While childhood cardiovascular risk factors are used to predict risk for clinical outcomes and base therapies, it may be a fluctuation in such risk factor measurements that has the most impact.
Cardiovascular risk factors, such as BMI, blood pressure, and lipid levels, are commonly used to predict patients’ risk for cardiovascular events and diagnosis of obesity, hypertension and dyslipidemia. These measures guide the initiation of preventative therapies including blood pressure lowering and lipid-lowering drugs. Because these measures can vary from person to person due to genetics, physiological and behavioral factors, the variability of these measures and how it affects future outcomes and diagnoses has recently become of interest. Thus far, research has shown that greater variability in BMI, blood pressure and lipid levels, independent of the actual levels, is associated with future adverse outcomes including adverse events, cognitive dysfunction and mortality. While this has been studied consistently in middle-aged and elderly populations, there is little research regarding the effects of childhood variability in cardiovascular risk factors on the risk of future diabetes.
A recent study analyzed patient data from the Bogalusa Heart Study (BHS) which repeatedly measured and prospectively collected cardiovascular risk factor data from patients through childhood, young adulthood and midlife. This provides an opportunity to assess the impact of cardiovascular risk factors on the risk of future diabetes without the interference of confounding risk factors or comorbidities often seen in adults and elderly populations. This study can deliver a solid background for initiating preventative therapies and lifestyle changes to young patients who possess risk factors that indicate high risk for future cardiovascular outcomes and diagnoses of diabetes.
The Bogalusa Heart Study encompassed 9 cross-sectional surveys of children aged 4-19 years old and 11 surveys of adults aged 20-58, previously examined as children. The study was conducted in Bogalusa, Louisiana, and consisted of 65% white and 35% black participants. About two-thirds of the adults did not have enough fasting glucose measurements recorded and were excluded; to increase the sample size, they included 1,718 adults who had enough data recorded at least four times during childhood. Exam data included BMI, blood pressure, total cholesterol, triglycerides, LDL cholesterol and HDL cholesterol. The mean follow-up period was 20.5 years. The primary outcome, diabetes, was defined based on fasting plasma glucose 126 mg/dL or use of insulin or oral anti-diabetes medications.
During the 20.5-year follow-up time period, 133 participants developed diabetes. Increased BMI variability and HCL variability in childhood were independently associated with development of diabetes. The population was separated into groups based on high or low levels of BMI and HDL and high or low variability of BMI and HDL. Significant results are as follows: the group with both high BMI value and high BMI variability were 2.91 (adjusted OR) times more likely to develop diabetes. The group with both low HDL and high HDL variability in childhood was 2.11 (adjusted OR) times more likely to develop diabetes in adulthood. Those with both high HDL and BMI variability were 2.20 (adjusted OR) times more likely to develop diabetes. No significant increased diabetes risk was seen in the group with low BMI but low BMI variability (OR 1.54 or in the group with low HDL but low HDL variability).
While this study has a large population and took place over a long time period, it also has some weaknesses. Diabetes was noted in participants based only on fasting plasma glucose, excluding many other measures of standard diagnoses, which may have underestimated the frequency of diabetes diagnoses. Also, this study took place within one community, and while a decent diversity by race was noted, this may not be very generalizable.
It is interesting to note that this study indicates that BMI and HDL variability is more impactful than actual levels of BMI and HDL on the development of diabetes. Previous experimental studies explained that fluctuating BMI is correlated with a greater increase in adipose tissue inflammation and insulin resistance than a persistent obese state. With this previous evidence, results observed from this study indicate that the pathways associating BMI variability and adult onset diabetes could be mediated by increased inflammation and insulin resistance. Fluctuation in childhood HDL may be a result of variability of lipid deposits, leading to instability of the vasculature and a resultant increase in diabetes risk.
- Previous experimental studies have shown that fluctuating BMI and HDL levels encourage adipose tissue inflammation, insulin resistance and damaged vasculature, increasing risk for diabetes.
- A recent study displayed a significant correlation between childhood variability in BMI / HDL and adult onset diabetes.
- BMI and HDL variability in children may be important risk factors to observe to recognize children who may require lifestyle management and potential preventative therapies.
Du, Tingting, et al. “Variabilities in Childhood Cardiovascular Risk Factors and Incident Diabetes in Adulthood: The Bogalusa Heart Study.” Diabetes Care, 2019, p. dc190430., doi:10.2337/dc19-0430.
Amber Satz, PharmD Candidate, LECOM School of Pharmacy