Endocrine Abstracts

Objectives: The extent and mechanisms of the diurnal variation in insulin sensitivity are poorly described. This study set out to assess the relative contributions of diurnal rhythm and length of fast to insulin sensitivity in normal healthy human subjects.

Methods: Nine healthy women (age 25.3±1.2 years, BMI 22.4±0.8 Kg/m2) ate a standardised meal before each of the four fasts, two ten-hour fasts ending at 0900 and 1700 and two thirteen-hour fasts ending at 0900 and 1200. The linear slope of arterialised plasma glucose decline3-15 min, was used to measure insulin sensitivity. The local ethical committee approved the study.

Results: Insulin sensitivity was lower at 17.00 compared to any other time (9.00 after 10 hr fast 208 ± 11, 9.00 after 13 hr fast 198 ± 14, 12.00 after 13 hr fast 172 ± 12, 17.00 after 10hr fast 118 ± 9 micromol/l/min p<0.001). NEFA (500 ± 56 vs 1076 ± 63 micromol/l p<0.001) and 3-beta-hydroxybutyrate (0.16±0.03 vs 0.43±0.09 mmol/l p<0.002) levels were lower at 9.00 than at 17.00. Triglyceride concentrations (1.17±0.16 vs 0.83±0.05 mmol/l p=0.014) and glucose concentrations(4.76 ± 0.16 vs 4.43 ± 0.11 mmol/l p=0.028) levels were higher in the morning than in the afternoon. Over the 4 tests compared in each subject with 9.00 after 10hr fast defined as baseline concentration changes (delta) in NEFA levels were negatively correlated with changes in insulin sensitivity (r = -0.613, p<0.001), whilst changes in glucose levels were positively correlated with those of insulin sensitivity (r = 0.799 p<0.001). The length of a fast had no effect on any of the measured variables.

Conclusion: Insulin sensitivity and NEFA have a diurnal variation. They were both unaffected by the length of fasting. Elevated NEFA concentrations were statistically inversely correlated with insulin sensitivity. These studies have not determined whether this association is causal.