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.
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
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.
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.
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.
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.
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.
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
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.
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.