Evidence map›Paper›PMID 41612504›Full record

ArticleDiabetology & metabolic syndrome2026

A U-shaped association between vitamin D and ketone levels in type 2 diabetes: a metabolic state-dependent dual regulation mechanism.

Xiang-Yu Chen, Yang Zhang, Xiang-Xin Wang, Li-Ying Hao, Mei Xue, Wen-Hua Xiao

Abstract read
In one paragraph

Article in Diabetology & metabolic syndrome, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Xiang-Yu Chen *Department of Endocrinology, Peking University Third Hospital Qinhuangdao Hospital, Qinhuangdao, 066000, China.
Yang Zhang *Department of Endocrinology, Peking University Third Hospital Qinhuangdao Hospital, Qinhuangdao, 066000, China.
Xiang-Xin WangDepartment of Endocrinology, Peking University Third Hospital Qinhuangdao Hospital, Qinhuangdao, 066000, China.
Li-Ying HaoDepartment of Endocrinology, Peking University Third Hospital Qinhuangdao Hospital, Qinhuangdao, 066000, China.
Mei Xue *Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. xuem1993@163.com.
Wen-Hua Xiao *Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, 100191, China. xiaowenhua@bjmu.edu.cn.

Funding

National Natural Science Foundation of China 82300928Qinhuangdao S&T Plan Program 202401A089
6 · The paper itself

Abstract

backgroundBeyond bone health, vitamin D plays a pivotal role in glucose and lipid homeostasis. Vitamin D deficiency is prevalent in type 2 diabetes (T2DM), potentially exacerbating β-cell dysfunction and dysregulated energy substrate utilization. This study aimed to characterize the complex, potentially non-linear relationship between serum 25-hydroxyvitamin D [25(OH)D], β-hydroxybutyrate (β-OHB), and pancreatic β-cell reserve.

methodsHospitalized T2DM patients were enrolled, excluding those with acute complications or severe organ dysfunction. C-peptide area under the curve (AUC₀–₃h) from a steamed bread meal test was used to assess β-cell reserve. Multiple linear and logistic regressions were employed to evaluate the 25(OH)D-β-OHB association, adjusting for covariates including demographics, glycemic control, lipid profile, comorbidities, and medications (Metformin, SGLT2 inhibitors, insulin). Non-linearity was examined using mean-centered quadratic terms, with robustness verified via Bootstrap resampling and restricted cubic spline (RCS) analysis.

resultsNo independent linear association was observed between 25(OH)D and ln(β-OHB + 0.01) in the overall population (P > 0.05). However, multivariate logistic regression identified 25(OH)D as an independent risk factor for elevated ketones (β-OHB ≥ 0.27 mmol/L; OR = 1.053, P = 0.006), an effect that was more pronounced in the preserved β-cell function group (C-peptide AUC ≥ 8 ng/mL⋅h; OR = 1.062, P = 0.011). Notably, a significant U-shaped relationship between 25(OH)D and β-OHB was confirmed in patients with stable metabolic status (HbA1c ≤ 8.5% and C-peptide AUC ≥ 8 ng/mL⋅h), with an inflection point at 20.5–22.4 ng/mL.

conclusionA robust U-shaped non-linear association exists between serum 25(OH)D and β-OHB, indicating a dual regulatory role of vitamin D in ketone metabolism. Maintaining 25(OH)D at a moderate level (~ 21 ng/mL) may optimize energy substrate utilization, a process significantly modulated by β-cell reserve. These findings underscore the clinical necessity for individualized vitamin D monitoring and precision intervention in T2DM management.

Indexed as

C-peptideMetabolic homeostasisNonlinear associationType 2 diabetes mellitusVitamin dΒ-hydroxybutyrate

Identifiers

PMID41612504
PMCPMC12933978

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.