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Long-term metabolic effects of a high birth weight
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Pediatrisk inflammations- och metabolismforskning samt barnhälsa)ORCID iD: 0000-0002-1751-0408
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The intrauterine environment influences foetal growth as well as future response to risk factors for disease. This occurs partly through epigenetic mechanisms. Thus, birth weight is a possible risk marker of adult disease. Low birth weight is a well-known risk factor for adult disease, particularly when associated with obesity and a U-shaped relationship between birth weight and several metabolic diseases has been suggested.

In this thesis we investigated associations between a high birth weight and risk of adult disease, e.g. obesity, cardiovascular disease, type 2 diabetes and gestational diabetes.

By analyses of national register data on 759 999 subjects up to the age of 37 years, we could demonstrate an increased risk of type 2 diabetes in males, but not in females, with a high birth weight (>2 SDS). The increase was particularly pronounced in males with a birth weight >3 SDS. There was an association between high birth weight and obesity in males and females, but no such relation was seen for hypertension or serum lipid abnormalities.

In a clinical study, 27 cases with a birth weight ≥4 500 grams were compared with 27 controls with normal birth weight, regarding risk factors for cardiovascular disease and diabetes. The cases had a greater radial artery intima thickness and intima:media ratio compared with the controls indicating early atherosclerotic changes. Body mass index, body composition, insulin sensitivity, lipid profiles, blood pressure, resting energy expenditure and respiratory quotient did not differ between cases and controls, but females with a high birth weight had a more disadvantageous distribution of body fat.

In order to investigate associations between birth weight and pregnancy outcomes, register data on 305 893 females was analysed. The results demonstrated an association between the female´s own birth weight and offspring birth weight. A high maternal birth weight was associated with increased risk of obesity. The risk of gestational diabetes was increased in females with a low, but not a high birth weight.

In conclusion, subjects with a moderately high birth weight did not differ substantially from those with a normal birth weight regarding risk factors for cardiovascular disease. However, differences in arterial wall dimensions were demonstrated in a clinical investigation, and there were differences in BMI and risk of type 2 diabetes on a population level. Since risks are most pronounced in subjects with a birth weight >3 SDS, this group is in particular need of follow up and disease preventive measures.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 48
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1525
Keywords [en]
Body composition, Cardiovascular risk factors, Gestational diabetes, Glucose tolerance, High birth weight, Insulin sensitivity, Large for gestational age, Obesity, Offspring macrosomia, Type 2 diabetes
National Category
Pediatrics
Research subject
Endocrinology and Diabetology
Identifiers
URN: urn:nbn:se:uu:diva-369263ISBN: 978-91-513-0534-9 (print)OAI: oai:DiVA.org:uu-369263DiVA, id: diva2:1270255
Public defence
2019-02-13, Rosénsalen, Akademiska Barnsjukhuset, Ing 95/96 NBV, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2019-01-22 Created: 2018-12-12 Last updated: 2019-02-18
List of papers
1. A high birth weight is associated with increased risk of type 2 diabetes and obesity
Open this publication in new window or tab >>A high birth weight is associated with increased risk of type 2 diabetes and obesity
2015 (English)In: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 10, no 2, p. 77-83Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The association between low birth weight and adult disease is well known. Less is known on long-term effects of high birth weight.

OBJECTIVE: This study aims to investigate whether a high birth weight increases risk for adult metabolic disease.

METHODS: Swedish term single births, 1973-1982 (n = 759 999), were studied to age 27.5-37.5 years using Swedish national registers. Hazard ratios (HRs) were calculated in relation to birth weight for type 2 diabetes, obesity, hypertension and dyslipidaemia.

RESULTS: Men with birth weights between 2 and 3 standard deviation score (SDS) had a 1.9-fold increased risk (HR 1.91, 95% confidence interval [CI] 1.25-2.90) of type 2 diabetes, whereas those with birth weights above 3 SDS had a 5.4-fold increased risk (HR 5.44, 95% CI 2.70-10.96) compared to men with birth weights between -2 and 2 SDS. The corresponding HRs for women were 0.60 (95% CI 0.40-0.91) and 1.71 (95% CI 0.85-3.43) for birth weights 2-3 SDS and >3 SDS, respectively. Men with birth weights between 2 and 3 SDS had a 1.5-fold increased risk (HR 1.47, 95% CI 1.22-1.77) of obesity. The corresponding risk for women was 1.3-fold increased (HR 1.32, 95% CI 1.19-1.46). For men and women with birth weights above 3 SDS, the risks of adult obesity were higher, HR 2.46 (95% CI 1.63-3.71) and HR 1.85 (95% CI 1.44-2.37), respectively.

CONCLUSIONS: A high birth weight, particularly very high, increases the risk of type 2 diabetes in male young adults. The risk of obesity increases with increasing birth weight in both genders.

National Category
Pediatrics
Identifiers
urn:nbn:se:uu:diva-238292 (URN)10.1111/ijpo.230 (DOI)000351432400001 ()24916852 (PubMedID)
Available from: 2014-12-11 Created: 2014-12-11 Last updated: 2018-12-12Bibliographically approved
2. High birth weight was associated with increased radial artery intima thickness but not with other investigated cardiovascular risk factors in adulthood
Open this publication in new window or tab >>High birth weight was associated with increased radial artery intima thickness but not with other investigated cardiovascular risk factors in adulthood
2018 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 12, p. 2152-2157Article in journal (Refereed) Published
Abstract [en]

AIM: This study investigated whether a high birth weight was associated with increased risk factors for cardiovascular disease when Swedish adults reached 34-40.

METHODS: We studied 27 subjects born at Uppsala University Hospital in 1975-1979, weighing at least 4500 g, and compared them with 27 controls selected by the Swedish National Board of Welfare with birth weights within ±1 standard deviations scores and similar ages and gender. The study included body mass index (BMI), blood pressure, lipid profile, haemoglobin A1c (HbA1c), C-reactive protein (CRP) and high-frequency ultrasound measurements of intima-media thickness, intima thickness (IT) and intima:media ratio of the carotid and radial arteries.

RESULTS: Subjects with a high birth weight did not differ from controls with regard to BMI, blood pressure, lipid profile, high-sensitivity CRP, HbA1c or carotid artery wall dimensions. However, their radial artery intima thickness was 37% greater than the control group and their intima:media ratio was 44% higher.

CONCLUSION: Our findings indicate that a high birth weight was associated with increased radial artery intima thickness, but not with other investigated cardiovascular risk factors, at 34-40 years of age. The clinical implications of these findings should be investigated further, especially in subjects born with a very high birth weight.

Keywords
Cardiovascular risk factors, High birth weight, Intima thickness, Intima:media ratio, Large for gestational age
National Category
Pediatrics Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-364690 (URN)10.1111/apa.14414 (DOI)000449638100022 ()29791055 (PubMedID)
Funder
Novo Nordisk
Available from: 2018-10-31 Created: 2018-10-31 Last updated: 2019-01-22Bibliographically approved
3. High birth weight was not associated with altered body composition or impaired glucose tolerance in adulthood
Open this publication in new window or tab >>High birth weight was not associated with altered body composition or impaired glucose tolerance in adulthood
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Aim To investigate whether a high birth weight was associated with an increased proportion of body fat or with impaired glucose tolerance in adulthood.

Methods Our cohort comprised 27 subjects with birth weights of 4,500 g or more, and 27 controls with birth weights within ±1 SDS, born at Uppsala University Hospital 1975-1979. The subjects were 34-40 years old at the time of study.

Anthropometric data was collected, and data on body composition was obtained by air plethysmography and bioimpedance and was estimated with a three compartment model. Indirect calorimetry, blood sampling for fasting insulin and glucose as well as a 75 g oral glucose tolerance test were also performed. Insulin sensitivity was assessed using homeostasis model assessment 2 (HOMA2) and Matsuda index. Areas under the curves were calculated for insulin and glucose.

Results There were no differences in body mass index, body composition or insulin sensitivity between subjects with a high birth weight and controls.

Conclusion Adult subjects, born with a moderately high birth weight, did not differ from those with birth weights within ±1 SDS regarding body composition or glucose tolerance

Keywords
Body composition, Glucose tolerance, High birth weight, Insulin sensitivity, Obesity
National Category
Medical and Health Sciences Pediatrics
Research subject
Endocrinology and Diabetology
Identifiers
urn:nbn:se:uu:diva-369022 (URN)
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-12Bibliographically approved
4. Females with a high birth weight have increased risk of offspring macrosomia and obesity, but not of gestational diabetes
Open this publication in new window or tab >>Females with a high birth weight have increased risk of offspring macrosomia and obesity, but not of gestational diabetes
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Aim This study investigated how maternal birth weight was related to offspring birth weight, as well as to risk of obesity in pregnancy and gestational diabetes.

Methods The cohort (N= 305 893) comprises females born term and singleton in Sweden 1973-1995, studied at the time of their first pregnancy. Information regarding their birth weight, BMI and complications during pregnancy was retrieved from the Swedish Medical Birth Register in addition to data on their mothers and offspring.

Results A maternal birth weight between 2-3 SDS was associated with a more than threefold increased risk of having an offspring with a birth weight between 2-3 SDS, OR 3.83 (3.44-4.26), or >3 SDS, OR 3.55 (2.54-4.97). Corresponding ORs for a maternal birth weight >3 SDS were 5.38 (4.12-7.01) and 6.98 (3.57-13.65), respectively. Risk of obesity in pregnancy was also related to maternal birth weight with OR 1.52 (1.42-1.63) for a birth weight corresponding to 2-3 SDS and 2.06 (1.71-2.49) for a birth weight >3 SDS. The risk of gestational diabetes was increased in females with a low (<2 SDS) birth weight, OR 2.49 (2.00-3.12), but not in those with a high birth weight.

Conclusion Being born with a high birth weight was associated with increased risk of offspring macrosomia and obesity during pregnancy. The risks were most pronounced for subjects with a very high birth weight. A low, but not a high birth weight was associated with increased risk of gestational diabetes.

Keywords
Birth weight, Gestational diabetes, Large for gestational age, Obesity, Offspring macrosomia
National Category
Pediatrics
Research subject
Endocrinology and Diabetology; Endocrinology and Diabetology
Identifiers
urn:nbn:se:uu:diva-369088 (URN)
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-12Bibliographically approved

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