Folate, vitamin B12 and total homocysteine levels in Arab adolescent subjects: reference ranges and potential determinants.

BACKGROUND & AIMS: Elevated circulating fasting total homocysteine (tHcy) concentration is associated with an increased risk of occlusive vascular disease in adults. Important determinants of tHcy levels are folate, vitamin B(12) and vitamin B(6). This study aimed to investigate age, gender, and body mass as determinants of folate, vitamin B(12) and tHcy levels in Arab older children and adolescents and to propose population, gender and age-specific reference ranges for these biomarkers. METHODS & RESULTS: 774 (316 boys, 458 girls) healthy 10-19 yr olds attending secondary schools in Kuwait were assessed for anthropometry and fasting blood levels of Hcy, folate and vitamin B(12). The mean (95% CI) serum levels of tHcy, folate and vitamin B(12) were respectively 6.57 µmol/L (6.42-6.73), 16.0 ng/ml (15.6-16.3) and 354.3 pg/ml (343.0-365.7). Boys had significantly higher tHcy and folate concentrations than the girls, although vitamin B(12) levels were greater in the latter. Folate and vitamin B(12) levels decreased significantly with age, while correspondingly, tHcy levels increased, with mean values (µmol/L) for boys (6.71; 8.25) and girls (5.36; 6.67) aged 10-14 yr and 14-19 yr respectively. Bivariate and multivariate analyses with adjustment for confounders such as age, gender, need for dietary control and socio-demographic variables indicated that the independent determinants of levels of tHcy were age, gender and body mass. CONCLUSION: There is an age-related increase in tHcy in adolescents reflecting decreased levels of folate and vitamin B(12), with the suggestion that age-related reference ranges for these biomarkers be used. These observations may have implications for prevention of future atherogenic disease.

Apolipoprotein E polymorphism and clinical disease phenotypes in Arab patients with schizophrenia.

BACKGROUND: Apolipoprotein E (APOE) is polymorphic, and may be involved in the pathogenesis and clinical expression of schizophrenia. This study aimed to investigate the frequency of specific APOE genotypes and alleles in a schizophrenic Arab population and evaluate the association of specific APOE types with clinical phenotypes of the disease. SUBJECTS AND METHODS: Two age-matched groups of subjects were studied: (1) healthy controls, n = 165; (2) patients with schizophrenia (SZ), n = 207. Each subject was evaluated for age and mode of onset of disease, family history of psychosis, disease severity and outcome over the years of illness. APOE genotyping was performed by a validated PCR-RFLP technique. RESULTS AND DISCUSSION: Genotype E3E2 and allele E2 were less frequent in the patients with schizophrenia (p = 0.04), and both APOE types tended to be more common in male than female schizophrenic patients (p = 0.08). Schizophrenic patients with a positive family history of psychosis had lower frequencies of genotype E3E2 and allele E2 (both p = 0.04). Genotype E3E4 and allele E4 were least common in patients with an age at onset of disease >31 years (OR: 5.5, 95% CI: 1.1-27.4), particularly in males. CONCLUSION: APOE genetic polymorphism potentially influences susceptibility to schizophrenia and may be associated with aspects of its phenotypic expression, particularly gender, age of onset and family history of psychotic illness. This relationship of APOE with schizophrenia is likely to be race- and gender-specific.

Insulin-like growth factor (IGF)-I, IGF-II and IGF-binding protein (IGFBP)-3 levels in Arab subjects with coronary heart disease.

OBJECTIVE: Insulin-like growth factors (IGF-I, IGF-II) and their binding protein (IGFBP-3) may be risk markers for coronary heart disease (CHD). This study aimed to assess the levels and determinants of the serum levels of IGF-I, IGF-II and IGFBP-3 in Arab patients with established CHD. MATERIAL AND METHODS: Two groups of subjects were matched for age, gender, BMI and waist-hip ratio (WHR): (i) CHD (n = 105), median age 51.0 (range 40.0-60.0) years; (ii) controls (n = 97) aged 49.0 (range 37.0-60.0) years. We measured fasting serum levels of glucose and lipoproteins (total cholesterol, triglycerides, LDL, HDL, apo B), insulin, HOMA-IR, IGF-I, IGF-II and IGFBP-3 and compared the results between groups. The effects of body mass and the metabolic syndrome (MS) on IGF levels were also examined, and linear correlations were sought between the various parameters. RESULTS: The levels of IGF-I, IGF-II and IGFBP-3 were significantly lower (all p<0.01) for the CHD group than for the control group. These differences were not influenced by BMI or with the presence of MS. In CHD, there were no significant correlations between levels of IGF-I and IGF-II and age, BMI, WHR, lipoprotein concentrations and insulin sensitivity, although IGFBP-3 had weakly significant relationships with some of the lipoproteins. CONCLUSIONS: Levels of IGF-I, IGF-II and IGFBP3 are reduced in male Arab patients with CHD, and did not appear influenced by traditional CHD risk factors such as age, BMI, insulin sensitivity and presence of MS. Perturbations in the IGF/IGFBP-3 axis may be potential additional targets for pharmacological manipulation in CHD.

Associations of blood homocysteine concentrations in Arab schizophrenic patients.

BACKGROUND: This study aimed to evaluate the blood homocysteine concentration in Arab patients with schizophrenia and assess its associations with clinical phenotypes of the disease. SUBJECTS AND METHODS: 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. Plasma homocysteine levels (Hcys) were measured by immunoassay and serum levels of other biochemical parameters were measured by routine Autoanalyzer techniques. RESULTS AND DISCUSSION: Group HC was heavier (body mass index, BMI) while SZ had greater waist-hip ratio (WHR) and plasma Hcys levels. In SZ, there were significant correlations between Hcys and BMI, triglycerides and HDL. Hcys levels in SZ were highest in the younger male patients. CONCLUSION: Schizophrenic patients have increased blood Hcys levels which correlate with components of the metabolic syndrome. Hcys levels were highest in the younger male patients and were not influenced by prognostic features of the disease.

Prostate cancer risk: the significance of differences in age related changes in serum conjugated and unconjugated steroid hormone concentrations between Arab and Caucasian men.

INTRODUCTION: Factors responsible for the low incidence of clinical prostate cancer (3-8/100,000 men/year) in the Arab population remain unclear, but may be related to changes in steroid hormone metabolism. We compared the levels of serum conjugated and unconjugated steroids between Arab and Caucasian populations, to determine if these can provide a rational explanation for differences in incidence of prostate cancer between the two populations. PATIENTS/METHOD: Venous blood samples were obtained from 329 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-80 years. Samples were also obtained from similar Arab men with newly diagnosed prostate cancer or benign prostatic hyperplasia (BPH). The samples were taken between 8:00 am and 12:00 noon. Serum levels of total testosterone, (TT), sex hormone binding globulin (SHBG), free androgen index (FAI); adrenal C19-steroids, dehydroepiandrosterone sulphate (DHEAS) and androstenedione (ADT) were determined using Immulite kits (Diagnostic Systems Laboratories Inc, Webster Texas, USA). The results obtained in Arab men were compared with those reported for similarly aged Chinese, German and White USA men. RESULTS: In all four ethnic groups, median TT and FAI declined with age, while SHBG increased with age. However, the mean TT and SHBG was significantly lower (p < 0.01) and the FAI significantly higher in Arab men (p < 0.01) compared to German men only in 21-30 years age group. In the other age groups the levels of TT and SHBG were higher in the Germans but the differences were not statistically significant. In all the racial groups serum levels of DHEAS and ADT reached a peak by about 20 years of life, and then declined progressively. The mean DHEAS in American Caucasians aged 20-29 years was 11.4 micromol/l compared to 6.22 micromol/l in the Arabs (p < 0.001). The mean DHEAS in USA Caucasians aged 70-79 years was 2.5 micromol/l compared to 1.8 micromol/l (p < 0.03) in the Arabs. There was no significant difference in mean serum levels of DHEAS between German and USA men. Similarly, there was no significant difference in the level of the hormones between Arab and Chinese men. Arab men with newly diagnosed prostate cancer had high serum TT, SHBG and DHEAS compared to those without the disease. CONCLUSIONS: The mean TT and SHBG was significantly lower in Arab men compared to Caucasian men especially in early adulthood. Caucasians have significantly higher serum levels of the precursor androgens DHEAS and ADT especially in early adulthood compared to Arab men. These observations of low circulating androgens and their adrenal precursors in Arab men may partially account for the decreased risk for prostate cancer among Arab men.

Putative role of serum insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) levels in the development of prostate cancer in Arab men.

INTRODUCTION: The incidence of clinical prostate cancer in the Arab population is among the lowest in the world. High serum IGF-1 level has been implicated as a possible risk factor for the development of prostate cancer in Caucasians. The purpose of this study was to determine serum IGF-1 and IGFBP-3 levels in healthy Arab men and in Arab men with newly diagnosed benign prostatic hyperplasia (BPH) and prostate cancer, and to compare these values with values reported in Caucasians. PATIENTS AND METHODS: Subjects were recruited in two groups: (a) indigenous, healthy Arab men aged 15-90 y (n = 383); (b) Arab men with newly diagnosed prostate cancer (n = 30) or BPH (n = 40). Blood was obtained from fasting patients and volunteers, between 8:00 a.m. and 12:00 noon. The serum concentrations of IGF-1 and IGFBP-3 were determined using Immunoradiometric assay (IRMA) kits. RESULTS: As in Caucasians, serum IGF-1 and IGFBP-3 levels declined with age in Arab men. The mean +/- s.d. of serum IGF-1 levels in healthy Arab men in the age group 15-20, 51-60, 61-70 y were lower (376.2 +/- 153.2, 134.9 +/- 105.7 and 89.6 +/- 48.4 ng/ml, respectively), compared to values reported for similarly aged Caucasians. Arab men with newly diagnosed prostate cancer had significantly higher serum IGF-1 level (P < 0.01) and lower IGFBP-3 levels (P < 0.01) compared to age-matched Arabs without the disease. CONCLUSIONS: Arab men have lower serum IGF-1 levels compared to Caucasians and this may be an important factor in the explanation of the low incidence of prostate cancer in the Arab population.

Apolipoprotein E polymorphism and lipoprotein levels in a Gulf Arab population in Kuwait: a pilot study.

BACKGROUND: APOE polymorphism is believed to confer susceptibility to coronary heart disease (CHD) and Alzheimer's disease. It is well known that patterns of APOE polymorphisms differ between populations and ethnic groups, although most of the data available so far have been in whites. SUBJECT AND METHODS: We evaluated the frequencies of APOE genotypes and their relationships with serum levels of lipids, lipoproteins and apolipoproteins in two groups of Gulf Arab citizens: a control population of healthy voluntary blood donors (n=106), and a group of patients presenting to the lipid clinic for the first time with combined hyperlipidaemia (CH) (n=41). In both groups, fasting serum total cholesterol (TC), triglycerides (TG), HDL, LDL and apolipoprotein A1 and B levels were measured by routine autoanalyzer methods, and APOE genotyping was performed by validated PCR methods. The lipid and lipoprotein levels were related to the specific APOE allele frequencies. RESULTS: Allele frequencies were 5.7% for *E2, 85.4% for *E3, and 9.0% for *E4 in the healthy blood donor group. An essentially similar pattern was seen in the patients with CH. This APOE allelic distribution conforms to patterns described in Chinese, whites and South Asians. In both the blood donor and CH groups there were no consistent links between specific APOE pattern and serum lipoproteins, as would have been predicted from APO *E2 and APO *E4 frequencies. CONCLUSIONS: We conclude that APOE allelic patterns in healthy Kuwaiti blood donors and a smaller group of patients with CH do not satisfactorily predict circulating blood levels of lipids and lipoproteins.

HLA determinants of susceptibility to multiple sclerosis in an Arabian Gulf population.

BACKGROUND: An association between HLA antigens and susceptibility to multiple sclerosis (MS) has been established, especially in Caucasian populations. Such associations have not been as clearly defined in many Arab populations, where even the frequencies of specific HLA antigens remain unclear OBJECTIVE: The study was designed to (i) investigate the frequencies of HLA Class I and II antigens in Kuwaiti Arabs with MS, and; (ii) assess possible inter-relationships between HLA Class II antigens and such clinical phenotypic variables in MS as age at onset, gender, disease subtype and scale of disability. SUBJECTS AND METHODS: HLA Class I (A, B, C) and Class II (DR, DQ) antigens' tissue-typing was performed by the standard complement-dependent microlymphocytotoxicity technique in two groups of age- and sex-matched Kuwaiti subjects: (i) 67 patients with definite MS (48 relapsing remitting, 19 relapsing-progressive) and (ii) 145 unrelated healthy controls. The frequencies of specific HLA types were then compared between patients with controls, and in the former, related to specified clinical parameters. RESULTS: The frequencies for the Class I antigens: A9, A10, A19, A33, B5 and CW4 appeared higher with the presence of MS, although the numbers of positive subjects were rather low. For the Class II antigens, frequencies of DR4, DQ5, DQ6, DQ7 and DQ8 were increased while those for DR6 and DR1 were decreased in the patients with MS. HLA types DR15 and DR4 were present at higher frequencies in patients with a younger age at disease onset; DR15 also appeared more frequent in the female patients. CONCLUSION: There is a trend towards an association between HLA Class II antigens (DR4, DQ6, DQ7 and DQ8) and MS in Kuwaiti subjects. Additionally, it appeared that DR4 and DR15 were more frequent in females and those with an early onset of the disease. These patterns of HLA Class II determinants of susceptibility to MS differ from reports in some other populations, and may reflect the recognized variability in genetic influence on HLA and disease expression.

Risk factors, subtypes and outcome of ischaemic stroke in Kuwait--a hospital-based study.

OBJECTIVE: To report on stroke subtypes, associated risk factors and outcome in Kuwait. METHODS: The records of 62 patients (30 male, 32 female) admitted with diagnosis of stroke to Kuwait Oil Company Hospital, Kuwait, a tertiary care hospital, during a 5-year period (1995-1999), were retrospectively reviewed. RESULTS: Small artery infarction was the most common subtype and occurred in 37 subjects (59.7%); less common were atherosclerotic large artery strokes (19 patients, 30.6%) and strokes of cardio-embolic origin (6 patients, 9.7%). Identifiable risk factors or associated morbidities were hypertension (72.5%), diabetes mellitus (69.4%), ischaemic heart disease (14.5%), history of migraine (8.1%), lone atrial fibrillation (5.0%), and valvular heart disease (1.6%). The most important determinants of a deleterious 30-day outcome, as indicated by severe disability or death, were female gender, lack of use of anti-platelet drugs, presence of a large artery infarction stroke subtype, and cardio-embolic stroke. CONCLUSION: Prevalence of hypertension and diabetes is high among patients with stroke in Kuwait, with rates higher than those found in any previous reports from the Gulf region. Two unusual observations were that women had a rather high frequency of stroke, and infarction of the small artery was more common than that of the large artery. Outcome, as indicated by severe disability or death, was worse among women, elderly patients, and those with large artery atherosclerotic and cardio-embolic strokes. There is some evidence that such a deleterious outcome might be ameliorated with use of anti-platelet drugs.

Associations of plasma homocysteine concentration in subjects with type 2 diabetes mellitus.

We investigated the potential relationship between hyperhomocysteinemia and the presence of coronary heart disease (CHD) and chronic complications in a consecutive series of 358 (156 men) Kuwaiti type 2 diabetic subjects. The median (2.5(th), 97.5(th) percentiles) fasting plasma concentration of total homocysteine (tHcy) in the patients was 10.2 (5.4, 19.1) micromol/l. Fasting tHcy concentration was significantly (p<0.001) higher among men [11.3 (7.1, 24.6) micromol/l] compared to women [8.8 (5.3, 16.3) micromol/l]. Of the 57 patients with a history of CHD and/or electrocardiographic (ECG) evidence of CHD, 9 (16%) had hyperhomocysteinemia (tHcy > or =15 micromol/l) compared to 8.3% (25 of 301) of patients without evidence of CHD. In univariate analysis, plasma tHcy concentration was significantly (p<0.01) higher in those diabetic subjects with history of CHD and/or abnormal ECG. Although hyperhomocysteinemia was more common in patients with microalbuminuria (15%) compared to patients with normoalbuminuria (12%), there was no significant association between hyperhomocysteinemia and the degree of albuminuria. After controlling for age and sex, multiple regression analyses showed significant associations of plasma tHcy concentration with glycated hemoglobin (p<0.05), plasma concentrations of creatinine (p<0.001) and apolipoprotein-B (p<0.05), but not with smoking, neuropathy or retinopathy. It seems that the association of hyperhomocysteinemia with diabetic microvascular complications is mediated by the confounding effect of other factors like age, sex and plasma creatinine concentration. In conclusion, we have found a univariate association between hyperhomocysteinemia and CHD but not with microalbuminuria, neuropathy and retinopathy. Although routine estimation of plasma homocysteine may be useful, the association with cardiovascular disease or microvascular complications in patients with type 2 DM deserves prospective studies.

Association of C-reactive protein with coronary heart disease risk factors in patients with type 2 diabetes mellitus.

The assessment of markers of systemic inflammation, such as C-reactive protein (CRP) and interleukin 6 (IL6), could be used to identify persons at high risk of coronary heart disease (CHD). This study evaluates the relationship of CRP and IL6 with CHD risk factors in patients with type 2 diabetes mellitus (DM) with CHD and age and sex matched type 2 DM controls without CHD. CRP, IL-6, total plasma homocysteine (tHcy), lipoprotein (a) [Lp(a)] and sialic acid (SA) were determined in 55 type 2 diabetic patients with CHD and 51 age- and sex-matched type 2 diabetic controls without CHD. Multivariate and logistic regression analyses were used to relate these markers with CHD risk factors. CRP (P=0.02) and tHcy (P=0.03) were significantly higher in patients with CHD compared with the control group even after correction for age and sex. IL6, Lp(a), SA and lipid parameters were not significantly different between the two groups of patients. After adjustment for potential confounders, the odds ratio (OR) for elevated CRP was 2.00 (95% confidence interval [CI], 1.12-3.58) (P=0.02) but the OR for IL6 was 3.41 95% CI, 0.70-17.17 (P=0.14). Partial correlation analyses of CRP and IL6 with other variables showed significant correlation of CRP with tHcy, and SA in patients with CHD only. Our results support the inclusion of CRP (high-sensitivity assay), in the risk assessment of diabetic subjects.

Effect of insulin on transport kinetics of alpha-aminoisobutyric acid in the perfused human placental lobule in vitro.

BACKGROUND: The limited data available on the role of insulin on maternal-fetal transport of amino acids prompted us to undertake this study. METHODS: Transport kinetics of a model amino acid, alpha-aminoisobutyric acid (AIB) was investigated in perfusion of isolated human placental lobules in vitro in non steady-state conditions and the effect of therapeutic dose of insulin was assessed in parallel series of perfusions. National Culture and Tissue Collection medium diluted with Earle's buffered salt solution was used as the perfusate and tritiated water was used as the reference marker for comparison. RESULTS: In five successful perfusions with insulin, differential transport rate indices of AIB for 10, 25, 50, 75 and 90% of efflux fractions in the fetal venous outflow averaged 0.76, 1.03, 1.02, 1.09, 1.04 and 1.03 times those of reference values, respectively. The indices differed significantly than in controls for 10, 25 and 50% efflux fractions, but not in the case of 75 and 90% efflux values. The AIB transport fraction (TF), expressed as percentage of injected maternal dose, averaged 29.4 +/- 5.4% and 38.7 +/- 6.2% of the corresponding reference marker value in control and insulin series, respectively. With regards to the pharmacokinetic transport parameters, the absorption and elimination rates of the amino acid were significantly higher in the study group than in the control. CONCLUSION: We conclude that insulin, in physiological and therapeutic doses, stimulates maternal-fetal AIB transport in vitro, in the perfused human placental lobule.

Serum lipoprotein(a) concentration as a cardiovascular risk factor in Kuwaiti type 2 diabetic patients.

Serum lipoprotein(a) [Lp(a)], a risk factor for coronary heart disease (CHD) in some nondiabetic populations, is largely under genetic control and varies among ethnic and racial groups. We evaluated serum Lp(a) concentration and its relationship with traditional CHD risk factors (age, sex, smoking, hypertension, dyslipidemia) as well as stage of diabetic nephropathy in 345 type 2 diabetic patients. Lp(a) concentration was skewed with median (2.5th, 97.5th percentiles) of 25.0 (8.1, 75.7) mg/dl. Twenty-three of 55 (41.8%) patients with CHD had increased (>30 mg/dl) Lp(a) compared with 102 of 290 (35.1%) patients without CHD (P=.35). Twelve of 27 (44.4%) female patients with CHD had increased Lp(a) compared to 11 of 28 (39.3%) males (P=.70). Lp(a) was significantly (P<.05) higher in females than males, but the logistic regression analysis showed significant association of Lp(a), LDL-C, and duration of diabetes mellitus (DM) with CHD in male patients only. Although female patients with CHD and macroalbuminuria had significantly (P<.05) higher Lp(a) than normoalbuminuric female patients without CHD, no such association was found in males and no significant association was found between Lp(a) and the degree of albuminuria. Partial correlation analysis controlling for age, sex, and BMI showed significant correlation of Lp(a) with total cholesterol only (P=.03) and no correlation was found with other lipid parameters. Multiple regression analysis did not show significant associations of Lp(a) with standard CHD risk factors, HbA(1c), and plasma creatinine. This study is in agreement with studies in other populations, which showed that Lp(a) may not be an independent risk factor for CHD in patients with DM. However, as Lp(a) could promote atherogenesis via several mechanisms, follow-up studies in our patients will confirm if increased Lp(a) concentration can partly account for the poorer prognosis when diabetic patients develop CHD.

Homocysteine and endogenous markers of renal function in type 2 diabetic patients without coronary heart disease.

The aim of this study was to assess parameters of renal function and other determinants of plasma homocysteine in type 2 diabetic patients without coronary heart disease (CHD). Fasting plasma homocysteine, serum cystatin C and serum creatinine were determined in 183 (75 men, 108 women) Type 2 diabetic patients without clinical evidence of CHD. Creatinine clearance was calculated and parameters such as blood pressure, body mass index (BMI), and glycated haemoglobin (HbA(1c)) were assessed. The urine albumin:creatinine ratio was used to classify patients as normo-, micro- or macroalbuminuric. One hundred and ten patients were normoalbuminuric, 67 patients were microalbuminuric and six patients were macroalbuminuric. There was no statistically significant difference in plasma homocysteine concentration between patients with normoalbuminuria and microalbuminuria. There was a trend towards increasing plasma homocysteine with decreasing glomerular filtration rate (GFR) (r=-0.46; P<0.0001). There was statistically significant correlation between plasma homocysteine and age (r=0.37), serum cystatin C (r=0.47), and serum creatinine (r=0.56). Plasma homocysteine concentration was significantly higher in patients with BMI<30 kg/m(2) and showed significant inverse correlation with weight (r=-0.16; P=0.03) and body mass index (r=-0.24; P=0.001). Homocysteine and serum creatinine were significantly higher in males than females and higher in smokers than non smokers but was not associated with glycemic control and duration of diabetes. In conclusion, elevated homocysteine concentration in patients with type 2 DM without CHD is related to age, gender, smoking, BMI and GFR. Follow up studies will provide further information on the association between hyperhomocysteinemia and the development of cardiovascular disease.

Hypergammaglobulinemic purpura of Waldenström: report of 3 cases with a short review.

Benign hypergammaglobulinemic purpura of Waldenström (HGPW) is an uncommon cause of non-thrombocytopaenic purpura that may create diagnostic difficulties. The presence of constitutional symptoms associated with prominent immunological abnormalities may raise alarm, leading to extensive and often unnecessary investigations. This report describes 3 young women with HGPW. Clinical features were characterised by recurrent episodes of bilateral asymmetrical palpable purpuric lesions on the lower extremities that were precipitated by a prolonged increase in hydrostatic pressure (e.g. prolonged standing, tight stockings etc.) associated with constitutional features. In one patient the condition was secondary to Sjögren's syndrome with type IV renal tubular acidosis. Laboratory abnormalities included a persistently elevated erythrocyte sedimentation rate, marked polyclonal hypergammaglobulinemia, and high titers of rheumatoid factor and anti-nuclear antibody of the anti-SSA (anti-Ro)/anti-SSB(anti-La) subsets. This topic is reviewed briefly with the emphasis that in its 'primary' form this condition could be considered a 'benign' systemic immunoinflammatory disease that requires neither extensive investigations nor any aggressive form of therapy. Greater awareness of HGPW may increase the frequency of its diagnosis, especially in the patient group with non-thrombocytopenic purpura or the so-called cutaneous vasculitic syndromes with 'palpable purpura'.

Relation of serum total sialic acid concentrations with diabetic complications and cardiovascular risk factors in Kuwaiti Type 2 diabetic patients.

Serum total sialic acid is a marker of the acute phase response. Elevated levels have also been associated with cardiovascular disease in the general Caucasian population and especially in Type 2 diabetic subjects. The purpose of this study was to estimate serum total sialic acid concentrations among Kuwaiti Type 2 diabetic subjects and to investigate its association with macro and microvascular diabetes-related complications in that population. Serum total sialic acid levels were estimated by an enzymatic spectro-photometric assay in two groups of subjects: (i) 358 Kuwaiti Type 2 diabetics (156 men and 202 women) referred for their annual evaluation to the specialised diabetic clinic at the main university teaching hospital in Kuwait, and (ii) 47 healthy age and sex matched non-diabetic Kuwaiti control population (13 men and 34 women). Serum sialic acid levels were significantly higher (P<0.001) among the diabetic patients (mean+/-S.D.) (81.2+/-13.2 mg/dl) compared to the non-diabetic controls (66.9+/-11.0 mg/dl). Kuwaiti diabetic women had significantly higher concentrations compared to diabetic men (85.2+/-12.1 vs. 75.9+/-13.0 mg/dl, P<0.001). Among the controls there was no significant gender difference in sialic acid levels of women, (68.3+/-11.6 mg/dl) versus men (63.2+/-8.2 mg/dl). The gender difference in the diabetic patients was unrelated to the degree of obesity. Significant correlations were found between serum total sialic acid concentrations and such cardiovascular risk factors as plasma levels of apolipoprotein B, low density lipoprotein cholesterol, triglycerides and uric acid in the diabetic subjects. Furthermore, there was a significant elevation in serum total sialic acid concentrations with increasing urinary albumin excretion, P<0.001, but not with retinopathy or neuropathy.

Beneficial changes in serum apo A-1 and its ratio to apo B and HDL in stable hyperlipidaemic subjects after Ramadan fasting in Kuwait.

BACKGROUND: In patients with metabolic and nutritional disorders such as diabetes and hyperlipidaemia, where strict compliance to advice on timing and composition of food intake is important, the prolonged daylight fasting during the month of Ramadan could produce undesirable biochemical consequences. AIM: The study aimed to compare pre- and post-Ramadan lipid and lipoprotein profiles in stable Kuwaiti hyperlipidaemic subjects attending a Lipid Clinic. SUBJECTS AND METHODS: The study population comprised 64 adult Kuwaitis (33 M, 31 F) who had been attending a Lipid Clinic for at least 12 months and were considered stable, without any acute systemic illness. At each clinic visit, the following parameters were measured: weight, total cholesterol (TC), triglycerides (TG), HDL, LDL, apo A-1, apo B, glucose and uric acid. These biochemical parameters were measured by routine automated analyzer techniques. The pre-Ramadan values comprised the means of two measurements taken at about 3 month and 1 month before commencement of Ramadan. Post-Ramadan values were obtained within 1 month of the end of the Ramadan fast. The parameters so obtained were compared in the whole group, and then according to gender, glycaemic status and modality of treatment (diet alone or with a fibrate or statin). RESULTS AND DISCUSSION: In the nondiabetic subjects, apo A-1 and apo A-1/apo B and apo A-1/HDL ratios were increased post-Ramadan (P<0.001). Weight did not change and the other lipid parameters-TC, TG, LDL, apo B-did not worsen. These observations, more consistent in the men than in the women, and in subjects treated with a fibrate or a statin rather than on diet alone, indicate a favorable coronary heart disease (CHD) risk profile. In the diabetic patients, these changes in the apo A-1 level and its ratio to HDL and apo B were also present, but TC and apo B levels increased, the latter significantly (P<0.05). These divergent effects in diabetic patients could variably influence CHD risk liability. Serum uric acid levels were also simultaneously reduced post-Ramadan in the non-diabetic subjects and those on statin treatment. CONCLUSION: When pre- and post-Ramadan lipid and lipoprotein profiles were compared in stable hyperlipidaemic subjects attending a Lipid Clinic in Kuwait, the most consistent changes post-Ramadan were increased levels of apo A-1 and apo A-1/apo B and apo A-1/HDL ratios and reduced uric acid levels. Body weight remained essentially unchanged and the other lipoprotein and lipid parameters were not worsened. These results suggest that Ramadan fasting in hyperlipidaemic subjects might favorably influence CHD risk.

Apo(a) isoforms do not predict risk for coronary heart disease in a Gulf Arab population.

It is well recognized that blood lipoprotein A [Lp(a)] levels constitute an important risk factor for atherosclerotic vascular disease. In some populations, mainly Caucasian, Lp(a) levels and coronary heart disease (CHD) risk are determined by the pattern of apolipoprotein a [apo(a)] polymorphism. It is currently unclear if these observations apply to other populations and ethnic groups. The aim of the current study is to determine to what extent known apo(a) polymorphisms associate with development of CHD in a Kuwaiti Arab population. Serum Lp(a) levels were measured by enzyme-linked immunosorbent assay and apo(a) isoforms determined by a high-resolution sodium dodecyl sulphate/agarose gel electrophoresis with immunoblotting in two groups of Kuwaiti subjects: healthy controls (n = 140) and subjects with CHD (n = 140). Blood lipids and anthropometric parameters were also determined in these subjects by standard methods. Serum Lp(a) levels were greater in those with CHD than in those in the healthy group (P < 0.001). There was no consistent trend in the pattern of serum Lp(a) levels found with specific apo(a) isoforms in either group of subjects. There was, therefore, no simple relationship between the isoform pattern (and number of kringle-IV repeats) and serum Lp(a) concentration, unlike in certain other populations. Additionally, almost identical proportions of subjects in either group had single-banded (homozygous, approximately 70%), double-banded (heterozygous, approximately 23%) and no-band (null, approximately 7%) phenotypes. The distribution of the five identified isoforms (F, S1, S2, S3 and S4) also was almost identical for both groups of subjects, whether homozygous or heterozygous, and whether classified into fast-moving (F, S1 and S2) or slow-moving (S3 and S4) isoforms. We conclude that the frequency and pattern of distribution of apo(a) phenotypes did not differ significantly between healthy control Kuwaiti Arab subjects and those with CHD. It is thus unlikely that an individual's apo(a) phenotype can predict both serum Lp(a) level and risk for CHD, irrespective of race and/or ethnic grouping.

Metabolic and anthropometric determinants of serum Lp(a) concentrations and Apo(a) polymorphism in a healthy Arab population.

BACKGROUND: Blood lipoprotein(a) Lp(a) concentrations are an important risk factor for atherosclerosis. The basis for this atherogenic property of Lp(a) and the factors that influence its cross-population levels, however, remain poorly understood. OBJECTIVES: To investigate the relationship between serum Lp(a) and metabolic and anthropometric parameters in a healthy Kuwaiti population. DESIGN: Cross-sectional study. SUBJECTS: 177 (72 male, 105 female) randomly recruited healthy Kuwait Arabs aged 17-60 y MEASUREMENTS: Metabolic parameters in serum: Lp(a), apo(a) phenotypes, lipids and lipoproteins, glucose and urate. Anthropometric parameters: body mass index (BMI) and waist:hip-ratio (WHR). RESULTS: The distribution of Lp(a) concentrations was positively skewed (median 153 mg/l, range 0-1086). Women had higher concentrations-(194, 0-1086) than men (117, 0-779), P = 0.069. Lp(a) and insulin concentrations were significantly higher when the men and women were obese. In all subjects, there were significant correlations between Lp(a) and BMI (r = 0.23), total cholesterol (TC) (r = 0.17) and LDL (r = 0.20). Lp(a) correlated only with glucose in men (r = 0.28). In women it correlated with age (r = 0.20), BMI (r = 0.30), BP (r = 0.20), TC (r = 0.20) and LDL (r = 0.26). Multivariate analyses confirmed BMI and low-density lipoprotein (LDL) as the significant determinants of serum Lp(a). On apo (a) phenotyping, 114 (67%), 51 (30%) and 6 (4%) had single, double and null phenotypes respectively. The isoforms and their corresponding kringle IV repeat numbers were: F (14 repeats in 3%, mean Lp(a) 497 mg/l); S1 (19 repeats in 14%, mean 245 mg/l); S2 (23 repeats in 16%, mean 264 mg/l); S3 (27 repeats in 35%, mean 236 mg/l); and S4 (35 repeats in 28%, mean 235 mg/l). DISCUSSION AND CONCLUSION: The results from the Kuwaiti population studied suggest that: (1) serum Lp(a) concentrations and distribution are similar to the pattern in Caucasians and Asians but not African-Americans or Africans; (2) serum Lp(a) is variably influenced by BMI and LDL--the impact of either factor differs between the sexes; (3) there is a high frequency of the single-banded phenotype; (4) contrary to reports in some Caucasian and Asian populations, there is no simple relationship between kringle IV repeat numbers and plasma Lp(a) concentrations.

The relationships between insulin and plasminogen activator inhibitor 1 levels: assessment in groups of subjects with dyslipidaemia and hypertension.

Elevated plasminogen activator inhibitor-1 (PAI-1) levels have been described in some populations to associate with hyperinsulinaemia in the metabolic syndrome which predisposes to coronary heart disease (CHD). This association, if consistently present, could provide more evidence for a synergistic role for insulin resistance and altered fibrinolysis in the pathogenesis of CHD. To test the hypothesis further therefore, we explored the relationships between the fasting levels of insulin and PAI-1 and lipids in groups of non-diabetic Arab subjects classified as: A: normolipidaemic (n = 148); B: hyperlipidaemic: (n = 99), subdivided into - C: normotensive (n = 71) and D: hypertensive (n = 28); and E: patients with CHD (n = 12). In Group A, fasting insulin (FI) was 7.2+/-(SD) 3.4 mU/l, PAI-1 30.6+/-9.7 ng/ml, both levels significantly lower (P < 0.05) than in Group B as a whole (FI 9.7+/-5.2, PAI-1 36.9+/-10.6), or as normotensive Group C (FI 9.4+/-5.4, PAI-1 36.7+/-10.3) or hypertensive Group D (FI 10.9+/-4.8, PAI-1 37.2+/-11.5). These values were highest in the hyperlipidaemic hypertensive Group D. There were no significant differences relative to the hyperlipidaemic phenotype of predominant hypercholesterolaemia, hypertriglyceridaemia or mixed hyperlipidaemia. PAI-1 (34.7+/-13.8) and FI (7.0+/-2.4) levels in Group E with CHD were similar to those of Group A but lower than values seen in Groups B, C and D. Consistent positive correlations (r = 0.32-0.41, P <0.01) were demonstrable in all the groups between PAI-1 and triglycerides levels. There were also significant correlations between insulin and PAI-1 (r = 0.20, P<0.1) in all the subjects (grouped as a whole, n = 259) and in normolipidaemic Group A (r = 0.29, P < 0.01) but not in any of the hyperlipidaemic groups or in patients with CHD. This study therefore suggests that levels of insulin and PAI-1 are increased in hyperlipidaemic subjects, particularly when also hypertensive. The further observation of significant correlations between insulin and PAI-1 levels only in normolipidaemic subjects and not those who were hyperlipidaemic or with CHD is at variance with observations in Caucasians in whom strong positive correlations between insulin and PAI-1 had suggested that elevated PAI-1 levels should constitute one more component of the metabolic syndrome which strongly predisposes to CHD. Whether this is a racial variation or an artifact of the insulin/PAI-1 assay methodology is unclear and deserves further study.