Lipid Levels and Risk of Diabetic Polyneuropathy in 2 Danish Type 2 Diabetes Cohorts.

BACKGROUND AND OBJECTIVES: Reduction of blood lipids may aid in preventing diabetic polyneuropathy (DPN), but evidence remains conflicting. We investigated the association between lipid parameters and DPN risk in individuals with type 2 diabetes mellitus (T2DM). METHODS: We conducted a population-based cohort study of individuals with newly diagnosed T2DM and a cross-sectional study using a clinically recruited T2DM cohort. Triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and non-HDL cholesterol were measured in routine diabetes care. Each lipid parameter was categorized according to the latest cutoffs in clinical guidelines on dyslipidemia. DPN was assessed with validated hospital diagnosis codes in the population-based cohort and with the Michigan Neuropathy Screening Instrument questionnaire in the clinical cohort. We calculated hazard ratios (HRs) using Cox regression and prevalence ratios (PRs) using Poisson regression. RESULTS: We included 61,853 individuals in the population-based cohort (median age 63 [quartiles 54-72] years) and 4,823 in the clinical cohort (median age 65 [quartiles 57-72] years). The incidence rate of hospital-diagnosed DPN in the population-based cohort was 3.6 per 1000 person-years during a median follow-up of 7.3 years. Achieving guideline targets for HDL, LDL, and non-HDL cholesterol showed no association with DPN risk. By contrast, adjusted HRs (95% CI) for DPN were 1.02 (0.89-1.18) for triglyceride levels between 150 and 204 mg/dL (1.7-2.3 mmol/L) and 1.28 (1.13-1.45) for levels >204 mg/dL (2.3 mmol/L). In the clinical cohort with a DPN prevalence of 18%, DPN associated strongly with triglycerides >204 mg/dL (2.3 mmol/L) with an adjusted PR (95% CI) of 1.40 (1.21-1.62). The prevalence of DPN was modestly elevated for individuals with HDL cholesterol <39 mg/dL (1.0/1.3 mmol/L) in men and <50 mg/dL (1.3 mmol/L) in women (PR 1.13 [0.99-1.28]) and for individuals with non-HDL cholesterol >131 mg/dL (3.4 mmol/L) (PR 1.27 [1.05-1.52]). In both cohorts, spline models showed an increasing risk of DPN starting from triglyceride levels >124 mg/dL (1.4 mmol/L). All results were similar among statin users. DISCUSSION: High triglyceride levels are a strong DPN risk factor. Future intervention studies shall determine whether triglyceride reduction is more important for DPN prevention than reduction of other lipids.

Risk of mortality and recurrence after first-time stroke among patients with type 2 diabetes: A Danish nationwide cohort study.

INTRODUCTION: The prognosis for stroke patients with type 2 diabetes mellitus (T2DM) remains poorly understood. We examined the risk of mortality and stroke recurrence in stroke patients with T2DM and stroke patients without diabetes. PATIENTS AND METHODS: We conducted a population-based cohort study including all patients diagnosed with a first-time ischemic stroke (n = 131,594) or intracerebral hemorrhage (ICH, n = 15,492) in Denmark, 2005-2021. Patients with T2DM were identified using hospital diagnosis codes and glucose-lowering drug prescriptions. We calculated risks, risk differences, and risk ratios, standardized by age, sex, and calendar year of stroke admission. RESULTS: Following ischemic stroke, the 5-year standardized mortality was 46.1% for patients with T2DM and 35.4% for patients without diabetes (standardized risk difference: 10.7% [95% CI 9.9-11.6]; risk ratio: 1.3 [95% CI 1.3-1.3]). The 5-year risk of recurrence following ischemic stroke was 12.7% for patients with T2DM and 11.3% for those without diabetes (risk difference: 1.4% [95% CI 0.9-2.0]; risk ratio: 1.1 [95% CI 1.1-1.2]). Following ICH, the 5-year mortality was 62.8% for patients with T2DM and 53.0% for patients without diabetes (risk difference: 9.8% [95% CI 7.2-12.4)]; risk ratio: 1.2 [95% CI 1.1-1.2]). The 5-year risk of recurrence after ICH was 9.1% for patients with T2DM and 9.7% for patients without diabetes. DISCUSSION AND CONCLUSION: Stroke patients with T2DM were at increased risk of mortality. The risk of stroke recurrence was slightly higher for ischemic stroke patients with T2DM than patients without diabetes, while no difference was observed among ICH patients.

Risk of Bleeding and Venous Thromboembolism after Colorectal Cancer Surgery in Patients with and without Type 2 Diabetes: A Danish Cohort Study.

Background Bleeding and venous thromboembolism (VTE) are adverse outcomes after colorectal cancer (CRC) surgery. Type 2 diabetes (T2D) clusters with bleeding and VTE risk factors. We examined the bleeding and VTE risk in patients with T2D undergoing CRC surgery and the prognosis after these adverse outcomes. Methods We conducted a prognostic population-based cohort study of 48,295 patients with and without T2D undergoing surgery for incident CRC during 2005 to 2019. Patients with T2D were diagnosed in a hospital setting or had redeemed a glucose-lowering drug prescription; the remaining cohort was patients without diabetes. We estimated the 30-day and 1-year risks of bleeding and VTE and used a Fine-Gray model to compute age-, sex-, and calendar year-adjusted subdistribution hazard ratios (SHRs). The Kaplan-Meier method was used to calculate 1-year mortality after bleeding or VTE. Results Within 30 days after CRC surgery, the risk of bleeding was 2.7% in patients with T2D and 2.0% in patients without diabetes (SHR: 1.30 [95% confidence interval [CI]: 1.10-1.53]). For VTE, the 30-day risks were 0.6% for patients with T2D and 0.6% for patients without diabetes (SHR: 1.01 [95% CI: 0.71-1.42]). The SHRs for bleeding and VTE within 1 year after CRC surgery were similar. The 1-year mortality was 26.0% versus 24.9% in the bleeding cohort and 25.8% versus 27.5% in the VTE cohort for patients with T2D versus without diabetes, respectively. Conclusion Although absolute risks were low, patients with T2D have an increased risk of bleeding but not VTE after CRC surgery.

Cohort Profile: Better Health in Late Life.

Purpose: Humans are living longer and may develop multiple chronic diseases in later life. The Better Health in Late Life cohort study aims to improve our understanding of the risks and outcomes of multimorbidity in the Danish population. Methods: A randomly-selected sample of Danish residents who were 50-65 years of age received a questionnaire and an invitation to participate in this study. Respondents completed an online survey between October 2021 and January 2022 which addressed topics that included self-assessed health, mental health, sleep, specific medical conditions, use of painkillers, diet, alcohol consumption, smoking, physical activity, and body composition. This information was linked to the Danish health and social registries (some established in 1943 and onwards) that maintain data on filled prescriptions, hospital records, socioeconomic status, and health care utilization. Results: Responses were received from 115,431 of the 301,244 residents invited to participate (38%). We excluded respondents who answered none of the questions as well as those who provided no information on sex or indicated an age other than 50-65 years. Of the 114,283 eligible respondents, 54.8% were female, 30.3% were overweight, and 16.7% were obese. Most participants reported a weekly alcohol consumption of less than seven units and 13.3% were current smokers; 5.2% had a history of hospitalization for solid cancer, and 3.0%, 2.3%, 2.0%, and 0.9% reported chronic pulmonary disease, diabetes, stroke, and myocardial infarction, respectively. The most frequently filled prescriptions were for medications used to treat the nervous system and cardiovascular diseases (38.1% and 37.4%, respectively).

Leisure-Time Physical Activity and Risk of Microvascular Complications in Individuals With Type 2 Diabetes: A UK Biobank Study.

OBJECTIVE: The aim of this study was to determine dose-response associations, including the minimal effective level, between leisure-time physical activity and risk of incident neuropathy, nephropathy, and retinopathy. RESEARCH DESIGN AND METHODS: This cohort study included 18,092 individuals with type 2 diabetes from the UK Biobank. Self-reported leisure-time physical activity was converted into MET-hours per week. Participants were categorized into no physical activity (0 MET-h/week), below recommendations (0-7.49 MET-h/week), at recommendations (7.5-14.9 MET-h/week), and above recommendations (≥15 MET-h/week). Microvascular complications were identified from hospital inpatient records using diagnosis codes. We used Cox proportional hazards regression analysis to calculate adjusted hazard ratios (aHRs) and restricted cubic splines to identify the minimal effective level of physical activity. RESULTS: During a median follow-up of 12.1 years, 672 individuals (3.7%) were diagnosed with neuropathy, 1,839 (10.2%) with nephropathy, and 2,099 (11.7%) with retinopathy. Any level of physical activity was associated with a lower risk of neuropathy and nephropathy but not retinopathy. Compared with those reporting no physical activity, the aHR of neuropathy was 0.71 (95% CI 0.53, 0.90) below recommendations, 0.73 (0.56, 0.96) at recommendations, and 0.67 (0.52, 0.87) above recommendations. Corresponding aHRs for nephropathy were 0.79 (0.68, 0.92), 0.80 (0.67, 0.95), and 0.80 (0.68, 0.95). The association with retinopathy was weaker, with aHRs of 0.91 (0.78, 1.06), 0.91 (0.77, 1.08), and 0.98 (0.84, 1.15), respectively. CONCLUSIONS: Any level of leisure-time physical activity was associated with a lower risk of neuropathy and nephropathy but not retinopathy in individuals with type 2 diabetes. For both neuropathy and nephropathy, the minimal effective physical activity level may correspond to <1.5 h of walking per week.

Triglycerides and risk of cardiovascular events in statin-treated patients with newly diagnosed type 2 diabetes: a Danish cohort study.

BACKGROUND: Elevated triglyceride levels are a clinically useful marker of remnant cholesterol. It is unknown whether triglycerides are associated with residual cardiovascular risk in CVD-naïve patients with newly diagnosed type 2 diabetes mellitus (T2DM), who are already on statin therapy. We aimed to assess the association between triglyceride levels and risk of major cardiovascular events (MACE) in statin-treated patients with newly diagnosed T2DM managed in routine clinical care. METHODS: This cohort study included newly diagnosed T2DM patients without a previous diagnosis of cardiovascular disease in Northern Denmark during 2005-2017. Individual triglyceride levels while on statin treatment were assessed within 1 year after T2DM diagnosis. The primary outcome was a composite of myocardial infarction, ischemic stroke, or cardiac death (MACE). Patients were followed from one year after T2DM diagnosis until 30 April 2021, MACE, emigration, or death. We used Cox regression to compute hazard ratios (HRs) controlling for confounding factors. RESULTS: Among 27,080 statin-treated patients with T2DM (median age 63 years; 53% males), triglyceride levels were < 1.0 mmol/L in 17%, 1.0-1.9 mmol/L in 52%, 2.0-2.9 mmol/L in 20%, and ≥ 3.0 mmol/L in 11%. During follow-up, 1,957 incident MACE events occurred (11.0 per 1000 person-years). Compared with triglyceride levels < 1.0 mmol/L, confounder-adjusted HRs for incident MACE were 1.14 (95% CI 1.00-1.29) for levels between 1.0 and 1.9 mmol/L, 1.30 (95% CI 1.12-1.51) for levels between 2.0 and 2.9 mmol/L, and 1.44 (95% CI 1.20-1.73) for levels ≥ 3.0 mmol/L. This association was primarily driven by higher rates of myocardial infarction and cardiac death and attenuated only slightly after additional adjustment for LDL cholesterol. Spline analyses confirmed a linearly increasing risk of MACE with higher triglyceride levels. Stratified analyses showed that the associations between triglyceride levels and MACE were stronger among women. CONCLUSIONS: In statin-treated patients with newly diagnosed T2DM, triglyceride levels are associated with MACE already from 1.0 mmol/L. This suggests that high triglyceride levels are a predictor of residual cardiovascular risk in early T2DM and could be used to guide allocation of additional lipid-lowering therapies for CVD prevention.

The Prevalence of Polyneuropathy in Type 2 Diabetes Subgroups Based on HOMA2 Indices of ß-Cell Function and Insulin Sensitivity.

OBJECTIVE: Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of ß-cell function and insulin sensitivity. RESEARCH DESIGN AND METHODS: We estimated ß-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM. Patients were categorized into subgroups of hyperinsulinemic (high HOMA2-B, low HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and insulinopenic (low HOMA2-B, high HOMA2-S) T2DM. After a median follow-up of 3 years, patients filled the Michigan Neuropathy Screening Instrument questionnaire (MNSIq) to identify DPN (score ≥ 4). We used Poisson regression to calculate adjusted prevalence ratios (PRs) for DPN, and spline models to examine the association with HOMA2-B and HOMA2-S. RESULTS: A total of 3,397 (77%) patients filled in the MNSIq. The prevalence of DPN was 23% among hyperinsulinemic, 16% among classical, and 14% among insulinopenic patients. After adjusting for demographics, diabetes duration and therapy, lifestyle behaviors, and metabolic syndrome components (waist circumference, triglycerides, HDL cholesterol, hypertension, and HbA1c), the PR of DPN was 1.35 (95% CI 1.15-1.57) for the hyperinsulinemic compared with the classical patients. In spline analyses, we observed a linear relation of higher DPN prevalence with increasing HOMA2-B, independent of both metabolic syndrome components and HOMA2-S. CONCLUSIONS: Hyperinsulinemia marked by high HOMA2-B is likely an important risk factor for DPN beyond metabolic syndrome components and insulin resistance. This should be considered when developing interventions to prevent DPN.

Health registries as research tools: a review of methodological key issues.

Health registries provide opportunities for conducting large-scale, population-based studies, but attention must be devoted to their specific limitations. Herein, we describe potential limitations that may affect the validity of registry-based research. Our review includes descriptions of 1) populations, 2) variables, 3) medical coding systems for medical information and 4) selected key methodological challenges. Knowledge of such factors and epidemiological study designs in general is likely to increase the quality of registry-based research and reduce potential biases.

Four-year HbA1c and LDL-cholesterol trajectories among individuals with mental disorders and newly developed type 2 diabetes.

The impact of different types of mental disorders on long-term glycemic and lipid trajectories following newly diagnosed type 2 diabetes (T2D) remains unknown. We used real-world clinical data in a population-based cohort to fill this knowledge gap. We found that individuals with new T2D and preexisting personality, anxiety, unipolar depression, or psychotic disorder had higher mean HbA1c levels over 4 years following the onset of T2D, whereas no differences were found regarding LDL-C levels. This knowledge should be considered in the management of T2D in these vulnerable groups.

Statin Therapy and Risk of Polyneuropathy in Type 2 Diabetes: A Danish Cohort Study.

OBJECTIVE: Statins may reduce the risk of diabetic polyneuropathy (DPN) as a result of lipid-lowering and anti-inflammatory effects, but statins have also been associated with neurotoxicity. We examined whether statin therapy affects the risk of DPN. RESEARCH DESIGN AND METHODS: We identified all Danish patients with incident type 2 diabetes during 2002-2016. New users initiated statins between 180 days before and 180 days after their first diabetes record, while prevalent users had initiated statins before that period. Patients were followed for incident DPN using validated hospital diagnosis codes, starting 180 days after their first diabetes record. Cox proportional hazard analysis was used to compute adjusted hazard ratios (aHRs) for DPN. RESULTS: The study cohort comprised 59,255 (23%) new users, 75,528 (29%) prevalent users, and 124,842 (48%) nonusers; median follow-up time was 6.2 years (interquartile range 3.4-9.6). The incidence rate of DPN events per 1,000 person-years was similar in new users (4.0 [95% CI 3.8-4.2]), prevalent users (3.8 [3.6-3.9]), and nonusers (3.8 [3.7-4.0]). The aHR for DPN was 1.05 (0.98-1.11) in new users and 0.97 (0.91-1.04) in prevalent users compared with statin nonusers. New users had a slightly increased DPN risk during the first year (1.31 [1.12-1.53]), which vanished after >2 years of follow-up. Findings were similar in on-treatment and propensity score-matched analyses and with additional adjustment for pretreatment blood lipid levels. CONCLUSIONS: Statin therapy is unlikely to increase or mitigate DPN risk in patients with type 2 diabetes, although a small acute risk of harm cannot be excluded.

The 2017 Oslo conference report on neglected tropical diseases and emerging/re-emerging infectious diseases - focus on populations underserved.

BACKGROUND: In 2017, the Centre for Global Health (CGH) at the University of Oslo in collaboration with the Coalition for Epidemic Preparedness Innovations (CEPI) and the Norwegian Agency for Development Cooperation (Norad) held a meeting to discuss together with leading figures in disease control, research and development the issue of neglected tropical diseases and emerging/re-emerging infectious diseases. This commentary has taken up this discussion and the conclusions drawn at this meeting to make a case for the opportunity the Sustainable Development Goals (SDGs) provide in highlighting the interconnectedness of factors that are relevant in the successful fight against neglected tropical diseases (NTDs) and emerging infectious diseases (EIDS). MAIN BODY: Despite NTDs being endemic and EIDS being epidemic, in order to prevent both disease groups effectively, it is important to appreciate that they share essential health determining factors, namely: neglect, poverty, a lack of access to clean water and sanitation facilities and an absence of or severely limited provision of healthcare as well as in many cases a zoonotic nature. Instead of looking to "simple disease management" for the answer, the SDGs help to understand the interplay of multiple priority areas and thereby help to promote a more holistic approach to addressing these two disease groups. CONCLUSIONS: Their commonalities mean that the Global Health community should leverage opportunities and efforts in the prevention and elimination of both NTDs and EIDs. Doing so using a One Health approach is considered to offer a "public health best-buy". Concrete solutions are proposed.

Variations in pediatric asthma hospitalization rates and costs between and within Nordic countries.

BACKGROUND: We assessed variations in hospitalization parameters and costs among asthmatic children in four Nordic countries by geographic location and age groups. METHODS: Cross-sectional, county-level aggregate data on asthma-related hospitalizations in 1999, obtained from public national databases for children < 15 years old from Denmark, Sweden, Norway, and Finland, together with country-specific asthma management cost were used to estimate the incidence of first hospital admission (per 1,000), length of hospital stay (LOS), and hospitalization cost. Longitudinal patient-specific data from 1998/1999 were used to calculate the relative hazard of readmission (RHR) using a multivariate Cox proportional hazards model. RESULTS: Nordic incidence of first hospital admission in 1999 was 2.17 per 1,000 children, readmission was noted in 16% of the patients, mean LOS was 2.64 days, and total hospitalization cost was almost 14 million dollars. Hospitalization incidence, RHR, and costs were significantly higher in children < 5 years old compared with school children 6 to 14 years old. Hospital LOS, incidence of first hospital admission, and cost per child were the highest in Denmark, though RHR did not differ significantly from Sweden. CONCLUSIONS: Large variations in all parameters were observed between and within countries. Given the similarities among the four countries studied, these results may, among other reasons, indicate different efficiencies of the various asthma management plans between and within them. The presented measures of hospitalization patterns could prove to be valuable quality-of-care measures to guide further improvements in asthma management.