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.

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.

Dietary fiber--an overview.

Diabetes diets should aim at ensuring an ideal body weight with normoglycemia and normolipidemia. The consensus recommendations of various diabetes associations suggest that these goals are most likely to be achieved by diets high in complex carbohydrates and fiber and low in fat. A typical diabetes diet containing 55-60% energy as carbohydrate (at least 66% complex), less than 30% energy as fat, 0.8 g.kg-1 desirable body wt.day-1 protein, and approximately 40 g fiber/day, improves glycemic control, reduces levels of serum atherogenic lipids, decreases blood pressure in those with hypertension, and reduces body weight in the obese. This diet also reduces insulin requirements in the insulin-treated patient and can promote discontinuation of insulin therapy in those with non-insulin-dependent diabetes mellitus. This article presents our experience with high-fiber high-carbohydrate diets and reviews knowledge on the likely mechanisms of action of fiber, its long-term effectiveness, and the concerns about its long-term safety. We suggest that reports on the risk of hypertriglyceridemia from on the risk of hypertriglyceridemia from high-carbohydrate diets are inconsistent and invalidated if those diets are also high in fiber content. Similarly, we urge some caution in prescribing high-monounsaturated fat diets as an alternative to high-carbohydrate diets, at least until the long-term implications of the former are clearer. We believe that there is no compelling reason to change the current diabetes diets, which should continue to be high in carbohydrate and fiber content.

Serum insulin and glucose concentrations in people at risk for type II diabetes. A comparative study of African Americans and Nigerians.

OBJECTIVE: To examine the phases of acute insulin release and glucose homeostasis in people of African descent with and without a positive family history of type II diabetes who reside in geographically diverse environments. The prevalence of type II diabetes in people of African descent varies considerably depending on the country of habitat. Family history is recognized as an important risk factor for the development of the disease. RESEARCH DESIGN AND METHODS: We studied serum glucose and insulin concentrations--before and after intravenous glucose challenge--in glucose-tolerant, first-degree relatives of African-American (n = 18) and Nigerian (n = 20) type II diabetic patients and their respective healthy control subjects (African American, n = 9; Nigerian, n = 18) living in their native countries. The acute first- (t = 0-5 min) and second-phase (t = 10-60 min) insulin releases were calculated as the sum of incremental insulin responses to the intravenous glucose stimulation. RESULTS: Mean serum glucose levels and glucose decay constant (KG) were not different in the African Americans and Nigerians. Fasting serum insulin in the African-American relatives was significantly greater than the Nigerian relatives (16.0 +/- 3.0 vs. 5.8 +/- 1.7 mU/L, P < 0.05). In contrast, FSI levels in the African-American control subjects were similar to Nigerian control subjects (6.3 +/- 1.4 vs. 4.5 +/- 1.8 mU/L). Acute first- and second-phase insulin levels were 2-3 times (P < 0.01) greater in African Americans than Nigerians, irrespective of family history of diabetes. Comparing the African-American relatives with healthy control subjects, we found significantly (P < 0.05) higher FSI in the relatives; whereas the acute first- (272 +/- 44 vs. 222 +/- 55 mU/L) and second-phase (388 +/- 61 vs. 235 +/- 53 mU/L) serum insulin release tended to be greater, but not significantly different in the relatives. In contrast, the acute first (101 +/- 15 vs. 120 +/- 20 mU/L) and second phase (88 +/- 14 vs. 111 +/- 17 mU/l) of insulin release were slightly lower, but not significantly different, in the Nigerian relatives versus the Nigerian healthy control subjects. In a subgroup of nonobese African-American (n = 11) and Nigerian (n = 11) relatives, and African-American (n = 8) and Nigerian (n = 7) healthy control subjects with a body mass index < 30 kg/m2, the mean fasting and post-stimulation serum glucose were not different. However, serum insulin concentrations in the African Americans were significantly different from those of the Nigerians. The pattern of insulin responses in the nonobese subjects was similar to those of the respective African-American and Nigerian groups. CONCLUSIONS: Our preliminary study demonstrates greater serum insulin responses and, perhaps, insulin resistance in glucose-tolerant African Americans than in their Nigerian counterparts, irrespective of family history of diabetes and obesity. We conclude that the antecedent lesions leading to the development of type II diabetes may be different in the first-degree relatives of African-American and Nigerian diabetic patients.

Acetate tolerance and the kinetics of acetate utilization in diabetic and nondiabetic subjects.

We investigated acetate utilization in humans by randomly intravenously infusing acetate (2.5 mmol/min) or bicarbonate (2.8 mmol/min) over 60 min into nine nondiabetic and six non-insulin-dependent diabetic subjects followed with or without bolus intravenous glucose (20 g/m2 body surface area). The acetate metabolic clearance rate (MCR) was greater in the nondiabetic subjects (50.4 +/- 14.9 vs 25.0 +/- 6.5 mL.min-1.kg-1, p less than 0.01) as were acetate elimination rate constant (Kac) (0.031 +/- 0.003 vs 0.026 +/- 0.004/min, p less than 0.01) and basal turnover rate (8.56 +/- 3.65 vs 4.92 +/- 1.03 mumol.min-1.kg-1, p less than 0.01); acetate half-time was thus shorter in the nondiabetics (22.6 +/- 2.2 vs 27.2 +/- 3.8 min, p less than 0.01). Kac was reduced and half-time was prolonged in all the subjects (p less than 0.001) when glucose was available. Prior acetate or bicarbonate infusion had no influence on either the KG rate constant of glucose elimination or the postglucose insulin responses in both subject groups. These results suggest that the infused acetate did not worsen glucose tolerance, glucose impaired acetate utilization unlike reported in ruminants, and acetate is rapidly metabolized in humans although at a slower rate in diabetics.

The prevalence of insulin resistance and other cardiovascular disease risk factors in healthy elderly southwestern Nigerians.

We assessed the prevalence of coronary heart disease (CHD) risk factors including insulin resistance in 500 (205 males, 295 females) healthy elderly (age > 55 years) indigenous, low socioeconomic group Yorubas residents in either an urban slum (n = 240) or a rural town (n = 260) in southwestern Nigeria. Anthropometric indices, blood pressure and fasting plasma levels of glucose, lipids, insulin and insulin resistance were measured. The results indicated that: (i) gross obesity (4.4%), diabetes (1.6%), hyperlipidaemia (0.2%) and cigarette smoking (4.8%) were relatively uncommon in the population, although the prevalence of hypertension (30%) was higher than previously reported from this population; (ii). the subjects had a relatively high prevalence of multiple CHD risk factors (about 20% had > 4 risk factors), an observation considered paradoxical in view of the reportedly low CHD prevalence in this population; (iii) these CHD risk factors (increased body mass and blood pressure (BP), hyperinsulinaemia and insulin resistance) were more prevalent in the women and in urban residents; (iv) hyperinsulinaemia (20%) and insulin resistance (35%) were common in the population, and were associated, on regression analyses, to such other CHD risk factors as BP and body mass, particularly in women, suggesting, as in Caucasians, that insulin resistance could be an important index of CHD risk; and (v) the excess of multiple CHD risk factors in the women, is due at least in part, to their increased tendency to obesity (8%) and reduced physical activity (83%). This study concludes that: (i) despite the high prevalence of multiple risk factors in this population, CHD prevalence is low, indicating the supremacy of such major risk factors as diabetes and hyperlipidaemia (relatively uncommon here) in the development of CHD; and (ii) potentially the greatest CHD risk is in the elderly women especially if relatively overweight, physically inactive and resident in an urban centre. While further confirmatory studies are necessary in younger subjects and across societal socioeconomic strata, our results nonetheless suggest that attempts to maintain the CHD prevalence at low levels in this population should include efforts directed at reducing excess body weight particularly in women, and advice on maintenance of a traditional diet to keep lipid levels and diabetes prevalence low.

The effects of changes in plasma nonesterified fatty acid levels on oxidative metabolism during moderate exercise in patients with non-insulin-dependent diabetes mellitus.

Blood levels of intermediary metabolites were measured and indirect calorimetry was performed in 10 otherwise healthy, non-insulin-dependent diabetic (NIDDM) patients before, during, and after 30 minutes of moderate exercise on three occasions in random order at weekly intervals with (1) heparin treatment to increase preexercise plasma nonesterified fatty acid (NEFA) levels (HEPARIN); (2) acipimox, a nicotinic acid analogue, to reduce preexercise plasma NEFA levels (ACIPIMOX); and (3) no manipulation of preexercise plasma NEFA levels (NIL). With ACIPIMOX, preexercise blood levels were significantly reduced for NEFAs and glycerol (P < .01) and marginally reduced for acetoacetate and 3-hydroxybutyrate (NS) compared with preexercise levels for the other two treatments; these low levels seen with acipimox treatment increased only slightly during exercise and the postexercise period. Plasma NEFA levels increased by approximately 150% (P < .001) with HEPARIN at the same times. The levels of ketone bodies during either NIL or HEPARIN increased rapidly postexercise by approximately 90% to 110% for both acetoacetate and 3-hydroxybutyrate (both P < .01). Plasma insulin levels tended to be lowest (despite similar plasma glucose levels during the three treatments) with ACIPIMOX, while growth hormone (hGH) and, perhaps, noradrenaline levels were highest both during and after exercise. The respiratory quotient (RQ) was highest with ACIPIMOX (P < .05 for exercise and postexercise periods compared with the other two treatments), which, compared with NIL, reduced fat oxidation by 27% and 60% and increased carbohydrate oxidation by 29% and 74% during and after exercise, respectively (all P < .05). These changes in substrate oxidation due to ACIPIMOX were almost opposite to those observed with HEPARIN.(ABSTRACT TRUNCATED AT 250 WORDS)

Glycaemia and body mass as determinants of plasma lecithin: cholesterol acyltransferase activity in Nigerian patients with non-insulin dependent diabetes mellitus.

There is an inverse correlation between plasma high density lipoprotein (HDL) concentrations and atherogenic vascular morbidity risk. An important pathway for modulating circulating HDL levels is the reaction catalysed by the plasma enzyme, lecithin:cholesterol acyltransferase (LCAT). Thus, determinants of LCAT activity should influence plasma HDL levels and be accessible targets for intervention. We therefore assessed such determinants in Nigerian patients with non-insulin dependent diabetes mellitus (NIDDM), classified into age- and sex-matched groups of obese (body mass index, BMI, > 25 kg/m2) and non-obese (BMI < 25 kg/m2). Our results indicated that 10 obese diabetic patients had significantly reduced plasma LCAT activity and HDL levels and increased plasma triglyceride (TG) levels, in comparison with the observations in 9 non-obese diabetic patients (all P < 0.05). Furthermore, worsening of glycaemic control, when oral hypoglycaemic treatment was discontinued for 1 week in 10 diabetic (5 obese) patients, further reduced fasting levels of HDL and plasma LCAT activity (both P < 0.05). Although plasma HDL concentrations and LCAT activity levels did not correlate significantly, the latter nonetheless had a significant inverse relationship with fasting plasma glucose levels in the obese diabetic subjects (r -0.51, P < 0.05). These results indicate that glycaemia and body mass are important determinants of plasma LCAT activity. Both variables are subject to pharmacological and dietary intervention with the objective of increasing circulating HDL levels.

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.

Plasma acetate levels in response to intravenous fat or glucose/insulin infusions in diabetic and non-diabetic subjects.

We measured plasma levels of acetate, glucose, insulin, fatty acids and 'ketone bodies' (KB), during fat infusion and continuous simultaneous infusion of insulin and glucose according to a computerized algorithm to maintain fasting euglycaemia and derive indices of tissue insulin sensitivity (hyperinsulinaemic euglycaemic clamping HEC). (i) Plasma acetate levels (mmol/l) approximately doubled (0.14 +/- (SEM) 0.02 to 0.25 +/- 0.02, p less than 0.01) during INTRALIPID infusion in 7 non-diabetic individuals while total 'ketone bodies' and non-esterified fatty acids (NEFAs) increased 10-fold. (ii) Early in the HEC, plasma acetate levels decreased as did NEFAs in 13 non-diabetic (0.17 +/- 0.01 to 0.12 +/- 0.01, p less than 0.001) and 9 diabetic (0.22 +/- 0.02 to 0.15 +/- 0.01, p less than 0.005) individuals. However while acetate levels later rose to fasting values in the non-diabetics, they remained low in the diabetics. NEFA levels were low throughout the clamp but glucose flux was increased as judged from the glucose infusion even with maintained euglycaemia. The change in acetate values during the second hour of the clamp correlated with neither BMI nor two indices of insulin sensitivity (glucose metabolic clearance rate and steady state glucose infusion rate). These results accord with acetate production from glucose and fat oxidation, via acetyl CoA. The differing metabolism of acetate in the second hour of clamping between diabetics and non-diabetics may reflect altered post-receptor glucose metabolism with the onset of diabetes.

The relationship of plasma acetate with glucose and other blood intermediary metabolites in non-diabetic and diabetic subjects.

In investigating the interrelations of plasma acetate with glucose metabolism, we established that fasting plasma acetate levels (mmol/l) were greater in the diabetic than non-diabetic individuals (p less than 0.001). Plasma acetate and glucose levels correlated in all subjects (non-diabetic and diabetic) as a whole (rs 0.28, p less than 0.0001) and in the diabetics alone (rs 0.35, p less than 0.001). After i.v. glucose (20 g/m2 body surface area), plasma acetate levels increased further in the diabetic and non-diabetic individuals. Plasma acetate also increased when non-diabetic individuals consumed 75 g oral glucose. Moreover, while plasma acetate levels had returned to fasting values by 90 min in the non-diabetic subjects after oral and i.v. glucose, levels remained elevated in the diabetics after i.v. glucose. The K rate constant of glucose elimination after i.v. glucose in the diabetics correlated negatively with acetate values at many time points. In the non-diabetics, changing acetate and glucose levels after oral glucose also correlated at multiple time points. These results suggest that the plasma acetate level is influenced by variations in glycaemia and provide further evidence for an impaired rate of acetate metabolism in diabetes.

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.

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.

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.

Glucose and insulin responses to intravenous glucose challenge in relatives of Nigerian patients with non-insulin-dependent diabetes mellitus.

We analysed blood insulin and glucose concentrations before and during frequently sampled intravenous glucose tolerance tests (FSIGT) in 2 groups of Nigerian subjects: (A) Control group (n = 18), without a positive family history of diabetes mellitus, and (B) Experimental group (n = 16), comprising age-, sex- and body mass-matched first-degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM). In comparison with Group A subjects, those in Group B had: (i) higher fasting plasma glucose level (mean +/- S.E.M. 4.1 +/- 0.1 vs. 3.8 +/- 0.11 mmol/l, P < 0.05); (ii) similar fasting serum insulin levels (6.7 +/- 5.0 vs. 5.8 +/- 5.6 mU/l, P = NS); (iii) lower mean incremental area under the first-phase (t = 0-10 min) post-glucose challenge insulin curve (376.9 +/- 8.8 vs. 435.6 +/- 5.6 mU/min l-1, P < 0.05); (iv) increased incremental area under the second-phase (t = 10-182 min) post-glucose challenge insulin curve (432.9 +/- 11.5 vs. 161.3 +/- 8.7 mU/min l-1, P < 0.05); (v) reduced KG rate constant of glucose elimination (0.97 +/- 0.12 vs. 1.41 +/- 0.12%/min, P < 0.05). These results suggest that the subjects with a positive family history of NIDDM have a reduced beta-cell insulin secretory reserve (from reduced first-phase insulin response), tendency to rebound hyperinsulinemia during the latter phase of the insulin secretory response, a degree of tissue insulin insensitivity (as evident from high fasting plasma glucose despite similar insulin levels) and a diminished glucose disposal rate, in comparison with subjects without a family history of NIDDM. These features predict subsequent development of diabetes and suggest that as in Caucasians, first-degree relatives of Nigerian patients with NIDDM are at greater risk for future development of the 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'.

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.