Thirty years of personal experience in hyperglycemic crises: Diabetic ketoacidosis and hyperglycemic hyperosmolar state

Division of Endocrinology, Diabetes, and Metabolism, University of Tennessee Health Science Center, 920 Madison Avenue #909, Memphis, TN 38163, USA.
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.31). 06/2008; 93(5):1541-52. DOI: 10.1210/jc.2007-2577
Source: PubMed

ABSTRACT Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) cause major morbidity and significant mortality in patients with diabetes mellitus. For more than 30 yr, our group, in a series of prospective, randomized clinical studies, has investigated the pathogenesis and evolving strategies of the treatment of hyperglycemic crises. This paper summarizes the results of these prospective studies on the management and pathophysiology of DKA.
Our earliest studies evaluated the comparative efficacy of low-dose vs. pharmacological amounts of insulin and the use of low-dose therapy by various routes in adults and later in children. Subsequent studies evaluated phosphate and bicarbonate therapy, lipid metabolism, ketosis-prone type 2 patients, and use of rapid-acting insulin analogs as well as leptin status, cardiac risk factors, proinflammatory cytokines, and the mechanism of activation of T lymphocytes in hyperglycemic crises.
The information garnered from these studies resulted in the creation of the 2001 American Diabetes Association (ADA) technical review on DKA and HHS as well as the ADA Position and Consensus Paper on the therapy for hyperglycemic crises.
Areas of future research include prospective randomized studies to do the following: 1) establish the efficacy of bicarbonate therapy in DKA for a pH less than 6.9; 2) establish the need for a bolus insulin dose in the initial therapy of DKA; 3) determine the pathophysiological mechanisms for the absence of ketosis in HHS; 4) investigate the reasons for elevated proinflammatory cytokines and cardiovascular risk factors; and 5) evaluate the efficacy and cost benefit of using sc regular insulin vs. more expensive insulin analogs on the general ward for the treatment of DKA.

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    • "Even in developed countries, newly diagnosed diabetes accounts for 10 to 22% of cases of hyperglycaemic crisis [5]. However, mortality due to DKA and HHS has been reduced in most developed settings, being smaller than 5% for DKA in specialized centres and around 11% for HHS [6] [7] [8], yet remains high in non-specialized centres, deprived areas and in unusual circumstances such as humanitarian dis- asters. The current consensus for the management of hyperglycaemic crises relies upon intravenous (IV) insulin administered by syringe pumps, rehydration, correction of electrolyte imbalances and treatment of associated conditions, with regular 2- to 4-hour monitoring of serum electrolytes, creatinine, glucose and pH until stable [9]. "
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    ABSTRACT: Management of hyperglycaemic crises requires expensive and labour-intensive procedures that are not achievable in all clinical settings. Intramuscular (IM) insulin therapy is a more feasible alternative, but remains insufficiently evaluated. We report here on an audit of clinical outcomes of a simple management protocol that involves IM insulin therapy, careful rehydration and inexpensive monitoring in a resource-limited setting. In June 2006, we began the routine use of a protocol based on IM insulin administration, careful rehydration and affordable monitoring for the management of hyperglycaemic crises in Yaoundé Central Hospital. Clinical records of patients admitted for hyperglycaemic crises 6 months before and 6 months after introduction of the protocol were independently coded and compared for clinical outcomes, including the 48-hour death rate as a primary endpoint. Secondary endpoints were blood glucose (BG) normalization and duration of hospital stay. A total of 112 patients' files fulfilled the inclusion criteria, including 57 before and 55 after the introduction of the IM protocol (intervention). Patients of the pre-intervention group were aged 56.4+/-2.1 years versus 53.9+/-2.3 years in the intervention group (p=0.41), with 23% versus 40%, respectively, with newly diagnosed diabetes (p=0.05), and 45% versus 41%, respectively, with significant ketosis on admission (p=0.84). As for the primary endpoint, 15.8% of the pre-intervention group died within 48 hours of admission versus 3.6% in the intervention group (p=0.03). BG was normalized within 24 hours of admission in 28.1% patients of the pre-intervention group versus 90.9% of the intervention group (p<0.001). However, the overall duration of hospitalization was similar in both groups. Septic shock, ketosis and high serum creatinine on admission were associated with poor outcomes in both groups. The proposed protocol using IM insulin can be safely used to treat hyperglycaemic crises, with mortality rates comparable to those in specialized centres in developed countries.
    Diabetes & Metabolism 09/2009; 35(5):404-9. DOI:10.1016/j.diabet.2009.04.006 · 2.85 Impact Factor
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    ABSTRACT: Die diabetische Ketoazidose (DKA) und der hyperosmolare hyperglykämische Status (HHS) sind lebensbedrohliche akute Komplikationen eines Diabetes mellitus. Die Behandlung sollte außer bei milden Fällen auf einer internistischen Intensivstation erfolgen. Klinisch unterscheidet sich die DKA vom HHS durch das Vorliegen einer metabolischen Azidose. Trotz dieses Unterschieds ist die Therapie der DKA und des HHS prinzipiell gleich. Sie besteht aus der intravenösen Gabe von Insulin und der Korrektur der Hypovolämie, sowie der Elektrolytveränderungen. Durch die Anwendung eines standardisierten Behandlungsprotokolls kann eine niedrige Sterblichkeit erreicht werden.
    09/2012; 107(6). DOI:10.1007/s00063-012-0114-1
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    ABSTRACT: Diabetic ketoacidosis (DKA) remains a significant complication of diabetes in both the United States and around the world. Diabetic ketoacidosis remains a significant complication of diabetes in both the United States and worldwide with its associated high rates of hospital admissions. Therefore, it becomes vital that the healthcare professional be able to manage the hyperglycemic crises associated with diabetes. Moreover, with increasing healthcare costs and a changing healthcare system, prevention of diabetic ketoacidosis remains essential. Though management of diabetic ketoacidosis has followed a set algorithm for many years, there are exciting management alternatives on the horizon such as subcutaneous insulin administration for uncomplicated DKA patients. By understanding DKA, including its pathogenesis, presentation, treatment, and prevention, admissions may be decreased and length of stay shortened.
    03/2012; 1(1). DOI:10.1007/s40138-012-0001-3
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