What are "normal" fasting blood glucose levels among Mexican children from 1 – 5 years of age, who do not have diabetes mellitus, type 1A (DM1)?

There are multiple studies investigating diabetic hyperglycemia and hypoglycemia.  There are several studies that refer verbatim to the "normoglycemia" present in people who do not live with DM.  There are no scientific studies that show the data needed to define normoglycemia in children without DM.

A reasonable clinical glycemic management plan for children and adolescents who have DM1 depends on knowledge of the typical or "normal" levels of the population of the same age and body weight, who do not have DM1.  These typical or normal glycemic levels are not scientifically defined or published.

The information obtained from the present study will be able to define the clinical goal of BG ranges similar to the "normal" ones and will allow comparison between the glycemic ranges currently recommended by the American Diabetes Association (ADA) and those currently found among the childhood population living without DM1.

The data collected in this study will also allow the design of a hyperglycemia control guidelines that are more effective than current, rarely implemented, preventive therapeutic recommendations. ^{1  2}

It is worth noting that official glycemic recommendations are rarely consistently taken into account or achieved by young people and adults living with DM. ^{1 2 3 4 5 6}

It is not known to what extent the current target glycemic values for Mexican children living with DM1 resemble those of healthy, appropriate body-weight children.  These children, because they do not have chronic or near-chronic diabetic hyperglycemia, will not suffer from microvascular diabetic complications.

Further documentation of the glycemic values of these Mexican children, in the fasting state and ideally postprandially, could well inform our definition of their true "normoglycemia."   Even more importantly, it can guide us clinically.

At the end of the day, greater knowledge of normoglycemia among children not living with DM1 could support, justify or rationalize more realistic glycemic recommendations for children living with this incurable condition.

The normal and natural non-diabetic infant glycemic amplitude should serve as a criterion for setting the glycemic ranges to be indicated or suggested for children who have DM1.  For the child who has DM1, understanding and maintaining approximate normoglycemia has an undoubtedly positive and preventive function.

The girl who does not have DM1 does not and will not show any "diabetic" physiological complications.  On the other hand, the person who has DM1 does not enjoy this security.  Could it be that the difference is only attributable to chronic diabetic hyperglycemia or recurrent diabetic hypoglycemia?

Children attending two kindergartens administered by the Foundation for Family Educational Assistance (FAE) and located in the State of Mexico participated: that of Colonia Sol, Ciudad Nezahualcóyotl (September 27, 2007), and that of Colonia Tlatel, Chimalhuacán (October 16, 2007). 

The criteria for inclusion in the study were:

The participant's parents provided informed consent by signing a form that was given to them to explain the nature and purpose of the scheduled investigative procedure and to clarify that any participation was not mandatory but purely voluntary.

The participating children were between > 12 and < 72 months of age, at the time of glucemic monitoring.

The criteria for exclusion in the study were:

The participant's mother was not born in the Republic of México.

The participant had not completed 8 hours of fasting.

The participant showed visible body weight higher or lower than normal body weight, that is, at the time of glycemic testing had a Body Mass Index ⁶  > the 5th percentile and < the 85th percentile, adjusted for her or his chronological age.

The participant had been diagnosed with DM1 or DM2, as reported by his or her parents or teachers.

The participant did not want to (tears, screams) or verbally refused to permit glycemic testing, even with prior written permission from his or her parents.

The parents of 97.8% of the combined pupils of the two kindergartens (396 children aged 8 to 82 months) gave their written informed consent for the children (180 females, 216 males) to take part in glycemic monitoring.

About a week after this testing, parents received a written copy of their child's BG result.

Methods

Glycemic measurements were carried out on two working days, between 7 and 10 in the morning, outdoors in the courtyard of each kindergarten. The unpaired Student's t statistical test makes it possible to evaluate differences between averages of groups of different sizes.  This test was used for all analyses of average fasting BG values.

Results

438 BG measurements were made, 396 of which were from children.

As a courtesy, the BG of the 42 adult staff members of the two kindergartens was also monitored, although their results were not included in the statistical analyses.

To optimize the determination of typical or "normal" childhood BG levels, the results of 93 children (24%) and 5 adults (12%) were excluded before performing statistical analyses, according to the criteria already detailed above for exclusion from the study.

Data from the remaining 303 children were analyzed (Tables 1 — 6).

Table 1:  Blood glucose values (mg/dL), for the total sample of all children

Fasting	Average BG	Standard Deviation	Range
All children included (n = 303)	74.08	9.81	46—91

Table 2:  Blood glucose values (mg/dL), children in Nezahualcóyotl 

Fasting	Average BG	Standard Deviation	Range	P
Males (n = 49)	82.88	5.84	68 – 91	.0237
Females (n = 40)	79.85	6.57	67 – 89
All children (n = 214)	81.52	6.33	67 – 91	.0001

Table 3:  Blood glucose values (mg/dL), children in Chimalhuacán

Fasting	Average BG	Standard Deviation	Range	P
Males (n = 110)	71.96	9.13	47 – 91	.0237
Females (n = 104)	69.96	9.49	46 – 90
All children (n = 214)	70.99	9.34	46 – 91	.0001

Table 4:  Blood glucose value (mg/dL), by sex and age, both populations combined

Fasting	Average BG	Standard Deviation	Range	P
Males (n= 159)	75.33	9.67	47—91	.02
12—23 months (n = 6)	81.50	6.09	71—91	.
24—35 months (n = 17)	76.00	13.68	47—90	.
36—47 months (n = 39)	75.31	11.99	53—91	.
48—59 months (n = 50)	74.00	7.55	62—90	.0028
60—71 months (n = 47)	75.72	8.07	57—89	.
Females (n= 144)	72.71	9.81	46—90	.
12—23 months (n = 15)	75.20	9.48	57—90	.
24—35 months (n = 18)	75.50	9.59	57—88	.
36—47 months (n = 37)	70.60	11.96	46—88	.
48—59 months (n = 37)	68.78	8.15	49—89	.
60—71 months (n = 37)	76.38	7.34	62—89	.

Table 5:  Distribution and frequency of BG values < 80 mg/dL

Range (mg/dL)	BG value frequencies	% of the sample
46—50	5
51—60	22
61—70	81
		= 108/303 = 35.6%
71—79	96
		= 204/303 = 67.3%

The glycemic values of the monitored adults are presented in Table 6 below, in order to allow comparison with those of the children.  Adult values were not formally a part of the published study.

Dr. Richard K. Bernstein, the author, our colleague Dra. Rosa Elena Yáñez and the websites www.diabetes-safari.com, www.continents.com, www.dm1dm2.com and www.ventajas.com have for many years defined a "normal" BG value in a child or adolescent or adult without any form of DM as between 71 and 99 mg/dL.

Data from these adults who are neither overweight nor obese and had no metabolic disorder confirm the accuracy of this published and recommended normal glycemic range as the safest and most capable of preventing or minimizing diabetic complications among those living with DM.

Fasting	Average BG	Standard Deviation	Range	P
Sexo masculino (n = 8)	83.25	9.65	70—100
Sexo femenino (n = 29)	81.76	8.95	62—99
Todos (n = 37)	82.08	8.99	62—100	.0001

The boys had faster fasting BG levels than girls. This difference was not seen between the sexes in the Chimalhuacán kindergarten.

3.  between the sexes of the total number of children (Table 4, P = .02).  The girls consistently tended to have lower BG levels than boys.

4.  among all students compared by sex and age.  At 48 – 59 months of age, the BG levels of fasting boys was ~ 5.22 mg/dL higher than that of the girls.  (Table 4, P = .0028).

5.  in the distribution and frequency of BG values among all children participating (Table 5).

Most of the glycemic values of fasting children (204 of 303 or 67.3%) were "low" (< 80 mg/dL).  Almost 36% (35.6%) of the children monitored had therapeutic hypoglycemia, that is, glycemic levels of < 71 mg/dL.  No glycemic value was found > 91 mg/dL among these children.

6.  between the global average fasting BG level of children and that of adults (Table 6, P = .0001).  This result confirms the presence of glycemic differences related not only to sex but also to age.

Comments

The results of this normative study indicate that for Mexican boys and girls aged 1 to 5 years who have a normal body weight and who are not diagnosed with DM or any other metabolic disorder, the average level of their fasting blood glucose level is ~ 74.1 mg/dL.

According to official recommendations for children who have DM1, this BG level is considered virtually equivalent to therapeutic or treatable hypoglycemia (< 70 mg/dL).

However, at this glycemic level and even at lower levels, the children monitored had no obvious or reported hypoglycemic signs or symptoms.  Therefore, it is likely to be an asymptomatic state of physiological hypoglycemia.

Possibly less than 70 mg/dL is not a really hypoglycemic value, and therefore there were no signs or symptoms.

The global BG average seen in this study is almost exactly the glycemic average of 74.7 mg/dL naturally maintained among pregnant women who have neither DM nor obesity, during the third and final trimester of their pregnancy. ⁷

After birth, it seems that Mexican children tend to maintain, at least for the first 5 years of extrauterine life, a glycemic state equivalent to that of the last 3 months of their uterine life.

67.3% of the 303 fasting children included in this study had blood glucose of < 79 mg/dL.  The accepted definition of therapeutic hypoglycemia is any BG value of < 70  mg/dL. ⁸ 

35.6% of this sample presented this level of therapeutic hypoglycemia. 9% of the children monitored had hypoglycemia of < 60 mg/dL, and 5% had biochemical hypoglycemia (< 54 – 50 mg/dL).^{8 9}

Among the Mexican children monitored, the presence of therapeutic and/or biochemical hypoglycemia in fasting is more frequent than anticipated.  The range of fasting BG detected among these "normal" prepubertal children is wide (46 – 91 mg/dL).

However, none of these children were using exogenous insulin or oral hypoglycemic agents.  None of the children reported symptoms of hypoglycemia or showed any signs of hypoglycemia.

The teachers did not comment on the presence of hypoglycemic signs or symptoms among their students.

On the other hand, no hyperglycemic value (> 100 mg/dL) was found. In fact, a glycemic value of > 91 mg/dL did not occur even once in the fasting state among these children.  So it appears that they are not at immediate risk of developing DM2.

Therapeutic or biochemical hypoglycemia caused by excessive or inexperienced use of exogenous insulin often causes dread and panic among children treated for DM1 and their parents or caregivers.

Although almost 70% of the children monitored had blood glucose of < 80 mg/dL, and they could not eat breakfast until after the BG measurements of all the students were finished, in this lengthy delay there was no tone of urgency or anxiety that frequently characterizes the response of children who have DM1 and their parents to current or imminent hypoglycemia.

Furthermore, no anxiety regarding lower than normal BG readings was observed among teachers or among these "normal" children living without DM.

In their case, however, and unlike children who use insulin therapy, the unpredictability of an additional and more dangerous glycemic decrease practically at any time does not condition their response.

As the present study demonstrates, the symptoms of hypoglycemia and the physical and mental discomfort that ordinarily accompany it may be absent in the child who does not have DM1, even when she or he has abnormally low BG concentrations (46 – 60 mg/dL).

Therefore, for children who have DM1 and for children who do not have DM, the diagnosis of hypoglycemia based only on a standardized specific BG value or the presence of known hypoglycemic symptoms and signs may not be ideal or logical.

Regular and periodic glycemic monitoring of the child who has DM1 is necessary and prudent, in order to discover in a timely fashion the arrival or presence of infantile hypoglycemia.

Other researchers ^{10 11} report that among young healthy men aged 26 – 45 years, elevated fasting glycemic levels (85 – 99 mg/dL), even when these are within the theoretical "normal" range (< 100 mg/dL),^{3 12} are strongly assocated with the development of DM2 in the medium and long term.

While fasting, each mg/dL of blood glucose above 80 mg/dL¹⁰ increases the risk of DM2 by 6%, regardless of other risk factors (e.g., BMI, dyslipidemia, hypertension, cardiovascular disease, smoking).

Smoking tobacco alone increases the risk of T2DM by 36%, according to a study of 46,578 participants who had fasting BG of < 100 mg/dL.¹¹   Because of their age, children generally have fewer possible risk factors (age, obesity, smoking, pregnancy) for predictive or indicative diabetic hyperglycemia than adults.

Like children, neonates typically have lower BG levels than adults.  After birth, the infant's BG tends to rise at a rate not yet clearly defined.¹³

The present study suggests that at least in the first 5 years of life of Mexican children who do not have DM, this supposed glycemic elevation is practically zero, especially among girls.

The American Diabetes Association, in their blood glucose recommendations for persons who have DM,³ recognizes without comment that adults and children who do not have DM will naturally have BG levels markedly different from and lower than those of individuals affected by DM.

In spite of the fact that several normative studies, including the present one, confirm lower glycemic levels in "normal" children than in adults without DM, official recommendations advocate illogically higher levels for children who have DM than for children and adults who have DM.

The differences between children and adults highlight the large discrepancy between the glycemic values of these children who do not have DM1 and those recommended (200 mg/dL) ³ even for children of the same age who do indeed have DM1.

The difference between the glycemic levels found in the present study of fasting children without DM of any type and the traditional and current officially recommended glycemic goals for children who have DM1 is enormous.

The appearance of diabetic complications in the adolescence and youth of individuals who have had DM1 from an early age is related to the high levels of BG recommended and effortlessly reached or exceeded.¹

As this study showed that Mexican girls tend to have lower BG levels than Mexican boys, the inescapable question is whether the glycemic values officially recommended as optimal for all children who have DM1 should be identical for boys and girls of an early age, as has always been the case.

From the results presented here, complementary questions arise, not yet answered by the data.

Are there any positive or negative effects of blood glucose levels of < 80 mg/dL on the learning capacity of children who have some level of hypoglycemia but lack the diagnosis of DM1?

Assuming that fasting BG represents the lowest glycemic level of the day, what is the highest level, as glycemia rises in the absorptive or postprandial state?  The answer to this question may inform the official determination of the "normal" postprandial glycemic excursion and average and, together with the data from the present study, define the upper and lower thresholds of the typical normoglycemia of Mexican children aged 1 - 5 years.

Acknowledgements

The author sincerely thanks Mr. Julio López of the Foundation for Family Educational Assistance for coordinating and facilitating the realization of the glycemic monitoring of the students and staff of the two institutions in his charge.

He also thanks the children and staff of these institutions who courageously and humorously participated in the study.  I thank Mr. Sergio Martínez of Abbott Laboratories in México for the timely provision of the Optium XCEED glucose meter and the large number of test strips required for this research.

The author thanks his colleague Lic. en Nutr. María Elena Morales, Certified Diabetes Educator, who donated her time and professional wisdom both during the planning of the study and during the morning collection of the data.

And, finally, I thank Lic. in Psic. Abimael Aguilar, Berlin, Germany, for his advice and guidance in advancing the completion of this article.

Bibliographic references

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