Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Glargine (Gan & Lee Glargine) Compared With Originator Insulin Glargine (Lantus) in Patients With Type 1 Diabetes After 26 Weeks Treatment.

OBJECTIVE: To compare the immunogenicity, safety, and efficacy of Gan & Lee insulin glargine (GL Glargine) with that of the originator insulin glargine (Lantus) in patients with type 1 diabetes mellitus (T1DM). METHODS: This was a phase 3, multicenter, randomized, open-label, equivalence study. Five hundred seventy-six subjects with T1DM were randomized 1:1 to receive either GL Glargine or Lantus treatment for 26 weeks. The primary end point was the percentage of subjects in each treatment group who developed treatment-induced anti-insulin antibody after baseline and up to visit week 26, which was evaluated using a country-adjusted logistic regression model. The study also compared the changes in glycated hemoglobin, and adverse events including hypoglycemia. RESULTS: The percentage of subjects positive for treatment-induced anti-insulin antibody by Week 26 was 25.8% in the GL Glargine treatment group and 25.3% in the Lantus treatment group, with a 90% confidence interval (-5.4, 6.5) of the difference in proportions that fell completely between the similarity margins (-11.3, 11.3). The least squares mean difference between treatment groups for changes in glycated hemoglobin was -0.08 (90% confidence interval: -0.23, 0.06), and the other immunogenicity and safety profiles were comparable. CONCLUSION: GL Glargine demonstrated similar immunogenicity, efficacy, and safety compared to Lantus over 26 weeks in patients with T1DM.

A Three-Arm Randomized Controlled Study Comparing Patient-Reported Outcomes in People With Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion or Multiple Daily Injections.

BACKGROUND: The aim of this study was to compare patient-reported outcomes (PROs) in people with type 1 diabetes using either continuous subcutaneous insulin infusion (CSII) with two different insulin patch pumps or multiple daily injections (MDIs). MATERIALS AND METHODS: In this randomized three-arm study, people with type 1 diabetes on MDI therapy were included and used either MDI, the Accu-Chek Solo micropump system (Solo) or Omnipod for 26 weeks. From weeks 26 to 39, all participants used CSII with Solo. Patient-reported outcomes were assessed using the diabetes technology questionnaire (DTQ); in addition, HbA1c values were measured. RESULTS: Overall, 181 participants were randomized (61 MDI arm, 62 Solo arm, 58 Omnipod arm) and 142 completed the study. After 26 weeks in the study, the DTQ "change" score in the Solo group (105.9 [100.6-111.2]; baseline-adjusted mean [95% confidence interval]) was significantly higher than in the MDI group (94.8 [89.6-100.0]) (P = .001). The comparison between the Solo group (105.1 [99.1-111.1]) and the Omnipod group (108.7 [103.1-114.4]) showed no significant differences (P = .382). HbA1c increased by 0.2% ± 0.7% in the MDI group and decreased in both pump groups (Solo group -0.2% ± 0.8% and Omnipod group -0.1% ± 0.8%). Differences in HbA1c between the Solo group and the MDI group were significant (P = .009), but not between the Solo group and the Omnipod group (P = .896). CONCLUSIONS: This study showed that switching from MDI to CSII improves both psychosocial well-being and physiological outcomes. Furthermore, there were no substantial differences between the established and the recently released patch pump. Trial registration at www.clinicaltrials.gov is NCT03478969.

Comparison of pre-and postoperative medication costs in patients who underwent bariatric surgery - a nationwide data analysis.

Introduction: Bariatric surgery has known health benefits and may lower the medication-related costs. This study aimed to assess the cost of medications prior to and after bariatric surgery in the Polish nationwide registry. Methods: The study included 2,390 adults. The analysis was conducted separately for a 12-month pre-operative period, and a 12-month postoperative period. The total costs of medication and cost per anatomical therapeutic chemical group were assessed and the mean cost per patient in the preoperative and postoperative periods was compared. Results: The study showed a significant increase in the overall medication costs and mean costs of medications per patient in the year after bariatric surgery. This increase was related mainly to low-molecular-weight heparins used in the 1st month after surgery. Alternatively, costs of medication used in the cardiovascular system diseases and anti-infectives decreased significantly. The total costs of hypoglycemic agents were reduced by 46%, antihypertensive medications by 29%, and lipid-lowering drugs by 38. Conclusions: In general, medication costs are higher in the first year after surgery. The increase results from the perioperative use of low-molecular-weight heparins, whereas a significant cost reduction of glucose-, lipid-lowering, antihypertensive, and anti-infective medications was observed.

A multicenter prospective randomized controlled trial investigating the effects of combustion-free nicotine alternatives on cardiovascular risk factors and metabolic parameters in individuals with type 2 diabetes who smoke: the DiaSmokeFree study protocol.

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.

Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial.

BACKGROUND: Insulin icodec (icodec) is a once-weekly basal insulin currently under development. ONWARDS 2 aimed to assess the efficacy and safety of once-weekly icodec versus once-daily insulin degludec (degludec) in basal insulin-treated type 2 diabetes. METHODS: This 26-week, randomised, open-label, active-controlled, multicentre, treat-to-target phase 3a trial was conducted in 71 sites in nine countries. Eligible participants with type 2 diabetes inadequately controlled on once-daily or twice-daily basal insulin, with or without non-insulin glucose-lowering agents, were randomly assigned (1:1) to once-weekly icodec or once-daily degludec. The primary outcome was change from baseline to week 26 in HbA1c; the margin used to establish non-inferiority of icodec compared with degludec was 0·3 percentage points. Safety outcomes (hypoglycaemic episodes and adverse events) and patient-reported outcomes were also assessed. The primary outcome was evaluated in all randomly assigned participants; safety outcomes were evaluated descriptively based on all randomly assigned participants who received at least one dose of trial product, with statistical analyses based on all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04770532, and is now complete. FINDINGS: Between March 5 and July 19, 2021, 635 participants were screened, of whom 109 were ineligible or withdrew, and 526 were randomly assigned to icodec (n=263) or degludec (n=263). From a mean baseline of 8·17% (icodec; 65·8 mmol/mol) and 8·10% (degludec; 65·0 mmol/mol), HbA1c was reduced to a greater extent with icodec than degludec (7·20% vs 7·42% [55·2 vs 57·6 mmol/mol], respectively) at week 26. This translates to an estimated treatment difference (ETD) of -0·22 percentage points (95% CI -0·37 to -0·08) or -2·4 mmol/mol (95% CI -4·1 to -0·8), demonstrating non-inferiority (p<0·0001) and superiority (p=0·0028). The estimated mean change from baseline to week 26 in bodyweight was +1·40 kg for icodec and -0·30 kg for degludec (ETD 1·70 [95% CI 0·76 to 2·63]). Overall rates of combined level 2 or level 3 hypoglycaemia were less than one event per patient-year of exposure for both groups (0·73 [icodec] vs 0·27 [degludec]; estimated rate ratio 1·93 [95% CI 0·93 to 4·02]). Overall, 161 (61%) of 262 participants receiving icodec and 134 (51%) of 263 participants receiving degludec experienced an adverse event; 22 (8%) and 16 (6%), respectively, experienced a serious adverse event. One serious adverse event (degludec) was assessed as being possibly related to treatment. No new safety issues were identified in relation to icodec compared with degludec in this trial. INTERPRETATION: Among adults with basal insulin-treated type 2 diabetes, treatment with once-weekly icodec versus once-daily degludec demonstrated non-inferiority and statistical superiority in HbA1c reduction after 26 weeks, associated with modest weight gain. Overall rates of hypoglycaemia were low, with numerically but not statistically significantly higher event rates of level 2 or level 3 hypoglycaemia with icodec versus degludec. FUNDING: Novo Nordisk.

Risk Factors for Osteoporosis among Patients with Inflammatory Bowel Disease-Do We Already Know Everything?

INTRODUCTION: There are many known risk factors for osteoporosis (OST) among patients with inflammatory bowel disease (IBD), one of which is physical activity. MATERIAL AND METHODS: The aim of the study is to assess the frequency and risk factors of OST among 232 patients with IBD compared to a group of 199 patients without IBD. The participants underwent dual-energy X-ray absorptiometry, laboratory tests, and completed a questionnaire about their physical activity. RESULTS: It was found that 7.3% of IBD patients suffered from OST. Male gender, ulcerative colitis, extensive inflammation in the intestine, exacerbation of disease, rare physical activity, other forms of physical activity, past fractures, lower levels of osteocalcin, and higher levels of C-terminal telopeptide of type 1 collagen were risk factors for OST. As many as 70.6% of OST patients were rarely physically active. CONCLUSIONS: OST is a common problem in IBD patients. OST risk factors differ significantly between the general population and those with IBD. Modifiable factors can be influenced by patients and by physicians. The key to OST prophylaxis may be regular physical activity, which should be recommended in clinical remission. It may also prove valuable to use markers of bone turnover in diagnostics, which may enable decisions regarding therapy.

General versus central adiposity as risk factors for cardiovascular-related outcomes in a high-risk population with type 2 diabetes: a post hoc analysis of the REWIND trial.

BACKGROUND: In clinical practice, anthropometric measures other than BMI are rarely assessed yet may be more predictive of cardiovascular (CV) risk. We analyzed the placebo group of the REWIND CV Outcomes Trial to compare several anthropometric measures as baseline risk factors for cardiovascular disease (CVD)-related outcomes in participants with type 2 diabetes (T2D). METHODS: Data from the REWIND trial placebo group (N = 4952) were analyzed. All participants had T2D, age ≥ 50 years, had either a previous CV event or CV risk factors, and a BMI of ≥ 23 kg/m2. Cox proportional hazard models were used to investigate if BMI, waist-to-hip ratio (WHR), and waist circumference (WC) were significant risk factors for major adverse CV events (MACE)-3, CVD-related mortality, all-cause mortality, and heart failure (HF) requiring hospitalization. Models were adjusted for age, sex, and additional baseline factors selected by LASSO method. Results are presented for one standard deviation increase of the respective anthropometric factor. RESULTS: Participants in the placebo group experienced 663 MACE-3 events, 346 CVD-related deaths, 592 all-cause deaths, and 226 events of HF requiring hospitalization during the median follow-up of 5.4 years. WHR and WC, but not BMI, were identified as independent risk factors of MACE-3 (hazard ratio [HR] for WHR: 1.11 [95% CI 1.03 to 1.21]; p = 0.009; HR for WC: 1.12 [95% CI 1.02 to 1.22]; p = 0.012). WC adjusted for hip circumference (HC) showed the strongest association with MACE-3 compared to WHR, WC, or BMI unadjusted for each other (HR: 1.26 [95% CI 1.09 to 1.46]; p = 0.002). Results for CVD-related mortality and all-cause mortality were similar. WC and BMI were risk factors for HF requiring hospitalization, but not WHR or WC adjusted for HC (HR for WC: 1.34 [95% CI 1.16 to 1.54]; p < 0.001; HR for BMI: 1.33 [95% CI 1.17 to 1.50]; p < 0.001). No significant interaction with sex was observed. CONCLUSIONS: In this post hoc analysis of the REWIND placebo group, WHR, WC and/or WC adjusted for HC were risk factors for MACE-3, CVD-related mortality, and all-cause mortality; while BMI was only a risk factor for HF requiring hospitalization. These findings indicate the need for anthropometric measures that consider body fat distribution when assessing CV risk.

Guidelines for the diagnosis and management of osteoporosis in Poland. Update 2022.

Guidelines to provide an update of the previously published Polish recommendations for the management of women and men with osteoporosis have been developed in line with advances in medical knowledge, evidence-based data, and new concepts in diagnostic and therapeutic strategies. A Working Group of experts from the Multidisciplinary Osteoporosis Forum and from the National Institute of Geriatrics, Rheumatology, and Rehabilitation in Warsaw performed a thorough comprehensive review of current relevant publications in the field (including all age groups of people and management of secondary osteoporosis), and they evaluated epidemiological data on osteoporosis in Poland and the existing standards of care and costs. A voting panel of all co-authors assessed and discussed the quality of evidence to formulate 29 specific recommendations and voted independently the strength of each recommendation. This updated practice guidance highlights a new algorithm of the diagnostic and therapeutic procedures for individuals at high and very high fracture risk and presents a spectrum of general management and the use of medication including anabolic therapy. Furthermore, the paper discusses the strategy of primary and secondary fracture prevention, detection of fragility fractures in the population, and points to vital elements for improving management of osteoporosis in Poland.

Cost of Surgical Treatment of Obesity and Its Impact on Healthcare Expense-Nationwide Data from a Polish Registry.

Weight loss surgery is linked to health benefits and may reduce the cost to the public healthcare systems. The aim of this study was to assess the cost and cost-structure in the one-year periods before and after a bariatric surgery in the Polish nationwide registry. The study included 2390 obese adults which underwent surgical treatment for obesity in 2017. The cost structure and the total costs per patient for one year before bariatric surgery, preoperatively, and for one year after surgery were analyzed. The total cost of the postoperative period was about PLN 3 million lower than during the preoperative period. After bariatric surgery, a reduction of approximately 59% in costs associated with hospital treatment was observed. The costs of outpatient specialist services, hospital treatment, psychiatric care, and addiction treatment also significantly decreased. There was a negative correlation between the changes in the cost of treatment of patients undergoing obesity surgery and their age. The health care cost during the period of one year after bariatric surgery is lower than in the year preceding the surgery (a greater cost difference is observed in younger people). This is mainly influenced by the reduction in costs associated with hospital treatment.

Atherosclerosis Risk Factors in Patients with Reactive Hypoglycemia.

Purpose: Glucose metabolism disorders are an established risk factor for atherosclerosis. Although reactive hypoglycemia (RH) can be classified as one of these disorders, its role as a potential atherosclerosis risk factor remains unclear. The aim of the study was to assess whether patients with RH have a higher risk of atherosclerosis. Patients and Methods: We recruited 178 patients (N=178) with suspected RH who were hospitalized after 2014 and underwent a prolonged 5-hour oral glucose tolerance test. The study cohort was divided into 2 groups depending on the results of the oral glucose tolerance test: Group 1 - subjects without RH (n=44), Group 2 -subjects with RH (n=134). Results: The analyzed groups differed significantly in terms of the following risk factors for atherosclerosis: high-density lipoprotein (HDL) cholesterol levels (54.3±18.8 mg/dL vs 63±18.5 mg/dL, p=0.003) and atherogenic indices (Castelli I: 3.7±1.2 vs 3.1±1.3, p=0.004; Castelli II: 2.1±0.9 vs 1.7±0.9, p=0.007; the atherogenic index of plasma: 0.34±0.33 vs 0.18±0.3, p=0.006; and the atherogenic coefficient: 2.7±1.2 vs 2.1±1.3, p=0.004). Univariate logistic regression showed that RH should not be considered to be a predictor of an increased atherogenic index of plasma (odds ratio [OR]=0.3 [95% confidence interval [CI] [0.16-0.7], p=0.002). Multivariate logistic regression revealed triglyceride levels (OR 1.14 [1.07-1.2], p=0.001) and body weight (OR 1.07 [1.03-1.12], p=0.002) to be independent risk factors for atherosclerosis. Conclusion: Atherosclerosis risk factors are no more prevalent in patients with RH. RH does not increase the risk of an abnormal atherogenic index of plasma.

A novel kidney disease index reflecting both the albumin-to-creatinine ratio and estimated glomerular filtration rate, predicted cardiovascular and kidney outcomes in type 2 diabetes.

BACKGROUND: The estimated glomerular filtration rate (eGFR) and the albumin-to-creatinine ratio (ACR) are risk factors for diabetes-related outcomes. A composite that captures information from both may provide a simpler way of assessing risk. METHODS: 9115 of 9901 Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) participants with both an ACR and eGFR at baseline were included in this post hoc epidemiologic analysis. The hazard of higher baseline levels of 1/eGFR and natural log transformed ACR (calculated as ln [ACR × 100] to eliminate negative values) and their interaction for incident major adverse cardiovascular events (MACE), kidney outcomes, and deaths was estimated. The hazard of the geometric mean of these two baseline measures (the kidney disease index or KDI) was also assessed. RESULTS: A non-linear relationship was observed between 1/eGFR and all three outcomes, and between ln [ACR × 100] and the kidney outcome. There was also a negative interaction between these two risk factors with respect to MACE and death. Conversely, a linear relationship was noted between the KDI and all three outcomes. People in the highest KDI fifth experienced the highest incidence of MACE, death, and the kidney outcome (4.43, 4.56, and 5.55/100 person-years respectively). C statistics for the KDI were similar to those for eGFR and albuminuria. CONCLUSIONS: The KDI combines the baseline eGFR and ACR into a novel composite risk factor that has a simple linear relationship with incident serious outcomes in people with diabetes and additional CV risk factors. Trial Registration clinicaltrials.gov NCT01394952.

[Association of antithyroid peroxidase antibodies with cardiac function in euthyroid women with type 1 diabetes mellitus - assessment with two-dimensional speckle­tracking echocardiography].

INTRODUCTION: The presence of diabetes is associated with loss of cardioprotection in premenopausal women; however, the mechanisms involved remain unknown. Autoimmune factors are suspected to play a role in cardiovascular complications, especially in type 1 diabetes (T1DM). The aim of this pilot study was to explore whether antithyroid peroxidase antibody (aTPO) as a marker of increased immune activity is related to cardiac dysfunction in young, asymptomatic women with T1DM. MATERIAL AND METHODS: Eighty-eight euthyroid women (59 with T1DM and 29 healthy controls) underwent physical examination, laboratory tests, thyroid ultrasound, and two-dimensional speckle-tracking echocardiography. According to the antiperoxidase antibodies (aTPO) titre, the T1DM women were divided into an aTPO positive (T1DM aTPO+) (n = 34) and an aTPO negative (T1DM aTPO-) (n = 25) group. The relationship between thyroid autoimmunity parameters and echocardiographic parameters was evaluated. RESULTS: Global longitudinal strain (GLS) was slightly reduced in the T1DM aTPO+ group compared to T1DM aTPO- and significantly compared to controls (p = 0.051 and p = 0.015, respectively). Although, the lower values of longitudinal strain of left ventricular were found in the majority of segments in the T1DM aTPO+ group in comparison to T1DM aTPO- and controls, significant differences were only found in the two-chamber view (specifically in the anterior segments) between the T1DM aTPO+ and T1DM aTPO- groups (p = 0.030) and in the four-chamber view (specifically in the anterolateral segments) between the T1DM aTPO+ group and controls (p = 0.021). Echocardiographic parameters of diastolic and systolic function of both ventricles were significantly correlated with parameters of thyroid autoimmunity. A logistic regression analysis showed that Hashimoto's thyroiditis (HT) duration [odds ratio (OR): 0.997, 95% confidence interval (CI): 0.995-0.999, p = 0.008), the dose of levothyroxine (OR: 0.814, 95% CI: 0.689-0.960, p = 0.013), and reduced echogenicity on thyroid ultrasound (OR: 0.309, 95% CI: 0.120-0.793, p = 0.013) had a significant influence on reduced GLS. CONCLUSIONS: Our results suggest that coexistence of aTPO with T1DM was associated with poorer myocardial function, particularly in the anterior and anterolateral segments, which may be related to an autoimmune factor. The impaired function of these segments is probably the first sign of myocardial systolic dysfunction in women with T1DM, which needs to be confirmed in further studies.

Seasonally Dependent Change of the Number of Fractures after 50 Years of Age in Poland-Analysis of Combined Health Care and Climate Datasets.

Aim: The incidence of fractures correlates with many independent and interrelated factors. The aim of the study was to examine trends in fracture incidence and to find possible reasons for changes. Materials and methods: A complete dataset of Polish population aged above 50 from the National Heath Fund­which is a single, state-owned payer for the health service procedures in Poland­covering the years between 2010 and 2015 was analyzed along with climate dataset. Results: The analysis indicated that there was a substantial and statistically significant decrease in the incidence of forearm and hip fractures (p = 0.007 and 0.007, respectively). On the other side, there was a statistically significant increase in incidence of humerus and lumbar fractures (p = 0.002, p < 0.001, respectively). The observed changes (especially decrease in forearm and hip fracture incidence) happened mostly in the cold season and were correlated to mean-temperature changes during the assessed time period. Conclusion: In the analysis based on the dataset obtained from fracture-related database collected in Poland in the years 2010−2015 in the population of patients over 50 years of age, we observed that the changes of fracture incidence during the observation period are associated with and may be dependent on the season (warmer versus colder) and on mean temperature increase during the observation period.

Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Evidence of effective smoking cessation interventions in patients with diabetes is limited. The unique behavioral and metabolic characteristics of smokers with type 2 diabetes warrants a randomized clinical trial of the smoking cessation drug varenicline. Objective: To evaluate the efficacy and safety of varenicline in patients with type 2 diabetes with an intention to quit smoking. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial recruited patients from 6 outpatient clinics in 5 hospitals in Catania, Italy. Patients with type 2 diabetes, who were smoking at least 10 cigarettes a day, and who intended to quit smoking were screened for eligibility. Eligible patients were randomized to either varenicline or placebo treatment. The trial consisted of a 12-week treatment phase followed by a 40-week follow-up, nontreatment phase. Intention-to-treat data analysis was performed from December 2020 to April 2021. Interventions: Varenicline, 1 mg, twice daily or matched placebo administered for 12 weeks. Patients in both treatment groups also received smoking cessation counseling. Main Outcomes and Measures: The primary efficacy end point of the study was the continuous abstinence rate (CAR) at weeks 9 to 24. Secondary efficacy end points were the CAR at weeks 9 to 12 and weeks 9 to 52 as well as 7-day point prevalence of abstinence at weeks 12, 24, and 52. Results: A total of 300 patients (mean [SD] age, 57.4 [0.8] years; 117 men [78.0%] in varenicline group and 119 men [79.3%] in placebo group) were randomized to receive varenicline (n = 150) or placebo (n = 150). The CAR at weeks 9 to 24 was significantly higher for the varenicline than placebo group (24.0% vs 6.0%; odds ratio [OR], 4.95; 95% CI, 2.29-10.70; P < .001). The CARs at weeks 9 to 12 (31.3% vs 7.3%; OR, 5.77; 95% CI, 2.85-11.66; P < .001) and weeks 9 to 52 (18.7% vs 5.3%; OR, 4.07; 95% CI, 1.79-9.27; P < .001) as well as the 7-day point prevalence of abstinence at weeks 12, 24, and 52 were also significantly higher for the varenicline vs placebo group. The most frequent adverse events occurring in the varenicline group compared with the placebo group were nausea (41 [27.3%] vs 17 [11.4%]), insomnia (29 [19.4%] vs 19 [12.7%]), abnormal dreams (19 [12.7%] vs 5 [3.4%]), anxiety (17 [11.4%] vs 11 [7.3%]), and irritability (14 [9.4%] vs 8 [5.4%]). Serious adverse events were infrequent in both groups and not treatment-related. Conclusions and Relevance: Results of this trial showed that inclusion of varenicline in a smoking cessation program is efficacious in achieving long-term abstinence without serious adverse events. Varenicline should be routinely used in diabetes education programs to help patients with type 2 diabetes stop smoking. Trial Registration: ClinicalTrials.gov Identifier: NCT01387425.

Efficacy and safety outcomes of dulaglutide by baseline HbA1c: A post hoc analysis of the REWIND trial.

AIM: To assess cardiovascular, glycaemic, weight and safety outcomes of long-term treatment with dulaglutide 1.5 mg compared with placebo in patients with a baseline HbA1c of less than 7% versus 7% or higher. MATERIALS AND METHODS: Intention-to-treat analyses were performed on REWIND participants with a baseline HbA1c measurement, using Cox proportional hazards regression and mixed model for repeated measures. Subgroup analyses with factors for baseline HbA1c categories and their interaction with treatment group, as well as analyses within the HbA1c subgroups, were conducted. Additionally, sensitivity analyses were performed for baseline HbA1c subgroups of 6.5% or less and more than 6.5%. RESULTS: Of the 9876 eligible participants, 3921 and 5955 had a baseline HbA1c of less than 7% and 7% or higher, respectively. Mean baseline HbA1c was 6.3% and 8.0% and the mean duration of diabetes was 9.0 and 11.6 years in the respective subgroups. The less than 7% subgroup was slightly older and less frequently insulin-treated. There was no evidence of a differential dulaglutide treatment effect on body mass index (BMI) reduction, cardiovascular or safety outcomes of interest between the baseline HbA1c subgroups. Treatment-by-baseline HbA1c group interaction was significant for HbA1c change from baseline (P < .001), with a greater reduction in the subgroup with higher baseline HbA1c values. Sensitivity analyses by baseline HbA1c subgroups of 6.5% or less and more than 6.5% showed similar results. CONCLUSIONS: The reduced incidence of cardiovascular events, and the reduction in BMI in participants treated with once-weekly dulaglutide, were independent of the baseline HbA1c level. Conversely, participants with a higher baseline HbA1c level had greater reductions in HbA1c. Dulaglutide has a positive benefit-risk profile and can be considered in patients with comparatively well-controlled HbA1c levels seeking optimal metabolic control and cardiovascular benefits.

Novel Indices of Cognitive Impairment and Incident Cardiovascular Outcomes in the REWIND Trial.

CONTEXT: Low cognitive scores are risk factors for cardiovascular outcomes. Whether this relationship is stronger using novel cognitive indices is unknown. METHODS: Participants in the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial who completed both the Montreal Cognitive Assessment (MoCA) score and Digit Substitution Test (DSST) at baseline (N = 8772) were included. These scores were used to identify participants with baseline substantive cognitive impairment (SCI), defined as a baseline score on either the MoCA or DSST ≥ 1.5 SD below either score's country-specific mean, or SCI-GM, which was based on a composite index of both scores calculated as their geometric mean (GM), and defined as a score that was ≥ 1.5 SD below their country's average GM. Relationships between these measures and incident major adverse cardiovascular events (MACE), and either stroke or death were analyzed. RESULTS: Compared with 7867 (89.7%) unaffected participants, the 905 (10.3%) participants with baseline SCI had a higher incidence of MACE (unadjusted hazard ratio [HR] 1.34; 95% CI 1.11, 1.62; P = 0.003), and stroke or death (unadjusted HR 1.60; 95% CI 1.33, 1.91; P < 0.001). Stronger relationships were noted for SCI-GM and MACE (unadjusted HR 1.61; 95% CI 1.28, 2.01; P < 0.001), and stroke or death (unadjusted HR 1.85; 95% CI 1.50, 2.30; P < 0.001). For SCI-GM but not SCI, all these relationships remained significant in models that adjusted for up to 10 SCI risk factors. CONCLUSION: Country-standardized SCI-GM was a strong independent predictor of cardiovascular events in people with type 2 diabetes in the REWIND trial.

[Is thyroid autoimmunity associated with subclinical atherosclerosis in young women with type 1 diabetes mellitus?]

INTRODUCTION: It has been hypothesized that autoimmunity may contribute to cardiovascular complications and may be an important trigger for processes leading to atherosclerosis, especially in type 1 diabetes mellitus (T1DM). This pilot study aimed to answer the question of whether markers of thyroid autoimmunity are associated with increased carotid intima-media thickness (cIMT) in young, asymptomatic T1DM women. MATERIAL AND METHODS: The study population consisted of 102 women, including 72 with T1DM and 30 healthy controls. All patients had thyroid hormones within the normal range. According to the antiperoxidase antibodies (aTPO) titre, the T1DM women were divided into an aTPO-positive (T1DM aTPO+) (n = 41) and an aTPO-negative (T1DM aTPO-) (n = 31) group. In all patients, aTPO, thyroglobulin antibody (aTG) titres, thyroid-stimulating hormone (TSH), free thyroxine (FT3), free triiodothyronine (FT4), lipid parameters, glycated haemoglobin, thyroid ultrasonography, and cIMT assessment were evaluated. The association of cIMT with different risk factors related to thyroid autoimmunity was determined. RESULTS: Carotid intima-media thickness was significantly greater in T1DM aTPO+ females (0.66 ± 0.10 mm) than in T1DM aTPO- (0.59 ± 0.11 mm) and healthy controls (0.58 ± 0.10 mm) (p = 0.007, p = 0.001, respectively). In all women cIMT was significantly, positively correlated with aTPO (p = 0.005, r = 0.273), Hashimoto's thyroiditis (HT) duration (p = 0.00015, r = 0.367), levothyroxine dose per week (p = 0.006, r = 0.269), and ultrasound features of HT (p = 0.004, r = 0.281) and inversely with fT3 concentration (p = 0.014, r = -0.243) and FT3/FT4 ratio (p = 0.042, r = -0.201). A logistic regression analysis showed that HT duration (OR: 1.102, 95% CI: 1.008-1.206, p = 0.032) and a positive history family of HT (OR: 3.909, 95%CI: 1.014-15.071, p = 0.045) were risk factors for increased cIMT. However, multivariate regression analysis showed that the studied parameters related to thyroid autoimmunity are not independent risk factors for increased cIMT. CONCLUSIONS: We expanded the data on cIMT in young women with T1DM and showed that thyroid autoimmunity, and in particular the duration of exposure to anti-thyroid antibodies, despite adequate levothyroxine substitution, is associated with subclinical atherosclerosis in young women with T1DM. However, thyroid-related parameters are not independent risk factors for increased cIMT in euthyroid women.

Effective Overall Glycaemic Control with Fast-Acting Insulin Aspart Across Patients with Different Baseline Characteristics: A Post Hoc Analysis of the Onset 9 Trial.

AIMS: To investigate the efficacy and safety of fast-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp) in participants with type 2 diabetes (T2D) across different subgroups. METHODS: We report on a post hoc analysis of onset 9, a 16-week trial of participants with T2D randomised to faster aspart (n = 546) or IAsp (n = 545). Participants were grouped by baseline HbA1c (< 7.0%, ≥ 7.0%), meal test bolus insulin dose (≤ 10 units [U], > 10 U to ≤ 20 U, > 20 U), body mass index (< 30 kg/m2, ≥ 30 to < 35 kg/m2, ≥ 35 kg/m2), and age (< 65 years, ≥ 65 years). Outcomes assessed were change from baseline in HbA1c and in 1-h postprandial glucose (PPG) increment, and severe or blood glucose (BG)-confirmed hypoglycaemia. RESULTS: Faster aspart provided reductions in HbA1c comparable to IAsp across all subgroups, with improved 1-h PPG control compared with IAsp in several subgroups. Faster aspart had comparable or improved rates of severe or BG-confirmed hypoglycaemia versus IAsp, particularly in participants with good glycaemic control (HbA1c < 7.0%), the elderly (≥ 65 years old), and those with insulin resistance (> 20 U meal test bolus insulin dose). CONCLUSIONS: Faster aspart provides effective overall glycaemic control, with improved early PPG control compared with IAsp across a range of patient characteristics. CLINICAL TRIAL REGISTRATION: NCT03268005.

Fast-acting insulin aspart (faster aspart) is a type of insulin used at mealtimes to reduce the spike in blood sugar resulting from that meal. Faster aspart works in the body more quickly and more effectively than insulin aspart (IAsp), the previous version of this insulin. The properties of insulins in the body can change according to certain patient characteristics. In this study, the researchers wanted to find out if there were differences between various subgroups of patients in the effectiveness and safety of faster aspart compared with IAsp in the treatment of type 2 diabetes. Data were used from a clinical trial (onset 9), in which 546 patients were treated with faster aspart and 545 were treated with IAsp. Patients were grouped by baseline glycated haemoglobin (HbA1c), meal test actual bolus insulin dose, body mass index, and age. Faster aspart provided reductions in HbA1c comparable to IAsp across all subgroups, with improved glucose control 1 hour after a meal compared with IAsp, in several subgroups. Faster aspart had comparable or improved rates of hypoglycaemia versus IAsp, particularly in participants with good glucose control, the elderly (≥ 65 years old), and those with insulin resistance. In summary, the researchers found that faster aspart provides effective overall glucose control, with improved early mealtime glucose control compared with IAsp across patients with a range of baseline characteristics.

Postprandial Glucose Excursions in Asian Versus Non-Asian Patients with Type 2 Diabetes: A Post Hoc Analysis of Baseline Data from Phase 3 Randomised Controlled Trials of IDegAsp.

INTRODUCTION: Increased postprandial glucose (PPG) is associated with high glycated haemoglobin levels and is an independent risk factor for cardiovascular diseases. The aim of this study was to compare PPG increments in Asian versus non-Asian adults with type 2 diabetes (T2D), who were insulin-naïve or insulin-experienced, from the phase 3 insulin degludec/insulin aspart (IDegAsp) clinical trials. METHODS: This was a post hoc analysis of data from 13 phase 3, randomised, parallel-group, open-label IDegAsp trials in patients with T2D. The pooled baseline clinical data were analysed for insulin-naïve and insulin-experienced groups; and each group was split into subgroups of Asian and non-Asian patients, respectively, and analysed accordingly. Baseline self-monitored blood glucose (SMBG) values at breakfast, lunch and the evening meal (before and 90 min after each meal) were used to assess PPG increments. The estimated differences in baseline SMBG increment between the Asian and non-Asian subgroups were analysed. RESULTS: Clinical data from 4750 participants (insulin-naïve, n = 1495; insulin-experienced, n = 3255) were evaluated. In the insulin-naïve group, the postprandial SMBG increment was significantly greater in the Asian versus the non-Asian subgroup at breakfast (estimated difference 28.67 mg/dL, 95% confidence interval [CI] 18.35, 38.99; p < 0.0001), lunch (17.34 mg/dL, 95% CI 6.47, 28.21; p = 0.0018) and the evening meal (16.19 mg/dL, 95% CI 5.04, 27.34; p = 0.0045). In the insulin-experienced group, the postprandial SMBG increment was significantly greater in the Asian versus non-Asian subgroup at breakfast (estimated difference 13.81 mg/dL, 95% CI 9.19, 18.44; p < 0.0001) and lunch (29.18 mg/dL, 95% CI 24.22, 34.14; p < 0.0001), but not significantly different at the evening meal. CONCLUSION: In this post hoc analysis, baseline PPG increments were significantly greater in Asian participants with T2D than in their non-Asian counterparts at all mealtimes, with the exception of the evening meal in insulin-experienced participants. Asian adults with T2D may benefit from the use of regimens that control PPG excursions. CLINICAL TRIAL NUMBERS: NCT02762578, NCT01814137, NCT01513590, NCT01009580, NCT01713530, NCT02648217, NCT01045447, NCT01365507, NCT01045707, NCT01272193, NCT01059812, NCT01680341, NCT02906917.

Predictors of Rehospitalization and Mortality in Diabetes-Related Hospital Admissions.

The risk factors of rehospitalization and death post-discharge in diabetes-related hospital admissions are not fully understood. To determine them, a population-based retrospective epidemiological survey was performed on diabetes-related admissions from the Polish national database. Logistic regression models were used, in which the dependent variables were rehospitalization due to diabetes complications and death within 90 days after the index hospitalization. In 2017, there were 74,248 hospitalizations related to diabetes. A total of 11.3% ended with readmission. Risk factors for rehospitalization were as follows: age < 35 years; male sex; prior hospitalization due to acute diabetic complications; weight loss; peripheral artery disease; iron deficiency anemia; kidney failure; alcohol abuse; heart failure; urgent, emergency, or weekend admission; length of hospitalization; and hospitalization in a teaching hospital with an endocrinology/diabetology unit. Furthermore, 7.3% of hospitalizations resulted in death within 90 days following discharge. Risk factors for death were as follows: age; neoplastic disease with/without metastases; weight loss; coagulopathy; alcohol abuse; acute diabetes complications; heart failure; kidney failure; iron deficiency anemia; peripheral artery disease; fluid, electrolytes, and acid-base balance disturbances; urgent or emergency and weekend admission; and length of hospitalization. We concluded that of all investigated factors, only hospitalization within an experienced specialist center may reduce the frequency of the assessed outcomes.