Type 2 Diabetes Mellitus Comorbidities Research Articles

Effects of IL-6R Expression on IL-6/STAT3/HIF-1α Signaling Pathway in a Mouse Model of Parkinson's Disease with Type 2 Diabetes Co-Morbidity.

More and more evidence has shown the process of Parkinson's disease (PD). Probably, inflammation exerts a crucial role between them. Therefore, the aim of this study was to analyze the impact of interleukin-6 receptor (IL-6R) expression on the IL-6/signal transducer and activator of transcription 3 (STAT3)/hypoxia-inducible factor-1α (HIF-1α) inflammatory signaling pathway within a mouse model of PD with type 2 diabetes mellitus (T2DM) as co-morbidity. We chose healthy wild-type C57BL/6J male mice at the age of 10 weeks to prepare a mouse model of PD with T2DM co-morbidity. Adeno-associated virus (AAV) overexpressing IL-6R or AAV IL-6R-shRNA genes were injected into the substantia nigra (SN) of the mice. The behavioral indices of the pole test were used for examining the motor function of the mice. Using immunofluorescence analysis, the impacts of IL-6R on the level of tyrosine hydroxylase (TH) and anti-ionized calcium-binding adaptor molecule 1 (IBA-1) on dopaminergic neurons and microglia were examined. Additionally, enzyme-linked immunosorbent assay (ELISA) was adopted for determining the expressions of HIF-1α and inflammatory cytokines like tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and IL-4 in the serum. In this study, the protein expression levels of TH, α-Synuclein (α-Syn), IBA-1, IL-6, IL-6R, phosphorylated and total signal transducer and activator of transcription 3 (p-STAT3 (Tyr705) and STAT3) and HIF-1α in the SN were tested via western blotting. To ascertain the mRNA expressions of TNF-α, IL-1β, IL-6, IL-4, and HIF-1α, we used quantitative Real-Time Polymerase Chain Reaction (RT-qPCR). IL-6R-shRNA treatment could markedly shorten the total time of PD in the T2DM co-morbidity mouse model based on the pole test results, reverse the decrease in TH-positive neurons stimulated by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), and lower the activation of microglia (all p < 0.05). Further, IL-6R-shRNA treatment hindered the expression of IL-6, p-STAT3 (Tyr705), and HIF-1α in the SN, lowered the levels of TNF-α, IL-1β, IL-6, IL-4, and HIF-1α in the serum, and mRNA expressions of TNF-α, IL-1β, IL-6, and HIF-1α in the SN (all p < 0.05). In contrast, IL-6R overexpression reduced TH levels, upregulated the level of IBA-1, IL-6, p-STAT3 (Tyr705), and HIF-1α, increased the level of IL-1β, TNF-α, IL-6, IL-4, and HIF-1α (all p < 0.05) in the serum and SN in the PD mouse model with T2DM as a co-morbidity. PD progression with T2DM as a co-morbidity can be boosted by AAV IL-6R-overexpression through upregulation of the IL-6/STAT3/HIF-1α axis. Conversely, AAV IL-6R-shRNA treatment suppressed the IL-6/STAT3/HIF-1α pathway and alleviated neuroinflammation, thus weakening the development of PD with T2DM as a co-morbidity.

Exploring the interconnected between type 2 diabetes mellitus and nonalcoholic fatty liver disease: Genetic correlation and Mendelian randomization analysis.

Epidemiological and clinical studies have indicated a higher risk of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), implying a potentially shared genetic etiology, which is still less explored. Genetic links between T2DM and NAFLD were assessed using linkage disequilibrium score regression and pleiotropic analysis under composite null hypothesis. European GWAS data have identified shared genes, whereas SNP-level pleiotropic analysis under composite null hypothesis has explored pleiotropic loci. generalized gene-set analysis of GWAS data determines pleiotropic pathways and tissue enrichment using eQTL mapping to identify associated genes. Mendelian randomization analysis was used to investigate the causal relationship between NAFLD and T2DM. Linkage disequilibrium score regression analysis revealed a strong genetic correlation between T2DM and NAFLD, and identified 24 pleiotropic loci. These single-nucleotide polymorphisms are primarily involved in biosynthetic regulation, RNA biosynthesis, and pancreatic development. generalized gene-set analysis of GWAS data analysis revealed significant enrichment in multiple brain tissues. Gene mapping using these 3 methods led to the identification of numerous pleiotropic genes, with differences observed in liver and kidney tissues. These genes were mainly enriched in pancreas, brain, and liver tissues. The Mendelian randomization method indicated a significantly positive unidirectional causal relationship between T2DM and NAFLD. Our study identified a shared genetic structure between NAFLD and T2DM, providing new insights into the genetic pathogenesis and mechanisms of NAFLD and T2DM comorbidities.

A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer's disease, and their co-morbidities.

The global prevalence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is rapidly increasing, revealing a strong association between these two diseases. Currently, there are no curative medication available for the comorbidity of T2DM and AD. Ceramides are structural components of cell membrane lipids and act as signal molecules regulating cell homeostasis. Their synthesis and degradation play crucial roles in maintaining metabolic balance in vivo, serving as important mediators in the development of neurodegenerative and metabolic disorders. Abnormal ceramide metabolism disrupts intracellular signaling, induces oxidative stress, activates inflammatory factors, and impacts glucose and lipid homeostasis in metabolism-related tissues like the liver, skeletal muscle, and adipose tissue, driving the occurrence and progression of T2DM. The connection between changes in ceramide levels in the brain, amyloid β accumulation, and tau hyper-phosphorylation is evident. Additionally, ceramide regulates cell survival and apoptosis through related signaling pathways, actively participating in the occurrence and progression of AD. Regulatory enzymes, their metabolites, and signaling pathways impact core pathological molecular mechanisms shared by T2DM and AD, such as insulin resistance and inflammatory response. Consequently, regulating ceramide metabolism may become a potential therapeutic target and intervention for the comorbidity of T2DM and AD. The paper comprehensively summarizes and discusses the role of ceramide and its metabolites in the pathogenesis of T2DM and AD, as well as the latest progress in the treatment of T2DM with AD.

Association of Type‐2 diabetes mellitus with voxelwise tau uptake patterns

AbstractBackgroundDysfunctional insulin signaling and elevated hemoglobin‐A1c (HbA1c) ‐ both associated with type‐2 diabetes mellitus (T2DM) ‐ may result in increased tau hyperphosphorylation, thereby increasing the risk of Alzheimer’s Disease (AD)‐related neuropathology in T2DM patients. Individuals with both AD and T2DM show different profiles of tauopathy compared to individuals with just AD. Here, we evaluated voxelwise tau‐PET patterns with and without T2DM to clarify T2DM‐associated patterns of tau deposition in cognitively intact older adults.MethodWe examined 502 cognitively intact adults from the Health and Aging Brain Study: Health Disparities who had available 18F‐PI‐2620 tau‐PET, florbetaben‐PET (Aβ) (n = 462), MRI T1‐weighted scans (Siemens‐3T), and blood HbA1c levels (n = 492) (Table1). Voxelwise regression models were run in SPM12 using warped 18F‐PI‐2620 standardized uptake value ratio (SUVR) images as the outcome variable (gray matter of the posterior cerebellum reference region) and covarying for age, sex, and education. The first model assessed the effect of T2DM consensus diagnosis on tau uptake. The second model examined the relationship between HbA1c and tau uptake. Both voxelwise regression models were rerun adding global Aβ‐SUVR, obesity, and hypertension as covariates (Figure1).ResultVoxelwise regressions were corrected at voxel p&lt;0.001, cluster FWE p&lt;0.05. T2DM diagnosis was associated with higher 18F‐PI‐2620 uptake in the medial and inferior occipital regions, posterior cingulate, and parahippocampus. Higher HbA1c levels were associated with more 18F‐PI‐2620 uptake in parietal and frontal regions. When covarying for global Aβ‐SUVR, obesity, and hypertension, T2DM diagnosis was associated with 18F‐PI‐2620 uptake in the posterior cingulate. In the HbA1c model, no clusters survived FWE correction after covarying for global Aβ‐SUVR, obesity, and hypertension (Figure1). ConclusionIndependent of common T2DM comorbidities and brain amyloid, T2DM subjects demonstrated a 18F‐PI‐2620 tau uptake pattern that was different from the characteristic age‐associated medial temporal lobe pattern. Our voxelwise approach allowed us to identify regions that may distinguish T2DM‐related pathology from AD‐related changes. The difference in significant clusters between models could be due to HbA1c levels being controlled by medication in some T2DM patients – an area for future study.

Cognitive deficits among people with schizophrenia and prediabetes or diabetes.

Both type 2 diabetes mellitus (T2DM) and schizophrenia are known to be associated with cognitive deficits. The impact of the comorbidities of T2DM or prediabetes (PD) on cognition among people with schizophrenia has been poorly researched. We evaluated the cognitive functioning of patients with schizophrenia and PD or T2DM and compared them to patients with schizophrenia with normal blood sugar. We retrospectively collated data on cognition, fasting blood glucose (FBG), lipids and other selected demographic and clinical variables of 171 patients with schizophrenia and 16 patients with schizoaffective disorder who were admitted to an inpatient rehabilitation facility in Western Australia from 2011 to 2018. The Brief Assessment of Cognition in Schizophrenia (BACS) was used to evaluate cognitive functioning. Parametric and non-parametric analyses were used to examine the study's aims. Sixty-six percent of the patients had normal blood sugar, 25% had PD and 9% had T2DM. The BACS composite score revealed an increasing gradient of cognitive deficits, ranging from mild to severe, between the normal, PD and T2DM groups, respectively. The T2DM group had a significantly lower composite score compared with the PD (p = 0.026) and normal groups (p < 0.001). On the BACS subtests, the scores of T2DM and PD patients were similar except for the token motor task, in which the T2DM group had significantly lower scores (p < 0.001). The T2DM group also had lower scores on the subtests of BACS, except memory tests, compared with those with normal blood sugar. There was no significant difference in the composite and subtest cognitive scores between the PD and normal groups. Our study revealed more pronounced cognitive deficits among patients with schizophrenia and dysglycaemia, particularly those with T2DM, compared with those with schizophrenia with normal blood sugar.

Type 2 diabetes mellitus is associated with manic morbidity in elderly patients with mood disorders.

The association between mood disorders, especially bipolar disorder (BD), and metabolic disorders, is long known. However, to which extent metabolic disorders affect the course of mood disorders in late life is still open to inquiring. To assess the impact of type 2 diabetes mellitus (T2DM) on late-life mood disorders a retrospective chart review was performed. Elderly depressive patients (≥ 65 years) diagnosed with Major Depressive Disorder (N = 57) or BD (N = 43) and followed up for at least 18 months were included and subdivided according to the presence of T2DM comorbidity. Vascular encephalopathy (39.1% vs. 15.6%, P = 0.021) and neurocognitive disorders (21.7% vs. 5.2%, P = 0.028), were more frequently reported in patients with T2DM than in those without. Patients with T2DM showed a greater percentage of follow-up time in manic episodes (r = -0.23, P = 0.020) and a higher rate of manic episode(s) during follow-up (21.7% vs. 5.2%, P = 0.028) than those without. When restricting longitudinal analyses to patients with bipolar spectrum disorders, results were confirmed. In line with the well-known connection between BD and metabolic disorders, our data support an association between T2DM and unfavorable course of illness in the elderly with BD.

Type 2 Diabetes Comorbidity and Cognitive Decline in Patients with Alzheimer's Disease.

Although insulin dysregulation and resistance likely participate in Alzheimer's disease (AD) etiologies, little is known about the correlation between type 2 diabetes mellitus (T2DM) and the progression of cognitive decline in patients with AD. To determine whether AD patients with T2DM experience more rapid cognitive decline than those without T2DM. All cognitive performance data and the presence or absence of T2DM comorbidity in patients with AD were derived from the US National Alzheimer's Coordinating Center's (NACC) Uniform Data Set (UDS). A search of the UDS identified 3,055 participants with AD who had more than one epoch completed. The data set culled clinically diagnosed AD dementia patients who were assessed for diabetes type identified during at least 1 visit. These patients were divided into 2 groups based on whether they had a diagnosis of T2DM. The data from these groups were then analyzed for differences in cognitive decline based on neuropsychological test battery scores and a Clinician Dementia Rating using a general linear model. Comparisons of the mean scores for 16 selected tests from the neuropsychological test battery showed no significant differences in baseline scores and scores at subsequent visits between the T2DM and nondiabetic groups. The results revealed no differences in cognitive decline metrics over the course of 5 visits in either study group. These data indicate that the presence of T2DM does not increase the rate of cognitive decline in AD. This finding contradicts expected disease burden and will need to be explored further.

Diabetes and Cardiorenal Complications: A Clinical Review of Existing Therapies and Novel Combinations, Focusing on SGLT2 Inhibitors.

Type 2 diabetes mellitus (T2DM) is a set of metabolic disorders specified by hyperglycemia as a result of abnormalities in insulin secretion or sensitivity. Chronic kidney disease (CKD) and cardiovascular disease (CVD) are the widespread co-morbidities of T2DM and share risk factors for onset and progression. Despite numerous mono- and combination therapies exist, the progression of diabetes complications remains a global health concern. Treatment options for diabetic- CKD and CVD include drugs targeting hyperglycemia, hypertension, albuminuria, hyperlipidemia and the renin-angiotensin aldosterone system (RAAS). The sodium-glucose co-transporter 2 channel (SGLT2) is abundantly present in proximal tubules of the kidney and its capacity to recover glucose and sodium from the glomerular filtrate limits urinary glucose and sodium excretion. SGLT2 inhibitors (SGLT2i) reduce sodium and glucose reabsorption in the proximal and thus increase urinary glucose excretion in T2DM. SGLT2i monotherapy can improve but dual SGLT2/RAAS inhibition or SGLT2i along with other classes of drugs are more effective in protecting the kidneys and the cardiovascular system in patients with and without diabetes. Combinations such as empagliflozin and linagliptin, ertugliflozin and metolazone, dapagliflozin and sacubitril- valsartan and many more show promising results. Here, we have reviewed the ongoing and completed clinical trials, addressed current theories, and discussed necessary future research to explain the possible risks and benefits of using an SGLT2i alone and in combination with existing antidiabetic drugs and drugs acting on the cardiovascular system.

A network-based study reveals multimorbidity patterns in people with type 2 diabetes

Patients with type 2 diabetes mellitus (T2DM) are at a heightened risk of living with multiple comorbidities. However, the comprehension of the multimorbidity characteristics of T2DM is still scarce. This study aims to illuminate T2DM's prevalent comorbidities and their interrelationships using network analysis. Using electronic medical records (EMRs) from 496,408 Chinese patients with T2DM, we constructed male and female global multimorbidity networks and age- and sex-specific networks. Employing diverse network metrics, we assessed the structural properties of these networks. Furthermore, we identified hub, root, and burst diseases within these networks while scrutinizing their temporal trends. Our findings uncover interconnected T2DM comorbidities manifesting as emergence in clusters or age-specific outbreaks and core diseases in each sex that necessitate timely detection and intervention. This data-driven methodology offers a comprehensive comprehension of T2DM's multimorbidity, providing hypotheses for clinical considerations in the prevention and therapeutic strategies.

Analysis of age-dependent gene-expression in human tissues for studying diabetes comorbidities

The study of the relationship between type 2 diabetes mellitus (T2DM) disease and other pathologies (comorbidities), together with patient age variation, poses a challenge for medical research. There is evidence that patients affected by T2DM are more likely to develop comorbidities as they grow older. Variation of gene expression can be correlated to changes in T2DM comorbidities insurgence and progression. Understanding gene expression changes requires the analysis of large heterogeneous data at different scales as well as the integration of different data sources into network medicine models. Hence, we designed a framework to shed light on uncertainties related to age effects and comorbidity by integrating existing data sources with novel algorithms. The framework is based on integrating and analysing existing data sources under the hypothesis that changes in the basal expression of genes may be responsible for the higher prevalence of comorbidities in older patients. Using the proposed framework, we selected genes related to comorbidities from existing databases, and then analysed their expression with age at the tissues level. We found a set of genes that changes significantly in certain specific tissues over time. We also reconstructed the associated protein interaction networks and the related pathways for each tissue. Using this mechanistic framework, we detected interesting pathways related to T2DM whose genes change their expression with age. We also found many pathways related to insulin regulation and brain activities, which can be used to develop specific therapies. To the best of our knowledge, this is the first study that analyses such genes at the tissue level together with age variations.

Depression is associated with heart failure in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of heart failure (HF). Depression, a common comorbidity of T2DM, may further increase the risk of heart failure (HF). We investigated the association between depression and incident HF in patients with T2DM. Depressive symptoms were assessed in the ACCORD Health-Related Quality of Life study participants at baseline, 12, 36, and 48 months using the nine-item Patient Health Questionnaire (PHQ-9). The severity of depressive symptoms was categorized as none (0-4 points), mild (5-9 points), or moderate-severe (10-24 points). Cox regression with PHQ-9 as a time-dependent covariate was used to assess the association between depression and incident HF. During the median follow-up of 8.1 years, 104 participants developed HF (incidence: 7.1/1,000 person-years). Half of the participants with moderate-severe depression were relieved and a significant percentage of participants without depression or with mild depression worsened to mild or moderate-severe depression during the follow-up period, respectively. Each unit increase in the PHQ-9 score was associated with a 5% higher risk of HF (hazard ratio [HR]:1.05, 95% confidence interval [CI]: 1.01-1.10). Patients with depression ever (HR: 2.23, 95% CI: 1.25-3.98) or persistent depression (HR: 2.13, 95% CI: 1.05-4.44) had a higher risk of HF than those without depression ever. Depressive symptoms change greatly in T2DM patients, depressive symptoms are an independent risk factor for HF. These results reinforce the importance of continuous evaluation and management of mental health status in T2DM patients with high HF risk.

The Role of Steroidomics in the Diagnosis of Alzheimer's Disease and Type 2 Diabetes Mellitus.

Epidemiological studies suggest an association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). This study aimed to investigate the pathophysiological markers of AD vs. T2DM for each sex separately and propose models that would distinguish control, AD, T2DM, and AD-T2DM comorbidity groups. AD and T2DM differed in levels of some circulating steroids (measured mostly by GC-MS) and in other observed characteristics, such as markers of obesity, glucose metabolism, and liver function tests. Regarding steroid metabolism, AD patients (both sexes) had significantly higher sex hormone binding globulin (SHBG), cortisol, and 17-hydroxy progesterone, and lower estradiol and 5α-androstane-3α,17β-diol, compared to T2DM patients. However, compared to healthy controls, changes in the steroid spectrum (especially increases in levels of steroids from the C21 group, including their 5α/β-reduced forms, androstenedione, etc.) were similar in patients with AD and patients with T2DM, though more expressed in diabetics. It can be assumed that many of these steroids are involved in counter-regulatory protective mechanisms that mitigate the development and progression of AD and T2DM. In conclusion, our results demonstrated the ability to effectively differentiate AD, T2DM, and controls in both men and women, distinguish the two pathologies from each other, and differentiate patients with AD and T2DM comorbidities.

HYPOVITAMINOSIS D EXACERBATES TYPE 2 DIABETIC COMORBIDITIES

Vitamin D deciency is one of the prominent nutritional deciencies in India that needs special attention. The effects of hypovitaminosis D on skeletal and cardiovascular functions are well known. However, its effect on metabolic disorders like type 2 diabetes mellitus (T2DM) is still left unexplored. In the present study, our primary aim is to nd out the potential effect of hypovitaminosis D in T2DM patients. The study was conducted on 250 T2DM patients mainly from Madhya Pradesh, India. Among them, 125 had hypovitaminosis D (case group) and were compared against the control group of 125 patients with normal serum vitamin D. We were mainly investigating the major T2DM-related complications including chronic kidney disease (CKD), coronary heart disease (CHD and recurrent infections. Major organ functions including liver, kidney, and cardiac functions were affected by hypovitaminosis D in T2DM patients when compared to control counterparts. We also noticed an association between hypovitaminosis D and the exacerbation of T2DM comorbidities. Our ndings show the importance of maintaining normal serum vitamin D levels in T2DM patients to avoid further complications.

Probing biological network in concurrent carcinomas and Type-2 diabetes for potential biomarker screening: An advanced computational paradigm

Type-2 diabetes mellitus (T2DM), the predominant form of diabetes in adults, is a co-morbid condition that exacerbates the severity of many other diseases, including cardiovascular disease, obesity, dyslipidemia, hypertension, and cancer. Among these, cancer is particularly concerning due to elevated mortality rates and a distinct lack of cost-effective therapeutic interventions. Identifying novel biomarkers for improved early cancer detection is imperative. Therefore, an integrated bioinformatics analysis was conducted to elucidate the co-morbid relationship between T2DM and five different types of cancer, namely bladder (BLCA), breast (BRCA), colon (CRC), liver (HCC), and prostate cancer (PRAD) and identification of novel biomarkers for early cancer detection in individuals with T2DM. A significant comorbid relationship was observed among T2DM, BLCA, and BRCA through gene expression and pathway enrichment analysis, while a moderate association was observed for between T2DM, and PRAD. Notably, we identified 18 significant hub proteins in the context of cancer and T2DM, along with 16 transcription factors and 5 miRNAs. Among these, the hub proteins ESR1, PIK3CA, GNAI1, ERBB2, NR3C1, SNCA, TGFBR2, as well as the micro RNAs hsa-mir-335–5p, hsa-mir-16–5p, and hsa-mir-93–5p hold promise for understanding the comorbidities of T2DM and cancers; and could serve as valuable disease biomarkers for clinical diagnosis and prognosis. This study, centred on bioinformatics analysis for biomarker identification in comorbidities, paves the way for future research encompassing wet lab experimentation and translational studies. These endeavours are poised to validate and facilitate the integration of these findings into the realm of personalized medicine.

A report of two cases of type 2 diabetes mellitus (T2DM): happy and longevity

Chronic hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is associated with the development of complications and the increase of risk of mortality. Patients with T2DM have a shorter life expectancy than non-diabetic population. It is attributed to cardiovascular disease, stroke, renal disease, and infection. Depression secondary to T2DM worsens the quality of life. On the contrary, positive emotions correlated strongly with long life expectancy. A number of mechanisms might explain this correlation. We reported two geriatric patients over 80 y.o. with T2DM comorbidity for more than 20 years. Discussion point of these cases is the subject’s longer life span compared to the average diabetic patient’s life expectancy and great quality of life despite the disease burden of chronic hyperglycemia in T2DM and cardiovascular risk.

Interdependence Between Body Weight, Depth of Inflammation and Functional Capacity of the Pancreas in Patients with Primary Osteoarthritis and Type 2 Diabetes

Osteoarthritis (OA) is the most common joint disease and the leading cause of disability. OA not only affects the quality of life and shortens the functionally active period, but also increases mortality due to the progression of comorbidities, such as obesity, insulin resistance, type 2 diabetes (T2DM), cardiovascular disease. The objective: to identify pathogenetic links between OA and T2DM in order to improve the approach to diagnostic and treatment. Materials and methods.Patients with primary OA and T2DM without exacerbation were divided into three groups according to body mass index (BMI): Group I – 33 patients, Group II – 35 patients, Group III – 34 patients. The mean age of the patients was 61.57±7.97 years (from 29 to 68 years). All patients with comorbidity of T2DM and OA were comparable according to clinical, gender criteria, severity of comorbid pathologies and received treatment. The control group included 30 healthy people. Results. A statistically significant increase in the level of ESR was found in all studied groups compared to the control group (р&lt;0.05). During the analysis of the CRP level in the studied groups, a statistically significant increase in the level of this indicator was found with increasing BMI (р&lt;0.05). A statistically significant progression of T2DM with increasing BMI was recorded for all indicators (р&lt;0.05). A statistically significant increase in total WOMAC index and VAS index with increasing BMI (р&lt;0.05) was established, which indicates the progression of primary OA in comorbidity with T2DM with increasing BMI. The obtained data demonstrated the clinical significance of body weight increase, the accumulation of adipose tissue, and the deepening of the functional insufficiency of the pancreas for the progression of joint and pain syndromes in OA on the background of T2DM. Conclusions. The results of the study showed a statistically significant increase in the manifestations of low-intensity inflammation and the progression of incretory and excretory insufficiency of the pancreas with an increase in the body mass index in patients with primary osteoarthritis (OA) and type 2 diabetes mellitus (T2DM). The interdependence of the inflammatory syndrome with the accumulation of adipose tissue and the deepening of obesity in patients with comorbidity of OA and T2DM has been proven. It is necessary to continue further studies of osteoarthritic changes in the joints in T2DM patients, to develop diagnostic schemes and drug therapy for the combined course of these diseases.

Cytokines, Chemokines, Insulin and Haematological Indices in Type 2 Diabetic Male Sprague Dawley Rats Infected with Trichinella zimbabwensis

Diabetes mellitus is a chronic metabolic disease induced by the inability to control high blood glucose level. Helminth-induced immunomodulation has been reported to prevent or delay the onset of type 2 diabetes mellitus (T2DM), which, in turn, ameliorates insulin sensitivity. Therefore, there is a need to understand the underlying mechanisms utilized by helminths in metabolism and the induction of immuno-inflammatory responses during helminthic infection and T2DM comorbidity. This study aimed at using a laboratory animal model to determine the cytokines, chemokines and haematological indices in diabetic (T2DM) male Sprague Dawley (SD) rats infected with Trichinella zimbabwensis. One hundred and two male SD rats (160–180 g) were randomly selected into three experimental groups (i. T2DM-induced group (D) ii. T. zimbabwensis infected + T2DM group (TzD) and iii. T. zimbabwensis-infected group (Tz)). Rats selected for the D group and TzD group were injected with 40 mg/kg live weight of streptozotocin (STZ) intraperitoneally to induce T2DM, while animals in the Tz and TzD group were infected with T. zimbabwensis. Results showed that adult T. zimbabwensis worm loads and mean T. zimbabwensis larvae per gram (lpg) of rat muscle were significantly higher (p &lt; 0.001) in the Tz group when compared to the TzD group. Blood glucose levels in the D group were significantly higher (p &lt; 0.001) compared to the TzD group. An increase in insulin concentration was observed among the TzD group when compared to the D group. Liver and muscle glycogen decreased in the D when compared to the TzD group. A significant increase (p &lt; 0.05) in red blood cells (RBCs) was observed in the D group when compared to the TzD and Tz groups. An increase in haematocrit, haemoglobin, white blood cells (WBCs), platelet, neutrophils and monocyte were observed in the D group when compared to the TzD group. TNF-α, IFN-γ, IL-4, IL-10 and IL-13 concentrations were elevated in the TzD group when compared to the D and Tz groups, while IL-6 concentration showed a significant reduction in the Tz when compared to the D and the TzD groups. A significant increase in CCL5 in the D and TzD groups was observed in comparison to the Tz group. CXCL10 and CCL11 concentration also showed an increase in the TzD group in comparison to the Tz and the D groups. Overall, our results confirm that T. zimbabwensis, a parasite which produces tissue-dwelling larvae in the host, regulates T2DM driven inflammation to mediate a positive protective effect against T2DM outcomes.

Effect and possible mechanisms of metformin as adjuvant therapy in the management of tuberculosis: A prospective study

ObjectiveTuberculosis (TB) is a deadly infectious ailment causing mortality and morbidity globally. The study objectives were to investigate the effect and possible mechanisms of metformin as adjuvant therapy in the management of tuberculosis. MethodsTB patients attending HAHC hospital, New Delhi (India) and had T2DM (Type-2 diabetes mellitus) comorbidity were enrolled. Study participants were categorized into metformin non-users and metformin users depending on the presence of metformin in their prescription. Whole blood was used for immunophenotyping of total T-Cells (CD45+CD3+), Helper T-Cells (Th) (CD45+CD3+ CD4+) and Cytotoxic T Cells (Tc) (CD45+CD3+CD8+) through flow cytometry. BD FACS Verse and BD LSR II were used for sample acquisition. ResultsEstimation of T-Cells (CD45+CD3+), Helper T-Cells (Th) (CD45+CD3+ CD4+) and Cytotoxic T Cells (Tc) (CD45+CD3+CD8+) levels at 2nd visit showed a larger T-Cells (CD45+CD3+) (p < 0.001), Helper T-Cells (Th) (CD45+CD3+ CD4+) (p = 0.004) and Cytotoxic T Cells (Tc) (CD45+CD3+CD8+) (p = 0.001) in metformin users in comparison with metformin non users. The use of metformin had significant effect on the conversion of sputum smear (p = 0.0318, unpaired t-test) in comparison with metformin non-users. ConclusionMetformin has potential to develop long-term immunity against TB infection and responsible for its protective impact in TB + T2DM comorbid patients. Metformin therapy improved T cells, Helper T cells and cytotoxic T cells in TB + T2DM comorbid patients and it can be prescribed as an adjuvant antitubercular medication unless contraindicated.

RWD95 Investigation into the Geriatric Population with Poorly Controlled Diabetes and the Effects on Hospitalizations

In 2020, the rates of diagnosed, undiagnosed, and prediabetes for the United States population >65 years old were 21.4%, 5.4%, and 24.2%, respectively. With 90-95% of diabetes diagnoses resulting in Type 2 Diabetes Mellitus (T2DM), there is a large focus on T2DM control. T2DM comorbidities occur from poor glycemic control, often accounting for morbidity and mortality. These comorbidities include Chronic Kidney Disease (CKD), neuropathy, retinopathy, and more. The relationship between diabetes and its comorbidities results in increased hospitalization, direct and indirect medical costs, and poor medication adherence.

Role of Diabetes Mellitus in Acute Coronary Syndrome Patients with Heart Failure and Midrange Ejection Fraction Who Have Undergone Percutaneous Coronary Intervention: A 3-Year Case-Series Follow-Up Retrospective Study.

BackgroundData are limited on the effect of diabetes mellitus (DM) on the prognosis of acute coronary syndrome (ACS) patients with heart failure with midrange ejection fraction (HFmrEF) who have undergone percutaneous coronary intervention (PCI). This study aimed to investigate the relationship between type 2 DM (T2DM) and 3-year outcomes in such a population.MethodsA total of 377 ACS patients with HFmrEF (left ventricular EF 40%–49%) who had undergone PCI (132 diabetic and 245 nondiabetic patients) were included in the analysis. The primary outcome was a composite end point of all-cause death or HF rehospitalization. Cox proportional-hazard regression analysis and Kaplan–Meier tests were used to assess the effect of DM on the primary outcome. Sensitivity analysis was conducted with propensity score–matching analysis.ResultsDuring a follow-up of 3 years, diabetic patients had higher incidence of the primary outcome than nondiabetic patients (96.1 vs 44.6 per 1,000 patient-years, incidence ratio 2.301, 95% CI 1.334–3.969; P=0.002). Multivariate analysis showed that DM was associated with a significant increase in the composite outcome of all-cause death or HF rehospitalization (adjusted HR 2.080, 95% CI 1.115–3.878; P=0.021). Sensitivity analysis further confirmed that DM was an independent prognostic factor of long-term adverse outcomes for ACS patients with HFmrEF who had undergone PCI (adjusted HR 3.792, 95% CI 1.802–7.980; P<0.001).ConclusionAmong ACS patients with HFmrEF who had undergone PCI, T2DM comorbidity was significantly associated with worse long-term outcomes.