We found in our cohort that boys aged 2 to 18 years have higher glucose levels. Children aged 2 to 5 years have significantly lower glucose than 15 to 18 year-olds and 11 to 14 year-olds have significantly higher glucose levels. There is a low but significant association between high BMI and higher glucose levels.
For over 100 years we have been looking at glucose as a fixed range, irrelevant of sex and age. Bass, in 1915, was among the first to determine the normal range of glucose levels in 60 children and found that it does not differ much from the range in adults. Rudesill and Henderson showed in 1941 that 98% of blood glucose levels in children were between 70 and 105 mg/dl. Both studies were small-scale and did not report differences in age groups nor between sexes.[2],[14] Normal fasting plasma glucose is defined today between 65–100 mg/dl (3.5–5.5 mmol/l) for all children excluding infants and is the same for both sexes.[15] The level of 109 mg/dl was chosen almost arbitrarily as the upper threshold of normal glucose in adults, because levels higher than 109 mg/dl are associated with greater risk of vascular complications and the development of diabetes—later coined “prediabetes”.[16] Population studies showed that lowering the threshold to 100 mg/dl proved a better predictor for the development of diabetes.[17]
In recent years, glucose levels in children were determined through glucose reference studies. CALIPER (Canadian Laboratory Initiative in Pediatric Reference Intervals) is a commonly referenced relatively small-scale study, which consisted of 2,188 children, newborn to 18 years of age. In this cohort, glucose did not vary by sex or age.[3] Larger cohort studies such as IDEFICS (“identification and prevention of dietary- and lifestyle-induced health effects in children and infants”) that surveyed 7,074 healthy children aged 3 to11 years in Europe between 2007–2010, found that boys have higher glucose levels than girls, and that there is a linear rise in glucose with age.[5] Lai showed that children younger than 5 years of age have glucose levels which are 10% lower than those found in older children, and that girls have lower glucose than boys in 4,326 children aged 3 to 15 years.[18] A reference study from India comprised of 7,618 school children, ages 11 to 18 years, found that boys had significantly higher glucose levels than girls. The glucose levels were consistent among the age groups, except for 14 year-old boys whose glucose levels were lower.[4]
Our study shows a slightly higher range of glucose in children, 72–107 mg/dl, than is generally reported in the literature,[15],[18] although some studies show even higher reported ranges.[19] In the MHS cohort, boys display higher glucose levels throughout all age groups, and children in puberty have higher glucose levels. The overall results suggest that younger children have lower glucose levels. These lower glucose levels raise questions about whether the cut off for hyperglycemia should be lowered in this age group. Additionally questioning if higher levels of glucose that are considered within the norm can predict adverse health issues later on in life.
A host of factors may affect glucose homeostasis including glucose intake, insulin and glucagon secretion, and endogenous liver glucose production (gluconeogenesis). The counterregulatory hormones such as growth hormone and cortisol are increased during fasting. In the fed state glycogenolysis, lipolysis and ketogenesis are suppressed.[15] During puberty there is insulin resistance (IR) and decreased insulin sensitivity in healthy children.[9] There is a correlation between the increase in growth hormone (GH), which is known to cause IR, and insulin like growth factor 1 (IGF1).[9],[20]
As for the sex differences in glucose levels, insulin levels are higher in girls than in boys in these age groups, and the higher insulin levels may indicate variable degrees of insulin resistance.[4, 5] In adults, it has been shown that the estrogen receptors affect the glucose transporters and through them glucose metabolism.[8] In our study as in others, boys have higher glucose levels than girls, even though T2DM is more prevalent in teenage girls.[21] This incongruity is yet to be explained.
Approximately 30% of the cohort had BMI measurements taken the same year as their glucose levels. Our results show that there is a weak correlation between BMI and glucose, as opposed to a study done in Sweden that showed no such correlation. [22], BMI is shown to be associated with glycemia, but it is dependant on individual variability and childhood obesity is not a strict predictor of hyperglycemia.[23] Obesity is a risk factor for T2DM in boys as well as girls, with the increase in world wide obesity a contributing factor to T2DM.[24]
There is a clinically small but statistically significant increase in glucose levels over the years of our study.
In Israel about 6% of children are obese.[25] Our results indicated there was no significant increase in BMI in this population of children during the years of the study. Neither was there a proportional increase in children with glucose levels higher than 100 mg/dl.