Type 2 Diabetes Subjects Research Articles

Taste Perception and Sweet Taste Preference in Type-2 Diabetic Subjects: Genomic And Metabolomic Factors Involved

Taste Perception and Sweet Taste Preference in Type-2 Diabetic Subjects: Genomic And Metabolomic Factors Involved

An Atypical Form of Diabetes Among Low Body Mass Index Individuals in India

Background: Diabetes among low BMI individuals has been recognized for over 60 years as an entity that is prevalent in low- and middle-income countries (LMICs), and formally classified as Malnutrition-Related Diabetes Mellitus by the World Health Organization (WHO) in 1985. However, the WHO withdrew this category in 1999, citing a lack of supportive evidence. Definitive metabolic characterization of these individuals is therefore essential to establish that this is a distinct form of diabetes. Methods: State-of-the-art, dynamic metabolic studies were used to characterize a group of underweight (BMI 18.3±0.2 kg/m2) Southern Indian individuals with diabetes (“Low BMI Diabetes”; LD) in whom all currently known forms of diabetes were excluded by careful immunogenetic analysis. They were compared with four demographically-matched groups: type 1 diabetes (T1D), type 2 diabetes (T2D), and two groups of non-diabetic subjects who were BMI-matched to LD and T2D. To overcome ‘glucose toxicity‘, all subjects with diabetes underwent correction of hyperglycemia. Insulin secretion was assessed by C-peptide deconvolution, following a mixed-meal tolerance test. Hepatic and peripheral insulin sensitivity were analyzed using tracer-based stepped hyperinsulinemic-euglycemic pancreatic clamp studies. Body composition was measured by Dual Energy Absorptiometry (DEXA) and hepatic and myocellular lipid contents were assessed by 1 H-nuclear-magnetic-resonance-spectroscopy. Findings: Metabolic profiles of LD subjects were distinct from T1D and T2D. Insulin secretion was substantially lower in LD than in T2D, yet higher than in T1D. Although insulin sensitivity varied among LD subjects, they were more insulin sensitive than T2D subjects. Their peripheral insulin sensitivity did not differ from T1D subjects. Endogenous glucose production, a marker of hepatic insulin resistance, was similar in LD compared to T1D subjects, yet lower than in T2D. LD subjects also showed heterogeneity of visceral adipose tissue (VAT) and hepatocellular fat, with VAT averaging higher than T1D subjects, while both were significantly lower than T2D subjects. Additionally, compared to lean-nondiabetic subjects, LD subjects had lower insulin secretion, similar peripheral and hepatic insulin sensitivity, and higher VAT and hepatocellular fat. Interpretation: These studies are the first to demonstrate that low BMI individuals with diabetes in LMICs have a unique metabolic profile. Following correction of glucose toxicity, these individuals are characterized by markedly impaired insulin secretion, variable peripheral insulin sensitivity, and heterogeneity in visceral and hepatocellular triglyceride levels. These findings demonstrate that diabetes among low BMI individuals in LMICs is a distinct entity that warrants further investigation. Funding Information: This study was supported by the Global Diabetes Institute of the Albert Einstein College of Medicine. Declaration of Interests: None declared. Ethics Approval Statement: These comprehensive metabolic studies were performed at the Department of Endocrinology, Christian Medical College (CMC) Vellore, India, in collaboration with the Global Diabetes Institute, Albert Einstein College of Medicine, New York, USA. Approval was obtained from the Institutional Review Boards of both institutions. The objectives of the study were explained to all participants and informed consent was obtained. The study protocol was conducted in accordance to the declaration of Helsinki.

Expression-Based Genome-Wide Association Study Links Osteopontin and Interleukin 1 Receptor Antagonist With Newly Diagnosed Type 1 Diabetes in Children

Background: Islet autoantibodies (IAbs) are currently most reliable indicators of islet autoimmunity. However, IAbs do not fully meet the need for the prediction and intervention of type 1 diabetes (T1D). We assumed that secreted proteins associated with T1D are great sources for serum biomarkers. Methods: In an attempt to identify additional biomarkers, we performed an expression-based genome-wide association study (eGWAS) using microarray data from 169 arrays of the pancreatic islets of T1D rodents (78 T1D cases and 91 controls). We ranked all 16,099 protein-coding genes by the likelihood of differential expression in the pancreatic islets. Our top 20 secreted proteins were screened using the serum samples from newly diagnosed children with diabetes. First, we screened 20 selected candidates with 170 sera including 100 T1D, and 50 type 2 diabetes (T2D) and 20 age matched healthy children. With 6 proteins showing significance, we further did validation study using the second independent set of 400 samples from newly diagnosed children with diabetes and age matched controls including 200 T1D, 100 T2D, and 100 age-matched controls. Findings: We identified 2 serum proteins were significantly changed in T1D vs both control and T2D and 5 serum proteins were significantly changed in both T1D and T2D vs control. Serum Osteopontin (OPN) levels were uniquely higher in T1D (p<0.0001) with no difference between T2D and healthy control subjects. Serum Interleukin 1 receptor antagonist (IL-1RA) levels were lower in T1D compared with both T2D (p<0.001) and healthy subjects (p<0.0001). Interpretation: Our results suggest that OPN and IL1RA could be the candidates of useful biomarkers for T1D in children. Funding Information: Juvenile Diabetes Research Foundation (JDRF) grant (2-SRA-2019-695-S-B), Diabetes Research Center (DRC) grant P30 DK116073. Declaration of Interests: No potential conflicts of interest relevant to this article were reported. The authors declare no conflict of interest associated with this manuscript. Ethics Approval Statement: Signed written informed consents were obtained from participants and the studies were approved by the Institutional Review Board of the University of Colorado.

Modeling of glycogen resynthesis according to insulin concentration: towards a system for prevention of late-onset exercise-induced hypoglycemia in Type 1 diabetes patients

One of the major barriers for physical activity in type 1 diabetes (T1D) patients is the risk of exercise-induced hypoglycemia, in particular the late-onset one. The identification of the relation between glycogen resynthesis rate after an exercise and insulin concentration would allow the development of new predictive models. The aim of the present work was thus to investigate this relation in T1D patients. We recruited 8 T1D subjects which underwent two 24-h observational experimental sessions: complete rest and a 3-hours treadmill walk. Glucose and insulin concentrations were measured throughout the two sessions. Comparing the data collected in the two sessions, the net glucose uptake was calculated; positive values were suggestive of glycogen repletion while negative values suggested liver glycogen breakdown. A significant correlation (r=0.742, p<0.001) was observed between insulin concentration and net glucose uptake, with the negative values corresponding to time periods showing the lowest insulin concentrations. In conclusion, the present study preliminarily assessed the impact of insulin concentration on the risk of late onset hypoglycemia, which is the first step towards a comprehensive and personalized system for prevention of exercise-induced hypoglycemia in Type 1 diabetes patients.

Common Variants Associated to Type 2 Diabetes in the Italian Population

Genome-wide association studies have identified numerous genetic variants for type 2 diabetes (T2D). Most genetic loci discovered to date were studied in Caucasians or Asian ancestry, however, there are no data regarding a quite large Italian sample. Therefore, we investigated T2D genetic susceptibility of 143 single nucleotide polymorphisms (SNPs) within 30 genes involved in glucose metabolism in a large Italian case-control study. For the study, 1875 Caucasian patients were selected from three Italian cohorts. Age, gender, BMI and fasting plasma glucose (FPG) values were collected. Population was split in cases and controls based on FPG values or T2D diagnosis. T2D subjects and whom with FPG higher that 126 mg/dL were recruited as cases whereas subjects with normal values of FPG were considered controls. In each subject 143 SNPs were genotyped. To evaluate the association between genetic variations and diabetes status, a logistic regression analysis, adjusted for age, sex and BMI, was performed. Overall, 948 (50.6%) had T2D. Twenty out of 143 variants within 11 different genes resulted significantly associated to T2D. Four of them were located into TCF7L2 gene and presented the highest odd ratio (from 1.42 to 1.57). At least two SNPs were located within KCNJ11, WFS1, ABCC8, JAZF1 and HNF1B genes and one SNP each was identified in ADAMTS9, IGF2BP2, FTO, G6PC2 and GCK genes. Our findings support the role of 11 genes involved in glucose homeostasis in T2D risk development in a large Italian population. We found that such genetic information may be advantageous for predicting T2D.

A Comparison of Neuropathy Quality of Life Tools: Norfolk QOL-DN, PN-QOL-97, and NeuroQOL-28

Aims To explore the effectiveness of the Norfolk QOL-DN (QOL-DN), PN-QOL-97, and NeuroQOL-28 as tools for early detection of diabetic peripheral neuropathy in overweight, obese, and inactive (OOI), prediabetes (PD), and type 2 diabetes (T2D) individuals. Methods Thirty-four adults were divided by A1C [(10 OOI, 13 PD, and 11 T2D] and the sural nerves were tested bilaterally via NC-Stat DPN Check, conducting a sural nerve conduction study (NCS). Participants were individually timed, filling out questionnaires (QOL-DN, NeuroQOL-28, and PN-QOL-97) at a self-selected pace. Data were analyzed and compared to NCS findings to determine the best instrument for early neuropathy detection, usability in screening settings, and application for individuals with OOI, PD, and T2D. Results Abnormal NCS results were obtained from 27 individuals, of which 25 were bilateral and symmetrical. Confirmed DSPN criteria were met for 24, and 1 case met criteria for subclinical neuropathy. Normal NCS findings, reported symptoms, and reduced bilateral sensation were found in 7 cases. The QOL-DN and NeuroQOL-28 significantly predict neuropathy criteria in OOI, PD, and T2D subjects. Analyses revealed the QOL-DN as the quickest for completion (M=5.17; SD=1.83), followed by the NeuroQOL-28 (M=5.58; SD=3.56), and the PN-QOL-97 (M=13.23; SD=3.606). Conclusions The QOL-DN and NeuroQOL-28 are valid early screening measures for DPN detection. Time completion studies revealed that the QOL-DN and NeuroQOL-28 may be used as excellent short screening measures, completed in approximately 6 minutes or less, with reasonable scoring for both. The NeuroQOL-28 is a better fit for immediate feedback, time constraints, or limited staff. Future investigations should evaluate these tools for detection in DPN-prone individuals and in subclinical populations screenings.

Organ-Specific Metabolic Pathways Distinguish Prediabetes, Type 2 Diabetes and Normal Tissues

Defects in pancreatic islets and the progression of multi-tissue insulin resistance in combination with environmental factors are the main causes of type 2 diabetes (T2D). Mass spectrometry-based proteomics of five key-metabolic tissues on a cohort of 42 multi-organ donors provided deep coverage of the proteomes of pancreatic islets, visceral adipose tissue (VAT), liver, skeletal muscle and serum. Enrichment analysis of gene ontology (GO) terms built a tissue-specific map of the chronological order of altered biological processes across healthy controls (CTRL), pre-diabetes (PD) and T2D subjects. This unique dataset allowed us to explore alterations of entire biological pathways and individual proteins in multiple tissues. We confirmed the significant decrease of the citric acid cycle and the respiratory electron transport in VAT and muscle of T2D and we provided a thorough visual representation of the complete set of downregulated proteins. Importantly, we found widespread novel alterations in relevant biological pathways including the increase in hemostasis in pancreatic islets of PD, the increase in the complement cascade in liver and pancreatic islets of PD and the elevation in cholesterol biosynthesis in liver of T2D. Overall, our findings suggest inflammatory, immune and vascular impairments in pancreatic islets as potentially causal factors of insufficient insulin production and increased glucagon levels in the early stages of T2D. In contrast alterations in lipid metabolism and mitochondrial function in the liver and VAT/muscle, respectively, became evident later in manifest T2D. This first multi-tissue proteomic map indicates the temporal order of tissue-specific metabolic dysregulation in T2D development.

Impaired capillary tube formation induced by elevated secretion of IL8 involves altered signaling via the CXCR1/PI3K/MMP2 pathway.

Angiogenesis is a multistep process requiring endothelial cell activation, migration, proliferation and tube formation. We recently reported that elevated secretion of interlukin 8 (IL8) by myotubes (MT) from subjects with Type-2 Diabetes (T2D) reduced angiogenesis by human umbilical vein endothelial cells (HUVEC) and human skeletal muscle explants. This lower vascularization was mediated through impaired activation of the phosphatidylinositol 3-kinase (PI3K)-pathway. We sought to investigate additional signaling elements that might mediate reduced angiogenesis. HUVEC were exposed to levels of IL8 equal to those secreted by MT from non-diabetic (ND) and T2D subjects and the involvement of components in the angiogenic response pathway examined. Cellular content of reactive oxygen species and Nitrate secretion were similar after treatment with [ND-IL8] and [T2D-IL8]. CXCR1 protein was down-regulated after treatment with [T2D-IL8] (p < 0.01 vs [ND-IL8] treatment); CXCR2 expression was unaltered. Addition of neutralizing antibodies against CXCR1 and CXCR2 to HUVEC treated with IL8 confirmed that CXCR1 alone mediated the angiogenic response to IL8. A key modulator of angiogenesis is matrix metalloproteinase-2 (MMP2). MMP2 secretion was higher after treatment with [ND-IL8] vs [T2D-IL8] (p < 0.01). MMP2 inhibition reduced tube formation to greater extent with [ND-IL8] than with [T2D-IL8] (p < 0.005). The PI3K-pathway inhibitor LY294002 reduced IL8-induced MMP2 release. IL8 regulation of MMP2 release was CXCR1 dependent, as anti-CXCR1 significantly reduced MMP2 release (p < 0.05). These results suggest that high levels of IL8 secreted by T2D MT trigger reduced capillarization via lower activation of a CXCR1-PI3K pathway, followed by impaired release and activity of MMP2.

Arterial Parameters in Type-2 Diabetes and Healthy Subjects by using Impedance Plethysmography: A Case-control Study

Introduction: A reduced blood supply to lower limb, due to arterial disease, is a common cause of foot ulceration in patients with Diabetes Mellitus (DM). Impedance Plethysmography (IPG) is based on the measurement of changes in the electrical resistance (impedance) caused by blood volume changes. Aim: To compare parameters of type-2 diabetic subjects with those of healthy subjects along with different age group and to associate with Blood Flow Index (BFI), Fasting Blood Sugar (FBS), Post-Prandial Blood Sugar (PP2BS) and Body Mass Index (BMI). Materials and Methods: This case-control study was conducted at Government Medical College and in UHTC, Bhavnagar, Gujarat, India, from May 2012 to August 2013 on 100 healthy subjects and 100 type-2 diabetic subjects. IPG arterial parameters like BFI, Pulse Arrival Time (PAT), Pulse Termination Time (PTT), Differential Pulse Arrival Time (DPAT), Z0 (Basal impedance) recorded. The data were analysed by unpaired t-test and ANOVA test. Results: This study had 200 subjects of age more than 30 years. The diabetic subjects included 56 males and 44 females whereas the healthy subjects included 67 males and 33 females. There was bilateral significant reduction of BFI, PAT at knee, ankle and calf segment among diabetics group in males and females; and a bilateral significant reduction of PTT at ankle segment among diabetic males and females. DPAT value increased at knee, calf and ankle segment on both sides in male and female; except right ankle segment in diabetic group in females as compared to healthy subjects. Z0 increased at knee, ankle and calf segment in diabetic group on both side in males and females. BFI decreased with an increase in the duration of diabetes. The effect of FBS, PP2BS and BMI in diabetic subjects suggested a negative association with BFI. Conclusion: There was decrease in BFI, PAT, PTT and increase in DPAT in the knee, calf and ankle region of diabetic subjects. BFI negatively correlated with FBS, PP2BS and BMI among diabetics and decreased with increased duration of DM

The impact of moderate combination exercise on HbA1c, IL-6, and TNF in type 2 diabetic and non-diabetic subjects: an interventional non-randomized clinical trial

Introduction: The main causes of worldwide increase in prevalence of type 2 diabetes are the daily consumption of excessive number of calories and sedentary lifestyle. Diabetes is usually accompanied by hypertension, lipid disorders and obesity that are considered as risk factors for developing diabetes. This study is designed to assess the benefit of a combined exercise programme (cardio “aerobic” and resistance) on HbA1c and the inflammatory markers (IL-6, and TNF) in type 2 diabetic (T2D) and non-diabetic (ND) subjects. Materials and methods: This is an interventional non randomized clinical trial conducted from 2016 to 2019 at exercise physiology laboratory at De Montfort University (DMU). Our target volunteers are T2D (HbA1c &gt; 6.4), and ND (HbA1c &lt; 5.8) with age group from 18-60 years old who are fit and able to do exercise. No restriction on weight. HbA1c, weight, BMI, waist and lung capacity were measured at baseline and at the 12th exercise session. In each exercise session the participant performed a combined exercise program consists of 30 min of resistance exercise followed by 20 min moderate cycling to be done twice a week for 6 weeks. Results: We enrolled 17 T2D intervention group 4 female and 13 male and 8 ND control group 5 female and 3 male. In both groups there was a significant reduction in HbA1c level after 6 weeks (P= 0.000). In T2D there were a significant weight reduction that decreased from (92.0± 4.3) to (90.0±4.5), (P&lt; 0.001), BMI reduction that decreased from (30.8± 1.0) to (30.2± 0.9), (P&lt; 0.001). In ND, the changes in weight reduction and BMI level were not significant. In T2D the changes in IL-6 level were only significant after the last exercise session. It was increased from 1.79±0.4 to 3.88±1.9 pg/ml (P=0.002), while it was not significant in ND group. In T2D and ND subjects, the changes in TNF level were insignificant. Conclusion: Development of combination exercise programs as a non-pharmacological intervention for diabetic and non-diabetic population are essential to decrease the prevalence of diabetes worldwide. In addition to conduction of public awareness events for proper implementation.

Evaluation of Hypoglycaemic Effects of Dipeptidyl Peptidase–4 Inhibitors and Biguanide on Type-2 Diabetic subjects: A six months trial

Objective: This trial was conducted to evaluate the effectiveness of oral hypoglycemic agents on diabetic control and biochemical parameters of known diabetic subjects.&#x0D; Introduction: T2DM occurs due to abnormal metabolism of carbohydrate, proteins and lipids leading to increased blood glucose characterized by polyuria and polydypsia due to relative 5deficiency or lack of insulin. Beside dietary control and insulin therapy, various oral hypoglycemic such as sulfonylurea biguanide, thiazolidinedione, DPP–4 inhibitors, glucagon–like peptide inhibitors and SGL2.&#x0D; &#x0D; Material and Methods: This comparative trial was carried out on previously diagnosed type–2 diabetic subjects. This trial was conducted at health care centers of District Nowshehra viz. NMC Nowshehra, DHQ Hospital Nowshehra, and ICS, Peshawar in collaboration with KMC and PIMC Peshawar, Khyber Pakhtunkhwa, Pakistan. A total of 200 known diabetic subjects were randomly recruited on the basis of predetermined selection criteria and were splited into two groups. Group A having 100 diabetic subjects was given DPP–4 inhibitor; Sitagliptin 50 mg two times a day alone for six (06) months while Group B comprising of 100 patients were treated with combination of DPP–4 inhibitor (Sitagliptin 50 mg 1BD) and Metformin in a dose of 500 mg two times a day. Venous blood samples were taken from each patient in both fasting (10–12 hour night long fast) and random (2 hour post prandial) state. FBS, RBS, HbA1C, S. creatinine and fasting S. lipid profile were determined by using spectrophotometric colorimetric methods using kits (procured from Elitech, Spain) at 03 and 06 months follow up. Inclusion criteria was subjects with T2DM of age 18 years and above. T2DM patients on insulin, diabetic nephropathy and retinopathy were excluded. The data was analyzed by using SPSS software version 20.&#x0D; Results: Significant results (p &lt; 0.05) were seen for glycemic control (FBS, RBS, HbA1C) in Group B as compare to Group A patients.

Effect of dietary supplementation with oat β-glucan for 3 months in subjects with type 2 diabetes: A randomized, double-blind, controlled clinical trial

• A 5 g serving of oat β-glucan can improve glycemic control. • Prolonged intake of oat β-glucan can modulate appetite/satiety regulating hormones. • Oat β-glucan and microcrystalline cellulose can modulate the gut microbiota towards a healthier profile. • Oat β-glucan is a nutrient with high potential for the treatment of diabetes. There is a growing interest in the use of functional foods. Studies indicate the contribution of β-glucans to glycemic control, but few have evaluated integrally the effect of this soluble dietary fiber on appetite-regulating hormones and microbiota in type-2 diabetes (T2D). We analyzed the effect of enriching a normal diet with oat β-glucan in thirty-seven T2D subjects. For 12 weeks, subjects consumed daily oat β-glucan or microcrystalline cellulose as control (5 g/day). We determined fasting glucose, C-peptide, insulin, HOMA, HbA1c, lipid profile, ghrelin, leptin, GLP-1, PYY, caloric intake, and intestinal microbiota. HbA1c decreased in the β-glucan group. Insulin, C-peptide and HOMA, Lactobacillus spp, and Butyrate-producing bacteria decreased in the β-glucan group (p < 0.05). Leptin (p < 0.05), GLP-1 (p < 0.01) and PYY (p < 0.001) were different between groups. The intake of 5 g/oat β-glucan for 12 weeks can help improve glycemic control, increase the feeling of satiety, and promote changes in the gut microbiota profile.

Continuous Glucose and Heart Rate Monitoring in Young People with Type 1 Diabetes: An Exploratory Study about Perspectives in Nocturnal Hypoglycemia Detection.

A combination of information from blood glucose (BG) and heart rate (HR) measurements has been proposed to investigate the HR changes related to nocturnal hypoglycemia (NH) episodes in pediatric subjects with type 1 diabetes (T1D), examining whether they could improve hypoglycemia prediction. We enrolled seventeen children and adolescents with T1D, monitored on average for 194 days. BG was detected by flash glucose monitoring devices, and HR was measured by wrist-worn fitness trackers. For each subject, we compared HR values recorded in the hour before NH episodes (before-hypoglycemia) with HR values recorded during sleep intervals without hypoglycemia (no-hypoglycemia). Furthermore, we investigated the behavior after the end of NH. Nine participants (53%) experienced at least three NH. Among these nine subjects, six (67%) showed a statistically significant difference between the before-hypoglycemia HR distribution and the no-hypoglycemia HR distribution. In all these six cases, the before-hypoglycemia HR median value was higher than the no-hypoglycemia HR median value. In almost all cases, HR values after the end of hypoglycemia remained higher compared to no-hypoglycemia sleep intervals. This exploratory study support that HR modifications occur during NH in T1D subjects. The identification of specific HR patterns can be helpful to improve NH detection and prevent fatal events.

Gingival crevicular fluid biomarkers in type 1 diabetes mellitus: A case-control study.

ObjectiveThe aim of the study is to compare the levels of Gingival Crevicular Fluid (GCF) interleukin 8 (IL‐8), matrix metalloproteinase 8 (MMP‐8) and advanced glycated‐end products (AGEs) in a cohort of type 1 diabetic (T1D) subjects and healthy controls.Material and methodsGCF samples and periodontal examination were assessed in 50 subjects with T1D (30 males and 20 females; mean age: 35.2 years) recruited from the Diabetology Unit of the Geneva University Hospitals and in 50 control subjects matched for gender, age and smoking status. Samples were assessed for IL‐8 and MMP‐8 using a bead array multianalyte detection system and for AGEs the ELISA. The two groups were compared using the Wilcoxon signed rank test.ResultsThe mean HbA1c differed significantly between the groups (8.3% for the T1D group vs. 5.2% for the control group, p < 0.001). T1D subjects had significantly more plaque and gingival inflammation and presented more sites with bleeding on probing compared to the controls. The GCF levels of IL‐8, MMP‐8 and AGEs did not differ significantly between the groups. Further analysis of the GCF markers in younger (<40 years) and older (≥40 years) cohorts, revealed no significant differences between younger diabetics and controls or between older diabetics and controls. When the groups were divided according to their glycemic status (HbA1c 6.1–8, and > 8%), again no significant differences could be identified for any of the biochemical markers.ConclusionsT1D subjects, particularly the younger ones, exhibited more inflammation compared to the matched healthy controls. Results on the GCF expression of IL‐8, MMP‐8 and AGEs did not differ between the groups. The diabetic population of our cohort was for the most part fairly‐controlled, with little if any complications and with presence of only mild type of periodontal disease, as 68% had gingivitis.

Exploring the Triple Interaction between the Host Genome, the Epigenome, and the Gut Microbiome in Type 1 Diabetes.

Type 1 diabetes (T1D) is an auto-immune disorder characterized by a complex interaction between the host immune system and various environmental factors in genetically susceptible individuals. Genome-wide association studies (GWAS) identified different T1D risk and protection alleles, however, little is known about the environmental factors that can be linked to these alleles. Recent evidence indicated that, among those environmental factors, dysbiosis (imbalance) in the gut microbiota may play a role in the pathogenesis of T1D, affecting the integrity of the gut and leading to systemic inflammation and auto-destruction of the pancreatic β cells. Several studies have identified changes in the gut microbiome composition in humans and animal models comparing T1D subjects with controls. Those changes were characterized by a higher abundance of Bacteroides and a lower abundance of the butyrate-producing bacteria such as Clostridium clusters IV and XIVa. The mechanisms by which the dysbiotic bacteria and/or their metabolites interact with the genome and/or the epigenome of the host leading to destructive autoimmunity is still not clear. As T1D is a multifactorial disease, understanding the interaction between different environmental factors such as the gut microbiome, the genetic and the epigenetic determinants that are linked with the early appearance of autoantibodies can expand our knowledge about the disease pathogenesis. This review aims to provide insights into the interaction between the gut microbiome, susceptibility genes, epigenetic factors, and the immune system in the pathogenesis of T1D.

Distribution of ABO and Rhesus Blood groups among Type-2 Diabetic subjects

ABO and Rh blood group systems have been associated with a number of diseases including type-2 diabetes mellitus (T2DM). Epidemiological studies have inconsistently associated ABO and Rhesus (Rh) blood groups with T2DM risk. To assess the distribution of ABO and Rh blood groups among type-2 diabetic subjects and to check the potential association between ABO and Rh blood groups with T2DM. This small retrospective case-control study was conducted at DM WIMS Hospital, Wayanad. One-year data (from Jan-18 to Jan-19) of fasting, postprandial or random plasma/serum glucose, HbA1c, ABO and Rh blood groups of Non- diabetic and type -2 diabetic subjects were collected from the Hospital Clinical Laboratory Medicine department. Among 280 randomly selected data, 147 are non-diabetic subjects, and 133 are confirmed and known cases of type 2 diabetic mellitus. Subjects with Blood group B has the highest distribution percentage among group-2 (59.39%) in comparison with group-1 (34.02%), followed by A (19.55%), O (18.79%), AB (2.27%). Statistical analysis using Chi-square test among ABO and Rh blood groups between group-1 and group-2 showed a significant (p&lt; 0.001) association of blood group “B +ve” and least association of blood group “O +ve” with T2DM. However, the Rh Blood groups evaluation for T2DM showed no clear association, as both Rh +ve and Rh -ve were uniformly distributed in the groups. The ABO and Rh blood groups may have a possible role to play in the development of T2DM. The subjects with B + ve blood group are at greater risk for T2DM and O + ve blood group individuals are at lower risk for T2DM. Keywords: Blood groups; ABO blood groups; Rh blood groups; Type 2 Diabetes Mellitus; distribution; association REFERENCES

Correlation of HbA1c with atherogenic index of plasma and endothelial dysfunction in type 2 diabetic subjects

Introduction: Endothelial dysfunction (ED) is a well known initial stage of atherosclerosis and cardiovascular disease (CVD) in general population. Recently studies shown increased HbA1c is a marker for cardiovascular risk in subjects with diabetes and without diabetes. Atherogenic index of plasma (AIP) is another risk factor for cardiovascular events. Hence, the study has been designed to assess the correlation of HbA1c with AIP and ED in type-2 diabetic subjects to forecast risk of cardiovascular events. Materials and Methods: Hundred subjects are enrolled into study with the age of 38 to 58 years, among these 50 were type 2 diabetic subjects and 50 were healthy controls. HbA1c was estimated by immuno-turbidimetric method. Nitric oxide (NO) was measured by kinetic cadmium reduction method and AIP was calculated by standard formula Log (triglyceride/HDL-c). ‘Kruskal Wallis’ test was used to perform statistical variables between the study groups. The association between the variables was executed by “Pearson correlation test”. Result: HbA1c level was shown to be significantly higher in type-2 diabetic subjects than healthy controls. Significant lower level of NO was observed in type-2 diabetic subjects than healthy controls. AIP level was significantly higher in type-2 diabetic subjects than healthy controls. The present study also observed significant correlation of HbA1c with NO and AIP. Conclusion: We have found that HbA1c has significant correlation with NO and AIP. Therefore, estimation of HbA1c may be a predictable marker for cardiovascular events in type-2 diabetic subjects. Keywords: Glycated hemoglobin, Atherogenic index of plasma, Nitric oxide, Cardiovascular disease.

Status of high sensitive C- reactive protein (hs-CRP) in NAFLD obese type-2 diabetic subjects

Introduction: Non alcoholic fatty liver disease (NAFLD) is a disease occurring in patients without any significant alcohol consumption. It includes a broad spectrum and advanced forms of liver diseases, from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis and is associated with diabetes mellitus, insulin resistance, obesity, dyslipidemia and metabolic syndrome. The aim of this study is to evaluate the metabolic significance of NAFLD in obese and type-2 diabetic subjects compare to healthy group of individuals and those independent factors associated with NAFLD. Materials and Methods: Our study was conducted in Govt. Medial College, Banda (UP) as well as G. R. Medical College, Gwalior (MP). A total of 200 subjects were involved in our study, diagnosis being based on ultrasonography. Out of these, 100 were obese with type-2 diabetic patients and 100 were healthy subjects. They were evaluated by measurement of BMI and several biochemical blood parameters such as fasting blood glucose, lipid profile, liver function tests (ALT, ALP and GGT) and hs-CRP level. Results: An increase in the BMI and levels of FBS, total cholesterol, triglycerides, LDL, VLDL, GGT, ALT, ALP and hs-CRP level and a decrease in HDL was observed in NAFLD group of individuals. The values of these biochemical markers were found higher in NAFLD patients and the variations were found to be statically significant. BMI and triglycerides were positively correlated with fatty liver. Conclusion: Obesity, hyperglycemia, dyslipidemia and increased liver enzymes and hs-CRP level are seen more commonly in non alcoholic fatty liver in type-2 diabetic obese patients. Keywords: NAFLD, BMI, High sensitive C-reactive protein.

FKBPL is associated with metabolic parameters and is a novel determinant of cardiovascular disease

Type 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). As disturbed angiogenesis and endothelial dysfunction are strongly implicated in T2D and CVD, we aimed to investigate the association between a novel anti-angiogenic protein, FK506-binding protein like (FKBPL), and these diseases. Plasma FKBPL was quantified by ELISA cross-sectionally in 353 adults, consisting of 234 T2D and 119 non–diabetic subjects with/without CVD, matched for age, BMI and gender. FKBPL levels were higher in T2D (adjusted mean: 2.03 ng/ml ± 0.90 SD) vs. non-diabetic subjects (adjusted mean: 1.79 ng/ml ± 0.89 SD, p = 0.02), but only after adjustment for CVD status. In T2D, FKBPL was negatively correlated with fasting blood glucose, HbA1c and diastolic blood pressure (DBP), and positively correlated with age, known diabetes duration, waist/hip ratio, urinary albumin/creatinine ratio (ACR) and fasting C-peptide. FKBPL plasma concentrations were increased in the presence of CVD, but only in the non-diabetic group (CVD: 2.02 ng/ml ± 0.75 SD vs. no CVD: 1.68 ng/ml ± 0.79 SD, p = 0.02). In non-diabetic subjects, FKBPL was positively correlated with an established biomarker for CVD, B-type Natriuretic Peptide (BNP), and echocardiographic parameters of diastolic dysfunction. FKBPL was a determinant of CVD in the non-diabetic group in addition to age, gender, total-cholesterol and systolic blood pressure (SBP). FKBPL may be a useful anti-angiogenic biomarker in CVD in the absence of diabetes and could represent a novel CVD mechanism.

Increased leukotriene B4 plasma concentration in type 2 diabetes individuals with cardiovascular autonomic neuropathy

Background and aimA low-grade inflammation is associated with cardiac autonomic neuropathy (CAN) and increased concentration of leukotriene B4 (LTB4) was found in individuals with type 1 diabetes and definitive CAN. This cross-sectional study evaluated plasma concentration of LTB4 and of other inflammatory mediators, namely, tumor necrosis factor (TNF), interleukin (IL)1B, and IL10 in individuals with type 2 diabetes (T2D) and different degrees of CAN, and correlated these inflammatory mediators with the degree of glycemic control and with a surrogate marker of insulin resistance.MethodsTNF, IL1B, IL10 and LTB4 plasma concentrations were measured in 129 T2D subjects (62% women with [median] age of 63 years, disease duration of 8 years and HbA1c of 7.3%) with or without CAN. The Lipid accumulation product index was used as a surrogate marker of insulin resistance.ResultsLTB4 concentration was significantly higher in those presenting incipient CAN (69.7 ± 16.6 pg mL-1) and definitive CAN (71.5 ± 15.7 pg mL-1) versus those without CAN (57.0 ± 13.9 pg mL-1). The groups without CAN and with incipient CAN were pooled (group without definitive CAN) and compared to those with definitive CAN. LTB4 concentration was higher in the latter group, as well as TNF concentration, while IL10 concentration was lower in this group. After adjustment for confounding variables, only LTB4 concentration remained significantly different between the groups with and without definitive CAN. Plasma concentration of LTB4 did not correlate with the degree of glycemic control. After sorting the participants by sex, a borderline weak correlation was found between LTB4 and the Lipid accumulation product index in women.ConclusionIn the T2D setting, circulating LTB4 concentration seems to be associated with cardiovascular dysautonomia.