A temporary regulation to manage an impending shortage due to extraordinary prescribing patterns of chloroquines observed during early phase of COVID-19 epidemic.

Background: Chloroquine and hydroxychloroquine (C/HC) received considerable international media attention due to anticipated treatment effect in COVID-19. This led to increased prescriptions threatening to generate product shortages for patients prescribed within approved indications.We evaluated effects of a temporary regulation mandating pharmacies to only dispense C/HC prescribed by physicians with defined specialties.

Hoarding of insulin and oral antidiabetics in the first phase of the COVID-19 pandemic: Regulatory actions taken to avoid shortage.

Objective: To report on hoarding of prescribed medicines, with focus on insulins, in the early phase of the COVID-19 pandemic and on regulatory actions taken to avoid shortage.

Materials And Methods: The National Prescribed Drug Register which utilizes the Anatomic Therapeutic Chemical (ATC) Classification System and covers the total Swedish population was used. We calculated the number of packages of insulins (ATC code A10A), oral anti-diabetics (A10B), and all medicines across all ATC codes combined (A-S) dispensed per week in 2019 and 2020.

Plasma proteomic signatures of a direct measure of insulin sensitivity in two population cohorts.

Aims/hypothesis: The euglycaemic-hyperinsulinaemic clamp (EIC) is the reference standard for the measurement of whole-body insulin sensitivity but is laborious and expensive to perform. We aimed to assess the incremental value of high-throughput plasma proteomic profiling in developing signatures correlating with the M value derived from the EIC.

Methods: We measured 828 proteins in the fasting plasma of 966 participants from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study and 745 participants from the Uppsala Longitudinal Study of Adult Men (ULSAM) using a high-throughput proximity extension assay.

Validation of myocarditis diagnoses in the Swedish patient register for analyses of potential adverse reactions to COVID-19 vaccines.

Background: Coronavirus disease 2019 (COVID-19) mRNA vaccines are associated with an increased risk of myocarditis using hospital discharge diagnoses as an outcome. The validity of these register-based diagnoses is uncertain.

Methods: Patient records for subjects < 40 years of age and a diagnosis of myocarditis in the Swedish National Patient Register were manually reviewed.

Loci for insulin processing and secretion provide insight into type 2 diabetes risk.

Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait.

Association between atherogenic lipids and GnRH agonists for prostate cancer in men with T2DM: a nationwide, population-based cohort study in Sweden.

Background: Gonadotropin-releasing hormone agonists (GnRH) used in prostate cancer (PCa) are associated with atherogenic dyslipidaemia. It can be assumed that GnRH need to be used with greater caution in men with type 2 diabetes mellitus (T2DM). This study investigated association of GnRH with atherogenic lipids (AL) in PCa men with T2DM.

Association of Gonadotropin-Releasing Hormone Agonists for Prostate Cancer With Cardiovascular Disease Risk and Hypertension in Men With Diabetes.

Importance: Men with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Meanwhile, gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer (PCa) are associated with increased risk of CVD.

Objective: To evaluate the association between GnRH agonist use, PCa diagnosis per se, and CVD risk in men with type 2 diabetes.

Self-reported physical activity and different cardiovascular diseases-Results from updated measurements over 40 years.

Background: Self-reported leisure-time physical activity (PA) has previously been linked to risk of cardiovascular disease (CVD). We now aim to investigate the strength of associations between PA and different CVDs and how the risk varies with age.

Methods: PA and traditional CV risk factors assessed by a questionnaire on a four-level scale in 2,175 men at age 50 years in the ULSAM study.

The profile of the COvid-19 VACcination register SAFEty study in Sweden (CoVacSafe-SE).

Background: The coronavirus disease 2019 (COVID-19) vaccines have been rapidly implemented in national vaccination programs world-wide after accelerated approval processes. The large population exposure achieved in very short time requires systematic monitoring of safety. The Swedish Medical Products Agency has launched a project platform for epidemiological surveillance to detect and characterise suspected adverse effects of COVID-19 vaccines in Sweden.

Exploring the association between use of gonadotropin releasing hormones agonists and prostate cancer diagnosis per se and diabetes control in men with type 2 diabetes mellitus: a nationwide, population-based cohort study.

Background: Gonadotropin Releasing Hormones agonists (GnRH), which are first line treatment for metastatic prostate cancer (PCa), increase risk of type 2 diabetes mellitus (T2DM). This study aims to quantify the association of use of GnRH with diabetes control in PCa men with T2DM.

Methods: Nationwide population-based cohort study in the Swedish National Diabetes Register and Prostate Cancer data Base Sweden 4.

Changes in leisure-time physical activity during the adult life span and relations to cardiovascular risk factors-Results from multiple Swedish studies.

Objective: To evaluate how self-reported leisure-time physical activity (PA) changes during the adult life span, and to study how PA is related to cardiovascular risk factors using longitudinal studies.

Methods: Several Swedish population-based longitudinal studies were used in the present study (PIVUS, ULSAM, SHE, and SHM, ranging from hundreds to 30,000 participants) to represent information across the adult life span in both sexes. Also, two cross-sectional studies were used as comparison (EpiHealth, LifeGene).

Association of type 2 diabetes mellitus and antidiabetic medication with risk of prostate cancer: a population-based case-control study.

Background: Prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are prevalent conditions that often occur concomitantly. However, many aspects of the impact of T2DM, particularly the duration of T2DM and antidiabetic medications, on PCa risk are poorly understood.

Methods: To assess the association of duration of T2DM and antidiabetic medication with PCa risk, we designed a matched case-control study, including 31,415 men with PCa and 154,812 PCa-free men in Prostate Cancer data Base Sweden (PCBaSe) 4.

SPISE and other fasting indexes of insulin resistance: risks of coronary heart disease or type 2 diabetes. Comparative cross-sectional and longitudinal aspects.

Fasting insulin resistance indexes are used extensively nowadays. We intended to analyze a new recently presented fasting index, SPISE (sensitivity formula: 600 × HDL-cholesterol/triglycerides/BMI), in comparison with three previously known fasting indexes, regarding correlation with the insulin clamp index, and for the predictive effects of future long-term risks of coronary heart disease (CHD) or manifest type 2 diabetes. A total of 1049 71-year-old male subjects from the Swedish ULSAM study, median follow-up 8 years, were included.

The impact of muscle function, muscle mass and sarcopenia on independent ageing in very old Swedish men.

Background: Preserved functions of daily life and cognition are cornerstones of independent aging, which is crucial for maintaining a high quality of life. The aim of this study was to examine the impact of sarcopenia, and its underlying components, on independent ageing in a cohort study of very old men.

Methods: The presence of sarcopenia and independent ageing at a mean age of 87 was investigated in 287 men from the Uppsala Longitudinal Study of Adult Men.

Relative Prognostic Importance and Optimal Levels of Risk Factors for Mortality and Cardiovascular Outcomes in Type 1 Diabetes Mellitus.

Background: The strength of association and optimal levels for risk factors related to excess risk of death and cardiovascular outcomes in type 1 diabetes mellitus have been sparsely studied.

Methods: In a national observational cohort study from the Swedish National Diabetes Register from 1998 to 2014, we assessed relative prognostic importance of 17 risk factors for death and cardiovascular outcomes in individuals with type 1 diabetes mellitus. We used Cox regression and machine learning analyses.

ADAMTS9 Regulates Skeletal Muscle Insulin Sensitivity Through Extracellular Matrix Alterations.

The rs4607103 C allele is one of the few gene variants proposed to increase the risk of type 2 diabetes through an impairment of insulin sensitivity. We show that the variant is associated with increased expression of the secreted ADAMTS9 and decreased insulin sensitivity and signaling in human skeletal muscle. In line with this, mice lacking selectively in skeletal muscle have improved insulin sensitivity.

Pragmatic clinical trials in the context of regulation of medicines.

The pragmatic clinical trial addresses scientific questions in a setting close to routine clinical practice and sometimes using routinely collected data. From a regulatory perspective, when evaluating a new medicine before approving marketing authorization, there will never be enough patients studied in all subgroups that may potentially be at higher risk for adverse outcomes, or sufficient patients to detect rare adverse events, or sufficient follow-up time to detect late adverse events that require long exposure times to develop. It may therefore be relevant that post-marketing trials sometimes have more pragmatic characteristics, if there is a need for further efficacy and safety information.

Can the Plasma Concentration Ratio of Triglyceride/High-Density Lipoprotein Cholesterol Identify Individuals at High Risk of Cardiovascular Disease During 40-Year Follow-Up?

Background: The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) is a simple way to estimate insulin resistance. We aimed to evaluate the TG/HDL-C ratio as a simple clinical way to identify apparently healthy individuals with insulin resistance and enhanced risk of future cardiovascular disease (CVD).

Methods: One thousand seven hundred twenty men, aged 50 years, free from diabetes and CVD when evaluated at baseline in 1970-1974 were followed for 40 years regarding incident CVD (myocardial infarction and/or ischemic stroke, n = 576).

Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

Background: Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. We investigated whether the excess risk of death and cardiovascular events among patients with type 2 diabetes could be reduced or eliminated.

Methods: In a cohort study, we included 271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of age, sex, and county.

Does a prostate cancer diagnosis affect management of pre-existing diabetes? Results from PCBaSe Sweden: a nationwide cohort study.

Objectives: Both prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are increasingly prevalent conditions, which frequently coexist in men. Here, we set out to specifically examine the impact of a PCa diagnosis and its treatment on T2DM treatment.

Setting: This study uses observational data from Prostate Cancer database Sweden Traject.

A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus.

Prostate cancer (PCa) and type two diabetes mellitus (T2DM) are both increasing prevalent conditions and often occur concurrently. However, the relationship between the two is more complex than just two prevalent conditions co-existing. This review systematically explores the literature around the interplay between the two conditions.

Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation.

Background And Aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels.