Diabetic Group Research Articles

Reliability and utility of blood glucose levels in the periodontal pockets of patients with type 2 diabetes mellitus: a cross-sectional study

Background Several studies have measured gingival blood glucose (GBG) levels, but few have confirmed systematic bias using Bland–Altman analysis. This study compared the effectiveness of GBG levels with that of fingertip blood glucose (FTBG) levels using Bland–Altman and receiver operating characteristic (ROC) analyses. Methods A total of 15 healthy volunteers and 15 patients with type 2 diabetes were selected according to inclusion and exclusion criteria. Each group comprised eight male and seven female participants. The GBG and FTBG levels were measured using a self-monitoring blood glucose device after periodontal examination. Pearson’s product‒moment correlation and simple linear regression analyses were performed. In addition, Bland‒Altman analysis was also performed to assess the degree of agreement between the two methods. ROC analysis was conducted to determine the sensitivity, specificity, and cutoff values for patients with diabetes. The area under the ROC curve (AUC) was used to identify significant differences. Results The mean GBG and FTBG levels were 120 ± 44.8 mg/dL and 137 ± 45.1, respectively, for the whole sample. The mean GBG and FTBG levels were 145 ± 47.2 mg/dL and 163 ± 49.1, respectively, in the diabetes group. The mean GBG and FTBG levels in the nondiabetes group were 95.3 ± 25.2 and 111 ± 18.8, respectively. Patients with diabetes were more likely to have a probing pocket depth (PPD) of ≥4 mm at the sampled site. Pearson’s product‒moment correlation and simple linear regression analyses revealed a significant correlation between the GBG and FTBG measurements. Bland–Altman analysis revealed that GBG and FTBG measurements differed significantly among all participants; however, no significant differences were observed among the patients with diabetes (mean difference (MD) ± standard deviation (SD) = −18.1 ± 34.2, 95% confidence interval (CI) [−37.0 to 0.88]) or among the participants with a PPD of ≥4 mm (MD ± SD = −15.2 ± 30.4, 95% CI [−30.8 to 0.43]). The sensitivity, specificity, and cutoff values of the GBG measurements for detecting diabetes were 80%, 93%, and 123.5 mg/dL, respectively. The sensitivity, specificity, and cutoff values of the FTBG measurements for detecting diabetes were 73%, 87%, and 134.0 mg/dL, respectively. No significant differences were observed between the AUCs (0.078, 95% CI [−0.006 to 0.161]). Conclusions The GBG measurements aligned with the FTBG measurements in the patients with diabetes and among the participants with a PPD of ≥4 mm. Patients with diabetes were more likely to have a PPD of ≥4 mm at the sampled site, GBG levels can be used to screen for type 2 diabetes in dental clinics.

Influence of Diabetes Mellitus on Neurological Recovery in Older Patients With Cervical Spinal Cord Injury Without Bone Injury: A Retrospective Multicenter Study.

Retrospective study. To investigate the impact of diabetes mellitus on neurological recovery and determine the relationship between moderate-severe diabetes and neurological recovery in patients with cervical spinal cord injury (CSCI) without bone injury. A retrospective study was conducted on 389 consecutive patients aged ≥65 years with CSCI without bone injury across 33 medical institutes. The patients were divided into a nondiabetic group (n = 270) and a diabetic group (n = 119). Neurological outcomes were compared between the two groups through propensity score matching. The impact of moderate-severe diabetes (defined as hemoglobin A1c ≥ 7.0% or requiring insulin treatment) on neurological recovery was evaluated through multiple linear regression analysis. Propensity score matching revealed no significant differences between the diabetic and nondiabetic groups in terms of American Spinal Injury Association (ASIA) impairment scale grade and mean total ASIA motor scores (AMS) at 6 months post-injury. Multiple linear regression analysis indicated that age on admission (B = -0.34; 95% confidence interval [CI], -0.59 to -0.08; P = 0.01), dementia (B = -16.50; 95% CI, -24.99 to -8.01; P < 0.01), and baseline total AMS (B = -0.62; 95% CI, -0.72 to -0.51; P < 0.01) were negative predictors of neurological recovery at 6 months post-injury. The presence of moderate-severe diabetes did not influence neurological recovery at 6 months post-injury. Diabetic patients with CSCI without bone injury achieved improvements in neurological function comparable to those of nondiabetic patients. Moderate-severe diabetes did not affect neurological recovery in patients with CSCI without bone injury.

Cardioimmunology in Health and Diseases: Impairment of the Cardio-Spleno-Bone Marrow Axis Following Myocardial Infarction in Diabetes Mellitus

A comprehensive understanding of the cardio-spleen-bone marrow immune cell axis is essential for elucidating the alterations occurring during the pathogenesis of diabetes mellitus (DM). This study investigates the dynamics of immune cell kinetics in DM after myocardial infarction (MI) over time. MI was induced in diabetic and healthy control groups using C57BL/N6 mice, with sacrifices occurring at days 1, 3, 7, and 28 post-MI to collect heart, peripheral blood (PB), spleen, and bone marrow (BM) samples. Cell suspensions from each organ were isolated and analyzed via flow cytometry. Additionally, the endothelial progenitor cell-colony-forming assay (EPC-CFA) was performed using mononuclear cells derived from BM, PB, and the spleen. The results indicated that, despite normal production in BM and the spleen, CD45+ cells were lower in the PB of DM mice at days 1 to 3. Further analysis revealed a reduction in total and pro-inflammatory neutrophils (N1s) in PB at days 1 to 3 and in the spleen at days 3 to 7 in DM mice, suggesting that DM-induced alterations in splenic neutrophils fail to meet the demand in PB and ischemic tissues. Infiltrating macrophages (total, M1, M2) were reduced at day 3 in the DM-ischemic heart, with total and M1 (days 1–3) and M2 (days 3–7) macrophages being significantly decreased in DM-PB compared to controls, indicating impaired macrophage recruitment and polarization in DM. Myeloid dendritic cells (mDCs) in the heart were higher from days 1 to 7, which corresponded with the enhanced recruitment of CD8+ cells from days 1 to 28 in the DM-infarcted myocardium. Total CD4+ cells decreased in DM-PB at days 1 to 3, suggesting a delayed adaptive immune response to MI. B cells were reduced in PB at days 1 to 3, in myocardium at day 3, and in the spleen at day 7, indicating compromised mobilization from BM. EPC-CFA results showed a marked decrease in definitive EPC colonies in the spleen and BM from days 1 to 28 in DM mice compared to controls in vitro, highlighting that DM severely impairs EPC colony-forming activity by limiting the differentiation of EPCs from primitive to definitive forms. Taking together, this study underscores significant disruptions in the cardio-spleen-bone marrow immune cell axis following MI in DM, revealing delayed innate and adaptive immune responses along with impaired EPC differentiation.

Association between stress hyperglycemia ratio and postoperative major adverse cardiovascular and cerebrovascular events in noncardiac surgeries: a large perioperative cohort study

BackgroundThere has been a concerning rise in the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) following noncardiac surgeries (NCS), significantly impacting surgical outcomes and patient prognosis. Glucose metabolism abnormalities induced by stress response under acute medical conditions may be a risk factor for postoperative MACCE. This study aims to explore the association between stress hyperglycemia ratio (SHR) and postoperative MACCE in patients undergoing general anesthesia for NCS.MethodsThere were 12,899 patients in this perioperative cohort study. The primary outcome was MACCE within 30 days postoperatively, defined as angina, acute myocardial infarction, cardiac arrest, arrhythmia, heart failure, stroke, or in-hospital all-cause mortality. Kaplan-Meier curves visualized the cumulative incidence of MACCE. Cox proportional hazard models were utilized to assess the association between the risk of MACCE and different SHR groups. Restricted cubic spline analyses were conducted to explore potential nonlinear relationships. Additionally, exploratory subgroup analyses and sensitivity analyses were performed.ResultsA total of 592 (4.59%) participants experienced MACCE within 30 days after surgery, and 1,045 (8.10%) within 90 days. After adjusting for confounding factors, compared to the SHR T2 group, the risk of MACCE within 30 days after surgery increased by 1.34 times (95% CI 1.08–1.66) in the T3 group and by 1.35 times (95% CI 1.08–1.68) in the T1 group respectively. In the non-diabetes group, the risk of MACCE within 30 days after surgery increased by 1.60 times (95% CI 1.21–2.12) in the T3 group and by 1.61 times (95% CI 1.21–2.14) in the T1 group respectively, while no statistically significant increase in risk was observed in the diabetes group. Similar results were observed within 90 days after surgery in the non-diabetes group. Additionally, a statistically significant U-shaped nonlinear relationship was observed in the non-diabetes group (30 days: P for nonlinear = 0.010; 90 days: P for nonlinear = 0.008).ConclusionIn this large perioperative cohort study, we observed that both higher and lower SHR were associated with an increased risk of MACCE within 30 and 90 days after NCS, especially in patients without diabetes. These findings suggest that SHR potentially plays a key role in stratifying cardiovascular and cerebrovascular risk after NCS.

Beclin1/LC3II/P62 autophagy pathway activation is involved in the protective action of C-peptide against prostate injury in a rat model of type 1 diabetes

One of the undesirable complications of diabetes is sexual dysfunctions in males which may affect their fertility. This research aims to study the effect of C-peptide administration on the prostate of diabetic rats and focusing on exploring the role of the autophagy pathway in diabetic prostate and whether it is involved in C-peptide action. Forty adult male Wistar albino rats were separated into control group, diabetic group, diabetic + C-peptide and diabetic + C-peptide + 3-Methyladenine (autophagy inhibitor). Serum metabolic parameters and prostatic specific antigen (PSA) were measured. Markers of oxidative stress, inflammation, fibrosis, cell proliferation and cell autophagy were evaluated in prostate tissues using biochemical, western blotting and immunohistochemical techniques. C-peptide administration ameliorated the effects of diabetes on the prostate through its hypoglycaemic, antioxidant, anti-inflammatory, and antiproliferative effects which were reversed with autophagy inhibition. Thus, we concluded that C-peptide prevented the effects of diabetes on the prostate through stimulation of the autophagy pathway.

The Effect of Aerial Part of Melissa Officinalis L. Hydro-Alcoholic Extract on Pituitary- Gonadal Axis Function in Diabetic Male Mice

Background: Melissa officinalis L. ( lemon balm) is one of the more widely cultivated medicinal and aromatic plants that has long been used in traditional medicine to treat many disorders. The present study investigates Melissa officinalis L. hydro-alcoholic extract regarding pituitary-gonadal axis in diabetic mice. Methods: 45 NMRI mice with a mean weight of 35.6±4.5 g were divided into five groups: control group (0.2 ml of physiological serum intraperitoneally injection), diabetic mice (without treatment), and three experiment groups (diabetic groups receiving 50, 100 and 200 mg/kg of Melissa officinalis extract intraperitoneally injection). Melissa officinalis extract was injected intraperitoneally for 14 days. At the end of the experiment, blood samples were taken to determine the biochemical indicators level (glucose, LH, FSH, and testosterone), and the left testicle was weighed and examined histologically. Results: The results showed that the lowest amount of glucose and the highest level of LH were observed in the treatment group at a dose of 100 mg/kg of Melissa officinalis extract. The highest level of FSH was observed at a dose of 200 mg/kg. Histological study of the testis showed a more favorable condition in the experimental group of 200 mg/kg of lemon balm extract (P&lt;0.05). Conclusion: It can be concluded that the use of Melissa officinalis extract is efficient in reducing glucose, improving the levels of LH, FSH, and testosterone in diabetic mice, affecting testicular weight, and improving testicular tissue indices and reproductive function of rats.

Agmatine alleviates diabetic-induced hyposalivation in rats: A histological and biochemical study

Diabetic patients commonly experience hyposalivation, which can cause challenges with eating, swallowing, dry mouth, and speaking. It also raises the likelihood of developing periodontal disease. This study aimed to evaluate if agmatine could improve the rate of salivation in rats with hyposalivation induced by streptozotocin (STZ). Five groups of Wistar rats were utilized with 10 animals in each group. They were classified as follows; Negative control group (G1), agmatine (G2) group, and Nicotinamide (NA)-STZ (G3) group; received a single intraperitoneal dose of 65 mg/kg of STZ after NA injection. NA was administered to protect residual β cells and enhance their insulin secretion; NA-STZ + Metformin (G4) Metformin-treated diabetic group; at day 10 diabetic rats received 50mg/kg orally for 28 days, and NA-STZ + Agmatine (G5) at day 10 diabetic rats received a daily intraperitoneal dose of 300 mg/kg Agmatine for 28 days. The salivary flow rate was assessed weekly. Then, the animals were euthanized, both parotid (PG) and submandibular (SMG) salivary glands were dissected, and the following parameters were assessed; salivary glands' histopathology, aquaporin 5 (AQP5), caspase-3, E-cadherin expressions, inflammatory markers and finally, salivary glands' oxidative stress status. Agmatine has alleviated the salivary glands' dysfunction in STZ-induced diabetic rats. It normalized diabetes mellitus-associated salivary glands' abnormalities including histopathological abnormalities, decreased AQP5 and E-cadherin expressions, increased caspase-3 expression, and oxidative stress and inflammatory parameters. Agmatine alleviates diabetes mellitus-associated hyposalivation. It can promote PGs and SMGs function through its histological and AQP5 expression improvements.

A Comparative Study on the Impact of Fasting on Blood Glucose and Blood Pressure Among Diabetic and Non-Diabetic Individuals During Ramadan, Kurdistan Region, Iraq

Objective: The primary aim of this research was to evaluate the differential effects of regular and fasting dietary patterns on blood glucose levels and blood pressure among diabetic patients and non-diabetic control group. A comprehensive analysis was conducted to compare physiological responses on fasting versus non-fasting days during the holy Ramadan month. Methods: This observational study involved 92 participants, with a subset of 38 diabetic patients and 54 non-diabetic control group, aged 19-76 years, who were observed on regular and fasting days. Participants were monitored for pre-prandial, postprandial, evening blood sugar, and fasting blood glucose levels, as well as blood pressure. Statistical analysis was performed using paired sample t-tests to compare mean ± SD between regular and fasting days of both groups. The study cohort consisted of male and female adults diagnosed with type 1 or type 2 diabetes. Exclusion criteria included individuals under 18 years, pregnant women, and patients unable to fast during the study period. Results: Statistical analysis revealed significant differences in fasting blood glucose levels during Ramadan compared to non-fasting days. In the diabetic group, significant changes were observed in fasting blood glucose levels during Ramadan compared to after Ramadan ( postprandial blood sugar p=0.04, evening blood sugar p=0.019). In contrast, the non-diabetic group also showed significant changes in blood glucose levels during Ramadan compared to after Ramadan (postprandial blood sugar p=0.001, evening blood sugar p=0.020). Blood pressure showed no significant differences between these periods, suggesting that fasting does not alter blood pressure significantly in diabetic individuals. Additionally, a two-way ANOVA demonstrated significant dietary influences on post-Iftar glucose levels in non-diabetics (p&lt;0.001), but not in diabetics, suggesting differential metabolic responses to dietary intake during Ramadan. These findings emphasize the critical need for personalized dietary management and continuous monitoring to optimize diabetic care during fasting. Conclusion: Fasting significantly influences blood glucose levels in diabeticand non-diabetic individuals but does not affect blood pressure. This study underscores the necessity for personalized medical guidance and balanced meal planning to minimize complications and enhance diabetes management during fasting. Further research is warranted to explore the long-term effects of different fasting practices on diabetic health outcomes.

Serum metabolomics signature of maternally inherited diabetes and deafness by gas chromatography-time of flight mass spectrometry.

The aim of this study was to identify a metabolic signature of MIDD as compared to healthy controls and other types of diabetes. We performed a comprehensive serum metabolomic analysis using gas chromatography-time of flight mass spectrometry (GC-TOFMS) in participants diagnosed with MIDD (n = 14), latent autoimmune diabetes in adults (LADA) (n = 14), type 2 diabetes mellitus (n = 14), and healthy controls (n = 14). Each group was matched for gender and age. There were significant metabolic differences among MIDD and other diabetic and control groups. Compared with control, MIDD patients had high levels of carbohydrates (glucose, galactose, mannose, sorbose, and maltose), fatty acids (2-Hydroxybutyric acid, eicosapentaenoic acid, and octadecanoic acid), and other metabolites (alanine, threonic acid, cholesterol, lactic acid, and gluconic acid), but low level of threonine. Compared with LADA, MIDD patients had high levels of threonic acid and some amino acids (alanine, tryptophan, histidine, proline, glutamine, and creatine) but low levels of serine. Compared with type 2 diabetes mellitus, MIDD patients had high levels of citrulline, creatine, 3-Amino-2-piperidone, but low levels of ornithine, fatty acids (arachidonic acid and octadecanoic acid), and intermediates of the tricarboxylic acid cycle (malic acid and succinic acid). Our study identified a specific metabolic profile related to glycolysis and the tricarboxylic acid cycle in MIDD that differs from healthy controls and other types of diabetes. This unique metabolic signature provides new perspectives for understanding the pathophysiology and underlying mechanisms of MIDD.

Veeraswamy Seshiah: Father of Gestational Diabetes in India

Professor Dr. V. Seshiah, MD, FRCP, DSc, (Hony), is a distinguished professor at Tamil Nadu's Dr. MGR Medical University and established the First Department of Diabetology in India at Madras Medical College in 1978. He was the patron of the Research Society for the Study of Diabetes in India and the founder patron of the Diabetes in Pregnancy Study Group, India (DIPSI). Additionally, he served as the Vice-Chair of the Executive Board of the International Association of Diabetes and Pregnancy Study Group. Dr. V Balaji and Dr. V Seshiah Diabetes Care Center &amp; Research Institute, which he founded, received the Army Decorations "SAMAR SEVA STAR" and "SAINYA SEVA MEDAL" in 1965 with clasp HIMALAYAS. Dr. Seshiah was also the recipient of the DR. B.C.ROY National Award was given in 1988 for developing diabetology as the Indian College of Physicians provided a specialty in the country and the Master Teacher Award. Moreover, he was honored with the Lifetime Achievement Award by the International Diabetes Federation in 2017, being the first Indian to receive this award. In 2022, the President of India, Mr. Kovind, presented the Padma Shri to Dr. Veeraswamy Seshiah for Medicine.

Oral self-care practices, oral health status and treatment needs in diabetic and non-diabetic patients undergoing orthodontic treatment

Background: Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia resulting either from defects in insulin secretion, action, or both, affecting almost all tissues in body, including those in oral cavity and hence the aim of this study is to assess oral self-care practices, oral health status and treatment needs of diabetic and non-diabetic patients undergoing orthodontic treatment. Methods: A cross-sectional descriptive study was conducted among 120 each diabetic and non-diabetic patients ranging from 14-35 years undergoing orthodontic treatment. Data was collected using pre tested questionnaire for oral self-care practices and WHO proforma (1997) was used for assessing oral health status and treatment needs. Data was analyzed using SPSS version 17. Results: The present study revealed that there was not much difference in the oral hygiene practices among both groups. Percentage of oral mucosal lesions, Pocket formation, Loss of Attachment and mean DMFT was high among diabetic group when compared to non-diabetics. Conclusions: Since the prevalence of periodontitis is more among diabetic, the oral hygiene practices have to be improved. The oral complications of diabetes can be prevented by combined effect of dentist and the Physician by emphasizing the patients for periodic review to dentist for improving the oral health.

Assessment of cardiac and skeletal muscle metabolites using 1H-MRS and chemical-shift encoded magnetic resonance imaging: Impact of diabetes, RAGE, and DIAPH1.

Diabetes affects metabolism and metabolite concentrations in multiple organs. Previous preclinical studies have shown that receptor for advanced glycation end products (RAGE, gene symbol Ager) and its cytoplasmic domain binding partner, Diaphanous-1 (DIAPH1), are key mediators of diabetic micro- and macro-vascular complications. In this study, we used 1H-Magnetic Resonance Spectroscopy (MRS) and chemical shift encoded (CSE) Magnetic Resonance Imaging (MRI) to investigate the metabolite and water-fat fraction in the heart and hind limb muscle in a murine model of type 1 diabetes (T1D) and to determine if the metabolite changes in the heart and hind limb are influenced by (a) deletion of Ager or Diaph1 and (b) pharmacological blockade of RAGE-DIAPH1 interaction in mice. Nine cohorts of male mice, with six mice per cohort, were used: wild type non-diabetic control mice (WT-NDM), WT-diabetic (WT-DM) mice, Ager knockout non-diabetic (RKO-NDM) and diabetic mice (RKO-DM), Diaph1 knockout non-diabetic (DKO-NDM), and diabetic mice (DKO-DM), WT-NDM mice treated with vehicle, WT-DM mice treated with vehicle, and WT-DM mice treated with RAGE229 (antagonist of RAGE-DIAPH1 interaction). A Point Resolved Spectroscopy (PRESS) sequence for 1H-MRS, and multi-echo gradient recalled echo (GRE) for CSE were employed. Triglycerides, and free fatty acids in the heart and hind limb obtained from MRS and MRI were compared to those measured using biochemical assays. Two-sided t-test, non-parametric Kruskal-Wallis Test, and one-way ANOVA were employed for statistical analysis. We report that the results were well-correlated with significant differences using MRI and biochemical assays between WT-NDM and WT-DM, as well as within the non-diabetic groups, and within the diabetic groups. Deletion of Ager or Diaph1, or treatment with RAGE229 attenuated diabetes-associated increases in triglycerides in the heart and hind limb in mice. These results suggest that the employment of 1H-MRS/MRI is a feasible non-invasive modality to monitor metabolic dysfunction in T1D and the metabolic consequences of interventions that block RAGE and DIAPH1.

The Quantitative InVivo Assessment of Diabetic andNon-Diabetic Skin Wound Healing Using Phasor-FLIM Approach.

A quantitative assessment of wound status in a murine model was developed using phasor plot presentation of fluorescence lifetime imaging microscopy (FLIM) data. The quantitative assessment is based on calculating Bhattacharyya distance between g coordinates of FLIM data phasor plot density distributions of wound and healthy skin. The approach was validated for both diabetic and non-diabetic mice wounds, including during low-dose photodynamic therapy (LDPDT). Analysis revealed a shift in the FLIM data phasor plot g coordinates, suggesting altered metabolic processes involved in wound healing. Bhattacharyya distances in the LDPDT groups were closer to zero compared to the control group, which was not treated by LDPDT. Bhattacharyya distances in the non-diabetic LDPDT groups were closer to zero compared to the diabetic LDPDT groups that is consistent with the literature regarding the positive role of LDPDT in accelerating wound healing and the role of diabetes mellitus in impairing wound healing.

Comparing the ability of GRACE 2.0 and GRACE 3 scores for predicting in-hospital mortality in patients with and without diabetes

Abstract Background Sex-specific refinement of GRACE 2.0 was published as GRACE 3.0 (G3). The relative ability of G3 in predicting in-hospital mortality in diabetic patients has not been explored. Purpose Explore the ability of G3 in determining in-hospital mortality in patients with and without diabetes. Methods Retrospective cohort analysis of data on NSTEMI and UA patients admitted in two hospitals between 2010 and 2019 entered into the Myocardial Infarction National Audit Project database. All baseline characteristics and G2, G3 scores were recorded. In hospital death was recorded from hospital records. The discriminative power of the G2 score was determined by comparing the area under the receiver operating characteristic curve (c-statistics). Accuracy of calibration was evaluated by plotting the mean predicted vs observed mortality in each decile of predicted risk, Hosmer-Lemeshow (HL) goodness-off it test and the Nagelkerke R2 (NR2). Results G3 was calculated in 2768 patients (age 69±14yrs, 62.3% male, 877(31.7%) with diabetes. Median risk for the cohort was 1.3%, (95% CI 1.2 to 1.4). G3 risk was higher in patients with diabetes (median 2.0 IQR 0.6 to 5.5 vs 1.0 IQR 0.3 to 3.7, p&amp;lt;0.0001). In-hospital mortality occurred in 68 (2.5%) patients with no difference between the diabetes groups (3.1% and 2.2% died in the DM and non-DM groups respectively). In the whole cohort, G3 reclassified 139(7.5%) patients in low-intermediate to high risk-category and 159(17.4%) patients in high to low-intermediate category. 10.1% and 6.5% were upgraded and 16.1% and 18.1% were downgraded in DM and non-DM groups. Overall discriminatory power of G3 (AUC 0.87, 95% CI 0.86 to 0.88, p&amp;lt;0.0001) was excellent but no different from G2 (AUC 0.86 95% CI 0.85 to 0.88, p&amp;lt;0.0001) (δAUC 0.009, p=0.461). In patients with diabetes, G3 yielded higher AUC (AUC 0.85, 95% CI 0.83 to 0.87, p&amp;lt;0.0001) than G2 (AUC 0.82, 95% CI 0.79 to 0.84, p&amp;lt;0.00101) but this was not statistically significant (δAUC 0.031, p=0.142). In patients without DM, the difference was smaller (δAUC 0.002, p=0.906). Neither G2 (δAUC 0.061, p=0.185) nor G3 (δAUC 0.028, p=0.473) was better in discrimination in DM compared to non-DM groups (Fig1A,B). In the diabetic group, calibration plot for the G3 score showed suboptimal calibration with consistent overestimation of the risk across all risk deciles (Figure1C), with the HL test showing significant differences between the observed and predicted values (p &amp;lt;0.0001) and the NR2 was low 0.09. The GRACE 2 score showed better calibration (Fig1D) (HL: p=0.09, NR2 0.11). In patients without diabetes, calibration plot for the G3 (HL: p= 0.17; NR2 0.33) (Fig1E) and G2 (HL: p=0.15, NR2 0.25) (Fig1F) shows similar pattern of overestimation of the risk less so for latter. Conclusion G3 and G2 shows excellent discrimination for in-hospital mortality in both diabetic and non-diabetic patients. G2 seems to show better calibration than G3 for diabetic patients.

Diabetes Mellitus influence in Lipoprotein(a) gene expression and association to coronary artery disease

Abstract Introduction Lp(a) and type 2 diabetes mellitus are both known and established risk factors for the development of coronary artery disease (CAD). Lp(a) levels are 75% to 95% heritable and predominately determined by single-nucleotide variants at the LPA gene; rs3798220 is one of the most studied variants and accounts for a significant portion of Lp(a) levels. Whether diabetes could influence the LPA rs3798220 account for Lp(a) levels is unknown. Aim Evaluate whether there is a different association between polymorphism LPA rs3798220 T&amp;gt;C and Lp(a) levels and their association with CAD in diabetic and non-diabetic populations. Methods 3,209 subjects (mean age 59.3±8.9 years, 76.3% male were selected from the data set of the Research Center. The LPA rs3798220 T&amp;gt;C was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). This genetic variant has a minor allele frequency (MAF) &amp;lt;2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. Lp(a) biochemical levels were measured in all participants. From the 3,209 participants, 810 had diabetes, and 2399 were no diabetics. For each group, chi-squared tests were used to determine the association of CAD prevalence by genotype, and t-tests were used to evaluate differences in CAD prevalence by Lp(a) levels. Results In non-diabetic subjects, LPA TC was significantly associated with CAD in non-diabetic subjects compared with TT (p&amp;lt;0.0001). Similarly, Lp(a) was higher in the CAD population (37.2±39.7) compared to the healthy population (25.6±30.0) (p&amp;lt;0.0001). In diabetic group, Lp(a) was higher in the CAD population (38.5±41.4) compared to the population without CAD (23.9±29.2) (p&amp;lt;0.0001). Nevertheless, there was no difference in genotype between CAD and non-CAD patients (p=0.710). Conclusion The LPA rs3798220 T&amp;gt;C variant in non-diabetic group can explain high Lp(a) levels and their association with CAD. However, in patients with diabetes, Lp(a) is elevated in CAD patients besides the fact that no significant genotype differences were displayed. Non-genetic influences like behavioural factors or even epigenetic changes may probably explain high Lp(a) levels in this population.

Histological Change of Placenta in Diabetic Pregnant Women in Comparison to Normal Pregnant Women

Background: The placenta is a foeto-maternal organ and its alterations is directly related to the disease’s length and severity. The human placenta experiences a number of functional and structural pathologic alterations when complicated by metabolic disorder such as diabetes mellitus. Methods: This cross-sectional comparative study was conducted over a period of threeyears from January 2019 to December 2021 at the Department of Anatomy, Rajshahi Medical College, Rajshahi, in collaboration with the Department of Obstetrics and Gynaecology, Rajshahi Medical College Hospital and Diabetic Hospital Rajshahi, Bangladesh. The study was carried out on 70 pregnant women, among them 35 diabetics and 35 non-diabetics. The fibrinoid necrosis, syncytial knot and immature villi of the placenta were studied in diabetic and non-diabetic pregnant women. SPSS software, version-24 was used for data analysis, with a p-value &lt; 0.05 indicating statistically significance for all tests. Results: The diabetic and non-diabetic pregnant women groups were almost identical in terms of attachment of umbilical cord to placenta with marginal attachment being more often found in either group (p = 0.829). Histological examination of placenta showed that fibrinoid necrosis was common in placenta of diabetic mothers than that of the normal mothers (p &lt; 0.001). Syncytial knot and immature villi were higher in the former group than those in the latter group, here p values were also less than .001. Conclusion: Histological findings (fibrinoid necrosis, syncytial knot and immature villi) were more in placenta of diabetic mother and they were highly significant different between the groups. EWMCJ Vol. 12, No. 1&amp;2, January-July 2024: 27-33

New Insights on the potential therapeutic effects of glibenclamide and Obeticholic acid against Alloxan-Induced diabetes mellitus in rat model

Diabetes mellitus (DM) represents a highly prevalent metabolic disorder across the globe. This study aimed to determine the ameliorative efficacy of glibenclamide (Gli) and obeticholic acid (OCA) against biochemical and pathological changes related to alloxan-induced diabetes. Twenty male Wistar rats were allocated into four groups; Control group, Diabetic group: received intraperitoneal injection of alloxan (120 mg/kg) for induction of diabetes, Diabetic + Gli group: Diabetic rats treated daily with oral Gli (5 mg/kg) and Diabetic + OCA group: Diabetic rats treated daily with oral OCA (10 mg/kg). All rats were subjected to 30 days treatments. Our results indicated that Gli successfully ameliorated hyperglycemia and dyslipidemia with a significant decline in serum pancreatic lipase activity and increased insulin level, while OCA had the same effect but without any enhancement in serum insulin levels. Additionally, the disturbances in liver function-related parameters and the evoked oxidative stress, interleukin(IL)-6 and IL-10 in the liver and pancreas were abrogated upon treatment with Gli and OCA. Furthermore, Gli and OCA increased AMP-activated protein kinase (P-AMPK), insulin receptor substrate 1 (IRS1), farnesoid X receptor (FXR), and glucagon-like peptide-1 receptor (GLP-1R) expressions and downregulated sterol regulatory element binding protein-1c mRNA expression. Besides, Gli and OCA have alleviated diabetes-induced histopathological distortions in hepatic and pancreatic tissues and enhanced the immunoexpression of insulin, and proliferating cell nuclear antigen with decreased immune reactivity of glucagon within pancreatic tissues. Gli and OCA decreased the immune reactivity of nuclear factor kappa B and increased the glycogen content of hepatic tissues. In conclusion, OCA is efficacious in the management of dyslipidemia and hyperglycemia of DM and its related oxidative stress.

The use of metabolomics and machine learning algorithms to predict post-transplant diabetes mellitus in renal transplant patients on Tacrolimus therapy.

Tacrolimus (TAC) has significantly improved kidney graft survival following transplantation, though it is associated with adverse side effects. The most prevalent complication resulting from excessive TAC exposure is the onset of de novo diabetes mellitus (DM), a condition that can negatively impact both renal graft function and patient outcomes. De novo DM is linked to an increased risk of chronic transplant dysfunction, as well as cardiovascular morbidity and mortality. Although the underlying mechanisms remain unclear, emerging research in the field of omics shows promise. The aim of this study was to investigate the metabolomic profile of kidney transplant patients who developed de novo DM, in comparison to those who did not, following TAC exposure, using untargeted metabolomic analysis through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and machine learning algorithms. A cohort of 34 kidney transplant patients on a Tacrolimus regimen for at least 6 months was enrolled in the study, with serum samples collected from each patient. Comprehensive profiling of serum metabolites was performed, enabling the classification of patients into de novo diabetes mellitus and non diabetes groups. The metabolomic analysis of serum was conducted using UHPLC-MS. Of the 34 patients, 16 were diagnosed with TAC-induced diabetes. A total of 334 metabolites were identified in the serum samples, of which 10 demonstrated a significant correlation with the de novo diabetes mellitus group. Most of these metabolites were linked to alterations in lipid metabolism. The application of metabolomics in kidney transplant patients undergoing a Tacrolimus regimen is both feasible and effective in identifying metabolites associated with de novo diabetes mellitus. This approach may provide valuable insights into the metabolic alterations underlying TAC-induced diabetes.

International dietary quality index and its association with diabetes in RaNCD cohort study

Diabetes and its complications pose a significant threat to global health. Various factors contribute to the development of diabetes, with diet being an important trigger. The Dietary Quality Index-International (DQI-I) serves as an indicator of changes in diet and its association with chronic diseases, including diabetes. The aim of this study is to examine the association between DQI-I and diabetes in adults. Data from the first phase of the Ravansar Non-Communicable Disease Cohort Study (RaNCD) were used for this cross-sectional study. The study included individuals from western Iran aged between 35 and 65 years. The DQI-I was used to assess diet quality and the essential aspects of a healthy diet. Multiple logistic regression analyses were performed to compare DQI-I total score and diabetes. A total of 7,079 individuals were included, including 608 diabetic and 6,471 healthy individuals. The mean DQI-I score was 60.51 ± 8.47 in healthy individuals and 63.12 ± 8.64 in diabetics. The odds of developing diabetes were higher in individuals with a higher DQI-I (adjusted odds ratio: 1.49, 95% CI: 1.30–1.73). The variety was 13.43 ± 4.47 in diabetics and 12.59 ± 4.79 in healthy individuals. Adequacy was 33.23 ± 3.71 in diabetics and 33.79 ± 3.37 in healthy individuals. Moderation was 13.27 ± 6.05 in diabetics and 11.79 ± 5.47 in healthy individuals. The overall balance was 2.88 ± 2.21 in the healthy group and 2.61 ± 2.13 in the diabetics. The macronutrient ratio was 2.15 ± 1.88 in the healthy group and 2.04 ± 1.84 in the diabetics. The fatty acid ratio was 0.72 ± 1.29 in the healthy group and 0.56 ± 1.17 in the diabetic group. The overall balance score was higher in the healthy subjects. The DQI-I total score was higher in diabetics, indicating a positive association between diabetes and the DQI-I. Therefore, the importance of continuous dietary management and education of diabetic patients should be emphasized.

Knockout of the Carbohydrate Responsive Element Binding Protein Enhances Proliferation and Tumorigenesis in Renal Tubules of Mice

Glycogen-storing so-called clear cell kidney tubules (CCTs), precursor lesions of renal cell carcinoma, have been described in diabetic rats and in humans. The lesions show upregulation of the Akt/mTOR-pathway and the related transcription factor carbohydrate responsive element binding protein (ChREBP), which is supposedly pro-oncogenic. We investigated the effect of ChREBP-knockout on nephrocarcinogenesis in streptozotocin-induced diabetic and normoglycemic mice. Diabetic, but not non-diabetic mice, showed CCTs at 3, 6 and 12 months of age. Glycogenosis was confirmed by periodic acid schiff reaction and transmission electron microscopy. CCTs in ChREBP-knockout mice consisted of larger cells and occurred more frequently compared to wildtype mice. Progression towards kidney tumors was observed in both diabetic groups but occurred earlier in ChREBP-knockout mice. Proliferative activity assessed by BrdU-labeling was lower in 1-week-old but higher in 12-month-old diabetic ChREBP-knockout mice. Surprisingly, renal neoplasms occurred spontaneously in non-diabetic ChREBP-knockout, but not non-diabetic wildtype mice, indicating an unexpected tumor-suppressive function of ChREBP. Immunohistochemistry showed upregulated glycolysis and lipogenesis, along with activated Akt/mTOR-signaling in tumors of ChREBP-knockout groups. Immunohistochemistry of human clear cell renal cell carcinomas revealed reduced ChREBP expression compared to normal kidney tissue. However, the molecular mechanisms by which loss of ChREBP might facilitate tumorigenesis require further investigation.