Abayomi O. Akanji

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.

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 disorders clinical expression. It is suggested that there may be an inflammatory component to schizophrenia which is associated with aspects of its clinical phenotype.

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/m2 (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.

Diabetic Dyslipidaemia in Kuwait

About 15% of the adult Kuwaiti population has type 2 diabetes and over 50% are hyperlipidaemic by current diagnostic criteria. Not surprisingly, coronary heart disease (CHD) is the leading cause of death in Kuwait. Reports from coronary care units in Kuwait suggest that 40–80% of the CHD patients were diabetic and 50–80% hyperlipidaemic. The pattern worldwide is similar. International guidelines have therefore consistently recognised diabetes as a major risk factor for CHD. In our Lipid Clinic population in Kuwait, about 30% are diabetic. The commonest lipid abnormalities seen in Kuwaiti diabetic patients, as elsewhere, are hypertriglyceridaemia with low HDL levels and variable LDL levels. About 75% of the subjects had either mixed hyperlipidaemia or predominant hypertriglyceridaemia. There are possibly some compositional changes in LDL in the diabetic subjects in that there were important differences in the statistical relationships between LDL and HDL and their respective apolipoproteins – apo B and apo A-1 in diabetic as compared to non-diabetic subjects. Other important observations made in diabetic subjects in Kuwait are: (i) similar serum Lp (a) levels and pattern of apo(a) polymorphism with non-diabetic subjects, with no demonstrable relationship between serum levels of Lp(a) and insulin/insulin sensitivity, although with CHD, Lp(a) levels were increased; (ii) diabetic hyperlipidaemic subjects had elevated PAI-1 levels with significant correlations between blood PAI-1 and insulin levels suggesting underlying insulin resistance (syndrome X). Various landmark trials of cholesterol-lowering therapies in the prevention of CHD have consistently demonstrated near-normalization of the increased CHD risk in diabetes. Our experience in Kuwait suggests that diabetic patients and others with mixed hyperlipidaemia benefit from tight glycaemic control, appropriate advice on diet and exercise with regular reinforcement by continuing contact with professional dietitians and regular availability of drugs where prescribed. Often, it is the regular compliance with medication that is important, rather than the specific medication used particularly where HMG CoA reductase inhibitors (statin drugs) are not always available. A useful guideline for management of dyslipidaemia in diabetes is suggested.

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.

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.

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.

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.

Determinants of glycated LDL levels in nondiabetic and diabetic hyperlipidaemic patients in Kuwait

BACKGROUND Glycation and oxidative modification of lipoproteins enhance the uptake of these lipids by macrophages in the early stages of atherogenesis. Measurement of blood levels of modified LDL particles could thus constitute another useful modality in identifying subjects at high risk of coronary atherosclerosis (CHD). OBJECTIVE To measure the glycated LDL level and assess its associations with other metabolic parameters in diabetic and nondiabetic hyperlipidaemic subjects attending a Lipid Clinic in Kuwait. SUBJECTS AND METHODS One hundred thirty-three hyperlipidaemic (HL) (72 nondiabetic (ND); 61 diabetic (D)) patients and 42 healthy control (HC) subjects had their fasting serum samples analyzed for glucose, total cholesterol (TC), triglycerides (TG), urate, HDL, LDL (by routine autoanalyzer methods), apolipoproteins A1 and B (by nephelometry), fructosamine (by spectrophotometry) and glycated LDL (gLDL) by ELISA. RESULTS The serum gLDL level was significantly higher in HL [D+ND] than in HC (p<0.001). Within the HL group, the DHL patients had higher levels than the NDHL [p<0.001]. These differences were maintained when the gLDL level was also expressed as a percentage of the apo B concentration. The gLDL level correlated positively (p<0.01) with those of glucose, TC, TG and LDL and negatively with HDL (p<0.05) in all the subjects as a whole, healthy and hyperlipidaemia [HC+HL]. In the HL (D+ND) group as a whole, gLDL correlated significantly only with glucose [p<0.01]. In group DHL, however, gLDL correlated significantly with glucose, fructosamine and LDL [all p<0.05]. As expected, fructosamine levels were highest in the DHL group. The significant correlations established between fructosamine and the different analytes measured in the different subject groups were essentially similar to those observed for gLDL, except for the finding of persistent significant negative correlations of fructosamine with LDL in all the subject groups. CONCLUSIONS (i) Serum gLDL levels are increased in hyperlipidaemic patients and are further increased with diabetes, suggesting that the significant glycation of LDL occurs in all hyperlipidaemic patients irrespective of their glycaemic status. (ii) The significant correlation of gLDL with glucose and fructosamine in diabetic patients would suggest its potential utility as another index of medium term glycaemic control. (iii) gLDL is easily measurable and its values could provide additional information in ascertaining an individuals aggregate CHD risk.

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.