Severity, Duration, and Mechanisms of Insulin Resistance during Acute Infections*

Abstract

Acute infections provoke insulin resistance. These experiments were designed to study the severity, duration, and mechanisms of insulin resistance caused by acute infections. First, we studied eight patients [mean age, 29 +/- 11 (+/- SD) yr; body mass index, 23 +/- 2 kg/m2] with acute viral or bacterial infections during the acute stage of their infection and 1-3 months after recovery. The rate of glucose infusion required to maintain normoglycemia during hyperinsulinemia (approximately 500 pmol/L) was used as a measure of insulin action. During infection, the glucose requirements in the patients [21 +/- 2 (+/- SE) mumol/kg.min] were 52% less than those in weight- and age-matched normal subjects (44 +/- 2 mumol/kg.min; P less than 0.001). Compared to data from a large group of normal subjects, the resistance to insulin during infection corresponded to that predicted for a weight-matched 84-yr-old normal person or an age-matched obese person with a body mass index of 37 kg/m2. One to 3 months after recovery, the patients' glucose requirements were still significantly lower (37 +/- 3 mumol/kg.min; P less than 0.02) than those in matched normal subjects. To assess the mechanism of insulin resistance, seven additional patients were studied during the acute stage of infection using a low dose insulin infusion (plasma insulin, 215 pmol/L) combined with a [3-3H]glucose infusion and indirect calorimetry. Again, the glucose requirements were 59% lower in the patients (14 +/- 2 mumol/kg.min) than in matched normal subjects (34 +/- 2 mumol/kg.min; P less than 0.001). This decrease was due to a defect in glucose utilization (18 +/- 2 vs. 37 +/- 1 mumol/kg.min; P less than 0.001, patients vs. normal subjects) rather than impaired suppression of glucose production (4 +/- 1 vs. 3 +/- 1 mumol/kg.min, respectively). Total carbohydrate oxidation rates were similar in both groups (16 +/- 2 vs. 14 +/- 1 mumol/kg.min, respectively), whereas the apparent glucose storage was neglible in the patients (2 +/- 1 mumol/kg.min) compared to that in normal subjects (22 +/- 2 mumol/kg.min; P less than 0.001). We conclude that acute infections induce severe and long-lasting insulin resistance, which is localized to glucose-utilizing pathways. The rate of carbohydrate oxidation is normal during infections, whereas the rate of nonoxidative glucose disposal, as determined by indirect calorimetry, is nearly zero. The apparent blockade in glucose storage could result from diminished glycogen synthesis, accelerated glycogenolysis, or both.

Effects of endotoxin lipopolysaccharide administration on the somatotropic axis

“…In our study insulin secretion was decreased after acute, but not during chronic LPS administration. Several alterations in carbohydrate metabolism have been described during acute endotoxemia, such as insulin resistance (Virkamaki & Yki-Järvinen 1994), reduced or increased plasma insulin and increased secretion of glucagon (Yki-Järvinen et al 1989, Bundz et al 1995. However, insulin and glycemia alterations last only 2-3 h.…”

Direct control of hepatic glucose production by interleukin-13 in mice

“…In response to endotoxin, the body exhibits transient systemic insulin resistance, in an attempt to spare glucose for utilization by immune cells (40)(41)(42). It is therefore conceivable that in addition to resolving inflammation, one of the main functions of IL-13 is to restore glucose homeostasis that is disrupted by proinflammatory actions.…”

The Role of Genetic Predisposition in Diagnosis and Therapy of Periodontal Diseases in Type 1 Diabetes Mellitus

“…In patients with poorly controlled DM, an improvement of the metabolic control may improve the periodontal condition. [61][62][63][64] Conversely, periodontal disease can interfere with the control of DM and can increase the insulin requirements in previously stable patients. [65][66][67]56,68,2,69 Smoking is associated with an increased intensity of periodontitis.…”