Effect of 8-week oral supplementation with 3-µg cyano-B12 or hydroxo-B12 in a vitamin B12-deficient population.

PURPOSE: We compare the effect of 8-week oral supplementation with cyano-B12 (currently used in vitamin pills) and hydroxo-B12 (predominant form in the diet) in a population with nutritional vitamin B12 deficiency. METHODS: Fifty-one healthy Indian adults with baseline serum cobalamin < 200 pmol/L were supplied for 8 weeks with daily oral supplements of 3-µg cyano-B12 (n = 15), 3-µg hydroxo-B12 (n = 16), or a placebo (n = 20). Blood at baseline, and each following week, was examined for total cobalamin, holotranscobalamin, methylmalonic acid, and homocysteine. RESULTS: The study groups did not differ at baseline and were characterized by [median (range)] serum cobalamin [128 (68-191) pmol/L], holotranscobalamin [16 (6-41) pmol/L], methylmalonic acid [0.8 (0.3-1.7) µmol/L], homocysteine [17.9 (8.5-100.9) µmol/L], and a combined indicator of B12 status 4cB12 of - 1.65 (- 0.64 to - 4.07). The group supplemented with cyano-B12 showed a higher increase in total serum cobalamin than the group treated with hydroxo-B12, while other biomarkers changed comparably in the two groups. After 8 weeks of treatment, the biomarker values of the supplemented groups (pooled) differed significantly from the placebo group. Yet, the vitamin B12 status was still poor [cobalamin: 168 (87-302) pmol/L; holotranscobalamin: 19 (8-45) pmol/L; methylmalonic acid: 0.7 (0.2-1.7) µmol/L; homocysteine: 17.2 (2.6-96.8) µmol/L; 4cB12 = - 1.34 (- 0.33 to - 3.3)]. CONCLUSION: 8-week supplementation with 3-µg cyano-B12 elevated serum cobalamin more than 3 µg hydroxo-B12, but all other biomarkers changed similarly in both groups. Supplementation with 3 µg vitamin B12 did not reverse the low status in individuals with nutritional vitamin B12 deficiency. CLINICAL TRIAL REGISTRY OF INDIA: REF/2017/02/013343.

Identification of vitamin B12 deficiency in vegetarian Indians.

The prevalence of a sub-clinical vitamin B12 deficiency in the vegetarians is high. Total serum vitamin B12 concentration alone does not reliably reflect vitamin B12 status. Holotranscobalamin (holo-TC) II is a bioactive B12 fraction promoting specific uptake of B12 by cells and the circulating concentration reflects the intake of B12, whereas total homocysteine (tHcy) indicates the metabolic ability. In this study, we investigated the diagnostic value of circulating holo-TC, B12, folate and homocysteine in vegetarians who were at risk of B12 deficiency. B12-related biomarkers were measured in 119 young, healthy graduate vegetarians. None was folate deficient. As per reported definition, half were B12 deficient; 70 % of males and 50 % of females had low plasma holo-TC concentrations; and 92 % of males and half of females had hyperhomocysteinaemia. None had any clinical signs of B12 deficiency. Receiver operating characteristic curve analysis demonstrated similar AUC at the B12 concentration of 100 and 150 pmol/l when holo-TC (0·777 and 0·784) and homocysteine (0·924 and 0·928) were used as variables. Cut-off value of 100 pmol/l resulted in the highest sensitivity of 77·78 % and specificity of 71·05 % with a predictive value of 19·6 pmol/l for holo-TC and a sensitivity of 82·72 % and specificity of 89·7 % with a predictive value of 21·7 µmol/l for homocysteine. The combination of B12, holo-TC and tHcy improves the diagnostic accuracy at these cut-offs, and we suggest that for the young Indian vegetarians the cut-off for plasma B12 and holotrancobalamin is 100 pmol/l and 19·6 pmol/l, respectively, and for homocysteine it is 17·6 (females) and 27 µmol/l (males) for identifying B12 deficiency.

Increase in circulating holotranscobalamin after oral administration of cyanocobalamin or hydroxocobalamin in healthy adults with low and normal cobalamin status.

PURPOSE: To investigate the absorption of synthetic cyanocobalamin and natural occurring hydroxocobalamin in populations with low and normal cobalamin (vitamin B12) status. METHODS: We included adults with low (n = 59) and normal (n = 42) cobalamin status and measured the change in serum holotranscobalamin (ΔholoTC) before and after 2 day administration of different doses of cyanocobalamin and hydroxocobalamin (CobaSorb test). In the low status group, the test was performed using a cross-over design with identical doses of both cobalamin forms (1.5, 3, and 6 µg, respectively). In the normal status group, the test was performed with either 3, 6, and 9 µg cyanocobalamin (n = 28), or with 9 µg cyanocobalamin and 9 µg hydroxocobalamin (n = 14). RESULTS: In both groups, median ΔholoTC (pmol/L) was higher after intake of cyanocobalamin compared to (hydroxocobalamin) [low status: 1.5 µg: 19 (6); 3 µg: 23 (7); 6 µg: 30 (14); normal status: 9 µg: 30 (13) pmol/L]. Independent of B12 form, no difference was observed in ΔholoTC between those receiving 1.5 and 3 µg in the low status group or 6 and 9 µg cyanocobalamin in the normal status group. However, in both groups, administration of 6 µg cobalamin resulted in a significant higher ΔholoTC than did 3 µg [low status: p = 0.02 (0.009) for cyanocobalamin (hydroxocobalamin); normal status: p = 0.03 for cyanocobalamin]. CONCLUSIONS: Administration of cyanocobalamin resulted in a more than twofold increase in holoTC in comparison with hydroxocobalamin. The absorptive capacity was reached only by doses above 3 µg cobalamin. Our results underscore the importance of using the same form of cobalamin when comparing uptake under different conditions. CLINICAL TRIAL REGISTRY NUMBER: NCT02832726 at https://clinicaltrials.gov and 2016/09/012147 at Clinical Trials Registry India.

Daily milk intake improves vitamin B-12 status in young vegetarian Indians: an intervention trial.

BACKGROUND: Asymptomatic Indian lacto vegetarians, who make up more than half of the Indian population in different geographic regions, have distinctly low vitamin B-12 concentrations than non- vegetarians. Vegetarians consume milk but it seems that the amount is not enough to improve vitamin B-12 status or vitamin B-12 concentration in milk itself may be low. The aim of this study was to determine if daily milk consumption can improve vitamin B-12 status. METHODS: Fifteen male and 36 female, young healthy post-graduate volunteers participated. Blood from ten participants (4 males and 6 females) was collected (day-1). They continued their regular diet for next fourteen days and on day-15, blood of all 51 participants was collected, plasma vitamin B-12 concentration was measured and were divided into two groups; Normal (vitamin B-12 >148 pmol/L, n = 22) and Vitamin B-12 deficient (<148 pmol/L, n = 29), the remaining plasma was stored. All participants consumed 600 ml. of non-enriched buffalo milk (200 × 3) during the day along with their usual diet. Next day blood was collected for plasma holotranscobalamin II measurement. Subjects from deficient group continued to drink 400 ml of milk daily for next 14 days and blood was collected on day-30. Plasma holotranscoabalamin II (day-1, 15, 16, 30), vitamin B-12, folate, total homocysteine, creatinine and hematoloical parameters (day-1, 15, 30), and milk vitamin B-12 concentrations (day-15, 16, 30) were measured. RESULTS: Fifty seven per cent of the participants were vitamin B-12 deficient and 65% were hyperhomocysteinemic. No significant difference in biomarkers was observed when there was no intervention. Plasma holotranscobalamin II concentration increased from 19.6 to 22.27 pmol/L (p < 0.0001) 24 hrs after milk load in the whole group. Plasma vitamin B-12 increased from 92.5 to 122 pmol/L and tHcy concentrations decreased from 31.9 to 24.9 µ mol/L (p < 0.0001 for both) 14 days after regular milk intake in vitamin B-12 deficient subjects. CONCLUSIONS: Regular intake of milk improved vitamin B-12 status of vitamin B-12 deficient vegetarians indicating a potential dietary strategy to improve the vitamin status.

Factors associated with subtherapeutic levels of oral posaconazole tablet: a detailed analysis from a tertiary care center in India.

OBJECTIVES: Posaconazole is a broad-spectrum triazole antifungal, with activity against various clinically important fungi. The delayed release (DR) tablet of posaconazole has been shown to have a superior pharmacokinetic profile in comparison with the oral suspension. METHODS: We retrospectively analyzed the factors associated with posaconazole levels <1.25 µg/ml in 164 patients receiving the DR tablet for therapeutic purposes. RESULTS: Of the 164 patients, 53 (32.3%) showed subtherapeutic trough levels of posaconazole. The use of proton pump inhibitors (95% CI 1.41-3.91; P-value = 0.028) and the presence of diarrhea (95% CI 1.95-6.93; P-value = 0.001) were significantly associated with subtherapeutic levels. A total of 13 of the 21 patients receiving posaconazole tablets through a nasogastric tube had therapeutic levels. CONCLUSION: This is the largest study from India that analyzed factors associated with subtherapeutic levels of the DR tablet of posaconazole. These findings reinforce the importance of therapeutic drug monitoring. Unlike in previous studies, obesity and hypoalbuminemia were not found to be significant factors in our settings. The use of proton pump inhibitors and diarrhea remained significant factors, as found in previous studies. Administering the DR tablet of posaconazole through a nasogastric tube may be a viable option.

Cyano-B12 or Whey Powder with Endogenous Hydroxo-B12 for Supplementation in B12 Deficient Lactovegetarians.

Lactovegetarians (n = 35) with low vitamin B12 (B12) status were intervened for eight weeks capsules containing cyano-B12 (CN-B12), (2 × 2.8 µg/day), or equivalent doses of endogenous B12 (mainly hydroxo-B12 (HO-B12)) in whey powder. Blood samples were examined at baseline, every second week during the intervention, and two weeks post-intervention. The groups did not differ at baseline in [global median (min/max)] plasma B12 [112(61/185)] pmol/L, holotranscobalamin [20(4/99)] pmol/L, folate [13(11/16)], the metabolites total homocysteine [18(9/52)] µmol/L and methylmalonic acid [0.90(0.28/2.5)] µmol/L, and the combined indicator of B12 status (4cB12) [-1.7(-3.0/-0.33)]. Both supplements caused significant effects, though none of the biomarkers returned to normal values. Total plasma B12 showed a higher increase in the capsule group compared to the whey powder group (p = 0.02). However, the increase of plasma holotranscobalamin (p = 0.06) and the lowering of the metabolites (p > 0.07) were alike in both groups. Thereby, the high total plasma B12 in the capsule group was not mirrored in enhanced B12 metabolism, possibly because the B12 surplus was mainly accumulated on an "inert" carrier haptocorrin, considered to be of marginal importance for tissue delivery of B12. In conclusion, we demonstrate that administration of whey powder (HO-B12) or capsules (CN-B12) equivalent to 5.6 µg of B12 daily for eight weeks similarly improves B12 status but does not normalize it. We document that the results for plasma B12 should be interpreted with caution following administration of CN-B12, since the change is disproportionately high compared to the responses of complementary biomarkers.

Comparative Bioavailability of Synthetic B12 and Dietary Vitamin B12 Present in Cow and Buffalo Milk: A Prospective Study in Lactovegetarian Indians.

We assessed improvements in the vitamin B12 status of Indian lactovegetarians receiving four weeks supplementation with natural B12 in milk versus cyano-B12 in capsules. Three groups (n = 22, 23, 22) received daily oral doses of cyano-B12 (2 × 0.76 µg) or milk (2 × 200 mL) from a cow or buffalo (amounting to B12 ≈ 2 × 0.76 µg). Their blood was examined at baseline and each following week. The baselines (median (min/max)) indicated a low B12 status: plasma B12 (116(51/314)) pmol/L, holotranscobalamin (holoTC) (30(7/119)) pmol/L, total homocysteine (Hcy) (24(10/118)) µmol/L, methylmalonic acid (MMA) (0.58(0.15/2.2)) µmol/L and combined B12 index (cB12) (-1.32 - (-3.12/+0.29)). Shifts from the baselines (B12, holoTC, cB12) and ratios to the baselines (Hcy, MMA) were analyzed over time. The cyano-B12 treatment gave more total B12 in plasma at week one (+29 pmol/L, p = 0.004) but showed no further increase. Other biomarkers changed more comparably between the three groups (p ≥ 0.05): holoTC showed a transient spike that leveled off, Hcy finally decreased to 0.8 × baseline, while MMA showed marginal changes. The combined indexes improved comparably (p = 0.6) in all groups (+0.2(-0.3/+0.9), p ≤ 0.002). In conclusion, the tested formulations similarly improved B12 status, but did not normalize it.

Role of Parathyroid Hormone in Determination of Fat Mass in Patients with Vitamin D Deficiency.

BACKGROUND: Obesity has become a global epidemic and it is rising is Asia. Vitamin D deficiency (VDD) is widely prevalent in the Indian subcontinent. Studies have linked VDD to obesity and shown correlation between parathyroid hormone (PTH), 25-hydroxy Vitamin D (25(OH)D), and fat mass (FM). However, studies on the role of PTH among subjects with VDD are lacking. OBJECTIVE: The objective of this study is to study the role of PTH in the determination of FM in participants with VDD. SUBJECTS: Five hundred and fifty-one adults (m:247, f:304) were included in this study. MATERIALS AND METHODS: Total and regional (trunk, arm, and leg) FM was assessed by dual X-ray absorptometry. Biochemical and hormonal parameters such as calcium, phosphorus, alkaline phosphatase, ionic calcium, 25(OH)D, and PTH were also analyzed. RESULTS: The mean age of the study population was 58.8 ± 15.8 years (Male: [63.3 ± 13.1], Female: [55.2 ± 16.9]). FM and body mass index were significantly lower in females with higher levels of serum 25(OH)D. Total FM was negatively correlated with serum 25(OH)D (r = -0.363, P < 0.0001) and positively correlated with serum PTH (r: 0.262, P < 0.0001) in females only. Females with VDD and secondary hyperparathyroidism had higher FM than those with normal PTH. CONCLUSIONS: Females with VDD had higher total and regional FM. However, this correlation was evident only in those with high serum PTH levels, suggesting a potential role of PTH in the accumulation of FM.

Lean Body Mass and Bone Health in Urban Adolescents From Northern India.

OBJECTIVE: To prepare percentile charts of lean body mass (LBM) among Indian urban children and adolescents; and to evaluate gender differences in LBM, and its relation with pubertal status. DESIGN: Secondary data analysis. SETTING: School in city of Delhi, India. PARTICIPANTS: 1403 apparently healthy children and adolescents (826 boys) with mean (SD) age 13.2 (2.7) years. OUTCOME MEASURE: Lean body mass assessed by dual energy absorptiometry. RESULTS: Total and regional lean mass were greater in older age groups in both sexes. LBM showed rising trends up to the age of 18 years in boys, whereas it plateaued after the age of 15 years in girls. The age-associated increase in LBM was significantly higher in boys (130%) compared to girls (83%) (P<0.001). Total and regional lean mass increased with progression of pubertal staging in both genders. During pubertal development, LBM almost doubled (100% increase) from stage-2 to stage-5 in boys, as opposed to a 73% rise in girls (P<0.001). Total and regional lean mass and Appendicular skeletal muscle mass index (ASMI) was positively correlated with age, body mass index (BMI), serum 25(OH)D, total fat mass, and bone mineral content (BMC). Relation between LBM and BMC remained significant even after adjusting for age, fat mass and various biochemical parameters. CONCLUSION: Total and regional LBM rise with age and pubertal maturation in both genders, but more so in boys when compared to girls. LBM has direct bearing on BMC even after adjusting for age, fat mass and biochemical parameters.

Relationship of lean mass and obesity in Indian urban children and adolescents.

BACKGROUND: The association of obesity and lean mass (LM) has not been examined well in children and adolescents, and it remains controversial. OBJECTIVE: The objective of this study was to evaluate the relationship of body mass index (BMI) categories and regional obesity with total and regional LM in children and adolescents. METHODS: A total of 1408 children and adolescents (boys 58.9%; girls 41.1%) divided according to BMI (normal weight 79.5%, overweight 16.0%, and obese 4.5%) were included in this cross-sectional study. Total and regional LM and fat mass were measured by DXA. Leg and arm fat-to-total fat ratio (LATR) indicative of subcutaneous fat and trunk fat-to-total fat ratio (TTR), an indicator of visceral fat, were calculated. RESULTS: Mean age of the study population was 13.2 ± 2.7 years (boys - 13.0 ± 2.7; girls - 13.4 ± 2.8 years). Total LM (TLM) and its regional distribution were higher in overweight and obese groups when compared with those with normal BMI in both genders. TLM was comparable between overweight and obese in both genders. TLM per unit of fat progressively decreased from normal to obese categories. The difference in LM per unit fat between BMI categories persisted after adjustment for age, height, and sexual maturity score. TLM increased across the quartiles of TTR, but decreased with an increment in subcutaneous fat (quartiles of LATR). CONCLUSIONS: Obese children and adolescents apparently have higher LM than normal BMI children, but have lower LM per unit of fat. Subcutaneous fat had a negative impact and visceral fat had a positive impact on TLM.

Association of dietary factors with severity of coronary artery disease.

BACKGROUND: Cardiovascular disease has taken epidemic proportions during past decades. Cardiovascular risk factors contribute to progression of coronary lesions, worsening the patient's prognosis. This study was planned to analyze the association of dietary factors with severity of coronary artery disease (CAD) in Indian patients. METHODS: Three hundred patients with known coronary disease above the age of 25 years were included in this study. Blood samples were collected for biochemical markers. Patients were stratified according to severity of CAD [number of vessel involved-single (SVD), double (DVD), triple (TVD)]. RESULTS: Mean age of the patient was 60.9 ± 12.4 years. Subjects with TVD, DVD, SVD in the study were 52.3%, 25.3% and 22.3% respectively. Patients with TVD had higher body mass index, triglycerides, HOMA-Insulin Resistance, hsCRP and lower high density cholesterol. Diabetes mellitus, hypertension and dyslipidemia were more common in TVD patients. Among macronutrients, patients with TVD had higher intake of carbohydrate and lower intake of protein and dietary fibers. There was no association of total fat intake with CAD, however, intake of palmitic acid was higher among patients with TVD. Intake of vitamins namely niacin, riboflavin, thiamine, B6, and vitamin-C decreased with increase in severity. With increase in severity of CAD, mineral intake (potassium, calcium, magnesium, phosphorus, sulfur, iron, chromium, copper, manganese, and zinc) decreased. CONCLUSIONS: Dietary factors are associated with severity of coronary artery disease. Low intake of protein, fiber, vitamins, minerals and high intake of carbohydrate and fat was associated with higher probability of having severe CAD.

Comparison of body composition between professional sportswomen and apparently healthy age- and sex-matched controls.

INTRODUCTION: In view of the relationship between physical activity and nutrition on body composition, we assessed lean and fat mass and BMC (total and regional) in professional Indian sportswomen and compared it with apparently healthy age- and sex-matched females. MATERIALS AND METHODS: This cross-sectional study included 104 sportswomen and an equal number of age-matched normal healthy females (controls). They were evaluated for anthropometry and body composition (fat, lean mass, and bone mineral content (BMC) by DXA. RESULTS: Mean age (19.1 ± 1.3 vs. 19.4 ± 1.5 years) and body mass index (21.34 ± 3.02 vs. 21.26 ± 4.05 kg/m(2)) were comparable in both groups. Sportswomen had higher intake of energy, macronutrients, calcium, phosphorus and magnesium. Total lean mass (33.67 ± 3.49 vs. 31.14 ± 3.52 kg, P < 0.0001), appendicular skeletal muscle index (5.84 ± 0.57 vs. 5.46 ± 0.63 kg/m(2); P < 0.0001) and BMC (2.27 ± 0.32 vs. 2.13 ± 0.34 kg, P < 0.002) was significantly higher and percentage fat mass was significantly lower (33.1 ± 7.5 vs. 37.0 ± 8.3; P < 0.0001) among sportswomen when compared to controls. CONCLUSIONS: Indian sportswomen have a higher total and regional lean mass, BMC, and lower percentage fat mass when compared with healthy females. Physical activity, energy, protein and calcium intake were positively associated with lean mass and BMC.

Assessment and relation of total and regional fat mass with bone mineral content among Indian urban adolescents.

BACKGROUND: Fat mass (FM) has been shown to have an effect on bone mass accrual. Though gender and ethnic differences in body composition and bone accrual during puberty have been reported, there are limited data available for Indian children and adolescents. OBJECTIVE: To generate age and gender based percentile charts of FM among urban Indian children and adolescents and to evaluate the relationship with pubertal status and bone mineral content (BMC). SUBJECTS: There were 1403 children and adolescents (boys: 826; girls: 577) in the study. METHODS: Total and regional FM, BMC, and pubertal staging were assessed. Fat mass index (FMI), FM/height ratio and BMC/FM ratio, were calculated. RESULTS: The age of the study population ranged from 5 to 18 years, with a mean age of 13.2 ± 2.7 years (boys: 13.0 ± 2.7; girls: 13.4 ± 2.8 years). Total and regional FM as well as FMI increased with increasing age in both genders. The highest percent increase in mean total FM occurred in the age group > 8-11 years and decreased thereafter. The total and regional FM was higher in more advanced stages of pubertal maturation. There was no difference in total and regional FM between genders in prepubertal group. The age and pubertal associated increase in FM was significantly higher in girls than boys (p < 0.0001). Total as well as regional FM and FMI were positively correlated with age, body mass index, total lean mass, and BMC even after adjusting for age, lean mass, and biochemical parameters. CONCLUSIONS: Total and regional FM increased with age and pubertal maturation in both genders. FM was positively correlated with BMC.

Association of metabolic syndrome with severity of coronary artery disease.

BACKGROUND: South Asians are more prone to develop metabolic syndrome (MetS). The additive predictive value of components of MetS for cardiovascular diseases is still debated. We undertook this study to evaluate the association of MetS and its components with severity of coronary artery disease (CAD). MATERIALS AND METHODS: Three hundred patients with known coronary disease above the age of 25 years were included in this study. Blood samples were collected for biochemical markers. Patients were stratified into subjects with and without MetS (International Diabetes Federation, IDF, criteria) and severity of CAD (number of vessel involved). RESULTS: Mean age of the patient in the study was 60.9 ± 12.4 years (male, M: 72%; female, F: 28%). MetS was present in 64% patients. Patients with MetS had more severe CAD compared to those without MetS. Triple vessel disease (TVD) was present in 62.5% of patients with MetS compared to 34.3% among without MetS (P < 0.0001). The percent number of patients with TVD showed increasing trend with increasing number of components of MetS (0-0%; 1-20%; 2-27.5%; 3-47.8%; 4-72.6%; 5-78.3%; Chi square for trend < 0.0001). Inflammatory markers [interleukin (IL) 6: 77.67 ± 79.48 vs. 41.21 ± 60.72 pg/ml, P < 0.0001; tumor nuclear factor (TNF)-α: 28.0 ± 47.49 vs 20.43 ± 24.5 pg/ml, P < 0.0001; high sensitive C-reactive protein (hsCRP): 14.30 ± 9.91 vs. 7.02 ± 7.18 mg/L, P < 0.0001], insulin resistance [homeostatic model analysis insulin resistance (HOMA-IR): 22.33 ± 23.37 vs. 10.86 ± 13.90, P < 0.0001] were higher and insulin sensitivity [quantitative insulin check index (QUICKI): 0.26 ± 0.03 vs. 0.30 ± 0.04, P < 0.0001] was significantly lower in subjects with MetS compared to subjects without MetS. Among lipids, total cholesterol were comparable but triglyceride (175 ± 42 vs. 179 ± 48 vs. 180 ± 47 mg/dl, P < 0.0001) was high and high-density lipoprotein (HDL; 44.72 ± 7.63 vs. 39.96 ± 8.70 vs. 36.05 ± 8.84, P < 0.0001) was low in subjects with TVD compared to others. Similarly, percentage of patients with diabetes (7.5% vs. 26.3% vs. 63.7%, P < 0.0001) and hypertension (34.3% vs. 56.6% vs. 77.7%, P < 0.0001) were higher in subjects with TVD compared to others. CONCLUSIONS: There is a strong correlation of MetS and its components with severity of CAD.

Study of pattern of dyslipidemia and its correlation with cardiovascular risk factors in patients with proven coronary artery disease.

INTRODUCTION: Dyslipidemia is a primary, widely established as an independent major risk factor for coronary artery disease (CAD). Asians differs in prevalence of various lipid abnormalities than non-Asians. Hence, this study was conducted with objective to evaluate the lipid abnormalities and there correlation with traditional and non-traditional risk factors in known subjects with CAD. MATERIALS AND METHODS: We studied the pattern and association of dyslipidemia with cardiovascular risk factors in 300 (Male: 216; Female: 84, age: 60.9 ± 12.4 years, range: 25-92 years) angiographically proved CAD patients. All patients were evaluated for anthropometry and cardiovascular risk factors and blood samples were collected for biochemical and inflammatory markers. RESULTS: Hypercholesterolemia, hypertriglyceridemia and low high density lipoprotein (HDL) was present in 23.3%, 63.0% and 54.6% in the total study population respectively. A total of 41.3% had atherogenic dyslipidemia (raised triglycerides [TG] and low HDL). Percentage of patients with type-2 diabetes mellitus and hypertension were higher in subjects with atherogenic dyslipidemia. Insulin sensitivity was low; insulin and insulin resistance (IR) along with inflammatory markers were high in subjects with atherogenic dyslipidemia. Patients with atherogenic dyslipidemia had significantly lower serum vitamin B12 levels and higher homocysteine (Hcy) levels. Hypertriglyceridemia was positively correlated with insulin, homeostasis model assessment of IR, Hcy, interleukin-6, Tumor necrosis factor-alpha, highly sensitive C-reactive protein and negatively with vitamin B12 and quantitative insulin check index and an opposite correlation of all quoted parameters was observed with low HDL. The correlation of traditional and non-traditional risk factors was stronger with low HDL and high TG compared with hypercholesterolemia. CONCLUSIONS: Hypertriglyceridemia and low HDL cholesterol is common in patients with CAD compared with hypercholesterolemia. This suggests that different preventive strategy is required in Indian patients with CAD.

Calcium homeostasis, and clinical or subclinical vitamin D deficiency--can a hypothesis of "intestinal calcistat" explain it all?

The main physiological function of vitamin D is maintenance of calcium homeostasis by its effect on calcium absorption, and bone health in association with parathyroid gland. Vitamin D deficiency (VDD) is defined as serum 25-hydroxy vitamin D (25OHD) levels <20 ng/ml. Vitamin D insufficiency is called when serum 25OHD levels are between 20-29 ng/ml, though existence of this entity has been questioned. Do all subjects with VDD have clinical disease according to this definition? Analysis of published studies suggests that calcium absorption in inversely correlated with serum 25OHD levels and calcium intake. We hypothesize that there exist an intestinal calcistat, which controls the calcium absorption independent of PTH levels. It consists of calcium sensing receptor (CaSR) on intestinal brush border, which senses calcium in intestinal cells and vitamin D system in intestinal cells. CaSR dampens the generation of active vitamin D metabolite in intestinal cells and decrease active transcellular calcium transport. It also facilitates passive paracellular diffusion of calcium in intestine. This local adaptation adjusts the fractional calcium absorption according the body requirement. Failure of local adaptation due to decreased calcium intake, decreased supply of 25OHD, mutation in CaSR or vitamin D system decreases systemic calcium levels and systemic adaptations comes into the play. Systemic adaptations consist of rise in PTH and increase in active vitamin D metabolites. These adaptations lead to bone resorption and maintenance of calcium homeostasis. Not all subjects with varying levels of VDD manifest with secondary hyperparathyroidism and decreased in bone mineral density. We suggest that rise in PTH is first indicator of VDD is rise in PTH along with decrease in BMD depending on duration of VDD. Hence, subjects with any degree of VDD with normal PTH and BMD should not be labeled as vitamin D deficient. These subjects can be called subclinical VDD, and further studies are required to assess beneficial effect of vitamin D supplementation in this subset of population. This hypothesis further highlights pitfalls in treatment of hypoparathyroidism.

Vitamin B12 deficiency and hyperhomocysteinemia as correlates of cardiovascular risk factors in Indian subjects with coronary artery disease.

BACKGROUND AND PURPOSE: Folate and vitamin B12 are essential components in the metabolism of homocysteine (Hcy). Hyperhomocysteinemia has been implicated in endothelial dysfunction and cardiovascular disease. However, the association of Hcy, vitamin B12, and folic acid with cardiovascular risk factors in patients with coronary artery disease (CAD) has not been studied in Indian patients. This study was conducted with the aim to evaluate the relationship of vitamin B12, folic acid, and Hcy levels with cardiovascular risk factors in subjects with known CAD. METHODS AND SUBJECTS: Three hundred patients (216 men; 84 women; aged 25-92 years) who had CAD on angiography were included in this study consecutively. All patients were evaluated for anthropometry and cardiovascular risk factors, and blood samples were collected for biochemical, nutritional, and inflammatory markers. RESULTS: Percentage of vitamin B12 and folate deficiency was 86.7% and 2.7%, respectively. Hyperhomocysteinemia was present in 95.3% patients. Vitamin B12 levels were significantly lower and Hcy levels were significantly higher in subjects with dyslipidemia, DM, and/or hypertension. Serum vitamin B12 was inversely associated with triglyceride and very low-density lipoprotein (VLDL) and positively with high-density lipoprotein (HDL). Hcy was positively associated with triglyceride and VLDL and negatively with HDL. Vitamin B12 was inversely correlated with inflammatory markers (high-sensitivity C-reactive protein and interleukin-6) directly related to insulin resistance whereas Hcy showed the opposite pattern. CONCLUSIONS: Serum vitamin B12 deficiency and hyperhomocysteinemia are related with cardiovascular risk factors in Indian patients with CAD.

Differences in traditional and non-traditional risk factors with special reference to nutritional factors in patients with coronary artery disease with or without diabetes mellitus.

INTRODUCTION: There is an increase in awareness about the role of nutritional factors in chronic non-communicable diseases. We therefore conducted this study with an aim to assess the relationship between nutritional factor (vitamin B12 and homocysteine [Hcy]) and its association with insulin resistance and inflammatory markers, and differences in traditional and non-traditional risk factors among diabetics and non-diabetics in known cases of coronary artery disease (CAD). MATERIALS AND METHODS: Three hundred consecutive patients with known coronary disease on coronary angiography, who were >25 years old were included in this study. All cases were interviewed using a questionnaire. Blood samples were analyzed for insulin, vitamin B12, Hcy and inflammatory markers (highly sensitive C-reactive protein [hsCRP], interleukin-6 [IL-6], Tumor necrosis factor-alfa [TNF-α]). Insulin resistance was calculated with homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Mean age of the patients was 60.95 ± 12.3 years. Body mass index and waist hip ratio were comparable in both groups. Triglyceride, very low-density lipoprotein and HbA1C were significantly higher and high-density lipoprotein (HDL) was significantly lower in patients with diabetes. Patients with diabetes had significantly high levels of IL-6, hsCRP and TNF-α compared with non-diabetic patients. Insulin resistance was twofold higher in diabetic patients. Serum vitamin B12 levels were significantly lower and Hcy was significantly higher in the diabetic group compared with the non-diabetic patients. HbA1C, HOMA-IR and Hcy levels were positively correlated with inflammatory markers in the total study population and in the non-diabetic patients; but, in diabetic patients, HbA1C and Hcy showed this relation. CONCLUSIONS: Vitamin B12 deficiency is common in the diabetic population. Hcy levels were higher in diabetics compared with non-diabetics, and were related to glycemic level and insulin resistance in diabetic patients. Patients with diabetes had higher traditional risk factors than patients without diabetes in known patients with CAD. Glycemic status was associated with insulin resistance and inflammatory markers.

Adipokines (adiponectin and plasminogen activator inhhibitor-1) in metabolic syndrome.

BACKGROUND: The clustering of cardiovascular risk factors is termed the metabolic syndrome (MS), which strongly predicts the risk of diabetes and cardiovascular disease (CVD). Adipokines may contribute to the development of obesity and insulin resistance and may be a causal link between MS, diabetes and CVD. Hence, we studied the adipokines - adiponectin and plasminogen activator inhibitor-1 (PAI-1) - in subjects with MS. MATERIALS AND METHODS: We studied 50 subjects with MS diagnosed by International Diabetes Federation (IDF) criteria and 24 healthy age- and sex-matched controls. Clinical evaluation included anthropometry, body fat analysis by bioimpedance, highly sensitive C-reactive protein, insulin, adiponectin, and PAI-1 measurement. RESULTS: Subjects with MS had lower adiponectin (4.01 ± 2.24 vs. 8.7 ± 1.77 µg/ml; P < 0.0001) and higher PAI-1 (53.85 ± 16.45 vs. 17.35 ± 4.45 ng/ml; P < 0.0001) levels than controls. Both were related with the number of metabolic abnormalities. Adiponectin was negatively and PAI-1 was positively associated with body mass index, waist hip ratio (WHR), body fat mass, percent body fat, and all the parameters of MS, except HDL where the pattern reversed. WHR and triglycerides were independent predictors of adipokines in multiple regression analysis. Receiver operating characteristic curve analysis showed that adiponectin (6.7 µg/ml) and PAI-1 (25.0 ng/ml) levels predicted the MS with high sensitivity, specificity and accuracy in Indian population. CONCLUSIONS: Subjects with MS have lower adiponectin and higher PAI-1 levels compared to healthy controls. Lifestyle measures have been shown to improve the various components of MS, and hence there is an urgent need for public health measures to prevent the ongoing epidemic of diabetes and CVD.