This study aims at investigating the influence of the prevailing blood glucose level on the metabolic deterioration that follows a nocturnal interruption of a continuous sc insulin infusion (CSII). Fifteen CSII-treated, C-peptide negative, diabetic patients have been studied CSII was interrupted from 2300 h to 0500 h. Blood was collected hourly from 2200 h to 0600 h. According to blood glucose (BG) levels at 2300 h, patients were classified as hypoglycemic (BG between 1.5 and 2.5 mmol/L, n = 5), normoglycemic (BG between 4.0 and 8.0 mmol/L, n = 5), or hyperglycemic (BG between 9.0 and 15.0 mmol/L, n = 5). At 2300 h, BG (mean +/- SEM) was 1.9 +/- 0.1, 6.2 +/- 0.7 and 11.2 +/- 1.0 mmol/L, respectively. After 6 h of CSII interruption, BG increased to 13.5 +/- 1.3, 14.1 +/- 1.2, and 19.4 +/- 1.2 mmol/L, respectively. At 2300 h, plasma 3-OH-butyrate levels were similar in the three groups (around 150 micromol/L). At 0500 h, significantly higher values were obtained for hyperglycemic (1460 +/- 127 micromol/L) than for normoglycemic (868 +/- 150 micromol/L) or hypoglycemic (837 +/- 80 micromol/L) patients. Enhanced lipolysis in initially hyperglycemic patients may contribute to accelerated ketogenesis and metabolic degradation. In conclusion, the metabolic deterioration that follows CSII interruption is influenced by the initial metabolic situation. Hypoglycemic patients deteriorate more rapidly, and hyperglycemic patients suffer a more important degradation. The latter are prone to rapid ketoacidosis if accidental CSII interruption occurs.