Type 2 Diabetes Mellitus Subjects Research Articles

Hyperglycemia impairs EAAT2 glutamate transporter trafficking and glutamate clearance in islets of Langerhans: implications for type 2 diabetes pathogenesis.

Pancreatic endocrine cells employ a sophisticated system of paracrine and autocrine signals to synchronize their activities, including glutamate which controls hormone release and β-cell viability by acting on glutamate receptors expressed by endocrine cells. We here investigate whether alteration of the Excitatory Amino Acid Transporter 2 (EAAT2), the major glutamate clearance system in the islet, may occur in type 2 diabetes mellitus (T2DM) and contribute to β-cell dysfunction. Increased EAAT2 intracellular localization was evident in islets of Langerhans from T2DM subjects as compared with healthy control subjects, despite similar expression levels. Chronic treatment of islets from healthy donors with high glucose concentrations led to the transporter internalization in vesicular compartments and reduced [H3]-D-glutamate uptake (65±5% inhibition), phenocopying the findings in T2DM pancreatic sections. The transporter relocalization was associated to decreased Akt phosphorylation protein levels, suggesting an involvement of the PI3K/Akt pathway in the process. In line with this, PI3K inhibition by 100 µM LY294002 treatment in human and clonal β-cells, caused the transporter relocalization in intracellular compartments and significantly reduced the glutamate uptake compared to control conditions, suggesting that hyperglycemia changes the trafficking of the transporter to the plasma membrane. Upregulation of the glutamate transporter upon treatment with the antibiotic ceftriaxone rescued hyperglycemia-induced β-cells dysfunction and death. Our data underscore the significance of EAAT2 in regulating islet physiology and provide a rationale for potential therapeutic targeting of this transporter to preserve β-cell survival and function in diabetes.

Links among Obesity, Type 2 Diabetes Mellitus, and Osteoporosis: Bone as a Target.

Obesity, type 2 diabetes mellitus (T2DM) and osteoporosis are serious diseases with an ever-increasing incidence that quite often coexist, especially in the elderly. Individuals with obesity and T2DM have impaired bone quality and an elevated risk of fragility fractures, despite higher and/or unchanged bone mineral density (BMD). The effect of obesity on fracture risk is site-specific, with reduced risk for several fractures (e.g., hip, pelvis, and wrist) and increased risk for others (e.g., humerus, ankle, upper leg, elbow, vertebrae, and rib). Patients with T2DM have a greater risk of hip, upper leg, foot, humerus, and total fractures. A chronic pro-inflammatory state, increased risk of falls, secondary complications, and pharmacotherapy can contribute to the pathophysiology of aforementioned fractures. Bisphosphonates and denosumab significantly reduced the risk of vertebral fractures in patients with both obesity and T2DM. Teriparatide significantly lowered non-vertebral fracture risk in T2DM subjects. It is important to recognize elevated fracture risk and osteoporosis in obese and T2DM patients, as they are currently considered low risk and tend to be underdiagnosed and undertreated. The implementation of better diagnostic tools, including trabecular bone score, lumbar spine BMD/body mass index (BMI) ratio, and microRNAs to predict bone fragility, could improve fracture prevention in this patient group.

Correlation of periodontal inflamed surface area with glycated hemoglobin, interleukin-6 and lipoprotein(a) in type 2 diabetes with retinopathy.

The two-way relationship between periodontitis and type 2 diabetes mellitus (T2DM) is well established. Prolonged hyperglycemia contributes to increased periodontal destruction and severe periodontitis, accentuating diabetic complications. An inflammatory link exists between diabetic retinopathy (DR) and periodontitis, but the studies regarding this association and the role of lipoprotein(a) [Lp(a)] and interleukin-6 (IL-6) in these conditions are scarce in the literature. To determine the correlation of periodontal inflamed surface area (PISA) with glycated Hb (HbA1c), serum IL-6 and Lp(a) in T2DM subjects with retinopathy. This cross-sectional study comprised 40 T2DM subjects with DR and 40 T2DM subjects without DR. All subjects were assessed for periodontal parameters [bleeding on probing (BOP), probing pocket depth, clinical attachment loss (CAL), oral hygiene index-simplified, plaque index (PI) and PISA], and systemic parameters [HbA1c, fasting plasma glucose and postprandial plasma glucose, fasting lipid profile, serum IL-6 and serum Lp(a)]. The proportion of periodontitis in T2DM with and without DR was 47.5% and 27.5% respectively. Severity of periodontitis, CAL, PISA, IL-6 and Lp(a) were higher in T2DM with DR group compared to T2DM without DR group. Sig-nificant difference was observed in the mean percentage of sites with BOP between T2DM with DR (69%) and T2DM without DR (41%), but there was no significant difference in PI (P > 0.05). HbA1c was positively correlated with CAL (r = 0.351, P = 0.001), and PISA (r = 0.393, P ≤ 0.001) in study subjects. A positive correlation was found between PISA and IL-6 (r = 0.651, P < 0.0001); PISA and Lp(a) (r = 0.59, P < 0.001); CAL and IL-6 (r = 0.527, P < 0.0001) and CAL and Lp(a) (r = 0.631, P < 0.001) among study subjects. Despite both groups having poor glycemic control and comparable plaque scores, the periodontal parameters were higher in DR as compared to T2DM without DR. Since a bidirectional link exists between periodontitis and DM, the presence of DR may have contributed to the severity of periodontal destruction and periodontitis may have influenced the progression of DR.

Sustained Release of Salicylic Acid for Halting Peri-Implantitis Progression in Healthy and Hyperglycemic Systemic Conditions: A Gottingen Minipig Model.

To develop a peri-implantitis model in a Gottingen minipig and evaluate the effect of local application of salicylic acid poly(anhydride-ester) (SAPAE) on peri-implantitis progression in healthy, metabolic syndrome (MS), and type-2 diabetes mellitus (T2DM) subjects. Eighteen animals were allocated to three groups: (i) control, (ii) MS (diet for obesity induction), and (iii) T2DM (diet plus streptozotocin for T2DM induction). Maxillary and mandible premolars and first molar were extracted. After 3 months of healing, four implants per side were placed in both jaws of each animal. After 2 months, peri-implantitis was induced by plaque formation using silk ligatures. SAPAE polymer was mixed with mineral oil (3.75 mg/μL) and topically applied biweekly for up to 60 days to halt peri-implantitis progression. Periodontal probing was used to assess pocket depth over time, followed by histomorphologic analysis of harvested samples. The adopted protocol resulted in the onset of peri-implantitis, with healthy minipigs taking twice as long to reach the same level of probing depth relative to MS and T2DM subjects (∼3.0 mm), irrespective of jaw. In a qualitative analysis, SAPAE therapy revealed decreased levels of inflammation in the normoglycemic, MS, and T2DM groups. SAPAE application around implants significantly reduced the progression of peri-implantitis after ∼15 days of therapy, with ∼30% lower probing depth for all systemic conditions and similar rates of probing depth increase per week between the control and SAPAE groups. MS and T2DM conditions presented a faster progression of the peri-implant pocket depth. SAPAE treatment reduced peri-implantitis progression in healthy, MS, and T2DM groups.

Taste Dysfunction and its Relationship to HbA1C Level and Disease Duration in Type 2 Diabetes Mellitus Patients with Autonomic Neuropathy

Background and Aim: Type 2 diabetes mellitus (T2DM) effect quality of life very much and causes variouscomplications. Diabetic autonomic neuropathy (DAN) is one of the common complications in diabetes. Thuspresent study was aimed at determining taste dysfunction in a population of T2DM subjects and its correlation with HbA1c level.Material and Methods: This was an observational cross sectional study which was carried over a period of one year in the department of medicine, Tertiary care institute of India. The 100 patients of T2DM with autonomicneuropathy and 100 healthy controls were taken for the study. Autonomic neuropathy was assessed clinically.Chemical taste test using four solutions of basic tastes (sweet, sour, salty, bitter) were done.Results: There was a significant difference between the 2 groups in terms of HbA1c (%) (p≤0.05), with the median HbA1c (%) being highest in the chemical taste dysfunction: sweet: yes group. Strength of association (Point- Biserial correlation)=0.49. There was a significant difference between the various groups in terms of distribution of chemical taste dysfunction: Sweet (p≤0.05). There was no significant difference between the groups in terms of duration of T2DM (years) (p&gt;0.05).Conclusion: The study found a significant correlation between taste dysfunction and HbA1C level and bloodsugar fasting level in type 2 diabetes mellitus patients. Alteration in taste was mainly for sweet. Sour, and bitter did not show any difference in case groups compared to controls.

Efficacy of Integrated Ayurveda Treatment in Type 2 Diabetes mellitus with special reference to Prameha: A Randomised controlled Trial

Background: Diabetes mellitus (DM) is marked by persistent hyperglycemia, often due to insulin resistance. Type 2 diabetes mellitus (T2DM) constitutes 90% of cases and shares similarities with Prameha, a disorder characterized by frequent urination. Aims and objectives: This study aimed to compare Integrated Ayurveda Treatment (IAT) with standard diabetic treatment for Prameha. Materials and methods: A randomized, controlled open-label trial involved 200 T2DM subjects with HbA1C above 7%, taking metformin (≥1g /day). They were assigned to Standard Dietary Treatment (SDT) or IAT. SDT comprised metformin, dietary, and lifestyle modifications, while IAT included metformin with Ayurvedic medicine, specific Ayurveda diet, and yoga. Observation and result: Observations favoured Ayurveda treatment over standard diabetes treatment for most Prameha preliminary symptoms (purvarupa). Regarding Prameha rupa (symptoms), IAT significantly outperformed than SDT. Also, Ayurveda treatment group, led to improvements in HbA1C, fasting and postprandial blood sugar, and insulin resistance parameters compared to standard treatment group. Conclusion: Integrating Madhumeha ghana vati, ayurveda diet, and yoga with standard treatment yielded positive subjective and objective outcomes for Prameha, without significant adverse events. This suggests the potential benefits of combining Ayurvedic approaches with conventional care in managing prameha. 

Identification of potential serum biomarkers associated with HbA1c levels in Indian type 2 diabetic subjects using NMR-based metabolomics

BackgroundThe prevalence of type 2 diabetes mellitus (T2DM), a progressive metabolic disorder characterized by chronic hyperglycemia and the development of insulin resistance, has increased globally, with worrying statistics coming from children, adolescents, and young adults from developing countries like India. Here, we investigated unique circulating metabolic signatures associated with prediabetes and T2DM in an Indian cohort using NMR-based metabolomics. Materials and methodsThe study subjects included healthy volunteers (N = 101), prediabetic subjects (N = 75), and T2DM patients (N = 108). Serum metabolic profiling was performed using 1H NMR spectroscopy and major perturbed metabolites were identified by multivariate analysis and receiver operating characteristic (ROC) modules. ResultsOf the 36 aqueous abundant metabolites, 24 showed a statistically significant difference between healthy volunteers, prediabetics, and established T2DM subjects. On performing multivariate ROC curve analysis with 5 commonly dysregulated metabolites (namely, glucose, pyroglutamate, o-phosphocholine, serine, and methionine) in prediabetes and T2DM, AUC values obtained were 0.96 (95 % confidence interval (CI) = 0.93, 0.98) for T2DM; and 0.88 (95 % CI = 0.81, 0.93) for prediabetic subjects, respectively. ConclusionWe propose that the identified metabolite panel can be used in the future as a biomarker for clinical diagnosis, patient surveillance, and for predicting individuals at risk for developing diabetes.

Performance of Primary Care Physicians in the Management of Glycemia, Lipids, and Blood Pressure among People with Type 2 Diabetes: A Cross-Sectional Study.

Background: Our study aimed to evaluate the performance of primary healthcare physicians (PCPs) in managing glycemia, lipids, and blood pressure in people with type 2 diabetes mellitus (T2DM) in Catalonia, Spain. Methods: We included 3267 PCPs with 367,132 T2DM subjects in a cross-sectional analysis of the SIDIAP (Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària) database for the year 2017. Results: 63.1% of PCPs were female, with an average practice size of 1512 subjects. T2DM individuals had a mean (standard deviation) age of 70 (±12.2) years old, a mean body mass index (BMI) of 30.2 (±5.21) kg/m2, and a median diabetes duration of 8.8 years. Overall, 42.6% of subjects achieved target glycemic control (glycated hemoglobin < 7%). Notably, 59.2% maintained blood pressure < 140/90 mmHg during the 12-month study period. The multivariable analysis identified positive associations between glycemic control and female PCPs, practice sizes (1000-1500 people), a higher proportion of patients aged ≥ 65 years, and rural practices. Combined glycemic, lipid, and blood pressure target attainment was associated with medium-sized practices and those with a higher proportion of patients aged ≥ 65 years. Conclusions: Practice size, patient age distribution, and rurality are factors associated with the performance of PCPs in the control of glycemia, lipids, and blood pressure in T2DM subjects in primary health care centers in our region.

Candida Variety in the Oral Cavity of Mexican Subjects with Type 2 Diabetes Mellitus and TLR2 Gene Expression.

The aim was to diagnose Candida in the oral cavity of subjects with type 2 diabetes mellitus (T2DM) using a genotyping technique and compare the results with those from conventional diagnosis by Papanicolaou (Pap) staining. Palatal mucosa smears were performed on 18 dental care patients diagnosed with T2DM and grade I, II, and III prosthetic stomatitis who met the inclusion criteria; 18 healthy control subjects were also included in the study. Hemoglobin A1c (HbA1c) levels were determined from total blood. Using exfoliative cytology, the Pap staining technique was used to diagnose candidiasis. Exfoliative cytology was also used for molecular diagnosis; DNA was obtained for Candida genotyping, and RNA was used for gene expression studies. Clinical patterns indicated that all subjects were positive for Candida; however, Pap analysis revealed only three positive subjects, whereas end-point polymerase chain reaction (PCR) analysis revealed 15 subjects with some type of Candida. The most common Candida species found were Candida guilliermondii (38.8%), Candida krusei (33.3%), Candida tropicalis, and Candida lusitaniae (22.2%). Interestingly, the coexpression of different species of Candida was found in various patients. In all patients, HbA1c levels were increased. Gene expression analysis showed a significant decrease (p ≤ 0.05) in TLR2 expression in positive subjects, whereas TLR4 expression did not differ significantly among patients. The end-point PCR technique showed better sensitivity for the diagnosis of Candida when compared with the diagnosis by Pap staining. T2DM subjects showed an increased presence of C. guilliermondii that was correlated with decreased TLR2 expression.

Sodium glucose cotransporter 2 inhibitors with cardiac arrhythmias in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized placebo-controlled trials.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiac arrhythmias, which increases serious morbidity and mortality. Novel hypoglycemic drug sodium glucose cotransporter 2 (SGLT2) inhibitor has shown sufficient cardiovascular benefits in cardiovascular outcome trials. This systematic review and meta-analysis aimed to investigate the relationship between SGLT2 inhibitors and cardiac arrhythmias in patients with T2DM. We searched on PubMed and ClinicalTrials.gov for at least 24 weeks of randomized double-blind placebo-controlled trials involving T2DM subjects assigned to SGLT2 inhibitors or placebo as of May 5, 2023. Risk ratio (RR) with 95% confidence interval (CI)were used for binary variables. Primary outcomes included atrial arrhythmias, ventricular arrhythmias, bradyarrhythmias, cardiac arrest, and atrial fibrillation/atrial flutter. Secondary outcomes comprised atrial fibrillation, atrial flutter, ventricular fibrillation, ventricular tachycardia, atrioventricular block, and sinus node dysfunction. We included 32 trials covering 60,594 T2DM patients (SGLT2 inhibitor 35,432; placebo 25,162; mean age 53.9 to 68.5 years). SGLT2 inhibitors significantly reduced the risk of atrial arrhythmias (RR 0.86; 95%CI 0.74-0.99; P = 0.04) or atrial fibrillation/flutter (RR 0.85; 95%CI 0.74-0.99; P = 0.03) compared to placebo; in subgroup analysis, SGLT2 inhibitors achieved a consistent effect with overall results in T2DM with high cardiovascular risk or follow-up > 1 year populations. There was no substantial evidence to suggest that SGLT2 inhibitors reduced the risk of ventricular arrhythmias (RR 0.94; 95%CI 0.71-1.26; P = 0.69) and cardiac arrest (RR 0.88; 95%CI 0.66-1.18; P = 0.39). A neutral effect of SGLT2 inhibitors on bradyarrhythmias was observed (RR 1.02; 95%CI 0.79-1.33; P = 0.85). SGLT2 inhibitors had no significant impact on all secondary outcomes compared to placebo, while it had borderline effect for atrial fibrillation. SGLT2 inhibitors were associated with a reduced risk of atrial arrhythmias in patients with T2DM. Our results support the use of SGLT2 inhibitors in T2DM with high cardiovascular risk populations. We also recommend the long-term use of SGLT2 inhibitors to achieve further benefits.

High-Throughput Microfluidic Extraction of Platelet-free Plasma for MicroRNA and Extracellular Vesicle Analysis.

Cell-free RNAs and extracellular vesicles (EVs) are valuable biomarkers in liquid biopsies, but they are prone to preanalytical variabilities such as nonstandardized centrifugation or ex vivo blood degradation. Herein, we report a high-throughput and label-free inertial microfluidic device (ExoArc) for isolation of platelet-free plasma from blood for RNA and EV analysis. Unlike conventional inertial microfluidic devices widely used for cell sorting, a submicrometer size cutoff (500 nm) was achieved which completely removed all leukocytes, RBCs, platelets, and cellular debris based on differential lateral migration induced by Dean vortices. The single-step operation also reduced platelet-associated miRNAs (∼2-fold) compared to centrifugation. We clinically validated ExoArc for plasma miRNA profiling (39 samples) and identified a 7-miRNA panel that detects non-small cell lung cancer with ∼90% sensitivity. ExoArc was also coupled with size exclusion chromatography (SEC) to isolate EVs within 50 min with ∼10-fold higher yield than ultracentrifugation. As a proof-of-concept for EV-based transcriptomics analysis, we performed miRNA analysis in healthy and type 2 diabetes mellitus (T2DM) subjects (n = 3 per group) by coupling ExoArc and ExoArc+SEC with quantitative polymerase chain reaction (RT-qPCR) assay. Among 293 miRNAs detected, plasmas and EVs showed distinct differentially expressed miRNAs in T2DM subjects. We further demonstrated automated in-line EV sorting from low volume culture media for continuous EV monitoring. Overall, the developed ExoArc offers a convenient centrifugation-free workflow to automate plasma and EV isolation for point-of-care diagnostics and quality control in EV manufacturing.

Osseointegration of implant surfaces in metabolic syndrome and type-2 diabetes mellitus.

This in vivo study evaluated the bone healing response around endosteal implants with varying surface topography/chemistry in a preclinical, large transitional model induced with metabolic syndrome (MS) and type-2 diabetes mellitus (T2DM). Fifteen Göttingen minipigs were randomly distributed into two groups: (i) control (normal diet, n = 5) and (ii) O/MS (cafeteria diet for obesity induction, n = 10). Following obesity induction, five minipigs from the obese/metabolic syndrome(O/MS) group were further allocated, randomly, into the third experimental group: (iii) T2DM (cafeteria diet + streptozotocin). Implants with different surface topography/chemistry: (i) dual acid-etched (DAE) and (ii) nano-hydroxyapatite coating over the DAE surface (NANO), were placed into the right ilium of the subjects and allowed to heal for 4 weeks. Histomorphometric evaluation of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO) within implant threads were performed using histomicrographs. Implants with NANO surface presented significantly higher %BIC (~26%) and %BAFO (~35%) relative to implants with DAE surface (%BIC = ~14% and %BAFO = ~28%, p < .025). Data as a function of systemic condition presented significantly higher %BIC (~28%) and %BAFO (~42%) in the control group compared with the metabolically compromised groups (O/MS: %BIC = 14.35% and %BAFO = 26.24%, p < .021; T2DM: %BIC = 17.91% and %BAFO = 26.12%, p < .021) with no significant difference between O/MS and T2DM (p > .05). Statistical evaluation considering both factors demonstrated significantly higher %BIC and %BAFO for the NANO surfacerelative to DAE implant, independent of systemic condition (p < .05). The gain increase of %BIC and %BAFO for the NANO compared with DAE was more pronounced in O/MS and T2DM subjects. Osseointegration parameters were significantly reduced in metabolically compromised subjects compared with healthy subjects. Nanostructured hydroxyapatite-coated surfaces improved osseointegration relative to DAE, regardless of systemic condition.

CD36 gene variant rs1761667(G/A) as a biomarker in obese type 2 diabetes mellitus cases

BackgroundSeveral reports discussed a connection between CD36 genotypes associated with obesity, influencing the development of Type 2 diabetes mellitus (T2DM). Therefore, this study examines the prognostic value of CD36 polymorphism rs1761667 (G/A) in individuals with obese T2DM. The investigation also explores the correlation between this genetic variation and the clinical/biochemical parameters of the subjects.MethodsBlood samples of a total of 475 subjects from north India were collected from the outpatient unit (OPD), Department of Medicine, KGMU, Lucknow as per inclusion/exclusion criteria. Anthropometric details of study subjects were recorded and biochemical parameters were estimated in 250 T2DM cases, 75 obese T2DM cases, and 150 controls. The CD36 gene variant rs1761667 (G/A) was subject to genotypic analysis using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method, utilizing specific primers and HhaI enzyme. All statistical analysis was done using SPSS (ver. 21.0) and Prism (5.01) software.ResultsFasting plasma glucose (FPG), systolic blood pressure (SBP), post-prandial glucose (PPG) were significant in T2DM subjects. Lipid profile such as Total Cholesterol (TC), Low-Density Lipoprotein (LDL) and Very Low-Density Lipoprotein (VLDL) were also found significantly associated with obese T2DM cases. GA and AA genotypes of rs1761667 (G/A) showed significant associations in obese T2DM cases. The GA genotype demonstrated a considerable association (P < 0.001) with a 2.77-fold increased susceptibility to the high risk of T2DM. The AA genotype was found to be significantly associated (P = 0.008) with 2.94-fold higher risk of T2DM in obesity while 9.33 folds significant risk of developing obesity in T2DM cases.ConclusionsThe risk of obesity in T2DM cases can be assessed by genotyping the CD36 genetic variant rs1761667 (G/A). However, raised FPG, PPG, TC, LDL, and VLDL showed poor prognosis in obese T2DM cases. CD36 gene variant can be proposed as a prognostic biomarker for risk prediction of T2DM and obesity, while anthro-biochemical risk factors as preventive biomarker.

Inverse relationship between platelet Akt activity and hippocampal atrophy: A pilot case-control study in patients with diabetes mellitus.

Akt plays diverse roles in humans. It is involved in the pathogenesis of type 2 diabetes mellitus (T2DM), which is caused by insulin resistance. Akt also plays a vital role in human platelet activation. Furthermore, the hippocampus is closely associated with memory and learning, and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without dementia. To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM patients. Platelet-rich plasma (PRP) was prepared from the venous blood of patients with T2DM or age-matched controls. The pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt, p38 mitogen-activated protein (MAP) kinase and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Phosphorylation levels were quantified by densitometric analysis. Hippocampal volume was analysed using a voxel-based specific regional analysis system for Alzheimer's disease on magnetic resonance imaging, which proposes the Z-score as a parameter that reflects hippocampal volume. The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects, whereas the levels of phosphorylated Akt corrected with GAPDH were not. However, this relationship was not observed in the control patients. These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM patients. Our findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.

Upregulation of Anti-Angiogenic miR-106b-3p Correlates Negatively with IGF-1 and Vascular Health Parameters in a Model of Subclinical Cardiovascular Disease: Study with Metformin Therapy.

Well-controlled type 1 diabetes mellitus (T1DM) is regarded as a model of subclinical cardiovascular disease (CVD), characterized by inflammation and adverse vascular health. However, the underlying mechanisms are not fully understood. We investigated insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) levels, their correlation to miR-106b-3p expression in a subclinical CVD model, and the cardioprotective effect of metformin. A total of 20 controls and 29 well-controlled T1DM subjects were studied. Plasma IGF-1, IGFBP-3 levels, and miR-106b-3p expression in colony-forming unit-Hills were analyzed and compared with vascular markers. miR-106b-3p was upregulated in T1DM (p < 0.05) and negatively correlated with pro-angiogenic markers CD34+/100-lymphocytes (p < 0.05) and IGF-1 (p < 0.05). IGF-1 was downregulated in T1DM (p < 0.01), which was associated with increased inflammatory markers TNF-α, CRP, and IL-10 and reduced CD34+/100-lymphocytes. IGFBP-3 had no significant results. Metformin had no effect on IGF-1 but significantly reduced miR-106b-3p (p < 0.0001). An Ingenuity Pathway analysis predicted miR-106b-3p to inhibit PDGFA, PIK3CG, GDNF, and ADAMTS13, which activated CVD. Metformin was predicted to be cardioprotective by inhibiting miR-106b-3p. In conclusion: Subclinical CVD is characterized by a cardio-adverse profile of low IGF-1 and upregulated miR-106b-3p. We demonstrated that the cardioprotective effect of metformin may be via downregulation of upregulated miR-106b-3p and its effect on downstream targets.

Serum Vitamin D Levels and Vascular Endothelial Growth Factor in Patients with Type 2 Diabetes Mellitus: A Cross-sectional Study

Introduction: Diabetes Mellitus (DM) is the most common noncommunicable disease and the fifth leading cause of death worldwide. Recent research has demonstrated that low Vitamin D levels and high Vascular Endothelial Growth Factor (VEGF) in middle-aged and elderly populations represent a risk factor for Type 2 Diabetes Mellitus (T2DM). Aim: To estimate the Vitamin D and VEGF levels in study subjects with T2DM and healthy controls and to correlate the Vitamin D level and VEGF with HbA1c % in study subjects with T2DM. Materials and Methods: A cross-sectional study was undertaken from October 2014 to November 2016 at the Department of Medicine in collaboration with the Department of Biochemistry, Bangalore Medical College and Research Institute, Bangalore. The study included 50 T2DM subjects on oral hypoglycaemic agents for five years and 50 age and sexmatched healthy controls selected randomly from the general population. In all the study subjects, Random Blood Glucose (RBG), LFT, Renal Function Test (RFT), HBA1c, serum Vitamin D, and serum VEGF were estimated. Student t-test and Chisquare/Fisher-Exact test were used to find the significance of study parameters between cases and controls. Multivariate logistic regression analysis was done to assess the risk factors for DM. Results: The mean age of the cases was 50.9±9.7 years and of controls was 49.76±7.7 years. Among the 50 cases, 19 (38%) were men and 31 (62%) were women. Among the 50 controls, 27 (54%) were men and 23 (46%) were women. The mean Body Mass Index (BMI) among cases was 27.21±4.59 and in controls was 24.82±2.63 (p-value=0.0016). The mean serum 25(OH) Vitamin D levels in cases were 11.39±3.32 ng/mL and in controls were 28.06±11.14 ng/mL (p-value &lt;0.001). The mean serum VEGF levels in cases were 97.52±16.96 pg/mL and in controls were 56.37±17.74 pg/mL (p-value &lt;0.001). Conclusion: The present study found that subjects with T2DM have lower serum 25(OH) Vitamin D levels and higher serum VEGF levels than those without T2DM. Serum Vitamin D decreases and serum VEGF-A levels increase with increasing HbA1c%, correlating with vascular complications.

Haemostatic and Haematological Parameters among Type 2 Diabetes Patients in A Tertiary Health Facility in Ondo State, Nigeria: A Cross-sectional Study

Background: Type 2 diabetes mellitus (T2DM) remains one of the non-communicable metabolic disorders associated with serious thrombotic outcomes and risk of cardiovascular disease, which can be fatal. Aim: This study was therefore aimed at comparing the levels of haemostatic and haematological parameters of T2DM and non-diabetic subjects. The study also determines the relationship between haemostatic parameters with haematological parameters among the T2DM subjects. Methods: Total of 150 participants, comprising “75” of those with diabetes and those without diabetes, were recruited for the study. Blood samples were collected for the analysis of full blood count, Factor V, VII, and tissue plasminogen activator inhibitor-1 (TPA I-1). Test of significance of means was carried out using the One-Way Analysis of variance test, while relationships were tested using Pearson correlation and logistic regression. Results: The results revealed significantly higher levels of Factor V, VII, and TPA I-1 among participants with diabetes when compared with those without diabetes. However, significantly lower levels of red cell parameters and red cell indices were observed in the participants with diabetes. In addition, with the exception of lymphocyte and eosinophil levels, all other white blood cells(WBC), platelets, and differential leukocyte parameters were significantly higher in the subjects with diabetes. Moreover, there was a significant positive correlation between Factors V and VII, TPA I – 1 and Factor VII, TPA I-1 and platelets, Factor VII and Haematocrit (HCT) levels in diabetic subjects. Conclusion: Conclusively, the correlation between pro-coagulant and hypofibrinolytic factors may be accountable for the hypercoagulability and thrombotic events which characterize T2DM, thereby providing an insight into factor-specific management of the disease with haematological parameters assisting routinely predict factor levels thereafter increasing the ease of prognosis of T2DM.

Association between Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism with Diabetic Peripheral Neuropathy and Its Importance as a Genetic Biomarker

Background: Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of type 2 diabetes mellitus (T2DM) with a prevalence ranging from 18.8% to 61.9% in India. For patients with T2DM, identifying those who are at risk of developing DPN is crucial for planning and implementing secondary preventive interventions, as well as for stepping up efforts to address risk factors. Very few studies have discovered a connection between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and the onset and progression of DPN in T2DM. Objectives: The current study intends to investigate the relationship between ACE gene I/D polymorphism with T2DM and DPN subjects among the South Tamil Nadu regional population. Materials and Methods: Thirty T2DM patients with DPN, 30 T2DM patients without DPN, and 30 control (nondiabetic) subjects were enrolled in this study. DPN was diagnosed using clinical and neurophysiological evaluation. Blood samples were collected and subjected to relevant investigations including blood glucose, glycated hemoglobin, serum creatinine, and serum lipids. Polymerase chain reaction amplification was performed to genotype the DNA for ACE I/D polymorphism using specific primers. Results: The ACE genotypes were distributed as II, 17 (57%); DD, 3 (10%); and ID, 10 (33%) in control group; II, 7 (23%); DD, 11 (37%); and ID, 12 (40%) in T2DM without DPN group, II, 3 (10%); DD, 16 (53%); and ID, 11 (37%) in T2DM with DPN group. The frequency of DD genotype was significantly higher in T2DM (P = 0.03) and T2DM patients with DPN (P = 0.001) compared to controls. The DD genotype versus II genotype was found to be associated with an increased risk of DPN (odds ratio [OR] = 10.28; 95% confidence interval [CI] =2.55–41.37). The D allele was more frequent among T2DM patients with DPN (71.6%) followed by T2DM patients (56.6%) compared to controls (26.6%). The D allele (vs. the I allele) is associated with an increased risk of T2DM (OR = 3.59, 95% CI = 1.670–7.742) and DPN (OR = 6.95, 95% CI = 3.120–15.507). Conclusion: The D allele and DD genotype of the ACE gene may both be risk factors for T2DM; in fact, the D allele of this polymorphism may potentially be linked to the development of DPN in T2DM patients. This finding implies that it may be possible to prevent DPN by early detection by identifying defects in ACE I/D polymorphisms in the south Indian regional population.

Fasting hepatic insulin clearance reflects postprandial hepatic insulin clearance: a brief report

BackgroundHepatic insulin clearance (HIC) is an important pathophysiology of type 2 diabetes mellitus (T2DM). HIC was reported to decrease in patients with type 2 diabetes and metabolic syndrome. HIC is originally calculated by post-load insulin and C-peptide from the oral glucose tolerance test (OGTT). However, OGTT or meal tolerance tests are a burden for patients, and OGTT is not suitable for overt diabetes due to the risk of hyperglycemia. If we can calculate the HIC from the fasting state, it is preferable. We hypothesized that fasting HIC correlates with postprandial HIC in both participants with T2DM and without diabetes. We investigated whether fasting HIC correlates with postprandial HIC in overt T2DM and nondiabetes subjects (non-DM) evaluated by using glucose clamp and meal load.MethodsWe performed a meal tolerance test and hyperinsulinemic–euglycemic clamp in 70 subjects, 31 patients with T2DM and 39 non-DM subjects. We calculated the postprandial C-peptide AUC-to-insulin AUC ratio as the postprandial HIC and the fasting C-peptide-to-insulin ratio as the fasting HIC. We also calculated whole-body insulin clearance from the glucose clamp test.ResultsThe fasting HIC significantly correlated with postprandial HIC in T2DM (r_S = 0.82, P < 0.001). Nondiabetes subjects also showed a significant correlation between fasting and postprandial HIC (r_S = 0.71, P < 0.001). Fasting HIC in T2DM was correlated with BMI, HbA1c, gamma-glutamyl transpeptidase, HOMA-IR, HOMA-beta, M/I, and whole-body insulin clearance. Fasting HIC in nondiabetes subjects was correlated with HOMA-IR and HOMA-beta.ConclusionsThese results suggest that fasting HIC is strongly correlated with postprandial HIC in both overt T2DM and non-DM patients, as evaluated by the meal test and glucose clamp method. Fasting HIC could be a convenient marker of HIC.

Optical Coherence Tomography Measurements in Type 1 Diabetic Subjects with Low and Moderate Daily Physical Activity.

Background: Physical activity is nowadays recognized as a protective factor against cardiovascular conditions, being cost-effective and easy to implement. Through its positive effects on hemodynamic and oxidative stress, different intensities in daily physical activity could influence diabetic macular edema (DME) in type 1 Diabetes Mellitus (DM). Methods: With the help of a spectral domain optical coherence tomography (OCT) device, we studied the macular thickness and ETDRS map parameters in type 1 DM patients who were classified into two groups: low and moderate intensity routine physical activity status, using the international physical activity questionnaire (IPAQ). All subjects received comparable anti-VEGF treatment. Results: Having a long disease evolution, patients with type 1 DM (T1DM) with moderate physical activity displayed better OCT measurements in specific retinal sectors than their counterparts with low physical activity. Variables such as age and body mass index (BMI) can influence the level of physical activity in T1DM patients. Conclusions: This study showed a lower prevalence of DME in T1DM subjects with moderate physical activity levels, revealing lower values for ETDRS OCT parameters in specific retinal sectors. The macular volumes (mm3) were significantly lower in the right eye for this group of subjects. Abbreviations: BMI = body mass index, CMT = central macular thickness, DM = diabetes mellitus, DME = diabetic macular edema, DR = diabetic retinopathy, FT = foveal thickness, II = inferior inner thickness, IO = inferior outer thickness, IPAQ = international physical activity questionnaire, LE = left eye, OCT = optical coherence tomography, MMT = maximal macular thickness, mMT = minimal macular thickness, MV = macular volume, NI = nasal inner thickness, NO = nasal outer thickness, QoL = quality of life, RE = right eye, SI = superior inner thickness, SO = superior outer thickness, T1DM = type 1 diabetes mellitus, T2DM = type 2 diabetes mellitus, TI = temporal inner thickness, TO = temporal outer thickness.