Sunday, October 13, 2013

High Dietary Fat Contributes To Insulin Resistance And Diabetes

Tom Hanks recently admitted he's been diagnosed with type 2 diabetes. Hanks is 57 years old:

There has been much talk in diabetes circles about Hanks' diagnosis. Subsequently, there has been much talk about the role of sugar and carbohydrate in diabetes development. Unfortunately, there has not been much talk about the role of dietary fat in diabetes development.

The topic of dietary fat and its role in diabetes' development comes up often here. Here's one post that delved into how a high-fat diet contributes to insulin resistance (and subsequently to diabetes, since a body that is resistant to insulin leads to a blood stream with higher levels of glucose that can't enter cells). The study that post referred to was:

Mitochondrial H2O2 Emission And Cellular Redox State Link Excess Fat Intake To Insulin Resistance In Both Rodents And Humans, Journal of Clinical Investigation, 2009

That study highlighted the role of mitochondria. Here are a few excerpts:
"High dietary fat intake leads to insulin resistance in skeletal muscle, and this represents a major risk factor for type 2 diabetes and cardiovascular disease."

"Here we show that in skeletal muscle of both rodents and humans, a diet high in fat increases the H2O2-emitting potential of mitochondria, shifts the cellular redox environment to a more oxidized state."

"An oversupply of lipids overwhelms the β-oxidation and TCA cycle pathways, generating metabolic intermediates that otherwise are not present." This surplus of intermediates causes "an exponential increase in the rate of H2O2 emission from mitochondria."
So, a high-fat diet overwhelms pathways in mitochondria which results in production of more hydrogen peroxide (H2O2). And that "emission of H2O2 from the mitochondria provides a means of initiating an appropriate counterbalance response — shifting the redox state and decreasing insulin sensitivity in an attempt to restore metabolic balance." This response to a high-fat diet is a natural adaptation.

Here's a more recent review. It describes the same mechanism:

High-Fat Load: Mechanism(s) Of Insulin Resistance In Skeletal Muscle, International Journal of Obesity Supplements, December 2012
"Skeletal muscle from sedentary obese patients is characterized by depressed electron transport activity, reduced expression of genes required for oxidative metabolism, altered mitochondrial morphology and lower overall mitochondrial content. These findings imply that obesity, or more likely the metabolic imbalance that causes obesity, leads to a progressive decline in mitochondrial function, eventually culminating in mitochondrial dissolution or mitoptosis.

A decrease in the sensitivity of skeletal muscle to insulin represents one of the earliest maladies associated with high dietary fat intake and weight gain. Considerable evidence has accumulated to suggest that the cytosolic ectopic accumulation of fatty acid metabolites, including diacylglycerol and ceramides, underlies the development of insulin resistance in skeletal muscle. However, an alternative mechanism has recently been evolving, which places the etiology of insulin resistance in the context of cellular/mitochondrial bioenergetics and redox systems biology.

Overnutrition, particularly from high-fat diets, generates fuel overload within the mitochondria, resulting in the accumulation of partially oxidized acylcarnitines, increased mitochondrial hydrogen peroxide (H2O2) emission and a shift to a more oxidized intracellular redox environment. Blocking H2O2 emission prevents the shift in redox environment and preserves insulin sensitivity, providing evidence that the mitochondrial respiratory system is able to sense and respond to cellular metabolic imbalance.

Mitochondrial H2O2 emission is a major regulator of protein redox state, as well as the overall cellular redox environment, raising the intriguing possibility that elevated H2O2 emission from nutrient overload may represent the underlying basis for the development of insulin resistance due to disruption of normal redox control mechanisms regulating protein function, including the insulin signaling and glucose transport processes."
In sum, a high-fat diet contributes to the development of insulin resistance and type 2 diabetes. It does so by a natural response of mitochondria to overnutrition.


Bix said...

Interesting ... at one point Hanks referred to his doctor as "he" and later "her".

I also thought it was odd that Letterman congratulated him, on his diabetes? "Good for you and congratulations."

The timing and phrasing and audience response to all this seemed off. Like it was staged or rehearsed and not delivered properly.

Also, they both kept saying that there was a "special diet" for diabetes. There isn't. Not unless you are taking a medication. The best diet for someone with type 2 diabetes is the same as the best diet for any healthy adult.

Bix said...

One more thing ... Letterman said "I suffer from 'the high blood sugar.'" That's the term everyone in Philly uses! Or "the sugars." Maybe it's left over from the time diabetes was detected by tasting urine.

It doesn't help dispel the notion that sugar causes or exacerbates diabetes. Sugar doesn't cause diabetes. People think it's simple ... sugar in, sugar out. And all the while they plate up the burgers and fries, the chicken nuggets, the popcorn shrimp, bacon & egg sandwiches, hot dogs, Philly cheese steaks, hoagies....... As long as it's not sugar!

Angela and Melinda said...

My Italian, Brooklyn-born mom-in-law used to say of a friend with diabetes, "Oh yeah, she's got shuggah...."

Anonymous said...

Great information re fat and diabetes - everyone has been programmed to think "sugar". I am filing this in my health security board.

Gary Clyne