24th October 2021, Dr Chee L Khoo
Last fortnight we explored the disease burden in patients who have high lipids from a very young age and the effect on their future cardiovascular risk. This consideration allows us to think about who should be aggressively treated and whom we can just safely watch, at least for a few years. It would be nice to be able identify who we should screen for high lipids from a young age so that we can start lifestyle measures early. Who do we suspect may have high lipids? Who are more likely to have high lipids amongst our innocent looking young patients?
Lipids levels in any individual is not always predictable. Many overweight people can have normal lipid levels while it is not uncommon to have a skinny or fit and muscular patient with extreme high lipid levels. Obviously, there is a major contribution from our genes. Data from the National Health and Nutrition Examination Survey showed that from 2011 to 2012 approximately one in five US children and adolescents aged 8–17 years had an adverse concentration of total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C) or non-high-density-lipoprotein cholesterol (non-HDL-C) (1). Further, a recent meta-analysis from China indicated that the pooled prevalence of dyslipidaemia including high TC, high triglyceride (TG), high LDL-C or low HDL-C among Chinese children and adolescents was estimated as 25.3% (2).
The presence of gestational diabetes mellitus (GDM) has adverse future health effects not only in mothers but also in offsprings. This is not just for insulin resistance and diabetes but future adverse health effects in the offspring include any of the elements of metabolic syndrome especially for dyslipidaemia and CVD (3,4). As CVD incidence may be traced back to the maternal GDM (5) and has an association with dyslipidaemia in childhood, more investigations have focused on the impact of maternal GDM on lipid profiles of the offspring. The results of previous studies were inconsistent (6-9).
A recent Chinese study explored the influence of maternal gestational diabetes mellitus (GDM) on dyslipidaemia in the offspring. The Tianjin GDM screening project aimed to evaluate the lipid profile in 3 to 9 years old children who were born to mothers with and without a history of GDM (10). Tianjin is the fourth largest city in China with more than 12 million residents. All pregnant women in the 6 districts in Tianjin underwent a 1-h oral glucose tolerance test (OGTT) with 50-g glucose load. Women with a 1 hour glucose reading ≥7.8 mmol/L were invited to undergo a 2-h OGTT with 75-g glucose load. Women were considered to have GDM if their fasting glucose was > 7.0 mmol/L and/or 2 hour glucose >7.8 mmol/L. (Women who had fasting >7.0 mmol/L and/or 2 hour glucose >11.1 mmol/L have technically, diabetes in pregnancy but in this study, they were considered GDM).
Out of 76,325 women who were screened between 2005 and 2009, 4644 were diagnosed with GDM according to the above criteria and 71681 women did not. 1263 women agreed to participate in the study. 572 GDM mother-child pairs and 572 non-GDM mother-child pairs were randomly selected and compared. Every mother completed a self-administered questionnaire including socio-demographic characteristics (age, marital status, education, income, and occupation); family history of diabetes; pregnancy outcomes (pre-pregnancy weight, weight gain during pregnancy and number of children); lifestyle in the past year including smoking status, alcohol intake and physical activity.
Similarly, children’s information was collected by another questionnaire completed by their mothers including children’s general information, such as gender, birth date, age, birth weight, birth length, lactation/feeding, lactation duration, dietary habits, daily energy intake, sleeping time, screen watching time and outdoor physical activity time.
Mother-child pairs underwent physical examination and the children provided blood samples via peripheral capillary blood after 8 hour fasting.
Mothers with GDM were older at delivery, had a higher pre-pregnancy BMI and less weight gain during pregnancy compared with women without GDM. Children of GDM mothers had higher birth weight and Z score for BMI for age, longer screen watching time and outdoor activity time, less sleeping time and higher prevalence of overweight or obesity than offspring of non-GDM mothers.
Children born to mothers with GDM had significantly higher mean values of TG, non-HDL-C, TG/HDL-C ratio and lower mean values of HDL-C than children of non-GDM mothers. Children of GDM mothers showed increased risks of low HDL-C and high TG/HDL-C ratio compared with children of non-GDM mothers.
There were a variety of confounder risk factors that might obviously influence the children’s
lipid profile, such as children’s birth weight, outdoor physical activity time, daily energy intake, screen watching time, sleeping time, z-score for BMI for age, and maternal pre-pregnancy BMI, gestational weight gain and history of hypercholesterolemia.
In summary, maternal GDM was associated with an increased risk of dyslipidaemia in offspring during early childhood aged from 3 to 9 years old. The most obvious impacts on the lipid profile were increased risks of low HDL-C and high triglycerides/HDL-C ratio among children born to GDM mothers. In primary care, we know who these women and children are. We look after them before, during and after their pregnancies. Not only do we need to follow up the women with GDM closely for the development of future diabetes, we also need to pay attention to the offsprings who has an increased risk of elements of metabolic syndrome.
From last fortnight’s discussion on the burden of disease in dyslipidaemia in the young, we do need to intervene early. That’s the advantage of being a family doctor looking after generations of patients.
- Kit BK, Kuklina E, Carroll MD, Ostchega Y, Freedman DS, Ogden CL. Prevalence of and trends in dyslipidemia and blood pressure among US children and adolescents, 1999–2012. JAMA pediatrics. 2015;169(3):272-279.
- Ding W, Dong H, Mi J. Prevalence of dyslipidemia in Chinese children and adolescents: a Meta-analysis. Zhonghua liu xing bing xue za zhi= Zhonghua liuxingbingxue zazhi. 2015;36(1):71-77.
- Johns EC, Denison FC, Norman JE, Reynolds RM. Gestational diabetes mellitus: mechanisms, treatment, and complications. Trends Endocrinol Metab. 2018;29(11):743-754.
- Damm P, Houshmand-Oeregaard A, Kelstrup L, Lauenborg J, Mathiesen ER, Clausen TD. Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark. Diabetologia. 2016;59(7):1396-1399.
- Oken E, Gillman MW. Fetal origins of obesity. Obes Res. 2003;11(4):496-506.
- Retnakaran R, Ye C, Hanley A, et al. Effect of maternal gestational diabetes on the cardiovascular risk factor profile of infants at 1 year of age. Nutr Metab Cardiovasc Dis. 2013;23(12):1175-1181.
- West N, Crume T, Maligie M, Dabelea D. Cardiovascular risk factors in children exposed to maternal diabetes in utero. Diabetologia. 2011;54(3):504-507.
- Tam WH, Ma RCW, Yang X, et al. Glucose intolerance and cardiometabolic risk in children exposed to maternal gestational diabetes mellitus in utero. Pediatrics. 2008;122(6):1229-1234.
- Wilk M, Horodnicka-Jozwa A, Molęda P, Petriczko E, Safranow K, Walczak M. Assessment of selected lipid parameters in in children exposed to gestational diabetes (GDM) in utero. Pediat Endocrinol. Diabet Metabol. 2016;22(4).
- Yang X, Leng J, Liu H, Wang L, Li W, Li W, Yang X, Liu M, Hu G. Maternal gestational diabetes and childhood hyperlipidemia. Diabet Med. 2021 Nov;38(11):e14606. doi: 10.1111/dme.14606. Epub 2021 Jun 2. PMID: 34021927; PMCID: PMC8511106.