Plasma levels and dietary intake of minerals in patients with type 2 diabetes and chronic kidney disease: A case-control study.

BACKGROUND AND AIM: Diabetic kidney disease (DKD) is the primary cause of chronic kidney disease (CKD) worldwide. Altered mineral levels leading to adverse outcomes are widely reported in diabetes but limited in DKD, in the Indian scenario, hence this study was taken up to address this issue. METHODS: A hospital-based case-control study was taken up with 54 healthy controls (C) and 140 subjects with type 2 diabetes wherein 74 subjects with diabetes and CKD formed the DKD group, and 66 subjects with diabetes but no CKD formed the diabetic no-chronic kidney disease (DNCKD) group. High-resolution inductively coupled plasma mass spectrometry was used to evaluate the blood levels of minerals (calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), and selenium (Se)), and a raw food-based food frequency questionnaire for dietary intakes. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (mL/min/1.73 m2) and albuminuria. Spearman's rank correlation was used to evaluate the relationship between the categorical variables. RESULTS: The median values of plasma Ca in the DKD group were significantly lower compared with the DNCKD and C groups (10.5 mg/dL vs. 11.0 mg/dL and 11.7 mg/dL, p<0.001). Furthermore, plasma Ca levels lowered with declining kidney function, as evidenced by the eGFR and albuminuria segregation. Dietary intake of minerals did not correlate with the corresponding plasma levels. However, in the DKD group, eGFR correlated positively with the plasma levels of Ca (r= 0.422, p=0.001), Cr (r= 0.351, p=0.008), Mn (r= 0.338, p=0.011), Fe (r= 0.403, p=0.002), Cu (r= 0.274, p=0.041) and negatively with Se (r= -0.486, p<0.001). CONCLUSION: Plasma Ca levels are lower in the DKD group with a strong positive association with eGFR, indicating its role in predicting the onset and progression of kidney function decline.

Telomere length and vitamin B12.

Telomeres are non-coding nucleoprotein structures consisting of a highly conserved tandem repeat DNA sequence that caps the ends of chromosomes in eukaryotes. Telomeres confer chromosomal stability, protect the genome from nucleolytic degradation, avoid aberrant recombination and improper repair, and prevent random fusion of chromosomes. The end-replication problem results in telomere shortening with every cell division, eventually leading to cellular senescence and aging. Telomere length (TL) is thereby an ideal candidate for "biological aging." Telomeres possess guanine-rich repeats, which are highly susceptible to oxidative stress. Epidemiological studies have indicated the association of telomere attrition with mortality and various age-related diseases. Micronutrients comprising vitamins and minerals act as potential modulators of stress and can influence TL. Research has indicated that vitamin B12 (B12) regulates oxidative stress and maintains genomic stability, thereby influencing telomere integrity and cellular aging. The deficiency of B12 leads to elevated levels of homocysteine, which reduces the methylation potential and increases oxidative stress, thereby compromising the TL. Telomere shortening and mitochondrial dysfunction are independently linked to aging. However, they are connected through telomerase reverse transcriptase activity, which regulates mitochondrial biogenesis. Further, experimental evidence indicated the positive association of B12 with relative TL and mitochondrial DNA copy number, an indirect index of mitochondrial biogenesis. The present chapter provides some insights into the role of B12 in influencing TL. Exploring their association might open new avenues to understand the pathophysiology of aging and age-related diseases.

Relative telomere length and mitochondrial DNA copy number variation with age: Association with plasma folate and vitamin B12.

Telomere attrition and mitochondrial DNA variations are implicated in the biological aging process and genomic stability can be influenced by nutritional factors. This study aims to analyze the relative telomere length (rTL) and mitochondrial DNA copy number (mtCN) in aged individuals and their association with plasma folate and vitamin B12 levels. This community-based cross-sectional study involves 428 subjects (<60 years: 242 & ≥60 years: 186). Quantitative real-time PCR was used to measure rTL and mtCN variation, and radioimmunoassay to measure plasma folate and vitamin B12 levels. The subjects in the ≥60 years age group have significantly shorter telomeres and lower mtCN compared to the <60 years age group. A significant positive correlation was observed between the rTL and mtCN, and both of them were positively associated with plasma folate and vitamin B12 levels. In the ≥60 age group; folate and vitamin B12 positively correlated with rTL and vitamin B12 with mtCN. The study revealed a decline of rTL and mtCN with age in the Indian population and their association suggests that they may co-regulate each other with age. In conclusion, folate and vitamin B12 may delay aging by preventing the reduction in rTL length and mtCN.

Micronutrient intakes and status assessed by probability approach among the urban adult population of Hyderabad city in South India.

PURPOSE: To assess the dietary inadequacies of micronutrients and the associated factors among the apparently healthy urban adults. METHODS: This community-based cross-sectional study involved 300 urban adults (distributed into age groups: 21-40, 41-60, and > 60 years) residing in Hyderabad city, South India. Hemoglobin in whole blood, ferritin, folate, and vitamin B12 (B12) in plasma was estimated. Dietary intakes were assessed by three 24-h dietary recalls and calculated the probability of adequacy (PA) using estimated average requirement. RESULTS: The prevalence of anemia (30%), iron deficiency (ID, 23%), and iron deficiency anemia (IDA, 14.3%) was independent of age but higher in women. While folate deficiency (32.2%) was independent of age and gender, B12 deficiency (35.5%) varied by both age and gender. The PA of iron (89%) was higher, while that of folate, B12, and zinc (1-11%) were noticeably low. The mean PA (MPA) across the ten micronutrients was 38%, independent of age and gender, but associated with the educational status. Energy intake was a strong predictor of the MPA. Cereals and millets predominantly contributed to the intake of thiamine, niacin, zinc, and iron; green leafy vegetables and fruits to vitamins A, C, folate, and iron; animal foods to B12; and milk and milk products to calcium, vitamin A, riboflavin, and B12. The unadjusted and adjusted logistic regression models revealed that micronutrient inadequacy was associated with greater risk of IDA and folate deficiency. CONCLUSIONS: These results indicate a higher prevalence of micronutrient deficiencies among the healthy urban adults possibly due to the inadequacy of multiple micronutrients.

Circulating levels of Hsp27 in microvascular complications of diabetes: Prospects as a biomarker of diabetic nephropathy.

AIM: Heat shock protein 27 (Hsp27) is a small heat shock protein known to protect the cells from apoptosis under stress. In the present study, we determined the plasma Hsp27 levels in type 2 diabetes subjects without and with microvascular complications- diabetic retinopathy (DRe), diabetic nephropathy (DNe), and diabetic neuropathy (DNu) to understand if it could serve as a marker for these complications. METHODS: This is a hospital-based case-control study with 754 subjects including 247 controls, 195 subjects with diabetes, 123 with DRe, 80 with DNe and 109 with DNu. Plasma Hsp27 levels were measured by ELISA. RESULTS: The mean plasma Hsp27 was higher in the DNe group (631.5±355.2) compared to the control (496.55±308.54), diabetes (523.41±371.01), DRe (494.60±391.48) and DNu (455.21±319.74) groups with a p-value of 0.018. Receiver operating characteristic (ROC) curve analysis of Hsp27 in DNe group showed an area under the curve (AUC) of 0.617. Spearman correlation analysis shows a positive correlation of plasma Hsp27 with serum creatinine (p=0.053, r-value 0.083). Gender, age and BMI did not affect the plasma Hsp27 levels. CONCLUSION: The plasma Hsp27 levels in the DNe group are higher compared to the control and other complications, thereby it could be explored to be used as a potential biomarker of DNe.