Department of Psychiatry, Aalborg University Hospital, Brandevej 5, 9220, Aalborg, Denmark.
Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
Diabetologia. 2017 Sep;60(9):1678-1690. doi: 10.1007/s00125-017-4320-5. Epub 2017 Jun 7.
AIMS/HYPOTHESIS: Diabetic ketoacidosis (DKA) is a potentially fatal metabolic emergency of both type 1 and type 2 diabetes. Although there is a reduced risk of type 1 diabetes in schizophrenia, the incidence of DKA is tenfold higher than that of the general population. Thus, we aimed to investigate associations between exposure to antipsychotic medication (within 3 months prior to event) and DKA, type 1 diabetes and type 2 diabetes. We also reported related, clinically relevant outcomes.
Using a nested case-control study design, we identified cases of DKA, type 1 diabetes and type 2 diabetes in a previously diabetes-naive population with schizophrenia in Denmark from 1995 to 2014. Cases were matched (by age, sex and year of schizophrenia onset) 1:5 to schizophrenic control individuals who were alive and had not emigrated prior to event. Conditional logistic regression was used to compute ORs with 95% CIs. Other outcomes included diabetes aetiology of DKA, in-hospital mortality, DKA readmissions and temporal trends of use of insulin and oral glucose-lowering agents.
Of 29,955 individuals with schizophrenia, we identified 28 individuals with DKA, 90 with type 1 diabetes and 2140 with type 2 diabetes. These were matched to 137, 410 and 9861 individuals in the control group, respectively. Antipsychotic exposure was associated with DKA (OR 2.60; 95% CI 1.06, 6.38) and type 2 diabetes (OR 1.64; 95% CI 1.48, 1.83). A trend towards increased risk of type 1 diabetes was found but remained insignificant (OR 1.38; 95% CI 0.84, 2.29). Diabetes aetiology of DKA was type 1 in eight cases and type 2 in 14 cases. Of the remaining six cases of DKA, aetiology could not be determined, as four were fatal within 8 days and for two, no prescriptions for insulin and oral glucose-lowering agents were redeemed. Of all DKA cases, six had more than one episode of DKA, and of all type 1 diabetes and type 2 diabetes cases, four and 11, respectively, had at least one episode. Use of insulin and oral glucose-lowering agents was higher among individuals with DKA relative to those with type 1 diabetes and type 2 diabetes.
CONCLUSIONS/INTERPRETATION: Antipsychotic exposure was associated with DKA and type 2 diabetes in a previously diabetes-naive schizophrenia population. Antipsychotic-associated DKA is relevant not only for psychiatrists but also for other physicians who may manage and admit such patients.
目的/假设：糖尿病酮症酸中毒（DKA）是 1 型和 2 型糖尿病潜在的致命代谢急症。虽然精神分裂症患者患 1 型糖尿病的风险降低，但 DKA 的发病率比一般人群高 10 倍。因此，我们旨在研究抗精神病药物暴露（在事件发生前 3 个月内）与 DKA、1 型糖尿病和 2 型糖尿病之间的关联。我们还报告了相关的、临床相关的结果。
使用巢式病例对照研究设计，我们从丹麦一个先前无糖尿病的精神分裂症人群中确定了 1995 年至 2014 年期间的 DKA、1 型糖尿病和 2 型糖尿病病例。病例按年龄、性别和精神分裂症发病年份与存活且在事件发生前未移民的精神分裂症对照个体 1:5 配对。使用条件逻辑回归计算比值比（OR）及其 95%置信区间（CI）。其他结果包括 DKA 的糖尿病病因、住院死亡率、DKA 再入院率以及胰岛素和口服降糖药使用的时间趋势。
在 29955 名精神分裂症患者中，我们发现 28 名 DKA 患者、90 名 1 型糖尿病患者和 2140 名 2 型糖尿病患者。这些病例分别与对照组中的 137 名、410 名和 9861 名患者相匹配。抗精神病药物暴露与 DKA（OR 2.60；95%CI 1.06，6.38）和 2 型糖尿病（OR 1.64；95%CI 1.48，1.83）相关。1 型糖尿病的风险呈上升趋势，但仍无统计学意义（OR 1.38；95%CI 0.84，2.29）。DKA 的糖尿病病因在 8 例中为 1 型，在 14 例中为 2 型。在其余 6 例 DKA 中，无法确定病因，因为 4 例在 8 天内死亡，对于 2 例，没有兑现胰岛素和口服降糖药的处方。所有 DKA 病例中，有 6 例有不止一次 DKA 发作，所有 1 型糖尿病和 2 型糖尿病病例中，分别有 4 例和 11 例至少有一次发作。与 1 型糖尿病和 2 型糖尿病患者相比，DKA 患者使用胰岛素和口服降糖药的比例更高。
结论/解释：在先前无糖尿病的精神分裂症人群中，抗精神病药物暴露与 DKA 和 2 型糖尿病相关。抗精神病药物相关的 DKA 不仅与精神科医生有关，也与可能管理和收治此类患者的其他医生有关。
