Young Seok Song 1, You-Cheol Hwang 2, Hong-Yup Ahn 3, Cheol-Young Park 1

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Comparison of the Usefulness of the Updated Homeostasis Model Assessment (HOMA2) with the Original HOMA1 in the Prediction of Type 2 Diabetes Mellitus in Koreans Young Seok Song 1, You-Cheol Hwang 2, Hong-Yup Ahn 3, Cheol-Young Park 1 1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, 3 Department of Statistics, Dongguk University, Seoul, Korea

Young Seok Song

Background The pathophysiology of type 2 diabetes mellitus (T2DM) involves insulin resistance (IR) and β-cell dysfunction. Accordingly, estimating IR and β-cell function is essential for screening high-risk subjects for T2DM and making a treatment plan. There are several methods for estimating IR and β-cell function, including the euglycemic or hyperinsulinemic euglycemic clamp, frequently sampled intravenous glucose tolerance, C-peptide to glucose ratio, and homeostasis model assessment (HOMA) model

The Aim of study The primary purpose of this study was to compare the predictive ability of HOMA1 and HOMA2 for diabetes in Korean population.

Subjects & Method (1) A retrospective observational study of participants in a medical health checkup program at the Health Promotion Center at Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, from January 2001 to December 2012. Participants were divided into a normal glucose tolerance (NGT) group and a pre-diabetes group according to fasting glucose and glycosylated hemoglobin levels. Anthropometric and laboratory data were measured at the baseline checkup, and HOMA values were calculated at the baseline and follow-up checkups. The hazard ratios (HRs) of the HOMA1 and HOMA2 values and the prevalence of diabetes at follow-up were evaluated using Kaplan-Meier analysis and multivariable Cox proportional hazards model

Subjects N=136,158 N= 31,464 history of diabetes taking oral hypoglycemic agents fasting blood glucose 126 mg/dl or HbA1c 6.5% at the baseline missing data pregnant subjects ect N=104,694

: Calculation of HOMA Method (2) HOMA1-IR was defined as [fasting insulin (μu/ml) fasting glucose (mmol/l)]/22.5. HOMA1-β was calculated using (20 fasting insulin)/(fasting glucose 3.5). HOMA2-IR and HOMA2-β data were calculated with a HOMA2 calculator released by the Diabetes Trials Unit, University of Oxford: HOMA Calculator. This calculator is available at: http://www. dtu.ox.ac.uk/homacalculator/index.php (updated January 8, 2013). HOMA1-β and HOMA2-β have a negative correlation with diabetes risk, so we took the inverse value to compare them with HOMA-IR or HOMA2- IR.

RESULTS

Baseline characteristics of the study participants

Univariate Cox proportional hazards analysis model of HOMA values for developing type 2 diabetes mellitus

Kaplan-Meier curves for the cumulative prevalence of T2D for the quartile of HOMA values in the normal glucose tolerance group

Kaplan-Meier curves for the cumulative prevalence of T2D for the quartile of HOMA values in the pre-diabetic group

Kaplan-Meier curves for the cumulative prevalence of T2D for the quartile of HOMA values in the non-diabetic group

Multivariate a Cox proportional hazards analysis model of HOMA values for developing T2D

Summary All of the HOMA values except HOMA1-β and HOMA2-β in the NGT group were significant predictors of the progression to diabetes. In the NGT group, there was no significant difference in HOMA1-IR and HOMA2-IR In the pre-diabetes group, HOMA2-β was a more powerful marker than HOMA1-IR or HOMA1-β In the non-diabetic group (NGT+pre-diabetes), HOMA2-β was also a stronger predictor of diabetes than HOMA1-IR or HOMA1-β

Conclusion HOMA2 is more predictive than HOMA1 for the progression to diabetes in pre-diabetes or non-diabetic Koreans.

Homeostatic model assessment The original HOMA (HOMA1) has been broadly used due to its simplicity and cost effectiveness. Previous studies show that an increase of HOMA1-IR and a decrease of HOMA1-β are associated with an increased incidence of diabetes and future cardiovascular events in patients with T2DM. An updated HOMA (HOMA2), the correctly solved computer model that considers such variations, was announced in 1998. HOMA2 was recalibrated to give steady-state β-cell function (% B) and insulin sensitivity (% S) of 100% in normal young adults when using currently available assays for insulin, specific insulin, or C-peptide available at: http://www. dtu.ox.ac.uk/homacalculat or/index.php (updated January 8, 2013).