Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?

There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor β (TGFβ), insulin-like growth factor (IGF) and Wnt-β-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes.

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Assessment of vitamin D status and its association with insulin resistance among type 2 diabetic subjects

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20184877 ◽

2018 ◽

Vol 6 (12) ◽

pp. 3825

Author(s):

Jaitra Bhattacharya

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Serum Vitamin ◽

Serum Vitamin D ◽

Vitamin D Levels ◽

Type 2 Diabetic

Background: The 21st century has seen the rise of diabetes mellitus as one of the major metabolic issues as is vitamin D deficiency which has been found to be pandemic worldwide. The present study is an endeavor to study the status of serum vitamin D levels in relation to the glycemic and insulin resistance status in type 2 diabetes mellitus patients.Methods: The present is a cross-sectional study with a sample size of 100 type 2 diabetic subjects in the age group of 30-60 years. Serum vitamin D and Insulin levels were estimated using the ELISA technique. HbA1c levels were measured using immunoturbidimetric assays and plasma glucose levels were determined using glucose oxidase- peroxidase method.Results: The fasting plasma glucose, HbA1c and serum insulin levels were found to be significantly higher in those with vitamin D levels below the normal cut-off value of less than 30ng/ml (p value <0.01). Also, the insulin resistance calculated using HOMA-IR was found to be higher in those subjects having vitamin D deficiency or insufficiency.Conclusions: Hence, the study suggests that vitamin D deficiency contributes to further insulin resistance and poorer long-term diabetic control in type 2 diabetes mellitus subjects.

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The role of vitamin D deficiency and elevated inflammatory biomarkers as risk factors for the progression of diabetic nephropathy in patients with type 2 diabetes mellitus

Open Chemistry ◽

10.1515/chem-2021-0107 ◽

2021 ◽

Vol 19 (1) ◽

pp. 1183-1192

Author(s):

Ahmad El Askary ◽

Amal F. Gharib ◽

Mazen Almehmadi ◽

Maha Mahfouz Bakhuraysah ◽

Abdulaziz Ali Al Hajjiahmed ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Type 2 Diabetes ◽

Vitamin D ◽

Type 2 Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Vitamin D Deficiency ◽

Diabetic Patients ◽

Tnf Α

Abstract Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Albuminuria is the most sensitive marker for the early recognition of DN. Therefore, we aimed to study the risk factors of albuminuria as a marker of DN among diabetic patients. The study included 41 patients with type 2 diabetes mellitus (T2DM), 50 type 2 diabetic nephropathy (T2DN) patients with macroalbuminuria, 43 T2DN patients with microalbuminuria and 38 healthy controls. Logistic regression was used to detect the most significant risk factors for albuminuria. A high statistically significant difference was found between the groups regarding age, sex, body mass index (BMI), diabetes mellitus (DM) duration, glucose, glycated haemoglobin (HbA1c), creatinine, glomerular filtration rate (GFR), lipid profile, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), the albumin–creatinine ratio (ACR), vitamin D, total parathyroid hormone (PTH), urea, total calcium and chemerin (p < 0.001). It was found that the duration of DM, BMI, glucose, GFR, total cholesterol (TC), low-density lipoprotein (LDL), TNF-α, IL-6, CRP, ACR, vitamin D, PTH and chemerin are significant albuminuria risk factors in DN. Vitamin D deficiency and associated inflammatory mediators such as chemerin, TNF-α, IL-6 and CRP are the most essential risk factors for albuminuria in T2DM patients.

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Vitamin D Deficiency Is Significantly Associated with Retinopathy in Type 2 Diabetes Mellitus: A Case-Control Study

Nutrients ◽

10.3390/nu14010084 ◽

2021 ◽

Vol 14 (1) ◽

pp. 84

Author(s):

José M. Castillo-Otí ◽

Ana I. Galván-Manso ◽

María R. Callejas-Herrero ◽

Luís A. Vara-González ◽

Fernando Salas-Herrera ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Type 2 Diabetes ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Case Control Study ◽

Case Control ◽

Treatment Of Diabetes ◽

Control Study

Aim: Results from meta-analyses point to an association between vitamin D deficiency and the onset of diabetic retinopathy (DR). The objectives of the present study were to evaluate the association of vitamin D for the development of DR and to determine the levels of vitamin D associated with a greater risk of DR. Methods: Between November 2013 and February 2015, we performed a case-control study based on a sample of patients with diabetes in Spain. The study population comprised all patients who had at least one evaluable electroretinogram and recorded levels of 25(OH)D. We collected a series of analytical data: 25(OH)D, 1,25(OH)2D, iPTH, calcium, albumin, and HbA1c. Glycemic control was evaluated on the basis of the mean HbA1c values for the period 2009–2014. A logistic regression analysis was performed to identify the variables associated with DR. Results: The final study sample comprised 385 patients, of which 30 (7.8%) had DR. Significant differences were found between patients with and without DR for age (69.54 vs. 73.43), HbA1c (6.68% vs. 7.29%), years since diagnosis of diabetes (10.9 vs. 14.17), level of 25(OH)D (20.80 vs. 15.50 ng/mL), level of 1,25(OH)2D (35.0 vs. 24.5 pg/mL), treatment with insulin (14.9% vs. 56.7%), hypertension (77.7% vs. 100%), cardiovascular events (33.2% vs. 53.3%), and kidney failure (22.0% vs. 43.3%). In the multivariate analysis, the factors identified as independent risk factors for DR were treatment of diabetes (p = 0.001) and 25(OH)D (p = 0.025). The high risk of DR in patients receiving insulin (OR 17.01) was also noteworthy. Conclusions: Levels of 25(OH)D and treatment of diabetes were significantly associated with DR after adjusting for other risk factors. Combined levels of 25(OH)D < 16 ng/mL and levels of 1,25(OH)2D < 29 pg/mL are the variables that best predict the risk of having DR with respect to vitamin D deficiency. The risk factor with the strongest association was the treatment of type 2 diabetes mellitus. This was particularly true for patients receiving insulin, who had a greater risk of DR than those receiving insulin analogues. However, further studies are necessary before a causal relationship can be established.

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Diabetes Prevention: Vitamin D Supplementation May Not Provide Any Protection If There Is No Evidence of Deficiency!

Nutrients ◽

10.3390/nu11112651 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2651 ◽

Cited By ~ 1

Author(s):

Uwe Gröber ◽

Michael F. Holick

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Vitamin D Supplementation ◽

Vitamin D Status ◽

The Metabolic Syndrome ◽

Supplement Group ◽

Increased Risk

The results of epidemiological and several interventional studies suggest an association between vitamin D deficiency and an increased risk of developing insulin resistance or type 2 diabetes. Various studies have indicated that a lack of vitamin D must be regarded as a pathogenic factor for type 2 diabetes and the metabolic syndrome, since a vitamin D deficiency (25(OH)D < 20 ng/mL) increases insulin resistance and reduces insulin secretion from beta cells in the pancreas. A recent study by Pittas et al. did not show a clear preventive effect of vitamin D supplementation with respect to the risk of developing type 2 diabetes. In terms of this study, it must be remembered that more than 70% of the participants in both the vitamin D supplement group and the placebo group did not have a vitamin D deficiency. In medical and pharmaceutical practice, more attention should be paid to vitamin D deficiency than has previously been accorded. Vitamin D status can be assessed objectively when necessary by laboratory testing of the serum 25(OH)D levels. Type 2 diabetes patients benefit from improving their vitamin D status with respect to their glucose metabolism and decreased mortality risk. Patients with insulin resistance who are vitamin D deficient should be treated with an appropriate amount of vitamin D to achieve circulating levels of 25(OH)D of 40–60 ng/mL.

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Vitamin D and diabetes mellitus: an update 2013

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/0004-2730000002535 ◽

2014 ◽

Vol 58 (1) ◽

pp. 1-8 ◽

Cited By ~ 14

Author(s):

Luiz Henrique Maciel Griz ◽

Francisco Bandeira ◽

Mônica Andrade Lima Gabbay ◽

Sergio Atala Dib ◽

Eduardo Freese de Carvalho

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Vitamin D ◽

Type 1 Diabetes ◽

Vitamin D Deficiency ◽

Pancreatic Beta Cells ◽

Increased Risk ◽

Geographical Regions

Vitamin D deficiency and diabetes mellitus are two common conditions and they are widely prevalent across all ages, races, geographical regions, and socioeconomic conditions. Epidemiologic studies have shown association of vitamin D deficiency and increased risk of chronic diseases, such as cancer, cardiovascular disease, type 2 diabetes, and autoimmune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The identification of 1,25(OH)2D receptors and 1-α-hydroxilase expression in pancreatic beta cells, in cells of the immune system, and in various others tissues, besides the bone system support the role of vitamin D in the pathogenesis of type 2 diabetes. Observational studies have revealed an association between 25(OH) D deficiency and the prevalence of type 1 diabetes in children and adolescents. This review will focus on the concept of vitamin D deficiency, its prevalence, and its role in the pathogenesis and risk of diabetes mellitus and cardiovascular diseases.

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The relationship between microvascular complications and vitamin D deficiency in type 2 diabetes mellitus microvascular complications and vitamin D deficiency

Endocrine Abstracts ◽

10.1530/endoabs.35.p130 ◽

2014 ◽

Author(s):

Celil Usluogullari ◽

Fevzi Balkan ◽

Sedat Caner ◽

Rifki Ucler ◽

Cafer Kaya ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Vitamin D ◽

Type 2 Diabetes Mellitus ◽

Vitamin D Deficiency ◽

Microvascular Complications ◽

The Relationship

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High Prevalence of Vitamin D Deficiency and Correlation with Cystatin-C and Other Cardiovascular and Renal Risk Biomarkers in Patients with Type 2 Diabetes Mellitus Complicated with Hypertension

Current Diabetes Reviews ◽

10.2174/1573399816666200516174352 ◽

2020 ◽

Vol 17 (1) ◽

pp. 81-90

Author(s):

Mohammad J. Alkhatatbeh ◽

Sajedah A. Smadi ◽

Khalid K. Abdul-Razzak ◽

Nesreen A. Saadeh

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Vitamin D ◽

Type 2 Diabetes Mellitus ◽

Vitamin D Deficiency ◽

Cystatin C ◽

P Values ◽

Renal Biomarkers ◽

Risk Biomarkers

Background: Vitamin D is increasingly investigated as having a role in Type 2 Diabetes Mellitus (T2DM) and its cardiovascular and renal complications. Objective: This study aimed to investigate the association between 25-hydroxyvitamin D (25-OHD) and biomarkers of cardiovascular and renal complications, including cystatin-C. Methods: This cross-sectional study involved 117 participants with T2DM that was not complicated with cardiovascular or renal diseases except hypertension. 25-OHD was measured by electrochemiluminescence immunoassay, while cystatin-C was measured by enzyme-linked-immunosorbent-assay. Other biomarkers, including lipids, creatinine, urea and glycemic measures, were determined by the routine biochemistry assays. Results: The prevalence of vitamin D deficiency was 74.36%. There was no significant difference in cardiovascular and renal biomarkers, including glucose, HbA1c, lipids, urea, creatinine and cystatin-C between participants with adequate and deficient vitamin D (p-values>0.05). Participants with adequate vitamin D were older in age, more obese and having lower eGFR (p-values<0.05). 25-OHD was weakly correlated with age, duration of DM, urea, creatinine and inversely correlated with eGFR (rvalues< 0.32, p-values<0.05). Although creatinine and cystatin-C were directly correlated (r=0.42, pvalue< 0.001), cystatin-C and 25-OHD were not correlated (p-value>0.05). Hypertensive participants were more obese, having a longer duration of DM and higher urea and cystatin-C compared to nonhypertensive participants (p-values<0.05). Binary logistic regression analysis revealed that hypertension could be predicted from increased BMI. Conclusion: 25-OHD was not found to be correlated with cardiovascular risk biomarkers, but it was correlated with renal biomarkers, including urea, creatinine and eGFR. Cystatin-C and 25-OHD were not observed to be correlated to each other, but both were correlated to renal function. Obesity was a significant predictor of hypertension.

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