Diabetic Hyperglycemia Research Articles

Duration of diabetes, glycemic control, and low heart rate variability: The atherosclerosis risk in communities (ARIC) study

Persons with long-standing, poorly controlled diabetes or recent hyperglycemia had the highest burden of cardiac autonomic neuropathy. Cardiac autonomic neuropathy contributed to elevated long-term incidence of cardiovascular disease and mortality even in persons with well-controlled diabetes.

Decreasing malondialdehyde levels and body mass index of type II diabetes mellitus with obesity using cowpea sprout (Vigna unguiculata) yogurt

Hyperglycemia in diabetes is associated with obesity and increases the production of free radicals which is the beginning of the development of oxidative stress. This study aimed to determine the effect of cowpea sprout yogurt (CowpeaS-Yo) on body mass index (BMI) and malondialdehyde (MDA) levels in type-2 diabetes mellitus (T2DM) with obese patients. This study used a pretest-posttest control group design, with 20 women with T2DM with obesity, which was randomly divided into two groups of ten women in each group. Group I was given CowpeaS-Yo, while group II was given a placebo as a control, 200 mL/day, for 2 months. Before and after the intervention, the subject's weight and height were measured, and 1 mL of their blood sample was taken, to check their plasma MDA levels. Data were analyzed using a paired sample t-test. After two months of intervention, BMI decreased significantly from 28.53±2.27 to 24.56±2.55 kg/m2 (P = 0.002) in the group receiving CowpeaS-Yo, as well as decreased plasma MDA levels from 7.49±0.72 to 6.24±0.59 nmol/mL (P = 0.015) compared to the control group. In conclusion, CowpeaS-Yo was able to control body weight and improve the antioxidant status of T2DM in obese patients.

Molecular mechanism of ectopic lipid accumulation induced by methylglyoxal via activation of the NRF2/PI3K/AKT pathway implicates renal lipotoxicity caused by diabetes mellitus.

Patients with chronic kidney disease (CKD) have a high incidence of dyslipidemia comprising high triglyceride (TG) and low high-density lipoprotein (HDL)-cholesterol levels. An abnormal increase of TGs within cells can lead to intracellular lipid accumulation. In addition to dyslipidemia, hyperglycemia in diabetes may elicit ectopic lipid deposition in non-adipose tissues. Hyperglycemia increases intracellular levels of methylglyoxal (MG) leading to cellular dysfunction. A deficit of glyoxalase I (GLO1) contributes to dicarbonyl stress. Whether dicarbonyl stress induced by MG causes renal lipotoxicity through alteration of lipid metabolism signaling is still unknown. In this study, mice with high fat diet-induced diabetes were used to investigate the renal pathology induced by MG. NRK52E cells treated with MG were further used in vitro to delineate the involvement of lipogenic signaling. After treatment with MG for 12 weeks, plasma TG levels, renal fatty changes, and tubular injuries were aggravated in diabetic mice. In NRK52E cells, MG activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and sterol regulatory element-binding protein 1 (SREBP1), resulting in stimulation of fatty acid synthase. The intracellular accumulation of lipid droplets was mainly contributed by TGs, which increased the oxidative stress accompanied by high Nrf2 expression. In addition, MG time-dependently activated cyclin D, cyclin-dependent kinase 4 (CDK4), and cleaved caspase-3, evidencing that G0/G1 arrest was associated with apoptosis of NRK52E cells. In conclusion, our studies revealed the mechanism of lipotoxicity caused by MG. The target of such dicarbonyl stress may become a promising therapy for diabetic CKD.

Intense simplified strategy for newly diagnosed type 2 diabetes in patients with severe hyperglycaemia: multicentre, open label, randomised trial

ObjectiveTo evaluate whether the intense simplified strategy, which comprises short term intensive insulin therapy (SIIT) followed by subsequent oral antihyperglycaemic regimens, could improve long term glycaemic outcomes in patients with...

Maternal periconception hyperglycemia, preconception diabetes, and risk of major congenital malformations in offspring.

What are the roles of maternal preconception diabetes and related periconceptional hyperglycemia on the risk of major congenital malformations (MCMs) in offspring? Maternal periconceptional glycated hemoglobin (HbA1c) levels over 5.6% were associated with an increased risk of congenital heart defects (CHD) in the offspring, and maternal preconception diabetes was associated with an increased risk of CHD, including when HbA1c levels were within euglycemic ranges. Maternal preconception diabetes has been linked with MCMs in the offspring. However, evidence concerning associations with specific periconception serum measures of hyperglycemia, and susceptibility of different organ systems, is inconsistent. Moreover, limited evidence exists concerning the effectiveness of antidiabetic medications in mitigating diabetes-related teratogenic risks. A large Israeli birth cohort of 46534 children born in 2001-2020. Maternal HbA1c test results were obtained from 90 days before conception to mid-pregnancy. Maternal diabetes, other cardiometabolic conditions, and MCMs in newborns were ascertained based on clinical diagnoses, medication dispensing records, and laboratory test results using previously validated algorithms. Associations were modeled using generalized additive logistic regression models with thin plate penalized splines. Maternal periconceptional HbA1c value was associated with CHD in newborns, with the risk starting to increase at HbA1c values exceeding 5.6%. The association between HbA1c and CHD was stronger among mothers with type 2 diabetes mellitus (T2DM) compared to the other diabetes groups. Maternal pre-existing T2DM was associated with CHD even after accounting for HbA1C levels and other cardiometabolic comorbidities (odds ratio (OR)=1.89, 95% CI 1.18, 3.03); and the OR was materially unchanged when only mothers with pre-existing T2DM who had high adherence to antidiabetic medications and normal HbA1c levels were considered. The rarity of some specific malformation groups limited the ability to conduct more granular analyses. The use of HbA1c as a time-aggregated measure of glycemic control may miss transient glycemic dysregulation that could be clinically meaningful for teratogenic risks. The observed association between pre-existing diabetes and the risk of malformations within HbA1c levels suggests underlying causal pathways that are partly independent of maternal glucose control. Therefore, treatments for hyperglycemia might not completely mitigate the teratogenic risk associated with maternal preconception diabetes. The work was supported by NIH grants K99ES035433, R01HD097778, and P30ES000002. None of the authors reports competing interests. N/A.

Efficacy and Safety of Intravenous Tenecteplase Versus Alteplase in Treating Acute Ischemic Stroke With Diabetes and Admission Hyperglycemia.

The aim of this study was to investigate the efficacy and safety of tenecteplase versus alteplase in patients with acute ischemic stroke, considering their diabetes history and admission hyperglycemia status. This was a post hoc analysis of the TRACE-2 (Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-2) randomized clinical trial that enrolled patients in China between June 2021 and May 2022. Eligible patients with acute ischemic stroke for standard intravenous thrombolysis, but ineligible for endovascular thrombectomy, were randomly assigned (1:1) to tenecteplase or alteplase within 4.5 hours of symptom onset. Admission hyperglycemia was defined as plasma glucose >7.8 mmol/L. The primary efficacy and safety outcome were excellent functional outcome at 90 days (modified Rankin Scale score of 0-1) and symptomatic intracranial hemorrhage within 36 hours, respectively. The Cochran-Mantel-Haenszel χ2 test was used for the outcomes. Of the 1382 patients included, 369 (26.7%) had a history of diabetes, and 482 (34.9%) experienced admission hyperglycemia. The primary efficacy outcome, comparing tenecteplase to alteplase, was achieved in 93 (56.7%) versus 97 (48.3%) among patients with a history of diabetes (P=0.11) and 335 (64.6%) versus 300 (62.2%) among those without diabetes (P=0.45), respectively. The primary efficacy outcome for tenecteplase versus alteplase was comparable among patients with and without admission hyperglycemia (57.5% versus 53.9%, P = 0.44; 65.4% versus 60.4%, P=0.12, respectively). No significant difference in the risk of symptomatic intracranial hemorrhage within 36 hours was observed between tenecteplase and alteplase, regardless of diabetes history or admission hyperglycemia. This study demonstrated that intravenous tenecteplase exhibits similar clinical outcomes compared with alteplase, irrespective of the patient's glucose metabolism status. URL: https://clinicaltrials.gov; Unique identifier: NCT04797013.

Prevalence of Hypertension in Type 2 Diabetes Mellitus in the Working Area of Jatibaru Community Health Center in 2023

The World Health Organization (WHO) predicts an increase in the number of diabetes mellitus sufferers in Indonesia from 8.4 million people in 2000 to around 21.3 million people in 2030. The prevalence of type 2 diabetes increases with age and changes in unhealthy lifestyles. Several studies show that the incidence of hyperglycemia in diabetes is closely related to hypertension. According to the American Diabetes Association (ADA) 2017, two out of three people with diabetes have high blood pressure. At the Jatibaru Community Health Center, based on 2023 data, it is known that hypertension and diabetes are always included in the data on the 10 most common diseases every month. Based on this background and related to the incidence of Hypertension and type 2 diabetes mellitus is still relatively high, so researchers are interested to knowing the picture hypertension in type 2 diabetes mellitus in the Jatibaru. This research is a descriptive study with a cross-sectional approach using secondary data taken from Non-Communicable Disease data. The population in this study were all adult and elderly respondents registered in the non-communicable disease program register, who based on anamnesis, physical and laboratory examination, were diagnosed with type 2 diabetes mellitus and hypertension. The sample was taken by purposive sampling. In this research, it was found that people with hypertension and diabetes mellitus were found in all adult and elderly age categories. The distribution of hypertension and type 2 diabetes mellitus patients continues to increase with increasing age, the prevalence of sufferers being more female than male. As many as 65% of the total type 2 diabetes mellitus sufferers also experience hypertension.

Metabolomics Revealed the Effects of Momordica charantia L. Saponins on Diabetic Hyperglycemia and Wound Healing in Mice.

Momordica charantia L. saponins (MCS) may promote wound-healing properties but the underlying mechanisms are unclear. This study aimed to examine the effects and mechanisms of MCS on diabetic wounds. The results have shown that higher MCS intake lowered fasting blood glucose levels, serum lipids, and lipopolysaccharides in diabetic mice. MCS-treated diabetic mice exhibited faster wound healing than the diabetic control groups. After three days, the diabetic control groups exhibited a wound area reduction of only 19.3%, while a 39.75% reduction was observed following high-dose MCS treatment. Five potential biomarkers were screened in the metabolomics study. The results revealed that MCS mainly regulated glycerophospholipid metabolism, fructose and mannose metabolism, steroid hormone biosynthesis, pyrimidine metabolism, and the Krebs cycle, thus affecting wound healing. Overall, MCS could not only exert a hypoglycemic effect but also promote diabetic wound healing, making it a potential treatment option for diabetes-related wounds.

ZBED3 exacerbates hyperglycemia by promoting hepatic gluconeogenesis through CREB signaling

BackgroundElevated hepatic glucose production (HGP) is a prominent manifestation of impaired hepatic glucose metabolism in individuals with diabetes. Increased hepatic gluconeogenesis plays a pivotal role in the dysregulation of hepatic glucose metabolism and contributes significantly to fasting hyperglycemia in diabetes. Previous studies have identified zinc-finger BED domain-containing 3 (ZBED3) as a risk gene for type 2 diabetes (T2DM), and its single nucleotide polymorphism (SNPs) is closely associated with the fasting blood glucose level, suggesting a potential correlation between ZBED3 and the onset of diabetes. This study primarily explores the effect of ZBED3 on hepatic gluconeogenesis and analyzes the relevant signaling pathways that regulate hepatic gluconeogenesis. MethodsThe expression level of ZBED3 was assessed in the liver of insulin-resistant (IR)-related disease. RNA-seq and bioinformatics analyses were employed to examine the ZBED3-related pathway that modulated HGP. To investigate the role of ZBED3 in hepatic gluconeogenesis, the expression of ZBED3 was manipulated by upregulation or silencing using adeno-associated virus (AAV) in mouse primary hepatocytes (MPHs) and HHL-5 cells. In vivo, hepatocyte-specific ZBED3 knockout mice were generated. Moreover, AAV8 was employed to achieve hepatocyte-specific overexpression and knockdown of ZBED3 in C57BL/6 and db/db mice. Immunoprecipitation and mass spectrometry (IP-MS) analyses were employed to identify proteins that interacted with ZBED3. Co-immunoprecipitation (co-IP), glutathione S-transferase (GST) - pulldown, and dual-luciferase reporter assays were conducted to further elucidate the underlying mechanism of ZBED3 in regulating hepatic gluconeogenesis. ResultsThe expression of ZBED3 in the liver of IR-related disease models was found to be increased. Under the stimulation of glucagon, ZBED3 promoted the expression of hepatic gluconeogenesis-related genes PGC1A, PCK1, G6PC, thereby increasing HGP. Consistently, the rate of hepatic gluconeogenesis was found to be elevated in mice with hepatocyte-specific overexpression of ZBED3 and decreased in those with ZBED3 knockout. Additionally, the knockdown of ZBED3 in the liver of db/db mice resulted in a reduction in hepatic gluconeogenesis. Moreover, the study revealed that ZBED3 facilitated the nuclear translocation of protein arginine methyltransferases 5 (PRMT5) to influence the regulation of PRMT5-mediated symmetrical dimethylation of arginine (s-DMA) of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), which in turn affects the phosphorylation of CREB and ultimately promotes HGP. ConclusionsThis study indicates that ZBED3 promotes hepatic gluconeogenesis and serves as a critical regulator of the progression of diabetes.

Long-term diabetic hyperglycaemia modifies social behaviour in rats

Diabetes is a known risk factor for cognitive decline and mood disorders. However, the effects of long-term diabetic hyperglycaemia on the various dimensions of social behaviours, such as play or aggression, remains to be fully elucidated. In this study, we evaluated the social behaviour in a nicotinamide-streptozotocin rat model of long-term diabetic hyperglycaemia, in the absence of glucose-lowering treatments. Five months following induction of hyperglycaemia, we scored affiliative/exploratory or aggressive social interactions between pairs of unacquainted rats in a neutral arena. Our results demonstrate alterations in the behaviour of long-term diabetic rats faced with social novelties. Specifically, diabetic hyperglycaemic rats engaged in hyper-sociable and hyper-aggressive encounters. Interestingly, social interactivity was not associated with the degree of hyperglycaemia in affiliative/exploratory or in aggressive social interactions, in our long-term diabetic rat model. Altogether, our data suggest a lack of social appropriateness in long-term diabetic hyperglycaemic rats which is independent of the degree of hyperglycaemia. These findings support the importance of a tight glycaemic control in the management of diabetes at every stage of the disease and enlighten the importance of impaired glycaemic control as a novel metabolic player impacting the neural networks of social behaviours.

The measurement of plasma fructosamine as a diagnostic tool to improve the interpretation of plasma glucose and proteins in alpacas (Vicugna pacos).

This study assesses the use of fructosamine as a diagnostic tool for hyperglycemia in alpacas in view of their sensitivity to stress and susceptibility to conditions like lipid mobilization syndrome. Plasma fructosamine, like in diagnosing diabetes in cats and dogs, can reveal long-term blood glucose trends, differentiating stress-induced spikes from persistent diabetic hyperglycemia. In 125 alpacas presented as patients of a veterinary clinic, plasma glucose and fructosamine concentrations were compared for correlations with findings of the general clinical examination, laboratory parameters, demographic data, and a behavioral stress assessment processed by using principal component analysis. Hyperglycemia was observed on admission of 71% (89/125) of the animals. This was significantly associated with a higher concentration of serum cortisol and a higher behavioral stress scoring. Fructosamine above the reference limit was detected in only 15% (13/89) of the hyperglycemic individuals. In addition to a positive correlation of fructosamine to glucose concentration, positive relationships with different plasma proteins were detected. A relationship to stress parameters was not observed. These findings underscore stress as a significant trigger for hyperglycemia in alpacas and suggest fructosamine as a valuable parameter for distinguishing between stress-induced and diabetic hyperglycemia. However, the dependence of fructosamine formation on total plasma protein concentration should be considered to avoid misinterpretation.

Diabetes and Early Development: Epigenetics, Biological Stress, and Aging.

Pregestational diabetes, either type 1 or type 2 diabetes, induces structural birth defects including neural tube defects and congenital heart defects in human fetuses. Rodent models of type 1 and type 2 diabetic embryopathy have been established and faithfully mimic human conditions. Hyperglycemia of maternal diabetes triggers oxidative stress in the developing neuroepithelium and the embryonic heart leading to the activation of proapoptotic kinases and excessive cell death. Oxidative stress also activates the unfolded protein response and endoplasmic reticulum stress. Hyperglycemia alters epigenetic landscapes by suppressing histone deacetylation, perturbing microRNA (miRNA) expression, and increasing DNA methylation. At cellular levels, besides the induction of cell apoptosis, hyperglycemia suppresses cell proliferation and induces premature senescence. Stress signaling elicited by maternal diabetes disrupts cellular organelle homeostasis leading to mitochondrial dysfunction, mitochondrial dynamic alteration, and autophagy impairment. Blocking oxidative stress, kinase activation, and cellular senescence ameliorates diabetic embryopathy. Deleting the mir200c gene or restoring mir322 expression abolishes maternal diabetes hyperglycemia-induced senescence and cellular stress, respectively. Both the autophagy activator trehalose and the senomorphic rapamycin can alleviate diabetic embryopathy. Thus, targeting cellular stress, miRNAs, senescence, or restoring autophagy or mitochondrial fusion is a promising approach to prevent poorly controlled maternal diabetes-induced structural birth defects. In this review, we summarize the causal events in diabetic embryopathy and propose preventions for this pathological condition. KEY POINTS: · Maternal diabetes induces structural birth defects.. · Kinase signaling and cellular organelle stress are critically involved in neural tube defects.. · Maternal diabetes increases DNA methylation and suppresses developmental gene expression.. · Cellular apoptosis and senescence are induced by maternal diabetes in the neuroepithelium.. · microRNAs disrupt mitochondrial fusion leading to congenital heart diseases in diabetic pregnancy..

Contemporary Concepts of the Role of Pro-inflammatory Cytokines in COVID-19-Induced Pneumonia in the Context of Metabolic Disorders (Review)

Objective — to analyse and summarise literary sources regarding contemporary concepts of the significance of pro-inflammatory cytokines in pneumonia caused by COVID-19 amidst metabolic disorders. Materials and methods. An analytical and bibliosemantic approach was utilised in the study. Google Scholar and PubMed databases were employed for the search using keywords such as «pro-inflammatory cytokines», «COVID-19», «pneumonia», «insulin resistance», «type 2 diabetes mellitus» and «metabolic disorders». Results and discussion. Diabetes mellitus and hyperglycemia are among the major comorbidities in patients with COVID-19, leading to unfavorable outcomes. Diabetes is a chronic condition affecting millions worldwide. By 2030, it is projected to become a leading cause of non-communicable mortality. Hyperglycemia in COVID-19, irrespective of insulin resistance or a history of diabetes, heralds an unfavorable prognosis. Patients with type 2 diabetes mellitus exhibit elevated inflammation levels associa­ted with obesity, insulin resistance and comorbidities such as hypertension, obesity, cardiovascular diseases and dyslipidemia. Chronic inflammation with enhanced inflammatory response to infection and viral load escalation leads to a potent systemic immune response — the «cytokine storm», closely associated with increased severity of COVID-19. There is increasing evidence that COVID-19-induced respiratory failure may be attributed to defective immune response characterised by rapid proliferation and hyperactivation of T cells, macrophages, natural killer cells and hyperproduction of chemical mediators, including pro-inflammatory cytokines, leading to increased vascular permeability and multiorgan failure. Conclusions. In our view, COVID-19 induces polyorgan distress, creating an imbalance between cellular and cytokine immune systems, resulting in hyperinflammatory cytokine storm affecting systemic homeostasis. The presence of COVID-19 in patients with diabetes mellitus, who already have immune dysregulation, exacerbates their overall condition.

Establishment and characterization of a mouse model for studying kidney repair in diabetes.

The prognosis of acute kidney injury (AKI) is markedly worse in diabetic patients. Diabetes not only exaggerates the severity of AKI but may also prevent kidney repair or recovery from AKI. Little is known about the cellular and molecular basis of defective kidney repair in diabetes. One obstacle in studying kidney repair in diabetes is the lack of suitable animal models. Specifically, diabetes increases AKI severity, making it difficult to induce the same level of AKI in diabetic and non-diabetic animals to compare their kidney repair. Here, we have identified a time-window of 4 days immediately after the completion of streptozotocin (STZ) treatment in mice when blood glucose has yet to rise. Within this time-window, renal ischemia-reperfusion injury (IRI) induced the same level of AKI in STZ-treated mice [127.2±12.82 mg/dL blood urea nitrogen (BUN), 2.275±0.4728 serum creatinine] and vehicle solution-treated mice (128.6±11.83 mg/dL BUN, 2.087±0.4748 mg/dL serum creatinine]. By day 5-6, the post-AKI kidney entered into the phase of kidney repair when diabetic hyperglycemia started in STZ-treated mice, providing the opportunity to study the effect of diabetes on kidney repair without affecting initial AKI. In this model, kidney repair was indeed impaired by diabetes (116.5±8.052 mg/dL BUN and 1.382±0.2732 mg/dL serum creatinine in IR+vehicle group; 136.6±8.740 mg/dL BUN and 1.916±0.3756 mg/dL serum creatinine in IR+STZ group). The impairment was associated with decreased tubular cell proliferation and increased tubular cell senescence, peritubular capillary (PTC) rarefaction, inflammation, and 40.90% more interstitial fibrosis.

The deubiquitinase OTUB1 inhibits gluconeogenesis by stabilizing YWHAB

Hepatic gluconeogenesis plays a crucial role in maintaining glucose homeostasis and serves as a potential therapeutic target for type 2 diabetes, while its underlying mechanisms are not fully understood. This study elucidates the role of the deubiquitinase OTU domain-containing ubiquitin aldehyde binding protein 1 (OTUB1) in gluconeogenesis. We found that hepatic OTUB1 expression is reduced in both db/db mice and patients with type 2 diabetes. Deletion of hepatic OTUB1 significantly elevates fasting blood glucose levels and increases the expression of key gluconeogenic genes. Conversely, overexpression of OTUB1 in hepatocytes mitigates diabetic hyperglycemia and enhances insulin sensitivity. It is known that the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein β (YWHAB) functions as an inhibitor of hepatic gluconeogenesis by interacting with forkhead box protein O (FOXO1) and glucagon receptor (GPCR), but its own modification mechanism remains unclear. Our findings indicate that OTUB1 interacts with YWHAB and deubiquitinates it through a catalytic process, which in turn suppresses gluconeogenesis. Therefore, OTUB1 plays a pivotal role in inhibiting hepatic gluconeogenesis, highlighting its potential as a therapeutic target for type 2 diabetes.

Evaluating the Impact of Nutritional Risk on Stress-Induced Hyperglycemia and Trauma Patient Outcomes.

Stress-induced hyperglycemia (SIH) and malnutrition are common in trauma patients and are linked to worse outcomes. This study examined the influence of nutritional status, determined by the Geriatric Nutritional Risk Index (GNRI), on the incidence of SIH in trauma patients. A retrospective analysis was conducted on adult trauma patients admitted to a Level I trauma center from 1 January 2009 to December 31, 2021. Patients were categorized into four groups: SIH, diabetic hyperglycemia (DH), diabetic normoglycemia (DN), and non-diabetic normoglycemia (NDN). Nutritional status was assessed using GNRI: high risk (GNRI < 82), moderate risk (82 ≤ GNRI < 92), low risk (92 ≤ GNRI ≤ 98), and no risk (GNRI > 98). Incidence of SIH and outcomes were analyzed across GNRI groups. SIH was associated with higher mortality across all GNRI groups compared to NDN, with the highest rate (45.7%) in the high-risk group. Mortality decreased as GNRI increased in all glucose groups. NDN patients had the lowest mortality rates across GNRI groups. There was no correlation between GNRI and SIH incidence (p = 0.259). SIH significantly influenced mortality across all nutritional status groups, with the highest impact in malnourished patients. Although malnutrition did not affect SIH incidence, both SIH and poor nutritional status independently contributed to worse trauma outcomes. Targeted management of hyperglycemia and nutritional deficiencies is crucial for improving survival.

Relationship Between Oxidative Stress in the Rotator Cuff and Transcutaneous Advanced Glycation End-Products Measurement in Diabetic Rats.

Diabetes mellitus increases oxidative stress due to hyperglycemia, resulting in the degeneration of rotator cuff tissue. Currently, there is no established method to non-invasively assess the extent of this oxidative stress. To address this, we aimed to investigate the relationship between the accumulation of advanced glycation end-products (AGEs), a marker of oxidative stress, and transcutaneous autofluorescence intensity in rotator cuff tissue harvested from diabetic rats. Ten control Sprague-Dawley (SD) rats and streptozotocin-induced diabetic rats (n = 10 per group) were used. The rats were euthanized eight and 16 weeks after the induction of diabetes, and rotator cuff attachment sites were collected and histologically analyzed. Prior to euthanasia, autofluorescence intensity was measured transcutaneously in the rotator cuff area. The expressions of AGEs and type I collagen were evaluated immunohistochemically with specific antibodies and the stained areas were quantified. All data were statistically analyzed using the Mann-Whitney U test. Correlation analysis was performed for skin autofluorescence intensity and the percentage of AGEs staining area using Spearman's rank correlation coefficient. The immunohistochemical expression of AGEs at the rotator cuff attachment sites and transcutaneous AGEs measurements were significantly higher in diabetic rats than in the control group at 16 weeks. There was no significant difference in the level of type 1 collagen between the two groups. This study reveals that the accumulation of AGEs in rotator cuff tissue increases due to prolonged hyperglycemia in diabetes. In addition, transcutaneous skin fluorescence intensity may be related to histological oxidative stress at the rotator cuff.

Maintaining Stabilization of Blood Sugar Levels in Diabetes Mellitus Patients with Foot Exercises: Case Report

The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs. Physical activity is one of the factors that affect glycemic management. This case study aims to maintain the stability of blood sugar levels in DM patients by applying leg exercises. The design of this research is a case report with a nursing process approach carried out on Diabetes Mellitus patients with nursing problems of unstable blood sugar levels. Nursing care was carried out for seven days at the Muhammadiyah Ponorogo General Hospital. The intervention implemented is foot exercises. The results of the case study are presented in the form of nursing documentation. The case study results showed that the patient's blood sugar levels tended to be stable starting on the second day of the intervention.Exercise-induced glycemic control is mostly explained by an increase in whole-body insulin sensitivity. The long-term advantages of frequent exercise on glycemic control appear to be related to the cumulative effect of transitory gains in insulin sensitivity and glycemic control after each bout of exercise, rather than structural changes in insulin sensitivity. Keywords: blood sugar level; diabetes mellitus; foot exercise

Systemic/Immune-Modulation of Olea europaea Leaf Extract in Fetuses of Alloxan-Induced T1 Diabetic Rats.

Maternal glucose is the principal macronutrient that sustains fetal growth. Prolonged exposure of the fetus to hyperglycemia from the early stages of pregnancy accelerates the maturation of the stimulus-secretion coupling mechanism in β cell autoimmunity, which leads to early hyperinsulinemia in type 1 diabetes mellitus (T1DM). Nowadays, diabetes mellitus (DM) is the most common medical complication of pregnancy, and among young women, the prevalence of overt diabetes and undiagnosed hyperglycemia is rising. Even though conventional medication is effective in treating DM, it is expensive and has harmful side effects. Herbal medicine will thus incorporate alternative therapy and be more effective and less toxic. Due to their bioactive components, olive leaves (Olea europaea) are frequently used medicinally; however, little is known about how this plant affects the immune system when it comes to diabetes. The current study used a pregnant mother rat model of alloxan-induced T1DM to examine the antidiabetic properties and embryonic safety of olive leaves. Forty adult female Sprague Dawley rats were split up into four groups as follows: nondiabetic, diabetic, olive, and diabetic-olive groups. All the mother rats were sacrificed on the 20th day of pregnancy, and fetuses were collected for further investigations. In diabetic pregnant mothers, fetuses had systemic modulation-negative effects. These effects were significantly reversed when the diabetic groups were supplemented with extracts from olive leaves. The findings showed that the olive leaf extract inhibits the diabetogenic effect mediated by alloxan with effective and protective systemic immunomodulation during embryonic development.

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.