Type 2 Diabetes Mellitus Control Research Articles

Dependence of heart rate variability on indicators of type 1 diabetes mellitus control.

The aim of our study was to evaluate the influence of the main indicators of type 1 diabetes mellitus (T1DM) control on heart rate variability (HRV). We examined 62 patients at the age of 18-45 years with an average T1DM duration of 11.0 (5.0; 18.0) years. HRV in the time and frequency range was evaluated by analyzing a 24-hour Holter electrocardiogram (ECG). The following laboratory parameters were used as markers of course and compensation of T1DM: C-peptide, HbA1c, blood creatinine, albuminuria (AU), estimated glomerular filtration rate (eGFR) by CKD-EPI formula. In addition, the maximum and minimum blood glucose levels and the blood glucose range (maximum minus minimum blood glucose values) were conducted by continuous glucose monitoring system iPro2 (Medtronic MiniMed, USA). The daily monitoring of electrocardiogram (ECG) was made in parallel with long term monitoring of blood glucose. Echocardiography in all patients was performed to exclude organic heart disease and the possibility of its influence on HRV. Poor control of T1DM negatively influences HRV through decrease in both frequency and time characteristics. The blood glucose range can be an additional negative factor for cardiovascular system in T1DM patients, regardless of HbA1c, whereas it positively correlates with HRV- relative hypersympathicotonia markers: LF/HF 24-h, ρ=0.43 (p<0.05), LF/HF day ρ=0.37 (p<0.05), ρ=0.38 LF/HF night. Diabetic nephropathy is another factor of cardiovascular disease progression in T1DM, since its criteria have reliably negative (for eGFR) and positive (for AU) correlations of mean force with all HRV characteristics. Selected markers of T1DM control cause 45, 73% of variance in HRV, mainly affecting TP 24-h, TP daytime, VLF 24-h, VLF daytime. Reduction of these frequency HRV characteristics may indicate autonomic neuropathy in patients with poor control of T1DM.

Association of Serum PSP/REG Iα with Renal Function in Type 2 Diabetes Mellitus.

Purpose Pancreatic stone protein/regenerating protein I (PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG IMethods This cross-sectional study was conducted at Zhongda Hospital, affiliated with Southeast University in China. Serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG IResults Serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG IP < 0.05). The level of PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG IConclusions Serum PSP/REG Iα level is significantly upregulated in T2DM patients and reflects renal function in both T2DM and nondiabetic control groups. The relationship between PSP/REG Iα and eGFR suggested that PSP/REG Iα might be a potential indicator of renal dysfunction.α) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG I

Dynamic Phenotypes and Molecular Mechanisms to Understand the Pathogenesis of Diabetic Nephropathy in Two Widely Used Animal Models of Type 2 Diabetes Mellitus.

ObjectiveWe aimed to characterize the pathogenesis of diabetic nephropathy (DN) in two commonly used type 2 diabetes mellitus (T2DM) animal models and explore the preliminary molecular mechanisms underlying DN in two models.MethodsTo verify the effect of hyperglycemia on renal tissue, we observed the cell growth inhibition rate by adding different concentration of glucose to cell supernatant. After that, a chemically-induced T2DM model was established by administering streptozotocin (STZ) to Sprague Dawley (SD) rats in combination with high fat feeding. In addition, a spontaneous T2DM model was established by feeding 8 weeks old KK-Ay mice a high-fat diet during a period of over 20 weeks. Animal body weight, fasting blood glucose (FBG), insulin tolerance, lipid metabolism, renal function, and renal pathology were periodically measured (once every 2 or 4 weeks) over a duration of 20 weeks. At the 12th week, an Affymetrix gene chip assay was performed on the renal tissues extracted from the T2DM animal models and control animals. Through screening for the differentially expressed genes, some key genes were selected for PCR validation.ResultsHigh level of glucose could inhibit the growth of kidney cells. Besides, KK-Ay mice were found to have high FBG and abnormal insulin tolerance. Renal dysfunction and pathology were observed at the 4th week following the start of model creation, which increased in severity over the length of the experiment. The T2DM SD rats also showed high FBG, abnormal glucose tolerance and abnormal lipid metabolism, but the renal function and renal pathology changed only slightly within 20 weeks. Gene profiling in animal kidneys and subsequent analyses and validation revealed differentially expressed genes and enriched pathways in DN.ConclusionKK-Ay mice with both high fasting glucose and insulin resistance were more likely to develop diabetic nephropathy than STZ-induced diabetic SD rats with low fasting glucose or only insulin resistance. The KK-Ay mice model showed earlier onset of the typical pathological characteristics associated with T2DM and obvious renal lesions suggestive of kidney damage.

Phytopharmacological Strategies in the Management of Type 2 Diabetes Mellitus.

Type 2 Diabetes Mellitus (T2DM) is a chronic disease which corresponds to 90% of the worldwide cases of diabetes, mainly due to epigenetic factors such as unhealthy lifestyles. First line therapeutic approaches are based on lifestyle changes, most of the time complemented with medication mostly associated with several side effects and high costs. As a result, the scientific community is constantly working for the discovery and development of natural therapeutic strategies that provide lower financial impact and minimize side effects. This review focus on these nature-based therapeutic strategies for prevention and control of T2DM, with a special emphasis on natural compounds that present pharmacological activity as dipeptidyl peptidase-4 (DPP4), alpha-amylase, alpha-glucosidase, lipase, and protein tyrosine phosphatase 1B (PTP1B) inhibitors.

Going Beyond the Visible in Type 2 Diabetes Mellitus: Defense Mechanisms and Their Associations With Depression and Health-Related Quality of Life.

IntroductionClinical psychological features may impact a person’s aptitude to deal with chronic diseases, leading to emotional distress, suffering, and a worse perceived quality of life (QoL). Chronic diseases are largely represented, and their incidence is constantly increasing all over the world. Type 2 Diabetes Mellitus (T2DM) is one of the most common chronic diseases and it is very difficult to manage, demanding long term self-management, which improves the perceived QoL. The aim of this study was to explore defense mechanisms, depression, QoL, time since diagnosis, and metabolic control in T2DM patients.Methods51 patients with T2DM were assessed through a psychodiagnostic battery: Beck Depression Inventory-II, the 36-Item Short Form Health Survey, including indexes of Physical and Mental Component Summary and the Defense Mechanisms Inventory. Times since DM diagnosis and glycated hemoglobin values were detected.ResultsParticipants were mainly female (62.74%), with a mean age of 66.1 years. T2M time since diagnosis was 11.77 years (SD = 7.1). Mild depression was detected (with an overall score between 13 and 19). Projection was significantly associated with higher depression and with lower physical well-being; Principalization was negatively associated with depression and positively with both physical and mental well-being. Turning Against Self correlated positively with physical well-being and negatively with mental well-being. Reversal was associated with lower depression and higher mental well-being. A negative high correlation emerged between depression and mental well-being. Finally, a significant relationship was found between Projection and higher time since diagnosis (r = 0.31, p < 0.05).ConclusionThe correlations between defense mechanisms, depression and health-related QoL highlight the potential personification and protagonization, which may increase over time due to the illness intrusiveness and worsening of diabetes symptoms. The positive association between defensive strategies and well-being measures should be cautiously considered.

Self-management of type 2 diabetes mellitus utilizing technology based mobile medical assisted blood glucose management: Study protocol for a prospective, multi-center, observational study

IntroductionDiabetes mellitus is a major health concern globally as well as in China. Currently, the blood glucose (BG) control and patient outcome of diabetes are less than optimal, due to the poor adherence to established evidence-based treatment guidelines and low utilization of preventive care services by both providers and patients. Evidence suggest the benefit of mobile technology-based applications in improving BG monitoring and management in type 2 diabetes mellitus (T2DM). This study is designed to evaluate the effectiveness, safety and timeliness of the mobile internet technology in improving outpatients blood glucose self-management of Chinese T2DM. Methodsand Analysis: This is a prospective, single-arm, multi-center, observational study involving 250 hospitals across China. Patients aged ≥18 and ≤ 80 years with a diagnosis of T2DM and poor glycemic control, who were willing to receive premixed insulin analogues and could use their own WeChat account independently, were included in the study. The primary outcome of the study is to assess the benefit of programme based on change in hemoglobin A1c (HbA1c) from baseline to 3 months. Secondary outcomes included proportion of patients achieving HbA1c<7% at 3 months, change in fasting and postprandial glucose levels from baseline, incidence of hypoglycemia, frequency of self-monitoring blood glucose (SMBG), the patient behavior of BG monitoring on platform and the association of BG control with health care professionals (HCP)-patient interaction. The mobile based technology intervention can improve the HbA1c and BG levels in the patients receiving premixed insulin analogues and that the adherence of SMBG was increased and the incidence of hypoglycemia was decreased. Additionally, early detection of treatment-related hypoglycemia or other complications will contribute to timely therapeutic adjustments and lifestyle modifications under HCP's recommendations through the seamless HCP-patients interaction based on the mobile application. Ethics and disseminationThe study protocol was approved by the ethics committees from each study site according to the International Conference on Harmonization guidelines for Good Clinical Practice and conformed to Declaration of Helsinki. The results of the analyses will be shared with all the participating hospitals and will be published in peer-reviewed journals. No personal information will be included in the findings. RegistrationThis study was registered at chictr.org.cn (ChiCTR 1900021191).

Efficacy and Safety of Once-Weekly Dulaglutide in Type 2 Diabetes Patients Using Insulin: Exploratory Subgroup Analysis by Insulin Regimen.

PurposeIn East Asian patients, type 2 diabetes mellitus (T2DM) is characterized primarily by β-cell dysfunction, with lower insulin secretion than in Caucasian individuals. Therefore, bolus insulin and premixed insulin containing a bolus insulin component are important therapeutic tools in Japan, in addition to basal insulin. This subgroup analysis is stratified by insulin regimen and uses data from a phase 4, randomized, placebo-controlled, double-blind and subsequent open-label study in Japan to assess the efficacy and safety of once-weekly dulaglutide combined with various insulin therapies.MethodsThis multicenter study enrolled Japanese patients with T2DM and inadequate glycemic control [glycated hemoglobin A1c (HbA1c) ≥ 7.5% to ≤ 10.5%] on insulin therapy [basal (B), premixed (PM), or basal bolus (BB)] in combination with or without one or two oral antidiabetic agents. Randomized participants received once-weekly dulaglutide 0.75 mg (n = 120) or placebo (n = 39) during a 16-week double-blind treatment period, and dulaglutide during a 36-week open-label extension. In this subgroup analysis, efficacy measures were changes from baseline in HbA1c, 7-point self-monitored blood glucose profiles, and body weight. Safety measures were incidence of adverse events and hypoglycemia during the first 16 weeks.ResultsAt week 16, least squares mean differences (95% CI) regarding changes from baseline in HbA1c for each insulin regimen versus placebo were: B: − 1.62% (− 1.96, − 1.28), PM: − 1.78% (− 2.25, − 1.30), and BB: − 1.15% (− 1.54, − 0.77); p < 0.001 dulaglutide vs. placebo for each subgroup. No significant differences in body weight changes were observed between dulaglutide and placebo for any insulin regimen. Gastrointestinal symptoms were the most commonly observed adverse events in dulaglutide-treated patients. Hypoglycemia incidence rates were: B: dulaglutide 38.5% vs. placebo 23.5%; PM: dulaglutide 38.5% vs. placebo 44.4%; BB: dulaglutide 50.0% vs. placebo 30.8%.ConclusionsOverall, dulaglutide was generally well tolerated and improved glycemic control significantly versus placebo, regardless of insulin regimen.Trial RegistrationClinicalTrials.gov identifier, NCT02750410.Electronic supplementary materialThe online version of this article (10.1007/s13300-020-00765-6) contains supplementary material, which is available to authorized users.

Effectiveness of Physical Exercise on the Glycemic Control of Type 2 Diabetes Mellitus Patients: A Systematic Review

Introduction: Type 2 diabetes mellitus (T2DM) is one of the main causes of increasing global health morbidity and mortality for diabetes cases. Increasing the glycemic control in patients with T2DM is not enough if it is only treated with anti-hyperglycemic drugs. Physical exercise is an activity that is planned, structured and carried out to improve health or physical fitness and it is an effective way to improve glycemic control. The aim of this study was to search and review the research on effectiveness of physical exercise on glycemic control in T2DM.Methods: We searched the scientific literature on T2DM and physical exercise in the ScienceDirect, ProQuest, Scopus, Ebsco and Pubmed databases for original research studies and then we reviewed them systematically. Of the 1145 articles retrieved, 14 studies were obtained by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodResults: Aerobic physical exercise improved the glycemic control of T2DM and it was widely used and significant for glycemic control. The schedule of 3 times a week for 60 minutes per session over 2 months was widely used and significant when it came to reducing blood glucose and hemoglobin A1c (HbA1c).Conclusion: This systematic review could be used as evidence when carrying out aerobic physical exercise interventions for the purpose of glycemic control.

Laboratory Parameters of Hemostasis, Adhesion Molecules, and Inflammation in Type 2 Diabetes Mellitus: Correlation with Glycemic Control.

Background: Type 2 diabetes mellitus (T2DM) is characterized by a prothrombotic state, predisposing to vascular complications. Some related markers, linking thrombophilia to hemostasis and inflammation, however, have been poorly explored in relation to patients’ glycemia. We therefore investigated the association of laboratory hemostatic parameters, circulating adhesion molecules (ADMs), white blood cell (WBC) count, and neutrophil/lymphocyte ratio (NLR) with T2DM and glycemic control. Research design: In this study, 82 subjects, grouped into T2DM patients (n = 41) and healthy individuals (n = 41) were enrolled. To evaluate glycemic control, the T2DM cohort was expanded to 133 patients and sub-classified according to glycated hemoglobin (HbA1c) <7% and ≥ 7% (n = 58 and n = 75, respectively). We assessed glycemia, HbA1c, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), platelet and leukocyte parameters, vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and selectins (E-, P-, L-). Results: PT % activity, PAI-1, VCAM-1, WBC, and neutrophil counts were significantly higher in T2DM patients than in healthy subjects. Poor glycemic control (HbA1c ≥ 7%) was correlated with increased PT activity (p = 0.015), and higher levels of E-selectin (p = 0.009), P-selectin (p = 0.012), and NLR (p = 0.019). Conclusions: Both T2DM and poor glycemic control affect some parameters of hemostasis, inflammation, and adhesion molecules. Further studies are needed to establish their clinical utility as adjuvant markers for cardio-vascular risk in T2DM patients.

Associations between Vitamin D and Type 2 Diabetes Mellitus: The Role of Vitamin D Receptor and Binding Protein

Background: Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by β-cell dysfunction and resistance for insulin. Vitamin D is necessary for insulin secretion so it is a crucial factor in the development of T2DM. This study was done to investigate the association between serum 25-hydroxy Vitamin D [25(OH)3D], VDR (Vitamin D receptor) and VDBP (Vitamin D binding protein) with type 2 diabetic patients compared to control subjects. Subjects and Methods: This study carried out 110 female patients who were previously diagnosed with type 2 diabetes and 110 age, sex and weight matched as controls. All participants were subjected to full history taking, clinical examination and assessment of fasting blood glucose, HbA1c , lipid profile, 25-hydroxy Vitamin D [25(OH)3D], VDR and VDBP. Results: Results showed that the level of 25(OH)3D was significantly lower in diabetic group compared to controls and was significantly negatively correlated with glycated hemoglobin, serum total cholesterol and low density lipoprotein cholesterol in type 2 DM. Decreasing Vitamin D level was significantly associated with decreasing VDR. No significant association was found between Vit D and VDBP levels. Conclusions: Vitamin D deficiency is frequent in diabetic patients and associated with poor control and outcome. This suggests a role of Vitamin D in the pathogenesis and control of T2DM. Serum VDBP in diabetes may be independent to the level of 25(OH)3D and needs further studies.

P207 Synergetic effect of amino acid and ketone metabolism underlies empagliflozin-mediated cardioprotection in the type 2 diabetic heart

Abstract Funding Acknowledgements Boehringer Ingelheim Background Although emerging evidence has indicated that sodium glucose cotransporter 2 (SGLT2) inhibitors restore impaired cardiac energetics in type 2 diabetes mellitus (T2DM), the underlying molecular mechanisms have yet to be established. Augmented utilization of ketone is one proposed hypothesis, but depletion of succinyl-CoA triggered by the conversion of ketone back to acetyl-CoA by SCOT (succinyl-CoA:3-oxoacid CoA transferase) may hamper oxidative capacity of the tricarboxylic acid (TCA) cycle, which also requires succinyl-CoA. The recent finding that empagliflozin augments systemic amino acid metabolism in patients with T2DM led us to hypothesize that the anaplerotic effect of amino acid on the TCA cycle complements ketone oxidation. Methods and Results Myocardial infarction (MI) was induced in T2DM rats (OLETF) and control rats (LETO). Survival rate at 48 hours after MI was significantly lower in OLETF than in LETO (40% vs 84%), and empagliflozin treatment (10 mg/kg/day, 14 days) before MI improved the survival rate in OLETF to 70%. Metabolome analysis was performed using heart tissues from the non-infarct region 12 hours after MI. Using principal component analysis, data from 92 metabolites that were detected were compressed into 2 dimensions, and the first component (PC1) clearly separated empagliflozin-treated OLETF from non-treated LETO and OLETF. Analysis of factor loading of each metabolite for PC1 revealed that branched chain amino acids leucine, isoleucine and valine, the latter two of which can be oxidized to succynyl-CoA, and β-hydroxybutyrate were the top four metabolites that characterized empagliflozin treatment. Furthermore, in comparison to LETO, OLETF treated with empagliflozin showed 50% higher levels of glutamine and glutamate, both of which can replenish the TCA cycle at the level of α-ketoglutarate. In OLETF, empagliflozin significantly increased the TCA cycle intermediates citrate, cis-aconitate and malate by 74%, 119% and 59%, respectively. OLETF showed 86% higher lactate and 38% lower ATP than those in LETO, but levels of the metabolites were normalized by empagliflozin, suggesting improved glucose oxidation. Conclusions The present analyses showed that amino acid and ketone metabolism are metabolic pathways that are most affected by empagliflozin. Coordination of these "starvation-induced pathways" may underlie the favorable metabolic effect of empagliflozin in T2DM hearts.

Non-Targeted Metabolomic Analysis Reveals Serum Phospholipid Alterations in Patients with Early Stages of Diabetic Foot Ulcer.

Diabetic foot ulcer (DFU) is a common complication of type 2 diabetes mellitus (T2DM) characterized by ulcer formation, which can lead to the amputation of lower extremities. However, the metabolic alterations related to this complication are not completely elucidated. Therefore, we carried out a metabolomic analysis of serum samples obtained from T2DM adult patients diagnosed with diabetic foot ulcer in a cross-sectional, observational, and comparative study. Eighty-four volunteers were classified into the following groups: without T2DM (control group, n = 30) and with T2DM and different stages of diabetic foot ulcer according to Wagner-Meggitt classification system: DFU G0 (n = 11), DFU G1 (n = 14), DFU G2 (n = 16), and DFU G3 (n = 13). The non-target metabolomic profile followed by chemometric analysis revealed that lysophosphatidylethanolamine (16:1) could be proposed as key metabolite related to the onset of diabetic foot ulcer; however, this phospholipid was not affected by diabetic foot ulcer progression. Therefore, further studies are necessary to validate these phospholipids as biomarker candidates for the early diagnosis of diabetic foot ulcer in T2DM patients.

The relationship between Helicobacter pylori infection and control of type 2 diabetes mellitus

Backgrou nd Dyspepsia is a common symptom with a heterogeneous pathophysiology. It occurs in at least 20% of the population. Helicobacter pylori is one of the most common human bacterial pathogen that is present in ∼50% of the global population. It normally is a resident of gastric epithelium. Type 2 diabetes mellitus (T2DM) is a major public health problem, with increasing prevalence globally. It is a metabolic disorder that occurs owing to insulin resistance and relative insulin deficiency. Objectives To study the association between H. pylori infection and T2DM and glycated hemoglobin (HbA1c) and comparing it with nondiabetic patients. Patients and methods This cross-section study was conducted on 60 patients with age more than or equal to 35 years, of either sex, with history of dyspepsia. There were 20 (33%) males and 40 (67%) females, and their ages ranged between 35 and 62 years, with mean age of 46.5±9.15 years. They were divided into two groups of patients: group I included 30 patients with T2DM, and group II included 30 nondiabetic patients. Patients in group II are subdivided into two groups (according to HbA1c results): group IIA (prediabetic) included 13 patients, and group IIB (nondiabetic) included 17 patients. Results H. pylori infection is significantly associated with T2DM, and the incidence of H. pylori in type 2 diabetic patients was significantly higher than nondiabetic patients. H pylori infection is significantly associated with HbA1c level, and HbA1c in H. pylori-positive group was significantly higher than H. pylori-negative group. Moreover, H. pylori infection is significantly associated with prediabetes, and the incidence of H. pylori in prediabetic patients was significantly higher than nondiabetic patients. Conclusion The incidence of H. pylori infection was significantly higher in T2DM and prediabetes than nondiabetic patients. Moreover, H. pylori was significantly associated with increased HbA1c level. Further studies are needed to evaluate the effect of H. pylori eradication in glycemic control of T2DM and prediabetes and the effect of glycemic control on reinfection with H. pylori.

Patient-related Factors Associated with type-2 Diabetes Mellitus Control in Peri-Urban Primary Care Setting South Africa

Patient-related Factors Associated with type-2 Diabetes Mellitus Control in Peri-Urban Primary Care Setting South Africa

Full title: High glucose protects mesenchymal stem cells from metformin-induced apoptosis through the AMPK-mediated mTOR pathway

Micro- and macro-vascular events are directly associated with hyperglycemia in patients with type 2 diabetes mellitus (T2DM), but whether intensive glucose control decreases the risk of diabetic cardiovascular complications remains uncertain. Many studies have confirmed that impaired quality and quantity of mesenchymal stem cells (MSCs) plays a pathogenic role in diabetes. Our previous study found that the abundance of circulating MSCs was significantly decreased in patients with T2DM, which was correlated with the progression of diabetic complications. In addition, metformin-induced MSC apoptosis is one of the reasons for the decreased quantity of endogenous or exogenous MSCs during intensive glucose control. However, the role of glucose in metformin-induced MSC apoptosis during intensive glucose control in T2DM remains unknown. In this study, we found that metformin induces MSC apoptosis during intensive glucose control, while high glucose (standard glucose control) could significantly reverse its adverse effect in an AMPK-mTOR pathway dependent manner. Thus, our results indicate that the poorer clinical benefit of the intensive glucose control strategy may be related to an adverse effect due to metformin-induced MSC apoptosis during intensive glucose control therapy in patients with T2DM.

Association between lncRNA and GCKR gene in type 2 diabetes mellitus

ObjectiveTo screen long non-coding RNA (lncRNA) related to glucokinase regulatory protein gene (GCKR), its differential expression was analyzed in patients with Type 2 diabetes mellitus (T2DM) and control samples. The correlation of lncRNA with GCKR was verified and its potential value as a molecular marker of T2DM was assessed. MethodsLymphocyte RNA was extracted from five patients with T2DM and five patients with non-T2DM. The expression profiles of circulating lncRNAs and mRNAs were obtained by microarray. Bioinformatics analysis was used to screen lncRNAs associated with the GCKR gene in 127 patients with T2DM and 130 patients with non-T2DM were selected. The expression levels of the GCKR gene and lncRNA (ENST00000588707.1 and TCONS_00004187) in the T2DM group and control group were verified by real-time PCR. Additionally, a correlation analysis was conducted. The value of circulating ENST00000588707.1 and TCONS_00004187 as biomarkers for the diagnosis of T2DM was performed by receiver operating characteristic curve analysis. ResultsWe identified 68 lncRNAs and 74 mRNAs differentially expressed from the expression profile. Compared with the control group, the expression levels of the GCKR gene and lncRNA ENST00000588707.1 and TCONS_00004187 in the T2DM group were significantly lower (P < 0.05). The correlation analysis revealed that ENST00000588707.1 and TCONS_00004187 were correlated with GCKR gene expression and glycolipid metabolism (P < 0.05). ROC analysis showed that the area under the curve value of ENST00000588707.1 between T2DM patients and non-T2DM patients was 0.816 (95% CI: 0.764-0.869, sensitivity 72.0%, specificity 80.3%) and the AUC value of TCONS_00004187 was 0.826 (95% CI: 0.774-0.879, sensitivity 81.6%, specificity 61.3%). ConclusionlncRNA ENST0000588707.1 and TCONS_00004187 could serve as potential biomarkers for T2DM, which could involve in glycolipid metabolism by regulating the GCKR gene.

Prevalence and Monitoring of Diabetes Among Adults with Sickle Cell Disease: A Single Institution Experience

Background: Sickle cell disease (SCD) is the most common hereditary red blood cell disorder in the United States (USA) and primarily affects African-Americans. Of the four most common sickle cell genotypes, SS and Sβ0 are associated with greater severity, including more ischemia due to sickling and more profound microvascular changes from chronic sickling, as compared to those with the Sβ+ and SC genotypes. African-Americans suffer from high rates of Type 2 Diabetes mellitus (T2DM), a disease associated with deleterious microvascular changes when blood glucose is poorly controlled. Recent epidemiologic studies suggest the prevalence of T2DM among African-Americans with and without SCD in the USA are similar around 15-20% and that patients with SCD and T2DM are more likely to be overweight than those without T2DM (Zhou etal., Br J Haematol, 2019). However, the prevalence of diabetes among the different genotypes of SCD remains unknown (Skinner etal., Br J Haematol, 2019). Furthermore, the HbA1C, which is often used to screen, diagnose and monitor long-term control of T2DM in patients is not reliable in patients with SCD and data suggests that fructosamine may be a more reliable marker in this patient population (Smaldone, 2008). If SCD patients with T2DM are undiagnosed or undertreated, they may develop preventable complications related to their vasculopathy. In this study, we assessed both the prevalence of T2DM among adults with various SCD genotypes at our institution and the methods of monitoring long-term control among these patients. Methods: The University of North Carolina (UNC) Sickle Cell Database was used to conduct a single- institution, retrospective cross-sectional study of sickle cell patients and matched controls. A query of electronic medical records identified adult patients &gt; 18 years old with both SCD (SC, Sβ+, SS, or Sβ0) and T2DM seen in the UNC Hospital system in the past 5 years Age, race, gender, BMI, and the frequency of fructosamine and HbA1C values were evaluated. Patients were divided into 2 groups - less severe (SC/Sβ+) vs. more severe (SS/Sβ0). Controls without T2DM were randomly selected from the database and matched 2:1 to cases based on SCD genotype, age, race, and gender for body mass index (BMI) comparisons. Unadjusted statistical tests were used to examine how the group with the more severe SCD genotype (SS/Sβ0) differed from the less severe genotype group (SC/Sβ+) based on T2DM diagnosis and BMI. Results: We identified 444 adult patients with SS, Sβ0, SC, or Sβ+ - 283 patients with more severe SCD (SS/Sβ0) and 161 patients with less severe SCD (SC/Sβ+). Twenty-six patients had a co-diagnosis of T2DM; all identified as African-American (see Table 1). A significantly higher proportion of the less severe SCD group were diagnosed with T2DM as compared to the more severe group (χ2 =10.13, p = 0.001). A higher proportion of patients diagnosed with T2DM and SCD had a BMI of 25kg/m2 (i.e. overweight) or greater (76.9%) compared to matched controls (59.6%, χ2 = 2.29, p = 0.13) (see Table 2). Of the patients diagnosed with SCD and T2DM within our database, 81% had an HbA1C resulted in the EMR within the past 5 years and 62% had a fructosamine resulted during the same time period; in the past 6 months 31% had an HbA1C resulted and 19% of patients had a fructosamine resulted. Conclusion: Patients in the less severe SCD group were more likely to be diagnosed with T2DM in our cohort as compared to the more severe genotype group. Notably, the T2DM prevalence for both the severe group (10.6%) and less severe group (3.2%) was lower than that reported by Zhou et al., 2019, suggesting under diagnosis of T2DM among adults with SCD. Our findings also suggest patients with SCD who are overweight or obese may be at risk for T2DM. Variability in the monitoring of T2DM among SCD patients was evident by the ordering patterns of fructosamine and HbA1C. Hematologists treating patients with SCD should be aware of the inaccuracy of HbA1C in this patient population and ensure patients with SCD and T2DM are monitored appropriately. Further investigation is needed to determine if our findings are applicable to larger cohorts. Disclosures Little: Hemex Health, Inc.: Patents &amp; Royalties; GBT: Research Funding. Carden:GBT: Honoraria; NIH: Research Funding.

Psychological interventions for patients with type 2 diabetes mellitus. A systematic review and meta-analysis

Background Affordable interventions to improve metabolic control of Type 2-Diabetes Mellitus are increasingly necessary. Aim To review systematically the existing literature on the effects of psychological interventions on Type-2 Diabetes Mellitus compensation. Material and Methods We performed a systematic literature review and meta-analysis on the effectiveness of psychological interventions implemented for Type-2 Diabetes Mellitus patients. Research included the following electronic databases: PubMed, Bireme, Web of Science, SciELO, Embase, EBSCOhost, SCOPUS, Psychology Database. Results Most studies showed a decrease in the level of glycated hemoglobin after interventions, which applied different initiatives complementary to standard medical treatment. Mainly, these interventions encompassed training for self-monitoring and control of diabetes based on cognitive behavioral psychology, counseling, self-assessment and physical-spiritual work based on transpersonal psychology. Conclusions Psychological tools could be an adjunct to the standard medical treatment for patients with Type-2 Diabetes Mellitus, reducing glycated hemoglobin levels and improving self-regulation, disease awareness and adherence from the self-efficacy perception perspective.

SLC22A1 And ATM Genes Polymorphisms Are Associated With The Risk Of Type 2 Diabetes Mellitus In Western Saudi Arabia: A Case-Control Study.

IntroductionType 2 diabetes mellitus (T2DM) is a major global health problem that is progressively affected by genetic and environmental factors. The aim of this study is to determine the influence of solute carrier family 22 member 1 (SLC22A1) rs628031 and rs461473, and ataxia telangiectasia mutated (ATM) rs11212617 polymorphisms on the risk of T2DM in Saudi Arabia by considering many parameters associated with glycemic control of T2DM, such as body mass index (BMI), fasting blood glucose, glycated hemoglobin (HbA1c), and triglyceride.MethodsIn a case-control study, genomic DNA from controls and diabetic groups was isolated and genotyped for each single-nucleotide polymorphism.ResultsThere were significant correlations between T2DM and both BMI and HbA1c. Significant associations between G/G and A/G genotypes of rs628031 and rs461473 variants of SLC22A1 and high levels of HbA1c were detected. Therefore, G was predicted to be the risk allele among the assessed SLC22A1 variants. A significant correlation was observed between A/A and A/C genotypes of the rs11212617 polymorphism of ATM and elevated HbA1c. Relative risk calculation confirmed A to be the risk allele in the T2DM population.ConclusionOur study showed the risk of the assessed SLC22A1 and ATM variants on glycemic control parameters in diabetic patients.

Neuregulin-4 is associated with plasma glucose and increased risk of type 2 diabetes mellitus.

Neuregulin-4 is a cytokine with many functions and is primarily produced by fat tissue. The aim of the study was to observe the relationship between serum neuregulin-4 levels and diabetes regulation in type 2 diabetes mellitus (T2DM), and to compare neuregulin-4 levels of diabetic subjects with those in healthy controls. Patients with T2DM were included to the study. Healthy subjects were enrolled as controls. Subjects with T2DM with glycated haemoglobin (HbA1c) <7% were classed as well controlled and those with HbA1c >7% were classed as poorly controlled. Neuregulin-4 levels of the study and control groups were compared. The neuregulin-4 levels of the poorly controlled T2DM, well-controlled T2DM and control groups were significantly different (p = 0.005). Neuregulin-4 was significantly correlated with fasting plasma glucose (r = 0.247, p = 0.002) but not with HbA1c. In a regression analysis model, 0.1 point elevation in neuregulin-4 levels increased the rate of existence of T2DM 4.4-fold (odds ratio 4.4, 95% confidence interval 1.26-15.1; p = 0.02). Neuregulin-4 is significantly increased in patients with T2DM compared with control subjects, which means that it could be a marker of T2DM. Since neuregulin-4 was correlated with fasting glucose, we suggest that elevated neuregulin-4 could predict poor control in T2DM for short periods when HbA1c is not useful.&nbsp; Moreover, one unit elevation in neuregulin-4 (0.1 ng/ml) increases the rate of existence of T2DM 4.4-fold, independently from other variables.