Diurnal Variation in Glucose Tolerance: Cyclic Suppression of Insulin Action and Insulin Secretion in Normal-Weight, But Not Obese, Subjects

The relative roles of insulin sensitivity, insulin secretion, and glucose effectiveness to the diurnal rhythm of glucose tolerance were examined in normal-weight (n = 12) and obese (n = 11) subjects. Two frequently sampled intravenous glucose tolerance tests were performed in each subject at 0800 on one occasion and 1800 on a separate day. Tests were preceded by identical fasts of 10–12 h. In nonobese subjects, glucose tolerance, expressed as the 10- to 16-min K_G value (K_GS), was much reduced in the evening (AM 2.98 ± 0.45, PM 1.86 ± 0.33 min⁻¹ P < 0.002). In the obese subjects, tolerance was lower in the morning than normal-weight subjects (2.19 ± 0.31 min⁻¹), but unlike in nonobese subjects, tolerance was not significantly reduced during the day (1.90 ± 0.18 min⁻¹ P > 0.40). The reduction in glucose tolerance in the normal-weight subjects was caused by diminished insulin sensitivity (parameter S₁, AM 15.4 ± 2.9, PM 10.2 ± 1.9 × 10⁻⁵ min⁻¹/pM, P < 0.01) and reduced β-cell responsivity to glucose. The evening decrease in the latter was reflected both in first-phase plasma insulin (AM 2466 ± 441, PM 1825 ± 381 pM/10 min, P < 0.05) and the potentiation slope (AM 462 ± 68, PM 267 ± 35 pM/mM, P < 0.01). In contrast, consistent with no diurnal variation in glucose tolerance, obese subjects exhibited no decline in insulin sensitivity in the evening (AM 3.6 ± 0.7, PM 4.9 ± 1.0 × 10⁻⁵ min⁻¹/pM). A marginally significant decline in (β-cell responsiveness was observed in the obese group (potentiation slope AM 388 ± 78, PM 233 ± 58 pM/mM, P < 0.05). Glucose tolerance is maintained when the pancreas adequately compensates for prevailing insulin resistance, a relationship described by the disposition index (S_I, × Φ₁). This product decreased 46% in nonobese subjects from morning to evening (P < 0.05), reflecting the inability of the pancreas to overcome prevailing insulin resistance, and resulting in evening glucose intolerance. No diurnal decline in the disposition index was observed in obese subjects. The diurnal rhythms in insulin sensitivity and secretion in nonobese subjects are not consistent with known rhythms in growth hormone or cortisol, but could be due to the effects of a putative diurnal rhythm of sympathetic activity, which would suppress both insulin sensitivity and secretion in the evening. The absence of a rhythm in the obese could reflect an autonomic or hormonal dysfunction that may be related to body-weight regulation.