Insulin Action Research Articles

Rutin alleviates advanced glycosylation end products-induced insulin resistance by inhibiting SOCS3/IRS1 and activating PI3K/AKT signaling pathways in HepG2 cells

The accumulation of advanced glycosylation end products (AGEs) from food in the body disrupts normal physiological insulin activity and causes insulin resistance. This study compared the effects of ten types of polyphenols on AGEs production in both chemical and food models. It also investigated the impact of polyphenols on AGEs-induced insulin resistance in HepG2 cell models. Results showed that luteolin had the strongest inhibitory effect on fluorescent AGEs in the three chemical models. Rutin exhibited the most potent capacity to inhibit AGEs in biscuit models. Moreover, rutin alleviated the glucose metabolism disorders induced by representative AGEs (methylglyoxal-modified bovine serum albumin, MGO-BSA) in HepG2 cells. Mechanistic studies revealed that rutin could inhibit the phosphorylation of insulin receptor substrate 1 (IRS1) and the activity of suppressor of cytokine signaling 3 (SOCS3), while activating the phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) to alleviate the MGO-BSA-induced insulin resistance in HepG2 cells.

Methylglyoxal induces death in human brain neuronal cells (SH-SY5Y), prevented by metformin and dapagliflozin

Diabetes mellitus is a metabolic disorder caused by a dysfunction in insulin action or secretion, leading to an elevation in blood glucose levels. It is a highly prevalent condition and as a result, the NHS spends 10 % of its entire budget on diabetes mellitus care, that is equivalent to £10 billion a year. Diabetes mellitus has been linked with vascular and neurological complications which may be associated with the progression of neurodegeneration and Alzheimer's disease. Chronic hyperglycaemia increases the production of the reactive oxidant species (ROS) such as methylglyoxal (MGO). MGO has been linked with vascular complications, neuropathy and cytotoxicity. The main aim of this study was to investigate the potential beneficial effect of antidiabetic agents such as metformin and dapagliflozin on human brain neuronal cells (SH-SY5Y) treated with MGO. SH-SY5Y cells were cultured in DMEM/F12 media and subjected overnight incubation with one of the following treatment conditions: Control (untreated); MGO (1 μM); MGO (100 μM); metformin (100 μM) + MGO (100 μM); and dapagliflozin (10 μM) + MGO (100 μM). Several assays were conducted to explore the effect of the treatment groups on the SH-SY5Y cells. These included: MTT assay; LDH assay, peroxynitrite fluorescence assay, and laser scanning confocal microscopy. MGO (100 μM) led to significant cell injury and damage and significantly reduced the survival of the cells by approximately 50–75 %, associated with significant increase in peroxynitrite. The addition of metformin (100 μM) or dapagliflozin (10 μM) represented significant protective effects on the cells and prevented the cell damage caused by the high MGO concentration. As a result, the findings of this research reveal that MGO-induced cell damage may partly be mediated by the generation of peroxynitrite, while the antidiabetic agents such as metformin and dapagliflozin prevent brain cell death, which potentially may play prophylactic roles against the risk of dementia in diabetic patients.

Ozenoxacin suppresses sebum production by inhibiting mTORC1 activation in differentiated hamster sebocytes.

Acne vulgaris is a complex condition involving factors that affect the pilosebaceous unit. A primary manifestation of acne pathology is the development of comedones, often linked to the overproduction of sebum resulting from 5α-dihydrotestosterone (5α-DHT) and insulin activity. Ozenoxacin is a topical quinolone that exhibits potent antibacterial activity against Cutibacterium acnes (C. acnes). It is commonly used to treat acne associated with this bacterium; however, its effect on sebum production within the sebaceous glands remains unclear. In this study, the effects of ozenoxacin on sebum production were examined using insulin- and 5α-DHT-differentiated hamster sebocytes. Ozenoxacin showed a dose-dependent inhibition of lipid droplet formation and triacylglycerol (TG) production, which is a major component of sebum. In addition, it suppressed the expression of diacylglycerol acyltransferase 1, stearoyl-CoA desaturase-1, and perilipin-1 mRNA, all important factors involved in sebum synthesis, in a dose-dependent manner. Moreover, ozenoxacin decreased phosphorylated 40S ribosomal protein S6 levels downstream of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1), without altering the phosphorylation of Akt, an upstream regulator of mTORC1, in both insulin- and 5α-DHT-treated hamster sebocytes. Interestingly, nadifloxacin, but not clindamycin, exhibited a similar suppression of sebum production, albeit with lesser potency compared with ozenoxacin. Furthermore, a topical application of a 2% ozenoxacin-containing lotion to the auricle skin of hamsters did not affect the size of the sebaceous glands or epidermal thickness. Notably, it decreased the amount of TG on the skin surface. The results provide novel insights into the sebum-inhibitory properties of ozenoxacin, indicating its potential efficacy in controlling microbial growth and regulating sebum production for acne management.

Effects of chronic treatment with metformin on brain glucose hypometabolism and central insulin actions in transgenic mice with tauopathy

Brain glucose hypometabolism and insulin alterations are common features of many neurological diseases. Herein we sought to corroborate the brain glucose hypometabolism that develops with ageing in 12-months old Tau-VLW transgenic mice, a model of tauopathy, as well as to determine whether this model showed signs of altered peripheral glucose metabolism. Our results demonstrated that 12-old months Tau mice exhibited brain glucose hypometabolism as well as basal hyperglycemia, impaired glucose tolerance, hyperinsulinemia, and signs of insulin resistance. Then, we further studied the effect of chronic metformin treatment (9 months) in Tau-VLW mice from 9 to 18 months of age. Longitudinal PET neuroimaging studies revealed that chronic metformin altered the temporal profile in the progression of brain glucose hypometabolism associated with ageing. Besides, metformin altered the content and/or phosphorylation of key components of the insulin signal transduction pathway in the frontal cortex leading to significant changes in the content of the active forms. Thus, metformin increased the expression of pAKT-Y474 while reducing pmTOR-S2448 and pGSK3β. These changes might be related, at least partially, to a slow progression of ageing, neurological damage, and cognitive decline. Metformin also improved the peripheral glucose tolerance and the ability of the Tau-VLW mice to maintain their body weight through ageing. Altogether our study shows that the tau-VLW mice could be a useful model to study the potential interrelationship between tauopathy and central and peripheral glucose metabolism alterations. More importantly our results suggest that chronic metformin treatment may have direct beneficial central effects by post-transcriptional modulation of key components of the insulin signal transduction pathway.

Suppression of gp130 attenuated insulin-mediated signaling and glucose uptake in skeletal muscle cells

The aim of the present study was to investigate the effects of Oncostatin M receptor (OSMR) subunit gp130 knockdown on insulin-stimulated glucose metabolism-related signaling pathways and glucose uptake in skeletal muscle cells. siRNA-mediated gp130 knockdown was conducted in C2C12 muscle cells, and insulin was added and incubated for 1 h. The cells were cultivated to analyze the mRNA levels of gp130, phosphorylation of STAT3, and glucose metabolism-regulated signaling pathways, and OSM levels in the culture medium were analyzed. The phosphorylation of STAT 3 was significantly decreased in gp130−/− cell. The insulin stimulation was significantly increased in both gp130−/− and gp130+/+ and the phosphorylation of IRS-1 Ser 1101 was significantly decreased in gp130−/−. PI3-kinase activity and Akt Thr 308 phosphorylation were significantly decreased in gp130−/−. The insulin-stimulated increase in glucose uptake rate was significantly attenuated in gp130−/−. In the culture medium, OSM levels were significantly lower in gp130+/+compared to gp130−/− cell. In conclusion, the knockdown of gp130 caused a decrease in STAT 3 phosphorylation and resulted in the attenuation of insulin-mediated glucose metabolism signaling in skeletal muscle cells. Thus, an excessive increase in extracellular OSM may induce blunted insulin action in skeletal muscle cells.

Serum immunoglobulin concentrations and risk of type 2 diabetes mellitus in adults: a prospective cohort study from the TCLSIH study

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48–0.85), 0.94 (0.72–1.23), 0.68 (0.50–0.92) and 1.62 (1.24–2.11) (P for trend was < 0.01, 0.84, 0.02 and < 0.0001), respectively, suggesting that serum IgG and IgM concentrations were inversely associated with the incidence of T2DM, and IgA levels were positively associated with the risk of T2DM in a general adult population.

Effect of Swimming Exercise on Levels of Blood Glucose, Adiponectin, Glucose-6-Phosphatase and Lipid Profile in Diabetic Wistar Rats

Diabetes mellitus is a chronic metabolic condition that causes persistent hyperglycemia due to insulin action or secretion. Regular physical exercise has been reported to improve glycemia and lipid profile in diabetes. However, literature is scare on the effects of swimming exercise on the serum levels of adiponectin and glucose 6 phosphatase in Wister rats with diabetes This study therefore, investigated the effects of swimming exercise on adiponectin, glucose 6-phosphatase and lipid profile in male Wistar rats with streptozotocin-induced diabetes. This study was carried out on 25 male Wistar rats grouped into five groups (n=5/group): group 1=control, group 2=diabetes, group 3=diabetes treated with metformin, group 4=non-diabetes and swimming exercise, group 5=diabetes and swimming exercise. Animals in groups 2, 3, and 5 were induced with Streptozotocin (STZ) 50 mg/kg intraperitoneally. After 72 hours of diabetes induction, animals with a blood glucose level of ≥ 200 mg/dl were confirmed diabetics and used for the study. Group 3 animals were treated with metformin 200mg/kg giving orally for 28 days. Animals in groups 4 and 5 were subjected to swimming exercises for 5-10 minutes during the first week until they could swim freely for 30 minutes. The animals were then allowed to swim 5 days per week for 28 days. Swimming exercise for 28 days significantly reduced blood glucose, glucose-6-phosphatase (G6Ppase), Lactate dehydrogenase (LDH), Total cholesterol (TC), and Low-density lipoprotein (LDL) levels but caused significant increase in adiponectin and High-density lipoprotein (HDL) levels in diabetic rats compared with untreated diabetic rats. There was a significant decrease in triglyceride (TG) of diabetic animals caused by swimming for 28 days. This study demonstrated that swimming exercise for 28 days may help lower glucose level and improve insulin sensitivity by increasing adiponectin level and decreasing G6Pase activity in diabetic rats. Also, swimming exercise may help improve lipid profile in diabetic rats.

Elemental Profiling of Common Anti-diabetic Medicinal Plants of Swat and Peshawar Districts of Khyber Pakhtunkhwa (KPK) Province of Pakistan: An Investigation Using PIXE and ICP-OES.

The use of medicinal plants is integral to addressing liver, heart, lung, and other metabolic issues. These plants are rich in vitamins, minerals, flavonoids, and alkaloids, which collectively help in lowering intestinal glucose absorption and increasing insulin secretion by pancreatic tissues. Elemental analysis, encompassing major, minor, and trace elements, was performed on various parts (leaves, roots, and seeds) of 16 anti-diabetic medicinal plants collected from different regions of Swat and Peshawar in Khyber Pakhtunkhwa (KPK), Pakistan. This analysis utilized proton-induced X-ray emission (PIXE) and inductively coupled plasma optical emission spectroscopy (ICP-OES) techniques. Our PIXE and ICP-OES analysis revealed the presence of major (Ca, K, S, P), minor (Si, Cl), and trace (Al, Mn, Fe, Ni, Cu, Zn, Se, Cr, and Sc) elements in various parts (leaves, roots, and seeds) of the 16 anti-diabetic medicinal plants studied. Specifically, elements such as Ca, K, Cr, Cu, Mn, Zn, and Se were detected, all of which are known to contribute in maintaining normal glucose metabolism. Notably, Zn and Se are crucial trace elements for the synthesis, secretion, and action of insulin. Significant Zn concentrations were observed in ten anti-diabetic medicinal plants: Albizia lebbeck (AL), Atropa acuminata (AA), Avena fatua (AF), Citrus medica (CM), Commiphora wightii (CW), Cymbopogon citratus (CC), Daucus carota (DC), Ziziphus mauritiana (FM), Hyoscyamus niger (HN), and Martynia annua (MA), and significant Se concentrations were observed in twelve medicinal plants, i.e., Albizia lebbeck (AL), Allium sativum (AS), Atropa acuminata (AA), Avena fatua (AF), Cannabis sativa (CS), Capparis spinosa (CaS), Commiphora wightii (CW), Cymbopogon citratus (CC), Datura alba (DA), Daucus carota (DC), Ziziphus mauritiana (FM), and Hyoscyamus niger (HN). Our study's elemental analysis using PIXE and ICP-OES on various parts of 16 medicinal plants identified a significant number of useful elements. Elements such as Ca, K, S, P, Al, Si, Cl, Mn, Fe, Ni, Cu, Zn, Se, and Cr were identified and quantified. These findings support the potential use of these plants in managing diabetes and highlight the importance of elemental profiling in understanding their therapeutic properties.

Evaluasi Rasionalitas Insulin Pada Pasien Diabetes Mellitus Tipe 2 Rawat Jalan di RSUD Kota Madiun Periode 2022

Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia that occurs due to defects in insulin secretion, insulin action or both. Diabetes mellitus (DM) is currently a global health threat. Various epidemiological studies have shown an increase in the incidence and prevalence of DM in the world. Based on data from the profile of the East Java Health Office in 2021, it is estimated that DM patients in Madiun City rank fourth in the East Java region. . Objective: This research was conducted to determine the evaluation of the rationality of insulin in type 2 DM patients in the Outpatient Hospital of Madiun City Hospital for the period 2022. Methods: This research method is in the form of an observational research, retrospective data collection in the form of medical records of history of type 2 diabetes mellitus patients at Outpatient Hospital at RSUD Madison City. The total population in this study in the period January - December 2022 was 165 patients. Results: From the 62 type 2 DM patients who were outpatients at Madiun City Regional Hospital, it was found that 14.52% using single insulin and 12.90% used Detemir insulin. The use of the insulin combination was 85.48% and the Detemir – Aspart insulin combination was 58.06%. Conclusion: Evaluation of the rationality of insulin use showed that the correct drug was 100% and the correct dose was 93,55%.

Effects of kaempherol-3-rhamnoside on metabolic enzymes and AMPK in the liver tissue of STZ-induced diabetes in mice

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia. It involves disturbances in carbohydrate, fat, and protein metabolism due to defects in insulin secretion, insulin action, or both. Novel therapeutic approaches are continuously being explored to enhance metabolic control and prevent complications associated with the disease. This study investigates the therapeutic potential of kaempherol-3-rhamnoside, a flavonoid, in managing diabetes by modulating the AMP-activated protein kinase (AMPK) pathway and improving metabolic enzyme activities in streptozotocin (STZ) -induced diabetic mice. Diabetic mice were treated with varying doses of kaempherol-3-rhamnoside and/or insulin over a 28-day period. Glycolytic and gluconeogenesis enzyme activities in the liver, fasting blood glucose levels, serum insulin levels, lipid profiles and oxidative stress markers were assessed. Treatment with kaempherol-3-rhamnoside significantly improved glycolytic enzyme activities, reduced fasting blood glucose, and enhanced insulin levels compared to diabetic controls. The compound also normalized lipid profiles and reduced oxidative stress in the liver, suggesting its potential in reversing diabetic dyslipidemia and oxidative damage. Furthermore, kaempherol-3-rhamnoside activated the AMPK pathway, indicating a mechanism through which it could exert its effects. Kaempherol-3-rhamnoside exhibits promising antidiabetic properties, potentially through AMPK pathway activation and metabolic enzyme modulation. These findings support its potential use as an adjunct therapy for diabetes management. Further clinical studies are warranted to validate these results in human subjects.

A mixed meal tolerance test predicts onset of type 2 diabetes in Southwestern Indigenous adults

Background/ObjectiveTo identify predictors of incident type 2 diabetes using a mixed meal tolerance test (MMTT).MethodsAdult Indigenous Americans without diabetes (n = 501) from a longitudinal cohort underwent at baseline a 4-h MMTT, measures of body composition, an oral glucose tolerance test, an intravenous glucose tolerance test for acute insulin response (AIR), and a hyperinsulinemic-euglycemic clamp for insulin action (M). Plasma glucose responses from the MMTT were quantified by the total and incremental area under the curve (AUC/iAUC).ResultsAt follow-up (median time 9.6 [inter-quartile range: 5.6–13.5] years), 169 participants were diagnosed with diabetes. Unadjusted Cox proportional hazards models, glucose AUC180-min (HR: 1.98, 95% CI: 1.67, 2.34, p < 0.0001), AUC240-min (HR: 1.93, 95% CI: 1.62, 2.31, p < 0.0001), and iAUC180-min (HR: 1.43, 95% CI: 1.20, 1.71, p < 0.0001) were associated with an increased risk of diabetes. After adjustment for covariates (age, sex, body fat percentage, M, AIR, Indigenous American heritage) in three subsequent models, AUC180-min (HR: 1.44, 95% CI: 1.10, 1.88, p = 0.007) and AUC240-min (HR: 1.41, 95% CI: 1.09, 1.84, p < 0.01) remained associated with increased risk of diabetes.ConclusionsGlucose responses to a mixed meal predicted the development of type 2 diabetes. This indicates that a mixed nutritional challenge provides important information on disease risk.Clinical Trial RegistryClinicalTrials.gov identifier : NCT00340132, NCT00339482

A mixed meal tolerance test predicts onset of type 2 diabetes in Southwestern Indigenous adults

Background/ObjectiveTo identify predictors of incident type 2 diabetes using a mixed meal tolerance test (MMTT).MethodsAdult Indigenous Americans without diabetes (n = 501) from a longitudinal cohort underwent at baseline a 4-h MMTT, measures of body composition, an oral glucose tolerance test, an intravenous glucose tolerance test for acute insulin response (AIR), and a hyperinsulinemic-euglycemic clamp for insulin action (M). Plasma glucose responses from the MMTT were quantified by the total and incremental area under the curve (AUC/iAUC).ResultsAt follow-up (median time 9.6 [inter-quartile range: 5.6–13.5] years), 169 participants were diagnosed with diabetes. Unadjusted Cox proportional hazards models, glucose AUC180-min (HR: 1.98, 95% CI: 1.67, 2.34, p < 0.0001), AUC240-min (HR: 1.93, 95% CI: 1.62, 2.31, p < 0.0001), and iAUC180-min (HR: 1.43, 95% CI: 1.20, 1.71, p < 0.0001) were associated with an increased risk of diabetes. After adjustment for covariates (age, sex, body fat percentage, M, AIR, Indigenous American heritage) in three subsequent models, AUC180-min (HR: 1.44, 95% CI: 1.10, 1.88, p = 0.007) and AUC240-min (HR: 1.41, 95% CI: 1.09, 1.84, p < 0.01) remained associated with increased risk of diabetes.ConclusionsGlucose responses to a mixed meal predicted the development of type 2 diabetes. This indicates that a mixed nutritional challenge provides important information on disease risk.Clinical Trial RegistryClinicalTrials.gov identifier : NCT00340132, NCT00339482

Differential Mitochondrial Adaptation of the Slow and Fast Skeletal Muscles by Endurance Running Exercise in Streptozotocin-Induced Diabetic Mice.

The skeletal muscle is the main organ responsible for insulin action, and glucose disposal and metabolism. Endurance and/or resistance training raises the number of mitochondria in diabetic muscles. The details of these adaptations, including mitochondrial adaptations of the slow and fast muscles in diabetes, are unclear. This study aimed to determine whether exercise training in streptozotocin (STZ)-induced mice leads to differential adaptations in the slow and fast muscles, and improving glucose clearance. Eight-week-old mice were randomly distributed into normal control (CON), diabetes (DM), and diabetes and exercise (DM+Ex) groups. In the DM and DM+Ex groups, mice received a freshly prepared STZ (100 mg/kg) intraperitoneal injection on two consecutive days. Two weeks after the injection, the mice in the groups ran on a treadmill for 60 min at 20 m/min for a week and subsequently at 25 m/min for 5 weeks (5 days/week). The analyses indicated that running training at low speed (25 m/min) enhanced mitochondrial enzyme activity and expression of lactate and glucose transporters in the plantaris (low-oxidative) muscle that improved whole-body glucose metabolism in STZ-induced diabetic mice. There were no differences in glucose transporter expression levels in the soleus (high-oxidative) muscle. The endurance running exercise at 20-25 m/min was sufficient to induce mitochondrial adaptation in the low-oxidative muscles, but not in the high-oxidative muscles, of diabetic mice. In conclusion, the present study indicated that running training at 25 m/min improved glucose metabolism by increasing the mitochondrial enzyme activity and glucose transporter 4 and monocarboxylate transporter 4 protein contents in the low-oxidative muscles in STZ-induced diabetic mice.

Diabetes-associated genetic variation in MTNR1B and its effect on islet function

Abstract Context Multiple common genetic variants have been associated with type 2 diabetes but the mechanism by which they predispose to diabetes is incompletely understood. One such example is variation in MTNR1B which implicates melatonin and its receptor in the pathogenesis of type 2 diabetes. Objective To characterize the effect of diabetes-associated genetic variation at rs10830963 in the MTNR1B locus on islet function in people without type 2 diabetes. Design The association of genetic variation at rs10830963 with glucose, insulin, C-peptide, glucagon and indices of insulin secretion and action were tested in a cohort of 294 individuals who had previously undergone an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell responsivity to glucose and Disposition Indices were measured using the oral minimal model. Setting The Clinical Research and Translation Unit at Mayo Clinic, Rochester, MN. Participants Two cohorts were utilized for this analysis: one cohort was recruited on the basis of prior participation in a population-based study in Olmsted County. The other cohort was recruited on the basis of TCF7L2 genotype at rs7903146 from the Mayo Biobank. Intervention Two-hour, 7-sample OGTT Main Outcome Measures Fasting, nadir and integrated glucagon concentrations. Results One or 2 copies of the G-allele at rs10830963were associated with increased post-challenge glucose and glucagon concentrations compared to subjects with the CC genotype. Conclusions The effects of rs10830963 on glucose homeostasis and predisposition to type 2 diabetes are likely to be partially mediated through changes in α-cell function.

Association of skeletal muscle karyopherin α1 and α2 with myogenesis and insulin action.

Association of skeletal muscle karyopherin α1 and α2 with myogenesis and insulin action.

Diabetes Management: Herbal Remedies and Emerging Therapies

Abstract: Diabetes is a chronic disease affecting millions worldwide, characterized by inadequate insulin production or malfunctioning insulin action, leading to elevated blood sugar levels. Its prevalence is escalating globally, with estimates projecting a rise from 2.8% to over 5.4% of the world's population by 2025. In India, diabetes poses a significant health challenge, especially in urban areas. While conventional medications are widely available, herbal remedies have gained popularity due to their potential for fewer side effects and lower costs. Herbal remedies have been employed for centuries in diabetes management and have been extensively studied for their blood sugar regulatory properties. Prominent herbs studied for their potential to manage diabetes include gymnema, cinnamon, fenugreek, and bitter melon. These herbs are believed to enhance insulin sensitivity, reduce glucose absorption in the intestines, and improve glucose metabolism. This review highlights emerging alternative treatment options, such as stem cell therapy and gene therapy, in the field of diabetes management. Stem cell therapy aims to regenerate insulin-producing cells or enhance their function, while gene therapy targets the underlying genetic factors contributing to diabetes. These innovative approaches hold promise for more effective and personalized treatments in the future. It is essential to emphasize that any diabetes treatment or remedy should be discussed with a healthcare professional. Diabetes management requires a personalized approach based on individual needs and medical history. The integration of herbal remedies and alternative treatment options into conventional diabetes management warrants further research to determine their efficacy, safety, and potential for widespread implementation

The Diagnostic Value of Monocyte Count/HDL Cholesterol Ratio as a New Marker in Diabetic Retinopathy

Abstract Background Diabetes mellitus is a set of metabolic diseases characterized by chronic hyperglycemia as a consequence of lack in insulin action, secretion, or both. All of which lead to long-term damage and dysfunction of different organs predominantly the eyes, kidneys, nerves, heart, and blood vessels. Aim of the Work The aim of the study is to investigate the diagnostic value of MHR in diabetes and whether it can be utilized as an indicator of diabetic retinopathy. Patients and Methods This study was a case control study on 100 patients attending diabetes outpatient clinic at Ain shams university hospital 30 male, 70 female. 50 patient with diabetic retinopathy and 50 patient without retinopathy to detect the MHR in each group and to detect whether it can be utilized as an indicator of diabetic retinopathy. Results In this study there is a significant correlation between diabetic retinopathy and MHR, MHR being higher in patient with diabetic retinopathy, with a cut-off level of &amp;gt; 0.01 with 74% sensitivity and 64% specificity. Our study showed a significant relation between long standing duration of diabetes mellitus and diabetic retinopathy. Also there was significant relation between diabetic retinopathy with high glycemic profile with fasting blood sugar and 2 hour post prandial blood sugar and Hba1c. The study also show that there is no significant relation between diabetic retinopathy and weight, height, BMI. Conclusion Diabetic retinopathy (DR) is a major complication of diabetes mellitus (DM), which remains a leading cause of visual loss in working-age populations. MHR being higher in patient with diabetic retinopathy. And can be it can be utilized as an indicator of diabetic retinopathy.

Study of the Relationship between Insulin Resistance, Iron Status Markers and Body Weight in a Sample of Egyptian Population

Abstract Background Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels. Aim of the Work The aim of this study is to investigate the relationship between insulin Resistance, iron Status Markers and body Weight in a sample of Egyptian population. Patients and Methods Our study was case control study conducted on 90 subjects their age was ranging form18 to 70 from diabetes outpatient clinic, and they were divided into 3 groups: Group (1): Non-obese non-diabetic as a control group, Group (2): Obese non diabetic and group (3): Obese diabetic. Results In our study, there was no statistical significant difference found between the three studied groups regarding iron study, Also our study showed that there was statistically non significant correlation between (ferritin level and TIBC), and (ferritin level, HOMA IR), but there was statistical significant positive correlation found between TIBC and FBS (p- value 0.045),Similarly, we did not observe either abnormally high or low ferritin values in our study on subjects with obesity. We found no association between this marker and body weight, in contrast with others. In our study, the higher insulin and HOMA-IR values observed in the subjects with TSAT&amp;lt;20% = 4.2(1.4-11.6) than those with TSAT &amp;gt;20% =2.4 (1.15-6.95), but statistically non significant p- value. The present study also showed that There was statistical significant positive correlation between (T.SAT, serum ferritin), (T.SAT, S.iron) and (T.SAT,SBP) (with p-value 0.03). Our study also showed that there was no statistical significant difference found between patients with T.sat ≤ 20% and those with T.sat &amp;gt; 20% regarding all the studied parameters except ferritin level and iron level was found higher in patients with T.sat &amp;gt;20% than those with T. sat ≤20% with p-value &amp;lt;0.001 and &amp;lt;0.001 respectively. Conclusion Characteristics of iron deficiency or iron overload were not observed in subjects with overweight/obesity and diabetic patients. Our results suggest a complex metabolic dysregulation.

Identification of key biomarkers for early warning of diabetic retinopathy using BP neural network algorithm and hierarchical clustering analysis

Diabetic retinopathy is one of the most common microangiopathy in diabetes, essentially caused by abnormal blood glucose metabolism resulting from insufficient insulin secretion or reduced insulin activity. Epidemiological survey results show that about one third of diabetes patients have signs of diabetic retinopathy, and another third may suffer from serious retinopathy that threatens vision. However, the pathogenesis of diabetic retinopathy is still unclear, and there is no systematic method to detect the onset of the disease and effectively predict its occurrence. In this study, we used medical detection data from diabetic retinopathy patients to determine key biomarkers that induce disease onset through back propagation neural network algorithm and hierarchical clustering analysis, ultimately obtaining early warning signals of the disease. The key markers that induce diabetic retinopathy have been detected, which can also be used to explore the induction mechanism of disease occurrence and deliver strong warning signal before disease occurrence. We found that multiple clinical indicators that form key markers, such as glycated hemoglobin, serum uric acid, alanine aminotransferase are closely related to the occurrence of the disease. They respectively induced disease from the aspects of the individual lipid metabolism, cell oxidation reduction, bone metabolism and bone resorption and cell function of blood coagulation. The key markers that induce diabetic retinopathy complications do not act independently, but form a complete module to coordinate and work together before the onset of the disease, and transmit a strong warning signal. The key markers detected by this algorithm are more sensitive and effective in the early warning of disease. Hence, a new method related to key markers is proposed for the study of diabetic microvascular lesions. In clinical prediction and diagnosis, doctors can use key markers to give early warning of individual diseases and make early intervention.

Diabetes-associated Genetic Variation in MTNR1B and Its Effect on Islet Function.

Multiple common genetic variants have been associated with type 2 diabetes, but the mechanism by which they predispose to diabetes is incompletely understood. One such example is variation in MTNR1B, which implicates melatonin and its receptor in the pathogenesis of type 2 diabetes. To characterize the effect of diabetes-associated genetic variation at rs10830963 in the MTNR1B locus on islet function in people without type 2 diabetes. The association of genetic variation at rs10830963 with glucose, insulin, C-peptide, glucagon, and indices of insulin secretion and action were tested in a cohort of 294 individuals who had previously undergone an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell responsivity to glucose, and Disposition Indices were measured using the oral minimal model. The Clinical Research and Translation Unit at Mayo Clinic, Rochester, MN. Two cohorts were utilized for this analysis: 1 cohort was recruited on the basis of prior participation in a population-based study in Olmsted County. The other cohort was recruited on the basis of TCF7L2 genotype at rs7903146 from the Mayo Biobank. Two-hour, 7-sample OGTT. Fasting, nadir, and integrated glucagon concentrations. One or 2 copies of the G-allele at rs10830963 were associated with increased postchallenge glucose and glucagon concentrations compared to subjects with the CC genotype. The effects of rs10830963 on glucose homeostasis and predisposition to type 2 diabetes are likely to be partially mediated through changes in α-cell function.