ORIGINAL ARTICLE

Association between diabetes and amyotrophic lateral sclerosis in Sweden D. Mariosaa, F. Kamelb, R. Belloccoa,c, W. Yea and F. Fanga Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; bEpidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA; and cDepartment of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy

Keywords:

amyotrophic lateral sclerosis, diabetes, epidemiology, insulin dependence, metabolic and endocrine disorders, motor neuron disease, neurological disorders, neuromuscular diseases, research methods Received 28 June 2014 Accepted 28 October 2014 European Journal of Neurology 2015, 0: 1–7 doi:10.1111/ene.12632

Background and purpose: Energy metabolism is altered in patients with amyotrophic lateral sclerosis (ALS) but the role of diabetes is largely unknown. Methods: A population-based case control study was conducted of 5108 ALS cases and 25 540 individually matched population controls during 1991– 2010. Information on ALS and pre-existing diabetes was retrieved from the Swedish Patient Register to explore the association of ALS with diabetes overall and with insulin-dependent or non-insulin-dependent diabetes specifically. Variation of the association by diabetes duration and age was also studied. Results: In total, 224 ALS cases (4.39%) and 1437 controls (5.63%) had diabetes before the index date, leading to an overall inverse association between diabetes and ALS risk [odds ratio (OR) 0.79, 95% confidence interval (CI) 0.68–0.91]. The association was strong for non-insulin-dependent diabetes (OR 0.66, 95% CI 0.53–0.81) but not for insulin-dependent diabetes (OR 0.83, 95% CI 0.60–1.15) and varied as a function of diabetes duration, with the strongest association observed around 6 years after first ascertainment of diabetes. The association was age-specific; the inverse association was noted only amongst individuals aged 70 or older. In contrast, for younger individuals (80% of hospital-based specialist care visits. Diagnoses of diabetes were identified using the codes ICD9 250 and ICD-10 E10–E11. In a sensitivity analysis, information on use of antidiabetic medications extracted from the Swedish Prescribed Drug Register was also used in order to include additional diabetes patients. This was done for the subsample with index dates between 2006 and 2010 since the Prescribed Drug Register contains information on all dispensed prescriptions of the Swedish population from 1 July 2005 onwards. All drugs are coded according to the Anatomical Therapeutic Chemical Classification System (ATC codes). Antidiabetic drugs are coded A10A or A10B. Diabetes onset was classified as early if the age at first ascertainment was ≤30 years or as late otherwise. Diabetes duration was defined as the time interval between the first available diabetes record in the Patient Register and the index date. In the main analyses, these two variables were calculated using information available after 1987. Since restricting ascertainment to 1987 onward might underestimate the duration and overestimate the age at diabetes onset, in a sensitivity analysis diabetes patients were further identified from records during the years 1964– 1986 when the Inpatient Register was available but not yet nationwide (ICD-7 260, ICD-8 250). Patients were categorized as insulin-dependent if their ICD-10 code was E10 and as non-insulin-dependent if it was E11. In a sensitivity analysis, insulindependent status was also assigned to patients who had ever been prescribed insulin (ATC code A10A) and non-insulin-dependent status to those who were prescribed other drugs (ATC code A10B). The analyses on insulin dependence excluded individuals with unknown insulin dependence status (i.e. absence of ICD-10 codes or with both ICD-10 E10 and E11). Because diabetes without complications was recorded with specific ICD codes (ICD-9 250.0, ICD-10 E10.9 and E11.9), cases of diabetes with complications were defined as those with at least one diagnosis of diabetes with complications before the index date.

© 2015 EAN

PREMORBID DIABETES AND ALS

Covariates

The Swedish Population and Housing Census in 1990 provided information on socioeconomic status (blue collar, white collar, self-employed/farmers, other). The Swedish Education Register was established in 1985 by Statistics Sweden and annually collects information on the highest level of formal education attained for each Swedish resident. Education achieved before the index date was categorized as ≤9 years, 9–12 years and university or doctoral studies. Statistical analysis

Analyses were performed using Stata version 12.1 (StataCorp, College Station, TX, USA). Conditional logistic regression models were fitted to estimate the odds ratios (ORs) for the association of ALS with diabetes, with 95% confidence intervals (CIs). Estimates were adjusted for matching variables only or additionally for education and socioeconomic status. Control sampling was repeated 100 times and the observed distribution of the ORs was plotted. Analyses stratified by age at index date (9 and ≤12 years University or doctoral studies Missing Socioeconomic status, n (%) Blue collar White collar Self-employed/farmer Other

© 2015 EAN

Controls

Men

Women

Total

Men

Women

Total

2872 67.37 (12.18) 144 (5.0)

2236 69.36 (12.18) 80 (3.6)

5108 68.24 (12.22) 224 (4.4)

14 360 67.36 (12.18) 899 (6.3)

11 180 69.37 (12.18) 538 (4.8)

25 540 68.24 (12.22) 1437 (5.6)

707 (24.6) 1513 (52.7) 652 (22.7)

519 (23.2) 1201 (53.7) 516 (23.1)

1226 (24.0) 2714 (53.1) 1168 (22.9)

3535 (24.6) 7565 (52.7) 3260 (22.7)

2595 (23.2) 6005 (53.7) 2580 (23.1)

6130 (24.0) 13 570 (53.1) 5840 (22.9)

1243 (44.3) 1037 (37.0) 523 (18.7) 69

1050 (48.4) 773 (35.6) 346 (16.0) 67

2293 (46.1) 1810 (36.4) 869 (17.5) 136

6395 (45.8) 5033 (36.0) 2550 (18.2) 382

5539 (51.3) 3526 (32.7) 1730 (16.0) 385

11 934 (48.2) 8559 (34.5) 4280 (17.3) 767

1733 1875 649 851

5178 5385 1598 2199

3721 3584 1475 2400

992 1115 337 428

(34.5) (38.8) (11.7) (14.9)

741 760 312 423

(33.1) (34.0) (14.0) (18.9)

(33.9) (36.7) (12.7) (16.7)

(36.1) (37.5) (11.1) (15.3)

(33.3) (32.1) (13.2) (21.5)

8899 8969 3073 4599

(34.8) (35.1) (12.0) (18.0)

4

D. MARIOSA ET AL.

Table 2 Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association of amyotrophic lateral sclerosis with diabetes (DM)

Variables

No. of cases with DM

No. of controls with DM

Overall 224 1437 Age at the index date (years)

Association between diabetes and amyotrophic lateral sclerosis in Sweden.

Energy metabolism is altered in patients with amyotrophic lateral sclerosis (ALS) but the role of diabetes is largely unknown...
315KB Sizes 1 Downloads 11 Views