Continuous hypoxia is associated with insulin resistance, altered glucose metabolism, and increased sympathetic nervous activity. This study examined the effect of 2 successive exposures to intermittent hypercapnic hypoxia (IHH) on glucose metabolism and insulin sensitivity in neonatal piglets. Piglets were assigned to 2 groups. One group was exposed to 2 x 90 minutes of hypercapnic hypoxia (8% O(2), 7% CO(2)), intermittently in 6-minute cycles alternating with 6-minute air. The second group was given 2 x 90 minutes of air. Blood pressure, blood gases, glucose, insulin, and lactate were measured during exposures. Insulin sensitivity was assessed using the euglycemic clamp before and after the exposures. Piglets in the IHH group exhibited reduced PO(2) (from 111.4 +/- 14.2 to 43.3 +/- 21.7), increased PCO(2) (from 33.6 +/- 1.9 to 49.4 +/- 5.4), and lactic acidosis. Compared with air, IHH decreased blood glucose (control [CON] 4.44 +/- 0.72 mmol/L vs IHH 2.67 +/- 1.2 mmol/L, P = .007), insulin (CON 12.5 +/- 7.4 microU/mL vs IHH 3.6 +/- 3.1 microU/mL, P = .03), and mean arterial pressure (CON 143.0 +/- 7.9 mm Hg vs IHH 112.5 +/- 9.5 mm Hg, P < .001) over 90 minutes. Maximal insulin-stimulated glucose disposal was not different between the groups on either day, nor was endogenous glucose production. Overall, exposure to hypoxia in an intermittent pattern reduced sympathetic drive as indicated by blood pressure and did not alter insulin sensitivity, resulting in decreases in blood glucose and insulin. We speculate that an intermittent hypoxic stimulus results in failure of initiation of compensatory responses to increased energy requirements that would usually be observed during sustained exposure to hypoxia.