Childhood Obesity and Pre-Diabetes Linked with Premature Death

Obesity, glucose intolerance, and hypertension in childhood are strongly linked with premature death from endogenous causes in young adulthood and middle age, according to the results of a new epidemiological study….

Those in the highest quarter of the group for blood sugar levels without being diabetic had a rate of premature death from disease that was 73 percent higher than those children in the lowest group of blood sugar levels, researchers found.

Lead investigator Dr. Paul Franks (Umeå University Hospital, Sweden) stated that, "The linking factor here is almost certainly the obesity…. When we adjusted the risk associated with glucose levels and blood pressure for obesity, the effect of those risk factors substantially diminished. We also know the causal mechanisms with blood pressure, glucose, and obesity suggest that obesity is probably the primary metabolic derangement that causes hyperglycemia and high blood pressure, and not the other way around."

The purpose of this study was to study the effect of childhood risk factors for cardiovascular disease on adult mortality. In a cohort of 4,857 American Indian children aged five to 19 years without diabetes, body-mass index (BMI), glucose tolerance, blood pressure, and cholesterol levels were assessed to determine the extent to which they predicted premature death. The analyses included data from the date of the baseline examination until the person’s death, their 55th birthday, or the end of 2003. During a median follow-up of 24 years, there were 166 deaths, 3.4% of the cohort, from endogenous causes. Of these deaths, 59 were attributed to alcoholic liver disease, 22 to cardiovascular disease, 21 to infections, 12 to cancer, 10 to diabetes or diabetic nephropathy, nine to alcohol poisoning or drug overdose, and 33 to other causes.

BMI was associated with a significantly increased risk of premature death from endogenous causes, with those in the highest quartile having a mortality rate 230% greater than those in the lowest BMI quartile. The two-hour plasma glucose level assessed during an oral glucose-tolerance test was not associated with premature death, but children with elevated blood glucose, those in the highest quartile, had a 73% greater risk of premature death than those in the lowest quartile.

Incidence-Rate Ratios for Premature Death (Quartile 4 vs Quartile 1)

Variable	Premature death from endogenous causes, incidence-rate ratio (95% CI)
BMI	2.30 (1.46–3.62)
2-h glucose	1.73 (1.09–2.74)
Total cholesterol	1.28 (0.81–2.02)
Systolic blood pressure	1.34 (0.83–2.15)
Diastolic blood pressure1	1.40 (0.89–2.19)

In models looking only at children with impaired glucose tolerance, there was no significant association with premature death.

"That might sound slightly counterintuitive, that these children with impaired glucose tolerance, those at the top end, are not the ones really driving mortality," explained Franks. "The feeling is that this is a population with a well-known risk for diabetes, so children diagnosed with the highest glucose levels, even though they are not diabetic, might have been picked up by the medical services early on and treated, which would make them less prone to the consequences of hyperglycemia. The children just below that level, they still have high glucose, they’re the ones really driving the mortality rate in this study. The take-home message from this is that having a threshold for high glucose and saying that we’re only going to intervene when it is above that threshold might not be good enough."

Elevated cholesterol levels, on the other hand, were not associated with early mortality, although investigators caution against concluding that hypercholesterolemia in childhood is not harmful.

There was no significant association observed between systolic and diastolic blood pressure and premature death, but when investigators used a childhood definition of hypertension, one that takes three measurements and is standardized for height, there was a 57% increase in the risk of premature death among hypertensive children.

"What we don’t know is, if we intervene in these children, would we decrease the mortality rates? And we don’t yet know the best way to intervene. Weight loss is not normally considered an appropriate strategy in children; instead, we try to get them to migrate toward a healthy growth trajectory. The message for frontline therapists is healthy diet and physically active lifestyles," said Franks.