Long-term risk of stroke in type 2 diabetes patients with diabetic ketoacidosis: A population-based, propensity score-matched, longitudinal follow-up study

Abstract

Aim

To investigate the long-term risk of stroke in type 2 diabetes (T2D) patients with previous episodes of diabetic ketoacidosis (DKA).

Methods

This retrospective nationwide population-based cohort study was conducted using Taiwan's National Health Insurance database. Claims data from 2000 to 2002 were extracted for 3572 T2D patients with DKA and 7144 controls matched for age, gender, diabetes complications severity index, frequency of clinical visits and baseline comorbidities. Patients with type 1 diabetes (T1D), identified by glucagon C-peptide stimulation or glutamic acid decarboxylase (GAD) antibody blood tests and possession of a catastrophic illness certificate were excluded. All patients were tracked until a new stroke diagnosis, death or the end of 2011.

Results

Of the 3572 selected patients, 270 with DKA and 404 of the 7144 controls were diagnosed with a new stroke, giving an incidence rate ratio (IRR) of 1.56 (95% CI: 1.34–1.82; P < 0.0001). DKA patients had a higher risk of ischaemic stroke than those without DKA (IRR: 1.62, 95% CI: 1.34–1.96; P < 0.0001), and DKA patients with hypertension and hyperlipidaemia were at even greater risk of stroke. Also, DKA patients were at particular risk for stroke during the first half-year following DKA diagnosis. After adjusting for patient characteristics and comorbidities, these patients were 1.55 times more likely to have a stroke than those without DKA (95% CI: 1.332–1.813, P < 0.0001).

Conclusion

T2D patients with previous DKA have a higher risk of stroke, especially ischaemic strokes.

Introduction

Stroke is a leading cause of death and disability in Taiwan [1]. Diabetes mellitus is an independent predictor of the incidence of ischaemic stroke [2], and chronic hyperglycaemia has been associated with infarct expansion and poorer functional outcomes [3]. One meta-analysis has associated diabetes with a two-fold increase in risk for vascular disease, independent of other conventional risk factors [4]. A hyperglycaemic crisis may further increase stroke risk. Wang et al. [5] reported that patients diagnosed with a hyperosmolar hyperglycaemic state (HHS) had a higher risk of ischaemic stroke the following year.

Diabetic ketoacidosis (DKA), a serious acute metabolic complication of diabetes, is characterized by uncontrolled hyperglycaemia, higher anion gap metabolic acidosis and increased total body ketone concentrations [6]. DKA is usually a consequence of absolute or relative insulin deficiency, increased concentrations of counter-regulatory hormones and peripheral insulin resistance [7]. In nationwide population-based studies, the mortality rate in children with DKA varied from 0.15% to 0.30% [8], [9] whereas, in developing countries, it is higher, ranging from 3.4% to 13.4% [10], [11], [12]. In adults, the overall mortality rate is < 1%, but increases to > 5% in the elderly and in patients with concomitant life-threatening illnesses [6], [13]. The morbidity and mortality in children and adolescents with DKA can mostly be attributed to intracerebral complications in the acute stage, the most common ones being cerebral oedema [14].

Studies of subsequent stroke risk in type 2 diabetes (T2D) patients with DKA are scarce. One case study from Okamura et al. [15] reported the occurrence of acute infarction in a 79-year-old woman with DKA. However, while the current guidelines for the treatment of DKA focus on the acute phase, the long-term prognosis for T2D patients with previous episodes of DKA has rarely been addressed. It is also not known whether patients with T2D who have had DKA episodes are also at an increased risk of macrovascular complications or whether DKA can be considered a risk marker for long-term complications.

For these reasons, a population-based National Health Insurance (NHI) dataset in Taiwan was used to perform a longitudinal 10-year follow-up study to examine the relationship between DKA and the long-term risk of stroke in patients with T2D.