scholarly journals Circulating microRNAs from early childhood and adolescence are associated with pre-diabetes at 18 years of age in women from the PMNS cohort

2021 ◽  
Author(s):  
Mugdha V. Joglekar ◽  
Pooja S. Kunte ◽  
Wilson K.M. Wong ◽  
Dattatray S. Bhat ◽  
Sarang N. Satoor ◽  
...  
Keyword(s):  
Birth Cohort ◽  
Glucose Intolerance ◽  
Maternal Nutrition ◽  
Childhood And Adolescence ◽  
Age Validation ◽  
Circulating Micrornas ◽  
Nutrition Study ◽  
Normal Glucose ◽  
Glucose Tolerant ◽  
Leave One Out

A high (20%) prevalence of glucose intolerance at 18-years was seen in women from the Pune Maternal Nutrition Study (PMNS) birth cohort. Here, we provide preliminary longitudinal analyses of circulating microRNAs in normal glucose tolerant (NGT@18y, N=10) and glucose intolerant (N=8) women (ADA criteria) at 6-, 12- and 17-years of their age using discovery analysis (OpenArray platform). Machine-learning workflows involving Lasso with bootstrapping/leave-one-out cross-validation (LOOCV) identified microRNAs associated with glucose intolerance at 18-years of age. Several microRNAs, including miR-212-3p, miR-30e-3p and miR-638, stratified glucose-intolerant women from NGT at childhood. Our results suggest that circulating microRNAs in childhood could predict pre-diabetes at 18-years of age. Validation of these findings in males and remaining participants from the PMNS birth cohort will provide a unique opportunity to study novel epigenetic mechanisms in the life-course progression of glucose intolerance and enhance current clinical risk prediction of pre-diabetes and progression to type 2 diabetes.

scholarly journals Poor In Utero Growth and Reduced β-Cell Compensation and High Fasting Glucose from Childhood Are Harbingers of Glucose Intolerance in Young Indians

2021 ◽  
Author(s):  
Chittaranjan S Yajnik ◽  
Souvik Bandopadhyay ◽  
Aboli Bhalerao ◽  
Dattatray S Bhat ◽  
Sanat B Phatak ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Intolerance ◽  
Early Life ◽  
Maternal Nutrition ◽  
Fasting Glucose ◽  
Childhood And Adolescence ◽  
Parents And Children ◽  
Nutrition Study ◽  
Normal Glucose ◽  
High Fasting Glucose

<i>Objective</i> <p>India is a double world capital for early life undernutrition and type 2 diabetes. We aimed to characterise lifecourse growth and metabolic trajectories in those developing glucose intolerance as young adults, in the Pune Maternal Nutrition Study (PMNS). </p> <p><i>Research design and Methods</i></p> <p>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 beta cell compensation accounting for prevailing insulin sensitivity. <b><i></i></b></p> <p><i>Results</i></p> <p>At 18 years (N=619) 37% men and 20% women were glucose intolerant (184 prediabetes, 1 diabetes) despite 48% being underweight (BMI<18.5 kg/m<sup>2</sup>). 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 the glucose intolerant had consistently lower compensatory insulin secretion from childhood. Participants in the highest quintile of fasting glucose at 6 and 12 years had a 2.5- and 4.0-fold higher risk respectively of 18-year glucose intolerance; this finding was replicated in two other cohorts. <b><i></i></b></p> <p><i>Conclusion</i></p> Inadequate compensatory insulin secretory response to decreasing insulin sensitivity from early life is the major pathophysiology underlying glucose intolerance in thin rural Indians. Smaller birth size, maternal pregnancy hyperglycemia, and higher glycemia in childhood herald future glucose intolerance, mandating a strategy for diabetes prevention from early life, preferably intergenerationally.

scholarly journals Poor In Utero Growth and Reduced β-Cell Compensation and High Fasting Glucose from Childhood Are Harbingers of Glucose Intolerance in Young Indians

2021 ◽  
Author(s):  
Chittaranjan S Yajnik ◽  
Souvik Bandopadhyay ◽  
Aboli Bhalerao ◽  
Dattatray S Bhat ◽  
Sanat B Phatak ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Intolerance ◽  
Early Life ◽  
Maternal Nutrition ◽  
Fasting Glucose ◽  
Childhood And Adolescence ◽  
Parents And Children ◽  
Nutrition Study ◽  
Normal Glucose ◽  
High Fasting Glucose

<i>Objective</i> <p>India is a double world capital for early life undernutrition and type 2 diabetes. We aimed to characterise lifecourse growth and metabolic trajectories in those developing glucose intolerance as young adults, in the Pune Maternal Nutrition Study (PMNS). </p> <p><i>Research design and Methods</i></p> <p>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 beta cell compensation accounting for prevailing insulin sensitivity. <b><i></i></b></p> <p><i>Results</i></p> <p>At 18 years (N=619) 37% men and 20% women were glucose intolerant (184 prediabetes, 1 diabetes) despite 48% being underweight (BMI<18.5 kg/m<sup>2</sup>). 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 the glucose intolerant had consistently lower compensatory insulin secretion from childhood. Participants in the highest quintile of fasting glucose at 6 and 12 years had a 2.5- and 4.0-fold higher risk respectively of 18-year glucose intolerance; this finding was replicated in two other cohorts. <b><i></i></b></p> <p><i>Conclusion</i></p> Inadequate compensatory insulin secretory response to decreasing insulin sensitivity from early life is the major pathophysiology underlying glucose intolerance in thin rural Indians. Smaller birth size, maternal pregnancy hyperglycemia, and higher glycemia in childhood herald future glucose intolerance, mandating a strategy for diabetes prevention from early life, preferably intergenerationally.

scholarly journals Poor in-utero growth, reduced beta cell secretion and high plasma glucose in childhood are harbingers of glucose intolerance in young Indians

2020 ◽  
Author(s):  
Chittaranjan S Yajnik ◽  
Souvik Bandopadhyay ◽  
Aboli Bhalerao ◽  
Dattatray S Bhat ◽  
Sanat Phatak ◽  
...  
Keyword(s):  
Beta Cell ◽  
Birth Cohort ◽  
Glucose Intolerance ◽  
Plasma Glucose ◽  
Maternal Nutrition ◽  
In Utero ◽  
Childhood And Adolescence ◽  
Cell Secretion ◽  
Insulin Metabolism ◽  
Beta Cell Secretion

AbstractBackgroundIndia is the world’s paradoxical double capital for early life undernutrition and type 2 diabetes. The Pune Maternal Nutrition Study (PMNS) birth cohort offered a unique opportunity to investigate childhood growth and glucose-insulin metabolism as precursors to glucose intolerance in young adulthood.MethodsPMNS is a community-based pre-conceptional birth cohort established in 1993, with serial information on parents, and on their children through pregnancy, childhood and adolescence. We compared the children’s growth and glucose-insulin indices between those who were and were not glucose intolerant at age 18 years (ADA criteria). We developed a prediction model for 18-year glucose intolerance and replicated it in two other cohorts (Extended PMNS and Pune Children’s Study).FindingsAt age 18 years (N=619) 37% men and 20% women were glucose intolerant even though 48% were underweight (BMI<18.5 kg/m2). Glucose intolerant participants were shorter at birth, and had lower insulin secretion (both sexes) and insulin insensitivity (men) in childhood than those with normal glucose tolerance. Fasting plasma glucose (FPG) concentrations at 6- and 12-years of age strongly predicted glucose intolerance at 18 years. The risk was 2.5 times higher in the highest compared to the lowest quintile at 6 years, and 4.5 times at 12 years. Comparable findings were seen in the other cohorts. Mothers of glucose intolerant participants had higher glycemia in pregnancy.InterpretationGlucose intolerance in young rural Indians can be traced to linear growth faltering in-utero, reduced beta-cell secretion and higher glycemia since childhood. Our findings mandate a strategy for diabetes prevention starting much earlier than the current practice.

scholarly journals Maternal vitamin B12, folate during pregnancy and neurocognitive outcomes in young adults of the Pune Maternal Nutrition Study (PMNS) prospective birth cohort: study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e046242
Author(s):  
Rishikesh V Behere ◽  
Gopikrishna Deshpande ◽  
Souvik Kumar Bandyopadhyay ◽  
Chittaranjan Yajnik
Keyword(s):  
Young Adults ◽  
Functional Connectivity ◽  
Birth Cohort ◽  
Maternal Nutrition ◽  
Brain Mri ◽  
Brief Symptom Inventory ◽  
Research Center ◽  
Neurocognitive Outcomes ◽  
Nutrition Study ◽  
Hospital Research

IntroductionThe Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that intrauterine and early life exposures significantly influence fetal development and risk for disease in later life. Evidence from prospective birth cohorts suggests a role for maternal B12 and folate in influencing neurocognitive outcomes in the offspring. In the Indian setting, B12 deficiency is common during the pregnancy while rates of folate deficiency are lower. The long-term influences of maternal nutrition during the pregnancy on adult neurocognitive outcomes have not been examined. The Pune Maternal Nutrition Study (PMNS) is a preconceptional birth cohort into its 24th year and is considered a unique resource to study the DOHaD hypothesis. We found an association between maternal B12 status in pregnancy and child’s neurocognitive status at 9 years of age. We now plan to assess neurocognitive function and MRI measurements of brain structural–functional connectivity at young adult age to study its association with maternal nutritional exposures during the pregnancy.Methods and analysisAs part of ongoing prospective follow-up in young adults of the PMNS at the Diabetes Unit, KEM Hospital Research Center, Pune India, the following measurements will be done: neurocognitive performance (Standardised Tests of Intelligence, Verbal and Visual Memory, Attention and Executive Functions), temperament (Adult Temperament Questionnaire), psychopathology (Brief Symptom Inventory and Clinical Interview on Mini Neuropsychiatric Interview 7.0). Brain MRI for structural T1, resting-state functional connectivity and diffusion tensor imaging will be performed on a subset of the cohort (selected based on exposure to a lower or higher maternal B12 status at 18 weeks of pregnancy).Ethics and disseminationThe study is approved by Institutional ethics committee of KEM Hospital Research Center, Pune. The results will be shared at national and international scientific conferences and published in peer-reviewed scientific journals.Trial registration numberNCT03096028

Plasma glycated CD59 predicts postpartum glucose intolerance after gestational diabetes

2021 ◽  
Author(s):  
Katrien Benhalima ◽  
Diane D Ma ◽  
Annouschka Laenen ◽  
Chantal Mathieu ◽  
Jose A Halperin
Keyword(s):  
Gestational Diabetes ◽  
Glucose Intolerance ◽  
Predictive Value ◽  
Characteristic Curve ◽  
Ethnic Origin ◽  
Tolerance Test ◽  
Blood Levels ◽  
Oral Glucose ◽  
Normal Glucose ◽  
Glucose Tolerant

Aims: To assess whether in women with gestational diabetes mellitus (GDM), postpartum plasma glycated CD59 (pGCD59) levels predict conversion to glucose intolerance diagnosed with an oral glucose tolerance test (OGTT). Methods: Blood levels of pGCD59 were measured in a case-control study of 105 women with GDM who underwent a 75g OGTT three months postpartum. The 35 postpartum glucose intolerant cases were individually matched for age, BMI, ethnic origin and parity with 70 women with GDM but normal postpartum OGTT (controls). The GDM cohort (105) was also matched with 105 normal glucose tolerant women during pregnancy. pGCD59 was measured by ELISA in standard peptide units (SPU). Results: Mean pGCD59 postpartum was significantly higher in cases than in controls (1.5 ± 0.6 SPU vs. 1.0 ±0.6 SPU, p<0.001). The area under the receiving operating characteristic curve (AUC) in cases versus controls was 0.72 (95% CI 0.62-0.83) for postpartum pGCD59 and 0.50 (95% CI 0.36-0.61) for postpartum HbA1c. A 0.5-unit increase in postpartum pGCD59 was associated with an OR of 3.3 (95% CI 1.82-6.16, p<0.001) for glucose intolerance postpartum. A pGCD59 cut-off postpartum of 0.9 SPU had a sensitivity of 85.7% (95% CI 69.7-95.2%), specificity of 47.8% (95% CI 35.6-60.2%), positive predictive value of 45.4% (95% CI 33.1-58.2%) and negative predictive value of 86.8% (95% CI 71.9-95.6%). pGCD59 in pregnancy was a poor predictor for glucose intolerance postpartum [AUC of 0.61 (95% CI 0.50-0.72)]. Conclusions: pGCD59 might identify women at low risk for glucose intolerance postpartum and could help to avoid an OGTT.

scholarly journals Exposure to Gestational Diabetes Is a Stronger Predictor of Dysmetabolic Traits in Children Than Size at Birth

2018 ◽  
Vol 104 (5) ◽  
pp. 1766-1776 ◽  
Author(s):  
Freja Bach Kampmann ◽  
Anne Cathrine Baun Thuesen ◽  
Line Hjort ◽  
Sjurdur Frodi Olsen ◽  
Sara Monteiro Pires ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Birth Cohort ◽  
Gestational Age ◽  
Metabolic Profile ◽  
Large For Gestational Age ◽  
Independent Effect ◽  
Birth Cohort Study ◽  
Childhood And Adolescence ◽  
Size At Birth ◽  
Cardiometabolic Traits

Abstract Context and Objective Being born small or large for gestational age and intrauterine exposure to gestational diabetes (GDM) increase the risk of type 2 diabetes in the offspring. However, the potential combined deleterious effects of size at birth and GDM exposure remains unknown. We examined the independent effect of size at birth and the influence of GDM exposure in utero on cardiometabolic traits, body composition, and puberty status in children. Design, Participants, and Methods The present study was a longitudinal birth cohort study. We used clinical data from 490 offspring of mothers with GDM and 527 control offspring aged 9 to 16 years, born singleton at term from the Danish National Birth Cohort with available birthweight data. Results We found no evidence of a U-shaped association between size at birth (expressed as birthweight, sex, and gestational age adjusted z-score) and cardiometabolic traits. Body size in childhood and adolescence reflected the size at birth but was not reflected in any metabolic outcome. No synergistic adverse effect of being born small or large for gestational age and exposure to GDM was shown. However, GDM was associated with an adverse metabolic profile and earlier onset of female puberty in childhood and adolescence independently of size at birth. Conclusion In childhood and adolescence, we found GDM was a stronger predictor of dysmetabolic traits than size at birth. The combination of being born small or large and exposed to GDM does not exacerbate the metabolic profile in the offspring.

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