Glycemic control is impaired in the evening in prediabetes through multiple diurnal rhythms.

Aims: Recent studies suggest that circadian rhythms regulate glucose metabolism, weight loss, and even drug efficacy. Moreover, molecules targeted at the circadian clock show promise in treating metabolic disease. Therefore, this study set out to better characterize interactions among diurnal rhythms in prediabetes.

Methods: Ten subjects with prediabetes completed oral glucose tolerance tests at 0700h and 1900h on the same day. Lipids and hormones were also measured.

Results: Two-hour and three-hour glucose tolerances were worse in the evening by 40±52mg/dl (p=0.02) and 62±46mg/dl (p=0.001), respectively. These impairments were explained by lower insulin sensitivity (OGIS; 5.14±1.02 vs. 4.74±0.77mg/kg/min; p=0.03) and 2-hour AUC insulin levels (87.4±37.6 vs. 69.8±40.2mU∙hr/l; p=0.02) in the evening. Intriguingly, more insulin resistant subjects had weaker rhythms in insulin sensitivity (r=-0.66; p=0.04) but enhanced rhythms in insulin (r=-0.67; p=0.03) and cortisol (r=-0.78; p=0.008) levels. Importantly, the rhythms in cortisol primarily but also insulin sensitivity drove the declines in evening glucose tolerance (r=0.86; p=0.002).

Conclusions: Glycemic control is dramatically impaired in the evening in people with prediabetes, particularly when the cortisol rhythm is weak, but is unrelated to the rhythm in insulin levels. Therefore, food intake at dinnertime may need to be curbed in prediabetes.