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Biomedical subjects

W M Wan Nazaimoon

Publications and source records attributed to W M Wan Nazaimoon.

8 recordsLinked to original sources

Prevalence of glutamic acid decarboxylase antibodies amongst young Malaysian diabetics.

This study determined the prevalence of glutamic acid decarboxylase antibodies (GAD Ab) in a group of 926 young Malaysian diabetics of three ethnic groups, Malay, Chinese, and Indian. Patients were clinically diagnosed to be Type 1 or Type 2 before the age of 40 years. The overall GAD Ab positivity was 17.4% (161/926), significantly higher in the Type 1 than the Type 2 diabetics (35.5%, 116/329 vs. 7.5%, 45/597, P=0.0001). Compared to GAD Ab negative patients, seropositive diabetics were diagnosed at younger age (21.2+/-0.9 vs. 27.4+/-0.3 y, P=0.0001), had lower fasting (289+/-27.4 vs. 640+/-17.6 pmol/l, P=0.0001) and post-glucagon C-peptide levels (527+/-51.8 vs. 1030+/-28.9 pmol/l, P=0.0001). There were no racial differences in the prevalence of GAD Ab; of the total Type 1, 30.8, 36.4, and 39.4% were Malay, Chinese, and Indian diabetics, respectively and of the total Type 2, 8.8, 8.2, and 4.4% were Malay, Chinese, and Indian diabetics respectively. There was a curvilinear relationship between GAD Ab and the post-glucagon C-peptide levels, suggesting that GAD Ab do play a role in the beta-cells destruction and could be an important immune marker for the LADA group. This study reconfirmed previous reports that the autoimmune mechanisms in the Type 1 Asian diabetics are indeed different from the Caucasians, and further investigations should be carried out to explain the differences.

Adolescent

Systolic hypertension and duration of diabetes mellitus are important determinants of retinopathy and microalbuminuria in young diabetics.

This cross-sectional study looked at the prevalence of microalbuminuria and retinopathy in a cohort of 926 young, Type 1 and Type 2 diabetes mellitus (DM) patients, and determined the factors which were associated with these microvascular complications. The prevalence of microalbuminuria, defined as the albumin:creatinine ratio > or = 2.5 (for males) or > or = 3.5 mg/mmol (for females), was 13.4% in Type 1 DM, 69.5% in insulin-requiring Type 2 DM and 16% in Type 2 DM treated only with oral hypoglycemic agents. Compared to those with normal renal functions, these patients were older (P < or = 0.01), had significantly elevated blood pressures (P < 0.01 or P = 0.0001), and in the case of Type 1 DM, with a higher body mass index (P = 0.0001) and waist-hip ratio (P < 0.01). The prevalence of diabetic retinopathy in Type 1 DM was found to increase with the duration of diabetes, from 1.4% in the newly-onset (< 5 years), to 9.9% in those with 5-10 years disease, to 35% among patients with more than 10 years of diabetes (P < 0.0001). In this study, it was also observed that 10% of the Type 2 DM patients already had retinopathy within 5 years of diagnosis, and the prevalence increased significantly to 42.9% (P < 0.0001) among patients who had been diabetics for more than 10 years. Stepwise multiple regression analysis showed that besides the disease duration, systolic blood pressure was the most common and significant determinant for both microalbuminuria and retinopathy in both types of DM, thus implying that in order to reduce the risk of microvascular complications in diabetes mellitus, systolic and not just the diastolic blood pressure, should be effectively controlled.

Adult

Insulin-like growth factor-binding protein-3 (IGFBP-3) but not insulin-like growth factor-I (IGF-I) remains elevated in euthyroid TSH-suppressed Graves' disease.

Thyroid hormones have been shown to be involved in the regulation of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) expression. This is a cross-sectional study to look at the effects of thyroid hormone status on the circulating levels of IGF-I and IGFBP-3 in a group of 127 patients, aged 20-80 years, who were hyperthyroid, hypothyroid, rendered euthyroid and clinically euthyroid with normal free thyroxine (fT4), but suppressed thyroid stimulating hormone (TSH) levels. TSH was measured by the IMx (Abbott) ultrasensitive assay, while radioimmunoassays for total T3 and T4 were performed using kits from ICN, USA; fT4 and fT3 using kits from DPC USA; IGF-I and IGFBP-3 using kits from Nichols Institute Diagnostics B.V., Netherlands. Differences in the levels of IGF-I between the 4 groups of patients were significant only in the patients aged 20-40. Mean (+/-SEM) IGF-I levels of hypothyroid patients (169+/-19ng/ml) was significantly lower than hyperthyroid (315+/-26 ng/ml, p=0.003), euthyroid patients (241+/-19 ng/ml, p=0.002) and patients with suppressed TSH (308+/-29 ng/ml, p=0.02). The IGF-I levels of the hyperthyroid and suppressed TSH patients were, however, comparable to age-matched normal subjects (281+/-86 ng/ml). Although there was no difference in mean IGFBP-3 levels between the 4 groups of patients, the levels in the patients aged 20-40 with hyperthyroidism (3.7+/-0.9 microg/ml) and suppressed TSH (3.9+/-1.2 microg/ml) were significantly higher (p=0.02) than age-matched normal subjects (3.1+/-0.8 microg/ml). The IGF-I levels of the thyroid patients aged 20-40 showed significant negative correlation to TSH and positive correlations to the thyroid hormones. Hence, whilst low IGF-I is associated with hypothyroidism, high IGFBP-3 is associated with hyperthyroidism. Our finding that IGFBP-3 remained significantly elevated in patients with suppressed TSH but normalised fT4 and fT3 is important as it suggests a prolonged tissue effect of thyroid hormones on IFGBP-3. As such patients have been shown to have higher risk for atrial fibrillation, the significance and possible role of IGFBP-3 in these conditions should be further elucidated in future studies.

Adult

Plasma renin and aldosterone in thyroid diseases.

The effect of thyroid hormones on the renin-angiotensin-aldosterone system has not been fully resolved. Highly specific immunoassays for measurement of renin, aldosterone, free T4 (fT4), free T3 (fT3) and ultrasensitive TSH enables a direct and more accurate measurement of these hormones. We investigated the relationship between plasma renin, aldosterone and thyroid hormones in the basal state and after intravenous frusemide. This is a cross-sectional study involving 37 patients with thyrotoxicosis, 42 rendered euthyroid with normal fT4, fT3 and TSH levels, 17 with euthyroid levels of fT4 and fT3 but suppressed TSH, and 11 with hypothyroidism. Basal plasma renin was significantly higher in thyrotoxicosis (63.4 +/- 9.8 microU/ml, mean +/- SEM) compared to euthyroid (32.7 +/- 4.4 microU/ml) and hypothyroid (26.7 +/- 9.8 microU/ml). Basal plasma renin for euthyroid with suppressed TSH (41.0 +/- 7.4 microU/ml) was significantly higher than hypothyroid (p = 0.02). Basal plasma aldosterones were not significantly different except for suppressed TSH (157.7 +/- 13 pg/ml), which was higher than normal (109.9 +/- 10.4 pg/ml; p = 0.04). Following frusemide, plasma renin and aldosterone were significantly increased in all groups. Plasma renin was highly correlated to fT3 (r = 0.405, p < 0.001), total T3 (r = 0.359, p < 0.001), fT4 (r = 0.331, p < 0.001) and TSH (r = 0.300, p < 0.001) in the basal state, but less to total T4 (r = 0.248, p < 0.01). Plasma renin correlated poorly to serum aldosterone (r = 0.212, p < 0.03). This study clearly showed that regulation of renin was mainly influenced by fT3, and that aldosterone response to frusemide was blunted in thyrotoxicosis despite normal electrolytes.

Aldosterone

Effects of iodine deficiency on insulin-like growth factor-I, insulin-like growth factor-binding protein-3 levels and height attainment in malnourished children.

OBJECTIVE: The expression and synthesis of IGF-I and IGFBP-3 have been shown to be regulated by hormones and nutrition. We study the effects of malnutrition and iodine deficiency on these growth factors and the height attainment of a group of children. DESIGN: We measured serum IGF-I and IGFBP-3 levels in a group of Malaysian aborigine children from three jungle settlements; Sinderut and Pos Lanai are known for iodine deficiency and endemic goitre, and Gombak is an iodine replete area with better socioeconomic status. PATIENTS: A total of 246 children were studied, 188 in the age group 4-10 years and 88 in the age group 11-15 years. MEASUREMENTS: All children were assessed anthropometrically and height standard deviation score (SDS) were calculated using the CDC Anthropometric Software package. Malnutrition was confirmed clinically and according to the WHO definition of malnutrition. IGF-I and IGFBP-3 were determined by radioimmunoassay, and T4 and TSH by immunoradiometric assay. RESULTS: Based on the height SDS, Sinderut and Pos Lanai children were significantly more malnourished and stunted than the Gombak children P = 0.0001). T4 levels were significantly lower (P = 0.0001) amongst the 4-10-years old Sinderut (81 +/- 2 nmol/l) than in Pos Lanai (101 +/- 3 nmol/l) or Gombak (123 +/- 3 nmol/l) children. Similar findings were also seen in the older children; mean T4 levels of those from Sinderut and Pos Lanai (83 +/- 3 and 88 +/- 4 nmol/l respectively), were low (P = 0.0001) compared to Gombak (118 +/- 3 nmol/l). Conversely, TSH levels in both age groups of Sinderut children were significantly elevated (P = 0.0001) (3.5 +/- 0.2 and 3.9 +/- 0.3 mU/l respectively) compared to age-matched groups from Pos Lanal (2.1 +/- 0.1 and 2.2 +/- 0.2 mU/l respectively) and Gombak (1.5 +/- 0.1 and 1.5 +/- 0.2 mU/l respectively). IGF-I and IGFBP-3 correlated significantly with the height SDS of the children, In both the 4-10 (r = 0.400, P = 0.0001 and r = 0.365, P = 0.0001 respectively) and 11-15 years age groups (r = 0.324, P = 0.002 and r = 0.533, P = 0.0001 respectively). Correlation between IGFBP-3 and T4 levels was more significant in the younger children (r = 0.412, P = 0.0001). Association between IGF-I and T4 levels was significant only in the 4-10 years age group (r = 0.237, P = 0.001). CONCLUSIONS: Varying duration and degree of exposure to malnutrition and iodine deficiency resulted in different mean levels of T4, TSH, IGF-I and IGFBP-3 in the three areas. The strong positive associations between IGF-I and IGFBP-3 levels and height SDS suggest that these biochemical measurements are indeed useful indicators of growth and nutritional status in children. The significant correlations between T4 and IGFBP-3 and IGF-1 suggests the importance of thyroid hormones in regulating the synthesis of these growth factors. The age-related increase of these growth factors even amongst malnourished, iodine deficient children implies that age-matched reference ranges are essential for proper evaluation of laboratory results.

Adolescent

Thyroid function and pubertal development in malnutrition.

Thyroid function and pubertal development of aborigines (Orang Asli) and Malays at different socioeconomic strata were assessed among 1136 subjects aged 7 years and above. Anthropometric measurements, goitre and pubertal staging were done. Serum thyroxine (T4), triiodothyronine (T3) and growth hormone were measured using radioimmunoassays (RIA) and serum thyroid stimulating hormone (TSH) by immunoradiometric assays (IRMA). It was found that serum T3 in children was significantly higher in Malays from rural areas, girls and children aged less than 13 years. However, in adults, T3 was significantly associated with anthropometric indices. On the contrary, serum T4 levels were higher among children from urban areas. In adults, serum T4 levels were significantly related to nutritional status and they increased according to the levels of social development, being lowest in remote areas and highest in urban areas. However, serum TSH levels were significantly higher in Orang Asli at all ages and among malnourished children. By using multiple regression, apart from age, gender and ethnicity, nutritional status was a significant predictor for T3 levels in children and adults. Presence of goitre was an important factor which determined the T4 levels in children and adults after controlling for other factors. It was also a predictor for TSH levels in children but not in adults. Fasting serum growth hormone (GH) levels were significantly higher among less privileged groups and decreased according to social development. Serum growth hormone was negatively correlated with anthropometric indices and had a significant association with malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Serum thyroid stimulating hormone (TSH) in malnutrition: preliminary results.

This is a report of a cross sectional study involving 3 groups of children, moderately malnourished (BMI < 15), mildly malnourished (BMI 15-18) and well nourished (BMI > 18) to determine the differences in hormonal and biochemical parameters between the groups. The children were of age range from 7-17 years old. The children were from the same area with exposure to the same food, drinking water and environment. There were significant differences in the nutritional indices between the three groups. No differences were observed in levels of triiodothyronine (T3), thyroxine (T4) and T3:T4 ratio. Significant difference however was found in the TSH levels using highly sensitive IRMA TSH assays. Moderately malnourished children had higher TSH levels (p < 0.05) compared to mildly malnourished and well-nourished children. No difference was found between the mildly malnourished and well-nourished groups. There were no significant differences in serum cortisols done at similar times, fasting growth hormone and calcium. Serum alanine transminase (ALT) however was higher in moderately malnourished than in well-nourished children. Thus using highly sensitive IRMA TSH assays, we were able to detect differences in TSH levels even though T3, T4 and T3:T4 ratio, cortisol, growth hormone and calcium were normal, implying in moderately malnourished children, a higher TSH drive to maintain euthyroid state.

Adolescent

Development of an in-house radioimmunoassay for human growth hormone.

A simple and sensitive double-antibody radioimmunoassay for human growth hormone (HGH) was developed, optimised and validated. The anti-hGH sera raised in 2 rabbits were highly specific with low cross-reactions of 0.19% and 0.3% with human placental lactogen and 0.21% and 0.13% with human prolactin. The mean sensitivity of the assay determined from 28 assays was found to be 0.4 +/- 0.2 mIU/L. Mean recovery of added exogenous hGH was 98.8 +/- 6.8%. Linearity studies of samples diluted at 1:2, 1:4 and 1:8 gave values of 101.3 +/- 5.3%, 109.6 +/- 13.4% and 97.3 +/- 13% respectively of those expected. The reproducibility of the assay was good; within assay coefficient of variation for serum samples with GH concentrations of 2.7, 13.6 and 28.2 mU/l ranged from 5.1 to 8.3% while the inter-assay precision varied from 4.9 to 10.3%. The in-house assay showed good correlation (r = 0.96, p less than 0.001) with a commercial HGH RIA kit (Dainabot, Japan). A reference normal adult fasting GH level of less than 7 mIU/l was established from 95 samples assayed by this method.

Animals