Relationship of Critical Illness Associated Hyperglycemia and Subsequent Development of Type 2 Diabetes

Patients with hyperglycemia during acute illness who are not diagnosed with diabetes should be considered a population at increased risk for developing diabetes… 

Critical illness is commonly complicated by hyperglycemia caused by mediators of stress and inflammation. Severity of disease is the main risk factor for development of hyperglycemia, but not all severely ill develop hyperglycemia and some do even in mild disease. Researchers hypothesized that acute disease only exposes a latent disturbance of glucose metabolism which puts those patients at higher risk for developing diabetes.

The increase in blood glucose during acute illness is a consequence of complex mechanisms that are a part of stress and inflammatory responses. Cortisol is the main mediator of stress response, but other stress hormones such as catecholamines, glucagon and growth hormone also have hyperglycemic effects. Mediators of systemic inflammatory response, such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α), cause hyperglycemia and peripheral insulin resistance by inducing the release of stress hormones. They also alter insulin receptor signaling and create insulin resistance. Due to these actions, glucose uptake in fat and muscle cells is reduced and hepatic gluconeogenesis is not suppressed despite hyperglycemia. Consequent to inhibition of pancreatic beta-cells by cytokines and catecholamines, insulin concentrations may be normal or even decreased. Medical interventions, such as enteral and parenteral nutrition, administration of vasopressors and glucocorticoids, add even further to disturbed glucose homeostasis. Despite the fact that endocrine and metabolic changes probably occur in all acutely ill patients, evident hyperglycemia is not present in all of them. Its occurrence is certainly associated with the severity of illness, and has been associated with unfavorable outcomes in several acute conditions. Nevertheless, all patients with severe infections, severe myocardial infarction or other critical illnesses do not develop hyperglycemia and some will have hyperglycemia even in milder disease. A patient’s predisposition (pancreatic reserve and baseline insulin resistance) obviously plays an important part in the development of hyperglycemia. Researchers hypothesized that hospital acquired hyperglycemia reveals this predisposition, that is, those patients are at risk for developing Type 2 diabetes in the period subsequent to acute illness.

Medical patients with no history of impaired glucose metabolism or other endocrine disorder admitted to an intensive care unit between July 1998 and June 2004 were considered for inclusion. Glucose was measured at least two times a day, and patients were divided into the hyperglycemia group (glucose ≥7.8 mmol/l) and normoglycemia group. An oral glucose tolerance test was performed within six weeks after discharge to disclose patients with unknown diabetes or pre-diabetes who were excluded. Patients treated with corticosteroids and those terminally ill were also excluded from the follow-up which lasted for a minimum of five years with annual oral glucose tolerance tests.

A five-year follow-up was completed for 398 patients in the normoglycemia group, of which 14 (3.5%) developed Type 2 diabetes. In the hyperglycemia group 193 patients finished follow-up and 33 (17.1%) developed Type 2 diabetes. The relative risk for Type 2 diabetes during five years after the acute illness was 5.6 (95% confidence interval (CI) 3.1 to 10.2).

Hyperglycemia occurring during critical illness in non-diabetic medical patients is associated with increased risk of developing diabetes in the five-year period after the discharge. Stress and inflammation during acute illness seem to reveal an inherent disorder of glucose metabolism which in the following years leads to development of diabetes. Patients with hyperglycemia during acute illness who are not diagnosed with diabetes before or during the hospitalization should be considered a population at increased risk for developing diabetes. They should, therefore, be followed-up, in order to be timely diagnosed and treated.