Health-related quality of life for normal glycaemia, prediabetes and type 2 diabetes mellitus: Cross-sectional analysis of the ADDITION-PRO study.

AIMS: We estimated and compared health-related quality of life for individuals with normal glucose tolerance, prediabetes and diabetes. METHODS: Participants in the ADDITION-PRO study, Denmark, who attended a health assessment between 2009 and 2011, and who completed the 3-level EuroQoL 5-dimensions (EQ-5D-3L) questionnaire were included. For the present study, they were classified as normal glucose tolerance, prediabetes and diabetes (screen-detected and known) using the 2019 American Diabetes Association criteria. Prediabetes was defined as impaired fasting glucose, impaired glucose tolerance or HbA1c between 5.7-6.4% (39-47 mmol/mol). EQ-5D-3L data were converted into utility scores using Danish and UK values, where '1' equals full health and '0' equals death. Regression models estimated the association between utility and the different glucose health states. RESULTS: The mean EQ-5D-3L score in the sample population was 0.86 ± 0.17 (median 0.85, interquartile range 0.76 to 1) using UK values. Almost half of the sample (48%) reported full health with an EQ-5D score of '1'. Individuals with known diabetes reported the lowest EQ-5D-3L utility scores (0.81 ± 0.20), followed by individuals with screen-detected diabetes (0.85 ± 0.19), prediabetes (0.86 ± 0.17) and normal glucose tolerance (0.90 ± 0.15). The differences were statistically significant for normal glucose and known diabetes relative to prediabetes, after adjusting for sex, age, smoking, BMI and physical activity. These findings also held using Danish values albeit the differences were of smaller magnitude. CONCLUSIONS: Having prediabetes and diabetes was significantly associated with lower health-related quality of life relative to normal glucose tolerance. Our estimates will be useful to inform the value of interventions to prevent diabetes or prediabetes.

Use of prescription medication in the last years of life: a population-based comparison of two oldest old Danish birth cohorts born 10 years apart.

INTRODUCTION: Age limits for diagnostics and treatments have been largely removed and replaced by an active diagnostic and treatment practice among the oldest old and has led to concerns about potential overtreatment during the last years of life. METHODS: Use of prescription medication in the last years of life was assessed from 1995 to 2012 for the entire 1905 and 1915 Danish birth cohorts using nationwide register data. Medication use was quantified as the number different pharmacy-redeemed drugs during 120 days up to a given date. RESULTS: For both cohorts, prescription medication use increased with proximity to death and calendar year, while age at death had little impact; use in the 1915 cohort was markedly higher than in the 1905 cohort. Average number of prescription medications varied from below 3 to above 9 depending on age, calendar year and proximity to death. From 1995 to 2005, average number of prescription medications for a 90-year-old person in the last month of life increased from 6.0 to 8.7. Out of 90-year-old persons dying in 2005, 82% were exposed to polypharmacy, up from 63% in 1995. CONCLUSIONS: Prescription medication use accelerates throughout the last of years life among two Danish oldest old cohorts born 10 years apart, with substantially larger use in the most recent cohort. This pattern suggests an increase in drug prescribing regimens in the period 1995-2012, reinforcing the need for evidence-based guidelines on medications in the particularly vulnerable population of the oldest old patients in their last years of life.

Effect of an entry-to-care intervention on diabetes distress in individuals with newly diagnosed type 2 diabetes: a study protocol for a cluster-randomized trial.

BACKGROUND: Diabetes distress (DD) affects at least 36% of T2DM patients and is often associated with insufficient support and care. This study examines an intervention that targets DD through enhanced cross-sectoral collaboration and treatment during the first 3 months following diagnosis. The intervention aims to improve care and self-management and to reduce DD. METHODS AND INTERVENTION: The study is designed as a cluster-randomized trial with the intervention focusing on four key elements of diabetes care: effective cross-sectoral communication and information sharing, systematic care, a "one-stop-shop" health screening and start-up conversation at the municipality, and improving patient insights into own care. This study requires 32 clusters (16/arm) to achieve 80% power and a 5% significance cut-off, with 270 patients required. GP recruitment occurred from May to Dec 2022. Patient recruitment is ongoing from May 2022 to Aug 2023. GPs were randomized 1:1 using computer-generated blocks of six. Participating GPs are located in Southern Denmark and are not participating in other trials. Patients must be 18 + years of age, have a T2DM diagnosis, and be fluent in spoken and written Danish. DD is the primary outcome and will be measured at baseline, at four months, and again at a 12-month follow-up. Secondary outcomes include quality of care, self-management, quality of life, and clinical factors. Tertiary outcomes comprise depression, stress, resilience, sleep quality, and social network quality. CONCLUSION: This study is among the first clinical trials exploring the development of DD from diagnosis to 12 months post-diagnosis. Many previous interventions did not directly target DD as the primary outcome. This research provides new insights into DD progression in patients newly diagnosed with T2DM and examines an intervention designed to lower DD in early diabetes stages, contributing to a better understanding of the development of DD and how this intervention affects patient well-being. TRIAL REGISTRATION: ClinicalTrial.gov NCT05571306. Registered on 07 October 2022.

Trends in Incidence of Hip Fracture and Hip Replacement in Denmark, 1996 to 2018.

Importance: The past several decades have witnessed substantial changes in treatments that are particularly relevant for older patients. Objectives: To assess changes in national-level incidence rates of fracture- and musculoskeletal-related (ie, arthritis-related) hip replacement procedures for individuals aged 40 to 104 years over a 23-year period in Denmark. Design, Setting, and Participants: This cohort study used national Danish health registers to include the Danish population aged 40 to 104 years from January 1, 1996, to December 31, 2018. Data were analyzed from May 31, 2022, to February 14, 2024. Main Outcomes and Measures: Age- and period-specific incidence rates of hip fracture and hip replacement stratified on fracture-related vs arthritis-related indication. Results: From 1996 to 2018, a total of 3 664 979 individuals were followed up for a mean (SD) of 14.6 (7.7) years, resulting in a follow-up time of 53 517 861 person-years and 158 982 (first) hip fractures, of which 42 825 involved fracture-related hip replacement procedures. A further 104 422 individuals underwent arthritis-related hip replacement. During the first 2 decades of the 21st century, hip fracture rates declined by 35% to 40% for individuals aged 70 to 104 years, and the proportion of the population undergoing fracture-related hip replacement increased by 50% to 70%, with modest variation across those aged 75 to 99 years. Rates of arthritis-related hip replacements peaked for individuals aged 75 to 79 years, but with the largest relative rate increase (75%-100%) occurring for those aged 80 to 94 years, primarily from 2001 to 2015, whereafter it remained nearly unchanged. The decline in rates of arthritis-related hip replacement after 75 to 79 years of age was gradual and did not suggest an upper age limit for access to arthritis-related hip replacement. Conclusions and Relevance: The findings of this cohort study suggest that during the past several decades in Denmark, the incidence of hip fractures declined by 35% to 40% among patients aged 80 to 104 years, while the proportion receiving fracture-related hip replacement remained relatively constant after 75 years of age. During the first decades of the 21st century, arthritis-related hip replacement incidence increased by 50% to 100% among older patients and stabilized hereafter, with no apparent cutoff age for this type of procedure. These patterns indicate a positive overall trend with declining hip fracture incidence over the last decades in Denmark, and the observed hip replacement incidence suggests that age is currently not a major determining factor guiding this type of surgery.

Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes.

Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual ß-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.

Sense of Coherence is associated with LDL-cholesterol in patients with type 1 diabetes - The PROLONG-Steno study.

AIM: It is a constant challenge for people with type 1 diabetes to maintain appropriate levels of HbA1c, blood pressure and blood lipids in order to prevent or delay deleterious effects of their illness. This study sought to investigate if Sense of Coherence (SOC) is associated with clinical risk factors in people with type 1 diabetes. METHODS: Questionnaire data, including measure of SOC, was collected from 125 patients with long duration of type 1 diabetes and linked to electronic patient records to obtain clinical measures on HbA1c, blood pressure, and blood lipids. Linear regressions and generalized additive models were applied to explore the associations between SOC and clinical biomarkers. RESULTS: Mean age of the participants was 60.7 years (standard deviation = 10.0), 44.0% were men. Medium and high SOC were associated with lower levels of LDL-cholesterol (p = 0.005). This association was non-linear with medium and high levels of SOC being advantageous whereas low SOC was associated with elevated levels of LDL-cholesterol. Moreover, we observed non-significant tendencies to associations between low SOC and low HDL-cholesterol, and elevated HbA1c. CONCLUSIONS: Findings from this study suggest that high SOC may be protective against elevated LDL-cholesterol among people with type 1 diabetes. Interventions to improve self-management among people with low SOC may prove effective to prevent deterioration of metabolic risk factors.

Association between protein signals and type 2 diabetes incidence.

Understanding early determinants of type 2 diabetes is essential for refining disease prevention strategies. Proteomic technology may provide a useful approach to identify novel protein patterns potentially related to pathophysiological changes that lead up to diabetes. In this study, we sought to identify protein signals that are associated with diabetes incidence in a middle-aged population. Serum samples from 519 participants in a nested case-control selection (167 cases and 352 age-, sex- and BMI-matched normoglycemic control subjects, median follow-up 14.0 years) within the Whitehall-II cohort were analyzed by linear matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Nine protein peaks were found to be associated with incident diabetes. Rate ratios for high peak intensity ranged between 0.4 (95% CI, 0.2-0.8) and 4.0 (95% CI, 1.7-9.2) and were robust to adjustment for main potential confounders, including obesity, lipids and C-reactive protein. The proteins associated with these peaks may reflect diabetes pathogenesis. Our study exemplifies the utility of an approach that combines proteomic and epidemiological data.

Vesicular stomatitis virus modified with single chain IL-23 exhibits oncolytic activity against tumor cells in vitro and in vivo.

Viruses are potentially attractive agents for development as novel oncolytic agents. Reverse genetic approaches allow for the attenuation of candidate viruses and can enhance their ability to exploit inherent cellular and molecular properties of tumors, including deficiencies in interferon (IFN) signaling. Vesicular stomatitis virus (VSV) is a promising oncolytic agent for exactly these reasons. VSV infection of immunocompetent mice is usually rapidly cleared due to the virus' sensitivity to type I IFN responses. However, in tumors that are unable to activate the IFN response, VSV is able to replicate without inhibition, resulting in cell destruction. Unfortunately, when VSV is introduced into mice intranasally or systemically via therapeutic doses into tumor-bearing rodents, hosts may develop fatal encephalitis. We have previously found that a recombinant VSV expressing the pro-inflammatory cytokine interleukin-23 (IL-23) is significantly attenuated in the central nervous system (CNS). As a result of this, we hypothesized that attenuation in the CNS is partially a result of enhanced NO response as a result of IL-23 signaling. Infection of the CNS with this virus (designated VSV23) is characterized by decreased viral replication, morbidity, and mortality. We have now extended those studies which reveal that VSV23 maintains oncolytic capacity in vitro in multiple cell lines including NB41A3 neuroblastomas, L929 adipose-derived cells, immortalized BHK-21 cells, and the murine mammary derived JC cells. Additionally, in vivo VSV23 infection results in JC tumor destruction and induces enhanced memory responses against tumor cells.