Euglycemic-hyperinsulinemic clamps were performed on six healthy untrained individuals to determine whether exercise that induces muscle damage also results in insulin resistance. Clamps were performed 48 h after bouts of predominantly 1) eccentric exercise [30 min, downhill running, -17% grade, 60 +/- 2% maximal O2 consumption (VO2max)], 2) concentric exercise (30 min, cycle ergometry, 60 +/- 2% VO2max), or 3) without prior exercise. During the clamps, euglycemia was maintained at 90 mg/dl while insulin was infused at 30 mU.m-2.min-1 for 120 min. Hepatic glucose output (HGO) was determined using [6,6-2H]glucose. Eccentric exercise caused marked muscle soreness and significantly elevated creatine kinase levels (273 +/- 73, 92 +/- 27, 87 +/- 25 IU/l for the eccentric, concentric, and control conditions, respectively) 48 h after exercise. Insulin-mediated glucose disposal rate was significantly impaired (P less than 0.05) during the clamp performed after eccentric exercise (3.47 +/- 0.51 mg.kg-1.min-1) compared with the clamps performed after concentric exercise (5.55 +/- 0.94 mg.kg-1.min-1) or control conditions (5.48 +/- 1.0 mg.kg-1.min-1). HGO was not significantly different among conditions (0.77 +/- 0.26, 0.65 +/- 0.27, and 0.66 +/- 0.64 mg.kg-1.min-1 for the eccentric, concentric, and control clamps, respectively). The insulin resistance observed after eccentric exercise could not be attributed to altered plasma cortisol, glucagon, or catecholamine concentrations. Likewise, no differences were observed in serum free fatty acids, glycerol, lactate, beta-hydroxybutyrate, or alanine. These results show that exercise that results in muscle damage, as reflected in muscle soreness and enzyme leakage, is followed by a period of insulin resistance.

The effect of hyperglycemia on hormone levels, metabolite levels, and memory performance was examined in 22 subjects with very mild and mild probable dementia of the Alzheimer type (DAT) and in 12 normal elderly adults. Subjects were tested in 3 plasma glucose conditions (fasting baseline, 175 mg/dl, and 225 mg/dl) at initial and 18-month follow-up sessions. Initially, adults with very mild DAT showed memory facilitation and elevations in plasma insulin in the 225-mg/dl glucose condition relative to baseline. At follow-up, very mild DAT patients whose dementia had progressed showed significant decreases in insulin and hyperglycemic memory facilitation. Changes in basal insulin and cortisol levels over time were correlated with memory changes for DAT subjects. These results suggest that glucoregulatory abnormalities may contribute to the pathophysiology of DAT.

Ala and terbutaline produce sustained glucose recovery from hypoglycemia in IDDM and are therefore potentially useful agents for the treatment of mild or moderate iatrogenic hypoglycemia, or the prevention of iatrogenic hypoglycemia, when food intake is not anticipated over the following several hours.

These data demonstrate substantial glycemic responses to Ala and terbutaline, through different mechanisms, in IDDM patients. Thus, Ala and terbutaline represent potential new approaches to the treatment, and perhaps the prevention, of iatrogenic hypoglycemia in IDDM.

No abstract