Morten Charles

Prevalence of Neuropathy and Peripheral Arterial Disease and the Impact of Treatment in People With Screen-Detected Type 2 Diabetes: The ADDITION-Denmark study

OBJECTIVE There is limited evidence on how intensive multifactorial treatment (IT) improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice. We examined the effects of early detection and IT of type 2 diabetes in primary care on the prevalence of diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) 6 years later in a pragmatic, cluster-randomized parallel group trial. RESEARCH DESIGN AND METHODS A stepwise screening program in 190 general practices in Denmark was used to identify 1,533 people with type 2 diabetes. General practices were randomized to deliver either IT or routine care (RC) as recommended through national guidelines. Participants were followed for 6 years and measures of DPN and PAD were applied. RESULTS We found no statistically significant effect of IT on the prevalence of DPN and PAD compared with RC. The prevalence of an ankle brachial index ≤0.9 was 9.1% (95% CI 6.0–12.2) in the RC arm and 7.3% (5.0–9.6) in the IT arm. In participants tested for vibration detection threshold and light touch sensation, the prevalence of a least one abnormal test was 34.8% (26.7–43.0) in the RC arm and 30.1% (24.1–36.1) in the IT arm. CONCLUSIONS In a population with screen-detected type 2 diabetes, we did not find that screening followed by IT led to a statistically significant difference in the prevalence of DPN and PAD 6 years after diagnosis. However, treatment levels were high in both groups.

Low Peripheral Nerve Conduction Velocities and Amplitudes Are Strongly Related to Diabetic Microvascular Complications in Type 1 Diabetes: The EURODIAB Prospective Complications Study

OBJECTIVE Slow nerve conduction velocity and reduction in response amplitude are objective hallmarks of diabetic sensorimotor polyneuropathy. Because subjective or clinical indicators of neuropathy do not always match well with the presence of abnormal nerve physiology tests, we evaluated associations to nerve conduction in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Nerve conduction studies were performed in the distal sural and ulnar sensory nerves and the peroneal motor nerve in 456 individuals with type 1 diabetes who participated in the follow-up visit of the EURODIAB Prospective Complications Study (EPCS). We used multivariate regression models to describe associations to decreased nerve conduction measures. RESULTS In addition to an effect of duration of diabetes and A1C, which were both associated with low nerve conduction velocity and response amplitude, we found that the presence of nephropathy, retinopathy, or a clinical diagnosis of neuropathy was associated with low nerve conduction velocity and amplitude. In the case of nonproliferative retinopathy, the odds ratio (OR) for being in lowest tertile was 2.30 (95% CI 1.13–4.67) for nerve conduction velocity. A similar OR was found for each 2% difference in A1C (2.39 [1.68–3.41]). CONCLUSIONS We show that the presence of other microvascular diabetes complications, together with diabetes duration and A1C, are associated with low nerve conduction velocity and amplitude response and that cardiovascular disease or risk factors do not seem to be associated with these measures.

Long-term Risk of Dementia in Persons With Schizophrenia: A Danish Population-Based Cohort Study.

IMPORTANCE Although schizophrenia is associated with several age-related disorders and considerable cognitive impairment, it remains unclear whether the risk of dementia is higher among persons with schizophrenia compared with those without schizophrenia. OBJECTIVE To determine the risk of dementia among persons with schizophrenia compared with those without schizophrenia in a large nationwide cohort study with up to 18 years of follow-up, taking age and established risk factors for dementia into account. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study of more than 2.8 million persons aged 50 years or older used individual data from 6 nationwide registers in Denmark. A total of 20 683 individuals had schizophrenia. Follow-up started on January 1, 1995, and ended on January 1, 2013. Analysis was conducted from January 1, 2015, to April 30, 2015. MAIN OUTCOMES AND MEASURES Incidence rate ratios (IRRs) and cumulative incidence proportions (CIPs) of dementia for persons with schizophrenia compared with persons without schizophrenia. RESULTS During 18 years of follow-up, 136 012 individuals, including 944 individuals with a history of schizophrenia, developed dementia. Schizophrenia was associated with a more than 2-fold higher risk of all-cause dementia (IRR, 2.13; 95% CI, 2.00-2.27) after adjusting for age, sex, and calendar period. The estimates (reported as IRR; 95% CI) did not change substantially when adjusting for medical comorbidities, such as cardiovascular diseases and diabetes mellitus (2.01; 1.89-2.15) but decreased slightly when adjusting for substance abuse (1.71; 1.60-1.82). The association between schizophrenia and dementia risk was stable when evaluated in subgroups characterized by demographics and comorbidities, although the IRR was higher among individuals younger than 65 years (3.77; 3.29-4.33), men (2.38; 2.13-2.66), individuals living with a partner (3.16; 2.71-3.69), those without cerebrovascular disease (2.23; 2.08-2.39), and those without substance abuse (1.96; 1.82-2.11). The CIPs (95% CIs) of developing dementia by the age of 65 years were 1.8% (1.5%-2.2%) for persons with schizophrenia and 0.6% (0.6%-0.7%) for persons without schizophrenia. The respective CIPs for persons with and without schizophrenia were 7.4% (6.8%-8.1%) and 5.8% (5.8%-5.9%) by the age of 80 years. CONCLUSIONS AND RELEVANCE Individuals with schizophrenia, especially those younger than 65 years, had a markedly increased relative risk of dementia that could not be explained by established dementia risk factors.

Long-term mortality of persons with severe mental illness and diabetes: a population-based cohort study in Denmark

BACKGROUND Persons with severe mental illness (SMI) have excess mortality, which may partly be explained by their high prevalence of diabetes. METHOD We compared the overall and cause-specific mortality in persons with SMI and diabetes with that of the general Danish population between 1997 and 2009 by linking data from Danish national registries. RESULTS The cohort counted 4 734 703 persons, and during follow-up 651 080 persons died of whom 1083 persons had SMI and diabetes. Compared with the background population, the overall mortality rate ratios (MRRs) for persons with SMI and diabetes were 4.14 [95% confidence interval (CI) 3.81-4.51] for men and 3.13 (95% CI 2.88-3.40) for women. The cause-specific MRRs for persons with SMI and diabetes were lowest for malignant neoplasms (women: MRR = 1.98, 95% CI 1.64-2.39; men: MRR = 2.08, 95% CI 1.69-2.56) and highest for unnatural causes of death (women: MRR = 12.31, 95% CI 6.80-22.28; men: MRR = 7.89, 95% CI 5.51-11.29). The cumulative risks of death within 7 years of diabetes diagnosis for persons with SMI and diabetes were 15.0% (95% CI 12.4-17.6%) for those younger than 50 years, 30.7% (95% CI 27.8-33.4%) for those aged 50-69 years, and 63.8% (95% CI 58.9-68.2%) for those aged 70 years or older. Among persons suffering from both diseases, 33.4% of natural deaths were attributed to diabetes and 14% of natural deaths were attributed to the interaction between diabetes and SMI. CONCLUSIONS Long-term mortality is high for persons with SMI and diabetes. This calls for effective intervention from a coordinated and collaborating healthcare system.

Effect of Intensive Multifactorial Treatment Compared With Routine Care on Aortic Stiffness and Central Blood Pressure Among Individuals With Screen-Detected Type 2 Diabetes: The ADDITION-Denmark study

OBJECTIVE Diabetes is associated with increased brachial and central blood pressure and aortic stiffness. We examined the effect of intensive multifactorial treatment in general practice on indices of peripheral and central hemodynamics among patients with screen-detected diabetes. RESEARCH DESIGN AND METHODS As part of a population-based screening and intervention study in general practice, 1,533 Danes aged 40–69 years were clinically diagnosed with screen-detected diabetes. General practitioners were randomized to provide intensive multifactorial treatment or routine care. After a mean follow-up of 6.2 years, an unselected subsample of 456 patients underwent central hemodynamic assessments by applanation tonometry. Central pressure was derived from the radial pulse wave. Aortic stiffness was assessed as carotid-femoral pulse wave velocity (aPWV). The intervention effect on each index of central hemodynamics was analyzed by mixed-effects models adjusted for heart rate, cluster randomization, age, and sex. RESULTS At screening, median age was 59.2 years (interquartile range 55.2–64.6); 289 patients (63%) were in the intensive treatment group, and 278 patients (61%) were men. Patients in the intensive treatment group had a 0.51 m/s (95% CI −0.96 to −0.05, P = 0.03) lower aPWV compared with routine care. Respective differences for central augmentation index (−0.84% [−2.54 to 0.86]), pulse pressure (0.28 mmHg [−1.75 to 2.32]), and systolic (−1.42 mmHg [−4.47 to 1.64]) and diastolic (−1.79 mmHg [−3.72 to 0.14]) blood pressure were not statistically significant. CONCLUSIONS Intensive multifactorial treatment of screen-detected diabetes during 6 years in general practice has a significant impact on aortic stiffness, whereas the effects on other hemodynamic measures are smaller and not statistically significant.

Thirty-Day Mortality After Infection Among Persons With Severe Mental Illness: A Population-Based Cohort Study in Denmark

OBJECTIVE Persons with severe mental illness die 15-20 years earlier on average than persons without severe mental illness. Although infection is one of the leading overall causes of death, no studies have evaluated whether persons with severe mental illness have a higher mortality after infection than those without. METHOD The authors studied mortality rate ratios and cumulative mortality proportions after an admission for infection for persons with severe mental illness compared with persons without severe mental illness by linking data from Danish national registries. RESULTS The cohort consisted of all persons hospitalized for infection during the period 1995-2011 in Denmark (N=806,835), of whom 11,343 persons had severe mental illness. Within 30 days after an infection, 1,052 (9.3%) persons with a history of severe mental illness and 58,683 (7.4%) persons without a history of severe mental illness died. Thirty-day mortality after any infection was 52% higher in persons with severe mental illness than in persons without (mortality rate ratio=1.52, 95% CI=1.43-1.61). Mortality was increased for all infections, and the mortality rate ratios ranged from 1.27 (95% CI=1.15-1.39) for persons hospitalized for sepsis to 2.61 (95% CI=1.69-4.02) for persons hospitalized for CNS infections. Depending on age, 1.7 (95% CI=1.2-2.2) to 2.9 (95% CI=2.0-3.7) more deaths were observed within 30 days after an infection per 100 persons with a history of severe mental illness compared with 100 persons without such a history. CONCLUSIONS Persons with severe mental illness have a markedly elevated 30-day mortality after infection. Some of these excess deaths may be prevented by offering individualized and targeted interventions.

The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy: the ADDITION Denmark study†

Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross‐sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION‐Denmark study with short‐term screen‐detected Type 2 diabetes (duration ~ 5.8 years).

Prevalence of Sexual Concerns and Sexual Dysfunction among Sexually Active and Inactive Men and Women with Screen‐Detected Type 2 Diabetes

Abstract Introduction Type 2 diabetes negatively impacts sexual health. Only limited information is available regarding sexual health among sexually inactive patients with type 2 diabetes. Aim The aim of this study was to examine the prevalence of sexual concerns among sexually active and sexually inactive men and women with type 2 diabetes and of sexual dysfunction (SD) among sexually active. Methods Data from the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen‐Detected Diabetes in Primary Care‐Denmark study was used. A total of 1,170 Danish patients with screen‐detected type 2 diabetes attended a health examination, including assessment of sexual concerns using self‐report questionnaires and of SD using the Female Sexual Function Index (FSFI‐R) and the International Index of Erectile Function (IIEF‐5) instruments. Main Outcome Measures The main outcome measures used regarding sexual concerns are the following: prevalence of failure to fill sexual needs, of experiencing sexual distress, finding it important to have a good sexual life, and additionally, prevalence of SD. Results Data regarding sexual activity status during the last 12 months were available among 583 men and 377 women. Seventeen percent of men and 47% of women reported to be sexually inactive, among whom 57% of men and 42% of women reported failure to fill sexual needs; 31% of men and 10% of women that it was important to have a good sexual life, and 32% of men and 11% of women that they were experiencing sexual distress. Around half of men and women were excluded from the SD analysis, mainly because of reporting lack of sexual intercourse during the last 4 weeks. Among those included, 54% of men and 12% of women were found to have SD. Conclusions Sexual inactivity is highly prevalent among middle‐aged and older men and women with early type 2 diabetes and these patients often have sexual concerns. The high exclusion rates when assessing SD using the FSFI‐R and IIEF‐5 instruments makes it difficult to draw conclusions regarding the prevalence. Sexual health should be broadly assessed in both sexually active and sexually inactive people with type 2 diabetes. Bjerggaard M, Charles M, Kristensen E, Lauritzen T, Sandbæk A, and Giraldi A. Prevalence of sexual concerns and sexual dysfunction among sexually active and inactive men and women with screen‐detected type 2 diabetes. Sex Med 2015;3:302–310.

Variation in prescribing of lipid‐lowering medication in primary care is associated with incidence of cardiovascular disease and all‐cause mortality in people with screen‐detected diabetes: findings from the ADDITION‐Denmark trial

To examine variation between general practices in the prescription of lipid‐lowering treatment to people with screen‐detected Type 2 diabetes, and associations with practice and participant characteristics and risk of cardiovascular events and all‐cause mortality.

Ten-Year Mortality after a Breast Cancer Diagnosis in Women with Severe Mental Illness: A Danish Population-Based Cohort Study

Background Breast cancer is the leading cause of cancer death in women worldwide. Nevertheless, it is unknown whether higher mortality after breast cancer contributes to the life-expectancy gap of 15 years in women with severe mental illness (SMI). Methods We estimated all-cause mortality rate ratios (MRRs) of women with SMI, women with breast cancer and women with both disorders compared to women with neither disorder using data from nationwide registers in Denmark for 1980–2012. Results The cohort included 2.7 million women, hereof 31,421 women with SMI (12,852 deaths), 104,342 with breast cancer (52,732 deaths), and 1,106 with SMI and breast cancer (656 deaths). Compared to women with neither disorder, the mortality was 118% higher for women with SMI (MRR: 2.18, 95% confidence interval (CI): 2.14–2.22), 144% higher for women with breast cancer (MRR: 2.44, 95% CI: 2.42–2.47) and 327% higher for women with SMI and breast cancer (MRR: 4.27, 95% CI: 3.98–4.57). Among women with both disorders, 15% of deaths could be attributed to interaction. In a sub-cohort of women with breast cancer, the ten-year all-cause-mortality was 59% higher after taking tumor stage into account (MRR: 1.59, 95% CI: 1.47–1.72) for women with versus without SMI. Conclusions The mortality among women with SMI and breast cancer was markedly increased. More information is needed to determine which factors might explain this excess mortality, such as differences between women with and without SMI in access to diagnostics, provision of care for breast cancer or physical comorbidity, health-seeking-behavior, and adherence to treatment.