Defects In Insulin Secretion Research Articles

A critique of measurement of defective insulin secretion and insulin sensitivity as a precision approach to gestational diabetes.

Precision medicine approaches to gestational diabetes mellitus (GDM) have categorised patients according to disease pathophysiology (insulin resistance, insulin insufficiency or both), and demonstrated associations with clinical outcomes. We aimed to assess whether using enhanced processing to determine indices of insulin secretion and sensitivity is analytically robust, reproducible in a different population, and useful diagnostically and prognostically in clinical practice. A total of 1308 pregnant women with one or more risk factors for GDM who underwent a 75 g OGTT at one of nine hospital sites were recruited to this observational study. Specimens were collected for determination of glucose levels using standard and enhanced procedures, HbA1c and insulin analysis. GDM diagnosis and management followed National Institute for Health and Care Excellence guidance. We categorised women into pathophysiological subtypes: insulin-resistant GDM (HOMA2-S < 25th centile of the population with normal glucose tolerance [NGT]), insulin-insufficient GDM (HOMA2-B < 25th centile), both or neither. We assessed associations with pregnancy outcomes using logistic regression. Using enhanced specimen handling, 1027/1308 (78.5%) women had NGT, with 281/1308 (21.5%) being classified as having GDM. Of this group, 135/281 (48.0%) had insulin-resistant GDM, 73/281 (26.0%) had insulin-insufficient GDM and 2/281 (0.7%) had both insulin-resistant and insulin-insufficient GDM. Unexpectedly, 71 patients (25.3%) had GDM with both HOMA2-S and HOMA2-B ≥25th centile (GDM-neither). This novel subgroup appeared to be relatively insulin-sensitive in the fasting state but developed marked post-load hyperglycaemia and hyperinsulinaemia, suggesting an isolated postprandial defect in insulin sensitivity that was not captured by HOMA2-B or HOMA2-S. Women within most GDM subgroups had comparable pregnancy outcomes to those of normoglycaemic women, and HOMA2-B and HOMA2-S were weak predictors of pregnancy outcomes. Maternal BMI predicted a similar number of outcomes to HOMA2-S, suggesting that there was no additional predictive value in adding HOMA2-S. Similar findings were obtained when using different indices and standard specimen handling techniques. Precision categorisation of GDM using HOMA2-S and HOMA2-B does not provide useful diagnostic or prognostic information, but did distinguish a novel subgroup of patients with GDM, characterised by an isolated postprandial defect in insulin sensitivity.

Comparative Study of Human Serum Paraoxonase-1 (PON-1) Activity in Type 2 Diabetes Mellitus: Insights into Oxidative Stress and Antioxidant Defence

Diabetes mellitus is a disease characterized by chronic high blood sugar levels resulting from defects in insulin secretion, insulin action, or both. Prolonged high blood glucose can increase production of reactive oxygen species, leading to elevated oxidative stress. The enzyme paraoxonase-1 (PON1), made in the liver and transported on high-density lipoprotein (HDL), acts as an antioxidant and can counter oxidative stress. This study aimed to compare PON1 activity between healthy controls, obese type 2 diabetics, and non-obese type 2 diabetics. There were 30 healthy controls, 30 obese type 2 diabetics (group I), and 30 non-obese type. Additionally, fasting lipid profiles, fasting plasma glucose, uric acid, albumin, and total bilirubin levels were determined using a clinical chemistry analyzer. The goal was to evaluate differences in PON1 activity as well as metabolic parameters between the three study groups. The results In comparison to the healthy control group, the diabetes group had Significantly higher blood sugar, serum cholesterol, serum triglycerides, serum LDL, and serum uric acid levels, Compared to the healthy control group, PON was Significantly lower in group II patients, Conclusion that Obese type 2 DM patients had significantly lower PON1 and HDL-C levels, which may indicate That the overweight has lessened biochemical functions for these substances. As dyslipidemia, insulin resistance, and high blood pressure are thought to be crucial factors in the cause of metabolic conditions in obese people, the reduced paraoxonase level may increase their likelihood of developing these conditions.

ASSOCIATION OF TRIGLYCERIDE / HIGH-DENSITY LIPOPROTEIN RATIO (TG/HDL RATIO) TO SPECIFIC RISK FACTORS OF DIABETES AND PREDIABETES

Background: Diabetes is a group of metabolic diseases characterized by hyperglycemia due to defects in insulin secretion, insulin action, or both. Prediabetes is a precursor before the diagnosis of diabetes. Patients with prediabetes and diabetes have several risk factors, one of which is dyslipidemia. The TG/HDL ratio is found to be positively associated with insulin resistance and CVD. This study was conducted to determine whether there is a relationship between TG/HDL ratio and the incidence of prediabetes and diabetes. Method: This analytic cross-sectional study was conducted on July-December 2023. The study samples were prediabetic and diabetic patients who met the acceptance criteria of the study subjects. They were tested for BMI, BG, HbA1C and lipid profile. Data analysis used paired t test and Pearson correlation Result: In this study, BMI was greater in the prediabetes group than the diabetes group. There was a negative correlation between age, BG and HDL levels on TG/HDL ratio in prediabetic and diabetic patients. There was a significant relationship between fasting BG, 2 hours after meals BG, HbA1C and TG/HDL ratio when compared between the prediabetes and the diabetes group. Conclusion: In this study, there was no association between TG/HDL ratio in prediabetes and diabetes. Keywords: Prediabetes, diabetes, TG, HDL, HbA1c

Ethnopharmacological Insights into Diabetes Management: Exploring Medicinal Flora of Shivalik range of Himalaya in Uttarakhand

Diabetes mellitus is a chronic metabolic disorder which is commonly found life-threatening disease and it continuously reducing the life expectancy. It is characterized by hyperglycaemia (raised blood sugar level) resulting from defects in insulin secretion, action, or both. Since thousands of years, medicinal plants are being used by our ancestors for the prevention, treatment or even cure the diabetes mellitus. Utilization of these herbal plants is increasing rapidly last two to three decades due to their lesser toxicity and cost effectiveness property as compared to synthetic drugs. In this review, approximately 30 medicinal plants were described which are native to India and traditionally used by the people living in shivalik range of Himalaya in Uttarakhand (specially Dehradun &amp; Haridwar) for the treatment of diabetes mellitus. The data about these plants was collected from science direct, PubMed, web of science, scopus, mdpi, google scholar and different other search engines and websites. This review was conferred in a systematic way as it includes botanical name, family, vernacular name, parts used and pharmacological uses of plants in a tabulated form. There are various scientific evidences behind the uses of some medicinal plants which have been mentioned along with the summary of individual medicinal plant. In this review, all the plants and herbs are easily available in these regions of Uttarakhand and local people traditionally uses these plants as vegetable, seasoning, flavouring and usually consume as a part of their diet. There are some limitations of phytotherapy which limit it to completely replace the allopathic therapy as less bioavailability, less rate of absorption and slow rate of dissolution. But by using various advanced dosage forms (phytosomes, neosomes, liposomes, nanoparticles, nanobubbles, nano diamonds, nanosphere etc.) and method of delivery (various invasive and non-invasive methods) which can bypass these all problems associated with the potency and efficacy of phytochemicals.

Importância do profissional farmacêutico no tratamento DIABETES MELLITUS

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia, caused by defects in insulin secretion, action, or both. When chronic, hyperglycemia can lead to damage in organs such as the kidneys, eyes, nerves, and blood vessels. Affecting over 140 million people worldwide, it is one of the most common non-communicable diseases.

CD36 inhibition corrects lipid-FetuinA mediated insulin secretory defects by preventing intracellular lipid accumulation and inflammation in the pancreatic beta cells

CD36 is a multifunctional protein involved in long chain fatty acid uptake and immune modulation in different cells. Recently it was reported that increased expression of CD36 is evident in the islets of diabetic obese individuals. In this present study we investigated the role of CD36 in regulating intracellular lipid accumulation and inflammation in beta cells and its implication on secretory dysfunction. Additionally, we have elucidated the potential role of fetuinA, a circulatory glycoprotein and an endogenous ligand of TLR4, for aggravating lipid accumulation and insulin secretory defects in beta cells. MIN6 mouse insulinoma cells when incubated with palmitate and fetuinA together showed activation of TLR4-NFkB inflammatory cascade and increased uptake of palmitate, which was rescued by CD36 functional inhibition or knockdown. Moreover, glucose stimulated insulin secretion was restored with consequent downregulation of IL-1β secretion. TLR4 inhibition also decreased intracellular lipid content with a reduction of CD36, suggesting functional crosstalk between them. At physiological level, excess fetuinA in the islet milieu of HFD fed C57BL/6J mice or exogenous fetuinA administration (i.p.) promoted lipid accumulation in the islets resulting in decreased insulin secretion with increased CD36 expression. Interestingly, CD36 inhibition in HFD mice with a pharmacological inhibitor Salvianolic acid B attenuated inflammation, reduced intracellular lipid accumulation in beta cells and restored insulin secretory function. Therefore, our results suggest that inhibition of CD36 protects beta cells from the derogatory effects of lipid and fetuinA and restores secretory function and can be considered as a therapeutic target for obesity mediated beta cell dysfunction.

Effects of Short-Term Treatment with α-Lipoic Acid on Neuropathic Pain and Biomarkers of DNA Damage in Patients with Diabetes Mellitus.

Diabetes mellitus (DM) is a complex and heterogenous disease classified as a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. It leads to various complications, some of which are macrovascular or microvascular complications, like diabetic polyneuropathy (DPN), having a profound impact on patients' quality of life. Oxidative stress (OS) is one of the significant mechanisms in the development and progression of DPN. Thus, targeting OS pathways by antioxidants, such as α-lipoic acid (ALA), could represent a promising therapeutic strategy for alleviating neuropathic symptoms. The aim of our study was to evaluate whether short-term (from 4 to 9 days) intravenous administration of ALA could cause any measurable improvement in subjects with DM. Sixteen subjects with DM (six type 1 and ten type 2) and sixteen nondiabetic subjects matched by sex and age were recruited to this study. Only subjects with DM received treatment with ALA (600 mg daily). Pain intensity and biomarkers of DNA damage including plasma concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), frequency of micronucleated lymphocytes (MN), and frequency of sister-chromatid exchanges (SCEs), were measured before and after the treatment with ALA. Pain intensity and 8-OHdG levels were significantly lower in DM subjects after the ALA treatment than before the treatment. However, no changes in the frequency of SCEs and MN were observed. Our results show some evidence that even a short-term intravenous treatment with ALA could be beneficial for diabetic subjects, reducing pain intensity and concentration of 8-OHdG in blood plasma.

Bone fragility in Type 2 Diabetes Mellitus. Influence of sex and cardiovascular disease in a pilot study using metabolomics

Type 2 diabetes mellitus (T2DM) is one of the most common worldwide metabolic disorders, characterized by insulin resistance (IR) and defective insulin secretion by pancreatic β-cells which leads to multiple complications such as bone fragility. This complication might be influenced by other factors such as gender and cardiovascular disease (CVD). However, it is unclear why a certain T2DM group develops bone fragility, and what the molecular mechanism is. Metabolomics is a powerful approach to the study of human metabolism, especially in complex diseases such as T2DM. Thus, this study aimed to identify significant metabolites associated with bone fragility in T2DM patients. To achieve this, 81 individuals were enrolled and classified as T2DM patients (D, n=28), T2DM with bone fragility (D-Frag, n=25), or age-matched non-diabetic subjects (ND, n=28) as the control group. Serum samples were collected and analyzed using liquid chromatography and gas chromatography, both coupled to mass spectrometry (LC-MS and GC-MS, respectively). Samples were compared within four different scenarios: 1) the classical comparison of D vs ND to corroborate previous studies; 2) D-Frag vs D to explore the metabolites mainly associated with bone fragility; 3) the same comparison using male data (MD-Frag vs MD) to study as a more homogeneous model of bone fragility as in women, bone fragility could be mainly associated with hormonal stage and pregnancy; and 4) MD-Frag-CVD vs MD-CVD to explore the influence of bone fragility in the male-based model with CVD considering that most of the T2DM patients suffer from CVD. After analysis of these scenarios, our results suggest that acylcarnitines and glycerophospholipids, among other metabolites, are involved in the development of bone fragility in T2DM.

Comparative study of blood glucose and glycated hemoglobin in type 2 diabetics in Lubumbashi city

Introduction: Diabetes mellitus is a complex disease, with polymorphic clinical expression and diverse etiopathogenesis, creating an absolute (insufficiency of secretion) or relative (resistance, etc.) defect in insulin effect. This defect in insulin secretion and/or action leads to chronic hyperglycemia with disturbances in carbohydrate, lipid and protein metabolism. Objective: The objective of our study was to establish the relationship between variations in blood sugar and glycated hemoglobin (HbA1c) in type 2 diabetics in Lubumbashi city. Methods: The study involved a sample of 39 known type 2 diabetics treated at the University Clinics of Lubumbashi. Venous blood samples were taken from all patients for the measurement of blood glucose after the 1st, 2nd and 3rd month of antidiabetic treatment and for the measurement of HbA1c after the 3rd month of treatment. Results: The average blood glucose concentrations obtained after the 1st, 2nd and 3rd month of treatment were respectively 180.28 ± 51.09 mg/dl ; 154.20 ± 49.33mg/dl and 135.58 ± 36.45 mg/dl while the percentage of HbA1c after the 3rd month of treatment was 5.90 ± 0.55. Statistical analysis showed that the average blood glucose obtained after the 1st month of treatment was significantly higher (P&lt;0.05) than those obtained after the 2nd and 3rd months of treatment. There was no significant difference between the average blood glucose obtained after the 2nd month of treatment and that obtained after the 3rd month of treatment. Furthermore, a positive correlation (r=0.56) was found between average blood glucose and HbA1c. Conclusion: On the one hand, our results show that the antidiabetic treatment followed by the patients was effective and, on the other hand, they highlight the need to associate the measurement of blood glucose with that of HbA1c in the diagnosis and treatment monitoring in diabetic patients.

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

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

The mitochondrial enzyme pyruvate carboxylase restricts pancreatic β-cell senescence by blocking p53 activation.

Defective glucose-stimulated insulin secretion (GSIS) and β-cell senescence are hallmarks in diabetes. The mitochondrial enzyme pyruvate carboxylase (PC) has been shown to promote GSIS and β-cell proliferation in the clonal β-cell lines, yet its physiological relevance remains unknown. Here, we provide animal and human data showing a role of PC in protecting β-cells against senescence and maintaining GSIS under different physiological and pathological conditions. β-cell-specific deletion of PC impaired GSIS and induced β-cell senescence in the mouse models under either a standard chow diet or prolonged high-fat diet feeding. Transcriptomic analysis indicated that p53-related senescence and cell cycle arrest are activated in PC-deficient islets. Overexpression of PC inhibited hyperglycemia- and aging-induced p53-related senescence in human and mouse islets as well as INS-1E β-cells, whereas knockdown of PC provoked senescence. Mechanistically, PC interacted with MDM2 to prevent its degradation via the MDM2 binding motif, which in turn restricts the p53-dependent senescent program in β-cells. On the contrary, the regulatory effects of PC on GSIS and the tricarboxylic acid (TCA) anaplerotic flux are p53-independent. We illuminate a function of PC in controlling β-cell senescence through the MDM2-p53 axis.

IER3IP1 mutations cause neonatal diabetes due to impaired proinsulin trafficking.

Immediate early response 3 interacting-protein 1 (IER3IP1) is an endoplasmic reticulum resident protein, highly expressed in pancreatic cells and the developing brain cortex. Homozygous mutations in IER3IP1 have been found in individuals with microcephaly and neonatal diabetes, yet the underlying mechanism causing beta cell failure remains unclear. Here, we utilized differentiation of genome edited-stem cells into pancreatic islet cells to elucidate the molecular basis of IER3IP1 neonatal diabetes. Using CRISPR-Cas9, we generated two distinct IER3IP1-mutant human embryonic stem cell lines: a homozygous knock-in model of a patient mutation (IER3IP1V21G), and a knockout model (IER3IP1-/-). While these mutant stem cell lines differentiated normally into definitive endoderm and pancreatic progenitors, we observed that IER3IP1-KO stem cell derived-islets (SC-islets) presented a significant decrease in beta cell numbers and elevated ER stress. Retention Using Selective Hooks (RUSH) assay revealed three-fold reduction in ER-to-Golgi trafficking of proinsulin in IER3IP1 mutant beta cells. Additionally, IER3IP1 mutant SC-islets implanted into immunocompromised mice displayed defective human insulin secretion, indicating the deleterious impact of IER3IP1 mutations on beta cell function. Our study provides valuable insights into the role of IER3IP1 in human beta cell biology and establishes a useful model to investigate ER-to-Golgi trafficking defects within beta cells.

The High Estradiol Environment after IVF Causes the Increased Risk of Glucose Metabolic Dysfunction in Offspring.

Assisted reproductive technology (ART) is associated with increased metabolic risks in offspring. The effect of high maternal estradiol (E2) levels during early pregnancy on the glucose metabolism of offspring remains unclear. To evaluate glucose metabolism in in vitro fertilization (IVF)-conceived children and assess whether high E2 exposure during early pregnancy is associated with metabolic alterations. This retrospective analysis included 500 singletons aged 3-10 years born after fresh embryo transfer (ET) (n=200), frozen ET (n=100), and natural conception (NC) (n=200) from a university hospital. Children underwent anthropometric measurements and examinations for fasting glucose, insulin, and lipid levels. A mouse model of high E2 exposure during early pregnancy was established to study glucose and insulin tolerance, and insulin secretion. Compared with NC, children born after fresh ET showed higher fasting glucose/insulin levels, increased insulin resistance, and higher incidence of impaired fasting glucose, which might be associated with a higher maternal E2 levels. Frozen ET showed intermediate results. In mice, offspring exposed to high E2 levels during gestation exhibited impaired glucose/insulin tolerance and defects in insulin secretion. High maternal E2 levels in early pregnancy are associated with altered glucose metabolism and increased metabolic risks in IVF-conceived children. Further studies are needed to elucidate the underlying mechanisms.

9179 Type 2 Diabetes Alters Metabolic Fuel Selection During Intermittent Fasting

Abstract Disclosure: M.O. Conn: None. D.M. Marko: None. J.D. Schertzer: None. Type 2 Diabetes Alters Metabolic Fuel Selection During Intermittent Fasting Diabetes is characterized by elevated blood glucose resulting from defective insulin secretion and/or insulin resistance. Intermittent fasting, a popular weight loss strategy involving periodic reduction of caloric intake, can improve glycemia. Fasting shifts metabolism from carbohydrates to free fatty acids and ketones. However, high blood insulin can inhibit lipolysis and alter metabolic substrate selection in prediabetes, resulting in muscle catabolism to maintain energy homeostasis. Clinical studies have observed a significant decrease in muscle mass in subjects with obesity and diabetes. Our research aims to characterize lean mass versus fat loss after intermittent fasting in a mouse model of obesity and type 2 diabetes (T2D) and investigate the role of muscle alanine catabolism. We hypothesized that intermittent fasting would promote less lipolysis and more muscle alanine catabolism, causing more muscle loss in diabetic mice than controls. We compared male db/db mice manifesting obesity, hyperglycemia, and hyperinsulinemia to age-matched db/+ (control) mice. Our lab established a 5:2 repeated fasting protocol of ad-libitum access to food for 5 days a week and 2 days of fasting on non-consecutive days. Blood glucose was monitored weekly in fed and fasted states to assess glycemic control. While intermittent fasting lowered fasted blood glucose in both groups, no significant body weight or metabolic tissue mass changes were observed. Metabolic cage data demonstrated increased reliance on fat-based substrates for energy in control mice that underwent intermittent fasting during feeding and fasting periods. Diabetic mice did not show significant changes in the fasted state, but intermittent fasting led to increased reliance on carbohydrate oxidation during re-feeding periods, indicating impaired metabolic flexibility. After 10 weeks, the mice were sacrificed, and metabolic tissue histology (adipose, liver, skeletal muscle) will be performed. We will also analyze serum markers (alanine, fatty acids, glycerol, glucose, insulin) and the activity of the metabolic enzyme alanine transaminase (ALT) in the muscle and liver. This experiment will improve our understanding of how lipolysis and protein breakdown in muscle regulate lean mass versus fat mass loss in obesity and T2D, leading to more effective tailoring of fasting to specific populations. Presentation: 6/3/2024

A narrative review on the role of naturopathy in the management of diabetes mellitus

Abstract: Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Alternative therapies with antihyperglycemic effects are increasingly sought after by patients with diabetes. Some potential alternative treatments for diabetes include yoga and naturopathy, which encompass hydrotherapy, massage therapy, mud therapy, acupuncture, and more. While there are review articles on various alternative therapies for diabetes individually, no known reviews have reported the collective effect of naturopathy therapies, including acupuncture, on diabetes. This comprehensive review was conducted using PubMed/Medline and Google Scholar electronic databases, aiming to provide evidence-based effects of naturopathy therapies such as hydrotherapy, mud therapy, fasting therapy, diet therapy, massage therapy, magnetotherapy, acupuncture, and reflexology, commonly practiced in India, on the management of diabetes. The literature suggests that these treatment modalities significantly improve type 2 diabetes mellitus (T2DM). However, more studies are needed to understand the comprehensive effects of administering these treatments, either individually or in combination, in effectively treating T2DM.

Thyroid Nodules and Insulin Resistance in Type 2 Diabetes Patients

Abstract Background Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. DM can result from deterioration in function and//or a loss of mass in pancreatic tissue. The disease burden of DM is expected to increase in the next few years and decades. The Atlas of the International DM Federation estimated that 537 million adults (20–79 years) were living with DM in 2022, and this number could increase to 643 million by 2030 and 781 million by 2045 Aim of the Work To find out the association between Insulin resistance and thyroid nodules in T2DM. Patients and Methods This study was a Case-control study that was conducted to find association between insulin resistance and thyroid nodules in T2DM cases. The present study was carried out on 80 patients attending Ain Shams University internal medicine department and endocrinology outpatient clinic during the period from August 2021 to May 2023. Results Therefore, the aim of the current work is to find out the assosciation between insulin resistance and thyroid nodules in T2DM. Our study showed that fasting insulin and HOMI-IR were significantly higher in diabetic patients with nodules than in diabetic patients without nodules (P = 0.029 &amp; P = 0.001 respectively). Our study also showed that fasting insulin and HOMI-IR were predictive risk factors for thyroid nodules. Moreover, our results revealed that fasting insulin &amp; IR were positively correlated with thyroid nodule volume and size. Our study showed that there was a significant increase in the mean of FT4 levels in diabetic patients with thyroid nodules (when compared to diabetic patients without thyroid nodules (P = 0.043). Yet, no significant correlation was found between Thyroid nodule volume, Thyroid nodule size, and IR with FT4. The binary logistic regression analysis showed that FT4 was a risk factors for thyroid nodule in the T2DM patients. Furthermore, the results showed that there was a significant increase in the mean of TPO levels in diabetic patients with thyroid nodules when compared to diabetic patients without thyroid nodules (P = 0.038). The binary logistic regression analysis showed that TPO was risk factor for thyroid nodule in the T2DM patients. There was a significant increase in the mean value of fasting blood glucose level in diabetic groups with thyroid nodules when compared to those without thyroid nodules (P &amp;lt; 0.001). Pearson's correlation test also showed significant positive correlation between thyroid nodule size and fasting blood glucose (r = 0.400, P = 0.010) as well as fasting blood insulin (r = 0.440, P = 0.005). The binary logistic regression analysis showed that FBG, PPGL were risk factors for thyroid nodule in the T2DM patients. Conclusion Our research demonstrates that IR is strong risk factors for thyroid nodule occurrence but its prevalence in diabetic cases is not evaluated in our study. So, it is of great clinical significance to perform thyroid Ultrasonography on patients with T2DM. The independent correlates of TNs were multifactorial, and there existed differences in different physiological states

Exploring the Potential of Moringa Oleifera Phytochemicals as Inhibitors of Dipeptidyl Peptidase-4 (DPP-4) in Diabetes Mellitus: A Molecular Docking Approach

Abstract Diabetes mellitus (DM) is a global health concern characterized by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both. Type 2 diabetes (T2DM), the most prevalent form, is largely driven by obesity and a sedentary lifestyle, contributing to over 95% of diabetes cases worldwide. The current treatment regimens for T2DM, including Dipeptidyl Peptidase-4 (DPP-4) inhibitors, aim to enhance insulin secretion but are often associated with adverse side effects. This has intensified the search for natural, safer alternatives with comparable efficacy. Moringa oleifera, a highly valued plant with an extensive history in traditional medicine, has shown promising antidiabetic properties. This research explores the potential of Moringa oleifera-derived phytochemicals as natural DPP-4 inhibitors using in-silico molecular docking techniques. The study identifies and evaluates the binding affinities of these phytochemicals to the DPP-4 enzyme, aiming to predict their inhibitory potential and minimal side effects, thereby contributing to the development of novel, safer hypoglycemic drugs. The results indicate the compounds’ potential as effective DPP-4 inhibitors with promising hypoglycemic properties. Specifically, piceatannol exhibited the highest binding affinity of -7.9 kcal/mol, whereas vanillic acid had the lowest at -5.7 kcal/mol. This study underscores the potential of Moringa oleifera as a natural, safer alternative in the development of novel anti-diabetic drugs, contributing to the growing body of research on plant-based therapeutics for diabetes management.

CNPAS2 induced β cell dysfunction by regulating KANK1 expression in type 2 diabetes.

Diabetes mellitus type 2 (T2DM) is formed by defective insulin secretion with the addition of peripheral tissue resistance of insulin action. It has been affecting over 400 million people all over the world. To explore the pathogenesis of T2DM and to develop and implement new prevention and treatment strategies for T2DM. Receiver operating characteristic (ROC) curve analysis was used to conduct diagnostic markers. The expression level of genes was determined by reverse transcription-PCR as well as Western blot. Cell proliferation assays were performed by cell counting kit-8 (CCK-8) tests. At last, T2DM mice underwent Roux-en-Y gastric bypass surgery. We found that NPAS2 was significantly up-regulated in islet β cell apoptosis of T2DM. The ROC curve revealed that NPAS2 was capable of accurately diagnosing T2DM. NPAS2 overexpression did increase the level of KANK1. In addition, the CCK-8 test revealed knocking down NPAS2 and KANK1 increased the proliferation of MIN6 cells. At last, we found that gastric bypass may treat type 2 diabetes by down-regulating NPAS2 and KANK1. This study demonstrated that NPAS2 induced β cell dysfunction by regulating KANK1 expression in type 2 diabetes, and it may be an underlying therapy target of T2DM.

Redox Status as a Key Driver of Healthy Pancreatic Beta-Cells.

Redox status plays a multifaceted role in the intricate physiology and pathology of pancreatic beta-cells, the pivotal regulators of glucose homeostasis through insulin secretion. They are highly responsive to changes in metabolic cues where reactive oxygen species are part of it, all arising from nutritional intake. These molecules not only serve as crucial signaling intermediates for insulin secretion but also participate in the nuanced heterogeneity observed within the beta-cell population. A central aspect of beta-cell redox biology revolves around the localized production of hydrogen peroxide and the activity of NADPH oxidases which are tightly regulated and serve diverse physiological functions. Pancreatic beta-cells possess a remarkable array of antioxidant defense mechanisms although considered relatively modest compared to other cell types, are efficient in preserving redox balance within the cellular milieu. This intrinsic antioxidant machinery operates in concert with redox-sensitive signaling pathways, forming an elaborate redox relay system essential for beta-cell function and adaptation to changing metabolic demands. Perturbations in redox homeostasis can lead to oxidative stress exacerbating insulin secretion defect being a hallmark of type 2 diabetes. Understanding the interplay between redox signaling, oxidative stress, and beta-cell dysfunction is paramount for developing effective therapeutic strategies aimed at preserving beta-cell health and function in individuals with type 2 diabetes. Thus, unraveling the intricate complexities of beta-cell redox biology presents exciting avenues for advancing our understanding and treatment of metabolic disorders.

Association of Anemia and Diabetic Retinopathy Among Patients With Type 2 Diabetes Mellitus: Retrospective Cross-Sectional Study.

Introduction Type 2 diabetes mellitus (T2DM) is a common metabolic disorder characterized by the combination of defective insulin secretion and the inability of insulin-sensitive tissues to respond appropriately to insulin. Diabetic retinopathy (DR) is a common microvascular complication that can result in a preventable cause of blindness. Research to determine the prevalence of anemia among diabetic patients is necessary to assess whether treatment practices should be changed. Anemia is a common complication in patients with T2DM and has been associated with the progression of DR. In this study, our aim is to determine the prevalence of DR and its association with hemoglobin levels in patients diagnosed with T2DM in Dubai, UAE. Methods In this retrospective cross-sectional study, we extracted the data using electronic medical records. The study was performed over a span of three years in Dubai from 2019 to 2022. A total of 368 T2DM patients were included based on retinal exam findings classified into mild, moderate, severe non-proliferative retinopathy, and proliferative retinopathy. Descriptive statistics were used for categorical (frequency, percentage) and continuous variables (mean, SD), with chi-square/Fisher exact tests for categorical associations, ANOVA for continuous variables, and multiple logistic regression to identify DR risk factors, using OR, 95% CI, and p < 0.05 for significance. Results The prevalence of anemia (defined as hemoglobin levels ≤13 mg/dL for men and ≤12 mg/dL for women) was observed in 39.4% of individuals with DR aged between 40 and 88 years; 60.6% of the patients had normal hemoglobin, while 91 individuals (24.7%) exhibited mild anemia, 53 individuals (14.4%) showed moderate anemia, and only one individual (0.3%) had severe anemia. DR grading was as follows: mild non-proliferative DR (16.8%), moderate non-proliferative DR (30.2%), severe non-proliferative DR (13.3%), and proliferative DR (39.7%). Macular edema was present in 59.2% of patients, showing a statistically significant association with more severe DR stages (p < 0.0001). No significant association was found between hemoglobin levels and DR severity (p = 0.568). However, among males, a significant difference in mean hemoglobin levels across DR grades was observed (p = 0.009), with higher hemoglobin levels associated with lower odds of severe DR (OR = 0.775, p = 0.036). Macular edema strongly predicted DR severity, with significant odds ratios across all stages (p < 0.0001). Conclusions There is a significant prevalence of anemia among the examined population. DR severity was notably associated with lower hemoglobin levels in males, and macular edema was significantly linked to more severe stages of DR. Vigilant monitoring and integrated care for both anemia and DR are crucial to optimize patient outcomes and mitigate complications. Regular retinopathy screening is essential for early detection and timely intervention, particularly considering the challenges posed by anemia, such as delayed wound healing and increased infection risk post-screening.