Monday, January 03, 2011

Diabetes Is A Disorder Of Fat Metabolism

When it comes to diabetes, eating a high-fat diet is not a good idea. Dietary fat is linked to a condition known as insulin resistance. Insulin resistance manifests as:
  • Poor glucose clearance.
  • Inability to suppress glucose output from the liver.
  • High insulin levels.
Insulin resistance is a harbinger of type 2 diabetes. But ... Insulin resistance can be reversed. And reduction of dietary fat can help reverse it.

This is how Dr. Barnard's prescription for a low-fat diet works in diabetes reversal. As fat accumulates within cells, it interferes with the action of insulin. (One mechanism - fat impairs the movement of the glucose transporter GLUT4 to the cell membrane).

Many studies address this. Here's one I read recently:
Mitochondrial H2O2 Emission And Cellular Redox State Link Excess Fat Intake To Insulin Resistance In Both Rodents And Humans, Journal of Clinical Investigation, 2009

This study advances our understanding of just how fat impairs insulin action. And it homes in on the mitochondria, specifically, the mitochondria's ability to adjust the cell's redox state. ("Redox" is short for reduction-oxidation.)

Here's the abstract:
"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. Mitochondrial dysfunction and oxidative stress have been implicated in the disease process, but the underlying mechanisms are still unknown. 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, and decreases the redox-buffering capacity in the absence of any change in mitochondrial respiratory function. Furthermore, we show that attenuating mitochondrial H2O2 emission, either by treating rats with a mitochondrial-targeted antioxidant or by genetically engineering the overexpression of catalase in mitochondria of muscle in mice, completely preserves insulin sensitivity despite a high-fat diet. These findings place the etiology of insulin resistance in the context of mitochondrial bioenergetics by demonstrating that mitochondrial H2O2 emission serves as both a gauge of energy balance and a regulator of cellular redox environment, linking intracellular metabolic balance to the control of insulin sensitivity."
"... 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."

H2O2 is short for hydrogen peroxide ... the same peroxide that's used as an antiseptic. Peroxide is a strong oxidizing agent, that's how it works in killing microorganisms. Here we see that eating a high-fat diet brings about an oxidized state (because mitochondria emit more H2O2), which lowers insulin sensitivity. This is evident in the diagram, where mitochondrial H2O2 emission was higher in males 4 hours after a high-fat meal, and 5 days after a high-fat diet.
"The results of the present study suggest that the biological status of skeletal myofibers, including the degree of insulin sensitivity, is functionally linked to the redox state of the cell. With this mechanism, the reducing potential of the electron transport system provides a means for the cell to sense metabolic imbalance, while the 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."
If this is true, that the redox state is a controlling factor in insulin sensitivity ... then giving people diabetes drugs which cause cells to take up more glucose may actually be a problem, since that glucose undergoes oxidation once in the cell (via respiration):
"... pharmacological approaches designed to improve insulin-stimulated glucose uptake without a corresponding increase in metabolic demand may exacerbate the underlying problem, pushing the intracellular redox environment further toward an oxidized state."
Want to avoid diabetes? Eat a minimally-processed, low-fat, plant-based diet. Stay active.

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