Type 2 Diabetes Subjects Research Articles

Decreased expression of programmed death-1 on CD8+ effector memory T lymphocytes correlates with the pathogenesis of type 1 diabetes.

Chronic inflammation of autoimmune diseases, including type 1 diabetes (T1D), is mainly mediated by memory T(Tm) cells, predominantly effector memory T (Tem) cells. The roles of the programmed death-1 (PD-1) receptor on lymphocytes have been well studied in tumor and other infection models. However, little is known about the relationship between the expression of PD-1 on CD8+ Tem cells and the pathogenesis of T1D. A total of 52 patients diagnosed with T1D and 39 gender-, age-, and ethnically matched health control individuals were enrolled in this study. Peripheral blood mononuclear cells from these individuals were isolated and analyzed by flow cytometry. We evaluated the frequencies of PD-1+ CD8+ memory T cell subsets from patients' peripheral blood with T1D and the spleen cells of nonobese diabetic (NOD) mice in the present study. We also investigated the effects of blocking PD-1/PD-L1 pathway on islet's inflammation in NOD mice. Frequencies of PD-1+ CD8+ Tem cells were decreased significantly in PBMC of patients with T1D (40.73 ± 12.72 vs 47.43 ± 15.56, *p < 0.05). The frequencies of PD-1+ CD8+ Tem cells were decreased in patients with T1D who were positive for two or more autoantibodies compared with the patients with one autoantibody (13.46% vs 46.95 ± 12.72%, *p < 0.05). Meanwhile, the frequencies of PD-1+ CD8+ central memory T (Tcm) cells were also significantly decreased in patients with two or more autoantibodies compared with other groups (≥ 2AAb vs HC 33.1 ± 8.92% vs 43.71 ± 11.78%, *p < 0.05; ≥ 2AAb vs AAb-33.1 ± 8.92% vs 41.65 ± 11.2%, *p < 0.05; ≥ 2AAb vs 1AAb 33.1 ± 8.92% vs 48.09 ± 10.58%, ***p < 0.001). The frequencies of PD-1+CD8+ Tem cells were positively correlated with fasting serum C-peptide levels (r = 0.4308, *p < 0.05) and C-peptide levels 2h after meal in T1D patients (r = 0.5723, **p < 0.01). The frequencies of PD-1+CD8+ Tcm cells were only negatively correlated with the levels of HbA1c (r = -0.2992, *p < 0.05). Similarly, the frequencies of PD-1+CD8+ Tem were significantly decreased in intervention group (anti-mouse PD-1 mAb) compared with the control group (14.22 ± 6.455% vs 27.69 ± 9.837%, *p < 0.05). Pathologically, CD8, PD-1 and PD-L1 were strongly expressed in the islets of diabetic mice after PD-1 blockade. It is the first report of the expression of PD-1 on CD8+ Tem cells in T1D in the present study. Our observations suggest that the PD-1/PD-L1 signal pathway on CD8+ Tem cells of T1D subjects might identify a new pathway for delaying the occurrence and development by inhibiting autoimmunity.

Rapid Improvement in Time in Range After the Implementation of an Advanced Hybrid Closed-Loop System in Adolescents and Adults with Type 1 Diabetes.

Background: Advanced hybrid closed-loop (AHCL) systems represent the next step of automation intended to maximize normoglycemia in people with type 1 diabetes (T1D). In the AHCL MiniMed 780G system, different algorithm glucose targets for insulin infusion are available and autocorrection boluses are delivered. The aim was to prospectively evaluate the impact of the implementation of this AHCL system in a clinical setting. Materials and Methods: T1D subjects using a sensor-augmented pump with predictive low-glucose suspend (SAP-PLGS) were upgraded to AHCL. Baseline, every 3 days, 2-week and 1-month sensor and pump data were downloaded. Glucose target was set to 100 mg/dL and active insulin time to 2 h for all the subjects. Time in different glucose ranges was compared. Results: Fifty-two T1D subjects were included (age: 43 ± 12 years, 73% females, diabetes duration: 27 ± 11 years, HbA1c: 7.2% ± 0.9%, time in SAP-PLGS: 5 ± 2 years). Time in range (TIR) 70-180 mg/dL increased from 67.3% ± 13.6% at baseline to 79.6% ± 7.9% at 1 month (P = 0.001). Time in hyperglycemia >180 and >250 mg/dL decreased from 29.4% ± 15.1% to 17.3% ± 8.6% and from 6.9% ± 7.8% to 2.5% ± 2.4%, respectively (P = 0.001). No differences in time in hypoglycemia <70 or <54 mg/dL were found. Time in Auto Mode was 97% ± 4%, and autocorrection insulin was 31% ± 14% of bolus insulin. Four hours postprandial glucose was improved from 162 ± 26 mg/dL at baseline to 142 ± 16 mg/dL at 1 month (P = 0.001). No severe hypoglycemia or diabetic ketoacidosis episodes occurred. Conclusion: AHCL systems allow well-controlled T1D patients to rapidly increase their TIR. The most aggressive settings allow optimal outcomes in TIR, without increasing hypoglycemia frequency.

Insulin Receptor-Expressing T Cells Appear in Individuals at Risk for Type 1 Diabetes and Can Move into the Pancreas in C57BL/6 Transgenic Mice.

Insulin receptor (IR) expression on the T cell surface can indicate an activated state; however, the IR is also chemotactic, enabling T cells with high IR expression to physically move toward insulin. In humans with type 1 diabetes (T1D) and the NOD mouse model, a T cell-mediated autoimmune destruction of insulin-producing pancreatic β cells occurs. In previous work, when purified IR+ and IR- T cells were sorted from diabetic NOD mice and transferred into irradiated nondiabetic NOD mice, only those that received IR+ T cells developed insulitis and diabetes. In this study, peripheral blood samples from individuals with T1D (new onset to 14 y of duration), relatives at high-risk for T1D, defined by positivity for islet autoantibodies, and healthy controls were examined for frequency of IR+ T cells. High-risk individuals had significantly higher numbers of IR+ T cells as compared with those with T1D (p < 0.01) and controls (p < 0.001); however, the percentage of IR+ T cells in circulation did not differ significantly between T1D and control subjects. With the hypothesis that IR+ T cells traffic to the pancreas in T1D, we developed a (to our knowledge) novel mouse model exhibiting a FLAG-tagged mouse IR on T cells on the C57BL/6 background, which is not susceptible to developing T1D. Interestingly, these C57BL/6-CD3FLAGmIR/mfm mice showed evidence of increased IR+ T cell trafficking into the islets compared with C57BL/6 controls (p < 0.001). This transgenic animal model provides a (to our knowledge) novel platform for investigating the influence of IR expression on T cell trafficking and the development of insulitis.

Safety and Feasibility Evaluation of Step Count Informed Meal Boluses in Type 1 Diabetes: A Pilot Study.

Physical activity can cause glucose fluctuations both during and after it is performed, leading to hurdles in optimal insulin dosing in people with type 1 diabetes (T1D). We conducted a pilot clinical trial assessing the safety and feasibility of a physical activity-informed mealtime insulin bolus advisor that adjusts the meal bolus according to previous physical activity, based on step count data collected through an off-the-shelf physical activity tracker. Fifteen adults with T1D, each using a continuous glucose monitor (CGM) and an insulin pump with carbohydrate counting, completed two randomized crossover daily visits. Participants performed a 30 to 45-minute brisk walk before lunch and lunchtime insulin boluses were calculated based on either their standard therapy (ST) or the physical activity-informed bolus method. Post-lunch glycemic excursions were assessed using CGM readings. There was no significant difference between visits in the time spent in hypoglycemia in the post-lunch period (median [IQR] standard: 0 [0]% vs physical activity-informed: 0 [0]%, P = NS). Standard therapy bolus yielded a higher time spent in 70 to 180 mg/dL target range (mean ± standard: 77% ± 27% vs physical activity-informed: 59% ± 31%, P = .03) yet, it was associated with a steeper negative slope in the early postprandial phase (P = .032). Use of step count to adjust mealtime insulin following a walking bout has proved to be safe and feasible in a cohort of 15 T1D subjects. Physical activity-informed insulin dosing of meals eaten soon after a walking bout has a potential of mitigating physical activity related glucose reduction in the early postprandial phase.

Plasma heat shock protein response to euglycemia in type 2 diabetes

IntroductionGlucose variability is associated with mortality and macrovascular diabetes complications. The mechanisms through which glucose variability mediates tissue damage are not well understood, although cellular oxidative stress is likely involved....

Platelet Protein-Related Abnormalities in Response to Acute Hypoglycemia in Type 2 Diabetes.

IntroductionPatients with severe COVID-19 infections have coagulation abnormalities indicative of a hypercoagulable state, with thromboembolic complications and increased mortality. Platelets are recognized as mediators of inflammation, releasing proinflammatory and prothrombotic factors, and are hyperactivated in COVID-19 infected patients. Activated platelets have also been reported in type 2 diabetes (T2D) patients, putting these patients at higher risk for thromboembolic complications of COVID-19 infection.MethodsA case-control study of T2D (n=33) and control subjects (n=30) who underwent a hyperinsulinemic clamp to induce normoglycemia in T2D subjects: T2D: baseline glucose 7.5 ± 0.3mmol/l (135.1 ± 5.4mg/dl), reduced to 4.5 ± 0.07mmol/l (81 ± 1.2mg/dl) with 1-hour clamp; Controls: maintained at 5.1 ± 0.1mmol/l (91.9 ± 1.8mg/dl). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was used to determine a panel of platelet proteins.ResultsProthrombotic platelet proteins were elevated in T2D versus controls: platelet factor 4 (PF4, p<0.05); platelet glycoprotein VI (PGVI p<0.05); P-selectin (p<0.01) and plasminogen activator inhibitor I (PAI-1, p<0.01). In addition, the antithrombotic platelet-related proteins, plasmin (p<0.05) and heparin cofactor II (HCFII, p<0.05), were increased in T2D. Normalization of glucose in the T2D cohort had no effect on platelet protein levels.ConclusionT2D patients have platelet hyperactivation, placing them at higher risk for thromboembolic events. When infected with COVID-19, this risk may be compounded, and their propensity for a more severe COVID-19 disease course increased.Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT03102801, identifier NCT03102801.

Serum uric acid measurement and its correlation with urinary albumin-creatinine ratio in type-2 Diabetic subjects

Increased serum uric acid (SUA) is known to play a critical role in the development of type-2 diabetes mellitus (T2DM) as well as in progression of its complications. Hyperuricemia is an independent risk factor for kidney dysfunction in patients with diabetes. The appearance of albuminuria is the first sign of kidney damage and the mechanisms of hyperuricemia-induced renal injury mainly include oxidative stress, endothelial dysfunction, renal fibrosis, and inflammation. To determine the possible association of SUA with urinary albumin-creatinine ratio (ACR) in type-2 diabetic subjects, data with lab investigations of SUA and urinary ACR of 95 confirmed and known cases of T2DM were collected from the laboratory medicine department, DMWIMS Hospital, Wayanad Kerala. Based on the urinary albumin excretion values, diabetic subjects were divided into three groups (Normoalbuminuric, microalbuminuric &amp; macroalbuminuric groups). A significant increase in mean ACR from group-1--&gt;group-2--&gt;group- 3 was observed which is proportional to an increase in mean SUA levels suggesting that increase in SUA may be responsible for increased urinary albumin excretion. This study shows a positive correlation between SUA and ACR. Keywords: Serum uric acid; diabetes mellitus; hyperuricemia; kidney damage; T2DM; albuminuria; urinary albumin-creatinine ratio; diabetic nephropathy

Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes.

Insulin resistance is defined as a complex pathological condition of abnormal cellular and metabolic response to insulin. Obesity and consumption of high-fat diet lead to ectopic accumulation of bioactive lipids in insulin-sensitive tissues. Intracellular lipid accumulation is regarded as one of the major factors in the induction of insulin resistance and type 2 diabetes (T2D). A significant number of studies have described the involvement of ceramides and other sphingolipids in the inhibition of insulin-signaling pathway in both skeletal muscles and the liver. Adverse effects of sphingolipid accumulation have recently been linked to the activation of protein kinase Cζ (PKCζ) and protein phosphatase 2A (PP2A), which, in turn, negatively affect phosphorylation of serine/threonine kinase Akt [also known as protein kinase B (PKB)], leading to decreased glucose uptake in skeletal muscles as well as increased gluconeogenesis and glycogenolysis in the liver. Sphingolipids, in addition to their direct impact on the insulin signaling pathway, may be responsible for other negative aspects of diabetes, namely mitochondrial dysfunction and deficiency. Mitochondrial health, which is characterized by appropriate mitochondrial quantity, oxidative capacity, controlled oxidative stress, undisturbed respiratory chain function, adenosine triphosphate (ATP) production and mitochondrial proliferation through fission and fusion, is impaired in the skeletal muscles and liver of T2D subjects. Recent findings suggest that impaired mitochondrial function may play a key role in the development of insulin resistance. Mitochondria stay in contact with the endoplasmic reticulum (ER), Golgi membranes and mitochondria-associated membranes (MAM) that are the main places of sphingolipid synthesis. Moreover, mitochondria are capable of synthesizing ceramide though ceramide synthase (CerS) activity. Recently, ceramides have been demonstrated to negatively affect mitochondrial respiratory chain function and fission/fusion activity, which is also a hallmark of T2D. Despite a significant correlation between sphingolipids, mitochondrial dysfunction, insulin resistance and T2D, this subject has not received much attention compared to the direct effect of sphingolipids on the insulin signaling pathway. In this review, we focus on the current state of scientific knowledge regarding the involvement of sphingolipids in the induction of insulin resistance by inhibiting mitochondrial function.

To Study the Comparison of Liver Function Variables among Type-2 Diabetic Patients and Non Diabetic Subjects in a Tertiary Care Hospital of Western Rajasthan

To Study the Comparison of Liver Function Variables among Type-2 Diabetic Patients and Non Diabetic Subjects in a Tertiary Care Hospital of Western Rajasthan

Parallel Multi-Omics in High-Risk Subjects for the Identification of Integrated Biomarker Signatures of Type 1 Diabetes.

Background: Biomarkers are crucial for detecting early type-1 diabetes (T1D) and preventing significant β-cell loss before the onset of clinical symptoms. Here, we present proof-of-concept studies to demonstrate the potential for identifying integrated biomarker signature(s) of T1D using parallel multi-omics. Methods: Blood from human subjects at high risk for T1D (and healthy controls; n = 4 + 4) was subjected to parallel unlabeled proteomics, metabolomics, lipidomics, and transcriptomics. The integrated dataset was analyzed using Ingenuity Pathway Analysis (IPA) software for disturbances in the at-risk subjects compared to controls. Results: The final quadra-omics dataset contained 2292 proteins, 328 miRNAs, 75 metabolites, and 41 lipids that were detected in all samples without exception. Disease/function enrichment analyses consistently indicated increased activation, proliferation, and migration of CD4 T-lymphocytes and macrophages. Integrated molecular network predictions highlighted central involvement and activation of NF-κB, TGF-β, VEGF, arachidonic acid, and arginase, and inhibition of miRNA Let-7a-5p. IPA-predicted candidate biomarkers were used to construct a putative integrated signature containing several miRNAs and metabolite/lipid features in the at-risk subjects. Conclusions: Preliminary parallel quadra-omics provided a comprehensive picture of disturbances in high-risk T1D subjects and highlighted the potential for identifying associated integrated biomarker signatures. With further development and validation in larger cohorts, parallel multi-omics could ultimately facilitate the classification of T1D progressors from non-progressors.

Real-world outcomes with different technology modalities in type 1 diabetes

Background and aimsSeveral treatment modalities are available for type 1 diabetes (T1D), including continuous glucose monitoring (CGM) and flash glucose monitoring (FGM) with MDI, sensor-augmented pumps with predictive low-glucose suspend function (SAP-PLGS) and hybrid closed-loop systems (HCL). The aim of the study was to evaluate the real-world benefits obtained with these treatment modalities. Methods and resultsA cross-sectional study was performed, selecting 4 groups of T1D subjects, regarding their treatment modalities, paired by age, sex and diabetes duration. A comparison was performed, concerning time in different glucose ranges in 2-week sensor downloads. Estimated HbA1c, glycaemic variability measures and sensor use were also compared.302 T1D people were included (age: 39 ± 12 years, 47% male, diabetes duration: 21 ± 10 years, estimated HbA1c: 7.28 ± 0.84% (56 ± 9 mmol/mol), baseline HbA1c: 7.4 ± 1.0% (57 ± 11 mmol/mol), length of use of the device 8 [3−21] months). Group 1 (CGM + MDI) and 2 (FGM + MDI) showed no differences in time in different glucose ranges. Group 4 (HCL) showed a higher time 70–180 mg/dl and a lower time in hypoglycaemia than group 3 (SAP-PLGS). Group 1 and 2 showed lower time 70–180 mg/dl, higher time in hyperglycaemia and higher glycaemic variability measures than group 3. Group 4 was superior to groups 1 and 2 in all the outcomes. ConclusionReal-life achievements in glycaemic control and glycaemic variability are described. HCL offer the maximum benefit in terms of time in range and hypoglycaemia protection, compared to CGM + MDI, FGM + MDI and SAP-PLGS.

Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study

BackgroundEmpagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has demonstrated cardiovascular and renal protection in patients with type 2 diabetes (T2D). We hypothesized that empaglifozin (EMPA) could modulate ectopic fat stores and myocardial energetics in high-fat-high-sucrose (HFHS) diet mice and in type 2 diabetics (T2D).MethodsC57BL/6 HFHS mice (n = 24) and T2D subjects (n = 56) were randomly assigned to 12 weeks of treatment with EMPA (30 mg/kg in mice, 10 mg/day in humans) or with placebo. A 4.7 T or 3 T MRI with 1H-MRS evaluation–myocardial fat (primary endpoint) and liver fat content (LFC)–were performed at baseline and at 12 weeks. In humans, standard cardiac MRI was coupled with myocardial energetics (PCr/ATP) measured with 31P-MRS. Subcutaneous (SAT) abdominal, visceral (VAT), epicardial and pancreatic fat were also evaluated.The primary efficacy endpoint was the change in epicardial fat volume between EMPA and placebo from baseline to 12 weeks. Secondary endpoints were the differences in PCr/ATP ratio, myocardial, liver and pancreatic fat content, SAT and VAT between groups at 12 weeks.ResultsIn mice fed HFHS, EMPA significantly improved glucose tolerance and increased blood ketone bodies (KB) and β-hydroxybutyrate levels (p < 0.05) compared to placebo. Mice fed HFHS had increased myocardial and liver fat content compared to standard diet mice. EMPA significantly attenuated liver fat content by 55%, (p < 0.001) but had no effect on myocardial fat.In the human study, all the 56 patients had normal LV function with mean LVEF = 63.4 ± 7.9%. Compared to placebo, T2D patients treated with EMPA significantly lost weight (− 2.6 kg [− 1.2; − 3.7]) and improved their HbA1c by 0.88 ± 0.74%. Hematocrit and EPO levels were significantly increased in the EMPA group compared to placebo (p < 0.0001, p = 0.041). EMPA significantly increased glycosuria and plasma KB levels compared to placebo (p < 0.0001, p = 0.012, respectively), and significantly reduced liver fat content (− 27 ± 23 vs. − 2 ± 24%, p = 0.0005) and visceral fat (− 7.8% [− 15.3; − 5.6] vs. − 0.1% [− 1.1;6.5], p = 0.043), but had no effect on myocardial or epicardial fat. At 12 weeks, no significant change was observed in the myocardial PCr/ATP (p = 0.57 between groups).ConclusionsEMPA effectively reduced liver fat in mice and humans without changing epicardial, myocardial fat or myocardial energetics, rebutting the thrifty substrate hypothesis for cardiovascular protection of SGLT2 inhibitors.Trial registration NCT, NCT03118336. Registered 18 April 2017, https://clinicaltrials.gov/ct2/show/NCT03118336

Renal function, serum magnesium levels and mortality in COVID-19 patients with type 2 diabetes.

Patients with type 2 diabetes (T2D) and Latin American subjects in particular are at an increased risk of developing severe COVID-19 and mortality. Altered renal function and lower magnesium levels have been reported to play important roles in the pathophysiology of T2D. The aim of the study was to investigate the relationship between renal function, serum magnesium levels and mortality in T2D patients with COVID-19. In this retrospective study, we characterized 118 T2D and non-diabetic subjects hospitalized with COVID-19. Patients were clinically characterized and electrolyte, renal function and inflammatory markers were evaluated. Patients were grouped according to their estimated glomerular filtration rate (eGFR <60 mL/min per 1.73 m2). T2D patients had lower eGFR and serum magnesium levels when compared to non-diabetics (59.7 ± 32.8 vs. 78.4 ± 33.8 mL/min per 1.73 m2, P = 0.008 and 1.9 ± 0.3 vs. 2.1 ± 0.3 mEq/L, P = 0.012). Survival was worse in T2D patients with eGFR levels less than 60 mL/min per 1.73 m2 as estimated by Kaplan-Meier analyses (log-rank test <0.0001). The Cox model for T2D patients showed that eGFR (HR 0.970, 95% CI 0.949 to 0.991, P = 0.005) and magnesium (HR 8.025, 95% CI 1.226 to 52.512, P = 0.030) were associated with significantly increased risk of death. Reduced eGFR and magnesium levels were associated with increased mortality in our population. These results suggest that early assessment of kidney function, including magnesium levels, may assist in developing effective treatment strategies to reduce morbidity and mortality among Latin American COVID-19 patients with T2D.

Frequencies of CD8 and DN MAIT Cells Among Children Diagnosed With Type 1 Diabetes Are Similar to Age-Matched Controls.

Mucosal-associated invariant T (MAIT) cells have been implicated in various forms of autoimmunity, including type 1 diabetes (T1D). Here, we tested the hypothesis that CD8 and double negative (DN) MAIT cell frequencies were altered among diagnosed T1D subjects compared to controls. To do this, we analyzed cryopreserved peripheral blood mononuclear cells (PBMCs) from age-matched T1D and control children using flow cytometry. We observed that CD8 and DN MAIT cell frequencies were similarly abundant between the two groups. We tested for associations between MAIT cell frequency and T1D-associated parameters, which could reveal a pathogenic role for MAIT cells in the absence of changes in frequency. We found no significant associations between CD8 and DN MAIT cell frequency and levels of islet cell autoantibodies (ICA), glutamate decarboxylase 65 (GAD65) autoantibodies, zinc transporter 8 (ZNT8) autoantibodies, and insulinoma antigen 2 (IA-2) autoantibodies. Furthermore, CD8 and DN MAIT cell frequencies were not significantly associated with time since diagnosis, c-peptide levels, HbA1c, and BMI. As we have examined this cohort for multiple soluble factors previously, we tested for associations between relevant factors and MAIT cell frequency. These could help to explain the broad range of MAIT frequencies we observed and/or indicate disease-associated processes. Although we found nothing disease-specific, we observed that levels of IL-7, IL-18, 25 (OH) vitamin D, and the ratio of vitamin D binding protein to 25 (OH) vitamin D were all associated with MAIT cell frequency. Finally, previous cytomegalovirus infection was associated with reduced CD8 and DN MAIT cells. From this evaluation, we found no connections between CD8 and DN MAIT cells and children with T1D. However, we did observe several intrinsic and extrinsic factors that could influence peripheral MAIT cell abundance among all children. These factors may be worth consideration in future experimental design.

Role of PDT as an adjunct to SRP on whole salivary RANKL and OPG ratio in type-2 diabetic and normoglycemic individuals with chronic periodontitis.

The aim was to assess the effect of scaling and root planing (SRP) with and without adjunct photodynamic therapy (PDT) on the levels of osteoprotegerin (OPG) receptor activator of NF-kappa B ligand (RANKL) in the unstimulated whole saliva (UWS) of type-2 diabetic and normoglycemic individuals with chronic periodontitis (CP). Type-2 diabetic and normoglycemic subjects with CP (Groups 1 and 2, respectively) were divided into test- (SRP + PDT) and control (SRP only) groups. Patient demographics were recorded; and periodontal parameters (marginal bone loss [MBL], probing depth [P.D], plaque index [PI], gingival index [GI], and clinical attachment loss [CAL]) were assessed at baseline and at 3-months-follow-up. Rate of flow of unstimulated whole saliva and levels of RANKL and osteoprotegerin were measured at both time intervals. P < 0.05 was considered statistically significant. Eighty-four persons with CP (42 with and 42 without type-2 DM) were included. At baseline, clinicoradiographic parameters were comparable in all groups. At 3-months of follow-up, there was no significant difference in the clinicoradiographic parameters in all groups. At 3-months of follow-up, there was no significant reduction in whole salivary RANKL and osteoprotegerin levels among individuals in the test and control groups among CP patients with and without CP. The whole salivary RANKL/OPG ratio remains high in patients with poorly-controlled type-2 DM after SRP with or without adjunct PDT.

STUDY OF SERUM VITAMIN-D IN TYPE-2 DIABETES MELLITUS PATIENTS.

Background: Type-2 diabetes mellitus (T2DM) is a progressive and chronic disease characterized by both β-cell dysfunction and increased insulin resistance. Diabetes mellitus is now considered a giant killer disease of the 21st century with its vicious prongs in the South-East Asian countries, specially India, which is rightly said to be the ''Diabetes Capital'' of the world. Vitamin D has important effects on insulin action, and may impact on a number of pathways which may be of importance in the development of type 2 diabetes mellitus. Materials &amp; Methods: In this study 62 Type-2 diabetic patients, 62 healthy controls were enrolled. Biochemical analytes measured were Serum glucose (Fasting Blood Sugar &amp; Post Prandial Blood Sugar), Glycosylated Haemoglobin, Serum Vitamin-D. Results: The mean Serum Vitamin-D in Type-2 diabetic subjects were (16.3 ±3.0) while in healthy subjects(controls) the values were (39.3±5.2) respectively. These values were found to be statistically highly signicant(p&lt;0.001). Conclusion: Serum Vitamin-D levels were decreased in Type 2 diabetic subjects as compared to the values in healthy subjects(controls).

Association of ADIPOQ rs266729 and rs1501299 gene polymorphisms and circulating adiponectin level with the risk of type 2 diabetes in a population of Iran: a case-control study.

Mutation in various regions of the adiponectin (ADIPOQ) gene is described to be associated with type 2 diabetes (T2D). Our aim was to investigate the association between rs1501299 (SNP + 276G > T) and rs266729 (SNP-11377 C > G) polymorphisms of ADIPOQ gene and susceptibility to T2D in an Iranian population. This is a case-control study. A total of 210 subjects including 100 patients with T2D and 110 healthy controls were selected from an Iranian population. SNP-11377 C > G and SNP + 276G > T polymorphisms were investigated using the Tetra ARMS-PCR method. The genotypes frequency of the SNP-11377 C > G polymorphism (P = 0.21) and SNP + 276G > T polymorphism (P = 0.10) were in agreement with the Hardy-Weinberg equilibrium. The genotype and allele frequencies for rs266729 polymorphism showed a significant difference between the T2D and control groups. Further, the frequencies of the genotypes of GG (OR = 2.43, P = 0.031), GG + GG (OR = 2.11, P < 0.01) and G allele (OR = 1.6, P = 0.041) in SNP-11377 C > G polymorphism was significantly associated with an increased risk of T2D compared to control group. While, there was no significant association between the different genotypes of SNP + 276G > T polymorphism and the risk of T2D in an Iranian population. The circulating adiponectin level in T2D subjects had significant difference compared to the control group in rs266729 polymorphism. We concluded that ADIPOQ rs266729 (SNP-11377 C > G) gene polymorphism but no rs1501299 is associated with increased risk of T2D in our population.

TCR+/BCR+ dual-expressing cells and their associated public BCR clonotype are not enriched in type 1 diabetes

Ahmed and colleagues recently described a novel hybrid lymphocyte expressing both a B and Tcell receptor, termed double expresser (DE) cells. DE cells in blood of type 1 diabetes (T1D) subjects were present at increased numbers and enriched for a public B cell clonotype. Here, we attempted to reproduce these findings. While we could identify DE cells by flow cytometry, we found no association between DE cell frequency and T1D status. We were unable to identify the reported public B cell clone, or any similar clone, in bulk B cells or sorted DE cells from T1D subjects or controls. We also did not observe increased usage of the public clone VH or DH genes in B cells or in sorted DE cells. Taken together, our findings suggest that DE cells and their alleged public clonotype are not enriched in T1D. This Matters Arising paper is in response to Ahmed etal. (2019), published in Cell. See also the response by Ahmed etal. (2021), published in this issue.

The Psychometric Properties of General Adherence Scale in Chinese (GAS-C) in Patients with Type 2 Diabetes Using Insulin.

PurposeTranslate General Adherence Scale (GAS) into Chinese and test its psychometric properties in middle-aged and elderly type 2 diabetes (T2D) patients using insulin in the Han people of urban China.Subjects and MethodsWe translated the GAS into Chinese and established General Adherence Scale in Chinese (GAS-C). 136 T2D subjects were selected for testing GAS-C’s reliability and validity, of which 100 study subjects were retested with GAS-C two weeks later. The other 200 T2D subjects were selected for performing Confirmatory Factor Analysis(CFA). The ceiling effect and floor effect of GAS-C data were checked.ResultsNo data was lost in our research. In exploratory factor analysis(EFA), the Kaiser-Meyer-Olkin measure of sampling adequacy (KMO) =0.899, Bartlett’s Test’s χ2=611.821 (df=10 p<0.001). The communalities of the items were between 0.740 and 0.862; The values of Measure of Sampling Adequacy (MSA) were between 0.883 and 0.945. All five items entered the factor analysis process. A common factor was extracted, and it could explain 81.403% of the total variance. CFA validated the.one-factor model was good fits with the data of GAS-C (Ratio of Chi-square to Degrees of Freedom (CMIN/DF)=2.032, Goodness of Fit Index (GFI) =0.981, Comparative Fit Index (CFI) =0.996, Tucker–Lewis Index (TLI) =0.992, Root Mean Square Residual (RMR) =0.011, Root Mean Square Error of Approximation (RMSEA) =0.072). Correlation analysis was performed between GAS-C and MMAS-8 to calculate the criterion-related validity (r=0.542 p<0.001). The internal consistency reliability α=0.942, Intraclass Correlation Coefficient (ICC)= 0.941 (95% CI 0.924–0.955). The correlation coefficient r of the test-retest reliability was 0.772 (p<0.001). Spearman-Brown coefficient of split-half was 0.939. There was no floor effect and ceiling effect on the data.ConclusionGAS-C has good reliability and validity. It can be used for general adherence studies of middle-aged and elderly type 2 diabetic patients using insulin in the Han people of Chinese cities.

Epigenome-Wide Association Study Identifies Differentially Methylated Sites and Pathways Associated with Antidiabetic Drugs in Subjects with Metabolic Syndrome

Background: Hyperglycaemia can strongly alter the epigenetic signatures in many tissues, influencing cardiovascular risk. Several epigenome-wide association studies (EWAS) have identified differentially methylated regions between type-2 diabetic (T2D) subjects and non- diabetic controls. However, EWAS in subjects with metabolic syndrome (MS) depending on T2D and medications used are still scarce. Our aim was to identify methylation signatures and pathways in subjects with MS depending on the T2D status and diabetes treatment. Methods: We studied 414 subjects with metabolic syndrome (aged 55-75 years) from a Mediterranean population (Predimed Plus-Valencia study). We considered 5 groups: 61% non- diabetics, 3% T2D treated with lifestyle; 27% TD2 on metformin, 4.5%TD2 on other drugs (different from insulins) and 5%T2D on insulin (plus other medications). We analyzed the whole DNA methylation by the Illumina EPIC methylation array (850K methylation sites). After quality control, EWAS were carried out using the Partek Genomic suite and pathway enrichment analysis with KEGG. Results: After adjustment for batch effect, sex, age, BMI and smoking, we obtained statistically significant differences of M-values when comparing the 5 groups. The top-ranked were: cg27024081 (in LARS; P=3.4x10-14); cg06611426 (GRASP; P=6.8x10-9) and cg17385679 (SNPS2; P=1.1x10-8). Pathway enrichment analysis identified as more relevant these pathways: Base excision repair (P=3.7x10-13); mTOR signaling pathway (P=5x10-5) and Basal cell carcinoma (P<0.01); Likewise, compared only T2D subjects receiving different treatments, obtaining as top-ranked the Hypertrophic cardiomyopathy and the Dilated cardiomyopathy pathways. Conclusion: Our results indicate a strong influence of hyperglycemia and T2D drugs on methylation including genes in both T2D and cardiovascular diseases.