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Age-dependent FRAX-based assessment and intervention thresholds for therapeutic decision making in osteoporosis in the Malaysian population

Ratnasingam J, Niyaz M, Mariyappan S, Ong T, Chan SP, Hew FL, et al.

Arch Osteoporos, 2024 Mar 20;19(1):18.
PMID: 38503995 DOI: 10.1007/s11657-024-01371-w

Fracture risk stratification is crucial in countries with limited access to bone density measurement. 24.8% women were in the high-risk category while 30.4% were in the low-risk category. In the intermediate risk group, after recalculation of fracture risk with bone density, 38.3% required treatment. In more than half, treatment decisions can be made without bone density.
PURPOSE: We aimed to examine the role of age-dependent intervention thresholds (ITs) applied to the Fracture Risk Assessment (FRAX) tool in therapeutic decision making for osteoporosis in the Malaysian population.
METHODS: Data were collated from 1380 treatment-naïve postmenopausal women aged 40-85 years who underwent bone mineral density (BMD) measurements for clinical reasons. Age-dependent ITs, for both major osteoporotic fracture (MOF) and hip fracture (HF), were calculated considering a woman with a BMI of 25 kg/m2, aged between 40 and 85years, with a prior fragility fracture, sans other clinical risk factors. Those with fracture probabilities equal to or above upper assessment thresholds (UATs) were considered to have high fracture risk. Those below the lower assessment thresholds (LATs) were considered to have low fracture risk.
RESULTS: The ITs of MOF and HF ranged from 0.7 to 18% and 0.2 to 8%, between 40 and 85years. The LATs of MOF ranged from 0.3 to 11%, while those of HF ranged from 0.1 to 5.2%. The UATs of MOF and HF were 0.8 to 21.6% and 0.2 to 9.6%, respectively. In this study, 24.8% women were in the high-risk category while 30.4% were in the low-risk category. Of the 44.8% (n=618) in the intermediate risk group, after recalculation of fracture risk with BMD input, 38.3% (237/618) were above the ITs while the rest (n=381, 61.7%) were below the ITs. Judged by the Youden Index, 11.5% MOF probability which was associated with a sensitivity of 0.62 and specificity of 0.83 and 4.0% HF probability associated with a sensitivity of 0.63 and a specificity 0.82 were found to be the most appropriate fixed ITs in this analysis.
CONCLUSION: Less than half of the study population (44.8%) required BMD for osteoporosis management when age-specific assessment thresholds were applied. Therefore, in more than half, therapeutic decisions can be made without BMD based on these assessment thresholds.
Continuous glucose monitoring results in lower HbA1c in Malaysian women with insulin-treated gestational diabetes: a randomized controlled trial

Paramasivam SS, Chinna K, Singh AKK, Ratnasingam J, Ibrahim L, Lim LL, et al.

Diabet Med, 2018 08;35(8):1118-1129.
PMID: 29663517 DOI: 10.1111/dme.13649

AIMS: To determine if therapeutic, retrospective continuous glucose monitoring (CGM) improves HbA1c with less hypoglycaemia in women with insulin-treated gestational diabetes mellitus (GDM).
METHODS: This prospective, randomized controlled, open-label trial evaluated 50 women with insulin-treated GDM randomized to either retrospective CGM (6-day sensor) at 28, 32 and 36 weeks' gestation (Group 1, CGM, n = 25) or usual antenatal care without CGM (Group 2, control, n = 25). All women performed seven-point capillary blood glucose (CBG) profiles at least 3 days per week and recorded hypoglycaemic events (symptomatic and asymptomatic CBG
Fulltext Practical guide in using insulin degludec/insulin aspart: A multidisciplinary approach in Malaysia

Chan SP, Mumtaz M, Ratnasingam J, Tan ATB, Lim SC, Rosman A, et al.

Malays Fam Physician, 2023;18:31.
PMID: 37292224 DOI: 10.51866/cpg.255

Insulin degludec/insulin aspart (IDegAsp) co-formulation provides both basal and mealtime glycaemic control in a single injection. The glucose level-lowering efficacy of IDegAsp is reported to be superior or non-inferior to that of the currently available insulin therapies with a lower rate of overall hypoglycaemia and nocturnal hypoglycaemia. An expert panel from Malaysia aims to provide insights into the utilisation of IDegAsp across a broad range of patients with type 2 diabetes mellitus (i.e. treatment-naive or insulin-naive patients or patients receiving treatment intensification from basal-only regimens, premixed insulin and basal-bolus insulin therapy). IDegAsp can be initiated as once-daily dosing for the main meal with the largest carbohydrate content with weekly dose adjustments based on patient response. A lower starting dose is recommended for patients with cardiac or renal comorbidities. Dose intensification with IDegAsp may warrant splitting into twice-daily dosing. IDegAsp twice-daily dosing does not need to be split at a 50:50 ratio but should be adjusted to match the carbohydrate content of meals. The treatment of patients choosing to fast during Ramadan should be switched to IDegAsp early before Ramadan, as a longer duration of titration leads to better glycated haemoglobin level reductions. The pre-Ramadan breakfast/lunch insulin dose can be reduced by 30%-50% and taken during sahur, while the preRamadan dinner dose can be taken without any change during iftar. Education on the main meal concept is important, as carbohydrates are present in almost all meals. Patients should not have a misconception of consuming more carbohydrates while taking IDegAsp.
Fulltext Maintenance vitamin D3 dosage requirements in Chinese women with post menopausal osteoporosis living in the tropics

Venugopal Y, Hatta SFWM, Musa N, Rahman SA, Ratnasingam J, Paramasivam SS, et al.

Asia Pac J Clin Nutr, 2017 May;26(3):412-420.
PMID: 28429905 DOI: 10.6133/apjcn.042016.10

BACKGROUND AND OBJECTIVES: Vitamin D3 (cholecalciferol) dose required to maintain sufficiency in non- Caucasian women with postmenopausal osteoporosis (PMO) inthe tropics has not been well studied. Some guidelines mandate 800-1000 IU vitamin D/day but the Endocrine Society (US) advocates 1500-2000 IU/day to maintain 25-hydroxyvitamin-D (25(OH)D) concentration at >75 nmol/L. We aimed to establish oral cholecalciferol dose required to maintain 25(OH)D concentration at >75 nmol/L in PMO Chinese Malaysian women, postulating lower dose requirements amongst light-skinned subjects in the tropics.

METHODS AND STUDY DESIGN: 90 Chinese Malaysian PMO women in Kuala Lumpur, Malaysia (2°30'N) with baseline serum 25(OH)D levels >=50 nmol/L were recruited. Prior vitamin D supplements were discontinued and subjects randomized to oral cholecalciferol 25,000 IU/4-weekly (Group-A) or 50,000 IU/4-weekly (Group- B) for 16 weeks, administered under direct observation. Serum 25(OH)D, PTH, serum/urinary calcium were measured at baseline, 8 and 16 weeks.

RESULTS: Baseline characteristics, including osteoporosis severity, sun exposure (~3 hours/week), and serum 25(OH)D did not differ between treatment arms. After 16 weeks, 91% of women sufficient at baseline, remained sufficient on 25,000 IU/4-weekly compared with 97% on 50,000 IU/4-weekly with mean serum 25(OH)D 108.1±20.4 and 114.7±18.4 SD nmol/L respectively (p=0.273). At trial's end, 39% and 80% of insufficient women at baseline attained sufficiency in Group A and Group B (p=0.057). Neither dose was associated with hyperparathyroidism or toxicity.

CONCLUSIONS: Despite pretrial vitamin D supplementation and adequate sun exposure, 25.6% Chinese Malaysian PMO women were vitamin D insufficient indicating sunshine alone cannot ensure sufficiency in the tropics. Both ~900 IU/day and ~1800 IU/day cholecalciferol can safely maintain vitamin D sufficiency in >90% of Chinese Malaysian PMO women. Higher doses are required with baseline concentration <75 nmol/L.
Maternal lipids are associated with newborn adiposity, independent of GDM status, obesity and insulin resistance: a prospective observational cohort study

Samsuddin S, Arumugam PA, Md Amin MS, Yahya A, Musa N, Lim LL, et al.

BJOG, 2020 03;127(4):490-499.
PMID: 31778255 DOI: 10.1111/1471-0528.16031

OBJECTIVE: To determine the association between maternal lipaemia and neonatal anthropometrics in Malaysian mother-offspring pairs.
DESIGN: Prospective observational cohort study.
SETTING: Single tertiary multidisciplinary antenatal clinic in Malaysia.
POPULATION: A total of 507 mothers: 145 with gestational diabetes mellitus (GDM); 94 who were obese with normal glucose tolerance (NGT) (pre-gravid body mass index, BMI ≥ 27.5 kg/m2 ), and 268 who were not obese with NGT.
METHODS: Maternal demographic, anthropometric, and clinical data were collected during an interview/examination using a structured questionnaire. Blood was drawn for insulin, C-peptide, triglyceride (Tg), and non-esterified fatty acid (NEFA) during the 75-g 2-hour oral glucose tolerance test (OGTT) screening, and again at 36 weeks of gestation. At birth, neonatal anthropometrics were assessed and data such as gestational weight gain (GWG) were extracted from the records.
MAIN OUTCOME MEASURES: Macrosomia, large-for-gestational-age (LGA) status, cohort-specific birthweight (BW), neonatal fat mass (NFM), and sum of skinfold thickness (SSFT) > 90th centile.
RESULTS: Fasting Tg > 95th centile (3.6 mmol/L) at screening for OGTT was independently associated with LGA (adjusted odds ratio, aOR 10.82, 95% CI 1.26-93.37) after adjustment for maternal glucose, pre-gravid BMI, and insulin sensitivity. Fasting glucose was independently associated with a birthweight ratio (BWR) of >90th centile (aOR 2.06, 95% CI 1.17-3.64), but not with LGA status, in this well-treated GDM cohort with pre-delivery HbA1c of 5.27%. In all, 45% of mothers had a pre-gravid BMI of <23 kg/m2 and 61% had a pre-gravid BMI of ≤ 25 kg/m2 , yet a GWG of >10 kg was associated with a 4.25-fold risk (95% CI 1.71-10.53) of BWR > 90th centile.
CONCLUSION: Maternal lipaemia and GWG at a low threshold (>10 kg) adversely impact neonatal adiposity in Asian offspring, independent of glucose, insulin resistance and pre-gravid BMI. These may therefore be important modifiable metabolic targets in pregnancy.
TWEETABLE ABSTRACT: Maternal lipids are associated with adiposity in Asian babies independently of pre-gravid BMI, GDM status, and insulin resistance.
Fulltext Asian Best Practices for Care of Diabetes in Elderly (ABCDE)

Kalra S, Dhar M, Afsana F, Aggarwal P, Aye TT, Bantwal G, et al.

Rev Diabet Stud, 2022 Jun 30;18(2):100-134.
PMID: 35831938 DOI: 10.1900/RDS.2022.18.100

The elderly population with diabetes is diverse with the majority experiencing a decline in physical and mental capabilities, impacting the entire diabetes management process. Therefore, a need for geriatric-specific guidelines, especially for the Asian population, was identified and subsequently developed by an expert panel across government and private institutions from several Asian countries. The panel considered clinical evidence (landmark trials, position papers, expert opinions), recommendations from several important societies along with their decades of clinical experience and expertise, while meticulously devising thorough geriatric-specific tailored management strategies. The creation of the ABCDE best practices document underscores and explores the gaps and challenges and determines optimal methods for diabetes management of the elderly population in the Asian region.
A summary of the Malaysian Clinical Practice Guidelines on the management of postmenopausal osteoporosis, 2022

Ong TIW, Lim LL, Chan SP, Chee WSS, Ch'ng ASH, Chong EGM, et al.

Osteoporos Sarcopenia, 2023 Jun;9(2):60-69.
PMID: 37496985 DOI: 10.1016/j.afos.2023.06.002

OBJECTIVES: The aim of these Clinical Practice Guidelines is to provide evidence-based recommendations to assist healthcare providers in the screening, diagnosis and management of patients with postmenopausal osteoporosis (OP).
METHODS: A list of key clinical questions on the assessment, diagnosis and treatment of OP was formulated. A literature search using the PubMed, Medline, Cochrane Databases of Systematic Reviews, and OVID electronic databases identified all relevant articles on OP based on the key clinical questions, from 2014 onwards, to update from the 2015 edition. The articles were graded using the SIGN50 format. For each statement, studies with the highest level of evidence were used to frame the recommendation.
RESULTS: This article summarizes the diagnostic and treatment pathways for postmenopausal OP. Risk stratification of patients with OP encompasses clinical risk factors, bone mineral density measurements and FRAX risk estimates. Non-pharmacological measures including adequate calcium and vitamin D, regular exercise and falls prevention are recommended. Pharmacological measures depend on patients' fracture risk status. Very high-risk individuals are recommended for treatment with an anabolic agent, if available, followed by an anti-resorptive agent. Alternatively, parenteral anti-resorptive agents can be used. High-risk individuals should be treated with anti-resorptive agents. In low-risk individuals, menopausal hormone replacement or selective estrogen receptor modulators can be used, if indicated. Patients should be assessed regularly to monitor treatment response and treatment adjusted, as appropriate.
CONCLUSIONS: The pathways for the management of postmenopausal OP in Malaysia have been updated. Incorporation of fracture risk stratification can guide appropriate treatment.
Fulltext Are the 2009 Institute of Medicine gestational weight gain recommendations applicable in a contemporary South-East Asian pregnancy cohort? Results of a prospective analysis

Tai YT, Khoo JK, Lim QH, Lim LL, Paramasivam SS, Ratnasingam J, et al.

PLoS One, 2025;20(1):e0316837.
PMID: 39761286 DOI: 10.1371/journal.pone.0316837

Gestational Weight Gain (GWG) modulates pregnancy outcomes and long-term offspring metabolic health. The 2009 Institute of Medicine (IOM) GWG recommendations have largely been validated in Caucasian and mono-ethnic East Asian cohorts. Asians are at higher metabolic risk at a lower body mass index (BMI), and this has prompted the World Health Organization (WHO) to identify lower BMI cut-offs for risk evaluation amongst Asians. This prospective observational cohort study aimed to determine if 2009 IOM GWG thresholds are applicable in a contemporary multi-ethnic South-East Asian cohort. We recruited 875 mothers from an urban Malaysian tertiary clinic during screening for gestational diabetes mellitus (GDM) from 2014-2021. Data collected included measures of insulin-sensitivity, total GWG (maternal weight at delivery-self-reported pre-gravid weight), and neonatal anthropometrics (birthweight and skinfold-thickness measured with Harpenden calipers). BMI was stratified by Caucasian (overweight ≥25kg/m2, obese ≥30kg/m2) as well as Asian (overweight ≥23kg/m2, obese ≥27.5kg/ m2) cut-offs, and patients categorized by 2009 IOM GWG reference ranges. The cohort comprised 67% Malay-, 23% Chinese- and 10% Indian-descent mothers with a high prevalence of overweight/obesity (Asian cut-offs 56.9% vs Caucasian 44%). When Asian BMI cut-offs were deployed, excessive GWG incidence increased (34.1% → 40.6%) whilst inadequate GWG declined (30% → 24.8%) (p<0.05). Upon multivariate-analysis (adjusting for age, parity, race, GDM, insulin-sensitivity, baby-gender) excessive GWG categorized with Caucasian BMI cut-offs was significantly associated with increased risk of macrosomia (adjusted odds ratio (aOR) 8.65, 95% confidence interval (CI) 1.07-70.01), Neonatal-Fat-Mass (NFM) >90th centile (aOR 2.14, 95% CI 1.02-4.45) and Sum-of-Skinfold Thickness (SSFT) >90th centile (aOR 3.88, 95% CI 1.77-8.51). Excessive GWG by Asian cut-offs was also associated with increased risk of SSFT >90th centile (aOR 5.75, 95% CI 2.35-14.10). Inadequate GWG by both Caucasian and Asian BMI cut-offs was associated with Small-for-Gestational-Age (SGA) status (aOR 4.30, 95% CI 2.48-7.45 and aOR 3.66, 95% CI 2.13-6.30 respectively). In conclusion, the 2009 IOM GWG recommendations, using either Caucasian or regional Asian BMI cut-offs, are applicable in a contemporary Malay majority South-East Asian cohort in terms of predicting abnormal neonatal adiposity. Importantly, the association with neonatal adiposity is independent of increased maternal insulin resistance characteristic of Asians.