Background: Sedentary lifestyles, urbanization and improvements in socio-economic status have had serious effects on the burden of diabetes across the world. Diabetes is one of the 10 leading causes of death globally, and individuals with diabetes have a 2–3-fold increased risk of all-cause mortality. Adipose tissue is increasingly understood as a highly active endocrine gland that secretes many biologically active substances, including adipocytokines. However, the exact and discrete pathophysiological links between obesity and T2DM are not yet fully elucidated. Methods: In the current study, we present the association of five diverse adipocytokines, adiponectin, leptin, resistin, visfatin and chemerin, with T2DM in 87 patients (46 males and 41 females) with type 2 diabetes mellitus and 85 healthy controls (44 males and 41 females) from the Asir region of Saudi Arabia. The patients were divided into four groups: normal BMI, overweight, obese and severely obese. The baseline biochemical characteristics, including HbA1c and anthropometric lipid indices, such as BMI and waist–hip ratio, were determined by standard procedures, whereas the selected adipokine levels were assayed by ELISA. Results: The results showed significantly decreased levels of adiponectin in the T2DM patients compared to the control group, and the decrease was more pronounced in obese and severely obese T2DM patients. Serum leptin levels were significantly higher in the females compared to the males in the controls as well as all the four groups of T2DM patients. In the male T2DM patients, a progressive increase was observed in the leptin levels as the BMI increased, although these only reached significantly altered levels in the obese and severely obese patients. The serum leptin levels were significantly higher in the severely obese female patients compared to the controls, patients with normal BMI, and overweight patients. The leptin/adiponectin ratio was significantly higher in the obese and severely obese patients compared to the controls, patients with normal BMI, and overweight patients in both genders. The serum resistin levels did not show any significant differences between the males and females in thr controls or in the T2DM groups, irrespective of the BMI status of the T2DM patients. The visfatin levels did not reveal any significant gender-based differences, but significantly higher levels of visfatin were observed in the T2DM patients, irrespective of their level of obesity, although the higher values were observed in the obese and highly obese patients. Similarly, the serum chemerin levels in the controls, as well as in T2DM patients, did not show any significant gender-based differences. However, in the T2DM patients, the chemerin levels showed a progressive increase, with the increase in BMI reaching highly significant levels in the obese and severely obese patients, respectively. Conclusion: In summary, it is concluded that significantly altered concentrations of four adipokines, adiponectin, leptin, visfatin and chemerin, were found in the T2DM patient group compared to the controls, with more pronounced alterations observed in the obese and highly obese patients. Thus, it can be surmised that these four adipokines play a profound role in the onset, progression and associated complications of T2DM. In view of the relatively small sample size in our study, future prospective studies are needed on a large sample size to explore the in-depth relationship between adipokines and T2DM.

/pdf/differential-association-of-selected-adipocytokines-29e897sy.pdf

Differential Association of Selected Adipocytokines, Adiponectin, Leptin, Resistin, Visfatin and Chemerin, with the Pathogenesis and Progression of Type 2 Diabetes Mellitus (T2DM) in the Asir Region of Saudi Arabia: A Case Control Study

Recent reports indicate that the hypoxia-induced factor (HIF1α) and the Warburg effect play an initiating role in glucotoxicity, which underlies disorders in metabolic diseases. WWOX has been identified as a HIF1α regulator. WWOX downregulation leads to an increased expression of HIF1α target genes encoding glucose transporters and glycolysis’ enzymes. It has been proven in the normoglycemic mice cells and in gestational diabetes patients. The aim of the study was to determine WWOX’s role in glucose metabolism regulation in hyperglycemia and hypoxia to confirm its importance in the development of metabolic disorders. For this purpose, the WWOX gene was silenced in human normal fibroblasts, and then cells were cultured under different sugar and oxygen levels. Thereafter, it was investigated how WWOX silencing alters the genes and proteins expression profile of glucose transporters and glycolysis pathway enzymes, and their activity. In normoxia normoglycemia, higher glycolysis genes expression, their activity, and the lactate concentration were observed in WWOX KO fibroblasts in comparison to control cells. In normoxia hyperglycemia, it was observed a decrease of insulin-dependent glucose uptake and a further increase of lactate. It likely intensifies hyperglycemia condition, which deepen the glucose toxic effect. Then, in hypoxia hyperglycemia, WWOX KO caused weaker glucose uptake and elevated lactate production. In conclusion, the WWOX/HIF1A axis downregulation alters glucose metabolism and probably predispose to metabolic disorders.

/pdf/the-wwox-hif1a-axis-downregulation-alters-glucose-metabolism-14va9wfh.pdf

The WWOX/HIF1A Axis Downregulation Alters Glucose Metabolism and Predispose to Metabolic Disorders

Pro-inflammatory adipokines have a multifunctional role in adipogenesis, angiogenesis, glucose homeostasis, and inflammation. The aim of the present study is to evaluate the effect of running a 100 km ultra-marathon on serum levels of two adipokines: resistin and chemerin. Fifteen male participants complete a medical questionnaire and their body composition is assessed. Serum resistin, chemerin, high sensitivity C-reactive protein (hs-CRP), glucose, and lactate levels are measured at baseline and post-race. During-race data on fluid and food consumption and energy expenditure are calculated. There is a higher (p < 0.001) post-race concentration of resistin and hs-CRP compared with resting values, with no change in chemerin levels. There is an inverse correlation of the change in resistin levels with post-run glucose values (r = 0.742, p < 0.001) and a positive correlation between changes in hs-CRP and energy expenditure (r = 0.782, p < 0.001). The present results show the impact of running an ultra-marathon on serum levels of pro-inflammatory markers released by adipose tissue. It is difficult to establish whether these results may be due to the stress of exercise, high energy expenditure or caloric deficit. However, we suggest that an addition of resistin to traditional pro-inflammatory markers (including CRP) may improve the assessment of inflammation in conditions of high-energy expenditure.

The Effect of the Ultra-Marathon Run at a Distance of 100 Kilometers on the Concentration of Selected Adipokines in Adult Men.

Objective Hyperglycemia and insulin resistance (IR) put obese women with Type 2 diabetes mellitus (T2DM) at risk for cardiovascular disease (CVD). Methods 150 T2DM women aged 30–45 were studied cross-sectionally at Madinah Hospital lab to find T2DM risk factors and their association with adiponectin/leptin levels. Results Women with T2DM showed greater fasting blood glucose (FBG), hemoglobin A1c (HbA1c), triglycerides (TG), body mass index (BMI), waist circumference (WC), insulin resistance (IR), high-sensitivity C-reactive protein (hs-CRP), and CVD risk (high atherogenic index of plasma (AIP) and leptin), but decreased high-density lipoprotein (HDL-cholesterol) and poor insulin sensitivity with low adiponectin. Obese women with T2DM had increased leptin and reduced adiponectin. Leptin levels were significantly related to IR, BMI, and AIP (B= 3.97, P= 0.02) but not WC. Leptin levels were negatively correlated with insulin sensitivity (IS) and HDL-c (P< 0.05). In linear regression analysis, adiponectin levels had a significant association with IS and HDL-c (P= 0.03, P= 0.04) but an inverse relationship with IR, BMI, WC (B=−2.91, P= 0.04), and AIP (P< 0.05). Conclusion Increased leptin levels are related to high IR, AIP, and BMI among T2DM female patients. Similarly, adiponectin levels decrease IS and HDL-c. Therefore, obese T2DM women with high leptin and low adiponectin levels should be periodically checked to avoid or decrease consequences like CVD.

https://www.dovepress.com/getfile.php?fileID=91136

Association of Serum Leptin and Adiponectin Concentrations with Type 2 Diabetes Biomarkers and Complications Among Saudi Women

PURPOSE
To investigate serum leptin levels in patients with type 2 diabetes mellitus (T2DM) and the relationship between leptin levels and T2DM complications and prevalence.


METHODS
A total of 355 patients, 282 cases with T2DM and 73 normal controls, were recruited at 1st Medical Centre, Chinese PLA General Hospital (Beijing, China) between November 2013 and July 2014. Levels of serum leptin, biochemical markers and sexual hormones were measured, and clinical characteristics were retrieved through the electronic medical record system.


RESULTS
Leptin levels in females were higher than that in males. Leptin levels in T2MD patients were positively correlated with body mass index, percent body fat, triglyceride, cystatin C homocysteine and salivary acid, and negatively correlated with glycosylated serum protein and glycosylated albumin levels. Leptin levels in males were positively correlated with systolic pressure and estradiol, and negatively correlated with testosterone and high density lipoprotein cholesterol. Sex (female) was positively correlated with the duration of disease. Leptin levels in T2DM patients with complications such as hypertension, diabetic nephropathy, diabetic peripheral neuropathy and coronary heart disease were higher than that in patients without such complications. Leptin levels in females with diabetic retinopathy and diabetic macroangiopathy were higher than that in patients without such complications, but there was no difference in males.


CONCLUSIONS
Leptin has significant gender differences. Leptin levels are related to body mass index, percent body fat and sex hormone level in T2DM patients and may affect short-term blood glucose control in T2DM patients. Leptin levels are related to complications in patients with T2DM and affect the prevalence rates of complications.

/pdf/effect-of-leptin-levels-of-type-2-diabetes-mellitus-and-rojge1rf.pdf

Effect of Leptin Levels of Type 2 Diabetes Mellitus and Diabetic Complications.

ObjectiveTo investigate the relationships among serum resistin, adiponectin, and leptin and microvascular complications in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 120 patien...

https://journals.sagepub.com/doi/pdf/10.1177/0300060519870407

Relationships among resistin, adiponectin, and leptin and microvascular complications in patients with type 2 diabetes mellitus.

Diabetes remains a long standing public health issue among the Chinese population, with an incidence of up to 11.6%, of which type 2 diabetes mellitus (T2DM) accounts for 85%–95%. During this study, we aimed to elucidate the value of high-frequency ultrasonography (HFUS) combined with serum resistin on vascular remodeling (VR) in carotid atherosclerosis (CA) among patients suffering from T2DM. A total of 432 T2DM were recruited and assigned into the short T2DM duration group ( 10 years), while another 172 healthy cases were recruited as the control group. The intima-media thickness (IMT) as well as plaque score, detection rate and type were detected by the HFUS. The respective blood pressure readings were measured and pulse pressure was calculated accordingly. The serum resistin level, remodeling incidence and type, levels of total cholesterol (TC), fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), high-density liproprotein cholesterol (HDL-C), and triglyceride (TG) were measured. The correlation between IMT, the plaque detection rate and blood pressure were analyzed. A receiver operating characteristic (ROC) curve was constructed in order to evaluate the impact of VR in CA on T2DM patients who were solely using HFUS and serum resistin respectively, as well as a combination of HFUS with serum resistin. As In comparison with the control group, the short, middle and long T2DM duration groups all displayed increased IMT, plaque score and detection rate, serum resistin level and VR incidence, especially for the long T2DM duration group. Levels of TC, TG, FBG and LDL-C were much higher while HDL-C was lower among patients with T2DM than those in the control group. A positive correlation was detected between the disease course and IMT. The detection rate of plaque with thickening IMT exhibited upregulated levels when compared to those with normal IMT. The HFUS, serum resistin and HFUS combined with serum resistin respective areas under the ROC curve were 0.873, 0.867 and 0.923, respectively, suggesting that the combination of HFUS and serum resistin was superior to that of individual HFUS or individual serum resistin in regard to the impact of VR in CA on T2DM patients. The results of this study revealed that the combination of HFUS and serum resistin was superior to individual HFUS or individual serum resistin in relation to its ability to evaluate the impact of VR in CA in patients with T2DM.

Evaluation of Vascular Remodeling in Carotid Atherosclerosis Among Type 2 Diabetes Mellitus Patients Using High-Frequency Ultrasonography Combined with Serum Resistin.

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Papers

Relationships among resistin, adiponectin, and leptin and microvascular complications in patients with type 2 diabetes mellitus.

Evaluation of Vascular Remodeling in Carotid Atherosclerosis Among Type 2 Diabetes Mellitus Patients Using High-Frequency Ultrasonography Combined with Serum Resistin.