Effect of multi-nutrient insufficiency on markers of one carbon metabolism in young women: response to a methionine load.

BACKGROUND/OBJECTIVES: Multi-nutrient insufficiencies as a consequence of nutritional and economic factors are common in India and other developing countries. We have examined the impact of multi-nutrient insufficiency on markers of one carbon (1C) metabolism in the blood, and response to a methionine load in clinically healthy young women. SUBJECTS/METHODS: Young women from Pune, India (n=10) and Cleveland, USA (n=13) were studied. Blood samples were obtained in the basal state and following an oral methionine load (50 mg/kg of body weight in orange juice). Plasma concentrations of vitamin B12, folate and B6 were measured in the basal state. The effect of methionine load on the levels of methionine, total homocysteine, cysteine, glutathione and amino acids was examined. RESULTS: Indian women were significantly shorter and lighter compared with the American women and had lower plasma concentration of vitamins B12, folate and B6, essential amino acids and glutathione, but higher concentration of total homocysteine. The homocysteine response to methionine load was higher in Indian women. The plasma concentrations of glycine and serine increased in the Indian women after methionine (in juice) load. A significant negative correlation between plasma B6 and homocysteine (r= -0.70), and plasma folate and glycine and serine levels were observed in the Indian group (P<0.05) but not in the American group. CONCLUSIONS: Multi-nutrient insufficiency in the Indian women caused unique changes in markers of whole body protein and 1C metabolism. These data would be useful in developing nutrient intervention strategies.

Cord IGF-I concentrations in Indian newborns: associations with neonatal body composition and maternal determinants.

BACKGROUND: Indian newborns have been described as 'thin-fat' compared with European babies, but little is known about how this phenotype relates to the foetal growth factor IGF-I (insulin-like growth factor I) or its binding protein IGFBP-3. OBJECTIVE: To assess cord IGF-I and IGFBP-3 concentrations in a sample of Indian newborns and evaluate their associations with neonatal adiposity and maternal factors. METHODS: A prospective cohort study of 146 pregnant mothers with dietary, anthropometric and biochemical measurements at 28 and 34 weeks gestation. Neonatal weight, length, skin-folds, circumferences, and cord blood IGF-I and IGFBP-3 concentrations were measured at birth. RESULTS: Average cord IGF-I and IGFBP-3 concentrations were 46.6 (2.2) and 1269.4 (41) ng mL(-1) , respectively. Girls had higher mean IGF-I than boys (51.4 ng mL(-1) vs. 42.9 ng mL(-1) ; P < 0.03), but IGFBP-3 did not differ. Cord IGF-I was positively correlated with all birth size measures except length, and most strongly with neonatal sum-of-skin-folds (r = 0.50, P < 0.001). IGFBP-3 was positively correlated with ponderal index, sum-of-skin-folds and placenta weight (r = 0.21, 0.19, 0.16, respectively; P < 0.05). Of maternal demographic and anthropometric characteristics, only parity was correlated with cord IGF-I (r = 0.27, P < 0.001). Among dietary behaviours, maternal daily milk intake at 34 weeks gestation predicted higher cord IGF-I compared to no-milk intake (51.8 ng mL(-1) vs. 36.5 ng mL(-1) , P < 0.01) after controlling for maternal characteristics, placental weight, and newborn gestational age, sex, weight and sum-of-skin-folds. Sum-of-skin-folds were positively associated with cord IGF-I in this multivariate model (57.3 ng mL(-1) vs. 35.1 ng mL(-1) for highest and lowest sum-of skin-fold quartile, P < 0.001). IGFBP-3 did not show significant relationships with these covariates. CONCLUSION: In this Indian study, cord IGF-I concentration was associated with greater adiposity among newborns. Maternal milk intake may play a role in this relationship.

Trier social stress test in Indian adolescents.

OBJECTIVE: To test the Trier Social Stress Test for children (TSST-C) in a cohort of Indian adolescents. DESIGN: Cohort study. SETTING: Holdsworth Memorial Hospital, Mysore, India. PARTICIPANTS: Adolescent children (N=273, 134 males; mean age 13.6 yrs) selected from an ongoing birth cohort; 269 completed the test. INTERVENTION: Performance of 5-minutes each of public- speaking and mental arithmetic tasks in front of two unfamiliar 'evaluators'. OUTCOME MEASURES: Salivary cortisol concentrations were measured at baseline and at regular intervals after the TSST-C. Continuous measurements of heart rate, finger blood pressure, stroke volume, cardiac output and systemic vascular resistance were carried out before, during and for 10 minutes after the TSST-C using a finger cuff. RESULTS: Cortisol concentrations [mean increment (SD): 6.1 (6.9) ng/mL], heart rate [4.6 (10.1) bpm], systolic [24.2 (11.6) mmHg] and diastolic blood pressure [16.5 (7.3) mmHg], cardiac output [0.6 (0.7) L/min], stroke volume [4.0 (5.6) mL] and systemic vascular resistance [225 (282) dyn.s/cm5] increased significantly (P<0.001) from baseline after inducing stress. CONCLUSIONS: The TSST-C produces stress responses in Indian adolescents of a sufficient magnitude to be a useful tool for examining stress physiology and its relationships to disease outcomes in this population.

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 ß 0.201, R 2 7.7%), current consumption of cow's milk (std ß 0.194, R 2 3.3%) and whether breast feeding was stopped before 2y (std ß -0.234 R 2 7.2%). Child's 2y tHcy concentration was high (11.4 ± 3.6 µm) and predicted by lower pregnancy vitamin B12 (std ß -0.206, R 2 4.1%), lack of vitamin supplementation (std ß -0.256, R 2 5.6%) in pregnancy and whether currently breastfed (std ß 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.

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.

Prediction of body-fat percentage from skinfold and bio-impedance measurements in Indian school children.

BACKGROUND/OBJECTIVES: Few equations for calculating body-fat percentage (BF%) from field methods have been developed in South-Asian children. The objective of this study was to assess agreement between BF% derived from primary reference methods and that from skinfold equations and bio-impedance analysis (BIA) in Indian children. SUBJECTS/METHODS: We measured BF% in two groups of Indian children. In Pune, 570 rural children aged 6-8 years underwent dual-energy X-ray absorptiometry (DXA) scans. In Mysore (18)O in doubly labeled water was administered to 59 urban children aged 7-9 years. We conducted BIA at 50 kHz and anthropometry, including sub-scapular and triceps skinfold thicknesses. We used the published equations of Wickramasinghe, Shaikh, Slaughter and Dezenburg to calculate BF% from anthropometric data and the manufacturer's equation for BIA measurements. We assessed agreement with values derived from DXA and doubly labeled water using Bland-Altman analysis. RESULTS: Children were light and thin on average compared with international standards. There was poor agreement between the reference BF% values and those from all equations. Assumptions for Bland-Altman analysis were not met for Wickramasinghe, Shaikh and Slaughter equations. The Dezenberg equations under-predicted BF% for most children (mean difference in Pune -13.4, LOA -22.7, -4.0 and in Mysore -7.9, LOA (-13.7 and -2.2). The mean bias for the BIA equation in Pune was +5.0% and in Mysore +1.95%, and the limits of agreement were wide; -5.0, 15.0 and -7.8, 11.7 respectively. CONCLUSIONS: Currently available skinfold equations do not accurately predict BF% in Indian children. We recommend development of BIA equations in this population using a four-compartment model.

Effect of physiological doses of oral vitamin B12 on plasma homocysteine: a randomized, placebo-controlled, double-blind trial in India.

BACKGROUND/OBJECTIVES: Vitamin B(12) (B(12)) deficiency is common in Indians and a major contributor to hyperhomocysteinemia, which may influence fetal growth, risk of type II diabetes and cardiovascular disease. The purpose of this paper was to study the effect of physiological doses of B(12) and folic acid on plasma total homocysteine (tHcy) concentration. SUBJECTS/METHODS: A cluster randomized, placebo-controlled, double-blind, 2 x 3 factorial trial, using the family as the randomization unit. B(12) was given as 2 or 10 microg capsules, with or without 200 microg folic acid, forming six groups (B(0)F(0), B(2)F(0), B(10)F(0), B(0)F(200), B(2)F(200) and B(10)F(200)). Plasma tHcy concentration was measured before and after 4 and 12 months of supplementation. RESULTS: From 119 families in the Pune Maternal Nutrition Study, 300 individuals were randomized. There was no interaction between B(12) and folic acid (P=0.14) in relation to tHcy concentration change and their effects were analyzed separately: B(0) vs. B(2) vs. B(10); and F(0) vs. F(200). At 12 months, tHcy concentration reduced by a mean 5.9 (95% CI: -7.8, -4.1) micromol/l in B(2), and by 7.1 (95% CI: -8.9, -5.4) micromol/l in B(10), compared to nonsignificant rise of 1.2 (95% CI: -0.5, 2.9) micromol/l in B(0). B(2) and B(10) did not differ significantly. In F(200), tHcy concentration decreased by 4.8 (95% CI: -6.3, -3.3) micromol/l compared to 2.8 (95% CI: -4.3, -1.2) micromol/l in F(0). CONCLUSION: Daily oral supplementation with physiological doses of B(12) is an effective community intervention to reduce tHcy. Folic acid (200 microg per day) showed no additional benefit, neither had any unfavorable effects.

Low plasma vitamin B12 in pregnancy is associated with gestational 'diabesity' and later diabetes.

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS/INTERPRETATION: 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.

Adiposity, inflammation and hyperglycaemia in rural and urban Indian men: Coronary Risk of Insulin Sensitivity in Indian Subjects (CRISIS) Study.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether the higher prevalence of insulin resistance and glucose intolerance in urban compared with rural Indian men is related to their higher adiposity (percentage body fat) and the associated inflammatory state. METHODS: We studied 149 rural, 142 urban slum and 150 urban middle-class male residents (age 30-50 years), who were selected by stratified random sampling. We measured body fat (bioimpedance), waist circumference, glucose tolerance (75 g OGTT), insulin resistance [homeostasis model assessment (HOMA-IR)], beta cell function (insulinogenic index) and inflammatory markers (total leucocyte count, IL-6, TNF-alpha and C-reactive protein). RESULTS: Adiposity, waist circumference, HOMA-IR, insulinogenic index and both fasting and 120 min plasma glucose concentrations increased progressively from rural through to urban slum and urban middle-class men. Inflammatory markers were higher in urban than in rural men. Adiposity was strongly related to HOMA-IR (r = 0.57, p < 0.001) and to insulinogenic index and glycaemic parameters (r = 0.25, p < 0.001 for both). Adiposity explained approximately two thirds of the difference in HOMA-IR between the urban middle-class men and the rural and slum residents, but its contribution to the difference in insulinogenic index and 120 min plasma glucose concentration was not significant. Inclusion of C-reactive protein, IL-6 and total leucocyte count in the models did not further explain these results, nor did the inclusion of waist circumference. There was a significant residual difference after these adjustments. CONCLUSIONS/INTERPRETATION: Adiposity is a major contributor to the difference in insulin resistance between rural and urban Indian men; there was no additional contribution from inflammation or central obesity. Other unmeasured factors also seem to contribute to the metabolic differences between rural and urban men.

Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study.

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/INTERPRETATION: Low maternal vitamin B12 and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India.

Vitamin B12 deficiency and hyperhomocysteinemia in rural and urban Indians.

BACKGROUND: Low vitamin B12 concentration in South Asian Indians is common, but the exact prevalence is not known. AIM: To investigate prevalence and associations of low vitamin B12 concentration and hyperhomocysteinemia in rural and urban Indian men living in and around Pune, Maharashtra. METHOD: We studied 441 middle-aged men (149 rural, 142 slum and 150 urban middle-class residents, mean age 39 y). Data on lifestyle, socio-economic status, nutrition and medical history were obtained. Circulating concentrations of vitamin B12, folate, ferritin, total homocysteine (tHcy), and haematological indices, and cardiovascular risk variables were measured. RESULTS: Median plasma B12 concentration was low (110 pmol/L): Overall, 67% of men had low vitamin B12 concentration (<150 pmol/L) and 58% had hyperhomocysteinemia (>15 micromol/L). Of the urban middle class, 81% had low vitamin B12 concentration and 79% had hyperhomocysteinemia. Low vitamin B12 concentration contributed 28% to the risk of hyperhomocysteinemia (population attributable risk) while low red cell folate contributed 2%. Vegetarians had 4.4 times (95% CI 2.1, 9.4) higher risk of low vitamin B12 concentrations and 3.0 times (95% CI 1.4, 6.5) higher risk of hyperhomocysteinemia compared to those who ate non-vegetarian foods frequently. Urban middle-class residence was an additional independent risk factor of hyperhomocysteinemia (odds ratio 7.6 (95% CI 2.5, 22.6), compared to rural men). Low vitamin B12 concentration was related to lower blood haemoglobin concentration and higher mean corpuscular volume, but macrocytic anemia was rare. CONCLUSION: Low vitamin B12 concentration and hyperhomocysteinemia are common in Indian men, particularly in vegetarians and urban middle class residents. Further studies are needed to confirm these findings in other parts of India.

Body fat measurement in Indian men: comparison of three methods based on a two-compartment model.

UNLABELLED: Obesity is a major risk factor for diabetes and related disorders. The current classification of obesity is based on body mass index (BMI, kg/m(2)), which is a surrogate for the total body fat. Since the relationship between BMI and body fat varies in different populations, an independent validation of the BMI-body fat relationship in the population of interest is desirable. OBJECTIVES: (1) To study the validity of field methods of measuring body fat (multiple skinfolds and bioimpedance) against a criterion method (deuterium dilution) and (2) To compare the prevalence of obesity (WHO 2000 criteria for BMI) with adiposity (body fat >25%) in middle-aged Indian men in rural and urban Pune. DESIGN: Community-based multistage stratified random sampling of middle-aged men from rural and urban Pune for study of body composition and cardiovascular risk. A third of these men, selected to represent wide BMI distribution, were studied for body fat measurements by specific methods. SUBJECTS: A total of 141 healthy men, approximately similar number from rural, urban slums and middle class from Pune. They were 39.3 (+/-6.2) y old and had a BMI of 21.9 (+/-3.7) kg/m(2). MEASUREMENTS: Anthropometry (height, weight and multiple skinfold thicknesses) by trained observers using standardised technique to calculate body fat by Durnin and Womersley's equation. Total body water and body fat by bioelectrical impedance analysis (BIA) and deuterium oxide dilution (D(2)O). RESULTS: Mean total body fat was 14.3 kg (23.0%) by anthropometry, 16.5 kg (26.0%) by BIA and 15.3 kg (24.6%) by D(2)O method. Although there was a good correlation between fat estimation by three methods (r= approximately 0.9, P<0.001 all), compared to D(2)O method anthropometry underestimated body fat by 1.0 kg and BIA overestimated fat by 1.2 kg (P<0.001 both). Using the standard cut-point of 25% body fat for 'adiposity' 29.5% rural, 46.0% slum and 75.0% middle class men were adipose. These proportions were considerably higher than the number of men who were 'preobese' (BMI> or =25-29.9 kg/m(2), 9.0% rural, 22.0% urban slums and 27.0% urban middle class) and 'obese' (BMI >30 kg/m(2), 4.0% urban slums, none in rural and urban middle class). CONCLUSION: We recommend that future studies assessing risk for chronic diseases in Indians should measure adiposity by anthropometry (multiple skinfolds) or BIA (calibrated for Indians) rather than relying only on BMI cut-points.

Cloning of an Arabidopsis patatin-like gene, STURDY, by activation T-DNA tagging.

Activation T-DNA tagging can generate dominant gain-of-function mutants by overexpression of a particular endogenous gene. We identified an activation-tagged mutant, sturdy, exhibiting a stiff inflorescence stem, thicker leaves, shorter siliques, larger seeds, round-shaped flowers, and delayed growth. It is most important that unlike its wild-type counterpart, this mutant is less prone to lodging. Cloning of STURDY revealed that in sturdy, there is an open reading frame containing a single intron encoding a patatin-like homolog. The T-DNA is inserted into the 3' region of the second exon. The mutant phenotype was shown to be the result of overexpression of STURDY by mRNA analysis and transgenic studies. Preliminary histological studies have revealed an increase in cell number in the inflorescence stem of mutant plants; however, additional studies are needed to better understand the overexpression phenotype.

Circulating lipids and cardiovascular risk in newly diagnosed non-insulin-dependent diabetic subjects in India.

Circulating concentrations of total cholesterol, triglycerides, non-esterified fatty acids (NEFA), glycerol, and 3-hydroxybutyrate (3-HB) were measured in 133 subjects with normal glucose tolerance (NGT), 78 with impaired-glucose-tolerance (IGT) and 189 non-insulin dependent (Type 2) diabetic (NIDDM) patients. Plasma cholesterol concentration was similar in the three groups; NGT (4.2 (2.3-7.5) mmol l-1, median (range)), IGT (4.7 (2.7-6.3)) and NIDDM (4.3 (2.3-6.9)). Plasma triglycerides (NGT 0.88 (0.37-2.80), IGT 1.26 (0.43-3.82) and NIDDM 1.38 (0.62-3.91) mmol l-1) and NEFA (NGT 0.81 (0.29-1.58), IGT 1.02 (0.33-1.87) and NIDDM 1.02 (0.48-2.77) mmol l-1) were higher in the two hyperglycaemic groups, but blood 3-HB concentration was similar in the three groups. Plasma cholesterol concentration in these subjects is lower than that reported in white Caucasians in the UK and USA and migrant Indian NIDDM patients in the UK. In NIDDM patients plasma cholesterol concentration was related to age, body mass index (BMI), and plasma glucose concentration while plasma triglyceride concentration was related to plasma NEFA and insulin (IRI) concentration. Evidence of ischaemia on electrocardiography in patients with diabetes was associated with higher age, blood pressure, plasma triglyceride, glucose, and IRI concentrations.

Ketosis resistance in fibrocalculous pancreatic diabetes: II. Hepatic ketogenesis after oral medium-chain triglycerides.

A majority of patients with fibrocalculous pancreatic diabetes (FCPD) do not become ketotic even in adverse conditions. It is not clear whether this ketosis resistance is due to reduced fatty acid release from adipose tissue or to impaired hepatic ketogenesis. We tested hepatic ketogenesis in FCPD patients using a ketogenic challenge of oral medium-chain triglycerides (MCTs) and compared it with that in matched insulin-dependent diabetes mellitus (IDDM) patients and healthy controls. After oral MCTs, FCPD patients showed only a mild increase in blood 3-hydroxybutyrate (3-HB) concentrations (median: fasting, 0.13 mmol/L; peak, 0.52) compared with IDDM patients (fasting, 0.44; peak, 3.39) and controls (fasting, 0.04; peak, 0.75). Plasma nonesterified fatty acid (NEFA) concentrations were comparable in the two diabetic groups (FCPD: fasting, 0.50 mmol/L; peak, 0.79; IDDM: fasting, 0.91; peak, 1.04). Plasma C-peptide concentrations were low and comparable in the two diabetic groups. Plasma glucagon concentrations were higher in IDDM patients in the fasting state, but declined to levels comparable to those in FCPD patients after oral MCTs. Plasma carnitine concentrations were comparable in the two groups of patients. It is concluded that the failure to stimulate ketogenesis under these conditions could be partly due to inhibition of a step beyond fatty acid entry into the mitochondria.

Fetal growth and glucose and insulin metabolism in four-year-old Indian children.

Studies in Britain have shown that adults who had a low birthweight have high plasma glucose concentrations 30 and 120 min after an oral glucose load, and an increased risk of Type 2 diabetes and impaired glucose tolerance. Both Type 2 diabetes and low birthweight are common in India. To determine whether low birthweight is associated with reduced glucose tolerance in Indian children, glucose tolerance tests were carried out on 379 4-year-old children, whose birthweights were recorded, in Pune, India. Among 201 children who had been looked after on the routine postnatal wards at birth, those with lower birthweights had higher plasma glucose and insulin concentrations 30 min after an oral glucose load, independently of their current size (p = 0.01 and 0.04, respectively). Mean glucose and insulin concentrations were 8.1 mmol l-1 and 321 pmol l-1 in children whose birthweight had been 2.4 kg or less, compared with 7.5 mmol l-1 and 289 pmol l-1 in those who weighted more than 3.0 kg. Among 178 children who had been looked after in the Special Care Baby Unit, those with lower birthweights also had higher plasma insulin concentrations at 30 min but there were no trends with plasma glucose. Our findings suggest that Indian children with reduced intra-uterine growth have reduced glucose homeostasis after a glucose challenge. This is consistent with the hypothesis that Type 2 diabetes mellitus in India may be programmed in fetal life.

The relationship between obesity, plasma immunoreactive insulin concentration and blood pressure in newly diagnosed Indian type 2 diabetic patients.

The association of blood pressure with clinical and biochemical measures was studied in 185 newly diagnosed Type 2 diabetic patients, 74 impaired-glucose-tolerant (IGT) and 128 non-diabetic control subjects. Hyperglycaemic subjects were older than control subjects (controls 40 (24-59) years, IGT 48 (29-64) years, diabetic 43 (29-60) years, median (5th-95th centile) both p < 0.05). They were also more obese (body mass index (BMI) controls 23.5 kg m-2 (17.2-29.9), IGT 26.0 kg m-2 (19.8-33.9), diabetic 24.2 kg m-2 (19.3-32.2)) and with a greater waist-hip ratio (controls 0.83 (0.70-0.98), IGT 0.88 (0.75-0.98), diabetic 0.89 (0.75-1.00)). Blood pressure was significantly higher in both IGT (systolic 127 mmHg (108-162), diastolic 84 mmHg (66-99)) and diabetic patients (systolic 130 mmHg (104-160), diastolic 84 mmHg (66-102)) compared to non-diabetic controls (systolic 120 mmHg (100-151), diastolic 80 mmHg (60-94)). Univariate analysis showed that in diabetic patients systolic blood pressure was related to age (r = 0.17, p < 0.05), BMI (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting and post glucose, r = approximately 0.25, p < 0.01) but not to C-peptide concentrations; diastolic blood pressure to BMI (r = 0.35, p < 0.001), waist-hip ratio (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting r = 0.30, p < 0.001, post glucose r = approximately 0.20, p < 0.05) but not to C-peptide concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary albumin excretion rate (AER) in newly-diagnosed type 2 Indian diabetic patients is associated with central obesity and hyperglycaemia.

Urinary albumin excretion rate (AER) was measured in non-diabetic controls (n = 143) and newly diagnosed impaired glucose tolerant (IGT, n = 64) and non-insulin-dependent (type 2) diabetic patients (n = 146). AER progressively increased from non-diabetic [3.7 (1.1-51.3) micrograms/min, median (5-95th centile)] to IGT [4.8 (1.3-53.7)] and diabetic [7.3 (1.4-91.6)] groups. Eight percent of non-diabetic, 19% of IGT and 23% of type 2 diabetic patients showed 'microalbuminuria' (AER, 20-200 micrograms/min) (non-diabetic vs diabetic P less than 0.01, non-diabetic vs IGT NS, IGT vs diabetic NS). AER was directly related to waist-hip ratio (P less than 0.001) and HbA1 (P less than 0.01) in diabetic patients; 80% of diabetic patients with microalbuminuria were men (P less than 0.06 compared to 'normoalbuminuric' diabetic patients). Association of AER with waist-hip ratio was present in men as well as women. Thus, in the newly diagnosed type 2 Indian diabetic patients AER is associated with central obesity in addition to its well known association with hyperglycaemia. Our findings offer a possible explanation for the increased risk of proteinuria in diabetic men than in women because men are centrally more obese. It could also explain previous reports of higher AER in migrant Asian diabetic patients in the U.K. compared to native white Caucasian diabetic patients because Asians are known to be more centrally obese.