Lipid Accumulation Product Index Predicts New-Onset Type 2 Diabetes Among Non-Obese Koreans: A 12-Year Longitudinal Study

Figures & data

Figure 1 Flowchart for the selection of study participants.

Table 1 Baseline Characteristics of the Study Population According to Lipid Accumulation Product Quartiles

		Quartile of LAP Index
	Total	Q1	Q2	Q3	Q4	P value*
	n = 4281	n = 1050	n = 1075	n = 1075	n = 1080
LAP (cm x mmol/l)	25.4 ± 19.7	≤12.7	12.8–20.1	20.2–31.6	≥31.7
Age (years)	51.5 ± 8.9	50.2 ± 9.0	50.2 ± 8.5	51.9 ± 8.9	53.9 ± 8.8	<0.001
Male sex (%)	43.8	55.7	46.9	40.7	32.2	<0.001
Body mass index (kg/m^2)	22.3 ± 1.8	21.0 ± 1.8	22.4 ± 1.5	22.9 ± 1.4	23.2 ± 1.3	<0.001
Waist circumference (cm)	77.0 ± 6.1	70.8 ± 4.6	75.7 ± 4.4	78.9 ± 4.3	82.4 ± 4.0	<0.001
Systolic blood pressure (mmHg)	117.9 ± 17.8	112.7 ± 15.9	116.1 ± 17.5	118.8 ± 17.5	123.9 ± 18.3	<0.001
Diastolic blood pressure (mmHg)	77.9 ± 11.0	74.9 ± 10.6	76.8 ± 10.9	78.5 ± 10.6	81.4 ± 11.0	<0.001
Fasting plasma glucose (mmol/l)	4.5 ± 0.5	4.5 ± 0.4	4.5 ± 0.5	4.5 ± 0.5	4.6 ± 0.5	0.006
2-h postprandial plasma glucose (mmol/l)	6.1 ± 1.7	5.9 ± 1.7	6.0 ± 1.6	6.2 ± 1.6	6.5 ± 1.6	<0.001
Hemoglobin A1c (%)	5.5 ± 0.3	5.4 ± 0.3	5.5 ± 0.3	5.5 ± 0.3	5.6 ± 0.4	<0.001
Total cholesterol (mmol/l)	4.8 ± 0.9	4.6 ± 0.8	4.7 ± 0.8	4.8 ± 0.8	5.1 ± 0.9	<0.001
Triglyceride (mmol/l)	1.5 ± 0.9	1.0 ± 0.3	1.2 ± 0.3	1.5 ± 0.4	2.4 ± 1.2	<0.001
HDL-cholesterol (mmol/l)	1.2 ± 0.3	1.3 ± 0.3	1.3 ± 0.3	1.2 ± 0.2	1.1 ± 0.2	<0.001
C-reactive protein (mg/L)	0.2 ± 0.6	0.2 ± 0.5	0.2 ± 0.6	0.2 ± 0.4	0.2 ± 0.9	0.187
Current smoker (%)	25.7	30.6	26.6	23.6	22.0	<0.001
Alcohol drinking (%)^†	45.9	48.4	49.6	44.7	40.9	<0.001
Regular exercise (%)^‡	25.2	26.7	23.9	28.0	22.4	0.007
Family history of diabetes (%)	9.9	9.3	10.5	10.6	9.2	0.554
Impaired fasting glucose (%)	3.0	2.1	3.4	3.3	3.4	0.234
Impaired glucose tolerance (%)	16.9	14.9	14.2	17.4	21.1	<0.001

Notes: Data are expressed as the mean ± SD or percentage. *P-values were calculated using ANOVA or the chi-squared test. ^†Alcohol intake ≥ twice/week. ^‡Moderate intensity physical exercise ≥ three times/week.

Abbreviations: LAP, lipid accumulation product; HDL, high-density lipoprotein.

Table 2 Incidence of Type 2 Diabetes During the Follow-Up Study

Year Range	Follow-Up	n	Incidence Cases (n)	Incidence Rate Over 2 Years
2001–2002	Baseline	4281
2003–2004	2 years	4000	128	3.2
2005–2006	4 years	3563	124	3.5
2007–2008	6 years	3197	113	3.5
2009–2010	8 years	3209	96	3.0
2011–2012	10 years	3010	84	2.8
2013–2014	12 years	2790	63	2.2

Figure 2 Kaplan–Meier plots indicating the cumulative probability of being diagnosed with diabetes after the baseline survey.

Figure 3 Age- and sex-adjusted LAP index at baseline according to the incidence of diabetes.

Table 3 Hazard Ratios and 95% Confidence Intervals for Incident Type 2 Diabetes According to LAP Quartiles

		LAP Quartiles
		Q1	Q2	Q3	Q4
		n = 1050	n = 1075	n = 1075	n = 1080
New cases of diabetes, n		103	128	144	233
Mean follow-up, years		9.3 ± 3.5	9.4 ± 3.5	9.1 ± 3.7	9.1 ± 3.6
Pearson-years of follow-up		9787	10,142	9812	9777
Incidence rate/1000 person -years		10.5	12.6	14.7	23.8
Model 1	HR (95% CI)	1.00 (reference)	1.35 (0.99–1.82)	1.64 (1.20–2.23)	2.52 (1.84–3.44)
	P value	–	0.052	0.002	< 0.001
Model 2	HR (95% CI)	1.00 (reference)	1.32 (0.97–1.79)	1.59 (1.16–2.17)	2.43 (1.78–3.33)
	P value	–	0.073	0.003	< 0.001
Model 3	HR (95% CI)	1.00 (reference)	1.32 (0.97–1.79)	1.51 (1.11–2.06)	2.14 (1.56–2.94)
	P value	–	0.073	0.009	< 0.001

Notes: Model 1: adjusted for age, sex, and body mass index. Model 2: adjusted for age, sex, body mass index, smoking status, alcohol intake, and physical activity. Model 3: adjusted for age, sex, body mass index, smoking status, alcohol intake, physical activity, mean arterial blood pressure, family history of diabetes, and impaired glucose tolerance.

Table 4 Sex-Based Subgroup Analysis for Incident Type 2 Diabetes According to LAP Quartiles

			LAP Quartiles
			Q1	Q2	Q3	Q4
Model 1	Men	HR	1.00 (reference)	1.45 (0.99–1.13)	1.48 (0.97–2.26)	2.88 (1.93–4.32)
		P value	–	0.059	0.070	< 0.001
	Women	HR	1.00 (reference)	1.26 (0.76–2.07)	1.88 (1.15–3.06)	2.29 (1.36–3.84)
		P value	–	0.369	0.011	0.001
Model 2	Men	HR	1.00 (reference)	1.39 (0.95–2.04)	1.41 (0.92–2.16)	2.78 (1.85–4.17)
		P value	–	0.093	0.113	< 0.001
	Women	HR	1.00 (reference)	1.27 (0.77–2.10)	1.88 (1.15–3.06)	2.25 (1.34–3.78)
		P value	–	0.342	0.011	0.002
Model 3	Men	HR	1.00 (reference)	1.37 (0.93–2.02)	1.24 (0.82–1.90)	2.20 (1.46–3.32)
		P value	–	0.108	0.313	< 0.001
	Women	HR	1.00 (reference)	1.30 (0.79–2.15)	1.99 (1.22–3.26)	2.26 (1.34–3.82)
		P value	–	0.297	0.006	0.002

Notes: Model 1: adjusted for age and body mass index. Model 2: adjusted for age, body mass index, smoking status, alcohol intake, and physical activity. Model 3: adjusted for age, body mass index, smoking status, alcohol intake, physical activity, mean arterial blood pressure, family history of diabetes, and impaired glucose tolerance.

Table 5 LAP Index versus body Mass Index, Waist circumference and HOMA-IR for predicting type 2 Diabetes

	Pairwise Comparison of C-Index			Ability to Classify T2DM
	Difference	95% CI	P value	Cutoff value	Sensitivity (%)	Specificity (%)	C-Index	P value
LAP index, Q1-4 vs body mass index, kg/m^2	0.06	0.03 to 0.09	< 0.001
LAP index, Q1-4 vs waist circumference, cm	0.02	0.01 to 0.05	0.016
LAP index, Q1-4 vs HOMA-IR	0.05	0.02 to 0.09	0.001
LAP index				29.6	43.6	74.2	0.606	< 0.001
Body mass index, kg/m^2				23.1	41.6	63.7	0.528	0.056
Waist circumference, cm				77.1	59.9	51.4	0.566	< 0.001
HOMA-IR				1.68	34.4	75.0	0.538	0.004

Abbreviations: LAP, lipid accumulation product; HOMA-IR, homeostasis model assessment of insulin resistance; C-index, concordance index; T2DM, type 2 diabetes mellitus.