Abstract
This study aimed to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) concentrations and ketosis risk in adults with newly diagnosed type 2 diabetes mellitus (T2DM). A total of 1266 newly diagnosed T2DM patients were consecutively enrolled. Participants were categorized into ketosis-prone T2DM (KPDM, n = 243) and non-ketosis-prone T2DM (n = 1023) groups based on urinary ketone status. Serum 25(OH)D levels, metabolic parameters, and the neutrophil-to-lymphocyte ratio were measured. The KPDM group demonstrated significantly lower 25(OH)D levels (median 15.05 vs 17.50 ng/mL, P < .001) and a higher prevalence of vitamin D deficiency (<20 ng/mL: 69.9% vs 61.5%, P = .03). Seasonal variation analysis revealed consistently lower 25(OH)D levels in KPDM patients than in non-ketosis-prone T2DM patients during the summer–autumn months (17.25 vs 20.30 ng/mL, P < .001). Multivariate logistic regression revealed vitamin D deficiency, younger age, an elevated neutrophil-to-lymphocyte ratio, and increased hemoglobin A1c levels as independent predictors of ketosis development. Vitamin D deficiency is independently associated with increased odds of ketosis susceptibility in new-onset T2DM patients.
Keywords: 25-hydroxyvitamin D, diabetes mellitus, ketosis-prone diabetes, type 2
1. Introduction
The prevalence of diabetes mellitus, a chronic global health threat, is steadily increasing worldwide, resulting in a substantial disease burden. In addition to its classical role in calcium–phosphorus homeostasis and skeletal health, vitamin D has pleiotropic effects on diabetes pathophysiology.[1] Vitamin D plays a critical role in maintaining pancreatic β-cell function and insulin sensitivity.[2] Studies have shown that individuals with vitamin D deficiency face a higher risk of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) than do those with sufficient vitamin D status, suggesting that reduced vitamin D levels may increase diabetes risk.[3,4] Previous research in patients with T1DM revealed a strong association between vitamin D deficiency and diabetic ketoacidosis, with vitamin D-deficient individuals being more prone to diabetic ketoacidosis than individuals with adequate levels.[5] Recent studies have identified a subset of diabetes patients who present with ketosis at initial diagnosis and who test positive for urinary ketones but who clinically resemble patients with T2DM without evidence of pancreatic β-cell autoimmunity.[6–8] An increasing number of scholars refer to this condition as ketosis-prone T2DM (KPDM).[6,9] However, whether the occurrence of ketosis in these KPDM patients is linked to vitamin D deficiency remains understudied. This research aims to investigate vitamin D levels in newly diagnosed type 2 diabetes patients and their relationship with ketosis, along with relevant influencing factors.
2. Subjects and methods
2.1. Subjects
Newly diagnosed T2DM patients hospitalized at Cangzhou Central Hospital between January 2019 and December 2023 were consecutively enrolled. Only patients aged ≥18 years were included. This study received ethical approval from the Ethics Committee of Cangzhou Central Hospital and strictly adhered to the ethical principles outlined in the Declaration of Helsinki. Written informed consent was obtained from all the participants.
2.1.1. Inclusion criteria
Newly diagnosed T2DM meeting the 1999 World Health Organization diagnostic criteria for diabetes, with no history of glucose-lowering medication use and a disease duration ≤1 year.
Negative results for glutamic acid decarboxylase antibody, islet cell antibody, and insulin autoantibody in serum.
Spontaneous ketosis diagnosis required fulfillment of the following criteria: urinary ketones ≥1+ and the absence of identifiable triggers for ketosis (e.g., infection, surgery, trauma, or the administration of large glucose infusions).
2.1.2. Exclusion criteria
Gestational diabetes or other specific types of diabetes.
Secondary diabetes.
Poor general condition (e.g., severe hepatic or renal dysfunction).
History of malignancy.
Current use of medications affecting vitamin D metabolism (e.g., vitamin D supplements, glucocorticoids).
Based on the presence or absence of ketosis, patients were divided into 2 groups: those with KPDM and those with non-ketosis-prone T2DM (NKPDM). Annual admissions were categorized into winter–spring (December–May) and summer–autumn (June–November) periods.[10] Vitamin D status was clinically categorized as follows: deficiency (serum 25-hydroxyvitamin D [25(OH)D] concentration < 20 ng/mL), insufficiency (21–<30 ng/mL), and sufficiency (≥30 ng/mL).[11]
2.2. Research methods
2.2.1. Clinical data collection
Detailed interviews were conducted to collect data on comorbidities, treatment history, significant family history, and smoking/alcohol habits. Physical measurements were performed, including height and weight (measured without shoes or outerwear). Body mass index (BMI) was calculated as weight (kg) divided by height squared (m2). Blood pressure was measured twice using a standard mercury sphygmomanometer while participants were at rest, and the average value was recorded.
2.2.2. Laboratory biochemical tests
Fasting venous blood samples were collected the following morning to measure the levels of 25(OH)D, plasma glucose, C-peptide, hemoglobin A1c (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), uric acid (UA), triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, neutrophil and lymphocyte counts, and diabetes-related antibodies, including glutamic acid decarboxylase antibody, islet cell antibody, and insulin autoantibody. The plasma glucose concentration was tested by the hexokinase method. HbA1c was measured by high-performance liquid chromatography. ALT, AST, Cr, UA, and serum lipid levels were detected by an automatic biochemical instrument. Serum 25(OH)D levels and C-peptide and diabetes-related antibody levels were measured by the electrochemiluminescence method. The hemogram (neutrophils and lymphocytes) parameters were measured using an automated hematology analyzer. The vitamin D samples were evenly distributed across the years.
2.2.3. Insulin sensitivity and β-cell function indices
The updated Homeostatic Model Assessment 2 was calculated using HOMA2 Calculator software (Oxford University Innovation, Oxford, United Kingdom) (downloaded from https://www.dtu.ox.ac.uk/homacalculator). Fasting plasma glucose and fasting C-peptide levels were input into the software to derive the insulin resistance index (homeostasis model assessment of insulin resistance) and β-cell function index (homeostasis model assessment of insulin secretion [HOMA2-%B]).
2.3. Statistical analysis
Statistical analyses were performed using SPSS 25.0 software (IBM Corp., Armonk). No variables in the final analytical dataset contained missing values. Continuous data were expressed as medians (interquartile range), and between-group comparisons were conducted using the Mann–Whitney U test. Categorical data were presented as percentages and analyzed using the χ2 test. Variables with P < .1 in the univariate analysis were further subjected to binary logistic regression analysis to identify factors influencing ketosis proneness in newly diagnosed T2DM patients. Power analysis indicated that 29 KPDM and 115 NKPDM participants would provide 90% power to detect clinically significant differences. P < .05 was considered to indicate statistical significance.
3. Results
3.1. Vitamin D nutritional status and seasonal variations in newly diagnosed type 2 diabetes patients
Among the 1266 newly diagnosed T2DM patients, 13.4% (n = 170) had sufficient vitamin D levels, 23.5% (n = 297) had insufficient levels, and 63.1% (n = 799) were vitamin D deficient. In the KPDM group, 9.1% (n = 22) had sufficient vitamin D levels, 21% (n = 51) had insufficient levels, and 69.9% (n = 170) were deficient. In the NKPDM group, 14.5% (n = 148) had sufficient vitamin D levels, 24% (n = 246) had insufficient levels, and 61.5% (n = 629) were deficient. Compared with their NKPDM counterparts, the KPDM group demonstrated a significantly greater prevalence of vitamin D deficiency (61.5% vs 69.9%; P < .05; Fig. 1).
Figure 1.
Bar graphs show the prevalence rates of vitamin D sufficiency, insufficiency, and deficiency between the NKPDM and KPDM groups. KPDM = ketosis-prone type 2 diabetes mellitus, NKPDM = non-ketosis-prone type 2 diabetes mellitus, VD = vitamin D.
As shown in Figure 2, clinically relevant seasonal patterns were observed in both cohorts, and seasonal variations revealed significantly elevated 25(OH)D concentrations during the summer–autumn period than during the winter–spring period. In the NKPDM group, patients admitted during the winter–spring period exhibited significantly lower serum 25(OH)D concentrations than those admitted during the summer–autumn period (14.50 ng/mL [10.90, 19.00] vs 20.30 ng/mL [15.40, 27.35]; P < .001). This seasonal variation was observed in the KPDM cohort as well (13.70 ng/mL [10.20–18.70] vs 17.25 ng/mL [12.05–24.20]; P < .001). During the winter–spring period, no significant difference in 25(OH)D levels was observed between the 2 groups. However, in the summer–autumn period, the 25(OH)D concentration was significantly lower in the KPDM group than in the NKPDM group (17.25 ng/mL [12.05, 24.20] vs 20.30 ng/mL [15.40, 27.35]; P < .001).
Figure 2.
Bar graphs illustrate seasonal variations in serum 25(OH)D concentrations between patients with NKPDM and KPDM. 25(OH)D = 25-hydroxyvitamin D, KPDM = ketosis-prone type 2 diabetes mellitus, NKPDM = non-ketosis-prone type 2 diabetes mellitus, VD = vitamin D.
3.2. Comparison of clinical characteristics between KPDM and NKPDM patients
Serum 25(OH)D concentrations were markedly lower in KPDM patients than in NKPDM patients (15.05 ng/mL [10.98, 21.48] vs 17.50 ng/mL [13.00, 23.57]; P < .001). In addition, compared with the NKPDM group, the KPDM group was younger, had a lower HOMA2-%B score, and had higher HbA1c and AST levels. No significant differences in sex, BMI, systolic blood pressure, diastolic blood pressure, ALT levels, neutrophil-to-lymphocyte ratio (NLR), Cr levels, UA levels, or lipid profiles were detected between the 2 groups (Table 1).
Table 1.
Clinical and anthropometric characteristics of the KPDM and NKPDM groups.
| Total | NKPDM | KPDM | P value | |
|---|---|---|---|---|
| n (men/women) | 1266 (789/477) | 1023 (632/391) | 243 (157/86) | .421 |
| Age (yr) | 49.00 (38.00, 57.00) | 51.00 (39.00, 58.00) | 40.00 (32.75, 55.00) | .000 |
| BMI (kg/m2) | 26.50 (24.21, 29.30) | 26.50 (24.22, 29.34) | 26.68 (24.09, 29.13) | .689 |
| SBP (mm Hg) | 132 (122, 144) | 132 (122, 145) | 132 (121, 141) | .171 |
| DBP (mm Hg) | 86 (79, 95) | 86 (79, 95) | 87 (79, 95) | .635 |
| HOMA2-IR (pmol/L, mmol/L) | 1.50 (1.00, 2.10) | 1.50 (1.00, 2.10) | 1.30 (0.80, 2.00) | .129 |
| HOMA2-%B (pmol/L, mmol/L) | 71.20 (45.60, 100.48) | 73.00 (47.25, 101.55) | 60.30 (38.10, 91.90) | .003 |
| HbA1c (%) | 9.50 (7.60, 11.30) | 9 (7.4, 10.9) | 10.9 (9.60, 12.13) | .000 |
| ALT (U/L) | 26.50 (18.20, 44.50) | 26.35 (18.30, 43.75) | 27.50 (17.85, 48.95) | .435 |
| AST (U/L) | 20.70 (15.80, 30.15) | 20.30 (15.80, 29.10) | 21.90 (16.50, 36.20) | .033 |
| NLR | 1.62 (1.27, 2.20) | 1.60 (1.26, 2.16) | 1.67 (1.29, 2.34) | .09 |
| Cr (μmol/L) | 58.00 (48.00, 68.00) | 59.00 (49.00, 68.00) | 56.00 (46.00, 68.25) | .210 |
| UA (μmol/L) | 313.00 (247.50, 386.00) | 310.00 (249.00, 384.00) | 320.50 (237.75, 394.00) | .633 |
| TG (mmol/L) | 1.77 (1.18, 2.77) | 1.79 (1.20, 2.80) | 1.67 (1.09, 2.62) | .184 |
| TC (mmol/L) | 4.98 (4.06, 5.88) | 4.97 (4.08, 5.83) | 5.01 (4.03, 6.00) | .811 |
| HDL-C (mmol/L) | 0.97 (0.83, 1.14) | 0.98 (0.84, 1.13) | 0.96 (0.80, 1.22) | .699 |
| LDL-C (mmol/L) | 3.14 (2.41, 3.83) | 3.13 (2.43, 3.81) | 3.16 (2.38, 3.91) | .760 |
| 25(OH)D (ng/mL) | 17.00 (12.58, 22.85) | 17.50 (13.00, 23.57) | 15.05 (10.98, 21.48) | .000 |
Data are medians (IQR).
25(OH)D = 25-hydroxyvitamin D, ALT = alanine aminotransferase, AST = aspartate aminotransferase, BMI = body mass index, Cr = creatinine, DBP = diastolic blood pressure, HbA1c = hemoglobin A1c, HDL-C = high-density lipoprotein cholesterol, HOMA2-%B = homeostasis model assessment of insulin secretion, HOMA2-IR = homeostasis model assessment of insulin resistance, IQR = interquartile ranges, LDL-C = low-density lipoprotein cholesterol, NKPDM = non-ketosis-prone type 2 diabetes mellitus, NLR = neutrophil-to-lymphocyte ratio, SBP = systolic blood pressure, TC = total cholesterol, TG = triglycerides, UA = uric acid.
3.3. Clinical characteristics of T2DM patients stratified by vitamin D levels
As detailed in Table 2, participants were categorized into 3 groups according to serum 25(OH)D concentrations: deficiency (<20 ng/mL), insufficiency (20–<30 ng/mL), and sufficiency (≥30 ng/mL). Significant differences were observed among the groups in terms of ketosis proneness, sex, age, BMI, HOMA2-%B score, Cr levels, and total cholesterol levels. The vitamin D deficiency group had a significantly greater rate of ketosis proneness than did the other 2 groups, highlighting vitamin D’s multifaceted role in metabolic homeostasis.
Table 2.
Comparison of clinical characteristics among different vitamin D groups.
| VD sufficiency | VD insufficiency | VD deficiency | P value | |
|---|---|---|---|---|
| n (men/women) | 170 (138/32) | 297 (206/91) | 799 (445/354) | .000 |
| Prevalence of KPDM (%) | 12.9 | 17.2 | 21.3 | .026 |
| Age (yr) | 53.0 (41.8, 60.0) | 51.0 (39.0, 58.0) | 47.0 (36.0, 57.0) | .000 |
| BMI (kg/m2) | 25.76 (23.44, 27.50) | 26.72 (24.19, 29.37) | 26.78 (24.40, 29.68) | .006 |
| SBP (mm Hg) | 130.0 (119.5, 142.5) | 132 (122.5, 144.0) | 132 (122, 144) | .207 |
| DBP (mm Hg) | 84.0 (78.0, 92.0) | 87.0 (80.0, 96.0) | 86.0 (79.0, 95.0) | .077 |
| HOMA2-IR (pmol/L, mmol/L) | 1.50 (0.93, 2.10) | 1.4 (0.9, 2.0) | 1.5 (1.0, 2.2) | .376 |
| HOMA2-%B (pmol/L, mmol/L) | 76.20 (51.45, 109.50) | 64.70 (43.20, 86.60) | 71.6 (45.05, 101.70) | .014 |
| HbA1c (%) | 9.50 (7.80, 11.40) | 9.65 (7.40, 11.30) | 9.40 (7.70, 11.20) | .706 |
| ALT (U/L) | 27.50 (18.30, 44.03) | 27.70 (18.37, 44.75) | 25.90 (18.0, 44.6) | .873 |
| AST (U/L) | 20.00 (15.80, 32.40) | 20.80 (15.60, 28.78) | 21.00 (16.00, 30.40) | .812 |
| NLR | 1.68 (1.26, 2.29) | 1.59 (1.29, 2.14) | 1.62 (1.26, 2.20) | .856 |
| Cr (μmol/L) | 62.0 (52.0, 70.0) | 60.0 (52.5, 69.0) | 57.0 (46.0, 66.0) | .000 |
| UA (μmol/L) | 323.00 (259.25, 376.75) | 317.50 (255.00, 401.00) | 302.00 (243.00, 386.00) | .307 |
| TG (mmol/L) | 1.65 (1.05, 2.61) | 1.75 (1.15, 2.61) | 1.79 (1.22, 2.86) | .119 |
| TC (mmol/L) | 4.72 (3.92, 5.57) | 4.92 (3.99, 5.85) | 5.07 (4.17, 5.94) | .010 |
| HDL-C (mmol/L) | 0.96 (0.80, 1.09) | 0.98 (0.83, 1.11) | 0.98 (0.84, 1.20) | .092 |
| LDL-C (mmol/L) | 2.98 (2.30, 3.74) | 3.13 (2.44, 3.89) | 3.17 (2.45, 3.83) | .222 |
Data are medians (IQR).
ALT = alanine aminotransferase, AST = aspartate aminotransferase, BMI = body mass index, Cr = creatinine, DBP = diastolic blood pressure, HbA1c = hemoglobin A1c, HDL-C = high-density lipoprotein cholesterol, HOMA2-%B = homeostasis model assessment of insulin secretion, HOMA2-IR = homeostasis model assessment of insulin resistance, IQR = interquartile ranges, KPDM = ketosis-prone type 2 diabetes mellitus, LDL-C = low-density lipoprotein cholesterol, NLR = neutrophil-to-lymphocyte ratio, SBP = systolic blood pressure, TC = total cholesterol, TG = triglycerides, UA = uric acid, VD = vitamin D.
3.4. Influencing factors for ketosis proneness in newly diagnosed T2DM patients
Using the occurrence of ketosis as the dependent variable and variables with P < .1 in the univariate analysis (age, systolic blood pressure, HOMA2-%B, HbA1c, AST, NLR, and 25(OH)D) as independent variables, binary logistic regression analysis was conducted. Multivariate analysis revealed 4 independent predictors of ketosis onset: hypovitaminosis D, younger age, elevated NLR, and higher HbA1c levels. This implicates interplay between micronutrient status, chronic inflammation, and glycemic dysregulation in ketosis pathogenesis (Table 3).
Table 3.
Multivariate logistic regression analysis of risk factors for ketosis proneness in newly diagnosed T2DM patients.
| Variables | B | OR | 95% CI | P |
|---|---|---|---|---|
| 25(OH)D | −0.034 | 0.967 | 0.940–0.994 | .015 |
| Age | −0.042 | 0.959 | 0.942–0.977 | .000 |
| NLR | 0.269 | 1.309 | 1.123–1.525 | .001 |
| HbA1c | 0.365 | 1.441 | 1.293–1.607 | .000 |
25(OH)D = 25-hydroxyvitamin D, CI = confidence interval, HbA1c = hemoglobin A1c, NLR = neutrophil-to-lymphocyte ratio, OR = odds ratio, T2DM = type 2 diabetes mellitus.
4. Discussion
This study explored the relationship between serum 25(OH)D levels and ketosis proneness in newly diagnosed T2DM patients and revealed a significant association between vitamin D deficiency and ketosis onset. The results demonstrated that compared with NKPDM patients, KPDM patients not only had significantly lower vitamin D levels but also exhibited pronounced vitamin D deficiency even during the summer and autumn periods. Furthermore, vitamin D deficiency was closely linked to abnormalities in metabolic indices, including β-cell function (HOMA2-%B), BMI, and lipid profiles, suggesting that vitamin D may play a critical role in the pathogenesis of ketosis in patients with T2DM.
Historically, spontaneous ketosis proneness was considered a hallmark of T1DM. However, recent studies have reported that both type 1 diabetes and type 2 diabetes can manifest with ketosis as an initial symptom.[6,12] Since the late 1960s, researchers have identified patients whose clinical features were categorized as intermediate, placing them between patients with type 1 diabetes and type 2 diabetes. The term “ketosis-prone diabetes mellitus” was proposed in 2002, leading to clearer recognition and diverse classification schemes for this subtype.[8] In 2019, the World Health Organization classified autoimmune diabetes and KPDM under the hybrid category.[13] KPDM has garnered widespread attention because of its distinct clinical and metabolic features. Our comparison of clinical characteristics between KPDM and NKPDM patients revealed that KPDM patients were younger and had lower HOMA2-%B levels and higher HbA1c and AST levels than the NKPDM patients. These findings indicate more severe pancreatic β-cell dysfunction in patients with KPDM, which aligns with the findings of prior studies.[14,15] However, some studies argue that insulin resistance is more pronounced in KPDM,[16] whereas others report that both insulin resistance and β-cell dysfunction are more severe in KPDM than in NKPDM.[17,18] These discrepancies may stem from variations in study design, sample size, population demographics, or assessment methods, necessitating large-scale studies for validation.
Previous research suggests a gender disparity in ketosis-prone diabetes, with a higher prevalence in males.[19] In this study, 64.6% of the KPDM patients were males, whereas 35.4% were females. However, males were also predominant in the NKPDM group, with no statistically significant difference in gender ratios between the groups, which is consistent with prior observations reported by Lu et al.[16] Thus, our cohort does not support a gender-specific predisposition to ketosis in T2DM, warranting multicenter, large-scale studies to clarify this aspect.
Among the 1266 newly diagnosed T2DM patients, the overall vitamin D deficiency rate was 63%, closely mirroring Esteghamati et al’s finding of 62.9%.[20] Our study revealed significantly higher vitamin D deficiency rates in the KPDM group, along with elevated ketosis detection rates in vitamin D-deficient T2DM patients. Moreover, 25(OH)D levels independently predicted ketosis risk, which is consistent with existing evidence.[14] While our continuous model provides a comprehensive assessment, future studies may benefit from evaluating predefined clinical thresholds to enhance interpretability for practitioners. Vitamin D contributes to glucose homeostasis by modulating pancreatic β-cell function and peripheral insulin sensitivity.[21] Its deficiency may exacerbate the vicious cycle of insulin insufficiency and insulin resistance, thereby increasing the risk of ketosis. In addition, the anti-inflammatory properties of vitamin D may indirectly influence the likelihood of ketosis by suppressing lipolysis and ketogenesis.[22] Notably, this study is the first to identify the NLR as an independent risk factor for ketosis in newly diagnosed T2DM patients. An elevated NLR, a marker of systemic inflammation, reflects a proinflammatory state dominated by neutrophils and impaired anti-inflammatory lymphocyte activity. In T2DM, hyperglycemia promotes advanced glycation end-product accumulation, activating neutrophils to release reactive oxygen species and proteases.[23,24] Oxidative stress induces lymphocyte DNA damage and apoptosis,[25] increasing the NLR. Notably, vitamin D deficiency may initiate a proinflammatory cascade that increases the NLR. This finding is supported by the results of cell experiments demonstrating that active vitamin D suppresses proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-8, and IL-12) and promotes the anti-inflammatory cytokine IL-10.[26] Consequently, vitamin D deficiency can lead to chronic inflammation, thereby increasing the NLR. This mechanistic link explains why both vitamin D deficiency and elevated NLR independently predicted ketosis in our model, with vitamin D deficiency potentially acting as an upstream driver of inflammation. These findings suggest that inflammatory responses may mediate the link between vitamin D deficiency and ketosis proneness. While HOMA2-%B reflects β-cell dysfunction, its exclusion from the final model may be attributed to the role of HbA1c as an upstream mediator of glucotoxicity, which directly influences ketosis risk. HbA1c integrates both glycemic exposure and its downstream effects on β-cell function, making it a more robust predictor in the context of our adjusted model.
In this study, the seasonal variations in vitamin D levels exhibited population-specific patterns: both groups had higher 25(OH)D levels during the summer–autumn period than during the spring–winter period, yet ketosis-prone individuals remained significantly deficient even during the summer–autumn period. This implies intrinsic defects in vitamin D metabolism, potentially due to reduced cutaneous synthesis, inadequate dietary intake, or vitamin D-binding protein gene polymorphisms.[27] These observations suggest that exposure to sunlight alone may insufficiently correct vitamin D deficiency in high-risk ketosis populations, necessitating targeted supplementation.
5. Limitations
Given the observational nature and single-center setting of this study, the representativeness of the sample population may be limited, and causal inferences cannot be drawn. In addition, vitamin D measurements could be confounded by the acute phase of illness, while key influencing factors such as diet and physical activity levels were not evaluated; despite multivariate adjustments, residual confounding may persist. To obtain a more comprehensive understanding of the role of vitamin D, future studies should adopt multicenter designs, incorporate repeated measurements during recovery phases, systematically document environmental exposures, and conduct prospective cohort studies or intervention trials on vitamin D supplementation for ketosis prevention.
6. Conclusion
Vitamin D deficiency is independently associated with increased odds of susceptibility to ketosis in new-onset T2DM. Its synergistic effects with inflammatory responses and glucotoxicity are linked to accelerated metabolic decompensation. Seasonal vitamin D monitoring and personalized supplementation strategies for high-risk populations may represent potential approaches to mitigate ketosis risk in patients with T2DM. From a clinical perspective, these findings suggest that vitamin D status warrants consideration for monitoring in new T2DM patients who are at risk for ketosis.
Acknowledgments
We are very grateful to all participants for their support of this study.
Author contributions
Conceptualization: Cuiliu Li, Guangya Wang.
Data curation: Cuiliu Li, Yunna Zhang, Xiaopeng Zhao.
Formal analysis: Cuiliu Li, Yunna Zhang, Jinxiu Xu.
Investigation: Cuiliu Li.
Software: Cuiliu Li, Xiaopeng Zhao, Nairui Zhao.
Validation: Xiaopeng Zhao, Guangya Wang.
Methodology: Nairui Zhao.
Supervision: Nairui Zhao, Guangya Wang.
Project administration: Jinxiu Xu.
Resources: Jinxiu Xu.
Writing – original draft: Cuiliu Li.
Writing – review & editing: Cuiliu Li, Yunna Zhang, Xiaopeng Zhao, Nairui Zhao, Guangya Wang.
Abbreviations:
- 25(OH)D
- 25-hydroxyvitamin D
- ALT
- alanine aminotransferase
- AST
- aspartate aminotransferase
- BMI
- body mass index
- Cr
- creatinine
- HbA1c
- hemoglobin A1c
- HOMA2-%B
- homeostasis model assessment of insulin secretion
- IL
- interleukin
- KPDM
- ketosis-prone type 2 diabetes mellitus
- NKPDM
- non-ketosis-prone type 2 diabetes mellitus
- NLR
- neutrophil-to-lymphocyte ratio
- T1DM
- type 1 diabetes mellitus
- T2DM
- type 2 diabetes mellitus
- UA
- uric acid
Informed consent was obtained from all individual participants included in the study.
The study was approved by the Ethics Committee of Cangzhou Central Hospital and was conducted in accordance with the Declaration of Helsinki.
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Li C, Zhang Y, Zhao X, Zhao N, Xu J, Wang G. Serum 25-hydroxyvitamin D levels and their association with ketosis in patients with newly diagnosed type 2 diabetes. Medicine 2026;105:17(e48304).
Contributor Information
Cuiliu Li, Email: licuiliu1989@163.com.
Yunna Zhang, Email: zhangyunna1987@163.com.
Xiaopeng Zhao, Email: nairuizhao1984@163.com.
Nairui Zhao, Email: nairuizhao1984@163.com.
Jinxiu Xu, Email: jinxiuxu1976@163.com.
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