@Gardiner 2666 wrote:

If a person is pre-diabetic or diabetic with elevated insulin levels, I’m not clear on whether the elevated insulin leads to inflammation or if the reverse is actually the case (i.e. inflammation leads to elevated insulin). If the insulin leads to inflammation, would using a drug such as Metformin decrease general levels of inflammation and cytokines in the body?

If so, might Metformin be beneficial for conditions such as asthma, IBS, allergies etc?

Insulin is Pro-Inflammatory.
Inflammatory cytokine signaling can lead to insulin resistance.
It is a positive feedback loop with several intermediary signaling systems.

Diabetes Type 2 has multiple features including:
1. An activate sympathetic nervous system.
2. Elevated inflammatory cytokines
3. Suboptimal Thyroid signaling
4. Nutritional deficiencies.
5. etc. etc.

Although Metformin is useful in reducing insulin resistance in the liver, which leads to reduced blood sugar – which can then reduce insulin production, it can also lead to problems.

Metformin, for example, impairs sugar absorption in the intestines. The non-absorbed sugars can end up causing diarrhea, electrolyte abnormalities, impaired nutrient absorption, and changes in gut bacterial population – which if pathogenic can lead to activation of the immune system and inflammation.

Metformin does not address systemic insulin resistance. It instead causes an imbalance between the brain’s need for sugar and the liver’s production of sugar (gluconeogenesis) – where liver production is lower than the brain’s needs. This may lead distress within the nervous system, an increase in stress signaling and other down-stream problems including inflammatory changes. Metformin, when use in monotherapy, may increase the risk for Alzheimer’s disease, for example, perhaps as a result of these changes in metabolism and intercellular signaling. This is why combining Metformin with other teratments that can reduce systemic insulin resistance is important.

Since a possible outcome is an increase in inflammatory signaling (which will vary depending on the person – some have less, some have more, some have none, etc.), Metformin if this outcome occurs, would not be a good choice in a person who already has inflammatory changes – such as allergies, asthma, IBS, etc.

Note that this scenario may not often occur, but it also can. And one has to be on the lookout for its presence and ramifications.

It is thus important to consider not just the initial effects of an intervention, such as Metformin, but also the downstream cascade or web of changes in signaling and metabolism that determine the final outcome.