Uncovering the Therapeutic Potential of Phosphocreatine in Diabetic Retinopathy: Mitigating Mitochondrial Dysfunction and Apoptosis via JAK2/STAT3 Signaling Pathway.

Diabetic retinopathy (DR) stands as a prevalent complication of diabetes mellitus, causing damage to the delicate retinal capillaries and potentially leading to visual impairment. While the exact underlying cause of DR remains elusive, compelling research suggests that mitochondrial energy deficiency and the excessive generation of reactive oxygen species (ROS) play pivotal roles in its pathogenesis. Recognizing that controlling hyperglycemia alone fails to reverse the defects in retinal mitochondria induced by diabetes, current strategies seek to restore mitochondrial function as a means of safeguarding against DR. To address this pressing issue, a comprehensive study was undertaken to explore the potential of phosphocreatine (PCr) in bolstering mitochondrial bioenergetics and providing protection against DR via modulation of the JAK2/STAT3 signaling pathway. Employing rat mitochondria and RGC-5 cells, the investigation meticulously assessed the impact of PCr on ROS production, mitochondrial membrane potential, as well as the expression of crucial apoptotic and JAK2/STAT3 signaling pathway proteins, utilizing cutting-edge techniques such as high-resolution respirometry and western blotting. The remarkable outcomes revealed that PCr exerts a profound protective influence against DR by enhancing mitochondrial function and alleviating diabetes-associated symptoms and biochemical markers. Notably, PCr administration resulted in an upregulation of antiapoptotic proteins, concomitant with a downregulation of proapoptotic proteins and the JAK2/STAT3 signaling pathway. These significant findings firmly establish PCr as a potential therapeutic avenue for combating diabetic retinopathy. By augmenting mitochondrial function and exerting antiapoptotic effects via the JAK2/STAT3 signaling pathway, PCr demonstrates promising efficacy both in vivo and in vitro, particularly in counteracting the oxidative stress engendered by hyperglycemia. In summary, our study sheds light on the potential of PCr as an innovative therapeutic strategy for diabetic retinopathy. By bolstering mitochondrial function and exerting protective effects via the modulation of the JAK2/STAT3 signaling pathway, PCr holds immense promise in ameliorating the impact of DR in the face of oxidative stress induced by hyperglycemia.

Disordered Eating Behaviors and Insulin Restriction in Saudi Adolescents and Young Adults with Type 1 Diabetes.

Background and Objectives: The prevalence of disordered eating behaviors (DEBs) in type 1 diabetes (T1D) has been studied globally; however, data from Saudi Arabia and Arab-speaking countries are scarce. This study aimed to measure the prevalence of DEBs and associated clinical characteristics in adolescents and young adults with T1D, and the impact of DEBs on glycemic parameters. Materials and Methods: A total of 265 adolescents and young adults with T1D (aged 12-25 years) were recruited randomly from the registry at the Jazan Endocrinology and Diabetes Center, Saudi Arabia. Participants completed the Diabetes Eating Problem Survey-Revised (DEPS-R) questionnaire. Other measures included hemoglobin A1c (HbA1c) in addition to sociodemographic, anthropometric, and clinical data. Results: The prevalence of DEBs among T1D was 27.2%. Females (32.5%) had a higher proportion of DEBs than males (18.6%) (p = 0.01). About 27% of the participants reported insulin restriction. A history of hospital admission in the previous 6 months due to DKA and frequent hypoglycemia was more frequently reported in T1D participants with DEBs compared to those without (p = 0.03). Participants with DEBs had higher HbA1c and higher BMI compared to those without DEBs. Conclusions: Adolescents and young adults with T1D with disordered eating and insulin restriction have higher glycated hemoglobin, and are at higher risk of DKA. Routine screening for DEBs should be an essential element in diabetes care, especially among highly vulnerable groups.

Validation of the Arabic Version of Diabetes Eating Problem Survey-Revised (DEPS-R) among Adolescents with Type 1 Diabetes.

Disordered eating behaviors (DEBs) in type 1 diabetes (T1D) have been studied globally in different age groups. However, there is no validated diabetes-specific questionnaire in the Arabic language for the screening of DEBs. This study aimed to translate the Diabetes Eating Problem Survey-Revised scale (DEPS-R) into the Arabic language and study its psychometric properties in adolescents with T1D. We adopted the forward-backward procedure to translate the DEPS-R questionnaire into Arabic. The validation study enrolled 258 Saudi adolescents with T1D aged 12-18 years who completed the Arabic DEPS-R questionnaire and the EAT-26. The Arabic DEPS-R showed good construct validity and reliability (Cronbach's alpha = 0.86). The factor analysis revealed a three-factor structure of DEPS-R which explains 54.4 % of the variance. In total, 30.6% of the participants are at high risk for DEBs (DEPS-R score ≥ 20). The psychometric properties of the Arabic DEPS-R are satisfactory, consistent with the original scale and translations in other languages. These results support the validity of the Arabic DEPS-R for assessment of DEBs in the T1D Arabic population.

Barriers and Attitudes of Primary Healthcare Physicians to Insulin Initiation and Intensification in Saudi Arabia.

Saudi Arabia is a country with high prevalence of diabetes, uncontrolled diabetes, and diabetes-related complications. Poor glycemic control is multifactorial and could be explained in part by physician and patient reluctance toward insulin or insulin inertia. This study aimed to address physician barriers toward insulin therapy in primary care settings. It included 288 physicians from 168 primary healthcare centers (PHC) in the Jazan region of Saudi Arabia. Participants responded to questionnaire investigating physicians' attitude and barriers to insulin initiation and intensification in PHCs. In physician opinion, the most common barriers among their patients were fear of injection, lack of patient education, fear of hypoglycemia, and difficult administration. Physicians were reluctant to initiate insulin for T2D patients mostly due to patient non-adherence to blood sugar measurement, non-adherence to appointment or treatment, elderly patients, or due to patient refusal. Physicians' fear of hypoglycemia, lack of staff for patient education, and lack of updated knowledge were the primary clinician-related barriers. Exaggerated fears of insulin side effects, patient non-adherence, limited staff for patient's education, patient refusal, and inadequate consultation time were the main barriers to insulin acceptance and prescription.

Congenital generalized lipodystrophy in two siblings from Saudi Arabia: A case report.

Congenital generalized lipodystrophy type 1 (CGL1) is a very rare autosomal recessive genetic mutation with generalized lipoatrophy and metabolic complications. We report CGL1 in two Saudi female siblings with lipoatrophy, diabetes mellitus, hypertriglyceridemia, steatohepatitis, and acanthosis due to very rare homozygous 1-acylglycerol-3-phosphate O-acyltransferase ß (AGPAT2) genetic variant.

Association of lipid peroxidation and interleukin-6 with carotid atherosclerosis in type 2 diabetes.

Enhanced lipid peroxidation and elevated interleukin-6 levels are common in type 2 diabetes mellitus patients. Atherosclerotic vascular complications greatly contribute to morbidity and mortality in diabetes. The aim of this study was to assess the relation of lipid peroxidation and interleukin-6 with carotid atherosclerosis in type 2 diabetes mellitus. METHODS: This cross-sectional study included 90 type 2 diabetes mellitus male patients with age ≥ 40 years and 30 healthy male subjects matched for age. All of them were subjected to measuring of 8-iso prostaglandin F2α as a marker of lipid peroxidation, interleukin-6 and carotid intima media thickness as a marker of carotid atherosclerosis. RESULTS: Both 8-iso prostaglandin F2α and interleukin-6 were found to have significant positive correlation with carotid intima media thickness (P < 0.001) and both were found to be significant predictors of the presence of subclinical carotid atherosclerosis in multiple regression analysis. CONCLUSION: Lipid peroxidation and interleukin-6 may play an important role in atherogenesis in type 2 diabetes mellitus and limiting their effects may reduce atherosclerotic vascular complications in type 2 diabetes mellitus.

Echocardiographic association of epicardial fat with carotid intima-media thickness in patients with type 2 diabetes.

BACKGROUND: Epicardial fat is recognized as active endocrine organ and as emerging risk factor for cardio-metabolic diseases. The aim of this study was to explore the relationship between epicardial fat and carotid intima-media thickness in type 2 diabetes patients. METHODS: Epicardial fat thickness was measured in 76 type 2 diabetes patients without clinical atherosclerotic cardiovascular disease and 30 age- and sex-matched controls. In addition to laboratory tests, all patients underwent transthoracic echocardiography for epicardial fat thickness and ultrasonographic examination of carotid intima-media thickness. RESULTS: Patients with diabetes had higher epicardial fat thickness and carotid intima-media thickness than those of the controls (6.23 ± 1.27 mm vs 4.6 ± 1.03 mm, p < 0.001 and 0.77 ± 0.150 mm vs 0.58 ± 0.08 mm, p < 0.001, respectively). Epicardial fat thickness was correlated significantly with age, duration of type 2 diabetes, body mass index, waist circumference, HbA1c, carotid intima-media thickness, Homeostasis Model Assessment Index for insulin resistance and lipid profile in the type 2 diabetic patients. Stepwise regression analysis showed that carotid intima-media thickness, duration of diabetes, triglyceride and body mass index were the independent predictors of epicardial fat thickness, with carotid intima-media thickness the most important predictor (ß = 3.078, t = 4.058, p < 0.001). Receiver operating characteristic curve analysis was done and cut-off high-risk epicardial fat thickness value of 6.1 mm was determined with a sensitivity and specificity of 71.4% and 72%, respectively. CONCLUSION: Patients with type 2 diabetes have higher carotid intima-media thickness and epicardial fat thickness. Epicardial fat thickness was found to be a strong predictor of subclinical atherosclerosis.

Association of fasting glucagon-like peptide-1 with oxidative stress and subclinical atherosclerosis in type 2 diabetes.

AIM: Glucagon-like peptide-1(GLP-1) is a gut hormone that beside its main function in glucose homeostasis may play a role as an anti-oxidant and anti-atherosclerotic factor. The aim of this study was to estimate fasting total GLP-1 level in type 2 diabetes (T2DM) patients and to determine its relation with oxidative stress and atherosclerotic vascular changes. METHODS: The study included 60 T2DM male patients with age ≥40 and 30 healthy male subjects matched for age. All of them were subjected to measuring of fasting total GLP-1, 8-iso prostaglandin F2α (8-iso PGF2α) as a marker of oxidative stress and carotid intima media thickness (CIMT) as a marker of subclinical atherosclerosis. RESULTS: Fasting total GLP-1 was not significantly different in diabetics in comparison with healthy subjects (p = 0.52). Fasting total GLP-1 was found to have significant negative correlations with both 8-iso PGF2α (p < 0.05) and CIMT (p < 0.001). CONCLUSION: Endogenous fasting GLP-1 appears to have anti-oxidant and anti-atherosclerotic effects in T2DM.

Fibroblast growth factor 21 association with subclinical atherosclerosis and arterial stiffness in type 2 diabetes.

AIM: To evaluate the association of serum FGF21 with subclinical atherosclerosis and pulse wave velocity, a marker of arterial stiffness, in type 2 diabetes Egyptian patients. PATIENTS AND METHODS: Fasting serum FGF21 was measured in 120 type 2 diabetes patients without clinical atherosclerotic cardiovascular disease (mean age 51.1 ±â€¯7.7 years; 63.3 women). In addition to basic laboratory tests, serum adiponectin and ultrasonographic examination of CIMT, ankle brachial index (ABI) and carotid-femoral pulse wave velocity (cfPWV) were performed. RESULTS: Patients with subclinical atherosclerosis have higher serum FGF21 than those without (218 ±â€¯66.8 pg/mL Vs 170 ±â€¯43.1 pg/mL, P < 0.001). FGF21 correlated positively with CIMT and cfPWV (P < 0.001) regardless of patient gender. In logistic regression analysis, circulating FGF21 was found to be an independent predictor for subclinical atherosclerosis (P = 0.023) in addition to dyslipidemia, hypertension and adiponectin. FGF21 was also found to be an independent determinant of cfPWV in stepwise multiple regression analysis. ROC curve analysis was done and cutoff high risk FGF21 level of 184 pg/mL for the prediction of subclinical atherosclerosis with a sensitivity and specificity of 66.7%. CONCLUSIONS: Serum FGF21 levels correlated with carotid intima media thickness and predict subclinical atherosclerosis. Serum FGF21 is also correlated positively with cfPWV and arterial stiffness in type 2 diabetes patients.