The association of cell adhesion molecules and selectins (VCAM-1, ICAM-1, E-selectin, L-selectin, and P-selectin) with microvascular complications in patients with type 2 diabetes: A follow-up study.

Objective: Chronic hyperglycemia induces pathogenic changes in the vascular endothelium and leads to the development of microvascular complications in patients with type 2 diabetes mellitus. Early identification of markers of diabetes complications may help to minimize the risk of the development and progression of microvascular complications. Methods: This follow-up study was conducted in type 2 diabetic cohort aged between 30-70 years. Out of 160 eligible participants, 70 of them completed follow-up. Levels of cell adhesion molecules and selectins (VCAM-1, ICAM-1, E-selectin, L-selectin and P-selectin) at baseline and follow-up were measured using Randox Evidence biochip analyzer (UK). Development of microvascular complications (diabetic neuropathy, retinopathy and nephropathy) was evaluated. Results: During the follow-up (2 years, median), 31 (44.3%) developed diabetic neuropathy, 10 (14.3%) developed diabetic retinopathy and, 27 (38.6%) developed diabetic nephropathy. A significant difference in levels of cell adhesion molecules and selectins were found in type 2 diabetic patients with and without microvascular complications. Multiple logistic regression analysis reveals that baseline level of VCAM-1 is significantly associated with microvascular complications; diabetic neuropathy(p=0.028), retinopathy (p=0.007) and nephropathy(p=<0.001). Additionally, levels of P-selectin (p=0.05) and L-selectin (p=0.008) is associated with diabetic nephropathy while retinopathy associated with L-selectin (p=0.005) only. Conclusion: Cell adhesion molecules and selectins are indicators of microvascular complication among patients with type 2 diabetes (T2D). Association of these markers with the development of microvascular complications may provide additive information for developing strategies for diabetes management and prediction of microvascular complications.

Cytokines Involved in COVID-19 Patients with Diabetes: A Systematic Review.

BACKGROUND: Hyperglycemic condition and compromised immune system may contribute to the progression of COVID-19 infection and increase the disease severity, relatively requiring a longer recovery period among diabetic patients. OBJECTIVE: A systematic review was conducted to examine cytokine levels, the prevalence of risk factors, and other comorbidities in COVID-19 patients with and without diabetes mellitus during the early COVID-19 outbreak. METHODS: A systematic literature search was conducted in PubMed central, PMC Europe databases, and Web of Science, evaluating the articles published between Dec 1st, 2019, and June 15th, 2020. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: The systematic search generated 14,960 articles and ended up with 9 articles, of which 8 articles involved data on the comparison of cytokines in diabetic and non-diabetic subjects with COVID-19, while 4 of them involved data on cytokines in the diabetes patients compared either by the severity of diseases or the rate of survival. Among the studied cytokines, interleukin-6, interleukin- 8, and tumor necrosis factor-α may cause the worst prognosis or fatality among diabetic patients. Increased cytokine levels indicate higher mortality and are linked to risk factors and comorbidities, such as hypertension and cardiovascular disease. Management of diabetes by insulin treatment may reduce the rate of mortality among diabetic patients but may be contraindicated in diabetic patients with COVID-19 who had at least one previous comorbidity, especially hypertension and CVD. CONCLUSION: The pathophysiological mechanisms linked to cytokine storm in diabetic patients may lead to the design of treatment strategies in the future, thus improving early diagnosis of the disease and mitigating cytokine storm-associated morbidity and mortality.

Risk factors of chronic kidney disease among type 2 diabetic patients with longer duration of diabetes.

Background: Chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM) is the major cause of end stage renal disease, characterized by proteinuria with a subsequent decline in glomerular filtration rate. Although hyperglycemia is the major risk factor for the development and progression of kidney disease among diabetic patients, many other risk factors also contribute to structural and functional changes in the kidneys. As recommended by Kidney Disease Improving Global Outcomes (KDIGO), CKD classification based on cause and severity, links to risk of adverse outcomes including mortality and kidney outcomes. Objective: The aim of this study is to investigate the involvement of risk factors associated with the severity of CKD among participants with longer duration of diabetes. This study also aims to find whether number of risk factors vary among risk of CKD progression categories based on KDIGO classification. Material and methods: This cross-sectional study retrospectively selected 424 participants from type 2 diabetic cohort and categorized them based on the classifications for the diagnosis of kidney diseases in patients with diabetes, according to the KDIGO guidelines. Odds ratios and 95% CI of each risk factors according to severity of renal disease were determined. Results: Based on KDIGO classification, participants with type 2 diabetes (T2D) were categorized in to low risk (n=174); moderately increased risk (n=98); and high/very high risk (n=152). Type 2 diabetic participants with risk factors such as, hyperlipidemia, hypertension, DM duration ≥15 years and diabetic retinopathy showed a high/very high risk of CKD progression when compared with low-risk category. While T2D participants with risk factors such as, lack of exercise, hypertension, and diabetic retinopathy showed a moderately increased risk of CKD progression. In addition, participants with highest number of risk factors were significantly distributed among high/very high risk of CKD progression category. Conclusion: This study findings conclude that patients with T2DM and duration of ≥15 years, hyperlipidemia, hypertension and diabetic retinopathy have an increased prevalence of advanced CKD. In addition to this, increased number of risk factors could be an indicator of the severity of CKD in T2D.

Association of sex hormone binding globulin with gestational age and parity in gestational diabetes mellitus.

OBJECTIVE: Recent research on sex hormone binding globulin (SHBG) has emphasized its role in the prediction of gestational diabetes mellitus (GDM) development. SHBG is associated with glucose tolerance status, and its level is regulated by prenatal and perinatal factors during pregnancy. This study aimed to determine the levels of SHBG in pregnant women with normal glucose tolerance and those with GDM in association with parity and gestational age (weeks). MATERIALS AND METHODS: This cross-sectional study enrolled 218 pregnant women (165 controls and 53 women with GDM). Serum SHBG levels were analyzed using enzyme-linked immunosorbent assay. The association of SHBG with gestational age was assessed using multivariate regression analysis after adjustment for GDM-related risk factors. RESULTS: Parity sub-group analyses indicated the presence of significant differences in the SHBG levels between nulliparous women in the GDM and control groups (p = .04). Moreover, in the GDM group, SHBG was significantly associated with gestational age beyond the risk factors of GDM. CONCLUSION: This study demonstrated a strong association between SHBG and gestational age in women with GDM. Our findings suggest that parity and gestational age should be considered in the analysis of SHBG as a marker for GDM diagnosis.

Level of hormones in menopause in relation to diabetic retinopathy among type 2 diabetic women.

Hormonal transition among middle-aged women with type 2 diabetes may exert an impact in the development of diabetic retinopathy (DR). In this cross-sectional study, we aimed to assess the levels of estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in the presence of DR and their relationship with risk factors for DR among pre- and post-menopausal women with type 2 diabetes. Serum levels of estradiol, FSH, and LH were measured using the immunoassay technique. All statistical analysis was performed using SPSS software. From the 255 participants, diabetes duration-matched, 35 premenopausal, and 57 postmenopausal women were selected for analysis. The levels of estradiol, LH, and FSH were found to be similar in participants with and without DR among pre- and post-menopausal women with diabetes. Estradiol level was not found to be related with the risk factors of DR among women with type 2 diabetes. In conclusion, female sex hormone, estradiol is not related to the presence of DR. Further prospective studies are necessary to reveal the mechanistic role of this hormone in the development of DR.

Variation in the Level of Thyroid Markers in Association with Inflammation in Patients with Type 2 Diabetes.

BACKGROUND: A possible relationship between thyroid hormones and glucose metabolism in diabetes has already been established. OBJECTIVES: We aimed to evaluate the thyroid function markers and their relationship with inflammation, which is considered as a pathogenic condition of diabetes. METHODS: This cross-sectional study included 276 patients with type 2 diabetes. Serum levels of thyroid (TSH, FT4, and FT3) and inflammatory markers (CRP, IL-6, and TNF-α) were measured. RESULTS: The mean age of the subjects was 55.2 years and mean diabetes duration of 16.8 years. The inflammatory markers showed significant differences with the tertiles of TSH and thyroid hormones. TSH was significantly correlated with inflammatory markers, IL-6 (r = 0.13, P = 0.020) and TNF-α (r = 0.17, P = 0.003), while FT4 had a correlation only with TNF-α (r = 0.25, P = <0.001). FT3 was negatively correlated with inflammatory marker IL-6 (r = -0.14, P = 0.020), HbA1c (r = -0.12, P = 0 .040), and HOMA-IR (r = -0.17, P = 0.010). CONCLUSION: Abnormalities in the thyroid hormone metabolism are related to the increased inflammatory activity as well as insulin resistance, and are associated with the disorders of glucose metabolism.

VCAM-1, ICAM-1 and selectins in gestational diabetes mellitus and the risk for vascular disorders.

Aim: Levels of VCAM-1, ICAM-1 and selectins in gestational diabetes mellitus (GDM) subjects are an indication of endothelial dysfunction predicting the future metabolic consequence via metabolic memory effect. Materials & methods: This cross-sectional study was conducted in 92 pregnant women and serum endothelial cell adhesion molecules were measured using Randox biochip analyzer. Results: Significantly elevated serum level of VCAM-1 was found in GDM subjects and in greater than equal to one parity categorized GDM group when compared with control. The correlation of parity and P-selectin was statistically significant in GDM subjects. Conclusion: Elevated levels of endothelial cell adhesion molecules in GDM women indicate an imbalance in vascular function. Transient hyperglycemia during pregnancy may induce persistent modifications to the memory cells and GDM subjects are more prone to develop future consequences.

Low magnesium level as an indicator of poor glycemic control in type 2 diabetic patients with complications.

AIM: Alteration in the metabolism of magnesium have an influence on different metabolic and signaling pathways involved in development of diabetes and its progression. Reduced magnesium level was associated with diabetes related complications. The aim of this study is to determine the serum levels of magnesium in diabetic patients having different complications and the association of magnesium with status of glycemic control. MATERIALS AND METHODS: This study was conducted among 88 type 2 diabetic patients, subdivided into two groups according to diabetic complications (with complications n = 55; without complications n = 33) and biochemical variables were measured. RESULTS: The serum magnesium level was decreased in diabetic patients having any complications (P = 0.039) or independent complication (nephropathy, P = 0.437; retinopathy, P = 0.038; neuropathy, P = 0.012 and macrovascular complication, P = 0.039), also decrease with increase in number of diabetic complications. Serum magnesium showed an inverse relation with glycemic parameters (HbA1c (r = -0.323; P = 0.002) and fasting blood glucose (r = - 0.321; P = 0.002)). CONCLUSION: The low levels of magnesium in diabetic complications, indicates the poor glycemic control in diabetic patients. Hence, maintaining the sufficient level of magnesium can control glycemia, thereby prevent the development of diabetic complications.

Potential role of serum fetuin-A in relation with pro-inflammatory, chemokine and adhesion molecules in diabetic kidney disease: a case-control study.

Inflammatory cytokine, adipokine and adhesion molecules are known to play a key role in pathogenesis of diabetic kidney disease (DKD). In this study, our aim was to investigate the role of fetuin-A in relation with pro-inflammatory cytokines (IL-6, IL-18), adipokines (adiponectin, leptin), chemokine (MCP-1), and adhesion molecules (ICAM-1, VCAM-1) in control and DKD subjects. We recruited a total of 224 type 2 diabetic (T2D) subjects. The control subjects were T2D with a normal albumin excrete (albumin-to-creatinine ratio-ACR ≤ 30 mg/g creatinine) and estimated glomerular filtration rate (eGFR) ≥ 60 (ml/min/1.73 m2), while cases were T2D subjects with albumin excrete (ACR ≥ 30 mg/g creatinine) and eGFR ≤ 60 (ml/min/1.73 m2). FBS, HbA1c, lipid profile (TC, LDL, HDL, triglyceride), ALT, AST, GGT, serum creatinine, BMI, blood pressure was evaluated in all the study subjects. Randox evidence biochip analyzer was used for measuring inflammatory cytokines, adipokines, and adhesion molecules by chemiluminescent assay. Serum fetuin-A and IL-18 were measured by ELISA kits. Serum fetuin-A levels were significantly decreased in DKD cases compare to control group [456.8 (299.2-649.0) µg/ml versus 670.6 (573.0-726.1) µg/ml; p < 0.001)]. Serum fetuin-A levels correlates significantly with IL-6, IL-18, TNF-α, PAI-1, leptin, resistin and ACR (p < 0.001). This study concludes that serum fetuin-A and pro-inflammatory markers (IL-18, IL-6, IL-1α and TNF-α) might play an important role in the pathophysiology and inflammatory process of DKD.

Significance of glycated LDL in different stages of diabetic nephropathy.

AIM: The aim of this study was to investigate the role of elevated glycated LDL (low-density lipoprotein) in the progression of diabetic kidney disease among type 2 diabetes (T2D) subjects. MATERIALS AND METHODS: This case-control observational study is a part of Saudi Diabetes Kidney Disease (SAUDI-DKD) study conducted during the period from April 2014 to June 2015. This study cohort is divided into two groups; the first group was T2D patients without diabetic nephropathy (DN) (n = 24) and the second group was T2D with DN (n = 45). Serum glycated LDL levels were determined by ELISA. Pearson's correlation analysis was performed, and the diagnostic accuracy was assessed using the area under the ROC curve. RESULTS: There was a threefold increase of serum glycated LDL level among diabetic subjects when compared with non-diabetic subjects and this level progressively increased with the progression of DN. The glycated LDL was found to have a significant diagnostic accuracy with AUC of 0.685 and 0.775 for cases with microalbuminuria and macroalbuminuria respectively. CONCLUSION: The glycated LDL could play a significant role in predicting diabetic patients who are susceptible to develop DN among T2D patients.

Serum adipokines (adiponectin and resistin) correlation in developing gestational diabetes mellitus: pilot study.

Adiponectin and resistin are adipose tissue-derived proteins with antagonistic actions; adiponectin has insulin sensitive properties while resistin is involved in the development of insulin resistance. We analyzed adiponectin and resistin levels in gestational diabetes mellitus (GDM) women to evaluate the association of these adipokines in a very high diabetes prevalence population. An age-matched case-control study of GDM and normal pregnant women in Saudi population. We recruited 90 pregnant women at 24-32 weeks of gestation. Glucose levels (fasting, 1, 2, and 3 h) and lipid parameters (cholesterol, triglyceride, HDL cholesterol, LDL cholesterol) were measured. Serum adiponectin and resistin levels were analyzed using Randox evidence biochip analyzer. Pearson's correlation coefficient was used to determine the association of adiponectin and resistin with GDM risk factors. GDM women showed significantly low adiponectin and high resistin levels when compared with control group. Pearson's correlation analysis of adiponectin and resistin in all the subjects with various GDM risk factors showed a negative association of adiponectin (r = -0.32, p = .05) and a positive correlation of resistin (r = 0.41, p = .01) with LDL cholesterol. This study analyzes adiponectin and resistin levels together, as accumulating evidences shows that these are involved in the pathophysiology of GDM. This is going to help to determine in conjunction with traditional risk factors the incremental value of circulating adiponectin and resistin in developing GDM.

Resistin role in development of gestational diabetes mellitus.

Diabetes is estimated to be one of the major causes of deaths in most countries due to its high prevalence rate, which was 8.8% in 2015. Hyperglycemia detected during pregnancy is known as gestational diabetes mellitus and it increases the potential risk of development of Type 2 diabetes in mothers with its varying prevalence rate of 1-14% in different populations. It also leads to the higher risk of developing abnormal glucose tolerance and obesity in their child at an early age. Recent studies show that potential mediators of insulin resistance such as adipokines - adiponectin, leptin and resistin are important for glucose and lipid metabolism. Adipokines are directly involved in the regulation of insulin secretion and insulin sensitivity in the liver, muscle and adipose tissue. It is also involved in inflammation, adipose tissue accumulation, adverse fat distribution and subsequently affects glucose metabolism. This review highlights the role of resistin (an adipokine) in the development of gestational diabetes mellitus.