We performed a retrospective analysis of patients admitted with DKA between October 2003 and October 2008. DKA was diagnosed based on American Diabetes Association criteria (¹⁰). Demographic and biochemical data were extracted from the medical records of the patients including serum pH, bicarbonate, sodium, potassium, blood urea nitrogen (BUN), serum creatinine, osmolality, “ketones,” arterial pO₂ and pCO₂, as well as level of consciousness. Serum effective osmolality was calculated as reported before (¹⁰).

Patients were categorized by mental status into alert versus altered (semi-comatose and comatose).

We recorded 216 cases of DKA in patients aged 37.7 ± 12.4 years, 57.9% of whom were males, whereas 21 and 15% had type 2 diabetes and new-onset diabetes, respectively. Average blood glucose level was 658.6 ± 276.0 mg/dl, whereas mean serum osmolality and pH were 304 ± 31.6 mOsm/kg and 7.14 ± 0.15, respectively. Serum sodium and potassium were 131.6 ± 6.5 and 5.4 ± 3.5 mEq, respectively. The clinical and biochemical characteristics of the patients according to mental status are shown in Table 1. Variables that demonstrated a significant difference between the two groups were entered into a multiple regression model shown in supplemental Table 1 (available in an online appendix at http://care.diabetesjournals.org/cgi/content/full/dc10-0102/DC1). As can be seen, only pH emerged as an independent determinant of level of consciousness in this cohort of patients with DKA.

To further elucidate the influence of acidosis measured by arterial pH and effective serum osmolality on the level of consciousness at presentation, we determined the odds ratio of depressed sensorium in all 216 subjects by quartiles of pH and osmolality (see supplemental Fig. 1 in the online appendix). Supplemental Fig. 1 clearly demonstrates that arterial pH is the prime determinant of mental status in DKA, which appeared to act synergistically with hyperosmolarity to produce depressed consciousness. In patients with severe acidosis (lowest pH quartile ≤7.03), the odds ratio for altered sensorium was 1 if serum osmolality was in the lowest quartile (≤287), but increased almost threefold to 2.8 among patients in the highest quartile of osmolality (≥316). However, in the absence of severe acidosis, worsening hyperosmolarity was not significantly associated with altered sensorium (odds ratio <1). Therefore, although acidosis was required for depressed sensorium to occur, the likelihood of altered mentation was higher in the presence of elevated serum osmolality. A total of 45 patients (20.8%) were in the lowest pH quartile, while 52 patients (24.1%) were in the highest osmolality quartile (≥316 mOsm/kg). Fifteen subjects (6.9%) had a combination of low pH and high osmolality. This latter category represented the patients with the highest likelihood of having depressed level of consciousness (odds ratio 2.81). Mortality, which was recorded in 0.9% of the cases, occurred in patients who had presented with severe acidosis and sepsis. The combination of severe acidosis and hyperosmolarity predicted altered sensorium with sensitivity of 61% and specificity of 87% (supplemental Table 2 and supplemental Fig. 2).

We have demonstrated that acidosis measured by arterial pH at presentation is the prime determinant of mental status in DKA. Severe acidosis appeared to act in concert with hyperosmolarity in a synergistic manner to produce depressed sensorium in these patients. Therefore, a combination of acidosis and hyperosmolarity at presentation may identify a subset of patients with severe DKA (7% in this study) who may benefit from more aggressive treatment and monitoring. Identifying this class of patients, who are at a higher risk for poorer prognosis, may be helpful in triaging them, thus further improving the outcome.

The dominant effect of acidosis on mental status obtained in this study is consistent with the findings of other clinical studies (⁶,⁷).

Some studies have reported that depressed sensorium in DKA is attributable to elevated serum osmolality (⁸,⁹). However, despite some biochemical similarities between these two hyperglycemic crises, there are notable differences that may suggest different pathogenic mechanisms. We observed that hyperosmolarity, which was associated with depressed sensorium in a univariate model, did not prove to be an independent predictor of altered sensorium in a multivariate analysis. However, in the presence of hypertonicity, the likelihood of altered mental status was increased in patients with severe acidosis. Studies that reported hyperosmolarity as the sole etiology of altered consciousness DKA did not perform logistic regression (⁸) as we have done. This could be a confounding factor, since up to 30% of patients with DKA may have high serum osmolality (⁹,¹¹).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

No potential conflicts of interest relevant to this article were reported.

E.A.N.: research design, data collection, statistical analysis, manuscript writing, and review of manuscript. L.N.R.: data extraction and collation, statistical analysis, and manuscript writing. A.E.K.: research design, manuscript writing, and critical review of manuscript for intellectual content. A.N.K.: data extraction and collation and manuscript writing. J.Y.W.: statistical analysis and manuscript writing.

We acknowledge the efforts of the following residents in internal medicine and fellows in endocrinology who assisted with data collection: Jevaria Ahmed, MD, Swaroopa Bartakke, MD, Malini Gupta-Ganguli, MD, Omid Rad Pour, MD, Amanda Long, DO, and Sadiya Zaidi, MD.