The roles of vitamin D and cathelicidin in type 1 diabetes susceptibility

Cristelo, Cecília; Machado, Alexandra; Sarmento, Bruno; Gama, Miguel

doi:10.1530/ec-20-0484

Cited by 8 publications

(5 citation statements)

References 64 publications

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“…Vitamin D is thought to be protective against the development of type I diabetes by modulating the immune system by dampening the autoimmune response, decreasing selfdestructive islet cell auto-antibodies produced by beta-cells, and, thus, preserving the betacell mass of the pancreas. In murine models of type I diabetes mellitus, supplementation with the active form of vitamin D, calcitriol, prevented the onset of diabetes, which further supported the role of vitamin D in the prevention of type I diabetes [19,20]. For type II diabetes, vitamin D was thought to enhance insulin sensitivity; however, a recent metaanalysis of 18 randomized controlled trials found no benefit of vitamin D supplementation on the markers of insulin sensitivity [21].…”

Section: Discussionmentioning

confidence: 92%

Vitamin D Status and Risk of Cystic Fibrosis-Related Diabetes: A Retrospective Single Center Cohort Study

Peng

Alvarez

et al. 2021

Nutrients

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Objective: Cystic fibrosis-related diabetes (CFRD) affects up to half of the people with cystic fibrosis (CF) by adulthood. CFRD is primarily caused by pancreatic dysfunction that leads to insufficient insulin release and/or insulin resistance. Exocrine pancreatic insufficiency in people with CF is associated with fat-soluble vitamin malabsorption, including vitamins A, D, E, and K. This study examined the relationship between vitamin D status, assessed by serum 25-hydroxyvitamin D (25(OH)D), and the development of CF-related diabetes (CFRD) in adults with CF. Methods: This was a retrospective cohort study of adults seen at a single CF center. The data were extracted from the electronic medical records and the Emory Clinical Data Warehouse, a data repository of health information from patients seen at Emory Healthcare. We collected age, race, the first recorded serum 25-hydroxyvitamin D (25(OH)D) concentration, body mass index (BMI), and onset of diabetes diagnosis. Log-rank (Mantel–Cox) tests were used to compare the relative risk of CFRD onset in the subjects with stratified vitamin D status and weight status. A sub-group analysis using chi-square tests assessed the independence between vitamin D deficiency and CFRD risk factors, including gender and CF mutation types (homozygous or heterozygous for F508del, or others). Unpaired t-tests were also used to compare the BMI values and serum 25(OH)D between the CF adults based on the CFRD development. Results: This study included 253 subjects with a mean age of 27.1 years (±9.0), a mean follow-up time period of 1917.1 (±1394.5) days, and a mean serum 25(OH)D concentration of 31.8 ng/mL (±14.0). The majority (52.6%) of the subjects developed CFRD during the study period. Vitamin D deficiency (defined as 25(OH)D < 20 ng/mL) was present in 25.3% of the subjects. Close to two thirds (64.1%) of the subjects with vitamin D deficiency developed CFRD during the study. Vitamin D deficiency increased the risk of developing CFRD (chi-square, p = 0.03) during the course of the study. The time to the onset of CFRD stratified by vitamin D status was also significant (25(OH)D < 20 ng/mL vs. 25(OH)D ≥ 20 ng/mL) (95% CI: 1.2, 2.7, p < 0.0078). Conclusion: Our findings support the hypothesis that adults with CF and vitamin D deficiency are at a higher risk of developing CFRD and are at risk for earlier CFRD onset. The maintenance of a serum 25(OH)D concentration above 20 ng/mL may decrease the risk of progression to CFRD.

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Section: Discussionmentioning

confidence: 92%

Vitamin D Status and Risk of Cystic Fibrosis-Related Diabetes: A Retrospective Single Center Cohort Study

Peng

Alvarez

et al. 2021

Nutrients

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“…Given the previously reported role of CAMP in diabetes type 1 [ 25 ], as well as the present finding of its significant increase during an OGTT, future studies might involve hyperinsulinemic-euglycemic clamp techniques in order to evaluate CAMP kinetics under conditions of elevated insulin and constant glucose levels. In particular, such approaches might elucidate putative associations of insulin sensitivity and systemic CAMP regulation.…”

Section: Discussionmentioning

confidence: 97%

“…This finding suggests a considerable short-term induction of CAMP expression and secretion by insulin, glucose, and/or incretins. Of note, CAMP has previously been reported to be linked to diabetes mellitus type 1 [ 25 ], and its circulating levels have been suggested as a marker for diabetic nephropathy [ 26 ]. While a recent study reported decreased CAMP serum concentrations in T2D patients [ 27 ], results from previously published studies are somewhat incongruent with this observation [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating Concentrations of Cathelicidin Anti-Microbial Peptide (CAMP) Are Increased during Oral Glucose Tolerance Test

Höpfinger,

Karrasch,

Schäffler

et al. 2023

IJMS

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Recent investigation has revealed the significant role of Cathelicidin antimicrobial peptide (CAMP) in infection defense and innate immunity processes in adipose tissue. Meanwhile, knowledge of its regulation and functions in metabolic contexts as an adipokine remains sparce. The present study investigated the postprandial regulation of circulating CAMP levels during oral glucose tolerance tests (OGTTs). Eighty-six metabolically healthy volunteers participated in a standardized 75 g-2 h-OGTT setting. The effects of exogenous glucose, insulin, and incretins on CAMP expression in human adipocyte culture (cell-line SGBS) were studied in vitro. CAMP concentrations in blood serum samples were measured by ELISA techniques and adipocyte gene expression levels were quantified by real-time PCR. Of note, base-line CAMP serum quantities were negatively correlated with HDL cholesterol levels as well as with the anti-inflammatory adipokine adiponectin. During the 2 h following glucose ingestion, a significant rise in circulating CAMP concentrations was observed in considerable contrast to reduced quantities of fatty acid binding proteins (FABP) 2 and 4 and dipeptidyl peptidase 4 (DPP4). In SGBS adipocytes, neither differing glucose levels nor insulin or incretin treatment significantly induced CAMP mRNA levels. According to our data, glucose represents a positive postprandial regulator of systemic CAMP. This effect apparently is not mediated by the regulatory impact of glucose metabolism on adipocyte CAMP expression.

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“…Vitamin D is a candidate for protection against T1D due to its anti-inflammatory effects, role in regulation of the immune system and induction of T regulatory cells, which modulate autoimmune risk (8). Cathelicidin was recently proposed to link vitamin D with the gut microbiota and protective effects on beta-cell function (173). Further evidence stems from the higher incident cases of T1D observed at northern latitudes and in winter months compared to summer, where sunlight exposure inversely correlates with T1D cases on a monthly basis (174).…”

Section: Vitamin Dmentioning

confidence: 99%

Environmental Determinants of Type 1 Diabetes: From Association to Proving Causality

2021

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The rising incidence of type 1 diabetes (T1D) cannot be ascribed to genetics alone, and causative environmental triggers and drivers must also be contributing. The prospective TEDDY study has provided the greatest contributions in modern time, by addressing misconceptions and refining the search strategy for the future. This review outlines the evidence to date to support the pathways from association to causality, across all stages of T1D (seroconversion to beta cell failure). We focus on infections and vaccinations; infant growth and childhood obesity; the gut microbiome and the lifestyle factors which cultivate it. Of these, the environmental determinants which have the most supporting evidence are enterovirus infection, rapid weight gain in early life, and the microbiome. We provide an infographic illustrating the key environmental determinants in T1D and their likelihood of effect. The next steps are to investigate these environmental triggers, ideally though gold-standard randomised controlled trials and further prospective studies, to help explore public health prevention strategies.

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The roles of vitamin D and cathelicidin in type 1 diabetes susceptibility

Cited by 8 publications

References 64 publications

Vitamin D Status and Risk of Cystic Fibrosis-Related Diabetes: A Retrospective Single Center Cohort Study

Vitamin D Status and Risk of Cystic Fibrosis-Related Diabetes: A Retrospective Single Center Cohort Study

Circulating Concentrations of Cathelicidin Anti-Microbial Peptide (CAMP) Are Increased during Oral Glucose Tolerance Test

Environmental Determinants of Type 1 Diabetes: From Association to Proving Causality

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