Effect of oral semaglutide on energy intake, appetite, control of eating and gastric emptying in adults living with obesity: A randomized controlled trial.

AIM: To investigate the effects of once-daily oral semaglutide 50 mg on energy intake, appetite, control of eating and gastric emptying. METHODS: A clinical pharmacology, double-blind study was conducted in 61 adults with obesity randomized to once-daily oral semaglutide (dose-escalated to 50 mg) or placebo for 20 weeks. Energy intake was measured during an ad libitum lunch, and participant-reported appetite ratings and Control of Eating Questionnaire responses were assessed. Gastric emptying was measured using paracetamol absorption following a standardized breakfast. RESULTS: The relative change from baseline in ad libitum energy intake at week 20 (primary endpoint) was -39.2% points (95% confidence interval -59.0%, -19.4%) with semaglutide compared with placebo. Body weight was reduced by 9.8% with semaglutide and by 1.5% with placebo. Semaglutide reduced hunger, increased fullness and satiety, and was associated with fewer food cravings and better control of eating versus placebo. No statistically significant difference in gastric emptying was observed at week 20. CONCLUSIONS: In participants with obesity, once-daily oral semaglutide 50 mg reduced energy intake, body weight and appetite, and improved control of eating. There was no evidence of delayed gastric emptying at week 20, as measured through paracetamol absorption.

Hemostatic Effects of Exercise-Related Hypoglycemia in Male Persons With Type 1 Diabetes.

CONTEXT: People with type 1 diabetes (T1D) are at increased risk of thrombosis, however, the underlying mechanisms remain unclear. Hypoglycemia induced at rest can induce coagulation activation, but little is known about the hemostatic effects of exercise-related hypoglycemia in people with T1D. OBJECTIVE: We compared hemostatic profiles of individuals with T1D with healthy controls and explored hemostatic effects of hypoglycemia, induced with or without exercise, in participants with T1D. METHODS: Thrombelastography (TEG) was used for a baseline hemostatic comparison between fifteen men with T1D and matched healthy controls. In addition, the participants with T1D underwent two euglycemic-hypoglycemic clamp days in a randomized, crossover fashion. Hypoglycemia was induced with the participants at rest (Hypo-rest) or during exercise (Hypo-exercise). TEG provides data on the rate of coagulation activation (R-time), the rate of clot formation (K-time, α-Angle), the maximum clot amplitude (MA), the functional fibrinogen contribution to the clot strength (MA-FF) and the fibrinolysis (LY-30). RESULTS: The T1D group exhibited shorter R-time and K-time and a greater α-Angle compared to the controls. During the clamp experiments, Hypo-exercise induced an increased clot strength (MA) with a mean difference from baseline of 2.77 mm [95% confidence interval 2.04; 3.51] accompanied with a decreased fibrinolysis (LY-30) of -0.45 percentage points [-0.60; -0.29]. Hypo-rest resulted in increased functional fibrinogen (MA-FF) of 0.74 mm [0.13; 1.36] along with an increased fibrinolysis (LY-30) of 0.54 percentage points [0.11; 0.98]. CONCLUSION: Individuals with T1D exhibit a hypercoagulable hemostatic profile compared to healthy controls and exercise-related hypoglycemia may increase the susceptibility to thrombosis via both procoagulant and antifibrinolytic effects.

Effects of oral roflumilast therapy on body weight and cardiometabolic parameters in patients with psoriasis - results from a randomized controlled trial (PSORRO).

BACKGROUND: Weight loss is reported with oral roflumilast, which is approved for chronic obstructive pulmonary disease (COPD). Recently, the drug has shown efficacy in psoriasis, a disease strongly linked to overweight/obesity. OBJECTIVE: To describe the effects of oral roflumilast on body weight and cardio-metabolic parameters in patients with psoriasis. METHODS: Posthoc analyses from the PSORRO study, where patients with moderate-to-severe plaque psoriasis were randomized 1:1 to oral roflumilast 500 µg once-daily or placebo for 12 weeks, followed by active, open-label treatment through week 24 in both groups. Changes in body weight, blood pressure, gastrointestinal symptoms, and laboratory tests were registered. No lifestyle or dietary interventions were applied. RESULTS: Forty-six patients were randomized. Baseline characteristics across groups were comparable; mean weight was 103.6 kg. In patients receiving roflumilast, median weight change was -2.6% and -4% at week 12 and 24, respectively. Corresponding numbers were 0.0% and 1.3% in patients initially allocated to placebo. Reduced appetite was more frequent with active therapy. No changes in blood pressure or laboratory tests were observed. LIMITATIONS: Posthoc analyses and low numbers. CONCLUSION: Oral roflumilast induced weight loss and reduced appetite, which support the growing evidence of roflumilast as an attractive treatment alternative for patients with psoriasis.

Signs of Glucagon Resistance After a 2-Week Hypercaloric Diet Intervention.

CONTEXT: Hyperglucagonemia is observed in individuals with obesity and contributes to the hyperglycemia of patients with type 2 diabetes. Hyperglucagonemia may develop due to steatosis-induced hepatic glucagon resistance resulting in impaired hepatic amino acid turnover and ensuing elevations of circulating glucagonotropic amino acids. OBJECTIVE: We evaluated whether glucagon resistance could be induced in healthy individuals by a hypercaloric diet intervention designed to increase hepatic fat content. METHODS: We recruited 20 healthy male individuals to follow a hypercaloric diet and a sedentary lifestyle for 2 weeks. Amino acid concentrations in response to infusion of glucagon were assessed during a pancreatic clamp with somatostatin and basal insulin. The reversibility of any metabolic changes was assessed 8 weeks after the intervention. Hepatic steatosis was assessed by magnetic resonance spectroscopy. RESULTS: The intervention led to increased hepatic fat content (382% [206%; 705%], P < .01). Glucagon infusion led to a decrease in the concentration of total amino acids on all experimental days, but the percentage change in total amino acids was reduced (-2.5% ± 0.5% vs -0.2% ± 0.7%, P = .015) and the average slope of the decline in the total amino acid concentration was less steep (-2.0 ± 1.2 vs -1.2 ± 0.3 µM/min, P = .016) after the intervention compared to baseline. The changes were normalized at follow-up. CONCLUSION: Our results indicate that short-term unhealthy behavior, which increases hepatic fat content, causes a reversible resistance to the effect of glucagon on amino acid concentrations in healthy individuals, which may explain the hyperglucagonemia associated with obesity and diabetes.

Different Effects of Once-weekly and Once-daily Administered GLP-1RA Semaglutide and Liraglutide on Bile Acid Diarrhea.

Bile acid diarrhea (BAD) is a socially debilitating disease. Typical symptoms include loose stools, urgency, and high stool frequency. Recently, we reported the superior efficacy of the glucagon like-peptide 1 receptor agonist (GLP-1RA) liraglutide (administered subcutaneously once daily) in reducing daily bowel movements compared with the traditionally used bile acid sequestrant colesevelam (considered the standard of care). This has generated proposals of testing longer acting and more potent GLP-1RAs for treating BAD. Here, we present a patient with severe BAD who experienced minimal effect of the once-weekly administered GLP-1RA semaglutide, but total remission of BAD symptoms during treatment with liraglutide.

Management of dyslipidaemia in individuals with severe mental illness: a population-based study in the Greater Copenhagen Area.

Background: Severe mental illness (SMI) is associated with increased cardiovascular risk. Dyslipidaemia is a potentially modifiable risk factor, which may be inadequately managed in patients with SMI. Objectives: To assess management of dyslipidaemia in patients with SMI versus healthy controls (HCs) in 2005 and 2015. Design and methods: Using Danish registers, we identified adult patients with SMI in the Greater Copenhagen Area (schizophrenia spectrum disorders or bipolar disorder) with ⩾1 general practitioner contact in the year before 2005 and 2015, respectively, and HCs without SMI matched on age and gender (1:5). Outcomes were lipid-profile measurements, presence of dyslipidaemia and redemption of lipid-lowering pharmacotherapy. Differences in outcomes between patients with SMI and controls were measured with multivariable logistic regression. Results: We identified 7217 patients with SMI in 2005 and 9939 in 2015. After 10 years, patients went from having lower odds of lipid measurements to having higher odds of lipid measurements compared with HCs [odds ratio (OR)2005 0.70 (99% confidence interval (CI) 0.63-0.78) versus OR2015 1.34 (99% CI 1.24-1.44); p2005versus2015 < 0.01]. Patients had higher odds of dyslipidaemia during both years [OR2005 1.43 (99% CI 1.10-1.85) and OR2015 1.23 (99% CI 1.08-1.41)]. Patients went from having lower odds of receiving lipid-lowering pharmacotherapy to having higher odds of receiving lipid-lowering pharmacotherapy [OR2005 0.77 (99% CI 0.66-0.89) versus OR2015 1.37 (99% CI 1.24-1.51); p2005versus2015 < 0.01]. However, among persons at high cardiovascular risk, patients had lower odds of receiving lipid-lowering pharmacotherapy during both years, including subsets with previous acute coronary syndrome [OR2005 0.30 (99% CI 0.15-0.59) and OR2015 0.44 (99% CI 0.24-0.83)] and ischaemic stroke or transient ischaemic attack (TIA) [OR2005 0.43 (99% CI 0.26-0.69) and OR 2015 0.61 (99% CI 0.41-0.89)]. Conclusion: These results imply an increased general awareness of managing dyslipidaemia among patients with SMI in the primary prophylaxis of cardiovascular disease. However, secondary prevention with lipid-lowering drugs in patients with SMI at high cardiovascular risk may be lacking.

Characterization of Postprandial Bile Acid Profiles and Glucose Metabolism in Cerebrotendinous Xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare inherited disease characterized by sterol 27-hydroxylase (CYP27A1) deficiency and, thus, a lack of bile acid synthesis with a marked accumulation of 7α-hydroxylated bile acid precursors. In addition to their renowned lipid-emulgating role, bile acids have been shown to stimulate secretion of the glucose-lowering and satiety-promoting gut hormone glucagon-like peptide 1 (GLP-1). In this paper, we examined postprandial bile acid, glucose, insulin, GLP-1 and fibroblast growth factor 19 (FGF19) plasma profiles in patients with CTX and matched healthy controls. Seven patients and seven age, gender and body mass index matched controls were included and subjected to a 4 h mixed meal test with regular blood sampling. CTX patients withdrew from chenodeoxycholic acid (CDCA) and statin therapy three weeks prior to the test. Postprandial levels of total bile acids were significantly lower in CTX patients and consisted of residual CDCA with low amounts of ursodeoxycholic acid (UDCA). The postprandial plasma glucose peak concentration occurred later in CTX patients compared to controls, and patients' insulin levels remained elevated for a longer time. Postprandial GLP-1 levels were slightly higher in CTX subjects whereas postprandial FGF19 levels were lower in CTX subjects. This novel characterization of CTX patients reveals very low circulating bile acid levels and FGF19 levels, aberrant postprandial glucose and insulin profiles, and elevated postprandial GLP-1 responses.

MRI-Based Quantification of Pan-Alimentary Function and Motility in Subjects with Diabetes and Gastrointestinal Symptoms.

Background: Diabetes-induced gastrointestinal (GI) symptoms are common but difficult to correctly diagnose and manage. We used multi-segmental magnetic resonance imaging (MRI) to evaluate structural and functional GI parameters in diabetic patients and to study the association with their symptomatic presentation. Methods: Eighty-six participants (46 with diabetes and GI symptoms, 40 healthy controls) underwent baseline and post-meal MRI scans at multiple timepoints. Questionnaires were collected at inclusion and following the scans. Data were collected from the stomach, small bowel, and colon. Associations between symptoms and collected data were explored. Utilizing machine learning, we determined which features differentiated the two groups the most. Key Results: The patient group reported more symptoms at inclusion and during MRI scans. They showed 34% higher stomach volume at baseline, 40% larger small bowel volume, 30% smaller colon volume, and less small bowel motility postprandially. They also showed positive associations between gastric volume and satiety scores, gastric emptying time and reflux scores, and small bowel motility and constipation scores. No differences in gastric emptying were observed. Small bowel volume and motility were used as inputs to a classification tool that separated patients and controls with 76% accuracy. Conclusions: In this work, we studied structural and functional differences between patients with diabetes and GI symptoms and healthy controls and observed differences in stomach, small bowel, and colon volumes, as well as an adynamic small bowel in patients with diabetes and GI symptoms. Associations between recorded parameters and perceived symptoms were also explored and discussed.

Hepatic Fibrosis Evaluated in Patients with Type 2 Diabetes with and without Chronic Kidney Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), and particularly liver fibrosis, has been suggested as a risk factor of chronic kidney disease (CKD). Given that NAFLD affects every fourth person globally, better insight is needed. Our aim was to investigate the association between hepatic fibrosis and CKD in patients with type 2 diabetes and to compare different methods for diagnosing liver fibrosis in this study population. METHODS: Cross-sectional study including patients with type 2 diabetes with CKD stages 3-5 (N = 50) or without CKD (N = 50). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 with or without proteinuria. Three methods were used to detect significant liver fibrosis defined as either ≥8 kilopascal measured by transient elastography (FibroScan®), fibrosis-4 (FIB-4) score ≥2.67, or NAFLD fibrosis score (NFS) >0.675. RESULTS: Significant liver fibrosis was found in 38% and 28% of the patients with and without CKD, respectively, using at least one of the three methods. Both FIB-4 score and NFS were significantly higher in patients with CKD (p < 0.0009 and p < 0.0001, respectively), although insignificant after adjustments for age, sex, body mass index, and duration of diabetes. In patients without CKD, a significant association between steatosis and fibrosis was observed (p = 0.0007). CONCLUSION: Our data do not support any strong independent association between liver fibrosis and established CKD as assessed by FibroScan, FIB-4 score, and NFS, respectively.

Value of gym-based group exercise versus usual care for young adults receiving antipsychotic medication: study protocol for the multicenter randomized controlled Vega trial.

BACKGROUND: Exercise is recommended to protect physical health among people with severe mental illness and holds the potential to facilitate long-term recovery. An inclusive exercise community provides an opportunity for life skill training and social connectedness and may reduce the experience of loneliness and internalized stigmatization which together may improve personal recovery. Using a pragmatic randomized design, we aim to examine the effectiveness of a gym-based exercise intervention tailored to young adults in antipsychotic treatment (i.e., Vega Exercise Community) compared to usual care. It is hypothesized that the Vega Exercise Community will be superior to usual care for personal recovery at four months. METHODS: The trial will be conducted at four sites in Denmark from which 400 participants, aged 18 to 35 years, who are in current treatment with antipsychotic medications for the management of schizophrenia spectrum or affective disorders, will be recruited. Participants will be randomized (2:1) to Vega Exercise Community or usual care. Vega Exercise Community includes three weekly group-based exercise sessions hosted in commercial functional training centers delivered by certified Vega instructors. After four months, participants in Vega Exercise Community will be randomized (1:1) to minimal versus extended support with regards to sustained physical activity. Data will be collected at baseline, four, six and 12 months. The primary outcome is personal recovery assessed by Questionnaire about the Process of Recovery at four months. Behavioral symptoms, health-related quality of life, metabolic health, and program costs will be evaluated to further determine the effectiveness and cost-effectiveness of the Vega Exercise Community. Finally, the quality of life and physical and mental health of the participants' primary relative will be evaluated. DISCUSSION: The results of this trial may have important implications for health, sustained physical activity, and recovery for individuals in treatment with antipsychotics. Given the pragmatic design, positive results may readily be implemented by mental health care professionals to promote exercise as an integrated part of treatment of severe mental illness. TRIAL REGISTRATION: Clinical Trials.gov (NCT05461885, initial registration June 29th, 2022). WHO Universal Trial Number (UTN): U1111-1271-9928.

Effect of 10-Day Treatment with 50 mg Prednisolone Once-Daily on Haemostasis in Healthy Men-A Randomised Placebo-Controlled Trial.

Synthetic corticosteroids are widely used due to their anti-inflammatory and immunosuppressant effects. Their use has been associated with venous thromboembolism, but it is unknown whether thromboembolism has a causal relationship with corticosteroid treatment. In a randomised, double-blind, placebo-controlled trial in normal to overweight healthy men, the effect of the corticosteroid prednisolone on haemostasis using either 50 mg prednisolone or matching placebo once daily for ten days was investigated. The primary outcome was a change from baseline in the viscoelastic measurement maximal amplitude of clot in kaolin-activated thromboelastography (TEG). Changes from baseline in other TEG measurements, D-dimer, von Willebrand factor (VWF) antigen, and ristocetin cofactor activity (RCo), antithrombin, protein C, prothrombin, fibrinogen, INR, APTT, and platelet count were secondary outcomes. Thirty-four men participated in this study. Compared to placebo, prednisolone treatment did not affect maximal amplitude of clot (difference -0.77 (95% confidence interval (CI) -2.48, 0.94) mm, p = 0.37, missing: n = 2), but it altered VWF antigen (28%, p = 0.0004), VWF:RCo (19%, p = 0.0006), prothrombin (5%, p = 0.05), protein C (31%, p < 0.0001), antithrombin (5%, p = 0.013), and fibrinogen (-15%, p = 0.004). Thus, prednisolone treatment did not alter TEG-assessed maximal amplitude of clot, despite that it affected prothrombotic markers (increased prothrombin, VWF antigen, VWF:RCo, prothrombin, and decreased fibrinogen) and increased antithrombotic markers (protein C and antithrombin).

Bile acid diarrhoea.

Bile acid diarrhoea is a socially debilitating disease caused by irritation of the colonic mucosa due to a spillover of bile acids from the small intestine into the colon. Studies estimate a prevalence of 1-2% of the adult population, but many patients never seek help or are misdiagnosed. Bile acid diarrhoea is treated with bile acid sequestrants, however, new research shows superior effect on reported symptoms with the glucagon-like peptide 1 receptor agonist liraglutide.

Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin - a case series.

Metformin is the currently accepted first-line treatment for antipsychotic-associated weight gain (AAWG). However, not all patients benefit from metformin. Glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown promise in the management of obesity in the general population, with preliminary evidence supporting efficacy in AAWG. Semaglutide is a weekly injectable GLP-1RA which received recent approval for obesity management and noted superiority over other GLP-1RAs. This study explored the efficacy and tolerability of semaglutide in AAWG among individuals with severe mental illness. A retrospective chart review of patients treated with semaglutide in the Metabolic Clinic at the Center for Addiction and Mental Health (CAMH) between 2019 and 2021 was conducted. Patients failing a trial of metformin (<5% weight loss or continuing to meet criteria for metabolic syndrome) after 3 months at the maximum tolerated dose (1500-2000 mg/day) were initiated on semaglutide up to 2 mg/week. The primary outcome measure was a change in weight at 3, 6, and 12 months. Twelve patients on weekly semaglutide injections of 0.71 ± 0.47 mg/week were included in the analysis. About 50% were female; the average age was 36.09 ± 13.32 years. At baseline, mean weight was 111.4 ± 31.7 kg, BMI was 36.7 ± 8.2 kg/m2, with a mean waist circumference of 118.1 ± 19.3 cm. A weight loss of 4.56 ± 3.15 kg (p < 0.001), 5.16 ± 6.27 kg (p = 0.04) and 8.67 ± 9 kg (p = 0.04) was seen at 3, 6, and 12 months, respectively, after initiation of semaglutide with relatively well-tolerated side-effects. Initial evidence from our real-world clinical setting suggests that semaglutide may be effective in reducing AAWG in patients not responding to metformin. Randomized control trials investigating semaglutide for AAWG are needed to corroborate these findings.

Serum lipidome unravels a diagnostic potential in bile acid diarrhoea.

OBJECTIVE: Bile acid diarrhoea (BAD) is debilitating yet treatable, but it remains underdiagnosed due to challenging diagnostics. We developed a blood test-based method to guide BAD diagnosis. DESIGN: We included serum from 50 treatment-naive patients with BAD diagnosed by gold standard 75selenium homotaurocholic acid test, 56 feature-matched controls and 37 patients with non-alcoholic fatty liver disease (NAFLD). Metabolomes were generated using mass spectrometry covering 1295 metabolites and compared between groups. Machine learning was used to develop a BAD Diagnostic Score (BDS). RESULTS: Metabolomes of patients with BAD significantly differed from controls and NAFLD. We detected 70 metabolites with a discriminatory performance in the discovery set with an area under receiver-operating curve metric above 0.80. Logistic regression modelling using concentrations of decanoylcarnitine, cholesterol ester (22:5), eicosatrienoic acid, L-alpha-lysophosphatidylinositol (18:0) and phosphatidylethanolamine (O-16:0/18:1) distinguished BAD from controls with a sensitivity of 0.78 (95% CI 0.64 to 0.89) and a specificity of 0.93 (95% CI 0.83 to 0.98). The model was independent of covariates (age, sex, body mass index) and distinguished BAD from NAFLD irrespective of fibrosis stage. BDS outperformed other blood test-based tests (7-alpha-hydroxy-4-cholesten-3-one and fibroblast growth factor 19) currently under development. CONCLUSIONS: BDS derived from serum metabolites in a single-blood sample showed robust identification of patients with BAD with superior specificity and sensitivity compared with current blood test-based diagnostics.

Liraglutide treatment is associated with progression of coronary artery fibrous plaque: a prospective 1-year follow-up study in asymptomatic patients with type 2 diabetes.

OBJECTIVE: The objective of this study was to assess the association between clinically indicated liraglutide treatment and coronary artery plaque progression during 1-year follow-up in asymptomatic diabetes. METHODS: Patients were divided into a group receiving liraglutide (Lira+) and a group not receiving liraglutide (Lira-). Coronary computed tomography angiography (CCTA) was performed to assess total atheroma volume (TAV) and subtypes of plaque volumes (dense calcium, fibrous, fibrous-fatty, and necrotic core plaque) and the plaque progression during one year follow-up. RESULTS: Fifty-five patients (27%) receiving liraglutide and 149 (73%) how did not were included. Changes in TAV during 1-year of follow-up were similar in the two groups (38 ± 180 (Lira+) vs. -1 ± 160 mm3 (Lira-), P = 0.13). A greater increase in fibrous plaque volume was seen in the Lira + vs. the Lira- group (34 ± 129 vs. -2 ± 101 mm3, P = 0.04). Changes over 1-year in the other plaque subtypes were similar in the two groups. Treatment duration of liraglutide was not associated with changes in TAV. CONCLUSION: In patients with T2D without known prior coronary artery disease, liraglutide treatment was associated with a significant increase in coronary artery fibrous plaque volume during 1-year follow-up.

The potential of colchicine for lowering the risk of cardiovascular events in type 1 diabetes.

In type 1 diabetes, average life expectancy is reduced by ˃10 years as compared with outside of diabetes. Residual cardiovascular risk defines high cardiovascular event rate despite modern, guideline-recommended standard of care of established risk factors like hypertension, dyslipidaemia, and glycaemic control, and it adds importantly to these lost years of life in type 1 diabetes due to atherosclerotic cardiovascular diseases like myocardial infarction and ischaemic stroke. With a growing understanding of inflammation as an important driver of atherosclerotic cardiovascular disease, residual inflammatory risk is a novel and common risk factor and a promising target for lowering residual cardiovascular risk in type 1 diabetes. Interestingly, the inexpensive anti-inflammatory agent colchicine reduced the risk of major adverse cardiovascular events by 25% in cardiovascular outcome trials in the secondary prevention of atherosclerotic cardiovascular disease. Here, we summarize the role of inflammation as a driver of atherosclerosis and review current evidence linking inflammation and atherosclerotic cardiovascular disease in type 1 diabetes. Also, we provide an overview of the evidence base for targeting residual inflammatory risk with colchicine for lowering residual cardiovascular risk in type 1 diabetes.

Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is suggested as a risk factor for chronic kidney disease (CKD). The incidence of NAFLD is rising globally in parallel to the increasing incidences of obesity and type 2 diabetes. Diabetes remains the leading cause of CKD, but the co-existence of NAFLD, CKD, and type 2 diabetes is not well elucidated. Here, we evaluated the prevalence of NAFLD in patients with type 2 diabetes with and without CKD. METHODS: This was a cross-sectional study including 50 patients with type 2 diabetes and CKD stages 3-5 (no dialysis), and 50 patients with type 2 diabetes without CKD. Liver fat content was estimated by proton magnetic resonance spectroscopy and magnetic resonance imaging proton density fat fraction. NAFLD was defined as liver fat fraction ≥5.6% according to guidelines. RESULTS: Mean age was 72 ± 4.9 years in patients with CKD and 65.9 ± 7.8 years in patients without CKD (p < 0.0001). Three out of four participants were men. BMI was 28.6 ± 3.5 kg/m2 and 27 ± 4.0 kg/m2 in patients with and without CKD, respectively (p = 0.0087). NAFLD was identified in 22 (44%) patients with CKD and 19 (38%) patients without CKD (p = 0.6845). Median (IQR) liver fat fraction was 4.7% (3.0-8.5) and 4.1% (2.9-7.7) in patients with and without CKD, respectively (difference in geometric means 5.3%, 95% CI -23; 45, p = 0.7463). CONCLUSION: These findings do not support any association between NAFLD and CKD (stages 3-5) in patients with type 2 diabetes.

Incidental finding of non-alcoholic steatohepatitis-cirrhosis.

Summary: A 72-year-old man with type 2 diabetes volunteered to participate in the control group of a clinical study. The study evaluated non-alcoholic fatty liver disease in patients with kidney disease. The patient was followed at a gastroenterology department due to Crohn's disease and post-operative bile acid malabsorption. The patient had no symptoms or biochemical findings suggesting liver disease. Surprisingly, a transient elastography (FibroScan®) suggested advanced fibrosis with a median of 16.1 kPa. A liver biopsy showed non-alcoholic steatohepatitis (NASH)-cirrhosis. The diagnosis was only made incidentally and highlights how NASH-cirrhosis may be overlooked due to the lack of symptoms. Learning points: Clinicians treating high-risk populations, including patients with type 2 diabetes and/or components of the metabolic syndrome, should be aware of the frequently occurring co-existence with non-alcoholic fatty liver disease (NAFLD) and especially non-alcoholic steatohepatitis (NASH). Liver enzymes may be in the normal range even in people with steatosis, NASH, or even cirrhosis. The diagnosis of NAFLD should include evaluation of hepatic fibrosis as this is the most important prognostic factor for liver-related complications and mortality. Guidelines about systematic screening for NAFLD in patients with type 2 diabetes are incongruent.