Clinical Outcomes in Patients With Isolated or Combined Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State: A Retrospective, Hospital-Based Cohort Study

Abstract

Many patients with hyperglycemic crises present with combined features of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). The implications of concomitant acidosis and hyperosmolality are not well known. We investigated hospital outcomes in patients with isolated or combined hyperglycemic crises. RESEARCH DESIGN AND METHODSWe analyzed admissions data listing DKA or HHS at two academic hospitals. We determined 1) the frequency distributions of HHS, DKA, and combined DKA-HHS (DKA criteria plus elevated effective osmolality); 2) the relationship of markers of severity of illness and clinical comorbidities with 30-day all-cause mortality; and 3) the relationship of hospital complications associated with insulin therapy (hypoglycemia and hypokalemia) with mortality. RESULTSThere were 1,211 patients who had a first admission with confirmed hyperglycemic crises criteria, 465 (38%) who had isolated DKA, 421 (35%) who had isolated HHS, and 325 (27%) who had combined features of DKA-HHS. After adjustment for age, sex, BMI, race, and Charlson Comorbidity Index score, subjects with combined DKA-HHS had higher in-hospital mortality compared with subjects with isolated hyperglycemic crises (adjusted odds ratio [aOR] 2.7; 95% CI 1.4, 4.9; P 5 0.0019). In all groups, hypoglycemia (<40 mg/dL) during treatment was associated with a 4.8fold increase in mortality (aOR 4.8; 95% CI 1.4, 16.8). Hypokalemia £3.5 mEq/L was frequent (55%). Severe hypokalemia (£2.5 mEq/L) was associated with increased inpatient mortality (aOR 4.9; 95% CI 1.3, 18.8; P 5 0.02). CONCLUSIONSCombined DKA-HHS is associated with higher mortality compared with isolated DKA or HHS. Severe hypokalemia and severe hypoglycemia are associated with higher hospital mortality in patients with hyperglycemic crises.

Clinical profiles, Outcomes and Risk Factors among Type 2 Diabetic Inpatients with Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State: A Hospital-Based Analysis over a 6-Year Period

“…Previous studies have reported that some patients with HEs could have combined features of HHS and DKA [12,13]. However, the characteristics and prognosis of patients with combined DKA-HHS in China are still largely unclear.…”

The importance of hyperosmolarity in diabetic ketoacidosis

“…Another retrospective analysis of 312 adults showed that hyperosmolarity was strongly associated with mortality in isolation, but that only age remained a significant predictor as part of a multivariate analysis [8]. The largest review prior to this study is the recent article by Pasquel et al [9] characterizing 1211 admissions to a single institution with hyperglycaemic crises. In their study, hyperosmolarity was associated with increased mortality and complications such as deep vein thrombosis, but was not a significant predictor after controlling for age, sex, BMI, ethnicity and comorbidities.…”

“…Following the original description of HHS, it was noted that up to 30% of people present with overlapping features of both HHS and ketoacidosis [5], and those with mixed presentations were reported to have a mortality intermediate between the two conditions [7,8]. A more recent retrospective study by Pasquel et al [9] evaluated 1211 hospital admissions with hyperglycaemic crises, and suggested that those with mixed presentations may actually have an even higher mortality than either isolated ketoacidosis or HHS. Despite these concerns, current guidelines from both the UK and USA contain no diagnostic criteria or treatment recommendations for mixed presentations [10], although their optimal fluid and electrolyte management may differ from typical ketoacidosis [11].…”

“…However, not all studies have demonstrated increased mortality in people with hyperosmolarity [14], and one series suggested the apparent relationship between osmolarity and mortality may be confounded by the association of both factors with increasing age [8]. The largest study to date by Pasquel et al above noted an increase in mortality in those with hyperosmolarity, but this effect lost statistical significance after controlling for multiple potential confounders [9].…”

Diabetes at the front door. A guideline for dealing with glucose related emergencies at the time of acute hospital admission from the Joint British Diabetes Society (JBDS) for Inpatient Care Group*

“…If this is > 320 mOsmol/kg, hyperosmolar hyperglycaemic syndrome should be diagnosed, and treated accordingly [10]. Be aware that a mixed picture of hyperosmolar hyperglycaemic state and diabetic ketoacidosis can occur [13]. If this is the case, insulin treatment should be started sooner rather than later.…”