Different characteristics of diabetic ketoacidosis between type 1 and type 2 diabetes patients in Malaysia

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1 Asian Biomedicine Vol. 3 No. 2 April 2009; Brief communication (original) Different characteristics of diabetic ketoacidosis between type 1 and type 2 diabetes patients in Malaysia Hasniza Zaman Huri a, Grace Tan Kuan Foong a, Rokiah Pendek b, Riyanto Teguh Widodo a a Department of Pharmacy, b Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia Background: Diabetic ketoacidosis (DKA) is increasing in patients with type 2 diabetes in Asian countries. However, there is little information regarding the frequency and characteristics of DKA for Malaysian population. Objective: To identify the different clinical and biochemical features of DKA between adult patients with type 1 and type 2 diabetes. Methods: A cross-sectional, retrospective study was performed at University Malaya Medical Centre (UMMC) between January 2000 and December All patients (aged >18 years) with type1 or type 2 diabetes were included in this study. Clinical and biochemical characteristics of DKA were studied. Precipitating factors for the development of DKA were also identified. Results: One hundred and twenty patients (61.9%) presented with DKA had type 2 diabetes. Both type 1 and type 2 patients had similar symptoms. Nausea (44.0%) and vomiting (66.4%) were most common symptoms of DKA. Infection (40.5%) was main precipitating factors of DKA. Blood ph level in previously-diagnosed type 1 diabetes patients was lower than that in previously-diagnosed type 2 diabetes (7.18±0.18 vs. 7.26±0.16, p<0.0001). Conclusion: A high proportion of DKA occurs in patients with type 2 diabetes. DKA developed severely in newly-diagnosed type 2 diabetes patients more than in previously-diagnosed type 2 diabetes patients. Keywords: Diabetes mellitus, diabetes ketoacidosis (DKA), type 2 diabetes mellitus. Diabetic ketoacidosis (DKA) is a major complication of diabetes [1]. The annual incidence rate for DKA ranges from 4.6 to 8 episodes per 1000 patients with diabetes in Western countries [2]. There is an increase in frequency of hosptalization for DKA in Asia as well. In Korea, the episodes of DKA had increased sevenfold along with a tenfold increase in diabetic admission between 1982 and 2002 [3]. It is traditionally assumed that DKA occurs in patients with type 1 diabetes mellitus and not in patients with type 2 diabetes. However, it has become apparent that DKA does occur in type 2 diabetic patients. Since the prevalence of type 2 diabetes is higher compared to type 1 diabetes, DKA is presented with type-2 diabetic patients more than with type 1 diabetic patients [3-5]. Thus, DKA can no longer be considered as distinctive characteristics of type 1 diabetes mellitus. Correspondence to: Hasniza Zaman Huri, Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. hasnizazh@um.edu.my A number of studies have been carried out on DKA in diabetic patients [6-8]. However, there is little information regarding the frequency and characteristics of DKA for Malaysian population. The objective of this paper was to study characteristics of DKA in Malaysian diabetic patients. By adapting the methodology from the previous studies [6-8], we evaluated different manifestations and biochemical profiles of DKA between type 1 and type 2 diabetes and compared the data with the previous reports [6-8]. Materials and methods A cross-sectional, retrospective study was performed at University of Malaya Medical Centre (UMMC) between January 2000 and December The study population consisted of all adult patients (aged > 18 years) with a diagnosis of DKA. Patients who fulfilled the requirements of the International Classification of Diseases Tenth Revision (ICD-10) codes for diabetic ketoacidosis [9], were included in this study. For patient who was admitted

2 202 H. Zaman Huri, et al. to hospital for more than one episode of DKA, each episode was counted as a separate entity. Data on patient demographics (such as age, sex and ethnicity), types of diabetes, duration of diabetes, presenting symptoms, precipitating factors of DKA, vital signs (such as blood pressure, respiration rate, body temperature and oxygen saturation), biochemical presentations at the time of admission, and duration of hospitalization were collected from patients medical records. We defined precipitating factors of DKA as conditions leading to the development of DKA, based on physicians diagnosis and information obtained from the patient s medical record. For patient presenting more than one factor, we accounted the main precipitating factor. Patients were classified as type 1 or type 2 diabetes mellitus based on medical and treatment histories. These two groups were further subdivided into either previously-diagnosed diabetes (type 1 or type 2) or newly-diagnosed diabetes (type 1 or type 2). Patients were classified as previouslydiagnosed diabetes either type 1 or type 2 if they had prior history of diabetes mellitus. In addition, patients who were diagnosed as having diabetes mellitus on current admissions were classified as newly-diagnosed diabetes. statistical software (version 13) was used for the analysis of data collected in this study. Categorical data were expressed as numbers or percentages and continuous data were expressed as mean ± SD. Chi- Square test was used to analyze categorical data. All continuous data were tested for normality using Kolmogorov-Smirnov test. Normally distributed data was analysed using t-test, while Mann-Whitney test was used for not normally distributed data. The p-values less than 0.05 were considered as statistically significance. Results Two hundred sixty five patients were admitted to UMMC with a diagnosis of DKA (either E10.1 or E11.1 for the sub-classification of disease under ICD- 10). Out of 265 patients, 243 met the inclusion criteria, and 194 patients were included in this study. Table 1 reveals the symptoms presented by the patients. Nausea and vomiting were the most frequently reported clinical symptoms. In this study, infection (40.5%) was the most common precipitating factor of DKA. Urinary tract infection (24.8%) was the most common types of infection, followed by pneumonia (19.0%). The biochemical parameters measured at the time of admission were summarized in Table 2 and 3. Statistics Statistical Package for Social Science (SPSS) Table 1. Frequency of symptoms in patients with DKA. Symptoms Previously- Previously- Newly- Newlydiagnosed diagnosed diagnosed diagnosed type 1 diabetes type 2 diabetes type 1 diabetes type 2 diabetes Nausea 59 (56.2) 44 (37.0) 2 (33.3) 9 (31.0) Vomiting 87 (82.9) 69 (58.0) 4 (66.7) 12 (41.4) Polyuria 34 (32.4) 47 (39.5) 5 (83.3) 20 (69.0) Polydipsia 28 (26.7) 39 (32.8) 5 (83.3) 21 (72.4) Abdominal pain 38 (36.2) 24 (20.2) 3 (50.0) 5 (17.2) Weight loss 12 (11.4) 13 (10.9) 4 (66.7) 10 (34.5) Polyphagia 3 (2.9) 9 (7.6) 1 (16.7) 2 (6.9) Data was expressed as number (percentage). Note that the number of symptoms was not added up to the total number of admissions because patients usually presented more than one symptom.

3 Vol. 3 No. 2 April 2009 Diabetic ketoacidosis in Malaysia 203 Table 2. Biochemical profiles at the time of admissions in patients with DKA. Biochemical profiles Previously- Previously- Newly- Newlydiagnosed type 1 diagnosed type 2 diagnosed type 1 diagnosed type 2 diabetes diabetes diabetes diabetes ph 7.18 ± ± ± ± 0.12 po 2 (kpa) 14.5 ± ± ± ± 8.9 pco 2 (kpa) 2.8 ± ± ± ± 1.4 Serum glucose (mmol/l) 34.1 ± ± ± ± 15.1 Serum creatinine (mol/l) ± ± ± ± Serum sodium (mmol/l) ± ± ± ± 6.7 Serum potassium (mmol/l) 5.2 ± ± ± ± 1.2 Serum chloride (mmol/l) 92.2 ± ± ± ± 7.4 Serum bicarbonate (mmol/l) 9.2 ± ± ± ± 6.6 Serum urea (mmol/l) 8.8 ± ± ± ± 9.3 WBC count (1/mm 3 ) 15.5 ± ± ± ± 7.6 Neutrophils (%) 76.2 ± ± ± ± 10.7 Lymphocytes (%) 15.9 ± ± ± ± 9.6 Monocytes (%) 5.3 ± ± ± ± 2.8 Anion gap (mmol/l) 32.3 ± ± 9.1* 27.7 ± ± 8.4 Effective osmolality (mosm/l) ± ± 18.5* ± ± Data was expressed as mean±sd. 2[measured Na (mmol/l)] + Glucose (mmol/l). p <0.05 for comparison vs previously diagnosed type 1 diabetes group by Mann-Whitney test. p <0.05 for comparison vs previously-diagnosed type 1 diabetes group by t-test. Table 3. Levels of urine ketone at the time of admission in patient with DKA. Levels of Previously- Previously- Newly- Newlyurine ketone diagnosed diagnosed diagnosed diagnosed type 1 diabetes type 2 diabetes type 1 diabetes type 2 diabetes number (%) number (%) number (%) number (%) 4 positive 21 (20.0) 16 (13.4) 1 (16.7) 8 (27.6) 3 positive 49 (46.7) 38 (31.9) 3 (50.0) 5 (17.2) 2 positive 17 (16.2) 27 (22.7) 2 (33.3) 9 (31.0) 1 positive 13 (12.4) 24 (20.2) 0 (0.0) 6 (20.7) Negative 5 (4.8) 14 (11.8) 0 (0.0) 1 (3.4) Discussion The present study proved the occurrence of DKA in type 2 diabetes patients in Malaysia. More than half of the type 2 diabetes patients had DKA due to poor glycemic control, compared to type 1 patients. Majority of type 2 diabetes patients presented other comorbid diseases that affect the management of hyperglycemia. Presumably, the incidence of DKA might be increased by lack of awareness and limited assess to medical services. Both the type 1 and type 2 diabetes patients presented similar symptoms of DKA. The frequency of developing any symptom of DKA was almost the same between both types of diabetes. Nausea and vomiting were the two most frequently presented symptoms. This result agrees with previous report by Newton and Raskin [6]. However, our results might be underestimated because our health care professionals were required to ask the patients about the symptoms for medical recordings. In our study, the potassium level was higher in previously-diagnosed type 1 diabetes than previouslydiagnosed type 2 diabetes patients, but the value did not reach statistically significant level. Newton and Raskin [6] noted significant difference in serum potassium level between previously-diagnosed type 1

4 204 H. Zaman Huri, et al. and type 2 diabetes patients. This discrepancy might come from the number of subjects. Our study included more previously-diagnosed type 2 diabetes patients than previously-diagnosed type 1 diabetes. The present biochemical profiles were different between previously-diagnosed type 1 and type 2 diabetes patients. The serum glucose levels for type 2 diabetes patients were lower than that for the type 1 diabetes patients. This different serum glucose levels might be due to residual insulin secretion in type 2 diabetes [1]. Previously-diagnosed type 1 diabetes patients have lower serum bicarbonate, lower blood ph, higher anion gap and more ketone bodies in urine than previously-diagnosed type 2 diabetes patients. In type 1 diabetes patients, as a consequence of increase production of ketoacids, acidosis might develop more severely than type 2 diabetes patients. This may be the reason because type 1 diabetes patients do not have insulin reserve to reduce ketogenesis. The ketoacids will dissociate and hydrogen ions are released. These excess hydrogen ions will bind to the bicarbonate. As a result, the serum bicarbonate levels are decreased. When the bicarbonate stores are depleted, the blood ph will become lower. Apart from that, the excess ketone bodies are circulating in the blood in anionic form and this increases the anion gap [10]. In addition, the abundant ketone bodies in the circulation will eventually lead to ketonuria [11]. Therefore, patients with type 1 diabetes have greater ketone levels in urine compared with type 2 diabetes patients. In our study, newly-diagnosed type 2 diabetes patients developed more severe DKA compared to previously-diagnosed type 2 diabetes patients. Presumably, newly-diagnosed diabetes patients were admitted to hospital under worse conditions because they were not aware of the symptoms of DKA. The blood ph and serum bicarbonate for newly-diagnosed type 2 diabetes patients were lower compared with previously-diagnosed type 2 diabetes. The serum glucose level in newly-diagnosed type 2 diabetes patients was higher than that in previously-diagnosed type 2 diabetes patients. This difference might be due to antidiabetic treatments to reduce the acidosis and hyperglycaemia for previously-diagnosed type 2 diabetes patients. We note that these results did not concur with the previous studies [6-8], probably due to variation in patients demographics, especially the ethnic groups. In conclusion, the occurrence of DKA in type 2 diabetes patients was significant. Type 1 and type 2 diabetes mellitus patients presented different biochemical characteristics. Type 2 diabetes patients developed less severe acidosis, milder ketonuria and milder hyperglycemia compared to type 1 diabetes patients. However, the newly-diagnosed type 2 diabetes patients developed more severe DKA compared to previously-diagnosed type 2 diabetes patients. Infections were the most common precipitating factors of DKA. The authors have no conflict of interest to declare. References 1. Powers AC. Diabetes mellitus, in: Braunwald E, Fauci AS, Isselbacher KJ, Kasper DL, Hauser SL, Longo DL, et al. editors. Harrison s Principles of Internal Medicine. 15 th edition. New York:McGraw-Hill. 2001, pp Faich GA, Fishbein HA, Ellis SE. The epidemiology of diabetic acidosis: a population-based study. Am J Epidemiol. 1983; 117: Ko SH, Lee WY, Lee JH, Kwon HS, Lee JM, Kim SR, et al. Clinical characteristics of diabetic ketoacidosis in Korea over the past two decades. Diabet Med. 2005; 22: Jabbar A, Farooqui K, Habib A, Islam N, Haque N, Akhter J. Clinical characteristics and outcomes of diabetic ketoacidosis in Pakistan adults with type 2 diabetes mellitus. Diabet Med. 2004; 21: Musey VC, Lee JK, Crawford R, Klatka MA, McAdams D, Philips LS. Diabetes in urban African-Americans: cessation of insulin therapy is the major precipitating cause of diabetic ketoacidosis. Diabetes Care. 1995; 18: Newton CA, Raskin P. Diabetic ketoacidosis in type 1 and type 2 diabetes mellitus: clinical and biochemical differences. Arch Intern Med. 2004; 164: Westphal SA. The occurrence of diabetic ketoacidosis in non-insulin dependent diabetes and newly diagnosed diabetic adults. Am J Med. 1996; 101: Balasubramanyam A, Zern JW, Hyman DJ, Pavlik V. New profiles of diabetic ketoacidosis: type 1 vs type 2 diabetes and the effect of ethnicity. Arch Intern Med. 1999; 159: World Health Organization, International Statistical Classification of Diseases and Related Health Problems 10 th Revision [online]. Available: classifications/apps/icd/icd10online. (Assessed 20 July 2005).

5 Vol. 3 No. 2 April 2009 Diabetic ketoacidosis in Malaysia Chiasson JL, Aris-Jilwan N, Belanger R, Bertrand S, Beauregard H, Ekoe JM, et al. Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Can Med Assoc J. 2003; 168: White NH. Management of diabetic ketoacidosis. Reviews Endocri Metab Disorder. 2003; 4: