Progression Of Diabetic Complications Research Articles

Obstructive Sleep Apnea Syndrome in Type 2 Diabetes Mellitus, Case Report and Review of Literature

Humans spend almost 33% of their life sleeping, therefore, poor sleep quality can have both short-term and long-term consequences on an individual's quality of life. Obstructive sleep apnea syndrome (OSA) is the most common sleep disorder characterized by respiratory cessation for at least 10 seconds, associated with a decreased oxygen saturation. OSA is a risk factor for heart rhythm disorders. The presence of heart rhythm disorders correlates with the severity of OSA, especially in middle-aged patients with type 2 diabetes mellitus (DM). The metabolic consequences of OSA contribute to a general imbalance. When circadian rest and activity rhythms are disrupted, hormonal and metabolic regulations also become desynchronized. OSA has an important role in the development of insulin resistance, increased diabetes risk and altered glycemic control in patients with type 2 DM. Taking into account that OSA is an independent risk factor that contributes to the appearance and the progression of diabetes complications, we aimed to present the case of a male patient with type 2 diabetes, aged 70 years old in whom the diagnosis of OSA was established using nocturnal polysomnography. Furthermore, in order to demonstrate the relationships between OSA, poor diabetes control and cardiovascular risk, during polysomnograhy Holter monitoring and continuous glucose monitoring was also performed.

Difficulties and prospects of standardized management of type 1 diabetes

Type 1 diabetes patients require lifelong dependence on insulin therapy. It is a long-term challenge for patients to effectively deliver exogenous insulin to maintain glucose levels within the individual's target range as safely as possible for preventing the development and progression of diabetes complications. The management of type 1 diabetes involves multidisciplinary collaboration, referral from different hospitals, and effective diabetes education and management for patients and family members. Compared with the more mature diseases management system in the United States and the United Kindom, the standardized management of type 1 diabetes patients in China started late. Moreover, there are still some difficulties at present. Whereas, with the exploration and efforts of the hospitals at all levels for the management of type 1 diabetes patients, standardization of type 1 diabetes management will gradually step forward and truly realize the lifelong management for patients.

Epigenetic Modifications and Non-Coding RNA in Diabetes-Mellitus-Induced Coronary Artery Disease: Pathophysiological Link and New Therapeutic Frontiers.

Diabetes mellitus (DM) is a glucose metabolism disorder characterized by chronic hyperglycemia resulting from a deficit of insulin production and/or action. DM affects more than 1 in 10 adults, and it is associated with an increased risk of cardiovascular morbidity and mortality. Cardiovascular disease (CVD) accounts for two thirds of the overall deaths in diabetic patients, with coronary artery disease (CAD) and ischemic cardiomyopathy as the main contributors. Hyperglycemic damage on vascular endothelial cells leading to endothelial dysfunction represents the main initiating factor in the pathogenesis of diabetic vascular complications; however, the underlying pathophysiological mechanisms are still not entirely understood. This review addresses the current knowledge on the pathophysiological links between DM and CAD with a focus on the role of epigenetic modifications, including DNA methylation, histone modifications and noncoding RNA control. Increased knowledge of epigenetic mechanisms has contributed to the development of new pharmacological treatments (“epidrugs”) with epigenetic targets, although these approaches present several challenges. Specific epigenetic biomarkers may also be used to predict or detect the development and progression of diabetes complications. Further studies on diabetes and CAD epigenetics are needed in order to identify possible new therapeutic targets and advance personalized medicine with the prediction of individual drug responses and minimization of adverse effects.

IDF21-0460 How many urine samples are required for diagnosis and monitoring of diabetic kidney disease?

Background: Measurement of the albumin/creatinine ratio (UACR) from a random spot urine sample is commonly used for diabetic kidney disease (DKD) assessment. High day-to-day variability presents a challenge for both monitoring and diagnosis. Guidelines recommend performing multiple UACR tests for diagnosis, but consensus on the number of tests required has not been reached. Aim: To determine the within-individual variability of random spot UACR in people with type 2 diabetes and its implications for the number of samples required for monitoring and diagnosis of DKD. Method: People with type 2 diabetes (n=383; 66±9 years, 69% male) participating in the Progression of Diabetic Complications (PREDICT) prospective cohort study provided four random spot urine samples within a four-week period. UACR was measured according to standard hospital pathology laboratory protocols. Participants were classified as having normo- (69%; UACR <3mg/mmol), micro- (26%; UACR 3-30mg/mmol) or macroalbuminuria (5%; UACR>30mg/mmol), per the geometric mean of four samples. Within-individual variability was characterised by 95% limits of agreement (range encompassing 95% of differences between one/two/three samples vs. the mean of four). Relative reliability (the degree to which an individual maintains their rank in a population over repeated measures) was based on the intraclass correlation coefficient (ICC). We also determined the diagnostic accuracy of classifying albuminuria (UACR ≥3mg/mmol) based on a randomly selected subset of one/two/three samples (vs. mean of four using area under receiver operating characteristic [AUROC] curve analyses). Results: The 95% limits of agreement were derived for log-transformed UACR data (due to skewness), and then back-transformed to produce 95% limits as a ratio. These 95% limits (Table 1) showed that a single sample could be expected to be between 0.44 and 2.34 times the four-sample mean. This variability narrowed to 0.64/1.57 for the two-sample mean, and 0.75/1.28 for the three-sample mean. Relative reliability was more favourable (ICC=0.88 [0.87–0.90]).Table 1Agreement between UACR assessed using one/two/three urine samples, compared with the mean of four samplesOne sampleTwo samplesThree samples95% limits of agreement of one/two/three sample mean (X), with the four-sample mean (Y)Upper limit of ratio (X/Y)2.341.571.28Lower limit of ratio (X/Y)0.440.640.75Diagnostic metrics using classification of four-sample mean as the reference standardAUROC0.9540.9890.995Sensitivity82.4%91.6%92.4%Specificity90.9%95.5%98.5%PPV80.3%90.1%96.5%NPV92.0%96.2%96.7%Correctly classified88.3%94.3%96.6% Open table in a new tab AUROC curve analyses and corresponding diagnostic test metrics were calculated (Table 1). The AUROC was 0.95 for a single sample compared with the four-sample classification, rising to 0.99 for when two/three samples were averaged, respectively. Similarly, sensitivity was >80% for one sample, rising to >90% for two-sample and three-sample means. Discussion: The wide limits of agreement between results from one/two/three urine samples compared with four, suggests multiple samples are necessary to monitor UACR on a continuous scale. However, the high ICC and AUROC values for even a single UACR measurement suggest that this variability has only modest impact on diagnosis/classification. A higher number of repeated UACR measurements may be required for DKD monitoring, than for diagnosis.

Glycaemic variability assessment based on self-measured blood glucose data as an alternative to continuous glucose monitoring

RELEVANCE. Traditional criteria for assessing glycemic control (HbA1c, fasting plasma glucose, and postprandial glycemia) have limited information value for assessing the risk of adverse outcomes in diabetes mellitus (DM). It was found that increased glycemic variability (GV) has a clear relationship with the risk of developing severe hypoglycemia. GV is an independent predictor of diabetes vascular complications, general and cardiovascular mortality in type 2 diabetes. Currently, the mechanisms of severe GV negative effect on the occurrence and progression of diabetes complications have been studied. According to the international consensus on the use of continuous glucose monitoring (CGM) in 2017 and 2019, the calculation of the coefficient of variation (КВ) based CGM data is used to assess GV with the optimal recommended duration of monitoring at least 14 days (Tab.1). However, the CGM procedure has its limitations: it is expensive, usually carried out within 5-7 days maximum. PURPOSE. To develop a unified method for GV assessing acceptable for widespread use in routine practice by comparing the CV calculated using CGM and self-measured blood glucose (SMBG) with the calculation of the minimum period and minimum number of measurements without loss of correlation. MATERIALS AND METHODS. The retrospective analysis based on routine research of CGM and SMBG data (583 measurements) in 35 patients with T1D. The patients performed self-control during ~ 17 days (95 CI: 14.88-18.43). The simulation was carried out by the Monte Carlo method, for each patient m = 1500 times were taken from the CGM data during each day. The following parameters were determined by the method of simulation modeling: the time of the first measurement, the number of measurements per day, the duration of the self-control period to maximize the sensitivity and specificity of the algorithm. RESULTS. An algorithm was developed and validated for assessing CV according to SMBG data, which provides for: at least 7 measurements per day. The duration of the self-control period at least 14 days. The maximum error in assessing the variability is observed when the CV value calculated from SMBG data falls within the range of 35% - 40%, which requires CGM. If CV value below 35% and above 40% it can be concluded with an accuracy of at least 95% that the true CV is low or high. CONCLUSIONS. The resulting algorithm for assessing the CV according to SMBG data provides a sensitivity and specificity of at least 96% and 84%, respectively.

Genetic variants of ALR (-106C → T /-12C → G) and serum PKC-δ are associated with peripheral neuropathy in Egyptian diabetic patients with impaired handwriting.

Diabetic peripheral neuropathy can injure the hand median nerve and cause extensive nerve damage. PKC and ALR are associated with progression of diabetic complications. We hypothesized a genetic association between the ALR polymorphisms (-106C → T/-12C → G) and elevated serum PKC-δ levels in diabetic neuropathy and its adverse effects on handwriting in Egyptian population. One hundred DPN were compared with 100 DP and 100 healthy volunteers. ALR -106C → T/-12C → G variants were studied using the PCR-RFLP method. A routine set of standard laboratory markers was determined. Serum PKC-δ concentration was determined by ELISA. Logistic regression analysis and areas under the receiver characteristic curves (AUCs) were evaluated to investigate the predictors of diabetic neuropathy. Arabic handwriting was analyzed based on the recognition of functional features, word shape, and ascending/descending parts of letters. Individuals carrying ALR-106C → C and -12G → G had a significantly higher risk of developing diabetic neuropathy than individuals with -106C → T and -12C → G genotypes (P = 0.01, P = 0.02). Carriers of the (-106C → T) CC and (-12C → G) GG genotypes had significantly increased serum levels of PKC-δ, FBG, TC, and LDL-c. PKC- δ serum levels were significantly correlated with glycemic and lipid indicators (P < 0.001). PKC-δ is a significant predictor of diabetes with or without neuropathy at a cutoff value of 16.6, sensitivity was 89%, and specificity 100%. All DPN showed complete deterioration of handwriting after the onset of diabetic neuropathy. The genetic variants ALR-106C → C / -12G → G and PKC-δ in serum may help in the detection and treatment of diabetic neuropathy in Egyptian population before writing performance is affected.

The Role of Bone-Derived Hormones in Glucose Metabolism, Diabetic Kidney Disease, and Cardiovascular Disorders.

Bone contributes to supporting the body, protecting the central nervous system and other organs, hematopoiesis, the regulation of mineral metabolism (mainly calcium and phosphate), and assists in respiration. Bone has many functions in the body. Recently, it was revealed that bone also works as an endocrine organ and secretes several systemic humoral factors, including fibroblast growth factor 23 (FGF23), osteocalcin (OC), sclerostin, and lipocalin 2. Bone can communicate with other organs via these hormones. In particular, it has been reported that these bone-derived hormones are involved in glucose metabolism and diabetic complications. Some functions of these bone-derived hormones can become useful biomarkers that predict the incidence of diabetes and the progression of diabetic complications. Furthermore, other functions are considered to be targets for the prevention or treatment of diabetes and its complications. As is well known, diabetes is now a worldwide health problem, and many efforts have been made to treat diabetes. Thus, further investigations of the endocrine system through bone-derived hormones may provide us with new perspectives on the prediction, prevention, and treatment of diabetes. In this review, we summarize the role of bone-derived hormones in glucose metabolism, diabetic kidney disease, and cardiovascular disorders.

Diabetic Complications: An Update on Pathobiology and Therapeutic Strategies.

Despite the advent of novel therapies which manage and control diabetes well, the increased risk of morbidity and mortality in diabetic subjects is associated with the devastating secondary complications it produces. Long-standing diabetes majorly drives cellular and molecular alterations, which eventually damage both small and large blood vessels. The complications are prevalent both in type I and type II diabetic subjects. The microvascular complications include diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, while the macrovascular complications include diabetic heart disease and stroke. The current therapeutic strategy alleviates the complications to some extent but does not cure or prevent them. Also, the recent clinical trial outcomes in this field are disappointing. Success in the drug discovery of diabetic complications may be achieved by a better understanding of the underlying pathophysiology and by recognising the crucial factors contributing to the development and progression of the disease. In this review, we discuss the well-studied cellular mechanisms leading to the development and progression of diabetic complications. In addition, we also highlight the various therapeutic paradigms currently in clinical practice.

Maternal diabetes and neonatal outcome

Diabetes during pregnancy is more and more frequent worldwide because of the rising incidence of its known risk factors, such as high body mass index, sedentary lifestyle, and hypercaloric diets. It can be either a preexisting condition, or it can be first diagnosed during pregnancy, usually between the 24th and the 28th week of gestation, when it receives the name of gestational diabetes mellitus. Both preexisting diabetes mellitus and gestational diabetes mellitus may have severe maternal and newborn consequences, especially if there is insufficient control of the maternal glycemic levels and progression of diabetes complications, such as microvascular disease and nephropathy. Infants of diabetic mothers may experience excessive birth weight or, on the contrary, low birth weight, trauma at birth, cardiomyopathy, respiratory distress syndrome, hypoglycemia, hypocalcemia, jaundice, or polycythemia. This study’s aim is to gather and synthesize available information about maternal diabetes and its impact on fetal development and newborn outcome.

Skin Autofluorescence a Non-Invasive Biomarker of Ages and Its Association to Metabolic Parameters in a Greek Diabetic Population

Objectives This cross-sectional study aims to evaluate the association between advanced glycation end-products (AGEs) accumulation, assessed by skin autofluorescence (SAF) measured using the AGE Reader, and the prevalence of several metabolic variables in a diabetic population. Methods The measurement of SAF has become a non-invasive method of assessing the accumulation of AGEs as a marker of the long-term impact of glycemic and oxidative stress in humans. In contrast to blood glucose and to hemoglobin A1C (HbA1c), which reflect a short period of glucose levels, the AGE is a marker of the metabolic legacy effect and reflect a long period of glucose levels. AGEs play a pivotal role in the development and progression of diabetic complications. SAF has been validated as a simple, non-invasive method for assessment of AGEs accumulation in the body. Results In this study 100 diabetic patients were participated. We non-invasively measured SAF, in all the participants using the AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands). We also measured the body mass index (BMI), the blood pressure and the patients underwent arterial duplex sonogram (Doppler examination) in the legs at the level of the ankle and calculated the ankle-branchial index (ABI), which is an important index for diagnosing peripheral artery disease, which is a severe complication of diabetes. The SAF was positive correlated with age, duration of diabetes and systolic blood pressure (BP) and was negative correlated with ABI. Conclusion The measurement of SAF has become a non-invasive and reliable method of assessing the accumulation of AGEs in humans. In contrast to blood glucose and to HbA1c, which reflect a short period of glucose levels, the AGEs reflect a long period of glucose levels, correlate with certain metabolic parameters and with peripheral artery disease.

The Potential Role of Curcumin in Modulating the Master Antioxidant Pathway in Diabetic Hypoxia-Induced Complications.

Oxidative stress is the leading player in the onset and development of various diseases. The Keap1-Nrf2 pathway is a pivotal antioxidant system that preserves the cells’ redox balance. It decreases inflammation in which the nuclear trans-localization of Nrf2 as a transcription factor promotes various antioxidant responses in cells. Through some other directions and regulatory proteins, this pathway plays a fundamental role in preventing several diseases and reducing their complications. Regulation of the Nrf2 pathway occurs on transcriptional and post-transcriptional levels, and these regulations play a significant role in its activity. There is a subtle correlation between the Nrf2 pathway and the pivotal signaling pathways, including PI3 kinase/AKT/mTOR, NF-κB and HIF-1 factors. This demonstrates its role in the development of various diseases. Curcumin is a yellow polyphenolic compound from Curcuma longa with multiple bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Since hyperglycemia and increased reactive oxygen species (ROS) are the leading causes of common diabetic complications, reducing the generation of ROS can be a fundamental approach to dealing with these complications. Curcumin can be considered a potential treatment option by creating an efficient therapeutic to counteract ROS and reduce its detrimental effects. This review discusses Nrf2 pathway regulation at different levels and its correlation with other important pathways and proteins in the cell involved in the progression of diabetic complications and targeting these pathways by curcumin.

The Fate Status of Stem Cells in Diabetes and its Role in the Occurrence of Diabetic Complications.

Diabetes mellitus (DM) is becoming a growing risk factor for public health worldwide. It is a very common disease and is widely known for its susceptibility to multiple complications which do great harm to the life and health of patients, some even lead to death. To date, there are many mechanisms for the complications of diabetes, including the generation of reactive oxygen species (ROS) and the abnormal changes of gas transmitters, which ultimately lead to injuries of cells, tissues and organs. Normally, even if injured, the body can quickly repair and maintain its homeostasis. This is closely associated with the repair and regeneration ability of stem cells. However, many studies have demonstrated that stem cells happen to be damaged under DM, which may be a nonnegligible factor in the occurrence and progression of diabetic complications. Therefore, this review summarizes how diabetes causes the corresponding complications by affecting stem cells from two aspects: stem cells dysfunctions and stem cells quantity alteration. In addition, since mesenchymal stem cells (MSCs), especially bone marrow mesenchymal stem cells (BMMSCs), have the advantages of strong differentiation ability, large quantity and wide application, we mainly focus on the impact of diabetes on them. The review also puts forward the basis of using exogenous stem cells to treat diabetic complications. It is hoped that through this review, researchers can have a clearer understanding of the roles of stem cells in diabetic complications, thus promoting the process of using stem cells to treat diabetic complications.

Achievement of treatment targets predicts progression of vascular complications in type 1 diabetes

Background and aimTo study the association between achievement of guideline-defined treatment targets on HbA1c, low-density lipoproteins (LDL-C), and blood pressure with the progression of diabetic complications in patients with type 1 diabetes (T1D). MethodsThe study included 355 patients at baseline and 114 patients with follow-up data after 3–5 years. Outcome variables were the progression of diabetic kidney disease, retinopathy, or cardiovascular disease (CVD). We used logistic regression and other machine learning algorithms (MLA) to model the association of achievement of treatment targets and probability of progression of complications. ResultsAchievement of the target blood pressure was associated with 96% lower odds of a new CVD event (0.04 (95% CI 0.00, 0.53), p = 0.016), and 72% lower odds of progression of any complication (0.28 (95% CI 0.09, 0.89), p = 0.027. Achievement of HbA1c target was associated with lower odds of composite complication progression by 82% (0.18 (95% CI 0.04, 0.88), p = 0.034.) None of the patients who achieved HbA1c target progressed in CVD. MLA demonstrated good accuracy for the prediction of progression of CVD (AUC 0.824), and lower accuracy for other complications. ConclusionThe achievement of blood pressure and HbA1c treatment targets is associated with lower odds of vascular complication of T1D in a real life study.

Significance of Glycemic Variability in Diabetes Mellitus.

The goal of diabetes treatment is to maintain good glycemic control, prevent the development and progression of diabetic complications, and ensure the same quality of life and life expectancy as healthy people. Hemoglobin A1c (HbA1c) is used as an index of glycemic control, but strict glycemic control using HbA1c as an index may lead to severe hypoglycemia and cardiovascular death. Glycemic variability (GV), such as excessive hyperglycemia and hypoglycemia, is associated with diabetic vascular complications and has been recognized as an important index of glycemic control. Here, we reviewed the definition and evaluated the clinical usefulness of GV, and its relationship with diabetic complications and therapeutic strategies to reduce GV.

Impact of the COVID-19 pandemic and lockdown restrictions on psychosocial and behavioural outcomes among Australian adults with type 2 diabetes: Findings from the PREDICT cohort study.

AimTo examine psychosocial and behavioural impacts of the novel coronavirus disease 2019 (COVID‐19) pandemic and lockdown restrictions among adults with type 2 diabetes.MethodsParticipants enrolled in the PRogrEssion of DIabetic ComplicaTions (PREDICT) cohort study in Melbourne, Australia (n = 489 with a baseline assessment pre‐2020) were invited to complete a phone/online follow‐up assessment in mid‐2020 (i.e., amidst COVID‐19 lockdown restrictions). Repeated assessments that were compared with pre‐COVID‐19 baseline levels included anxiety symptoms (7‐item Generalised Anxiety Disorder scale [GAD‐7]), depressive symptoms (8‐item Patient Health Questionnaire [PHQ‐8]), diabetes distress (Problem Areas in Diabetes scale [PAID]), physical activity/sedentary behaviour, alcohol consumption and diabetes self‐management behaviours. Additional once‐off measures at follow‐up included COVID‐19‐specific worry, quality of life (QoL), and healthcare appointment changes (telehealth engagement and appointment cancellations/avoidance).ResultsAmong 470 respondents (96%; aged 66 ± 9 years, 69% men), at least ‘moderate’ worry about COVID‐19 infection was reported by 31%, and 29%–73% reported negative impacts on QoL dimensions (greatest for: leisure activities, feelings about the future, emotional well‐being). Younger participants reported more negative impacts (p < 0.05). Overall, anxiety/depressive symptoms were similar at follow‐up compared with pre‐COVID‐19, but diabetes distress reduced (p < 0.001). Worse trajectories of anxiety/depressive symptoms were observed among those who reported COVID‐19‐specific worry or negative QoL impacts (p < 0.05). Physical activity trended lower (~10%), but sitting time, alcohol consumption and glucose‐monitoring frequency remained unchanged. 73% of participants used telehealth, but 43% cancelled a healthcare appointment and 39% avoided new appointments despite perceived need.ConclusionsCOVID‐19 lockdown restrictions negatively impacted QoL, some behavioural risk factors and healthcare utilisation in adults with type 2 diabetes. However, generalised anxiety and depressive symptoms remained relatively stable.

313-OR: Disparities in Preventive Care Utilization among Patients with Diabetes in the Diabetes Belt and Surrounding Areas

Objective: Preventive care has been shown to reduce both the incidence and progression of diabetic complications. American Diabetes Association treatment guidelines recommend annual preventive care such as annual doctor visits and A1c tests. Our objective is to compare utilization rates of four annually recommended preventive services for persons with diabetes in the Diabetes Belt and those in the surrounding area. Methods: We used 2015 Medicare claims data to identify preventive service utilization using ICD9/10 and CPT/HCPCS codes. Diabetes Belt consists of 644 counties in the Appalachian region and southeastern part of US that had diabetes prevalence over 11% in 2008 compared to ~8.5% in the rest of the country. Surrounding counties include 118 counties that are adjacent but not contiguous to the Diabetes Belt counties. Results: Patients in the Belt had significantly lower utilization than those in surrounding counties for all four preventive services: foot exam, 81% vs. 88%; eye exam, 53% vs. 58%; microalbuminuria test, 31% vs. 34%; one or more A1c tests, 73% vs. 74%. After adjusting for age, sex, and race/ethnicity, patients in the Diabetes Belt had 38%, 18%, 16%, and 11% lower odds of using foot exams, microalbuminuria tests, eye exams, and A1c tests, respectively, compared to those in the surrounding counties (p for all comparisons &amp;lt; 0.001). Even after adjusting for socioeconomic, access-to-care factors, and service availability, patients in the Diabetes Belt had consistently lower rates of utilization for these four services than surrounding counties. Conclusion: Patients with diabetes in the Diabetes Belt are doubly jeopardized for diabetic complications because of higher prevalence diabetes and lower preventive care utilization than surrounding counties. Health policy makers may want to pay more attention to the Diabetes Belt in reducing the regional differences in the utilization of these services. Disclosure M. Sohn: None. H. Kang: None. T. L. Mcmurry: None. S. Kim: None. J. M. Lobo: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK113295)

Vitamin D Deficiency Induces Macrophage Pro-Inflammatory Phenotype via ER Stress-Mediated Activation of Renin-Angiotensin System

Chronic inflammation and local activation of the renin-angiotensin-aldosterone system (RAAS) play a pivotal role in the pathogenesis and progression of diabetic complications. In patients with type 2 diabetes (T2DM), the prevalence of vitamin D deficiency is almost twice that of non-diabetics, and vitamin d deficiency nearly doubles the risk of developing hypertension and cardiovascular complications compared to diabetics with normal vitamin D levels. Interestingly, mice lacking the vitamin D receptor (VDR) in macrophages (KODMAC) develop renin-dependent hypertension, insulin resistance, and inflammation via up-regulation of macrophage ER stress. Macrophages also express all major components of the RAAS system. However, little is known about the regulation of macrophage-generated renin and its role in modulating the sequelae of VDR signaling in macrophage function and cytokine production. This study found that KODMAC macrophages and vitamin D-deficient macrophages have increased expression and secretion of renin, angiotensin II, ACE, and AT1 receptor and that adhesion, migration, and cytokine release were also increased. Inhibition of ER stress in KODMAC macrophages and vitamin D-deficient macrophages with 4-Phenylbutyric acid (PBA) reduced RAS gene expression and macrophage pro-inflammatory phenotype. Renin 1c gene deletion decreased macrophage adhesion, migration, and cytokine release compared to macrophages with disrupted VDR signaling. Notably, disruption of VDR signaling induced peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression in macrophages, and upregulation of renin expression in response to vitamin D deficiency was blunted in PCG1α-deficient macrophages. In conclusion, our findings delineate a mechanism by which impaired VDR signaling induces ER stress to drive PGC1α-dependent expression of renin and RAAS hyperactivation, thereby altering macrophage function and cytokine production. These data implicate RAAS as an essential mediator of VDR-mediated macrophage function and support ongoing investigations of VDR and RAAS modulation as therapeutic approaches in the management of T2DM and its complications.

Study of Omentin-1 and Chemerin as Predictors of Coronary Artery Disease in Elderly Patients, with Retrospective Studying of their Relation to Diabetes Mellitus Type 2

Monocyte chemoattractant protein-1 (MCP-1) is the first discovered and most extensively studied chemotactic cytokines (CC = chemokine). Many studies on its role in the etiologies of obesity- and diabetes-related diseases have been increased exponentially during the past two decades. MCP-1, a chemokine involved in monocyte chemotaxis can be consistently found at high levels in the patients with type 2 diabetes mellitus. MCP1 may be an early predictor of complications of diabetes. Objective: Assessment of the levels of MCP-1 and other biochemical markers in diabetic subjects compared to a healthy group, which in turn can be beneficial to clarify the correlations of MCP-1 levels in diabetes mellitus with other clinical and biochemical parameters. Patients and methods: Eighty-one participants including both male and female, of cross-matched ages ranging between 30 – 60 years old were included in this study. They were divided into three equal groups: group I (control group), group II (recently diagnosed T2DM) and group III (old diagnosed T2DM more than 10 years). Results: The highest level of MCP-1 was found in the old diagnosed diabetic group while the lowest level was found in the non-diabetic control group. The LSD statistical analysis showed there was significant difference between all groups of the study. Our results showed that serum MCP-1 was elevated in cases of the group 3 (old diagnosed diabetic patients) who were suffering from diabetic nephropathy (9/27), diabetic retinopathy (9/27) and the last 9/27 were suffering of neuropathy. Conclusion: The MCP-1 level is increased in type 2 Diabetic patients and significantly increased with the progression of diabetes complications as diabetic retinopathy, diabetic nephropathy and diabetic neuropathy.

Evaluation of Monocyte Chemoattractant Protein 1(MCP-1) as a Predictor of Complications in Type 2 Diabetes Mellitus in Zagazig University Hospital

ABSTRACT Background: Monocyte chemoattractant protein-1 (MCP-1) is the first discovered and most extensively studied chemotactic cytokines (CC = chemokine). Many studies on its role in the etiologies of obesity- and diabetes-related diseases have been increased exponentially during the past two decades. MCP-1, a chemokine involved in monocyte chemotaxis can be consistently found at high levels in the patients with type 2 diabetes mellitus. MCP1 may be an early predictor of complications of diabetes. Objective: Assessment of the levels of MCP-1 and other biochemical markers in diabetic subjects compared to a healthy group, which in turn can be beneficial to clarify the correlations of MCP-1 levels in diabetes mellitus with other clinical and biochemical parameters. Patients and methods: Eighty-one participants including both male and female, of cross-matched ages ranging between 30 – 60 years old were included in this study. They were divided into three equal groups: group I (control group), group II (recently diagnosed T2DM) and group III (old diagnosed T2DM more than 10 years). Results: The highest level of MCP-1 was found in the old diagnosed diabetic group while the lowest level was found in the non-diabetic control group. The LSD statistical analysis showed there was significant difference between all groups of the study. Our results showed that serum MCP-1 was elevated in cases of the group 3 (old diagnosed diabetic patients) who were suffering from diabetic nephropathy (9/27), diabetic retinopathy (9/27) and the last 9/27 were suffering of neuropathy. Conclusion: The MCP-1 level is increased in type 2 Diabetic patients and significantly increased with the progression of diabetes complications as diabetic retinopathy, diabetic nephropathy and diabetic neuropathy.

Risk factors of the development of vascular and neuropathic complications in patients with type 2 diabetes mellitus and autoimmune thyroiditis

Issues of the formation and progression of late complications of diabetes mellitus remain interesting and foreground today, especially in cases of type 2 diabetes mellitus (dm) combined with other endocrine diseases. The pathogenetic relation between the mechanisms leading to blood vessels and nerves damage against the background of diabetes mellitus, and, for example, mechanisms of autoimmune thyroid abnormality (ait), is far from being unambiguous, but the very fact of its existence cannot be denied.Purpose: to determine the predominant type of comorbidity (trans-syndromal, trans-nosological or chronological) and the level of comorbidity according to the disease rating scale (cirs) in patients with type 2 diabetes and ait, to study the structure of later complications of diabetes mellitus in this group of patients and to assess the contribution of certain factors to increased risk of complications.Methods. 428 patients were examined in a specialized endocrinology department, and two groups were formed: an observation group — 213 people with diagnosed type 2 diabetes and ait, and a comparison group — 215 people with a diagnosis of type 2 diabetes. These groups were comparable in age, the duration of diabetes, body mass index, correction of the disease. The analysis included clinical and laboratory parameters, the results of hormones level studies (tsh, free t4, insulin, c-peptide) and antibodies (at-tpo), thyroid ultrasonography, calculation of the insulin resistance index (homa) and the comorbidity index (cirs — cumulative illness rating scale) followed by a correlation-regression analysis of statistical data. The state of the peripheral nervous system was evaluated with the use of electromyography in patients of both groups, and the severity of diabetic neuropathy was evaluated with the use of the neuropathy disability score and vas (visual analogue scale) scales. The state of the vascular system was studied according to the data of ultrasound examination of the vessels of the lower extremities, echocardiography, and ophthalmoscopy.Results. The obtained data made it possible to determine the factors infl uencing the risk of type 2 diabetes complications developement, and to establish that neuropathic complications begin and progress faster in patients with comorbid endocrine pathology, however, there is no such dependence for vascular complications. According to the linear regression equation of the dependence of total complications on the duration of the disease, it was revealed that the development of vascular complications in patients with combined endocrinopathy occurs even more slowly than in patients with diabetes. The contribution of diabetes compensation and identifi ed risk factors to the progression of diabetic complications was less important for patients with endocrinopathies. As for evaluating the contribution of individual parameters, the most signifi cant were the duration of diabetes mellitus, albuminuria, atherosclerosis of the vessels of the lower extremities.Conclusion. In addition to the known risk factors for the development and progression of vascular complications, in patients with overlapping endocrinopathy, the preservation of residual insulin secretion and renal function (chronic kidney disease, proteinuria) were important. the prevalence of “total” Complications in the group of patients with combined endocrine pathology was lower, however, neuropathic complications in the same group were observed more often,т which indicates the primary eff ect of thyroid dysfunction on the structure of the nervous tissue.