Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability. METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT. RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT. DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.

Tools for Enhancement and Quality Improvement of Peer Assessment and Clinical Care in Endocrinology and Metabolism.

Members of the College of Physicians and Surgeons of Ontario Endocrinology and Metabolism Peer Review Network have been involved in a quality improvement project to help standardize the peer assessment of physicians practicing in endocrinology and metabolism. This has included developing state-of-the-art summaries of common endocrine problems by Canadian experts in endocrinology and metabolism. These tools have been developed in response to the educational needs, as identified by peer reviewers, of practicing endocrinologists in Ontario. These pedagogical tools aim not only to standardize the documentation of the clinical performance of endocrinologists but also to make the process more transparent and to improve the quality of patient care in Ontario. This article summarizes the project and also provides the tools developed for the endocrinology and metabolism section of the College of Physicians and Surgeons of Ontario.

N-of-1 (single-patient) trials for statin-related myalgia.

BACKGROUND: Statin-related myalgia is difficult to distinguish from other conditions causing myalgia and may often lead to statin discontinuation. OBJECTIVE: To compare the effect of statin rechallenge with placebo in patients with prior statin-related myalgia and to determine whether patients resumed statin therapy after evaluating the results. DESIGN: N-of-1 trial with 3 double-blind, crossover comparisons separated by 3-week washout periods. (Clinicaltrials.gov: NCT01259791) SETTING: Tertiary care lipid clinic. PATIENTS: Patients with prior statin-related myalgia with or without mild elevation of creatine kinase levels. INTERVENTION: Rechallenge with the statin that was previously associated with myalgia within 3 weeks of open-label use versus matching placebo. MEASUREMENTS: Weekly visual analogue scale (VAS) scores for myalgia and specific symptoms (VAS myalgia score and symptom-specific VAS score, respectively), pain interference scores, and pain severity scores were recorded during the 3-week periods when patients were receiving placebo or statin. The primary outcome was the VAS myalgia score (range, 0 to 100 mm). RESULTS: Eight patients (mean age, 66 years [SD, 8 years]; 88% women, all with high 10-year Framingham cardiovascular risk) participated in n-of-1 trials. Seven patients completed 3 treatment pairs, and 1 completed 2 treatment pairs. For each n-of-1 trial, no statistically significant differences were seen between statin and placebo in the VAS myalgia score, symptom-specific VAS score, pain interference score, and pain severity score. Five patients resumed open-label statin treatment, with a median posttrial follow-up of 10 months. LIMITATION: Results are limited by the small sample size and cannot be extended to patients with longer onset of myalgia after statin initiation. CONCLUSION: In selected patients with a history of statin-related myalgia whose symptoms are difficult to evaluate, n-of-1 trials may be a useful method for determining statin tolerability. PRIMARY FUNDING SOURCE: Western University, London, Ontario, Canada.

Intra-thoracic fat volume is associated with myocardial infarction in patients with metabolic syndrome.

BACKGROUND: Visceral adiposity is increased in those with Metabolic Syndrome (MetS) and atherosclerotic disease burden. In this study we evaluate for associations between intra-thoracic fat volume (ITFV) and myocardial infarction (MI) in patients with MetS. METHODS: Ninety-four patients with MetS, MI or both were identified from a cardiovascular CMR clinical registry. MetS was defined in accordance to published guidelines; where-as MI was defined as the presence of subendocardial-based injury on late gadolinium enhancement imaging in a coronary vascular distribution. A healthy control group was also obtained from the same registry. Patients were selected into the following groups: MetS+/MI- (N = 32), MetS-/MI + (N = 30), MetS+/MI + (N = 32), MetS-/MI- (N = 16). ITFV quantification was performed using signal threshold analysis of sequential sagittal CMR datasets (HASTE) and indexed to body mass index. RESULTS: The mean age of the population was 59.8 ± 12.5 years. MetS+ patients (N=64) demonstrated a significantly higher indexed ITFV compared to MetS- patients (p = 0.05). Patients in respective MetS-/MI-, MetS+/MI-, MetS-/MI+, and MetS+/MI + study groups demonstrated a progressive elevation in the indexed ITFV (22.3 ± 10.6, 28.6 ± 12.6, 30.6 ± 12.3, and 35.2 ± 1.4 ml/kg/m(2), (p = 0.002)). Among MetS+ patients those with MI showed a significantly higher indexed ITFV compared to those without MI (p = 0.02). CONCLUSIONS: ITFV is elevated in patients with MetS and incrementally elevated among those with evidence of prior ischemic myocardial injury. Accordingly, the quantification of ITFV may be a valuable marker of myocardial infarction risk among patients with MetS and warrants further investigation.

Improving the efficiency of virtual insulin teaching for patients admitted to hospital through the COVID-19 pandemic: a quality improvement initiative.

BACKGROUND: Throughout the COVID-19 pandemic, many areas of medicine transitioned to virtual care. For patients with diabetes admitted to hospital, this included diabetes education and insulin teaching. Shifting to a virtual model of insulin teaching created new challenges for inpatient certified diabetes educators (CDE). OBJECTIVE: We advanced a quality improvement project to improve the efficiency of safe and effective virtual insulin teaching throughout the COVID-19 pandemic. Our primary aim was to reduce the mean time between CDE referral to successful inpatient insulin teach by 0.5 days. DESIGN, SETTING, PARTICIPANTS: We conducted this initiative at two large academic hospitals between April 2020 and September 2021. We included all admitted patients with diabetes who were referred to our CDE for inpatient insulin teaching and education. INTERVENTION: Alongside a multidisciplinary team of project stakeholders, we created and studied a CDE-led, virtual (video conference or telephone) insulin teaching programme. As tests of change, we added a streamlined method to deliver insulin pens to the ward for patient teaching, created a new electronic order set and included patient-care facilitators in the scheduling process. MAIN OUTCOME AND MEASURES: Our main outcome measure was the mean time between CDE referral and successful insulin teach-back. Our process measure was the percentage of successful insulin pen deliveries to the ward for teaching. As balance measures, we captured the percentage of patients with a successful insulin teach, the time between insulin teach and hospital discharge, and readmissions to hospital for diabetes-related complications. RESULTS: Our tests of change improved the efficiency of safe and effective virtual insulin teaching by 0.27 days. The virtual model appeared less efficient than usual in-person care. CONCLUSIONS: In our centre, virtual insulin teaching supported patients admitted to hospital through the pandemic. Improving the administrative efficiency of virtual models and leveraging key stakeholders remain important for long-term sustainability.

Strategies For Enhancing Equity, Diversity, and Inclusion in Medical School Admissions-A Canadian Medical School's Journey.

Background: Medical schools aim to select and train future physicians representative of and able to serve their diverse population needs. Enhancing equity, diversity, and inclusion (EDI) in admissions processes includes identifying and mitigating barriers for those underrepresented in medicine (URM). Summary of Innovations: In 2017, Schulich School of Medicine and Dentistry (Western University, Ontario, Canada) critically reviewed its general Admissions pathways for the Doctor of Medicine (MD) program. Till that time, interview invitations were primarily based on academic metrics rather than a holistic review as for its Indigenous MD Admissions pathway. To help diversify the Canadian physician workforce, Schulich Medicine utilized a multipronged approach with five key changes implemented over 2 years into the general MD Admissions pathways: 1. A voluntary applicant diversity survey (race, socioeconomic status, and community size) to examine potential barriers within the Admissions process; 2. Diversification of the admissions committee and evaluator pool with the inclusion of an Equity Representative on the admissions committee; 3. A biosketch for applicants' life experiences; 4. Implicit bias awareness training for Committee members, file reviewers and interviewers; and 5. A specific pathway for applicants with financial, sociocultural, and medical barriers (termed ACCESS pathway). Diversity data before (Class of 2022) vs. after (Class of 2024) these initiatives and of the applicant pool vs. admitted class were examined. Conclusion: For the Class of 2024, the percentage of admitted racialized students (55.2%), those with socioeconomic challenges (32.3%), and those from remote/rural/small town communities (18.6%) reflected applicant pool demographics (52.8, 29.9, and 17.2%, respectively). Additionally, 5.3% (vs. 5.6% applicant pool) of admitted students had applied through ACCESS. These data suggest that barriers within the admissions process for these URM populations were potentially mitigated by these initiatives. The initiatives broadly improved representation of racialized students, LGBTQ2S+, and those with disability with statistically significant increases in representation of those with socioeconomic challenges (32.3 vs. 19.3%, p = 0.04), and those with language diversity (42.1 vs. 35.0%, p = 0.04). Thus, these changes within the general MD admissions pathways will help diversify the future Canadian physician workforce and inform future initiatives to address health equity and social accountability within Canada.

Evaluation of adipose tissue volume quantification with IDEAL fat-water separation.

PURPOSE: To validate iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) for adipose tissue volume quantification. IDEAL allows MRI images to be produced only from adipose-containing tissues; hence, quantifying adipose tissue should be simpler and more accurate than with current methods. MATERIALS AND METHODS: Ten healthy controls were imaged with 1.5 Tesla (T) Spin Echo (SE), 3.0T T1-weighted spoiled gradient echo (SPGR), and 3.0T IDEAL-SPGR. Images were acquired from the abdomen, pelvis, mid-thigh, and mid-calf. Mean subcutaneous and visceral adipose tissue volumes were compared between the three acquisitions for each subject. RESULTS: There were no significant differences (P>0.05) between the three acquisitions for subcutaneous adipose tissue volumes. However, there was a significant difference (P=0.0002) for visceral adipose tissue volumes in the abdomen. Post hoc analysis showed significantly lower visceral adipose tissue volumes measured by IDEAL versus 1.5T (P<0.0001) and 3.0T SPGR (P<0.002). The lower volumes given by IDEAL are due to its ability to differentiate true visceral adipose tissue from other bright structures like blood vessels and bowel content that are mistaken for adipose tissue in non-fat suppressed images. CONCLUSION: IDEAL measurements of adipose tissue are equivalent to established 1.5T measurement techniques for subcutaneous depots and have improved accuracy for visceral depots, which are more metabolically relevant.

Narrative review: statin-related myopathy.

Statin-related myopathy is a clinically important cause of statin intolerance and discontinuation. The spectrum of statin-related myopathy ranges from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. Observational studies suggest that myalgia can occur in up to 10% of persons prescribed statins, whereas rhabdomyolysis continues to be rare. The mechanisms of statin-related myopathy are unclear. Options for managing statin myopathy include statin switching, particularly to fluvastatin or low-dose rosuvastatin; nondaily dosing regimens; nonstatin alternatives, such as ezetimibe and bile acid-binding resins; and coenzyme Q10 supplementation. Few of these strategies have high-quality evidence supporting them. Because statin-related myopathy will probably become more common with greater numbers of persons starting high-dose statin therapy and the increasing stringency of low-density lipoprotein cholesterol level targets, research to better identify patients at risk for statin myopathy and to evaluate management strategies for statin-related myopathy is warranted.

The end of the road for CETP inhibitors after torcetrapib?

PURPOSE OF REVIEW: Because high-density lipoprotein cholesterol (HDL-C) levels are inversely related to cardiovascular disease (CVD), raising HDL-C levels would seem intuitively valuable. However, the recent failure of the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib to decrease CVD has raised doubts regarding HDL-C raising in general and CETP inhibition in particular for CVD prevention. We briefly discuss the complexity of HDL metabolism, caveats of CETP inhibition, possible mechanisms for torcetrapib's failure, and the potential utility of other CETP inhibitors. RECENT FINDINGS: Torcetrapib likely failed because of off-target effects, since other CETP inhibitors, such as dalcetrapib (JTT-705/R1658) or anacetrapib (MK-0859), do not increase blood pressure, a specific pressor effect of tocetrapib that appears to be CETP-independent. In small human trials of short duration, anacetrapib and dalcetrapib appear to improve the lipoprotein profile without obvious adverse effects, so far. SUMMARY: The relationship between HDL metabolism, pharmacologic CETP inhibition, and atherosclerosis requires further elucidation. There seems to be sufficient evidence that evaluation of CETP inhibitors such as dalcetrapib and anacetrapib should proceed, if cautiously, since it remains uncertain whether the increased CVD risk with torcetrapib was related to agent-specific off-target effects or more generally to CETP inhibition as a mechanism to raise HDL.

Genetics of metabolic syndrome: is there a role for phenomics?

Metabolic syndrome (MetS) is a common complex trait consisting of the clustering of abdominal obesity, hypertension, dyslipidemia, and dysglycemia. MetS is found in about 25% of the population in the United States and is associated with increased risk for type 2 diabetes and cardiovascular disease. Despite research into possible genetic influences for MetS, no consistently reproducible genetic markers have been obtained, partially due to lack of agreement on the definition of the phenotype. Because phenotypic precision is essential for genomic interrogation, the evolving discipline of clinical phenomics, which uses objective and systematic acquisition of phenotypic data (ie, "deep phenotyping"), may help evaluate the genetic influences of MetS. This article reviews evidence that MetS has a genetic component and the potential applicability of clinical phenomics for the genetic evaluation of MetS using the example of hierarchical cluster analysis of phenotypic components of lipodystrophy syndromes, which serve as monogenic models of MetS.

Genetics of metabolic syndrome.

Metabolic syndrome (MetS) is a common phenotype, affecting about 24% of the US population. It is associated with an increased risk for type 2 diabetes and cardiovascular disease. Although there is no universally accepted definition for MetS, affected individuals commonly have a cluster of features, including abdominal obesity, hypertension, dyslipidemia, and dysglycemia. Recently, there has been extensive interest in potential genetic contributions to MetS. At present, no single gene or cluster of genes has been consistently replicated for MetS among different populations, likely due to the complex interplay between gene and environment necessary for expression of this phenotype. We review recent studies regarding the genetic contributions to MetS.

Emerging antidyslipidemic drugs.

BACKGROUND: Many patients at high risk for coronary heart disease (CHD) fail to reach target lipid levels with currently available medications, and a small but clinically relevant proportion of patients experience adverse effects. Thus, additional pharmaceutical strategies are required to fill these gaps in efficacy and tolerability. OBJECTIVE: To provide an overview of both current and emerging antidyslipidemic drugs. METHODS: For the current antidyslipidemic drugs, we focus primarily on statins, bile acid sequestrants, fibrates, ezetimibe, and niacin. Emerging antidyslipidemic drugs herein discussed were identified by searching the Pharmaprojects database for 'hypercholesterolemia drugs' (Phase II or Phase III), 'HDL-based therapies', and 'PCSK9 inhibition'. RESULTS/CONCLUSIONS: Combinations of currently existing medications are most easily applicable. Meanwhile, strategies to raise HDL-C rely on a deep understanding of the complexity of HDL metabolism. Furthermore, novel approaches to further reduce LDL-C warrant careful evaluation of benefit-risk ratio. Finally, the medical community will have to rely on late-phase CHD outcome studies as the final arbiter of clinical application for any new antidyslipidemia treatment.

Increase of urinary 5-hydroxyindoleacetic acid excretion but not serum chromogranin A following over-the-counter 5-hydroxytryptophan intake.

BACKGROUND: 5-hydroxyindoleacetic acid (5-HIAA) excretion is commonly measured for biochemical detection of carcinoid tumours. A 77-year-old woman was referred for elevated 24 h urine 5-HIAA excretion (510 micromol/day; normal is less than 45 micromol/day) and serum chromogranin A (CgA) (72.1 U/L; normal is less than 18 U/L), both subsequently normalized after discontinuation of 5-hydroxytryptophan (5-HTP). 5-HTP, a precursor of serotonin, is not commonly listed as a substance that increases 5-HIAA levels in urine. The effect of 5-HTP on CgA has not been previously described. OBJECTIVES: To determine whether, and to what extent, oral 5-HTP increases urine 5-HIAA excretion and serum CgA levels in healthy volunteers. PATIENTS AND METHODS: A randomized, prospective, double-blind, placebo-controlled crossover study, with a four-day washout period, was performed in a general community setting. Eight healthy subjects aged 22 to 58 years were recruited by advertising. Bedtime ingestion of 5-HTP 100 mg/day was compared with placebo ingestion for 10 days. Twenty-four hour urine excretion of 5-HIAA and serum CgA were the main outcome measures. RESULTS: Median (range) urinary 5-HIAA excretion was 204 micromol/day (22 micromol/day to 459 micromol/day) during 5-HTP intake, compared with 18 micromol/day (12 micromol/day to 36 micromol/day) during placebo intake (P=0.017). 5-HTP did not affect clinical symptoms or serum CgA levels. CONCLUSIONS: Oral 5-HTP increases urinary 5-HIAA excretion with considerable interindividual variation. In a small number of subjects, oral 5-HTP did not affect serum CgA levels. Therefore, increased 5-HIAA levels with normal CgA levels may suggest 5-HTP ingestion. The use of over-the-counter 5-HTP should be excluded as the cause of increased urinary 5-HIAA levels before initiating diagnostic tests to search for a carcinoid tumour. 5-HTP should be added to popular references as a substance that may cause increased 5-HIAA excretion.

Canadian Cardiovascular Society Position Statement on Familial Hypercholesterolemia: Update 2018.

Familial hypercholesterolemia (FH) is the most common monogenic disorder causing premature atherosclerotic cardiovascular disease. It affects 1 in 250 individuals worldwide, and of the approximately 145,000 Canadians estimated to have FH, most are undiagnosed. Herein, we provide an update of the 2014 Canadian Cardiovascular Society position statement on FH addressing the need for case identification, prompt recognition, and treatment with statins and ezetimibe, and cascade family screening. We provide a new Canadian definition for FH and tools for clinicians to make a diagnosis. The risk of atherosclerotic cardiovascular disease in patients with "definite" FH is 10- to 20-fold that of a normolipidemic individual and initiating treatment in youth or young adulthood can normalize life expectancy. Target levels for low-density lipoprotein cholesterol are proposed and are aligned with the Canadian Cardiovascular Society guidelines on dyslipidemia. Recommendation for the use of inhibitors of proprotein convertase kexin/subtilisin type 9 are made in patients who cannot achieve therapeutic low-density lipoprotein cholesterol targets on maximally tolerated statins and ezetimibe. The writing committee used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology in the preparation of the present document, which offers guidance for practical evaluation and management of patients with FH. This position statement also aims to raise awareness of FH nationally, and to mobilize patient support, promote knowledge translation, and availability of treatment and health care resources for this under-recognized, but important medical condition.

Dietary fat intake and relationship to serum lipid levels in HIV-infected patients with metabolic abnormalities in the HAART era.

OBJECTIVE: To evaluate dietary intake and its relationship to lipid parameters in HIV-infected patients with metabolic abnormalities. METHOD: We prospectively determined dietary intake (4-day food records or 24-h recall) in 356 HIV-infected patients and 162 community-derived HIV-negative controls evaluated for metabolic studies between 1998-2005. Differences in dietary intake between HIV-infected patients and non-HIV-infected controls, in relation to the established 2005 USDA (United States Department of Agriculture) Recommended Dietary Guidelines, were determined. The relationship between dietary fat intake and serum lipid levels among HIV-infected individuals was also evaluated. RESULTS: Assessment of dietary intake in this group of HIV-infected patients demonstrated increased intake of total dietary fat (P < 0.05), saturated fat (P = 0.006), and cholesterol (P = 0.006) as well as a greater percentage of calories from saturated fat (P = 0.002) and from trans fat (P = 0.02), despite similar caloric intake to the control individuals. A significantly higher percentage of HIV-infected patients were above the 2005 USDA Recommended Dietary Guidelines for saturated fat (> 10%/day) (76.0% HIV vs. 60.9% controls, P = 0.003), and cholesterol (> 300 mg/day) (49.7% HIV vs. 37.9% controls, P = 0.04). Saturated fat intake was strongly associated with triglyceride level [triglyceride level increased 8.7 mg/dl (parameter estimate) per gram of increased saturated fat intake, P = 0.005] whereas total fat was inversely associated with triglyceride level [triglyceride level decreased 3.0 mg/dl (parameter estimate) per gram of increased total fat intake, P = 0.02] among HIV-infected individuals. CONCLUSIONS: Increased intake of saturated fat is seen and contributes to hypertriglyceridemia among HIV-infected patients who have developed metabolic abnormalities. Increased saturated fat intake should be targeted for dietary modification in this population.

Management Strategies for Statin-Associated Muscle Symptoms: How Useful Is Same-Statin Rechallenge?

BACKGROUND: Statin-associated muscle symptoms (SAMS) are common. Rechallenge with the same statin (same-statin rechallenge) has recently been included as part of a proposed scoring index for diagnosing SAMS, but data regarding tolerability and efficacy of same-statin rechallenge, compared with other strategies, is minimal. In this study we evaluated the tolerability, percent change in low-density lipoprotein cholesterol (LDL-C), and proportion of patients achieving their LDL-C targets among 3 common management strategies-same-statin rechallenge, switching to a different statin (statin switch), and use of nonstatin medications only. METHODS: We performed a retrospective analysis of 118 patients referred to our tertiary care centre for management of SAMS, defined as development of muscle-related symptoms with 2 or more statins. Baseline and last follow-up lipid parameters were documented. Patients were classified as tolerant of a strategy if, at their last follow-up, they remained on that strategy. RESULTS: After a median follow-up of 17 months, most (n = 79; 67%) patients were able to tolerate a statin. Tolerability was similar among the 3 treatment strategies (71% same-statin rechallenge vs 53% statin switch vs 57% for nonstatin therapy only; P = 0.11). Those in the same-statin rechallenge and statin switch groups achieved greater LDL-C reductions compared with those who only tolerated nonstatins (-38.8 ± 3.4% vs -36.4 ± 2.9% vs -17.3 ± 4.5%; P = 0.0007). A greater proportion of patients in the same-statin rechallenge group achieved their target LDL-C compared with those in the nonstatin therapy only group (50% vs 15%; odds ratio, 6.8; 95% confidence interval, 1.5-40.7; P = 0.04). CONCLUSIONS: Among individuals with a history of SAMS, most will tolerate statin therapy. Same-statin rechallenge was highly tolerable and efficacious. Thus, same-statin rechallenge might warrant increased utilization.

Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial.

AIM: To evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH). METHODS: Twelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy. RESULTS: Sitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 µg/mL vs 3.9 ± 2.7 µg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mmol/L, P = 0.19) but did trend towards improved adiponectin levels only (mean difference, 0.60 µg/mL, P = 0.095). No significant changes in anthropometrics, liver enzymes, other adipocytokines, lipid profile, thrombosis parameters, or adipose distribution were demonstrated. The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment, and the Spearman correlation coefficients ranged from r = 0.819 (baseline) to r = 0.878 (post-treatment), P = 0.002. CONCLUSION: Sitagliptin does not improve fibrosis score or NAS after 24 wk of therapy. The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis.

APOA1 related amyloidosis: a case report and literature review.

OBJECTIVES: Amyloidosis results from local or systemic extracellular deposition of insoluble protein fibrils and is associated with certain rare mutations in APOA1 encoding apolipoprotein (apo) A-I. DESIGN AND METHODS: In a patient with renal-predominant amyloidosis with neuropathy, we found the APOA1 G26R mutation. CONCLUSIONS: While the spectrum of APOA1 mutations provides no particular mechanistic insights, molecular diagnosis may still be important due to clinical differences between amyloidosis resulting from mutation in APOA1 vs. other genes.