Circulating insulin-like growth factor-binding protein 1 (IGFBP-1) normally has a close inverse relationship to insulin secretion, which results in a characteristic diurnal variation. However, in type 2 diabetes the correlation with insulin may be lost and IGFBP-1 concentrations relatively increased. The aim of this study was to determine the effect of nutritional deprivation on the diurnal patterns of IGFBP-1 regulation in type 2 diabetes mellitus. After a baseline assessment period, food intake was reduced over 48 hours to 627.6 kJ/d (150 kcal/d) for 72 hours and increased again over 24 hours to baseline (refeeding). Blood samples were taken at 2-hour intervals, for 24 hours in the baseline period, 48 hours during nutritional deprivation, and 24 hours during refeeding. Six individuals with type 2 diabetes were compared with 2 groups that were selected for normal fasting glucose and insulin levels and comprised 6 obese and 6 lean subjects. During energy (caloric) restriction, fasting insulin levels decreased to a similar extent in each study group. At baseline, IGFBP-1 concentrations were similar in each of the study groups and at the end of the period of energy (caloric) restriction the 6:00 AM fasting levels had increased by 144% in the obese control group and by 245% in the lean individuals (each P < .001). In the patients with type 2 diabetes there was a blunted increase in IGFBP-1 concentrations with nutritional deprivation by 33% compared with baseline. During refeeding after nutritional deprivation the IGFBP-1 response to insulin was restored in the individuals with diabetes. In conclusion, patients with type 2 diabetes mellitus have altered IGFBP-1 regulation, relating to impaired hepatic insulin sensitivity, which improves after a period of energy (caloric) restriction.