Delaying time to first nocturnal void may have beneficial effects on reducing blood glucose levels. - Beyond the Abstract

In the March 2016 issue of Endocrine, Juul and co-workers representing Ferring Pharmaceuticals and universities in Ghent, Belgium; Atlanta, GA; and Aarhus, Denmark published an intriguing correlation between glycaemia and sleep quality (1).

In a post-hoc analysis of a large population (841 patients mostly suffering from nocturnal polyuria), the authors found a correlation between random blood glucose levels and the length of the First Uninterrupted Sleep Period (FUSP); prolonged FUSP was associated with significantly lower glucose levels, even when potential confounders were incorporated in a multiple regression analysis.

The magnitude of the apparent positive effect of FUSP was modest; the authors calculated that a 3-hour increase in FUSP might cause a 0.26 mmol/L (4.7 mg/dL) lowering of blood glucose levels. Importantly, the baseline glucose levels strengthened the correlation between FUSP and glucose; at higher levels the effect may thus be more pronounced (a decrease in blood glucose of 0.72 mmol/l (13 mg/dL) per 3-hour increase in FUSP is expected at baseline levels of 7 mmol/L (125 mg/dL)). Although numerically small, the correlations were statistically highly significant.

With some reservations (2), glucose levels can be considered a proxy for cardiometabolic health status. Sleep disturbances are complicated by poor metabolic health (3) but except for successfully treated sleep apnoea (4) we lack evidence of efficacious interventions.

The mechanism behind the finding is not obvious. Although the analyses included placebo-treated patients, most glucose samples were obtained during desmopressin treatment. Thus, a direct drug effect must be considered. A simple dilution seems unlikely since no weight changes were detected. Vasopressin per se may have important effects on the immune system and could thereby ameliorate the low-grade inflammation associated with pre-diabetes (5,6), however the precise mechanisms seem to be far from clarified (6).

Apart from possible effects of desmopressin, the results presented here provide further fuel to initiating interventional protocols focussing on sleep quality itself (7). Among the subjects for further study is nocturia, which was studied here. 

The interpretation of the data presented here is of course hampered by a lack of well-established metabolic end-points such as insulin levels, HbA1c levels and a rigorous protocol for glucose sampling. Nevertheless, the preliminary conclusion that intervention resulting in a prolonged FUSP may be of cardiometabolic benefit will hopefully ignite further research.


Written By:

Juul KV1, Jessen N2, Bliwise DL3, van der Meulen E4, Nørgaard JP5.

Faculty of Medicine and Health Sciences, University of Ghent, 9000, Ghent, Belgium.
Department for Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
Program in Sleep, Aging and Chronobiology, Emory University School of Medicine, Atlanta, GA, USA.
Ferring International PharmaScience Center, Copenhagen, Denmark.
Faculty of Medicine and Health Sciences, University of Ghent, 9000, Ghent, Belgium.


1. Delaying time to first nocturnal void may have beneficial effects on reducing blood glucose levels. Juul KV, Jessen N, Bliwise DL, van der Meulen E, Nørgaard JP. Endocrine. 2016 Mar 22. [Epub ahead of print]
2. Cardiometabolic risk profiles and carotid atherosclerosis in individuals with prediabetes identified by fasting glucose, postchallenge glucose, and hemoglobin A1c criteria. Marini MA, Succurro E, Castaldo E, Cufone S, Arturi F, Sciacqua A, Lauro R, Hribal ML, Perticone F, Sesti G. Diabetes Care. 2012 May;35(5):1144-9. doi: 10.2337/dc11-2032
3. Effects of poor and short sleep on glucose metabolism and obesity risk. Spiegel K, Tasali E, Leproult R, Van Cauter E. Nat Rev Endocrinol. 2009 May;5(5):253-61. doi: 10.1038/nrendo.2009.23
4. Treatment of obstructive sleep apnea improves cardiometabolic function in young obese women with polycystic ovary syndrome. Tasali E, Chapotot F, Leproult R, Whitmore H, Ehrmann DA. J Clin Endocrinol Metab. 2011 Feb;96(2):365-74. doi: 10.1210/jc.2010-1187
5. Corticotropin-releasing factor, vasopressin, and prostaglandins mediate, and nitric oxide restrains, the hypothalamic-pituitary-adrenal response to acute local inflammation in the rat. Turnbull AV, Rivier C. Endocrinology. 1996 Feb;137(2):455-63
6. Vasopressin: friend or foe? Knepper MA, Star RA. Nat Med. 2008 Jan;14(1):14-6. doi: 10.1038/nm0108-14
7. The impact of sleep amount and sleep quality on glycemic control in type 2 diabetes: A systematic review and meta-analysis. Lee SW, Ng KY, Chin WK. Sleep Med Rev. 2016 Feb 9. pii: S1087-0792(16)00017-4. doi: 10.1016/j.smrv.2016.02.001

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