Through the eyes of the A1C: a call to re-examine stress hyperglycemia.

I n this issue of Critical Care Medicine, Stegenga et al (1) report, from the PROWESS study on safety and efficacy of recombinant human activated protein C, that among patients with severe sepsis, those with a medical history of diabetes had mortality similar to those without pre-existing diabetes as determined 28 and 90 days after admission. Although persons having diabetes, compared with those not having diabetes, are at increased risk for development of infection and for mortality consequent to infection, the current report, as well as some earlier reports, fail to show differences according to presence or absence of diabetes between diseasespecific mortality rates once infection is established. The effect of diabetes may differ according to type of infection, setting, definition of diabetes, method of case ascertainment, comorbidities, and additional variables (2–11). In 1985, Bryan et al (2) reported that among 300,547 patients treated and released at four major hospitals over the 5-yr period (1977–1981), the death rates attributed to bacteremia were 2.5 per 1000 diabetic patients vs 1.4 per 1000 nondiabetic patients. Although the mortality rates for episodes of bacteremia were similar among diabetic and nondiabetic patients, because of the increased incidence of bacteremic episodes among patients with diabetes patients compared with control subjects, 19.4 per 1000 (301 of 15,497) vs. 9.4 per 1000 (2677 of 285,050), respectively (p .001), the patients with diabetes were nearly twice as likely to die as a result of bacteremia. In an Ontario population-based study comparing patients having diabetes with matched nondiabetic control subjects (n 513,749 in each group), it was shown in a retrospective cohort study that the risk ratio for patients with diabetes for death attributable to infection was as high as 1.92 (confidence interval, 1.79–2.05) (6). MacFarlane et al (3) found that among 22,830 hospitalized patients, only 10.4% were diabetic, but of 168 patients having episodes of bacteremia, 29.2% had diabetes (p .001 for diabetes among bacteremic patients vs. diabetes among all admissions). Carton et al (5), in a study of 101,392 admissions, found the rate of bacteremia to be 26.8 episodes per 1000 patients with diabetes (152 of 5667) compared with 15.5 per 1000 nondiabetic patients (1488 of 95,725; p .001). In the evaluation of 598 pneumonia case subjects and 5980 matched control subjects, the adjusted odds ratio (95% confidence interval) for developing communityacquired pneumococcal bacteremia reported by Thomsen et al (8) from Denmark was 1.5 (1.1–2.0) for patients having diabetes. Although some reports have indicated a higher rate of morbidity or mortality from pneumonia (10, 11), nevertheless, the pneumonia case fatality rate in the presence of diabetes has not been found to be consistently higher than in nondiabetic patients (9). More generally, the infectious diseasespecific fatality rate among hospitalized patients is not consistently reported to be increased by the presence of diabetes (Table 1). Using the stated method of case ascertainment by retrospective collection of diabetes-related chart history from the parent study, Stegenga et al identified 22.7% (188 of 830) of patients as having diabetes before admission and classified the remainder as nondiabetic for the purpose of their analyses. The baseline plasma glucose was 239 9 mg/dL among 178 patients having diabetes, 152 3 mg/dL among 608 patients not previously known to have had diabetes, and overall 172 3 mg/dL for 786 patients. At baseline, the patients classified as diabetic were older, and, as might be expected for a comparison between patients having diabetes and nondiabetic patients, and they had a higher Sequential Organ Failure Assessment renal score and lower hematology score than nondiabetic patients. At 28 days, the mortality rates in the two groups, respectively, were 31.4% (59 of 188) and 30.5% (196 of 642), and at 90 days 39.1% (70 of 179) and 39.0% (238 of 610), for the diabetes and nondiabetes groups, respectively. Because the Stegenga study relied on history of diabetes rather than objective tests of glycemia for classification, some patients with diabetes may have been misclassified as nondiabetic. Among the remaining patients in the nondiabetic group, stress hyperglycemia appears to have been prevalent. The term stress hyperglycemia traditionally refers to hyperglycemia developing in response to severe illness in a nondiabetic individual, a common hospital problem. Among hospitalized patients, gradations of hyperglycemia correlate with mortality across a wide spectrum of illnesses (9, 11–17). Umpierrez et al (12) reported that 38% (718 of 1886) of adult admissions to a general hospital had hyperglycemia, defined as fasting blood glucose 126 mg/dL or random blood glucose 200 mg/dL on two or more determinations. Identifying a subgroup of the 718 hyperglycemic patients having no history of diabetes, the investigators reported that 12% (223 of 1886) had new hyperglycemia, whereas 26% (495 of 1886) had known diabetes. Mortality among patients with normoglycemia was 1.7% (20 of 1168), among those having known diabetes 3.0% (15 of 495), and among those having new hyperglycemia 16% (36 of 223), both p . 01. Rady et al (13) showed that among 7285 intensive care unit admissions, mortality rate in the hospital in the control group was 5% (230 of 4459), among the patients with diabetes was 6% (61 of 1083), and among the nondiabetic patients treated for hyperglycemia was *See also p. 539.