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Circadian variations in glucose control


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Al wrote, on the list:



The free full-text previous paper by the senior author may add detail.




> The Scientist »

> The Nutshell

> Circadian Clock Controls Sugar Metabolism

> The body's circadian rhythm has more of an effect on glucose tolerance

> than one's eating and sleeping patterns, a study shows.


> By Anna Azvolinsky | April 17, 2015



> Humans' 24-hour circadian clock plays a leading role in glucose

> tolerance, according to a study published Moday (April 13) in PNAS.

> Researchers in Boston have found that, because of body's circadian

> rhythm, human glucose tolerance is reduced during the evening hours,

> even when "day" and "night" times are experimentally reversed.




> "We showed that glucose levels after identical meals were 17 percent

> higher [indicating lower glucose tolerance] in the evening than in the

> morning, independent of when a participant had slept or had their

> meals," study coauthor Christopher Morris, an instructor of medicine at

> the Division of Sleep and Circadian Disorders at Harvard Medical School,

> wrote in an e-mail to The Scientist.




This is consistent with my own experience, which has always puzzled me: my postprandial glucose is always higher after my second meal (started 7 or so hours before bedtime, finished no later than 5 hours before bedtime) than after my first (until recently started upon getting up, which until recently was 6 hours after bedtime). Varying the size of first meal, amount of exercise before eating, etc., didn't make a difference. Exercise after the second meal knocked down blood glucose dramatically of course, but only while exercising, and for a surprisingly brief time after. Then it would shoot back up. (I believe Dean mentioned experiencing the same thging.) Eating very small dinners helps a bit, eating next to nothing at dinner of course made a difference, but otherwise it was clear that my body coulddn't knock down blood glucose as well later in my circadian cycle.



Endogenous circadian system and circadian misalignment impact glucose

tolerance via separate mechanisms in humans.

Morris CJ, Yang JN, Garcia JI, Myers S, Bozzi I, Wang W, Buxton OM, Shea

SA, Scheer FA.

Proc Natl Acad Sci U S A. 2015 Apr 13. pii: 201418955. [Epub ahead of




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Interesting ... that matches a pattern said to be characteristic of diabetic patients for many years, and was part of what motivated the development of drugs specifically targeting early-phase insulin release. However, the effect has subsequently been reported as less dramatic, and fairly unremarkable in healthy normals, and if anything seems to be higher after breakfast:

Continuous interstitial glucose measurement was performed under everyday life conditions (2 days) ... [with] breakfast, lunch, and dinner [consumed] at the same time points ... (7:30 AM, 12:30 PM, 6:00 PM)... The mean 24-hour interstitial glucose concentration under everyday life conditions was 89.3 ± 6.2 mg/dl (mean ± SD, n = 21), and mean interstitial glucose concentrations at daytime and during the night were 93.0 ± 7.0 and 81.8 ± 6.3 mg/dl, respectively. The highest postprandial glucose concentrations were observed after breakfast: 132.3 ± 16.7 mg/dl (range 101–168 mg/dl); peak concentrations after lunch and dinner were 118.2 ± 13.4 and 123.0 ± 16.9 mg/dl, respectively. Mean time to peak glucose concentration was between 46 and 50 minutes.(1)



Mean interstitial glucose in 21 healthy volunteers consuming self-selected meals under everyday life conditions .(1)


Interestingly, in fact, these subjects were also releasing more insulin early on at breakfast and still dealing with higher peak glucose, albeit that they then then turn off insulin earlier:



Areas under the curve (above baseline) after intake of free choice meals under everyday life conditions.(1)

The big confounder is that left to their own devices, the subjects were following the usual American pattern of consuming fewer Calories and disproportionately less protein and fat at breakfast than at the later meals: roughly a third fewer Calories, but only half the protein and fat (Table 2). And the investigators found, unsurprisingly, that

After ingestion of standardized meals ... Meals with a higher fiber, protein, and fat content induced a smaller increase and a slower decrease of postprandial glucose concentrations with peak values of 99.2 ± 10.5 and 122.1 ± 20.4 mg/dl, respectively.(1)

Unfortunately, they didn't take the additional step of continuous glucose testing the subjects over the course of one or more days with standardized meals with the same macronutrient balance and energy fed at each meal.
My guess is that the more "diabetic-like" glucose profile in some CR folk is due to impaired insulin release rather than reduced insulin sensitivity per se, based on evidence of impaired glucose tolerance related to low insulin release in Calorie-restricted humans, rodents, and nonhuman primates (skip down to "the usual understanding of the effects of CR on glucose metabolism is overly simplistic").

1: Freckmann G, Hagenlocher S, Baumstark A, Jendrike N, Gillen RC, Rössner K, Haug C. Continuous glucose profiles in healthy subjects under everyday life conditions and after different meals. J Diabetes Sci Technol. 2007 Sep;1(5):695-703. PubMed PMID: 19885137; PubMed Central PMCID: PMC2769652.

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