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Lower brain glucose levels found in people with obesity, type 2 diabetes

https://www.sciencedaily.com/releas...71019100957.htm

Quote:

Glucose levels are reduced in the brains of individuals with obesity and type 2 diabetes compared to lean individuals, according to a new Yale study. The finding might explain disordered eating behavior -- and even a higher risk of Alzheimer's disease -- among obese and diabetic individuals, the researchers said.

The study was published Oct. 19 in JCI Insight.

Both obesity and type 2 diabetes are linked to decreased metabolism in the brain. This hypometabolism is also associated with Alzheimer's disease, but researchers have not pinpointed why. To examine the mechanism, the Yale team studied brain glucose levels in three different groups of adults: individuals who are lean and healthy, and those with either obesity or poorly controlled type 2 diabetes.

After fasting overnight, the study participants received intravenous infusions of glucose for two hours. During the infusions, the researchers used a brain scanning technique -- magnetic resonance spectroscopy -- to measure levels of glucose in the brain.

While blood glucose levels among the participants were similar, the researchers detected significant differences in brain glucose. Among the obese and diabetic participants, "we found decreased or blunted entry of glucose into the brain," said first author and assistant professor of medicine Janice Hwang, M.D.

That blunting could be one mechanism that undermines the ability of the brain to sense glucose, she noted.

The researchers also rated participants' hunger, satisfaction, and fullness before and after the infusions. "The lean people who had more glucose entry into the brain also felt more full, even though they hadn't eaten overnight," she said.

Hwang explained further: "Glucose is the most primitive signal to the brain that you've eaten. Could it be that obese individuals are not getting sugar into the brain, and not sensing it; thus the feedback loop to stop eating could also be blunted?"

The study points to the importance of sugar transport from the blood into the brain as both a target for further research and possible pharmacological intervention in people with obesity and type 2 diabetes, the researchers noted.

Two solutions. Thirty bananas a day/rice diet/juice fasting. Eat nothing but sugars, otherwise you're wasting calories on food that won't raise your brain glucose levels. Just kidding. Sort of. Or side step the issue, a low carb or ketogenic diet isn't going to raise your blood glucose much, so satiety must work a little differently.

Thinking back, trying to remember Dr. Fung's comments on insulin resistance, and the different kinds, liver specifically and wasn't there also brain insulin resistance? Meaning, glucose not being taken up by the brain tissue because of insulin resistance? Wouldn't that explain it? Given that these people were either obese or poorly controlled diabetics, IR is more or less assumed.

I would also wonder about inflammation, which could also be assumed in those two groups, being a factor.

There are studies where insulin administered to a mouse's brain is effective against obesity. For a while, "insulin is not obesogenic types" were very fond of this as evidence for their case. It's hard to say how bad an argument I think that is nicely. Systemic insulin has the whole body fighting over whatever glucose there is in the blood. Locally elevated insulin--you get those localized fat pads people can get when they inject insulin in the same spot for years on end. In the brain--you get a small area taking up a little more glucose. Massive insulin will starve the whole body of glucose. Local elevation of glucose just has local cells taking in more nutrients. It's the difference between starving the brain of nutrients, and increasing nutrition locally. So-called obesity researchers who write popular blogs sometimes skip the distinction. This is stupid. See? Hard to say it nicely. :lol:

Here's the full paper we're discussing here: https://insight.jci.org/articles/view/95913

On this forum, from experience, we know carbs cause obesity, i.e. carbohydrates stimulate insulin stimulate excess fat accumulation. We know this not from a hypothesis, but from direct observation and experiments.

In the paper we're discussing here, it says in the introduction "Glucose is the primary energy source for the brain, which consumes more glucose (~60% of total glucose-derived energy) than any other organ in the body (3).", but this directly opposes the facts we know about carbs and obesity and the effect of low-carb on all of it. Facts trump hypothesis. Facts win. Glucose is not the primary energy source for the brain.

In this paper, check Table 2, it's much more pertinent than anything else. See ghrelin and leptin. From personal experience, I promise that ghrelin is a very, very, very potent stimulator of hunger. Leptin opposes ghrelin, it shuts down hunger, causes satiety, and absolutely effective for leptin deficiency (doh!), but completely ineffective for leptin resistance (doh?). And check insulin too, it's ridiculously ridiculous high for T2DM subjects.

Now check Figure 3. It reminds me of the graphs from the 7 Country Study by Ancel Keys. Can't see any tendency at a glance, must be drawn on top based on statistics. Red flag. Too few subjects. Red flag. I could imagine they didn't have enough money for hundreds of subjects, but it was financed by Pfizer and Regeneron where there's literally tons of money for that kind of crap. Call me cynical.

I was about to write something smart, but the experiment and results are just too complicated for me, they don't fit what I know. I prefer simple to explain it all, like money from big pharma.

Ok, forget everything I wrote above. This is the only thing I need to know:

Quote:

Experimental protocol. On the evening prior to MRS scanning, individuals with T2DM were admitted to the Yale University Hospital Research Unit and placed on a standard hospital protocol insulin drip overnight to normalize plasma glucose levels. T2DM participants received an average of 8.4 ± 2 units of insulin overnight, and mean plasma glucose levels were 126 ± 6 mg/dl overnight. The insulin infusion was maintained until the start of the scanning. At the start of scanning, the insulin infusion rate was fixed at 1 unit/hour for the duration of the study in order to minimize risk of ketosis. Neither lean nor obese participants received any exogenous insulin.

I dunno... glucose seems to be a primary fuel unless somebody's on a very strict ketogenic diet.

Quote:

Glucose uptake by the brain on chronic high-protein weight-loss diets with either moderate or low amounts of carbohydrate
Gerald E. Lobley (a1), Alexandra M. Johnstone (a1), Claire Fyfe (a1), Graham W. Horgan (a2) ...
https://doi.org/10.1017/S0007114513002900Published online: 05 September 2013
Abstract
Previous work has shown that hunger and food intake are lower in individuals on high-protein (HP) diets when combined with low carbohydrate (LC) intakes rather than with moderate carbohydrate (MC) intakes and where a more ketogenic state occurs. The aim of the present study was to investigate whether the difference between HPLC and HPMC diets was associated with changes in glucose and ketone body metabolism, particularly within key areas of the brain involved in appetite control. A total of twelve men, mean BMI 34·9 kg/m2, took part in a randomised cross-over trial, with two 4-week periods when isoenergetic fixed-intake diets (8·3 MJ/d) were given, with 30 % of the energy being given as protein and either (1) a very LC (22 g/d; HPLC) or (2) a MC (182 g/d; HPMC) intake. An 18fluoro-deoxyglucose positron emission tomography scan of the brain was conducted at the end of each dietary intervention period, following an overnight fast (n 4) or 4 h after consumption of a test meal (n 8). On the next day, whole-body ketone and glucose metabolism was quantified using [1,2,3,4-13C]acetoacetate, [2,4-13C]3-hydroxybutyrate and [6,6-2H2]glucose. The composite hunger score was 14 % lower (P= 0·013) for the HPLC dietary intervention than for the HPMC diet. Whole-body ketone flux was approximately 4-fold greater for the HPLC dietary intervention than for the HPMC diet (P< 0·001). The 9-fold difference in carbohydrate intakes between the HPLC and HPMC dietary interventions led to a 5 % lower supply of glucose to the brain. Despite this, the uptake of glucose by the fifty-four regions of the brain analysed remained similar for the two dietary interventions. In conclusion, differences in the composite hunger score observed for the two dietary interventions are not associated with the use of alternative fuels by the brain.

https://www.cambridge.org/core/jour...05D0A9F1C172A6A

22 grams of carbohydrate a day, 30 percent of calories as protein, the rest fat--only a 5 percent lower supply of glucose to the brain. Four times the ketone flux of people on the higher carb diet--but that's four times an extremely low contribution to energy that ketones provide on a high carb diet.

Never mind that it's 12 subjects 4 weeks. Instead, consider only this undeniable conclusion.

Dietary carbs is not necessary to feed the brain all the glucose it apparently needs.

Gut microbiome alterations in Alzheimer’s disease
https://www.nature.com/articles/s41598-017-13601-y

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Alterations in the composition of this complex ecosystem have been associated with the development of a variety of gastrointestinal and metabolic diseases including inflammatory bowel disease (IBD), obesity, diabetes, and insulin resistance10. More recently, the influence of gut microbiota on central nervous system function – often referred to as the gut-brain axis – has received significant attention, and alterations in the gut microbiome have been associated with neurological conditions including autism spectrum disorder, multiple sclerosis, and Parkinson’s disease11,12,13.
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