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Fulltext The SAD-MEN questionnaire: a new and reliable questionnaire for assessing sexual dysfunction in Asians with diabetes

Chung CM, Lu MZ, Wong CY, Goh SG, Azhar MI, Lim YM, et al.

Diabet Med, 2016 May;33(5):674-80.
PMID: 26202696 DOI: 10.1111/dme.12864

AIM: The aim of this study is to construct a new tool for the assessment of sexual dysfunction among men with diabetes that is valid and reliable across different ethnicities, languages and socio-economic backgrounds in South East Asia.
METHODS: Focus group interviews were conducted to determine the construct of the questionnaire. Content and face validity were assessed by a panel of experts. A pilot study was conducted to validate the Sexual Dysfunction in Asian Men with Diabetes (SAD-MEN) questionnaire in English and Malay. The International Index of Erectile Function-5 (IIEF-5) was used for comparison. Construct validity was assessed using exploratory factor analysis, reliability was determined using Cronbach's α (> 0.700), and test-retest reliability using Spearman's rank correlation coefficient.
RESULTS: The SAD-MEN questionnaire yielded moderate face and content validity, with high reliability as shown by Cronbach's α values of 0.949 for sexual performance and 0.775 for sexual desire for the English version. The Malay language questionnaire had a Cronbach's α value of 0.945 for sexual performance and 0.750 for sexual desire. Test-retest reliability using Spearman's test gave correlation coefficients of r = 0.853, P = 0.000 for the English language questionnaire and r = 0.908, P = 0.000 for the Malay language questionnaire.
CONCLUSION: The SAD-MEN questionnaire is a valid and reliable tool by which to assess sexual dysfunction in English- and Malay-speaking Malaysian and South East Asian men with diabetes.
Fulltext Diabetes quality of life perception in a multiethnic population

Goh SG, Rusli BN, Khalid BA

Qual Life Res, 2015 Jul;24(7):1677-86.
PMID: 25492728 DOI: 10.1007/s11136-014-0885-3

The aim of this study was to determine ethnic differences and predictors of the perception of quality of life (QOL) in a multiethnic Malaysian population with type 2 diabetes.
Fulltext Development and validation of the Asian Diabetes Quality of Life (AsianDQOL) Questionnaire

Goh SG, Rusli BN, Khalid BA

Diabetes Res Clin Pract, 2015 Jun;108(3):489-98.
PMID: 25790899 DOI: 10.1016/j.diabres.2015.02.009

To construct a type-2 diabetes specific quality of life (QOL) tool for Asian populations that is valid and reliable across different ethnicities, languages, and socio-economic backgrounds.
Fulltext Evolution of diabetes management in the 21st century: the contribution of quality of life measurement in Asians

Goh SG, Rusli BN, Khalid BA

Asia Pac J Clin Nutr, 2015;24(2):190-8.
PMID: 26078234 DOI: 10.6133/apjcn.2015.24.2.04

Diabetes mellitus (DM) is a complex and chronic disease with multiple complications leading to increased mortality and poor quality of life. Current studies have shown that lowering glycosylated haemoglobin (HbA1c) confers protection against microvascular complications. However, with more intensive glucose control to achieve HbA1c of less than 6.5%, there seems to be a significant increased risk of mortality and cardiovascular events. The current recommendation worldwide is for "tailoring" of DM management to risk and also quality of Life (QOL) which is a crucial component in determining the success or failure of DM management. In Asia, DM has become a health crisis but there is a lack of QOL assessment tool that is specific for Asians with wide spectrum of ethnicity, languages, religions and socio-economic differences. In this review, we discuss the evolution of DM management over the decade and the issues pertaining to QOL among people living with diabetes in Asia.
Fulltext Knowledge of diabetes and lifestyle behaviour amongst indigenous population in Peninsular Malaysia

Ahmad B, Khalid BA, Quek KF, Anuar Z, Phipps ME

Med J Malaysia, 2013 Aug;68(4):309-14.
PMID: 24145258 MyJurnal

A cross-sectional study involving seven Orang Asli
settlements located in three different states in Peninsular
Malaysia; Johor, Selangor and Perak.
Prevalence of diabetes in Malaysia and usefulness of HbA1c as a diagnostic criterion

Wan Nazaimoon WM, Md Isa SH, Wan Mohamad WB, Khir AS, Kamaruddin NA, Kamarul IM, et al.

Diabet Med, 2013 Jul;30(7):825-8.
PMID: 23413941 DOI: 10.1111/dme.12161

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.
Predictors of ischaemic heart disease in a Malaysian population with the metabolic syndrome

Yeow TP, Khir AS, Ismail AA, Ismail IS, Kamarul Imran M, Khalid BA, et al.

Diabet Med, 2012 Nov;29(11):1378-84.
PMID: 22803824 DOI: 10.1111/j.1464-5491.2012.03741.x

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.
Influencing factors of glycaemic control in patients attending different types of urban health care settings in Malaysia

Ahmad B, Khalid BA, Zaini A, Hussain NA, Quek KF

Diabetes Res Clin Pract, 2011 Jul;93(1):e12-4.
PMID: 21397969 DOI: 10.1016/j.diabres.2011.02.020

The objective of this study was to elucidate influencing factors of HbA1C in various health care settings. The glycaemic control was suboptimal in all settings. Multivariate analysis confirmed three factors were significant in HbA1C outcome; insulin (p=0.000), medication (p=0.043) and ethnicity (p=0.000).
Fulltext The effects of short-term, rapid glycemic control on the peroneal nerve function and serum VCAM-1 and AGE in type 2 diabetic patients in Malaysia

Norlinah MI, Hamizah R, Md Isa SH, Wan Nazaimoon WM, Khalid BA

Indian J Med Sci, 2009 Apr;63(4):131-8.
PMID: 19414982

BACKGROUND: The role of endothelial injury and circulating adhesion molecule in the development and progression of diabetic peripheral neuropathy in the long-term has been established previously.
AIMS: To study the effects of short-term glycemic control using insulin and oral hypoglycemic agent therapy (OHA) on the peroneal nerve function and vascular cell adhesion molecule-1 (VCAM-1) and advanced glycation endproducts (AGE) levels in type 2 diabetic patients.
SETTINGS AND DESIGN: A randomized controlled study involving poorly controlled (HbA1c, 7.5%-11%) type 2 diabetic patients attending the endocrinology outpatient center in a tertiary hospital in Kuala Lumpur.
MATERIALS AND METHODS: Twenty-nine patients were randomized to receive insulin (n=15) or OHA (n=14) for 8 weeks. The glycemic variables (HbA1c, fasting plasma glucose [FPG], fructosamine), VCAM-1, serum AGE and the peroneal motor conduction velocity (PMCV) were measured at baseline and at 4-week intervals.
STATISTICAL ANALYSIS USED: Paired 't' test or Kruskal Wallis test; and the unpaired 't' test or Mann-Whitney U test were used for within-group and between-group analyses, respectively. Correlation was analyzed using Spearman's correlation coefficient.
RESULTS: Within-group analysis showed significant progressive improvement in HbA1c at weeks 4 and 8 in the insulin group. The PMCV improved significantly in both groups by week 8, and by week 4 (P = 0.01) in the insulin group. PMCV correlated negatively with VCAM-1 (P = 0.031) and AGE (P = 0.009) at week 8.
CONCLUSION: Aggressive glycemic control with insulin improves the peroneal nerve function within 4 weeks. Improvement in the serum VCAM-1 and AGE levels correlated significantly with improvement in peroneal nerve conduction velocity only in the insulin group.
Study site: Tertiary endocrinology outpatient center in Kuala Lumpur, Malaysia
Islet autoimmunity status in Asians with young-onset diabetes (12-40 years): association with clinical characteristics, beta cell function and cardio-metabolic risk factors

Thai AC, Mohan V, Khalid BA, Cockram CS, Pan CY, Zimmet P, et al.

Diabetes Res Clin Pract, 2008 May;80(2):224-30.
PMID: 18207602 DOI: 10.1016/j.diabres.2007.12.003

In this paper, the islet autoimmunity status and relation to clinical characteristics, beta cell function and cardio-metabolic risk factors in young-onset Asian diabetic patients are evaluated at baseline. The study population consisted of 912 patients (from China, India, Malaysia and Singapore) with age 12-40 years and diabetes duration <12 months. Autoantibodies to glutamic acid decarboxylase (GADA) and tyrosine phosphatase (IA-2A), beta cell function and cardio-metabolic risk parameters were assessed. Among our young patient cohort, 105 (11.5%) patients were GADA and/or IA-2A positives (Ab +ve). Ab +ve patients were younger, leaner, had more severe hyperglycaemia and lower beta cell function. The frequency of metabolic syndrome was significantly lower in Ab +ve patients (27%) compared to Ab -ve patients (54%). However, a substantial proportion of patients in both groups of patients had atherogenic dyslipidaemia, hypertension and albuminuria (micro or macro). In our study cohort, only one in 10 Asian youth with new-onset diabetes had evidence of islet autoimmunity. At least 60% of Ab +ve and 50% of Ab -ve patients demonstrated classical features of type 1 and type 2 diabetes respectively. Regardless of autoimmunity status, the cardio-metabolic risk factors, in particular atherogenic dyslipidaemia, hypertension and albuminuria were common in our patients with young-onset diabetes.
Fulltext Prevalence of insulin resistance in schizophrenia in HUKM

Fairuz AR, Maniam T, Khalid BA

Med J Malaysia, 2007 Oct;62(4):290-3.
PMID: 18551931 MyJurnal

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
Fulltext ACTH producing pulmonary carcinoid and pituitary macroadenoma: a fortuitous association?

Wong M, Isa SH, Kamaruddin NA, Khalid BA

Med J Malaysia, 2007 Jun;62(2):168-70.
PMID: 18705457

We report a case of a 45 year-old man who presented initially with a non-functioning pituitary macroadenoma. A routine chest radiography done preoperatively revealed a right lung nodule which was confirmed by computed tomography (CT) of the thorax. Transfrontal hypophysectomy was performed while a conservative approach was taken for the lung nodule. Four years later, he presented acutely with adrenocorticotrophic hormone (ACTH) dependent Cushing's syndrome which resolved following a right lobectomy. Histological examination revealed an atypical carcinoid. To our knowledge, this is the first reported case of an ectopic ACTH secreting pulmonary carcinoid found in association with a non-functioning pituitary macroadenoma.
Fulltext Masking of central diabetes insipidus and hypogonadotrophic hypogonadism by germ cell tumour in suprasellar--pineal region

Isa SH, Wong M, Khalid BA

Med J Malaysia, 2006 Dec;61(5):630-2.
PMID: 17623967

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.
Fulltext Microalbuminuria prevalence study in hypertensive type 2 diabetic patients in Malaysia

Kong NC, Chia YC, Khalid BA, Juwita S, Samiah Yasmin AK, Yap LY, et al.

Med J Malaysia, 2006 Oct;61(4):457-65.
PMID: 17243524 MyJurnal

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
Fulltext The role of endoscopic endonasal approach to pituitary tumours: HUKM experience

Gendeh BS, Doi M, Selladurai BM, Khalid BA, Jegan T, Misiran K

Med J Malaysia, 2006 Aug;61(3):343-8.
PMID: 17240587

Surgery for pituitary tumours at our institution was performed by rhinosurgical route by combined procedure by otolaryngologist and neurosurgeons. A retrospective review of case records of patients who had endonasal endoscopic transphenoidal approach for pituitary tumours from September 1998 to December 2004 was performed. A total of 81 trans-sphenoidal surgeries were performed during this study period. Only 68 case records with adequate information were available for review, 56 patients were included in the study and 12 were excluded. There were 24 males (42%) and 32 females (58%). The ethnic distribution, were 29 Malays, 24 Chinese, 2 Indian and 1 others. The age ranged from 16 years to 76 years, with a mean of 46 years. The majority of our patients presented with visual symptoms (38), headache (28), menstrual cycle disturbance or impotence (14) and acromegalic features (16). Forty patients had macroadenoma (71%) and 16 had microadenomas (29%). Thirty-six patients out of 40 macro-adenomas had suprasellar extensions (90%). Only eleven patients had lumbar drain inserted prior to commencement of the surgery and the majority of these were macroadenomas. The common complications encountered were diabetes insipidus (4), cerebrospinal fluid leak (2), meningitis (3), epistaxis (2), septal perforation (2), intercavernous sinus haemorrhage (3) and anterior pituitary insufficiency (2). Our study reveals that endonasal trans-sphenoidal approach is a safe and effective method of management of pituitary adenomas.
Fulltext Use of the denaturing gradient gel electrophoresis (DGGE) method for mutational screening of patients with familial hypercholesterolaemia (FH) and Familial defective apolipoprotein B100 (FDB)

Azian M, Hapizah MN, Khalid BA, Khalid Y, Rosli A, Jamal R

Malays J Pathol, 2006 Jun;28(1):7-15.
PMID: 17694954 MyJurnal

Familial hypercholesterolaemia (FH) and Familial defective apolipoprotein B100 (FDB) are autosomal dominant inherited diseases of lipid metabolism caused by mutations in the low density lipoprotein (LDL) receptor and apolipoprotein B 100 genes. FH is clinically characterised by elevated concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), presence of xanthomata and premature atherosclerosis. Both conditions are associated with coronary artery disease but may be clinically indistinguishable. Seventy-two (72) FH patients were diagnosed based on the Simon Broome's criteria. Mutational screening was performed by polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE). Positive mutations were subjected to DNA sequencing for confirmation of the mutation. We successfully amplified all exons in the LDL receptor and apo B100 genes. DGGE was performed in all exons of the LDL receptor (except for exons 4-3', 18 and promoter region) and apo B100 genes. We have identified four different mutations in the LDL receptor gene but no mutation was detected in the apo B 100 gene. The apo B100 gene mutation was not detected on DGGE screening as sequencing was not performed for negative cases on DGGE technique. To our knowledge, the C234S mutation (exon 5) is a novel mutation worldwide. The D69N mutation (exon 3) has been reported locally while the R385W (exon 9) and R716G (exon 15) mutations have not been reported locally. However, only 4 mutations have been identified among 14/72 patients (19.4%) in 39 FH families. Specificity (1-false positive) of this technique was 44.7% based on the fact that 42/76 (55.3%) samples with band shifts showed normal DNA sequencing results. A more sensitive method needs to be addressed in future studies in order to fully characterise the LDLR and apo B100 genes such as denaturing high performance liquid chromatography. In conclusion, we have developed the DNA analysis for FH patients using PCR-DGGE technique. DNA analysis plays an important role to characterise the type of mutations and forms an adjunct to clinical diagnosis.
Improvement in C-reactive protein and advanced glycosylation end-products in poorly controlled diabetics is independent of glucose control

Md Isa SH, Najihah I, Nazaimoon WM, Kamarudin NA, Umar NA, Mat NH, et al.

Diabetes Res Clin Pract, 2006 Apr;72(1):48-52.
PMID: 16253380 DOI: 10.1016/j.diabres.2005.09.011

We studied the efficacy of four different treatment regimens (sulphonylurea and metformin+/-acarbose versus glimepiride and rosiglitazone versus glimepiride and bedtime NPH insulin versus multiple actrapid and NPH insulin injections) in poorly controlled type 2 diabetes subjects on hs-CRP, VCAM-1 and AGE at 4, 8 and 12 weeks of treatment. Multiple insulin injections rapidly improved HbA(1c) by 0.6+/-0.9% (p<0.005), 1.2+/-1.3% (p<0.0005) and 1.3+/-1.4% (p<0.0005) at week 4, at week 8 and week 12, respectively. Subjects who continued their existing combination treatment of sulphonylurea, metformin+/-acarbose also showed a significant reduction in HbA(1c) (p<0.05). Although effective in reducing glycemic parameters, there was no reduction in CRP levels in either treatment group. The treatment regimen consisting of rosiglitazone and glimepiride significantly lowered hs-CRP by -2.6 (3.9) mg/L (p<0.05) at week 12 in spite of no improvement in blood glucose. AGE improved in all groups irrespective of type of treatment, glycaemic control and CRP levels. Our data indicate rapid glycaemic control alone does not necessarily result in improvement in markers of inflammation in type 2 diabetes patients.
Fulltext An open label comparative study of glimepiride versus repaglinide in type 2 diabetes mellitus Muslim subjects during the month of Ramadan

Anwar A, Azmi KN, Hamidon BB, Khalid BA

Med J Malaysia, 2006 Mar;61(1):28-35.
PMID: 16708731 MyJurnal

This study was conducted to compare the treatment efficacy between a prandial glucose regulator, repaglinide and a new sulphonylurea, glimepiride in Muslim Type 2 diabetic patients who practice Ramadan fasting. Forty-one patients, previously treated with a sulphonylurea or metformin, were divided to receive either repaglinide (n=20, preprandially three-times daily) or glimepiride (n=21, preprandially once daily) 3 months before the month of Ramadan. During Ramadan, patients modified their eating pattern to two meals daily, and the triple doses of repaglinide were redistributed to two preprandial doses. Four point blood glucose monitoring were performed weekly during the month of Ramadan and the subsequent month. Measurements of the 4-point blood glucose were significantly lower in the glimepiride group compared to the repaglinide group both during and after Ramadan. The glycaemic excursion was better in the morning for the repaglinide group and better in the afternoon and evening for the glimepiride group during the Ramadan period. There was no statistically significant difference in the incidence of hypoglycaemia between the two groups during and after Ramadan. There was no difference in the glycaemic excursion post-Ramadan. The longer duration of action of glimepiride may offer an advantage over repaglinide during the 13.5 hours of fast in Ramadan for diabetic patients.
Fulltext Syndrome of inappropriate antidiuretic hormone caused by continuous lumbar spinal fluid drainage after transphenoidal surgery

Norlela S, Azmi KN, Khalid BA

Singapore Med J, 2006 Jan;47(1):75-6.
PMID: 16397727

A 53-year-old acromegalic woman had cerebrospinal fluid rhinorrhoea following transphenoidal surgery for a pituitary microadenoma. A continuous lumbar spinal fluid drainage catheter was inserted and on the sixth postoperative day, she developed hyponatremia with features of syndrome of inappropriate antidiuretic hormone (SIADH) requiring hypertonic saline administration. Over-drainage is potentially hazardous and close biochemical monitoring is required. To our knowledge, this is the first reported case of SIADH caused by continuous lumbar drainage in an adult.
Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone

Ahmad NS, Khalid BA, Luke DA, Ima Nirwana S

Clin Exp Pharmacol Physiol, 2005 Sep;32(9):761-70.
PMID: 16173934

1. Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or alpha-tocopherol acetate in Wistar rats. 2. The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and alpha-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure alpha-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines. 3. Supplementation with the palm oil tocotrienol mixture or alpha-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of alpha-tocopherol acetate (P < 0.05). 4. Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of alpha-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes.

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