1001-P: HOMA2 IR and HOMA2 Beta on Onset and Progression of Diabetes in Young to Middle-Aged Subjects
Authors: FAN BAOQI , WU HONGJIANG , SHI MAI , YANG AIMIN , TAM CLAUDIA H. , LAU ERIC S.H. , MAO DANDAN , LIM CADMON K.P. , KONG ALICE P. , CHOW ELAINE , MA RONALD C. , LUK ANDREA , CHAN JULIANA C. 
Published: June 2021

Background: The roles of insulin deficiency (ID) and resistance (IR) in young patients with type 2 diabetes (T2D) are uncertain. We explored the associations of HOMA2 IR and HOMA2 %B using fasting C peptide and plasma glucose (FPG) with incident T2D and insulin use in Chinese aged 18-50 years.
Methods: Cohort 1 included subjects without T2D in 1998-2002 with glycemic status ascertained in 2012-2013. Cohort 2 included patients with T2D (1995-2014) with documentation of glycemic deterioration (continuous insulin use or failure of 2 oral drugs).
Results: In cohort 1, 62 subjects developed (T2D-progressors) and 285 did not develop T2D (T2D-non-progressors) during 10-year follow-up. In cohort 2 (n=737), 293 (39.8%) required insulin after a median follow-up period of 8.6 years. At baseline, T2D-non-progressors had lower HOMA2 IR [median (IQR) 0.77 (0.60, 1.06)] vs. 1.06 (0.81, 1.38)] and similar HOMA2 %B [84.3 (72, 111.5) vs. 85.1 (75.6, 100.7)] compared with T2D-progressors. Non-insulin-requiring T2D patients had lower HOMA2 IR [1.47 (1.02, 2.11) vs. 1.76 (1.19, 2.42)] and higher HOMA2 %B [62.4 (39.4, 87.4) vs. 45.4 (25.8, 71.8)] than insulin-requiring patients. When stratified by median values and using low HOMA2 %B plus low HOMA2 IR as referent, subjects with high HOMA2 %B plus high HOMA2 IR had age and sex-adjusted odds ratio (95% CI) of 2.47 (1.28, 4.93) and those with low HOMA2% B plus high HOMA2 IR had 5.27 (2.27, 12.84) of incident T2D. In the T2D cohort, using high HOMA2 %B plus low HOMA2 IR as referent, the hazard ratio (95% CI) for insulin use increased with low HOMA2 %B [2.18 (1.47, 3.23)], high HOMA2 IR [2.45 (1.64, 3.64)] and low HOMA2 %B plus high HOMA2 IR [4.25 (2.82, 6.41)] adjusted for age, sex and disease duration. These associations were attenuated after adjusting for obesity, FPG, HbA1c and TG/HDL-C.
Conclusions: In young to middle-aged Chinese, progressive worsening in IR and ID contribute to onset of T2D and insulin requirement, which can be attenuated by early control of metabolic factors.

Disclosure
B. Fan: None. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. A. Luk: None. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. H. Wu: None. M. Shi: None. A. Yang: None. C. H. Tam: None. E. S. H. Lau: None. D. Mao: None. C. K. P. Lim: Stock/Shareholder; Self; GemVCare Ltd. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum.