# Birthweight and risk of chronic kidney disease after a type 2 diabetes diagnosis in the DD2 cohort

## TL;DR

Low birthweight is linked to a higher risk of chronic kidney disease in people recently diagnosed with type 2 diabetes.

## Contribution

This study is the first to investigate the association between birthweight and chronic kidney disease risk in a type 2 diabetes cohort.

## Key findings

- Low birthweight (<2500 g) was associated with a 5.5% higher 10-year risk of CKD compared to normal birthweight.
- Each 1 kg decrease in birthweight correlated with a 6.6% increase in urine albumin/creatinine ratio.
- High birthweight did not significantly increase CKD risk compared to normal birthweight.

## Abstract

Low birthweight (LBW) is associated with younger age, less obesity and more hypertension among people recently diagnosed with type 2 diabetes, as well as increased cardiovascular morbidity and mortality risk. It is not known whether LBW is associated with an increased risk of incident chronic kidney disease (CKD) among people with a type 2 diabetes diagnosis.

Original midwife records were retrieved for 5982 participants with recently diagnosed type 2 diabetes enrolled in the Danish Center for Strategic Research in Type 2 Diabetes (DD2) cohort between 2010 and 2024. They were followed until first incident CKD diagnosis, defined as either two eGFR measurements <60 ml/min per 1.73m2 or two urine albumin/creatinine ratio (UACR) measurements >3 mg/mmol, each 90–365 days apart. Confounder-standardised 10 year risks of CKD were estimated, with death considered as a competing risk. Adjusted hazard ratios (aHRs) for CKD were computed using Cox and spline regression analyses. All analyses were controlled for differences in sex, age at enrolment, calendar year at birth, family history of diabetes and born-at-term status. Mixed-effects models were used to examine the trajectories of eGFR and UACR following enrolment.

A total of 1501 incident CKD endpoints occurred, corresponding to an incidence rate of 42.4 per 1000 person-years over a median follow-up time of 8.3 years. Spline models with birthweight as a continuous measure showed progressively increasing aHRs for CKD with decreasing birthweight. The 10-year standardised risk of CKD was 36.0% in people with LBW (<2500 g) and 30.6% in people with a normal birthweight (2500–4000 g), yielding a risk difference (RD) of 5.5% (95% CI −0.5%, 11.8%) and an aHR of 1.23 (95% CI 0.98, 1.55). People with type 2 diabetes and high birthweight (>4000 g) had a similar 10-year standardised CKD risk compared with normal birthweight (33.1% and 30.6%, respectively). This yielded an RD of 2.5% (95% CI −1.6%, 6.7%) and an aHR of 1.10 (95% CI 0.93, 1.29). In mixed-effects models examining eGFR and UACR trajectories, each 1 kg decrease in birthweight was associated with a 6.6% (95% CI 1.9, 11.1) increase in UACR, whereas no association was found for eGFR.

A history of LBW was associated with elevated risk of CKD among people with a recent type 2 diabetes diagnosis, although the precision of risk estimates was limited.

The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-024-06357-4.