Fasting insulin reliably shows insulin resistance

Insulin resistance requires elevated levels of insulin to promote cellular uptake of glucose from the bloodstream. Higher levels of insulin do harm throughout the brain and body long before blood glucose levels go up (either fasting or during a glucose tolerance test) as the compensatory system fails. How should clinicians detect early stages of insulin resistance that occur before elevations in blood glucose or HgbA1c? Research published in the International Journal of Obesity offers evidence that fasting plasma insulin reliable detects insulin resistance, at least in cases of obesity. The authors state:

"Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables."

Using reference ranges for hepatic and peripheral insulin sensitivity calculated from healthy non-obese men, they examined data for data from both non-obese and obese men who using two-step EHCs using (insulin infusion dose 20 and 60 mU m⁻² min⁻¹, respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. They succeeded in showing that the obese subjects with insulin resistance could be discriminated from those with normal insulin sensitivity by the fasting insulin level:

"Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (R_d) were 46.5% and 37.3 μmol kg⁻¹ min⁻¹, respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had R_d within the reference range. Obese men with R_d <37.3 μmol kg⁻¹ min⁻¹ did not differ from insulin-sensitive obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol) and homeostasis model assessment of insulin resistance (HOMA-IR) (4.5±2.2 vs 2.7±1.4). Insulin-resistant obese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l⁻¹."

Body mass index (BMI), body composition, fasting glucose and cholesterol were not good predictors of insulin resistance but the fasting plasma insulin level was. [I'm surprised that they didn't include triglycerides levels which are particularly sensitive to insulin levels.] Note: fasting insulin >74 pmol l⁻¹ = >10.7 μU/ml.There are a number of benign and wholesome agents along with lifestyle adjustments that can be employed to ameliorate insulin resistance. This study shows that 10.7 μU/ml can be used as a clinical decision level for more aggressive targeting of IR. Moreover, it stands to reason that this biomarker can be used for slim but 'metabolically obese' patients. The authors conclude:

"Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l⁻¹ with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings."