Screening for Abnormalities of Carbohydrate Metabolism in Teens

Abstract

The epidemic of childhood overweight has led to what is believed to be an explosion of abnormalities of glucose regulation in children and youth. These abnormalities progress in those with genetic susceptibility from overweight to insulin resistance to pre-diabetes and culminate with the diagnosis of type 2 diabetes.1Kaufman F.R. Type 2 diabetes in children and youth: a new epidemic.J Pediatr Endocrinol Metab. 2002; 15: 737-744Crossref PubMed Google Scholar Presently, the numbers of children affected with abnormalities of glucose metabolism and the interplay of puberty, ethnicity/race, adiposity, fitness and socioeconomic status are not known because sufficient population-based studies have not been performed.Addressing the need to perform population based assessments of glucose abnormalities, Dolan et al2Dolan L.M. Bean J. D'Alessio D. Cohen R.M. Morrison J.A. Goodman E. et al.The frequency of abnormal carbohydrate metabolism and diabetes in a population based screening of adolescents.J Pediatr. 2005; 146: 751-758Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar studied a large cohort (n = 2501) of non-Hispanic white and black students in grades 5-12 in the Princeton School District in Cincinnati, Ohio. Students were screened with weight and fasting plasma glucose and insulin. An oral glucose tolerance test (OGTT) was performed for those with (1) body mass index (BMI) > 85th percentile for age and sex, (2) fasting plasma insulin > 2 SD above the mean of the participants of the same race, sex, and stage of sexual development, or (3) fasting plasma glucose ≥110 mg/dL. More than one third, 39.66% (992/2501), of the students met criteria to be evaluated with an OGTT, and 887 actually had an OGTT performed. The results of the OGTT were used to place the students in one of 4 categories: (1) normoglycemic (fasting glucose < 110 mg/dL and 2-hour glucose < 140 mg/dL), (2) carbohydrate intolerant (either a fasting glucose ≥110 mg/dL and < 126 mg/dL and 2-hour glucose ≤140 mg/dL or fasting glucose < 110 mg/dL and 2-hour ≥140 but < 200 mg/dL), (3) pre-diabetic (one fasting glucose ≥126 mg/dL and/or 2-hour glucose ≥200 mg/dL), or (4) diabetic (both fasting glucose values >126 mg/dL). Those students found to have diabetes were assessed with regard to whether they had type 1 or type 2 diabetes.Dolan et al found a surprisingly low rate of abnormalities of glucose metabolism for the entire student group. Carbohydrate intolerance was found in only 2.48% (2.0% with impaired fasting glucose only, 0.4% with impaired glucose tolerance only, and 0.1% with both), pre-diabetes in 0.28% and diabetes in 0.36%, with only one third of the subjects with diabetes appearing to have type 2 disease. Even in the high-risk group of 887 subjects, 9 had impaired glucose tolerance, 3 had both impaired glucose tolerance and impaired fasting glucose, and 7 had pre-diabetes. The percentage of high-risk students with carbohydrate intolerance in Dolan et al's large population-based study was dramatically lower than what has been found in studies in high-risk populations in the clinical setting. In the context of clinical studies in high-risk subjects, reports of impaired glucose tolerance have been at least 10-fold higher. For example, Sinha et al3Sinha R. Fisch G. Teague B. Tamborlane W.V. Banyas B. Allen K. et al.Prevalence of impaired glucose tolerance among children and adolescents with marked obesity.N Engl J Med. 2002; 346: 802-810Crossref PubMed Scopus (1393) Google Scholar found impaired glucose tolerance (defined only a 2-hour glucose value ≥140 mg/dL and < 200 mg/dL) in 25% of overweight children 4-10 years of age and in 21% of overweight adolescents 11-18 years of age referred to their center for evaluation of obesity. Similarly, Goran et al4Goran M.I. Bergman R.N. Avilla Q. Watkins M. Ball G.D.C. Shaibi G.Q. et al.Impaired glucose tolerance and reduced B-cell function in overweight Latino children with a positive family history for type 2 diabetes.J Clin Endocrinolo Metab. 2004; 89: 207-212Crossref PubMed Scopus (197) Google Scholar reported that impaired glucose tolerance was found in 28% of a select group of overweight Hispanic youth with a positive family history of type 2 diabetes. Gomez-Diaz et al5Gomez-Diaz R. Aguilar-Salinas C.A. Moran-Villota S. Barradas-Gonzalez R. Herrera-Marquez R. Lopez M.C. et al.Lack of agreement between the revised criteria of impaired fasting glucose and impaired glucose tolerance in children with excess body weight.Diabetes Care. 2004; 27: 2229-2233Crossref PubMed Scopus (25) Google Scholar reported fasting plasma glucose levels > 110 mg/dL in 6.2% of 4-17 year old overweight children; 13.3% had fasting plasma glucose values > 100 mg/dL cutoff, and 14.8% had impaired glucose tolerance. This would suggest that even with almost 50% ethnic/racial minority students, a high percentage with a BMI > 85th percentile (34.99%) and the majority of subjects in or completing puberty (88%), screening a population of “normal” children, and then further evaluating a group believed to be at high risk, does not yield a cohort of subjects with glucoregulatory abnormalities comparable to what is found in clinic-based studies.The fact that the authors altered established definitions of carbohydrate intolerance and pre-diabetes may lead to difficulties in interpreting this study. The authors lumped impaired fasting glucose and impaired glucose tolerance into their definition of carbohydrate intolerant. Both have been previously defined as pre-diabetes by the American Diabetes Association.6Expert Committee on the Diagnosis and Classification of Diabetes Mellitus Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.Diabetes Care. 2003; 26: S5-S20PubMed Google Scholar In addition, the authors used pre-diabetic to refer to glucose values, either fasting or during the oral glucose tolerance test that were in the diabetic range. By altering definitions, the authors have added to potential confusion with regard to how their results will be compared to past and future studies.A Consensus Panel convened by the American Diabetes Association in 20007American Diabetes Association Type 2 Diabetes in children and adolescents. Consensus Statement.Diabetes Care. 2000; 23: 381-389Crossref PubMed Scopus (997) Google Scholar recommended that testing for type 2 diabetes be performed in “at-risk youth.” Diabetes screening was recommended for children and youth with obesity and a positive family history of type 2 diabetes, those belonging to certain race/ethnic groups such as American Indian/Native American, black, Hispanic, Asian/Pacific Islander, and those having evidence of insulin resistance with hypertension, acanthosis nigricans, dyslipidemia, or polycystic ovarian disease. This recommendation to screen for type 2 diabetes was made, in the absence of sufficient data concerning the natural history of type 2 diabetes in pediatric subjects, because of the following: 1. It was presumed the disease was common among the general population, as well as among easily identifiable high-risk groups; 2. The disease was serious in terms of morbidity and mortality; 3. The disease had a prolonged latency period during which time there were no symptoms; 4. The screening test was adequately sensitive and specific; and 5. Intervention was available to prevent or delay disease onset or treat at an early stage. Screening was recommended in pediatric subjects because of a concern that the longer duration of diabetes would lead to an excess of both microvascular and macrovascular complications and to increased medical costs.The results of the very low rate of undiagnosed diabetes in students in the Princeton School District, coupled with prior Third National Health and Nutrition Examination Survey8Fagot-Campagna A. Saaddiine J.B. Flegal K.M. Beckles G.L. Diabetes, impaired fasting glucose and elevated HbA1c in U.S. adolescents: the Third National Health and Nutrition Examination Survey.Diabetes Care. 2001; 24: 834-837Crossref PubMed Scopus (140) Google Scholar findings of a very low rate of undiagnosed diabetes in children and youth, call into question when screening for type 2 diabetes in children should be done. This study suggests that screening all children for abnormalities of glucose metabolism is not indicated because of the very low yield. At this time, screening children and youth for diabetes should not be brought to community and school settings. Screening high-risk children might be indicated, but it appears that using BMI, fasting glucose and insulin levels does not identify a cohort of children with sufficient risk to justify screening. Further analysis and studies need to be done to better define high-risk children who would benefit from having an OGTT performed to diagnose where they fall on the spectrum of glucose abnormalities. The epidemic of childhood overweight has led to what is believed to be an explosion of abnormalities of glucose regulation in children and youth. These abnormalities progress in those with genetic susceptibility from overweight to insulin resistance to pre-diabetes and culminate with the diagnosis of type 2 diabetes.1Kaufman F.R. Type 2 diabetes in children and youth: a new epidemic.J Pediatr Endocrinol Metab. 2002; 15: 737-744Crossref PubMed Google Scholar Presently, the numbers of children affected with abnormalities of glucose metabolism and the interplay of puberty, ethnicity/race, adiposity, fitness and socioeconomic status are not known because sufficient population-based studies have not been performed. Addressing the need to perform population based assessments of glucose abnormalities, Dolan et al2Dolan L.M. Bean J. D'Alessio D. Cohen R.M. Morrison J.A. Goodman E. et al.The frequency of abnormal carbohydrate metabolism and diabetes in a population based screening of adolescents.J Pediatr. 2005; 146: 751-758Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar studied a large cohort (n = 2501) of non-Hispanic white and black students in grades 5-12 in the Princeton School District in Cincinnati, Ohio. Students were screened with weight and fasting plasma glucose and insulin. An oral glucose tolerance test (OGTT) was performed for those with (1) body mass index (BMI) > 85th percentile for age and sex, (2) fasting plasma insulin > 2 SD above the mean of the participants of the same race, sex, and stage of sexual development, or (3) fasting plasma glucose ≥110 mg/dL. More than one third, 39.66% (992/2501), of the students met criteria to be evaluated with an OGTT, and 887 actually had an OGTT performed. The results of the OGTT were used to place the students in one of 4 categories: (1) normoglycemic (fasting glucose < 110 mg/dL and 2-hour glucose < 140 mg/dL), (2) carbohydrate intolerant (either a fasting glucose ≥110 mg/dL and < 126 mg/dL and 2-hour glucose ≤140 mg/dL or fasting glucose < 110 mg/dL and 2-hour ≥140 but < 200 mg/dL), (3) pre-diabetic (one fasting glucose ≥126 mg/dL and/or 2-hour glucose ≥200 mg/dL), or (4) diabetic (both fasting glucose values >126 mg/dL). Those students found to have diabetes were assessed with regard to whether they had type 1 or type 2 diabetes. Dolan et al found a surprisingly low rate of abnormalities of glucose metabolism for the entire student group. Carbohydrate intolerance was found in only 2.48% (2.0% with impaired fasting glucose only, 0.4% with impaired glucose tolerance only, and 0.1% with both), pre-diabetes in 0.28% and diabetes in 0.36%, with only one third of the subjects with diabetes appearing to have type 2 disease. Even in the high-risk group of 887 subjects, 9 had impaired glucose tolerance, 3 had both impaired glucose tolerance and impaired fasting glucose, and 7 had pre-diabetes. The percentage of high-risk students with carbohydrate intolerance in Dolan et al's large population-based study was dramatically lower than what has been found in studies in high-risk populations in the clinical setting. In the context of clinical studies in high-risk subjects, reports of impaired glucose tolerance have been at least 10-fold higher. For example, Sinha et al3Sinha R. Fisch G. Teague B. Tamborlane W.V. Banyas B. Allen K. et al.Prevalence of impaired glucose tolerance among children and adolescents with marked obesity.N Engl J Med. 2002; 346: 802-810Crossref PubMed Scopus (1393) Google Scholar found impaired glucose tolerance (defined only a 2-hour glucose value ≥140 mg/dL and < 200 mg/dL) in 25% of overweight children 4-10 years of age and in 21% of overweight adolescents 11-18 years of age referred to their center for evaluation of obesity. Similarly, Goran et al4Goran M.I. Bergman R.N. Avilla Q. Watkins M. Ball G.D.C. Shaibi G.Q. et al.Impaired glucose tolerance and reduced B-cell function in overweight Latino children with a positive family history for type 2 diabetes.J Clin Endocrinolo Metab. 2004; 89: 207-212Crossref PubMed Scopus (197) Google Scholar reported that impaired glucose tolerance was found in 28% of a select group of overweight Hispanic youth with a positive family history of type 2 diabetes. Gomez-Diaz et al5Gomez-Diaz R. Aguilar-Salinas C.A. Moran-Villota S. Barradas-Gonzalez R. Herrera-Marquez R. Lopez M.C. et al.Lack of agreement between the revised criteria of impaired fasting glucose and impaired glucose tolerance in children with excess body weight.Diabetes Care. 2004; 27: 2229-2233Crossref PubMed Scopus (25) Google Scholar reported fasting plasma glucose levels > 110 mg/dL in 6.2% of 4-17 year old overweight children; 13.3% had fasting plasma glucose values > 100 mg/dL cutoff, and 14.8% had impaired glucose tolerance. This would suggest that even with almost 50% ethnic/racial minority students, a high percentage with a BMI > 85th percentile (34.99%) and the majority of subjects in or completing puberty (88%), screening a population of “normal” children, and then further evaluating a group believed to be at high risk, does not yield a cohort of subjects with glucoregulatory abnormalities comparable to what is found in clinic-based studies. The fact that the authors altered established definitions of carbohydrate intolerance and pre-diabetes may lead to difficulties in interpreting this study. The authors lumped impaired fasting glucose and impaired glucose tolerance into their definition of carbohydrate intolerant. Both have been previously defined as pre-diabetes by the American Diabetes Association.6Expert Committee on the Diagnosis and Classification of Diabetes Mellitus Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.Diabetes Care. 2003; 26: S5-S20PubMed Google Scholar In addition, the authors used pre-diabetic to refer to glucose values, either fasting or during the oral glucose tolerance test that were in the diabetic range. By altering definitions, the authors have added to potential confusion with regard to how their results will be compared to past and future studies. A Consensus Panel convened by the American Diabetes Association in 20007American Diabetes Association Type 2 Diabetes in children and adolescents. Consensus Statement.Diabetes Care. 2000; 23: 381-389Crossref PubMed Scopus (997) Google Scholar recommended that testing for type 2 diabetes be performed in “at-risk youth.” Diabetes screening was recommended for children and youth with obesity and a positive family history of type 2 diabetes, those belonging to certain race/ethnic groups such as American Indian/Native American, black, Hispanic, Asian/Pacific Islander, and those having evidence of insulin resistance with hypertension, acanthosis nigricans, dyslipidemia, or polycystic ovarian disease. This recommendation to screen for type 2 diabetes was made, in the absence of sufficient data concerning the natural history of type 2 diabetes in pediatric subjects, because of the following: 1. It was presumed the disease was common among the general population, as well as among easily identifiable high-risk groups; 2. The disease was serious in terms of morbidity and mortality; 3. The disease had a prolonged latency period during which time there were no symptoms; 4. The screening test was adequately sensitive and specific; and 5. Intervention was available to prevent or delay disease onset or treat at an early stage. Screening was recommended in pediatric subjects because of a concern that the longer duration of diabetes would lead to an excess of both microvascular and macrovascular complications and to increased medical costs. The results of the very low rate of undiagnosed diabetes in students in the Princeton School District, coupled with prior Third National Health and Nutrition Examination Survey8Fagot-Campagna A. Saaddiine J.B. Flegal K.M. Beckles G.L. Diabetes, impaired fasting glucose and elevated HbA1c in U.S. adolescents: the Third National Health and Nutrition Examination Survey.Diabetes Care. 2001; 24: 834-837Crossref PubMed Scopus (140) Google Scholar findings of a very low rate of undiagnosed diabetes in children and youth, call into question when screening for type 2 diabetes in children should be done. This study suggests that screening all children for abnormalities of glucose metabolism is not indicated because of the very low yield. At this time, screening children and youth for diabetes should not be brought to community and school settings. Screening high-risk children might be indicated, but it appears that using BMI, fasting glucose and insulin levels does not identify a cohort of children with sufficient risk to justify screening. Further analysis and studies need to be done to better define high-risk children who would benefit from having an OGTT performed to diagnose where they fall on the spectrum of glucose abnormalities. Frequency of Abnormal Carbohydrate Metabolism and Diabetes in a Population-based Screening of AdolescentsThe Journal of PediatricsVol. 146Issue 6PreviewTo document the frequency of glucose intolerance in adolescents in a population-based study of primarily African-American/Non-Hispanic whites in an urban-suburban school district. Full-Text PDF