EFFECT OF HYPERGLYCEMIA ON OUTCOME OF ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE.

HbA1c levels Difference in HbA1c levels of Group I and Group II patients was found to be statistically significant. Mean duration of hospital stay of patients having HbA1c >6 (9.78±1.74 days) was found to be higher than that having HbA1c ≤6 (6.77±2.08 days). Difference in hospital stay of patients with HbA1c levels ≤6 and HbA1c >6 was found to be statistically significant. No association was found between HbA1c levels and the COPD GOLD stage. Among the 107 patients enrolled in our study a total of 6 deaths were recorded. All 6 patients belonged to GOLD stage D as indicated by their past medical records and past history. Of these 6 patients, 5 patient‟s RBS at admission was more than 200 mg/dl. It was observed in our study that the percentage of mortality increased as the random blood glucose level increased.

930 severity was determined according to GOLD classification criteria. On the basis of history, acute exacerbation was diagnosed by the following criteria: 1. Recent rapid worsening of dyspnea 2. Increase in Sputum Purulence 3. Increase in Sputum volume Patients who did not give consent, gave history of bronchial asthma, interstitial lung disease, pulmonary tuberculosis / bronchiectasis, concomitant cardiac disease, renal disease, liver disease or malignancy were excluded. All patients of AECOPD who fulfilled the inclusion criteria, admitted in Department of Medicine, KGMU, Lucknow, were enrolled for the study. Random blood sugar level was estimated by GOD-POD method (glucose oxidaseperoxidase, kits by Erba) method at the time of admission. A 2mL peripheral blood sample was taken for Glycosylated hemoglobin (HBA1C). The length of hospital stay of each patient was recorded in days. If a patient expired during the course of the hospital stay, then it was recorded as an outcome. A composite adverse outcome was defined as, death or length of stay longer than the median length of stay for analysis. Data was entered in structured tables for comparison where the study population was divided into groups or quartiles according to different age groups, blood glucose levels and HBA1C.

Methods:-
AECOPD Patients were enrolled and their informed consent were taken. A detailed clinical history and physical examination was carried out for every subject. In the clinical history duration of COPD with history of exacerbation and treatment were inquired. All patients were subjected to a CAT questionnaire (COPD Assessment Test) and MMRC (Modified Medical Research council) dyspnea scale, on the basis of which disease severity was calculated. History of presence of risk factor like smoking, hypertension, dyslipidemia, diabetes mellitus, and presence of any other chronic disease was inquired. Following Biochemical investigations were also carried outhaemogram, renal function test, liver function test, PT-INR, HBA1C, blood sugar (fasting and post prandial), CXR-PA view, fasting lipid profile, sputum routine microscopy, 2D Echo examination, Pulmonary function test.

Results:-
A total of 107 COPD patients were enrolled in the study of which 6 patients died. So that only 101 patient underwent follow up. Demographic details of 101 patients enrolled in the study are as under: Out of 101 COPD patients enrolled in the study, 66 (65.35%) had random blood sugar levels ≤200 mg/dl were classified as Group I and rest 35 (34.65%) patients having random blood sugar levels >200 mg/dl were classified as Group II (Hyperglycemic). Sub categorization was done on the basis of RBS and is listed as under: Our study showed that the duration of hospital stay among patients of Group II (9.63±2.04 days) was found to be significantly higher as compared to Group I (6.89±2.08 days). A subsequent increase in duration of hospital stay was observed among Subgroup Ia (6.00±1.93 days), Subgroup Ib (6.89±2.08 days), Subgroup Ic (8.63±1.09 days) and Group II (9.63±2.04 days) was observed. Subgroup analysis was done using the ANOVA test (Analysis of Variance) and the results were found to be statistically significant with p value <0.001. Table-3 shows intergroup comparison of the duration of illness and hospital stay as follows-  In our study of the 107 patients enrolled, 6 deaths were reported. All 6 patients belonged to GOLD stage D as indicated by their past medical records and past history. Amongst these 6 patients, 5 patient"s RBS at admission was more than 200 mg/dl. The percentage of mortality increased as the random blood glucose level increased. All deaths reported were in patients over 66 years of age.

Discussion:-
Patients enrolled in our study ranged between 48 & 88 years, with the median age being 69 years and mean age of patients was 67.92±8.82 years ( Table 1). Only 7 (6.93%) patients were aged 41-55 years and 32 (31.68%) 56-65 years. Most common age group was 66-75 years (46.53). Out of the 101 COPD patients enrolled in the study, 66 (65.35%) had random blood sugar levels ≤200 mg/dl were classified as Group I and the remaining 35 (34.65%) patients having random blood sugar levels >200 mg/dl were classified as Group II (Hyperglycemic). Group I was further divided in three subgroups -31 (30.69%) patients had random blood sugar levels <140 mg/dl were classified as Subgroup Ia, 19 (18.81%) patients having random blood sugar levels 140-170 mg/dl were classified as Subgroup Ib and 16 patients having random blood sugar levels 171-200 mg/dl were classified as Subgroup Ic. Duration of hospital stay among patients of Group II (9.63±2.04 days) was found to be significantly higher as compared to Group I (6.89±2.08 days). A subsequent increase in duration of hospital stay was observed among Subgroup Ia (6.00±1.93 days), Subgroup Ib (6.89±2.08 days), Subgroup Ic (8.63±1.09 days) and Group II (9.63±2.04 days) was observed. This association was found to be statistically significant (p<0.001). Majority of patients of Group I (80.30%) had HbA1c levels <6% while majority of patients of Group II (65.71%) had HbA1c levels >6%. Difference in HbA1c levels of Group I and Group II patients was found to be statistically significant. Mean duration of hospital stay of patients having HbA1c >6 (9.78±1.74 days) was found to be higher than that having HbA1c ≤6 (6.77±2.08 days). Difference in hospital stay of patients with HbA1c levels ≤6 and HbA1c >6 was found to be statistically significant. No association was found between HbA1c levels and the COPD GOLD stage. Among the 107 patients enrolled in our study a total of 6 deaths were recorded. All 6 patients belonged to GOLD stage D as indicated by their past medical records and past history. Of these 6 patients, 5 patient"s RBS at admission was more than 200 mg/dl. It was observed in our study that the percentage of mortality increased as the random blood glucose level increased.
In the study done by Pramila et al; 2016, the hyperglycemia was assumed as random blood glucose levels >140 mg/dl. Out of 100 patients 35% (n=35) were normoglycemic and 65% (n=65) were hyperglycemic [5] . Statistically significant relation was found between the quartiles of RBS ≤140 mg/dl with 171-200 mg/dl&≥201 mg/dl with p value 0.01. This study inferred that RBS more than 170 mg/dl is detrimental in AECOPD patients. Archer et al; 2011, in his prospective, non-randomized, single arm study of intensive glycemic control in AECOPD patients demonstrated that intensive glucose control can be achieved within the acute medical ward with a similar safety and efficacy to that achieved in patients admitted to an intensive care unit, and the control of blood sugar could potentially have some benefit in AECOPD patients [6] . Burt, et al; 2014, reported that the length of hospital stay is increased by 10% (21hours) for each 18 mg/dl increase in mean glucose (P=0.01)10. In this study the blood glucose levels of 47 patients were monitored continuously using a device to measure interstitial glucose levels to determine the pattern of hyperglycemia in patients receiving prednisolone for AECOPD. Higher mean daily glucose levels were positively associated with longer hospital stays; this relationship with length of stay was not significant for other markers of disease severity [7] . Naghamjafar md et al; 2015, Hyperglycemia has been associated with increased morbidity, increased mortality, and longer lengths of stay, and more hospital costs in patients with both medical and surgical conditions [8] . In a study by Deepali J. Kamdar, Dharmeshkumar Patel; 2017, A statistically significant relationship was obtained between male gender, smoking history (odd ratio of 1.5), number of pack years (p = 0.029), history of prior admission (odds ratio of 2), longer duration of illness (p = 0.045), elevated blood sugar levels (p = 0.035) [9] .
Acute exacerbation of COPD, much like any other critical illness, is associated with hyperglycemia due to the stress related hormonal response to acute illness and possibly some of the medications routinely used in the treatment of AECOPD. While several studies have previously suggested that hyperglycemia has adverse outcomes in patients with AECOPD, but the pathophysiology underlying these outcomes is yet to be determined. Further research is needed on the various outcomes in AECOPD in patients with deranged blood sugar, using a larger sample size and taking into consideration a design that will provide more insight into the pathophysiology. In addition, a study on predefined targets of glycemic control and outcomes is needed [156] .

Conclusion:-
Our study corroborates the evidence gathered from studies by previous authors and implicates hyperglycemia as a potentially harmful and correctable abnormality in critically ill patients and support ongoing consideration of hyperglycemia as a therapeutic target to improve outcomes in hospitalized patients of AECOPD. The finding that the magnitude of mortality risk from hyperglycemia depends on the underlying disease suggests that the degree of benefit from glucose-lowering may differ among patients with certain conditions. The results gathered from our study suggest that strict control of blood sugar in the prehospitalisation period as well as during hospital stay results in better outcomes such as shortened duration of hospital stay; decreased mortality and morbidity.

Limitations:-
This was a single centre study and majority of the patients were in GOLD stage C or D. The study was carried out on a limited patient population, so we recommend a multicentre study with a larger sample size so that the true relation between hyperglycemia, HbA1C and outcome of Acute Exacerbation of COPD is established.