Why Blood Sugar Can Be “Normal” in Patients with Insulin Resistance
Insulin resistance may be diagnosed with markers such as high levels of C-peptide and/or fasting insulin, despite normal blood sugar levels. This can occur due to several physiological and pathological conditions, with the main culprit being the rising levels of insulin effectively clearing out excess glucose, which is what it is designed to do.
In conditions like prediabetes, obesity, and metabolic syndrome, the body's cells become resistant to the effects of insulin. To compensate, the pancreas produces more insulin. Despite the high insulin levels, blood sugar levels can remain normal because the excess insulin manages to keep glucose levels in check.
Women with PCOS, for example, often have insulin resistance with marked increases in fasting insulin and C-peptide levels, yet the insulin resistance may go undiagnosed if only blood sugar levels are tested. This is because the body's compensatory mechanisms can maintain normal blood sugar levels despite the resistance.
Mechanisms Involved:
Compensatory Hyperinsulinemia: In response to insulin resistance, the pancreas increases insulin production to maintain normal glucose levels. C-peptide, released in equal amounts with insulin, also rises.
Regulation by Counter-regulatory Hormones: Hormones such as glucagon, epinephrine, and cortisol can counterbalance the effects of high insulin, preventing hypoglycemia and maintaining normal blood sugar levels.
Increased Insulin Clearance: In some cases, increased clearance of insulin from the blood can prevent hypoglycemia despite high production, thus maintaining normal glucose levels and normal insulin levels.
Understanding these mechanisms is crucial in diagnosing and managing conditions associated with insulin resistance and hyperinsulinemia, and underscores why testing for blood sugar levels alone does little to alert patients of metabolic dysfunction before serious damage to the pancreas has been sustained.
References
American Diabetes Association. (2021). Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2021.
Saenz, A., Fernandez-Esteban, I., Mataix, A., Ausejo, M., Roque, M., & Moher, D. (2005). Metformin monotherapy for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews, (3).
Dunaif, A., & Thomas, A. (2001). Current concepts in the polycystic ovary syndrome. Annual Review of Medicine, 52(1), 401-419.
