Postmenopausal osteoporosis is the commonest cause of osteoporosis. It is associated with increased free radical activity induced by the oestrogen-deficient state. Therefore, supplementation with palm-oil-derived tocotrienols, a potent antioxidant, should be able to prevent this bone loss. Our earlier studies have shown that tocotrienol was able to prevent and even reverse osteoporosis due to various factors, including oestrogen deficiency. In this study we compared the effects of supplementation with palm tocotrienol mixture or calcium on bone biomarkers and bone formation rate in ovariectomised (oestrogen-deficient) female rats. Our results showed that palm tocotrienols significantly increased bone formation in oestrogen-deficient rats, seen by increased double-labeled surface (dLS/Bs), reduced single-labeled surface (sLS/BS), increased mineralizing surface (MS/BS), increased mineral apposition rate (MAR), and an overall increase in bone formation rate (BFR/BS). These effects were not seen in the group supplemented with calcium. However, no significant changes were seen in the serum levels of the bone biomarkers, osteocalcin, and cross-linked C-telopeptide of type I collagen, CTX. In conclusion, palm tocotrienol is more effective than calcium in preventing oestrogen-deficient bone loss. Further studies are needed to determine the potential of tocotrienol as an antiosteoporotic agent.
Congenital hypothyroidism (CH) with multinodular goiter (MNG) is uncommonly seen in children. However, CH associated with goiter is often caused by defective Thyroid peroxidase (TPO) gene. In this study, we screened for mutation(s) in the TPO gene in two siblings with CH and MNG and their healthy family members. The two sisters, born to consanguineous parents, were diagnosed with CH during infancy and received treatment since then. They developed MNG during childhood despite adequate L-thyroxine replacement and negative thyroid antibody screening. PCR-amplification of all exons using flanking primers followed by DNA sequencing revealed that the two sisters were homozygous for a novel c.1502T>G mutation. The mutation is predicted to substitute valine for glycine at a highly conserved amino acid residue 501 (p.Val501Gly). Other healthy family members were either heterozygotes or mutation-free. The mutation was not detected in 50 healthy unrelated individuals. In silico analyses using PolyPhen-2 and SIFT predicted that the p.Val501Gly mutation is functionally "damaging." Tertiary modeling showed structural alterations in the active site of the mutant TPO. In conclusion, a novel mutation, p.Val501Gly, in the TPO gene was detected expanding the mutation spectrum of TPO associated with CH and MNG.
Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.
Background. Oxidative stress induced by reactive oxygen and nitrogen species is critically involved in the impairment of β -cell function during the development of diabetes. Methods. HIT-T15 cells were cultured in 5% CO2 and then preincubated with Gelam honey extracts (20, 40, 60, and 80 µg/mL) as well as quercetin (20, 40, 60, and 80 µM), prior to stimulation by 20 and 50 mM of glucose. Cell lysate was collected to determine the effect of honey extracts and quercetin on the stress activated NF- κ B, MAPK pathways, and the Akt (ser473) activated insulin signaling pathway. Results. HIT-T15 cells cultured under hyperglycemic conditions demonstrated insulin resistance with a significant increase in the levels of MAPK, NF- κ B, and IRS-1 serine phosphorylation (ser307); however, Akt expression and insulin contents are significantly decreased. Pretreatment with quercetin and Gelam honey extract improved insulin resistance and insulin content by reducing the expression of MAPK, NF- κ B, and IRS-1 serine phosphorylation (ser307) and increasing the expression of Akt significantly. Conclusion. Gelam honey-induced differential expression of MAPK, NF- κ B, IRS-1 (ser307), and Akt in HIT-T15 cells shows that Gelam honey exerts protective effects against diabetes- and hyperglycemia-induced oxidative stress by improving insulin content and insulin resistance.
Male osteoporosis is a health problem which deserves more attention as nearly 30% of osteoporotic fractures happen in men aged 50 years and above. Although men do not experience an accelerated bone loss phase and testosterone deficiency is not a universal characteristic for aged men, osteoporosis due to age-related testosterone deficiency does have a negative impact on bone health status of men. Observations from epidemiological studies indicate that elderly men with higher testosterone can preserve their BMD better and thus are less prone to fracture. Observations on men with estrogen resistance or aromatase deficiency indicate that estrogen is equally important in the maintenance of bone health status. This had been validated in several epidemiological studies which found that the relationships between estrogen and bone health indices are significant and sometimes stronger than testosterone. Studies on the relationship between quantitative ultrasound and bone remodeling markers suggest that testosterone and estrogen may have differential effects on bone, but further evidence was needed. In conclusion, both testosterone and estrogen are important in the maintenance of bone health in men.
Aim. The present study was conducted to determine the glycaemic effects of sitagliptin in type 2 diabetes patients. Methods. Data was collected from patient medical records of a major teaching hospital in Malaysia, from 2009 to 2012. Glycated hemoglobin (HbA1c) values prior to and up to 12 months after the initiation of sitagliptin were analysed. The change in HbA1c values was accounted for based on a generalized linear model generated using the Generalized Estimating Equations (GEE) method. Results and Discussion. Of the 457 patients, 53.6% were elderly and 81.4% were overweight. The mean HbA1c (standard deviation) before initiation of sitagliptin was 8.5 (1.4)%. This dropped to 7.7 (1.4)%, 3 to 6 months after initiation of sitagliptin, with a mean difference of 0.8% (95% confidence interval (CI): 0.7-1.0; P < 0.001). However, this value increased to 8.0 (1.7)% after 7 to 12 months on sitagliptin (P = 0.002) with a mean difference from baseline of 0.6% (95% CI: 0.4-0.7; P < 0.001). Conclusion. In routine clinical practice, sitagliptin produces a significant reduction in mean HbA1c (0.8%) within the first 6 months of use which corresponds to efficacy data obtained in controlled clinical trials. However, this reduction was lesser, 7 to 12 month later.
Dipeptidyl-4 (DPP-4) inhibitors are oral antidiabetic agents recently introduced to Malaysia. Thus, limited data is available on their utilization patterns and factors associated with their use. This study aims to analyse the utilization patterns of DPP-4 inhibitors, factors that influenced the choice of agent, and the rationale for treatment with DPP-4 inhibitors in patients with type 2 diabetes mellitus. This retrospective study was conducted to address the utilization pattern of DPP-4 inhibitors and factors that influence choice in type 2 diabetes mellitus patients. 299 subjects taking either sitagliptin or vildagliptin from September 2008 to September 2012 were included in the study. Sitagliptin was more frequently prescribed than vildagliptin. Of the patients prescribed DPP-4 inhibitors, 95% received combinations of these and other agents, whereas only 5% were prescribed DPP-4 inhibitors as monotherapy. Factors affecting the utilization of DPP-4 inhibitors included age (P = 0.049) and concomitant use of beta blockers (P = 0.045) and aspirin (P = 0.008). Early identification of factors associated with DPP-4 inhibitors is essential to enhance quality use of the drugs.
The aim of this study was to determine the behavioral outcome in children with CAH and to identify the risk factors that may influence it. Participants (aged 6-18 years) included 29 girls and 20 boys with CAH and unaffected siblings (25 girls and 17 boys). Psychological adjustment was assessed with parent reports on the Child Behavior Checklist (CBCL). Information about disease characteristics was obtained from medical records. Our study reveals that there was higher incidence of parent-reported problem of anxious/depressed and withdrawn/depressed behaviours, somatic complaints, social, thought, and attention problems, and rule-breaking, aggressive, internalizing, and externalizing behaviour among children with CAH compared to controls. The prevalence of internalizing behaviour problems was higher in CAH boys compared with that of controls. Psychosocial adjustment of girls with CAH was found to be similar to unaffected female controls and was within the normal population range. Family income may be associated with behavioral outcome. Glucocorticoid dose may reflect disease severity which may be associated with behavioral outcome. We conclude that internalizing behavioral problem was prevalent among boys with CAH reflecting maladaptive adjustment in coping with chronic illness. This highlighted the importance of psychological and social support for the patients and their families.
The prevalence of Type 2 diabetes is rising rapidly in both developed and developing countries. Asia is developing as the epicentre of the escalating pandemic, reflecting rapid transitions in demography, migration, diet, and lifestyle patterns. The effective management of Type 2 diabetes in Asia may be complicated by differences in prevalence, risk factor profiles, genetic risk allele frequencies, and gene-environment interactions between different Asian countries, and between Asian and other continental populations. To reduce the worldwide burden of T2D, it will be important to understand the architecture of T2D susceptibility both within and between populations. This review will provide an overview of known genetic and nongenetic risk factors for T2D, placing the results from Asian studies in the context of broader global research. Given recent evidence from large-scale genetic studies of T2D, we place special emphasis on emerging knowledge about the genetic architecture of T2D and the potential contribution of genetic effects to population differences in risk.
Background. Increased susceptibility of diabetic mellitus (DM) patients to infection, including tuberculosis (TB), is well documented. The prevalence of DM in Malaysia is reaching epidemic proportions. In this study, we sought to assess risk factors for TB and the impact of DM on the outcome of TB treatment. Methods. TB patients, diabetic patients, and diabetic patients with TB were divided into three groups of 200 subjects each. Data were obtained from patients' medical files at the beginning and end of the study period. Prevalence rates of DM and HIV among TB patients were assessed. Prognosis, TB-related complications, anatomical site of infection, and duration of infection and diabetes were also examined. Results. The prevalence rates of HIV and DM amongst TB patients were 7.7 and 30%, respectively. The diabetic TB patient group contained more males (72%) and smokers (45.5%) compared to the nondiabetic group (58.3% and 33.5%, resp.). Approximately 74% of diabetic patients were Mycobacterium sputum positive compared to only 51% of nondiabetic patients. Diabetic patients were also more likely to develop pulmonary TB (87%) compared to nondiabetic TB patients (59%). Diabetic TB patients had a higher mortality rate (7.5%) compared to the TB only and DM only groups (1 and 2%, resp.). The duration of TB symptoms was longer in nondiabetic TB patients compared to diabetic TB patients (4.5 versus 2.6 months, resp.). Diabetes antedated TB by a mean time of 4 years. Conclusions. We found a higher number of sputum-smear-positive cases and pulmonary TB cases as well as a greater number of males and higher mortality rate in diabetic patients compared to nondiabetic patients.
The aim of this study is to determine the behavioural problems of children with 46XY disorders of sex development (DSD) with genital ambiguity and to identify the risk factors that may influence behaviour. The 27 participants (aged 6-18 years) consisted of 21 patients raised as boys and 6 patients raised as girls. Control data were obtained from a representative sibling of each patient who was matched for age and gender. The study tool used was the Child Behaviour Checklist (CBCL), which is a parent-administered questionnaire. The analysis of the behavioural scores revealed that the patient group had poorer scores in the total, externalizing, and internalizing realms. This group also had poorer scores in the anxious-depressed, social, and rule-breaking realms as compared to the control group. In addition, the XY-F group had higher scores (more pathological) than the XY-M group, although the difference in the scores was not statistically significant. A comparison of the prevalence of patients with scores in the clinical range with that of the control group was not statistically significant. These findings support the current recommendations that psychological counselling should be an integral part of the professional support offered to patients with DSD.
Primary hypertension is widely believed to be a complex polygenic disorder with the manifestation influenced by the interactions of genomic and environmental factors making identification of susceptibility genes a major challenge. With major advancement in high-throughput genotyping technology, genome-wide association study (GWAS) has become a powerful tool for researchers studying genetically complex diseases. GWASs work through revealing links between DNA sequence variation and a disease or trait with biomedical importance. The human genome is a very long DNA sequence which consists of billions of nucleotides arranged in a unique way. A single base-pair change in the DNA sequence is known as a single nucleotide polymorphism (SNP). With the help of modern genotyping techniques such as chip-based genotyping arrays, thousands of SNPs can be genotyped easily. Large-scale GWASs, in which more than half a million of common SNPs are genotyped and analyzed for disease association in hundreds of thousands of cases and controls, have been broadly successful in identifying SNPs associated with heart diseases, diabetes, autoimmune diseases, and psychiatric disorders. It is however still debatable whether GWAS is the best approach for hypertension. The following is a brief overview on the outcomes of a decade of GWASs on primary hypertension.
Metabolic syndrome (MetS) is an important predictor of cardiovascular diseases in adulthood. This study aims to examine the clinical utility of triglyceride to high-density lipoprotein ratio (TG : HDL-C) in identifying cardiometabolic risk and insulin resistance (IR) among children with obesity, in comparison with MetS as defined by the International Diabetes Federation (IDF). Data of 232 children with obesity aged 10-16 years were obtained from our study, MyBFF@school study, conducted between January and December 2014. Children were divided into tertiles of TG : HDL-C ratio. The minimum value of the highest tertile was 1.11. Thus, elevated TG : HDL-C ratio was defined as TG : HDL-C ≥1.11. Children with MetS were categorized based on the definition established by the IDF. Out of 232 children, 23 (9.9%) had MetS, out of which 5.6% were boys. Almost twofold of boys and girls had elevated TG : HDL-C ratio compared to MetS: 13.8% vs. 5.6% and 13.8% vs. 4.3%, respectively. Children with elevated TG : HDL-C ratio had lower fasting glucose compared to children with MetS (boys = 5.15 ± 0.4 vs. 6.34 ± 2.85 mmol/l, p=0.02; girls = 5.17 ± 0.28 vs. 6.8 ± 4.3 mmol/l, p=0.03). Additionally, boys with elevated TG : HDL-C ratio had a higher HDL-C level compared to those with MetS (1.08 ± 0.18 vs. 0.96 ± 0.1 mmol/l, p=0.03). There was no significant difference across other MetS-associated risk factors. Overall, TG : HDL-C ratio demonstrated higher sensitivity (42.7% vs. 12.9%) but lower specificity (74.8% vs. 93.2%) than MetS in identifying IR, either in HOMA-IR ≥2.6 for prepubertal children or HOMA-IR ≥4 for pubertal children. TG : HDL-C ratio in children with obesity is thus as useful as the diagnosis of MetS. It should be considered an additional component to MetS, especially as a surrogate marker for IR.
Glycemic control among patients with prediabetes and type 2 diabetes mellitus (T2D) in Malaysia is suboptimal, especially after the continuous worsening over the past decade. Improved glycemic control may be achieved through a comprehensive management strategy that includes medical nutrition therapy (MNT). Evidence-based recommendations for diabetes-specific therapeutic diets are available internationally. However, Asian patients with T2D, including Malaysians, have unique disease characteristics and risk factors, as well as cultural and lifestyle dissimilarities, which may render international guidelines and recommendations less applicable and/or difficult to implement. With these thoughts in mind, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed by an international task force of diabetes and nutrition experts through the restructuring of international guidelines for the nutritional management of prediabetes and T2D to account for cultural differences in lifestyle, diet, and genetic factors. The initial evidence-based global tDNA template was designed for simplicity, flexibility, and cultural modification. This paper reports the Malaysian adaptation of the tDNA, which takes into account the epidemiologic, physiologic, cultural, and lifestyle factors unique to Malaysia, as well as the local guidelines recommendations.
Baicalein (BC), a flavonoid, which lacks the qualities of reproductive health and shows adverse effects, is tested in this study. Inseminated mice were injected with 30, 60, and 90 mg BC/Kg body weight on gestation days 11, 13, 15, and 17. The F1 BC-exposed males of each dosage were divided into six groups. First three groups (n = 6 from each BC dosage) were used for assessment of reproductive performance, the others (n = 4 from each BC dosage) were administered with testosterone 4.16 mg/kg body weight on postnatal days 21, 31, and 41. The reproductive health of adult F1 males at the age of 55 and 60 was tested. Prenatal BC exposure showed reduced fertility after cohabitation with control females. The BC exposure significantly reduced the body weight, tissue indices, and sperm parameters (motility, count, viability, and daily sperm count) and altered the sperm membrane in a hypoosmotic swelling test. A downward trend was observed in testicular steroidogenic marker enzymes (3β- and 17β-steroid dehydrogenases) and serum testosterone, whereas increase in serum titers of FSH and LH along with altered the testicular histology. Conversely, testosterone (4.16 mg/kg body weight) partially recovered reduced male reproductive health by BC. BC impaired male reproductive health due to low levels of testosterone is reverted by external testosterone is evidenced in this study.