Hyperglycemic Crises in Adult Patients With Diabetes

Abbas E. Kitabchi, PHD, MD; Guillermo E. Umpierrez, MD; John M. Miles, MD; Joseph N. Fisher, MD


Diabetes Care. 2009;32(7):1335-1343. 

In This Article

Precipitating Factors

The most common precipitating factor in the development of DKA and HHS is infection[1,4,10]. Other precipitating factors include discontinuation of or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and drugs[10,13,14]. In addition, new-onset type 1 diabetes or discontinuation of insulin in established type 1 diabetes commonly leads to the development of DKA. In young patients with type 1 diabetes, psychological problems complicated by eating disorders may be a contributing factor in 20% of recurrent ketoacidosis. Factors that may lead to insulin omission in younger patients include fear of weight gain with improved metabolic control, fear of hypoglycemia, rebellion against authority, and stress of chronic disease.

Before 1993, the use of continuous subcutaneous insulin infusion devices had also been associated with an increased frequency of DKA[23]; however, with improvement in technology and better education of patients, the incidence of DKA appears to have reduced in pump users. However, additional prospective studies are needed to document reduction of DKA incidence with the use of continuous subcutaneous insulin infusion devices[24].

Underlying medical illness that provokes the release of counterregulatory hormones or compromises the access to water is likely to result in severe dehydration and HHS. In most patients with HHS, restricted water intake is due to the patient being bedridden and is exacerbated by the altered thirst response of the elderly. Because 20% of these patients have no history of diabetes, delayed recognition of hyperglycemic symptoms may have led to severe dehydration. Elderly individuals with new-onset diabetes (particularly residents of chronic care facilities) or individuals with known diabetes who become hyperglycemic and are unaware of it or are unable to take fluids when necessary are at risk for HHS[10,25].

Drugs that affect carbohydrate metabolism, such as corticosteroids, thiazides, sympathomimetic agents, and pentamidine, may precipitate the development of HHS or DKA[4]. Recently, a number of case reports indicate that the conventional antipsychotic as well as atypical antipsychotic drugs may cause hyperglycemia and even DKA or HHS[26,27]. Possible mechanisms include the induction of peripheral insulin resistance and the direct influence on pancreatic ß-cell function by 5-HT1A/2A/2C receptor antagonism, by inhibitory effects via α2-adrenergic receptors, or by toxic effects[28].

An increasing number of DKA cases without precipitating cause have been reported in children, adolescents, and adult subjects with type 2 diabetes. Observational and prospective studies indicate that over half of newly diagnosed adult African American and Hispanic subjects with unprovoked DKA have type 2 diabetes[28–32]. The clinical presentation in such cases is acute (as in classical type 1 diabetes); however, after a short period of insulin therapy, prolonged remission is often possible, with eventual cessation of insulin treatment and maintenance of glycemic control with diet or oral antihyperglycemic agents. In such patients, clinical and metabolic features of type 2 diabetes include a high rate of obesity, a strong family history of diabetes, a measurable pancreatic insulin reserve, a low prevalence of autoimmune markers of ß-cell destruction, and the ability to discontinue insulin therapy during follow-up[28,31,32]. This unique, transient insulin-requiring profile after DKA has been recognized mainly in blacks and Hispanics but has also been reported in Native American, Asian, and white populations[32]. This variant of diabetes has been referred to in the literature as idiopathic type 1 diabetes, atypical diabetes, “Flatbush diabetes,” type 1.5 diabetes, and more recently, ketosis-prone type 2 diabetes. Some experimental work has shed a mechanistic light on the pathogenesis of ketosis-prone type 2 diabetes. At presentation, they have markedly impaired insulin secretion and insulin action, but aggressive management with insulin improves insulin secretion and action to levels similar to those of patients with type 2 diabetes without DKA[28,31,32]. Recently, it has been reported that the near-normoglycemic remission is associated with a greater recovery of basal and stimulated insulin secretion and that 10 years after diabetes onset, 40% of patients are still non–insulin dependent[31]. Fasting C-peptide levels of >1.0 ng/dl (0.33 nmol/l) and stimulated C-peptide levels >1.5 ng/dl (0.5 nmol/l) are predictive of long-term normoglycemic remission in patients with a history of DKA[28,32].


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