Background Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding Novo Nordisk, Denmark

Objective: We have aimed to study the relation between Hashimoto's thyroiditis (HT) and thyroid autoantibodies and oxidative stress parameters in euthyroid, subclinical and overt hypothyroid stages. Design and methods: A total of 124 patients were included in the study; 93 of whom were newly diagnosed with HT (31 patients in each of the euthyroid, subclinical hypothyroid and overt hypothyroid subgroups), aged over 18 and had not received any prior treatment and 31 of whom were healthy volunteers. Results: Total oxidant status (TOS) and oxidative stress index (OSI) levels were higher, and total antioxidant status (TAS) and total thiol and arylesterase levels were lower in the overt hypothyroid group compared to other groups. TOS and OSI levels increased, and TAS levels decreased significantly in each phase from euthyroid, subclinical hypothyroid, to overt hypothyroid subgroups among HT patients. There was a negative correlation between TAS, log (paraoxonase1) and paraoxonase1/HDL and anti-thyroid peroxidase and a negative correlation between anti-thyroglobulin and total thiol. It was also determined that overt hypothroidism was an individual predictor that effects all of the oxidative stress parameters, but not total thiol, levels. Conclusion: Our results suggest that oxidative stress increases continuously during the development of subclinical hypothyroidism and overt hypothyroidism in patients with HT. To determine whether this is a cause or result, randomized, controlled trials that study the effect of antioxidant treatment on the development of overt hypothyroidism and its consequences, e.g., increase in total cholesterol levels, may be performed in euthyroid and/or subclinical hypothyroid patients with HT.

In this study, we aimed to examine dynamic thiol/disulfide homeostasis in type 1 diabetes mellitus (T1DM) and identify the factors associated with thiol oxidation. Thirty-eight subjects (18 male, 20 female) diagnosed with T1DM and 38 (17 male, 21 female) healthy volunteers without any known diseases were included in the study. Thiol/disulfide homeostasis concentrations were measured by a newly developed method (Erel & Neselioglu) in this study. After native thiol, total thiol and disulfide levels were determined; measures such as disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol were calculated. In T1DM patients, compared to the control group, disulfide (p = 0.024), disulfide/native thiol (p < 0.001), and disulfide/total thiol (p < 0.001) were determined higher, while native thiol (p = 0.004) and total thiol (p < 0.001) levels were much lower. In the patient group, a positive correlation was determined between c-reactive protein (r = 325, p = 0.007; r = 316, p = 0.010, respectively), fasting blood glucose (r = 279, p = 0.018; r = 251, p = 0.035, respectively), and glycosylated hemoglobin (r = 341, p = 0.004; r = 332, p = 0.005, respectively) and rates of disulfide/native thiol and disulfide/total thiol. We determined that thiol oxidation increase in T1DM patients compared to the control group. We thought that hyperglycemia and chronic inflammation might be the major cause of increase in oxide thiol form. In order to determine the relationship between the status of autoimmunity and dynamic thiol/disulfide in T1DM, dynamic thiol/disulfide homeostasis in newly diagnosed-antibody positive-T1DM patients is required to be investigated.

The incidence of cancer in thyroid nodules < 1 cm does not appear to be lower than in larger nodules and may even be higher. Physicians should consider obtaining biopsy samples from subcentimeter hypoechoic nodules that contain microcalcification and have a relatively round shape (LA/SA < 1.5).