OBJECTIVELatent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype.RESEARCH DESIGN AND METHODSWe performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects (n = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 2,779 vs. 10,396).RESULTSThe leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring PFKFB3, encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1–associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes.CONCLUSIONSOur results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.

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ObjectiveTo verify the previously reported association between long-term use of β2-adrenoreceptor (β2AR) agonist and antagonist with reduced and increased risk of Parkinson disease (PD), respectively.MethodsWe obtained odds ratios (ORs) associating time of β2AR agonist and antagonist use with PD risk in nationwide Danish health registries.ResultsWe included 2,790 patients with PD and 11,160 controls. Long-term β2AR agonist use was associated with reduced PD risk (OR 0.57, 95% confidence interval [CI] 0.40–0.82) in this cohort. Unexpectedly, short-term β2AR agonist use was equally associated (OR 0.64, 95% CI 0.42–0.98). Because β2AR agonists are prescribed mostly for chronic obstructive pulmonary disease (COPD), often caused by long-term nicotine abuse, we analyzed other markers of smoking. Diagnosis of COPD (OR 0.51, 95% CI 0.37–0.69) and use of inhaled corticosteroids (OR 0.78, 95% CI 0.59–1.02) or inhaled anticholinergics (OR 0.41, 95% CI 0.25–0.67) were also inversely associated with PD. Increased PD risk was not found for all β2AR antagonists but only for propranolol and metoprolol. Associations were markedly stronger for short-term than long-term use.ConclusionWe confirmed β2AR agonist use to be associated with reduced PD risk and β2AR antagonist use with increased PD risk. However, our data indicate the association of β2AR agonists to be indirectly mediated by smoking, which is repeatedly associated with reduced risk of PD. The association of β2AR antagonists indicates reverse causation, with PD symptoms triggering their prescription rather than β2AR antagonists causing PD. Thus, current epidemiologic data do not support a causal link between β2AR agonists and antagonists and PD risk.

In analyzing data from 2 large population-based studies of twins in Denmark, we found no association between PPI use and cognitive decline.

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