|Year : 2018 | Volume
| Issue : 2 | Page : 79-84
Clinical and laboratory profile of diabetic ketoacidosis in elderly with type 2 diabetes mellitus
B Anupama1, P Chandrasekhara2, MS Krishnamurthy2, Mohsin Aslam3
1 Department of Medicine, Guntur Government Hospital, Guntur, Andhra Pradesh, India
2 Department of Medicine, MVJ Medical College and Research Hospital, Bengaluru, Karnataka, India
3 Consultant Physician, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
|Date of Submission||29-Apr-2018|
|Date of Acceptance||17-Jul-2018|
|Date of Web Publication||26-Dec-2018|
Dr. Mohsin Aslam
Asian Institute of Gastroenterology, Somajiguda, Hyderabad - 500 082, Telangana
Source of Support: None, Conflict of Interest: None
INTRODUCTION: Diabetic ketoacidosis (DKA) in elderly is rare and poses a special problem because of high degree of mortality, comorbidity, age-related impairment of functional ability, and increased chances of hypoglycemia.
OBJECTIVES: The main objective is to study the precipitating factors, clinical and laboratory profile of DKA in elderly.
MATERIALS AND METHODS: A total of 100 type 2 diabetes mellitus (T2DM) patients, ≥60 years, admitted in a rural tertiary medical center were included in this study.
RESULTS: Most of them had prolonged diabetes with mean duration of 7.3 ± 4.6 years. 24 patients were newly detected diabetes mellitus. Systemic infections seen in 67 patients (respiratory –32.8%, sepsis – 28.4%, acute gastroenteritis – 22.4%, and urinary tract infections– 16.4%), were the main precipitating factors, followed by noncompliance to drugs (34). Osmotic symptoms were reported by most (62) followed by pain abdomen (56). Dehydration was seen in 72 patients, whereas altered sensorium in 48. Blood glucose at presentation (493.12 ± 72.38 mg/dl) and HbA1c levels (9.63 ± 0.94%) were found to be elevated with lowered arterial pH (7.14 ± 0.07) and bicarbonate (13.7 ± 4.2 mEq/L). 22 had severe acidosis and 10 had mild acidosis. There was no mortality in the present series.
CONCLUSION: DKA is more common in T2DM than anticipated. The most common precipitating factor is infection followed by noncompliance even in elderly. Majority had poor glycemic control. All elderly diabetic patients with high serum glucose level must be investigated for ketosis as the symptoms of DKA are minimal and morbidity and mortality are high in these patients.
Keywords: Diabetic ketoacidosis, elderly, infections, poor compliance, type 2 diabetes mellitus
|How to cite this article:|
Anupama B, Chandrasekhara P, Krishnamurthy M S, Aslam M. Clinical and laboratory profile of diabetic ketoacidosis in elderly with type 2 diabetes mellitus. BLDE Univ J Health Sci 2018;3:79-84
|How to cite this URL:|
Anupama B, Chandrasekhara P, Krishnamurthy M S, Aslam M. Clinical and laboratory profile of diabetic ketoacidosis in elderly with type 2 diabetes mellitus. BLDE Univ J Health Sci [serial online] 2018 [cited 2019 Nov 12];3:79-84. Available from: http://www.bldeujournalhs.in/text.asp?2018/3/2/79/248543
Diabetic ketoacidosis (DKA), which is an acute metabolic complication of diabetes mellitus (DM), was not curable before the insulin was discovered. Its incidence rate varies from 0.46%–0.8% of diabetic admissions in developed nations. However, its incidence is higher in Asia, Africa, and Polynesia.,, Earlier it was considered that DKA occurred only in persons with type 1 diabetes mellitus (T1DM) and T2DM was associated with hyperosmolar hyperglycemic state without ketosis as insulinopenia is not absolute in T2DM. However, in a North American study of African-Americans, ~60% of T2DM adults presented with DKA. Nearly half of African or Hispanic descent patients presenting with DKA are diagnosed with T2DM, whereas only less than 10% of Caucasian patients presenting with DKA are T2DM. Therefore, although DKA occurs T1DM, it can happen in T2DM also.
Infections, discontinuation of medication, inadequate insulin therapy, or newly diagnosed diabetes and myocardial infarction are some of the leading causes for the development of DKA in T2DM.
Insulinopenia, elevation of counterregulatory stress hormones, and increase in free fatty acids are responsible for development of DKA in T2DM.
It is postulated that the stressors precipitating DKA cause a relative deficiency of insulin. Chronic exposure of islet cells to high levels of glucose from free fatty acids may cause impairment of insulin secretion resulting in this relative insulin deficiency. Insulin deficiency prevents glucose being utilized by tissues within the body and increases gluconeogenesis in the liver, both resulting in hyperglycemia.
Insulin deficiency and the increased production of counterregulatory hormones causes lipolysis. This breakdown of fatty acids in the body results in the release of acetyl coenzyme Acetyl, which in turn, is converted into ketones-acetone, acetoacetate, and beta-hydroxybutyrate. This is ketosis and is what causes acidosis to occur. Beta-hydroxybutyrate can initially be present in the body without the presence of acidosis as the acidity is buffered by bicarbonate in the body, resulting in low bicarbonate in the blood until reserves become depleted and acidosis takes over.
Glucagon is a major positive regulator of hepatic gluconeogenesis and ketogenesis. It is suggested that the hyperglucagonemia in addition to the insulin deficiency may be an important factor in determining the degree of hyperglycemia and hyperketonemia in the early stages.
Few people have classic osmotic symptoms of hyperglycemia (weight loss, polydipsia, and polyuria) at diagnosis. Others present with acidotic symptoms (hurried respiration and altered sensorium). Symptoms and physical signs usually develop over 24 h. DKA in elderly is rare and poses a special problem because of high degree of mortality, comorbidity, age-related impairment of functional ability, and increased chances of hypoglycemia. Hence, we intended to study the precipitating factors, clinical and laboratory profile of DKA in elderly with T2DM.
| Materials and Methods|| |
One hundred T2DM patients, aged 60 years and more, admitted for DKA over 2 years at a rural tertiary medical center were analyzed to determine the precipitating factors, clinical and laboratory profile.
DKA was confirmed by the presence of hyperglycemia, positive urine ketone test results, and high anion gap metabolic acidosis. Individuals who had been managed at some point with diet or an oral hypoglycemic agent (OHA) and with no prior history of DKA and those without prior history of diabetes, whose insulin treatment could be shifted to OHAs were classified as T2DM.
The severity of acidosis was classified as mild, moderate, and severe based on pH and bicarbonate levels. Mild acidosis pH 7.2–7.3, bicarbonate 15–18 mEq/L, moderate acidosis pH 7.1–7.2, bicarbonate 10–14 mEq/L, severe acidosis pH <7.1, and bicarbonate <15 mEq/L. All patients were subjected to detailed history and physical examination with routine and relevant laboratory investigation for diabetes-related complications and DKA including arterial blood gases, HbA1c, chest X-ray, and electrocardiography were done. The treatment was started promptly with insulin infusion and other supportive measures. The aim was to achieve ketone-free urine with near-normal acid–base balance and electrolytes. The insulin infusion was discontinued, 1 h after administration of subcutaneous insulin, once the patient had a resolution of their metabolic status including the ketone-free urine and was able to tolerate oral feeding.
Blood glucose was analyzed by glucose oxidase using semi-autoanalyzer. HbA1C was analyzed by NYCOCARD KIT using Nycocard Reader II. HbA1c of 5.7% to 6.3% is considered as prediabetic state and HbA1c ≥6.3% was diagnosed to be diabetic.
Patients of either gender aged >60 years, who at presentation had symptoms of ketosis and or patients with random serum glucose >250 mg/dl were screened for ketosis and those with urinary ketone bodies positive were included in the study.
Patients with T1DM, secondary diabetes, and those with chronic infections were excluded from the study.
All the data were entered on Excel and analysis was done using Excel package. Unless otherwise specified, all data were expressed in mean ± standard deviation. Univariate analysis was carried out to study the differences in mean level among the factors. Statistical Package for Social Sciences version 15 (IBM Corporation) for Windows was the statistical package used for all statistical analysis of data collected in the course of the study.
| Results|| |
During the study period, 100 T2DM patients aged >60 years, admitted for DKA were included in the present study. [Table 1] shows the baseline characteristics of the study population.
|Table 1: Baseline characteristics of patients with diabetic ketoacidosis (n=100)|
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Of total 100 T2DM hospital admissions studied for DKA, 59 were male and 41 were female, with male predominance 3:2. The mean age of patients was 65.8 ± 2.4 years. Most of them had prolonged diabetes with mean duration of 7.3 ± 4.6 years, with a maximum duration of 25 years. Notably, 24 patients presented with ketosis as the presenting manifestation. Among comorbidities, 59 patients were found to have hypertension, 47 patients with dyslipidemia, and 28 patients with cardiovascular disorder in the form of ischemic heart disease. Thirty patients had 2 or more associated comorbidities. Only 8 patients had no associated comorbidities [Table 2].
|Table 2: Associated comorbidities in patients with type 2 diabetes mellitus presenting with diabetic ketoacidosis (n=100)|
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More than three-fourth (78) of the patients had a normal body mass index (BMI). Only 8 were obese diabetics [Figure 1].
|Figure 1: Graph showing the distribution of cases according to body mass index|
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Symptoms of DKA were similar as seen in type I DKA. Polyuria and polydipsia were reported by most (62) DKA patients followed by colic pain abdomen (56) and constitutional symptoms – fever, loss of appetite, dizziness, and lethargy (52). Nausea and vomiting were seen in 47 patients with DKA. Thirty-three patients had shortness of breath.
Signs of dehydration (decreased skin turgor and dryness of mucous membrane) was recorded in 72 patients, whereas altered sensorium in nearly half (48) of the patients with DKA. Acetone breath was the least observed sign, documented in 18 patients. Most of the patients were afebrile (98.8 ± 1.1°F) with isolated systolic hypertension (136.9 ± 15.5 mmHg) at the time of presentation.
Patients had elevated blood glucose (493.12 ± 72.38 mg/dl) levels at presentation with lowered arterial pH (7.14 ± 0.07) and bicarbonate (13.7 ± 4.2 mEq/L). Time taken for urine ketone bodies to disappear was 5.4 ± 1.2 days. Patients with DKA had poor control of diabetes with HbA1c of 9.63 ± 0.94% [Table 3].
|Table 3: Biochemical and hematological profiles of diabetic ketoacidosis patients at the time of admission|
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Based on the severity of acidosis, most (68%) of them presented with moderate degree of acidosis (pH 7.1–7.2), 22% had severe acidosis (pH <7.1), and only 10% had mild acidosis (pH 7.2–7.3) [Figure 2].
In the present study, systemic infections seen in 67 patients (respiratory – 32.8%, sepsis – 28.4%, acute gastroenteritis (AGE) – 22.4% and urinary tract infections – 16.4%), were the main precipitating factors, followed by noncompliance to drugs seen in 34 patients. Acute kidney injury was seen in patients with sepsis, AGE with severe dehydration, and severe urinary tract infection [Table 4].
Nearly all patients had 1 or more micro- and macrovascular complications of diabetes, indicating that they had long duration of diabetes and poor control of serum glucose [Table 5].
| Discussion|| |
There is increasing prevalence of T2DM worldwide and the prevalence is higher in developing nations including India, which contributes the most in global burden of DM. Moreover, in developing countries like India due to poor socioeconomic status, many patients of T2DM had poor compliance and poor glycemic control which precipitate DKA. DKA is a common acute complication of DM. Although more classically associated with T1DM, DKA can happen in patients with clinical courses and metabolic features of T2DM.,,, Increased incidence is seen in rural population. In the present study of elderly T2DM with DKA, the mean age was 65.8 ± 2.4 years, with significant male predominance.
DKA may be the first manifestation of diabetes, refer to as DKA-onset diabetes. The situation is common in the pediatric patients with the percentage of about 24% to 58%.,, However, in adult DKA patients, the percentage is less common, ranging from 7% to 27%., In our study, 24% patients had DKA-onset diabetes. In a study by Yan et al., 24% patient had DKA-onset DM. Fifty percent patients were detected to have DM at admission in a study by Wang et al. In a study done at Taiwan, the percentage of DKA-onset diabetes was 24.5% in T2DM like the present study.
In the present study, hypertension was the most common associated comorbidity seen in more than half of DKA patients, followed by dyslipidemia and cardiovascular disorders. Similar results were seen in a Malaysian study – hypertension (54.5%), dyslipidemia (43%), and cardiovascular disorders (35.6%). 30 patients had more than one comorbidities and only 8 patients had no chronic comorbidities. In a study by Usman et al., more than half (52.3%) of DKA patients had multiple chronic comorbidities and 28% had no comorbidities. These multiple comorbidities may add to the drug burden resulting in poor drug compliance and increase stress leading to DKA.
Hyperglycemia, ketosis, and degree of acidosis are the contributing factors for the development of symptoms of DKA. These factors have their own distinct signs and symptoms; polyuria, polydipsia, and dehydration result from hyperglycemia; ketosis causes shortness of breath, tachypnea, and Kussmaul breathing More Details; abdominal pain; and decreased sensorium may be induced by severe acidosis. However, most of these clinical features are overlapped by all three factors.
In the present study, polyuria and polydipsia (62) were the most common complaints followed by pain abdomen (56), constitutional symptoms (52), nausea and vomiting (47) were the presentation in patients with DKA. Similarly, dehydration (72) was the most observed sign followed by altered sensorium (48) and Kussmaul breathing (26). Similar features seen in a Malaysian study by Usman et al., chief complaints registered by patients were nausea and vomiting (61.4%), followed by constitutional symptoms (51.6%) and polyuria and polydipsia (44.7%). Pain abdomen was seen in 31% of patients with DKA. Dehydration was most commonly observed sign followed by constitutional signs.
DKA is confirmed by the presence of ketones in either urine or serum. Arterial pH and bicarbonate levels are the chief indicators for severity of DKA. Although values for serum glucose (493.12 ± 72.38) were higher at the time of admission in the present study, the mean arterial pH (7.14 ± 0.07) and bicarbonate level (13.7 ± 4.2) of patients reciprocate mild-to-moderate episode of DKA. Based on severity of the episode, we found that around two-third (68%) had moderate degree of DKA. Similar findings were observed in other studies,,, [Table 6].
In the present study, systemic infections were the main precipitating factors, followed by noncompliance to drugs which were consistent with the literature [Table 7]. Some patients had more than one precipitating factor – noncompliant to the medications and presenting with infections. Apart from infections and noncompliance to medications, pancreatitis, herb administration, gouty arthritis, and pregnancy have been reported. No obvious precipitating factor identified in 9.6%–10.2% of cases.,
|Table 7: Depicting precipitating factors for diabetic ketoacidosis in various studies|
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All T2DM patients with DKA had 1 or more micro- and macrovascular complications of diabetes, indicating that they had long duration of diabetes and poor glycemic control. Most of the patients also had 1 or more chronic comorbid conditions adding to drug burden and poor compliance with the medications leading to poor control of diabetes and predisposing to infections and DKA.
| Conclusion|| |
Our findings suggest that DKA in elderly is common in rural population. The precipitating factors in T2DM ketoacidosis patients are similar as in young diabetes – infections followed by noncompliance of treatment, even in rural population. Presentation of DKA in elderly is also similar, but they present later in the disease course due to indifference or ignorance of the disease. Education of diabetic patient about symptoms of ketoacidosis, such as weakness, abdominal pain, nausea, vomiting, and drowsiness are mandatory for early diagnosis and treatment.
All elderly diabetic patients with high serum glucose level must be investigated for ketosis as the symptoms of DKA are minimal and morbidity and mortality are high in these patients. The screening for diabetes in the elderly should not be neglected.
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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], [Table 5], [Table 6], [Table 7]