The Role of Vitamin D in Diabetes Ketosis and Ketoacidosis

Diabetes mellitus (DM) is a common endocrine and metabolic disorder, and diabetes ketosis (DK) is a significant acute complication. Individuals with type 1 DM (T1DM) are inherently at risk for diabetic ketoacidosis (DKA). Individuals with T2DM may develop DK under certain conditions, including infection, interruption of insulin therapy, stress, or excessive alcohol consumption. Recent studies have indicated that vitamin D supplementation reduces the risk of progression from prediabetes to T2DM and that it may also be involved in the prevention of diabetes complications. Yet most previous research has been observational correlations rather than interventional trials.

The relationship between metabolic, cardiovascular, and autoimmune diseases and 25[OH]D levels has been explored in several studies. A retrospective study conducted in Morocco examined 200 pediatric patients (aged 1–18 years) with T1DM during 2019 and 2023. The results suggested a possible link between vitamin D and the risk of developing DKA. Specifically, patients with DKA had lower levels of 25[OH]D compared to those without DKA at the onset of T1DM. Furthermore, more severe acidosis was associated with lower concentrations of 25[OH]D [1]. Vitamin D levels also appear to be associated with ketosis episodes in individuals with ketosis-prone type 2 diabetes (KPT2D). In these patients, serum 25[OH]D has been found to be an independent factor that helps prevent bouts of ketosis episodes [2]. These findings suggest that vitamin D deficiency may predispose patients to a greater risk of metabolic decompensation in both T1DM and T2DM settings.

Vitamin D supplementation combined with lifestyle changes has been recommended to those with a high risk of DM as a means of diabetes risk reduction and improvement of impaired glucose regulation (IGR). However, its effects seem to be more marked in nonobese individuals, and evidence that this also applies to obese populations remains limited [3, 4]. Notably, pediatric studies demonstrate compelling associations between vitamin D status and diabetes management. A 3-month intervention with vitamin D in pediatrics diagnosed with T1DM and vitamin D deficiency reduced HbA1c levels, underscoring its potential role in glycemic optimization [5]. Another prospective study, which included 90 patients with uncontrollable T1DM and vitamin D deficiency at the Specialized Center for Endocrinology and Diabetes in Baghdad, Iraq, showed a high frequency of vitamin D deficiency, closely related to poor glycemic control [6]. Studies in children have shown that pediatrics with DKA tend to have lower median 25[OH]D levels than those without DKA. This supports the recommendation to include vitamin D supplements in managing T1DM and acute diabetes crises [7]. Preclinical validation emerges from diabetic Wistar rat models, where vitamin D supplementation attenuated fasting hyperglycemia and suppressed ketogenesis markers, suggesting therapeutic modulation of metabolic decompensation [8].

Mechanistically, vitamin D deficiency exacerbates both the pathogenesis and severity of DKA through multifactorial pathways. One possible explanation is that acidosis may lead to the inactivity of 1-alpha-hydroxylase and increased loss of vitamin D-binding proteins through the kidneys. Additionally, the presence of vitamin D receptors (VDRs) on pancreatic β-cells highlights the important role of vitamin D in regulating insulin production and secretion [9]. Clinically, vitamin D deficiency can contribute to the disease and worsen problems with insulin production and release in T1DM. Severe DKA episodes transiently depress serum 25[OH]D levels. If vitamin D levels stay low after DKA recovery, it may suggest ongoing vitamin D deficiency [10].

In summary, vitamin D supplementation demonstrates pleiotropic benefits in attenuating diabetes progression and reducing DK and DKA incidence, particularly in pediatric and nonobese populations. Additional research and clinical trials are needed to clarify the underlying mechanisms and improve treatment approaches. We recommend considering vitamin D supplementation as a supportive therapy for managing DK and DKA. Further studies are also necessary to confirm this relationship and identify the ideal vitamin D dosage for preventing metabolic complications in diabetes.

Cui Zhang: conceptualization, writing – original draft, formal analysis, writing – review and editing. Jia Liu: writing – review and editing (equal). Sumita Cholekho: writing – review and editing (equal). Qin Pei: writing – review and editing (equal). Huiwen Tan: writing – review and editing (equal), supervision.

The authors have nothing to report.

The authors declare no conflicts of interest.

LLM has been used to proofread the article.