Pathophysiology Of Type Research Articles

Evaluation of Interleukin-6 Levels in Patients with Type 2 Diabetes Mellitus

Background: It has been suggested that inflammatory processes play an important role in the pathogenesis of type 2 diabetes. Individuals who develop type 2 diabetes show signs of low-grade inflammation years before disease onset. This low-grade inflammation has been assumed to be implicated in the pathogenetic mechanisms that cause type 2 Diabetes Mellitus. Inflammatory mediators such as the IL-6 family of cytokines have been proposed to be involved in the events that lead to type 2 diabetes. IL-6 has immunoregulatory actions been proposed to affect glucose homeostasis and metabolism directly and indirectly by action on skeletal muscle cells, adipocytes, hepatocytes, pancreatic b-cells and neuroendocrine cells. Many studies have suggested the role of IL-6 in the pathogenesis of type 2 diabetes mellitus. However, no references have been observed in Bangladesh regarding IL-6 and its association with type 2 diabetes mellitus. It thus may highlight the importance of low-grade inflammation in the pathophysiology of type 2 diabetes mellitus. The purpose of this study was to evaluate type 2 diabetes patients' levels of interleukin-6. Materials and methods: A hospital-based cross-sectional observational study was carried out in the Department of Biochemistry Chittagong Medical College, Department of Endocrinology of Chittagong Medical College Hospital and Chattogram Diabetic Hospital. One hundred (100) type 2 diabetes mellitus patient was included in the study by nonprobability consecutive sampling. Important variables in this study were serum IL-6, BMI, waist circumference and duration of Diabetes Mellitus. Results: The mean serum IL-6 level was 10.08±0.39 pg/ml in patients with type 2 Diabetes Mellitus. Serum IL-6 was positively correlated (r 0.33, p <0.01) with waist circumference and duration of diabetes mellitus (r 0.26, p <0.05). The mean IL-6 was significantly different between BMI groups (F (2,97) =5.39, p=0.006) and was higher in the obese group (10.52±4.00) compared to the overweight and normal BMI (6.78±1.95) and overweight (8.08±3.15) group. Conclusion: It can be concluded that type 2 diabetes mellitus patients had increased serum levels of IL-6. It can give an insight into the possible role of sub clinical inflammation among patients with type 2 Diabetes Mellitus. IAHS Medical Journal Volume 6(2) December 2023; 53-57

Molecular circadian clock disruption in the leukocytes of individuals with type 2 diabetes and overweight, and its relationship with leukocyte–endothelial interactions

Aims/hypothesisAlterations in circadian rhythms increase the likelihood of developing type 2 diabetes and CVD. Circadian rhythms are controlled by several core clock genes, which are expressed in nearly every cell, including immune cells. Immune cells are key players in the pathophysiology of type 2 diabetes, and participate in the atherosclerotic process that underlies cardiovascular risk in these patients. The role of the core clock in the leukocytes of people with type 2 diabetes and the inflammatory process associated with it are unknown. We aimed to evaluate whether the molecular clock system is impaired in the leukocytes of type 2 diabetes patients and to explore the mechanism by which this alteration leads to an increased cardiovascular risk in this population.MethodsThis is an observational cross-sectional study performed in 25 participants with type 2 diabetes and 28 healthy control participants. Clinical and biochemical parameters were obtained. Peripheral blood leukocytes were isolated using magnetic bead technology. RNA and protein lysates were obtained to assess clock-related gene transcript and protein levels using real-time PCR and western blot, respectively. Luminex XMAP technology was used to assess levels of inflammatory markers. Leukocyte–endothelial interaction assays were performed by perfusing participants’ leukocytes or THP-1 cells (with/without CLK8) over a HUVEC monolayer in a parallel flow chamber using a dynamic adhesion system.ResultsParticipants with type 2 diabetes showed increased BMAL1 and NR1D1 mRNA levels and decreased protein levels of circadian locomotor output cycles kaput (CLOCK), cryptochrome 1 (CRY1), phosphorylated basic helix-loop-helix ARNT like 1 (p-BMAL1) and period circadian protein homologue 2 (PER2). Correlation studies revealed that these alterations in clock proteins were negatively associated with glucose, HbA1c, insulin and HOMA-IR levels and leukocyte cell counts. The leukocyte rolling velocity was reduced and rolling flux and adhesion were enhanced in individuals with type 2 diabetes compared with healthy participants. Interestingly, inhibition of CLOCK/BMAL1 activity in leukocytes using the CLOCK inhibitor CLK8 mimicked the effects of type 2 diabetes on leukocyte–endothelial interactions.Conclusions/interpretationOur study demonstrates alterations in the molecular clock system in leukocytes of individuals with type 2 diabetes, manifested in increased mRNA levels and decreased protein levels of the core clock machinery. These alterations correlated with the impaired metabolic and proinflammatory profile of the participants with type 2 diabetes. Our findings support a causal role for decreased CLOCK/BMAL1 activity in the increased level of leukocyte–endothelial interactions. Overall, our data suggest that alterations in core clock proteins accelerate the inflammatory process, which may ultimately precipitate the onset of CVD in patients with type 2 diabetes.Graphical

Pink1 gene: a key player in the pathophysiology of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a complicated metabolic condition with insulin resistance and poor glucose metabolism. Emerging evidence indicates the significance of (PTEN-induced putative kinase 1 (Pink1) in the progression of diseases. Pink1 encodes a protein kinase, which regulates and maintains mitochondrial activity, this mostly affects mitophagy and energy generation. Mutations in the Pink1 gene have been associated to oxidative stress, mitochondrial malfunction, and impaired cellular energy output. The presence of insulin resistance and T2DM may be caused by each of these characteristics. To understand Pink1 potential function in the development of diabetes, this review paper investigates the molecular mechanisms through which it influences glucose metabolism and insulin signaling. Based on preclinical investigations, there is potential for developing innovative therapeutic strategies that specifically target Pink1. These strategies could aim to regulate insulin resistance, improve glucose metabolism, and preserve beta-cell function among individuals diagnosed with diabetes. The following areas of research include figuring out how precisely Pink1 functions in diabetes, translating preclinical findings into clinical settings, exploring precision medicine approaches that specifically target Pink1, and identifying possible therapeutic targets within the Pink1 pathway. This review aims to enhance our understanding of Pink1 impact on T2DM and develop personalized treatments for metabolic disorders. Furthermore, it underscores the significance of persisting with this type of investigation to enhance diabetes treatment strategies.

Concomitant Autoimmune Pancreatitis Type 2 and Colitis Ulcerosa in a 10 Years-Old Girl

Autoimmune pancreatitis (AIP) has gained significant attention in recent years, with a notable increase in diagnoses due to the diagnostic utility of immunoglobulin G4 (IgG4). Despite the well-known IgG4-related type 1 AIP, a less recognized subtype known as type 2 AIP exists, which is distinct from type 1 AIP and not associated with IgG4. Type 2 AIP presents similar clinical symptoms and imaging findings as type 1 AIP, making its diagnosis challenging without specific serum markers. Tissue confirmation of neutrophilic injury to the pancreatic ducts, known as a granulocytic epithelial lesion, is crucial for diagnosing type 2 AIP. Some cases of type 2 AIP are linked to inflammatory bowel disease, particularly ulcerative colitis, but the exact relationship between the two conditions remains unclear. Questions remain regarding the pathophysiology of type 2 AIP, the possibility of similar granulocytic injuries in other organs, and the characteristics of pediatric cases. In this case report we present a concomitant autoimmune pancreatitis type 2 and colitis ulcerosa in a 10 years-old girl. The patients follow-up showed amelioration of the clinical symptoms due to the present medication.

Leptin and ghrelin dynamics: unraveling their influence on food intake, energy balance, and the pathophysiology of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired glucose homeostasis. In recent years, there has been growing interest in the role of hunger and satiety hormones such as ghrelin and leptin in the development and progression of T2DM. In this context, the present literature review aims to provide a comprehensive overview of the current understanding of how ghrelin and leptin influences food intake and maintain energy balance and its implications in the pathophysiology of T2DM. A thorough literature search was performed using PubMed and Google Scholar to choose the studies that associated leptin and ghrelin with T2DM. Original articles and reviews were included, letters to editors and case reports were excluded. This narrative review article provides a comprehensive summary on mechanism of action of leptin and ghrelin, its association with obesity and T2DM, how they regulate energy and glucose homeostasis and potential therapeutic implications of leptin and ghrelin in managing T2DM. Ghrelin, known for its appetite-stimulating effects, and leptin, a hormone involved in the regulation of energy balance, have been implicated in insulin resistance and glucose metabolism. Understanding the complexities of ghrelin and leptin interactions in the context of T2DM may offer insights into novel therapeutic strategies for this prevalent metabolic disorder. Further research is warranted to elucidate the molecular mechanisms underlying these hormone actions and to explore their clinical implications for T2DM prevention and management.

Allogeneic platelet-rich plasma inhibits ferroptosis in promoting wound repair of type 2 diabetic ulcers

Increasing evidence has revealed the emerging role of ferroptosis in the pathophysiology of type 2 diabetes mellitus (T2DM) and its complications. Platelet-rich plasma (PRP) has been demonstrated to facilitate the healing of T2DM ulcers. However, the mechanism by which PRP repairs T2DM ulcers remains unclear. Here, we sought to investigate the interaction between PRP and ferroptosis in repairing T2DM ulcers. The results showed that the cellular activity, proliferation, and migration of fibroblasts were down-regulated, and the cellular activity and normal function of vascular endothelial cells were impaired in the high glucose environment or under RSL3 conditions (a GSH peroxidase 4 inhibitor and ferroptosis inducer). Additionally, both cells experienced over-activation of multiple forms of reactive oxygen species (ROS) and lipid peroxidation. In the T2DM rat model, we observed a decreased rate of ulcer wound healing, impaired proliferative capacity, diminished vascular regeneration, and marked inflammation and hyperfibrosis. More importantly, there was typical damage to mitochondria, increased levels of iron ions, and consistent alterations in protein expression of ferroptosis-related factors. These factors include cyclooxygenase-2 (COX2), glutathione peroxidase 4 (GPX4), transferrin receptor (TFRC), and Solute Carrier Family 7 Member 11 (SLC7A11), among others. Due to the strong association between ferroptosis and T2DM ulcers, the use of allogeneic platelet-rich plasma (Al-PRP) exhibited physiological effects similar to those of the ferroptosis inhibitor Ferrostatin-1 (Fer-1). In vivo experiments, both drugs inhibited a range of impediments to wound healing caused by T2DM and ameliorated the adverse effects associated with ferroptosis. Moreover, Al-PRP attenuated the impairment of normal cellular function, activation of ROS and lipid peroxidation induced by high glucose or RSL3. These results suggested that ferroptosis was involved in the development of T2DM ulcers, which could be treated with Al-PRP by inhibiting ferroptosis, and inhibition of ferroptosis may be a suitable treatment strategy for T2DM ulcers.

Importance of Inflammatory Markers as Common Risk Factors in Diabetes Mellitus and Acute Ischemic Stroke

Diabetes mellitus is a chronic inflammatory condition and it may lead to various secondary complications such as acute ischemic stroke. The common connecting pathophysiology in Type 2 Diabetes Mellitus (T2DM) and Acute Ischemic Stroke (AIS) are the inflammatory pathways. In the present study we compared and evaluated the Neutrophil lymphocyte ratio, Platelet lymphocyte ratio and C - reactive protein between Diabetes Mellitus and Acute ischemic stroke with Diabetes mellitus (AISDM).

The Role of Obesity in Type 2 Diabetes Mellitus-An Overview.

Obesity or excessive weight gain is identified as the most important and significant risk factor in the development and progression of type 2 diabetes mellitus (DM) in all age groups. It has reached pandemic dimensions, making the treatment of obesity crucial in the prevention and management of type 2 DM worldwide. Multiple clinical studies have demonstrated that moderate and sustained weight loss can improve blood glucose levels, insulin action and reduce the need for diabetic medications. A combined approach of diet, exercise and lifestyle modifications can successfully reduce obesity and subsequently ameliorate the ill effects and deadly complications of DM. This approach also helps largely in the prevention, control and remission of DM. Obesity and DM are chronic diseases that are increasing globally, requiring new approaches to manage and prevent diabetes in obese individuals. Therefore, it is essential to understand the mechanistic link between the two and design a comprehensive approach to increase life expectancy and improve the quality of life in patients with type 2 DM and obesity. This literature review provides explicit information on the clinical definitions of obesity and type 2 DM, the incidence and prevalence of type 2 DM in obese individuals, the indispensable role of obesity in the pathophysiology of type 2 DM and their mechanistic link. It also discusses clinical studies and outlines the recent management approaches for the treatment of these associated conditions. Additionally, in vivo studies on obesity and type 2 DM are discussed here as they pave the way for more rigorous development of therapeutic approaches.

Gene-environment interaction in the pathophysiology of type 1 diabetes.

Type 1 diabetes (T1D) is a complex metabolic autoimmune disorder that affects millions of individuals worldwide and often leads to significant comorbidities. However, the precise trigger of autoimmunity and disease onset remain incompletely elucidated. This integrative perspective article synthesizes the cumulative role of gene-environment interaction in the pathophysiology of T1D. Genetics plays a significant role in T1D susceptibility, particularly at the major histocompatibility complex (MHC) locus and cathepsin H (CTSH) locus. In addition to genetics, environmental factors such as viral infections, pesticide exposure, and changes in the gut microbiome have been associated with the development of T1D. Alterations in the gut microbiome impact mucosal integrity and immune tolerance, increasing gut permeability through molecular mimicry and modulation of the gut immune system, thereby increasing the risk of T1D potentially through the induction of autoimmunity. HLA class II haplotypes with known effects on T1D incidence may directly correlate to changes in the gut microbiome, but precisely how the genes influence changes in the gut microbiome, and how these changes provoke T1D, requires further investigations. These gene-environment interactions are hypothesized to increase susceptibility to T1D through epigenetic changes such as DNA methylation and histone modification, which in turn modify gene expression. There is a need to determine the efficacy of new interventions that target these epigenetic modifications such as "epidrugs", which will provide novel avenues for the effective management of T1D leading to improved quality of life of affected individuals and their families/caregivers.

Interplay of adiponectin and resistin in type 2 diabetes: Implications for insulin resistance and atherosclerosis

Aim: The study aims to investigate the association between type 2 diabetes and adipokines, particularly resistin and adiponectin, in insulin resistance. It also explores the potential of the resistin to adiponectin ratio as an indicator for these conditions Methods: This research involved 198 participants, including 100 patients with type 2 diabetes and 98 controls. It focused on measuring various biochemical parameters like HbA1c, fasting plasma glucose, lipid profiles (low-density lipoprotein, oxidized low-density lipoprotein, triglyceride, total cholesterol), and adipokines (resistin and adiponectin). The study utilized the Homeostasis Model Assessment of Insulin Resistance and Triglyceride-Glucose index to evaluate insulin resistance. Results: Type 2 diabetic patients exhibited higher levels of HbA1c, fasting plasma glucose, lipid profiles, and resistin, but lower adiponectin levels compared to controls. Adiponectin showed a negative correlation with insulin resistance, while resistin demonstrated a positive correlation. Both adipokines significantly related to atherogenic markers, with adiponectin offering protection against atherosclerosis and resistin augmenting it. Conclusion: The findings underscore the complex roles of resistin and adiponectin in the pathophysiology of type 2 diabetes, insulin resistance. The resistin to adiponectin ratio could be a useful biomarker for insulin resistance. These insights suggest potential therapeutic strategies for treating diabetes and preventing its complications.

An extended minimal model of OGTT: estimation of α- and β-cell dysfunction, insulin resistance, and the incretin effect.

Loss of insulin sensitivity, α- and β-cell dysfunction, and impairment in incretin effect have all been implicated in the pathophysiology of type 2 diabetes (T2D). Parsimonious mathematical models are useful in quantifying parameters related to the pathophysiology of T2D. Here, we extend the minimum model developed to describe the glucose-insulin-glucagon dynamics in the isoglycemic intravenous glucose infusion (IIGI) experiment to the oral glucose tolerance test (OGTT). The extended model describes glucose and hormone dynamics in OGTT including the contribution of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1), to insulin secretion. A new function describing glucose arrival from the gut is introduced. The model is fitted to OGTT data from eight individuals with T2D and eight weight-matched controls (CS) without diabetes to obtain parameters related to insulin sensitivity, β- and α-cell function. The parameters, i.e., measures of insulin sensitivity, a1, suppression of glucagon secretion, k1, magnitude of glucagon secretion, γ2, and incretin-dependent insulin secretion, γ3, were found to be different between CS and T2D with P values < 0.002, <0.017, <0.009, <0.004, respectively. A new rubric for estimating the incretin effect directly from modeling the OGTT is presented. The average incretin effect correlated well with the experimentally determined incretin effect with a Spearman rank test correlation coefficient of 0.67 (P < 0.012). The average incretin effect was found to be different between CS and T2D (P < 0.032). The developed model is shown to be effective in quantifying the factors relevant to T2D pathophysiology.NEW & NOTEWORTHY A new extended model of oral glucose tolerance test (OGTT) has been developed that includes glucagon dynamics and incretin contribution to insulin secretion. The model allows the estimation of parameters related to α- and β-cell dysfunction, insulin sensitivity, and incretin action. A new function describing the influx of glucose from the gut has been introduced. A new rubric for estimating the incretin effect directly from the OGTT experiment has been developed. The effect of glucose dose was also investigated.

Soluble urokinase plasminogen activator receptor, platelet aggregation, and carotid plaque thickness in diabetes: A cross-sectional analysis

BackgroundSoluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker strongly linked with cardiovascular disease in diabetes. By investigating its association with platelet aggregation levels and carotid plaque thickness, we can potentially improve the characterization of cardiovascular pathophysiology in type 1 (T1D) and type 2 diabetes (T2D). MethodsSuPAR was measured post-hoc in plasma collected in two cross-sectional studies including 1) individuals with T1D and 2) individuals with T2D without known cardiovascular disease. Platelet aggregation was analyzed employing impedance aggregometry using the agonists arachidonic acid (ASPI), adenosine diphosphate (ADP), and thrombin receptor activating peptide-6 (TRAP). Carotid plaque thickness was assessed bilaterally, and the thickest plaque (cPTmax) was analyzed. Correlations and associations of suPAR with platelet aggregation and cPTmax were assessed with Pearson's R and linear regressions adjusted for sex, age, C-reactive protein, estimated glomerular filtration rate, and platelet levels (only for aggregation analysis). ASPI analyses were only performed in participant not receiving aspirin treatment. Standardized estimates with 95 % confidence intervals are presented. ResultsTwo-hundred eighty-three with T1D (mean age 55 years, 44 % women) and 493 individuals with T2D (mean age 65 years, 33 % women) were included. SuPAR levels were positively correlated to platelet aggregation in both T1D (ADP: R = 0.18, p = 0.003; ASPI R = 0.13, p = 0.026) and T2D (ADP R = 0.14, p = 0.002; ASPI R = 0.14, p = 0.017). In adjusted linear regressions higher SuPAR levels were associated with higher ADP induced platelet aggregation in both T1D (26 (8, 44) AU/min, p = 0.004) and T2D (22 (3, 42) AU/min, p = 0.025), while associations to the other agonists were not conclusive. Higher suPAR levels were associated with thicker cPTmax in T1D (0.19 (0.07, 0.32) mm, p = 0.003), but not in T2D (p = 0.94). ConclusionHigher levels of suPAR, an inflammatory generalized disease biomarker, were associated with increased platelet aggregation and thicker cPTmax, in type 1 diabetes. Similar associations with platelet aggregation were found in type 2 diabetes, but not for carotid plaque thickness. These results suggest distinct cardiovascular pathomechanisms in T1D and T2D, although prospective studies are needed to confirm these findings.

Simvastatin, but not Pravastatin, Blocks L-Type Ca2+ Channels In Rat Islet -Cells, Inhibiting Glucose-Induced Cytosolic Ca2+ Signaling and Insulin Release

Patients with type 2 diabetes who have hypercholesterolemia frequently need to take HMG-CoA reductase inhibitors. A key factor in the pathophysiology of type 2 diabetes is altered pancreatic beta-cell activity, which results in a reduced ability of the pancreas to secrete insulin in response to glucose. The impact of HMG-CoA reductase inhibitors on -cell function must therefore be investigated. The regulation of -cell function is greatly influenced by the cytosolic Ca2+ concentration ([Ca2+]i). The current work looked at how HMG-CoA reductase inhibitors affected the [Ca2+]i signaling and insulin release that glucose-induced in rat islet -cells. Simvastatin, a lipophilic HMG-CoA reductase inhibitor, suppressed the initial phase increase and oscillation of [Ca2+]i caused by 8.3 mM glucose in single -cells at concentrations ranging from 0.1 to 3 g ml—1. The fewer Simvastatin-acid, a lipophilic inhibitor, decreased the first [Ca2+]i rise but was two orders of magnitude less effective. Pravastatin (100g ml—1), a hydrophilic inhibitor, has little impact on [Ca2+]. Simvastatin (0.3g ml–1) reduced glucose-induced insulin production from islets more effectively than simvastatin-acid (30g ml–1), whereas pravastatin (100g ml–1) had no effect. Simvastatin, but not pravastatin, showed a reversible blockage of the L-type Ca2+ channels in -cells in whole-cell patch clamp recordings. Simvastatin also prevented the opening of L-type Ca2+ channels, which is how L-arginine and HCl enhance [Ca2+] Conclusion: By blocking L-type Ca2+ channels in -cells, lipophilic HMG-CoA reductase inhibitors can prevent glucose-induced [Ca2+]i signaling and insulin secretion, and their inhibitory potencies are inversely correlated with their lipophilicities. Precaution must be takenWhen HMG-CoA reductase inhibitors are utilized in clinical settings, attention should be given to these findings, especially in type 2 diabetic patients.

Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease.

Hyperglucagonaemia contributes to the pathophysiology in type 2 diabetes (T2D), but the mechanisms behind the inappropriate glucagon secretion are not fully understood. Glucagon and amino acids are regulated in a feedback loop referred to as the liver-α cell axis. Individuals with non-alcoholic fatty liver disease (NAFLD) appear to be glucagon resistant, disrupting the liver-α cell axis resulting in hyperglucagonaemia and hyperaminoacidaemia. We investigated the associations between circulating glucagon, amino acids, and liver fat content in a cohort of individuals with T2D. We included 110 individuals with T2D in this cross-sectional study. Liver fat content was quantified using 1H magnetic resonance spectroscopy (MRS). Associations between liver fat content and plasma glucagon and amino acids, respectively, were estimated in multivariate linear regression analyses. Individuals with NAFLD (n = 52) had higher plasma glucagon concentrations than individuals without NAFLD (n = 58). The positive association between plasma glucagon concentrations and liver fat content was confirmed in the multivariable regression analyses. Plasma concentrations of isoleucine and glutamate were increased, and glycine and serine concentrations were decreased in individuals with NAFLD. Concentrations of other amino acids were similar between individuals with and without NAFLD, and no clear association was seen between liver fat content and amino acids in the regression analyses. MRS-diagnosed NAFLD in T2D is associated with hyperglucagonaemia and elevated plasma concentrations of isoleucine and glutamate and low plasma concentrations of glycine and serine. Whether NAFLD and glucagon resistance per se induce these changes remains to be elucidated.

Dopamine in the Regulation of Glucose Homeostasis, Pathogenesis of Type 2 Diabetes, and Chronic Conditions of Impaired Dopamine Activity/Metabolism: Implication for Pathophysiological and Therapeutic Purposes.

Dopamine regulates several functions, such as voluntary movements, spatial memory, motivation, sleep, arousal, feeding, immune function, maternal behaviors, and lactation. Less clear is the role of dopamine in the pathophysiology of type 2 diabetes mellitus (T2D) and chronic complications and conditions frequently associated with it. This review summarizes recent evidence on the role of dopamine in regulating insular metabolism and activity, the pathophysiology of traditional chronic complications associated with T2D, the pathophysiological interconnection between T2D and chronic neurological and psychiatric disorders characterized by impaired dopamine activity/metabolism, and therapeutic implications. Reinforcing dopamine signaling is therapeutic in T2D, especially in patients with dopamine-related disorders, such as Parkinson's and Huntington's diseases, addictions, and attention-deficit/hyperactivity disorder. On the other hand, although specific trials are probably needed, certain medications approved for T2D (e.g., metformin, pioglitazone, incretin-based therapy, and gliflozins) may have a therapeutic role in such dopamine-related disorders due to anti-inflammatory and anti-oxidative effects, improvement in insulin signaling, neuroinflammation, mitochondrial dysfunction, autophagy, and apoptosis, restoration of striatal dopamine synthesis, and modulation of dopamine signaling associated with reward and hedonic eating. Last, targeting dopamine metabolism could have the potential for diagnostic and therapeutic purposes in chronic diabetes-related complications, such as diabetic retinopathy.

Coronary Artery Disease: A Key Issue in Type 2 Myocardial Infarction: Systematic Review and Recent Findings.

Underlying coronary artery disease (CAD) is increasingly considered to be a key issue in the pathophysiology of type 2 myocardial infarction (T2MI). In T2MI, which is attributable to a mismatch between oxygen supply/demand, CAD is common and appears to be more severe than in type 1 myocardial infarction (T1MI). Little is known about the heterogeneous mechanisms that cause supply/demand imbalance and non-coronary triggers leading to myocardial ischemia or about how they are potentially modulated by the presence and severity of CAD. CAD seems to be underrecognized and undertreated in T2MI, even though previous studies have demonstrated both the short and long-term prognostic value of CAD in T2MI. In this literature review, we attempt to address the prevalence and severity of CAD, challenges in the discrimination between T2MI and T1MI in the presence of CAD, and the prognostic value of CAD among patients with T2MI.

Genetic associations of TMEM154, PRC1 and ZFAND6 loci with type 2 diabetes in an endogamous business community of North India.

More than 250 loci have been identified by genome-wide scans for type 2 diabetes in different populations. South Asians have a very different manifestation of the diseases and hence role of these loci need to be investigated among Indians with huge burden of cardio-metabolic disorders. Thus the present study aims to validate the recently identified GWAS loci in an endogamous caste population in North India. 219 T2D cases and 184 controls were recruited from hospitals and genotyped for 15 GWAS loci of T2D. Regression models adjusted for covariates were run to examine the association for T2D and fasting glucose levels. We validated three variants for T2D namely, rs11634397 at ZFAND6 (OR = 3.05, 95%CI = 1.02-9.19, p = 0.047) and rs8042680 at PRC1 (OR = 3.67, 95%CI = 1.13-11.93, p = 0.031) showing higher risk and rs6813195 at TMEM154 (OR = 0.28, 95%CI = 0.09-0.90, p = 0.033) showing protective effect. The combined risk of 9 directionally consistent variants was also found to be significantly associated with T2D (OR = 1.91, 95%CI = 1.18-3.08, p = 0.008). One variant rs10842994 at KLHDC5 was validated for 9.15mg/dl decreased fasting glucose levels (SE = -17.25-1.05, p = 0.027). We confirm the role of ZFAND6, PRC1 and TMEM154 in the pathophysiology of type 2 diabetes among Indians. More efforts are needed with larger sample sizes to validate the diabetes GWAS loci in South Asian populations for wider applicability.

Comparing the Intervention Effects of the Low-carbohydrate Diet and the Ketogenic Diet on Type 2 Diabetes

Diabetes is a serious issue in human society, and over 90 percent of all cases are type 2 diabetes. Type 2 diabetes is caused by multiple factors such as genetic factors, dietary factors, and metabolic factors. Since dietary factors are one of the causes of type 2 diabetes, scientists and doctors consider food therapy to be a feasible method to intervene in diabetes. Low-carbohydrate and ketogenic diets are applied by many people who want to lower their carbohydrate intake, reduce their blood glucose level, and lose weight. These two dietary patterns are often applied to patients with type 2 diabetes, too. This paper will describe about the causes and pathophysiology of type 2 diabetes, introduce the low-carbohydrate diet and the ketogenic diet respectively, and then compare their intervening effects on type 2 diabetes. Neither dietary pattern is the most suitable for type 2 diabetes treatment as the intervening effects are limited. Also, the side effects of the two dietary patterns must be considered when applying them to patients with type 2 diabetes.

Meta-analysis of the anti-oxidative and anti-inflammatory effects of hypoglycaemic plant-derived medicines.

The pivotal role of oxidative stress and inflammation in the pathophysiology of type 2 diabetes mellitus (T2DM) has been firmly established. However, the evidence concerning hypoglycaemic medicinal plants' antioxidant and anti-inflammatory effects remains inconclusive due to inconsistencies in prior studies. To address this gap, our study aims to perform a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) to consolidate previous research findings in this field. We conducted a comprehensive search in the PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases to identify relevant English randomized controlled trials (RCTs). Our study adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. All eligible studies that evaluated concurrently the antioxidative and anti-inflammatory effects of hypoglycaemic plant-derived supplements on type 2 diabetes mellitus (T2DM) were included in the meta-analysis. The meta-analysis itself was carried out using both fixed and random effects models to synthesize the findings from the selected studies. Our study included 47 trials with a total of 2636 participants, both male and female, aged between 20 and 79years, diagnosed with prediabetes, type 2 diabetes mellitus (T2DM), or metabolic syndrome. The meta-analysis revealed that plant-derived treatments, compared to placebos or other medicines, significantly improved oxidative stress (SMD = -0.36, 95% CI -0.64 to -0.09), inflammation (SMD = -0.47, 95% CI -0.63 to -0.31), total antioxidant capacity (SMD = 0.46, 95% CI 0.16-0.75), and antioxidant enzyme activity (SMD = 1.80, 95% CI 1.26-2.33). The meta-regression analysis showed that treatment duration exceeding 8weeks significantly impacted the heterogeneity of the oxidative stress data. Several hypoglycaemic plant-based treatments appear to positively affect T2DM patients by concurrently lowering oxidative stress and inflammatory indicators and boosting antioxidant enzyme activity. PROSPERO ID: CRD42021226147.

The pathophysiological role of intestinal dysbiosis in type 2 diabetes mellitus and the anti-diabetic potential of probiotics, prebiotics and fecal microbiota transplantation

Type 2 diabetes mellitus (DM2) is a multifactorial disease, and obesity plays the key role in the development thereof. It is believed that the global rise in vast proliferation of DM2 and obesity, recently viewed as an epidemic, is caused by urbanization, reduced physical activity and widely available high-calorie food. Recently, another “player” in the pathophysiology of type 2 diabetes mellitus has been discovered — the intestinal microbiota (IM). Numerous studies have shown the connection between the development of type 2 diabetes mellitus and IM. The review discusses the mechanisms, through which IM contributes to the development of DM2. The results of experimental and clinical studies on the eff ectiveness of the use of probiotics, prebiotics and fecal microbiota transplantation as a method of prevention and treatment of type 2 diabetes mellitus are given.