Suyog M. Joshi

Spuriously High Prevalence of Prediabetes Diagnosed by HbA1c in Young Indians Partly Explained by Hematological Factors and Iron Deficiency Anemia

OBJECTIVE To examine the influence of glycemic and nonglycemic parameters on HbA1c concentrations in young adults, the majority of whom had normal glucose tolerance. RESEARCH DESIGN AND METHODS We compared the diagnosis of normal glucose tolerance, prediabetes, and diabetes between a standard oral glucose tolerance test (OGTT; World Health Organization 2006 criteria) and HbA1c concentrations (American Diabetes Association [ADA] 2009 criteria) in 116 young adults (average age 21.6 years) from the Pune Children’s Study. We also studied the contribution of glycemic and nonglycemic determinants to HbA1c concentrations. RESULTS The OGTT showed that 7.8% of participants were prediabetic and 2.6% were diabetic. By ADA HbA1c criteria, 23.3% were prediabetic and 2.6% were diabetic. The negative predictive value of HbA1c was 93% and the positive predictive value was 20% (only 20% had prediabetes or diabetes according to the OGTT; this figure was 7% in anemic participants). Of participants, 34% were anemic, 37% were iron deficient (ferritin <15 ng/mL), 40% were vitamin B12 deficient (<150 pmol/L), and 22% were folate deficient (<7 nmol/L). On multiple linear regression analysis, HbA1c was predicted by higher 2-h glucose (R2 = 25.6%) and lower hemoglobin (R2 = 7.7%). When hematological parameters were replaced by ferritin, vitamin B12, and folate, HbA1c was predicted by higher glycemia (R2 = 25.6%) and lower ferritin (R2 = 4.3%). CONCLUSIONS The use of HbA1c to diagnose prediabetes and diabetes in iron-deficient populations may lead to a spuriously exaggerated prevalence. Further investigation is required before using HbA1c as a screening tool in nutritionally compromised populations.

Vitamin B12 and folate during pregnancy and offspring motor, mental and social development at 2 years of age

Insufficiency of vitamin B12 (B12) and folate during pregnancy can result in low concentrations in the fetus and have adverse effects on brain development. We investigated the relationship between maternal B12 and folate nutrition during pregnancy and offspring motor, mental and social development at two years of age (2 y). Mothers (n = 123) and their offspring (62 girls, 61 boys) from rural and middle-class urban communities in and around Pune city were followed through pregnancy up to 2 y. Maternal B12 and folate concentrations were measured at 28 and 34 weeks of gestation. At 2 y, the Developmental Assessment Scale for Indian Infants was used to determine motor and mental developmental quotients and the Vineland Social Maturity Scale for the social developmental quotient. Overall, 62% of the mothers had low B12 levels (<150 pmol/l) and one mother was folate deficient during pregnancy. Maternal B12 at 28 and 34 weeks of gestation was associated with offspring B12 at 2 y (r = 0.29, r = 0.32, P < 0.001), but folate was not associated with offspring folate. At 2 y, motor development was associated with maternal folate at 28 and 34 weeks of gestation. Mental and social development quotients were associated positively with head circumference and negatively with birth weight. In addition, pregnancy B12 and folate were positively associated with mental and social development quotients. Maternal B12 and folate during intrauterine life may favorably influence brain development and function. Pregnancy provides a window of opportunity to enhance fetal psychomotor (motor and mental) development.

Treatment of hyperglycaemia in newly diagnosed diabetic patients is associated with a reduction in oxidative stress and improvement in β-cell function

There exist several reports demonstrating enhancement in oxidative stress in diabetic patients; however, serial and comprehensive measurement of oxidative stress parameters in newly diagnosed diabetic patients is not yet reported. We measured the oxidative stress parameters in diabetic patients serially from the time of diagnosis and after starting treatment to study their association with glycaemia, insulin resistance and β‐cell function.

Child's homocysteine concentration at 2 years is influenced by pregnancy vitamin B12 and folate status.

Longitudinal studies investigating vitamin B12 and folate status of mothers and their offspring will provide a better understanding of intergenerational nutrition. During pregnancy and 2 years (2y) after delivery, we measured plasma vitamin B12 and folate concentrations in 118 women [aged (mean ± s.d.) 22.9 ± 3.9y] who attended a rural (n = 68) or an urban (n = 50) antenatal clinic in Pune, India. Cord blood vitamin B12 and folate were measured, and when the child was 2y total homocysteine (tHcy) was also measured. Demographic and diet measurements were recorded using standard methods. Pregnancy plasma vitamin B12 concentration at 34 weeks was low [median (25th, 75th), 115 (95, 147) pm]; 75% had low status (<150 pm). Plasma folate was high (mean ± s.d., 33 ± 21 nm); one had a folate concentration <7 pm. Cord plasma vitamin B12 and folate concentrations were higher than and positively associated with maternal concentrations. In stepwise regression, higher child vitamin B12 at 2y was predicted (total R 2 15.7%) by pregnancy vitamin B12 (std β 0.201, R 2 7.7%), current consumption of cows milk (std β 0.194, R 2 3.3%) and whether breast feeding was stopped before 2y (std β -0.234 R 2 7.2%). Childs 2y tHcy concentration was high (11.4 ± 3.6 μm) and predicted by lower pregnancy vitamin B12 (std β -0.206, R 2 4.1%), lack of vitamin supplementation (std β -0.256, R 2 5.6%) in pregnancy and whether currently breastfed (std β 0.268, R 2 8.4%). Low maternal vitamin B12 status in pregnancy and prolonged breast-feeding results in disturbed one-carbon metabolism in offspring at 2y. Supplementation of women of child-bearing age, particularly during pregnancy and lactation, may improve the homocysteine status of these children.

Gut Microbial Diversity Assessment of Indian Type-2-Diabetics Reveals Alterations in Eubacteria, Archaea, and Eukaryotes

Diabetes in India has distinct genetic, nutritional, developmental and socio-economic aspects; owing to the fact that changes in gut microbiota are associated with diabetes, we employed semiconductor-based sequencing to characterize gut microbiota of diabetic subjects from this region. We suggest consolidated dysbiosis of eubacterial, archaeal and eukaryotic components in the gut microbiota of newly diagnosed (New-DMs) and long-standing diabetic subjects (Known-DMs) compared to healthy subjects (NGTs). Increased abundance of phylum Firmicutes (p = 0.010) and Operational Taxonomic Units (OTUs) of Lactobacillus (p < 0.01) were observed in Known-DMs subjects along with the concomitant graded decrease in butyrate-producing bacterial families like Ruminococcaceae and Lachnospiraceae. Eukaryotes and fungi were the least affected components in these subjects but archaea, except Methanobrevibacter were significantly decreased in them. The two dominant archaea viz. Methanobrevibacater and Methanosphaera followed opposite trends in abundance from NGTs to Known-DMs subjects. There was a substantial reduction in eubacteria, with a noticeable decrease in Bacteroidetes phylum (p = 0.098) and an increased abundance of fungi in New-DMs subjects. Likewise, opportunistic fungal pathogens such as Aspergillus, Candida were found to be enriched in New-DMs subjects. Analysis of eubacterial interaction network revealed disease-state specific patterns of ecological interactions, suggesting the distinct behavior of individual components of eubacteria in response to the disease. PERMANOVA test indicated that the eubacterial component was associated with diabetes-related risk factors like high triglyceride (p = 0.05), low HDL (p = 0.03), and waist-to-hip ratio (p = 0.02). Metagenomic imputation of eubacteria depict deficiencies of various essential functions such as carbohydrate metabolism, amino acid metabolism etc. in New-DMs subjects. Results presented here shows that in diabetes, microbial dysbiosis may not be just limited to eubacteria. Due to the inter-linked metabolic interactions among the eubacteria, archaea and eukarya in the gut, it may extend into other two domains leading to trans-domain dysbiosis in microbiota. Our results thus contribute to and expand the identification of biomarkers in diabetes.

Response to Comment on: Hardikar et al. Spuriously High Prevalence of Prediabetes Diagnosed by HbA1c in Young Indians Partly Explained by Hematological Factors and Iron Deficiency Anemia. Diabetes Care 2012;35:797–802

We are grateful to Schindhelm et al. (1) for their interest in our article. We measured HbA1c during follow-up of a birth cohort in the hope of substituting it for an oral glucose tolerance test. We found a discrepancy between the results of the oral glucose tolerance test (World Health Organization, 1999) and HbA1c (American Diabetes Association, 2009): A large number of individuals were classified as having “prediabetes” by HbA1c when considered normal glucose tolerant by oral glucose tolerance test (2). This prompted us to investigate possible causes of this discrepancy. We found that a number of hematological parameters (lower hemoglobin …

IGF-I and IGFBP-3 concentrations at 2 years: associations with anthropometry and milk consumption in an Indian cohort

Background/objectivesTo ascertain associations between plasma insulin-like growth factor I (IGF-I), insulin-like growth factor-binding protein 3 (IGFBP-3) and their molar ratio at 2 y with neonatal size, infant growth, body composition at 2 y, and feeding practices in an Indian cohort.Subjects/methodsA cohort of 209 newborns, with 122 followed at 2 y. Anthropometry was conducted at birth and 2 y. IGF-I and IGFBP-3 concentrations were measured in cord blood and at 2 y. Maternal and child diet was assessed by food frequency questionnaires and maternal interviews. Multivariate regression was used to test for associations adjusting for confounding factors.ResultsMean 2 y plasma IGF-I and IGFBP-3 concentrations and IGF-I/IGFBP-3 were 49.4 ng/ml (95% CI: 44.1, 54.8), 1953.8 ng/ml (CI: 1870.6, 2036.9) ng/ml, and 0.088 (CI: 0.081, 0.095), respectively. IGF-I and IGF-I/IGFBP-3 were positively associated with current length, but not body mass index or adiposity. IGF-I was higher among those with greater change in length since birth. IGF-I concentrations were higher in children who drank the most milk (>500 vs. <250 ml per day: 65.6 vs. 42.8 ng/ml, p < 0.04), received other milk <6 months compared to ≥6 months (56.3 vs. 44.8 ng/ml, p < 0.05), and in those whose mothers consumed milk daily vs. less frequently in late pregnancy (56.4 vs. 42.7 ng/ml, p < 0.01). In multivariate regression, 2 y IGF-I concentration and IGF-I/IGFBP-3 were each positively associated with current length and milk intake. IGFBP-3 was not related to anthropometry or milk intake.ConclusionsPlasma IGF-I concentrations and IGF-I/IGFBP-3 at 2 y are positively associated with length at 2 y and current milk intake.