Test Details
Methodology
Nuclear Magnetic Resonance (NMR)
Use
The Lipoprotein Insulin Resistance Index (LP-IR) is intended to be used as an aid in assessing a patient’s insulin resistance status.1 The LP-IR assay combines six weighted lipoprotein measurements into a single composite score ranging from 0 (most insulin sensitive) to 100 (most insulin resistant).1 LP-IR scores identify individuals at higher risk of developing type 2 diabetes independent of glucose and body mass index.2-4 A clinical cutoff of 68 or higher indicates elevated insulin resistance and increased diabetes risk.2
Limitations
The LP-IR score is inaccurate if patient is non-fasting.
This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.
Custom Additional Information
The American College of Endocrinology Task Force on the Insulin Resistance Syndrome agreed that there was clinical value in identifying individuals with insulin resistance.5 A number of methods are used to assess insulin sensitivity.6,7 The gold standard is the glucose disposal rate (GDR) measured during a hyperinsulinemic-euglycemic clamp, which assesses glucose utilization largely by skeletal muscle and adipose tissue and provides a precise measure of insulin sensitivity.8 However, the hyperinsulinemic-euglycemic clamp requires an intravenous infusion and is therefore relegated to research settings.
LP-IR is a simple, high-throughput means for assessing a patient's insulin resistance with scores ranging from 0 (most insulin sensitive) to 100 (most insulin resistant).1 LP-IR scores are calculated using the results of six lipoprotein parameters that are known to be altered in patients with insulin resistance, metabolic syndrome and type 2 diabetes: large VLDL, small LDL, large HDL particle numbers and VLDL, LDL and HDL diameter size.1 LP-IR scores are moderately correlated with HOMA-IR scores because they both measure insulin resistance. However, HOMA-IR is more a reflection of peripheral (muscle) with hepatic insulin resistance, while LP-IR is a balanced reflection of both peripheral (adipocyte) and hepatic insulin resistance.1 Also, the HOMA-IR index has a large intra-individual variability and is therefore more applicable to epidemiologic studies than for individual clinical care calculations.9,10
LP-IR predicts incident type 2 diabetes with robust performance across multiple populations.2-4 In the PREVEND study, the highest versus lowest quartile showed a hazard ratio of 10.18 for incident diabetes, which remained significant (HR 3.02) after adjustment for clinical risk factors.2 The score adds predictive value to the Framingham Offspring diabetes prediction algorithm.2 A clinical cutoff of 68 or higher indicates elevated insulin resistance and increased diabetes risk.2 LP-IR correlates moderately with HOMA-IR (r = 0.51) and demonstrates associations with subclinical atherosclerosis and incident cardiovascular disease comparable to HOMA-IR.2,11 In patients with NAFLD, LP-IR reflects hepatic fat content, particularly in non-diabetic individuals.12
In summary, LP-IR scores provide a practical alternative to direct insulin measurement for assessing insulin resistance in clinical practice.2,11 Additionally, LP-IR can support early detection and guide lifestyle or treatment strategies aimed at improving insulin sensitivity and reducing diabetes risk.13-21
Specimen Requirements
Specimen
Spun NMR LipoTube (preferred), serum from a plain red-top tube, plasma from a lavender-top (EDTA-no gel) or green-top (heparin-no gel) tube
Volume
2 mL
Minimum Volume
1 mL
Container
NMR LipoTube (black-and-yellow-top tube) is the preferred container; plain red-top tube, lavender-top (EDTA-no gel) tube or green-top (heparin-no gel) tube
Collection Instructions
Collect specimen in NMR LipoTube (black-and-yellow-top tube), which is the preferred container. Plain red-top, green-top (heparin-no gel) or lavender-top (EDTA-no gel) tubes are also acceptable. Serum or plasma drawn in gel-barrier collection tubes other than the NMR LipoTube should not be used. The LipoTube is the only acceptable gel-barrier tube.
Gently invert tube eight to 10 times to mix contents and allow specimen to clot for 30 minutes upright at room temperature prior to centrifugation (plasma tubes should not clot). Centrifuge specimen within two hours of collection at 1600 to 1800 xg for 10 to 15 minutes to separate serum/plasma from the red cells and to avoid red cell contamination during shipment. If the sample cannot be centrifuged immediately, the sample should be refrigerated (at 2°C to 8°C) and centrifuged within 24 hours of collection. Note: Centrifuging the specimen while still cold may negatively affect the migration of the gel to the serum/red cell interface and may increase the likelihood of specimens being contaminated with red cells during shipment.
All specimens should be centrifuged by the client prior to shipment to Labcorp to ensure sample integrity. Do not open NMR LipoTube (black-and-yellow-top). Immediately after centrifugation, pipette separated red-top serum or green-top/lavender-top plasma into a transport tube and label accordingly (serum, heparin plasma, EDTA plasma). Keep samples refrigerated until shipment to the laboratory, and ship with frozen cool packs.
Stability Requirements
Refrigerated up to six days
Storage Instructions
Refrigerate all acceptable tube types as soon as possible after centrifugation and within 24 hours of collection. Keep refrigerated prior to shipment, and ship on frozen cool packs. Do not store at room temperature. Do not freeze the sample. Sample is stable refrigerated for six days.
Patient Preparation
Patient should be fasting for eight hours.
Causes for Rejection
Unspun specimens; plasma/serum contaminated with red cells; citrated plasma (light blue-top tube); gross hemolysis; specimen received in inappropriate container; specimen stored at room temperature for more than a total preanalytical time of 24 hours; specimen more than six days old
Footnotes
1. Shalaurova I, Connelly MA, Garvey WT, Otvos JD. Lipoprotein insulin resistance index: a lipoprotein particle-derived measure of insulin resistance. Metab Syndr Relat Disord. 2014 Oct;12(8):422-429. PubMed 24959989
2. Flores-Guerrero JL, Connelly MA, Shalaurova I, et al. Lipoprotein insulin resistance index, a high-throughput measure of insulin resistance, is associated with incident type II diabetes mellitus in the Prevention of Renal and Vascular End-Stage Disease study. J Clin Lipidol. 2019 Jan-Feb;13(1):129-137.e1. PubMed 30591414
3. Dugani SB, Akinkuolie AO, Paynter N, Glynn RJ, Ridker PM, Mora S. Association of Lipoproteins, Insulin Resistance, and Rosuvastatin With Incident Type 2 Diabetes Mellitus : Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2016 May 1;1(2):136-145. PubMed 27347563
4. Harada PHN, Demler OV, Dugani SB, et al. Lipoprotein insulin resistance score and risk of incident diabetes during extended follow-up of 20 years: The Women's Health Study. J Clin Lipidol. 2017 Sep-Oct;11(5):1257-1267.e2. PubMed 28733174
5. Einhorn D, Reaven GM, Cobin RH, et al. American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract. 2003 May-Jun;9(3):237-252. PubMed 12924350
6. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008 Jan;294(1):E15-E26. PubMed 17957034
7. Borai A, Livingstone C, Ferns GA. The biochemical assessment of insulin resistance. Ann Clin Biochem 2007 Jul;44(Pt. 4):324-342. PubMed 17594780
8. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214-223. PubMed 382871
9. Cree-Green M, Cai N, Thurston JE, et al. Using simple clinical measures to predict insulin resistance or hyperglycemia in girls with polycystic ovarian syndrome. Pediatr Diabetes. 2018 Dec;19(8):1370-1378. PubMed 30246333
10. Poon AK, Meyer ML, Reaven G, et al. Short-Term Repeatability of Insulin Resistance Indexes in Older Adults: The Atherosclerosis Risk in Communities Study. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2175-2181. PubMed 29618016
11. Flores-Guerrero JL, Been RA, Shalaurova I, Connelly MA, van Dijk PR, Dullaart RPF. Triglyceride/HDL cholesterol ratio and lipoprotein insulin resistance Score: Associations with subclinical atherosclerosis and incident cardiovascular disease. Clin Chim Acta. 2024 Jan 15;553:117737. PubMed 38142802
12. Vittal A, Shapses M, Sharma B, et al. Lipoprotein Insulin Resistance Index Reflects Liver Fat Content in Patients With Nonalcoholic Fatty Liver Disease. Hepatol Commun. 2020 Dec 29;5(4):589-597. PubMed 33860117
13. Ellsworth DL, Costantino NS, Blackburn HL, Engler RJ, Kashani M, Vernalis MN. Lifestyle modification interventions differing in intensity and dietary stringency improve insulin resistance through changes in lipoprotein profiles. Obes Sci Pract. 2016 Sep;2(3):282-292. PubMed 27708845
14. Bhanpuri NH, Hallberg SJ, Williams PT, et al. Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study. Cardiovasc Diabetol. 2018 May 1;17(1):56. PubMed 29712560
15. Tuccinardi D, Farr OM, Upadhyay J, et al. Lorcaserin treatment decreases body weight and reduces cardiometabolic risk factors in obese adults: A six-month, randomized, placebo-controlled, double-blind clinical trial. Diabetes Obes Metab. 2019 Jun;21(6):1487-1492. PubMed 30724455
16. Zhang R, Lin B, Parikh M, et al. Lipoprotein insulin resistance score in nondiabetic patients with obesity after bariatric surgery. Surg Obes Relat Dis. 2020 Oct;16(10):1554-1560. PubMed 32636175
17. Huffman KM, Parker DC, Bhapkar M, et al. Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE a multicentre, phase 2, randomised controlled trial. EClinicalMedicine. 2022 Jan 3;43:101261. PubMed 35028547
18. Wilson JM, Lin Y, Luo MJ, et al. The dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide improves cardiovascular risk biomarkers in patients with type 2 diabetes: A post hoc analysis. Diabetes Obes Metab. 2022 Jan;24(1):148-153. PubMed 34542221
19. Angelidi AM, Kokkinos A, Sanoudou D, et al. Early metabolomic, lipid and lipoprotein changes in response to medical and surgical therapeutic approaches to obesity. Metabolism. 2023 Jan;138:155346. PubMed 36375643
20. Grammer EE, McGee JE, Bartlett AN, et al. Effects of Weight Loss and Weight Maintenance on Lipoprotein Insulin Resistance Scores in Adults with Overweight and Obesity. Metab Syndr Relat Disord. 2024 Oct;22(8):598-607. PubMed 39163283
21. Millar SR, Navarro P, Harrington JM, Perry IJ, Phillips CM. The Nutri-Score nutrition label: Associations between the underlying nutritional profile of foods and lipoprotein particle subclass profiles in adults. Atherosclerosis. 2024 Aug;395:117559. PubMed 38692976