Repetitiveness of the oral glucose tolerance test in children and adolescents

BACKGROUNDData regarding the most suitable diagnostic method for the diagnosis of glucose impairment in asymptomatic children and adolescents are inconclusive. Furthermore, limited data are available on the reproducibility of the oral glucose tolerance test (OGTT) in children and adolescents who are obese (OB).AIMTo investigate the usefulness of the OGTT as a screening method for glucose dysregulation in children and adolescents.METHODSEighty-one children and adolescents, 41 females, either overweight (OW), OB or normal weight (NW) but with a strong positive family history of type 2 diabetes mellitus (T2DM), were enrolled in the present observational study from the Outpatient Clinic of Paediatric Endocrinology of the University Hospital of Patras in Greece. One or two 3-h OGTTs were performed and glucose, insulin and C-peptide concentrations were measured at several time points (t = 0 min, t = 15 min, t = 30 min, t = 60 min, t = 90 min, t = 120 min, t = 180 min).RESULTSGood repetitiveness was observed in the OGTT response with regard to T2DM, while low repetitiveness was noted in the OGTT response with regard to impaired glucose tolerance (IGT) and no repetitiveness with regard to impaired fasting glucose (IFG). In addition, no concordance was observed between IFG and IGT. During the 1^st and 2^nd OGTTs, no significant difference was found in the glucose concentrations between NW, OW and OB patients, whereas insulin and C-peptide concentrations were higher in OW and OB compared to NW patients at several time points during the OGTTs. Also, OW and OB patients showed a worsening insulin and C-peptide response during the 2^nd OGTT as compared to the 1^st OGTT.CONCLUSIONIn mild or moderate disorders of glucose metabolism, such as IFG and IGT, a diagnosis may not be reached using only one OGTT, and a second test or additional investigations may be needed. When glucose metabolism is profoundly impaired, as in T2DM, one OGTT is probably more reliable and adequate for establishing the diagnosis. Excessive weight and/or a positive family history of T2DM possibly affect the insulin and C-peptide response in the OGTT from a young age.     

Prevalence of impaired glucose metabolism in β-thalassemic children receiving hypertransfusions with a suboptimal dosage of iron-chelating therapy

A cross-sectional study of impaired glucose metabolism was carried out in 48 beta-thalassemic patients receiving hypertransfusions. An oral glucose tolerance test (OGTT) was performed using the method and criteria of the American Diabetes Association (ADA). Diabetes mellitus was diagnosed in two patients, and impaired glucose tolerance was found in four patients, giving a prevalence of impaired glucose metabolism of 12.5% in our patient population. The significant clinical characteristics associated with the diagnosis of impaired glucose metabolism were wasting (-2.15/-0.86 SDS, p = 0.025), stunting (-2.69/-1.22 SDS, p = 0.03), higher ferritin levels (8679/4710 mug/L, p = 0.005), splenectomy (50/9.5%, p = 0.012), and lower area under curve (AUC) of insulin secretion after OGTT (40.0/77.7, p = 0.002). The significant decrease of AUC insulin in thalassemic patients with an impaired glucose tolerance test suggests that the pathogenesis may originate from pancreatic beta-cell damage rather than from insulin resistance. In conclusion, the prevalence of impaired glucose tolerance in our population of thalassemic patients receiving hypertransfusions with suboptimal iron chelating therapy was 12.5%. The clinical characteristics of thalassemic patients who developed impaired glucose tolerance were wasting, stunting, higher ferritin levels, splenectomy, and lower AUC insulin.     

Efficacy and safety of acarbose in patients with cystic fibrosis and impaired glucose tolerance

Impaired glucose tolerance (IGT) is an increasingly frequent complication of cystic fibrosis (CF). In CF patients, a fast postprandial rise in plasma glucose is typically followed by a delayed but prolonged insulin response. Patients may develop symptoms of both hyper- and hypoglycaemia. The α-glucosidase inhibitor, acarbose, delays the hydrolysis and subsequent absorption of ingested carbohydrates. The aim of this study was to investigate the efficacy of acarbose in CF patients with IGT. During a 2-week inpatient period for treatment of Pseudomonas infection, 12 CF patients with IGT were studied in a double-blinded, randomized crossover trial. Each patient received acarbose (50 mg t.i.d.) for 5 days and placebo for 5 days (days 3–8 and days 10–14, respectively). Glucose, insulin and C-peptide responses to a standardized nutritional load were measured at baseline and at the end of each study period (Days 2, 8 and 14). Treatment with acarbose was associated with significant reductions in the mean value, mean peak values and the area under the curve of plasma glucose, insulin and C-peptide, compared to respective baseline values and placebo. Gastro-intestinal disturbances were recorded in 67% of patients during therapy with acarbose. Conclusion Acarbose has a positive therapeutic effect on glucose tolerance in cystic fibrosis patients, as shown by attenuation of postprandial plasma glucose increase and a significant decrease in insulin secretion response. However, acarbose treatment was associated with adverse gastro-intestinal effects that may prevent patients from accepting long-term therapy. Received: 1 December 1997 / Accepted in revised form: 15 September 1998     

The abnormalities of carbohydrate metabolism in Turner syndrome: analysis of risk factors associated with impaired glucose tolerance

An oral glucose tolerance test (OGTT) was performed in 103 patients with Turner syndrome (TS) who had normal fasting and postprandial glucose levels. The plasma glucose, insulin, C-peptide and proinsulin levels were measured every 30 min during the test. Using a homeostatic model assessment (HOMA) and a quantitative insulin sensitivity check index (QUICKI), the insulin resistance in TS patients was investigated. Diabetes mellitus and impaired glucose tolerance (IGT) were newly diagnosed in two and 18 patients respectively. There was a significant increase in mean plasma glucose, insulin, C-peptide and proinsulin reponse during an OGTT in the IGT group in contrast to the normal glucose tolerance (NGT) group ( P <0.05). There was a significant decrease in the quantitative insulin sensitivity check index (QUICKI) in the IGT group in contrast to the NGT group ( P <0.05). The fasting insulin and triglyceride levels strongly predicted the 2 h glucose level during the OGTT ( P <0.05). Conclusion:The oral glucose tolerance test is superior to the fasting and postprandial plasma glucose test for the early detection of abnormalities of carbohydrate metabolism in patients with Turner syndrome.     

儿童2型糖尿病和糖调节异常筛查方案的研究

目的评价及比较在不同特征人群中进行2型糖尿病（T2DM）和糖调节异常（IGR）筛查的效果及成本，优化和推荐儿童青少年T2DM筛查方案。方法采用分层整群随机抽样方法获取19 593例北京市中小学生，用空腹指末梢血糖（FCBG）对其进行T2DM和IGR筛查，FCBG异常者（≥5.6 mmol·L-1）采用1999年WHO口服葡萄糖耐量试验标准进行诊断。并参照美国糖尿病协会建议儿童青少年T2DM筛查的高危对象标准和Dean提出的诊断标准进行T2DM的分型诊断。将研究人群分为一般人群、超重/肥胖和肥胖组，分别计算回访率、血糖异常阳性率、直接医疗成本和确诊每例成本，根据成本 效果推荐儿童青少年T2DM筛查方案。结果一般人群组，FCBG异常者回访率为47.97%(225/469)，超重/肥胖和肥胖组FCBG异常者回访率分别为59.29%（83/140）和68.00%（51/75），差异有统计学意义。一般人群组T2DM/IGR确诊率最低，为1.67/1 000例；总花费11.21万元和确诊每例T2DM/IGR的花费0.35万元，最高。肥胖组T2DM/IGR确诊率最高，为8.09/1 000例；总花费1.62万元和确诊每例T2DM/IGR的花费0.11万元，最低，较一般人群组分别下降85.55%和68.57%。超重/肥胖组介于两者之间。肥胖、超重/肥胖与一般人群组相比，肥胖组有2例T2DM（33.33%，2/6）漏诊，超重/肥胖组没有T2DM 漏诊。建议在超重/肥胖组中进行T2DM和IGR筛查。进一步选择除超重/肥胖外，与T2DM相关的危险因素（黑棘皮病、T2DM家族史和青春期），随调查对象具有危险因素数量的增加，患病危险性增加，筛查依从性增高，T2DM/IGR确诊率升高，筛查总成本和每例成本降低，但是从调查对象具有3个或以上危险因素开始，对T2DM/IGR筛查敏感度下降，与在一般人群组筛查相比，在4个危险因素人群中进行筛查，将有83.33%的T2DM得不到确诊。结论 本大样本研究以成本 效果分析说明：在儿童中符合健康经济学的T2DM筛查方案是在达到超重标准，同时具有1个以上危险因素（黑棘皮病、T2DM家族史和青春期）儿童青少年中进行目的性筛查。     

Insulin resistance is associated with decreased clinical status in cystic fibrosis

Patients with cystic fibrosis (CF) frequently have impaired glucose tolerance and progression to diabetes (DM) with clinical features of both insulin-dependent and non-insulin-dependent diabetes. One feature of non-insulin-dependent DM is decreased insulin sensitivity, also known as insulin resistance. The goal of this study was to determine whether patients with CF exhibit insulin resistance and to determine the potential effect of insulin resistance on clinical status. We also sought to determine whether insulin resistance is associated with a specific CF genotype. We studied 18 patients with CF (8 with normal glucose tolerance, 5 with impaired glucose tolerance, 5 with DM), and 20 lean control subjects matched for age, weight, and sex. All control subjects had normal glucose tolerance. The clinical status for each CF patient was determined according to a modified National Institutes of Health scoring system. Each subject underwent a three-step hyperinsulinemic euglycemic clamp (insulin doses of 10, 40, 120 mU/m ² per minute). Results from the 120 mU/m ² per minute infusion defined maximal glucose disposal rate (defined in milligrams per kilogram body weight per minute) at steady state with peripheral insulin levels 195 ± 20 mU/ml. Subjects with CF demonstrated insulin resistance (control subjects = 13.6 ± 1.1, patients with CF = 10.2 ± 1.6 mg/kg per minute; p = 0.003). When each subgroup was compared separately with control subjects, all subgroups were statistically insulin resistant (glucose disposal rate, patients with CF and normal glucose tolerance = 10.8; those with impaired glucose tolerance = 8.4; those with DM = 10.1 mg/kg per minute), and the patients with CF with impaired glucose tolerance were the most insulin resistant. When plotted versus glucose disposal rate, a striking positive correlation between worsened clinical status and insulin resistance ( r = 0.85) is demonstrated. Furthermore, there is no correlation between insulin resistance and fasting blood glucose, subject age, or percent ideal body weight (all r values not significant). In conclusion, patients with CF exhibit insulin resistance that is associated with worsened clinical status. We believe it is the combination of insulin resistance and decreased insulin secretion that is responsible for the high incidence of CF-related diabetes. (J Pediatr 1997;130:948-56)     

Oral glucose tolerance test in children and adolescents: positives and pitfalls

Objectives:   To describe the glycaemic status (assessed by an oral glucose tolerance test (OGTT)) and associated comorbidities in a cohort of Australian children and adolescents at risk of insulin resistance and impaired glucose homeostasis (IGH).
Methods:   Twenty-one children and adolescents (three male, 18 female) (18 Caucasian, one Indigenous, two Asian) (20 obese, one lipodystrophy) referred to the Paediatric Endocrinology and Diabetes Clinic underwent a 2-h OGTT with plasma glucose and insulin measured at baseline, + 60 and + 120 min. If abnormal, the OGTT was repeated.
Results:   The mean (SD) age was 14.2 (1.6) years, BMI 38.8 (7.0) kg/m² and BMI-SDS 3.6 (0.6). Fourteen patients had fasting insulin levels >21 mU/L. Type 2 diabetes mellitus was diagnosed in one patient, impaired glucose tolerance (IGT) in four patients and impaired fasting glycaemia (IFG) in one patient. Despite no weight loss, only one patient had a persistently abnormal OGTT on repeat testing. Three patients with IGH were medicated with risperidone at the time of the initial OGTT. One patient who had persistent IGT had continued risperidone. The other two patients had initial OGTT results of IGT and diabetes mellitus type 2. They both ceased risperidone between tests and repeat OGTT showed normal glycaemic status.
Conclusions:   Use of fasting glucose alone may miss cases of IGH. Diagnosis of IGT should not be made on one test alone. Interpretation of glucose and insulin responses in young people is limited by lack of normative data. Larger studies are needed to generate Australian screening recommendations. Further assessment of the potential adverse effects of atypical antipsychotic medication on glucose homeostasis in this at-risk group is important.     

Acanthosis nigricans is a reliable cutaneous marker of insulin resistance in obese Japanese children

BACKGROUND: Acanthosis nigricans (AN) is a skin condition characterized by darkening and thickening of skin with formation of irregular folds, usually limited to a few specific areas of the body. Recently, AN has been reported to be linked to hyperinsulinemia and obesity. The aim of the present study was to determine whether or not the presence of AN in obese Japanese children is a reliable cutaneous marker. METHODS: The authors analyzed the clinical characteristics of 439 obese Japanese children (260 boys, 179 girls; mean age 10.1 years; mean percentage overweight 51.9%), who had visited Tsuruoka City Shonai Hospital in 1990-2000. Eighty-two of the 439 children were examined using an oral glucose tolerance test (OGTT). Of these children, the authors retrospectively studied 16 subjects: eight with AN and eight without AN (age range: 10.8-13.9 years; percentage overweight range: 54.3-97.0%). They were age and percentage obesity-matched males with normal glucose tolerance during OGTT. Females with normal glucose tolerance during OGTT were excluded from the 16 subjects because the number was too small and children with impaired glucose tolerance or type 2 diabetes during OGTT were also excluded because of glucose toxicity. Eighty-two children including the 16 subjects were analyzed at their first visit for the presence or absence of AN on the posterior of the neck, and for characteristics including age, birthweight, body height, bodyweight, percentage overweight, blood pressure, liver function markers serum lipid concentrations, fasting plasma glucose concentrations and insulin concentrations shown by the results of OGTT. RESULTS: (1) Children with AN showed significantly more glucose intolerance including impaired glucose tolerance and type 2 diabetes compared with those children without AN, and fasting plasma insulin concentrations were most significantly correlated with the presence of AN. (2) Insulin resistance based on fasting plasma insulin concentrations was seen in significantly more children with AN than in children without AN, even in age and percentage obesity-matched subjects with normal glucose tolerance during OGTT. CONCLUSIONS: Acanthosis nigricans could be a reliable cutaneous marker of insulin resistance in obese Japanese children.     

Frequency of abnormal carbohydrate metabolism and diabetes in a population-based screening of adolescents

OBJECTIVE: To 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. STUDY DESIGN: Measurement of fasting and 2-hour post-glucose load plasma glucose concentrations. RESULTS: Carbohydrate intolerance (either impaired fasting glucose, impaired glucose tolerance, or both) was identified in 8.0%, near-diabetes (1 fasting glucose > or = 126 mg/dL [7.0 mmol/L] and/or 2-hour glucose > or = 200 mg/dL [11.1 mmol/L]) in 0.3%, and diabetes in 0.36% (type 1A = 0.24%; type 2 = 0.08%; undiagnosed type 2 = 0.04%). A model for abnormal carbohydrate metabolism was constructed with regression analysis in the Carbohydrate Intolerance (CI)/near-diabetes group and with logistic regression in the entire study population. Risk factors for the development of CI/near-diabetes included having a 1 unit increase in body mass index (BMI) z-score and either being non-Hispanic white or in the pubertal group. Increased fasting glucose correlated with having puberty and decreased BMI z-score, whereas 2-hour glucose correlated with increased BMI z-score. By using National Health and Nutrition Survey (NHANES) III (1988-1994) definitions, impaired fasting glucose was present in 2.0% in this study versus 1.7% (NHANES III). CONCLUSION: The prevalence of CI/near-diabetes was 8.3%. Undiagnosed diabetes mellitus was rare. One third of adolescents with diabetes mellitus could be classified as having type 2 diabetes mellitus. The adult model of the progression of insulin resistance to type 2 diabetes mellitus in adolescents may be valid. Despite the increase in the overweight population since NHANES III, abnormalities in glucose metabolism have not changed significantly.     

Screening for gestational diabetes mellitus

The term 'gestational diabetes mellitus' is unsatisfactory as it refers to a heterogeneous group of women, including those with minimal abnormality of carbohydrate metabolism and those with undiagnosed type II diabetes. However, perinatal morbidity is increased even in the group of women who have only impaired glucose tolerance; the mothers are at increased risk of subsequent development of diabetes, and there may also be long-term implications for the offspring. Current research is aiming to define the blood glucose levels at which risks increase so that clinical management can be appropriately directed. When available, the criteria required to justify population screening in pregnancy should be satisfied. The glucose challenge and fasting glucose tests are the leading contenders as appropriate screening tests to determine who should have the diagnostic glucose tolerance test. However, until this is reviewed, the widely used scheme of risk factors as a screening method should continue, as it detects at least 50% of women with gestational diabetes.