Blood Glucose Concentration In Type Research Articles

Innovative approach for improved sustained delivery of metformin hydrochloride for its anti-hyperglycemic activity

Metformin hydrochloride, an antidiabetic agent, is useful in reducing the blood glucose concentration in Type II diabetes. It is also finding its use as a repurposed drug. The formulations consisted of micro drug delivery systems prepared by emulsification method and were evaluated in-vitro and in-vivo. Process variables like amount of polymer, speed of agitation and stirring, presence or absence of surfactant and cross linker offered a versatile approach towards obtaining the formulation though affected physicochemical properties of formulations. Discrete, spherical, and free-flowing microspheres, in the size range and granularity of 250 to 700µ were used to control the drug release rate. Drug release was diffusion controlled as evident from the Higuchi kinetics. The physical characteristics of the formulations were reproducible. Healthy and alloxan induced hyperglycaemic male albino mice were used for in-vivo experimentation by evaluating plasma glucose level reduction and % reduction in the blood glucose level after administration of pure drug and formulations. The results indicate significant sustained fall in the blood glucose level for about 10 hrs following formulation administration as compared to the pure drug.

Sliding-mode-based controllers for automation of blood glucose concentration for type 1 diabetes.

Destruction of β‐cells in pancreas causes deficiency in insulin production that leads to diabetes in the human body. To cope with this problem, insulin is either taken orally during the day or injected into the patient's body using artificial pancreas (AP) during sleeping hours. Some mathematical models indicate that AP uses control algorithms to regulate blood glucose concentration (BGC). The extended Bergman minimal model (EBMM) incorporates, as a state variable, the disturbance in insulin level during medication due to either meal intake or burning sugar by engaging in physical exercise. In this research work, EBMM and proposed finite time robust controllers are used, including the sliding mode controller (SMC), backstepping SMC (BSMC) and supertwisting SMC (second‐order SMC or SOSMC) for automatic stabilisation of BGC in type 1 diabetic patients. The proposed SOSMC diminishes the chattering phenomenon which appears in the conventional SMC. The proposed BSMC is a recursive technique which becomes robust by the addition of the SMC. Lyapunov theory has been used to prove the asymptotic stability of the proposed controllers. Simulations have been carried out in MATLAB/Simulink for the comparative study of the proposed controllers under varying data of six different type 1 diabetic patients available in the literature.

Localized Controlled Release of Bilirubin from β-Cyclodextrin-Conjugated ε-Polylysine To Attenuate Oxidative Stress and Inflammation in Transplanted Islets.

Islet transplantation has been considered the most promising therapeutic option with the potential to restore the physiological regulation of blood glucose concentrations in type 1 diabetes treatment. However, islets suffer from oxidative stress and nonspecific inflammation in the early stage of transplantation, which attributed to the leading cause of islet graft failure. Our previous study reported that bilirubin exerted antioxidative and anti-inflammatory effects on hypothermic preserved islets, which inspire us to utilize bilirubin to address the survival issue of grafted islets. However, the application of bilirubin for islet transplantation is limited by its poor solubility and fast clearance. In this study, we designed a supramolecular carrier (PLCD) that could improve the solubility of bilirubin and slowly release bilirubin to protect islets after cotransplantation. PLCD was synthesized by conjugating activated β-cyclodextrin (β-CD) to the side chain of ε-polylysine (PLL) and acted as a carrier to load bilirubin via host-guest interactions. The constructed bilirubin supramolecular system (PLCD-BR) significantly improved the solubility and prolonged the action time of bilirubin. In vitro results confirmed that PLCD-BR coculture substantially enhanced the resistance of islets to excessive oxidative stress and proinflammatory stimulation and maximumly maintained the islet function. In vivo, PLCD could prolong drug duration at the transplant site, and the localized released bilirubin could protect the islets from oxidative stress and suppress the production of inflammatory cytokines. Crucially, islet transplantation with PLCD-BR significantly extended the stable blood glucose time of diabetic mice and produced a faster glucose clearance compared to those cotransplanted with free bilirubin. Additionally, immunohistochemical analysis showed that PLCD-BR had superior antioxidative and anti-inflammatory abilities and beneficial effects on angiogenesis. These findings demonstrate that the PLCD-BR has great potentials to support successful islet transplantation.

Potential effect of opium addiction on lipid profile and blood glucose concentration in type 2 diabetic patients in Iran

ABSTRACTBackground: Diabetes is one of the most common chronic diseases in the world. People believe that opium improves blood glucose and lipid profiles in these patients and controversial studies show the effect of consumption of opium in controlling these indices. Accordingly, this study aimed to compare the serum levels of blood indices such as fasting blood glucose (FBS), Hemoglobin A1c (HbA1c) and lipid profile in opium users and non-users in type ΙΙ diabetic patients.Methods: In this cross-sectional study, among type II diabetic patients referred to the Diabetes Clinic of Birjand 45 opium users and 135 non-users were selected and entered the study by the convenience sampling method.Results: The results of this study showed that the mean serum levels of FBS, HbA1c, and serum lipid profiles were not significantly different between the two groups of opium users and non-users, but the levels of triglyceride (TG) were significantly 0.18 unit higher in the opium users, compared to non-opium users.Conclusion: According to the results, the use of opium does not affect the indices of blood glucose, HbA1c and serum lipid profiles except triglyceride in diabetic patients. The general belief that opioid use reduces biochemical indices does not seem to be correct.Abbreviations: FBS: fasting blood sugar; HbA1c: Hemoglobin A1c; LDL: low-density lipoprotein; HDL: High-density lipoproteins; HDL-C: High-density lipoproteins-cholesterol; BMI: Body mass index; IQR: Inter quartile range; TG: triglyceride; TC: total cholesterol; NS: non-significant; S: significant; ATN: Acute tubular necrosis

Data-Driven Disturbance Estimation and Control With Application to Blood Glucose Regulation

A data-driven control approach for nonlinear systems is proposed, called data-driven estimation and control (D2EC), which combines a disturbance estimator and a nonlinear control algorithm. The estimator provides a signal representing the unknown disturbances affecting the plant to control. This signal is used by the control algorithm to improve its performance. A real-data study is presented, concerned with the regulation of blood glucose concentration in type 1 diabetic patients. Preliminary tests of the D2EC approach are also carried out using a diabetic patient simulator, obtained from a revised version of the well-known University of Virginia/Padova model. Both the real-data and the simulator-based studies indicate that the proposed approach has the potential to become an effective tool in the context of diabetes treatment and, more in general, in the biomedical field, where accurate first-principle models can seldom be found and relevant disturbances are present.

Association of morning fasting blood glucose variability with insulin antibodies and clinical factors in type 1 diabetes.

The fasting blood glucose concentration in type 1 diabetes may vary without being much affected by diet and exercise. This study aimed to identify association of morning fasting blood glucose concentration variability with insulin antibodies and clinical factors. The subjects in this study were 54 patients with type 1 diabetes who had high variation of fasting blood glucose. The insulin antibody level was measured, and correlations of glycemic variability with antibody levels, binding rates, and other clinical factors were investigated. The standard deviation (SD) of the 30-day morning self-monitored fasting blood glucose concentration (FBG SD) was evaluated as an index of glycemic variability. The mean glucose level was 159.8±42.1 mg/dL and the FBG SD was 47.5±22.0 mg/dL. Glycemic variability (FBG SD) was positively correlated with insulin antibody level, but not with insulin antibody binding rate, and had a negative correlation with C-peptide immunoreactivity/plasma glucose (CPR/PG) and positive correlations with diabetes duration, basal insulin dose and bolus insulin dose. Glycemic variability was not correlated with BMI, HbA1c or age. In multiple regression analysis of glycemic variability, CPR/PG was the only significant related factor. The results showed that glycemic variability was mainly influenced by endogenous insulin secretion capacity and was high in patients with high insulin antibody levels. In some patients with a high insulin antibody titer, the antibody may have an effect on the variability of the fasting glucose concentration in type 1 diabetes.

Regulation of Blood Glucose Concentration in Type 1 Diabetics Using Single Order Sliding Mode Control Combined with Fuzzy On-line Tunable Gain, a Simulation Study.

Diabetes is considered as a global affecting disease with an increasing contribution to both mortality rate and cost damage in the society. Therefore, tight control of blood glucose levels has gained significant attention over the decades. This paper proposes a method for blood glucose level regulation in type 1 diabetics. The control strategy is based on combining the fuzzy logic theory and single order sliding mode control (SOSMC) to improve the properties of sliding mode control method and to alleviate its drawbacks. The aim of the proposed controller that is called SOSMC combined with fuzzy on-line tunable gain is to tune the gain of the controller adaptively. This merit causes a less amount of control effort, which is the rate of insulin delivered to the patient body. As a result, this method can decline the risk of hypoglycemia, a lethal phenomenon in regulating blood glucose level in diabetics caused by a low blood glucose level. Moreover, it attenuates the chattering observed in SOSMC significantly. It is worth noting that in this approach, a mathematical model called minimal model is applied instead of the intravenously infused insulin-blood glucose dynamics. The simulation results demonstrate a good performance of the proposed controller in meal disturbance rejection and robustness against parameter changes. In addition, this method is compared to fuzzy high-order sliding mode control (FHOSMC) and the superiority of the new method compared to FHOSMC is shown in the results.

A nonlinear blind identification approach to modeling of diabetic patients

Modeling, simulation and control have become effective tools for the treatment of type 1 diabetic patients in the last decades. The availability of reliable models able to predict and/or simulate the behavior of diabetic patients is thus fundamental in this context. Several models, based on first principles or black-box approaches, have been proposed to fulfill this need. However, a common problem to these approaches is that they are not able to recover or to systematically account for the various unmeasured signals which affect a diabetic patient (e.g. food, physical activity, emotions, etc.). In this paper, we propose a blind identification approach, which allows us to derive accurate models of type 1 diabetes patients and to efficiently recover the unmeasured input signals. A simulated example, regarding identification of the blood glucose concentration in type 1 diabetes patients, is presented to demonstrate the effectiveness of the proposed approach.

Breath acetone concentration decreases with blood glucose concentration in type I diabetes mellitus patients during hypoglycaemic clamps

Conventional wisdom is that breath acetone may be markedly elevated in type 1 diabetes, but that this only occurs during poor blood glucose control and/or intercurrent illness. In contrast, little is known about breath acetone at more representative everyday blood glucose levels in diabetes. We used selected ion flow tube mass spectrometry to monitor the breath of eight patients with type 1 diabetes mellitus during ‘insulin clamp’ studies in which insulin and glucose were infused into patients to lower blood glucose levels in steps from normal values into the low glucose (hypoglycaemic) range. The concentration of acetone in breath and the blood sugar concentration of the patients were monitored at each blood glucose concentration. The blood glucose level at the start of the study was typically about 6 mM L−1, whereas the breath acetone concentration at this blood glucose level was unexpectedly variable, ranging from 1 part-per-million to 21 ppm, in contrast to what was previously believed, i.e. that type 1 diabetes mellitus is characterized by high acetone levels. In all eight patients, the breath acetone declined linearly with blood glucose concentration.

Effects of pioglitazone and rosiglitazone combined with metformin on body weight in people with diabetes

Currently, pioglitazone and rosiglitazone are the thiazolidinediones available for clinical use. In the literature, there are different studies concerning the efficacy, safety and tolerability of thiazolidinediones as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin alone. Metformin and thiazolidinediones are both antihyperglycaemic drugs, both lower blood glucose concentrations in type 2 diabetes without causing overt hypoglycaemia and both require the presence of insulin to generate their therapeutic effects, but act without stimulating insulin secretion. Some authors reported that the improved glycaemic control obtained with thiazolidinediones is associated with an increase in body weight with an estimated 2-3 kg weight gain for every 1% decrease in HbA(1c) which could negate some of the benefits of the improved metabolic control. Some other authors, instead, reported that thiazolidinediones give a better improvement in the glycaemic control compared with metformin alone without giving weight gain. The emerging discrepancies from these studies could be because of the study design, the patient selection, the degree of glycaemic control and/or the methods to measure body weight. We have undertaken a thorough literature search on Medline and Embase to evaluate the effects of thiazolidinediones plus metformin combination in people with diabetes on the body weight.

Simulation Study on Type I Diabetic Patient

Maintaining glucose concentration in normoglycemic range in Type I diabetic patients is challenging. In this study H∞ control is applied for insulin delivery to prevent hyperglycemic levels in a type I diabetic patient. From a control theory point of view, the blood glucose regulation problem is reformulated as a tracking one. A glucose tolerance curve (GTC) validated from several patients is used as a reference model. Intra-and inter-patient variability poses a challenging task to control blood glucose concentration in diabetic patients. A data based robust controller is developed to control blood glucose concentration in type I diabetic patients in the presence of meal disturbances under patient-model mismatch. Simulation studies are performed on the diabetic patient model under feedback control which revealed that the proposed control strategy is able to control blood glucose concentration well within the acceptable limits and also compensate for slow parametric drifts.

Simulation Study on Closed Loop Control Algorithm of Type 1 Diabetes Mellitus Patients

It is challenging to maintain normoglycemic range of glucose concentration in type I diabetic patients. In this study H∞ control is applied for insulin delivery to prevent the hyperglycemic levels in a type I diabetic patient. From a control theory point of view, the blood glucose regulation problem is reformulated as a tracking one. A glucose tolerance curve (GTC) validated from several patients is used as reference model. Intra- and inter-patient variability poses a challenging task to control blood glucose concentration in diabetic patients. We develop a data based robust controller to control blood glucose concentration in type I diabetic (TIDM) patients in the presence of meal disturbances under patient—model mismatch. Simulation studies are performed on the diabetic patient model under feedback control. It is seen that the proposed control strategy is able to control blood glucose concentration well within the acceptable limits and also compensate for slow parametric drifts.

Expression of taste molecules in the upper gastrointestinal tract in humans with and without type 2 diabetes

Objective: Nutrient feedback from the small intestine modulates upper gastrointestinal function and energy intake; however, the molecular mechanism of nutrient detection is unknown. In the tongue, sugars are detected via...

Amelioration of glucose tolerance by hepatic inhibition of nuclear factor κB in db/db mice

Recent studies have identified the involvement of inhibitor IkappaB kinase (IKK) in the pathogenesis of insulin resistance. To investigate the mechanism involved, we examined the role of nuclear factor kappaB (NF-kappaB), the distal target of IKK, in hepatic glucose metabolism. To inhibit NF-kappaB activity, db/db mice were infected with adenovirus expressing the IkappaBalpha super-repressor. The IkappaBalpha super-repressor adenovirus infection caused a moderate reduction of NF-kappaB activity in liver. The treatment was associated with improved glucose tolerance, reduction in the serum insulin level, and increased hepatic triacylglycerol and glycogen contents, but had no effect on insulin-stimulated phosphorylation of Akt. On the other hand, quantification of mRNA in the liver revealed marked reduction of expression of gluconeogenic genes, such as those encoding phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, concurrent with reduced expression of gene encoding peroxisome proliferator-activated receptor gamma coactivator-1alpha (PPARGC1A, also known as PGC-1alpha). Furthermore, the production of super-repressor IkappaBalpha suppressed the increase in blood glucose level after pyruvate injection. Our results indicate that moderate inhibition of NF-kappaB improved glucose tolerance through decreased gluconeogenesis associated with reduced PGC-1alpha gene expression in db/db mice, and suggest that inhibition of NF-kappaB activity in liver is a potentially suitable strategy for the normalisation of blood glucose concentration in type 2 diabetes.

Effect of Carbohydrate Ingestion on the Glycemic Response of Type 1 Diabetic Adolescents During Exercise

Ingestion of a drink containing sufficient carbohydrates can result in avoidance of exercise-induced hypoglycemia in type 1 diabetic individuals. In a previous study (1), we analyzed the effect of ingesting a drink with 6% carbohydrate (0.636 g/kg) on blood glucose concentration in type 1 diabetic adolescents during 60 min of moderate exercise and after 30 min of recovery. At the end of the trial, blood glucose concentration was reduced by 21 mg/dl. Drink concentrations of >6% carbohydrate may help to prevent blood glucose reduction during exercise in type 1 diabetic subjects. However, the increased osmolality of high-carbohydrate drinks may cause gastrointestinal distress (2). This study aimed to determine whether carbohydrate solutions (8 and 10%) could prevent exercise blood glucose drops and to examine the gastrointestinal symptoms in type 1 diabetic adolescents. Sixteen subjects (10 males and 6 females, age 16.1 ± 0.6 years, weight 62.8 ± 9.8 kg, height 168.3 ± 13.6 cm) volunteered to participate in the study and provided written informed consent. The mean duration of the condition was 7.3 ± 0.01 years, HbA1c was 6.8 ± 3.3%, and there were no chronic complications. Subjects were taking intermediate-acting or ultralong-acting insulin. The ethical committee of Hospital de Clinicas de Porto Alegre approved the study. Both drinks were prepared by adding glucose and fructose to a solution with 4% sucrose and 2% …

Glycogen phosphorylase as a molecular target for type 2 diabetes therapy.

The regulation of the hepatic glucose output through glycogenolysis is an important target for type 2 diabetes therapy. Glycogenolysis is catalyzed in liver, muscle and brain by tissue specific isoforms of glycogen phosphorylase (GP). Because of its central role in glycogen metabolism, GP has been exploited as a model for structure-assisted design of potent inhibitors, which may be relevant to the control of blood glucose concentrations in type 2 diabetes. Several regulatory binding sites have been identified in GP, such as the catalytic, the allosteric, and the inhibitor binding sites. Protein crystallography has contributed significant structural information on the specificity and interactions that distinguish the binding sites, and also revealed a new unexpected binding site (new allosteric site). In this review, the kinetic, crystallographic binding, and physiological studies of a number of compounds, inhibitors of GP, are described, and the essential inhibitory and binding properties of specific compounds are analyzed in an effort to provide rationalizations for the affinities of these compounds and to exploit the molecular interactions that might give rise to a better inhibitor. These studies have given new insights into fundamental structural aspects of the enzyme enhancing our understanding of how the enzyme recognizes and specifically binds ligands, that could be of potential therapeutic value in the treatment of type 2 diabetes.

Selective inhibition of 11beta-hydroxysteroid dehydrogenase type 1 decreases blood glucose concentrations in hyperglycaemic mice.

Current pharmacological treatments for Type II (non-insulin-dependent) diabetes mellitus have various limitations. New treatments are needed to reduce long-term risks for diabetic complications and mortality. We tested a new principle for lowering blood glucose. It is well known that glucocorticoids in excess cause glucose intolerance and insulin resistance. The enzymes 11beta-hydroxysteroid dehydrogenase type 1 and type 2 inter-convert inactive and active glucocorticoids, thereby playing a major role in local modulation of agonist concentration and activation of corticosteroid receptors in target tissues. It has been hypothesized that selective inhibition of 11beta-hydroxysteroid dehydrogenase type 1 decreases excessive hepatic glucose production in hyperglycemia and diabetes. BVT.2733 is a new, small molecule, non-steroidal, isoform-selective inhibitor of mouse 11beta-hydroxysteroid dehydrogenase type 1. The aim of the present study is to test if selective inhibition of 11beta-hydroxysteroid dehydrogenase type 1 lowers blood glucose concentrations in a hyperglycaemic and hyperinsulinaemic mouse model. BVT.2733 was given to spontaneously hyperglycaemic KKA(y) mice for 7 days using subcutaneous osmotic mini-pumps. BVT.2733 lowered hepatic PEPCK and glucose-6-phosphatase mRNA, blood glucose and serum insulin concentrations compared with vehicle treated mice. In contrast, hepatic 11beta-hydroxysteroid dehydrogenase type 1 mRNA, liver function marker enzyme expression (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatases), daily food intake and body weight were not altered by the treatment. These results suggest that a selective inhibitor of human 11beta-hydroxysteroid dehydrogenase type 1 can become a new approach for lowering blood glucose concentrations in Type II diabetes.

Suppression of nocturnal fatty acid concentrations by bedtime carbohydrate supplement in type 2 diabetes: effects on insulin sensitivity, lipids, and glycemic control

Bedtime ingestion of slow-release carbohydrates leads to sustained nocturnal fatty acid suppression and improved glucose tolerance in type 2 diabetic patients. This study assessed the effects of 2 different doses of bedtime carbohydrate supplement (BCS) on morning glycemic control and glycated hemoglobin (Hb A(1c)) in type 2 diabetic patients. In addition, the effects of the high-dose BCS on insulin sensitivity and postprandial glucose and triacylglycerol concentrations were assessed. Two BCS doses were studied separately in 7-wk randomized, placebo-controlled, double-blind studies with either a parallel (low-dose BCS; n = 24 patients) or crossover (high-dose BCS; n = 14 patients) design. The effects of the low and high doses (0.30 and 0.55 g uncooked cornstarch/kg body wt, respectively) were compared with those of a starch-free placebo. Compared with the starch-free placebo, the high-dose BCS ( approximately 45 g) produced enhanced nocturnal glucose (P < 0.01) and insulin (P < 0.01) concentrations as well as a 32% suppression of fatty acid concentrations (P < 0.01). Moreover, glucose tolerance (P < 0.05) and C-peptide response (P < 0.05) improved after breakfast the next morning. The low-dose BCS ( approximately 25 g) improved fasting blood glucose concentrations (P < 0.05). However, there were no improvements in insulin sensitivity, postprandial triacylglycerol concentrations, or Hb A(1c) after 7 wk. Nocturnal fatty acid suppression by BCS improved fasting and postprandial blood glucose concentrations in type 2 diabetic patients the next morning. In contrast, no improvements in insulin sensitivity, postprandial triacylglycerol concentrations, or long-term glycemic control assessed by Hb A(1c) were seen after BCS supplementation.

The antihyperglycaemic effect of metformin: therapeutic and cellular mechanisms.

Metformin is regarded as an antihyperglycaemic agent because it lowers blood glucose concentrations in type 2 (non-insulin-dependent) diabetes without causing overt hypoglycaemia. Its clinical efficacy requires the presence of insulin and involves several therapeutic effects. Of these effects, some are mediated via increased insulin action, and some are not directly insulin dependent. Metformin acts on the liver to suppress gluconeogenesis mainly by potentiating the effect of insulin, reducing hepatic extraction of certain substrates (e.g. lactate) and opposing the effects of glucagon. In addition, metformin can reduce the overall rate of glycogenolysis and decrease the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake into skeletal muscle is enhanced by metformin. This has been attributed in part to increased movement of insulin-sensitive glucose transporters into the cell membrane. Metformin also appears to increase the functional properties of insulin- and glucose-sensitive transporters. The increased cellular uptake of glucose is associated with increased glycogen synthase activity and glycogen storage. Other effects involved in the blood glucose-lowering effect of metformin include an insulin-independent suppression of fatty acid oxidation and a reduction in hypertriglyceridaemia. These effects reduce the energy supply for gluconeogenesis and serve to balance the glucose-fatty acid (Randle) cycle. Increased glucose turnover, particularly in the splanchnic bed, may also contribute to the blood glucose-lowering capability of metformin. Metformin improves insulin sensitivity by increasing insulin-mediated insulin receptor tyrosine kinase activity, which activates post-receptor insulin signalling pathways. Some other effects of metformin may result from changes in membrane fluidity in hyperglycaemic states. Metformin therefore improves hepatic and peripheral sensitivity to insulin, with both direct and indirect effects on liver and muscle. It also exerts effects that are independent of insulin but cannot substitute for this hormone. These effects collectively reduce insulin resistance and glucotoxicity in type 2 diabetes.

Glycosylated haemoglobin and steady-state mean blood glucose concentration in Type 1 (insulin-dependent) diabetes.

Since glucose control and glycosylated haemoglobin varies asyncroneously, we have studied the steady-state relationship between these two factors. In Type 1 (insulin-dependent) diabetic patients with a constant haemoglobin A1c during the preceding 2 years, 15 ambulatory blood glucose profiles during a 5-week period showed a constant glucose level and provided a precise estimate of the mean blood glucose concentration. In addition, we studied 15 non-diabetic subjects who provided three glucose profiles and had one haemoglobin A1c determination performed. A good correlation was found for a curvilinear relationship (haemoglobin A1c = 2.07 X mean blood glucose0.596, r = 0.98). This close relationship indicates that glycosylated haemoglobin is a valuable, but not very sensitive, index of glucose control.