Distinct clinical characteristics and therapeutic modalities for diabetic ketoacidosis in type 1 and type 2 diabetes mellitus

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Abstract

Aims

Patients with type 1 diabetes often develop diabetic ketoacidosis (DKA). Reportedly, DKA in type 2 diabetes has higher mortality despite its limited occurrence. The exact clinical characteristics and therapeutic modalities yielding successful outcomes in DKA type 2 diabetes remain unknown.

Methods

This retrospective study compared the clinical features and detailed treatment of consecutive type 1 and type 2 diabetes patients hospitalized with DKA between January 2001 and December 2014.

Results

We report on 127 patients with type 1 and 74 patients with type 2 diabetes whose DKA was successfully treated. The most frequent precipitating cause for DKA was infectious disease for patients with type 1 diabetes and consumption of sugar-containing beverages for those with type 2 diabetes. Type 2 diabetes patients showed higher mean plasma glucose levels than those with type 1 diabetes (48.4 ± 21.6, vs. 37.1 ± 16.4 mmol/l, P < 0.01) and higher serum creatinine, blood urea nitrogen, and hemoglobin levels, which normalized after DKA resolution. Compared with type 1 diabetes patients, those with type 2 diabetes required distinctly higher daily total insulin dosage (35.9 ± 37.0 U, vs. 20.2 ± 23.3 U, P < 0.01), larger replacement fluid volumes (4.17 ± 2.69 L, vs. 2.29 ± 1.57 L, P < 0.01) and greater potassium supplementation (23.9 ± 36.5 mEq, vs. 11.2 ± 17.9 mEq, P < 0.01) to resolve DKA and reduce plasma glucose level to ≤ 16.7 mmol/l.

Conclusions

DKA patients with type 2 diabetes required management with a modified treatment protocol to resolve their profound hyperglycemia and dehydration compared with those with type 1 diabetes.

Introduction

Diabetic ketoacidosis (DKA) is one of the most serious acute metabolic complications of diabetes (Kitabchi, Umpierrez, Miles, & Fisher, 2009). Severe deficiency of insulin action causes acute hyperglycemia with metabolic acidosis secondary to the deterioration of fatty acid metabolism. The most common precipitating cause of DKA in type 1 diabetes is infection, ranging from simple viral infections to severe septicemia, followed by cardiovascular events, pancreatitis, trauma, and major surgery. Use of drugs that deteriorate insulin action and discontinuation of medication or inadequate disease management are also major precipitating causes (Musey et al., 1995, Umpierrez et al., 1997). However, precipitating factors for DKA and its clinical pathophysiology in type 2 diabetes are less clear, despite the increasing incidence of DKA episodes that is observed in multi-ethnic populations (Balasubramanyam, Zern, Hyman, & Pavlik, 1999), including African Americans (Umpierrez et al., 1995), Hispanics (Balasubramanyam et al., 1999, Pinto et al., 2008), and Asians (Jabbar et al., 2004, Yan et al., 2000), as well as in Caucasians (Pitteloud & Philippe, 2000). Patients with type 2 diabetes that present DKA are more likely to be obese and without autoimmune markers (Balasubramanyam et al., 1999, Newton and Raskin, 2004, Umpierrez and Kitabchi, 2003). Additionally, such patients are associated with worse clinical outcomes in terms of severity (Newton & Raskin, 2004) and mortality than those with type 1 diabetes (Barski et al., 2013, Henriksen et al., 2007, Jabbar et al., 2004). However, there are contrasting reports that did not demonstrate substantial differences regarding the major laboratory findings between the two groups at the time of DKA diagnosis (Balasubramanyam et al., 1999). To identify precipitating causes, clinical features and successful therapeutic modalities for patients with type 2 diabetes who develop DKA, we retrospectively analyzed the conditions that triggered DKA and detailed clinical and biochemical data during the in-hospital treatment course of all DKA patients admitted. The universal health coverage system in Japan has long allowed the performance of extensive laboratory tests and the practice of treatment modalities based on the then-current recommendations by nationwide specialty medical societies.

Section snippets

Patients

We reviewed the hospital admission records of all Japanese patients diagnosed with DKA for the 14-year period between January 2001 and December 2014 at the Department of Endocrinology, Diabetes and Metabolism at the Kitasato University Hospital. This hospital is a tertiary care center that serves southwestern Tokyo metropolitan area with an estimated catchment population of 1 million. All patients were ≥ 15 years of age. Type 1 diabetes and type 2 diabetes were diagnosed according to the

Results

We identified 211 DKA patients during the 14-year period. Three patients with type 2 diabetes died of combined septic shock, severe pneumonia and non-occlusive mesenteric ischemia before they could undergo the administration of glucose solution. Four patients were diagnosed with pancreatic diabetes. Exact therapeutic records on insulin/fluid infusion of 3 patients were not available prior to their referral to us. These patients were therefore excluded from the current analysis. Of the remaining

Discussion

American and European retrospective studies have shown that approximately 20% to 30% of DKA patients had type 2 diabetes (Newton and Raskin, 2004, Wang et al., 2008). We analyzed carefully our 67 new-onset patients that developed DKA and found that 29 (43.3%) of them had type 1 diabetes, while the other 38 (56.7%) had type 2 diabetes. The current study was performed in Japan where type 1 diabetes is very rare, with an annual incidence in children aged 0 to 14 years of 2.37 cases per 100,000

Conclusions

Our data demonstrate the distinct clinical features of DKA between patients with type 1 and type 2 diabetes. Patients with type 2 diabetes who developed DKA may be associated with more profound dehydration and hyperglycemia and require higher dosage and faster infusion rate of insulin, larger replacement fluid volume and potassium supplementation to successfully resolve the condition.

Acknowledgments

This study was supported in part by a Shogaku-Kifu Grant from Kitasato University medical school. No additional external funding was received for this study.

References (25)

  • E Kawasaki et al.

    Type 1 diabetes in Japan

    Diabetologia

    (2006)
  • U Keller

    Diabetic ketoacidosis: Current views on pathogenesis and treatment

    Diabetologia

    (1986)
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    Conflict of interest: No conflict of interest was declared.

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