Kuwaiti Patients Research Articles

Shortening of the leucocytes’ telomeres length in T2DM independent of age and telomerase activity

This study aimed to examine the role of plasma telomerase (TE), plasma insulin, patient's age and disease duration in determination of the leucocytes' telomeres length (LTL) in T2DM. Blood samples from Kuwaiti patients with T2DM (110) and non-diabetic subjects (94) were analyzed by SYBR Green Quantitative PCR for estimation of the Absolute Human Telomere Length and by ELISA for estimation of the TE activity and insulin level. The body mass index (BMI) and HOMA-IR were calculated. The results revealed marked shortening of the LTL in T2DM compared with the non-diabetic subjects (6.068, 2.276-11.652 vs. 10.979, 6.495-23.402kb), p < 0.001, while the TE concentration was comparable between the two groups (3.16, 0.00-6.02 vs. 4.16, 1.38-7.94 U/L, respectively), p 0.100. Importantly, in T2DM the LTL did not vary significantly with the disease duration (1month to 40years), p 0.959, and did not correlate with age, BMI, insulin-resistance, or glycemic parameters. Interestingly, there was a positive correlation between the LTL and insulin levels in T2DM (CC 0.211, p 0.0419). Finally, in non-diabetic subjects, HbA1c ≥ 6% was associated significantly with shorter LTL, this observation together with the lack of association of the LTL with the disease duration, suggests a causal role of short telomeres in T2DM development. This study confirmed the LTL shortening in T2DM in Kuwaiti Arabs, and showed that the LTL was independent of age and TE activity but positively influenced by insulin levels. Furthermore, the study suggested that telomeres shortening could be a risk factor for T2DM.

Medical Tourism Overseas: A Challenge to Kuwait’s Healthcare System

Introduction: The State of Kuwait spends large sums of governmental funds on sending patients abroad to receive medical treatment. This study aimed to explain the rationale behind receiving primary medical care overseas, given the expense and inconvenience, from the perspective of Kuwaiti patients whose applications were approved. Methods: The survey was designed based on recommendations from an expert panel of physicians working in Kuwait and aimed to give insight into outbound medical services as perceived by the Kuwaiti population. Using Google Forms, the survey was sent electronically to 1067 patients who received treatment abroad sponsored by the government in the year 2018, and 590 responses were returned. The study itself explored reasons for seeking treatment abroad, finances, preferred countries, and whether there were touristic reasons behind such practice. Data was analyzed using SPSS version 26. Results: Overall, males (52.3%) and females (47.7%) were equally represented in the study sample. The mean age for the study sample was 41±13.4 years. Approximately 45.3% of the respondents were married and had children. Of the remaining respondents, 21.9% were married with no children and 23.8% were single without children. All respondents received medical treatment abroad, and 52.3% of the married respondents and 47.7% of the single respondents stated that they received treatment once and more than once, respectively. Conclusion: Most Kuwaiti citizens do not have faith in the Kuwaiti medical system. Therefore, heavy investments are needed to send patients abroad.

Prevalence and Risk of Polypharmacy among Community-Dwelling, Elderly Kuwaiti Patients

Objectives: To estimate the prevalence of polypharmacy in community-dwelling, older Kuwaiti patients, describe the number and types of drugs used, and identify risk factors associated with polypharmacy. Subjects and Methods: This was a descriptive cross-sectional questionnaire-based survey in which we interviewed 500 community-dwelling Kuwaiti adults over 65 years of age. The data collection occurred during a 4-month period from March to July 2017. Results: Fifty-two percent (n = 260) of the patients were males, with a mean age of 71.73 ± 5.32 years. The prevalence of polypharmacy (5–8 drugs) and excessive polypharmacy (>8 drugs) was 58.4% (n = 292) and 10.2% (n = 51), respectively. The risk factors associated with an increased number of medicines used were: female gender (p = 0.019), a lower level of education (p = 0.003), a high number of hospital admissions (p = 0.000), clinics visited by the patient (p =0.000), and number of comorbidities (p = 0.000). The most commonly used medications (82.6% of the study population) were blood glucose-lowering agents, excluding insulin. Other commonly used medications were antihypertensive drugs and lipid-modifying agents. Conclusion: A significant sector of the older Kuwaiti patient population has a high prevalence of polypharmacy and is thus exposed to its potential hazards. The current study highlights the need to revise the drug-dispensing policy among community-dwelling, older Kuwaiti people, as well as to initiate educational programs among healthcare practitioners concerning prescribing issues in older individuals.

Cancer Survival by Stage at Diagnosis in Kuwait: A Population-Based Study.

Objective To examine the distribution of stage at diagnosis for 12 cancers in Kuwait, to estimate stage-specific net survival at 1 and 5 years after diagnosis, and to assess differences in stage-specific survival between Kuwait and the United States. Material and Methods Data were obtained from the Kuwait Cancer Registry, for Kuwaiti patients diagnosed during 2000–2013, with follow-up to 31 December 2015. The distribution of Surveillance Epidemiology and End Results (SEER) Summary Stage for 12 malignancies was examined. We estimated net survival by stage up to 5 years after diagnosis, controlling for background mortality with life tables of all-cause mortality in the general population by single year of age, sex, and calendar period. Survival estimates were age-standardised using the International Cancer Survival Standard (ICSS) weights. Results Only 14.2% of patients were diagnosed at a localised stage and 38.9% at the regional stage. The proportion of patients with known stage was 88.9% during 2000–2004 but fell to 59.4% during 2010–2013. During 2005–2009, 1- and 5-year survival for colon, rectal, breast, cervical, and prostate cancer was about 90% or higher for patients diagnosed at the localised stage. During 2004–2009, the proportion of patients diagnosed at a localised stage was lower in Kuwait than in the US for colon, breast, and lung cancer. Age-standardised 5-year net survival for all stages combined was lower in Kuwait than the US for colon, lung, and breast cancer, but stage-specific survival was similar. Conclusion Since stage-specific survival is similar in Kuwait and the US, late stage at diagnosis is likely to be a major contributing factor to the overall lower survival in Kuwait than in the US. Increasing public awareness of cancer risk factors and symptoms and investment in early detection will be vital to reduce the proportion of patients diagnosed at a late stage and to improve survival.

Factors associated with quality-of-life among Kuwaiti patients on maintenance hemodialysis

ABSTRACTMeasuring Quality-of-life (QOL) and determining its correlates for hemodialysis (HD) patients is important for interventions’ design and clinical decision-making. Three hundred and thirty-six patients with end-stage-renal-disease (ESRD) from six centers provided data using SF-36. Descriptive analysis of QOL was conducted and linear regression was used to model the relationship between QOL and several covariates.Patients have mean (SD) age 55.3 (13.4) years, mainly females (56.5%), between 41 and 60 years (47.9%), Married (61.6%), retired (45.5%), with income >1000 KD (51.2%). Most patients were diagnosed with ESRD ≥ one year ago (88.1%), have diabetes as primary cause of ESRD (38.1%), on dialysis for ≥ three years (50.0%). Significant differences in QOL were among gender (PV < 0.001), education levels (PV < 0.001), employment status (PV < 0.001), and income (PV = 0.003). Being male (PV = 0.047), employed (PV = 0.098) were associated with increase in QOL. Patients with income <500 KD (PV = 0.061), diagnosed with ESRD during last 6–12 months (PV = 0.049) were associated with decrease in QOL after adjusting for other covariates.In conclusion, QOL is worse among females, unemployed, those with income <500 KD, and those diagnosed with ESRD between 6 and 12 months. Interventions for patients with worse QOL will reduce hospitalizations, risk of cardiovascular events and other co-morbidities.

The Sub-Phenotypes of Sickle Cell Disease in Kuwait

Kuwaiti patients with sickle cell disease generally have a mild phenotype, but exhibit considerable heterogeneity, in spite of high Hb F levels. We have carried out a cross-sectional study of patients with sickle cell disease in the five major hospitals in Kuwait. Details of their hemoglobin (Hb) genotypes, clinical presentations and complications are presented. The study was over a span of 3 years and involved 396 patients, made up of 351 (88.6%) Kuwaitis and 45 (11.4%) expatriates. They were aged <1 to 73 years. Hb SS (βS/βS) was the most common (in 246 patients, i.e. 62.1%) followed by Hb S (HBB: c.20A>T)-β-thalassemia (Hb S-β-thal) in 138 (34.8%) and 11 (2.8%) Hb S/Hb D-Punjab (HBB: c.364G>C). Hb F ranged from 1.0 to 55.0%, with a mean of 21.2 ± 9.8%. The most common presentation was vaso-occlusive crises (VOCs), with 230 (54.8%) having had at least one prior to the study with 54 (13.2%) and 74 (18.9%) having between 2-3 and >3 VOCs, respectively. Hydroxyurea (HU) was prescribed to 157 (39.6%) patients. The most common complication was gallstones in 131 (33.1%), followed by acute splenic sequestration in 26.8% and avascular necrosis of the femoral head in 21.2% patients, respectively. Stroke, priapism and leg ulcers were rare. Gallstones, splenic sequestration and osteonecrosis were significantly more common in patients aged >16 years. Patients with Hb S-β-thal were similar to those with Hb SS in their clinical profiles. The phenotypic expression of sickle cell disease in Kuwaitis is unique in many respects. The role(s) of Hb F and other genetic modifiers require further elucidation.

759. Molecular Characterization and Epidemiology of Multidrug-Resistant Mycobacterium tuberculosis (MDR-TB) and Identification of Possible Cases of Local Transmission of MDR-TB in Kuwait

BackgroundIncreasing incidence of multidrug-resistant tuberculosis (MDR-TB) is hampering efforts to control TB. Kuwait is a low (25/100,000) TB incidence country and ~1% of Mycobacterium tuberculosis strains are resistant to rifampin, RIF and isoniazid, INH (MDR-TB). Analysis of resistance conferring mutations in seven genes was combined with spoligotyping for detecting local transmission of MDR-TB in Kuwait.MethodsMDR-TB strains (n = 131) from 88 TB patients and 50 susceptible strains were used. Susceptibility testing was done by MGIT 960 system, gMTBDRplus assay and PCR-sequencing of three regions of rpoB, katG codon 315 (katG315) + inhA regulatory region, embB (embB306/embB406/embB497 regions), rpsL + rrs-500–900 regions and pncA for RIF, INH, ethambutol (EMB), streptomycin (SM) and pyrazinamide (PZA), respectively. Sequencing data were used to construct phylogenetic tree by MEGA7 software. Spoligotypes were identified by SITVIT2 and phylogenetic tree was made by MIRU-VNTRplus software.ResultsMutations were detected in most isolates in rpoB, katG+inhA, embB, rpsL+rrs and pncA which confer resistance to RIF, INH, EMB, SM and PZA, respectively. Phylogenetic analysis of multi-locus concatenated sequences showed unique patterns for 51 patient’s isolates while 37 patient’s isolates grouped in 14 clusters. Spoligotyping identified 35 patterns (19 unique patterns and 69 patients’s isolates in 16 patterns) including 11 orphan patterns. Sixteen isolates yielded six clusters (each containing two to five isolates) by both fingerprinting methods.ConclusionOur study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified six potential cases of local transmission of MDR-TB involving two to five subjects (including five Kuwaiti patients) which had escaped detection by routine surveillance studies. Prospective detection of resistance conferring mutations thus identifies possible cases of local transmission of MDR-TB in low TB incidence countries.Disclosures All authors: No reported disclosures.

P063Killer-cell immunoglobulin-like receptors genotypes & haplotypes among kuwaiti families

Aim Inhibitory and activating immunoglobulin like receptor (KIR) family is a major determinant of NK cells activity against cancer. Specific KIR genotypes and/or haplotypes have been reported to influence the outcomes of hematopoietic cell transplantation and in association with a number of autoimmune disorders. The repertoire of KIR genes varies within and between populations, creating a diverse pool of KIR genotypes. The aim of this study was to characterize the genotypes and haplotypes of the KIR genes among 25 Kuwaiti Arab families. Methods A total of 75 individuals from 25 Kuwaiti Arab trios families (including father, mother and a child) were enrolled in this study. KIR genotyping was performed using Real-time PCR based KIR genotyping kit (Linkage Biosciences) from peripheral blood. Sequence specific primer amplification combined with a melting curve analysis method was used to identify 14 KIR genes and 2 KIR pseudogenes including both full length and deleted forms of 3DP1 and 2DS4. Interpretation and reporting of genotype with SureTyperTM software. Results The percentage for the presence of the KIR genes was found to be: KIR2DL1 97.2%, KIR2DL2 56.3%, KIR2DL3 88.7%, KIR2DL4 100%, KIR2DL5 62%, KIR2DP1 97.2%, KIR2DS1 35.2%, KIR2DS2 56.3%, KIR2DS3 42.3%, KIR2DS4 95.8%, KIR2DS5 31%, KIR3DL1 95.8%, KIR3DL2 100%, KIR3DL3 100%, KIR3DP1 100%, KIR3DS1 36.7%. The framework genes were present in 100% for all 75 individuals. The highest frequency of 97% is in 2DP1 and 2DL1 gene and lowest frequency of 31% among KIR genes is in 2DS5. Only 32% of the tested subjects were of AA haplotype genotype, making 68% Bx haplotype genotype. Conclusions Findings of this study are crucial to characterize and compare KIR gene and haplotype frequencies with other populations and also to provide a new data on KIR genotypes and haplotypes of the Kuwaiti Arab population based on family study to understand the population’s genetic makeup. Further, majority of Kuwaiti patients have a several healthy haploidentical relatives who could potentially donate, therefore donor activating KIR-based donor selection is an area of current interest.

Diabetes Self-Management: A Key to Better Health-Related Quality of Life in Patients with Diabetes

Objective: The aims of this study were to assess health-related quality of life (HRQOL) among adult patients with diabetes attending primary health care diabetes clinics in Kuwait and to examine the factors associated with the HRQOL of patients with diabetes. Methods: This cross-sectional study was conducted among 503 patients with diabetes attending 26 primary health care diabetes clinics in Kuwait. A self- administered questionnaire on participants’ socio-demographic and clinical characteristics, in addition to the Diabetes Self-Management Questionnaire (DSMQ) to assess patients’ diabetes self-management (DSM), was used. The SF-12 was employed to assess the HRQOL, producing the following 2 outcomes: physical health composite (PHC) and mental health composite (MHC). Results: The mean age of participants was 52 ± 0.8 years, and 53.1% were males and 49.0% were Kuwaitis. The median DSM sum score was 6.5. Male patients with diabetes showed a significantly better median DSM sum score than female patients with diabetes. The overall median score of HRQOL was 61.7/100, with a better median PHC versus MHC score of quality of life (66.7/100 and 56.7/100, respectively). Multivariate analysis revealed a significant direct association between DSM and better primary health composite and MHC scores. It also showed that female gender and reporting 2 or more diabetic complications were significantly associated with a poor PHC. Conclusions: Kuwaiti patients with diabetes showed a modest level of HRQOL. Patients’ DSM, gender, and diabetes complications were significant independent correlates to HRQOL. Appraisal of the HRQOL of patients with diabetes as an essential component of diabetes management in clinical settings is suggested. Further studies to examine the impact of good DSM on HRQOL improvement are needed.

The Prevalence of Smoking among Sample of Kuwait Asthmatics and Its Impact on the Response of the Treatment

Background: Bronchial asthma is one of the most common diseases in Kuwait. Smoking also is on the rise in Kuwait. We therefore conducted this study to at prevalence of smoking among sample of Kuwaiti patients and the impact on asthma control. Methods: Descriptive study of 50 outpatients who were prospectively assessed from single center (Al-Jahra Hospital) that diagnosed recently as bronchial asthma using American Thoracic Society/European Respiratory Society (ATS/ERS) criteria definitions of asthma between the period of 1st of April and 20th may 2013. Patients were divided into two groups: Group A smokers and Group B non-smokers. Pulmonary function test using spirometer and asthma control test (ACT) was done for every patient at the time of visit and after 4 weeks to determine the effect of smoking on asthma control as a primary outcome using GINA guidelines definition for Asthma control and treatment. Results: At study entry 30% of sample size were smoker asthmatics. Smokers showed worse symptoms of wheezing, cough, and shortness of breath compared to non-smokers asthmatics whereas non-smokers asthmatics were more likely to have seasonal symptoms and use salbutamol MDI. Both groups showed similar spirometry findings at study entry. At 4 weeks from the first visit there was a significant difference in symptoms and signs of bronchial asthma between the 2 groups. Both measures of asthma control test and spirometer results favoured non-smokers. Smokers asthmatics were more likely to use rescue salbutamol MDI and non-compliant. No hospital admissions or acute exacerbations during the period of the study. Conclusion: Smoking was associated with worse asthma control and poor compliance among asthmatics.

Coronary Artery Profile of Young Kuwaiti Males on Anabolic Steroids

Background: To Study the coronary artery profile in young Kuwaiti patients who are using anabolic steroids for bodybuilding. Subjects and methods: We have done a retrospective analysis of all young Kuwaiti male patients ≤ 30 years who underwent coronary angiogram in Sabah Al Ahmed Cardiac Center, Al Amiri Hospital during the period of 2014 to 2017. Patients were categorized into two groups, group A1 consisted of patents who were anabolic steroid users, while group A2 consisted of patients who were not anabolic steroid users. Chi-square test of independence was used to compare A1 and A2. Results: We had a total of 19 male patients’ ≤ 30 years of age who underwent coronary angiogram during 2014 to 2017. We found 31.6% were on anabolic steroids. Smoking was seen as the commonest risk factor with 94.3% of overall patients. Acute coronary syndrome was established among 68.4% patients, 83.3% of the patients in group A1 while only 61.5% were in group A2 (p=0.342). Normal coronary angiograms were reported in 16.7% in A1 and 30.8% in A2 (p=0.516). Slow flow was reported in 31.6% patients overall, group A1 had 33.3% and group A2 had 30.8% (p=0.911). Left anterior descending artery (LAD) was found culprit in 26.3% and right coronary artery (RCA) was found culprit in 26.3%. Conclusion: Incidence of acute coronary syndrome associated with anabolic steroid use was 83.3%, it was contributed to by LAD and RCA lesions along with slow flow phenomenon.

The Sickle β-Thalassemia Phenotype.

Sβ-thalassemia (Sβ-thal) is common among Gulf Arab patients with sickle cell disease, but the phenotype of this group had not been well-documented. We have studied a group of Kuwaiti patients and compared the phenotype in the homozygotes (SS) and Sβ-thal patients. Complete blood count, hemoglobin quantitation, serum bilirubin, and lactate dehydrogenase were determined with standard techniques. The patients were screened for α-globin genotype. The Sβ-thal patients were also screened for the HBG2 Xmn-1 polymorphism. β-Thal mutations were determined by arrayed primer extension or direct sequencing. There were 70 SS and 32 Sβ-thal patients with mean ages of 14.8±5.9 and 14.2±5.9 years, respectively. The Sβ-thal patients had more frequent, severe pain episodes per year compared with the SS, while the patterns among Sβ-thal and Sβ-thal patients were not significantly different. There were no differences in the frequencies of acute chest syndrome, gallstones, and blood transfusion in the SS and Sβ-thal patients. However, none of the Sβ-thal patients had been transfused. Among the Sβ-thal patients, 25 had β-thal and 7 had β-thal mutations, the most common being cd39 (C→T) and IVS-I-110 (G→A), respectively. Sβ-thal shows a severe phenotype in Kuwait, even among those with Sβ-thal, in whom the IVS-I-110 (G→A) mutation is predominant.

Factors Affecting Adherence to Statins in Hypercholesterolemic Kuwaiti Patients: A Cross-Sectional Study

Objective: This study examined statin adherence amongst Kuwaiti hypercholesterolemic patients in order to identify factors associated with poor adherence and to determine whether or not an association exists between statin adherence and the risk profile of coronary heart disease (CHD). Subjects and Methods: Two hundred hypercholesterolemic patients (30-69 years of age) were recruited from Kuwaiti primary healthcare clinics and interviewed about demographic characteristics, pre-existing self-reported medical conditions and prescribed medications. The Morisky Medication Adherence Scale was used to assess statin adherence (a self-reported, medication-adherence questionnaire divided into 3 levels, with a score of 8 denoting high adherence, 6 to <8 denoting medium adherence and <6 denoting low adherence). Data regarding anthropometric, psychological and serum risk factors were collected using 2 additional questionnaires, laboratory tests and bioelectrical impedance scales. Binary logistic regression was used to determine predictors of adherence and general linear modelling was used to test relationships between continuous outcomes and statin adherence. Results: Of the 200 participants, 117 (58.5%) reported low adherence, 83 (41.5%) reported medium adherence and no patients (0%) scored high adherence. Younger patients (aged 30-50 years) had lower adherence than older patients (>50 years) [odds ratio (OR) 1.05; 95% confidence interval (CI) 1.01-1.09] for every extra year; p < 0.01). Those without diabetes, i.e. 113 (56.5%), were less likely to report medium adherence than those with diabetes (OR 0.42; 95% CI 0.23-0.75; p < 0.01). Low statin adherence was associated with higher levels of plasma cholesterol (p < 0.001) and low-density lipoprotein (p < 0.01). Conclusion: In this study, there was a high prevalence of low statin adherence, especially among younger patients with fewer concomitant diseases. The results indicated an inverse relationship between statin adherence and CHD risk profile.

Association of Genetic Polymorphisms in the VKORC1 and CYP2C9 Genes with Warfarin Dosage in a Group of Kuwaiti Individuals

Warfarin is the most widely prescribed oral anticoagulant worldwide. The narrow therapeutic index and the large variation in the inter-individual dose of warfarin are problematic, since the side effects can be lethal. Single nucleotide polymorphisms (SNP) in CYP2C9 and VKORC1 have been shown to significantly affect warfarin dosage toleration and this effect varies among different populations. We aimed to investigate the effect of these SNPs on warfarin dosage in a sample of Kuwaiti patients. Kuwaiti patients who were taking a maintenance dose of warfarin were genotyped for CYP2C9*1, *2 and *3 and VKORC1 rs9923231, rs9934438, rs7294 and rs2884737. The association of these SNPs with the warfarin dose was evaluated. For CYP2C9, the CYP2C9 *1/*1 genotype required a higher dose (5.5 ± 3.3 mg/day) compared to non-*1/*1 (3.3 ± 1.7 mg/day) (p = 0.003). For VKORC1, the daily warfarin dose was significantly different (p = 0.001) among the three genotypes of rs9923231, rs9934438 and rs2884737, with carriers of the wild-type genotype requiring the highest dose compared to variant allele carriers (p ≤ 0.001-0.002). There was no association found between the daily warfarin dose and the rs7294 polymorphism. Our data showed that individuals carrying the wild-type allele of CYP2C9 or VKORC1 rs9923231, rs9934438 or rs2884737 are less sensitive than individuals with the variant alleles of these SNPs and therefore required a higher daily maintenance dose of warfarin. Our study confirms the association between SNPs in CYP2C9 and VKORC1 and warfarin dose tolerance in Kuwaiti patients.

Vitamin D deficiency and its correlation to hemoglobin A1C in adolescent and young adult type 1 diabetes mellitus patients

Background Some studies have described the relationship between autoimmune diabetes or type 1 diabetes mellitus (T1DM) and vitamin D deficiency. Few studies correlate between vitamin D deficiency and glycemic control. Purpose This study was conducted to appraise the status of vitamin D in adolescent and young adult T1DM patients and to correlate its deficiency to glycated hemoglobin (HbA1c). Patients and methods Around 63 Kuwaiti patients with T1DM were recruited in a descriptive cross-sectional study in April 2015. Serum level of vitamin D [25(OH)D] was measured using enzyme-linked immunosorbent assay, and glycemic control was measured by HbA1c using autoanalyzer. The relationship between vitamin D levels and HbA1c was analyzed by Spearman’s correlation. Among the participants, 21 (33.3%) were male and 42 (66.7%) were female. The mean age was 18.41±6.19, and the mean diabetes duration was 6.98±4.99. The mean vitamin D concentration was 47.29±2.91 nmol/l, with 38.1% of participants identified to have vitamin D deficiency and 19% identified to have vitamin D insufficiency. There were high levels of HbA1c (10.08±2.28), with a significant inverse correlation between HbA1c and vitamin D (r=−0.374 and P=0.003). Conclusion Low vitamin D in T1DM is extremely highly and closely correlated to HbA1c. We recommend that evaluation of the level of vitamin D in type 1 diabetic patients is very critical, and vitamin D supplementation may improve glycemic control.

Association of the insertion allele of the common ACE gene polymorphism with type 2 diabetes mellitus among Kuwaiti cardiovascular disease patients

The D allele of the common angiotensin-converting enzyme (ACE) I/D gene polymorphism (rs4646994) predisposes to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). However, results on which allele predisposes to disease susceptibility remain controversial in Asian populations. This study was performed to evaluate the association of the common ACE I/D gene polymorphism with both T2DM and CVD susceptibility in an Arab population. We genotyped the ACE I/D polymorphisms by direct allele-specific PCR in 183 healthy controls and 400 CVD patients with diabetes (n=204) and without (n=196). Statistical analysis comparing between the different groups were conducted using R statistic package "SNPassoc". Two genetic models were used: the additive and co-dominant models. The I allele was found to be associated with T2DM (OR=1.84, p=0.00009) after adjusting for age, sex and body mass index. However, there was no association with CVD susceptibility (p>0.05). The ACE I allele is found to be associated with T2DM; however, no association was observed with CVD. The inconsistency between studies is suggested to be attributed to genetic diversity due to the existence of sub-populations found in Asian populations.

Barriers to medication taking among Kuwaiti patients with type 2 diabetes: a qualitative study.

BackgroundNonadherence to medications among Kuwaitis with type 2 diabetes mellitus (T2DM) is believed to be a major barrier to appropriate management of the disease. Published studies of barriers to medication adherence in T2DM suggest a Western bias, which may not adequately describe the Kuwaiti experience.AimThe purpose of this study was to explore barriers to medication adherence among Kuwaiti adults with T2DM.MethodsSemi-structured interviews were conducted with 20 Kuwaiti patients with type 2 diabetes. The interviews were digitally recorded, transcribed, and analyzed using thematic analysis.ResultsBarriers to medication adherence were identified. Emerging themes were: 1) lack of education/awareness about diabetes/medications, 2) beliefs about medicines/diabetes, 3) spirituality and God-centered locus of control, 4) attitudes toward diabetes 5) perceptions of self-expertise with the disease and body awareness, 6) social stigma, 7) perceptions of social support, 8) impact of illness on patient’s life, 9) perceptions of health care providers’ attitudes toward patients, and 10) health system-related factors, such as access difficulties and inequalities of medication supply and services.ConclusionPersonal, sociocultural, religious, health care provider, and health care system-related factors may impede medication adherence among Kuwaitis with type 2 diabetes. Interventions to improve care and therapeutic outcomes in this particular population must recognize and attempt to resolve these factors.

Clinical and Molecular Characteristics of Non-Transfusion-Dependent Thalassemia in Kuwait

Although not regularly transfused, patients with non-transfusion-dependent thalassemia (NTDT) are prone to iron overload and its complications. Their molecular, phenotypical and laboratory characteristics vary in different populations and there is a need to document local prevailing patterns. We have reviewed the records of our patients with NTDT in Kuwait and documented their clinical and molecular characteristics in addition to iron status [serum ferritin and liver magnetic resonance imaging (MRI) T2*], management and complications. There were 41 patients, made up of 20 with β-thalassemia intermedia (β-TI), 18 with Hb H (β4) disease and three with Hb E (HBB: c.79G > A)-β-thalassemia (Hb E-β-thal); their ages ranged from 3 to 36 years (mean 12.5 ± 7.7). While 18 (43.9%) had been transfused at least once, only three (7.3%) had been transfused on multiple occasions. Three patients had serum ferritin >500 ng/mL; while four of 38 had mild or moderate liver iron overload. Seven (35.0%) of the β-TI patients were managed with hydroxyurea (HU) with good response. Other complications included five patients with gallstones and one each of hypothyroidism and moyamoya. The most common mutations among the β-TI patients were IVS-II-1 (G > A) and IVS-I-6 (T > C), while among the Hb H patients, the Saudi α2-globin gene polyadenylation (polyA) (AATAAA > AATAAG) mutation was responsible for all cases either as homozygotes (61.1%) or compound heterozygotes with the α-thal-2 (–α3.7) allele (33.3%). Although the pattern of NTDT in Kuwaiti patients is generally mild, there is a need to follow them to adulthood as the complications are cumulative and more prevalent in this group.

Altered activities of kininase II, an angiotensin converting enzyme, prekallikrein, and nitric oxide in Kuwaiti patients with type 2 diabetes.

The current investigation was conducted to examine kininase II or angiotensin converting enzyme (ACE), plasma prekallikrein (PK), and nitric oxide (NO) concentrations in healthy Kuwaiti subjects and newly diagnosed Kuwaiti type 2 diabetic patients before and after treatment for 6 weeks with metformin hydrochloride 500 mg twice daily after meal. With the consent of volunteers, blood and urine samples were collected after an overnight fasting. Samples were collected from the diabetic patients before and after treatment for 6 weeks. Enzyme linked immunosorbent assay (ELISA) was carried out on the aliquoted samples to measure the concentration of kininase II. NO was detected via colorimetry. Plasma Kininase II or ACE levels were significantly (P <0.01) increased by 18% in untreated diabetics when compared with healthy volunteers. However, after treatment there was a significant decrease of 20% in their ACE levels. Plasma prekallikrein levels were raised significantly (P <0.01) by 28% in diabetic patients in contrast with the control subjects and the levels were significantly reduced (P <0.0001) by 44% after treatment with metformin hydrochloride. NO levels were found to be significantly decreased in plasma by 56% and in urine by 62% in untreated diabetic patients as compared with the healthy subjects. However, when the treated diabetic patients were compared with untreated diabetics, there was an increase of 50% in plasma and 37% in urine samples. The high levels of kininase II, prekallikrein, and reduced NO may be partly responsible for the induction of renal, cardiac, and hypertensive complications associated with type 2 diabetes. Reduced NO level is an indication of endothelial dysfunction resulting in increased blood pressure. Oral anti-diabetic treatment is associated with protective effects through the reduction of kininase II (ACE), prekallikrein, and elevation of NO levels.

Association between Human Leukocyte Antigens (HLA-A, -B, and -DR) and end-stage renal disease in Kuwaiti patients awaiting transplantation

The number of patients with end stage renal disease (ESRD) is increasing considerably worldwide. Human Leukocyte Antigens (HLAs) are relevant for the expression of many immunological diseases and contribute to the development of different nephropathies. Therefore, we aimed from the present work to investigate the possible association between the frequency of HLA-A, -B, and –DR antigens and ESRD in Kuwaiti patients awaiting renal transplant. HLA-A, -B, and –DR typing was performed by complement-dependent cytotoxicity (CDC) method for 334 patients with ESRD awaiting renal transplantation and 191 healthy controls. The frequency of HLA-B8 antigen was significantly higher in ESRD patients (OR = 2.62, p = 0.001, pc = 0.038), and the frequency of HLA-A28, HLA-DR11 antigens was significantly higher in healthy controls (OR 0.42, p = 0.0001; pc = 0.0021, and OR = 0.44, p = 0.0007, pc = 0.01 respectively). While the HLA-B8 antigen may be a susceptibility risk factor for development of ESRD, the HLA-A28, and HLA-DR11 antigens may be protective against development of ESRD in Kuwaiti population.