Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study.

OBJECTIVES: Famine exposure in utero can 'programme' an individual towards type 2 diabetes and obesity in later life. We sought to identify, (1) whether Bangladeshis exposed to famine during developmental life are programmed towards diabetes and obesity, (2) whether this programming was specific to gestational or postnatal exposure windows and (3) whether epigenetic differences were associated with famine exposure. DESIGN: A historical cohort study was performed as part of a wider cross-sectional survey. Exposure to famine was defined through birth date and historical records and participants were selected according to: (A) exposure to famine in postnatal life, (B) exposure to famine during gestation and (C) unexposed. SETTING: Matlab, a rural area in the Chittagong division of Bangladesh. PARTICIPANTS: Young adult men and women (n=190) recruited to a historical cohort study with a randomised subsample included in an epigenetic study (n=143). OUTCOME MEASURES: Primary outcome measures of weight, body mass index and oral glucose tolerance tests (0 and 120 min glucose). Secondary outcome measures included DNA methylation using genome-wide and targeted analysis of metastable epialleles sensitive to maternal nutrition. RESULTS: More young adults exposed to famine in gestation were underweight than those postnatally exposed or unexposed. In contrast, more young adults exposed to famine postnatally were overweight compared to those gestationally exposed or unexposed. Underweight adults exposed to famine in gestation in utero were hyperglycaemic following a glucose tolerance test, and those exposed postnatally had elevated fasting glucose, compared to those unexposed. Significant differences in DNA methylation at seven metastable epialleles (VTRNA2-1, PAX8, PRDM-9, near ZFP57, near BOLA, EXD3) known to vary with gestational famine exposure were identified. CONCLUSIONS: Famine exposure in developmental life programmed Bangladeshi offspring towards diabetes and obesity in adulthood but gestational and postnatal windows of exposure had variable effects on phenotype. DNA methylation differences were replicated at previously identified metastable epialleles sensitive to periconceptual famine exposure.

Validity and reproducibility of resting metabolic rate measurements in rural Bangladeshi women: comparison of measurements obtained by Medgem and by Deltatrac device.

OBJECTIVE: To assess reproducibility and validity of resting metabolic rate (RMR) of Bangladeshi women as measured with the MedGem device and using the Deltatrac metabolic monitor as a reference; and (2) to evaluate the FAO/WHO/UNU basal metabolic rate (BMR)-prediction equations. DESIGN: In each of two sessions, resting oxygen consumption was measured in triplicate by MedGem and in triplicate by Deltatrac device. SETTING: Matlab area, the rural field research area of the Centre for Health and Population Research, Bangladesh (ICDDR,B). SUBJECTS: A total of 37 nonpregnant, nonlactating women, aged 27.6 +/- 4.5 y, BMI 20.8 +/- 3.1 kg/m(2) participated. RESULTS: The difference in oxygen consumption by MedGem and Deltatrac device was significantly level dependent. Within-subject within-session variations (expressed as CV) were 9.0 and 3.0% (P < 0.01) and within-subject between-session variations were 8.2 and 4.5% (P < 0.01) for MedGem and Deltatrac, respectively. Mean RMR measured by Deltatrac (5.17 +/- 0.51 MJ/day) was not significantly different from the BMR predicted by the FAO/WHO/UNU equations (5.16 +/- 0.42 MJ/day) in the second session and only 0.19 MJ/day higher than predicted in the first session (P < 0.05). CONCLUSION: Reproducibility and validity of the MedGem device was poor compared to the Deltatrac reference method. The FAO/WHO/UNU BMR-prediction equations give a good estimation of the BMR of rural, nonpregnant, nonlactating Bangladeshi women of 18-35 y. SPONSORSHIP: Wageningen University (The Netherlands) and ICDDR,B (Bangladesh).

Energy stress during pregnancy and lactation: consequences for maternal nutrition in rural Bangladesh.

OBJECTIVE: To assess the relationship of energy stress during pregnancy and lactation to maternal body stores in marginally nourished rural Bangladeshi women. SUBJECTS AND METHODS: Two-hundred and fifty-two women were followed from 5-7 months of pregnancy until 6 months postpartum. Energy intake was estimated during pregnancy and at 1, 3 and 6 month(s) postpartum using 24 h dietary recall. Body weight was measured on enrollment, another once or twice during pregnancy, and at 1, 3 and 6 month(s) postpartum. The weekly rates of pregnancy weight gain and postpartum weight changes were determined. Weight and length of the infants were measured at birth and at approximately 1, 3 and 6 month(s). RESULTS: Maternal energy intake at 5-7 months of gestation was 1464+/-416 kcal/day (mean+/-s.d.). Women gained a mean of 200 g/week or a total of 4 kg during the second half of pregnancy. An analysis of maternal weight showed no indication of accrual of fat stores during pregnancy. Dietary energy during lactation exceeded the intake during pregnancy by 248-354 kcal/day. Mothers lost an estimated average of 1 kg of weight during the first 6 months of lactation. The mean (+/-s.d.) birth weight was 2.55+/-0.38 kg, and the prevalence of low birth weight (<2500 g) was 48%. Infants exhibited some catch-up growth only during the first 3 months but overall growth during the first 6 months did not change from their relative status at birth when compared with NCHS reference. CONCLUSIONS: These rural Bangladeshi women failed to gain sufficient weight during the last half of pregnancy to maintain body weight during lactation when the energy demand is high. Poor growth of their primarily breastfed infants raises concern about the adequacy of lactation in this community.

Association between clinical type of diarrhoea and growth of children under 5 years in rural Bangladesh.

BACKGROUND: The role of diarrhoea in the aetiology of growth retardation in young children remains controversial. To evaluate this, a population-based, longitudinal study of young children aged 6-48 months was conducted in Matlab, a rural area of Bangladesh, between May 1988 and April 1989. METHODS: Data obtained from 584 children were examined by one-year (n = 412) and 3-month (n = 1220) growth periods. Each growth period was analysed based on clinical types of diarrhoea, namely, non-diarrhoea, non-dysentery diarrhoea (diarrhoea without blood), and dysentery (diarrhoea with blood). Weight and height gains were compared among the study groups initially by one-way analysis of variance followed by multivariate analysis adjusting for potential confounding variables. RESULTS: Compared to non-diarrhoea and non-dysentery diarrhoea, dysentery was associated with significantly lower annual weight gain (1866 g [P < 0.01] and 1550 g [P < 0.05] versus 1350 g, respectively) and height gain (6.51 cm and 5.87 cm versus 5.27 cm [P < 0.01], respectively). Both 3-month dysentery and non-dysentery intervals were significantly associated with less weight gain compared to non-diarrhoea intervals (490 g and 522 g versus 637 g [P: < 0.05], respectively). Dysentery intervals were also associated with significantly poorer height gain compared to other intervals (2.19 cm versus 2.42 cm [P < 0.05] and 2.46 cm [P < 0.01], respectively). CONCLUSIONS: The growth of young children is strongly influenced by the clinical type of diarrhoea and the impact is dependent on the proportion of dysentery episodes in the total diarrhoeal burden.

Direct hypoglossal nerve stimulation in obstructive sleep apnea.

OBJECTIVES: To determine the motor responses resulting from direct electrical stimulation of the hypoglossal (HG) nerve and to correlate these responses to changes in upper airway patency during sleep. DESIGN: The motor effects of direct electrical stimulation of the main trunk of the HG nerve and the branch that supplies the genioglossus muscle during anesthesia and wakefulness were assessed visually. Responses in airflow during sleep to HG nerve stimulation were assessed with standard polysomnographic techniques. SETTING: University medical center. PATIENTS: Fifteen patients undergoing a surgical procedure that involved the neck that exposed the HG nerve and 5 volunteer patients with obstructive sleep apnea constituted the study population. INTERVENTIONS: The main trunk (n = 3) and genioglossus branch (n = 2) of the HG nerve were stimulated electrically with a half-cuff tripolar electrode. RESULTS: Stimulation of the branch of the HG nerve that innervates the genioglossus muscle caused protrusion and contralateral deviation of the tongue. Stimulation of the main trunk of the HG nerve caused slight ipsilateral deviation and retrusion of the tongue. The arousal threshold for stimulation exceeded the motor recruitment threshold by 0.8 +/- 0.4 V. Inspiratory airflow increased in all patients by 184.5 +/- 61.7 mL/s (mean +/- SD; P = .02, analysis of variance) with stimulation. CONCLUSION: Direct HG nerve stimulation below the arousal threshold can improve airflow in patients with obstructive sleep apnea.