Association of Blood Levels of Vitamin D and Its Binding Protein with Clinical Phenotypes of Multiple Sclerosis.

BACKGROUND: Low vitamin D levels may synergize with changing levels of the vitamin D binding protein (DBP) to precipitate in the development and clinical progression of multiple sclerosis (MS). In this study, this hypothesis was explored in groups of Kuwaiti healthy controls and patients with different clinical phenotypes of MS. METHODS: Fasting serum concentrations of 25-hydroxyvitamin D [25(OH)D] and DBP were measured in 146 healthy controls and 195 patients with MS. The latter were classified according to the duration, type, and onset of the disease and the mode of treatment. Factors such as relapse/remitting, and the use of nutritional supplements were also considered. RESULTS: The DBP levels were significantly lower in the patients than in the controls. This was more evident in newly diagnosed drug-naïve patients than in those patients with more established MS. MS status and severity were negatively impacted by concurrently low levels of 25(OH)D and DBP. This was most clearly expressed in drug-naïve patients and in those with a disease in relapse. It was also established that the 25(OH)D level had a significant positive correlation with the duration of the disease. CONCLUSION: Lower levels of 25(OH)D and DBP appear to have a synergistic effect on MS status. This was most clearly demonstrated in patients who were newly diagnosed (drug-naïve) and in those patients who were in relapse.

Leptin, Obesity, and Hypertension: A Review of Pathogenetic Mechanisms.

The adipokine leptin is expressed at higher concentrations in obese subjects, who also incidentally have a higher prevalence of hypertension. The pathogenesis of this obesity-related hypertension is controversial and is believed to be related to many factors including increased sympathetic activity, abnormalities of the renin-angiotensin system, sodium retention, and an endotheliopathy acting independently or in concert with increased circulating leptin. This review discusses the potential mechanisms through which changes in leptin signal transduction pathways in tissues with the leptin receptor, especially the hypothalamus, mediate the pathogenetic relationships between obesity and hypertension. The hypothesis is explored that leptin effects on blood pressure (BP) are meditated by the downstream effects of hypothalamic leptin signaling and ultimately result in activation of specific melanocortin receptors located on sympathetic neurons in the spinal cord. The physiological consequences of this sympathetic activation of the heart and kidney are activation of the renin-angiotensin system, sodium retention and circulatory expansion and finally, elevated BP. This sequence of events has been elegantly demonstrated with leptin infusion and gene knockout studies in animal models but has not been convincingly reproducibly confirmed in humans. Further studies in human subjects on the specific roles of hypothalamic leptin in essential hypertension are indicated as elucidation of the signaling pathways should provide better understanding of the role of weight loss in BP control and afford an additional mechanism for pharmacologic control of BP in adults and children at risk of cardiovascular disease.

Sociocultural and Demographic Risk Factors for the Development of Multiple Sclerosis in Kuwait: A Case - Control Study.

INTRODUCTION: Immunological, genetic and environmental factors are believed to play important roles in the pathogenesis of Multiple Sclerosis (MS). There have been many studies on risk factors for MS but these have been mainly in Caucasian populations; robust studies in Arab populations remain relatively uncommon. This study therefore aimed to identify behavioral, socio-cultural, and demographic factors associated with development of MS in Kuwait, a high income Arab country, currently undergoing a demographic transition. SUBJECTS AND METHODS: In this case- control study, 195 Kuwaiti MS patients and 146 healthy age and sex-matched controls were recruited. Both groups of subjects were interviewed using a structured questionnaire, in relation to anthropometric, socio-cultural and demographic data, residence during the 1990/91 Gulf War and current and past medical history, including medications. We also clinically evaluated, and retrospectively reviewed medical records of patients to derive appropriate clinical information, including associated chronic medical illness requiring long-term treatment. RESULTS: On multiple logistic regression analysis after adjustment for potential confounders including age, gender and BMI, in all the subjects, a positive associations prevail with presence of MS and some sociocultural and demographic factors, which included non-Bedouin ethnicity (AOR 2, 95% CI 1.0-3.9, p 0.049), positive family history of MS (AOR 10.6, 95% CI 3.0-36.9), p < 0.001), and low daily sunlight exposure of < 15min/day (AOR 5.3, 95% CI 2.7-10.5 p < 0.001). In addition, while 41.8% of MS patients indicated at least one comorbidity, only 26.8% of the controls reported any associated physical illness, with the suggestion that presence of certain comorbidities might increase MS risk (AOR 2.4, 95% CI 1.3-4.7, p < 0.001). Other risk variables such as smoking status and mode of routine outdoor dressing were not significant in all the MS subjects taken as a whole, but demonstrated variably positive associations in the MS subgroup classified as those with established disease and those who were newly diagnosed and drug naïve. CONCLUSIONS: This study suggests that a positive family history of MS and presence of certain comorbidities appeared to be associated with an increased risk of developing MS. In contrast, relatively increased amount of daily sunlight exposure and Bedouin ethnicity appear to somewhat be protective. It is speculated that the relationship of sunlight exposure with MS might be due to vitamin D availability, and is deserving of further study.

Determinants of blood uric acid levels in a dyslipidemic Arab population.

OBJECTIVES: The objective of this study was to explore the relationships between circulating uric acid and lipid levels and components of the metabolic syndrome (MetS) in Arab dyslipidemic patients, a group already at high coronary artery disease risk. SUBJECTS AND METHODS: The medical records of 1,229 subjects (632 men, 597 women) referred for treatment of dyslipidemia and followed up for at least 12 months were reviewed. Serum levels of uric acid and lipids (total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein) and other variables in the National Cholesterol Education Program ATP III criteria definition of MetS were assessed at initial presentation and every 4- 6 months, under specific lipid-lowering treatment (statins and/or fibrates), in each of the subjects. Their respective associations were explored by appropriate logistic regression techniques with control for confounding risk factors, including age, gender and body mass index. RESULTS: 306 subjects (24.9%) of the study population were hyperuricemic; they were more likely to be men, obese and diabetic. Also the serum uric acid level (mean ± SD) was greater in men with MetS compared with men without (377.0 ± 98.0 vs. 361.6 ± 83.1 µmol/l, p < 0.05), an observation not reproduced in women. Uric acid levels had significant associations with the presence of fasting hyperglycemia, hypertension and large waist circumference (WC) in men, but only with large WC in women. With statin treatment, uric acid levels decreased by 10% within 1 year of treatment; with fibrates, uric acid levels remained unchanged or slightly increased. CONCLUSION: The data showed that hyperuricemia is common in dyslipidemic patients in Kuwait, where its important determinants are male sex, obesity, diabetes and statin treatment.

The insulin-like growth factor system, metabolic syndrome, and cardiovascular disease risk.

The metabolic syndrome is a combination of metabolic and clinical features that aggregate in individuals and increase cardiovascular disease (CVD) risk considerably. It is believed, although sometimes controversially, that the underlying basis for this syndrome is insulin resistance (IR) and accompanying compensatory hyperinsulinemia. Insulin and insulin-like growth factors (IGFs) have significant homology and interact with differing affinity with the same receptors. Therefore, their actions can be complementary, and this becomes particularly significant clinico-pathologically when their circulating levels are altered. This review of currently available information attempts to answer the following questions: (1) Is there any evidence for changes in the components of the IGF system in individuals with established CVD or with increased CVD risk as with the metabolic syndrome? (2) What are the underlying mechanisms for interactions, if any, between insulin and the IGF system, in the genesis of CVD? (3) Can knowledge of the pathophysiological changes in the IGF system observed in macrosomic newborn infants and growth hormone (GH)-treated children and adults explain some of the observations in relation to the IGF system and the metabolic syndrome? (4) Can the experimental and clinical evidence adduced from the foregoing be useful in designing novel therapies for the prevention, treatment, and assignment of prognosis in metabolic syndrome-associated disease, particularly ischemic heart disease? To answer these questions, we have performed a literature review using bibliographies from PubMed, Medline, and Google Scholar published within the last 10 years. We suggest that IGF-1 levels are reduced consistently in individuals with the metabolic syndrome and its components and in those with ischemic CVD. Such changes are also seen with GH deficiency in which these changes are partially reversible with GH treatment. Furthermore, changes are seen in levels and interactions of IGF-binding proteins in these disorders, and some of these changes appear to be independent of IGF-binding capability and could potentially impact on risk for the metabolic syndrome and CVD. The promising therapeutic implications of these observations are also discussed.

Determinants of blood levels of some thrombogenic biomarkers in healthy Arab adolescent subjects.

BACKGROUND: Acute coronary syndromes present clinically as a consequence of plaque rupture and thrombosis possibly related to altered homeostasis of thrombogenic factors. It is speculated that this vulnerability in adults should be predictable from blood levels of thrombogenic biomarkers in children and adolescents. This study aims to examine the determinants and blood levels of lipoprotein(a) [Lp(a)], fibrinogen (FBG) and plasminogen activator inhibitor-1 (PAI-1) in healthy adolescents stratified according to age group, gender and body mass. METHODS: A total of 774 (316 males 458 females) healthy adolescent Arab subjects aged 10-19 years and attending secondary schools in Kuwait were interviewed by a validated questionnaire for variables relating to socio-demographic variables, diet and physical activity. They also had anthropometry, BP measurement and determination of fasting blood levels of Lp(a), low density lipoprotein (LDL)-cholesterol, apolipoprotein (apo) B, PAI-1 activity and FBG. RESULTS: The median (interquartile range, IQR) plasma levels of PAI-1 activity, FBG, Lp(a) and apoB were respectively 1.59 (0.58-3.78) U/mL, 296 (190-417) mg/dL, 10.0 (4.8-21.0) mg/dL and 0.72 (0.60-0.85) g/L. Boys had significantly higher PAI-1, FBG and apoB concentrations than the girls, although Lp(a) levels were greater in the latter. The overweight and obese subjects tended to have higher levels of LDL, apoB, FBG and PAI-1 but not Lp(a). Furthermore, the younger adolescent males and females (age <14 years) consistently had higher FBG levels than the older ones (age >14 years). Lp(a) and PAI-1 levels did not appear significantly influenced by this age stratification. Bivariate and multivariate analyses with adjustment for putative body mass index (BMI) confounders indicated that the independent determinants of these biomarkers were (i) Lp(a): apoB, gender; (ii) PAI-1: BMI, apoB, diet; (iii) FBG: BMI, gender, age, family income; and (iv) apoB: BMI, gender and PAI-1. CONCLUSIONS: The blood levels of the prothrombotic biomarkers ;ibLp(a), PAI-1, and FBG;ic in healthy Kuwaiti adolescent subjects are variably influenced by age, gender, body mass and socio-demographic factors.

Metabolic syndrome in severe mental disorders.

The concept of metabolic syndrome in psychiatry provides a united front for confronting a series of metabolic changes that are predictive of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), which are highly prevalent in severe mental disorders (SMDs), such as schizophrenia, bipolar disorders, and severe depression. This review attempts to answer the following questions: (1) Is there evidence of significantly increased risk of metabolic syndrome in SMDs? (2) How is this evidence explained by stress theory and functional polymorphism? (3) What role can psychopharmacology and psychosocial therapies play in minimizing the problem? We have done a historical review using related literature from Medline. Compared with the general population, metabolic syndrome is two to three times more common in SMDs. The evidence for this predates the era of antipsychotic drugs. Altered glucose metabolism and dyslipidemia seem to be integral to SMDs. However, major psychotropic drugs are associated with metabolic syndrome, because of their activity at the appetite-stimulating receptors. SMDs seem to trigger a pathogenic cycle that fuels metabolic syndrome. To explain these findings, a neural diathesis-stress model has been proposed. Furthermore, candidate genes associated with receptors for weight gain are implicated. Using metformin (≥750 mg/day) may significantly reduce metabolic risks, and the data support consideration of this intervention for psychiatric patients taking antipsychotics. The obstacles to the implementation of the available guidelines for monitoring metabolic effects and changing unhelpful lifestyles need to be overcome by making monitoring mandatory and integration of physical exercise into routine care. Drug development and genotyping for the risk factors are future solutions.

Prevalence of the metabolic syndrome among female Kuwaiti adolescents using two different criteria.

Overweight and obesity are highly prevalent in Kuwait and they are associated with the metabolic syndrome (MS). The present study aims to assess the prevalence of the MS among Kuwaiti female adolescents aged 10-19 years. A cross-sectional random sample of 431, apparently healthy, Kuwaiti female adolescents drawn from several randomly selected schools was studied for the prevalence of the MS using the International Diabetes Federation (IDF) and the National Cholesterol Education Program Third Adult Treatment Panel (ATP III) modified for age diagnostic criteria. Clinical assessment included measurements of waist circumference, blood pressure, fasting blood glucose, HDL and TAG. Whichever criteria are used, the prevalence of the MS among female Kuwaiti adolescents was found to be high, which indicates an urgent need for intervention programmes to prevent increased CVD and type 2 diabetes mellitus. The IDF criteria tend to give higher values for the prevalence of the MS in comparison with the modified ATP III criteria (14.8 v. 9.1 %). There have been no diagnostic criteria specific for the MS for the Gulf Arab population as yet.

Circulating markers of inflammation and endothelial dysfunction in Arab adolescent subjects: reference ranges and associations with age, gender, body mass and insulin sensitivity.

INTRODUCTION: Important biochemical markers for the low-grade vascular inflammation and endothelial dysfunction that characterize the earliest events in the pathogenesis of atherosclerosis are CRP and the adhesion molecules ICAM-1 and VCAM-1. This study aims to evaluate, in healthy Arab adolescent subjects aged 10-19 yr, the reference ranges for these markers and their associations with such determinants as age, gender, body mass and insulin sensitivity. METHODS: There were 774 Kuwaiti subjects (316 boys and 456 girls) aged mean (SD) 14.5 (2.2) yr. All had detailed clinical examination, anthropometry (to derive BMI) and assessment of fasting serum levels of CRP, ICAM-1, VCAM-1 and insulin (and HOMA-IR) to derive their reference values. Associations with putative determinants were explored by logistic regression analyses. RESULTS AND DISCUSSION: The reference ranges (mean (SD)) were: CRP 0.28 (0.49) mg/dl; ICAM-1, 286 (119)ng/ml; VCAM-1, 1148 (352)ng/ml; HOMA-IR, 4.57 (5.05). These parameters were significantly higher in boys than in girls, and in the overweight/obese and those aged < or =14 yr. BMI was significantly and independently related to CRP and ICAM-1 even after adjusting for age, gender, socio-demographic factors, diet and exercise. Levels of these markers were significantly influenced by age and gender. CONCLUSION: BMI, age and gender are significant predictors of serum levels of circulating inflammatory biomarkers, particularly ICAM-1, CRP and HOMA-IR. These atherogenic processes therefore probably cluster together in early life in individuals at increased later heart disease risk. Preventive public health measures should therefore commence in early childhood.

Body mass and atherogenic dyslipidemia as major determinants of blood levels of B-type natriuretic peptides in Arab subjects with acute coronary syndromes.

INTRODUCTION: The plasma B-type natriuretic peptide (BNP) level is elevated in cardiac ischemia and may be useful in assessing prognosis in acute coronary syndromes (ACS). This study aimed to: (1) establish BNP levels and its determinants in a healthy Gulf Arab population and in a group of patients with acute myocardial infarction and (2) investigate associations between BNP levels and markers of myocardial damage (ejection fractions, cardiac troponin I [cTnI] levels) and inflammation (serum C-reactive protein [CRP]). SUBJECTS AND METHODS: We studied 2 groups of Arab subjects: (1) Healthy control (HC), 142 healthy control subjects; (2) Coronary heart disease (CHD), 257 patients with proven acute myocardial infarction within 1 day of admission. Each subject was assessed clinically, and ejection fractions (left ventricular ejection fraction [LVEF]) were determined by echocardiography in those with CHD. Fasting blood samples were processed for full blood counts and serum glucose, urea, creatinine, uric acid, and lipids (total cholesterol [TC], triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein [LDL], and apolipoprotein B [apoB]), cTnI, BNP, and high-sensitivity (hs) CRP levels. The results were compared between groups, and the associations of BNP with other parameters were explored. RESULTS: In comparison to HC, the CHD group had a greater waist-hip ratio (WHR) (P < 0.01), worse atherogenic profile, worse renal function, and higher values for CRP and BNP (all P < 0.001). There were no significant differences in values for BNP related to age, diabetes, hypertension, WHR, and hematocrit, although there was a consistent trend in both HC and CHD groups toward a negative relationship of BNP with body mass, TG, and apoB levels, and a positive relationship with HDL, independent only for HDL and apoB on multiple logistic regression. No correlations could be established with cTnI, CRP, and LVEF. The patterns of cross-correlations did not differ significantly with diabetic status. CONCLUSION: In an Arab population with CHD, blood levels of BNP are higher than in a healthy control population and appear correlated to body mass and atherogenic lipids but not CRP, troponin, or ejection fraction. BNP levels did not appear to be influenced by the classical CHD risk factors of diabetes, hypertension, cigarette smoking, hematocrit, or WHR. The independent link with atherogenic dyslipidemia suggests that BNP is important in atherogenesis and may not be just an index of cardiac contractile dysfunction.

Association of blood levels of C-reactive protein with clinical phenotypes in Arab schizophrenic patients.

Schizophrenia may be associated with inflammatory reactions and C-reactive protein (CRP) is a nonspecific serum protein marker for persisting inflammatory states. This study aimed to assess concentrations of high sensitivity CRP (hsCRP) in schizophrenic Arab patients and evaluate the relationships of hsCRP levels with aspects of clinical phenotypes of the disease. Two age-matched groups of subjects were studied: (1) healthy controls, HC, n=165; (2) patients with schizophrenia, SZ: n=207. Each subject was evaluated with a standard questionnaire for age at disease onset, family history, disease severity and outcome. Serum hsCRP levels were measured by immunoassay. The two groups of subjects were similar in age, ethnic composition and socioeconomic status. Those with SZ had significantly greater serum concentrations of hsCRP. There were significant associations between hsCRP and (i) age in both groups; (ii) body mass index (BMI) in HC but not in SZ. In the latter, hsCRP levels were: (a) marginally higher in women with later age of disease onset; (ii) highest with remission and with catatonic features; and (iii) lower with family history of psychosis. The study concludes that serum levels of hsCRP are increased in clinically stable Arab patients with schizophrenia and appear related to the disorder's clinical expression. It is suggested that there may be an inflammatory component to schizophrenia which is associated with aspects of its clinical phenotype.

LDL species heterogeneity in the atherogenic dyslipidemia of polycystic ovary syndrome.

One of the important risk factors for coronary heart disease is dyslipidemia. Several lipid abnormalities have been studied in patients with polycystic ovary syndrome (PCOS), but the relationship between PCOS and low-density lipoprotein (LDL) subclass pattern is not clear. A case-control study was designed to look into lipid differences, and LDL size was analyzed by a newly developed polyacrylamide tube gel electrophoresis method. Results indicated that only PCOS status and serum triglyceride levels were independently associated with LDL particle size. The apolipoprotein (Apo)A-I level was higher in PCOS patients with small dense LDL (sdLDL). PCOS seems to result in smaller LDL particle size and higher ApoA-I levels independent of triglyceride levels. After adjusting for triglyceride levels, other traits of insulin resistance syndrome (IRS) were not associated with LDL size phenotype, suggesting that the IRS-related sdLDL is linked most strongly to alterations in triglyceride levels.

Hypothyroidism results in small dense LDL independent of IRS traits and hypertriglyceridemia.

There is evidence of an association between hypothyroidism and coronary heart disease. We decided to look at the relationship between hypothyroidism and LDL subclasses' pattern including small, dense LDL to define a biochemical basis for better management of the CHD risk of these patients. We utilized a case-control design to evaluate differences in lipid parameters between cases and controls. Univariate analysis revealed that many factors were associated with LDL particle size. Binary logistic regression however revealed that only thyroid status and serum triglyceride (TG) levels were independently associated with LDL particle size. Results from this study support an independent association between LDL particle size phenotype and both plasma TG concentrations and thyroid status. After adjusting for TG levels, other insulin resistance syndrome (IRS) traits were not associated with LDL size phenotype, suggesting that the IRS related sdLDL is linked most strongly to alterations in TG levels.

Associations of blood levels of insulin-like growth factor (IGF)-I, IGF-II and IGF binding protein (IGFBP)-3 in schizophrenic Arab subjects.

BACKGROUND: Insulin-like growth factors (IGFs) are believed to be important in brain development and repair following neuronal damage. It is also speculated that IGFs are involved in the association of foetal and pre-adult growth with schizophrenia (SZ). METHODS: The aim of this study was to assess levels of IGF-I, IGF-II and IGF binding protein (IGFBP)-3 and their associations in male Arab patients with SZ (n=53) and healthy control subjects (HC; n=52). Anthropometric and demographic data were collected for each subject for whom blood specimens were analysed for serum lipoproteins, apolipoprotein B (apoB), IGF-I, IGF-II and IGFBP-3. RESULTS: The SZ group had lower serum total cholesterol, apoB and uric acid levels than the HC group (p<0.05). IGF-II levels were significantly higher in the SZ group (p=0.02) and correlated positively with levels of atherogenic lipoproteins--total cholesterol, low-density lipoprotein, apoB--and IGFBP-3. The pattern of correlations between the IGFs and the various parameters differed somewhat between the HC and SZ groups. CONCLUSIONS: These results demonstrate that IGF-II levels are increased in patients with SZ and show significant associations with atherogenic lipoproteins. We suggest a possible link between IGF-II metabolism and atherogenesis in SZ.

Associations of apolipoprotein E polymorphism with low-density lipoprotein size and subfraction profiles in Arab patients with coronary heart disease.

The APOE gene locus has 3 major alleles, E3, E4 and E2, which variably influence coronary heart disease (CHD) risk. Plasma low-density lipoprotein (LDL) profile, another major CHD risk factor, is characterized on the basis of size and density into 2 main patterns: large buoyant LDL and small dense LDL. The latter has also been linked with increased CHD risk. This study investigates associations of specific APOE allelic patterns with LDL size and subfraction profiles in patients with CHD and healthy control subjects. We recruited 2 groups of male subjects: (A) 65 apparently healthy control subjects, median age, 39.0 years (range, 25.0-60.0 years); (B) 50 patients with CHD, median age, 54.0 years (range, 40.0-76.0 years). APOE genotypes were determined by validated polymerase chain reaction-restriction fragment length polymorphism methods, and LDL size and subfractions were assessed by a high-resolution, nongradient polyacrylamide gel electrophoresis technique (LIPOPRINT, Quantimetrix, Redondo Beach, CA). Lipid and other biochemical analyses were done by autoanalyzer techniques. The associations of specific APOE alleles and genotypes with LDL size and subfraction patterns were then assessed. As expected, patients with CHD had a worse atherogenic lipoprotein profile (waist-hip ratio, LDL, uric acid, and apolipoprotein B) than the controls. APOE genotype and allele frequencies were similar for both groups. In either group, median percent large buoyant LDL (pattern A) was greater in controls (51.0% vs 46.5%, P<.001) and percent small dense LDL (pattern B) was greater with CHD (9.0% vs 3.0%, P<.001). The latter also had smaller median particle size (26.5 vs 26.9 nm, P<.001). In controls, percent LDL pattern B was significantly lower with APOE2 than with APO non-E2 (4.0% vs 0.0%, P<.05); in patients with CHD, E2 patients had smaller particle size, and pattern B was significantly lower with non-E2 than with E2 (15.0 vs 8.0, P<.05). With respect to E4, control non-E4 had a smaller median percent LDL pattern B than E4; otherwise, there were no significant findings in relation to APOE type and LDL size and subfractions in both subject groups. These results confirm observations in other populations of increased levels of small dense LDL in patients with CHD. Although the APOE allelic pattern, especially APOE2, could be related to LDL subfraction profiles in control subjects, such associations could not be demonstrated in those with CHD.

Do differences in age specific androgenic steroid hormone levels account for differing prostate cancer rates between Arabs and Caucasians?

OBJECTIVE: Factors responsible for the low incidence of clinical prostate cancer in the Arab population remain unclear, but may be related to differences in androgenic steroid hormone metabolism between Arabs and other populations, especially as prostate cancer is believed to be androgen dependent. We therefore measured the levels of serum androgenic steroids and their binding proteins in Arab men and compared results obtained with values reported for Caucasian populations to determine if any differences could at least partially account for differences in incidence of prostate cancer rates between the two populations. METHODS: Venous blood samples were obtained from 327 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-79 years. Samples were also obtained from 30 Arab men with newly diagnosed prostate cancer. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), derived free androgen index (FAI); adrenal C19 -steroids, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (ADT) were determined by chemiluminescent immunoassay. Age specific reference intervals, mean and median for each analyte were determined. Frequency distribution pattern for each hormone was plotted. The reference range for hormones with normal distribution was mean +/- 2SD and 2.5-97.5% for those with non-normal distribution. The mean serum levels of the hormones in Arab men with prostate cancer were compared with values in healthy age-matched Arab men. RESULTS: There was a significant decrease between the 21-29 years age group and the 70-79 years age group for TT (-38.77%), DHEAS (-70%), ADT (-36%) and FAI (-63.25%), and an increase for SHBG (+64%). The calculated reference ranges are TT (2.73-30.45 nmol/L), SHBG (6.45-65.67 nmol/L), FAI (14.51-180.34), DHEAS (0.9-11.0 micromol/L) and ADT (0.54-4.26 ng/mL). The mean TT, SHBG, DHEAS and ADT in Arab men were significantly lower than those reported for Caucasians especially in the 21-29 years age group. Arab men with newly diagnosed prostate cancer had higher serum TT (P < 0.7), ADT (P < 0.2), SHBG (P < 0.2) and lower DHEAS (P < 0.008) compared to aged matched controls. CONCLUSIONS: Serum TT, SHBG, DHEAS and ADT levels are significantly lower in Arab men compared to those reported for Caucasian men, especially in early adulthood. Arab men with newly diagnosed prostate cancer have higher circulating androgens compared to healthy controls. We suggest that low circulating androgens and their adrenal precursors in Arab men when compared to Caucasians may partially account for the relatively lower risk for prostate cancer among Arab men.

Reference intervals for important serum sex steroid hormones, prostate-specific antigen, insulin-like growth factor-1 and IGF binding protein-3 concentration in a normal Kuwaiti adult male population.

OBJECTIVES: The purpose of this study was to determine the age-specific reference ranges for some important male sex steroid hormones, prostate-specific antigen (PSA), insulin-like growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3), for the Kuwaiti population. SUBJECTS AND METHODS: Blood samples were taken from 398 consenting, fasting, healthy Kuwaiti males aged 15-80 years between 8.00 a.m. and 12.00 noon. The serum concentrations of total testosterone (TT), dehydro-epiandrosterone sulfate (DHEAS), androstenedione (ADT), sex hormone binding globulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, PSA, IGF-1 and IGFBP-3 were determined. A distribution curve was plotted and age-specific reference levels were determined for each analyte. The reference interval for parameters with a normal distribution (Gaussian) was mean +/- 2 SD, while for the non-normal distribution (non-Gaussian), it was 2.5-97.5 percentile. The reference intervals for the analytes obtained from this study were compared with those suggested by the kit manufacturers and currently used by the Ministry of Health, Kuwait Laboratories (MOHKL). RESULTS: Serum IGFBP-3 and ADT had normal distribution while other analytes had non-normal distribution. The reference intervals from this study, manufacturers kit and MOHKL were as follows: TT 3-31, 9-60, 8-35 nmol/l; DHEAS 0.9-11, 1.0-7.3, 2.2- 15.2 micromol/l; ADT 0.5-4.3, 0.8-2.8, 2.0-9.2 nmol/l; LH 1-11, 0.8-7.6, 0.4-5.7 mIU/l; FSH 0.5-11, 0.7-11.1, 1.1-13.5 mIU/l; prolactin 42-397, 53-360, 80-230 nmol/l; IGF-1 41-542, 78-956, 71-261 ng/ml; IGFBP-3 88- 2,090, 900-4,000, 900-4,000 ng/ml, and PSA 0-3.1, 0-4, 0-4 ng/ml, respectively. CONCLUSION: These data indicate that for Kuwaitis lower reference ranges must be used for serum TT, DHEAS, ADT, IGFBP-3 and PSA. There is no need to change the currently used reference interval for FSH whereas higher values must be used for LH, prolactin, and IGF-1.

The relationship of APOE genetic polymorphism with susceptibility to multiple sclerosis and its clinical phenotypes in Kuwaiti Arab subjects.

BACKGROUND: The possible pathogenetic relationship between APOE genetic polymorphism and susceptibility to a variety of neurodegenerative disorders, including multiple sclerosis, is controversial. Previous studies have been conducted in Caucasian subjects, with little or no data on subjects from the Arabian Gulf. We compared the frequencies of specific APOE genotypes and alleles in patients with multiple sclerosis (MS) with frequencies observed in a healthy control Kuwaiti Arab population to relate APOE frequencies with specific identifiable clinical features of the disease. METHODS: Two groups of subjects were studied: (i) 39 (17 M, 22 F) patients with clinical evidence of MS; (ii) 106 apparently healthy Kuwaitis recruited as control subjects. The MS patients had detailed clinical and laboratory evaluations, and APOE genotypes were determined in all the subjects (patients and controls) by validated PCR methods. Differences in frequencies of APOE alleles and associations of specific alleles with clinical features were assessed. RESULTS: There were no significant differences in allele frequencies between patients and controls, although there was a statistically insignificant trend towards lower APOE2 allele frequency in the patients (p=0.09). There was a significant association of the APOE4 allele with female gender in the patients (p<0.05). CONCLUSION: In Kuwaitis, a population with low MS prevalence, no statistically significant associations between APOE genetic polymorphism and susceptibility to MS could be established, but there was a trend towards a lower APOE2 frequency with MS and towards increased frequency of APOE4 in female patients and with severe disease.

Post-dialysis retention of blood lipoproteins and apolipoproteins in patients with end-stage renal disease on maintenance haemodialysis in Kuwait.

BACKGROUND: The commonest cause of death in patients with end-stage renal disease (ESRD) on maintenance haemodialysis (MHD) is coronary heart disease (CHD). It has been suggested that dyslipidaemia, an important CHD risk factor, may be worsened by dialysis. This study evaluated changes in blood lipoproteins and apolipoproteins after dialysis in ESRD patients on MHD. METHODS: The subjects were 57 (20 M, 37 F; 24 diabetic, 33 nondiabetic) patients with ESRD, aged 21-73 years, undergoing MHD at a major Dialysis Unit in Kuwait. Pre- and post-dialysis non-fasting blood samples were collected from each subject on the same day, and analyzed for plasma glucose, urate, triglycerides (TG), total cholesterol (TC), HDL, LDL and apolipoprotein (apo) A1 and B. Pre- and post-dialysis levels for each of the analytes were compared for the diabetic and non-diabetic subgroups of patients and linear correlations sought between Delta values (corresponding to differences between pre- and post-dialysis levels) of the lipoproteins and apolipoproteins. RESULTS: There was a general trend towards significant increases in post-dialysis TC, HDL, LDL, and non-HDL levels in both sub-groups, and additionally for the non-diabetic, TG, apo A1 and apo B. The pre- to post-dialysis increases were essentially similar for the diabetic and non-diabetic groups-Diabetic: TC 14%, HDL 25%, LDL 19%, non-HDL 16%, apo A1 14%, apo B 10%; Non-diabetic: TC 20%, TG 29%, HDL 25%, LDL 26%, non-HDL 21%, apo A1 14%, apo B 14%. Generally, there were significant correlations between Delta values for the lipoproteins and apolipoproteins (r, 0.50-0.92) in both groups. CONCLUSION: Levels of atherogenic lipoproteins increase post-dialysis in diabetic and non-diabetic patients with ESRD and the changing levels of these lipoproteins correlate significantly with corresponding changes in levels of apolipoproteins. The increase in lipid levels is therefore related to retention of apo A1 and B with each dialysis. We speculate that, with repeated dialysis, dyslipidaemia may get progressively worse and further accentuate CHD risk.

Obesity indices and major components of metabolic syndrome in young adult Arab subjects.

BACKGROUND: The major components of metabolic syndrome are atherogenic dyslipidaemia (AD) and insulin resistance (IR), and both predict risk for atherosclerotic cardiovascular disease even in healthy individuals. AIMS: To assess if, in a group of healthy young adult Arab subjects, a simple classification in high and normal scores on waist-hip ratio (WHR), body mass index (BMI) and waist circumference (WC) scales could predict atherogenic parameters for metabolic syndrome (AD, IR). SUBJECTS AND METHODS: The subjects [n = 177 (72 M, 105 F), aged 29.7 +/- 8.4 (SD) years], underwent physical evaluation, BP measurement and anthropometry [height (m), weight (kg), waist (WC) and hip circumference (HC, cm)]. The cut-off points for normal/high scores on the indices were: (1) BMI: 30 kg/m(2) (M and F); (2) WHR: 0.80 F, 0.95 M, and (3) WC: 90 cm F, 100 cm M). The biochemical indices measured on fasting serum were: (1) AD: total cholesterol (TC), triglycerides (TG), HDL, LDL, apo B, HDL/TC ratio, and (2) IR: insulin, urate, insulin/glucose ratio (IGR). RESULTS AND DISCUSSION: In the whole group of subjects, and in women separately considered, those with high indices (BMI, WHR, WC) had significantly increased levels of glucose, LDL, apo B, urate, mean BP, TG, insulin and IGR and lower values for HDL/TC ratio (all p < 0.05). In men, only urate, insulin and IGR levels were increased (p < 0.01) in the high-score groups. None of the indices showed any special superiority in describing the risk of AD or IR. CONCLUSION: In women, BMI, WHR and WC appeared equally good in identifying individuals at high risk of AD and IR while in men, these indices satisfactorily described the risk of IR but not of AD. It is important to re-emphasise the need to indicate gender distinctions in using anthropometry for CHD risk assessment.