Higher AIP Linked to Kidney and Nerve Complications in Type 2 Diabetes
Key Takeaways
- In a Shenzhen, China, cohort of people with type 2 diabetes and baseline LDL-C <2.6 mmol/L, the highest baseline AIP tertile was significantly associated with more composite microvascular complications than the lowest.
- The highest AIP tertile was significantly associated with diabetic nephropathy and peripheral neuropathy compared with the lowest tertile.
- The highest-versus-lowest AIP comparison was not statistically significant for diabetic retinopathy.
- The middle AIP tertile was significantly associated with nephropathy, but not with the composite outcome, compared with the lowest tertile.
In a recent cohort study, investigators retrospectively assembled electronic health records from community health service centers in Shenzhen, China, covering 2018–2024. The cohort comprised 16,469 people with physician-diagnosed type 2 diabetes, baseline LDL-C below the study threshold, measured baseline LDL-C, TG, and HDL-C, and no previous microvascular complications. Atherogenic index of plasma (AIP) was defined as log(TG/HDL-C), with both lipids measured in mmol/L; the exposure categories were T1 ≤−0.43, T2 −0.43–0.24, and T3 >0.24, with T1 as comparator.
The primary outcome combined incident diabetic retinopathy, nephropathy, and peripheral neuropathy identified in inpatient International Classification of Diseases, Tenth Revision (ICD-10) records. Follow-up ran from baseline examination to complication-related hospitalization or study end. Multivariable Cox models adjusted for age, sex, education, smoking, drinking, regular exercise, body mass index (BMI), diabetes duration, family history of diabetes, hypertension, and use of oral antidiabetic drugs, insulin, and statins. Medication use was identified from electronic prescriptions during observation, not necessarily at baseline.
Over a median follow-up of 4.6 years, the fully adjusted hazard ratio (HR) for the composite outcome was 1.34 (95% confidence interval [CI] 1.15–1.56) for the highest versus lowest AIP tertile. The middle-versus-lowest-tertile composite comparison was not statistically significant.
For diabetic nephropathy, the fully adjusted highest-versus-lowest-tertile estimate was HR 1.62 (95% CI 1.30–2.01); for diabetic peripheral neuropathy, it was HR 1.39 (95% CI 1.13–1.70). The retinopathy association was not statistically significant. Compared with the lowest tertile, the middle tertile was significantly associated with nephropathy, but not with the composite outcome, neuropathy, or retinopathy.
These observational associations do not establish that AIP causes microvascular complications; neither lowering AIP nor AIP-guided screening was tested for benefit. The authors noted incomplete glycated hemoglobin (HbA1c) records and possible residual glycemic confounding. AIP was measured at baseline, with limited longitudinal lipid measurements, and inpatient-only ICD-10 ascertainment could miss early or outpatient complications. Whether findings from this Shenzhen Chinese population apply to U.S. or other populations remains uncertain. The authors describe AIP as a potential complementary risk marker, not an established clinical tool.
The authors conclude that AIP may complement conventional LDL-C information when characterizing residual microvascular risk in type 2 diabetes, while its clinical utility awaits confirmation.
Clinician Questions
Does age modify the association between AIP and peripheral neuropathy in type 2 diabetes?
Among people with type 2 diabetes and baseline LDL-C below the study threshold in Zhang and colleagues’ Shenzhen cohort, investigators found a statistically significant age interaction: the association between higher baseline AIP and subsequent diabetic peripheral neuropathy was stronger in participants aged 65 years or older than in younger participants. The interaction does not establish an age-specific treatment benefit.
Did the AIP–microvascular complication association in type 2 diabetes persist in sensitivity analyses?
Among patients with type 2 diabetes and baseline LDL-C below the study threshold in Shenzhen, the association between baseline AIP and incident microvascular complications was broadly consistent in complete-case analyses, after excluding medication users, after additional adjustment for total cholesterol and LDL-C, and in a one-year-exclusion sensitivity analysis, although the methods describe excluding early complications while the results describe excluding follow-up shorter than one year. These checks did not eliminate residual-confounding or inpatient-ascertainment concerns.