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Stopping smoking is crucial for public health and especially for individuals with diabetes. Combustion-free nicotine alternatives like e-cigarettes and heated tobacco products are increasingly being used as substitutes for conventional cigarettes, contributing to the decline in smoking prevalence. However, there is limited information about the long-term health impact of those products in patients with diabetes. This randomized controlled trial aims to investigate whether switching from conventional cigarettes to combustion-free nicotine alternatives will lead to a measurable improvement in cardiovascular risk factors and metabolic parameters over a period of 2 years in smokers with type 2 diabetes. The multicenter study will be conducted in seven sites across four countries. A total of 576 smokers with type 2 diabetes will be randomly assigned (1:2 ratio) to either standard of care with brief cessation advice (Control Arm) or combustion-free nicotine alternatives use (Intervention Arm). The primary end point is the change in the proportion of patients with metabolic syndrome between baseline and the 2-year follow-up. Additionally, the study will analyze the absolute change in the sum of the individual factors of metabolic syndrome at each study time point. Patient recruitment has started in September 2021 and enrollment is expected to be completed by December 2023. Results will be reported in 2026. This study may provide valuable insights into cardiovascular and metabolic health benefits or risks associated with using combustion-free nicotine alternatives for individuals with type 2 diabetes who are seeking alternatives to tobacco cigarette smoking. The study protocol, informed consent forms, and relevant documents were approved by seven ethical review boards. Study results will be disseminated through articles published in high-quality, peer-reviewed journals and presentations at conferences., (© 2023. The Author(s).)

Introduction: Reducing exposure to cigarette smoke is an imperative for public health and for patients with diabetes. Increasingly, combustion-free nicotine delivery systems (C-F NDS) such as e-cigarettes and heated tobacco products are substituting conventional cigarettes and accelerating the downward trends in smoking prevalence. However, there is limited information about the long-term health impact in patients with diabetes who use C-F NDS. This randomised trial of type 2 diabetic cigarette smokers will test the hypothesis that following a switch from conventional cigarettes to C-F NDS a measurable improvement in metabolic syndrome (MetS) factors will be shown over the course of 2 years., Methods and Analysis: The study is multicentre and thus will take place in five locations in four countries in an ambulatory setting. A total of 576 patients with diabetes will be randomised (1:2 ratio) to either a control arm (Study Arm A), in which they will be offered referral to smoking cessation programmes or to an intervention arm (Study Arm B) assigned to C-F NDS use. Participants will be at least 23 years old and of any gender. Patient recruitment will start in February 2021 and is expected to be completed by December 2021. Primary outcome measures include fasting plasma glucose, blood pressure, triglycerides, high-density lipoprotein and waist circumference, while secondary feature absolute change in the sum of the individual factors of MetS and change in each individual factor of MetS measured at each study time point., Ethics and Dissemination: The approval of research ethics committee (REC) regarding the trial protocol, informed consent forms and other relevant documents is required to commence the study. Substantial amendments to the study protocol cannot be implemented until the REC grants a favourable opinion. The results of the study are intended to be published as articles in high quality peer-reviewed journals and disseminated through conference papers., Trial Registration Number: NCT04231838. Pre-results stage., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Previous genome-wide association studies (GWAS) identified IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 as candidate genes for insulin resistance and type 2 diabetes (T2D). We investigated the associations of these previously reported common variants in these genes with insulin resistance in overweight children from Romania and Moldova. Methods Six single nucleotide polymorphisms (SNPs), IGF1 (rs35767), IRS1 (rs2943634), GCKR (rs780094), PPARG (rs1801282), GCK1 (rs1799884) and KCTD15 (rs29941), were genotyped in 100 overweight children along with clinical and metabolic parameters. Homeostatic model assessment of insulin resistance (HOMA-IR) above 3.4 (defining insulin resistance) was used as the outcome. Results Children differed in insulin resistance status despite having similar body mass index (BMI) standard deviation scores (SDS) (World Health Organization, [WHO] reference). The identified predictors for altered insulin metabolism were higher cholesterol levels, higher diastolic blood pressure and higher waist-to-hip-ratio (as a marker for increased abdominal fat). None of the SNPs showed significant association with increase in the risk for insulin resistance in children (p range=0.478-0.724; odds ratio [OR] range=1.924-4.842); however, the risk allele in GCKR (rs780094, p=0.06, OR=6.871) demonstrated near statistical significance. Conclusions The interrogated risk alleles did not show any significant association with insulin resistance in children in our cohort; however, the GCKR (rs780094) might be a viable candidate in larger cohorts. The lack of replication of the proposed association may point to differences in linkage disequilibrium or effect modifiers across studies.

This article contains bibliographical data concerning the rheumatic clinical manifestations in hypothyroidism: polyarthralgias, lack of recent skill of fine movements of the hands, carpal tunnel syndrome or tarsal, degenerative arthropathy or acute type (gout, chondrocalcinosis), adhesive capsulitis (frozen shoulder syndrome), generalized muscular stiffness, hypothyroid myopathy, secondary osteoarthritis, Dupuytren's contracture, "trigger finger" (also called as stenosing tenosynovitis or trigger thumb) etc. and data on the short history, epidemiology, of these disorders. Review include 60 bibliographical sources.