|Ahead of print publication
Acute diabetic complications and implications of glycated hemoglobin levels (HbA1c) in the emergency department – Experience from a tertiary care centre of South India
Sudhakar Geratala Dhanapal, Gina Maryann Chandy, Joshua Vijay Joseph, Ramgopal Roshan Rajaram, Mamta Madhiyazhagan, Kundavaram Paul Prabhakar Abhilash
Department of Emergency Medicine, Christian Medical College, Vellore, Tamil Nadu, India
|Date of Submission||05-Jul-2021|
|Date of Decision||05-Nov-2021|
|Date of Acceptance||05-Nov-2021|
Gina Maryann Chandy,
Associate Professor, Department of Emergency Medicine, Christian Medical College, Vellore - 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: Uncontrolled diabetes leads to acute and chronic complications, both of which present to the emergency department (ED). Glycated hemoglobin (HbA1c) reflects glycemic history. This study was done to determine the correlation between acute diabetic complications and implications of HbA1c levels in ED. Materials and Methods: We conducted a prospective observational study between May 2019 and April 2020. Data was collected in a standard datasheet and analysed using Statistical Package for Social Sciences for Windows. Results: Our study included a total of 382 (0.5%) patients, among which 56% were male patients. Mean age was 57.9 (standard deviation ± 14.9) years. Based on their hemodynamic stability, majority (n = 291) were triaged as priority one. Acute diabetic complications included hypoglycemia-62% (238/382), diabetic ketoacidosis (DKA) - 26% (98/382) and hyperglycemic hyperosmolar state - 12% (46/382). Most common presenting complaints were unresponsiveness (49.7%) followed by breathing difficulty (31.6%) and fever (24.6%). Random blood sugar level at presentation was <70 mg/Dl in majority (62.3%) of them. Common precipitating factors were poor food intake (51%), infection (30%) and drug noncompliance (29.5%). Three-fourth of the study population was previously diagnosed to have diabetes mellitus and HbA1c >7 was seen in 227 (59%) patients. Bivariate and multivariate logistic regression analysis showed DKA (adjusted odds ratio [OR]: 5.2;95% confidence interval [CI]: 1.39–19.41; P = 0.014), noncompliance to medications (adjusted OR: 3.9; 95% CI: 1.4–10.76; P = 0.009) and poor oral intake (adjusted OR: 0.3; 95% CI: 0.14–0.59; P = 0.001) as independent predictors to have a HbA1c level >7. Approximately half (51.2%) the study population required admission while one patient died in the ED during resuscitation. Conclusion: Elderly male population were most commonly involved. Unresponsiveness was the most common presenting complain and hypoglycemia was the most common presenting clinical feature. Majority of the acute diabetic complications were precipitated by poor food intake, infection and noncompliance to medications. Hospital admission was warranted in majority of the study population. HbA1c in the ED is a useful parameter that would help plan further medication at discharge.
Keywords: Acute diabetic complications, diabetic ketoacidosis, emergency department, HbA1c, hyperglycemic hyperosmolar state, ypoglycemia
|How to cite this URL:|
Dhanapal SG, Chandy GM, Joseph JV, Rajaram RR, Madhiyazhagan M, Prabhakar Abhilash KP. Acute diabetic complications and implications of glycated hemoglobin levels (HbA1c) in the emergency department – Experience from a tertiary care centre of South India. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2022 Dec 7]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=335883
| Introduction|| |
Diabetes is a global endemic with rapidly growing prevalence in both developed and developing countries. The global burden of diabetes was estimated to be 154 million in 2000, with a prevalence of 4.2% in the general adult population. There were an estimated 37.76 million diabetics in India in 2004; 21.4 million in urban areas and 16.36 million in rural areas. Diabetes was estimated to be responsible for 109 thousand deaths, 1157 thousand years of life lost and for 2263 thousand disability-adjusted-life years during 2004.,
An individual's average blood glucose levels during the previous 2 to 3 months can be obtained by analysis of Glycated hemoglobin (HbA1c) in blood., Koenig et al. first proposed using the HbA1c as a biomarker for monitoring the levels of glucose among diabetic patients in 1976. This biomarker is a significant indicator of long-term glycemic control which reflects the cumulative glycemic history. It has some major advantages over fasting plasma glucose estimation for diagnosing diabetes mellitus (DM). HbA1c level and its interpretation is as follows: Normal <5.7%, prediabetes: 5.7%–6.4% and diabetes: ≥6.5%. In patients with high HbA1c level, the metabolic control is poor, leading to chronic hyperglycemia. However, the lack of availability of HbA1c test in remote areas, the high cost of the test, and faulty standardization techniques are certain limitations in using this test. Emergency department (ED) visits of patients with acute diabetic complications, inflict a significant burden on the health care system. Acute diabetic complications most commonly seen in the ED are hypoglycemia, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS).,, In these condition, single dose of insulin or drug omission, poor food intake and infection may trigger the development of hypoglycemia, ketoacidosis or hyperosmolar hyperglycemic state in diabetes., ED offers an opportunity to identify cases with uncontrolled or sub-optimally controlled DM or previously unrecognised DM or those who have pre-DM. Identifications of these complications and establishing a relation with HbA1c will help patients to initiate appropriate medication management and/or lifestyle changes and/or and DM self-management education., On the other hand it will also help in preventing recurrent ED visits for acute diabetic complications, and also prevent long-term DM complications.
Since there is a dearth of studies in India on correlation of HbA1c and acute diabetic complications in ED we conducted this prospective study. Our objectives were to determine factors that precipitate diabetic emergencies and to study their relationship to HbA1c.
| Materials and Methods|| |
This was a prospective observational study done in patients presenting to our ED with acute diabetic complications.
The present study was conducted in the ED of a 2900 bedded tertiary medical care centre in South India. Our ED is a 49-bed department and caters to need of around 300 patients/day. All adult emergency cases (>15 years), are managed in our ED, whereas all other pediatric emergencies are managed in pediatric casualty. Six priority I beds are dedicated exclusively for patients with hemodynamic compromise.
Aims and objectives
Our study aimed to determine the correlation between HbA1c values and acute diabetic complications in the ED. The objectives of the study were to assess glycemic control via Hba1c level testing, determine factors that precipitate diabetic emergencies and to study the relationship between HbA1c and ED outcome of these patients.
We included all patients (aged ≥18 years) presenting with acute diabetic complications such as DKA, HHS, and hypoglycemia during the study period of 11 months (May 2019–April 2020). Informed written consent was obtained from the patients themselves or their relatives. The following were excluded from the study: Those aged <18 years, who did not give consent for the study, with missing HbA1c values or incomplete chart documentation/missing data.
Data was collected using standard spread sheet, interviewing patient or patient's relatives and using clinical workstation. Canadian triage acuity scale system was used in triaging these patients based on their physiological stability. Demographic factors such as age, sex, onset of symptoms, characteristics of the complaints, patient risk factors, comorbidities and drug history were recorded and analysed.
Outcome of the patients from the ED with regards to HbA1c levels, precipitating factors, type of infection, percentage of patients getting admitted or discharged stable and death in ED.
Besides routine laboratory investigations and relevant radiological tests, HbA1c levels were sent at presentation from ED. HbA1c is a quantitative variable which is a scale variable to test the control of diabetes over a period. Based on HbA1c levels, we have segregated patients into groups and statistical analysis was done.
All consecutive patients who presented with acute diabetic complications were screened and those who consented to take part in study were recruited.
The information regarding the onset of symptoms, characteristics of the complaints, patient risk factors, comorbidities and drug history was obtained by directly questioning the relatives at presentation as a part of history taking, thereby minimizing the risk of recall bias.
To minimize the interviewer bias, a standard set of questions were asked according to the prepared clinical research form in advance.
The sample size was calculated based on Abejew AA et al., with 41f7.2% prevalence of acute diabetic complications, precision of 5% and confidence interval (CI) of 95%. Sample size calculated was 372.
Data analysis was done using Statistical Package for Social Sciences for Windows (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0, Armonk, NY, USA). Continuous variables were expressed as mean with standard deviation (SD) and nominal variables as numbers and percentages. Dichotomous variables were compared by using Chi-square tests. The categorical variables associated with outcome (in relation to HbA1c levels) were determined by bivariate logistic regression analysis and their 95% CIs calculated. A 2-sided P < 0.05 was considered statistically significant.
This study was approved by the Institutional Review Board before its commencement. Approval from the ethical committee was obtained (IRB Min. No. 11926 dated 06.03.2019). Patient confidentiality was maintained using unique identifiers and by password protected data entry software with restricted users.
| Results|| |
The ED attended to a total of 71,563 patients during the 11 months study period. The prevalence of acute diabetic related complications was 0.7% (n = 556), After making relevant exclusions as per the criteria mentioned in the methodology, 382 (0.5%) patients were screened and included in the study. The mean age of the study cohort was 57.9 (SD: ±14.9) years, with a male preponderance (56%: n = 213). Based on their physiological status at arrival, three-fourth (76.2%: n = 291) of the patients were triaged as Priority 1 and 23.8% (n = 91) were triaged as Priority 2 [Figure 1]. In this geographical location, it was noted that a majority of the population had the previous co-morbidity of Type II DM (89%: n = 340), hypertension (70%: n = 268), dyslipidemia (34.2%: n = 130), chronic kidney disease (16.2%: n = 62), Type I DM (10.2%: n = 39), gestational DM (0.8%: n = 3) and chronic liver disease (3.6%: n = 14). The patients presented with a multitude of symptoms including unresponsiveness (most common) (49.7%: n = 190), breathing difficulty (31.6%: n = 121), fever (24.6%: n = 94) and vomiting (21.4%: n = 82). Majority of them had a random blood sugar of <70 mg/Dl at ED triage. Clinical features at presentation and the vital signs are given in [Table 1]. Two thirds of the patients who was previously diagnosed to have DM were on oral hypoglycaemic drugs (61.5%: n = 235), while the remaining took insulin (20.4%: n = 78) or combination of both (18%: n = 68). Poor food intake (51.8%: n = 195) was the most common precipitating factor of an acute diabetic complication. This primarily was seen in the hypoglycemia subset, i.e., 81% (n = 193). Drug noncompliance in 113 (36%) and infections in 115 (30%) were the other major factors that precipitated these complications. Precipitating factors of each of the acute diabetic complications has been sub categorised and given in [Table 2]. Urinary tract infections (UTI) (40%: 14/35) were the most common precipitating infection for hypoglycaemia, followed by lower respiratory tract infection (LRTI) (28.6%: 10/35). Whereas LRTIs precipitated DKA (45.6%: 26/57) and HHS (47.8%: 11/23) more often. The mean HbA1c for hypoglycaemia patients was 6.94 (SD ± 1.87) whereas for DKA it was 11.44 (SD ± 2.22) and HHS was 11.08 (SD ± 2.23). Of those presenting with hypoglycemia, 87 (36.6%) patients had HbA1c level more than 7, among which four patients had HbA1c of 14. Most patients who eventually developed DKA or HHS had higher HbA1c's with the mean value not showing much difference for the two acute diabetic complications. [Figure 2] is based on HbA1c levels versus acute diabetic complications.
|Figure 2: Glycated haemoglobin levels versus acute diabetic complications|
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Bivariate and Multivariate logistic regression analysis revealed DKA (odds ratio [OR]: 5.2; 95% CI: 1.39–19.41; P = 0.014), drug noncompliance (OR: 3.9; 95% CI: 1.4–10.76; P = 0.009) and poor oral intake (OR: 0.3; 95% CI: 0.14–0.59; P = 0.001) to be independent risk factors for patients to have a higher HbA1c value (≥7). Poor food intake predisposed to hypoglycemia and was seen in patients with lower HbA1c levels [Table 3]. But here we see that the HbA1c levels are around 7, which is what is advised by American Diabetes Association. HbA1c level and ED outcomes are being depicted in [Table 4]. Majority of the patients with a high HbA1c value (≥7) required hospital admission. ED team treated and discharged 141 (36.9%) patients with a plan to follow up in the medicine outpatient department. Approximately half of the study population (51.2%: N-196) warranted an admission either in intensive care unit or ward for management of the underlying disease and optimisation of glycemic control. One patient (0.3%) succumbed to the illness during resuscitation in the ED. Remaining (11.5%: n = 44) were discharged at request after primary care in ED.
|Table 3: Univariate and multivariate logistic regression analysis of factors associated with HbA1c≥7|
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|Table 4: Comparison of emergency department outcome with Glycated hemoglobin levels|
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| Discussion|| |
Our study showed that HbA1c levels for patients presenting with acute diabetic complications were higher compared to American Diabetes Association recommended targets., Although the prevalence of both type 1 and Type 2 DM is increasing; the prevalence of Type 2 DM is increasing rapidly, because of sedentary life styles, obesity, aging population and as the country becomes more industrialized.,, HbA1c is used globally as a reliable indicator to assess glycemic status., It has an advantage over fasting plasma glucose, of being a more convenient random test that does not require overnight fasting. Our study showed that the most common acute diabetic emergency in ED was hypoglycemia seen in more than half of the population and males were more prone for this condition. Average HbA1c was 6.94 in those with hypoglycemia, thereby showing that inspite of liberal glycemic control, hypoglycemic events can occur due to other precipitating factors such as infections and poor oral intake. Majority of these patients required an in-hospital admission for correction of the underlying condition. Hypoglycemia the most common complication seen, followed by DKA and HHS in our study, whereas in the Hanumanthaiah et al. study, DKA was found to be most common. The possible explanation for this could be the diversity of the study population i.e., semi urban versus cosmopolitan. The epidemic of diabetes is due to the rapid transition associated with change in dietary patterns and reduced physical activity as evident from the increased prevalence in urban population., Choi et al., conducted a similar retrospective study on patients who visited the ED with hypoglycaemia, where the mean age and HbA1c levels were similar to ours. However this study showed a decreasing trend in patient numbers with hypoglycaemia during the study period, which was partly explained by the decrease in the use of sulfonylurea and increase in dipeptidyl peptidase 4 inhibitor.,, Whereas in our study 42 (17.6%) patients had recent history of drug change from OHA to insulin or adding sulfonylureas besides biguanides. Glycemic control maintaining HbA1c within the recommended norm, without an overtly strict control, did not seem to protect against hypoglycemia in our study population. A study from California revealed that those with very poor glycemic control tend to have higher risk of developing hypoglycemia., Hypoglycemia in well or poorly controlled diabetes can be attributed by poor food intake and infection, in our study it was predominantly UTI.
In our study population, DKA was precipitated by drug noncompliance and LRTIs, whereas, UTI was the precipitating factor in Hamed et al. study. The female predominance in this study must have been the reason for the higher prevalence of UTI, as it is the most common infection in women. The HbA1c levels were similar in patients with HHS and DKA. We observed most of the HHS patients were noncompliant to drug and presented with shortness of breath. This was in contrast to previous literature where infection was the most common precipitating factor. Polypharmacy, hesitation to take medication and lower educational status compounds noncompliance to the prescribed drug regimen. Our study showed that majority of the patients with a high HbA1c value (≥7) required admission for management of underlying diseases and optimisation of glycemic control.
As there are so many implications to the HbA1c test, there is a need for it to be done for all patients presenting to the ED with an acute diabetic complication.,, It provides a baseline estimate of general glycemic control that can aid in planning hospital admission or medications at discharge from ED.
Suggestions for future research
There is a dearth of research on HHS and its association with HbA1C levels. A large multi-centric study will help to understand this entity. Educating patients through various teaching methods on good glycemic control to prevent such complications and reassessing HbA1c and complication rates to see if there is a change. For the management of such complications in different ethnic groups, exclusive guidelines are to be defined.
Our study was confined to the ED and we reported only the ED outcome of these patients. It is a single centric study, hence might have referral bias. This study was conducted on adults and so cannot be generalized to the pediatric population. This will need a separate study within the pediatric population.
| Conclusion|| |
The most common acute diabetic emergency presenting to ED was hypoglycemia, which was seen despite accurate glycemic control (HbA1c at recommended levels). Those presenting with DKA and HHS had uncontrolled sugars with high HbA1c values. Poor oral intake, infections and noncompliance to medications were the most common precipitating factors and are independent risk factors for patients to have HbA1c values of more than 7. Determining the levels of HbA1c will help in a physicians decision making for ED disposition; where majority require in hospital admission.
Research quality and ethics statement
The authors of this manuscript declare that this scientific work complies with reporting quality, formatting and reproducibility guidelines set forth by the EQUATOR Network. The authors also attest that this clinical investigation was determined to require Institutional Review Board/Ethics Committee review, and the corresponding protocol/approval number is IRB Min. No. 11926 dated 06.03.2019. We also certify that we have not plagiarized the contents in this submission and have done a Plagiarism Check.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]