Late Phase Insulin Resistance and Secretion during the OGTT Independently Predict the Risk of Type 2 Diabetes

Late Phase Insulin Resistance and Secretion during the OGTT Independently Predict the Risk of Type 2 Diabetes Although HOMA IR and insulinog Although HOMA IR and insulinogenic index (IGI) ([Delta]insulin (0-30 min) / [Delta]glucose (0-30 min)) in the early phase during an OGTT are well-known risk factors of the type 2 diabetes (T2DM), not known is whether the late phase insulin resistance and secretion during an OGTT are associated with the risk of T2DM. While following 400 Japanese Americans for 10-11 years, 86 incident cases of T2DM occurred. Insulin resistance was estimated as [area under the curve of insulin between 60 and 120 min during an OGTT (AUC insulin 60-120 min)] x (AUC glucose 60-120 min) as reflecting the late phase insulin resistance and HOMA IR as early phase insulin resistance. Insulin secretion was estimated as (Incremental AUC insulin 60-120 min) / (Incremental AUC glucose 60-120 min) as reflecting late phase and IGI as early phase insulin secretion. After adjusting for age, family history of diabetes, BMI, gender, fasting plasma glucose, HOMA IR, and IGI, both late phase insulin resistance and secretion were independently associated with the risk of T2DM. Multiple-adjusted odds ratios (ORs) for late phase insulin resistance were 3.88 (95% CI, 1.31-11.50) in tertile 2 and 12.83 (3.96-41.62) in tertile 3 compared with tertile 1 and those for late phase insulin secretion were 0.28 (0.11-0.68) in tertile 2 and 0.26 (0.08-0.84) in tertile 3 compared with tertile 1. Both HOMA IR and IGI were associated with the risk of T2DM (OR per 1 SD increase 2.05 (1.24-3.37), 0.53 (0.31-0.90), respectively). The joint analysis of late phase insulin resistance and secretion in association with the risk of T2DM is shown in Table. In conclusion, late phase insulin resistance and secretion during an OGTT are independently associated with the risk of T2DM.

		Tertile of late phase insulin resistance
		1	2	3
		The cumulative incidence (%)
Tertile of late phase insulin secretion	1	4/53 (7.5)	25/61 (41.0)	7/18 (38.9)
	2	1/81 (1.2)	5/50 (10.0)	19/39 (48.7)
	3		1/22 (4.5)	24/76 (31.6)
		Multiple-adjusted odds ratio*
Tertile of late phase insulin secretion	1	5.18	22.8[dagger]	29.84[dagger]
	2	Reference	3.58	21.69[dagger]
	3		2.20	14.63[dagger]

*Adjusted for age, family history of T2DM, BMI, gender, fasting plasma glucose, HOMA IR, and IGI.
[dagger]P <0.05.

TOMOSHIGE HAYASHI, EDWARD J. BOYKO, KYOKO KOGAWA SATO, MARGUERITE J. MCNEELY, DONNA L. LEONETTI, STEVEN E. KAHN, WILFRED Y. FUJIMOTO 1356-P Osaka, Japan, Seattle, WA Epidemiology