Diabetes: Perhaps It's More About Fat Than Glucose

While there is much said and written about the role of glucose in diabetes, the role of fat - that which we consume as well as the management of lipid within the body - has gained importance. The late Dr. McGarry's¹ eloquent treatment of this lipid dysregulation theory back in 2001 deserves a revisit:

Banting Lecture 2001: Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes, Diabetes, 2002

His essential argument:

"... an abnormal accumulation of fat in muscle and other tissues plays an important role in the etiology of insulin resistance and possibly also in the demise of the β-cell in type 2 diabetes."

Some combination of the above characterize type 2 diabetes:

1. Insulin resistance (impairment in glucose clearance, as well as inability to suppress glucose output from liver).
   
2. Insulin insufficiency (impaired function of pancreatic β-cell).

According to McGarry, these dysfunctions may not result from the diabetic state, but may in fact be instrumental in its development.

The Connection Between Fat, Muscle, And Diabetes

Fat within muscle (intramuscular), as opposed to fat in layers and pockets between muscles (extramuscular), "was found to correlate more tightly with insulin resistance than any of the other commonly measured indexes, such as BMI, waist-to-hip ratio, or total body fat."

It may matter more where fat is located than how much fat is present. McGarry notes that:

• One may be obese but if the fat is not intramuscular it's been shown to result in less insulin resistance.
  
• One may be lean but if there is substantial intramuscular fat it's been shown to result in more insulin resistance.

Which came first, the insulin resistance or the intramuscular fat? Likely it was the fat:

When plasma free fatty acid levels were elevated in healthy people, it resulted in "a very significant suppression of insulin-mediated glucose uptake (IMGU) into muscle," in just a few hours.

In a rat model, restricting food by 30% led to lower triglyceride levels in plasma, liver, pancreas, and muscle, which in turn led to improved insulin sensitivity and lower glucose levels. McGarry says:

"Diet-induced lowering of tissue TG levels improves insulin sensitivity and essentially reverses the diabetes in animal models of type 2 diabetes."

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¹ John Denis McGarry, PhD