Lee · Diabetes 1992 · Repeated-measures comparative physiological study · n=23

Diurnal variation in glucose tolerance. Cyclic suppression of insulin action and insulin secretion in normal-weight, but not obese, subjects.

Cited 195 times in the scientific literature.

Level 3 - non-randomized controlled study

Controlled non-randomized physiological study with within-subject morning versus evening repeated measures.

PubMed 1587401 · doi:10.2337/diab.41.6.750 · record verified 2026-08-31

What was done

Researchers evaluated the diurnal rhythm of glucose tolerance, insulin sensitivity, insulin secretion, and glucose effectiveness in 12 normal-weight and 11 obese individuals. Each participant underwent two frequently sampled intravenous glucose tolerance tests (FSIVGTT)—one at 0800 and one at 1800 on separate days—each preceded by a 10–12 hour fast.

What was found

In normal-weight subjects, evening glucose tolerance (KG value) was significantly lower than morning tolerance (AM 2.98 ± 0.45 vs. PM 1.86 ± 0.33 min⁻¹, P < 0.002). This was accompanied by a decrease in insulin sensitivity (SI: AM 15.4 ± 2.9 vs. PM 10.2 ± 1.9 × 10⁻⁵ min⁻¹/pM, P < 0.01), reduced first-phase insulin response (AM 2466 ± 441 vs. PM 1825 ± 381 pM/10 min, P < 0.05), and a lower potentiation slope (AM 462 ± 68 vs. PM 267 ± 35 pM/mM, P < 0.01). In contrast, obese subjects had lower baseline morning glucose tolerance (2.19 ± 0.31 min⁻¹) with no significant evening reduction (PM 1.90 ± 0.18 min⁻¹, P > 0.40) and exhibited no decline in evening insulin sensitivity (AM 3.6 ± 0.7 vs. PM 4.9 ± 1.0 × 10⁻⁵ min⁻¹/pM).

Why it matters

This study shows that diurnal variation in glucose handling in healthy individuals is mediated by dual reductions in both insulin action and secretion, a cyclic variation that is absent or blunted in obesity.

Limits

The sample size was small (23 total participants). The use of intravenous glucose administration bypasses gut-derived incretin effects and oral digestion dynamics, and the abstract leaves out data on glucose effectiveness due to text truncation.

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