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Brief Report
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Diabetic Ketoacidosis as an Effect of Sodium-Glucose Cotransporter 2 Inhibitor: Real World Insights
Han-Sang Baek, Chaiho Jeong, Yeoree Yang, Joonyub Lee, Jeongmin Lee, Seung-Hwan Lee, Jae Hyoung Cho, Tae-Seo Sohn, Hyun-Shik Son, Kun-Ho Yoon, Eun Young Lee
Received January 22, 2024  Accepted May 13, 2024  Published online June 10, 2024  
DOI:    [Epub ahead of print]
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One of the notable adverse effects of sodium-glucose cotransporter 2 (SGLT2) inhibitor is diabetic ketoacidosis (DKA) often characterized by euglycemia. In this retrospective review of patients with DKA from 2015 to 2023, 21 cases of SGLT2 inhibitorassociated DKA were identified. Twelve (57.1%) exhibited euglycemic DKA (euDKA) while nine (42.9%) had hyperglycemic DKA (hyDKA). More than 90% of these cases were patients with type 2 diabetes mellitus. Despite similar age, sex, body mass index, and diabetes duration, individuals with hyDKA showed poorer glycemic control and lower C-peptide levels compared with euDKA. Renal impairment and acidosis were worse in the hyDKA group, requiring hemodialysis in two patients. Approximately one-half of hyDKA patients had concurrent hyperosmolar hyperglycemic state. Common symptoms included nausea, vomiting, general weakness, and dyspnea. Seizure was the initial manifestation of DKA in two cases. Infection and volume depletion were major contributors, while carbohydrate restriction and inadequate insulin treatment also contributed to SGLT2 inhibitor-associated DKA. Despite their beneficial effects, clinicians should be vigilant for SGLT2 inhibitor risk associated with DKA.
Original Articles
The Classification of Diabetic Patients Presenting Diabetic Ketoacidosis: The Characteristics of Fulminant Type 1 Diabetes.
Eun Hee Jang, Jeong Eun Yi, Seung Jae Lee, Sang Hoon Chun, Ki Hyun Baek, Ki Ho Song, Soon Jib Yoo, Jong Min Lee, Kun Ho Yoon, Moo Il Kang, Kwang Woo Lee, Mee Kyung Kim
Korean Diabetes J. 2008;32(5):428-434.   Published online October 1, 2008
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The aim of the study was to classify newly diagnosed diabetic patients who initially presented with diabetic ketoacidosis (DKA) into specific types of diabetes and to describe the clinical and biochemical characteristics of patients with fulminant type 1 DM in Korea. METHODS: Using data from 4 hospitals of CMC from 1 January 1999 to 1 March 2008, we identified all patients who manifested DKA when they were first diagnosed as diabetes. Clinical and laboratory data were reviewed from medical records. RESULTS: We identified 51 newly diagnosed diabetic patients manifested DKA. Among them, 14 (27.4%) patients were classified as autoimmune type 1 DM, 8 (15.7%) as antibody negative type 1 DM, 5 (9.8%) as fulminant type 1, 16 (31.4%) as type 2 DM and 8 (15.7%) as secondary DM. Five patients who fulfilled the criteria of fulminant type 1 DM were older (32.2 +/- 10.7 vs. 15.7 +/- 4.4 years, P = 0.010), had shorter duration of symptoms (4.2 +/- 2.7 vs.16.7 +/- 15.2 days, P = 0.014) and lower stimulated C-peptide levels (0.1 +/- 0.0 vs. 0.7 +/- 0.6 ng/mL, P = 0.050) compared with patients with autoimmune type 1 DM. CONCLUSION Newly diagnosed diabetic patients presenting with DKA composed of heterogenous types of diabetes. The prevalence of fulminant type 1 diabetes among them was 9.8% and the clinical and biochemical characteristics of these patients were different from those of autoimmune type 1 DM.


Citations to this article as recorded by  
  • A Case of Severe Diabetic Ketoacidosis in a Child with Type 2 Diabetes
    Jaesung Yu, Hyunju Jin, Joontae Ko, Hoseok Kang
    Journal of Korean Society of Pediatric Endocrinology.2011; 16(1): 46.     CrossRef
  • A Case of Fulminant Type 1 Diabetes Mellitus Complicated with Ischemic Ileitis
    Se-Won Oh, Ju-Ri Park, Yun-Jeong Lee, Hee-Yeong Kim, Ji-A Seo, Nan-Hee Kim, Kyung-Mook Choi, Sei-Hyun Baik, Dong-Seop Choi, Sin-Gon Kim
    Journal of Korean Endocrine Society.2009; 24(2): 116.     CrossRef
Clinical Characteristics and Outcomes of Diabetic Ketoacidosis at a Single Institution.
Jee In Lee, Tae Seo Sohn, Sang Ah Chang, Jung Min Lee, Bong Yun Cha, Ho Young Son, Hyun Shik Son
Korean Diabetes J. 2008;32(2):165-170.   Published online April 1, 2008
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  • 5 Crossref
AbstractAbstract PDF
AIMS: The aim of this study was to describe the clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in Hospital for past 6 years. METHODS: We reviewed the retrospective medical records of all patients admitted with a diagnosis of DKA from 2000 to 2005 in Uijeongbu St. Mary's Hospital. Clinical characteristics including precipitating factors and hospital mortality were analyzed. RESULTS: Seventy-eight patients (78 episodes) fulfilled criteria for inclusion in this study. Their mean age was 41.89 years. 66 episodes had a prior history of diabetes but DKA was the initial presentation in 12 episodes. 24.4% were on no treatment, 14.1% were using oral hypoglycemic agents and 53.8% were on insulin. Poor glycemic control were the most common precipitating factor (56.4%). There were 3 deaths. CONCLUSION: Our report is similar with past reports of DKA in Korea. but it is different that poor glycemic control is most common precipitating factor and mortality rate are lower than past reports. This observation suggests that many cases of DKA can be prevented by better access to medical care, proper education, and effective communication with a health care provider.


Citations to this article as recorded by  
  • Clinical and Laboratory Characteristics of Pediatric Diabetic Ketoacidosis: A Single-Center Study
    Iee Ho Choi, Min Sun Kim, Pyoung Han Hwang, Dae-Yeol Lee
    The Journal of Korean Diabetes.2017; 18(3): 193.     CrossRef
  • Clinical and Biochemical Characteristics of Elderly Patients With Hyperglycemic Emergency State at a Single Institution
    Yun Jae Shin, Dae In Kim, Dong Won Lee, Beung Kwan Jeon, Jung Geun Ji, Jung Ah Lim, Young Jung Cho, Hong Woo Nam
    Annals of Geriatric Medicine and Research.2016; 20(4): 185.     CrossRef
  • Evaluation of the Clinical Significance of Ketonuria
    Hae-Won Jung, Ile-Kyu Park
    Laboratory Medicine Online.2012; 2(1): 15.     CrossRef
  • A Case of Severe Diabetic Ketoacidosis in a Child with Type 2 Diabetes
    Jaesung Yu, Hyunju Jin, Joontae Ko, Hoseok Kang
    Journal of Korean Society of Pediatric Endocrinology.2011; 16(1): 46.     CrossRef
  • Clinical Characteristics of Patients with Hyperglycemic Emergency State Accompanying Rhabdomyolysis
    Soo Kyoung Kim, Jong Ha Baek, Kyeong Ju Lee, Jong Ryeal Hahm, Jung Hwa Jung, Hee Jin Kim, Ho-Su Kim, Sungsu Kim, Soon Il Chung, Tae Sik Jung
    Endocrinology and Metabolism.2011; 26(4): 317.     CrossRef
Case Reports
A Case of Diabetic Ketoacidosis in Gestational Diabetes Mellitus.
Myung Hwan Kim, Eui Dal Jung, Seung Pyo Hong, Gyu Hwan Bae, Sun Young Ahn, Eon Ju Jeon, Seong Yeon Hong, Ji Hyun Lee, Ho Sang Son
Korean Diabetes J. 2007;31(4):368-371.   Published online July 1, 2007
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Gestational diabetes mellitus (GDM) is defined as glucose intolerance of variant severity with onset or first recognition during present pregnancy. Recently the prevalence of GDM in Korean has reported as 1.7~4.0%. Diabetic ketoacidosis is a serious metabolic complication of diabetes with high mortality if undetected. Its occurrence is very rare in gestational diabetes patients, but is harmful to fetal and maternal health. A 26 years-old pregnant woman was admitted at 37 weeks gestation because of progressive generalized weakness, anorexia and weight loss. Initial physical examination reveals that she had been dehydrated, and blood pressure 130/80 mmHg, pulse rate 100/min, respiratory rate 20/min, and body temperature was 36.9 degrees C. Serum glucose was 545 mg/dL, pH 7.282, HCO3- 10.5 mmol/L, urine ketone 3+, urine glucose 2+ when initial laboratory work was done. She was treated with intravenous fluid and insulin under the impression of diabetic ketoacidosis. Her delivery was performed after 24 hours from admission because of suggestive fetal distress. After recovery, she is being treated with insulin at outpatient department. We experienced a appropriately treated case of diabetic ketoacidosis in pregnant woman with GDM, and report it with a literature review.
A Case of Ketosis-Prone Type 2 Diabetes Mellitus.
Dong Lim Kim, Suk Kyeong Kim, Kee Ho Song
Korean Diabetes J. 2007;31(3):293-296.   Published online May 1, 2007
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  • 1 Crossref
AbstractAbstract PDF
Ketosis-prone type 2 diabetes (KPD) has been characterized as diabetes with severe insulin deficiency at diagnosis associated with ketosis or ketoacidosis without a precipitating cause. Improvement in beta-cell function and insulin sensitivity by aggressive diabetic management could allow discontinuation of insulin therapy within a few month of therapy. These subjects are usually obese, have a strong family history of diabetes, absence of beta-cell autoimmune markers and lack of human leukocyte antigen genetic association. This clinical presentation has been reported primarily in African and African Americans, but rare in Asian and white person. We recently experienced a case of KPD in Korea and present it with literature review.


Citations to this article as recorded by  
  • A Case of Autoantibody-Positive Ketosis-Prone Diabetes Mellitus
    Bora Yoon, Gyuri Kim, Jae Hyun Bae, Yu Jung Yun, Yong Ho Lee, Byung Wan Lee, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Eun Seok Kang
    The Journal of Korean Diabetes.2016; 17(1): 60.     CrossRef
A Case of Acromegaly Presenting with Diabetic Ketoacidosis.
Jin Dong Kim, Tae Seo Sohn, Jee In Lee, Jick Hwan Hah, Yun Hwa Jung, Jung Min Lee, Sung Min Nam, Seung Won Lee, Hyun Shik Son
Korean Diabetes J. 2006;30(4):312-315.   Published online July 1, 2006
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AbstractAbstract PDF
In patients with acromegaly, glucose intolerance and diabetes mellitus are one of the frequent manifestations. And the type of diabetes in these patients is usually non-insulin dependent type secondary to insulin resistance caused by growth hormone excess. Therefore, the diabetes mellitus in these patients dose not tend to develop diabetic ketoacidosis. But we experienced and presented the case of a patient with acromegaly hospitalized due to the diabetic ketoacidosis without overt clinical manifestations of acromegaly. This case of acromegaly showed that growth hormone excess could cause diabetic ketoacidosis in the presence of relative insulin deficiency.
Two Cases of Diabetic Ketoacidosis Associated with Atypical Antipsychotics.
Seung Hee Lee, Kum Ho Yi, Eun A Kim, Seong Bin Hong, Moon Suk Nam, Yong Seong Kim
Korean Diabetes J. 2005;29(6):566-570.   Published online November 1, 2005
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AbstractAbstract PDF
Atypical antipsychotics have been widely used for the management of patients with schizophrenia and other psychotic disorders. However, they may be associated with a greater risk of metabolic abnormalities than others, including weight gain, hyperlipidemia, and new-onset type 2 diabetes mellitus or diabetic ketoacidosis (DKA). We report two cases of reversible DKA and new-onset DM that developed in patients treated with atypical antipsychotics. A 42-year-old male patient with schizophrenia who was on olanzapine admitted to the hospital because of DKA. He had been taking olanzapine for 5 months. Five months before the admission, his fasting serum glucose levels were 109 m/dL. Another 34-year-old male with no previous history of diabetes mellitus was admitted to the hospital and subsequently diagnosed with DKA. The patient had been taking risperidone. Clinicians should monitor blood glucose concentrations periodically in patients taking atypical antipsychotics.
A Case of Diabetic Ketoacidosis in a GAD Antibody-positive Diabetes Patients who Recently Experienced Hyperglycemic Hyperosmolar State.
Jang Won Son, Seok Hong Lee, Jung Ahn Lee, Jaetaek Kim, Yeon Sahng Oh, Soon Hyun Shinn
Korean Diabetes J. 2005;29(3):267-270.   Published online May 1, 2005
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AbstractAbstract PDF
The term latent autoimmune diabetes in adults(LADA) was introduced to define adult diabetic patients who initially do not require insulin, but they have the immune markers of type 1 diabetes and in a number of cases, these patients progress to insulin dependency. LADA patients have several features of classic type 1 diabetes in addition to islet cell antibody positivity, including high rates of HLA-DR3 and DR4. We describe here a case of a patient with a diagnosis of LADA who, having been diagnosed with type 2 diabetes, was affected with diabetic ketoacidosis. In April 2000, a 65-year-old man was admitted to Chung-Ang University Hospital due to his decreased cognitive ability. The patient was diagnosed with type 2 diabetes 30-years ago and he was diagnosed 6-month ago as being in a hyperglycemic hyperosmolar state. He was positive for antibodies against GAD(anti-GAD, 31U/mL). His weight was 70kg, height 167cm, BMI 25 kg/m2 and the blood pressure was 86/52mmHg. No abnormalities on the physical examination were found. His acid-base balance was pH 6.937, serum bicarbonate 2.2mmol/L and the anion gap 38; he also had a strong positive reaction for ketones in his urine and serum. During half a year, the fasting C-peptide level decreased from 0.65nmol/L to 0.13nmol/L, which means the rapid progression of beta-cell destruction. Intensive treatment of LADA with insulin may improve this type of patients' quality of life, and so potentially save the beta-cell function and perhaps lessening the risk of a hyperglycemic crisis
Original Article
A Case of MELAS(Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like Episodes) Syndrome Manifested by Diabetic Ketoacidosis.
Sung Hoon Jung, Eun Jung Kim, So Hi Im, Kang Ju, Kang hyun Choi, Seung Hyun Ko, Yu Bae Ahn, Ki Ho Song, Ho Young Son, Sung Kyung Park, Jeong Su Jun
Korean Diabetes J. 2004;28(3):231-237.   Published online June 1, 2004
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AbstractAbstract PDF
MELAS(mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) syndrome is a rare cause of mitochondrial encephalomyopathy, with variable clinical features, such as encephalomyopathy, lactic acidosis, stroke, diabetes, short stature, sensorineural hearing loss and basal ganglia calci-fication, etc. It can be confirmed by molecular genetic analysis that reveals the mitochondrial A3243G point mutation. Among the clinical manifestations in MELAS syndrome, diabetes mellitus is associated with impaired insulin secretion and often misdiagnosed type 1 diabetes. Herein, a rare case for the MELAS syndrome, with diabetes mellitus that came from ketoacidosis, is introduced. A 21-year-old woman, carried to the emergency department had a stuporous mentality. She was thin(BMI 16.1kg/m(2)), and had difficulty with her hearing capacity. According to the initial laboratory results, she showed the metabolic acidosis, hyperglycemia, ketonemia, and ketonuria. She was diagnosed as diabetic ketoacidosis and treated with insulin and hydration. Brain imaging from MRI, and a CT scan showed basal ganglia calcification, hemorrhagic infarction and diffuse brain atrophy. The markers for beta-cell autoimmunity were negative. Her electromyography suggested proximal myopathy. In addition, a molecular genetic analysis identified A3243G point mutation in the peripheral blood leukocytes from her, her mother and her sister.
Case Report
A Case of Severe Hypertriglyceridemia with Diabetic Ketoacidosis.
Dong Seop Choi, Jeong Heon Oh, Ie Byung Park, Jin Won Kim, Kyung Mook Choi, Yong Hyun Kim, Nan Hee Kim, Sang Jin Kim, Sei Hyun Baik
Korean Diabetes J. 1999;23(5):715-721.   Published online January 1, 2001
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AbstractAbstract PDF
Severe hypertriglyceridemia exceeding 5.6 mmol/L in diabetic ketoacidosis occasionally occur in patients with type 1 diabetes mellitus. The pattern of dyslipidemia is usually Fredrickson classification type lV. But it also exists in type III and type V. However, extreme triglyceridemia, triglyceride level exceeds 22.6 mmol/L, occur rarely in the modern era of insulin therapy. And the pattern is usually Fredrickson type I. The severe hypertriglyceridemia in diabetic ketoacidosis is mainly due to lipoprotein lipase deficiency, and secondly to insulin deficiency. The severity usually improves with insulin replacement. In patients with extreme hypertriglyceri-demia, serum electrolyte values of the patients are fallaciously low, and it leads to the misinterpretation of biochemical results and to the inappropriate treatment. We reported a case of a 25 years old female patient with diabetic ketoacidosis and extreme hypertriglyceridemia. At admission, the color of her serum was milky, her plasma triglyceride concentration was 144.7 mmol/L (12864 mg/dL), cholesterol was 25.5 mmol/L (982 mg/dl), and HDL-cholesterol was 0.77 mmol/L (40 mg/dL). The biochemical values at admission could not be measured. Empirical therapy was administered with the use of insulin and fluid. After the initial treatment with insulin and fluid, plasma triglyceride declined rapidly and was nearly normal after 72 hours. We also measured fasting blood glucose concentration and lipid profiles from her father and two sisters. Their plasma glucose and lipid profiles were normal.
Original Article
Metabolic Factors Influencing Serum Potassium Levels in Diabetic Ketoacidosis.
Sung Jin Kim, Seung Oh Suh, Sung Hee Ihm, Hyun Kyu Kim, Doo Man Kim, Jae Myung Yoo, Moon Gi Choi, Hyung Joon Yoo
Korean Diabetes J. 1999;23(5):661-668.   Published online January 1, 2001
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AbstractAbstract PDF
The serum K level is normal or high in the majority of patients with diabetic ketoacidosis (DKA) despite significant total body K+ deficits. This might be due to the combined effects of severe acidosis, insulin deficiency, volume contraction, hyperglycemia and hypertonicity that usually accompany DKA. The aim of this study was to investigate the most likely determinants of the serum K+ levels among metabolic derangements observed in DKA patients. METHODS: The subjects were 88 DKA patients who had normal or high initial serum K+ levels. We anaylzed the correlation between initial serum K' levels and metabolic parameters (arterial pH, arterial HCO(3-) level, anion gap, serum glucose level, osmolality, BUN and fasting C-peptide levels), by simple linear regression analysis and stepwise multiple regression analysis. RESULT: Serum K+ levels correlated significantly with initial arterial pH(r=-0.38, p<0.001), HCO(3-) (r=-0.35, p<0.001), anion gap(r=0.21, p<0.05), serum glucose (r=0.22, p<0.05) and fasting C-peptide (r=-0.33, p<0.05) levels. Among these, arterial HCO(3-), serum glueose and fasting C-peptide levels had significant and independent effects on serum K+ levels. These levels could account for about 33% of the observed variance in serum K+ levels. CONCLUSION: These results suggest that metabolic acidosis and hyperglycemia in DKA, which result primarily from insulin deficit, are the main determinants of increased serum K+ levels.

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