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.

Background: The ongoing outbreak of SARS-CoV-2 represents a significant challenge to international health. Several reports have highlighted the importance of ACE2 on the pathogenesis of COVID-19. The spike protein of SARS-CoV-2 efficiently binds to the angiotensin-converting enzyme 2 (ACE2) receptors and facilitates virus entry into the host cell. In the present study, we hypothesize that a functional insertion/deletion polymorphism-rs4646994 I/D and rs4240157 T > C in the ACE gene could be associated with SARS-CoV-2 infection and mortality. Methodology: This study included 117 consecutive COVID-19 patients and 150 age matched healthy controls (ACE2-rs4646994 I/D) and 100 age matched healthy controls with ACE2 rs4240157 T > C. We used Mutation specific PCR (MSP) for ACE2-rs4646994 I/D genotyping and amplification refractory mutation system (ARMS-PCR) for ACE2 rs4240157 T > C genotyping. Results: Results indicated that there were significant differences in the genotype distributions of ACE2-rs4646994 I/D polymorphisms (p < 0.030) and ACE2 rs4240157 T > C between COVID-19 patients and controls (p-values < 0.05). Higher frequency of DD genotype (48.71%) and D allele (0.67) was reported in COVID-19 patients than controls. Our results showed that the ACE2-DD genotype was strongly associated with increased COVID-19 severity (OR 2.37 (95%) CI = (1.19–4.70), RR = 1.39 (1.09–1.77), p < 0.013) and also a strong association was seen with ACE2-ID genotype with COVID-19 severity (OR 2.20 (95%) CI = (1.08–4.46), p < 0.020) in the codominant model. In allelic comparison, the D allele was strongly associated with COVID-19 severity (OR 1.58 (95% CI) (1.11–2.27), RR 1.21 (1.05–1.41) p < 0.010). A significant correlation of ACE2-I/D genotypes was reported with Age (p < 0.035), T2D (p < 0.0013), hypertension (p < 0.0031) and coronary artery disease (p < 0.0001). Our results indicated ACE2-DD genotype was strongly associated with increased COVID-19 mortality (OR 8.25 (95%) CI = (2.40 to 28.34), p < 0.008) and also ACE2-DD + DI genotype was strongly associated with increased COVID-19 mortality with OR 4.74 (95%) CI = (1.5214 to 14.7915), p < 0.007. A significant correlation was reported between COVID-19 patients and age matched controls (p < 0.0007). Higher frequency of heterozygosity TC (40%) followed by ACE2-CC genotype (24.78%) was reported among COVID-19 patients. Using multivariate analysis, ACE2–CT genotype was strong associated with SARS-CoV-2 severity with an OR 2.18 (95% CI) (1.92–3.99), p < 0.010 and also ACE2–CC genotype was linked with COVID-19 severity with an OR 2.66 (95% CI) (1.53–4.62), p < 0.005. A significant correlation of ACE2-T > C genotypes was reported with gender (p < 0.04), T2D (p < 0.035). ACE2-CC genotype was strongly associated with increased COVID-19 mortality OR 3.66 (95%) CI = (1.34 to 9.97), p < 0.011 and also ACE2-C allele was associated with COVID-19 mortality OR 2, 01 (1.1761–3.45), p < 0.010. Conclusions: It is concluded that ACE-DD genotype and D allele was strongly associated with increased COVID-19 patient severity. In addition, ACE I/D polymorphism were strongly associated with advanced age, diabetes and ischemic heart disease in COVID-19 patients whereas ACE-II genotype was a protective factor against the development of severe COVID-19. ACE2-DD genotype was strongly associated with increased COVID-19 mortality. Additionally, ACE2–CC and CT genotypes were strongly associated with COVID-19 severity. Therefore, our study might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.

Insulin resistance (IR) is a significant factor in the development and progression of metabolic-related diseases like dyslipidemia, T2DM, hypertension, nonalcoholic fatty liver disease, cardiovascular and cerebrovascular disorders, and cancer. The pathogenesis of IR depends on multiple factors, including age, genetic predisposition, obesity, oxidative stress, among others. Abnormalities in the insulin-signaling cascade lead to IR in the host, including insulin receptor abnormalities, internal environment disturbances, and metabolic alterations in the muscle, liver, and cellular organelles. The complex and multifaceted characteristics of insulin signaling and insulin resistance envisage their thorough and comprehensive understanding at the cellular and molecular level. Therapeutic strategies for IR include exercise, dietary interventions, and pharmacotherapy. However, there are still gaps to be addressed, and more precise biomarkers for associated chronic diseases and lifestyle interventions are needed. Understanding these pathways is essential for developing effective treatments for IR, reducing healthcare costs, and improving quality of patient life.

Background: Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in developing nations. The high prevalence of obesity and related diabetes cases are attributed to rapid economic progress, physical inactivity, the consumption of high-calorie foods, and changing lifestyles. Objectives: We investigated the roles of pro-inflammatory chemokines CCL1, 2, 4, and 5 in T2DM with varying levels of obesity in the Asir region of Saudi Arabia. Materials and Methods: In total, 170 confirmed T2DM subjects and a normal control group were enrolled. Demographic data, serum levels of CCL-1, 2, 4, and 5, and biochemical indices were assessed in the subjects and control groups by standard procedures. Results: T2DM subjects were divided into four groups: A (normal body weight), B (overweight), C (obese), and D (highly obese). We observed that male and female control subjects had similar mean serum concentrations of pro-inflammatory chemokines CCL-1, 2, 4, and 5. T2DM subjects in all the four groups showed significantly higher levels of all the four chemokines compared to the controls, regardless of gender. In T2DM subjects with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL-1, 2, and 4 in T2DM subjects with increasing BMI. Serum CCL5 levels increased significantly in all T2DM subject groups. The increase in CCL5 was more predominant in normal-weight people, compared to overweight and obese T2DM subjects. Conclusions: Male and female control subjects had similar serum levels of pro-inflammatory chemokines CCL-1, 2, 4, and 5. The progressive rise in blood concentrations of three pro-inflammatory chemokines CCL-1, 2, and 4 in T2DM subjects with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM subject groups. The selective and more pronounced increase in CCL5 in the T2DM group with normal BMI, compared to subjects with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 underexpression in overweight and obese T2DM subjects is due to some unexplained counterbalancing processes.

Insulin resistance (IR) is a significant factor in the development and progression of metabolic-related diseases like dyslipidemia, T2DM, hypertension, nonalcoholic fatty liver disease, cardiovascular and cerebrovascular disorders and cancer. The pathogenesis of IR depends on multiple factors including age, genetic predisposition, obesity, oxidative stress and other factors. Abnormalities in the insulin signaling cascade lead to IR in the host, including insulin receptor abnormalities, internal environment disturbances, and metabolic alterations in the muscle, liver and cellular organelles. The complex and multifaceted characteristics of insulin signaling and insulin resistance envisage its thorough and comprehensive understanding at the cellular and molecular level. Therapeutic strategies for IR include exercise, dietary interventions and pharmacotherapy. However, there are still gaps to be addressed, and more precise biomarkers for associated chronic diseases and lifestyle interventions are needed. Understanding these pathways is essential for developing effective treatments for IR, reducing healthcare costs and improving quality of patient life.

Diabetes mellitus constitutes a big challenge to the global health care system due to its socioeconomic impacts and very serious complications. The incidence and the prevalence rate are increased in the Gulf region including the KSA. Type 2 diabetes mellitus (T2DM) is caused by diverse risk factors including obesity, unhealthy dietary habits, physical inactivity, smoking and genetic factors. The molecular genetic studies have helped in the detection of many single nucleotide polymorphisms (SNP) with different diseases including cancers, cardiovascular diseases and T2DM. The glyoxalase 1 (GLO1) is a detoxifying enzyme and catalyzes the elimination of the cytotoxic product methylglyoxal (MG) by converting it to D-lactate, which is not toxic to tissues. MG accumulation is associated with the pathogenesis of different diseases including T2DM. In this study, we have investigated the association of the glyoxalase 1 SNPs (rs2736654) rs4746 C>A and rs1130534 T>A with T2DM using the amplification refractory mutation system PCR. We also measured the concentration of MG by ELISA in T2DM patients and matched heathy controls. Results show that the CA genotype of the GLO rs4647 A>C was associated with T2DM with OR = 2.57, p-value 0.0008 and the C allele was also associated with increased risk to T2DM with OR = 2.24, p-value = 0.0001. It was also observed that AT genotype of the rs1130534 was associated with decreased susceptibility to T2DM with OR = 0.3, p-value = 0.02. The A allele of rs1130534 was also associated with reduced risk to T2DM with PR = 0.27 = 0.006. In addition, our ELISA results demonstrate significantly increased MG concentrations in serum of the T2DM patients. We conclude that the GLO1 SNP may be associated with decreased enzyme activity and a resultant susceptibility to T2DM. Further well-designed studies in different and large patient populations are recommended to verify these findings.