Associations Between HbA1c and Glucose Time in Range Using Continuous Glucose Monitoring in Type 1 Diabetes: Cross-Sectional Population-Based Study.

INTRODUCTION: Continuous glucose monitoring (CGM) introduces novel indicators of glycemic control. METHODS: This cross-sectional study, based on the Swedish National Diabetes Register, examines 27,980 adults with type 1 diabetes. It explores the relationships between HbA1c (glycated hemoglobin) and various CGM-derived metrics, including TIR (time in range, representing the percentage of time within the range of 4-10 mmol/l for 2 weeks), TAR (time above range), TBR (time below range), mean glucose, standard deviation (SD), and coefficient of variation (CV). Pearson correlation coefficients and linear regression models were utilized for estimation. RESULTS: The analysis included 46% women, 30% on insulin pump, 7% with previous coronary heart disease and 64% with retinopathy. Mean ± SD values were age 48 ± 18 years, diabetes duration 25 ± 16 years, HbA1c 58.8 ± 12.8 mmol/mol, TIR 58.8 ± 19.0%, TAR 36.3 ± 20.0%, TBR 4.7 ± 5.4%, mean sensor glucose 9.2 ± 2.0 mmol/l, SD 3.3 ± 1.0 mmol/l, and CV 36 ± 7%. The overall association between HbA1c and TIR was - 0.71 (Pearson's r), with R2 0.51 in crude linear regression and 0.57 in an adjusted model. R2 values between HbA1c and CGM mean glucose were 0.605 (unadjusted) 0.619 (adjusted) and TAR (unadjusted 0.554 and fully adjusted 0.568, respectively), while fully adjusted R2 values were 0.458, 0.175 and 0.101 between HbA1c and CGM SD, CGM CV and TBR, respectively. CONCLUSIONS: This descriptive study demonstrates that the degree of association between HbA1c and new and readily available CGM-derived metrics, i.e., time in range (TIR), time above range (TAR), and CGM mean glucose, is robust in assessing the management of individuals with type 1 diabetes in clinical settings. Metrics from CGM that pertain to variability and hypoglycemia exhibit only weak correlations with HbA1c.

Home-Based Titration with Duodenal Infusion of Levodopa-Carbidopa Intestinal Gel in People with Parkinson's Disease: An Observational Feasibility Study.

Background: Testing and titration of the right levodopa equivalent dose are usually performed during a hospital admission. However, optimal dose titration in people with Parkinson's disease (PwPs) may depend on home environment, emotional stress, and physical activity of everyday life. Objective: Firstly, to evaluate the feasibility and safety of a home-based LCIG titration program and patients'/caregivers' satisfaction. Secondly, to identify barriers and facilitators for home-based titration. Method: This study assesses the feasibility and safety of home-based titration of levodopa duodenal infusions with the use of self-reported evaluation questionnaires with open-ended questions included, registration of total time used, and number of contacts/visits. A telemedicine solution was used to remotely monitor the patients, adjust treatment, and provide support and guidance to patients and caregivers. Results: Ten of 12 PwPs (5 females and 7 males) completed the total titration program. Eight of the 12 PwPs were dependent on help. These 8 PwPs also had a high burden of nonmotor symptoms (NMS). Cognitive impairments varied in severity (range 16-30). Time spent with home visits was on average 93.4 minutes (ranging from 35 to 180 minutes), and the length of the total titration (LCIG initiation to termination of titration) was on average 3.4 days with 2-5 (mean 3.2) contacts/visits with PD team members. The average score on the satisfaction evaluation questionnaires was lower in the caregiver group (mean 31.8) than the PwP outcome (mean 36.2). Conclusions: Telehealth-assisted home-based titration programs are feasible due to the length of the titration period, number of contacts, and time spent in PwPs' private homes, are rated satisfactory and safe by PwPs and caregivers, and may be a substitute for in-hospital treatment. Clinical recommendations including facilitators and barriers from a patient/caregiver perspective are displayed. This trial is registered with NCT4196647.

Greater persistence and adherence to basal insulin therapy is associated with lower healthcare utilization and medical costs in patients with type 2 diabetes: a retrospective database analysis.

INTRODUCTION: We aimed to assess persistence and adherence to basal insulin therapy, their association with all-cause healthcare resource utilization (HCRU) and direct medical costs, and predictors of persistence and adherence in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: A retrospective cohort study was conducted with US adults with type 2 diabetes initiating basal insulin therapy between January 1, 2016, and December 31, 2018, using IQVIA PharMetrics Plus claims data. Persistence and adherence were assessed during 1 year post-initiation per previous definitions. Demographic/clinical characteristics were assessed during the 1 year pre-initiation. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding variables. Post-IPTW, all-cause HCRU and direct medical costs were assessed during the first-year and second-year post-initiation by persistence and adherence status. Multivariable logistic regression was used to identify predictors of persistence and adherence. RESULTS: The final sample comprised 64,953 patients; 56.8% demonstrated persistence and 41.9% demonstrated adherence. Patients demonstrating persistence and adherence were significantly less likely to have a hospitalization than patients demonstrating non-persistence or non-adherence, respectively. In the second-year post-initiation, total mean all-cause direct medical costs per patient were lower for patients demonstrating persistence and significantly lower for patients demonstrating adherence. Prior use of both oral and injectable antidiabetic medication predicted persistence and adherence compared with patients with only prior oral antidiabetic medication use (persistence OR, 1.50 (95% CI, 1.44 to 1.57); adherence OR, 1.48 (95% CI, 1.42 to 1.55)). CONCLUSIONS: Persistence and adherence to basal insulin was associated with fewer hospitalizations and lower direct medical costs.

Real-world impact of once-weekly subcutaneous semaglutide after 2 years of follow-up: Results from a nationwide observational study in people with type 2 diabetes.

AIM: To investigate the impact of treatment with once-weekly subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), for up to 2 years in people with type 2 diabetes (T2D) managed in routine clinical practice. MATERIALS AND METHODS: The study was based on data from national registries. People who redeemed at least one prescription of semaglutide and had 2 years of follow-up were included. Data were collected at baseline and after 180, 360, 540 and 720 days of treatment (all timepoints ± 90 days). RESULTS: In total, 9284 people redeemed at least one semaglutide prescription (intention-to-treat) and 4132 people redeemed semaglutide continuously (on-treatment). For the on-treatment cohort, the median (interquartile range) age was 62.0 (16.0) years, diabetes duration was 10.8 (8.7) years, and glycated haemoglobin (HbA1c) level was 62.0 (18.0) mmol/mol at baseline. A subset of the on-treatment cohort, comprising 2676 people, had HbA1c measurements at baseline and at least once during 720 days. The mean (95% confidence interval) changes in HbA1c after 720 days were -12.6 (-13.6; -11.6) mmol/mol (P < 0.001) for GLP-1RA-naïve people, and -5.6 (-6.2; -5.0) mmol/mol (P < 0.001) for GLP-1RA-experienced people. Similarly, 55% of GLP-1RA-naïve people and 43% of GLP-1RA-experienced people reached a HbA1c target of ≤53 mmol/mol after 2 years. CONCLUSIONS: People treated with semaglutide in routine clinical practice experienced clinically relevant and sustained improvements in glycaemic control after 180, 360, 540 and 720 days, irrespective of former GLP-1RA exposure, effects which were comparable with those observed in clinical studies. These results support the use of semaglutide in routine clinical practice for the long-term management of T2D.

[Non-motor symptoms in Parkinson's disease].

Parkinson's disease is a neurodegenerative movement disorder with a broad spectrum of both motor- and non-motor symptoms. A new top-down model for pathogenesis has recently been suggested, supporting the hypothesis on onset of prodromal non-motor features several years before motor symptoms. Non-motor symptoms have a high prevalence and a substantial effect on quality of life and disease burden. There are limited therapies available for non-motor deficits, although increased focus on pharmacological and non-pharmacological treatments raises quality of life among patients, which is summarised and discussed in this review.

Correlates of serum IGF-1 in young children with moderate acute malnutrition: a cross-sectional study in Burkina Faso.

BACKGROUND: Serum insulin-like growth factor 1 (sIGF-1) is an important growth factor in childhood. However, studies on sIGF-1 among children from low-income countries are few, and the role of body composition is unknown. OBJECTIVES: To assess the associations of anthropometry, body composition, inflammation, and breastfeeding with sIGF-1 among children with moderate acute malnutrition (MAM). METHODS: A cross-sectional study based on admission data from 6- to 23-mo-old children with MAM participating in a nutrition intervention trial (Treatfood) in Burkina Faso. Linear regression analysis was used to identify correlates of sIGF-1. RESULTS: Among 1546 children, the median (IQR) sIGF-1 was 12 (8.2-18.3) ng/mL. sIGF-1 was highest at 6 mo, with a nadir ∼10-11 mo, and higher in girls than boys. Length-for-age z score (LAZ), weight-for-length z score (WLZ), and midupper arm circumference were positively associated with sIGF-1 (P ≤ 0.001). Fat-free mass (FFM) was also positively associated, as sIGF-1 increased 1.5 (95% CI: 0.5, 2.5) ng/mL for each 1-kg increase in FFM. However, the association disappeared after adjustment for height. Elevated serum C-reactive protein and α1-acid glycoprotein were negatively associated with sIGF-1 (P ≤ 0.001), as was fever (P < 0.001) but not a positive malaria test per se (P = 0.15). Children never breastfed had lower sIGF-1 (-5.1; 95% CI: -9.8, -0.3). CONCLUSIONS: LAZ and WLZ were positively and inflammation negatively associated with sIGF-1. As all children were moderately malnourished and many had inflammation, this probably explains the very low median sIGF-1. The association of FFM with sIGF-1 was fully explained by height. There was a marked age pattern, with a nadir in late infancy, confirming findings from smaller studies from well-nourished populations. There is a need for prospective studies to disentangle the role of sIGF-1 in growth and health. This trial was registered at https://www.isrctn.com as ISRCTN42569496.

Socioeconomic Inequality in Metabolic Control Among Children With Type 1 Diabetes: A Nationwide Longitudinal Study of 4,079 Danish Children.

OBJECTIVE: To examine inequality in glycemic control by maternal educational level among children with type 1 diabetes in a setting with universal access to health care. RESEARCH DESIGN AND METHODS: This was a longitudinal nationwide study of 4,079 Danish children with type 1 diabetes between the years 2000 and 2013. Children were divided into four groups based on mothers' education prebirth (≤high school [n = 1,643], vocational or 2-year college [n = 1,548], bachelor's degree [n = 695], ≥master's degree [n = 193]). Means of socioeconomic and treatment characteristics were compared between groups. HbA1c and the number of daily glucose tests were compared repeatedly from onset until 5 years after onset across groups. HbA1c was compared across daily blood glucose testing frequency and groups. Linear regression was used to compare HbA1c across groups with and without adjustment for socioeconomic and treatment characteristics. RESULTS: Large differences in HbA1c across maternal education were found. The mean level of HbA1c during follow-up was 59.7 mmol/mol (7.6%) for children of mothers with ≥master's degrees and 68.7 mmol/mol (8.4%) for children of mothers with ≤high school (difference: 9.0 mmol/mol [95% CI 7.5, 10.6]; 0.8% [95% CI 0.7, 1.0]). The associations were attenuated but remained significant after adjustment. Observable characteristics explained 41.2% of the difference in HbA1c between children of mothers with ≤high school and mothers with ≥master's degree; 22.5% of the difference was explained by more frequent blood glucose monitoring among the children with the highly educated mothers. CONCLUSIONS: Family background is significantly related to outcomes for children with type 1 diabetes, even with universal access to health care.

Sick of retirement?

This paper examines the causal effect of retirement on health and healthcare utilization using two identification strategies on Danish full population data. First, I use a reform of the statutory retirement age in an IV design. Second, I use a large discontinuity in retirement take-up at the earliest age of retirement (60) in a regression discontinuity design. The results show that early retirement leads to decreases in GP visits and hospitalizations of 8-10% in the short run. The reduction in GP visits is driven by a drop in female GP utilization, while both genders contribute equally to the decline in hospitalizations. Early retirement has no effect on health measured by comorbidities or mortality. Statutory retirement has no effect on health or healthcare utilization. The results suggest that gender, age at retirement and complier composition are important sources of heterogeneity.

PET/DW-MRI for evaluating treatment in chronic hepatitis C patients.

This feasibility study set out to investigate the use of FDG-PET/DW-MRI in chronic hepatitis C patients to examine changes in local liver inflammation after treatment with direct-acting antivirals (DAA). Twelve patients with chronic hepatitis C were prospectively enrolled, performing FDG-PET/DW-MRI prior to and after DAA treatment. PET/DW-MRI included PET acquisition 60 and 90 min after FDG-injection, DIXON, for attenuation correction, T2- and DW-MRI with 10 b-values between 0-700 s/mm2. The following parameters were measured from fusion of 3 volumes of interest (VOIs) placed in the liver parenchyma: Mean standard uptake value after 60 and 90 minutes (SUVmean60 and SUVmean90), total Apparent Diffusion Coefficient (ADC), perfusion fraction (PF), pseudo-diffusion (D*) and perfusion-free diffusion (D). We found PET/DW-MRI of chronic hepatitis C patients to be feasible. Patients were cooperative, tolerated the scans well and the image quality was acceptable. A total of 10 patients were available for final analysis. All patients achieved sustained virologic response and normalized alanine-aminotransferase (ALAT) levels after treatment with DAA. Perfusion fraction measured by DW-MRI changed significantly after treatment, from mean 0.21 (± 0.04) to 0.26 (± 0.06), P=0.005 and D* from 0.50 (± 0.13) × 10-3 s/mm2 to 0.62 (± 0.15) × 10-3 s/mm2, P=0.028. All other parameters, including FDG-uptake, was unchanged. These results suggest that liver perfusion is changed shortly after DAA treatment, with no significant change in inflammation. The study concludes that PET/DW-MR is feasible in quantifying perfusion and possibly inflammation in chronic hepatitis C patients and may be used to follow treatment.

Association of Type 1 Diabetes With Standardized Test Scores of Danish Schoolchildren.

Importance: Type 1 diabetes has been associated with cardiovascular disease and late complications such as retinopathy and nephropathy. However, it is unclear whether there is an association between type 1 diabetes and school performance in children. Objective: To compare standardized reading and mathematics test scores of schoolchildren with type 1 diabetes vs those without diabetes. Design, Setting, and Participants: Population-based retrospective cohort study from January 1, 2011, to December 31, 2015 (end date of follow-up), including Danish public schoolchildren attending grades 2, 3, 4, 6, and 8. Test scores were obtained in math (n = 524 764) and reading (n = 1 037 006). Linear regression models compared outcomes with and without adjustment for socioeconomic characteristics. Exposures: Type 1 diabetes. Main Outcomes and Measures: Primary outcomes were pooled test scores in math and reading (range, 1-100). Results: Among 631 620 included public schoolchildren, the mean (SD) age was 10.31 (SD, 2.42) years, and 51% were male; 2031 had a confirmed diagnosis of type 1 diabetes. Overall, the mean combined score in math and reading was 56.11 (SD, 24.93). There were no significant differences in test scores found between children with type 1 diabetes (mean, 56.56) and children without diabetes (mean, 56.11; difference, 0.45 [95% CI, -0.31 to 1.22]). The estimated difference in test scores between children with and without type 1 diabetes from a linear regression model with adjustment for grade, test topic, and year was 0.24 (95% CI, -0.90 to 1.39) and 0.45 (95% CI, -0.58 to 1.49) with additional adjustment for socioeconomic status. Conclusions and Relevance: Among Danish public schoolchildren, there was no significant difference in standardized reading and mathematics test scores of children with type 1 diabetes compared with test scores of children without diabetes.

Impaired Platelet Aggregation and Rebalanced Hemostasis in Patients with Chronic Hepatitis C Virus Infection.

Increased risk of both cardiovascular disease (CVD) and bleeding has been found in patients with chronic hepatitis C (CHC) infection, and a re-balanced hemostasis has been proposed. The aim of this study was to investigate functional whole blood coagulation and platelet function in CHC infection. The prospective study included 82 patients with CHC infection (39 with advanced liver fibrosis and 43 with no or mild liver fibrosis) and 39 healthy controls. A total of 33 patients were treated for CHC infection and achieved sustained virological response (SVR). Baseline and post-treatment blood samples were collected. Hemostasis was assessed by both standard coagulation tests and functional whole blood hemostatic assays (thromboelastograhy (TEG), and platelet aggregation (Multiplate). Patients with CHC and advanced fibrosis had impaired platelet aggregation both compared to patients with no or mild fibrosis and to healthy controls. Patients with CHC and advanced fibrosis also had lower antithrombin, platelet count, and coagulation factors II-VII-X compared to healthy controls. In contrast, TEG did not differ between groups. In treated patients achieving SVR, post-treatment platelet count was higher than pre-treatment counts (p = 0.033) and ADPtest, ASPItest, and RISTOhightest all increased post treatment (all p < 0.05). All Multiplate tests values, however, remained below those in the healthy controls. CHC-infected patients displayed evidence of rebalanced hemostasis with only partly hemostatic normalization in patients achieving SVR. The implications of rebalanced hemostasis and especially the impact on risk of CVD and bleeding warrants further studies.

Immune regulation in chronic hepatitis C virus infection.

The immunological result of infection with Hepatitis C virus (HCV) depends on the delicate balance between a vigorous immune response that may clear the infection, but with a risk of unspecific inflammation and, or a less inflammatory response that leads to chronic infection. In general, exhaustion and impairment of cytotoxic function of HCV-specific T cells and NK cells are found in patients with chronic HCV infection. In contrast, an increase in immune regulatory functions is found primarily in form of increased IL-10 production possibly due to increased level and function of anti-inflammatory Tregs. Thus, the major immune players during chronic HCV infection are characterized by a decrease of cytotoxic function and increase of inhibitory functions. This may be an approach to diminish intrahepatic and systemic inflammation. Finally, there has been increasing awareness of regulatory functions of epigenetic changes in chronic HCV infection. A vast amount of studies have revealed the complexity of immune regulation in chronic HCV infection, but the interplay between immune regulation in virus and host remains incompletely understood. This review provides an overview of regulatory functions of HCV-specific T cells, NK cells, Tregs, IL-10, and TGF-ß, as well as epigenetic changes in the setting of chronic HCV infection.