Effect Of Type 2 Diabetes Mellitus Research Articles

Effects of T2DM on cancer progression: pivotal precipitating factors and underlying mechanisms.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder affecting people worldwide. It is characterized by several key features, including hyperinsulinemia, hyperglycemia, hyperlipidemia, and dysbiosis. Epidemiologic studies have shown that T2DM is closely associated with the development and progression of cancer. T2DM-related hyperinsulinemia, hyperglycemia, and hyperlipidemia contribute to cancer progression through complex signaling pathways. These factors increase drug resistance, apoptosis resistance, and the migration, invasion, and proliferation of cancer cells. Here, we will focus on the role of hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with T2DM in cancer development. Additionally, we will elucidate the potential molecular mechanisms underlying their effects on cancer progression. We aim to identify potential therapeutic targets for T2DM-related malignancies and explore relevant directions for future investigation.

Effect of Type-2 Diabetes Mellitus on the Expression and Function of Smooth Muscle ATP-Sensitive Potassium Channels in Human Internal Mammary Artery Grafts.

Here we have shown for the first time altered expression of the vascular smooth muscle (VSM) KATP channel subunits in segments of the human internal mammary artery (HIMA) in patients with type-2 diabetes mellitus (T2DM). Functional properties of vascular KATP channels in the presence of T2DM, and the interaction between its subunits and endogenous ligands known to relax this vessel, were tested using the potassium (K) channels opener, pinacidil. HIMA is the most commonly used vascular graft in cardiac surgery. Previously it was shown that pinacidil relaxes HIMA segments through interaction with KATP (SUR2B/Kir6.1) vascular channels, but it is unknown whether pinacidil sensitivity is changed in the presence of T2DM, considering diabetes-induced vascular complications commonly seen in patients undergoing coronary artery bypass graft surgery (CABG). KATP subunits were detected in HIMA segments using Western blot and immunohistochemistry analyses. An organ bath system was used to interrogate endothelium-independent vasorelaxation caused by pinacidil. In pharmacological experiments, pinacidil was able to relax HIMA from patients with T2DM, with sensitivity comparable to our previous results. All three KATP subunits (SUR2B, Kir6.1 and Kir6.2) were observed in HIMA from patients with and without T2DM. There were no differences in the expression of the SUR2B subunit. The expression of the Kir6.1 subunit was lower in HIMA from T2DM patients. In the same group, the expression of the Kir6.2 subunit was higher. Therefore, KATP channels might not be the only method of pinacidil-induced dilatation of T2DM HIMA. T2DM may decrease the level of Kir6.1, a dominant subunit in VSM of HIMA, altering the interaction between pinacidil and those channels.

What Is the Role of the Carotid Baroreflex in Exaggerating the Exercise Pressor Reflex in Male UCD-Type 2 Diabetes Mellitus Rats?

Previous studies have shown that exercise evokes an excessive increase in blood pressure in individuals with type 2 diabetes mellitus (T2DM), which is mediated, in part, by an altered exercise pressor reflex. Importantly, in healthy individuals the arterial baroreflex modulates the pressor response to exercise; however, the effects of T2DM on this modulatory effect of the baroreflex remain unclear. Therefore, the purpose of this study was to characterize the arterial baroreflex function in T2DM rats and to determine whether the carotid baroreflex plays a role in exaggerating the exercise pressor reflex. We hypothesized that T2DM rats would present a baroreflex dysfunction that likely contributes to the exaggerated pressor response during muscle contraction. Experiments were performed on adult (8 ± 2 months old), male University of California Davis (UCD)-T2DM ( n=7; body weight: 640 ± 43 g) and healthy Sprague-Dawley rats ( n=3; body weight: 485 ± 29 g). Female rats were not included in this study because they become diabetic when they are much older (>10 months old). Cardiac baroreflex function was characterized in anesthetized T2DM and healthy rats using the modified Oxford technique, which involved sequential bolus infusions of sodium nitroprusside (10 μg/kg) and phenylephrine (10 μg/kg) to induce blood pressure decreases and increases, respectively. Overall cardiac baroreflex gain (i.e., slope of the relationship between systolic blood pressure and R-R interval) was calculated using logistic regression, while gains to blood pressure falling and rising were calculated separately using piecewise and linear regression. The role of the carotid baroreflex in exaggerating the exercise pressor reflex was tested by statically contracting the hindlimb muscles for 30 s after surgical sinoaortic denervation (SAD) in decerebrated T2DM ( n=1; body weight: 555 g) and healthy ( n=1; body weight: 519 g) rats. Carotid barointact T2DM ( n=8; body weight: 521 ± 38 g) and healthy rats ( n=8; body weight: 482 ± 56 g) were included as controls. The pressor responses were calculated as a change (Δ) in peak mean arterial pressure during 30 s contraction relative to baseline. Data are presented as mean ± SD. T2DM rats presented with lower overall baroreflex sensitivity (T2DM: 0.07 ± 0.02 ms/mmHg, healthy: 0.61 ± 0.81 ms/mmHg, p=0.044), as well as sensitivity to increases in blood pressure (T2DM: 0.14 ± 0.10 ms/mmHg , healthy: 0.28 ± 0.15 ms/mmHg, p=0.049) compared to healthy controls. In contrast, cardiac baroreflex gain during decreases in blood pressure were not different between groups (T2DM: 0.16 ± 0.07 ms/mmHg, healthy: 0.10 ± 0.06 ms/mmHg, p=0.109). Notably, SAD did not alter blood pressure response to muscle contraction in the T2DM rat (SAD: Δ32 mmHg vs barointact: Δ32 ± 12 mmHg), but evoked an exaggerated blood pressure response in healthy rat (SAD: Δ34 mmHg vs barointact: Δ12 ± 3 mmHg). Our preliminary findings suggest that despite an attenuated cardiac baroreflex function in T2DM rats, specifically during acute increases in blood pressure, carotid baroreflex dysfunction may not contribute significantly to the exaggerated exercise pressor reflex in diabetes. This project was supported by NIH R01 HL144723. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Impact of Type 2 Diabetes on Peripheral and Cerebral Hemodynamic Responses to Active Stand.

Although type 2 diabetes mellitus (T2DM) is an established risk factor for cognitive impairment, the underlying mechanisms remain poorly explored. One potential mechanism may be through effects of T2DM on cerebral perfusion. The current study hypothesized that T2DM is associated with altered peripheral and central hemodynamic responses to orthostasis, which may in turn be associated with cognitive impairment in T2DM. A novel use of function-on-scalar regression, which allows the entire hemodynamic response curve to be modeled, was employed to assess the association between T2DM and hemodynamic responses to orthostasis. Logistic regression was used to assess the relationship between tissue saturation index (TSI), T2DM, and cognitive impairment. All analyses used cross-sectional data from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA). Of 2984 older adults (aged 64.3 ± 8.0; 55% female), 189 (6.3%) had T2DM. T2DM was associated with many features that are indicative of autonomic dysfunction including a blunted peak heart rate and lower diastolic blood pressure. T2DM was associated with reduced TSI and also with greater odds of impaired performance on the Montreal Cognitive Assessment (odds ratio [OR]: 1.62; confidence interval [CI: 1.07, 2.56]; p = .019). Greater TSI was associated with lower odds of impaired performance (OR: 0.90, CI [0.81-0.99]; p = .047). T2DM was associated with impaired peripheral and cerebral hemodynamic responses to active stand. Both T2DM and reduced cerebral perfusion were associated with impaired cognitive performance. Altered cerebral perfusion may represent an important mechanism linking T2DM and adverse brain health outcomes in older adults.

Characterisation and Expression of Osteogenic and Periodontal Markers of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) from Diabetic Knee Joints.

Type 2 diabetes mellitus (T2DM) represents a significant health problem globally and is linked to a number of complications such as cardiovascular disease, bone fragility and periodontitis. Autologous bone marrow mesenchymal stem cells (BM-MSCs) are a promising therapeutic approach for bone and periodontal regeneration; however, the effect of T2DM on the expression of osteogenic and periodontal markers in BM-MSCs is not fully established. Furthermore, the effect of the presence of comorbidities such as diabetes and osteoarthritis on BM-MSCs is also yet to be investigated. In the present study, BM-MSCs were isolated from osteoarthritic knee joints of diabetic and nondiabetic donors. Both cell groups were compared for their clonogenicity, proliferation rates, MSC enumeration and expression of surface markers. Formation of calcified deposits and expression of osteogenic and periodontal markers were assessed after 1, 2 and 3 weeks of basal and osteogenic culture. Diabetic and nondiabetic BM-MSCs showed similar clonogenic and growth potentials along with comparable numbers of MSCs. However, diabetic BM-MSCs displayed lower expression of periostin (POSTN) and cementum protein 1 (CEMP-1) at Wk3 osteogenic and Wk1 basal cultures, respectively. BM-MSCs from T2DM patients might be suitable candidates for stem cell-based therapeutics. However, further investigations into these cells' behaviours in vitro and in vivo under inflammatory environments and hyperglycaemic conditions are still required.

SPIROMETRY EVALUATION OF PULMONARY FUNCTIONS IN TYPE 2 DIABETES MELLITUS PATIENTS: A CROSS-SECTIONAL STUDY

Background and Aims: Type 2 diabetes mellitus (T2DM) during the chronic stage elicits significant micro and macrovascular complication and imposes mortality and morbidity among the individuals. However, the effect of T2DM on the lung as a target end organ damage was not widely studied. Hence, the present study was done for the spirometry analysis of pulmonary functions in T2DM patients. Methods: This was a cross-sectional study conducted on 50 T2DM patients and they were subjected to spirometry evaluation. The restrictive pattern of lung functions was analyzed by evaluating the following parameters forced vital capacity (FVC) in liters, forced expiratory volume in 1 second (FEV1), and FEV1/FVC were evaluated. The association between lung function parameters and duration of diabetes, glycated hemoglobin (HbA1c) were also analyzed. Results: In this study among the diabetic patients, the mean FVC was 2.45±0.36 L, the mean FEVI was 1.82±0.12 (L/s) and the mean FEV1/FVC was 87.42±7.54, respectively. Regarding lung complication, out of 50 diabetic patients, 25 (50%) had normal lung functions, 16 (32%) had mild restriction and 9 (18%) had moderate restriction. The FVC, FEVI, and FEV1/FVC were significantly reduced in diabetic patients with moderate lung restriction as compared to normal and mild restriction patterns. Diabetes duration displayed no significant association with a decline in pulmonary function and FEV1/FVC showed weak significant negative correlation (r=−0.412; p=0.02) with HbA1c levels. Conclusion: The study shows that in diabetics patients there was a marked decline in pulmonary function and it might be due to uncontrolled diabetes-related complications.

Fecal metabolomics combined with 16S rRNA gene sequencing to analyze the effect of Jiaotai pill intervention in type 2 diabetes mellitus rats.

The occurrence and development of type 2 diabetes mellitus (T2DM) are closely related to gut microbiota. Jiaotai pill (JTP) is used to treat type 2 diabetes mellitus, with definite efficacy in clinical practice. However, it is not clear whether the therapeutic effect is produced by regulating the changes in gut microbiota and its metabolism. In this study, T2DM rat models were established by a high-fat diet and low-dose streptozotocin (STZ). Based on the pharmacodynamic evaluation, the mechanism of JTP in the treatment of type 2 diabetes mellitus was investigated by fecal metabolism and 16S rRNA gene sequencing. The results showed that JTP decreased blood glucose (FBG, HbA1c) and blood lipid (TC, TG, and LDL) levels and alleviated insulin resistance (FINS, IL-10) in T2DM rats. 16S rRNA gene sequencing results revealed that JTP increased microbiota diversity and reversed the disorder of gut microbiota in T2DM rats, and therefore achieved the therapeutic effect in T2DM. JTP regulated 13 differential flora, which were Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, Eubacteriaceae, Prevotellaceae, Ruminococcaceae, Clostridium_IV, Clostridium_XlVa, Eubacterium, Fusicatenibacter, Romboutsia, and Roseburia. Metabolomics analysis showed that JTP interfered with 13 biomarkers to play a therapeutic role in type 2 diabetes mellitus. They were L-Valine, Choline, L-Aspartic acid, Serotonin, L-Lysine, L-Histidine, 3-Hydroxybutyric acid, Pyruvic acid, N-Acetylornithine, Arachidonic acid, L-Tryptophan, L-Alanine, and L-Methionine. KEGG metabolic pathway analysis of the above differential metabolites and gut microbiota by using the MetaboAnalyst database and Picrust software. It was found that JTP treated type 2 diabetes mellitus by affecting metabolic pathways such as amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Spearman correlation analysis revealed high correlations for 7 pharmacological indicators, 12 biomarkers, and 11 gut microbiota. In this study, the therapeutic effect and potential mechanism of JTP on type 2 diabetes mellitus were preliminarily demonstrated by gut microbiota and metabolomics, which could provide a theoretical basis for the treatment of T2DM with JTP.

Bilateral carpal tunnel syndrome and motor dysfunction caused by gout and type 2 diabetes: A case report

Carpal tunnel syndrome (CTS) has been associated with gout and type 2 diabetes mellitus (T2DM). However, due to insufficient clinical understanding of gout-related CTS and reliance on the diagnostic importance of elevated serum uric acid levels, such cases are prone to missed diagnosis, misdiagnosis, and delayed treatment. In addition, the effect of T2DM on gout - induced carpal tunnel syndrome has not been reported. Herein, we present an unusual case of CTS and motor dysfunction caused by miliary tophaceous gout and T2DM. The patient presented to the hand and foot clinic with paresthesia of the fingers of both hands, especially at night. The patient was diagnosed with type 2 diabetes a month ago. Ultrasonography revealed bilateral transverse carpal ligament thickening with median nerve compression during hospitalization. The patient was successfully treated with carpal tunnel decompression and tendon release. The postoperative pathological examination revealed typical gout nodules. This case suggests that the presence of T2DM could accelerate tophi formation and worsen CTS symptoms, although no definitive proof in this regard has been described previously. Tophi formation may most likely cause the co-occurrence of CTS and flexor dysfunction in gout and incipient diabetes patients.

Different effects of cardiometabolic syndrome on brain age in relation to gender and ethnicity

BackgroundA growing body of evidence shows differences in the prevalence of cardiometabolic syndrome (CMS) and dementia based on gender and ethnicity. However, there is a paucity of information about ethnic- and gender-specific CMS effects on brain age. We investigated the different effects of CMS on brain age by gender in Korean and British cognitively unimpaired (CU) populations. We also determined whether the gender-specific difference in the effects of CMS on brain age changes depending on ethnicity.MethodsThese analyses used de-identified, cross-sectional data on CU populations from Korea and United Kingdom (UK) that underwent brain MRI. After propensity score matching to balance the age and gender between the Korean and UK populations, 5759 Korean individuals (3042 males and 2717 females) and 9903 individuals from the UK (4736 males and 5167 females) were included in this study. Brain age index (BAI), calculated by the difference between the predicted brain age by the algorithm and the chronological age, was considered as main outcome and presence of CMS, including type 2 diabetes mellitus (T2DM), hypertension, obesity, and underweight was considered as a predictor. Gender (males and females) and ethnicity (Korean and UK) were considered as effect modifiers.ResultsThe presence of T2DM and hypertension was associated with a higher BAI regardless of gender and ethnicity (p < 0.001), except for hypertension in Korean males (p = 0.309). Among Koreans, there were interaction effects of gender and the presence of T2DM (p for T2DM*gender = 0.035) and hypertension (p for hypertension*gender = 0.046) on BAI in Koreans, suggesting that T2DM and hypertension are each associated with a higher BAI in females than in males. In contrast, among individuals from the UK, there were no differences in the effects of T2DM (p for T2DM*gender = 0.098) and hypertension (p for hypertension*gender = 0.203) on BAI between males and females.ConclusionsOur results highlight gender and ethnic differences as important factors in mediating the effects of CMS on brain age. Furthermore, these results suggest that ethnic- and gender-specific prevention strategies may be needed to protect against accelerated brain aging.

A critical review of the relationship between type 1 diabetes mellitus, inhibition, and behavioral management.

Type 1 diabetes mellitus (T1DM) is a chronic and lifelong condition that requires adequate behavior management in order to meet desired health outcomes. The effects of T1DM on the neurocognitive functioning of affected individuals raise concerns about how the disease may influence executive functioning. Inhibition is a core component of executive functioning, and plays a vital role in self-regulation and the restriction of impulsive behaviors. Inhibition may thus play a vital role in the behavior management of people with T1DM. The aim of this study was to identify current gaps in existing knowledge regarding the relationship between T1DM, inhibition, and behavior management. This study employed a critical review design to analyze and synthesize the current scientific literature. Twelve studies were identified through an appraisal process, and the data extracted were thematically analyzed and integrated. The findings of this study indicate that a possible cycle arises between these three constructs, in which T1DM affects inhibition, inhibition affects behavior management, and poor behavior management affects inhibition. It is recommended that future research should focus more specifically on this relationship.

Childhood neurodevelopmental disorders and maternal diabetes: Apopulation-based cohort study.

To assess the risk of a wide spectrum of neurodevelopmental disorders (NDDs) in offspring of mothers with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). This retrospective cohort study included 877233 singletons born between 2004 and 2008 in Taiwan. Children were followed up to 2015 for diagnoses of NDDs, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), developmental delay, intellectual disability, cerebral palsy, and epilepsy/infantile spasms using health insurance claims data. We performed Cox regression models to estimate the relative risks of NDDs associated with maternal diabetes. Covariates included parental age, year of birth, child sex, family income, urbanization level, hypertensive disorder, and preterm delivery status. In utero there were 338 (0.04%) children exposed to T1DM, 8749 (1.00%) to T2DM, and 90 200 (10.28%) to GDM. The effect of T1DM on NDDs was the largest, followed by T2DM, then GDM. T1DM was associated with an increased risk of developmental delay, intellectual disability, and epilepsy/intellectual spasms in offspring. T2DM was associated with an increased risk of ASD, ADHD, developmental delay, intellectual disability, cerebral palsy, and epilepsy/intellectual spasms. GDM was associated with an increased risk of ASD, ADHD, and developmental delay. Maternal diabetes during pregnancy, including T1DM, T2DM, and GDM, is associated with an increased risk of some NDDs in offspring.

The Extraglycemic Effect of SGLT-2is on Mineral and Bone Metabolism and Bone Fracture.

Type 2 diabetes mellitus (T2DM) is a risk factor for osteoporosis. The effects of T2DM and anti-diabetic agents on bone and mineral metabolism have been observed. Sodium–glucose co-transporter 2 inhibitors (SGLT-2is) promote urinary glucose excretion, reduce blood glucose level, and improve the cardiovascular and diabetic nephropathy outcomes. In this review, we focused on the extraglycemic effect and physiological regulation of SGLT-2is on bone and mineral metabolism. SGLT-2is affect the bone turnover, microarchitecture, and bone strength indirectly. Clinical evidence of a meta-analysis showed that SGLT-2is might not increase the risk of bone fracture. The effect of SGLT-2is on bone fracture is controversial, and further investigation from a real-world study is needed. Based on its significant benefit on cardiovascular and chronic kidney disease (CKD) outcomes, SGLT-2is are an outstanding choice. Bone mineral density (BMD) and fracture risk evaluation should be considered for patients with a high risk of bone fracture.

Plasma metabolites associated with functional and clinical outcomes in heart failure with reduced ejection fraction with and without type 2 diabetes

Heart failure with reduced ejection fraction (HFrEF) is increasingly treated with medications for type 2 diabetes mellitus (T2DM). Whether metabolic derangements in HFrEF and T2DM are associated with differential outcomes remains unclear. Therefore, understanding molecular pathways in HFrEF and T2DM and their effects on clinical endpoints is important. The FIGHT trial randomized 300 individuals with HFrEF and a recent HF hospitalization to liraglutide (a GLP-1 receptor agonist) versus placebo to assess effects on mortality, HF rehospitalization, and 6-month change in NT-ProBNP. Although the trial showed no clinical benefit of liraglutide, the trial population was highly enriched for individuals with T2DM. Sixty metabolites were quantified via mass spectrometry in plasma from 254 FIGHT participants (N = 147 (57.9%) with T2DM). Principal components analysis reduced the high number of correlated metabolites into uncorrelated factors. The association of factor levels with 90-day changes in 6-min walk distance (6MWD) and NT-proBNP, and with time to mortality or HF hospitalization were evaluated. There were no changes in metabolite factors according to treatment assignment. However, in analyses stratified by T2DM status, changes in five plasma metabolite factors correlated with changes in functional outcomes beyond adjustment: factor 2 (branched-chain amino acids [BCAA]) correlated with changes in NT-proBNP (ρ = − 0.291, p = 4 × 10–4) and 6MWD (ρ= 0.265, p = 0.011); factor 1 (medium-chain acylcarnitines; ρ = 0.220, p = 0.008), factor 4 (long-chain dicarboxylacylcarnitines; ρ = 0.191, p = 0.019), factor 5 (long-chain acylcarnitines; ρ = 0.198, p = 0.017), and factor 8 (urea cycle metabolites; ρ = − 0.239, p = 4 × 10–3), correlated with change in NT-proBNP. Factor 4 was associated with time-to-event (HR = 1.513 [95% CI 1.208–1.896], p = 3 × 10–4) with a trend towards stronger prognostic effect in T2DM (T2DM: p = 1 × 10–3, non-T2DM: p = 0.1). We identified metabolites of BCAA, urea cycle and fatty acid metabolism as biomarkers of HFrEF outcomes, with observed differences in HFrEF patients with T2DM. Such biomarkers might enable future diagnostic or therapeutic interventions in individuals with HFrEF and T2DM.Trial Registration: Clinicaltrials.gov. Identifier: NCT01800968. First posted: February 28, 2013.

Lacunes and type 2 diabetes mellitus have a joint effect on cognitive impairment: a retrospective study.

ObjectiveTo evaluate the joint effects of cerebral small vessel disease (CSVD)-related imaging biomarkers in patients of type 2 diabetes mellitus (T2DM) with cognitive impairment.MethodsThis study is a retrospective cohort study. A total of 227 participants (115 patients with T2DM and 112 healthy control subjects) were enrolled in this study. Cognitive function assessments were evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment. The burden of CSVD markers, including the lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), and enlarged perivascular spaces (PVS), was identified by magnetic resonance imaging and evaluated using small vessel disease (SVD) scores (0–4). The subjects were divided into two groups based on the results of the cognitive function assessments. The synergy index was used to estimate the biological interactions between T2DM and lacunes.ResultsThere was a significant correlation between T2DM and cognitive impairment (p < 0.001, χ2 test). In patients with diabetes, cognitive impairment was significantly associated with both the presence of lacunes (p < 0.01, χ2 test) and increased total SVD burden scores (p < 0.01, χ2 test). Regarding CMBs, only the existence of lobar CMBs was correlated with cognitive impairment (p < 0.05, χ2 test). The joint effect tended to be larger than the independent effects of T2DM and lacunes on cognitive impairment (adjusted odds ratio [OR]: 7.084, 95% CI [2.836–17.698]; synergy index: 10.018, 95% CI [0.344–291.414]).ConclusionsT2DM and the presence of lacunes are significantly correlated with cognitive impairment. There was a joint effect of T2DM and lacunes on cognitive impairment.

Data-independent acquisition-based proteomics analysis correlating type 2 diabetes mellitus with osteoarthritis in total knee arthroplasty patients.

Background:To explore the effects of type 2 diabetes mellitus (T2DM) on osteoarthritis (OA), 12 bone tissue samples were obtained surgically from the human total knee arthroplasty patients and analyzed by quantitative proteomics.Methods:Based on patient clinical histories, patient samples were assigned to diabetes mellitus osteoarthritis (DMOA) and OA groups. A data-independent acquisition method for data collection was used with proteomic data analysis to assess intergroup proteomic differences. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis were used to further find the correlation between T2DM and OA.Results:GO functional analysis found 153 differentially expressed proteins between DMOA and OA groups, of which 92 differentially expressed proteins were significantly up-regulated and 61 were significantly down-regulated. Kyoto Encyclopedia of Genes and Genome pathway analysis found 180 pathways, including 9 pathways significantly enriched. Further data analysis revealed that 6 signaling pathways were closely associated with T2DM and OA.Conclusion:OA and DMOA onset and progression were closely related to synthesis and metabolism of extracellular matrix components (e.g., fibronectin, decorin, etc.). The effects of T2DM on OA occur though 2 major ways of oxidative stress and low-grade chronic inflammation, involving in 2 inhibited signaling pathways and 4 activated signaling pathways.

Effect of gender, diabetes duration, inflammatory cytokines, and vitamin D level on bone mineral density among Thai children and adolescents with type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is considered a risk factor for osteoporosis in adults; however, studies in bone mineral density (BMD) in children with T1DM reported conflicting results. The aim of this study was to compare BMD between T1DM youth and healthy controls, and to identify factors that affect BMD in T1DM youth. One hundred T1DM youths and 100 healthy controls (both groups aged 5-20 years) were recruited. BMD of total body, lumbar (L2-4), femoral neck, and total hip were assessed using dual energy X-ray absorptiometry. Blood investigations, including hemoglobin A1c (HbA1c), 25-hydroxyvitamin D, and inflammatory cytokines, were performed. Forty-four boys and 56 girls with T1DM were enrolled [mean age 14.5 ± 2.7 years, median (IQR) duration of T1DM 5.80 (2.97-9.07) years, and mean HbA1c entire duration 9.2 ± 1.4%]. T1DM girls had a lower height Z-score than control girls (p < 0.05), and 25-hydroxyvitamin D level was higher in T1DM youth than in controls (p < 0.001). After adjusting for pubertal status, height Z-score, and 25-hydroxyvitamin D, T1DM youth had a significantly lower lumbar BMD Z-score and femoral neck BMD than controls (p = 0.027 and p = 0.025, respectively). We also found that T1DM boys had a significantly lower lumbar BMD Z-score (p = 0.028), femoral neck BMD (p = 0.004), and total hip BMD (p = 0.016) than control boys. In contrast, these significant differences were not found in T1DM girls. Factors affecting BMD were different between T1DM boys and girls, and among different BMD sites. IL-13 was positively correlated with BMD in the total cohort and among girls. In boys - IL-2 and 25-hydroxyvitamin D were positively associated with BMD, and duration of diabetes was found to negatively affect BMD. Deleterious effect of T1DM on BMD is gender specific. The longer the duration of T1DM, the greater the deficit in BMD found among boys with T1DM.

Diabetes Mellitus and Dental Health in Children: A Review of Literature.

ABSTRACTAim and objectiveTo illustrate the most important general findings significant for dentists dealing with pediatric diabetic patients, as well as the effect of type 1 diabetes mellitus (T1DM) on children's oral health.BackgroundType 1 DM is considered to be the most popular type of diabetes in children and adolescents which has a strong impact on their lifestyle. Diabetes mellitus (DM) mainly affect organs and tissues that are affluent with blood vessels including kidneys, eyes, and nerves. Adding to that oral cavity is covered with epithelial tissues that are rich with small blood vessels.Materials and methodsAn electronic search of English scientific papers was accomplished using PubMed, Google Scholar, and King Abdulaziz University digital library. Search terms used were children, DM, dental health, gingival health, oral hygiene, periodontal health, and teeth eruption.Review resultsThirty-six articles were obtained from the electronic search and references of selected studies. In addition, other references were included from selected studies about DM and its relationship to oral health. Multiple studies confirmed that T1DM has a negative impact on oral hygiene, gingival and periodontal health, and teeth eruption. While other studies contradict these results.ConclusionThere are contradictory studies regarding the effect of T1DM on oral health in children and adolescents. Well-established high-quality research with clear and concise materials and methods are required to have representative results.Clinical significanceStudying the effect of T1DM on oral health in children and adolescents is indicated to set well-established guidelines to reach a high standard of care for those children.How to cite this articleMandura RA, El Meligy OA, Attar MH, et al. Diabetes Mellitus and Dental Health in Children: A Review of Literature. Int J Clin Pediatr Dent 2021;14(5):719–725.

CHRONIC MESENTERIC ISCHEMIA IN TYPE 2 DIABETES PATIENTS

BACKGROUND: Type 2 Diabetes mellitus (T2DM) currently effects 8.9% of the world's population.The macrovascular complications of diabetes are 3 times more common than the microvascular complications.Involvement of the vessels of gut in T2DM hasn't been studied exclusively like the other known macrovascular complications.This study focusses on the effect of T2DM on the Coeliac artery(CA) and Superior Mesenteric artery (SMA) which are the main source of blood supply to the organs derived from fore and midgut . METHODS: In our study over 2 years, 72 patients of T2DM were subjected to Duplex Ultrasonography.15 randomly selected patients who satised the Fasting Duplex velocity criteria and 15 randomly selected patients who did not were subjected to CT Angiography. RESULTS: We found that 22 patients (30.55%) out of the 72 had features suggestive of Chronic Mesenteric Ischemia (CMI) in both the coeliac artery and SMA on duplex ultrasound and 8 patients (26.66%) out of 30 had conrmed CMI by CT angiogram. CONCLUSION: th We found that every 4 diabetic had CMI. We would like to emphasize that the vasculature of the gut can be affected in T2DM and this should inspire a lot of research and prospective studies relating CMI to GIT manifestations of T2DM.

Impact of type 2 diabetes mellitus on clinical outcomes in patients with COVID-19 and cardiovascular disease

Abstract Introduction Cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) are independent risk factors for the severe course of COVID-19. Thus, all patients with COVID-19, T2DM and CVD should be constant medical control and receive adequate therapy for concomitant diseases. Purpose To study the effect of T2DM on the clinical outcomes of patients with COVID-19 and CVD. Methods Retrospective analysis of clinical outcomes of 1665 patients with a confirmed diagnosis of COVID-19, depending on the presence of CVD, T2DM and received therapy. Results The study included 866 men and 799 women; 299 patients (17.96%) had T2DM. The average age of the patients was 57.56±15.04 years. We noted a high prevalence of CVD: 747 patients (44.9%) had hypertension, 362 patients (21.7%) – coronary heart disease (CHD): 109 (6.5%) – myocardial infarction, 23 (1.4%) – exertional angina, 106 (6.4%) – atrial fibrillation, 98 (5.9%) – chronic heart failure. The patients with T2DM had hypertension in 80% of cases and CHD in 42%. Overall, 65.2% of patients had at least 1 concomitant CVD. Mortality of patients with COVID-19 without concomitant pathology was 0.5%, and in the patients with CHD – 20.7%, with hypertension – 12.9%. Mortality in the patients without T2DM was 7.4%, in the patients with T2DM – 14.0%. Hyperglycemia was associated with a higher mortality rate: the median of glycemia was 5.7 mmol/L in discharged patients and 7.2 mmol/L in deceased patients, regardless of the presence of T2DM (p&amp;lt;0.001). The deceased patients had a higher level of HbA1c compared to those discharged (7.8% vs 8.1%). 24.6% of patients received antihypertensive therapy: 15.5% of patients received ACE inhibitors or ARBs, 11.9% – beta-blockers, 7.1% – thiazide and thiazide-like diuretics, 3.1% – calcium channel blockers. Statins were received by 2.4% of patients, antiplatelet drugs – 2.1%. The mortality rate of patients with COVID-19 and hypertension who received antihypertensive therapy was comparable to the mortality rate of the patients without hypertension: 8.8% and 9.0%, respectively. A significant decrease in mortality was observed during therapy with ACE inhibitors/ARBs (OR 0.39, 95% CI 0.21–0.72, p&amp;lt;0.05), beta-blockers (OR 0.53, 95% CI 0.28–1, p&amp;lt;0.05). This decrease was more significant among patients with T2DM compared with patients without T2DM: a 2.27-fold decrease in mortality due to ACE inhibitors/ARBs in the group without T2DM (OR 0.44, 95% CI 0.2–0.96, p&amp;lt;0.05), in the T2DM group – 4.76 times (OR 0.21, 95% CI 0.07–0.6, p&amp;lt;0.05); decrease in mortality against the background of beta-AB in the group without T2DM – by 1.72 times (OR 0.58, 95% CI 0.26–1.37), in the group with T2DM – by 3 times (OR 0.33, 95% CI 0.12–0.97, p&amp;lt;0.05). Conclusion The presence of CVD and T2DM in the patients with COVID-19 worsens the prognosis of COVID-19. But the adequate therapy for concomitant diseases can have a positive effect on this group of patients. Funding Acknowledgement Type of funding sources: None.

Basement membrane proteins in various arterial beds from individuals with and without type 2 diabetes mellitus: a proteome study

BackgroundBasement membrane (BM) accumulation is a hallmark of micro-vessel disease in diabetes mellitus (DM). We previously reported marked upregulation of BM components in internal thoracic arteries (ITAs) from type 2 DM (T2DM) patients by mass spectrometry. Here, we first sought to determine if BM accumulation is a common feature of different arteries in T2DM, and second, to identify other effects of T2DM on the arterial proteome.MethodsHuman arterial samples collected during heart and vascular surgery from well-characterized patients and stored in the Odense Artery Biobank were analysed by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). We included ascending thoracic aortas (ATA) (n = 10 (type 2 DM, T2DM) and n = 10 (non-DM)); laser capture micro-dissected plaque- and media compartments from carotid plaques (n = 10 (T2DM) and n = 9 (non-DM)); and media- and adventitia compartments from ITAs (n = 9 (T2DM) and n = 7 (non-DM)).ResultsWe first extended our previous finding of BM accumulation in arteries from T2DM patients, as 7 of 12 pre-defined BM proteins were significantly upregulated in bulk ATAs consisting of > 90% media. Although less pronounced, BM components tended to be upregulated in the media of ITAs from T2DM patients, but not in the neighbouring adventitia. Overall, we did not detect effects on BM proteins in carotid plaques or in the plaque-associated media. Instead, complement factors, an RNA-binding protein and fibrinogens appeared to be regulated in these tissues from T2DM patients.ConclusionOur results suggest that accumulation of BM proteins is a general phenomenon in the medial layer of non-atherosclerotic arteries in patients with T2DM. Moreover, we identify additional T2DM-associated effects on the arterial proteome, which requires validation in future studies.