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.

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.

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.

SUBJECTS/METHODS: Using a crossover design, we conducted a randomised controlled trial in 53 free-living high-risk abdominally overweight subjects, comparing the effects of incorporating red palm olein (with palm olein as control) in a supervised isocaloric 2100 kcal diet of 30% en fat, two-thirds (45 g/day) of which were derived from the test oil for a period of 6 weeks each.

EVIDENCE ACQUISITION: A systematic search of all English-language medical literature published from 1980 till May 2016 using PubMed, Embase and Ovid was performed. Nine observational studies were evaluated after fulfilling the inclusion and exclusion criteria.

EVIDENCE SYNTHESIS: A total of 547 patients were examined. All studies used vitamin D2/D3 or calcifediol (25-hydroxyvitamin D3), There was significant improvement of serum 25(OH)D with unchanged serum iPTH level after vitamin D replacement, with pooled d+: 3.10 (95% CI 2.25 to 3.95), P<0.01 and pooled d+: 0.82 (95% CI -0.35 to 1.98), P=0.16 respectively. There was neither worsening of the pre-existing hypercalcemia (pooled d+: -0.27 [95% CI -1.09 to 0.64, P=0.56]) nor hypercalciuria (pooled d+: 3.64 [95% CI -0.55 to 7.83, P=0.09]). Two studies assessed in this meta-analysis reported unchanged bone density with vitamin D replacement.

OBJECTIVE: To assess the chronic effects of the substitution of refined carbohydrate or MUFA for SAFA on insulin secretion and insulin sensitivity in centrally obese subjects.

METHODS: Using a crossover design, randomized controlled trial in abdominally overweight men and women, we compared the effects of substitution of 7% energy as carbohydrate or MUFA for SAFA for a period of 6 weeks each. Fasting and postprandial blood samples in response to corresponding SAFA, carbohydrate, or MUFA-enriched meal-challenges were collected after 6 weeks on each diet treatment for the assessment of outcomes.

RESULTS: As expected, postprandial nonesterified fatty acid suppression and elevation of C-peptide, insulin and glucose secretion were the greatest with high-carbohydrate (CARB) meal. Interestingly, CARB meal attenuated postprandial insulin secretion corrected for glucose response; however, the insulin sensitivity and disposition index were not affected. SAFA and MUFA had similar effects on all markers except for fasting glucose-dependent insulinotropic peptide concentrations, which increased after MUFA but not SAFA when compared with CARB.

METHODS: Retrospective analysis of prospectively collected data on adult NAFLD patients who had two FibroScan examination within 6 months prior to liver biopsy. F3-F4 fibrosis was excluded using LSM cut-off of 7.9 kPa.

METHODS: We recruited 54 abdominally obese subjects to participate in a prospective cross-over design, single-blind trial comparing isocaloric 2000 kcal MUFA or carbohydrate-enriched diet with SFA-enriched diet (control). The control diet consisted of 15E% protein, 53E% carbohydrate and 32E% fat (12E% SFA, 13E% MUFA). A total of ∼7E% of MUFA or refined carbohydrate was exchanged with SFA in the MUFA-rich and carbohydrate-rich diets respectively for 6-weeks. Blood samples were collected at fasting upon trial commencement and at week-5 and 6 of each dietary-intervention phase to measure levels of cytokines (IL-6, IL-1β), C-reactive protein (CRP), thrombogenic markers (E-selectin, PAI-1, D-dimer) and lipid subfractions. Radial pulse wave analysis and a 6-h postprandial mixed meal challenge were carried out at week-6 of each dietary intervention. Blood samples were collected at fasting, 15 and 30 min and hourly intervals thereafter till 6 h after a mixed meal challenge (muffin and milkshake) with SFA or MUFA (872.5 kcal, 50 g fat, 88 g carbohydrates) or CARB (881.3 kcal, 20 g fat, 158 g carbohydrates)- enrichment corresponding to the background diets.

DESIGN: This was a cross-sectional study conducted among women in Kuala Lumpur, Malaysia. Sociodemographic characteristics, physical activity status, perceived depression and health-related quality of life were assessed via a self-administered questionnaire. Fasting blood samples were taken for the analysis of 25-hydroxyvitamin D, parathyroid hormone, fasting blood glucose and full lipid profile. Complex samples multiple logistic regression analysis was performed.

SETTING: Public secondary schools in Kuala Lumpur, Malaysia.

SUBJECTS: Seven hundred and seventy female teachers were included.

RESULTS: The mean age of participants was 41·15 (95 % CI 40·51, 41·78) years and the majority were ethnic Malays. Over 70 % of them had vitamin D deficiency (<20 ng/ml or <50 nmol/l) and two-thirds were at risk for depression. In the multivariate analysis, ethnic Malays (adjusted OR (aOR)=14·72; 95 % CI 2·12, 102·21) and Indians (aOR=14·02; 95 % CI 2·27, 86·59), those at risk for depression (aOR=1·88, 95 % CI 1·27, 2·79) and those with higher parathyroid hormone level (aOR=1·13; 95 % CI 1·01, 1·26) were associated with vitamin D deficiency, while vitamin D deficiency was negatively associated with mental health-related quality of life (Mental Component Summary) scores (aOR=0·98; 95 % CI 0·97, 0·99).

METHODS: The ARTEMIS-DM was a 26-week, prospective, interventional, single-arm, phase IV study (NCT03760991). Adults with T2DM previously uncontrolled (glycated haemoglobin [HbA1c] 7.5-10%) on BI were switched to Gla-300. The primary endpoint was change in HbA1c from baseline to 26 weeks. Key secondary endpoints were changes in HbA1c (week 12), fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG) and BI dose from baseline to week 26. The safety and tolerability of Gla-300 were also assessed.

RESULTS: A total of 372 (50% male) participants were included, with mean (standard deviation [SD]) age 60.9 (10.0) years, duration of diabetes 13.11 (7.48) years and baseline HbA1c 8.67 (0.77)% (71.22 [8.44] mmol/mol). A total of 222 (59.7%) participants were using insulin glargine 100 U/mL and 107 (28.8%) were using neutral protamine Hagedorn insulin as previous BI. There were clinically significant reductions in mean HbA1c (- 0.82%; primary endpoint), FPG and SMPG levels at week 26. With a pre-defined titration algorithm, mean Gla-300 dose increased from 27.48 U (0.35 U/kg) at baseline to 39.01 U (0.50 U/kg) at week 26. Hypoglycaemia events occurred in 20.4% of the participants; 1 (0.3%) participant had a severe hypoglycaemia event.

CONCLUSION: In people with T2DM uncontrolled on previous BI, switching to Gla-300 with optimal titration guided by an algorithm was associated with improved glycaemic control and low incidence of hypoglycaemia across multiple geographic regions.

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.