Children with strong family history of type 2 diabetes or CVD prone to have high cholesterol levels

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A new study published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) shows that children with a strong family history of cardiovascular disease (CVD) and/or type 2 diabetes were found to have cholesterol levels significantly higher than children with no family history of those conditions.

The research conducted by Dr Nina Berentzen, Dr Alet Wijga and Dr Annemieke Spijkerman (National Institute for Public Health and the Environment, Bilthoven, the Netherlands) and colleagues found that one third of the 12-year-olds studied had a strong family history of one or both diseases. This group also had unfavourable levels of cardiometabolic markers in the form of higher total cholesterol, and a higher ratio of total cholesterol to HDL cholesterol than the groups with moderate or no family history of disease. Children with elevated levels of these markers may also have a higher risk of heart attacks and strokes in adulthood.

Family history of disease reflects a complex combination of genetic, environmental and lifestyle characteristics that are shared by family members, and can provide valuable information about a multitude of factors that influence disease risk in children. This study considers both CVD in the form of heart attacks (referred to as myocardial infarction [MI]) and strokes, and type 2 diabetes which often occur together, and which share risk factors including high blood pressure, unhealthy diet, a lack of physical activity, and being overweight or obese.

While these conditions have been studied in the past, previous efforts lacked critical information about family history of CVD and type 2 diabetes. This study is therefore the first to investigate the occurrence of both diseases across two generations of parents and grandparents, and relate it to measurable risk factors in children.

A broad sample of children and their families involved in an ongoing Dutch population-based birth cohort study: The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) Study were invited to take part. Out of the original group of 3,963 children born in 1996/97, 1,511 participated in a clinical assessment at age 12, and around age 14, parents were asked to complete questionnaires which included items on their family history of CVD and diabetes. This provided a study population of 1,374 children (704 girls and 670 boys) who had both a clinical assessment at age 12 and parental reports on their family history of disease.

Parents were asked to report any history of MI, stroke and diabetes for both the biological parents and grandparents of the child, as well as the age at onset of those conditions. The family history for each child was then placed into one of three categories based on the severity of risk it presented. These was 'no family history' if they had no affected parents and grandparents, 'moderate family history' if they had 1-2 grandparents with late disease onset, and 'strong family history' if they had one affected parent, or at least one grandparent with early disease onset, or 3-4 grandparents with late disease onset. Early onset was defined as <55 y in grandfathers and <65 y in grandmothers for both MI and stroke, while for diabetes it was defined as <50 y for both grandfathers and grandmothers, as used in previous studies of this kind. Prevalence of CVD and diabetes in the parents of children involved in the study was found to be comparable to rates within the general age-matched Dutch population.

Children had a range of measurements taken at age 12, including BMI, waist circumference and cholesterol, blood pressure, and glycated haemoglobin (HbA1c), a standard method for assessing blood sugar control and diabetes status. Other characteristics used to describe the children taking part in the study were their sex, ethnicity (Dutch, Non-Dutch western, Non-Dutch non-western), age, pubertal development, as well as the age, education level and BMI of their parents.

The study found that: "Overall, children with a moderate family history of CVD and/or diabetes had no unfavourable cardiometabolic markers whereas children with a strong family history did, when compared to children with no family history." Adjusting for the BMI of the parents, and even factoring in the BMI of the child did little to change the effect estimates of the various cardiometabolic markers in those children with a strong family history of disease.

The authors state: "Our study is the first to investigate both diabetes and CVD history in two generations. Our findings add to the previous findings that in 12-year-old children from a contemporary cohort, history of MI and diabetes in parents and grandparents may be a relevant and important risk factor for unfavourable waist circumference, levels of cholesterol and HbA1c, and potentially for future cardiometabolic disease, largely independent of parental and child BMI."

Awareness of the links between cardiometabolic risk factors in children and family history may increase the motivation of families to follow healthy lifestyle guidelines but could also have implications for how preventive efforts are targeted. Often, the groups with the highest risk (lower income families and those from ethnic minorities) are the hardest to reach with preventive strategies.

Most of the associations between family disease history and cardiometabolic markers persisted, even after adjusting for the BMI of the parents and child. Using BMI as an indicator of lifestyle (such as diet or physical activity) shared within families could not completely explain the link between family disease history and the risk factors observed in the child. The authors note that: "even children with a healthy weight could be at risk for unfavourable levels of cardiometabolic markers if their parents or grandparents had MI or diabetes."

The authors say: "Future studies may especially focus on lifestyle behaviours that are passed on from one generation to the next since these may account for (part of) the association of diabetes/CVD in multiple generations with offspring cardiometabolic risk."

They conclude: "One third of the children in our study had a strong family history of CVD and/or diabetes. These children had higher levels of total cholesterol and a higher ratio of total cholesterol to HDL cholesterol than children with no family history. A strong family history of cardiovascular disease and diabetes was independently associated with unfavourable cardiometabolic markers specific to those diseases."

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