Exploring the relationship between vitamin D and leptin hormones in type 2 diabetes mellitus patients from Kuwait.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and obesity are prevalent in Kuwait. Vitamin D (VD) deficiency and leptin resistance are risk factors for both disorders. A correlation between the two risk factors has been suggested albeit inconsistently reported. Our objective was to determine the effect and association of VD and leptin levels and their related common variants with T2DM. METHODS: This case-control study included 203 Kuwaiti T2DM patients and 162 healthy Kuwaiti controls. Leptin and VD levels were measured using enzyme linked immunosorbent assays. Genotyping of LEP rs7799039, LEPR rs1137101, VDR rs2228570 and rs731236 was performed using Taqman genotyping assays. RESULTS: Leptin levels were higher in T2DM patients than controls, but vitamin D levels did not differ. No correlation was found between the levels of the two hormones. VDR rs731236G associated with T2DM risk (Odds ratio 1.66, p=0.0008). VDR haplotype analysis revealed GG/AA, GA/AA or GG/AG to associate with T2DM risk (p=0.01) and increased risk of diabetic neuropathy (p=0.002). VDR rs2228570GG associated with leptin levels in T2DM (p=0.01). Effect of LEP rs7799039 on leptin (p=0.01) and VD levels (p=0.02) was only evident in healthy controls. CONCLUSIONS: VDR rs731236G is associated with T2DM risk in Kuwait, and a VDR haplotype of a less active, low expressing VDR is associated with T2DM and diabetic neuropathy risk. Common variants in leptin and VD related genes appear to mediate the suggested positive correlation of both hormones however their influence is disrupted in T2DM.

Association between the lipoprotein lipase rs1534649 gene polymorphism in intron one with Body Mass Index and High Density Lipoprotein-Cholesterol.

Lipoprotein lipase (LPL) is an enzyme involved in lipid metabolism and distribution of fatty acids hence its role in the initiation and development of dyslipidemia and adiposity. Single nucleotide polymorphisms (SNPs) across the LPL gene have been associated with dyslipidemia, however, the association with obesity has been limited towards specific populations. This study examined the association between LPL gene polymorphisms with plasma lipid levels and body mass index (BMI) in the Kuwaiti population. We examined a total of 486 adults (303 and 183 females and males respectively) with plasma lipid levels and BMI. DNA samples were genotyped for two LPL gene polymorphisms (rs1534649 and rs28645722) using TaqMan allelic discrimination. The relationship between the genotypes with both plasma lipid levels and BMI were assessed using linear regression using "SNPassoc" package from R statistical software. Using an additive genetic model, linear regression analysis showed the T-allele of rs1534649 to be associated with increased BMI in a dose-dependent trend ß = 2.13 (95% CI 1.33-2.94); p = 1.7 × 10-7. In addition, a borderline significance was observed between the T-allele and low levels of high density lipoprotein-cholesterol ß = -0.04 (95% CI -0.08, -0.006); p = 0.02. There were no associations between rs28645722 and plasma lipid levels (p > 0.05). However, a trend was observed between the A-allele and increased BMI ß = 1.75 (95% CI 0.14-3.35); p = 0.03. Our study shows intron one polymorphism rs1534649 to increase the risk of obesity and dyslipidemia. Our findings warrant further investigation of the mechanism of LPL on the development of obesity along with the role of intron one and its impact on LPL gene activity.

Neutrophil gelatinase-associated lipocalin as a biomarker of nephropathy in sickle cell disease.

Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). In this case-control study, 74 sickle cell disease (SCD) patients (37 in steady state and 37 in VOC) and 53 control subjects had hematological and biochemical measurements including plasma and urine NGAL. Univariate and logistic regression analyses were used to find the associations between variables. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance characteristics of plasma and urine NGAL for detection of VOC. Plasma and urine NGAL, urine microalbumin:creatinine ratio, and urine protein:creatinine ratio were significantly higher in VOC. Microalbuminuria was present in 17.1% steady state and 32.0% VOC patients. Microalbuminuria showed significant correlations with age, plasma NGAL, WBC, and hemolytic parameters. Area under the ROC curve for plasma NGAL was 0.69 (95%CI = 0.567-0.813; p = 0.006) and 0.86 (95%CI = 0.756-0.954; p < 0.001) for urine NGAL. Urine NGAL cut-off value of 12.0 ng/mL had 95% sensitivity and 65% specificity. These results confirm the presence of nephropathy during VOC and suggest that plasma and urine NGAL would be useful in the identification of SCN. Urine NGAL should be used as the screening biomarker, and patients with VOC and urine NGAL > 12.0 ng/mL should be selected for aggressive management to prevent progression of renal damage.

Plasma 25-hydroxyvitamin D is positively associated with folate and vitamin B12 levels in adolescents.

Vitamin D affects the absorption of folate in vitro, and perhaps of vitamin B12 (B12). However, epidemiological studies on the association of vitamin D with folate and B12 are inconclusive. We hypothesized a positive association of plasma 25-hydroxyvitamin D [25(OH)D] with folate and B12 levels in adolescents. This hypothesis was tested in a cross-sectional study of healthy adolescents (11-16 years old; n = 1416), selected from public middle schools from across Kuwait, using stratified multistage cluster random sampling. Plasma 25(OH)D was measured by LC-MS/MS. Serum B12 and total folate in hemolyzed whole blood were analyzed with commercial kits; RBC and plasma folate were calculated from total folate. Data on potential confounders were collected from the parents and adolescents. In a univariable model, 25(OH)D as a continuous variable was positively associated with each of total, RBC, and plasma folate (P < .001). After adjusting for potential confounders, this association remained significant with total folate (ß = 2.0, P < .001) and red blood cell folate (ß = 1.8, P < .001), but not with plasma folate (ß = 0.2, P = .34). A similar pattern of association was evident when 25(OH)D was fitted as categorical variable. Correlation between B12 and 25(OH)D was weak but significant (ρ = 0.1, P < .001). 25(OH)D was positively associated with B12 in both univariable and multivariable models (P < .001) when fitted as a categorical variable only. Simultaneous quantile regression confirmed these results. We conclude that plasma 25(OH)D is positively associated with folate and B12 levels in adolescents. Properly designed large-scale randomized controlled trials are warranted to investigate the causal role of vitamin D in folate and B12 absorption.

The routine chemiluminescence assay for plasma 25-hydroxyvitamin D analysis does not overestimate the prevalence of vitamin D deficiency in adolescents.

Vitamin D deficiency (VDD) is a global public health problem. Inaccurate methods for measuring plasma 25-hydroxyvitamin D (25[OH]D) may have contributed to the reported high prevalence of VDD. We hypothesized that the most commonly used assay for vitamin D status, chemiluminescence immunoassay (CLIA), underestimates 25(OH)D levels and thus overestimates VDD. Using both liquid chromatography-tandem mass spectrometry and CLIA for plasma 25(OH)D, we evaluated the prevalence of VDD in adolescents (11-16 years-old; n = 410) by both methods in a cross-sectional study. Subjects were selected from public middle schools from all the 6 Governorates of Kuwait using stratified multistage cluster random sampling. Cohen κ agreement, linear regression, and Bland-Altman plots were used to evaluate the classification of VDD by the 2 methods. VDD (25[OH]D < 50 nmol/L) was 85.9% with CLIA and 81.2% with liquid chromatography-tandem mass spectrometry. There was a good agreement between the 2 methods in classifying the study subjects as deficient, insufficient, or sufficient (κ = 85.1%, P < .001). The between-assay bias was very small with a mean percentage difference < 1% from the mean value of the 25(OH)D as assessed by the 2 methods. These data did not support our hypothesis, and we conclude that the routine methods used for plasma 25(OH)D levels have no or little impact on evaluating VDD as a public health problem or in clinical management.

Season of birth and sugary beverages are predictors of Raven's Standard Progressive Matrices Scores in adolescents.

To investigate factors associated with cognitive functioning in healthy adolescents, a school-based cross-sectional study was conducted on 1370 adolescents aged 11-16 years that were randomly selected from all governorates of Kuwait. Raven's Standard Progressive Matrices (SPM), a non-verbal test of intelligence, was used to measure cognitive functioning of the study participants. Data on predictors of cognitive functioning were collected from parents and adolescents. Weight and height of the participants were measured in a standardized manner and blood samples were tested in an accredited laboratory under strict measures of quality control. In multivariable linear regression analysis, factors that showed significant association with the SPM score were gender (p = 0.002), season of birth (p = 0.009), place of residence (p < 0.001), father's (p < 0.001) and mother's (p = 0.025) educational level, type of housing (p < 0.001), passive smoking at home (p = 0.031), sleeping hours during weekends (p = 0.017), students' educational level (p < 0.001) and the frequency of consumption of sugary drinks (p < 0.001). The link between cognitive functioning and season of birth seems to be robust in various geographical locations including the Middle East. The association between sugary drinks and cognitive functioning highlights the importance of diet independently of obesity and support efforts to reduce consumption of sugary drinks among children.

Anemia and its associated factors among Adolescents in Kuwait.

We estimated the prevalence of anemia among school children and investigated factors associated with this problem in Kuwait. A cross-sectional study was conducted on 1415 adolescents randomly selected from middle schools in Kuwait. Hemoglobin, iron, ferritin, folate and vitamin B12, in addition to many other laboratory indicators, were measured in a venous blood sample. Data on risk factors for anemia were collected from parents and adolescents. Multiple logistic regression was used to investigate factors associated with anemia. The prevalence of anemia was 8.06% (95% CI: 6.69-9.60%), which was significantly higher among females compared to males (10.96% vs. 5.04%; p < 0.001). Mean (SD) Hb level was 133.7 (9.89) g/L and 130.00 (10.48) g/L among males and females, respectively (p < 0.001). The prevalence of mild, moderate and severe anemia was 5.94%, 1.91% and 0.21%, respectively. Gender, age, iron concentration and ferritin were associated with anemia in multivariable analysis. These data indicate that anemia among school children in Kuwait is of mild public health significance. Further reduction in anemia in school girls should focus on correcting iron deficiency. Surveillance systems for anemia may consider using a cut-off point that is specific for the method of blood sampling and the method of Hb measurement.

The stress-activated protein kinase pathway and the expression of stanniocalcin-1 are regulated by miR-146b-5p in papillary thyroid carcinogenesis.

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. Deciphering the pathophysiological mechanisms that contribute to PTC development is essential to the discovery of optimal diagnostic and therapeutic approaches. MiR-146b-5p has been identified as a cancer-associated microRNA highly up-regulated in PTC. This study explores the hypothesis that miR-146b-5p contributes to papillary thyroid carcinogenesis through regulation of cell signaling pathways in a manner that overcomes the cellular growth suppressive events and provides survival advantage. The effect of miR-146b-5p inhibition on major cancer related signaling pathways and expression of Stanniocalcin-1 (STC1), an emerging molecule associated with stress response and carcinogenesis, was tested in cultured primary thyroid cells using luciferase reporter assays, quantitative real-time PCR, immunofluorescence staining, and flow cytometry. Our results demonstrated that miR-146b-5p inhibits the JNK/AP1 pathway activity and down-regulates the expression of STC-1 in thyroid-cultured cells and in thyroid tissue samples. In the presence of miR-146b-5p, PTC cells were resistant to cell death in response to oxidative stress. This is a novel report that miR-146b-5p directly targets STC1 and regulates the activity of JNK/AP1 pathway. Considering the importance of the JNK/AP1 pathway and STC1 in mediating many physiological and pathological processes like apoptosis, stress response and cellular metabolism, a biological regulator of these pathways would have a great scientific and clinical significance.

Down-regulation of the human major histocompatibility complex class I chain-related gene A (MICA) and its receptor is mediated by microRNA-146b-5p and is a potential mechanism of immunoediting in papillary thyroid carcinoma.

Immune escape is one of the main reasons for the rapid progression of cancer and the poor efficacy of immunotherapy. Papillary thyroid cancer (PTC) is usually accompanied by intra-tumoral lymphocytic infiltration. The mechanisms regulating this tumor associated immune response or its evasion are not well understood. The major histocompatibility complex class I chain-related proteins A (MICA) and its receptor the natural killer group 2 member D (NKG2D) are major executers of the anti-tumor defense. This work aimed to study the expression and regulation of MICA-NKG2D and its association with the lymphocytic infiltration and miRNAs in PTC. Expression of MICA and NKG2D in thyroid tissues, and in cultured primary thyroid cancer cells and lymphocytes transfected with miR-146b-5p inhibitor/mimic was tested by RT-PCR. Results were confirmed by immunofluorescence staining and confocal microscopy. MICA is expressed in malignant and benign thyroid tissues with no association with aggressive behavior. Expression of MICA and NKG2D in PTC is concomitant with the presence of tumor associated lymphocytic response and is regulated by miR-146b-5p. MiR-146b-5p indirectly downregulates NKG2D expression in cancer cells and in lymphocytes. Overexpression of miR-146b-5p in PTC down-regulates MICA expression possibly to reduce the immunogenicity of the tumor cells. Targeting of the MICA-NKG2D axis by miR-146b-5p might be one of the ways adopted by thyroid cancer cells to aid the tumor in evading the immune response. The importance of our findings resides in the potential therapeutic use of MICA, NKG2D and miRNA-146b-5p as targets or modulators to enable the immune response against cancer.

Circulatory pattern of cytokines, adipokines and bone markers in postmenopausal women with low BMD.

Objective: In addition to some well-characterized bone turnover markers (BTMs), cytokines and adipokines have also been suggested to be linked to osteoporosis seen in menopause. However, there is much controversy on the possible association between these markers and bone mineral density (BMD). This study was aimed at measuring circulatory levels of selected cytokines, adipokines and BTMs in postmenopausal women with normal and low BMD. Methods: The study population included 71 post-menopausal women, of whom 25 had normal BMD, 31 had osteopenia and 13 had osteoporosis. Circulatory levels of selected pro-resorptive (TNF-α, IL-1ß, IL-6, IL-8, IL-12, IL-17), anti-resorptive (IFN-γ, IL-4, IL-10, IL-13, TGF-ß) and five adipokine markers (adiponectin, adipsin, lipocalin-2/NGAL, PAI-1 and resistin) were measured using the Multiplex system and read on the Magpix ELISA platform. Further, two bone turnover markers (PINP, CTX) as well as estradiol levels were assayed from the same samples. Results: While circulatory levels of cytokines were comparable between groups, women with low BMD had statistically significantly higher median circulatory levels of adipokines as compared to those with normal BMD. Further, while levels of CTX were not different between the two groups; PINP, PINP/CTX ratio and estradiol levels were significantly lower in women with low BMD. Levels of adiponectin, PINP, PINP/CTX ratio and estradiol correlated significantly with BMD of the hip and spine. Conclusion: The associations between various markers and BMD are complex and multivariate. Our data provide insights into the possible use of circulatory levels of cytokines, adipokines and bone turnover markers on the pathogenesis of postmenopausal osteoporosis because of the well-documented effects of these molecules on bone tissue and their relevance to osteoporosis.

Genetic association of LPL rs1121923 and rs258 with plasma TG and VLDL levels.

Lipoprotein lipase (LPL) is a rate-limiting enzyme for the hydrolysis of triglycerides (TG). Hundreds of genetic variants including single nucleotide polymorphisms have been identified across the 30Kb gene locus on chromosome 8q22. Several of these variants have been demonstrated to have genetic association with lipid level variation but many remain unresolved. Controversial reports on the genetic association of variants among different populations pose a challenge to which variants are informative. This study aimed to investigate "common" LPL variants (rs1121923, rs258, rs328, rs13702) and their possible role in plasma lipid level. Genotyping was performed using Realtime PCR. Based on the observed genotypes, the minor allele frequencies were A: 0.065 for rs1121923; C: 0.379 for rs258; G: 0.087 for rs328 and C: 0.337 for rs13702. Using linear regression, a lowering effect of rs1121923 (p = 0.024) on TG levels (-0.14 B coefficient: CI: -0.27--0.019) and rs258 (p = 0.013) on VLDL levels (B: -0.046; CI: -0.082--0.009) was observed indicating a "protective" role for the two variants. Moreover, the findings indicate the potential for including rs1121923 and rs258 in diagnostic panels for use as an estimator of "risk" scores for dyslipidemia.

Corrigendum to "Vitamin D-Binding Protein Clearance Ratio Is Significantly Associated with Glycemic Status and Diabetes Complications in a Predominantly Vitamin D-Deficient Population".

[This corrects the article DOI: 10.1155/2018/6239158.].

Plasma 25-Hydroxy Vitamin D Is Not Associated with Either Cognitive Function or Academic Performance in Adolescents.

Several observational studies have reported an association between low levels of vitamin D (VD) and poor cognition in adults, but there is a paucity of data on such an association in adolescents. We investigated the association between VD and cognitive function or academic achievement among 1370 adolescents, who were selected from public middle schools in Kuwait, using stratified multistage cluster random sampling with probability proportional to size. Plasma 25-hydroxy VD (25-OH-D) was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). An age-adjusted standard score (ASC), calculated from Raven's Standard Progressive Matrices test, was used to evaluate cognitive function; academic achievements were extracted from the schools' records. Data on various covariates were collected from the parents through a self-administered questionnaire and from the adolescents using face-to-face interviews. 25-OH-D was weakly correlated positively with ASC (ρ = 0.06; p = 0.04). Univariable linear regression analysis showed an association between 25-OH-D categories and ASC after adjusting for gender, but adjusting for parental education was sufficient to explain this association. Multivariable analysis showed no association between 25-OH-D and ASC after adjusting for potential confounders whether 25-OH-D was fitted as a continuous variable (p = 0.73), a variable that is categorized by acceptable cutoff points (p = 0.48), or categorized into quartiles (p = 0.88). Similarly, 25-OH-D was not associated with academic performance. We conclude that 25-OH-D is associated with neither cognitive function nor academic performance in adolescents.

Clinical Applications of Adiponectin Measurements in Type 2 Diabetes Mellitus: Screening, Diagnosis, and Marker of Diabetes Control.

BACKGROUND: Adipose tissue-derived adiponectin has pleiotropic protective effects with suppression of inflammatory and metabolic derangements that may result in insulin resistance, metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. The aim of this study was to evaluate adiponectin as a diagnostic marker of T2DM and diabetes control. METHODS: Fasting adiponectin, insulin, glucose, and HbA1c were determined in 376 patients with known T2DM and 575 subjects with undiagnosed diabetes but with family history of T2DM. Clinical and anthropometric data were recorded. Subjects were classified on the basis of degree of adiposity, insulin resistance (IR), and achievement of target HbA1c levels. Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic performance for undiagnosed DM. RESULTS: In undiagnosed subjects, adiponectin was significantly lower in subjects with IR and diabetic subjects compared with those without. The area under the adiponectin ROC curve for diagnosis of DM was 0.740. In known T2DM subjects, those with good control had significantly higher adiponectin (8.6 versus 7.4 µg/mL) compared to subjects with poor control. CONCLUSIONS: Adiponectin levels are associated with better glycemic control and could be a useful adjunct for screening for IR and T2DM. Therapeutic measures that increase adiponectin levels might be valuable targets for improving diabetes control and decreasing complications.

Vitamin D-Binding Protein Clearance Ratio Is Significantly Associated with Glycemic Status and Diabetes Complications in a Predominantly Vitamin D-Deficient Population.

Introduction: Studies have shown increased urine excretion of vitamin D-binding protein (VDBP) in patients with diabetic nephropathy (DN) resulting from postulated mechanisms linked to renal tubular damage. In this study, we evaluate the utility of VDBP clearance ratio as a novel determinant of glycemic status, DN, and other diabetes-associated complications. Methods: Levels of vitamin D, HbA1c, serum, urine concentrations of VDBP, and creatinine were measured in 309 subjects. The ratio of urine microalbumin to creatinine was determined to categorize subjects as normoalbuminuric (NAO), microalbuminuric (MIA), and macroalbuminuric (MAA). The VDBP clearance ratio was calculated. Results: Mean VDBP clearance ratios in NAO, MIA, and MAA were 0.7, 4, and 15, respectively. Significant positive correlations of VDBP clearance ratio were found with age, WC, SBP, DBP, TG, glucose, HbA1c, urine VDBP, urine microalbumin, and urine microalbumin/creatinine, and a significant negative correlation was found with the steady-state estimate of beta cell function (B%). Receiver operating curve (ROC) analyses of the use of VDBP clearance ratio for detection of albumin status shows a value of 0.81 for the area under the curve. Conclusions: The strong associations of VDBP clearance ratio with glycemic control and diabetes-associated complications suggest that this index could play a wider role in detection and/or pathogenesis and complications of diabetes.

Association of FTO rs9939609 with Obesity in the Kuwaiti Population: A Public Health Concern?

OBJECTIVE: To investigate the effect of the common fat mass and obesity-associated (FTO) gene polymorphism rs9939609 on body mass index (BMI) in one of the most obese populations worldwide. SUBJECTS AND METHODS: Genotypic data for FTO rs9939609 were available for 1,034 unrelated Kuwaiti adults obtained from Kuwait's Dasman Diabetes Institute and Kuwait University. The association between the FTO polymorphism with BMI as continuous and categorical (normal BMI [< 25] vs. overweight/obese [> 25]) variables was analyzed using both linear and logistic regression models, respectively, with the assumption of both dominant and additive genetic models performed using the SNPassoc package from R statistics. RESULTS: The A allele was associated with increased BMI (ß = 1.21; 95% CI = 0.16-2.26; p = 0.023). In concordance, the categorical BMI (normal vs. overweight/obese) also showed a significant association between the A allele and overweight/obesity (OR = 1.47; 95% CI = 1.01-2.12; p = 0.041). However, no association between the FTO variant was observed with cardiometabolic traits. CONCLUSION: We observed an association between the common FTO rs9939609 polymorphism and increased BMI (overweight/obesity) in Kuwaiti adults, which is consistent with previous research in other populations. Our findings encourage further investigation of genetic variants to elucidate the mechanisms involved in the development of obesity in such an obesogenic population.

Discriminatory miRNAs for the Management of Papillary Thyroid Carcinoma and Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features.

BACKGROUND: Papillary thyroid carcinoma (PTC) variants have several overlapping clinical and pathological features. The World Health Organization recently published a new classification of thyroid tumors containing significant revisions. Encapsulated papillary thyroid carcinoma (EPTC) has been recognized as a distinctive variant of PTC. The noninvasive encapsulated follicular variant of PTC has been reclassified as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Different neoplasms are associated with different outcomes and require different clinical management. The objective of this study was to explore the miRNA expression patterns specific for classic PTC (cPTC), EPTC, follicular variant of PTC, and NIFTP in order to identify biomarkers of diagnostic and prognostic utility aiming for better clinical decisions. METHODS: The expression of 84 miRNAs was determined by quantitative real-time polymerase chain reaction in 113 thyroid tissues of PTC (classic, encapsulated, and follicular), NIFTP, and hyperplasia lesions. Expression of the same miRNAs was tested in pre- and postoperative whole-blood samples. RESULTS: Several miRNAs were differentially expressed in the different groups. Expression profile of miRNAs in the tissue was similarly reflected in the circulation. Receiver operating characteristic curve analysis showed that miR-7-5p, miR-222-3p, and miR-146b-5p can discriminate between the different groups with high sensitivity and specificity. Downregulation of miR-144-3p, miR-15a-5p, miR-20a-5p, miR-32-5p miR-142-5p, miR-143-3p, and miR-20b-5p is associated with aggressive behavior in cPTC. Circulating miR-146b-5p, miR-222-3p, miR-155-5p, and miR-378a-3p are potential diagnostic and follow up biomarkers for PTC. CONCLUSION: Downregulation of miR-7-5p discriminates NIFTP from hyperplasia. Upregulation of miR-222-3p discriminates follicular variant of PTC from NIFTP. High levels of miR-146b-5p distinctively characterize cPTC. These miRNAs are useful biomarkers in the diagnosis of PTC and NIFTP, and help to avoid unnecessary thyroidectomy and improve clinical management.

Prospective evaluation of the effect of short-term oral vitamin d supplementation on peripheral neuropathy in type 2 diabetes mellitus.

OBJECTIVE: We aimed to assess the efficacy of short-term oral vitamin D supplementation on peripheral neuropathy in patients with type 2 diabetes. MATERIALS AND METHODS: This prospective, placebo-controlled trial included 112 type 2 diabetic patients with diabetic peripheral neuropathy (DPN) and vitamin D [25(OH)D] deficiency. Patients were sequentially assigned to a treatment group (n = 57) and a placebo group (n = 55). DPN was assessed using a neuropathy symptom score (NSS), a neuropathy disability score (NDS) and a nerve conduction study (NCS). Vitamin D status was determined by measuring the serum total 25(OH)D concentration. Patients received either oral vitamin D3 capsules or starch capsules once weekly for 8 weeks. The primary outcome was changes in NSS and NDS from baseline. The secondary outcome was changes in the NCS result. RESULTS: Serum 25(OH)D concentrations significantly improved after oral vitamin D supplementation in the treatment group when compared to the placebo group (32.8 ± 23.7 vs. 1.1 ± 3.6, p < 0.0001). Similarly, the improvement in NSS values was significantly greater in the treatment group than in the placebo group (-1.49 ± 1.37 vs. -0.20 ± 0.59, p < 0.001). No improvement was observed for NDS and NCS between the 2 groups after treatment. CONCLUSION: Short-term oral vitamin D3 supplementation improved vitamin D status and the symptoms of neuropathy in patients with type 2 diabetes.

Associations of TERC Single Nucleotide Polymorphisms with Human Leukocyte Telomere Length and the Risk of Type 2 Diabetes Mellitus.

Previous Studies have mapped putative loci that may probably regulate leukocyte telomere length (LTL). The strongest associations with LTL were reported for SNP rs12696304 and rs16847897 near the non-coding Ribose Nucleic Acid (RNA) molecule component (TERC) of telomerase enzyme on 3q26. It is unclear whether these identified loci coding functional components of telomerase, exert a similar effect on LTL in other populations or influence risk factors of Type 2 Diabetes Mellitus (T2DM). The present study was performed to: study the influence of TERC polymorphisms on LTL, human telomerase reverse transcriptase (hTERT), indices of obesity and explore the potential associations with T2DM. 225 T2DM patients and 245 age and sex matched controls were studied. Allelic Discrimination (AD) genotyping was utilized to determine TERC SNPs [rs12696304 and rs16847897]. hTERT, adiponectin, Insulin, Homeostasis Model Assessment (HOMA-IR), and LTL were measured. Body Mass Index (BMI) and waist circumference (WC) were recorded. [CC] genotype of rs16847897 was significantly associated with shorter LTL [OR = 1.6, p = 0.004], lower hTERT levels [OR = 0.4, p = 0.006], higher BMI [OR = 2.2, p = 0.006], larger WC [OR = 23.4, p = 0.007] and hypo-adiponectemia [OR = 0.6, p = 0.006]. [GG] genotype of rs12696304 was also significantly associated with shorter LTL [OR = 1.5, p = 0.004], lower hTERT [OR = 0.7, p = 0.006] but with larger WC[OR = 5.3, p = 0.004]. [CC] genotype of rs16847897 and [GG] genotype of rs12696304 together increased the risk of T2DM significantly [OR = 1.7, p = 0.004]. We provide insights connecting a structure that is critically involved in maintaining genomic stability with obesity and T2DM. Given the central role of telomere length in determining telomere function our findings may expand our understanding of the pathological mechanisms underlying age associated conditions such as T2DM.