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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: https://doi.org/10.4093/dmj.2024.0036    [Epub ahead of print]
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  • 12 Download
AbstractAbstract PDF
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
Complications
Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects with Type 2 Diabetes Mellitus
Yeoree Yang, Eun-Young Lee, Jae-Hyoung Cho, Yong-Moon Park, Seung-Hyun Ko, Kun-Ho Yoon, Moo-Il Kang, Bong-Yun Cha, Seung-Hwan Lee
Diabetes Metab J. 2018;42(6):496-512.   Published online September 28, 2018
DOI: https://doi.org/10.4093/dmj.2018.0026
  • 4,492 View
  • 42 Download
  • 10 Web of Science
  • 9 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus.

Methods

In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ≥6 measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements.

Results

A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%).

Conclusion

CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.

Citations

Citations to this article as recorded by  
  • Intensified glycemic control by HbA1c for patients with coronary heart disease and Type 2 diabetes: a review of findings and conclusions
    Jingyang Chen, Dong Yin, Kefei Dou
    Cardiovascular Diabetology.2023;[Epub]     CrossRef
  • Long-Term Risk of Cardiovascular Disease Among Type 2 Diabetes Patients According to Average and Visit-to-Visit Variations of HbA1c Levels During the First 3 Years of Diabetes Diagnosis
    Hyunah Kim, Da Young Jung, Seung-Hwan Lee, Jae-Hyoung Cho, Hyeon Woo Yim, Hun-Sung Kim
    Journal of Korean Medical Science.2023;[Epub]     CrossRef
  • Factors Associated with Diabetic Complication Index among Type 2 Diabetes Patients: Focusing on Regular Outpatient Follow-up and HbA1c Variability
    Haejung Lee, Gaeun Park, Ah Reum Khang
    Asian Nursing Research.2023; 17(5): 259.     CrossRef
  • The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study
    Natsumi Matsuoka-Uchiyama, Haruhito A. Uchida, Shugo Okamoto, Yasuhiro Onishi, Katsuyoshi Katayama, Mariko Tsuchida-Nishiwaki, Hidemi Takeuchi, Rika Takemoto, Yoshiko Hada, Ryoko Umebayashi, Naoko Kurooka, Kenji Tsuji, Jun Eguchi, Hirofumi Nakajima, Kenic
    Journal of Diabetes Research.2022; 2022: 1.     CrossRef
  • Perspectives of glycemic variability in diabetic neuropathy: a comprehensive review
    Xiaochun Zhang, Xue Yang, Bao Sun, Chunsheng Zhu
    Communications Biology.2021;[Epub]     CrossRef
  • Assessment of Functions of the Autonomic Nervous System in the Elderly with Different Comorbid Factors
    Sushma S., Medha Y. Rao, Shaikh Mohammed Aslam
    Journal of Neurosciences in Rural Practice.2020; 12: 80.     CrossRef
  • Prognostic irrelevance of plaque vulnerability following plaque sealing in high-risk patients with type 2 diabetes: an optical coherence tomography study
    Rosalia Dettori, Andrea Milzi, Kathrin Burgmaier, Mohammad Almalla, Martin Hellmich, Nikolaus Marx, Sebastian Reith, Mathias Burgmaier
    Cardiovascular Diabetology.2020;[Epub]     CrossRef
  • HbA1C Variability Is Strongly Associated With the Severity of Cardiovascular Autonomic Neuropathy in Patients With Type 2 Diabetes After Longer Diabetes Duration
    Yun-Ru Lai, Chih-Cheng Huang, Wen-Chan Chiu, Rue-Tsuan Liu, Nai-Wen Tsai, Hung-Chen Wang, Wei-Che Lin, Ben-Chung Cheng, Yu-Jih Su, Chih-Min Su, Sheng-Yuan Hsiao, Pei-Wen Wang, Jung-Fu Chen, Cheng-Hsien Lu
    Frontiers in Neuroscience.2019;[Epub]     CrossRef
  • Polyscore of Non-invasive Cardiac Risk Factors
    Alexander Steger, Alexander Müller, Petra Barthel, Michael Dommasch, Katharina Maria Huster, Katerina Hnatkova, Daniel Sinnecker, Alexander Hapfelmeier, Marek Malik, Georg Schmidt
    Frontiers in Physiology.2019;[Epub]     CrossRef
Clinical Care/Education
Reduction of Sulfonylurea with the Initiation of Basal Insulin in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Undergoing Long-Term Sulfonylurea-Based Treatment
Yeoree Yang, Jeong-Ah Shin, Hae Kyung Yang, Seung-Hwan Lee, Seung-Hyun Ko, Yu-Bae Ahn, Kun-Ho Yoon, Jae-Hyoung Cho
Diabetes Metab J. 2016;40(6):454-462.   Published online October 11, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.6.454
  • 4,376 View
  • 45 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   
Background

There were a limited number of studies about β-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of β-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin.

Methods

In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT.

Results

Among 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group.

Conclusion

Long-acting basal insulin replacement could improve the glycemic status and restore β-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.

Citations

Citations to this article as recorded by  
  • Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes: A Real-World, Prospective, Non-interventional Study Across Six Countries
    Gregory R. Fulcher, Shahid Akhtar, Saleh J. Al-Jaser, Johan Medina, Mafauzy Mohamed, Nemencio A. Nicodemus, Anne Helene Olsen, Kiran P. Singh, Adri Kok
    Advances in Therapy.2022; 39(8): 3735.     CrossRef
  • Use of Insulin Glargine 100 U/mL for the Treatment of Type 2 Diabetes Mellitus in East Asians: A Review
    Takahisa Hirose, Ching-Chu Chen, Kyu Jeung Ahn, Jacek Kiljański
    Diabetes Therapy.2019; 10(3): 805.     CrossRef
  • Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017
    Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
    Diabetes & Metabolism Journal.2017; 41(5): 367.     CrossRef
  • Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017
    Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
    The Korean Journal of Internal Medicine.2017; 32(6): 967.     CrossRef

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