Category Archives: diabetes

Dopamine regulates systemic glucose metabolism in humans

In Four. EPIC. Experiments (ter Horst et al., 2018)

Tl;dr: sunlight & breakfast in the morning.

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Dopamine receptors are downregulated in obese patients and are restored in long-term weight loss patients after bariatric surgery. It’s better to get your dopamine hit via sunlight than sugar duh.

This is some amazing science.

 

 

Experiment 1. 50-year old dude with severe OCD gets diagnosed with type 2 diabetes and is only able to get his glucose under control with metformin and 226 IU insulin. At 53, his OCD is treated with deep brain stimulation (DBS). His insulin requirements declined to 180 IU. He didn’t lose weight but went off quetiapine, so maybe coincidence because: 1. quetiapine is diabetogenic; and 2. DBS induces dopamine release.

Two-step hyperinsulinemic euglycemic clamp when DBS is turned off and turned on. BOOM! When it’s on, lower fasting insulin, and better insulin-induced suppression of liver glucose output, free fatty acids, & muscle glucose disposal! DBS improved insulin sensitivity in liver, adipose, and skeletal muscle.

For the rest of the discussion on these super-interesting experiments, head over to PatreonFive bucks a month for full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

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If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else

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Cycloset (bromocriptine)

 

 

Go for a walk.

And #eTRF.

 

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Mutual influence of sleep and circadian clocks on physiology and cognition

“The 24-hour sleep-wake cycle is one of the most prominent outputs of the circadian clock systems (Heyde et al., 2018)”

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Sleep disruption and circadian arrhythmia induce metabolic, cognitive, and immunological impairments. Is it causal? YES.

 

 

Sleep is highly conserved across the animal kingdom, since the dawn of time.

Interesting comparison: unlike hibernation or a coma, sleep is highly reversible. Lots of rebound regulation: lots of wakefulness makes you tired; lots of sleep leads to increased wakefulness.

Studies have shown improved memory performance after naps and extended sleep durations. Imo, you don’t need to go from 6 to 9.5 hours overnight, but keep that “9.5” on your radar.

Diet is easy, just eat like an adult. You can go 10 days without even eating! Try that with sleep. No, don’t try that. Most definitely incompatible with survival. Sleep deprivation impairs cognitive functions.

As a marker of health: cognitive function >>> how many reps you can do at the gym.

For the rest of this article (it doesnt suck, I promise!), head over to Patreon! Five bucks a month and there are many other options. It’s ad-free and you can cancel any time.

Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.

Affiliate links: It’s 2018, join Binance and get some damn cryptoassets or download Honeyminer and get some Bitcoins for free!

Still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HEREIf you have no idea what I’m talking about, read this then this.

20% off some delish stocks and broths from Kettle and Fire HERE

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else

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It STARTS with Sleep.

 

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The influence of ketones on intermediary metabolism

Two studies: one on infusion of D-b-hydroxybutyrate at three different level producing up to 2 mM at the highest level (Mikkelsen et al., 2014); and one on ingestion of a ketone monoester (R-3-hydroxybutyl-R-3-hydroxybutyrate) producing ~3.2 mM (Myette et al., 2018). Both studies were relatively small (n = 6 and 20, respectively) yet interesting.

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Mikkelsen: mainly justified the use of exogenous ketones in T2DM because of their ability to suppress hyperglycemia and hyperlipidemia. And justified ’em in CNS disorders because adherence is poor in this population and goes downhill with increasing disease severity. They’re anti-ketone salts because: 1) the GI distress and salt load with doses required to get into the 2-3 mM range; and 2) they’re often racemic mixtures of D- and L-b-hydroxybutyrate (“D” is the endogenous one).

 

 

As expected, increasing the infusion dose linearly increased plasma bHB:

Further, as expected, brain uptake increased in parallel to plasma levels:

Interestingly, muscle uptake seemed to become saturated and not increase much further… this may be related to the “muscle-sparing effect of fat-derived fuels,” in other words, muscle is sparing ketones for the brain like it does during late starvation.

For the rest of this article (it doesnt suck, I promise!), head over to Patreon! Five bucks a month and there are many other options. It’s ad-free and you can cancel any time.

Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.

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20% off some delish stocks and broths from Kettle and Fire HERE.

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. recommend Lion’s Mane for the brain and Reishi for everything else.

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ketones inhibit lipolysis

 

 

 

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Circadian rhythms, sleep deprivation, and human performance

“Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep-wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance (Goel et al., 2013).”

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Acute and chronic sleep restriction degrade neurobehavioral functions, attention, cognitive speed, and memory. Strictly according to the studies (not your n=1), < 5.5 hours is bad, < 7 hours is suboptimal, and ~ 9.5 hours may be optimal. Seems like a lot; who has time to sleep 9.5 hours?!

Above image shows cerebral blood flow (orange) in the same person’s brain during a Psychomotor Vigilance Test performed in the morning and afternoon. Interestingly, most participants perform better in the afternoon and this is associated with more blood going to a different part of the brain.

“Sleep is a ubiquitous biological imperative that appears to be evolutionarily conserved across species.” Mandatory for optimal attention and cognitive performance.

To get the rest of this article (it doesn’t suck, I promise) or if you just like what I do and want to support it, head over to Patreon! Five bucks a month and there are many other options. It’s ad-free and you can cancel any time.

Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.

Affiliate links: still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE.
If you have no idea what I’m talking about, read this then this.

20% off some delish stocks and broths from Kettle and Fire HERE.

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. recommend Lion’s Mane for the brain and Reishi for everything else.

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It STARTS with Sleep.

Social jet lag.

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As if we needed another study about breakfast. Or 4.

Exhibit A. Participants were given ~30 grams of whey, casein, or carbs 30 minutes before bed (Kinsey et al., 2014). [side note: the closer it is to bedtime, the less food is needed to mess up your rhythms. Worded another way, if you’re gonna have a big dinner, the earlier the better]. The following morning, you guessed it, they weren’t hungry for breakfast. And they had higher insulin levels. FFS. Worded another way, light early dinner -> lower insulin and more hungry for breakfast, in the morning.

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Dopamine and breakfast.

Light and food in the morning.

Metabolism is gimped at night.

Exhibit B1. Expecting mothers: “Across the whole cohort, night-time, but not day-time, carbohydrate intake was positively associated with glucose concentrations after the glucose load and inversely associated with early phase insulin secretion (P < 0.05)” (Chandler-Laney et al., 2016).

 

 

Evening is not the best time to carb… but it’s not just carbs… and it affects infants, too.

Affiliate discounts: if you’re still looking for a pair of hot blue blockers, Carbonshade  is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE. If you have no idea what I’m talking about, read this then this.

20% off some delish stocks and broths from Kettle and Fire HERE

If you want the benefits of  ‘shrooms but don’t like the taste, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS.

For full access to all articles and more (or if you just like what I do and want to support it), head over to Patreon! It’s only three bucks a month and there are many other options. It’s ad-free and you and you can cancel if it sucks 🙂

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Sunlight, Meal Timing, and Circadian Rhythms.

we’re talking some serious epigenetics

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Funded by Big ‘Shrooma

Reishi, the mushroom of longevity.

“The goal is to maintain or improve brain function and physical performance. And not get cancer.”

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‘Shrooms-every-day is part of my long-term anti-cancer plan. It’s not always a lot per serving, but I try to do the whole variety thing as much as possible, whatever’s available.

Maybe it’s one of those ice-age fairy tales fallacies, but cultures around the world have attributed a large number of health benefits to ‘shrooms for literally, thousands of years:

Ganoderma [reishi] has a very long history in East Asia as a medicinal mushroom dating back to the Chinese materia medica ‘Shen Nung Ben Cao Jing,’ written between 206 BC and 8 AD. It was considered a superior tonic for prolonging life, preventing aging, and boosting qi.”

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The importance of entraining skeletal muscle’s circadian clock (and how)

“Literally, every single model of skeletal muscle circadian arrhythmia mimics aging sedentary people who skip breakfast, stay up late, and get sick.”

But first, the human studies that confirm these newer findings aren’t restricted to preclinical models: 1) a randomized CROSSOVER study; two weeks of modest caloric restriction. Same diet; either 5.5 or 8.5 hours of sleep.

In other words, circadian rhythms broke or woke (Nedeltcheva et al., 2010):

 

 

Same diet & energy expenditure + circadian arrhythmia = lose less fat and more muscle. This is basically the opposite of optimal. Large error bars because it was a CROSSOVER study, although it still managed to reach statistical significance.

And this happened despite lower 24-hour insulin AUC (Nedeltcheva et al., 2012). GRAVITAS.

 

 

And in an ad lib setting, “Laboratory studies in healthy young volunteers have shown that experimental sleep restriction is associated with a dysregulation of the neuroendocrine control of appetite consistent with increased hunger and with alterations in parameters of glucose tolerance suggestive of an increased risk of diabetes” (Van Cauter et al., 2007).

 

 

Part 2. THE BETTER PART: The muscle clock, how it works, and how to fix it.

 

 

 

Similar to other peripheral circadian clocks (eg, liver, adipose, lung, etc.), the muscle clock is entrained by LIGHT via the central pacemaker located in the SCN and feeding (via an as of yet unclear mechanism), but also scheduled exercise.

Interestingly, mice who had been subjected to a 6-hour phase advance adapted faster if they exercised early in the active phase (would be morning for humans).

 

 

Much of these data are summarized in a review in Frontiers in Neuroscience (Aoyama and Shibata, 2017).

The muscle clock is entrained by timed exercise but also feeding. This was demonstrated by showing the circadian rhythms in a subset of muscle-specific genes in fed mice were absent in fasted mice.

It is thought that the muscle clock’s function is to prepare us for the transition from the resting/fasting phase (night) to the active/fed phase (day)… and although I like that phrasing, this seems somewhat subjective (and really hard  to test/prove even on a hypothetical level).

 

 

Part 3. The BEST part: impact of various muscle clock disruptions.

Hint: THEY’RE ALL BAD.

 

For the rest of this article (including my interpretation and advice), head over to Patreon!

Three bucks a month for access to all articles and there are many other options. And it’s ad-free.

If you’re on the fence considering it, try it out, you can cancel at any time! Also, there is a limited number of positions remaining at the $3 level.

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Allu-lujah: the new Quest Hero bars

On that sweetener in the new Quest Hero bars: allulose (formerly known as D-Psicose).

1. I’m sure they were quick to adopt the alternate nomenclature because it’s hard not so say Piss-cose lol

2. Nutrition-wise, Hero bars are basically Quest Lite. A bit less fibre. But I really think they’re getting much better at texture.

3. On to allulose. It’s not really like sugar – even though the FDA says it must be labeled as such – because it carries virtually no calories and actually blunts the blood glucose spike from a meal.

 

Exhibit A. n=20 healthy peole: 7.5 g D-psicose alone, 75 g maltodextrin alone, 75 g maltodextrin + 2.5, 5, or 7.5 g D-psicose (Iida et al., 2008)

amazeballs

 

 

 

 

 

Exhibit B. n=26, zero or 5g psicose with a standardized meal (Hayashi et al., 2010). Note: there are ~12 grams of allulose in a Hero bar.

It works better in diabetics.

 

 

They did a 12-week study where psicose was dosed 3 times a day, 5 grams each time, and showed it was perfectly healthy. Some markers even improved.

 

Exhibit C. Psicose metabolism (Iida et al., 2010)

In doses ranging from 5 to 30 grams, up to 70% is excreted intact and the rest does not go to farts.

It’s virtually calorie-free:

 

 

and is barely fermentable (compared to FOS):

 

 

compare to other low carb protein bars here, get the new Quest bars here, or just buy some straight allulose and experiment with it!

Mechanisms? 1) it’s not sugar, but it still enhances glucose disposal; and 2) some animal studies show it enhances liver glucose uptake. Idk.

If you like what I do and want to support it, head over to Patreon! Three bucks a month for access to all articles and there are many other options. Don’t hesitate, there are only a limited number of spaces left at the $3 level. It’s ad-free and you can cancel at any time 🙂

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The alkaline diet is bullshit. Proof: vinegar is the bomb

1. Whether it’s Balsamic, sherry, red wine, apple cider, or even plain distilled white, vinegar is a great condiment (P<0.05). Try cutting your favorite with a more concentrated one for more fun (be careful, it can burn you; I’d start with 1:20 or 5%).

2. It reduces the glucose and insulin response to a meal.

World’s coolest fatty acid?

 

 

Exhibit A: 20 g apple cider vinegar, 40 g water, and 1 tsp saccharine two minutes prior to “a white bagel, butter, and orange juice (87 g total carbohydrates)” (Johnston et al., 2004)

 

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High protein magic

Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: randomized control trial (Stentz et al., 2016)

n=12/group

Duration = 6 months

Diet: all food provided.  Mucho gusto!

 

Critique #1: if my calculations are correct, we’re comparing low protein (0.675 g/kg) to adequate (1.35 g/kg) (not “high”).

The diets were decent:

 

 

Results:

 

 

Author’s conclusion was that this was due to high protein alone, but I’d say it was at least partially due to weight loss.  BOTH groups lost weight and improved insulin sensitivity.  Statistically significant in both groups.

 




 

Glucose (A) and insulin (B) in response to a 75g OGTT (red is high protein, blue high carb):

 

 

I still say weight loss was the primary driver, but must concede, however, that protein did have a little magical effect: high carb group actually lost slightly more weight, but insulin sensitivity improved more in the high protein group.  The high protein magic: reduced insulin secretion yet still greater reduction in glycemia.

 




 

Well, maybe not magic…

 

 

Despite having more insulin, high carbers lost slightly more fat mass but way more muscle.  THAT’s high protein magic lol

 

However, the meal tolerance tests show a slightly different trend:

 

 

We expect glucose and insulin excursions to be greater in HC (blue), because they had a high carb meal whereas the HP group had a high protein meal.  From this perspective, if we graphed the results as “change from time zero,” I think the reduction in glycemia from baseline to 6 months would be similar in both groups suggesting weight loss as bigger factor.  We’d still give some props to high protein because it lowered glucose just as much despite having less insulin.  High protein magic.

 

Note to self: gotta stop saying this was “high protein.”  1.35 g/kg is not “high,” seriously.  But still, High protein magic haha

 

Oh and one other thing, high protein usually induces greater weight loss:

Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity (Skov et al., 1999)

High protein vs high carbohydrate hypoenergetic diet for the treatment of obese hyperinsulinemic subjects (Baba et al., 1999) (not ad lib)

Comparison of high-fat and high-proein diets with a high-carbohydrate diet in insulin-resistant obese women (McAuley et al., 2005)

The effect of a low-fat, high-protein or high-carbohydrate ad libitum diiet on weight loss maintenance and metabolic risk factors (Claessens et al., 2009)

 

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