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  1. 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.

  2. 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

  3. 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.
  4. Lim LL, Kitan N, Paramasivam SS, Ratnasingam J, Ibrahim L, Chan SP, et al.
    J Med Case Rep, 2015;9:277.
    PMID: 26619967 DOI: 10.1186/s13256-015-0757-7
    Determining the etiology of Cushing's syndrome is very challenging to endocrinologists, with most of the difficulty arising from subtype differentiation of adrenocorticotropic hormone-dependent Cushing's syndrome. We present the pitfalls of evaluating a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome in the transition period between adolescence and adulthood.
  5. Vethakkan SR, Walters JM, Gooley JL, Boston RC, Kay TW, Goodman DJ, et al.
    Transplantation, 2014 Jan 27;97(2):e9-11.
    PMID: 24434489 DOI: 10.1097/01.TP.0000437565.15965.67
  6. Oo MM, Tan Chung Zhen I, Ng KS, Tan KL, Tan ATB, Vethakkan SR, et al.
    BMJ Open, 2021 01 21;11(1):e039869.
    PMID: 33478961 DOI: 10.1136/bmjopen-2020-039869
    OBJECTIVE: To identify the prevalence of stage B heart failure (SBHF) in patients with type 2 diabetes mellitus (T2DM) with no history of cardiovascular disease (CVD).

    DESIGN: Observational study.

    SETTING: A single-centre study in which eligible patients were recruited from T2DM clinic. Following consent, patients completed a questionnaire and underwent physical examinations. Patients had blood drawn for laboratory investigations and had a transthoracic echocardiography.

    PARTICIPANTS: A total of 305 patients who were not known to have CVD were recruited. Patients with deranged liver function tests and end stage renal failure were excluded.

    MAIN OUTCOME MEASURES: Echocardiographic parameters such as left ventricular ejection fraction, left ventricular mass index (LVMI), left ventricular hypertrophy, left atrial enlargement and diastolic function were examined.

    RESULTS: A total of 305 patients predominantly females (65%), with mean body mass index of 27.5 kg/m2 participated in this study. None of them had either a history or signs and symptoms of CVD. Seventy-seven percent of patients had a history of hypertension and 83% of this study population had T2DM for more than 10 years. Mean HbA1c of 8.3% was recorded. Almost all patients were taking metformin. Approximately, 40% of patients were on newer anti-T2DM agents such as sodium-glucose cotransporter-2 and dipeptidyl peptidase 4 inhibitors. Fifty-seven percent (n=174) of the study population had SBHF at the time of study: diastolic dysfunction, increased LVMI and increased left atrial volume index (LAVI) were noted in 51 patients (17%), 128 patients (42%) and 98 patients (32%), respectively. Thirty-seven patients (12%) had both increase LVMI and LAVI.

    CONCLUSION: Our study has revealed a high prevalence of SBHF in T2DM patients without overt cardiac disease in Malaysia that has one of the highest prevalence of TDM in the world.

  7. Vethakkan SR, Venugopal Y, Tan AT, Paramasivam SS, Ratnasingam J, Razak RA, et al.
    Endocr Pract, 2012 11 29;19(1):e29-34.
    PMID: 23186972 DOI: 10.4158/EP12218.CR
    OBJECTIVE: To report a case of superior mesenteric artery (SMA) syndrome secondary to hypothalamic germinoma.

    METHODS: We describe the clinical presentation, diagnostic work-up, management, and clinical course of a patient admitted with SMA syndrome who was subsequently found to have a hypothalamic germinoma.

    RESULTS: An adolescent boy was admitted to the surgical ward with progressive weight loss over a 2 year period and postprandial vomiting. He was diagnosed with SMA syndrome based on evidence of proximal duodenal dilatation, extrinsic compression of the distal duodenum, and a narrowed aortomesenteric angle (16°). Investigations performed to exclude thyrotoxicosis unexpectedly revealed secondary hypothyroidism and further evaluation demonstrated evidence of pan-hypopituitarism. Psychiatric evaluation excluded anorexia nervosa and bulimia. Magnetic resonance imaging (MRI) of the brain revealed a heterogeneously enhancing hypothalamic lesion, but a normal pituitary gland. Hormone replacement with hydrocortisone, desmopressin, testosterone, and thyroxine resulted in weight gain and resolution of gastrointestinal symptoms. A transventricular endoscopic biopsy subsequently confirmed a hypothalamic germinoma and he was referred to an oncologist.

    CONCLUSION: SMA syndrome secondary to severe weight loss is an uncommon cause of upper gastrointestinal obstruction. While there have been reports of poorly controlled diabetes mellitus and thyrotoxicosis manifesting as SMA syndrome, there are no published reports to date of SMA syndrome secondary to hypothalamic/pituitary disease. Management of SMA syndrome is conservative, as symptoms of intestinal obstruction resolve with weight gain following treatment of the underlying cause. Awareness of this uncommon presentation of endocrine cachexia/hypothalamic disease will prevent unnecessary laparotomies and a misdiagnosis of an eating disorder.

  8. Lim LL, Brnabic AJ, Chan SP, Ibrahim L, Paramasivam SS, Ratnasingam J, et al.
    J Diabetes Investig, 2017 Jul;8(4):453-461.
    PMID: 27863088 DOI: 10.1111/jdi.12596
    AIMS/INTRODUCTION: Studies on the relative contributions of fasting and postprandial hyperglycemia (FH and PPH) to glycated hemoglobin (HbA1c ) in patients with type 2 diabetes have yielded inconsistent results. We aimed to assess the relationship by using continuous glucose monitoring in a multi-ethnic cohort.

    MATERIALS AND METHODS: A total of 100 adults with type 2 diabetes were assessed with 6-day continuous glucose monitoring and HbA1c . Area under the curve (AUC) ≥5.6 mmol/L was defined as AUCTOTAL . AUC equal to or greater than each preprandial glucose for 4-h duration was defined as AUCPPH . The total PPH (AUCTPPH ) was the sum of the various AUCPPH. The postprandial contribution to overall hyperglycemia was calculated as (AUCTPPH / AUCTOTAL ) × 100%.

    RESULTS: The present study comprised of Malay, Indian, and Chinese type 2 diabetes patients at 34, 34 and 28% respectively. Overall, the mean PPH significantly decreased as HbA1c advanced (mixed model repeated measures adjusted, beta-estimate = -3.0, P = 0.009). Age (P = 0.010) and hypoglycemia (P = 0.006) predicted the contribution difference. In oral antidiabetic drug-treated patients (n = 58), FH contribution increased from 54% (HbA1c 6-6.9%) to 67% (HbA1c ≥10%). FH predominance was significant in poorly-controlled groups (P = 0.028 at HbA1c 9-9.9%; P = 0.015 at HbA1c ≥10%). Among insulin users (n = 42), FH predominated when HbA1c was ≥10% before adjustment for hypoglycemia (P = 0.047), whereas PPH was numerically greater when HbA1c was <8%.

    CONCLUSIONS: FH and PPH contributions were equal in well-controlled Malaysian type 2 diabetes patients in real-world practice. FH predominated when HbA1c was ≥9 and ≥10% in oral antidiabetic drug- and insulin-treated patients, respectively. A unique observation was the greater PPH contribution when HbA1c was <8% despite the use of basal and mealtime insulin in this multi-ethnic cohort, which required further validation.

  9. Long Bidin MB, Khan AM, Tan FHS, Aziz NA, Ali NM, Kamaruddin NA, et al.
    J ASEAN Fed Endocr Soc, 2023;38(1):75-80.
    PMID: 37252416 DOI: 10.15605/jafes.038.01.06
    OBJECTIVE: This study aims to report the demographic features of patients with acromegaly, the disease burden, and the corresponding treatment patterns and outcomes in Malaysia.

    METHODOLOGY: This is a retrospective study that included patients from the Malaysian Acromegaly registry who were diagnosed with acromegaly from 1970 onwards. Data collected included patient demographics, clinical manifestations of acromegaly, biochemical results and imaging findings. Information regarding treatment modalities and their outcomes was also obtained.

    RESULTS: Registry data was collected from 2013 to 2016 and included 140 patients with acromegaly from 12 participating hospitals. Median disease duration was 5.5 years (range 1.0 - 41.0 years). Most patients had macroadenoma (67%), while 15% were diagnosed with microadenoma. Hypertension (49.3%), diabetes (37.1%) and hypopituitarism (27.9%) were the most common co-morbidities for patients with acromegaly. Majority of patients had surgical intervention as primary treatment (65.9%) while 20.7% were treated medically, mainly with dopamine agonists (18.5%). Most patients had inadequate disease control after first-line treatment regardless of treatment modality (79.4%).

    CONCLUSION: This registry study provides epidemiological data on patients with acromegaly in Malaysia and serves as an initial step for further population-based studies.

  10. Ooi YG, Sarvanandan T, Hee NKY, Lim QH, Paramasivam SS, Ratnasingam J, et al.
    Diabetes Metab J, 2024 Mar;48(2):196-207.
    PMID: 38273788 DOI: 10.4093/dmj.2023.0244
    People with type 2 diabetes mellitus have increased risk of chronic kidney disease and atherosclerotic cardiovascular disease. Improved care delivery and implementation of guideline-directed medical therapy have contributed to the declining incidence of atherosclerotic cardiovascular disease in high-income countries. By contrast, the global incidence of chronic kidney disease and associated mortality is either plateaued or increased, leading to escalating direct and indirect medical costs. Given limited resources, better risk stratification approaches to identify people at risk of rapid progression to end-stage kidney disease can reduce therapeutic inertia, facilitate timely interventions and identify the need for early nephrologist referral. Among people with chronic kidney disease G3a and beyond, the kidney failure risk equations (KFRE) have been externally validated and outperformed other risk prediction models. The KFRE can also guide the timing of preparation for kidney replacement therapy with improved healthcare resources planning and may prevent multiple complications and premature mortality among people with chronic kidney disease with and without type 2 diabetes mellitus. The present review summarizes the evidence of KFRE to date and call for future research to validate and evaluate its impact on cardiovascular and mortality outcomes, as well as healthcare resource utilization in multiethnic populations and different healthcare settings.
  11. Ratnasingam J, Karim N, Paramasivam SS, Ibrahim L, Lim LL, Tan AT, et al.
    Pituitary, 2015 Aug;18(4):448-55.
    PMID: 25134488 DOI: 10.1007/s11102-014-0593-6
    PURPOSE: Radiation fields for nasopharyngeal cancer (NPC) include the base of skull, which places the hypothalamus and pituitary at risk of damage. We aimed to establish the prevalence, pattern and severity of hypothalamic pituitary (HP) dysfunction amongst NPC survivors.

    METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function.

    RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01.

    CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.

  12. Chan WK, Tan AT, Vethakkan SR, Tah PC, Vijayananthan A, Goh KL
    Clin Res Hepatol Gastroenterol, 2014 Jun;38(3):284-91.
    PMID: 24736032 DOI: 10.1016/j.clinre.2014.02.009
    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both common among patients with diabetes mellitus.
    OBJECTIVE: The aim of this study is to determine if ultrasonography-diagnosed NAFLD is associated with prevalent ischemic heart disease (IHD) among patients with diabetes mellitus.
    METHODS: This is a cross-sectional study on consecutive patients seen at the Diabetic Clinic, University of Malaya Medical Centre. The medical record for each patient was reviewed for documented IHD. Patients without documented IHD but had symptoms and/or electrocardiographic changes suggestive of IHD were referred for cardiac evaluation.
    RESULTS: Data for 399 patients were analyzed. Mean age was 62.8±10.5 years with 43.1% male. NAFLD and IHD were present in 49.6 and 26.6%, respectively. The prevalence of IHD among patients with and without NAFLD was 24.7 and 28.4%, respectively (P=0.414). The prevalence of IHD was highest among the Indians (34.1%) followed by the Malays (29.2%) and the Chinese (20.1%). No association was found between NAFLD and IHD when analyzed according to ethnicity. On multivariate analysis, independent factors associated with IHD were older age, lower levels of physical activity, greater waist circumference and higher serum glycated hemoglobin level.
    CONCLUSIONS: Ultrasonography-diagnosed NAFLD was not associated with prevalent IHD among patients with diabetes mellitus in a multiracial Asian hospital clinic population.

    Study site: Diabetic clinc, University Malaya Medical Centre (UMMC)
  13. Ratnasingam J, Tan AT, Vethakkan SR, Paramasivam SS, Ibrahim L, Lim LL, et al.
    J Clin Endocrinol Metab, 2013 Mar;98(3):869-70.
    PMID: 23337722 DOI: 10.1210/jc.2012-3839
  14. Khan S, Saub R, Vaithilingam RD, Safii SH, Vethakkan SR, Baharuddin NA
    BMC Oral Health, 2015;15:114.
    PMID: 26419358 DOI: 10.1186/s12903-015-0098-3
    Chronic periodontitis (CP) is a global public health issue. Studies have suggested CP could be linked to obesity due to their similar pathophysiological pathway. The aim of this study is to determine the prevalence of CP and to assess the predictors for CP among the obese Malaysian population.
    METHODS: This is a cross-sectional study on obese participants. Obesity is defined as an individual who has Body Mass Index (BMI) ≥ 27.5 kg/m(2). A convenience sampling method was used. A total of 165 paricipants were recruited. This study involved answering questionnaires, obtaining biometric and clinical measurements of Visible plaque index (VPI), Gingival bleeding index (GBI), Probing pocket depth (PPD) and Clinical attachment loss (CAL). Data analysis was carried out using SPSS statistical software (SPSS Inc., version 20, US).
    RESULTS: A total of 165 participants; 67 (40.6%) males and 98 (59.4%) females participated in the study. Mean age of the participants was 43.9 (± 8.9). The prevalence of CP among the obese population was found to be 73.9%. Out of this, 43 and 55% were categorised as moderate and severe CP respectively. Around 64% of participants had sites with CAL ≥ 4 mm and participants with sites with PPD ≥ 4 mm were reported to be 25%. Around 83% of the participants had sites with GBI ≥ 30 and 92% of participants had sites with VPI ≥ 20%. GBI and VPI were found to have significantly higher odds for CP.
    CONCLUSION: Prevalence of CP was high among obese Malaysians. GBI and VPI were potential predictors for CP in this obese population.
  15. Kasim NB, Huri HZ, Vethakkan SR, Ibrahim L, Abdullah BM
    Biomark Med, 2016 Apr;10(4):403-15.
    PMID: 26999420 DOI: 10.2217/bmm-2015-0037
    Generally, obese and overweight individuals display higher free fatty acid levels, which stimulate insulin resistance. The combination of overweight or obesity with insulin resistance can trigger Type 2 diabetes mellitus (T2DM) and are primary contributing factors to the development of uncontrolled T2DM. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to becoming overweight or obese and developing related chronic complications, such as uncontrolled T2DM. This review specifically examines the genetic polymorphisms associated with overweight and obesity in patients with uncontrolled T2DM. Particularly, gene polymorphisms in ADIPOQ (rs1501299 and rs17300539), LepR (rs1137101 and rs1045895), IRS2 (rs1805092), GRB14 (rs10195252 and rs3923113) and PPARG (rs1801282) have been associated with overweight and obesity in uncontrolled T2DM.
  16. Chan WK, Tan AT, Vethakkan SR, Tah PC, Vijayananthan A, Goh KL
    Asia Pac J Clin Nutr, 2015;24(2):289-98.
    PMID: 26078246 DOI: 10.6133/apjcn.2015.24.2.15
    To study the dietary intake and level of physical activity (PA) of patients with diabetes mellitus and the association with non-alcoholic fatty liver disease (NAFLD).
  17. Lai LL, Wan Yusoff WNI, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK
    J Gastroenterol Hepatol, 2019 Aug;34(8):1396-1403.
    PMID: 30551263 DOI: 10.1111/jgh.14577
    BACKGROUND AND AIM: The recommendation in regard to screening for non-alcoholic fatty liver disease (NAFLD) among type 2 diabetes mellitus (T2DM) patients differs in major guidelines. The aim of this paper was to study the prevalence of NALFD and advanced fibrosis among T2DM patients.

    METHODS: This is a cross-sectional study of consecutive adult T2DM patients attending the Diabetes Clinic of a university hospital. Significant hepatic steatosis and advanced fibrosis was diagnosed based on transient elastography if the controlled attenuation parameter was ≥ 263 dB/m, and the liver stiffness measurement was ≥ 9.6 kPa using the M probe or ≥ 9.3 kPa using the XL probe, respectively. Patients with liver stiffness measurement ≥ 8 kPa were referred to the Gastroenterology and Hepatology Clinic for further assessment, including liver biopsy.

    RESULTS: The data of 557 patients were analyzed (mean age 61.4 ± 10.8 years, male 40.6%). The prevalence of NAFLD and advanced fibrosis based on transient elastography was 72.4% and 21.0%, respectively. On multivariate analysis, independent factors associated with NAFLD were central obesity (OR 4.856, 95% confidence interval [CI] 2.749-8.577, P = 0.006), serum triglyceride (OR 1.585, 95% CI 1.056-2.381, P = 0.026), and alanine aminotransferase levels (OR 1.047, 95% CI 1.025-1.070, P 

  18. Lai LL, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK
    Dig Dis Sci, 2020 02;65(2):623-631.
    PMID: 30684076 DOI: 10.1007/s10620-019-5477-1
    BACKGROUND AND AIMS: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of drugs that lower glucose by inducing renal glycosuria. We aimed to explore whether SGLT2 inhibitor added to the usual care for patients with type 2 diabetes mellitus (T2DM) and biopsy-proven nonalcoholic steatohepatitis (NASH) will benefit NASH histology.

    METHODS: In this investigator-initiated, single-arm, open-label, pilot study, nine biopsy-proven NASH patients with T2DM were given empagliflozin 25 mg daily for 24 weeks. Liver biopsy was repeated at the end of treatment. The histological outcomes were compared with the placebo group of a previous 48-week clinical trial.

    RESULTS: There was a significant reduction in body mass index (median change, Δ = -0.7 kg per m2, p = 0.011), waist circumference (Δ = -3 cm, p = 0.033), systolic blood pressure (Δ = -9 mmHg, p = 0.024), diastolic blood pressure (Δ = -6 mmHg, p = 0.033), fasting blood glucose (Δ = -1.7 mmol/L, p = 0.008), total cholesterol (Δ = -0.5 mmol/L, p = 0.011), gamma glutamyl transpeptidase (Δ = -19 U/L, p = 0.013), volumetric liver fat fraction (Δ = -7.8%, p = 0.017), steatosis (Δ = -1, p = 0.014), ballooning (Δ = -1, p = 0.034), and fibrosis (Δ = 0, p = 0.046). All histological components either remained unchanged or improved, except in one patient who had worsening ballooning. Empagliflozin resulted in significantly greater improvements in steatosis (67% vs. 26%, p = 0.025), ballooning (78% vs. 34%, p = 0.024), and fibrosis (44% vs. 6%, p = 0.008) compared with historical placebo.

    CONCLUSION: This pilot study provides primary histological evidence that empagliflozin may be useful for the treatment of NASH. This preliminary finding should prompt larger clinical trials to assess the effectiveness of empagliflozin and other SGLT2 inhibitors for the treatment of NASH in T2DM patients. Trial registry number ClincialTrials.gov number, NCT02964715.

  19. Tan EZ, Lai LL, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK
    J Gastroenterol Hepatol, 2021 Mar;36(3):751-757.
    PMID: 32583444 DOI: 10.1111/jgh.15160
    BACKGROUND: The effect of modest alcohol intake on prevalence of significant hepatic steatosis and severity of liver disease in patients with type 2 diabetes mellitus (T2DM) is unclear.

    METHODS: This is a cross-sectional study on T2DM patients. Modest alcohol intake was defined as alcohol intake ≤ 21 units/week in men and ≤ 14 units/week in women. Significant hepatic steatosis was diagnosed on the basis of controlled attenuation parameter > 263 dB/m, while advanced fibrosis was diagnosed on the basis of liver stiffness measurement ≥ 9.6 kPa using M probe or ≥ 9.3 kPa using XL probe. Patients with liver stiffness measurement ≥ 8.0 kPa were offered liver biopsy.

    RESULTS: Five hundred fifty-seven patients underwent transient elastography, and 71 patients underwent liver biopsy. The prevalence of modest drinking was 16.5%. Modest drinking was equally prevalent among ethnic Indians and Chinese at 22.9% and 23.3%, respectively, but uncommon among ethnic Malays at 1.7%. Modest drinkers were more likely to be male, smoked, and had significantly lower glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, and platelet count. There was no significant difference in the prevalence of significant hepatic steatosis or advanced fibrosis based on transient elastography and steatohepatitis or advanced fibrosis between modest drinkers and nondrinkers. The prevalence of significant hepatic steatosis was higher among ethnic Malays and Indians compared with ethnic Chinese, but the Chinese did not have a lower prevalence of more severe liver disease.

    CONCLUSION: Modest alcohol intake is not associated with higher prevalence of significant hepatic steatosis or more severe liver disease among patients with T2DM.

  20. Goh LY, Shahrom EE, Ganesan CC, Vethakkan SR, Goh KJ
    Neurology Asia, 2017;22(4):325-331.
    MyJurnal
    Objective: To determine prevalence and factors associated with neuropathic pain symptoms in a multiethnic cohort of Malaysian adult diabetic patients.
    Methods: This was aprospective cross-sectional observational study of hospital-based diabetic outpatients in Malaysia. Subjects were interviewed for their demographic data and medical history. The painDETECT questionnaire was used to screen for neuropathic pain symptoms and pain intensity was assessed using the numeric pain rating scale (NPRS). Neuropathy symptoms and signs were assessed using the Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS).
    Results:Of 242 patients,140 (58%) were women, with a mean age of 61 + 11.4 years (range 21 to 81). Ninety nine(40.9%) were Malay, 64 (26.4%) Chinese, 76 (31.4%) Indian and three (1.2%) were Eurasian. Mean duration of diabetes was 15.9+ 9.8 years (range 1 to 53) and 232 (95.9%) patients had Type II diabetes. Peripheral neuropathy,based on NSS and NDS criteria, was found in 83 (34.3%). Thirteen (5.4%) patients were found to likely have neuropathic pain symptoms and this was independently associated with peripheral neuropathy ((OR) = 3.40, 95% confidence interval (CI): 1.04, 11.14) and Indian ethnicity (OR = 5.44, 95% CI: 1.50,
    19.57)). Patients with neuropathic pain had higher average pain intensity scores.
    Conclusions: The prevalence of neuropathic pain symptoms in a Malaysian DM patient cohort was low and was associated with the severity of neuropathy symptoms and Indian ethnicity. The causes for ethnic differences are unknown and could be due socio-cultural or physiological differences in neuropathic pain perception.
    Study site: Diabetic clinic, University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
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