Nonalcoholic steatohepatitis (NASH) is often linked with disorders that are clearly associated with insulin resistance (IR): obesity, type 2 diabetes mellitus, and hypertriglyceridemia. We tested the hypotheses that (1) IR is an essential requirement for the development of NASH and (2) a high association between IR and liver disease is relatively specific for NASH. We measured body mass index (BMI), waist/hip ratio, and fasting serum lipid, insulin, C-peptide, and glucose levels in 66 patients with NASH (21 with advanced fibrosis and 45 with mild fibrosis). IR was determined by the homeostasis model assessment (HOMA). We also determined the strength of the association of NASH with insulin resistance syndrome (IRS) as defined by World Health Organization criteria. To assess whether the finding of IR was relatively specific to NASH rather than simply to obesity or liver disease, we compared the results of a subset of 36 patients with less-severe NASH with 36 age-and sex-matched patients with chronic hepatitis C virus (HCV) of comparable fibrotic severity. IR was confirmed in 65 patients (98%) with NASH, and 55 (87%) fulfilled minimum criteria for IRS. IR was found in lean as well as in overweight and obese patients. The IR values and the prevalence of IRS (75% vs. 8.3%) were significantly higher in those with NASH than in comparable cases of HCV. Hyperinsulinemia was attributable to increased insulin secretion rather than decreased hepatic extraction. N onalcoholic steatohepatitis (NASH) is characterized by morphological features indistinguishable from alcoholic liver disease in individuals who do not consume excess alcohol. 1 NASH can progress to cirrhosis, and death from liver failure is now the second-leading cause of death in these patients. 2 Although the prevalence of NASH appears to be increasing, the etiopathogenesis remains poorly understood.Associations with drug toxicity, weight-reducing operations, lipodystrophy, and other uncommon inherited syndromes are well documented but are rarely present in most patients with NASH. [1][2][3][4][5][6][7][8] Rather, attention has been drawn to the increased prevalence of common metabolic disorders in the "typical" patient with NASH. [1][2][3][4][5][6][7] Autopsy data indicate that NASH is at least 6 times more prevalent in obese individuals compared with lean subjects. 7 Type 2 diabetes mellitus or abnormalities of glucose tolerance are present in up to one third of patients with NASH, 8 often with hypertriglyceridemia and/or hypercholesterolemia. 9,10 The above metabolic disorders are also cardiovascular risk factors and often cluster together as syndrome X, which includes impaired glucose tolerance, dyslipidemia, and hypertension. 11 This disease cluster is also referred to as the metabolic or insulin resistance syndrome (IRS); the latter highlights a central role for insulin resistance (IR) in this disorder. 12,13 The expanded formulation of IRS includes central (visceral or truncal) adiposity, lipid abnormalities, hyperuricemia, polycystic ovarian syndrome, and...

BackgroundYoung people with type 1 diabetes experience elevated levels of emotional distress that impact negatively on their diabetes self-care, quality of life, and disease-related morbidity and mortality. While the need is great and clinically significant, a range of structural (eg, service availability), psychological (eg, perceived stigma), and practical (eg, time and lifestyle) barriers mean that a majority of young people do not access the support they need to manage the emotional and behavioral challenges of type 1 diabetes.ObjectiveThe aim of this study is to examine the effectiveness of a fully-automated cognitive behavior therapy-based mobile phone and Web-based psychotherapeutic intervention (myCompass) for reducing mental health symptoms and diabetes-related distress, and improving positive well-being in this vulnerable patient group.MethodsA two-arm randomized controlled trial will be conducted. Young people with type 1 diabetes and at least mild psychological distress will be recruited via outpatient diabetes centers at three tertiary hospitals in Sydney, Australia, and referred for screening to a study-specific website. Data will be collected entirely online. Participants randomized to the intervention group will use the myCompass intervention for 7 weeks, while at the same time a control group will use an active placebo program matched to the intervention on duration, mode of delivery, and interactivity.ResultsThe primary outcome will be mental well-being (ie, depression, anxiety, diabetes-related distress, and positive well-being), for which data will be collected at baseline, post-intervention, and after 3 months follow-up. Secondary outcomes will be functional (work and social functioning and diabetes self-care), biochemical measures (HbA1c), and mental health self-efficacy. We aim to recruit 280 people into the study that will be conducted entirely online. Group differences will be analyzed on an intention-to-treat basis using mixed models repeated measures.ConclusionsWe hypothesize that scores on the outcome measures will improve significantly for young people who use the mobile phone and Web-based intervention compared to the control group. myCompass is a public health intervention that is broadly available and free to use. If effective, the program has the capacity to provide convenient and accessible evidenced-based care to the large group of young people with type 1 diabetes who do not currently access the psychosocial support they need.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12614000974606; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366607 (Archived by WebCite at http://www.webcitation.org/6YGdeT0Dk).

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