Lipid accumulation product is a useful index for detecting insulin resistance
Insulin resistance (IR) contributes to a host of chronic disorders long before blood glucose crosses the line to type 2 diabetes. IR is a key factor in a wide range of disorders including cardiovascular disease, PCOS, fatty liver, and many more. A study just published in the European Journal of Clinical Nutrition offers evidence that lipid accumulation product (LAP, a combination of waist circumference and triglyceride level) can identify the presence of insulin resistance prior to diabetes. The authors state:
"Lipid accumulation product (LAP) is an index, which combines waist circumference (WC) and triglyceride (TG) reflecting lipid accumulation. The aims of the study were to explore the relationship between LAP and insulin resistance (IR) and to assess whether LAP was superior to WC and body mass index (BMI) in identifying IR."
They assessed 2524 non-diabetic subjects for blood pressure, anthropometric measurements, glucose levels, insulin levels and a fasting lipids; and calculated BMI, the homeostasis model assessment of insulin resistance (HOMA-IR) and LAP. The data showed that LAP is a particularly strong predictor of insulin resistance:
"In both sexes, BP, BMI, total cholesterol (TC), non high-density lipoprotein cholesterol (non-HDL-C), HOMA-IR, fasting and postprandial glucose levels increased across LAP quartiles, while HDL cholesterol (HDL-C) levels decreased across LAP quartiles. Pearson’s correlation analysis demonstrated that HOMA-IR was correlated with LAP, BMI, WC, TG, HDL-C and non-HDL-C in both sexes. Multivariate analysis demonstrated that LAP had a greater impact on HOMA-IR than BMI and WC."
LAP for men = (waist circumference [cm] – 65) x triglycerides [mmol/l] for men, and (waist circumference [cm] – 58) x triglycerides [mmol/l] for women. The authors conclude:
"LAP is closely associated with HOMA-IR and is a powerful index that outperforms BMI and WC in identifying IR [insulin resistance] in non-diabetic individuals."
Similar results were obtained in a clinical study published earlier in the European Journal of Endocrinology in which the authors examined the ability of LAP to detect metabolic syndrome (MS):
"Early detection of high-risk individuals for MS using accurate measures of insulin resistance (IR) could improve detection and prevention of CVD and diabetes. The aim of this study was to explore the ability of lipid accumulation product (LAP), compared with traditional measures of IR, to identify MS."
They assessed metabolic syndrome in 768 adults using the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) and International Diabetes Federation (IDF) criteria, and calculated insulin resistance with the homeostasis model assessment of IR and LAP in the usual way. As in the study above...
"LAP showed the highest diagnostic accuracy for MS-NCEP/ATP III and MS-IDF. Among males and females, different LAP cut-off values exhibited high sensitivity (78–85%) and specificity (78–85%)."
Again LAP, an inexpensive, non-invasive and easy method of investigation, demonstrated great value in detecting insulin resistance (and metabolic syndrome). The authors conclude:
"In non-diabetic adults LAP has a strong and reliable diagnostic accuracy for MS-IDF and, especially, MS-NCEP/ATP III among females and, in particular, among males from Spain."
The association of insulin resistance and cardiovascular risk is highlighted in a research article published in BMC Cardiovascular Disorders. The authors compared LAP to BMI in relation to eleven cardiovascular risk factors:
"The WC (estimated population minimum 65 cm for men and 58 cm for women) and TG concentration from the third National Health and Nutrition Examination Survey (N = 9,180, statistically weighted to represent 100.05 million US adults) were used to compute a "lipid accumulation product" [LAP = (WC-65) × TG for men and (WC-58) × TG for women] and to describe the population distribution of LAP. LAP and BMI were compared as categorical variables and as log-transformed continuous variables for their ability to identify adverse levels of 11 cardiovascular risk factors."
LAP outperformed BMI in almost every respect:
"When 23.54 million with ordinal LAP quartile > BMI quartile were compared with 25.36 million with ordinal BMI quartile > LAP quartile (regression models adjusted for race-ethnicity and sex) the former had more adverse risk levels than the latter for seven lipid variables, uric acid concentration, heart rate, systolic and diastolic blood pressure. Further adjustment for age did not materially alter these comparisons except for blood pressures. As continuous variables, LAP provided a consistently more adverse beta coefficient (slope) than BMI for nine cardiovascular risk variables, but not for blood pressures."
Since insulin resistance is fundamental to PCOS (polycystic ovary syndrome) we would expect to see an association with LAP. The authors of a paper published in The Journal of Clinical Endocrinology & Metabolism looked into it:
"Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances. Lipid accumulation product (LAP) is an emerging cardiovascular risk factor. We aimed to investigate the association of LAP with impaired glucose tolerance (IGT) in PCOS and control women."
They The calculated LAP in 392 PCOS and 140 control women (matched by BMI) within the same age range, collected metabolic, endocrine, and anthropometric measurements and performed oral glucose tolerance tests. The association with PCOS was clear:
"PCOS women had significantly higher LAP levels than control women in age-adjusted analyses. In PCOS and control women, age, BMI, blood pressure, fasting and stimulated glucose, fasting and stimulated insulin, and free testosterone progressively increased, whereas SHBG decreased across LAP quartiles. In PCOS and control women, receiver operating characteristic curve analysis revealed that the best cutoff value for LAP to define the presence of IGT was 44.1 and 41.8, respectively."
LAP clearly outperformed BMI and waist circumference:
"Odds ratios for IGT for PCOS women in the highest LAP, BMI, and waist-to-hip ratio quartile were 41.81 , 10.24 , and 18.45, respectively, when compared with PCOS women in the lowest LAP, BMI, and WHR quartile, respectively."
The authors note:
"Polycystic ovary syndrome (PCOS) is the most common female endocrine disorders with a prevalence of 5–10% in women of reproductive age. PCOS is characterized by hyperandrogenism, menstrual irregularity, and polycystic ovaries. Insulin resistance (IR) and central obesity seem to play a key role in the development of PCOS. The tendency to accumulate body fat in intraabdominal fat stores, which is frequently observed in PCOS, is linked to an increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease...LAP is an easily obtainable and cheap marker associated with IGT in PCOS and control women."
Insulin resistance, of course, is the driving force behind fat accumulation in the liver. The authors of research published in BMC Gastroenterology tested whether LAP could be used as an indication of liver steatosis (fatty liver):
"Liver steatosis is often found in association with common cardiometabolic disorders, conditions that may all occur in a shared context of abdominal obesity and dyslipidemia. An algorithm for identifying liver steatosis is the fatty liver index (FLI)...Because FLI and LAP share two components, namely waist circumference and fasting triglycerides, we evaluated the ability of LAP to identify liver steatosis in the same study population."
They examined 588 individuals aged 21 to 79 years with ultrasonography to classify liver steatosis as none, intermediate or severe. Among the 44% who had liver steatosis they evaluated the ability of log-transformed LAP (lnLAP) to identify it. LAP turned out to be useful in this context too:
"An ordinal proportional-odds model consisting of lnLAP and sex offered a reasonably accurate identification of liver steatosis. The odds of more severe vs. less severe steatosis increased for increasing values of lnLAP..."
Fatty liver is a growing public health issue. The authors' conclusion supports the utility of LAP as a practical screening measure:
"In a study sample of adults from Northern Italy, the simple calculation of LAP was a reasonably accurate approach to recognizing individuals with ultrasonographic liver steatosis. LAP may help primary care physicians to select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies."
Detecting and treating insulin resistance is relevant for a wide range of disorders in including cancers (see past and forthcoming posts), cardiovascular disease, neurodegenerative disorders and many more. I hope to see LAP much more widely used by clinicians of all kinds.