Family history as a risk for early-onset type 2 diabetes in Kenyan patients

Early-onset type 2 diabetes is regarded as disease occurring before the age of 40 years. It is well described, and increasing in prevalence, but there is little information from Africa. We therefore assessed the prevalence of early-onset type 2 diabetes in Nairobi, Kenya; and investigated its association with family history. Of 140 patients with type 2 diabetes, 33 (24%) had an early onset. There was a positive family history of diabetes in 85% of those with early onset, compared with 56% of those with usual onset (p=0.009). This suggests that relatives of those with early-onset type 2 diabetes should have regular diabetes screening

The effect of abdominal obesity on insulin sensitivity and serum lipid and cytokine concentrations in African women.

OBJECTIVES: Studies have shown clear associations of abdominal obesity with lipid and glucose metabolism and cytokine levels in a number of different population groups. However, no such studies have been performed in an African population in which visceral adipose tissue levels have been shown to be lower than in European subjects. DESIGN AND PATIENTS: Cross-sectional analysis in 124 African women. MEASUREMENTS: Fasting serum samples were taken from all subjects and anthropometric measurements obtained. Blood levels of glucose, insulin, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglyceride, interleukin (IL)-6, IL-8 and IL-18 were measured. Subjects were separated into normal and abnormal glucose tolerant groups and into tertiles according to waist circumference (WC). Insulin resistance was assessed using the homeostasis model assessment (HOMA). RESULTS: Abnormal glucose-tolerant subjects had higher WC, glucose and HOMA levels than the normal glucose-tolerant group. Increased WC was associated with higher triglyceride, insulin and HOMA levels and lower HDL levels. Multiple regression analyses showed that WC associated positively with HOMA and serum triglyceride levels and negatively with HDL levels. IL18 was a positive but weak determinant of the HOMA level and BMI correlated positively with serum IL-6 concentrations. CONCLUSIONS: Although previous studies have shown that African subjects have a lower visceral adipose depot size than European subjects, abdominal obesity is still associated with insulin resistance and dyslipidaemia. The association between abdominal obesity and metabolic dysfunction within this population is not dependent upon IL-6, IL-8 or IL-18.

The accuracy of urine dipsticks as a screening test for proteinuria in hypertensive disorders of pregnancy.

BACKGROUND: Proteinuria is used as a criterion in the classification system for hypertensive disorders of pregnancy including preeclampsia. The aim of the study was to evaluate the accuracy of dipstick urinalysis in a single voided urine sample and in an aliquot of a 24-hour urine collection in the assessment of proteinuria in hypertensive pregnant women, using the 24-hour urine protein excretion as the gold standard. METHODS: One hundred ninety-eight women who presented with hypertension in pregnancy were recruited at the antenatal clinic at King Edward VIII Hospital in Durban, South Africa, a tertiary referral center. Exclusion criteria included women with eclampsia, urinary tract infection, and chronic renal disease. Routine dipstick urinalysis (Bayer) was performed by midwives for proteinuria, and a 24-hour urine specimen was collected for quantitative protein assessment. A laboratory technician performed urine dipstick test for protein on a mixed aliquot of the 24-hour urine specimen. This result, together with that of the screening dipstick urinalysis, was compared to the 24-hour urine protein excretion. RESULTS: The results of the 198 patients were analyzed, of the total, 72 had preeclampsia. Using a value of = 0.3 g protein excretion per 24 hours (1 + to 4 + on urine dipsticks) as positive, sensitivity, specificity, and predictive values for dipstick urinalysis were calculated. The positive predictive value for dipstick urinalysis ranged from 64.9% (single voided urine sample) to 94.2% (24-hour urine aliquot). The negative predictive value ranged from 75.2% (single voided urine sample) to 84.2% (24-hour urine aliquot). CONCLUSION: Dipstick urinalysis is not very accurate: therefore, all women presenting with hypertension during pregnancy should have a 24-hour urine protein measurement.

Serum cystatin C for assessment of glomerular filtration rate in hypertensive disorders of pregnancy.

BACKGROUND: Assessment of renal function is important in the evaluation of the pregnant hypertensive patient. The aim of this study was to evaluate the diagnostic utility of cystatin C as a marker of glomerular filtration rate in hypertensive disorders of pregnancy and to correlate this with serum creatinine and creatinine clearance. METHODS: For our study, 198 women who presented with hypertension during pregnancy were recruited at the antenatal clinic of King Edward VIII Hospital in Durban, South Africa, a tertiary referral centre. Exclusion criteria included women with eclampsia, urinary tract infection and chronic renal disease. Routine dipstick urinalysis (Bayer) was performed by midwives to classify patients suffering from the different forms of hypertensive disorders of pregnancy and venous blood samples for determination of serum cystatin C and serum creatinine were collected. The 24-hour urine creatinine clearance was used as the "gold standard" for evaluation of glomerular filtration rate due to concerns of radiation exposure to pregnant women with the use of radio nucleotide markers. RESULTS: The results of testing the 198 women, 72 of whom had preeclampsia, were analyzed. Serum cystatin C showed a significant correlation with creatinine clearance at the 0.01 level (2-tailed) with an r-value of -0.311. Serum creatinine showed a significant correlation with creatinine clearance at the 0.01 level (2-tailed) with an r-value of -0.486. CONCLUSION: Serum cystatin C seems to reflect glomerular filtration rate reliably in hypertensive pregnant women and avoids the inaccuracy associated with the 24-hour urine collection, which is time consuming and subject to improper collection.

The effect of different apo(a) isoforms on plasminogen activation in black South African subjects.

OBJECTIVE: The present study evaluates the effect of different apolipoprotein(a) [apo(a)] isofroms on plasminogen activation. DESIGN: A cross-sectional study. SETTING: A rural village (Dikgale district) in the Northen Province of South Africa. SUBJECT: A total of 90 apparently healthy subjects (64 females and 36 males) aged 43 to 67 years participated in the study. RESULTS: The mean lipoprotein(a) [ Lp(a)] level in the subjects was 38.14 +/- 22.34 mg/dl. No association was found between Lp(a) isoforms. When the ratio of Lp(a):plasminogen was less then 1.3, a competitive inhibition was observed, but when the ratio exceeded 1.3, an uncompetitive inhibition was observed with all isoforms. CONCLUSION: The results of the present study suggest that the inhibition of plasminogen activation by Lp(a) is not dependent of apo(a) size.

Leptin and pre-eclampsia in black African parturients.

OBJECTIVE: To measure serum concentrations of the hormone leptin during late pregnancy in Black African women with pre-eclampsia, healthy normotensive pregnant women as controls and healthy normotensive non-pregnant women; secondly, to explore the relationship between leptin and obesity. DESIGN: Observational, cross sectional study. SETTING: Antenatal clinics, antenatal wards, gynaecology out patient and family planning clinics of a tertiary hospital, Durban, South Africa. POPULATION: Pregnant and non-pregnant Black African women. METHOD: Serum leptin was measured by a homologous radio-immunoassay technique. Simple anthropometric parameters were used to explore the relationship between leptin and obesity. In each group, leptin levels were compared between obese (body mass index, BMI > or = 30 kg m(-2)) and lean women. MAIN OUTCOME MEASURES: Serum leptin concentrations, anthropometric parameters, mean blood pressures and proteinuria. RESULTS: There were 68 women with pre-eclampsia, 92 healthy normotensive pregnant women (controls) and 32 healthy normotensive non-pregnant women. Serum leptin levels were higher in pregnant compared with non-pregnant women [26.66 (1.96) and 25.89 (1.65) vs 17.97 (2.11) ng/mL, P = 0.02]. Weight and BMI showed the greatest correlation with leptin both in pregnant (r = 0.61 and r = 0.58, respectively) and non-pregnant women (r = 0.74 and 0.79, respectively). There was no significant difference in the mean concentrations of leptin between women with and those without pre-eclampsia [26.66 (1.96) vs 25.89 (1.65) ng/mL, respectively, P = 0.95]. CONCLUSION: Pregnancy is a hyperleptinaemic state. There is no difference in serum leptin levels between Black African women with pre-eclampsia and healthy normotensive pregnant women. Serum leptin concentration is largely determined by the degree of adiposity.

Biochemical and molecular diagnosis of glutaric aciduria type 1 in a black South African male child: case report.

Glutaric aciduria type 1 (GA-1) is an inborn error of metabolism caused by a deficiency of the mitochondrial enzyme glutaryl-Co enzyme A dehydrogenase. GA-1 is not uncommon amongst Caucasians but to the best of our knowledge, it has previously not been reported in black African children. We present a case of GA-1 in a black South African boy who was referred to hospital at the age of five years and ten 10 months with dyskinesia and dystonia accompanied by chorea and athetosis. Radiological examination revealed enlarged basal cisterns with bilateral fluid collection around the sylvian fissures suggestive of GA-1. Analysis of urine showed raised levels of glutaric acid at 520 micromol/mmol creatinine (normal <2.0), 3-hydroxyglutaric acid at 113 micromol/mmol creatinine (normal <3.0) and a low blood carnitine level of 31.5 micromol/l (normal 35-84). A definitive diagnosis was reached through DNA analysis which revealed homozygosity for an A293T mutation in the glutaryl-Co-enzyme A dehydrogenase (GCDH) gene.

Collagen Ialpha1 and vitamin D receptor gene polymorphisms in South African whites, blacks and Indians.

OBJECTIVE: To determine whether polymorphic differences exist between black, white and Indian South Africans in genes associated with bone mineral density and osteoporosis. DESIGN: Genes selected were the vitamin D receptor (Apa I and Taq I polymorphisms) and collagen (Sp I transcription factor polymorphism) using standard molecular biology techniques. SETTING: Department of Chemical Pathology, Nelson R Mandela School of Medicine, University of Natal, Durban, South Africa. SUBJECTS: Healthy male and female blood donors living in the Durban metropolitan region, South Africa. The group comprised black Africans (n=264), white Caucasians (n=247) and Asians of Indian origin (n=194). RESULTS: No significant differences in genotypes were seen between white and Indian subjects. Blacks had a significantly higher frequency of the TT Taq I genotype and a significantly lower frequency of the Ss Sp I genotype. No ss genotype was detected in blacks. CONCLUSION: The very low frequency of the collagen Sp I s allele and higher frequency of the VDR T allele in blacks may be associated with the lower incidence of osteoporosis in this ethnic group.

Soluble transferrin receptors in anaemia of pregnancy.

Anaemia is one of the most common disorders in pregnancy. The most common cause is iron deficiency. Iron deficiency anaemia is relatively easy to diagnose using a serum ferritin of <15 ng/ml. However, because ferritin is an acute phase reactant, the diagnosis of iron deficiency anaemia in hospitalised or ill patients may be difficult, since serum ferritin may be normal or raised, even in the face of iron deficiency. Soluble transferrin receptor assay (STfR) may be useful in these situations because it reflects the degree of iron requirement in relation to supply, and it is not an acute phase reactant. This study was undertaken to detect subclinical anaemia in pregnant women and to correlate STfR assay with the current diagnostic tests for iron deficiency anaemia. One hundred and fifty-three consenting pregnant women seen at the antenatal clinic at King Edward VIII Hospital (KEH) were recruited. Women on haemantinics, who had renal failure, haemoglinopathy and blood transfusion in the past 3 months, were excluded. An ELISA technique was used for the assay of STfR while standard methodology was used for the other biochemical and haematological assays (FBC, urea, creatinine, c reactive protein and iron studies). One hundred and fifty subjects were included in the final analysis. Seventy-two (48%) had varying degrees of iron deficiency anaemia. In 70% (105) of the samples analysed, serum ferritin and STfR agreed on the presence/absence of iron deficiency anaemia. STfR and S:F were 75% and 86% sensitive; 63% and 82% specific, respectively. The calculated positive and negative predictive values are: STfR 64% and 75%; S:F 84% and 87%; Hb 58% and 57%; mean corpuscular volume 91% and 55%, respectively. Ferritin remains the gold standard for the diagnosis of iron deficiency anaemia. However, because ferritin is an acute phase reactant, soluble transferrin receptor assay may be a better test in ill and hospitalised patients where ferritin may be normal or elevated, despite iron deficiency.

Galactosaemia in black South African children.

OBJECTIVE: To evaluate the clinical and biochemical features of all black children confirmed to have galactosaemia from the KwaZulu Natal Province of South Africa. DESIGN: Prospective laboratory study. SUBJECTS: These included all black children with the presenting clinical features suggestive of the diagnosis of galactosaemia. SETTING: Department of Chemical Pathology, King Edward VIII Hospital, Durban, South Africa. METHOD: In each case, urine was screened for the presence of a reducing substance using urinary dipstick followed by thin layer chromatography to establish the presence of galactosaemia. The diagnosis of galacotosaemia was then confirmed by analysis of galactose-1 phosphate uridyl transferase (GALT) activity in the erythrocytes using the established Beutler enzyme assay procedure. Age and sex-matched samples were used as controls for GALT activity. The presenting clinical features of each patient on admission were also recorded. INTERVENTIONS: Patients confirmed to have galactosaemia were immediately placed on a galactose free diet. RESULTS: The age distribution of affected individuals varied from six weeks to 27 months with 60% of the children being males. The most common presenting clinical features were jaundice in 77% of the patients, failure to thrive 62%, and cataracts 54%. Four patients had complete absence of GALT activity. Two infants who displayed acute toxicity symptoms and positive urine galactose, exhibited normal GALT activity. CONCLUSION: GALT deficiency is the most common form of galactosaemia in black children in the KwaZulu Natal region. Cases of galactokinase or epimerase enzyme deficiency appear to be present. Further investigation is required to establish the occurrence and prevalence of the latter in affected individuals in this region.

Reference intervals for some biochemical parameters in the aged Kenyan population.

Serum levels for sodium, potassium, calcium, inorganic phosphate, urea nitrogen and creatinine were determined in 1101 male and 181 female patients aged 50 years and above. The determinations were carried out on the SMA II (Technicon Instruments Corp. Tarrytown, NY 10591) with a view to establish the reference intervals for this age group. Quality control of the analytical methods was carried alongside with the determinations. The data collected was used to determine the reference intervals using a simple statistical method. The results indicate that sodium and calcium intervals are low with values of 131-142 mMol/L and 1.94-2.32 mMol/L respectively, in the aged Kenyan population as compared to subjects living in the temperate environment while the interval for inorganic phosphate is comparatively high with a value of 1.2-1.97 mMol/L. Reference values for urea nitrogen, potassium and creatinine were found to be similar to those quoted for caucasians.

External quality control performance in clinical chemistry: experience in Kenya.

Analysis of eleven biochemical laboratory tests was done during an International External Quality Assessment Scheme (IEQAS) in which the clinical chemistry laboratory at Kenyatta National Hospital participated. Technicon SMA II continuous flow system was used in the biochemical analyses apart from glucose which was assayed manually by the glucose oxidase method. Using the standard deviation index (SDI), twenty six percent of the results were found to be outside the two standard deviation (2SD) limit. However, when variance index score (VIS) was used, 42% of the results were found to be outliers. Overall, our laboratory performed poorly compared to other laboratories in both the IEQAS and the United Kingdom External Quality Assurance Scheme (UKEQAS). This poor performance is attributed to the use of improper equipment which is not regularly maintained, lack of diagnostic reagents, lack of quality control (QC) materials and inadequate staff training in the field of quality control.

Maternal levels of alpha-fetoprotein in African women.

In a prospective and cross-sectional study, 147 serum samples from normal antenatal indigenous Kenyan women were analysed for alpha-fetoprotein (AFP) concentrations between 8 and 28 weeks gestation. There was progressive rise in AFP levels with gestation, most rapid between 12 and 24 weeks. There were wide variations in AFP concentrations at every gestation but no correlation was established with maternal age or parity. All the eleven women with very high AFP values had subsequent complications, including 2 abortions, 1 APH, 7 PET and one pair of twins. The need for more studies on the value of AFP in monitoring of pregnancy in the African set up is emphasised.

beta S-haplotypes and alpha-thalassemia along the coastal belt of Kenya.

In this paper, we present data on studies of beta S-haplotypes and alpha-thalassemia gene in subjects from the indigenous population of the Coast Province of Kenya Of the 7SS patients studied, four were homozygous for beta S-haplotype 20 characteristically associated with the severe form of sickle cell anemia found in the Central African Republic and Western Kenya. Two had haplotype 20 combined with haplotype 19 (Benin Type) and one had haplotype 20 combined with a new haplotype (20x). Alpha thalassaemia-2 gene (-3.7kb deletion) was detected in 45.6% of the 57AA subjects studied. An alpha globin gene triplication was detected in one subject whereas eight had gamma globin gene triplication.

Characterization of chromosomes with hybrid genes for Hb Lepore-Washington, Hb Lepore-Baltimore, Hb P-Nilotic, and Hb Kenya.

This study concerns the characterization of chromosomes with hybrid genes for Hb Lepore-Washington (44 chromosomes), for Hb Lepore-Baltimore (5 chromosomes), for Hb P-Nilotic (8 chromosomes), and for Hb Kenya (7 chromosomes) by determining a relatively large number of restriction enzyme polymorphism. Two, and possibly three, different Hb Lepore-Washington chromosomes were identified by specific haplotypes, while the haplotype of the Hb Lepore-Baltimore chromosome had its own characteristic pattern. A likely conclusion is that the crossovers leading to the formation of these chromosomes have occurred as independent events within the populations. Chromosomes with the delta beta-Lepore-Washington hybrid gene maintained specific characteristics (such as increased Hb F levels in heterozygotes, and high or low G gamma values in this Hb F) which have been observed in normal individuals with chromosomes having comparable haplotypes. Only one haplotype was observed for each of the chromosomes carrying either the beta delta-P-Nilotic hybrid gene or the A gamma beta hybrid gene of Hb Kenya.

Changes in plasma HDL-cholesterol in women using oral contraceptives in Kenya.

PIP: 125 black Kenyan women attending the Kenyatta National Family Welfare Clinic were randomly allocated to combined and fixed dose oral contraceptives (Eugynon: 500 mcg dl-norgestrel + 50 mcg ethinyl estradiol or Microgynon: 150 mcg levonorgestel + 30 mcg ethinyl estradiol). They were between 18-33 years of age with a mean of 25 +or- 7 years. The mean parity of this group was 3 and they had a mean education standard of 8 years. Fasting blood sampled were taken on recruitment (control cycle) and thereafter once for cycles 1, 3, 6, 9, and 12 during OC use. HDL-cholesterol was estimated in the sear. The 2 OCs elicited a significant decrease in levels of HDL-cholesterol (p0.01).^ieng

Haplotypes and alpha globin gene analyses in sickle cell anaemia patients from Kenya.

Over 60 patients from the Luo and Luhya tribes of Western Kenya, aged 1-23 years, with severe sickle cell anaemia were evaluated through haematological and gene mapping analyses. Nearly all (56 of 58 tested) were homozygous for haplotype 20 (Antonarakis et al, 1984) which is also frequently present in SS patients of the Central African Republic. All patients had a severe haemolytic anaemia with low Hb F levels and low levels of G gamma chains. An alpha-thalassaemia-2 heterozygosity (-alpha/alpha alpha; -3.7 kb deletion) was present in 26 of 53 patients tested; one patient was a homozygote [f(-alpha) = 0.255]. The alpha-thal-2 was type I in all but one subject with this deficiency; the one exception had an alpha-thal-2 heterozygosity, type II. Heterozygosity for the alpha-thal-2 did not affect the clinical condition nor the haematology; Hb F levels were somewhat lower in SS patients with -alpha/alpha alpha than in those with alpha alpha/alpha alpha. A high frequency was observed for the absence of an Xba I restriction site 5' to the zeta globin gene; the frequency of this anomaly [f(Xba I-)] was estimated at 0.39 for the chromosome with two alpha globin genes and at 0.74 for that with the alpha-thal-2 deletion. An Apa I restriction site polymorphism was observed in the IVS-II of the alpha 2 globin gene; 13 alpha 2 genes of 53 normal (alpha alpha/) chromosomes had this restriction site which was absent in the hybrid alpha globin gene of the -alpha/chromosome.