Insulin resistance (IR) is the most common metabolic alteration related to obesity and represents an important link between obesity and other metabolic and cardiovascular complications related to oxidative stress and inflammation [
In many developing countries, the nutritional transition and particularly the “westernization” of life-styles have caused a significant rise in obesity and comorbidities associated with IR, including T2D and ischemic cardiovascular disease [
Although hyperinsulinemic–euglycemic clamp is the gold standard method for assessment of insulin sensitivity, it is expensive and invasive. Alternative methods based on surrogate markers derived from fasting insulin and glucose, such as the homeostasis model assessment-insulin resistance (HOMA-IR), have been validated and proposed [
This research aims to determine the optimal cutoff value of HOMA-IR for MetS diagnosis in healthy adolescents, to examine whether IR assessed by using this cutoff value is related to anthropometric, metabolic, and cardiovascular risk profile, and to evaluate the association of IR with genetic, biological, and environmental factors.
We studied 667 16- to 17-year-old adolescents living in urban Santiago, from low to middle SES neighborhoods, who were part of an iron deficiency anemia preventive trial and follow-up study beginning in infancy [
A research physician used standardized procedures to measure the adolescent’s height (cm) to the nearest 0.1 cm, using a Holtain stadiometer and weight (kg) to the nearest 0.1 kg using a Seca scale. Body mass index (BMI) (Kg/m2) was calculated and obesity status was calculated according to WHO references. Measurements were taken twice, with a third measurement, if the difference between the first two exceeded 0.3 Kg for weight and 0.5 cm for height. Waist circumference was measured with nonelastic flexible tape at the high point of the iliac crest around the abdomen and recorded to 0.1 cm. Measurements were taken twice, with a third measurement, if the difference between the first two exceeded 1.0 cms. Dual-energy X-ray absorptiometry (DEXA) was used to measure fat mass (%) and fat-free mass (%). Fat-Free Mass Index (FFMI) was estimated according to Wells and Fewtrell [
After 15 minutes at rest and prior to the physical examination, systolic and diastolic blood pressures (SBP and DBP) were measured, three times on the nondominant arm using a standard mercury sphygmomanometer; the average value was used for analyses. Fasting serum total glucose (Gli), cholesterol, triglycerides (TG), high-density lipoprotein (HDL), insulin, adiponectin, and high sensitivity C-reactive protein (hs-CRP) levels were performed after a 12-hour overnight fast. Radioimmunoassay (RIA DCP Diagnostic Products Corporation, LA, USA) was used for insulin and adiponectin determinations. High sensitivity C-reactive protein (hs-CRP) was measured with a sensitive latex-based immunoassay (latex-enhanced nephelometry method). Glucose was measured with enzymatic-colorimetric test (QCA S.A. Amposta, Spain) and cholesterol profile (Col-HDL and TG mg/dL) was determined by analytical methodology dry (Vitros, Johnson & Johnson, Clinical Diagnostics Inc.). Values of hs-CRP ≥ 1.1 mg/L (75th percentile in our sample) were considered low-grade systemic inflammation and adiponectin ≤ 7.9
Food intake and physical activity (PA) habits were evaluated using validated and standardized self-report questionnaires, scored from 0 to 10, with higher scores denoting more nutritious food intake or more physical activity [
A standardized questionnaire of FHDM, including first- and second-degree relatives, was answered by the participant’s primary caregiver (father, mother, or grandparents). Reporting FHDM in at least one parent or grandparent was required to fit our definition of positive FHDM.
Data were analyzed using Stata for Windows version 12.0 (Lakeway Drive College Station, TX, US). A
Our sample was made up of 52.2% male and 47.8% female adolescents who were on average 16.8 (SD 0.3) years old. The prevalence of obesity was 16.2% whereas 9.4% of participants met criteria for MetS.
A HOMA-IR value of 2.6 showed the best sensitivity (59%) and specificity (87%) for diagnosing MetS (AUC: 0.821; correctly classified: 87%; LR+: 4.5) (Figure
ROC curve to determine the optimal cutoff value of HOMA-IR for MetS diagnosis in healthy adolescents.
As shown in Table
Background characteristics of adolescents in the sample by insulin sensitivity (
HOMA-IR < 2.6 |
HOMA-IR ≥ 2.6 |
Total sample |
| |
---|---|---|---|---|
Age (years) | 16.8 ± 0.3a | 16.9 ± 0.2 | 16.8 ± 0.3 | n.s. |
Anthropometrics | ||||
BMI ( |
0.48 ± 1.1 | 1.53 ± 1.2 | 0.65 ± 1.2 | <0.001 |
WC (cm) | 79.4 ± 9.9 | 90.4 ± 14.3 | 81.2 ± 11.4 | <0.001 |
Lean Mass (%) | 68.7 ± 11.4 | 62.0 ± 9.4 | 67.6 ± 11.1 | <0.001 |
Fat mass (%) | 27.9 ± 10.7 | 34.7 ± 9.4 | 29.0 ± 10.8 | <0.001 |
BMI |
52 (9.3)b | 44 (40.4) | 96 (14.4) | <0.001d |
CVM profile | ||||
SBP (mm Hg) | 111.1 ± 10.2 | 118.3 ± 10.7 | 112.2 ± 10.6 | <0.001 |
DBP (mm Hg) | 68.7 ± 7.0 | 72.1 ± 6.5 | 69.3 ± 7.0 | <0.001 |
TG (mg/dL) | 82.5 ± 45.5 | 118.2 ± 71.6 | 88.3 ± 50.1 | <0.001 |
HDL-chol (mg/dL) | 40.8 ± 10.6 | 36.6 ± 10.2 | 40.1 ± 10.6 | <0.001 |
Glucose (mg/dL) | 87.4 ± 8.8 | 94.2 ± 10.8 | 88.6 ± 9.5 | <0.001 |
Insulin ( |
6.3 ± 2.5 | 17.5 ± 7.0 | 8.1 ± 5.5 | <0.001 |
hs-CRP (mg/L) | 0.95 ± 1.9 | 1.10 ± 1.6 | 0.98 ± 1.9 | n.s. |
Adiponectin ( |
12.3 ± 5.5 | 9.2 ± 5.1 | 11.8 ± 5.5 | <0.001 |
Lifestyles habits | ||||
Unhealthy eating | 139 (24.9) | 20 (18.4) | 159 (23.8) | n.s. |
Physical inactivity | 209 (37.4) | 56 (51.4) | 265 (39.7) | 0.006d |
Prevalence rates of cardiovascular and metabolic risk factors by HOMA-IR. Error bars are 95% CI. Statistical significant difference by Pearson’s Chi2. Significance level:
Table
Association between IR and sex, obesity, sarcopenia, low adiponectin, life-style habits, and HFDM2 in adolescents (
Subjects with insulin resistance (HOMA-IR ≥ 2.6) | Crude ORa | ||
---|---|---|---|
|
% | ||
Overall | 109 | 16.32 | |
Obesity | |||
No | 65 | 11.4 | Ref. group |
Yes | 44 | 45.8 | 6.60 |
Sarcopenia | |||
No | 50 | 10.8 | Ref. group |
Yes | 59 | 35.1 | 4.87 |
Low adiponectin | |||
No | 74 | 13.6 | Ref. group |
Yes | 35 | 28.5 | 2.53 |
Physical inactivity | |||
No | 53 | 13.2 | Ref. group |
Yes | 56 | 21.1 | 1.77 |
Unhealthy food intake | |||
No | 89 | 17.5 | Ref. group |
Yes | 20 | 12.6 | 0.68 |
Family history T2Db | |||
No | 23 | 11.7 | Ref. group |
Yes | 74 | 18.8 | 1.73 |
Table
Influence of FHDM, physical inactivity, sarcopenia, obesity, and low adiponectin over the risk of insulin resistance (
Model 1 | Model 2 | Model 3 | Model 4 | |
---|---|---|---|---|
OR |
OR |
OR |
OR | |
FHDM | 1.74 |
1.74 |
1.72 |
1.80 |
Physical inactivity | 1.77 |
1.49 |
1.42 |
1.45 |
Sarcopenia | (⋯) | 4.25 |
2.27 |
2.56 |
Obesity | (⋯) | (⋯) | 3.25 |
2.92 |
Low adiponectin | (⋯) | (⋯) | (⋯) | 2.22 |
|
||||
Likelihood ratio (Chi2) | 11.46** | 48.5*** | 61.6*** | 69.8*** |
Hosmer-Lemeshow | <0.001 (0.99) | 0.39 (0.99) | 0.18 (0.99) | 1.21 (0.98) |
Correctly classified | 83.6% | 83.6% | 84.2% | 84.6% |
OR
In this cohort of healthy Chilean adolescents of low to middle SES, the optimal cutoff point of HOMA-IR for IDF MetS diagnosis was 2.6 (sensitivity: 59% and specificity: 87%). Adolescents with HOMA-IR ≥ 2.6 showed a significantly higher prevalence of obesity (40.4%), abdominal obesity (61.5%), hypertriglyceridemia (20.4%), high blood pressure (18.4%), fasting hyperglycemia (19.3%), and MetS (33.0%). Thus, HOMA-IR of 2.6 or higher would find young individuals with greater biological risk.
In adolescents, HOMA-IR values ranging from 2.2 to 5.3 have been reported as cutoff for diagnosing MetS, but these studies vary greatly in their design, sample size, age and nutritional status of participants, and degree of pubertal development [
In this sample, FHDM, obesity, sarcopenia, and low adiponectin were all independently associated with a significant increased risk of IR. All these factors have been recognized as important determinants of IR and TD2 in pediatric populations [
This research has limitations that should be considered when interpreting its results. One limitation is that we estimated sarcopenia from DEXA scans and calculated fat-free mass rather than a more direct method of assessing muscle mass [
This research provides results that confirm that in adolescents a value of HOMA-IR ≥ 2.6 is associated with greater cardiovascular and metabolic risk [
The authors declare that there is no conflict of interests regarding the publication of this paper.
This research was carried out with financial support from the National Heart Lung and Blood Institute (NHLBI) and National Institutes of Health (USA), under Grant R01HL088530-2980925. Dr. Correa-Burrows was sponsored by the Advanced Human Capital Program (Grant code: 79140003) and from the National Council for Scientific Research and Technology (CONICYT) (Chile).