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Vitamin D status, enterovirus infection, and type 1 diabetes in Italian children/adolescents
Giovanni Federico1, Angelo Genoni2, Anna Puggioni2
1Pediatric Diabetes Unit, Department of Pediatrics, University of Pisa Medical School, Pisa, Italy.
Insights
Enteroviral infections are linked to type 1 diabetes (T1D) onset in children. Lower vitamin D levels were observed in T1D cases, especially those with enterovirus (EV) infections, suggesting a potential role for vitamin D in T1D prevention.
Area of Science:
- Immunology
- Endocrinology
- Virology
Background:
- Type 1 diabetes (T1D) is an autoimmune disease with increasing incidence in children.
- Enteroviruses (EVs) are suspected environmental triggers for T1D.
- Vitamin D deficiency is common and may influence immune function and susceptibility to infections.
Purpose of the Study:
- To investigate the association between enteroviral infection, vitamin D status, and the clinical onset of type 1 diabetes in pediatric cases.
- To compare vitamin D levels in T1D patients with and without detectable enteroviral infections.
Main Methods:
- A case-control study involving 82 pediatric T1D cases and 117 matched controls.
- Enteroviral RNA detection in peripheral blood using a sensitive molecular method.
- Serum 25-hydroxyvitamin D [25(OH)D] concentration measurement to assess vitamin D status.
Main Results:
- Enteroviral RNA was detected in 65% of T1D cases but in none of the controls.
- T1D cases had significantly lower median serum 25(OH)D levels (54.4 nmol/L) compared to controls (74.1 nmol/L).
- Vitamin D deficiency (≤50 nmol/L) was more prevalent in T1D cases (48.8%) than in controls (17.9%).
- Virus-positive T1D cases exhibited lower vitamin D levels (median 48.2 nmol/L) than virus-negative T1D cases (median 61.8 nmol/L).
Conclusions:
- Enteroviral infection is frequently detected at the clinical onset of T1D in children.
- Lower vitamin D levels are associated with T1D onset and may be particularly pronounced in cases with enteroviral infections.
- These findings suggest that maintaining adequate vitamin D levels might be important in mitigating the diabetogenic risk posed by infectious agents like enteroviruses.
Abstract:
At the time of the clinical onset of type 1 diabetes (T1D), we investigated 82 pediatric cases in parallel with 117 non-diabetic controls matched by age, geographic area, and time of collection. The occurrence of an enteroviral infection was evaluated in peripheral blood using a sensitive method capable of detecting virtually all human enterovirus (EV) types. While non-diabetic controls were consistently EV-negative, 65% of T1D cases carried EVs in blood. The vitamin D status was assessed by measuring the concentration of 25-hydroxyvitamin D [25(OH)D] in serum. Levels of 25(OH)D were interpreted as deficiency (≤50 nmol/L), insufficiency (52.5-72.5 nmol/L), and sufficiency (75-250 nmol/L). In T1D cases, the median serum concentration of 25(OH)D was 54.4 ± 27.3 nmol/L vs 74.1 ± 28.5 nmol/L in controls (P = .0001). Diabetic children/adolescents showed deficient levels of vitamin D 25(OH)D (ie, 72.5 nmol/L) in 48.8% cases vs 17.9% in non-diabetic controls (P = .0001). Unexpectedly, the median vitamin D concentration was significantly reduced in virus-positive vs virus-negative diabetics (48.2 ± 22.5 vs 61.8 ± 31.2 nmol/L; P = .015), with deficient levels in 58.5% vs 31.0%, respectively. Thus, at the time of clinical onset, EV-positive cases had reduced vitamin D levels compared with EV-negative cases. This could indicate either that the virus-negative children/adolescents had been hit by a non-infectious T1D-triggering event, or that children/adolescents with proper levels of vitamin D had been able to rapidly clear the virus. Thus, it would be important to assess whether adequate vitamin D supplementation before or during the prediabetic phase of T1D may counteract the diabetogenic potential of infectious pathogens.
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