Type 2 diabetes, obesity, and risk of amyotrophic lateral sclerosis: A population-based cohort study.

BACKGROUND: Type 2 diabetes and obesity may be inversely associated with amyotrophic lateral sclerosis (ALS), but the evidence is controversial. METHODS: Using Danish, nationwide registries (1980-2016), we identified patients with a diagnosis of type 2 diabetes (N = 295,653) and patients with a diagnosis of obesity (N = 312,108). Patients were matched (1:3) to persons from the general population on birth year and sex. We computed incidence rates and Cox regression derived hazard ratios (HRs) of a diagnosis of ALS. In multivariable analyses, HRs were controlled for sex, birth year, calendar year, and comorbidities. RESULTS: We observed 168 incident cases of ALS (0.7 [95% confidence interval (CI): 0.6-0.8] per 10,000 person-years) among patients with type 2 diabetes and 859 incident cases of ALS (0.9 [95% CI: 0.9-1.0] per 10,000 person-years) among matched comparators. The adjusted HR was 0.87 (95% CI: 0.72-1.04). The association was present among men (adjusted HR: 0.78 [95% CI: 0.62-0.99]) but not women (adjusted HR: 1.03 [95% CI: 0.78-1.37]), and among those aged ≥60 years (adjusted HR: 0.75 [95% CI: 0.59-0.96]) but not younger. We observed 111 ALS events (0.4 [95% CI: 0.4-0.5] per 10,000 person-years) among obesity patients and 431 ALS events (0.5 [95% CI: 0.5-0.6] per 10,000 person-years) among comparators. The adjusted HR was 0.88 (95% CI: 0.70-1.11). CONCLUSIONS: Diagnoses of type 2 diabetes and obesity were associated with a reduced rate of ALS compared with general population comparators, particularly among men and patients aged 60 years or above. However, absolute rate differences were small.

Out-of-home care placement and mortality rate in early adulthood: identifying vulnerable subgroups in a nationwide cohort study.

Out-of-home care has been linked to excess mortality across the lifespan. We examined whether this association is modified by the age at first out-of-home care placement and the number of placements. In this population-based cohort study, we used register data covering all children born in Denmark between 1 and 1980 and 31 December 1999, totalling 1,111,193 individuals followed until 31 December 2018. We divided participants according to sex, out-of-home care status, age at first placement, and the number of placements. We estimated adjusted hazard ratios and hazard differences per 10,000 person-years for all-cause mortality and mortality due to suicide, accidents, and cancer between ages 18 and 39. 53,015 (4.8%) of the participants were placed in out-of-home care before age 18. The adjusted hazard ratio for all-cause mortality was 3.4 (95% CI 3.1-3.7) for males and 4.7 (4.0-5.4) for females, corresponding to 20.6 (19.0-22.2) and 10.3 (9.1-11.5) additional deaths per 10,000 individuals annually among males and females, respectively. Associations did not vary substantially according to age at first placement or the number of placements. Both males and females with a history of out-of-home care were more likely to die from suicide, accidents, and cancer compared with their peers. We show a markedly higher all-cause and cause-specific mortality among children who have been placed in out-of-home care, but contrary to our hypothesis, age at first placement and the number of placements did not modify this relation. These results warrant further investigation into potential target points for interventions that may prevent premature mortality in this group of disadvantaged individuals.

Motor Neuron Disease and Risk of Cancer: A Population-Based Cohort Study in Denmark.

BACKGROUND: Some neurogenerative diseases have been linked to a reduced risk of cancer, but the association between motor neuron disease and cancer risk is not well understood. We hypothesized that cancer risk would be lower among those with motor neuron disease and its most common subtype, amyotrophic lateral sclerosis. METHODS: We conducted a population-based cohort study of motor neuron disease and cancer risk using routinely collected data from population-based registries in Denmark. We examined cancer incidence among patients diagnosed with motor neuron disease between January 1980 and December 2013 followed through 2013. Using Danish national cancer rates for the study period, we computed standardized incidence ratios as a measure of relative risks. RESULTS: In the cohort of 5053 patients with a motor neuron disease, the overall standardized incidence ratio of any cancer was 1.17 (95% confidence interval [CI], 1.03-1.31); the corresponding standardized incidence ratio for amyotrophic lateral sclerosis was 1.24 (95% CI, 0.96-1.57). The standardized incidence ratios of any cancer in the cohort with motor neuron disease was 1.52 (95% CI, 1.22-1.87) for <1 year of follow-up; 0.87 (95% CI, 0.68-1.09) for years 1-5 of follow-up; and 1.22 (95% CI, 1.01-1.46) for >5 years of follow-up. Beyond one year of follow-up, patients in the motor neuron disease had elevated standardized incidence ratios for lymphoid leukemia, non-Hodgkin lymphoma, and basal cell skin cancer. CONCLUSION: Findings fail to support the hypothesis that motor neuron disease or amyotrophic lateral sclerosis is associated with reduced cancer incidence. An elevated risk of cancer during the first year of follow-up may be attributable to heightened surveillance.

Risk of amyotrophic lateral sclerosis and other motor neuron disease among men with benign prostatic hyperplasia: a population-based cohort study.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder. Sleep disturbance may interfere with clearance of abnormal proteins that aggregate in neurodegenerative diseases. The objective of this study was to examine the association between benign prostatic hyperplasia (BPH), a common disorder causing nocturia and sleep disturbance, and risk of ALS and other motor neuron disease (MND). We hypothesised that men with BPH, in comparison to men in the general population, would be at increased risk. DESIGN: This is a nationwide, population-based cohort study. SETTING: This study was conducted among the population of Denmark. PARTICIPANTS: We used linked Danish medical databases to identify all men with a first-time diagnosis of BPH between 1 January 1980 and 30 November 2013 and no prior diagnosis of MND (BPH cohort, n=223 131) and an age-matched general population comparison cohort of men without BPH or MND (n=1 115 642). PRIMARY OUTCOME MEASURE: The primary outcome is diagnosis of MND after the BPH diagnosis (index) date, with follow-up until MND diagnosis, emigration, death or 30 November 2013. RESULTS: We used Cox regression to compute adjusted HR, comparing men with and without BPH. After 34 years of follow-up, there were 227 cases of MND in the BPH cohort (incidence rate 0.13/1000 person-years) and 1094 MND cases in the comparison cohort (0.12/1000 person-years; HR 1.05, 95% CI 0.90 to 1.22). Risk did not vary by follow-up time. CONCLUSIONS: BPH is not associated with an increased risk of ALS and other MND. Future studies should examine the relation between other disorders that disrupt sleep and MND risk in men and women.