Free light chains (FLCs) are tumour markers of monoclonal gammopathies. Detection of urinary FLC or also known as Bence-Jones protein through urinary protein and its immunofixation electrophoreses (UPE and uIFE, respectively) have been considered the gold standard for its biochemical diagnosis. This is mainly due to their superior detection limits compared to their counterpart investigations in serum. However, urinalysis is limited in many ways. The emergence of serum FLC assay with markedly improved detection limit circumvents many of these problems and has gained much importance in biochemical investigations of monoclonal gammopathies. Nevertheless, they are not without limitations. This review discusses the advantages and limitations of serum and urinary FLC assays.

Introduction: Low 25-hydroxyvitamin D [25(OH)D] levels have not been consistently associated with bone mineral density (BMD). It has been suggested that calculation of the free/bioavailable 25(OH)D may correlate better with BMD. We examined this hypothesis in a cohort of Malaysian women. Materials and Methods: A cross-sectional study of 77 patients with rheumatoid arthritis (RA) and 29 controls was performed. Serum 25(OH)D was measured using the Roche Cobas E170 immunoassay. Serum vitamin D binding protein (VDBP) was measured using a monoclonal enzymelinked immunosorbent assay (ELISA). Free/bioavailable 25(OH)D were calculated using both the modified Vermuelen and Bikle formulae. Results: Since there were no significant differences between RA patients and controls for VDBP and 25(OH)D, the dataset was analysed as a whole. Calculated free 25(OH)D by Vermeulen was strongly correlated with Bikle (r = 1.00, p < 0.001). A significant positive correlation was noted between measured total 25(OH)D with free/bioavailable 25(OH) D (r = 0.607, r = 0.637, respectively, p < 0.001). Median free/bioavailable 25(OH)D values were significantly higher in Chinese compared with Malays and Indians, consistent with their median total 25(OH)D. Similar to total 25(OH)D, the free/bioavailable 25(OH)D did not correlate with BMD. Conclusion: In this first study of a multiethnic female Malaysian population, free/bioavailable 25(OH)D were found to reflect total 25(OH)D, and was not superior to total 25(OH)D in its correlation with BMD. Should they need to be calculated, the Bikle formula is easier to use but only calculates free 25(OH)D. The Vermuelen formula calculates both free/bioavailable 25(OH)D but is more complex to use.
bone mineral density

Dyslipidaemia is a recognised conventional risk factor for cardiovascular disease (CVD). However, even when traditional lipid parameters are normal, CVD risk can exist. Small dense lowdensity lipoprotein cholesterol (sdLDL) has appeared as a significant risk marker for CVD. This study aimed to determine the prevalence and associated factors of atherogenic lipoprotein Pattern B in the Malaysian population. Materials and Methods: This cross-sectional study included 150 subjects aged 30 years and above who attended a health screening in a Malaysian tertiary institution. Sociodemographics, clinical characteristics and laboratory parameters (lipids, glucose, and sdLDL) were obtained. Lipoprotein subfraction was analysed using the polyacrylamide gel electrophoresis method. Results: Malays and females made up the majority of subjects and the median age was 37 years. Normolipidaemic Pattern B was significantly higher in women (p=0.008). Significant independent predictors of Pattern B were gender (p=0.02), race (p=0.01), body mass index (BMI) [p=0.02] and lipid status (p=0.01). Triglyceride was the only independent predictor of sdLDL (p=0.001). Conclusion: The prevalence of Pattern B of 33% in this study was comparatively high, of which 6.7% were normolipidaemic. Chinese males with dyslipidaemia and increased BMI independently predicted Pattern B. Differences in triglyceride levels alone among these ethnic groups do not fully explain the differences in the prevalence of Pattern B although it was the only lipid parameter to independently predict sdLDL. Individuals with atherogenic normolipidaemia are at greater risk for a CVD event as they are not included in the protective measures of primary CVD prevention.

Background: Diabetes Mellitus (DM), characterised by chronic hyperglycaemia, exposes patients to acute and chronic complications, such as hypoglycaemia and vascular complications, respectively. The latter is associated with the degree of glycaemic control. Glycated haemoglobin (HbA1c) indicates long-term glycaemic control of the preceding 2-3 months. The practice of self-monitoring blood glucose (SMBG) is essential for insulin-treated diabetic patients to achieve optimum glycaemic control and prevent hypoglycaemia. Aim: The study aimed to determine the SMBG practice and frequency and its association with HbA1c and factors in insulin-treated diabetic patients. Methods: This was a cross-sectional study of insulin-treated diabetic patients attending follow-up at the diabetic clinic of Hospital Serdang from April 2015 to August 2015. Consented eligible patients completed validated selfadministered questionnaires. Patients’ HbA1c results were obtained from the hospital information system. Results: Ninetyone of 137 (66%) patients practiced SMBG and 46 (34%) did not. Although 82% had seen diabetic nurses, 54% of patients did not alter their treatment accordingly. Neither the practice nor the frequency of SMBG was significantly associated with differences in HbA1c levels (p=0.334 and p=0.116 respectively). Ethnicity and household income significantly affected SMBG practice. The presence and frequency of hypoglycaemia significantly increased the likelihood of SMBG practice (p<0.001) and frequency (p<0.001). Conclusions: The prevalence of SMBG practice in diabetic patients on insulin was 66%. However, SMBG was not followed by proper treatment alteration in 54% of patients. There was no association between SMBG practice and frequency with good glycaemic control. Hypoglycaemia significantly affected the practice and frequency of SMBG.
Insulin

Introduction of high-sensitivity cardiac troponin I (hscTn I) assays for routine clinical use in Malaysia requires determination of the 99th percentile upper reference limit (URL) for each assay to suit local context. Hence, this study aimed to determine the 99th percentile URL for hscTn I in the Malaysian population. A total of 250 (120 males and 130 females) healthy Malaysian blood donors aged 18 to 60 years old were recruited. Blood samples for hscTn I were measured using Abbott Diagnostics hscTn I assay on Architect i2000sr analyser. The 99th percentile was calculated using a non-parametric method and gender specific results were compared. The 99th percentile URL for hscTn I for the overall population was 23.7 ng/L, with gender specific values being 29.9 ng/L and 18.6 ng/L for male and female, respectively. Females had significantly lower hscTn I compared to males. This study confirms the use of gender specific 99th percentile URL for hscTn I for clinical use in a multi-ethnic Malaysian population.

The glycosylated haemoglobin (HbA1c) test is the most widely accepted laboratory test for evaluating long term glycaemic control. Patient’s understanding of HbA1c can lead to better glycaemic control. This study is aimed to determine the awareness and level of understanding of HbA1c among type 2 DM patients and its association with glycaemic control. A cross-sectional descriptive study among Type 2 DM patients undergoing routine follow up in an endocrine clinic of a tertiary centre in Malaysia. Patients were invited to answer a validated questionnaire which assessed their awareness and understanding of HbA1c. Their last HbA1c results were retrieved from the laboratory information system. A total of 92 participants were recruited. Fifty-six (60.9%) were aware of the term HbA1c. Fifty percent were categorised as having good HbA1c understanding, with age, monthly income and level of education being the factors associated with understanding. No significant association was noted between HbA1c understanding and glycaemic control, although more patients with good HbA1c understanding had achieved the target glycaemic control compared to those with poor understanding. The level of HbA1c awareness and understanding was acceptable. Factors associated with understanding were age, income and level of education. Continuing efforts however, must be made to improve patients understanding of their disease and clinical disease biomarkers.
Diabetes Mellitus, Type 2

The risk of coronary heart disease (CHD) is dramatically increased in diabetic patients due to their atherogenic lipid profile. The severity of CHD in diabetic patients has been found to be directly associated with glycated haemoglobin (HbA1c). According to the Malaysian Clinical Practice Guidelines on diabetes mellitus (DM), HbA1c level less than 6.5% reduces the risk of microvascular and macrovascular complications. Hence, this study aimed to determine the relationship between dyslipidaemia and glycaemic status in patients with type 2 DM (T2DM) patients in Hospital Putrajaya, a tertiary endocrine centre in Malaysia. This was a cross sectional, retrospective study of 214 T2DM patients with dyslipidaemia who had visited the endocrine clinic between January 2009 and December 2012. Significant correlations were found between fasting blood glucose (FBG) and HbA1c with total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL), non-high density lipoprotein cholesterol (non-HDL), LDL/HDL ratio and TC/HDL ratio; greater correlation being with HbA1c than FBG. In patients with HbA1c ≥ 6.5%, TC, TG, non-HDL and TC/HDL ratio were significantly higher than in patients with HbA1c < 6.5%. Non-HDL, LDL/HDL ratio, TC/HDL ratio and HbA1c were significantly lower in patients on statin treatment than nontreated patients (p<0.05). This significant association between glycaemic status and dyslipidaemia emphasises the additional possible use of HbA1c as a biomarker for dyslipidaemia as well as a potential indirect predictor of cardiovascular disease (CVD) risk in T2DM patients.

Multiple myeloma is a type of plasma cell dyscrasia, characterised by presence of paraprotein ormonoclonal (M)-protein in serum or urine. The M-protein may consist of an intact immunoglobulin,the heavy chain only or the light chain only. The latter, designated as light chain multiplemyeloma (LCMM) makes up almost 20% of myelomas. Clinical manifestation is often heraldedby hypercalcaemia, renal impairment, normocytic normochromic anaemia and bone lesions,reflecting end-organ damage, collectively known as the acronym CRAB. In particular, free lightchain nephrotoxicity accounts for the high prevalence of renal impairment seen in LCMM. Thiscase illustrates a typical presentation of LCMM with focal discussion on its initial and diagnostic,as well as prognostic biochemical investigations.

Bone-turnover marker (BTM) measurements in the blood or urine reflect the bone-remodeling rate and may be useful for studying and clinically managing metabolic bone diseases.Substantial evidence supporting the diagnostic use of BTMs has accumulated in recent years, together with the publication of several guidelines. Most clinical trials and observational and reference-interval studies have been performed in the Northern Hemisphere and have mainly involved Caucasian populations. This review focuses on the available data for populations from the Asia-Pacific region and offers guidance for using BTMs as diagnostic biomarkers in these populations. The procollagen I N-terminal propeptide and β-isomerized C-terminal telopeptide of type-I collagen (measured in plasma) are reference BTMs used for investigating osteoporosis in clinical settings. Premenopausal reference intervals (established for use with Asia-Pacific populations) and reference change values and treatment targets (used to monitor osteoporosis treatment) help guide the management of osteoporosis. Measuring BTMs that are not affected by renal failure, such as the bone-specific isoenzyme alkaline phosphatase and tartrate-resistant acid phosphatase 5b, may be advantageous for patients with advanced chronic kidney disease. Further studies of the use of BTMs in individuals with metabolic bone disease, coupled with the harmonization of commercial assays to provide equivalent results, will further enhance their clinical applications.

Introduction: Statins have several pleiotropic effects including its primary effect of lipid lowering that is important to prevent cardiovascular disease (CVD). Subjects often have heterogeneous responses to statin. This study aims to determine the biochemical effects of statins on lipid parameters among newly diagnosed dyslipidaemia subjects. Methods: This was a prospective observational study involving 118 newly diagnosed adults with dyslipidaemia from three government health clinics in Selangor, Malaysia. Biochemical analyses including fasting lipid profile [triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)] and apolipoproteins (apoA1, apoB) were taken at baseline and follow-up after a month on statin. Results: Majority of subjects (61.9%) were prescribed with lovastatin, with the rest on simvastatin. At baseline, the median values for all lipid profile parameters (TC, LDL-C, HDL-C) and non-conventional lipid parameters (LDL-C:HDL-C ratio, non-HDL-C, TC:HDL-C ratio, apoB:apoA1 ratio) were deranged except for TG and apoA1. On follow up, all parameters showed median values within the reference range except for HDL-C, non-HDL-C and TC:HDL-C ratio. There was significant difference in the effect of statins on lipid parameters including predictors of cardiovascular risk, simvastatin having better effects. Conclusions: Different statinshave varying effects on lipid parameters. Simvastatin showed significantly better effects compared to lovastatin. Non-HDL value should be included in the standard lipid profile report given its ease of use and implementation as it’s both a marker of coronary artery disease (CAD) risk stratification as well as an established determinant of goal attainment during therapy.