Abdullah Bennakhi

Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation

BackgroundExpression profile of the toll like receptors (TLRs) on PBMCs is central to the regulation of proinflammatory markers. An imbalance in the TLRs expression may lead to several types of inflammatory disorders. Furthermore, the dynamic regulation of inflammatory activity and associated impaired production of cytokines by peripheral blood mononuclear cells (PBMCs) in obese individulas remain poorly understood. Therefore, we determined the perturbation in TLRs (TLR2 and TLR4), their adaptor proteins (MyD88, IRAK1 and TRAF6) expression in PBMCs/subcutaneous adipose tissue (AT) as well as inflammatory cytokines changes in obese individuals.MethodsmRNA expression levels of TLR2, TLR4, IL-6, TNF-α and adaptor proteins were determined by RT-PCR. TLR2, TLR4 and adaptor proteins expression in AT was determined by immunohistochemistry.ResultsObese and overweight individuals showed significantly increased expression of TLR2, TLR4 and MyD88 in both PBMCs and AT as compared with lean individuals (P < 0.05). Interestingly, we found a remarkably higher expression of TLRs in obese and overweight individuals with type 2 diabetes (P < 0.05). Increased expression of TLR2, TLR4, MyD88 and IRAK1 correlated with body mass index (BMI) (TLR2: r = 0.91; TLR4: r = 0.88, P <0.0001; MyD88: r = 0.95, P < 0.0001; IRAK1 r = 0.78, P < 0.002). TLRs’ expression was also correlated with fasting blood glucose (FBG) (TLR2: r = 0.61, P < 0.002; TLR4: r = 0.52, P < 0.01) and glycated haemoglobin (HbA1c) ( TLR2: r = 0.44, P <0.03; TLR4: r = 0.48, P < 0.03). Transcript levels of IL-6 and TNF-α were highly elevated in obese subjects compared to lean subjects. There was a strong association of TLRs’ expression in PBMCs with TNF-α (TLR2: r = 0.92; TLR4: r = 0.92; P < 0.0001) and IL-6 (TLR2: r = 0.91, P < 0.0001; TLR4: r = 0.81; P < 0.001). Similarly adaptor proteins were significantly correlated with TNF-α (MyD88: r = 0.9, P < 0.0001; IRAK1: r = 0.86; P < 0.0002) and IL-6 (MyD88: r = 0.91, P < 0.0001; IRAK1: 0.77; P < 0.002).ConclusionsTLRs and adapter proteins were overexpressed in PBMCs from obese subjects, which correlated with increased expression of TNF-α and IL-6. This association may explain a potential pathophysiological link between obesity and inflammation leading to insulin resistance.

Risk factors for the development of diabetes mellitus in chronic hepatitis C virus genotype 4 infection.

Background and Aim:  A high occurrence of type 2 diabetes (T2D) in patients with chronic hepatitis C virus (HCV) infection has been reported in Kuwait and other countries. However, HCV genotype 4 has been underrepresented in all previous studies. Our aim was to investigate the viral and host risk factors associated with the development of T2D in patients with chronic hepatitis C genotype 4 infection in the absence of liver fibrosis and steatosis.

Vitamin D insufficiency in Arabs and South Asians positively associates with polymorphisms in GC and CYP2R1 genes.

Background A number of genetic studies have reported an association between vitamin D related genes such as group-specific component gene (GC), Cytochrome P450, family 2, subfamily R, polypeptide 1 (CYP2R1) and 7-dehydrocholesterol reductase/nicotinamide-adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) and serum levels of the active form of Vitamin D, 25 (OH) D among African Americans, Caucasians, and Chinese. Little is known about how genetic variations associate with, or contribute to, 25(OH)D levels in Arabs populations. Methods Allele frequencies of 18 SNPs derived from CYP2R1, GC, and DHCR7/NADSYN1 genes in 1549 individuals (Arabs, South Asians, and Southeast Asians living in Kuwait) were determined using real time genotyping assays. Serum levels of 25(OH)D were measured using chemiluminescence immunoassay. Results GC gene polymorphisms (rs17467825, rs3755967, rs2282679, rs7041 and rs2298850) were found to be associated with 25(OH)D serum levels in Arabs and South Asians. Two of the CYP2R1 SNPs (rs10500804 and rs12794714) and one of GC SNPs (rs1155563) were found to be significantly associated with 25(OH)D serum levels only in people of Arab origin. Across all three ethnicities none of the SNPs of DHCR7/NADSYN1 were associated with serum 25(OH)D levels and none of the 18 SNPs were significantly associated with serum 25(OH)D levels in people from South East Asia. Conclusion Our data show for the first time significant association between the GC (rs2282679 and rs7041), CYP2R1 (rs10741657) SNPs and 25(OH)D levels. This supports their roles in vitamin D Insufficiency in Arab and South Asian populations respectively. Interestingly, two of the CYP2R1 SNPs (rs10500804 and rs12794714) and one GC SNP (rs1155563) were found to correlate with vitamin D in Arab population exclusively signifying their importance in this population.

Diabetes and Ramadan: Practical Guidelines

Ramadan fasting is one of the five pillars of Islam and is compulsory for all healthy Muslims from puberty onwards. Exemptions exist for people with serious medical conditions, including many with diabetes, but a large number will participate, often against medical advice. Ensuring the optimal care of these patients during Ramadan is crucial. The International Diabetes Federation (IDF) and Diabetes and Ramadan (DAR) International Alliance have come together to deliver comprehensive guidelines on this subject. The key areas covered include epidemiology, the physiology of fasting, risk stratification, nutrition advice and medication adjustment. The IDF-DAR Practical Guidelines should enhance knowledge surrounding the issue of diabetes and Ramadan fasting, thereby empowering healthcare professionals to give the most up-to-date advice and the best possible support to their patients during Ramadan.

IL-33 is negatively associated with the BMI and confers a protective lipid/metabolic profile in non-diabetic but not diabetic subjects

ObjectiveRecent studies have demonstrated a protective role for IL-33 against obesity-associated inflammation, atherosclerosis and metabolic abnormalities. IL-33 promotes the production of T helper type 2 (Th2) cytokines, polarizes macrophages towards a protective alternatively activated phenotype, reduces lipid storage and decreases the expression of genes associated with lipid metabolism and adipogenesis. Our objective was to determine the level of serum IL-33 in non-diabetic and diabetic subjects, and to correlate these levels with clinical (BMI and body weight) and metabolic (serum lipids and HbA1c) parameters.MethodsThe level of IL-33 was measured in the serum of lean, overweight and obese non-diabetic and diabetic subjects, and then correlated with clinical and metabolic parameters.ResultsNon-lean subjects had significantly (P = 0.01) lower levels of IL-33 compared to lean controls. IL-33 was negatively correlated with the BMI and body weight in lean and overweight, but not obese (non-diabetic and diabetic), subjects. IL-33 is associated with protective lipid profiles, and is negatively correlated with HbA1c, in non-diabetic (lean, overweight and obese) but not diabetic subjects.ConclusionsOur data support previous findings showing a protective role for IL-33 against adiposity and atherosclerosis, and further suggest that reduced levels of IL-33 may put certain individuals at increased risk of developing atherosclerosis and insulin resistance. Therefore, IL-33 may serve as a novel marker to predict those who may be at increased risk of developing atherosclerosis.

Hepatitis C virus infection in a population with high incidence of type 2 diabetes: Impact on diabetes complications

A growing number of reports suggest a connection between hepatitis C virus (HCV) infection and type 2 diabetes (T2D). However, the association of HCV infection with diabetes-related complications has not yet been clarified. The aim of this study was to determine the prevalence of HCV infection in T2D-patients in Kuwait which has a high incidence of type 2 diabetes, and to investigate the association between HCV viremia and diabetes-related complications. A total of 438 patients with T2D (325 Kuwaitis and 113 Egyptians), and 440 control subjects, were enrolled for this study. HCV infection was assessed by testing for serum HCV-specific antibodies, and by detection of HCV RNA. HCV viral load and hemoglobin A1c (HbA1c) levels were assessed in patients with and without diabetes complications. Thirty one (7%) out of 438 T2D-patients had evidence of HCV infection compared to 4 (1%) out of 440 control adults (p<0.0001). The prevalence of HCV infection in Kuwaiti and Egyptian T2D-patients was 3% and 18%, respectively. Most of the HCV sequences detected in T2D patients and control subjects were of genotype 4. The HbA1c levels in T2D-patients with HCV viremia were significantly higher than those in HCV-negative patients. HCV viremia, female sex, age, family history of diabetes were found to be independent risk factors for diabetes complications. The results suggest that T2D-patients in Kuwait have higher prevalence of HCV infection than controls, and that HCV viremia is associated with diabetes-related complications.

Diabetes and associated cardiovascular risk factors in the State of Kuwait: the first national survey

Background:  Cardiovascular diseases (CVD) are the leading cause of mortality worldwide as well as in Kuwait. People with diabetes have two to five times greater risk of developing CVD as compared with non‐diabetic individuals. To date, little information exists on the prevalence and characteristics of cardiovascular risk factors in Kuwait. The objective of this survey was to address the growing burden of diabetes and related cardiovascular risk factors, and to estimate, for the first time, the prevalence of cardiovascular risk factors in the State of Kuwait.

Prevalence of childhood obesity in the state of Kuwait.

Overweight and obesity have reached an epidemic in Kuwait, with the highest rate of adult obesity in the region. National estimates of childhood obesity in Kuwait are scarce. The purpose of this study is to evaluate the prevalence of overweight and obesity among school children in Kuwait.

Cardiovascular disease risk factors in the South Asian population living in Kuwait: A cross-sectional study

High rates of diabetes and cardiovascular disease have been reported in South Asian immigrants in many countries. However, the prevalence and characteristics of cardiovascular disease risk factors among a South Asian population living in Kuwait have not yet been investigated. This study was therefore designed to estimate the prevalence of cardiovascular disease risk factors and determine whether they are independently associated with diabetes in such a population.

Gender Differences in Ghrelin Association with Cardiometabolic Risk Factors in Arab Population

Ghrelin is a stomach produced hormone that has been shown to have protective role against development of CVD which is a leading cause of death in the Arab world. The objective of this study is to examine the gender difference in association between traditional CVD risk factors and plasma ghrelin among Arabs. 359 Arab residents in Kuwait participated in a cross-sectional survey (≥20 years old): 191 were females and 168 were males. Plasma level of ghrelin was assessed using Luminex-based assay. Ghrelin levels were significantly higher in females (935 ± 78 pg/mL) than males (763 ± 65 pg/mL) (P = 0.0007). Females showed inverse association with WC (r = −0.23, P = 0.001) and HbA1C (r = −0.19, P = 0.0102) as well as SBP (r = −0.15, P = 0.0383) and DBP (r = −0.16, P = 0.0230), respectively. Higher levels of ghrelin were shown to associate with increased insulin resistance, as measured by HOMAIR, in male Arab subjects (P-trend = 0.0202) but not in females. In this study we show that higher ghrelin level was negatively associated with measures of obesity, HbA1C, and blood pressure in females and positively associated with increased insulin resistance in Arab males.