OBJECTIVE

To assess the effects of short-term antecedent hypoglycemia on responses to further hypoglycemia 2 days later in patients with IDDM.

RESEARCH DESIGN AND METHODS

We studied eight type I diabetic patients without hypoglycemia unawareness or autonomic neuropathy during two periods at least 4 weeks apart. On day 1, 2 h of either clamped hyperinsulinemic (60 mU · m−2 · min−1) hypoglycemia at 2.8 mmol/l or euglycemia at 5.0 mmol/l were induced. Hyperinsulinemic hypoglycemia was induced 2 days later with 40 min glucose steps of 5.0, 4.0, 3.5, 3.0, and 2.5 mmol/l. Catecholamine levels and symptomatic and physiological responses were measured every 10–20 min.

RESULTS

When compared with the responses measured following euglycemia, the responses of norepinephrine 2 days after hypoglycemia were reduced (peak, 1.4 ± 0.4 [mean ± SE] vs.1.0 ± 0.3 nmol/l [P < 0.05]; threshold, 3.4 ± 0.1 vs. 2.9 ± 0.1 mmol/l glucose [P < 0.01]). The responses of epinephrine (peak, 4.0 ± 1.4 vs. 3.5 ± 0.8 nmol/l [P = 0.84]; threshold, 3.8 ± 0.1 vs. 3.6 ± 0.1 mmol/l glucose [P = 0.38]), water loss (peak, 194 ± 34 vs. 179 ± 47 g−1 · m−2 · h−1 [P = 0.73]; threshold, 2.9 ± 0.2 vs. 2.9 ± 0.2 mmol/l glucose [P = 0.90]), tremor (peak, 0.28 ± 0.05 vs. 0.37 ± 0.06 root mean square volts (RMS V) [P = 0.19]; threshold, 3.2 ± 0.2 vs. 3.1 ± 0.2 mmol/l glucose [P = 0.70]), total symptom scores (peak, 10.6 ± 2.1 vs. 10.8 ± 1.9 [P = 0.95]; threshold, 3.3 ± 0.2 vs. 3.6 ± 0.1 mmol/l glucose [P = 0.15]), and cognitive function (four-choice reaction time: threshold, 2.9 ± 0.2 vs. 3.0 ± 0.2 mmol/l glucose [P = 0.69]) were unaffected.

CONCLUSIONS

The effect on hypoglycemic physiological responses of 2 h of experimental hypoglycemia lasts for 1–2 days in these patients with IDDM . The pathophysiological effect of antecedent hypoglycemia may be of shorter duration in IDDM patients, compared with nondiabetic subjects.

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