Surprising Interconnectedness – Insulin Resistance and Thyroid Resistance

 

Both insulin resistance (IR) and hypothyroid dynamics are quite common in our practices. When you think about the interconnectedness between the two, you might rightly point to their synergistic negative impact on metabolic health as a primary area of action.

But what about receptor resistance as another dynamic that ties the two together?

We know that with insulin resistance, cells have been so overloaded with glucose that they become unable (or unwilling?) to be signaled by insulin to continue to take up large amounts of sugar. In addition, the cell membrane, after being bombarded by extra glucose in the extracellular space, experiences inflammation and damage. 

A damaged cell membrane is more likely to impede the effects of all hormones when they try to function at the cell membrane or gain entry to the cell for the same.

Here is an interesting dynamic you may have not considered previously: what do you think happens to thyroid hormone levels in blood when we improve insulin sensitivity, restoring optimal glucose management?  Surprisingly, good research demonstrates that perhaps unexpected changes to T3 levels (the metabolically active thyroid hormone) can occur.

A small study in humans along with an accompanying in vitro component showed that metformin, while improving insulin resistance, actually caused a drop in T3 hormone levels without affecting TSH or T4. Perhaps a counterintuitive correlation, as one might expect the opposite: improve glucose markers and thyroid function markers will improve also. The authors state: “Type 2 diabetes is characterized, beyond the insulin resistance, by polyhormonal resistance… Metformin seems to improve T3 sensitivity in the cardiovascular system in euthyroid, type 2 diabetic patients, the mechanism of which may be supracellular.” 

This conclusion is calling our attention to the fact that an individual with insulin resistance is likely to have polyhormonal resistance – including to thyroid hormone. When we have resistance, the body will often increase hormone synthesis as an adaptive mechanism to try to force the desired cellular effects.  Resolve the excessive inflammation, reduce oxidative damage to the cell membrane and the intracellular environment, and the body will allow more T3 intracellular activity, thus reducing the need for excessive synthesis (and lowering serum concentration).

Here is a look at the other direction: what can thyroid hormone levels in the blood tell us about insulin resistance? It turns out that levels of Free T3 (fT3) in the upper quartile can be predictive of future insulin resistance (noting that these individuals are also likely to present with hypothyroid symptoms). The authors conclude: “In multiadjusted analyses, fT3 was reciprocally related to insulin sensitivity… In multiple regression models adjusting for sex, age, BMI, and baseline value of insulin sensitivity, higher baseline fT3 levels were significant predictors of decreases in insulin sensitivity. Moreover, baseline fT3 predicted follow-up increases in glycemia independently of sex, age, BMI, insulin sensitivity, β-cell glucose sensitivity, and baseline glycemia.”

I invite you to watch this short video to explore this interconnectedness further. Don’t overlook thyroid hormone resistance and be prepared if T3 levels drop after you helped your patient restore insulin sensitivity. Proactively look for insulin resistance dynamics if free T3 is trending at the upper limits of the reference range, especially if there is symptomatic evidence that hypothyroid function is present or worsening. It’s possible that oxidative damage is keeping T3 from having optimal cellular effects – both at the cell membrane and in the intracellular environment.

 A fascinating concept!  

For a deeper look at Functional Medicine approaches to restore proper glucose handling, you may want to revisit this practitioner education event titled Practitioner Missteps in Resolving Metabolic Dysfunction. Filled with pearls for your clinical toolbox!