Twelve cases of primary hyperparathyroidism operated by the Universiti Kebangsaan Malaysia Surgical Team from 1978 to 1989 were reviewed. There was a preponderance of Indian females in this series. The majority of the cases presented late and with complications. Renal calculi and bone disease were the commonest complications noted. Of the 12 patients, 9 had single parathyroid adenoma of which 4 were ectopically located, and 2 had hyperplasia of the parathyroids. These were all successfully operated. The remaining patient had 2 failed neck explorations. Failure at initial exploration was due to ectopic location of the glands. Meticulous surgical technique, knowledge of the anatomical variations of location of the parathyroid glands and availability of frozen section facility are essential for successful outcome.
This is a cross-sectional study to determine the prevalence of insulin resistance and its associated factors in Hospital UKM patients with schizophrenia using the Homeostatic Model Assessment (HOMA) model. Fasting glucose and insulin from 85 patients were obtained. Fasting glucose revealed 15% of the patients were diabetic, while another 15% had impaired fasting glucose. Using the HOMA model, 68% of the patients had insulin resistance. Univariate analyses found BMI (p < 0.001) and waist circumference (p < 0.001) to be associated with insulin resistance. The statistical significance disappeared after multivariate analyses. All patients with schizophrenia should be screened and managed as a group at high risk for development of diabetes with emphasis on body weight management.
Study site: inpatient and outpatients, Psychiatric department, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
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.
A survey was done to determine the prevalence of diabetes mellitus, hypertension and renal disease, as well as extent of diabetic control, amongst the workers of Malaysian Railways. The prevalence of diabetes was high at 6.6%, with 3.8% of these being insulin dependent diabetes. The highest prevalence was in Indians (16.0%) followed by Chinese (4.9%) and Malays (3.0%). Using HbA1 measurements, diabetic control was poor in 70.6% of the diabetics. Hypertension was found in 37% and proteinuria in 35%. Renal impairment was present in 30% of the diabetics. This survey shows that diabetes, hypertension and renal disease are high amongst the railway workers in Malaysia.
AIM: The prevalence of diabetes mellitus among Malaysians aged ≥ 30 years of age has increased by more than twofold over a 20-year period. This study aimed to determine the current status and to evaluate the diagnostic usefulness of the HbA(1c) cut-off point of 48 mmol/mol (6.5%).
METHODS: Using a two-stage stratified sampling design, participants aged ≥ 18 years were recruited from five zones selected to represent Malaysia. An oral glucose tolerance test was performed on all those not known to have diabetes.
RESULTS: A total of 4341 subjects were recruited. By World Health Organization criteria, the prevalence of diabetes mellitus was 22.9%; of that percentage, 10.8% was known diabetes and 12.1% was newly diagnosed diabetes. Diabetes was most prevalent amongst Indians (37.9%) and Malays (23.8%). Prevalence of new diabetes mellitus was only 5.5% (95% CI 4.9-6.3) when based on the HbA(1c) diagnostic criteria of 48 mmol/mol (6.5%) and, although the cut-off point was highly specific (98.1%), it was less sensitive (36.7%) compared with 45 mmol/mol (6.3%), which showed the optimal sum of sensitivity (42.5%) and specificity (97.4%) in identifying new diabetes mellitus.
CONCLUSION: This study recorded an overall diabetes prevalence of 22.6%, almost a twofold increase from 11.6% reported in 2006. This was likely attributable to the higher prevalence of new diabetes (12.1%) diagnosed following an oral glucose tolerance test. An HbA(1c) of 45 mmol/mol (6.3%) was found to be a better predictive cut-off point for detecting new diabetes in our multi-ethnic population.
OBJECTIVE: To determine the prevalence of diabetes mellitus and IGT in different ethnic groups living in the same physical environment and to find their relationship to nutritional status and dietary intake.
RESEARCH DESIGN AND METHODS: The study was conducted among Malays and Orang Asli in six rural and urban locations in Malaysia. OGTTs were performed on 706 adult subjects > or = 18 yr of age. WHO criteria were used for diagnosing diabetes mellitus and IGT.
RESULTS: The overall prevalence of diabetes mellitus and IGT among Orang Asli was 0.3 and 4.4% compared with 4.7 and 11.3%, respectively, among Malays. This increased prevalence of glucose intolerance among Malays was associated with higher levels of social development. Among rural Malays, the crude prevalence of diabetes in a traditional village was 2.8% and in the land scheme was 6.7%, whereas urban Malays had a prevalence of 8.2%. In contrast, the prevalence of IGT (10.5-14.8%) was higher among rural Malays, compared with 9.6% among urban Malays. Ethnic group, > or = 40 yr of age, an income > M$250, fewer daily activity, and obesity were associated with a higher prevalence of diabetes.
CONCLUSIONS: Diabetes mellitus and IGT, which were more common among Malays than Orang Asli, were associated with more affluent life-styles and modernization.
AIMS: Cardiovascular disease is the foremost cause of mortality in Malaysia but little is known about the prevalence of the metabolic syndrome and its associations with other known cardiovascular risk markers. We undertook a population-based study to examine these.
METHODS: For the study, 4341 subjects were selected using a multistage stratified sampling method. Subjects were interviewed for personal and past medical history. Biomedical markers and anthropometric indices were measured. The metabolic syndrome was defined using the harmonized criteria. The associations between the metabolic syndrome and cardiovascular risk markers, including high-sensitivity C-reactive protein, microalbuminuria and HbA(1c) were examined.
RESULTS: The prevalence of the metabolic syndrome was 42.5%. Subjects with the metabolic syndrome are significantly more likely to have higher BMI (> 25 kg/m(2)), HbA(1c) [≥ 42 mmol/mol (6.0%)], LDL (≥ 2.6 mmol/l), elevated albumin:creatinine ratio (> 2.5 μg/mmol creatinine for men, 3.5 μg/mmol creatinine for women) and high-sensitivity C-reactive protein (> 3 mg/l); odds ratio 5.48, 6.14, 1.44, 3.68 and 1.84, respectively, P < 0.001. The presence of an elevated albumin:creatinine ratio and high-sensitivity C-reactive protein are strong predictors for the presence of a higher number of positive criteria of the metabolic syndrome. HbA(1c) > 48 mmol/mol (6.5%) is associated with increased relative risk of elevated albumin:creatinine ratio, high-sensitivity C-reactive protein and LDL (relative risk 3.10, 2.46 and 1.65 respectively, P < 0.001).
CONCLUSIONS: We confirmed the high prevalence of the metabolic syndrome in Malaysia. Our study revealed a strong relationship between risk markers of elevated BMI, HbA(1c), LDL, albumin:creatinine ratio and high-sensitivity C-reactive protein with the presence of the metabolic syndrome, putting them at a statistically high risk for cardiovascular mortality.
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.
Vitamin E has been shown to affect bone metabolism. In this study we determined the effects of palm vitamin E and alpha-tocopherol on bone metabolism. Sprague-Dawley female rats fed with normal rat chow were divided into 4 groups and supplemented with either palm vitamin E 30 mg/kg rat weight, palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight. One group was not supplemented. Half of these rats were ovariectomised before supplementation was given for 10 months. As expected, bone mineral density of the ovariectomised rats fed on normal rat chow diet was lower compared to the intact rats. However, these changes were not seen in the supplemented group of rats. Both intact and ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight had a lower bone calcium content in both femoral and vertebral bones whilst rats fed palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight were able to maintain bone calcium content. Alkaline phosphatase activity was elevated in ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight and alpha-tocopherol 30 mg/kg rat weight compared to the intact rats. Alpha-tocopherol also reduced the activity of tartrate-resistant acid phosphatase post-ovariectomy. These findings indicate that both palm vitamin E and alpha-tocopherol maintained bone mineral density in ovariectomised rats but caused conflicting effects on bone calcium content. Further study is needed in order to determine the mechanisms involved.
The soleus muscles of hyperthyroid rats were used to investigate the effect of palm olein oil and soya bean oil on the production of lipid peroxidation products. It was found that palm olein oil but not soya bean oil significantly decreased malonaldehyde and conjugated diene levels of the soleus muscles of hyperthyroid rats. These findings suggest that palm olein per se produces less lipid peroxidation products than soya bean oil. Such an assay method gives a composite net picture of the propensity of an oil to produce lipid peroxidation products.
1. Sex steroids have been shown to regulate the biosynthesis of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). 2. In vitro studies showed that oestradiol (E2) or testosterone (T) can interfere with the bioassay of enzyme activity, but not progesterone (P4). 3. For in vivo studies, the activity of 11 beta-HSD in the testis of normal and adrenalectomized (ADX) adult male Wistar rats was determined following a daily IM injection of sex steroids for 7 days. 4. The 11 beta-HSD activity was significantly reduced (P < 0.01) either by E2 or T in normal and ADX rats. The enzyme activity in normal rats given both T and E2 was even lower (P < 0.001) than when E2 was given alone. 5. P4 given to normal and ADX rats increased the enzyme activity higher than normal (P < 0.001). 6. The presence of corticosteroids influenced the effects of E2, but not of T and P4, on 11 beta-HSD activity. 7. E2 and T downregulate 11 beta-HSD activity, whereas P4 increased it. E2 did not act through lowering T level.
The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) protects the testis from the inhibitory effects of corticosterone on testosterone (T) production. The objectives of the present studies were to determine the effects of deoxycorticosterone (DOC) and its mechanism of actions on testicular 11beta-HSD activity and plasma T levels after 7 days of treatment. The results revealed that at the end of 7 days treatment, DOC significantly increased testicular 11beta-HSD activity and plasma T levels in normal rats. However, the time course showed that high plasma T levels lowered 11beta-HSD activity on day 14 and by 21 days both the levels normalized. In adrenalectomized (ADX) rats, only the enzyme activity increased significantly but not plasma T levels. Spironolactone, a competitive inhibitor of mineralocorticoid receptor (MR), did not change testicular 11beta-HSD activity in both normal and DOC treated rats suggesting that DOC did not act through MR in increasing 11beta-HSD activity. On the other hand, spironolactone significantly decreased plasma T levels in DOC treated rats. Progesterone (P), a competitive inhibitor of glucocorticoid receptors (GR) or corticosterone significantly suppressed testicular enzyme activity and plasma T levels in DOC treated normal rats. Carbenoxolone which is an inhibitor of 11beta-HSD activity significantly depressed testicular 11beta-HSD activity and plasma T levels in DOC treated normal rats. This paper suggests that DOC increased testicular 11beta-HSD activity through GR; whilst increase in plasma T levels required functioning adrenal glands. The testicular 11beta-HSD is one of the regulators of T levels and vice versa.
Normal rats, on being repetitively stressed by being restrained in a tight container for two hours, had higher levels of plasma corticosterone compared to pre stress values. These rats also reacted to the stress by a behavioral response in which there was marked decrease in locomotor activity assessed by the open field test (pre stress: 71.3 +/- 2.6 squares crossed versus post stress: 14.3 +/- 2.5 squares crossed) by counting the number of squares entered by the rat over 5 minutes. By the 6th to 7th exposures to the repetitive stress, the rats adapted to the stress and had normal plasma corticosterone levels and locomotor activity scores comparable to the pre stress values. These responses to stress were completely blocked by the administration of 0.32 microg/100 g BW of naloxone i.p at 10 minutes prior to the stress. In rats fed with rat chow supplemented with 90 mg/kg rat chow or 150 mg/kg rat chow of vitamin E, there was significant reduction of the plasma corticosterone levels and improvement in the locomotor activity. Stress thus caused opioid mediated increase in plasma corticosterone and reduction in locomotor activity which could be blocked by naloxone. These stress responses probably also involved generation of oxygen free radicals which were scavenged by the vitamin E, thus reducing the effects of repetitive stress on locomotor activity and serum corticosterone levels.
1. The aim of this study was to investigate the effect of repeated exposure to stress on tail blood pressure (TBP) of normal as well as GCA (glycyrrhizic acid) and steroid treated rats. Male Sprague-Dawley rats (250 g) were exposed to ether vapour to achieve light anaesthesia prior to TBP recording. Rats were injected with either normal saline or naloxone prior to exposure to stress. Tail blood pressure was recorded daily for 2 weeks. 2. We found that ether stress caused a transient drop in TBP in control as well as in dexamethasone (DEX) treated rats. The stress-induced fall in blood pressure was reduced by naloxone in control rats but not in DEX treated rats. However the transient drop in TBP following stress was not seen in either GCA or deoxycorticosterone (DOC) treated rats. 3. We conclude that first, the reduction in TBP was due to the release of endogenous opioids caused by stress. Second, DOC may block the release of such endogenous opioids, preventing the drop in TBP in response to stress, while DEX did not. Third, GCA caused a similar mineralocorticoid effect on reversing stress induced hypotension.
Microalbuminuria is the earliest indicator of diabetic kidney disease and generalised vascular endothelial dysfunction. The Microalbuminuria Prevalence (MAP) Study was carried out to assess the prevalence of macroalbuminuria, microalbuminuria and normoalbuminuria in Asian hypertensive patients with type 2 diabetes on usual care. This paper presents a subanalysis of data from patients in Malaysia. In 733 analysed patients, the prevalence of macroalbuminuria and microalbuminuria was 15.7% and 39.7%, respectively. The high prevalence of diabetic nephropathy in these high-risk patients is a cause for concern, and the Malaysian Health Care system should be prepared for a pandemic of end-stage renal disease due to diabetic nephropathy.
Study site: six medical centres in Kuala Lumpur, Kota Bharu,
Kuching and Kota Kinabalu
Detection of microalbuminuria is important in the management of diabetic patients since it is predictive of development of proteinuria and nephropathy. Two sensitive and specific in-house ELISAs for microalbuminuria were established and validated. One of the ELISAs was based on antigen coating while the other employed antibody coating. Recovery and linearity experiments gave acceptable results of 100 +/- 10%, while precision results were <10% for intra-assay and <12% for inter-assay coefficients of variation (CVs). The standard curve ranged from 10-625 ug/l, equivalent to 0.2-12.5 mg/l for urine samples diluted 1:20 fold. When the antibody coated ELISA was compared to antigen coated ELISA, a correlation of r=0.996 was obtained. When compared to commercial kits, the in-house ELISAs gave good correlations of r=0.961 versus the Boehringer Mannheim Micral Test strips and r=0.940 versus Ames Microalb Turbidimetry. The normal microalbumin reference ranges determined for 12h, first morning and random urine samples were 0.7-5.3 mg, 0.1-10.2 mg/l and 0.8-26.1 mg/l respectively. The normal albumin excretion rate (AER) was 1.0-7.3 ug/min while untimed urine samples gave results of 0.1-0.9 and 0.2-1.6 mg/mmol after dividing by creatinine concentrations. The ELISAs were used to detect microalbuminuria in 338 random urine samples from diabetic patients. A high percentage 47.9% was found to be positive for microalbuminuria and 18.0% had macroalbuminuria >25 mg/mmol. Thus screening for microalbuminuria together with creatinine measurements using random urine samples can be used for management of diabetic patients.
AIM: To describe the clinical, biochemical and immunological characteristics of young-onset diabetes in Asia.
METHODS: Clinical, biochemical and immunological variables were assessed in 919 newly diagnosed (duration less than 12 months) young onset Asian diabetic patients aged between 12 and 40 years. The subjects constituted 57% Chinese, 29% Indians and 14% Malays, recruited from diabetes centres in China, Hong Kong, India, Malaysia and Singapore.
RESULTS: The mean age (+/- sd) was 31.6 +/- 7.2 years, with the majority (66%) in the 31-40 years age group. Mean body mass index (BMI) (+/- sd) was 25.3 +/- 5.0 kg/m2 with 47% exceeding the suggested Asian cut-off point for obesity (BMI > or = 25). Ethnic difference in clinical characteristics included BMI, blood pressure, mode of treatment and degree of insulin resistance. Most patients had a clinical presentation of Type 2 diabetes. About 10% had a classical combination of ketotic presentation, presence of autoimmune-markers and documented insulin deficiency indicative of Type 1 diabetes. Forty-eight percent were receiving oral hypoglycaemic agents (OHAs) while 31% were on diet only, 18% were receiving insulin and 2% were on a combination of insulin and OHA.
CONCLUSION: Young onset diabetes patients in Asia represent a heterogeneous group in terms of their clinical and biochemical characteristics and classical Type 1 diabetes is relatively uncommon. The 5-year follow up study will determine the progress of these patients and help to clarify the natural history.
An in-house radioimmunoassay (RIA) for the measurement of androstenedione levels in serum was established and validated. Levels of androstenedione were measured by RIA using serum samples from various normal population groups and patients with congenital adrenal hyperplasia (CAH). Analytical recovery and linearity results were > 95%, while intra- and inter-assay CVs were < 10% and < 22% respectively. The assay sensitivity was 0.5 nmol/l or 25 fmol/tube. In normal population groups, the highest androstenedione levels were found in preterm neonates (1.6-12.4 nmol/l), followed by adult females (1.5-10.2 nmol/l), adult males (1.6-8.0 nmol/l) and term neonates (0.8-8.8 nmol/l), while the lowest values were observed in prepubertal children (0.5-3.4 nmol/l). There were no significant differences in diurnal variation and between follicular and luteal phases. The range of androstenedione levels in untreated or poorly controlled CAH patients (7.6-355.0 nmol/l, median 42.5 nmol/l, n = 20) were significantly higher (p < 0.001) than the upper normal limit of 3.4 nmol/L for prepubertal children. The normal androstenedione reference ranges for paediatric and adult groups have thus been established.
A 44 year old lady with primary hypothyroidism presented with massive pericardial effusion without cardiac tamponade. Pericardial tap was done twice and the effusion resolved as the hypothyroid state improved. She remained hypertensive despite the euthyroid state. She was discharged well with L-thyroxine and anti-hypertensive therapy.
A patient with beta hCG-secreting germ cell carcinoma of the pineal and suprasellar regions presented with hydrocephalus, Parinaud's syndrome, hypopituitarism and polyuria. Central diabetes insipidus was strongly suspected although the water deprivation test was not diagnostic. The polyuria however, responded to ADH analogue when the hypothyroidism and hypocortisolism were treated. Pubertal development was evident and serum testosterone was normal despite the low FSH/LH, suggesting hCG stimulation of Leydig cells. This case illustrates that a beta hCG-germ cell tumour of the suprasellar region causing hypopituitarism can mask the presence of central diabetes insipidus and hypogonadotrophic hypogonadism.