Diabetes & Metabolism Journal

Brief Report

Complications
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; Diabetes Metab J. 2024;48(6):1169-1175. Published online June 10, 2024; DOI: https://doi.org/10.4093/dmj.2024.0036

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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.

Citations

Citations to this article as recorded by

Fallbericht einer Euglykämischen Diabetischen Ketoacidose unter SGLT-2-Inhibition bei einer geriatrischen Patientin: „Sick-Day-Off Drug“
Laura Wassermann, Michael Denkinger
Zeitschrift für Gerontologie und Geriatrie.2026; 59(1): 74. CrossRef
The evolution of C-peptide's role in diabetes care
Laura Briggs, Alexander Read, Sarah Darch, Emma L. Williams, Wann Jia Loh, Julia S. Kenkre
Current Opinion in Endocrinology, Diabetes & Obesity.2026; 33(1): 16. CrossRef
Diabetic ketoacidosis is not a simple consequence of hyperglycemia, it is biochemical event driven by PDK4-mediated inhibition of PDC
Ayah Al-Qasrawi
Medical Hypotheses.2026; 208: 111898. CrossRef
Diabetic ketoacidosis in patients with type 2 diabetes: Risk factors for mortality and adverse outcomes
Vishnu Chandrabalan, Timothy Howcroft, Mohammed Khalid Alkhalifah, Noorulanne Younis, Ebrahim Aldhafiri, Joseph M Pappachan
World Journal of Experimental Medicine.2026;[Epub] CrossRef
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Die Diabetologie.2026;[Epub] CrossRef
Dapagliflozin/Empagliflozin/Ertugliflozin

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Diabetes Mellitus at an Elderly Age
Andrej Zeyfang, Jürgen Wernecke, Anke Bahrmann
Experimental and Clinical Endocrinology & Diabetes.2025; 133(04): 168. CrossRef
SGLT2 Inhibitors and GLP-1 Receptor Agonists in Diabetic Kidney Disease: Evolving Evidence and Clinical Application
Jae Hyun Bae
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Cardiorenal outcomes and safety of SGLT2 inhibitors in patients with diabetes secondary to disorders of the exocrine pancreas: a nationwide population-based study
Kyoung Hwa Ha, Minae Park, Yujin Lee, Dae Jung Kim, Seung Jin Han
Diabetes & Metabolism.2025; 51(5): 101668. CrossRef
SGLT2 Inhibitors: From Structure–Effect Relationship to Pharmacological Response
Teodora Mateoc, Andrei-Luca Dumitrascu, Corina Flangea, Daniela Puscasiu, Tania Vlad, Roxana Popescu, Cristina Marina, Daliborca-Cristina Vlad
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Rui Hu, Congchao Lu, Yifan Liu, Mengli Yang, Hongya Xing, Kerui Dai, Jiyin Li, Hui Zheng, Xi Chen, Nai-Jun Tang
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Severe euglycemic ketoacidosis following combined therapy with GLP-1 receptor agonist and SGLT-2 inhibitor, refractory to standard treatment: a case report
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Response

Response: Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study (Diabetes Metab J 2013;37:117-24): Kee-Ho Song, Jung Min Kim, Jung-Hyun Noh, Yongsoo Park, Hyun-Shik Son, Kyong Wan Min, Kyung Soo Ko; Diabetes Metab J. 2013;37(3):214-215. Published online June 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.3.214

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Original Articles

Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study: Kee-Ho Song, Jung Min Kim, Jung-Hyun Noh, Yongsoo Park, Hyun-Shik Son, Kyong Wan Min, Kyung Soo Ko; Diabetes Metab J. 2013;37(2):117-124. Published online April 16, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.2.117

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Background

The purpose of this study was to evaluate change in glycosylated hemoglobin (HbA1c), side effects, and quality of life (QOL) after a 16-week treatment period with Biphasic insulin aspart 30/70 (BIasp30) in patients with type 2 diabetes mellitus (T2DM) who had been suboptimally controlled with oral antidiabetic drugs (OADs).

Methods

The study consisted of a 4-week titration period when concurrent OAD(s) were replaced with BIasp30 and followed by a 12-week maintenance period. All patients completed the Diabetes Treatment Satisfaction Questionnaire at the beginning and the end of the trial. Hypoglycemic episodes were recorded by the patient throughout the trial.

Results

Sixty patients were included, of whom 55 patients (92%) completed the full 16-week treatment period. Seven-point blood glucose was significantly improved as compared with the baseline, except for the postlunch blood glucose level. HbA1c at the end of period was significantly improved from 9.2% to 8.2% (P<0.001). Eleven percent (n=6) of patients achieved HbA1c values ≤6.5% and 22% (n=12) of patients achieved <7.0%. There were 3.4 episodes/patients-year of minor hypoglycemia and 0.05 episodes/patients-year of major hypoglycemia. QOL showed significant changes only in the acceptability of high blood glucose category (P=0.003).

Conclusion

Treatment with once or twice daily BIasp30 may be an option for the patients with T2DM suboptimally controlled with OADs in Korea. However, considering the low number of patients achieving the HbA1c target and the high postlunch blood glucose levels, additional management with another modality may be required for optimal control.

Citations

Citations to this article as recorded by

15 Years of Experience with Biphasic Insulin Aspart 30 in Type 2 Diabetes
Andreas Liebl, Viswanathan Mohan, Wenying Yang, Krzysztof Strojek, Sultan Linjawi
Drugs in R&D.2018; 18(1): 27. CrossRef
Basal‐prandial versus premixed insulin in patients with type 2 diabetes requiring insulin intensification after basal insulin optimization: A 24‐week randomized non‐inferiority trial
Sang‐Man Jin, Jae Hyeon Kim, Kyung Wan Min, Ji Hyun Lee, Kue Jeong Ahn, Jeong Hyun Park, Hak Chul Jang, Seok Won Park, Kwan Woo Lee, Kyu Chang Won, Young‐Il Kim, Choon Hee Chung, Tae Sun Park, Jee‐Hyun Lee, Moon‐Kyu Lee
Journal of Diabetes.2016; 8(3): 405. CrossRef
The optimal morning:evening ratio in total dose of twice‐daily biphasic insulin analogue in poorly controlled Type 2 diabetes: a 24‐week multi‐centre prospective, randomized controlled, open‐labelled clinical study
C. H. Jung, J.‐Y. Park, J. H. Cho, K.‐H. Yoon, H. K. Yang, Y.‐H. Lee, B. S. Cha, B.‐W. Lee
Diabetic Medicine.2014; 31(1): 68. CrossRef
Response: Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study (Diabetes Metab J2013;37:117-24)
Kee-Ho Song, Jung Min Kim, Jung-Hyun Noh, Yongsoo Park, Hyun-Shik Son, Kyong Wan Min, Kyung Soo Ko
Diabetes & Metabolism Journal.2013; 37(3): 214. CrossRef
Letter: Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study (Diabetes Metab J2013;37:117-24)
Byung-Wan Lee
Diabetes & Metabolism Journal.2013; 37(3): 212. CrossRef

Angiotensin II Inhibits Insulin Binding to Endothelial Cells: Su-Jin Oh, Won-Chul Ha, Jee-In Lee, Tae-Seo Sohn, Ji-Hyun Kim, Jung-Min Lee, Sang-Ah Chang, Oak-Kee Hong, Hyun-Shik Son; Diabetes Metab J. 2011;35(3):243-247. Published online June 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.3.243

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Background

Insulin-mediated glucose uptake in insulin target tissues is correlated with interstitial insulin concentration, rather than plasma insulin concentration. Therefore, insulin delivery to the interstitium of target tissues is very important, and the endothelium may also play an important role in the development of insulin resistance.

Methods

After treating bovine aortic endothelial cells with angiotensin II (ATII), we observed the changes in insulin binding capacity and the amounts of insulin receptor (IR) on the cell membranes and in the cytosol.

Results

After treatment of 10^-7M ATII, insulin binding was decreased progressively, up to 60% at 60 minutes (P<0.05). ATII receptor blocker (eprosartan) dose dependently improved the insulin binding capacity which was reduced by ATII (P<0.05). At 200 µM, eprosartan fully restored insulin binding capacity, althogh it resulted in only a 20% to 30% restoration at the therapeutic concentration. ATII did not affect the total amount of IR, but it did reduce the amount of IR on the plasma membrane and increased that in the cytosol.

Conclusion

ATII decreased the insulin binding capacity of the tested cells. ATII did not affect the total amount of IR but did decrease the amount of IR on the plasma membrane. Our data indicate that ATII decreases insulin binding by translocating IR from the plasma membrane to the cytosol. The binding of insulin to IR is important for insulin-induced vasodilation and transendothelial insulin transport. Therefore, ATII may cause insulin resistance through this endothelium-based mechanism.

Citations

Citations to this article as recorded by

Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle
Dino Premilovac, Emily Attrill, Stephen Rattigan, Stephen M Richards, Jeonga Kim, Michelle A Keske
Cardiovascular Research.2019; 115(3): 590. CrossRef
Angiotensin II type 2 receptor inhibits expression and function of insulin receptor in rat renal proximal tubule cells
Yang Yang, Caiyu Chen, Chunjiang Fu, Zaicheng Xu, Cong Lan, Yongchun Zeng, Zhi Chen, Pedro A. Jose, Ye Zhang, Chunyu Zeng
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Endothelial function, its relation to arterial hypertension and the possibility of its modulation
Vladislav Biel, Jan Novák, Luděk Pluháček, Jiří Špác
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Evidence to Consider Angiotensin II Receptor Blockers for the Treatment of Early Alzheimer’s Disease
Juan M. Saavedra
Cellular and Molecular Neurobiology.2016; 36(2): 259. CrossRef
Ameliorative effect of eprosartan on high-fat diet/streptozotocin-induced early diabetic nephropathy in rats
Mohamed A. Morsy, Gehan H. Heeba, Magda E. Mahmoud
European Journal of Pharmacology.2015; 750: 90. CrossRef
Metabolic actions of angiotensin II and insulin: A microvascular endothelial balancing act
Ranganath Muniyappa, Sahzene Yavuz
Molecular and Cellular Endocrinology.2013; 378(1-2): 59. CrossRef

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