Type 2 Diabetes Mellitus Subjects Research Articles

Obstructive Sleep Apnoea and Type 1 Diabetes Mellitus: A Neglected Relationship?

Obstructive sleep apnoea (OSA) is regarded as a major health condition, progressively affecting an increased number of people around the world. The interplay between OSA and type 2 diabetes mellitus (T2DM) has been extensively studied. However, little is known about the relationship between OSA and type 1 diabetes mellitus (T1DM). This review provides insight into the prevalence of OSA in T1DM and its relationship with diabetic complications. Studies have hitherto yielded contradictory results on the occurrence of OSA in T1DM. Indeed, the risk of OSA in T1DM has ranged from 1 in 10 to more than 1 in 2 T1DM subjects. This high occurrence was confirmed by objective polysomnography as well as widely used subjective questionnaires. Multiple studies revealed the important correlation between OSA and diabetes complications. Both microvascular (nephropathy, neuropathy and retinopathy) and macrovascular complications appear to be associated with OSA occurrence, although some associations were not significant due to inadequate data. In conclusion, T1DM subjects carry a higher risk of undiagnosed OSA. Additional studies are needed to clarify the exact correlation between the two conditions.

Unravelling Neuroinflammation-Mediated Mitochondrial Dysfunction in Mild Cognitive Impairment: Insights from Targeted Metabolomics

BackgroundThe prevalence of Type 2 Diabetes Mellitus (T2DM) is rising rapidly among the elderly due to age-related metabolic changes. Older adults with T2DM have a 50-65% increased risk of developing cognitive impairment, particularly mild cognitive impairment (MCI), which may progress to neurodegenerative conditions like Alzheimer's disease (AD). Recent studies underscore the significant roles of mitochondrial dysfunction, disrupted glutamate-glutamine cycling, hyperglycemia, and hyperprolinemia in cognitive decline. These interconnected metabolites—glucose, glutamine, glutamate, and proline—are potential targets for understanding the relationship between T2DM and cognitive impairment. Material and MethodThe present targeted NMR based metabolomics study aims to compare the blood plasma/serum metabolic profiles of these four metabolites in age and sex matched MCI (N=27) and T2DM patients (N=38) with respect to normal control (NC, N=23) subjects. The metabolic profiling was performed using 1H NMR spectroscopy. ResultsCompared to NC group, both T2DM and MCI groups exhibited elevated glucose levels. Circulatory glucose and glutamine levels were significantly higher in T2DM subjects than in MCI and NC subjects, while glutamate levels followed a similar trend in both T2DM and MCI groups. However, in MCI patients, circulatory proline and proline-to-glutamine (PQR) and glutamate-to-glutamine was significantly elevated compared to T2DM, while glutamine was significantly reduced. ConclusionThe decreased circulatory levels of glutamine and PQR demonstrated statistically significant correlation with the severity of the cognitive impairment as assessed based on Mini Mental State Examination (MMSE) score suggested augmented utilization of glutamine in MCI patients and accumulation to proline due to active neuro-inflammatory processes and impaired mitochondrial functioning in MCI brain.

Untargeted metabolomics combined with pseudotargeted lipidomics revealed the metabolite profiles of blood-stasis syndrome in type 2 diabetes mellitus

ObjectiveBlood-stasis syndrome (BSS), an important syndrome in Type 2 diabetes mellitus(T2DM), is associated with the pathophysiological mechanisms underlying diabetic vascular complications. However, BSS has not been fully characterized as of yet. Due to the strong correlation between BSS and vasculopathy, we hypothesized that the metabolic characteristics of BSS in T2DM (T2DM BSS) are highly specific. By combining untargeted metabolomics and pseudotargeted lipidomics approaches, this study aimed to comprehensively elucidate the metabolic traits of T2DM BSS, thereby providing novel insights into the vascular complications of diabetes and establishing a foundation for precision medicine. MethodsThe survey was conducted in Haidian District of Beijing from October 2021 to November 2021, and data collection was completed in January 2022. Liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS) based pseudotargeted lipidomics were performed to detect metabolites and lipids. Multivariate, univariate, and pathway analyses were utilized to investigate metabolic changes. The unique metabolites of BSS were obtained by inter-group comparisons and screening. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of metabolites. ResultsA total of 1189 participants completed the survey, of which 120 participants were recruited in this study and further divided into a discovery cohort (n = 90) and a validation cohort (n = 30). Among these, 21 participants were selected for psuedotargeted lipidomics analysis. 81 metabolites, mainly involving glycerophospholipids, were identified as unique metabolites of T2DM BSS, while fatty acyls (FAs) were identified as unique lipids. T2DM BSS was associated with significant dysregulation in glycerophospholipid metabolism and choline metabolism within cancer pathways as major metabolic disturbances. Furthermore, analyses of both the discovery and validation cohorts, indicated that LysoPC (20:5(5Z,8Z,11Z,14Z,17Z)/0:0) and LysoPC (15:0) had the greatest impact on distinguishing BSS. ConclusionAltered levels of glycerophospholipids and FAs have been associated with T2DM BSS. These results provide valuable mechanistic insights linked with the development of BSS in T2DM subjects.

Characteristic Changes of Prefrontal and Motor Areas in Patients with Type 2 Diabetes and Major Depressive Disorder During a Motor Task of Tai Chi Chuan: A Functional Near-Infrared Spectroscopy Study.

This cross-sectional study aims to identify the characteristic changes of prefrontal and motor areas during a tai chi chuan task in patients with Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) using wearable functional near-infrared spectroscopy (fNIRS). Three parallel groups (T2DM with DD group, T2DM group, and healthy group) were recruited from December 10, 2022, to May 31, 2023. Participants in three groups conducted a motor task of tai chi chuan designed by Eprime 3.0, and fNIRS was used to monitor the brain activation, functional connectivity (FC), and lateralization of prefrontal and motor areas. Correlation analyses were performed to examine the relationship between depressive symptoms and the function of prefrontal and motor areas. Ninety elder adults (aged ≥ 60), including 30 patients with T2DM and MDD, 30 patients with T2DM, and 30 healthy subjects, were enrolled. In contrast with the patients with T2DM and healthy subjects, the patients with T2DM and MDD had decreased activation and abnormal lateralization in prefrontal and motor areas and decreased FC among supplementary motor area, motor area, and dorsolateral prefrontal cortex (DLPFC). Furthermore, the oxyhemoglobin (HbO2) concentration value of DLPFC in patients with T2DM and MDD was negatively associated with scores of Hamilton Depression Scale-24 (HAMD-24). Patients with T2DM and MDD had characteristic functional changes in prefrontal and motor areas. DLPFC may be a potential target of diagnosis and intervention for patients with T2DM and MDD.

Glucose-Lowering Drugs and Primary Prevention of Chronic Kidney Disease in Type 2 Diabetes Patients: A Real-World Primary Care Study

Background/Objectives: The burden of chronic kidney disease (CKD) is increasing, as is the prevalence of type 2 diabetes mellitus (T2DM). Post-hoc analyses of clinical trials support that sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptors agonists (GLP-1RAs) prevent CKD in T2DM patients. Methods: We used the Spanish primary care database BIFAP to perform a retrospective cohort study with a nested case-control analysis to assess the incidence, risk factors, and the effect of glucose-lowering drugs (GLDs) on the primary prevention of CKD. Results: From a cohort of 515,701 T2DM subjects (2.75 million person-years), we found 89,075 incident CKD cases, yielding an overall incidence rate (95%CI) of 324.3 (322.1–326.5) per 10,000 person-years. In the nested case–control analysis, gout, hyperuricemia, and hyperkalemia were the factors showing the highest AORs. Long-term users (≥3 years) of GLP1-RAs and SGLT-2i, compared to other GLDs, showed a decreased risk for CKD (AOR = 0.85; 95%CI: 0.73–0.99 and AOR = 0.89; 95%CI: 0.74–1.08, respectively), and for incident CKD at KDIGO stages G3-G5 (AOR = 0.72; 95%CI: 0.56–0.94 and AOR = 0.64; 95%CI: 0.46–0.91, respectively). Conclusions: In a real-world primary care setting, the long-term use of GLP-1RAs and SGLT-2i, but not other GLDs, appeared to decrease the risk of incident CKD in T2DM, supporting a role in primary prevention of CKD.

Morphological Differences in the Abdominal Aorta Between Subjects With and Without Type 2 Diabetes.

Aim Chronic hyperglycemia is a well-known risk factor for the development of many macrovascular complications, but hyperglycemia may be reportedly protective against abdominal aneurysms. Materials and methods In this study, we evaluated morphological differences in the abdominal aorta between subjects with and without type 2 diabetes mellitus (T2DM) without abdominal aortic aneurysm and evaluated the correlation between imaging findings of computed tomography (CT) and diabetes-related parameters. Results The abdominal aortic diameter was significantly smaller in subjects with T2DM compared to non-diabetes mellitus (NDM) subjects (p=0.026). Abdominal aortic wall thickness assessed by contrast-enhanced CT was significantly greater in subjects with T2DM compared to NDM subjects (p=0.011). There was a significant single correlation between abdominal aortic diameter and age, gender, Brinkman index, HbA1c, and mean/max intima-media thickness (IMT). Multiple regression analysis showed that HbA1c was an independent negative factor affecting abdominal aortic diameter (t=-3.28, p=0.0036). And Brinkmann index was an independent factor affecting aortic wall thickness (t=2.23, p=0.034). Conclusion This study revealed the imaging characteristics of smaller abdominal aortic diameter and larger wall thickness in T2DM subjects compared to NDM subjects. The abdominal aortic wall thickening was significantly correlated with cervical IMT. Therefore, close examination for other diabetes-related macrovascular complications should be aggressively considered when these findings are present.

The KDR Gene rs2071559 and the VEGF Gene rs6921438 May Be Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus.

The aim of our study was to investigate an association between polymorphisms of either the VEGF (vascular endothelial growth factor) gene (rs6921438) or the KDR (kinase insert domain receptor) gene (rs2071559, rs2305948) and DN (diabetic nephropathy) in Caucasians with T2DM (type 2 diabetes mellitus). The second aim was to investigate the effect of either the VEGF gene (rs6921438) or the KDR gene (rs2071559, rs2305948) on the immune expression of either VEGF or KDR in the renal tissues of T2DM subjects (to test the functional significance of tested polymorphisms). The study included 897 Caucasians with T2DM for at least ten years (344 patients with DN and 553 patients without DN). Each subject was genotyped and analyzed for KDR (rs1617640, rs2305948) and VEGF (rs6921438) polymorphisms. Kidney tissue samples taken from 15 subjects with T2DM (autopsy material) were immunohistochemically stained for the expression of VEGF and KDR. We found that the rs2071559 KDR gene was associated with an increased risk of DN. In addition, the GG genotype of the rs6921438 VEGF gene had a protective effect. We found a significantly higher numerical area density of VEGF-positive cells in T2DM subjects with the A allele of the rs6921438-VEGF compared to the homozygotes for wild type G allele (7.0 ± 2.4/0.1 mm2 vs. 1.24 ± 0.5/0.1 mm2, respectively; p < 0.001). Moreover, a significantly higher numerical area density of KDR-positive cells was found in T2DM subjects with the C allele of rs2071559 (CC + CT genotypes) compared to the homozygotes for wild type T allele (9.7± 3.2/0.1 mm2 vs. 1.14 ± 0.5/0.1 mm2, respectively; p < 0.001) To conclude, our study showed that the presence of the C allele of the rs2071559 KDR gene was associated with a higher risk of DN, while the G allele of the rs6921438-VEGF conferred protection against DN in Slovenian T2DM subjects.

Sex-based differences in the associations between abdominal obesity and diabetic retinopathy in diabetic patients with normal weight

PurposeTo investigate sex-specific differences in associations of abdominal obesity indexes, systemic factors, and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) subjects with normal body mass index (BMI). MethodsThis cross-sectional study comprised 653 T2DM subjects (402 women and 251 men) with normal BMI (18.5 kg/m2<BMI<24.0 kg/m2). All participants completed a standard questionnaire and underwent comprehensive ocular and systemic examinations. Anthropometric parameters were measured and recorded, including weight, height, waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Sex-specific associated factors for DR were assessed using logistic regression models. ResultsIn the multivariate logistic regressions, the presence of any DR was associated with a longer duration of T2DM (OR = 1.07, p = 0.007) and higher HbA1c (OR = 1.40, p = 0.001) in women, while any DR was associated with younger age at T2DM diagnosis (OR = 0.94, p = 0.020) and higher HbA1c (OR = 1.29, p = 0.011) in men. For women, we identified a positive association between WC (OR = 1.07, p = 0.011), WHR (OR = 1.67, p = 0.002), and WHtR (OR = 1.57, p = 0.004) with any DR after adjusting for confounders, and the third tertiles of WC (OR = 2.29, p = 0.028), WHR (OR = 3.03, p = 0.003), and WHtR (OR = 2.84, p = 0.007) were at high risk of any DR. For men, there were no associations between abdominal obesity indexes and any DR in either continuous variables or categorical variables (all p > 0.05). Main conclusionsThere were sex differences in the relationships between WC, WHR, WHtR, and DR in this T2DM population with normal BMI. Our findings provide new insight into a sex-specific mechanism of DR and management of the condition.

The Role of Pro-Inflammatory Chemokines CCL-1, 2, 4, and 5 in the Etiopathogenesis of Type 2 Diabetes Mellitus in Subjects from the Asir Region of Saudi Arabia: Correlation with Different Degrees of Obesity.

Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in developing nations. The high prevalence of obesity and related diabetes cases are attributed to rapid economic progress, physical inactivity, the consumption of high-calorie foods, and changing lifestyles. We investigated the roles of pro-inflammatory chemokines CCL1, 2, 4, and 5 in T2DM with varying levels of obesity in the Asir region of Saudi Arabia. In total, 170 confirmed T2DM subjects and a normal control group were enrolled. Demographic data, serum levels of CCL-1, 2, 4, and 5, and biochemical indices were assessed in the subjects and control groups by standard procedures. T2DM subjects were divided into four groups: A (normal body weight), B (overweight), C (obese), and D (highly obese). We observed that male and female control subjects had similar mean serum concentrations of pro-inflammatory chemokines CCL-1, 2, 4, and 5. T2DM subjects in all the four groups showed significantly higher levels of all the four chemokines compared to the controls, regardless of gender. In T2DM subjects with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL-1, 2, and 4 in T2DM subjects with increasing BMI. Serum CCL5 levels increased significantly in all T2DM subject groups. The increase in CCL5 was more predominant in normal-weight people, compared to overweight and obese T2DM subjects. Male and female control subjects had similar serum levels of pro-inflammatory chemokines CCL-1, 2, 4, and 5. The progressive rise in blood concentrations of three pro-inflammatory chemokines CCL-1, 2, and 4 in T2DM subjects with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM subject groups. The selective and more pronounced increase in CCL5 in the T2DM group with normal BMI, compared to subjects with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 underexpression in overweight and obese T2DM subjects is due to some unexplained counterbalancing processes.

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

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 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 with decreased Akt phosphorylation protein levels, suggesting an involvement of the phosphoinositide 3-kinase (PI3K)/Akt pathway in the process. In line with this, PI3K inhibition by a 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.NEW & NOTEWORTHY The glutamate transporter SLC1A2/excitatory amino acid transporter 2 (EAAT2) is expressed on the plasma membrane of pancreatic β-cells and controls islet glutamate clearance and β-cells survival. We found that the EAAT2 membrane expression is lost in the islets of Langerhans from type 2 diabetes mellitus (T2DM) patients due to hyperglycemia-induced downregulation of the phosphoinositide 3-kinase/Akt pathway and modification of its intracellular trafficking. Pharmacological rescue of EAAT2 expression prevents β-cell dysfunction and death, suggesting EAAT2 as a new potential target of intervention in T2DM.

Serum Total Bilirubin and Oxidative Stress Status in Diabetic Retinopathy – A Hospital-Based Observational Study

Diabetic retinopathy (DR) is one of the common microvascular complications of Type 2 Diabetes Mellitus (T2DM). As an antioxidant, the serum total bilirubin is associated with vaso-occlusive disorders. Oxidative stress parameters such as Erythrocyte Glutathione (GSH) as an antioxidant and Malondialdehyde (MDA) as an oxidant are critical in the pathogenesis of diabetic complications. This study aimed to explore the possibilities of the endogenous protective role of serum total bilirubin on the retinal vasculature in DR patients by estimating and correlating the levels of serum total bilirubin, GSH, and MDA in DR cases. In this hospital-based case-control study, 288 participants were selected from R.L. Jalappa Hospital and Research Centre, Kolar, divided into three groups with 96 subjects per group. Group I: Controls, Group II: T2DM, and Group III: DR subjects. The fasting blood sugar, glycated hemoglobin, liver function test, and lipid profiles were estimated by standard methods. Oxidative stress parameters viz, GSH and MDA were assayed by chromogen 5,5'- di thiobis 2-nitrobenzoic acid (DTNB) and thiobarbituric acid reactive substances (TBARS) methods, respectively. The prevalence of DR was significantly lower among subjects with the highest bilirubin quartile than those with the lowest. There was a significant mean difference with p&lt;0.001 between the groups for total bilirubin, FBS, HbA1c, GGT, TC, TG, LDL, GSH, and MDA. A Negative correlation of serum total bilirubin with FBS (r = - 0.375), HbA1c (r = -0.351), and MDA(r=-0.323), and a positive correlation with GSH (r = 0.335) was observed in DR group with a significant p-value. T2DM subjects with higher levels of bilirubin within biological reference intervals were less likely to develop retinopathy. The severity of DR was inversely proportional to the total bilirubin levels. Therefore, serum total bilirubin levels could be a biomarker to predict the risk of developing retinopathy in people with T2DM.

T2DM/CKD genetic risk scores and the progression of diabetic kidney disease in T2DM subjects

This study aimed at understanding the predictive potential of genetic risk scores (GRS) for diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM) and Major Cardiovascular Events (MCVE) and All-Cause Mortality (ACM) as secondary outcomes. We evaluated 30 T2DM and CKD GWAS-derived single nucleotide polymorphisms (SNPs) and their association with clinical outcomes in a central European cohort (n = 400 patients). Our univariate Cox analysis revealed significant associations of age, duration of diabetes, diastolic blood pressure, total cholesterol and eGFR with progression of DKD (all P < 0.05). However, no single SNP was conclusively associated with progression to DKD, with only CERS2 and SHROOM3 approaching statistical significance. While a single SNP was associated with MCVE − WSF1 (P = 0.029), several variants were associated with ACM − specifically CANCAS1, CERS2 and C9 (all P < 0.02). Our GRS did not outperform classical clinical factors in predicting progression to DKD, MCVE or ACM. More precisely, we observed an increase only in the area under the curve (AUC) in the model combining genetic and clinical factors compared to the clinical model alone, with values of 0.582 (95 % CI 0.487–0.676) and 0.645 (95 % CI 0.556–0.735), respectively. However, this difference did not reach statistical significance (P = 0.06).This study highlights the complexity of genetic predictors and their interplay with clinical factors in DKD progression. Despite the promise of personalised medicine through genetic markers, our findings suggest that current clinical factors remain paramount in the prediction of DKD. In conclusion, our results indicate that GWAS-derived GRSs for T2DM and CKD do not offer improved predictive ability over traditional clinical factors in the studied Czech T2DM population.

The ABCA1 gene polymorphisms rs1800977 and rs2230806 are differentially associated with the risk for myocardial infarction in Slovenian subjects with type 2 diabetes mellitus

BackgroundThe adenosine triphosphate-binding cassette transporter A1 (ABCA1) is closely linked to various aspects of the regulation of whole-body cholesterol metabolism and atherosclerosis formation. The object of the study was to investigate the association between rs1800977 and rs2230806 polymorphisms in the ABCA1 gene and myocardial infarction (MI) in Slovenian subjects with type 2 diabetes mellitus (T2DM). Methods1590 T2DM patients (484 subjects with MI and 1106 controls) were included in this retrospective cross-sectional case–control study. After genotyping, Pearson χ2 test was used to compare the distribution of genotypes and alleles among the two groups. Logistic regression analysis adjusted for several risk factors for MI was performed. ResultsGenotype distribution showed significant association with MI in T2DM subjects for both selected polymorphisms in ABCA1 gene (p = 0.009 for rs2230806 and p = 0.042 for rs1800977). After applying corrections for confounding variables like age, waist circumference, diastolic blood pressure, serum high-density lipoprotein levels, gender and smoking several genetic models still showed significant associations with MI (dominant model for rs2230806 and dominant, overdominant and co-dominant for rs1800977). ConclusionOur study showed that presence of the T allele of the rs2230806 ABCA1 gene is associated with higher risk of MI, while the A allele of the rs1800977 conferred protection against MI in Slovenian T2DM subjects.

Is the urinary neutrophil gelatinase-associated lipocalin concentration in children and adolescents with type 1 diabetes mellitus different from that in healthy children?

Diabetic kidney disease (DKD) is one of the major microvascular complications of type 1 diabetes mellitus (T1DM). Some studies suggest that changes of renal tubular components emerge before the glomerular lesions thus introducing the concept of diabetic tubulopathy with urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a potential marker of DKD. This concept was not confirmed in all studies. In 198 T1DM patients with median age 15 years and diabetes duration over one year, an albumin/creatinine ratio (ACR) was determined and uNGAL measured in spot urine sample. Urine samples for ACR and uNGAL were also collected in the control group of 100 healthy children of similar age. There was no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects (6.9 (2.8-20.1) ng/mL vs 7.9 (2.9-21.0) ng/mL, P = 0.969 and 6.8 (2.2-18.4) ng/mg vs 6.5 (1.9-13.4) ng/mg, P = 0.448, respectively) or between T1DM subjects with albuminuria A2 and albuminuria A1 (P = 0.573 and 0.595, respectively). Among T1DM patients 168 (85%) had normal uNGAL concentrations, while in 30 (15%) patients uNGAL was above the defined cut-off value of 30.9 ng/mL. There was no difference in BMI, HbA1c and diabetes duration between patients with elevated uNGAL compared to those with normal uNGAL. We found no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects or between albuminuria A2 and albuminuria A1 T1DM subjects. Therefore, uNGAL should not be recommended as a single marker for detecting diabetic kidney disease in children and adolescents.

Širina distribucije eritrocita i trombocitni indeksi kao inflamatorni parametri kod pacijenata sa šećernom bolesti tipa 2 i disfunkcijom bubrega

Aim: To assess Red blood cell Distribution Width (RDW) and platelet indices values in patients with type 2 diabetes mellitus (T2DM) and to verify its association with kidney dysfunction (KD). Patients and Methods: A cross-sectional study included 149 T2DM subjects divided into two groups with (T2DM – KD; n=52) and without (T2DM-nKD; n=97) presence of kidney dysfunction and 30 healthy subjects. White Blood Cells (WBC) count, C-reactive protein (CRP), fibrinogen, RDW, platelet indices, urea, and creatinine, were measured in all participants. Kidney function was evaluated by the estimated glomerular filtration rate (eGFR) calculated using the simplified Modification of Diet in Renal Disease (MDRD) formula. Results: T2DM-KD subjects showed statistically significantly higher values of the parameters RDW (p&amp;lt;0.01), Mean Platelet Volume - MPV (p&amp;lt;0.01), Platelet Distribution Width-PDW (p&amp;lt;0.01), Platelecrit-PCT (p&amp;lt;0.01), and Platelet Mass Index-PMI (p&amp;lt;0.01) compared to T2DM-nKD subjects, and statistically significantly lower values of the WBC count in T2DM-KD subjects compared to subjects suffering from T2DM without kidney dysfunction (p&amp;lt;0.01). ROC curve analysis revealed that RDW (sensitivity of 80.8%, specificity of 78.3%), MPV (sensitivity of 75%, specificity of 78.4 %), and PDW (sensitivity of 80.8%, specificity of 83.5%) could be used as markers in distinguishing between T2DM subjects with and without kidney dysfunction. Conclusion: This study confirms the reliability of the RDW,MPV, and PDW as simple, low cost and useful markers in distinguishing between T2DM subjects with and without kidney dysfunction.

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.