Hyperglycemic Hyperosmolar Status Is Associated with Subsequent All-Cause Mortality in Elderly Adults with Type 2 Diabetes Mellitus.

Abstract

To the Editor: A hyperglycemic hyperosmolar syndrome (HHS) involves extremely high blood glucose levels and severe dehydration. Individuals with HHS have been reported to have a 5% to 20% greater risk of mortality.1 Hyperglycemic emergency is a major concern in elderly adults because mortality associated with the condition can be five times as high as in the general population because older adults are more likely to have concomitant illness or multiple comorbidities.2 The association between HHS and long-term outcomes has not been completely determined. A recent nationwide population-based cohort study twice the risk of mortality in subjects younger than 65 who have had a hyperglycemic crisis for up to 8 years after the episode, but elderly adults were not included in that study.3 The purpose of this study was to determine the prognosis of elderly adults with HHS. Individuals with a serum glucose level greater than 500 mg/dL from the emergency department between July 1, 2008 and September 30, 2010, were enrolled. Demographic and anthropometric characteristics, smoking status, history of hypertension, hyperlipidemia, cardiovascular disease, malignancy, medications after discharge from the emergency department, random glucose level, glycosylated hemoglobin (HbA1c), sodium, creatinine, and lipid profile were reviewed. Exclusion criteria were younger than 60, a history of occult malignancy, and death within 24 hours. Eligible individuals were grouped according to effective serum osmolality.4 Participants with an effective serum osmolality greater than 320 mOSM/L were classified as having HHS, and the rest as not having HHS. Date of death was obtained from the registry of the National Health Department of Taiwan. Cause of death was defined according to the first code on the death certificate. Cumulative event-free probabilities of mortality were estimated using Kaplan–Meier analysis. The log-rank test was used to identify significant differences. All relevant variables were tested using univariate Cox proportional analysis; those with P < .10 underwent multivariate Cox proportional analysis, and hazard ratios (HRs) with corresponding probability values were calculated. SPSS version 18 (IBM Corp., Armonk, NY) was used for data analysis. Seven hundred seventy-nine individuals with type 2 diabetes mellitus and a serum glucose level greater than 500 mg/dL who were admitted to the emergency department between July 1 and September 30, 2008, were enrolled. Mean follow-up duration was 1.7 years, during which 226 died (n = 63 (70%) with HHS; n = 163 (42%) without HHS, P < .001, log rank test; Figure 1). HHS was associated with all-cause mortality (HR = 2.02, 95% confidence interval (CI) = 1.55–2.65, P < .001), and the association was still significant after adjusting for other covariates, including age, mean arterial blood pressure, glucose, estimated glomerular filtration rate, and non-high-density lipoprotein cholesterol (HR = 1.71, 95% CI = 1.07–2.75, P = .02). The results of this study demonstrate that HHS, an acute complication of diabetes mellitus, was significantly associated with all-cause mortality in elderly adults (≥60) with type 2 diabetes mellitus. Hyperglycemia was found to be associated with higher mortality in individuals with and without diabetes mellitus hospitalized in a general ward.5 Moreover, elderly adults with in-hospital hyperglycemia, which was defined as a glucose level greater than 181 mg/dL, were 2.7 times as likely to die as those with a glucose level from 60 to 126 mg/dL.6 The worse outcomes in subjects in hyperglycemic crisis may be due to activation of inflammatory reactions.7 It has been reported that age and dehydration are associated with worse outcomes in elderly adults.8, 9 After correcting for other confounding factors such as age, race, sex, weight, activity, smoking, and chronic illness, dehydration was found to be independently associated with 8-year all-cause mortality.10 Because of this high prevalence of dehydration, elderly adults are at greater risk of HHS. The association between HHS and all-cause mortality may therefore be due to the effects of hyperglycemia, old age, and dehydration. There are several limitations to this study. First, selection bias could occur in a retrospective setting. Second, the study focused on the association between HHS and clinical outcomes in elderly Chinese adults, which limits its generalizability. Third, follow-up was too short to conclude the null association between HHS and cardiovascular death. Finally, causality should be confirmed in further prospective studies to validating these conclusions. The research was founded by Taipei Veterans General Hospital (V100C-204) and the National Science Council (NSC 99–2314-B-010–050-). Conflict of Interest: All authors declare they have received no support from any company for the submitted work; they have had no financial relationships with any companies that might have an interest in the submitted work in the previous 3 years and no other relationships or activities that could appear to have influenced the submitted work. Author Contributions: LHC: study design, data analysis, writing the manuscript. YWG: study design, data collection. HSC: study design, review and editing of manuscript, responsibility for content of the article. Sponsor's Role: None.