Control Of Plasma Glucose Levels Research Articles

Model of Factors Influencing Glycemic Control Behavior among Pregnant Women with Gestational Diabetes Mellitus A1

Gestational diabetes mellitus is glucose intolerance during pregnancy, increasing health risk in the mothers, feti, and subsequent children. Understanding the factors influencing glycemic control behaviors is necessary to control plasma glucose levels. This study developed and tested the Model of Factors Influencing Glycemic Control Behavior among Pregnant Women with Gestational Diabetes Mellitus A1. The Theory of Planned Behavior was used as a conceptual framework to guide the study. The participants were 252 pregnant women with the condition from two tertiary hospitals in Thailand, and whose blood glucose could be controlled by exercise and diet. Data were collected using a demographic data form and five scales on attitude, subjective norm, belief in self-control behavior, intention, and glycemic control behavior. Statistical analysis was conducted using SPSS version 18.0 and the Mplus statistical package version 7.0. Results showed that the modified model fitted with the empirical data and accounted for 51.8% of the variance of glycemic control behavior. Intention and belief in self-control behavior directly affected glycemic control behavior. Attitude, subjective norm and belief in self-control behavior indirectly affected glycemic control behavior via intention. Among these factors, intention had the most substantial effect on glycemic control behavior. These findings suggest that nursing interventions should enhance intention by reinforcing positive attitudes, belief in self-control behavior, and support from subjective norms to promote glycemic control behavior. This model needs to be applied and tested for effectiveness in clinical practice.

4. Painful diabetic polyneuropathy.

Pain as a symptom of diabetic polyneuropathy (DPN) significantly lowers quality of life, increases mortality and is the main reason for patients with diabetes to seek medical attention. The number of people suffering from painful diabetic polyneuropathy (PDPN) has increased significantly over the past decades. The literature on the diagnosis and treatment of diabetic polyneuropathy was retrieved and summarized. The etiology of PDPN is complex, with primary damage to peripheral nociceptors and altered spinal and supra-spinal modulation. To achieve better patient outcomes, the mode of diagnosis and treatment of PDPN evolves toward more precise pain-phenotyping and genotyping based on patient-specific characteristics, new diagnostic tools, and prior response to pharmacological treatments. According to the Toronto Diabetic Neuropathy Expert Group, a presumptive diagnosis of "probable PDPN" is sufficient to initiate treatment. Proper control of plasma glucose levels, and prevention of risk factors are essential in the treatment of PDPN. Mechanism-based pharmacological treatment should be initiated as early as possible. If symptomatic pharmacologic treatment fails, spinal cord stimulation (SCS) should be considered. In isolated cases, where symptomatic pharmacologic treatment and SCS are unsuccessful or cannot be used, sympathetic lumbar chain neurolysis and/or radiofrequency ablation (SLCN/SLCRF), dorsal root ganglion stimulation (DRGs) or posterior tibial nerve stimulation (PTNS) may be considered. However, it is recommended that these treatments be applied only in a study setting in a center of expertise. The diagnosis of PDPN evolves toward pheno-and genotyping and treatment should be mechanism-based.

GPCR-mediated effects of fatty acids and bile acids on glucose homeostasis.

Fatty acids and glucose are key biomolecules that share several commonalities including serving as energy substrates and as signaling molecules. Fatty acids can be synthesized endogenously from intermediates of glucose catabolism via de-novo lipogenesis. Bile acids are synthesized endogenously in the liver from the biologically important lipid molecule, cholesterol. Evidence abounds that fatty acids and bile acids play direct and indirect roles in systemic glucose homeostasis. The tight control of plasma glucose levels during postprandial and fasted states is principally mediated by two pancreatic hormones, insulin and glucagon. Here, we summarize experimental studies on the endocrine effects of fatty acids and bile acids, with emphasis on their ability to regulate the release of key hormones that regulate glucose metabolism. We categorize the heterogenous family of fatty acids into short chain fatty acids (SCFAs), unsaturated, and saturated fatty acids, and highlight that along with bile acids, these biomolecules regulate glucose homeostasis by serving as endogenous ligands for specific G-protein coupled receptors (GPCRs). Activation of these GPCRs affects the release of incretin hormones by enteroendocrine cells and/or the secretion of insulin, glucagon, and somatostatin by pancreatic islets, all of which regulate systemic glucose homeostasis. We deduce that signaling induced by fatty acids and bile acids is necessary to maintain euglycemia to prevent metabolic diseases such as type-2 diabetes and related metabolic disorders.

Abstract P249: Moderate-to-Severe Depression Symptoms Are Associated With Poorly Controlled Glucose Levels in Persons With Type 2 Diabetes Mellitus

Objective: To investigate whether the severity of depression symptoms is associated with poor long-term control of plasma glucose levels in individuals with type 2 diabetes. Methods: Electronic health record [EHR] data of 2842 individuals with mental illness enrolled in the Penn State Clinical Assessment and Rating Evaluation System [PCARES] registry were used. Demographics, body mass index [BMI], baseline type 2 diabetes mellitus [T2DM] status and all available glucose labs were extracted from the EHR. The nine-item patient health questionnaire [PHQ-9] was used to determine baseline depression symptoms. PHQ-9 scores greater than/equal to 10 indicated moderate-to-severe depression symptoms, whereas scores less than 10 indicated none-to-mild depression symptoms. While the baseline glucose measurement had to be within ± 90 days of the baseline PHQ-9 date, longitudinal glucose measurements had to be on or after this date and within one year of the second follow-up glucose lab test date. Each glucose lab test had to be within one year of the preceding lab test. There were 917 individuals that met the criteria for baseline and follow-up glucose measurements and contributed to the effective study sample. Linear mixed-effects models were used to assess the association between baseline depression and changes in glucose levels, with a focus on persons with baseline diabetes. Results are reported as beta-coefficients (standard errors [SE]) and P -values. Results: The study sample included 917 individuals, with 65% females (596 of 917) and 85% (780 of 917) Non-Hispanic Caucasians. The mean (SD) age, PHQ-9 score, BMI, and glucose were 47.7 (16.9) years, 12.0 (7.1), 31.6 (8.6) Kg/m 2, and 115.9 (48.8) mg/dl, respectively. At baseline, 62.0% had moderate-to-severe depression (569 of 917), and 37.1% of persons had T2DM (341 of 917). Among individuals without T2DM, there was no association between the severity of depression symptoms and follow-up glucose levels with a beta (SE) of 1.1 (1.1) and P =0.32. Among persons with T2DM (N=341), there was an average increase in glucose levels by 2.8 (2.1) mg/dl, P =0.17, per year of follow-up. When stratified by the severity of depression symptoms, individuals with moderate-to-severe depression symptoms had a significant increase in glucose levels at 6.2 (2.7) mg/dl, P =0.02, per year of follow-up, indicative of poor control of blood glucose levels. Whereas, among persons with none-to-mild depression symptoms, blood glucose levels showed a non-significant decline at 2.6 (3.4) mg/dl, P =0.45, per year of follow-up. Conclusions: In this clinic-based sample of persons with mental illness, moderate-to-severe depression symptoms were associated with significantly increasing blood glucose levels among persons with co-morbid T2DM. Our findings underscore integrated physical and mental healthcare services and routine depression screening among persons with diabetes.

The Impact of Insulin Staging in the Context of Pharmaceutical Care on Patients with Type 2 Diabetes Mellitus

The problem of polypharmacy and the nature of the disease make patients with type 2 diabetes mellitus highly vulnerable to drug therapy problems, especially those who are on insulin therapy. Despite this challenge, reaching the desired clinical outcome and using an appropriate insulin regimen are also considered a controversial issue among clinicians. The current study is designed to explore the impact of insulin staging regimens in the context of pharmaceutical care on patients with type 2 diabetes mellitus. This study is a randomized interventional comparative study of a few groups. It was conducted at the Diabetes and Endocrine Centre in Sulaymaniyah City in Iraq from January to August 2022. Patients with T2DM who were on insulin therapy were enrolled in this trial. The participants were divided into two groups, the interventional and non-interventional groups. The insulin regimen was modified, and pharmaceutical care process was performed for the intervention group. Drug therapy problems (DTPs) and clinical parameters were monitored both groups over the course of six months. A total of 67 patients with T2DM on insulin were included in this study, and of them, 73% were females, with a mean age of 57.34 ± 7.825 years. The groups were randomly divided into intervention and non-intervention groups. After six months of applying insulin staging in the context of pharmaceutical care, FPG (Mean Diff.= 72.25, 95% CI of diff.= 20.44 to 124.1), HbA1c (Mean Diff.= 2.087, 95% CI of diff.= 1.151 to 3.023) and DTP were significantly improved in the intervention group. Implementing the insulin staging approach within the context of the pharmaceutical care process showed a significant impact on controlling plasma glucose levels.

Microbiomes of Kefir Grains From Regions of Historical Origin and Their Probiotic Potential

Kefir has attracted interest in the scientific community due to its beneficial properties, such as: improving digestion, antimicrobial action, hypocholesterolemic, antihypertensive, and anti-inflammatory effects, control of plasma glucose levels, antioxidant, anticarcinogenic, and antiallergic activity. The comparative characteristics of the microbiomes of kefir grains (KG) obtained from the regions of their historical origin (Caucasus and China) is given. The diversity of their compositions was shown using classical microbiological and molecular genetic methods, including high-throughput sequencing of V4-region of bacterial 16S rRNA genes and the ITS1 region of the 18S-ITS1-5.8S-ITS2-28S complex of yeast rRNA. The species of the Lactobacillus genus are the most common of the bacterial cultures in kefir grains, while the most common of the yeast cultures is Pichia fermentans , as well as the rarer species of Yarrowia lipolytica and Galactomyces candidus .

Beneficial effects of carvedilol modulating potassium channels on the control of glucose.

The increased prevalence of hypertensive patients with type 2 diabetes mellitus (T2DM) is evident worldwide, leading to a higher risk of cardiovascular disease onset, which is substantially associated with disabilities and mortality in the clinic. In order to achieve the satisfyingly clinical outcomes and prognosis, the comprehensive therapies have been conducted with a beneficial effect on both blood pressure and glucose homeostasis, and clinical trials reveal that some kind of antihypertensive drugs such as angiotensin converting enzyme inhibitors (ACE-I) may, at least in part, meet the dual requirement during the disease management. As a nonselective β-blocker, carvedilol is employed for treating many cardiovascular diseases in clinical practice, including hypertension, angina pectoris and heart failure, and also exhibit the effectiveness for glycemic control and insulin resistance. Apart from alleviating sympathetic nervous system activity, several causes, such as lowering oxygen reactive species, may contribute to the effects of carvedilol on controlling plasma glucose levels, suggesting a feature of this drug having multiple targets. Interestingly, numerous distinct K+ channels expressed in pancreatic β-cells and peripheral insulin-sensitive tissues, which play a sentential role in glucose metabolism, are subjected to extensive modulation of carvdilol, establishing a linkage between K+ channels and drug's effects on the control of glucose. A variety of evidence shows that the impact of carvedilol on different K+ channels, including Kv, KAch, KATP and K2P, can lead to positive influences for glucose homeostasis, contributing to its clinical beneficial effectiveness in treatment of hypertensive patients with T2DM. This review focus on the control of plasma glucose conferred by carvedilol modulation on K+ channels, providing the novel mechanistic explanation for drug's actions.

Metformin Inhibits Na+/H+ Exchanger NHE3 Resulting in Intestinal Water Loss.

Glycemic control is the key to the management of type 2 diabetes. Metformin is an effective, widely used drug for controlling plasma glucose levels in diabetes, but it is often the culprit of gastrointestinal adverse effects such as abdominal pain, nausea, indigestion, vomiting, and diarrhea. Diarrhea is a complex disease and altered intestinal transport of electrolytes and fluid is a common cause of diarrhea. Na+/H+ exchanger 3 (NHE3, SLC9A3) is the major Na+ absorptive mechanism in the intestine and our previous study has demonstrated that decreased NHE3 contributes to diarrhea associated with type 1 diabetes. The goal of this study is to investigate whether metformin regulates NHE3 and inhibition of NHE3 contributes to metformin-induced diarrhea. We first determined whether metformin alters intestinal water loss, the hallmark of diarrhea, in type 2 diabetic db/db mice. We found that metformin decreased intestinal water absorption mediated by NHE3. Metformin increased fecal water content although mice did not develop watery diarrhea. To determine the mechanism of metformin-mediated regulation of NHE3, we used intestinal epithelial cells. Metformin inhibited NHE3 activity and the effect of metformin on NHE3 was mimicked by a 5′-AMP-activated protein kinase (AMPK) activator and blocked by pharmacological inhibition of AMPK. Metformin increased phosphorylation and ubiquitination of NHE3, resulting in retrieval of NHE3 from the plasma membrane. Previous studies have demonstrated the role of neural precursor cell expressed, developmentally down-regulated 4-2 (Nedd4-2) in regulation of human NHE3. Silencing of Nedd4-2 mitigated NHE3 inhibition and ubiquitination by metformin. Our findings suggest that metformin-induced diarrhea in type 2 diabetes is in part caused by reduced Na+ and water absorption that is associated with NHE3 inhibition, probably by AMPK.

Correlation between iron deficiency anemia and HbA1C levels in type 2 diabetes mellitus

The HbA1c levels, in general reflects the diabetic patients Glycaemic control status over the previous 3 months. HbA concentrations may be increased by Anaemia due to iron deficiency, independent of glycaemia in diabetic patients. Henceforth this study serves to find if there is a positive correlation between the iron deficiency anaemia status & the HbA1c levels amidst the diabetic population. Cases-100 iron-deficiency anaemia patients with diabetes having controlled plasma glucose levels, Controls -100 non-anaemic diabetic individuals. The study was done in the premises of Sree Balaji Medical College & Hospital. HbA levels was measured by ion exchange chromatography, ferritin by particle enhanced turbidometric immunoassay method, fasting plasma glucose by GOD - POD method. We found that HbA1c was elevated (7.3±0.9) in iron-deficient diabetic individuals compared to normal level (5.4±0.6) in controls. The study showed that there was a positive correlation between the iron deficiency anaemia status and increased HbA levels in the controlled diabetic population. Hence forth, the clinical significance of evaluating the iron deficiency anaemia status in diabetic patients has been proved to be significant in planning their further course of prompt diabetic management.

Association between iron deficiency anemia and HBA1C level in diabetic patients with controlled plasma glucose levels.

Objectives: To determine association of iron deficiency anemia on hba1c level in diabetic patients. Study Design: Cross Sectional Analytical study. Setting: Department of Pathology PIMS Hospital. Period: From June 2018 to December 2018 (6 months duration). Material & Methods: A total of 117 diagnosed cases of diabetes mellitus were included in the study. Pregnant women, patients with end-stage renal disease, hypothyroidism, +hemoglobinopathies, hemolytic anemia, chronic liver disease and malignancy, participants with poorly controlled diabetes, and patient from the northern areas were excluded from the study. Patients were divided according to their fasting plasma glucose (FPG) level. FPG of 126mg/dl was used as a cut-off point for dividing the study population into two groups, i.e controlled sugar level (FPG between 100 and 126 mg/d L) and well controlled sugar level (FPG less than 100 mg/d L). Variables such as Hemoglobin, serum ferritin, serum Hba1c level etc. Results: Mean age of study population in the present study was 56.97±7.29 years. Out of 117 cases, about 45(38.5%) cases were female and 72 (38.5%) were male. Male to female ratio was 1: 1.6.Mean FPG level was 103.3±7.6 in our study population. The mean hba1c levels in the sample was 6.42±0.70 %. Mean Hb levels were recorded as 11.5±2.7 and 10.9±3.03 g/dl, respectively in female and male. From a total of 117 cases, only 66 were identified as having iron deficiency anemia. Only 54 patients had plasma glucose greater than 100 mg/dl. Odds ratio for hba1c>6.5% in iron deficient was 3.90(p=0.001). Conclusion: Iron deficiency can cause elevated serum hba1c level. Health care providers, including physicians, must consider the iron status before prescribing diabetics treatment on the basis of serum hba1c level.

P6267Novel direct effects of SGLT2 inhibitor, Canagliflozin, on myocardial redox state in humans

Abstract Background Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that control plasma glucose levels by inhibiting reabsorption of glucose in kidney. Recent clinical trials have suggested a class effect of SGLT2 inhibitors in preventing hospitalization due to heart failure. However, the underlying mechanism has not been fully elucidated. Purpose We investigated the direct effect of the SGLT2 inhibitor, Canagliflozin (Cana), on myocardial redox state in humans. Methods The study included 48 patients undergoing cardiac surgery. Fresh myocardial tissues were incubated ex vivo with or without Cana and then used for superoxide quantification and Western immunoblotting. NADPH-oxidases activity was evaluated with NADPH 100μM stimulation, while nitric oxide synthase (NOS) coupling was assessed by using N(ω)-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). A human cardiomyocyte (HCM) cell line was also used for in vitro validation of the effects of Cana on myocardium. Results Ex vivo incubation of myocardium with Cana significantly reduced baseline (A) and NADPH-oxidase-derived O2·− (B) and improved NOS coupling reflected by positive L-NAME delta O2·− values (C). Regulation of NADPH-oxidases activity by Cana was found to result from reduced GTP-activation (D) and consequent membrane translocation (E) of Rac1, a key subunit of NADPH-oxidases. Cana also reduced tetrahydrobiopterin (BH4) oxidation, increasing its bioavailability (F), which is a key mechanism to improve NOS coupling. Incubation with Cana enhanced phosphorylation of AMPK, and the downstream signalling, ACC (not shown). Additional Compound C, which is inhibitor of AMPK, significantly reversed these effects of Cana (A, B, C, D, E, F). These findings were replicated in HCM (not shown). In line with these, Cana increased the ADP/ATP ratio of cytoplasm in HCM, which could provide an upstream mechanism for AMPK activation. Conclusions We demonstrate for the first time in humans, that Cana suppresses myocardial NADPH-oxidases activity and improves NOS coupling through an AMPK-mediated pathway. This could be an underlying mechanism for the cardioprotective effects of SGLT2 inhibitors.

Paeoniflorin protects pancreatic β cells from STZ-induced damage through inhibition of the p38 MAPK and JNK signaling pathways

Pancreatic β-cells are responsible for insulin secretion and control of plasma glucose levels. Accumulating evidences indicate a relationship between β-cell dysfunction/death and diabetes onset. Paeoniflorin (PF), a natural glycoside, has antihyperglycemic effect. However, the role of PF in pancreatic β-cells has not been examined. The aim of this study was to evaluate the protective effect of PF on streptozotocin (STZ)-induced β-cell damage. Our results showed that PF improved STZ-caused inhibitory effect on cell viability and insulin secretion ability in INS-1 cells. PF reduced caspase-3 activity and bax expression, and induced bcl-2 expression in STZ-treated INS-1 cells. PF resulted in a decrease in production of reactive oxygen species and MDA, and an increase in SOD activity in STZ-treated INS-1 cells. Furthermore, PF inhibited the phosphorylation of p38 and JNK, which is induced by STZ in INS-1 cells. The results suggested that PF protected INS-1 cells from STZ-induced cell damage. Meanwhile, PF suppressed the activation of p38 MAPK and JNK pathways in STZ-treated INS-1 cells. These results indicated that PF might be a natural anti-diabetic agent by improving pancreatic β-cells injury through inhibition of the p38 MAPK and JNK signaling pathways.

Cognitive impairment in patients with type 2 diabetes mellitus: prevalence, pathogenetic mechanisms, the effect of antidiabetic drugs

In recent years, a large amount of data has been accumulated on the relationship between cognitive impairment, dementia and diabetes mellitus. This article presents an overview of modern literature, including the definition of cognitive functions, the modern classification of cognitive impairment, pathogenetic mechanisms of diabetes mellitus influence on the development of cognitive impairment and dementia (neurogenesis, integrity of the blood-brain barrier, systemic inflammatory reactions, hyper- and hypoglycemia, insulin resistance, vascular dysfunction of the microvasculature and increase in glucocorticosteroids). The influence of anti-diabetic medications on cognitive functions has been examined in detail: insulin preparations, oral hypoglycemic agents of the biguanide group (metformin), thiazolidinediones (rosiglitazone and pioglitazone), sulfonylurea derivatives (glycazide, glipizide), a-glucosidase (acarbose) inhibitors, incretin-directed therapy (receptor agonists glucan-like peptide (exenatide and liraglutide) and inhibitors of dipeptidylpeptidase type 4 (sitagliptin, vildagliptin and alogliptin)), sodium glucose inhibitors cotransporter type 2. The data demonstrating a multidirectional effect on the cognitive functions of various antidiabetic drugs is presented, the possible influence on the rate of progression of cognitive impairment and the risk of dementia of intensive control of plasma glucose level in comparison with the standard decrease in patients with type 2 diabetes is analyzed.

PMD164 - THE MANAGEMENT OF GLYCAEMIC CONTROL IN DIABETIC PATIENTS (T2): THE ROLE OF GLYCATED ALBUMIN

The study aims at investigating the implications related to the introduction, in the Italian clinical practice, of glycated albumin (GA), as innovative glycemic control marker, for patients with type 2 diabetes assuming oral antiglycemic treatment (insulin-naïve), in addition to the traditional monitoring instruments (HbA1c/fasting plasma glucose). A Health Technology Assessment was conducted, considering the Italian NHS perspective. Data were gathered using specific questionnaires (completed by 14 Italian professionals) and systematically searching medical literature, for the assessment of EUnetHTA dimensions. Literature review stated that the introduction of GA could: i) reflect shorter-term control of plasma glucose level, being helpful in patients with hemoglobinopathy; ii) be a predictor of the relative risk in the development of diabetes complications; iii) increase the number of patient achieving therapeutic success after 3 months of therapy (97.0% vs 71.6%). The perceptions of the professionals (considering a 7-item Likert scale, ranging from -3 to +3) crystallized literature evidence, declaring a better safety (0.11 vs 0.65) and effectiveness (0.53 vs 1.80) profile, in adding GA to the traditional instruments. From an economic point of view, GA introduction would lead to fewer patients requiring a therapy switch (-89.44%), with an economic advantage of -1.06% (12 months). The cost-effectiveness analysis demonstrated that the innovative pathway would be the preferable technology (CEV: 225.53 vs 237.74). Low-level perceptions resulted with regard to equity aspects (0.13 vs 0.72), due to GA limited accessibility, whereas it would improve both patients (1.33 vs 2.17) and caregivers (0.83 vs 1.50) quality of life. While GA, in the short time, requires training courses and equipment update, in the long run, there would contain the above drawbacks, showing GA organizational benefits (0.01 vs 0.30). The study showed the strategic relevance of GA, in the improvement of diabetic patient clinical pathway, freeing-up NHS resources.

Free fatty acid can induce cardiac dysfunction and alter insulin signaling pathways in the heart

BackgroundInsulin resistance has been independently related to heart failure. However, the specific mechanisms of high FFA levels in the pathophysiology of heart failure in insulin-resistant states are remain largely unclear. This study investigated whether elevated circulating free fatty acids (FFA) levels result in impaired cardiac structure and function in vivo via insulin-related signaling pathways in myocardium.MethodsMale Wistar rats were randomly divided into the intralipid group (20% intralipid plus heparin infusion) and the control group (glycerol infusion). Blood samples were collected before and after 6-, 12-, and 24-h infusions. Cardiac structure and function were measured using echocardiography. Maximum velocity of myocardial contraction (+dP/dt max) and diastole (−dP/dt max) were measured using a physiological polygraph in vivo. Heart tissues were collected for western blotting.ResultsCompared with the control group, plasma FFA, plasma glucose, and serum insulin levels increased significantly in the intralipid group. With increasing infusion time, cardiac function in the intralipid group decreased gradually compared with the control group. After a 24-h infusion, early (E’, cm/s) diastolic peak velocities and (−dP/dt max) decreased significantly. Protein expression of phosphatidylinositol 3-kinase (PI3K), the serine/threonine kinase Akt, and phosphorylated Akt in myocardium increased after a 6-h infusion and decreased significantly after a 24-h infusion in the intralipid group. Protein expression of glucose transporter type 4 (GLUT4), Adenosine 5′-monophosphate -activated protein kinase (AMPK), phosphorylated AMPK(p-AMPK), and endothelial nitric oxide synthase (eNOS) in myocardium gradually decreased in the intralipid group.ConclusionsElevated FFA levels may impair cardiac function and cardiac dysfunction might result from myocardial insulin resistance with significant changes to PI3K-Akt-GLUT4 and AMPK-eNOS signaling pathways with increasing FFA levels.

Overnight Glucose Control with Dual- and Single-Hormone Artificial Pancreas in Type 1 Diabetes with Hypoglycemia Unawareness: A Randomized Controlled Trial.

The dual-hormone (insulin and glucagon) artificial pancreas may be justifiable in some, but not all, patients. We sought to compare dual- and single-hormone artificial pancreas systems in patients with hypoglycemia unawareness and documented nocturnal hypoglycemia. We conducted a randomized crossover trial comparing the efficacy of dual- and single-hormone artificial pancreas systems in controlling plasma glucose levels over the course of one night's sleep. We recruited 18 adult participants with hypoglycemia unawareness and 17 participants with hypoglycemia awareness, all of whom had documented nocturnal hypoglycemia during 2 weeks of screening. Outcomes were calculated using plasma glucose. In participants with hypoglycemia unawareness, the median (interquartile range [IQR]) percentage of time that plasma glucose was below 4.0 mmol/L was 0% (0-0) on dual-hormone artificial pancreas nights and 0% (0-10) on single-hormone artificial pancreas nights (P = 0.20). Additionally, participants with hypoglycemia unawareness experienced two hypoglycemic events (<3.0 mmol/L) on dual-hormone artificial pancreas nights and three hypoglycemic events on single-hormone artificial pancreas nights. In participants with hypoglycemia awareness, the median (IQR) percentage of time that plasma glucose was below 4.0 mmol/L was 0% (0-0) on both dual- and single-hormone artificial pancreas nights. Hypoglycemia awareness participants experienced zero hypoglycemic events on dual-hormone artificial pancreas nights and one event on single-hormone artificial pancreas nights. In this study, dual-hormone and single-hormone systems performed equally well in preventing nocturnal hypoglycemia in participants with hypoglycemia unawareness. Longer studies over the course of multiple days and nights may be needed to explore possible specific benefits in this population. ClinicalTrials.gov No. NCT02282254.

Impact of Iron Deficiency Anemia on Glycated Hemoglobin (HbA1c) Levels in Diabetics with Controlled Plasma Glucose Levels

BACKGROUND : Glycated hemoglobin (HbA 1 C) is used as a gold standard for monitoring glycemic control. American Diabetes Association (ADA) has certified HbA 1 C ≥ 6.5% as a diagnostic criterion for diabetes mellitus (DM). Recent studies suggest that conditions affecting erythrocyte turnover like Iron deficiency anemia (IDA) alters HbA 1 C levels but their results are conflicting. However the effect of IDA on HbA 1 C is rarely reported. To determine the impact of IDA on HbA 1 C levels among controlled diabetics [Fasting plasma glucose (FPG) <126mg/dl since last 6 months] independent of blood glucose concentration and its variation according to the degree of anemia. METHODS: This cross-sectional study carried out in SRM Medical College Hospital and Research Centre, Chennai includes totally 300 controlled diabetic patients –Type 2 DM (150 with IDA and 150 without IDA). Medical history recorded. HbA 1 C, complete hemogram and FPG were tested. RESULT: The mean HbA 1 C among controlled diabetics with IDA (7.86 ± 0.11%) was significantly higher than those without IDA (5.45 ± 0.038%) (P<0.05). HbA 1 C results were higher with the reduction of total hemoglobin (p< 0.05) CONCLUSION: IDA spuriously elevates HbA1C levels independent of blood glucose concentration in controlled-diabetics.HbA 1 C increases significantly as severity of anemia worsens. Thereby this study insists on the utter importance to exclude IDA and to correct it before any diagnostic or therapeutic decision is made based solely on HbA 1 C level.

Prolonged insulin treatment sensitizes apoptosis pathways in pancreatic β cells.

Insulin resistance results from impaired insulin signaling in target tissues that leads to increased levels of insulin required to control plasma glucose levels. The cycle of hyperglycemia and hyperinsulinemia eventually leads to pancreatic cell deterioration and death by a mechanism that is yet unclear. Insulin induces ROS formation in several cell types. Furthermore, death of pancreatic cells induced by oxidative stress could be potentiated by insulin. Here, we investigated the mechanism underlying this phenomenon. Experiments were done on pancreatic cell lines (Min-6, RINm, INS-1), isolated mouse and human islets, and on cell lines derived from nonpancreatic sources. Insulin (100nM) for 24h selectively increased the production of ROS in pancreatic cells and isolated pancreatic islets, but only slightly affected the expression of antioxidant enzymes. This was accompanied by a time- and dose-dependent decrease in cellular reducing power of pancreatic cells induced by insulin and altered expression of several ER stress response elements including a significant increase in Trb3 and a slight increase in iNos The effect on iNos did not increase NO levels. Insulin also potentiated the decrease in cellular reducing power induced by H2O2 but not cytokines. Insulin decreased the expression of MCL-1, an antiapoptotic protein of the BCL family, and induced a modest yet significant increase in caspase 3/7 activity. In accord with these findings, inhibition of caspase activity eliminated the ability of insulin to increase cell death. We conclude that prolonged elevated levels of insulin may prime apoptosis and cell death-inducing mechanisms as a result of oxidative stress in pancreatic cells.

The Effect of Sustained Inflammation on Hepatic Mevalonate Pathway Results in Hyperglycemia

Control of plasma glucose level is essential to organismal survival. Sustained inflammation has been implicated in control of glucose homeostasis in cases of infection, obesity, and type 2 diabetes; however, the precise role of inflammation in these complex disease states remains poorly understood. Here, we find that sustained inflammation results in elevated plasma glucose due to increased hepatic glucose production. We find that sustained inflammation suppresses CYP7A1, leading to accumulation of intermediate metabolites at the branch point of the mevalonate pathway. This results in prenylation of RHOC, which is concomitantly induced by inflammatory cytokines. Subsequent activation of RHO-associated protein kinase results in elevated plasma glucose. These findings uncover an unexpected mechanism by which sustained inflammation alters glucose homeostasis.

Performance evaluation of SD A1cCare as a HbA1c analyzer for point-of-care testing

ObjectivesSome studies have shown that a rapid feedback of HbA1c results is helpful for controlling plasma glucose levels. Point-of-care (POC) instruments that are fast, portable, and easy to use are suitable for rapid determination of HbA1c levels. Here, we evaluated the analytical performance of a newly developed POC HbA1c analyzer, SD A1cCare (SD Biosensor, Inc.). Design and methodsThe precision, linearity, and correlation with the Variant II Turbo instrument (Bio-Rad Laboratories, Inc.) were evaluated according to CLSI guidelines for SD A1cCare. All tests were performed according to the manufacturer instructions, and statistical analyses, including linear regression and Passing-Bablok regression, were performed. Bias from the IFCC reference targets was also evaluated with 12 duplicate specimens (n=24 in total). ResultsThe coefficients of variation based on EP9-A2 protocol were 2.6% in SI unit and 1.8% in NGSP unit. The calibration curve was linear, with R2=0.9911 in the range of 23.5 to 125.1 mmol/mol in SI units (4.3% to 13.6% in NGSP units). The results of the SD A1cCare correlated with those of the Variant II Turbo (r=0.986). Deviations from IFCC targets at 30, 60, and 90 mmol/mol IFCC levels were −1.95, −1.85, and −1.74 mmol/mol, respectively. ConclusionsThe SD A1cCare analyzer showed excellent precision, linearity, correlation with the Variant II Turbo analyzer, and accuracy with IFCC targets. Therefore, it may be suitable for HbA1c assays in the POC setting and in small laboratories.