By: Stan De Loach
The need to investigate and determine normoglycemia in Mexican children under the age of six begins with a lack of relevant published data. Another motive for reviewing the currently recommended glycemic goals for children and adolescents with type 1 stems from the well-known observation that children and adolescents who do not have type 1 do not develop microvascular diabetic complications. Today, thanks to insulin analogs and basal/bolus therapy regimens, children with type 1 have the option of achieving true euglycemia and of potentially benefiting from its advantages.
Clearly, diabetic complications are related to the principal marker of all diabetes: hyperglycemia, specifically, chronic hyperglycemia(1)(2). In order to recommend or suggest safe glycemic levels for children with type 1, it is important to know what constitutes a true “normal” glycemic range among similarly aged children who do not have diabetes. Any reasonable clinical plan for the glycemic management and self-management of children and adolescents with type 1 depends on knowledge of the typical or “normal” nondiabetic values for the general infantile population of the same body weight. These “normal” glycemic levels are not well defined or widely known.
The information gained from the present study may help define a clinical goal of glycemic values equivalent to, or at least similar to, “normal” childhood values. It may also permit a comparison between the glycemic ranges currently recommended by the American Diabetes Association (ADA) and a pattern of hyperglycemic control that may be even more favorable and preventive than the liberal therapeutic recommendations currently in international use(1)(2).
It is not known to what degree the current glycemic goals for Mexican children who have type 1, which are basically identical to those defined by the ADA, reflect the true glycemic values of Mexican children without type 1 and with appropriate body weight. Precisely because the latter do not exhibit chronic or near chronic hyperglycemia, they will not suffer microvascular diabetic complications unless at some point they should develop type 1 or type 2, followed by similar chronic or near chronic diabetic hyperglycemia.
The results of the study indicate that for Mexican children from one to six years of age who have normal body weight and do not have type 1, the mean level of fasting BG is around 74.1 mg/dL. This glycemic value is assumed to represent an approximate normal fasting BG for the children studied. According to the official recommendations for children of the same age who have type 1, this “normal” level of BG is considered practically equivalent to therapeutic hypoglycemia (70 mg/dL or less). Yet, at this level and at even lower levels, the children studied had no evident, self-reported, or other-reported hypoglycemic signs or symptoms. Thus, it is probable that the low glycemic values seen in these children, although generally considered hypoglycemic, are asymptomatic and “normal” and do not indicate disease or malnutrition.
The children’s global mean BG in this study is almost exactly the glycemic mean (74.7 mg/dL) naturally maintained among pregnant women during the third trimester of pregnancy who do not have diabetes and are not obese(7). It appears that after birth and for at least the first five years of extrauterine life, healthy Mexican children tend to maintain a glycemic state equivalent to that of their last three months of intrauterine life.
Of the 303 children included in this study, 67.3% had BG levels of 79 mg/dL or lower. The accepted definition of therapeutic hypoglycemia is any glycemic value less than 70 mg/dL(8). In this sample, 35.6% of the children presented at least this degree of therapeutic hypoglycemia; 9% had hypoglycemia of 60 mg/dL or less, and 5% had biochemical hypoglycemia (less than 50 mg/dL)(8)(9).
Therapeutic or biochemical hypoglycemia caused by excess or inexpert use of exogenous insulin routinely provokes terror and panic among parents of children whose diabetes is treated with insulin, and often among the children themselves. In this study, however, almost 70% of the children had BG levels of less than 80 mg/dL, and they were fasting and were not allowed to eat breakfast until after the BG monitoring of all the children in their kindergarten (89 and 214, respectively) had been completed. Nevertheless, in this lengthy interval, no hint of the anxiety or urgency that often characterizes children who have type 1 and their parents when confronted with a hypoglycemic threat or episode was seen among these “normal” children or among their teachers.
Young people with type 1 who employ daily insulin therapy may be conditioned by the unpredictability and risk of further or rapid reduction in BG to levels below 71 mg/dL, which may be dangerous. These “normal” children’s response to real but asymptomatic hypoglycemia was not so conditioned.
As the study’s results show, the symptoms of hypoglycemia and the physical and mental uneasiness that ordinarily accompany abnormally low BG levels can be absent in the child who does not have diabetes, even when the glycemic concentrations are in fact abnormally low (46 to 60 mg/dL). For this reason, in children with or without type 1, the diagnosis of hypoglycemia solely by either a specific glycemic value or the presence of known symptoms is not tenable, although habitual BG monitoring of children with diabetes is necessary and prudent in order to assure timely discovery of the presence of infantile hypoglycemia.
Illogically higher recommended levels
The ADA, in its glycemic recommendations for persons who have diabetes(3), recognizes that adults and children who do not have diabetes tend to differ in their fasting glycemic values. In spite of the fact that various normative studies, including the present one, confirm lower glycemic levels in “normal” children than in adults without diabetes, the official recommendations champion glycemic levels illogically higher for children who have diabetes than for adults who have diabetes.
The significant glycemic differences between children and adults found in this study highlight the large discrepancy between the glycemic values of these children who do not have type 1 and those recommended (110 to 200 mg/dL)(3) as optimal during the night, when fasting, for children of the same age who have type 1. These findings further suggest that “normal” Mexican children’s fasting BG levels are far from the fasting values of 100 to 180 mg/dL currently recommended by the ADA for children from zero to 12 years of age who have type 1.
The appearance of diabetic complications in the childhood, adolescence, and young adulthood of those who have had type 1 from an early age are related to high levels of BG, including levels within the officially recommended ranges, which, in spite of being elevated above the normal ranges found in the current study, are frequently surpassed in everyday practice(1).
Because young Mexican girls tended to have BG levels consistently lower than those of their male counterparts, the inevitable question is whether the glycemic levels officially recommended as optimal for children with type 1 should be identical for young boys and girls, as has long been the case.
From the results reported here, complementary questions arise, still unanswered by the data: Is there a positive or negative effect of BG levels below 80 mg/dL on the ability to learn in children who do not have diabetes? Supposing that the fasting BG level represents the lowest daily BG level achieved: what is the highest typical or “normal” glycemic level reached after eating? The response to these questions should inform the definition of the “normal” postprandial glycemic mean to be recommended. Together with the data from the present study, the answers may help define the upper and lower limits of the normoglycemia typical of Mexican children without diabetes from one to five years of age.
- DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New England Journal of Medicine, 1993, 329(14):977-986.
- Khan F, Green FC, Forsyth JS, Greene SA, Morris AD, Belch JF. Impaired microvascular function in normal children: Effects of adiposity and poor glucose handling. Journal of Physiology, 2003, 551(2):705-711. http://jp.physoc.org/cgi/content/full/551/2/705. Accessed 8 April 2009.
- American Diabetes Association. Standards of Medical Care in Diabetes-2009. Diabetes Care, 2009, 32:S17-S25.
- American Diabetes Association. Standards of medical care in diabetes: Clinical Practice Recommendations 2007. Diabetes Care, 2007, 30:S4-S41.
- Silverstein J, Klingensmith G, Copeland K, Plotnick L, Kaufman F, Laffel L, Deeb L, Grey M, Anderson B, Holzmeister LA, Clark N. Care of children and adolescents with type 1 diabetes. Diabetes Care, 2005, 28(1):186-212.
- http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=6826&nbr=4193. Accessed 8 April 2009.
- Parretti E, Mecacci F, Papini M, Cioni R, Carignani L, Mignosa M, La Torre P, Mello G. Third-trimester maternal glucose levels from diurnal profiles in nondiabetic pregnancies: Correlation with sonographic parameters of fetal growth. Diabetes Care, 2001, 24(8):1319-1323.
- Pérez Pastén E. Guía para el educador en diabetes. Soluciones Gráficas, México, DF, 1997, p. 137.
- Stobo JD, Traill TA, Hellmann DB, Ladenson PW, Petty BG. Principles and practice of medicine. McGraw-Hill Professional, New York , 1996, p. 332.
- Tirosh A, Shai I, Tekes-Manova D, Israeli E, Pereg D, Shochat T, Kochba I, Rudich A. Normal fasting plasma glucose levels and type 2 diabetes in young men. New England Journal of Medicine, 2005, 353:1454-1462.
- Nichols GA, Hillier TA, Brown JB. Normal fasting plasma glucose and risk of type 2 diabetes diagnosis. American Journal of Medicine, 2008, 121(6):519-524. http://www.amjmed.com/article/S0002-9343(08)00231-3/fulltext. Accessed 8 April 2009.
- Bernstein RK. Diabetes solution: The complete guide to achieving normal blood sugars. Little, Brown, Boston, 2003.
- LeRoith D, Taylor SI, Olefsky JM. Diabetes mellitus: A fundamental and clinical text. 3ra edición. Lippincott Williams & Wilkins, Philadelphia, 2004, p. 1258.
A Spanish version of this article was published in México, in Diabetes Hoy para el Médico y el Profesional de la Salud, 10(1), pp. 2179 – 2184, January 2009.