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Background: Methionine loading test (MLT) has been used primarily to identify defects in transsulfuration of homocysteine in cystathionine beta synthase deficiency. It may not be as useful to evaluate remethylation pathway, in vitamin B-12 and folate deficiencies. Objective: We used tracer isotope labelled MLT to interrogate transsulfuration and remethylation independently in vitamin B-12 deficiency. Design: We studied vitamin B-12 deficient women with a tracer labelled MLT before and eleven months after treatment with vitamin B-12. The fractional contribution of [13C]homocysteine to breath CO2 was used as a measure of transsulfuration, and difference in the intracellular enrichment of [13C]methionine and that of [C2H3]methionine as a measure of remethylation of homocysteine. Combined pre- and post-treatment results were analyzed to investigate the association between plasma vitamin B-12 concentrations and measures of homocysteine metabolism. Results: The subjects were 17 years old, with a BMI of 19.4 kg/m2. Treatment with vitamin B-12, 2µg/day increased plasma B-12 from 93 (78.7, 106.2) [median (25th, 75th centiles)] to 161.5 (125.5, 226.2) pmol/L; 44% were below <150pmol/L after treatment. Fasting homocysteine concentration was significantly lower and that of cysteine higher in subjects with B-12 levels >150pmol/L. The tracer estimated transsulfuration of homocysteine was lower and remethylation higher with B-12 levels >150pmol/L when compared with those <150pmol/L. Conclusions: The tracer labelled MLT in combination with fasting parameters is a robust way to estimate parameters of methionine metabolism and can be used in the field where prime-constant rate infusion studies cannot be done efficiently. [ABSTRACT FROM AUTHOR]

Low plasma concentrations of vitamin B-12 are common in Indians, possibly due to low dietary intakes of animal-source foods. Whether malabsorption of the vitamin contributes to this has not been investigated. A rise in the plasma holotranscobalamin (holo-TC) concentration after a standard dose of oral vitamin B-i 2 has been proposed as a measure of gastrointestinal absorption in people with normal plasma vitamin B-i 2 concentrations. We studied 313 individuals (children and parents, 109 families) in the Pune Maternal Nutrition Study. They received 3 doses of 10 μg (n = 191) or 2 μg (n = 122) of cyanocobalamin at 6-h intervals. A rise in plasma holo-TC of ⩾15% and >15 pmol/L above baseline was considered normal vitamin B-i 2 absorption. The baseline plasma vitamin B-12 concentration was <150 pmol/L in 48% of participants; holo-TC was <35 pmol/L in 98% and total homocysteine was high in 50% of participants (>10 μmol/L in children and >15 μmol/L in adults). In the 10 μg group, the plasma holo-TC concentration increased by 4.8-fold from (mean ± SD) 9.3 ± 7.0 pmol/L to 53.8 ± 25.9 pmol/L and in the 2 μg group by 2.2-fold from 11.1 ± 8.5 pmol/L to 35.7 ± 19.3 pmol/L. Only 10% of the participants, mostly fathers, had an increase less than the suggested cut-points. Our results suggest that an increase in plasma holo-TC may be used to assess vitamin B-12 absorption in individuals with low vitamin B-12 status. Because malabsorption is unlikely to be a major reason for the low plasma vitamin B-12 concentrations in this population, increasing dietary vitamin B-12 should improve their status. [ABSTRACT FROM AUTHOR]

Problem: While the testes represent an immune‐privileged organ, there is evidence that systemic inflammation is accompanied by local inflammatory responses. We therefore examined whether transient systemic inflammation caused any inflammatory and functional consequences in murine testes. Method of Study: Using a single systemic administration of Toll‐like receptor (TLR) agonists [lipopolysaccharide (LPS) or peptidoglycan (PG) or polyinosinic‐polycytidylic acid (polyIC)] in young adult male mice, we assessed testicular immune‐inflammatory landscape and reproductive functionality. Results: Our findings demonstrated a significant induction of testicular TNF‐α, IL‐1β and IL‐6 transcripts within 24 h of TLR agonist injection. By day 6, these cytokine levels returned to baseline. While there was no change in caudal sperm counts at early time points, eight weeks later, twofold decrease in sperm count and reduced testicular testosterone levels were evident. When these mice were subjected to mating studies, no differences in mating efficiencies or litter sizes were observed compared with controls. Nonetheless, the neonatal weights of progeny from LPS/PG/polyIC‐treated sires were significantly lower than controls. Postnatal weight gain up to three weeks was also slower in the progeny of LPS/polyIC‐treated sires. Placental weights at 17.5 days post‐coitum were significantly lower in females mated to LPS‐ and polyIC‐treated males. Given this likelihood of an epigenetic effect, we found lower testicular levels of histone methyltransferase enzyme, mixed‐lineage leukaemia‐1, in mice given LPS/PG/polyIC 8 weeks earlier. Conclusion: Exposure to transient systemic inflammation leads to transient local inflammation in the testes, with persistent sperm‐mediated consequences for foetal development. [ABSTRACT FROM AUTHOR]

Background: Vitamin B-12 deficiency is often considered synonymous with pernicious anemia, a rare condition in which severe malabsorption of the vitamin requires high-dose parenteral treatment. In developing countries such as India, inadequate dietary intake of B-12 due to socio-cultural factors leads to widely prevalent asymptomatic low B-12 status. In this scenario, lower doses of oral B-12 may be effective, safer and more affordable. Objective: To examine the effects of oral B-12 treatment at physiological doses on hematological and biochemical indices and peripheral nerve function in B-12 deficient rural Indian adolescent women. Methods: Thirty-nine women with B-12 deficiency who were excluded from a community based B-12 supplementation trial (Pune Rural Intervention in Young Adolescents (PRIYA)) received oral B-12 2μg/day, either alone (n = 19) or with multiple micronutrients (UNIMAPP formula + 20gm milk powder, n = 20) for 11 months. Hematological indices, nutrients (B-12, folate), metabolites (homocysteine) and peripheral nerve function (SUDOSCAN, Impetomedical, Paris and sensory nerve conduction velocity (NCV) of median and sural nerves) were assessed at baseline and after 11 months of B-12 treatment. Results: Results were similar in the two treatment allocation groups, which were therefore combined. At baseline, all women had B-12 concentration <100pmol/L, 79% were anemic and 33% had macrocytosis, but none had neuropathy. After 11 months of treatment, B-12 levels increased, while folate did not change. The prevalence of anemia fell to 59% and mean corpuscular volume (MCV) and plasma homocysteine concentrations decreased. Sudomotor nerve function in the feet improved by an average of 14.7%, and sensory conduction velocity in median and sural nerves increased by 16.2% and 29.4% respectively. Conclusion: We document clinically beneficial effects of supplementation with a physiological dose of oral B-12 in asymptomatic rural Indian adolescent women with very low B-12 status. These findings support a public health approach to tackle the widely prevalent low B-12 status in young Indians. [ABSTRACT FROM AUTHOR]

Background: Maternal nutrition influences fetal development and may permanently alter ("program") offspring body composition and metabolism, thereby influencing later risk of diabetes and cardiovascular (cardiometabolic) disease. The prevalence of cardiometabolic disease is rising rapidly in India.Objectives: To test the hypothesis that supplementing low-income Indian women with micronutrient-rich foods preconceptionally and during pregnancy has a beneficial impact on the children's body composition and cardiometabolic risk marker profiles.Methods: Follow-up of 1255 children aged 5-10 y whose mothers took part in the Mumbai Maternal Nutrition Project [Project "SARAS"; International Standard Randomised Controlled Trial Number (ISRCTN)62811278]. Mothers were randomly assigned to receive a daily micronutrient-rich snack or a control snack of lower micronutrient content, both made from local foods, in addition to normal diet, from before pregnancy until delivery. Children's body composition was assessed using anthropometry and DXA. Their blood pressure, plasma glucose, insulin, and lipid concentrations were measured. Outcomes were compared between allocation groups with and without adjustment for confounding factors.Results: Overall, 15% of children were stunted, 34% were wasted, and 3% were overweight. In the intention-to-treat analysis, there were no differences in body composition or risk markers between children in the intervention and control groups. Among children whose mothers started supplementation ≥3 mo before conception (the "per protocol" sample) the intervention increased adiposity among girls, but not boys. BMI in girls was increased relative to controls by 2% (95% CI: 1, 4; P = 0.01); fat mass index by 10% (95% CI: 3, 18; P = 0.004); and percent fat by 7% (95% CI: 1, 13; P = 0.01) unadjusted, with similar results in adjusted models.Conclusions: Overall, supplementing women with micronutrient-rich foods from before pregnancy until delivery did not alter body composition or cardiometabolic risk markers in the children. Subgroup analyses showed that, if started ≥3 mo before conception, supplementation may increase adiposity among female children. [ABSTRACT FROM AUTHOR]

Objective: India is a double world capital of early-life undernutrition and type 2 diabetes. We aimed to characterize life course growth and metabolic trajectories in those developing glucose intolerance as young adults in the Pune Maternal Nutrition Study (PMNS).Research Design and Methods: PMNS is a community-based intergenerational birth cohort established in 1993, with serial information on parents and children through pregnancy, childhood, and adolescence. We compared normal glucose-tolerant and glucose-intolerant participants for serial growth, estimates of insulin sensitivity and secretion (HOMA and dynamic indices), and β-cell compensation accounting for prevailing insulin sensitivity.Results: At 18 years (N = 619), 37% of men and 20% of women were glucose intolerant (prediabetes n = 184; diabetes n = 1) despite 48% being underweight (BMI <18.5 kg/m2). Glucose-intolerant participants had higher fasting glucose from childhood. Mothers of glucose-intolerant participants had higher glycemia in pregnancy. Glucose-intolerant participants were shorter at birth. Insulin sensitivity decreased with age in all participants, and those with glucose intolerance had consistently lower compensatory insulin secretion from childhood. Participants in the highest quintile of fasting glucose at 6 and 12 years had 2.5- and 4.0-fold higher risks, respectively, of 18-year glucose intolerance; this finding was replicated in two other cohorts.Conclusions: Inadequate compensatory insulin secretory response to decreasing insulin sensitivity in early life is the major pathophysiology underlying glucose intolerance in thin rural Indians. Smaller birth size, maternal pregnancy hyperglycemia, and higher glycemia from childhood herald future glucose intolerance, mandating a strategy for diabetes prevention from early life, preferably intergenerationally. [ABSTRACT FROM AUTHOR]

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 B12deficient (<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. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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)). Results: 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)) Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Disturbed one-carbon (1-C) metabolism in the mother is associated with poor fetal growth but causality of this relationship has not been established.Methods: We studied the association between maternal total homocysteine and offspring birthweight in the Pune Maternal Nutrition Study (PMNS, Pune, India) and Parthenon Cohort Study (Mysore, India). We tested for evidence of causality within a Mendelian randomization framework, using a methylenetetrahydrofolatereductase (MTHFR) gene variant rs1801133 (earlier known as 677C→T) by instrumental variable and triangulation analysis, separately and using meta-analysis.Results: Median (IQR) homocysteine concentration and mean (SD) birthweight were 8.6 µmol/l (6.7,10.8) and 2642 g (379) in the PMNS and 6.0 µmol/l (5.1,7.1) and 2871 g (443) in the Parthenon study. Offspring birthweight was inversely related to maternal homocysteine concentration—PMNS: –22 g/SD [95% confidence interval (CI): (–50, 5), adjusted for gestational age and offspring gender]; Parthenon: –57 g (–92, –21); meta-analysis: –40 g (–62, –17)]. Maternal risk genotype at rs1801133 predicted higher homocysteine concentration [PMNS: 0.30 SD/allele (0.14, 0.46); Parthenon: 0.21 SD (0.02, 0.40); meta-analysis: 0.26 SD (0.14, 0.39)]; and lower birthweight [PMNS: –46 g (–102, 11, adjusted for gestational age, offspring gender and rs1801133 genotype); Parthenon: –78 g (–170, 15); meta-analysis: –61 g (–111, –10)]. Instrumental variable and triangulation analysis supported a causal association between maternal homocysteine concentration and offspring birthweight.Conclusions: Our findings suggest a causal role for maternal homocysteine (1-C metabolism) in fetal growth. Reducing maternal homocysteine concentrations may improve fetal growth. [ABSTRACT FROM AUTHOR]

ObjectiveTo document iodine status in Indian pregnancies, associations with maternal diet and demographics, and offspring developmental measures.DesignLongitudinal study following mothers through pregnancy and offspring up to 24 months.SettingRural health-care centre (Vadu) and urban antenatal clinic (Pune) in the Maharashtra region of India.SubjectsPregnant mothers at 17 (n 132) and 34 weeks’ (n 151) gestation and their infants from birth to the age of 24 months.ResultsMedian urinary iodine concentration (UIC) was 203 and 211 μg/l at 17 and 34 weeks of pregnancy, respectively (range 26–800 μg/l). Using the UIC distribution adjusted for within-person variation, extreme UIC quartiles were compared for predictors and outcomes. There was no correlation between UIC at 17 and 34 weeks, but 24 % of those with UIC in the lowest quartile at 17 weeks had UIC in the same lowest quartile at 34 weeks. Maternal educational, socio-economic status and milk products consumption (frequency) were different between the lowest and highest quartile of UIC at 34 weeks. Selected offspring developmental outcomes differed between the lowest and highest UIC quartiles (abdominal circumference at 24 months, subscapular and triceps skinfolds at 12 and 24 months). However, UIC was only a weak predictor of subscapular skinfold at 12 months and of triceps skinfold at 24 months.ConclusionsMedian UIC in this pregnant population suggested adequate dietary provision at both gestational stages studied. Occasional high results found in spot samples may indicate intermittent consumption of iodine-rich foods. Maternal UIC had limited influence on offspring developmental outcomes. [ABSTRACT FROM AUTHOR]

Objective: To study the relationship between maternal circulating fuels and neonatal size and compare the relative effects of glucose and lipids.Research Design and Methods: The Pune Maternal Nutrition Study (1993-1996) investigated the influence of maternal nutrition on fetal growth. We measured maternal body size and glucose and lipid concentrations during pregnancy and examined their relationship with birth size in full-term babies using correlation and regression techniques.Results: The mothers (n = 631) were young (mean age 21 years), short (mean height 151.9 cm), and thin (BMI 18.0 kg/m(2)) but were relatively more adipose (body fat 21.1%). Their diet was mostly vegetarian. Between 18 and 28 weeks' gestation, fasting glucose concentrations remained stable, whereas total cholesterol and triglyceride concentrations increased and HDL-cholesterol concentrations decreased. The mean birth weight of the offspring was 2666 g. Total cholesterol and triglycerides at both 18 and 28 weeks and plasma glucose only at 28 weeks were associated directly with birth size. One SD higher maternal fasting glucose, cholesterol, and triglyceride concentrations at 28 weeks were associated with 37, 54, and 36 g higher birth weights, respectively (P < 0.05 for all). HDL-cholesterol concentrations were unrelated to newborn measurements. The results were similar if preterm deliveries also were included in the analysis (total n = 700).Conclusions: Our results suggest an influence of maternal lipids on neonatal size in addition to the well-established effect of glucose. Further research should be directed at defining the clinical relevance of these findings. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To study the relationship between maternal circulating fuels and neonatal size and compare the relative effects of glucose and lipids. RESEARCH DESIGN AND METHODS--The Pune Maternal Nutrition Study (1993-1996) investigated the influence of maternal nutrition on fetal growth. We measured maternal body size and glucose and lipid concentrations during pregnancy and examined their relationship with birth size in full-term babies using correlation and regression techniques. RESULTS--The mothers (n = 631) were young (mean age 21 years), short (mean height 151.9 cm), and thin (BMI 18.0 kg/m2) but were relatively more adipose (body fat 21.1%). Their diet was mostly vegetarian. Between 18 and 28 weeks' gestation, fasting glucose concentrations remained stable, whereas total cholesterol and triglyceride concentrations increased and HDL-cholesterol concentrations decreased. The mean birth weight of the offspring was 2666 g. Total cholesterol and triglycerides at both 18 and 28 weeks and plasma glucose only at 28 weeks were associated directly with birth size. One SD higher maternal fasting glucose, cholesterol, and triglyceride concentrations at 28 weeks were associated with 37, 54, and 36 g higher birth weights, respectively (P, 0.05 for all). HDL-cholesterol concentrations were unrelated to newborn measurements. The results were similar if preterm deliveries also were included in the analysis (total n = 700). CONCLUSIONS--Our results suggest an influence of maternal lipids on neonatal size in addition to the well-established effect of glucose. Further research should be directed at defining the clinical relevance of these findings. [ABSTRACT FROM AUTHOR]

A response by P. S. Hardikar and colleagues to a letter to the editor about their the article "Spuriously High Prevalence of Prediabetes Diagnosed by HbA1c in Young Indians Partly Explained by Hematological Factors and Iron Deficiency Anemia," in the 2012 issue is presented.

Abstract: Background: India is undergoing rapid epidemiological and nutritional transition largely as a consequence of rapid urbanisation. We investigated conventional and novel cardiovascular risk factors in rural and urban Indian men and studied their association with markers of vascular damage. Methods: We randomly selected and studied 149 rural, 142 urban slum residents and 150 urban middle class middle aged Indian men. We measured conventional (obesity, blood pressure, lipids, smoking habits) and novel (proinflammatory and prothrombotic factors) cardiovascular risk factors and markers of vascular damage (carotid intima media thickness (IMT), von Willebrand Factor (vWF), e-selectin). Results: There was a progressive increase in most of the conventional cardiovascular (CV) risk factors from rural to slum to urban middle class men. Plasminogen activator inhibitor-1 (PAI-1), platelet count, total homocysteine and C-reactive protein showed similar patterns. Carotid IMT was similar in the three groups; vWF was highest in rural and e-selectin in slum men. Adjusting for location, age explained 17%, obesity 3% and conventional risk factors 1% of the variance in carotid IMT, whilst novel cardiovascular risk factors were without any significant impact. Conclusions: Urbanisation increases obesity related as well as prothrombotic and proinflammatory CV risk factors in Indian men, but appears not to impact on IMT. [Copyright &y& Elsevier]

Objective: To examine the influence of glycemic and nonglycemic parameters on HbA(1c) 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 HbA(1c) 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 HbA(1c) concentrations.Results: The OGTT showed that 7.8% of participants were prediabetic and 2.6% were diabetic. By ADA HbA(1c) criteria, 23.3% were prediabetic and 2.6% were diabetic. The negative predictive value of HbA(1c) 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 B(12) deficient (<150 pmol/L), and 22% were folate deficient (<7 nmol/L). On multiple linear regression analysis, HbA(1c) was predicted by higher 2-h glucose (R(2) = 25.6%) and lower hemoglobin (R(2) = 7.7%). When hematological parameters were replaced by ferritin, vitamin B(12), and folate, HbA(1c) was predicted by higher glycemia (R(2) = 25.6%) and lower ferritin (R(2) = 4.3%).Conclusions: The use of HbA(1c) to diagnose prediabetes and diabetes in iron-deficient populations may lead to a spuriously exaggerated prevalence. Further investigation is required before using HbA(1c) as a screening tool in nutritionally compromised populations. [ABSTRACT FROM AUTHOR]

Objective: To study determinants of incident hyperglycemia in rural Indian mothers 6 years after delivery.Research Design and Methods: The Pune Maternal Nutrition Study collected information in six villages near Pune on prepregnant characteristics and nutrition, physical activity, and glucose tolerance during pregnancy. An oral glucose tolerance test (OGTT) was repeated 6 years after delivery.Results: A total of 597 mothers had an OGTT at 28 weeks' gestation; 3 had gestational diabetes (by World Health Organization 1999 criteria). Six years later, 42 of 509 originally normal glucose-tolerant mothers were hyperglycemic (8 diabetic, 20 with impaired glucose tolerance, and 14 with impaired fasting glucose). The hyperglycemic women had shorter legs and thicker skinfolds before pregnancy (P < 0.01, both), were less active and more hyperglycemic (2-h plasma glucose 4.8 vs. 4.4 mmol/l, P < 0.001) during pregnancy, and gained more weight during follow-up (6.0 vs. 2.7 kg, P < 0.001). Multivariate analysis revealed that total leukocyte count and blood pressure during pregnancy were additional independent predictors of 2-h glucose concentration at follow-up.Conclusions: Our results suggest that compromised linear growth, adiposity, inflammation, and less physical activity predispose to hyperglycemia in young rural Indian women. International cut points of diabetes risk factors are largely irrelevant in these women. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To study determinants of incident hyperglycemia in rural Indian mothers 6 years after delivery. RESEARCN DESIGN AND METHODS -- The Pune Maternal Nutrition Study collected information in six villages near Pune on prepregnant characteristics and nutrition, physical activity, and glucose tolerance during pregnancy. An oral glucose tolerance test (OGTT) was repeated 6 years after delivery. RESULTS -- A total of 597 mothers had an OGTT at 28 weeks' gestation; 3 had gestational diabetes (by World Health Organization 1999 criteria). Six years later, 42 of 509 originally normal glucose-tolerant mothers were hyperglycemic (8 diabetic, 20 with impaired glucose tolerance, and 14 with impaired fasting glucose). The hyperglycemic women had shorter legs and thicker skinfolds before pregnancy (P < 0.01, both), were less active and more hyperglycemic (2-h plasma glucose 4.8 vs. 4.4 mmol/l, P < 0.001) during pregnancy, and gained more weight during follow-up (6.0 vs. 2.7 kg, P < 0.001). Multivariate analysis revealed that total leukocyte count and blood pressure during pregnancy were additional independent predictors of 2-h glucose concentration at follow-up. CONCLUSIONS -- Our results suggest that compromised linear growth, adiposity, inflammation, and less physical activity predispose to hyperglycemia in young rural Indian women. International cut points of diabetes risk factors are largely irrelevant in these women. [ABSTRACT FROM AUTHOR]

A response by the authors to a commentary on their Pune Maternal Nutrition Study which indicates a lack of association between neonatal birth size and maternal high-density lipoprotein (HDL) levels is presented. They address the claim that the results of their study are unusual. They also discuss the significance of conducting large-scale studies of the influence of maternal lipids on newborn size in different populations and ethnicities.