vitamin-b-12 and Insulin-Resistance

Alzheimer's disease is a prevalent form of dementia, particularly among the elderly population. It is characterized by progressive cognitive decline and neurodegeneration. Despite numerous studies, the exact cause of Alzheimer's disease remains uncertain, and various theories have been proposed, including Aβ amyloid deposition in the brain and tau protein hyper-phosphorylation. This review article explores the potential pathogenesis of Alzheimer's disease, focusing on the effects of derangements in the levels of vitamin B12, folate, and homocysteine, as well as the impact of oral bacteria causing periodontitis and insulin resistance, and their relationship to Alzheimer's. Studies have shown that high levels of homocysteine and low levels of vitamin B12 and folate, are associated with an increased risk of developing Alzheimer's disease. The article also explores the link between Alzheimer's disease and oral bacteria, specifically dental infections and periodontitis, which contribute to the inflammatory processes in the nervous system of Alzheimer's patients. There could be derangement in the insulin signaling further causing disruption in glucose metabolism within the brain, suggesting that Alzheimer's disease may represent a form of type 2 diabetes mellitus associated with the brain, commonly known as type 3 diabetes. Neuroimaging techniques, including MRI, PET, and tau PET, can identify the predictive characteristics of Alzheimer's disease, with amyloid PET being the most useful in ruling out the disease. The article concludes by stressing the importance of understanding genetic and neuroimaging factors in the diagnosing and treating Alzheimer's disease.

Topics: Aged; Alzheimer Disease; Biomarkers; Diabetes Mellitus, Type 2; Folic Acid; Humans; Insulin Resistance; Vitamin B 12

This review brings together human and animal studies and reviews that examine the possible role of maternal vitamin B12 (B12) on fetal growth and its programming for susceptibility to chronic disease. A selective literature review was undertaken to identify studies and reviews that investigate these issues, particularly in the context of a vegetarian diet that may be low in B12 and protein and high in carbohydrate. Evidence is accumulating that maternal B12 status influences fetal growth and development. Low maternal vitamin B12 status and protein intake are associated with increased risk of neural tube defect, low lean mass and excess adiposity, increased insulin resistance, impaired neurodevelopment and altered risk of cancer in the offspring. Vitamin B12 is a key nutrient associated with one carbon metabolic pathways related to substrate metabolism, synthesis and stability of nucleic acids and methylation of DNA which regulates gene expression. Understanding of factors regulating maternal-fetal one carbon metabolism and its role in fetal programming of non communicable diseases could help design effective interventions, starting with maternal nutrition before conception.

Topics: Animals; Biomarkers; Chronic Disease; Diet, Vegetarian; DNA Methylation; Female; Fetal Development; Humans; Insulin Resistance; Lipogenesis; Maternal Nutritional Physiological Phenomena; Metabolic Networks and Pathways; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency is common in certain populations, such as in India, where there is also a rising prevalence of Type 2 diabetes, obesity and their complications. Human cohorts and animal models provide compelling data suggesting the role of the one-carbon cycle in modulating the risk of diabetes and adiposity via developmental programming. Early mechanistic studies in animals suggest that alterations to the cellular provision of methyl groups (via the one-carbon cycle) in early developmental life may disrupt DNA methylation and induce future adverse phenotypic changes. Furthermore, replacement of micronutrient deficits at suitable developmental stages may modulate this risk. Current human studies are limited by a range of factors, including the accuracy and availability of methods to measure nutritional components in the one-carbon cycle, and whether its disruptions exert tissue-specific effects. A greater understanding of the causal and mechanistic role of the one-carbon cycle is hoped to generate substantial insights into its role in the developmental origins of complex metabolic diseases and the potential of targeted and population-wide prevention strategies.

Topics: Adiposity; Carbon Cycle; Diabetes Mellitus, Type 2; Environmental Exposure; Female; Fetal Development; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Infant, Newborn; Insulin Resistance; Male; Maternal Nutritional Physiological Phenomena; Methylmalonic Acid; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Vitamin B 12; Vitamin B 12 Deficiency

India is world's capital for low birth weight (LBW), which is ascribed to intrauterine growth restriction (IUGR) rather than prematurity. An average Indian mother is short and thin and gives birth to a light and thin baby. Maternal undernutrition is thought to be a major factor in the aetiology of IUGR, and the undernutrition is usually thought to be a low macronutrient intake. The Pune Maternal Nutrition Study (PMNS) showed that the Indian babies were thin but fat (more adipose) compared to European babies, and that maternal intake of micronutrient-rich foods was a strong determinant of fetal size. Two thirds of the mothers had low vitamin B(12) concentrations, folate deficiency was rare, and high circulating concentrations of homocysteine predicted IUGR. Follow up of these children revealed that higher maternal folate in pregnancy predicted higher adiposity and insulin resistance at 6 years of age. The most insulin resistant children were born to mothers who were vitamin B(12) deficient and had high folate concentrations. Thus, PMNS suggests an important role for maternal one-carbon (1C) metabolism in fetal growth and programming of diabetes risk. This could be due to the role of 1C metabolism in synthesis of nucleic acids, genomic stability and the epigenetic regulation of gene function. In addition, methionine has important role in protein synthesis. These ideas are supported by animal studies. The next logical step in India will be to improve 1C metabolism in adolescents to effect intergenerational prevention of adiposity, diabetes and other related conditions.

Topics: Adiposity; Adolescent; Adult; Birth Weight; Carbon; Epigenesis, Genetic; Female; Fetal Development; Folic Acid; Humans; India; Infant, Low Birth Weight; Infant, Newborn; Insulin Resistance; Maternal Nutritional Physiological Phenomena; Pregnancy; Vitamin B 12; Vitamins

Metabolic syndrome (MS) is a worldwide medical problem characterized by a cluster of cardiovascular risk factors and metabolic modifications involving peripheral insulin resistance. Nonalcoholic steatohepatitis (NASH) represents the liver expression of this pathological condition. Both MS and NASH are characterized by proinflammatory status and increased oxidative stress. According this, we aimed to review the literature for considering a possible role for vitamins as therapeutical support in MS and NASH.

Topics: Adult; Animals; Antioxidants; Cells, Cultured; Clinical Trials as Topic; Endothelial Cells; Fatty Liver; Female; Folic Acid; Hepatitis; Homocysteine; Humans; Insulin Resistance; Male; Metabolic Syndrome; Oxidative Stress; Rats; Risk Factors; Silybin; Silymarin; Time Factors; Vitamin B 12; Vitamin D; Vitamins

This study was conducted to investigate and compare the effects of add-on folic acid and vitamin B12 supplementation on glycaemic control, insulin resistance and serum lipid profile in subjects with type 2 diabetes mellitus.. This study was a randomized, multi-arm, open-label clinical trial. 80 patients with type 2 diabetes and on stable oral antidiabetics were enrolled and 20 patients each were randomly allocated to one of the four groups - Group A: add-on Folic acid (5 mg/day); Group B: add-on Methylcobalamin (500 mcg/day); Group C: add-on Folic acid (5 mg/day) + Methylcobalamin (500 mcg/day) and Group D: Standard oral anti-diabetic drugs. The patients were followed up after 8 weeks.. HbA1c improved significantly in Groups B and C [median changes from baseline - 1.2 % (- 13 mmol/mol) and - 1.5 % (- 16 mmol/mol) respectively, p values 0.04 and 0.02 respectively] compared to Group D. Groups B and C also showed significant improvements in plasma insulin, insulin resistance and serum adiponectin compared to Group D. Serum homocysteine declined significantly in all three groups with add-on supplementation compared to standard treatment. No improvement in the lipid profile was noted in any of the groups.. Add-on supplementation with vitamin B12 improved glycaemic control and insulin resistance in patients with type 2 diabetes mellitus.

Topics: Adult; Diabetes Mellitus, Type 2; Dietary Supplements; Drug Therapy, Combination; Folic Acid; Glycemic Control; Humans; Insulin Resistance; Lipids; Middle Aged; Vitamin B 12

Obesity is a major public health problem and great risk for not only cardiovascular diseases but also cancer, musculoskeletal, and gynecological diseases. This study was aimed to investigate the association between serum Vitamin B12 (vitB12), body mass index (BMI), and nutritional status among obese women.. This cross-sectional study enrolled consecutive female subjects. The consumptions of red meat, fish, bovine liver, egg, and mushroom were recorded. According to the Dietary Reference Intakes, the patients were categorized as insufficiency and sufficiency. Three cutoff points were defined for vitB12 status: (1) Deficiency if vitB12 is <200 pg/mL; (2) insufficiency if vitB12 is 250-350 pg/mL, and (3) sufficient if vitB12 is ≥350 pg/mL. According to BMI, the patients were assigned to nonobese and obese groups. BMI, serum vitB12 level, consumptions of red meat, fish, bovine liver, egg, and mushroom were evaluated and compared between two groups.. Mean level of vitB12 was 247.8 ± 10.4 pg/mL and significantly associated with consumption of egg (P = 0.031), bovine liver (P = 0.004), mushroom (P = 0.040), and red meat (P = 0.003). VitB12 was significantly higher in nonobese than obese group (282.5 ± 106.8 vs. 242.5 ± 107.5 pg/mL, P = 0.001). The ratio of vitB12 deficiency was significantly higher in obese than nonobese group (37.6% vs. 24.7%; P = 0.019). VitB12 level was negatively correlated with BMI (r = -0.155; P< 0.001), but not insulin resistance (r = -0.172; P = 0.062).. Obesity was associated with low level of vitB12 in obese women, and more likely to be vitB12 deficient. Consumption of certain types of food contributes to increase vitB12 level.

Topics: Adult; Animals; Body Mass Index; Cardiovascular Diseases; Cattle; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Middle Aged; Nutritional Status; Obesity; Turkey; Vitamin B 12

Epidemiological data suggest that moderate red wine consumption reduces cardiovascular mortality and the incidence of diabetes. However, whether these effects are due to ethanol or to non-alcoholic components of red wine still remains unknown. The aim of the present study was to compare the effects of moderate consumption of red wine, dealcoholized red wine, and gin on glucose metabolism and the lipid profile.. Sixty-seven men at high cardiovascular risk were randomized in a crossover trial. After a run-in period, all received each of red wine (30 g alcohol/d), the equivalent amount of dealcoholized red wine, and gin (30 g alcohol/d) for 4 week periods, in a randomized order. Fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), plasma lipoproteins, apolipoproteins and adipokines were determined at baseline and after each intervention.. Fasting glucose remained constant throughout the study, while mean adjusted plasma insulin and HOMA-IR decreased after red wine and dealcoholized red wine. HDL cholesterol, Apolipoprotein A-I and A-II increased after red wine and gin. Lipoprotein(a) decreased after the red wine intervention.. These results support a beneficial effect of the non-alcoholic fraction of red wine (mainly polyphenols) on insulin resistance, conferring greater protective effects on cardiovascular disease to red wine than other alcoholic beverages. www.isrctn.org: ISRCTN88720134.

Topics: Adipokines; Aged; Apolipoproteins; Blood Glucose; Cardiovascular Diseases; Cholesterol; Cross-Over Studies; Diet; Ethanol; Fasting; Folic Acid; Glucose; Homeostasis; Homocysteine; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Polyphenols; Risk Factors; Triglycerides; Vitamin B 12; Wine

This study was conducted to evaluate the effects of two different oral contraceptives (OCs) on homocysteine (Hcy) metabolism in 20 women with polycystic ovary syndrome (PCOS).. Women were randomly allocated to receive either the biphasic OC containing 40/30 mug ethynylestradiol (EE)+25/125 mug desogestrel (DSG; n=10) or the monophasic OC containing 35 mug EE and 2 mg cyproterone acetate (CPA; n=10). Investigations were performed before and after 6 months of treatment. Fasting vitamin B(12), folate, Hcy and insulin sensitivity (SI), and glucose utilization independent of insulin (Sg), by the minimal model method, were evaluated.. Folate and vitamin B(12) were not significantly modified by either OC. EE/DSG decreased SI (2.53+/-0.35 vs. 1.68+/-0.45; p<.05), without modifying Hcy (9.54+/-0.7 micromol/L vs. 9.18+/-0.6 micromol/L). EE/CPA improved SI (1.47+/-0.38 vs. 3.27+/-0.48; p<.04) and decreased Hcy (9.8+/-1.9 micromol/L vs. 7.9+/-0.9 micromol/L; p<.05). This study indicates that in women with PCOS, EE/CPA, but not EE/DSG, improves IS and decreases fasting Hcy.

Topics: Adult; Blood Glucose; Contraceptives, Oral; Cyproterone Acetate; Desogestrel; Ethinyl Estradiol; Female; Folic Acid; Homocysteine; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome; Vitamin B 12

Elevated levels of plasma homocysteine (Hcy) have been implicated as a significant risk factor for cardiovascular disease. Although long-term treatment with metformin can increase Hcy levels in patients with type II diabetes mellitus or coronary heart disease, it is becoming an increasingly accepted and widespread medication in polycystic ovary syndrome (PCOS). In the literature, only one study has demonstrated that metformin increases Hcy levels in PCOS patients, but the effect of other insulin sensitizers on Hcy levels have not been reported previously in women with PCOS. We aimed to assess the effects of metformin and rosiglitazone on plasma Hcy levels in patients with PCOS.. Thirty women were randomized to two groups: 15 women in group 1 received 850 mg of metformin twice daily for 3 months. In group 2, 15 women received 4 mg of rosiglitazone for 3 months. In both groups, body mass index, menstrual pattern, and plasma total Hcy, insulin, glucose and lipid metabolism parameters were recorded at baseline and at 3 months.. Hcy levels increased from 8.93+/-0.49 to 11.26+/-0.86 micromol/l (P = 0.002) and from 10.70+/-0.86 to 12.36+/-0.81 micromol/l (P = 0.01) in the metformin and rosiglitazone groups, respectively. Apolipoprotein (Apo) A1 levels increased from 127.10+/-6.85 to 145.7+/-7.18 mg/dl (P = 0.018) in the metformin group. Total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein (a) and Apo B levels decreased in the metformin group, but the change was not significant. Total-C levels decreased from 161.15+/-8.94 to 150.23+/-8.73 mg/dl (P = 0.026), HDL-C decreased from 43.13+/-2.65 to 39.15+/-2.52 mg/dl (P = 0.005) and LDL-C levels decreased from 93.83+/-6.06 to 80.7+/-2.30 mg/dl (P = 0.021) in the rosiglitazone group.. Treatment with insulin sensitizers in women with PCOS may lead to increases in Hcy levels.

Topics: Adult; Anovulation; Blood Glucose; Body Weight; Female; Folic Acid; Homocysteine; Humans; Hypoglycemic Agents; Insulin Resistance; Lipids; Luteinizing Hormone; Metformin; Polycystic Ovary Syndrome; Rosiglitazone; Testosterone; Thiazolidinediones; Vitamin B 12

Although GnRH analogues are widely used to treat a variety of sex hormone-related diseases, little is known about their effect on metabolism. Therefore, we have evaluated the effect of a GnRH analogue, administered with or without raloxifene, on serum levels of lipoproteins, glucose, insulin and homocysteine (Hcy).. One hundred premenopausal women with symptomatic uterine leiomyomas were initially enrolled and randomized to receive 3.75 mg/28 days leuprolide acetate depot associated with 60 mg/day raloxifene hydrochloride (group A) or 1 placebo tablet/day (group B) for six cycles of 28 days. At entry and at cycle 6, subjects underwent anthropometric measurements, including body mass index and waist-to-hip ratio measurements, and blood chemistry assays for serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, Hcy, vitamin B(12) and folate concentrations. Insulin resistance was evaluated with the homeostasis model assessment (HOMA) score.. Baseline parameters were similar in the two groups. At cycle 6, TC, HDL-C, LDL-C and TG levels were significantly increased (P < 0.05) in group B. In group A, LDL-C levels were unchanged, and TC, HDL-C and TG levels were increased (P < 0.05). Serum TC and LDL-C levels differed (P < 0.05) between the groups. Glucose levels were unchanged between and within groups, whereas insulin levels and HOMA scores increased (P < 0.05) versus baseline in group B. Post-treatment Hcy levels were higher (P < 0.05) versus baseline in group B; they were unchanged in group A. Serum vitamin B(12) and folate concentrations were unchanged in both groups.. GnRH analogues alter serum lipoprotein and Hcy levels and increase insulin resistance. These acute metabolic changes may be prevented or reduced by raloxifene.

Topics: Adult; Blood Glucose; Body Constitution; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Delayed-Action Preparations; Female; Folic Acid; Homeostasis; Homocysteine; Humans; Insulin; Insulin Resistance; Leiomyoma; Leuprolide; Lipids; Middle Aged; Placebos; Premenopause; Raloxifene Hydrochloride; Triglycerides; Uterine Neoplasms; Vitamin B 12

Gestational diabetes mellitus (GDM) can adversely affect the health of the developing fetus. Women of South Asian origin are particularly at risk of developing GDM. Insulin resistance (IR) contributes to the etiology of GDM, and although studies have shown associations of vitamin B12 (B12) and folate status with GDM and IR, only a limited number of B12 and folate markers have been used.. We used a comprehensive panel of B12 and folate markers to examine their association with IR in pregnant women with diet-controlled GDM and normal glucose tolerance (NGT).. In this cross-sectional study, 59 British-Bangladeshi women (24 GDM and 35 NGT) with a mean age of 29 y, BMI (in kg/m2) 26.7 and gestational age 33 wk were recruited. Serum total B12, holotranscobalamin, folate, methylmalonic acid, plasma homocysteine, 5-methyltetrahydrofolate, and red cell folate (RCF) were measured along with other parameters. The independent sample t-test and chi-squared test were used to assess differences in markers between GDM and NGT women. Spearman's test was used to look for correlations. A simple multiple regression analysis was used to investigate if markers of B12 and folate status predicted IR, using the HOMA-IR and adjusting for age, GDM status, and BMI.. There were no differences in concentrations of B12 and folate markers between GDM and NGT women. In Spearman's analysis HOMA-IR correlated negatively with total serum B12 (P < 0.001) and holotranscobalamin (P < 0.05), and positively with BMI (P < 0.001), blood pressure (P < 0.05) and triglycerides (P < 0.05) in all women. MMA did not correlate with any of the B12 markers. In regression analysis, total B12 (β = -0.622, P = 0.004), RCF (β = 0.387, P = 0.018), and BMI (β = 0.024, P < 0.001) were the significant predictors of HOMA-IR variance.. Significant associations between markers of B12 and folate status with HOMA-IR were found during the third trimester in British-Bangladeshi women. B12 markers correlated poorly with each other.

Topics: Adult; Blood Glucose; Cross-Sectional Studies; Diabetes, Gestational; Female; Folic Acid; Glucose; Humans; Insulin; Insulin Resistance; Pregnancy; Pregnancy Trimester, Third; Vitamin B 12

We aimed to evaluate the association between vitamin B12, folate, homocysteine levels, and carotid intima-media thickness (CIMT) among children with obesity in whom vitamin deficiencies are more frequent.. Herein, 100 children with obesity (58 girls) were included (age, 5-18 years). Height, weight, body mass index (BMI), waist circumference (WC), puberty stage, blood pressure, and biochemical values were collected from medical records; standard deviations (SDS) and percentiles were calculated. Obesity was defined as BMI SDS of >+2SDS. Vitamin B12 and folate levels of <300 pg/mL and <4.8 ng/mL, respectively, were considered deficient. A radiologist quantified measurements from the carotid artery.. Mean patient age was 12.52 ± 3.63 years. The mean weight SDS, BMI SDS, and WC/height were +3.37 ± 0.93, +2.93 ± 0.55, and 0.65 ± 0.05, respectively. In pubertal cases, insulin (p<0.001), the homeostatic model assessment for insulin resistance (HOMA-IR) (p=0.001) and homocysteine (p=0.002) levels were higher; vitamin B12 (p<0.001) and folate (p<0.001) levels were lower than those in prepubertal ones. WC and HOMA-IR correlated with CIMT; however, homocysteine levels were not correlated with CIMT.. In our study, pubertal cases had lower vitamin B12 and folate levels as well as higher homocysteine levels. Although no correlation was identified between homocysteine levels and CIMT, this condition may be related to our study group comprising children, who had a shorter duration of obesity than those in adults. As CIMT was higher in children/adolescents with increased WC, it is proposed that they need central obesity more frequently and carefully follow-up.

Topics: Adolescent; Adult; Carotid Intima-Media Thickness; Child; Child, Preschool; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Insulin Resistance; Obesity; Risk Factors; Vitamin B 12

In daily life, the intake of dietary nutrients is mixed. However, evidence for the association between mixed dietary B vitamin intake and insulin resistance is limited. In this study, we estimated the joint effect of intake of various dietary B vitamins on insulin resistance.. This cross-sectional study used data from the National Health and Nutrition Examination Survey 2011-2018. We included 1,628 middle-aged and 1,058 older adults without diabetes. Multivariable logistic regression and Bayesian kernel machine regression models were constructed.. In the multivariable logistic regression, when all B vitamins were included in the model, the ORs (95% CIs) of insulin resistance were 3.06 (1.00-9.37) and 0.42 (0.19- 0.93) for the highest quartile of vitamin B-1 and B-12 intake in the middle-aged group when the lowest quartile was the reference. In the older group, no significant association was observed. In the Bayesian kernel machine regression analysis, a negative trend was noted between mixed B vitamin intake and insulin resistance in both examined groups. The univariate exposure-response function indicated that vitamin B-12 intake was negatively associated with insulin resistance in the middle-aged group, and that vitamin B-6 and dietary folate equivalent intakes were negatively associated with insulin resistance in older group. The bivariate exposure-response function indicated a potential interaction effect between dietary intake of vitamin B-12 and those of vitamin B-1, B-2, niacin, and dietary folate equivalent on insulin resistance in older people.. Our results suggest that mixed dietary B vitamin intake tends to decrease the OR of insulin resistance both in middle-aged and older people.

Topics: Aged; Bayes Theorem; Cross-Sectional Studies; Diabetes Mellitus; Dietary Supplements; Eating; Folic Acid; Humans; Insulin Resistance; Middle Aged; Nutrition Surveys; Vitamin B 12; Vitamin B Complex

Dairy cows suffer insulin resistance following parturition and lactogenesis. Several researchers attempted to reduce insulin resistance via dietary and parenteral supplementations of different substances to promote metabolic performance of dairy cows. Due to mechanisms of actions of butaphosphan in combination with cyanocobalamin, we hypothesized that this compound may reduce insulin resistance of dairy cows following parturition; hence, the effects of the intravenous administration of butaphosphan and cyanocobalamin to prepartum dairy cows on their insulin resistance after calving were evaluated. Twenty-four multiparous Holstein dairy cows were enrolled 3 weeks prior to parturition and divided into four equal groups, including control (Ctrl) and butaphosphan and cyanocobalamin (B+C) 1, 2, and 3. Ctrl cows received 15 mL of 0.9% NaCl solution and B+C 1, 2, and 3 groups intravenously received 2, 4, and 6 mL/100 kg BW of 10% butaphosphan and 0.005% cyanocobalamin combination over three periods of 3 consecutive days, including 21-19, 12-10, and 3-1 days before calving, respectively. Intravenous glucose tolerance test was performed weekly 1, 2, and 3 weeks after parturition to evaluate the insulin resistance phenomenon. Circulating levels of glucose, insulin, non-esterified fatty acids (NEFA), and beta-hydroxybutyric acid (BHBA) were assessed 1, 2, and 3 weeks after calving. Ctrl cows were the most insulin-resistant group, and B+C1 group was the most insulin-sensitive, followed by B+C2 and B+C3 groups. The NEFA and BHBA levels in the B+C3 group were significantly lower than those in the other groups. In conclusion, intravenous administration of butaphosphan and cyanocobalamin to the late-pregnant dairy cows may reduce their insulin resistance after calving.

Topics: 3-Hydroxybutyric Acid; Administration, Intravenous; Animals; Blood Glucose; Butylamines; Cattle; Diet; Fatty Acids, Nonesterified; Female; Humans; Insulin; Insulin Resistance; Lactation; Phosphinic Acids; Postpartum Period; Pregnancy; Vitamin B 12

Vitamin B12 and folate deficiency are not only linked to hematological, neurological, and cardiovascular diseases, but are also associated with insulin resistance. Metformin can decrease vitamin B12 and folate concentrations.. To examine (1) effects of short-term metformin treatment on serum holotranscobalamin (holoTC) and folate and (2) their association with insulin sensitivity in recent-onset type 2 diabetes.. This cross-sectional analysis comprised patients (known disease duration <12 months) on metformin monotherapy (MET, n = 123, 81 males, 53 ± 12 years) or nonpharmacological treatment (NPT, n = 126, 77 males, 54 ± 11 years) of the German Diabetes Study.. HoloTC (enzyme-linked immunosorbent assay), cobalamin, and folate (electrochemiluminescence); beta-cell function and whole-body insulin sensitivity, measured during fasting (HOMA-B, HOMA-IR) and intravenous glucose tolerance tests combined with hyperinsulinemic-euglycemic clamp tests.. HoloTC (105.4 [82.4, 128.3] vs 97 [79.7, 121.9] pmol/L) and folate concentrations (13.4 [9.3, 19.3] vs 12.7 [9.3, 22.0] nmol/L) were similar in both groups. Overall, holoTC was not associated with fasting or glucose-stimulated beta-cell function and insulin-stimulated glucose disposal. Cobalamin measurements yielded similar results in representative subgroups. In NPT but not MET, folate levels were inversely correlated with HOMA-IR (r = -0.239, P = .007). Folate levels did not relate to insulin sensitivity or insulin secretion in the whole cohort and in each group separately after adjustment for age, body mass index, and sex.. Metformin does not affect circulating holoTC and folate concentrations in recent-onset type 2 diabetes, rendering monitoring of vitamin B12 and folate dispensable, at least during the first 6 months after diagnosis or initiation of metformin.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Folic Acid; Folic Acid Deficiency; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin Resistance; Male; Metformin; Middle Aged; Prognosis; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Topics: Folic Acid; Humans; Insulin Resistance; Metabolic Syndrome; Obesity, Morbid; Vitamin B 12; Vitamin B 12 Deficiency

Low vitamin B12 and high folate during pregnancy are associated with visceral obesity and insulin resistance in offspring. In the general population, high folate exacerbates the increase of methylmalonic acid, a marker of vitamin B12 deficiency. However, the influence of vitamin B12 and folate and their related markers on insulin resistance and metabolic syndrome remains unknown in severe obesity.. To evaluate the influence of vitamin B12 and folate on HOMA-IR and components of metabolic syndrome in severe obesity.. 278 consecutive obese patients were assessed prospectively for HOMA-IR, red blood cell (RBC) folates, homocysteine and methylmalonic acid. We compared the associations with the components of metabolic syndrome during the preoperative multidisciplinary evaluation (period-1) and before bariatric surgery (period-2).. The HOMA-IR was higher in patients with highest tertile of RBC and either lowest tertile of plasma B12 or highest tertile of MMA (p < 0.034 and 0.011, respectively). Lg HOMA-IR was negatively correlated with Lg homocysteine (p < 0.0001) and positively correlated with Lg serum folate (p < 0.001). The independent predictors for HOMA-IR at period 2 were either BMI and homocysteine (model 1 without serum folate, p = 0.010 and p = 0.002, respectively) or BMI and MMA (model 2 without homocysteine, p = 0.030 and p = 0.004, respectively). Age and RBC folate remained independently associated with the number of metabolic syndrome components (p = 0.006 and 0.020, respectively).. RBC folate, homocysteine, and MMA predict HOMA-IR in severe obesity. Our findings challenge the benefit of folate fortified food in severe obesity, in particular in patients with a deficit of vitamin B12. The cohort study was registered at clinicaltrials.gov as NCT02663388.

Topics: Adult; Body Mass Index; Erythrocytes; Female; Folic Acid; Homocysteine; Humans; Insulin Resistance; Male; Metabolic Syndrome; Methylmalonic Acid; Middle Aged; Obesity, Morbid; Vitamin B 12; Vitamin B 12 Deficiency

Several observational studies have shown that low serum vitamin B-12 is associated with increased body mass index (BMI) and adverse cardiometabolic outcomes. However, it is unclear if these associations reflect a causal effect of vitamin B-12 on cardiometabolic risk factors and diseases, latent confounding, or reverse causality.. The aims of this study were to investigate 1) the possible causal relation between vitamin B-12 and indicators of body fat, lipid, and glucose variables; type 2 diabetes (T2D); and cardiovascular disease by using a 2-sample Mendelian randomization (MR) method and 2) the possible pleiotropic role of fucosyltransferase 2 (FUT2).. We selected 11 single nucleotide polymorphisms (SNPs) robustly associated with serum concentrations of vitamin B-12 in a previous genomewide association study (GWAS) in 45,576 individuals. We performed 2-sample MR analyses of the relation between vitamin B-12 and cardiometabolic risk factors and diseases with the use of publicly available GWAS summary statistics for 15 outcomes in ≤339,224 individuals. The robustness of results was tested with sensitivity analyses by using MR Egger regression and weighted-median estimation, and by performing additional analyses excluding a variant in the FUT2 gene, which may be pleiotropic.. We found a suggestive causal relation between vitamin B-12 and fasting glucose and β cell function [homeostatic model assessment (HOMA) of β cell function (HOMA-B)]. However, we found no evidence that serum concentrations of vitamin B-12 were causally related to BMI, waist-to-hip ratio, plasma leptin, body fat, fasting insulin, insulin resistance (from HOMA of insulin resistance), glycated hemoglobin, triglycerides, T2D, coronary artery disease, or HDL, LDL, or total cholesterol.. We found no evidence that serum concentrations of vitamin B-12 are causally related to body weight or the majority of cardiometabolic outcomes investigated. However, vitamin B-12 may have a causal effect on fasting glucose and HOMA-B, although these results will require replication in large independent data sets. This trialwas registered at http://www.isrctn.com/ISRCTN47414943 as ISRCTN47414943.

Topics: Blood Glucose; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fucosyltransferases; Galactoside 2-alpha-L-fucosyltransferase; Genome-Wide Association Study; Humans; Insulin Resistance; Leptin; Lipids; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors; Vitamin B 12

Phellinus linteus polysaccharide (PLP) has hypoglycemic effects, but mechanisms remain unclear. Male C57BL/6 J mice were either fed a normal diet (CON) or a high-fat high-fructose diet (HFD) for 16 weeks, and starting from week 12, HFD-fed animals in PLP group were orally given PLP. PLP administration significantly reduced fasting blood glucose level and ameliorated glucose intolerance. Differentially expressed genes involved in FOXO signaling pathway and in vitamin B12 (VB12) transport were identified between HFD and PLP group. HFD decreased the phosphatidylcholine (PC) to phosphatidylethanolamine (PE) ratio and S-adenosyl methionine to S-adenosyl homocysteine ratio, which were recovered by PLP treatment. Plasma VB12 levels in HFD group was lower than CON or PLP group, and PLP stimulated the proliferation of gut bacteria in genus Porphyromonas with capability of VB12 synthesis. In conclusion, PLP administration improved insulin resistance via modifying hepatic phospholipids metabolism and rescuing insulin signaling transduction.

Topics: Animals; Basidiomycota; Diet, High-Fat; Fructose; Fungal Polysaccharides; Hypoglycemic Agents; Insulin Resistance; Intestinal Mucosa; Intestines; Liver; Male; Mice; Mice, Inbred C57BL; Microbiota; Obesity; Phosphatidylcholines; S-Adenosylmethionine; Sucrose; Vitamin B 12

To assess whether adolescents with high body mass index (BMI), or fat mass index (FMI), in combination with insulin resistance (assessed with the Homeostatic Model Assessment [HOMA] index), had also lower blood vitamin B6, folate and vitamin B12 concentrations.. Six hundred and fifteen adolescents from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, with data on B-vitamins (both intakes and status), and BMI, FMI, HOMA, were selected. Intakes were assessed by two non-consecutive 24-h recalls. B-vitamins biomarkers were measured by chromatography and immunoassay. Analysis of covariance was applied to elucidate the differences in B-vitamins between combinations of groups defined according to the median of the z-scores of markers of body composition and insulin sensitivity.. When considering energy intakes and education of the mother in the model, in females, vitamin B6 intakes were higher in the high BMI/high HOMA group than in the high BMI-low HOMA group. Similarly, vitamin B6 intakes were higher in the high FMI/high HOMA group than in the low FMI/low HOMA group. Plasma vitamin B12 was significantly lower in males in the high FMI/high HOMA group than in the low FMI/low HOMA group, keeping also significant their trends throughout the groups, a fact that can be observed also for females (p < 0.05).. Adolescents with combined higher adiposity and higher HOMA insulin sensitivity showed lower vitamin B12 plasma concentrations. These differences do not seem to be explained by dietary vitamin B12 intake.

Topics: Adiposity; Adolescent; Biomarkers; Body Mass Index; Child; Cross-Sectional Studies; Educational Status; Europe; Female; Humans; Insulin Resistance; Male; Mothers; Vitamin B 12; Vitamin B Complex

Low vitamin B12 during pregnancy is associated with higher maternal obesity, insulin resistance (IR), and gestational diabetes mellitus. B12 is a key cofactor in one-carbon metabolism.. We hypothesize that B12 plays a role in epigenetic regulation by altering circulating microRNAs (miRs) during adipocyte differentiation and results in an adverse metabolic phenotype.. Human preadipocyte cell line (Chub-S7) was differentiated in various B12 concentrations: control (500 nM), low B12 (0.15 nM), and no B12 (0 nM). Maternal blood samples (n = 91) and subcutaneous adipose tissue (SAT) (n = 42) were collected at delivery. Serum B12, folate, lipids, plasma one-carbon metabolites, miR profiling, miR expression, and gene expression were measured.. Our in vitro model demonstrated that adipocytes in B12-deficient conditions accumulated more lipids, had higher triglyceride levels, and increased gene expression of adipogenesis and lipogenesis. MiR array screening revealed differential expression of 133 miRs involving several metabolic pathways (adjusted P < 0.05). Altered miR expressions were observed in 12 miRs related to adipocyte differentiation and function in adipocytes. Validation of these data in pregnant women with low B12 confirmed increased expression of adipogenic and lipogenic genes and altered miRs in SAT and altered levels of 11 of the 12 miRs in circulation. After adjustment for other possible confounders, multiple regression analysis revealed an independent association of B12 with body mass index (β: -0.264; 95% confidence interval, -0.469 to -0.058; P = 0.013) and was mediated by four circulating miRs targeting peroxisome proliferator-activated receptor γ and IR.. Low B12 levels in pregnancy alter adipose-derived circulating miRs, which may mediate an adipogenic and IR phenotype, leading to obesity.

Topics: 3T3 Cells; Adipocytes; Adipogenesis; Animals; Cells, Cultured; Circulating MicroRNA; Cross-Sectional Studies; Diabetes, Gestational; Female; Gene Expression Regulation; Humans; Insulin Resistance; Mice; Obesity; PPAR gamma; Pregnancy; Pregnancy Complications; Vitamin B 12; Vitamin B 12 Deficiency

To determine the relationship among vitamin B12 status, obesity severity, and metabolic syndrome and its components in obese children... This case-control study was conducted at the School of Medicine, Gaziosmanpasa University, Tokat, Turkey, from January 2012 and October 2014, and comprised cases of obese and healthy children. The obese children were divided into three groups according to body mass index-standard deviation score quartiles. Group 1 included the first quartile, group 2 included the second and third quartiles, and group 3 included the fourth quartile. Patients with a body mass index of >95th percentile, according to reference curves for Turkish children and adolescents, were considered obese.Patients with a body mass index between15th and 85th percentile were considered to have normal weight. The World Health Organisation's modified metabolic syndrome criteria for children were used to diagnose metabolic syndrome.SPSS 19 was used for data analysis.. Of the 256 participants, 153(59.8%) were obese and 103(40.2%) were healthy controls. The mean age of the obese children was 12.69±2.29 years and that of healthy controls was 13.05±2.48 years. Mean vitamin B12 levels were significantly lower among obese children than healthy volunteers (p<0.001). Age and body mass index-standard deviation score were significantly associated with vitamin B12 status (r= -0.175, p=0.030; r= -0.210, p=0.09, respectively).. Increase in body mass index-standard deviation score was associated with a decrease in vitamin B12 levels.

Topics: Adolescent; Case-Control Studies; Child; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Obesity, Morbid; Severity of Illness Index; Turkey; Vitamin B 12

We have demonstrated previously that severe but not moderate vitamin B12 deficiency altered body composition and induced adiposity in female C57BL/6 mice. This study aims to elucidate the effects of chronic transgenerational dietary vitamin B12 restriction on body composition and various biochemical parameters in the F1 generation offspring of our mouse models of severe and moderate vitamin B12 deficiency established earlier. Female weanling C57BL/6 mice received, ad libitum, for 4 weeks a (i) control diet, (ii) vitamin B12-restricted diet with pectin as dietary fiber (severely deficient diet), or (iii) vitamin B12-restricted diet with cellulose as dietary fiber (moderately deficient diet) and then mated with control males. The offspring of control and severely deficient dams continued on the respective diets of their mothers. Few moderately deficient dams were rehabilitated to control diet from parturition and their pups were weaned to control diet. Also, some offspring born to moderately B12 deficient dams were weaned to control diet, while others continued on the same diet as their mothers. Various parameters were determined in the F1 offspring after 12 and 36 weeks of feeding. The results indicate that both severe and moderate maternal vitamin B12 restrictions were associated with accelerated catch-up growth, increased body fat percentage, visceral adiposity, dyslipidemia, fasting hyperglycemia and insulin resistance in the F1 offspring. Inflammation, increased glucocorticoid and oxidative stress and poor antioxidant defence probably underlie these adverse effects. Rehabilitation from parturition but not weaning was beneficial in delaying the onset of the adverse outcomes in the offspring. © 2016 BioFactors, 43(3):400-414, 2017.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Composition; Diet; Dietary Fiber; Dyslipidemias; Female; Hyperglycemia; Inheritance Patterns; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Obesity; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Severity of Illness Index; Vitamin B 12; Vitamin B 12 Deficiency

Studies in South Asian population show that low maternal vitamin B12 associates with insulin resistance and small for gestational age in the offspring. Low vitamin B12 status is attributed to vegetarianism in these populations. It is not known whether low B12 status is associated with metabolic risk of the offspring in whites, where the childhood metabolic disorders are increasing rapidly. Here, we studied whether maternal B12 levels associate with metabolic risk of the offspring at birth.. This is a cross-sectional study of 91 mother-infant pairs (n = 182), of white Caucasian origin living in the UK. Blood samples were collected from white pregnant women at delivery and their newborns (cord blood). Serum vitamin B12, folate, homocysteine as well as the relevant metabolic risk factors were measured.. The prevalence of low serum vitamin B12 (<191 ng/L) and folate (<4.6 μg/L) were 40% and 11%, respectively. Maternal B12 was inversely associated with offspring's Homeostasis Model Assessment 2-Insulin Resistance (HOMA-IR), triglycerides, homocysteine and positively with HDL-cholesterol after adjusting for age and BMI. In regression analysis, after adjusting for likely confounders, maternal B12 is independently associated with neonatal HDL-cholesterol and homocysteine but not triglycerides or HOMA-IR.. Our study shows that low B12 status is common in white women and is independently associated with adverse cord blood cholesterol.

Topics: Adult; Blood Glucose; Body Mass Index; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Diet, Vegetarian; Female; Fetal Blood; Folic Acid; Gestational Age; Homocysteine; Humans; Insulin; Insulin Resistance; Maternal Nutritional Physiological Phenomena; Nutritional Status; Pregnancy; Risk Factors; Triglycerides; United Kingdom; Vitamin B 12; White People

Vitamin B12 and folate are critical micronutrients needed to support the increased metabolic demands of pregnancy. Recent studies from India have suggested that low vitamin B12 and folate concentrations in pregnancy are associated with increased obesity; however differences in diet, antenatal vitamin supplementation, and socioeconomic status may limit the generalisability of these findings. We aimed to explore the cross-sectional relationship of circulating serum vitamin B12 and folate at 28 weeks' gestation with maternal adiposity and related biochemical markers in a white non diabetic UK obstetric cohort.. Anthropometry and biochemistry data was available on 995 women recruited at 28 weeks gestation to the Exeter Family Study of Childhood Health. Associations between B12 and folate with maternal BMI and other obesity-related biochemical factors (HOMA-R, fasting glucose, triglycerides, HDL and AST) were explored using regression analysis, adjusting for potential confounders (socioeconomic status, vegetarian diet, vitamin supplementation, parity, haemodilution (haematocrit)).. Higher 28 week BMI was associated with lower circulating vitamin B12 (r = -0.25; P<0.001) and folate (r = -0.15; P<0.001). In multiple regression analysis higher 28 week BMI remained an independent predictor of lower circulating B12 (β (95% CI) = -0.59 (-0.74, -0.44) i.e. for every 1% increase in BMI there was a 0.6% decrease in circulating B12). Other markers of adiposity/body fat metabolism (HOMA-R, triglycerides and AST) were also independently associated with circulating B12. In a similar multiple regression AST was the only independent obesity-related marker associated with serum folate (β (95% CI) = 0.16 (0.21, 0.51)).. In conclusion, our study has replicated the previous Indian findings of associations between lower serum B12 and higher obesity and insulin resistance during pregnancy in a non-diabetic White British population. These findings may have important implications for fetal and maternal health in obese pregnancies.

Topics: Adiposity; Cross-Sectional Studies; Diet; Diet, Vegetarian; Dietary Supplements; Female; Folic Acid; Humans; Insulin Resistance; Life Style; Lipoproteins, HDL; Obesity; Pregnancy; Pregnancy Complications; Triglycerides; United Kingdom; Vitamin B 12; Vitamin B 12 Deficiency; White People

In an Indian birth cohort, higher maternal homocysteine concentration in pregnancy was associated with lower birthweight of the offspring. Lower maternal vitamin B12 and higher folate concentrations were associated with higher offspring insulin resistance. Disordered one-carbon metabolism during early development may increase later metabolic risk. We explored these associations in another birth cohort in India at three age points.. We measured plasma vitamin B12, folate and homocysteine concentrations at 30 ± 2 weeks' gestation in 654 women who delivered at one hospital. Neonatal anthropometry was recorded, and the children's glucose and insulin concentrations were measured at 5, 9.5 and 13.5 years of age. Insulin resistance was estimated using HOMA of insulin resistance (HOMA-IR).. Maternal homocysteine concentrations were inversely associated with all neonatal anthropometric measurements (p < 0.05), and positively associated with glucose concentrations in the children at 5 (30 min; p = 0.007) and 9.5 years of age (120 min; p = 0.02). Higher maternal folate concentrations were associated with higher HOMA-IR in the children at 9.5 (p = 0.03) and 13.5 years of age (p = 0.03). Maternal vitamin B12 concentrations were unrelated to offspring outcomes.. Maternal vitamin B12 status did not predict insulin resistance in our cohort. However, associations of maternal homocysteine and folate concentrations with birth size, and with childhood insulin resistance and glycaemia in the offspring, suggest a role for nutritionally driven disturbances in one-carbon metabolism in fetal programming of diabetes.

Topics: Adult; Female; Folic Acid; Homocysteine; Humans; Insulin Resistance; Pregnancy; Vitamin B 12; Young Adult

Emerging evidence indicates an association between obesity, metformin use and reduced vitamin B12 status, which can have serious hematologic, neurologic and psychiatric consequences. This study aimed to examine B12 status in obese adolescents with pre-diabetes and/or clinical features of insulin resistance. Serum B12 was measured using chemiluminescence immunoassay in 103 (43 male, 60 female) obese (mean body mass index (BMI) z-score ± SD (2.36 ± 0.29)), adolescents aged 10 to 17 years, median (range) insulin sensitivity index of 1.27 (0.27 to 3.38) and 13.6% had pre-diabetes. Low B12 (<148 pmol/L) was identified in eight (7.8%) and borderline status (148 to 221 pmol/L) in an additional 25 (24.3%) adolescents. Adolescents with borderline B12 concentrations had higher BMI z-scores compared to those with normal concentrations (2.50 ± 0.22 vs. 2.32 ± 0.30, p = 0.008) or those with low B12 concentration (2.50 ± 0.22 vs. 2.27 ± 0.226, p = 0.041). In conclusion, nearly a third of obese adolescents with clinical insulin resistance had a low or borderline serum B12 status. Therefore, further investigations are warranted to explore the cause and the impact of low B12 status in obese pediatric populations.

Topics: Adolescent; Biomarkers; Blood Glucose; Body Mass Index; Child; Female; Humans; Immunoassay; Insulin; Insulin Resistance; Male; New South Wales; Nutrition Assessment; Nutritional Status; Pediatric Obesity; Prediabetic State; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Both insulin resistance (IR) and vitamin D deficiency (VDD) are found to be associated with many cancer types. In this study, we evaluated the presence of IR and VDD in thyroid cancer patients based on controls. Total 344 papillary thyroid cancer and 116 controls were part of the study. Glucose, insulin, homeostasis model analysis-insulin resistance (HOMA-IR) (control group 2.12 ± 0.9 and patient group 3.6 ± 1.1; p < 0.0001), LDL were significantly high; HOMA-S and vitamin D3 levels (control group 19.11 ± 8 and patient group 17 ± 16; p = 0.004) were significantly low in the patient group. Vitamin D deficiency (64/108 in controls vs 166/235; p = 0.026) and insulin resistance (24/108; 115/235; p < 0.0001) were more frequent in papillary thyroid cancer patients. After regression analysis, tumor diameter showed significant association with log-HOMA-IR (B = 0.315; p = 0.017) and log-vitamin D3 (B = 0.207; p = 0.04). Vitamin D deficiency and insulin resistance frequencies show no difference between micro- and macropapillary thyroid cancers. Receiver operating characteristic curve shows the best cutoff point for tumor diameter showing that the presence of lymph node metastasis was 0.65 cm with 81.2 % sensitivity and 52 % specificity. Best cutoff point for the capsular invasion tumor diameter was 0.75 cm with 83.3 % sensitivity and 60.4 % specificity. No difference between follicular and classical type papillary thyroid carcinomas has been yet discovered. As a result, thyroid cancer patients are more insulin resistant and vitamin D3 deficient. Vitamin D3 levels and HOMA-IR index may affect tumor diameter. Tumor size that is lower than 1 cm (0.65-0.75 cm) may be related with capsular invasion and lymph node involvement.

Topics: Adult; Carcinoma; Carcinoma, Papillary; Case-Control Studies; Cholecalciferol; Female; Folic Acid; Homeostasis; Humans; Insulin Resistance; Male; Middle Aged; ROC Curve; Thyroglobulin; Thyroid Cancer, Papillary; Thyroid Neoplasms; Vitamin B 12

Concerns have been raised on whether a gluten-free diet affects the cardiovascular risk profile of coeliac patients.. To assess changes of multiple cardiovascular risk factors in coeliac patients evaluated before and during a gluten-free diet.. Retrospective analysis of the effects of 1-5 years of gluten-free diet on indicators of cardiovascular risk and on distribution in cardiovascular risk categories in 715 coeliac patients.. Compared to baseline, significant increases were found in body mass index (21.4±3.4 vs. 22.5±3.5; p<0.0001), total cholesterol (171.2±37.4mg/dL vs. 181.4±35.1mg/dL; p<0.0001), and γ-glutamyl transpeptidase (16.5±14.9 vs. 19.5±19.2U/L; p<0.0001). Significant reductions were found in serum triglycerides (87.9±49.5 vs. 80.2±42.8mg/dL; p<0.0001) and homocysteine (16.9±9.6 vs. 13.3±8.0μmol/L; p=0.018) during gluten-free diet. The proportion of patients included in an arbitrarily defined category of "lowest cardiovascular risk profile" decreased from 58% at baseline to 47% during gluten-free diet.. A gluten-free diet significantly affects cardiovascular risk factors in coeliac patients, but changes do not consistently point towards worse or better risk profiles, thus suggesting that the diet is unlikely to be atherogenic.

Topics: Adult; Body Mass Index; Cardiovascular Diseases; Celiac Disease; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, Gluten-Free; Female; Folic Acid; gamma-Glutamyltransferase; Homocysteine; Humans; Insulin Resistance; Male; Middle Aged; Retrospective Studies; Risk Factors; Triglycerides; Vitamin B 12; Young Adult

The burden of chronic noncommunicable diseases (NCDs) such as diabetes, obesity and cardiovascular disease is shifting rapidly to low- and middle-income countries. It calls for a review of the classic 'dogma' of genetic predisposition, precipitated by adult lifestyle. The paradigm of early life origins of chronic disease has focused attention on maternal health and nutrition as major determinants of the health of the offspring. India has high burden of maternal ill health and also of diabetes and cardiovascular disease, offering unique opportunities to study the links between the two. Pune studies showed that the Indian babies were thin but fat (more adipose) compared to European babies, and that maternal micronutrient status during pregnancy was a determinant of offspring size and body composition. Two thirds of the mothers had low vitamin B12 concentrations, while folate deficiency was rare. Higher circulating concentrations of homocysteine predicted smaller baby size. Follow-up studies revealed that higher maternal folate in pregnancy predicted higher adiposity and insulin resistance in the child at 6 years of age, and that low maternal vitamin B12 exaggerated the risk of insulin resistance. Low maternal vitamin B12 status is also associated with increased risk of neural tube defects and poor offspring cognitive functions. Our results suggest an important role for maternal one-carbon metabolism in offspring growth and programming of NCD risk. These ideas are supported by animal studies. Improvement of adolescent nutrition could effect intergenerational prevention of chronic diseases.

Topics: Adiposity; Adolescent; Adult; Animals; Body Weight; Carbon; Cardiovascular Diseases; Child; Chronic Disease; Diabetes Mellitus; Female; Folic Acid; Folic Acid Deficiency; Growth; Homocysteine; Humans; India; Infant; Infant, Newborn; Insulin Resistance; Maternal Nutritional Physiological Phenomena; Neural Tube Defects; Nutritional Status; Pregnancy; Pregnancy Complications; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

To investigate correlation of vitamin B12 with obesity insulin resistance, metabolic syndrome.. The cross-sectional and primary care-based study was carried out. Anthropometric, blood pressure measurements and bioelectric impedance analysis (BIA) were recorded. Vitamin B12, folic acid, hemogram, insulin, ferritin, iron, total iron binding capacity and other biochemical tests were assayed. The subjects were grouped as obesity, overweight, control, metabolic syndrome (MetS) and insulin resistance (IR). Correlation of vitamin B12 with body mass index (BMI), IR, age, and BIA was evaluated.. The study enrolled 976 patients (obesity: 414, overweight: 212, and control: 351). The mean age in groups of obesity, overweight and control were 35.9 ± 8.7, 28.9 ± 6.3 and 33.1 ± 8.7, respectively (p = 0.142). Vitamin B12 level was significantly lower in patients with obesity and overweight than healthy individuals (178.9 ± 25.2; 219.8 ± 78.5, and 328.5 ± 120.5, p less than 0.001, respectively). Vitamin B12 level was lower in patients with MetS (+/-) and IR (+/-), but insignificant (p = 0.075 and 0.058, respectively). Significant and negative correlation was observed between vitamin B12 and BMI (r =-0.221, p=0.001). No significant difference was observed between obese male and female patients (247.8 ± 89.1 versus 235.5 ± 89.3 pg/mL, respectively, p=0.090).. Low Vitamin B12 level was associated with obesity and overweight, but not with insulin resistance, metabolic syndrome and gender. Vitamin B12 was negatively correlated only with body mass index.

Topics: Adipose Tissue; Body Mass Index; Cross-Sectional Studies; Humans; Insulin Resistance; Metabolic Syndrome; Obesity; Overweight; Primary Health Care; Vitamin B 12

Asian Indians are an at-risk group for vitamin B12 deficiency (because of vegetarianism) and insulin resistance (IR). Vegetarianism and consequent vitamin B12 deficiency may be associated with IR. This study aimed to describe the vitamin B12 status of predominantly overweight/obese women of South Asian origin living in Auckland and to correlate serum vitamin B12 and vegetarian status with IR as part of the larger Surya Study looking at health and lifestyle in this population.. This was a cross-sectional study of 135 women at least 20 y of age who were not taking vitamin B supplements or medications that could affect vitamin B12 concentrations (serum vitamin B12 < 800 pmol/L). Data collection included serum vitamin B12, serum folate, measurements of IR (HOMA2-IR), and anthropometry. Vegetarian status was established for 124 subjects (90 non-vegetarians, 34 vegetarians).. Mean serum vitamin B12 was 227 pmol/L (95% confidence interval 210-245), serum folate was 19.1 nmol/L (18.0-20.2), and HOMA2-IR was 1.24 (1.13-1.36). Non-vegetarians had higher serum vitamin B12 levels (257 pmol/L, 235-281) than vegetarians (181 pmol/L, 159-207), P < 0.001. Vitamin B12 deficiency (<150 pmol/L) in vegetarians was 24% versus 9% in non-vegetarians. Non-vegetarians had increased body mass index (25.9 kg/m², 25.0-26.9, versus 23.9 kg/m², 22.6-25.3), waist circumference (81 ± 10.1 versus 75.8 ± 9.88 cm), and HOMA2-IR levels (1.30, 1.17-1.46, versus 1.00, 0.83-1.22). No correlation was found between serum vitamin B12 and HOMA2-IR. A significant positive correlation between non-vegetarian status and IR disappeared after controlling for body mass index.. This study population has a low serum vitamin B12 status, especially if vegetarian. The high rates of observed obesity may have overshadowed any other contributing factor to IR.

Topics: Adult; Body Mass Index; Cross-Sectional Studies; Diet, Vegetarian; Emigrants and Immigrants; Female; Folic Acid; Humans; India; Insulin Resistance; Middle Aged; New Zealand; Obesity; Overweight; Prevalence; Vitamin B 12; Vitamin B 12 Deficiency

Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) are complex diseases affected by both dietary intake and genetic background. Whether N-5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, high-sensitivity C-reactive protein (hs-CRP) and dietary components folate and vitamin B12 are associated with MS in Asian has not been determined.. We hypothesized that MTHFR gene C677T, folate, vitamin B12 and hs-CRP are associated with MS and factors related to MS in northern Han Chinese. To test this hypothesis, MTHFR C677T gene polymorphism was determined by PCR-RFLP, serum insulin, folate and vitamin B12 levels by radioimmunoassay, and hs-CRP by immunoturbidimetry in newly diagnosed T2DM patients with MS (118) and without MS (40), and in 55 healthy subjects.. Results indicated that MS-associated T2DM accounts for 75% of newly diagnosed T2DM in Han Chinese. Serum hs-CRP was higher and serum vitamin B12 was lower in subjects with TT genotype in comparison with those with CC or CT genotypes. Total T frequency was significantly higher in MS-associated T2DM patients (45.3%) compared to 26.3% in non-MS-associated T2DM patients. MTHFR C677T gene polymorphism and vitamin B12 levels were associated with MS-associated T2DM.. MTHFR C677T gene polymorphism may contribute to insulin resistance in Han Chinese with MS by increasing hs-CRP and decreasing vitamin B12, and consequently play an important role in development of MS-associated T2DM.

Topics: Aged; Asian People; C-Reactive Protein; Female; Folic Acid; Genetic Predisposition to Disease; Humans; Insulin Resistance; Male; Metabolic Syndrome; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Radioimmunoassay; Vitamin B 12

This study was designed to test the hypothesis that low plasma vitamin B(12) concentrations combined with high folate concentrations in pregnancy are associated with a higher incidence of gestational diabetes (GDM) and later diabetes.. Women (N = 785) attending the antenatal clinics of one hospital in Mysore, India, had their anthropometry, insulin resistance (homeostasis model assessment-2) and glucose tolerance assessed at 30 weeks' gestation (100 g oral glucose tolerance test; Carpenter-Coustan criteria) and at 5 years after delivery (75 g OGTT; WHO, 1999). Gestational vitamin B(12) and folate concentrations were measured in stored plasma samples.. Low vitamin B(12) concentrations (<150 pmol/l, B(12) deficiency) were observed in 43% of women and low folate concentrations (<7 nmol/l) in 4%. B(12)-deficient women had higher body mass index (p < 0.001), sum of skinfold thickness (p < 0.001), insulin resistance (p = 0.02) and a higher incidence of GDM (8.7% vs 4.6%; OR 2.1, p = 0.02; p = 0.1 after adjusting for BMI) than non-deficient women. Among B(12)-deficient women, the incidence of GDM increased with folate concentration (5.4%, 10.5%, 10.9% from lowest to highest tertile, p = 0.04; p for interaction = 0.2). Vitamin B(12) deficiency during pregnancy was positively associated with skinfold thickness, insulin resistance (p < 0.05) and diabetes prevalence at 5 year follow-up (p = 0.009; p = 0.008 after adjusting for BMI). The association with diabetes became non-significant after excluding women with previous GDM (p = 0.06).. Maternal vitamin B(12) deficiency is associated with increased adiposity and, in turn, with insulin resistance and GDM. Vitamin B(12) deficiency may be an important factor underlying the high risk of 'diabesity' in south Asian Indians.

Topics: Adult; Body Mass Index; Diabetes Mellitus; Diabetes, Gestational; Female; Folic Acid; Glucose Tolerance Test; Humans; Infant; Infant Mortality; Infant, Newborn; Insulin Resistance; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Socioeconomic Factors; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Polycystic ovary syndrome (PCOS) shares some or most components of metabolic cardiovascular syndrome, manifested by abdominal obesity, insulin resistance, dyslipidaemia and atherosclerosis. It has been previously demonstrated that folate and vitamin B(12) treatment improved insulin resistance in patients with metabolic syndrome. This study first investigated whether PCOS patients have lower or higher vitamin B(12), folate and homocysteine concentrations when compared with healthy, age and body mass index matched controls, and, then examined associations between vitamin B(12), folate, homocysteine and insulin resistance and obesity in PCOS patients. Homocysteine concentrations and homeostasis model assessment index were higher, whereas concentrations of vitamin B(12) were lower in PCOS patients with insulin resistance compared with those without insulin resistance. Serum vitamin B(12) concentrations were significantly lower in obese PCOS women in comparison with obese control women (P < 0.05). Fasting insulin, insulin resistance and homocysteine are independent determinants of serum vitamin B(12) concentrations in PCOS patients. Insulin resistance, obesity, and elevated homocysteine were associated with lower serum vitamin B(12) concentrations in PCOS patients.

Topics: Adult; Case-Control Studies; Female; Folic Acid; Homocysteine; Humans; Insulin Resistance; Obesity; Polycystic Ovary Syndrome; Vitamin B 12

Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B12, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years.. In the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B12, tHcy and methylmalonic acid (MMA) at 18 and 28 weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6 years.. Two-thirds of mothers had low vitamin B12 (<150 pmol/l), 90% had high MMA (>0.26 micromol/l) and 30% had raised tHcy concentrations (>10 micromol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28 weeks predicted higher offspring adiposity and higher HOMA-R (both p < 0.01). Low maternal vitamin B12 (18 weeks; p = 0.03) predicted higher HOMA-R in the children. The offspring of mothers with a combination of high folate and low vitamin B12 concentrations were the most insulin resistant.. Low maternal vitamin B12 and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India.

Topics: Adipose Tissue; Anthropometry; Body Composition; Body Mass Index; Child; Female; Folic Acid; Homocysteine; Humans; Insulin Resistance; Male; Methylmalonic Acid; Pregnancy; Pregnancy Complications; Vitamin B 12

Topics: Adipose Tissue; Cohort Studies; Cytosol; Female; Folic Acid; Humans; Insulin Resistance; Mitochondria; Models, Biological; Mothers; Obesity; Pregnancy; Pregnancy Complications; Vitamin B 12

We aim to assess serum total homocysteine (tHcy) associations with metabolic syndrome components and B-vitamins in women with gestational diabetes mellitus (GDM).. We studied 61 consecutive pregnant women, 44 with GDM and 17 with normal glucose tolerance (CG). Serum homocysteine levels were analyzed by ELISA, using Bio-Rad reagents. Serum folates and vitamin B(12) concentrations were determined by chemiluminescent immunoassay, free fatty acids (FFA) and lipids enzymatically.. Serum homocysteine levels were similar in both the GDM and the CG groups (8+/-2.0 vs 7.4+/-1.1 micromol/l, respectively). Women with GDM in comparison to CG women were characterized by higher values of homeostasis model of insulin resistance (HOMA-IR) (2.8+/-1.7 vs 1.6+/-0.9, P<0.01), serum triglycerides (2.7+/-0.9 vs 1.9+/-0.5 mmol/l, P<0.01) and FFA (0.6+/-0.2 vs 0.46+/-0.2 mmol/l, P<0.05). In GDM women serum tHcy correlated with vitamin B(12) (r= -0.47, P<0.01) and folates (r= -0.51, P<0.001); in CG women with HOMA-IR, a marker of insulin resistance (r= -0.49, P<0.05). In multiple regression analysis with serum tHcy as a dependent variable, folate and vitamin B(12) entered the analysis in GDM women (beta= -0.42 and -0.34, respectively, P<0.05), whereas in CG cystatin C and HOMA-IR entered the analysis (P<0.05).. In women with GDM, serum homocysteine is significantly associated with vitamin B(12) and folate levels, while in healthy pregnant women with HOMA-IR and with kidney function. The results suggest the importance of the B-group vitamins in regulation of serum tHcy levels in women with insulin resistance/gestational diabetes, what might be relevant in protection against pregnancy complications associated with elevated tHcy in GDM women.

Topics: Adult; Case-Control Studies; Diabetes, Gestational; Female; Folic Acid; Homocysteine; Humans; Insulin Resistance; Pregnancy; Vitamin B 12

A complex combination of adult health-related disorders can originate from developmental events that occur in utero. The periconceptional period may also be programmable. We report on the effects of restricting the supply of specific B vitamins (i.e., B(12) and folate) and methionine, within normal physiological ranges, from the periconceptional diet of mature female sheep. We hypothesized this would lead to epigenetic modifications to DNA methylation in the preovulatory oocyte and/or preimplantation embryo, with long-term health implications for offspring. DNA methylation is a key epigenetic contributor to maintenance of gene silencing that relies on a dietary supply of methyl groups. We observed no effects on pregnancy establishment or birth weight, but this modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin-resistant, and had elevated blood pressure-effects that were most obvious in males. The altered methylation status of 4% of 1,400 CpG islands examined by restriction landmark genome scanning in the fetal liver revealed compelling evidence of a widespread epigenetic mechanism associated with this nutritionally programmed effect. Intriguingly, more than half of the affected loci were specific to males. The data provide the first evidence that clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring, and modify adult health-related phenotypes.

Topics: Animals; Animals, Newborn; Blood Pressure; Body Composition; Diet; DNA Methylation; Embryo, Mammalian; Epigenesis, Genetic; Female; Fertilization; Folic Acid; Glucose; Heart Rate; Immunity; Insulin Resistance; Methionine; Pregnancy; Pregnancy Outcome; Sheep; Vitamin B 12; Vitamin B Complex

This study was performed to test whether plasma homocysteine concentrations are related to insulin resistance in healthy premenopausal women. For this purpose, the relationship between insulin resistance (as assessed by HOMA index) and fasting plasma homocysteine level was determined in 83 healthy volunteers. The results indicated that homocysteine concentrations did not vary as a function of HOMA index (r = -0.147). Plasma homocysteine concentrations also did not vary as a function of other parameters of insulin resistance such as HDL-cholesterol and triglycerides, which they correlated inversely with body mass index (BMI). Furthermore, when individuals were classified according to quartiles of insulin resistance (HOMA index), plasma homocysteine concentrations from the lowest to the highest quartiles were not significantly different. On the other hand, the HOMA index correlated significantly with triglyceride concentrations (r = 0.377, p< 0.001), HDL-cholesterol (r = -0.310, p< 0.01) and BMI (r = 0.468, p< 0.001). These results suggest that plasma homocysteine concentrations are not related to insulin resistance and/or metabolic abnormalities associated with it in premenopausal women.

Topics: Adolescent; Adult; Age Factors; Blood Glucose; Body Mass Index; Cholesterol, HDL; Female; Folic Acid; Homocysteine; Humans; Insulin; Insulin Resistance; Premenopause; Triglycerides; Uric Acid; Vitamin B 12

A moderate increase of total homocysteine (tHcy) plasma levels seems to increase cardiovascular disease (CVD) risk in Type 2 diabetic subjects, but its relationship with diabetes and insulin-resistance is still controversial. We examined whether mild hyperhomocysteinemia and its major genetic determinant would cluster with the metabolic syndrome (MS) in Type 2 diabetes. One hundred Type 2 diabetic subjects with and without MS were enrolled in the study. Fasting tHcy, vitamin B12, and folate plasma levels, insulin-resistance [assessed by homeostasis model assessment, (HOMAIR)] and the methylene tetrahydrofolate reductase (MTHFR) C677T genotype were assessed in all the participants. Geometric mean tHcy concentration and the prevalence of mild hyperhomocysteinemia, as commonly defined by tHcy >/=15 micromol/l, were comparable in diabetic subjects with and without MS, even after adjustment for age, sex, vitamin B12, folate and creatinine levels. In both groups, the MTHFR C677T genotype distribution was not significantly different from the Hardy-Weinberg equilibrium, with a TT homozygous frequency of 21% in subjects with and 18% in those without the syndrome (p=ns). tHcy plasma levels and the degree of insulin-resistance did not differ across MTHFR genotypes in both groups, even after multivariable adjustment. Overall, tHcy significantly correlated with creatinine (r=0.25; p=0.009) and trygliceride concentrations (r=0.24; p=0.02), but not with HOMAIR. At multivariate analysis, only creatinine was significantly correlated with tHcy levels (beta=0.42; p=0.001). In conclusion, hyperhomocysteinemia and the common C677T variant of MTHFR gene are not associated with MS in Type 2 diabetic subjects.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Insulin Resistance; Linear Models; Male; Metabolic Syndrome; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Obesity; Polymorphism, Genetic; Triglycerides; Vitamin B 12

There is evidence of an excess of acute cardiovascular (CV) events in marathon runners. High plasma total homocysteine (tHcy) concentrations are a recognised risk factor for CV events. Therefore, we investigated the changes in plasma tHcy concentrations 24h before and after a marathon race.. Twenty-two non-professional male athletes, mean age 35.6 (6.6), range 23-49 years, were studied the day before and 24 h after finishing a marathon race. None of the athletes was a carrier of the MTHFR 677TT genotype and no ingestion of supplements of vitamins (B12, B6, folic acid) was allowed.. Changes in plasma folate and plasma vitamin B12 concentrations were not detected post-race, but a significant increase in plasma tHcy concentrations was demonstrated. Plasma tHcy increased 19% 24h after the race. Before the race 20% of the subjects had a plasma tHcy concentration > 10 micromol/l (cut-off point for ischaemic heart disease risk), while after the race 50% had plasma tHcy concentrations> 10 micromol/l.. An increase in plasma tHcy concentrations was observed after a marathon race in non-professional not well-trained male athletes performing strong physical activity. The potential physiological or pathological implications of this finding are unknown.

Topics: Adult; Blood Glucose; Body Composition; Fasting; Fatty Acids, Nonesterified; Folic Acid; Homocysteine; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Myocardial Infarction; Risk Factors; Running; Vitamin B 12; Waist-Hip Ratio

High serum total homocysteine (tHcy) and lipoprotein (a) [Lp(a)] levels are independent risk factors for cardiovascular disease. In this study, we examined the relationship of tHcy and Lp(a) levels with the components of metabolic syndrome. Fifty-one patients diagnosed with metabolic syndrome (median age: 38 [range 25-48] years) and 50 healthy subjects (median age: 35 [26-48] years) were included in the study. We used the National Cholesterol Education Program criteria to define metabolic syndrome. Total tHcy concentrations were measured by using an IMX (Abbott Diagnostics, Abbott Park, IL, USA). Lipoprotein (a) was measured by immunonephelometry using Behring nephrometer method (Behring BN 100, Behring, Germany). Total homocysteine and Lp(a) levels were found to be higher in the metabolic syndrome group than in the control group (tHcy: 24.2 vs 13.4 micromol/l, P < 0.01 and Lp(a): 34.9 vs 15.8 mg/dl, P < 0.01). Vitamin B12 levels were lower in the metabolic syndrome group than in the control group (214 pg/ml vs 247 pg/ml, P < 0.01). In partial correlation, tHcy and Lp(a) concentrations were unrelated to metabolic syndrome or to the components of metabolic syndrome, including fasting serum triglycerides, HDL-cholesterol, fasting glucose, blood pressure, or body mass index. tHcy levels were strongly related only to the vitamin B12 concentration. The risk of cardiovascular disease is higher in patients with metabolic syndrome compared with the normal population. High tHcy and Lp(a) levels should be evaluated in this group of patients in addition to the evaluation of the parameters of metabolic syndrome.

Topics: Adult; Coronary Disease; Female; Folic Acid; Homocysteine; Humans; Insulin Resistance; Lipoprotein(a); Male; Metabolic Syndrome; Middle Aged; Reference Values; Risk Factors; Statistics as Topic; Turkey; Vitamin B 12

The purpose of this study was to determine whether polycystic ovary syndrome (PCOS) and nonclassic 21-hydroxylase deficiency (CAH) are related to hyperhomocysteinemia, and to investigate if there is a correlation between homocysteine levels and insulin sensitivity in women with PCOS and CAH. Fifty patients with PCOS, 50 patients with CAH and 25 control women were included in the study. Blood samplings were performed in the early follicular phase for measuring hormone profile, Vitamin B(12), folate, homocysteine levels and fasting blood glucose. Ovulatory status was assessed with timed serum progesterone measurements. Homeostasis model assessment-insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Mean homocysteine levels were found as (8.9 + 1.9 micromol/l and 17.7 + 3.6 micromol/l) in the normal group and PCOS respectively (p<0.001), but there was no statistical significance between nonclassic 21-hydroxylase deficiency (9.0 + 2.2 micromol/l) and control group. Most of the patients in PCOS group (35 of 50) were significantly insulin resistant. However, there was no insulin resistant patient in CAH or control group. When we compare the two subgroups of PCOS women, the patients with insulin resistance had significantly higher homocysteine levels than the ones who were not insulin resistant. There were positive correlations among serum homocysteine, insulin and androgen levels in PCOS patients. There were no correlations among these parameters in CAH and control groups. Increased homocysteine levels may contribute to increased cardiovascular disease risk in patients with PCOS. The reason for hyperhomocysteinemia seems to be related to insulin resistance but not high androgen levels.

Topics: Adrenal Hyperplasia, Congenital; Adult; Blood Glucose; Cholesterol; Estradiol; Female; Follicle Stimulating Hormone; Homocysteine; Humans; Insulin Resistance; Luteinizing Hormone; Polycystic Ovary Syndrome; Progesterone; Statistics, Nonparametric; Testosterone; Thyrotropin; Thyroxine; Vitamin B 12

Weak hyperhomocysteinemia is a risk factor for the development of atherothrombotic vascular complication. Their plasma levels are affected by nutritional and pharmacologic factors, tobacco, certain metabolic state and gender. In HIV+ patients, the wasting syndrome or chronic diarrheas could affect the levels of homocysteine (Hcy), as well as some adverse effects of the new antiretroviral therapies (lipodystrophy syndrome: insulin resistance and/or dislypemia). The levels of Hcy were evaluated in 53 HIV+ patients without any treatment and in 75 HIV+ under treatment with and without metabolic disturbances (n = 43; n = 32, respectively).. 32 HIV negative individuals. We looked for association with folic acid, vitamin B12, lipids, insulin resistance status, activation platelets (soluble P-selectin) and endothelial injury (soluble trombomodulin) markers; and also their relation with tobacco, disease status and kind of treatment. There were no statistically significant differences in the mean levels of vitamin B12, Hcy, P-selectin and insulin resistance status between the control group and the HIV+; 16.4% of the 128 HIV+ patients had Hcy > or = 15 mumol/L and the control group had 12.9% (p = 0.617). The levels of Hcy correlated with the levels of folic acid (Rho = -0.314, p < 0.01) and age (Rho = 0.277, p < 0.01) among HIV+. There were no statistically significant differences in the levels of Hcy neither between smokers and non smokers (p = 0.452) nor between HIV+ AIDS or HIV+ no AIDS (p = 0.774) nor with the use of certain antiretrovirals (p = 0.801). The hyperhomocysteinemia (a well known atherothrombotic risk factor) is not frequently associated with HIV infected patients. The levels of Hcy would not seem to be influenced either by the HIV condition or by the antiretroviral treatments or their adverse effects.

Topics: Adult; Anti-HIV Agents; Arteriosclerosis; Biomarkers; Case-Control Studies; Female; Folic Acid; HIV Infections; Homocysteine; Humans; Hyperhomocysteinemia; Insulin Resistance; Male; P-Selectin; Risk Factors; Smoking; Vitamin B 12

Although insulin resistance and elevated plasma homocysteine are associated with hypertension in adults, the role of these conditions in the initial phase of hypertension is largely unknown. We examined whether insulin resistance and disturbed homocysteine metabolism are present in young adults at the early stages of essential hypertension.. We measured physical characteristics, plasma levels of insulin, lipids, total homocysteine, and vitamins in 164 patients with essential juvenile hypertension (median age, 19 years; 92% males) and in 173 controls (median age, 18 years; 66% males). Furthermore, we analyzed the prevalence of six polymorphisms in four genes of the methionine cycle.. Patients with hypertension and controls differed significantly (P <.05) in body mass index, levels of insulin, high-density lipoprotein-cholesterol, fasting and post-load plasma homocysteine, and folates. Systolic blood pressure was correlated with homocysteine levels and inversely correlated with plasma folates. Logistic regression showed that fasting homocysteine, vitamin B(12), and low-density lipoprotein-cholesterol were associated with a significantly increased risk of juvenile hypertension. In contrast, the birth length, polymorphism c.2756 A-->G in the MTR gene and plasma folate were associated with a significantly decreased risk of juvenile hypertension.. Our study showed that essential hypertension in adolescents is associated with lower folate and higher homocysteine levels, and with signs of insulin resistance. These data suggest that hypertension in young individuals may be a part of early manifestation of insulin resistance syndrome, and that disturbed folate and homocysteine metabolism may play a role in the early stages of hypertension.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adolescent; Adult; Cystathionine beta-Synthase; Female; Ferredoxin-NADP Reductase; Folic Acid; Genetic Predisposition to Disease; Homocysteine; Humans; Hypertension; Insulin Resistance; Male; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Prevalence; Risk Factors; Vitamin B 12; Vitamin B 6

Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS).. We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991-1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995-1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 micromol/l in each phenotypic category and differences between categories were assessed with regression models.. The mean age of the subjects was 54 years (range 28-82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 micromol/l) and those without (9.4 micromol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 micromol/l) compared with those with 1 or no phenotype (9.3 micromol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007).. Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Albuminuria; Blood Glucose; Coronary Disease; Creatinine; Fasting; Female; Folic Acid; Glucose Tolerance Test; Homocysteine; Humans; Insulin; Insulin Resistance; Male; Massachusetts; Middle Aged; Risk Factors; Sex Factors; Vitamin B 12

The aim of this study was to determine the distribution of plasma total homocysteine (tHcy) concentrations in type 2 diabetic patients and to assess whether high tHcy values were related to chronic complications (particularly macroangiopathy and nephropathy) and/or the degree of insulin resistance.. Fasting tHcy levels were measured in 122 type 2 diabetic patients in whom the presence of chronic complications (e.g., macroangiopathy, microalbuminuria, macroproteinuria, decreased creatinine clearance, hypertension, retinopathy, and neuropathy) was recorded alongside an assessment of insulin resistance by the homeostasis model assessment (HOMA).. We found that 31% of the cohort (group 1) had raised tHcy (mean +/- 1 SD) values (20.8 +/- 5.1 micromol/l), whereas 69% (group 2) had normal values (10.2 +/- 2.0 micromol/l). The prevalence of macroangiopathy was higher in group 1 than in group 2 subjects (70 vs. 42%, P < 0.01); the prevalence of coronary artery disease was particularly higher in group 1 (46 vs. 21%, P < 0.02). The prevalence of impaired renal function, evidenced by decreased creatinine clearance, was higher in group 1 (32 vs. 10%, P < 0.005). Other clinical and biological characteristics of both groups were comparable, although group 1 had lower levels of folic acid than group 2 (5.2 +/- 2.9 vs. 7.0 +/- 3.4 ng/ml, P < 0.01). No differences were found for microalbuminuria (33 vs. 31%), retinopathy (45 vs. 42%), or neuropathy (70 vs. 59%) between groups 1 and 2, respectively The degree of insulin resistance was similar in groups 1 and 2 (46 +/- 21 and 42 +/- 20% of HOMA-insulin sensitivity) as was the assessment of beta-cell function (63 +/- 28 and 65 +/- 46%, respectively). No differences in tHcy levels were found between subjects receiving metformin and those not receiving metformin. In contrast, the plasma tHcy level was higher in diabetic patients treated with fibrates (P = 0.0016).. Elevated plasma tHcy levels in type 2 diabetes is associated with a higher prevalence of macroangiopathy and nephropathy when assessed from creatinine clearance indexes and is not associated with different degrees of insulin resistance.

Topics: Aged; Cohort Studies; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Female; Folic Acid; Homeostasis; Homocysteine; Humans; Hyperhomocysteinemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Logistic Models; Male; Metabolic Clearance Rate; Metformin; Middle Aged; Vitamin B 12