Associations of physiologic subtypes based on HOMA2 indices of β-cell function and insulin sensitivity with the risk of kidney function decline, cardiovascular disease, and all-cause mortality from the 4C study

Luo, P; Li, D; Guo, Y; Meng, X; Kan, R; Pan, L; Xiang, Y; Mao, B; He, Y; Wang, S; Yang, Y; Liu, Z; Xie, J; Zhang, B; He, W; Hu, S; Zhou, X; Yu, X

doi:10.1186/s12933-024-02496-5

Type 2 & other diabetes

Associations of physiologic subtypes based on HOMA2 indices of β-cell function and insulin sensitivity with the risk of kidney function decline, cardiovascular disease, and all-cause mortality from the 4C study

Cardiovasc DiabetolPublished 7 Nov 2024Retrospective cohort study

Main finding · Kidney function declineResultHazard ratio 11.50 95% CI 4.31–30.67

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Authors' conclusion

The classical subtype had the strongest correlation with the risk of kidney function decline, and the hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality, which should be considered for interventions with precision medicine.

Study context

Population: Participants of the 4C study categorized by HOMA2 indices of β-cell function and insulin sensitivity
Participants: 7,317 participants

Exposure: Physiologic subtypes based on HOMA2-B and HOMA2-S
Normaln = 1,488reference
Insulinopenicn = 2,179
Hyperinsulinemicn = 2,173
Classicaln = 1,477
Outcome: Kidney function decline, cardiovascular disease (CVD) events (fatal and nonfatal) and all-cause mortality
Follow-up: Up to 5 years

Main finding

Kidney function decline

Hazard ratio

11.50

95% CI 4.31–30.67

Classicalvs Normal

HR 11.50 (95% CI 4.31–30.67)

As reported in the abstract

Observational data: associations, not effects.

Further findings

Outcome	← Lower risk with hyperinsulinemic ←→ Higher risk with hyperinsulinemic →	HR (95% CI)
Fatal CVDHyperinsulinemicvs NormalHighest risk of CVD among subtypes	0.050.21520	6.56 (3.09–13.92)
All-cause mortalityHyperinsulinemicvs NormalHighest risk among subtypes	0.050.21520	4.56 (2.97–7.00)
	0.050.21520Hazard ratio (log scale)

Dose-dependent associations of HOMA2-B and HOMA2-S with outcomes

Spline analyses indicated dose-dependent associations of HOMA2-B and HOMA2-S with outcomes

Original publication

Associations of physiologic subtypes based on HOMA2 indices of β-cell function and insulin sensitivity with the risk of kidney function decline, cardiovascular disease, and all-cause mortality from the 4C study. Cardiovasc Diabetol. Published 7 November 2024. doi:10.1186/s12933-024-02496-5

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