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 Table of Contents  
ORIGINAL ARTICLES
Year : 2021  |  Volume : 12  |  Issue : 2  |  Page : 134-139

Admission hyperglycemia and its implications on outcome in patients attending medical intensive care units at Assiut University Hospital


Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt

Date of Submission24-Jun-2018
Date of Web Publication31-Mar-2021

Correspondence Address:
Prof. Lobna F El Toony
Department of Internal Medicine, Faculty of Medicine, Assuit University, Assuit.
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jod.jod_28_18

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  Abstract 

Background: Admission hyperglycemia is defined as any blood glucose (BG) level greater than 140 mg/dL (>7.8 mmol/L) in critical care unit (CCU) according to American Diabetes Association 2015. Stress hyperglycemia is related to multiple factors and can lead to insulin resistance and high hepatic glucose output. Aim: To determine the frequency, in-hospital mortality, and length of stay in a cohort of patients with admission hyperglycemia in unselected acute medically ill patients admitted to medical intensive care units (ICUs) (medical ICU and CCU) attending Internal Medicine Department, Assiut University Hospital, Assiut, Egypt, and to evaluate whether admission hyperglycemia or other comorbid conditions are responsible for outcome of critical ill patients. Subjects and Methods: This prospective, observational study involved 170 patients admitted at ICU unit of Internal Medicine Department at Assiut University Hospital between July and December 2016. Measurement of BG on admission to ICU was as following: normoglycemic if less than 140 mg/dL and hyperglycemic if more than 140 mg/dL. Then, follow up BG every 8h till either discharge or death or maximum 4 days in addition to fasting, postprandial BG, HbA1C, complete blood count and kidney function tests, serum sodium, serum potassium, arterial blood gases, and acute physiologic assessment and chronic health score were carried out. Results: This study included 170 patients, 35.3% were normoglycemic and 64.7% were hyperglycemic, which were further subdivided into 43% known diabetics, 14.1% stress hyperglycemia, and 7.6% newly discovered diabetics. Percentage of survivors was 72.9% versus non-survivors, which was 27.1%. Median hospital stay for all patients was 6 (4–28) days with in-hospital mortality of 46 (27.1%) patients. It was noticed that frequency of non-survivors was higher in patients with hyperglycemic versus that of survivors. Conclusion: Stress hyperglycemia and diabetes were independent predictors for in-hospital mortality in patients with admission hyperglycemia attending ICU.

Keywords: Admission hyperglycemia, APACHE II score, glycated hemoglobin, intensive care unit, stress-induced hyperglycemia


How to cite this article:
El Toony LF, El Zohri MH, Abo Elghait AA. Admission hyperglycemia and its implications on outcome in patients attending medical intensive care units at Assiut University Hospital. J Diabetol 2021;12:134-9

How to cite this URL:
El Toony LF, El Zohri MH, Abo Elghait AA. Admission hyperglycemia and its implications on outcome in patients attending medical intensive care units at Assiut University Hospital. J Diabetol [serial online] 2021 [cited 2021 Apr 16];12:134-9. Available from: https://www.journalofdiabetology.org/text.asp?2021/12/2/134/312659




  Introduction Top


Stress-induced hyperglycemia (SIH) is a common finding among critically ill patients, particularly among cardiovascular patients, neurocritical patients, and patients undergoing surgical procedures, even in the absence of preexisting Diabetes Mellitus (DM).[1] SIH occurs in critically ill patients in whom glucose tolerance was previously normal, with hyperglycemia resolving following recovery.[2] SIH is related to multiple causes that include inflammatory and neuroendocrine derangements in critically ill patients, which lead to insulin resistance and high hepatic glucose output.[3] Stress hyperglycemia (SH) is caused by endogenous and exogenous factors. Critical illness leads to activation of the hypothalamic-pituitary-adrenal axis, which results in the release of cortisol. Cortisol stimulates gluconeogenesis and decreases glucose utilization. Other counter-regulatory hormones (glucagon, catecholamine, and growth hormone) are also released.[4] Hypermetabolic state occurs in patients in a critical condition due to their disease, with intense activation of contraregulating hormones and cytokines, such as tumor necrosis factor alpha, interleukin 1 (IL-1), and IL-6, which are important insulin resistance mediators, thereby causing hyperglycemia.[5] This usually resolves as the acute illness or medico-surgical stress decreases but a small study showed that 60% of patients with admission hyperglycemia had confirmed diabetes at 1 year.[6] Severe hyperglycemia is a well-documented marker of illness severity rather than a direct cause of poor outcome.[7] There is evidence that developing hyperglycemia during an illness or acute surgery increases morbidity, the number of days spent in the intensive care unit (ICU) and in hospital, as well as the number of days with mechanically assisted respiration.[8] SH in critically ill patients is a common therapeutic challenge. There is no universally accepted insulin regimen for glycemic control in critically ill patients.[9] The American Diabetes Association 2016 recommends starting insulin in patients with persistent hyperglycemia above 180 mg/dL in critically ill patients and to maintain the glycemic range between 140 and 180 mg/dL. It also states that stricter glycemic control (110–140 mg/dL) can be appropriate for certain patients such as those with acute cardiac ischemia or patients with acute neurological event to avoid hypoglycemia.[10]


  Aim Top


To determine the frequency, in-hospital mortality, and length of stay in a cohort of patients with admission hyperglycemia in unselected acute medically ill patients admitted to medical intensive care units (medical ICU and critical care unit [CCU]) attending Internal Medicine Department, Assiut University Hospital, Assiut, Egypt, and to evaluate whether admission hyperglycemia or other comorbid conditions are responsible for outcome of critically ill patients.


  Subjects and Methods Top


Patients

This study was a prospective, observational, and noninterventional study, which involved 170 patients who were admitted at the ICU of Internal Medicine Department at Assiut University Hospital between July 1, 2016 and December 30, 2016.

Inclusion criteria: Both male and female patients more than 18 years of age hospitalized through the ICUs (medical ICU and CCU) for critical medical conditions according to acute physiologic assessment and chronic health (APACHE II) score were included.

Exclusion criteria: Patients with hypoglycemia (hypoglycemia was defined as the presence of blood glucose [BG] level <70 mg/dL) and patients who were discharged against medical advice were excluded as the outcome was unknown.

All patients in our study were subjected to the followings: Detailed history, clinical examination, systemic examination, and laboratory investigation including random BG on admission to ICU, which if less than 140 mg/dL was categorized as normoglycemic (NG). If more than 140 mg/dL was categorized as hyperglycemic, then follow-up BG should be checked on days of ICU every 8h till either discharge, death, or maximum 4 days in addition to fasting, postprandial glucose, glycated hemoglobin (HbA1C), also laboratory works including liver function test, complete blood count, kidney function tests, serum sodium, serum potassium, arterial blood gases, calculation of APACHE II, and calculation of length of stay by date of admission and date of discharge were carried out.

Statistical analysis

Data were collected and analyzed using Statistical Package for the Social Sciences (SPSS), version 20, (IBM, Armonk, New York). Continuous data were expressed in the form of mean ± standard deviation, whereas nominal data were expressed in the form of frequency (percentage). Chi-square test was used to compare the nominal data of different groups in the study, whereas Student’s t-test was used to compare the mean of two different groups and analysis of variance test for more than two groups. Multivariate regression analysis was used to determine the independent risk factors for mortality in patients admitted to ICU with hyperglycemia.

Ethics and consents: The study protocol was approved by the local ethics committee in the Faculty of Medicine, Assiut University, on June 23, 2015.


  Results Top


This study included 170 patients, those patients were classified into the following groups:

  1. NG: Patients with normal random blood sugar level less than 140 mg/dL and were not known to be diabetic or on oral hypoglycemic agents. This group included 60 (35.3%) patients.


  2. Hyperglycemic: Patients with random blood sugar level >140 mg/dL, included 110 (64.7%) patients and were subdivided into:
  3. Known diabetics (DM): Patients with a well-documented history or on medications for diabetes mellitus. This group included 73 (43%) patients.


  4. SH: Patients with HbA1C less than 6.5%. This group included 24 (14.1%) patients.


  5. Newly discovered diabetics (ND): Patients with HbA1C more than 6.5%. This group included 13 (7.6%) patients.


Demographic characteristics of the study population: No significant difference was observed between the ages of different groups. Diabetic group had statistical significant high frequency of hypertension, chronic kidney disease, and coronary artery disease (P values were 0.01, 0.02, and 0.04, respectively). Collagen diseases, in particular systemic lupus erythromatosis, were significantly frequent in patients with SH (5, 18.9% with P = 0.01). Presence of more than three comorbidities including DM was higher in diabetic group (42, 57.5%) compared to that in other groups with significant P value (0.01).

Clinical characteristics of the study population: The majority of patients included in each group were overweight. There was a wide range for the main cause of admission in each group. In general, myocardial infarction (MI) and pneumonia were the main cause of admission in the majority of all patients where each one occurred in 40 (23.5%) patients from the total number.

Average daily BG values for patients with hyperglycemia: This study showed that diabetic and newly discovered DM had significant differences between them regarding average daily BG over 4 days and HbA1C (P > 0.05) but both groups had significantly high values in comparison with patients with SH (P < 0.05) as shown in [Table 1]. The difference of average HbA1C between the different groups was present in [Figure 1]. The majority of the subjects were survivors as shown in [Figure 2].
Table 1: Average daily blood glucose values for those with hyperglycemia

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Figure 1: Glycated hemoglobin in the studied groups

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Figure 2: Survivors and non-survivors among the studied patients

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Hospital stay and outcome of the study population: Median hospital stay for all patients was 6 (4–28) days with in-hospital mortality of 46 (27.1%) patients of the total patients (170). It was noticed that the patients with SH associated with high mortality rate (37%). Regarding causes of death, MI and pneumonia were the most common causes in all patients and each group as shown in [Figure 3].
Figure 3: Mortality in each studied group

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Average daily BG values for survivors versus non-survivors: Although the range of hospital stay was higher in non-survivors than survivors (4–28 vs. 4–23 days), yet this had no significant value (P > 0.05). It was noticed that frequency of non-survivors was higher in patients with hyperglycemia 39 (84.8%) versus survivors 71 (57.3%) (P < 0001) as shown in [Table 2] and [Table 3].
Table 2: Outcome and medianhospital stay

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Table 3: Follow-up of survival with average daily blood glucose values for those with hyperglycemia

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The mortality rate was different greatly between patient groups. The highest mortality was noted in diabetes 43.5%, SH 37% followed by normoglycemia 15.2% and the least mortality was newly discovered diabetes 4.3% [Figure 3]. The difference between groups was statistically significant (P < 0001).

Multivariate regression analysis for predictors of in-hospital mortality in patients with hyperglycemia: It was found that the presence of greater than three comorbidities (95% confidence interval [CI], odds ratio [OR] = 1.2; P = 0.00), APACHE II score >15 (95% CI, OR = 1.7; P = 0.03), SH (95% CI, OR = 2.89; P = 0.00), and diabetes (95% CI, OR = 1.39; P = 0.00) were independent predictors for in-hospital mortality in patients with hyperglycemia as shown in [Table 4] and [Table 5].
Table 4: Percentage of survival/mortality rate within each group

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Table 5: Multivariate regression analysis for predictors of in-hospital mortality in patients with hyperglycemia

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Comorbidities included in the study were hypertension, chronic kidney disease, coronary artery disease, congestive heart failure, liver cirrhosis, chronic obstructive pulmonary disease, cerebrovascular stroke, malignant disease, collagen disease, and psychiatric disease.


  Discussion Top


Hyperglycemia associated with critical illness (also called SIH or stress diabetes) is a consequence of many factors, including increased cortisol, catecholamine, glucagon, growth hormone, gluconeogenesis, and glycogenolysis. Insulin resistance may also be a contributing factor as it has been observed in more than 80% of critically ill patients.[11]

Hyperglycemia was previously considered an adaptive response essential for survival and was not routinely controlled in ICUs. However, more recent evidence indicating that uncontrolled hyperglycemia is associated with poor outcomes has prompted efforts to routinely correct and prevent hyperglycemia in critically ill patients.[12]

Our study had included 170 patients admitted to ICU of Internal Medicine Department at Assiut University Hospital between July 1, 2016 and December 30, 2016. In our study, the overall prevalence of patients with hyperglycemia was 64.7% (43% with diabetes mellitus and 14.1% with SH), which was higher than that in the study carried out by Godinjak et al.,[4] where the overall prevalence of patients with hyperglycemia was 54% (35% with diabetes mellitus and 19% with a SH). Also, this percentage was higher than that in earlier studies where the prevalence of hyperglycemia was estimated at approximately 40% in studies carried out by Godinjak et al.[4] and Qaseem et al.[13] In a study conducted by Filippo et al.[14] in 2016, they found that patients with SH had higher in-hospital crude mortality (7.9%) than those with diabetes (5.7%) or those with normoglycemia (3.9%), which was in agreement with our study where SH was associated with the highest mortality rate (37%).

Further, we found strong association between in-hospital hyperglycemia and adverse outcome in the form of higher mortality irrespective of the presence of diabetes mellitus in patients admitted to ICU, which was consistent with a study by Dhakal et al.[15]

By multivariate regression analysis for predictors of in-hospital mortality in patients with hyperglycemia, it was found that the presence of greater than three comorbidities, including diabetes and APACHE II score >15, were independent predictors for in-hospital mortality in patients in the studied groups.


  Conclusion Top


SH and diabetes mellitus were independent predictors for in-hospital mortality in patients with hyperglycemia. Hyperglycemia is associated with increased risk of hospital complications and mortality in critically ill patients. So, meticulous and accurate intervention to control hyperglycemia, particularly in critically ill patients, is very important to reduce the morbidity, in-hospital stay, and lastly, the mortality in critically ill patients.

Recommendations

  1. Clinicians should have high index of suspicion of SH in critically ill patients, especially when considering administration of intravenous or oral glucose in sick patients.


  2. All critically ill patients should be subjected to BG monitoring and given appropriate management at the earliest stage to decrease morbidity and mortality.


  3. Measurement of HbA1C concentration during the hospital stay can assist in tailoring the glycemic management at discharge. Patients with HbA1C <6.5% can usually be discharged with no antidiabetic medications but just education. Patients with elevated HbA1C can be treated with insulin or oral antidiabetic agents or combination therapy.


  4. Patients with SH may be prone to develop diabetes in future life, so they should be advised for monitoring fasting, postprandial glucose, and HbA1C as follow-up.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Harp JB, Yancopoulos GD, Gromada J Glucagon orchestrates stress-induced hyperglycaemia. Diabetes Obes Metab 2016;18:648-53.  Back to cited text no. 1
    
2.
Dungan KM, Braithwaite SS, Preiser JC Stress hyperglycaemia. Lancet 2009;373:1798-807.  Back to cited text no. 2
    
3.
Robba C, Bilotta F Admission hyperglycemia and outcome in ICU patients with sepsis. J Thorac Dis 2016;8:E581.  Back to cited text no. 3
    
4.
Godinjak A, Iglica A, Burekovic A, Jusufovic S, Ajanovic A, Tancica, et al. Hyperglycemia in critically ill patients: Management and prognosis. Med Arh 2015;69:157-60.  Back to cited text no. 4
    
5.
McDonnell ME, Umpierrez GE Insulin therapy for the management of hyperglycemia in hospitalized patients. Endocrinol Metab Clin North Am 2012;41:175-201.  Back to cited text no. 5
    
6.
Greci LS, Kailasam M, Malkani S, Katz DL, Hulinsky I, Ahmadi R, et al. Utility of HbA(1c) levels for diabetes case finding in hospitalized patients with hyperglycemia. Diabetes Care 2003;26:1064-8.  Back to cited text no. 6
    
7.
Marik PE, Bellomo R Stress hyperglycemia: An essential survival response! Crit Care 2013;17:305.  Back to cited text no. 7
    
8.
Hsu CW Glycemic control in critically ill patients. World J Crit Care Med 2012;1:31-9.  Back to cited text no. 8
    
9.
Ali NA, O’Brien JM Jr, Dungan K, Phillips G, Marsh CB, Lemeshow S, et al. Glucose variability and mortality in patients with sepsis. Crit Care Med 2008;36:2316-21.  Back to cited text no. 9
    
10.
Diabetes Public Health Resource. Centers for Disease Control and Prevention. Hospital discharge rates for diabetes as any-listed diagnosis per 1,000 diabetic population, by age. United States. 1988–2009 [article online]. Available from https://www. cdc. gov/diabetes/statistics/ dmany/fig4. htm. [Last accessed on 2016 July 14].  Back to cited text no. 10
    
11.
Agus MS, Wypij D, Hirshberg EL, Srinivasan V, Faustino EV, Luckett PM, et al; HALF-PINT Study Investigators and the PALISI Network. Tight glycemic control in critically ill children. N Engl J Med 2017;376:729-41.  Back to cited text no. 11
    
12.
Finfer S, Chittock D, Li Y, Foster D, Ingra V, Bellomo R, et al. Intensive versus conventional glucose control in critically ill patients with traumatic brain injury: Long-term follow-up of a subgroup of patients from the NICE-SUGAR study. Intensive Care Med Indian J Endocrinol Metab 2015;21:137-41.  Back to cited text no. 12
    
13.
Qaseem A, Humphrey LL, Chou R, Snow V, Shekelle P; Clinical Guidelines Committee of the American College of Physicians. Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: A clinical practice guideline from the American College of Physicians. Ann Intern Med 2011;154:260-7.  Back to cited text no. 13
    
14.
Filippo P, Cristina B, Alessia F, Carlotta C, Andrea C, Francesco C, et al. The classification of hospitalized patients with hyperglycemia and its implication on outcome: Results from a prospective observational study in Internal Medicine. Intern Emerg Med 2016;11:649-56.  Back to cited text no. 14
    
15.
Dhakal M, Dhakal OP, Bhandari D Hyperglycemia in critically ill patients and its association with increased mortality. A hospital based observational study. Int J Med Res Rev 2016;4:525-530.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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