate, creatinine, urea) have revolutionized the practice of critical care medicine by providing tools to measure an array of these physiologically important species, simultaneously, in small volumes of undiluted whole blood. Indeed, all modern point-of-care whole blood analyzers used in hospitals worldwide now employ electrochemical sensor arrays as either single-use or multi-use devices for near-patient testing, especially in operating rooms, emergency rooms, intensive care units, etc. Some of the same or similar chemistries have also been adapted to create either single-use or continuous monitoring optical sensors (fluorescence, etc.). Further, nearly all blood glucometers as well as newer implantable subcutaneous glucose sensors now use electrochemical measurement principles to provide accurate glucose concentrations for millions of diabetic patients each and every day. A brief overview of these existing electrochemical/optical sensor technologies that have already had such a great impact in medicine will be provided during the introductory portion of this lecture.At the same time, there remain a number of unmet needs in medicine where electrochemical/optical chemical sensing devices could still play important analytical roles. Therefore, in the major portion of this presentation, the following research projects ongoing in our laboratories at the University of Michigan will be highlighted: 1) recent efforts to utilize electrochemical sensors for measurement of polyionic drugs and associated contaminants (including the anticoagulant heparin, low-molecular weight heparin, and inflammatory over-sulfated chondroitin sulfate (OSCS) contaminants in biomedical heparin preparations);1-2 2) research aimed at utilizing the same chemistry employed to make ion and polyion selective electrochemical sensors to create optical sensing films as well as optical sensing microfluidic devices that are able to quantitate species in volumes of << 1 µL;3 3) research related to the development of implantable electrochemical sensors for ions, gases, glucose, lactate, etc. that emit low levels of nitric oxide (NO) (a potent anti-platelet and antimicrobial agent) and that can potentially be used to continuously monitor critical care species intravenously in ICU patients with improved accuracy (see Fig. 1);4 and 4) efforts to use improved electrochemical/amperometric gas phase sensors for detecting nitric oxide (NO) in exhaled nasal/oral breath and also the use of NO and nitrogen dioxide (NO2) sensors to monitor and feedback control the levels of therapeutic gas phase NO being generated by novel photochemical and electrochemical gas phase generators.5-6 These gas phase NO generators can potentially replace use of very high cost compressed gas cylinders containing NO to provide controlled levels of NO gas on-demand for inhalation therapy of patients with pulmonary hypertension (including infants) and for use in the sweep gas of oxygenators to prevent clotting and Systemic Inflammatory Response Syndrome (SIRS) in patients undergoing open heart surgery.Literature Cited: L. Wang, S. Buchanan and M. E. Meyerhoff, “Rapid Detection of High Charge Density Polyanion Contaminants in Biomedical Heparin Preparations Using Potentiometric Polyanion Sensors,” Anal. Chem., 80, 9845-9847 (2008).K. Gemene and M. E. Meyerhoff, “Reversible Detection of Heparin and Other Polyanions by Pulsed Chronopotentiometric Polymer Membrane Electrode,” Anal. Chem., 82, 1612-1615 (2010).X. Wang, M. Sun, S. A. Ferguson, J. D. Hoff, Y. Qin, R. C. Bailey, and M. E. Meyerhoff, “Ionophore-Based Biphasic Chemical Sensing in Droplet Microfluidics,” Angew. Chem. Int. Ed., 58, 1-6 (2019).M. Frost and M. E. Meyerhoff, “Real-Time Monitoring of Critical Care Analytes in the Bloodstream with Chemical Sensors: Progress and Challenges,” Ann. Rev. Anal. Chem., 8, 171-192 (2015).J. Zajda, N. J. Schmidt, Z. Zheng, X. Wang and M. E. Meyerhoff, “Evaluation of Amperometric Platinized-Nafion-Based Gas Phase Sensor for Determining Nitric Oxide (NO) Levels in Exhaled Human Nasal Breath,” Electroanalysis 30, 1602-1607 (2018).Y. Qin, J. Zajda, H. Ren, J. Toomasian, T. Major, A. Rojas-Pena, B. Carr, T. Johnson , J. Haft, R. H. Bartlett, A. Hunt, N. Lehnert, and M. E. Meyerhoff, “Low Cost Portable Gas Phase Nitric Oxide (NO) Generator Based on Electrochemical Reduction of Nitrite for Potential Applications in Inhaled NO Therapy and Within the Sweep Gas/Cardiotomy Suction Air During Cardiopulmonary Bypass Surgery,” Mol. Pharmaceutics, 14, 3762-3771 (2017). Figure 1. Comparison of average error of PO2 levels using amperometric IV-oxygen sensing catheters with (n=4) and without (n=4) NO release chemistry placed into the arteries of pigs for 20 h. % deviation calculated vs. measurements made on discrete whole blood samples (heparinized syringe) on Radiometer blood-gas/electrolyte analyzer. Figure 1

Colorimetric Nanoplasmonics to Spot Hyperglycemia From Saliva.

Early diagnostics and point-of-care (POC) devices can save people’s lives or drastically improve their quality. In particular, millions of diabetic patients worldwide benefit from POC devices for frequent self-monitoring of blood glucose. Yet, this still involves invasive sampling processes, which are quite discomforting for frequent measurements, or implantable devices dedicated to selected chronic patients, thus precluding large-scale monitoring of the globally increasing diabetic disorders. Here, we report a non-invasive colorimetric sensing platform to identify hyperglycemia from saliva. We designed plasmonic multibranched gold nanostructures, able to rapidly change their shape and color (naked-eye detection) in the presence of hyperglycemic conditions. This “reshaping approach” provides a fast visual response and high sensitivity, overcoming common detection issues related to signal (color intensity) losses and bio-matrix interferences. Notably, optimal performances of the assay were achieved in real biological samples, where the biomolecular environment was found to play a key role. Finally, we developed a dipstick prototype as a rapid home-testing kit.

(Plenary) Electrochemical/Optical Sensors in Medicine: Meeting Needs for the 21st Century

Over the past 40 years, miniaturized potentiometric and amperometric sensors for ions (K+, Ca++, Na+, Mg++, Cl-, H+), gases (O2 and CO2), and nutrients/metabolites (glucose, lactate, creatinine, urea) have revolutionized the practice of critical care medicine by providing tools to measure an array of these physiologically important species, simultaneously, in small volumes of undiluted whole blood. Indeed, all modern point-of-care whole blood analyzers used in hospitals worldwide now employ electrochemical sensor arrays as either single-use or multi-use devices for near-patient testing, especially in operating rooms, emergency rooms, intensive care units, etc. Some of the same or similar chemistries have also been adapted to create either single-use or continuous monitoring optical sensors (fluorescence, etc.). Further, nearly all blood glucometers as well as newer implantable subcutaneous glucose sensors now use electrochemical measurement principles to provide accurate glucose concentrations for millions of diabetic patients each and every day. A brief overview of these existing electrochemical/optical sensor technologies that have already had such a great impact in medicine will be provided during the introductory portion of this lecture.At the same time, there remain a number of unmet needs in medicine where electrochemical/optical chemical sensing devices could still play important analytical roles. Therefore, in the major portion of this presentation, the following research projects ongoing in our laboratories at the University of Michigan will be highlighted: 1) recent efforts to utilize electrochemical sensors for measurement of polyionic drugs and associated contaminants (including the anticoagulant heparin, low-molecular weight heparin, and inflammatory over-sulfated chondroitin sulfate (OSCS) contaminants in biomedical heparin preparations);1-2 2) research aimed at utilizing the same chemistry employed to make ion and polyion selective electrochemical sensors to create optical sensing films as well as optical sensing microfluidic devices that are able to quantitate species in volumes of << 1 µL;3 3) research related to the development of implantable electrochemical sensors for ions, gases, glucose, lactate, etc. that emit low levels of nitric oxide (NO) (a potent anti-platelet and antimicrobial agent) and that can potentially be used to continuously monitor critical care species intravenously in ICU patients with improved accuracy (see Fig. 1);4 and 4) efforts to use improved electrochemical/amperometric gas phase sensors for detecting nitric oxide (NO) in exhaled nasal/oral breath and also the use of NO and nitrogen dioxide (NO2) sensors to monitor and feedback control the levels of therapeutic gas phase NO being generated by novel photochemical and electrochemical gas phase generators.5-6 These gas phase NO generators can potentially replace use of very high cost compressed gas cylinders containing NO to provide controlled levels of NO gas on-demand for inhalation therapy of patients with pulmonary hypertension (including infants) and for use in the sweep gas of oxygenators to prevent clotting and Systemic Inflammatory Response Syndrome (SIRS) in patients undergoing open heart surgery.Literature Cited: 1. L. Wang, S. Buchanan and M. E. Meyerhoff, “Rapid Detection of High Charge Density Polyanion Contaminants in Biomedical Heparin Preparations Using Potentiometric Polyanion Sensors,” Anal. Chem., 80, 9845-9847 (2008).2. K. Gemene and M. E. Meyerhoff, “Reversible Detection of Heparin and Other Polyanions by Pulsed Chronopotentiometric Polymer Membrane Electrode,” Anal. Chem., 82, 1612-1615 (2010).3. X. Wang, M. Sun, S. A. Ferguson, J. D. Hoff, Y. Qin, R. C. Bailey, and M. E. Meyerhoff, “Ionophore-Based Biphasic Chemical Sensing in Droplet Microfluidics,” Angew. Chem. Int. Ed., 58, 1-6 (2019).4. M. Frost and M. E. Meyerhoff, “Real-Time Monitoring of Critical Care Analytes in the Bloodstream with Chemical Sensors: Progress and Challenges,” Ann. Rev. Anal. Chem., 8, 171-192 (2015).5. J. Zajda, N. J. Schmidt, Z. Zheng, X. Wang and M. E. Meyerhoff, “Evaluation of Amperometric Platinized-Nafion-Based Gas Phase Sensor for Determining Nitric Oxide (NO) Levels in Exhaled Human Nasal Breath,” Electroanalysis 30, 1602-1607 (2018).6. Y. Qin, J. Zajda, H. Ren, J. Toomasian, T. Major, A. Rojas-Pena, B. Carr, T. Johnson , J. Haft, R. H. Bartlett, A. Hunt, N. Lehnert, and M. E. Meyerhoff, “Low Cost Portable Gas Phase Nitric Oxide (NO) Generator Based on Electrochemical Reduction of Nitrite for Potential Applications in Inhaled NO Therapy and Within the Sweep Gas/Cardiotomy Suction Air During Cardiopulmonary Bypass Surgery,” Mol. Pharmaceutics, 14, 3762-3771 (2017). Figure 1

Electrospun CuO-Nanoparticles-Modified Polycaprolactone @Polypyrrole Fibers: An Application to Sensing Glucose in Saliva.

A non-invasive method for detecting glucose is pursued by millions of diabetic patients to improve their personal management of blood glucose. In this work, a novel CuO nanoparticles (NPs) decorated polycaprolactone@polypyrrole fibers modified indium-tin oxide (denoted as CuO/PCL@PPy/ITO) electrode has been fabricated by electrospinning combined with the electrodeposition method for non-enzymatic detection of glucose in saliva fluid. The electrospun composite fibers exhibit high sensitivity for the glucose detection. The synergistic effect between CuO and PPy together with the unique three-dimensional net structure contributes the reliable selectivity, good test repeatability, large-scale production reproducibility in massive way, the reasonable stability and a high catalytic surface area to the sensor. Quantitative detection of glucose is determined in the linear range from 2 μM to 6 mM and the lowest detection limit is 0.8 μM. The CuO/PCL@PPy/ITO electrode shows potential for the non-invasive detection of salivary glucose.

Exercising Tactically for Taming Postmeal Glucose Surges.

This review seeks to synthesize data on the timing, intensity, and duration of exercise found scattered over some 39 studies spanning 3+ decades into optimal exercise conditions for controlling postmeal glucose surges. The results show that a light aerobic exercise for 60 min or moderate activity for 20–30 min starting 30 min after meal can efficiently blunt the glucose surge, with minimal risk of hypoglycemia. Exercising at other times could lead to glucose elevation caused by counterregulation. Adding a short bout of resistance exercise of moderate intensity (60%–80% VO2max) to the aerobic activity, 2 or 3 times a week as recommended by the current guidelines, may also help with the lowering of glucose surges. On the other hand, high-intensity exercise (>80% VO2max) causes wide glucose fluctuations and its feasibility and efficacy for glucose regulation remain to be ascertained. Promoting the kind of physical activity that best counters postmeal hyperglycemia is crucial because hundreds of millions of diabetes patients living in developing countries and in the pockets of poverty in the West must do without medicines, supplies, and special diets. Physical activity is the one tool they may readily utilize to tame postmeal glucose surges. Exercising in this manner does not violate any of the current guidelines, which encourage exercise any time.

Nanotechnology as an innovative approach for accelerating wound healing in diabetes

Poor wound healing is a major source of morbidity and mortality for millions of diabetic patients. Diabetic wounds can lead to severe infections, prolonged hospitalizations, amputations and an overall markedly decreased quality of life. Diabetic wounds fail to heal secondary to several perturbations in the wound healing process. Here, we present a review of the direct barriers to diabetic wound healing as well as innovative therapeutic options to improve outcomes in diabetic wounds.

A “plasmonic cuvette”: dye chemistry coupled to plasmonic interferometry for glucose sensing

AbstractA non-invasive method for the detection of glucose is sought by millions of diabetic patients to improve personal management of blood glucose over a lifetime. In this work, the synergistic advantage of combining plasmonic interferometry with an enzyme-driven dye assay yields an optical sensor capable of detecting glucose in saliva with high sensitivity and selectivity. The sensor, coined a “plasmonic cuvette,” is built around a nano-scale groove-slit-groove (GSG) plasmonic interferometer coupled to an Amplex–red/Glucose–oxidase/Glucose (AR/GOx/Glucose) assay. The proposed device is highly sensitive, with a measured intensity change of 1.7×105%/m (i.e., one order of magnitude more sensitive than without assay) and highly specific for glucose sensing in picoliter volumes, across the physiological range of glucose concentrations found in human saliva (20–240 μm). Real-time glucose monitoring in saliva is achieved by performing a detailed study of the underlying enzyme-driven reactions to determine and tune the effective rate constants in order to reduce the overall assay reaction time to ∼2 min. The results reported suggest that by opportunely choosing the appropriate dye chemistry, a plasmonic cuvette can be turned into a general, real-time sensing scheme for detection of any molecular target, with high sensitivity and selectivity, within extremely low volumes of biological fluid (down to femtoliters). Hereby, we present the results on glucose detection in artificial saliva as a notable and clinically relevant case study.

Betatrophin Fuels β Cell Proliferation: First Step toward Regenerative Therapy?

Millions of diabetic patients are waiting for better treatment options, ideally by replenishing the lost or dysfunctional insulin-producing β cell mass. Yi etal. (2013) now identify Betatrophin, a hormone that specifically increases β cell proliferation with promising therapeutic potential.

Insulin signalling to the kidney in health and disease

Ninety-one years ago insulin was discovered, which was one of the most important medical discoveries in the past century, transforming the lives of millions of diabetic patients. Initially insulin was considered only important for rapid control of blood glucose by its action on a restricted number of tissues; however, it has now become clear that this hormone controls an array of cellular processes in many different tissues. The present review will focus on the role of insulin in the kidney in health and disease.

Insulin Analogs and Cancer

Today, insulin analogs are used in millions of diabetic patients. Insulin analogs have been developed to achieve more physiological insulin replacement in terms of time-course of the effect. Modifications in the amino acid sequence of the insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs in respect to human insulin. However, these changes can also modify the molecular and biological effects of the analogs. The rapid-acting insulin analogs, lispro, aspart, and glulisine, have a rapid onset and shorter duration of action. The long-acting insulin analogs glargine and detemir have a protracted duration of action and a relatively smooth serum concentration profile. Insulin and its analogs may function as growth factors and therefore have a theoretical potential to promote tumor proliferation. A major question is whether analogs have an increased mitogenic activity in respect to insulin. These ligands can promote cell proliferation through many mechanisms like the prolonged stimulation of the insulin receptor, stimulation of the IGF-1 receptor (IGF-1R), prevalent activation of the extracellular-signaling-regulated kinase (ERK) rather than the protein kinase B (PKB/AKT) intracellular post-receptor pathways. Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar to those of insulin. In contrast, long-acting analogs behave differently. Although not all data are homogeneous, both glargine and detemir have been found to have a decreased binding to receptors for insulin but an increased binding to IGF-1R, a prevalent activation of the ERK pathway, and an increased mitogenic effect in respect to insulin. Recent retrospective epidemiological clinical studies have suggested that treatment with long-acting analogs (specifically glargine) may increase the relative risk for cancer. Results are controversial and methodologically weak. Therefore prospective clinical studies are needed to evaluate the possible tumor growth-promoting effects of these insulin analogs.

Infrared spectroscopic analysis of human interstitial fluid in vitro and in vivo using FT-IR spectroscopy and pulsed quantum cascade lasers (QCL): Establishing a new approach to non invasive glucose measurement

Interstitial fluid, i.e. the liquid present in the outermost layer of living cells of the skin between the Stratum corneum and the Stratum spinosum, was analyzed by Fourier transform infrared spectroscopy and by infrared spectroscopy using pulsed quantum cascade infrared lasers with photoacoustic detection. IR spectra of simulated interstitial fluid samples and of real samples from volunteers in the 850–1800 cm −1 range revealed that the major components of interstitial fluid are albumin and glucose within the physiological range, with only traces of sodium lactate if at all. The IR absorbance of glucose in interstitial fluid in vivo was probed in healthy volunteers using a setup with quantum cascade lasers and photoacoustic detection previously described [11]. A variation of blood glucose between approx. 80 mg/dl and 250 mg/dl in the volunteers was obtained using the standard oral glucose tolerance test (OGT). At two IR wavelengths, 1054 cm −1 and 1084 cm −1, a reasonable correlation between the photoacoustic signal from the skin and the blood glucose value as determined by conventional glucose test sticks using blood from the finger tip was obtained. The infrared photoacoustic glucose signal (PAGS) may serve as the key for a non-invasive glucose measurement, since the glucose content in interstitial fluid closely follows blood glucose in the time course and in the level (a delay of some minutes and a level of approx. 80–90% of the glucose level in blood). Interstitial fluid is present in skin layers at a depth of only 15–50 μm and is thus within the reach of mid-IR energy in an absorbance measurement. A non-invasive glucose measurement for diabetes patients based on mid-infrared quantum cascade lasers and photoacoustic detection could replace the conventional measurement using enzymatic test stripes and a drop of blood from the finger tip, thus reducing pain and being a cost-efficient alternative for millions of diabetes patients.

Noninvasive Diagnostic Devices for Diabetes through Measuring Tear Glucose

This article reviews the development of a noninvasive diagnostic for diabetes by detecting ocular glucose. Early diagnosis and daily management are very important to diabetes patients to ensure a healthy life. Commercial blood glucose sensors have been used since the 1970s. Millions of diabetes patients have to prick their finger for a drop of blood 4-5 times a day to check blood glucose levels--almost 1800 times annually. There is a strong need to have a noninvasive device to help patients to manage the disease easily and painlessly. Instead of detecting the glucose in blood, monitoring the glucose level in other body fluids may provide a feasible approach for noninvasive diagnosis and diabetes control. Tear glucose has been studied for several decades. This article reviews studies on ocular glucose and its monitoring methods. Attempts to continuously monitor the concentration of tear glucose by using contact lens-based sensors are discussed as well as our current development of a nanostructured lens-based sensor for diabetes. This disposable biosensor for the detection of tear glucose may provide an alternative method to help patients manage the disease conveniently.