Why Use LP-IR vs. Other Methods of Testing Insulin
AKA: Clinical Utility of the NMR Lipoprotein Insulin Resistance Score (LP-IR)
Insulin resistance (IR) is characterized by decreased liver, muscle, and adipose tissue sensitivity to insulin action. In response to IR, pancreas β-cell insulin secretion increases to maintain relative glycemic stability. In this compensated state, blood glucose levels remain minimally elevated for many years. Over time, progressive β-cell dysfunction occurs, leading to a decline in plasma insulin levels. The combination of worsening IR and declining insulin levels is responsible for increasing hyperglycemia and the development of T2D.
Several laboratory tests are available to assess IR. The most accurate tests (hyperinsulinemic-euglycemic clamp, insulin suppression test, and frequently sampled intravenous glucose tolerance test) require intravenous infusions and multiple venous blood samples to determine insulin sensitivity or resistance. As a result, these tests are used almost exclusively in clinical research settings.
Alternatively, various fasting blood tests are available to evaluate IR.
Fasting insulin levels rise with worsening IR and can serve as a screening test for IR. Several limitations hamper reliance on fasting insulin to quantify individual IR. First, there is substantial day-to-day variability in fasting insulin levels. Many experts advise averaging two or three fasting insulin readings to overcome this challenge. Second, insulin tests demonstrate considerable laboratory variability and are still being standardized. Third, the association of fasting insulin levels with IR is complex and dependent on glucose levels. The homeostasis model assessment of insulin resistance (HOMA-IR), an equation that uses both fasting insulin and fasting glucose, minimizes this challenge and better estimates IR versus fasting insulin alone.
Another option is to measure alterations in lipid and lipoprotein metabolism that are observed many years before the onset of hyperglycemia or increased plasma insulin. Specifically, IR individuals have higher levels of the large very-low-density lipoprotein particles (VLDL-P) and small LDL particles (LDL-P), as well as lower levels of large High density lipoprotein particles (HDL-P). In addition, mean VLDL particle sizes are generally greater and mean LDL and HDL sizes are smaller in IR, or pre-diabetic patients. The NMR Lipoprotein Insulin Resistance LP-IR Score is a weighted combination of these lipoprotein variables that range from 0 (most insulin sensitive) to 100 (most insulin resistant). The LP-IR score shows a strong, graded relationship with other measures of IR, including HOMA-IR and glucose disposal rate measured by the gold-standard hyperinsulinemic-euglycemic clamp method.
Beyond identifying IR, the LP-IR score has been shown to predict future type 2 diabetes (T2D) in the Multi-Ethnic Study of Atherosclerosis (MESA), the Women’s Health Study (WHS), the Prevention of Renal and Vascular End State Disease (PREVEND) Study, as well as in subjects on rosuvastatin treatment in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. The association of LP-IR scores with incident T2D persisted after adjustments for measures of insulin, HDL-C, triglycerides, HOMA-IR and when simultaneously adjusted for glucose and HOMA-IR or glucose and the TG-to-HDL-C ratio. Additionally, LP-IR scores predicted future T2 D even in individuals at low risk for T2D based on their clinical profiles. Lifestyle interventions producing weight loss and increased insulin sensitivity have been shown to significantly lower LP-IR scores, improve insulin sensitivity, lower glucose, and are associated with preventing or delaying the onset of T2D.
