ABSTRACT
BACKGROUND: Premature cardiovascular disease is the leading cause of death in people living with type 1 diabetes. Therapies are urgently needed to address cardiovascular risk in this group. Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist, has been shown to reduce cardiovascular events and improve weight and glycaemia in type 2 diabetes. Semaglutide may offer cardioprotective and metabolic benefits in type 1 diabetes. METHODS: We will study 60 adults aged 25-70 years with type 1 diabetes of duration at least 2 years, body mass index ≥25 kg/m2, HbA1c ≥7% and at least one cardiovascular risk factor (microalbuminuria, hypertension or anti-hypertensive treatment, hyperlipidemia or lipid lowering therapy, current smoking). Participants will receive semaglutide up to 1.0 mg weekly or matched placebo for 26 weeks. The primary outcome is carotid femoral pulse wave velocity, a measure of arterial stiffness, as a surrogate marker of cardiovascular risk. Potential mechanisms for metabolic changes will be explored including change in insulin sensitivity determined by hyperinsulinaemic-euglycaemic clamp; and incretin and pancreatic hormone action measured during mixed meal tolerance test. CONCLUSION: The REducing cardiometabolic risk with SEmaglutide in Type 1 diabetes study will investigate whether semaglutide, a long acting glucagon-like peptide receptor agonist, can improve markers of cardiometabolic health in T1D. Underlying mechanisms predicting response, including insulin resistance and incretin hormone status, will also be explored.
ABSTRACT
BACKGROUND: Young 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. OBJECTIVE: The 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: We 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 REGISTRATION: Australian 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).
ABSTRACT
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. In conclusion, most patients with NASH have IRS, and there is a near-universal association between NASH and IR irrespective of obesity. IR is present in mild as well as advanced cases of NASH but is unusual in chronic HCV of similar fibrotic severity.