1357-P: High Plasma Leptin Levels Are Associated with Low Birth Weight and Disease Severity in People with Recently Diagnosed Type 2 Diabetes
Authors: OBENG PRINCE A. , LÜHR HANSEN ALEKSANDER , ENGELHARD LEONIE M. , BRØNS CHARLOTTE , HIRSCHBERG JENSEN VERENA , HANSEN TORBEN , JESSEN NIELS , VESTERGAARD PETER , NIELSEN JENS S. , HOJLUND KURT , HECHT OLSEN MICHAEL , THOMSEN REIMAR W. , VAAG ALLAN A. 
Published: June 2024

Introduction & Objective: Low birth weight (BW) is associated with increased type 2 diabetes (T2D) severity and high plasma leptin levels in people without diabetes. In a cross-sectional study of 6402 people recently diagnosed with T2D, we examined if BW is associated with plasma leptin and if leptin is associated with clinical characteristics reflecting disease severity.
Methods: Plasma leptin levels were measured using a Meso Scale Discovery U-plex assay. The association between BW (exposure) and plasma leptin levels and then between leptin (exposure) and clinical T2D severity, at T2D diagnosis were assessed. We used linear regression to estimate continuous outcomes and log-binomial/robust Poisson regression to determine prevalence ratios (PRs) in categorical analyses. Analyses were first adjusted for sex, age, and T2D family history, then + BMI, and + BW.
Results: A 1kg lower BW was only associated with a 12.0% (95% CI: 8.0, 15.9) higher plasma leptin level when adjusted for BMI. A 20% increase in leptin was associated with 0.52kg/m2 (95% CI: 0.5, 0.54) higher BMI, 1.7% (95% CI: 1.5, 1.9) higher triglyceride, 3.8% (95% CI: 3.6, 4.0) higher plasma C-peptide, 6.0% (95% CI: 5.5, 6.5) higher hsCRP, 2.4% (95% CI: 2.2, 2.7) higher HOMA2-insulin secretion, and 3.7% (95% CI: 3.5, 3.9) lower HOMA2-insulin sensitivity. Having a plasma leptin level within the top 25% (&gt;34ng/ml) was associated with increased use of glucose-lowering medications (PR for insulin-and-oral/insulin only: 1.27 [95% CI: 1.01, 1.59]), Charlson Comorbidity Index score (PR ≥ 3, 1.57 [95% CI: 1.22, 2.00]), macro- (PR 1.25 [95% CI: 1.10, 1.42]) -and-microvascular (PR 1.22 [95% CI: 1.02, 1.45]) complications, compared to having the middle 50% leptin (6-34ng/ml). The associations remained robust when further adjusted for BMI and then BW.
Conclusion: Low BW is associated with elevated plasma leptin levels, potentially contributing to disease severity in people recently diagnosed with T2D.

Disclosure
P.A. Obeng: None. A. Lühr Hansen: None. L.M. Engelhard: None. C. Brøns: Stock/Shareholder; Novo Nordisk A/S. V. Hirschberg Jensen: None. T. Hansen: None. N. Jessen: None. P. Vestergaard: None. J.S. Nielsen: None. K. Hojlund: None. M. Olsen: Other Relationship; AstraZeneca, Novo Nordisk A/S. Advisory Panel; Novo Nordisk A/S. Other Relationship; Teva Pharmaceutical Industries Ltd. R.W. Thomsen: None. A.A. Vaag: None.

Funding
Danish Agency for Science (09-067009 and 09-075724), the Danish Health and Medicines Authority, the Danish Diabetes Association, the Region of Southern Denmark, and the Novo Nordisk Foundation (NNF17SA0030962-2, NNF20O0063292, and NNF17SA0030364).This study was conducted during Prince's scholarship period at Lund University, funded by the Swedish Institute.