Biomarkers of Blood Glucose Regulation: Fasting Insulin

Optimal Takeaways

The hormone insulin is vital to life and without it, cells wouldn’t be able to take up glucose and other nutrients needed for metabolism. However, fasting insulin levels above optimal may reflect metabolic dysfunction, obesity, insulin resistance, or early type 2 diabetes mellitus. As blood glucose increases, insulin responds and can become pathologically elevated if cells are unable to respond to it. Very low levels or absence of insulin can be a sign of type 1 diabetes mellitus or hypopituitarism.

Standard Range: 2-19 uIU/mL (13.89-131.94 pmol/L)

The ODX Range: 2-5 uIU/mL (13.89-34.72 pmol/L)

Low fasting insulin is associated with type 1 diabetes and hypopituitarism (Pagana 2019). Research also suggests that low insulin may be associated with an increased risk of atrial fibrillation and risk of hypertension (Johnson 2014).

High fasting insulin is associated with insulin resistance, metabolic syndrome, type 2 diabetes, obesity, fasting hypoglycemia, insulinoma, Cushing syndrome, acromegaly, and fructose or galactose intolerance. Increased fasting insulin may precede hyperglycemia by several years. Drugs may also increase insulin including corticosteroids, levodopa, and oral contraceptives (Pagana 2019). Complications following MI may also be associated with elevated fasting insulin (Yang 2019).

Overview

Insulin is an anabolic pancreatic hormone released primarily in response to increased blood glucose levels, although certain amino acids and fatty acids can influence insulin secretion as well (Newsholme 2012). Insulin helps transport glucose into cells, resulting in a decrease in circulating glucose. In the heart and vascular endothelium, insulin promotes the production of nitric oxide and vasodilation and has an anti-inflammatory and antioxidant effect. In its anabolic role, insulin increases glycogenesis and reduces gluconeogenesis, stimulates lipogenesis and protein synthesis, and inhibits lipolysis and protein breakdown (Vargas 2021). Insulin also stimulates cholesterol and VLDL synthesis in the liver (Newsholme 2001).

Fasting insulin should be evaluated at the same time as fasting glucose. Insulin above the optimal range is associated with hypertension, type 2 diabetes, and obesity (Chen 2005). Fasting insulin above 5.48 uIU/mL for men and 7.51 uIU/mL for women is considered an independent risk factor for insulin resistance and predicting type 2 diabetes when a fixed sensitivity of 75% is applied (Ghasemi 2015). In one study investigating insulin resistance, subjects who were nonobese maintained fasting insulin of 5-7 uIU/mL while obese and diabetic individuals had a level of 16 and 15 uIU/mL, respectively (Katz 2000).

Higher levels of fasting insulin are also associated with complications following myocardial infarction. Subjects experiencing left ventricular dilation had the highest fasting insulin at 21.67 uIU/mL (150 pmol/L) versus the lowest level at 5.61 uIU/mL (39 pmol/L) (Yang 2019).

However, some research has observed an inverse association between fasting insulin and risk of atrial fibrillation. Researchers note that insulin has a vasodilatory effect and increases blood flow. Low insulin levels are also associated with increased risk of hypertension in those at increased genetic risk for diabetes (Johnson 2014).

Serum levels of insulin may not fully reflect pancreatic production as almost half of the insulin secreted is metabolized by the liver. Therefore, C-peptide should also be assessed when assessing insulin status (Novac 2019).

References

Chen, Hui et al. “Assessing the predictive accuracy of QUICKI as a surrogate index for insulin sensitivity using a calibration model.” Diabetes vol. 54,7 (2005): 1914-25. doi:10.2337/diabetes.54.7.1914

Ghasemi, Asghar et al. “Cut-off points of homeostasis model assessment of insulin resistance, beta-cell function, and fasting serum insulin to identify future type 2 diabetes: Tehran Lipid and Glucose Study.” Acta diabetologica vol. 52,5 (2015): 905-15. doi:10.1007/s00592-015-0730-3

Johnson, Linda S B et al. “Low fasting plasma insulin is associated atrial fibrillation in men from a cohort study--the Malmö preventive project.” BMC cardiovascular disorders vol. 14 107. 24 Aug. 2014, doi:10.1186/1471-2261-14-107

Katz, A et al. “Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.” The Journal of clinical endocrinology and metabolism vol. 85,7 (2000): 2402-10. doi:10.1210/jcem.85.7.6661

Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.

Newsholme, E A, and G Dimitriadis. “Integration of biochemical and physiologic effects of insulin on glucose metabolism.” Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association vol. 109 Suppl 2 (2001): S122-34. doi:10.1055/s-2001-18575

Newsholme, Philip, and Mauricio Krause. “Nutritional regulation of insulin secretion: implications for diabetes.” The Clinical biochemist. Reviews vol. 33,2 (2012): 35-47.

Novac, Carmen et al. “Short Update on C-Peptide and its Clinical Value.” Maedica vol. 14,1 (2019): 53-58. doi:10.26574/maedica.2019.14.1.53

Vargas, Elizabeth, et al. “Biochemistry, Insulin Metabolic Effects.” StatPearls, StatPearls Publishing, 1 February 2021.

Yang, Chen Die et al. “Insulin resistance and dysglycemia are associated with left ventricular remodeling after myocardial infarction in non-diabetic patients.” Cardiovascular diabetology vol. 18,1 100. 7 Aug. 2019, doi:10.1186/s12933-019-0904-3