RESUMO
OBJECTIVE: To investigate insulin sensitivity and secretion in young adolescent girls with childhood onset polycystic ovarian syndrome (PCOS) and to identify the early metabolic derangement(s). STUDY DESIGN: Twelve obese girls with PCOS (age 12.0+/-0.7 years) were compared with 10 obese nonhyperandrogenic girls (control group). The groups were matched for age, percent body fat, and abdominal fat. All subjects underwent a 3-hour hyperinsulinemic (80 mu/m(2)/min)-euglycemic clamp to determine in vivo insulin sensitivity and a 2-hour hyperglycemic clamp (225 mg/dL) to determine insulin secretion. Fasting hepatic glucose production was determined with the use of [6,6-(2)H(2)]glucose. RESULTS: Fasting glucose and hepatic glucose production were comparable between the 2 groups, but fasting insulin was 2-fold higher in the PCOS group. The fasting glucose to insulin ratio was lower in the PCOS group versus the control group (1.9+/- 0.3 vs 3.1+/-0.3, P =.02). During the hyperinsulinemic-euglycemic clamp, insulin sensitivity was lower in the PCOS group (1.4+/-0.2 vs 2.7+/-0.3 mg/kg/min per microu/mL, P =.002). During the hyperglycemic clamp, insulin secretion was significantly higher in the PCOS group. Insulin sensitivity correlated negatively with fasting insulin (r = -0.71, P =.0002) and positively with the fasting glucose to insulin ratio (r = 0.79, P<.0001). CONCLUSION: Adolescent girls with PCOS have profound metabolic derangements detected early in the course of the syndrome, including (1) approximately 50% reduction in peripheral tissue insulin sensitivity, (2) evidence of hepatic insulin resistance, and (3) compensatory hyperinsulinemia. These observations may predict an increased risk of type 2 diabetes mellitus in adolescents with PCOS.
Assuntos
Diabetes Mellitus Tipo 2/etiologia , Hiperinsulinismo/etiologia , Resistência à Insulina/fisiologia , Insulina/sangue , Insulina/metabolismo , Obesidade/etiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Adolescente , Glicemia/análise , Composição Corporal , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Jejum , Feminino , Técnica Clamp de Glucose , Humanos , Hiperinsulinismo/sangue , Secreção de Insulina , Fígado/metabolismo , Obesidade/patologia , Fatores de TempoRESUMO
Type 2 diabetes mellitus is a disease of adults and has been considered rare in the pediatric population. Over the last decade, however, there has been a disturbing trend of increasing cases of type 2 diabetes in children, particularly adolescents, and with a greater proportion of minority children being affected. This article reviews the clinical characteristics of youth with type 2 diabetes, presents the risk factors associated with insulin resistance and type 2 diabetes, discusses treatment options, and projects future directions in research. The ultimate goal is to raise awareness of this challenging entity among healthcare professionals.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Grupos Minoritários , Adolescente , Criança , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Feminino , Hispânico ou Latino , Humanos , Indígenas Norte-Americanos , Masculino , México/etnologiaRESUMO
Fourteen black and 16 white healthy adolescents underwent a 2-hour hyperglycemic clamp (12.5 mmol/L) to investigate racial differences in insulin secretion and sensitivity. First-phase and second-phase insulin concentrations were higher in black subjects than in white subjects (first phase: 944 +/- 110 pmol/L vs. 462 +/- 52 pmol/L, p = 0.0003; second phase: 1050 +/- 146 pmol/L vs. 652 +/- 53 pmol/L, p = 0.0012). The insulin sensitivity index was lower in black adolescents (8.21 +/- 1.05) compared with white adolescents (12.55 +/- 1.42 mumol/kg per minute per picomole per liter, p = 0.02). These findings indicate that significant differences in insulin secretion and sensitivity are detectable in healthy black versus white adolescents.
Assuntos
População Negra , Resistência à Insulina , Insulina/metabolismo , População Branca , Adolescente , Glicemia , Criança , Técnica Clamp de Glucose , Humanos , Secreção de Insulina , Valores de ReferênciaRESUMO
OBJECTIVE: To determine whether acute hyperglycemia adversely affects mental efficiency to the same extent as acute mild hypoglycemia. STUDY DESIGN: We administered a battery of cognitive tests to adolescents studied at hyperglycemic (20 mmol/L (360 mg/dl)), hypoglycemic (3.3 mmol/L (60 mg/dl)), or euglycemic (5.5 mmol/L (100 mg/dl)) targets, which were maintained by an insulin-glucose clamp. The study included 36 children, 9 to 19 years of age (mean = 14.7 years), with diabetes duration more than 2 years (mean = 6.9 years). RESULTS: Cognitive test performance did not deteriorate during hyperglycemia. In contrast, there was a significant decline in performance on all cognitive tests during mild hypoglycemia. Autonomic symptoms did not change significantly during hyperglycemia or during the rapid return from hyperglycemia to euglycemia. Although significant increments in epinephrine and pancreatic polypeptide levels occurred during mild hypoglycemia, no changes in counterregulatory hormones occurred during hyperglycemia. An exploratory regression analysis demonstrated that changes in mental efficiency were best predicted by increases in pancreatic polypeptide, a marker of autonomic activation. CONCLUSION: These results confirm our previous finding that mild hypoglycemia causes transient decrements in cognitive function. In contrast, neither hyperglycemia, nor the rapid drop from acute hyperglycemia to euglycemia, affected symptoms, cognitive function, or counterregulatory hormone secretion.
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Diabetes Mellitus Tipo 1/fisiopatologia , Eficiência/fisiologia , Epinefrina/sangue , Hiperglicemia/fisiopatologia , Processos Mentais/fisiologia , Norepinefrina/sangue , Polipeptídeo Pancreático/sangue , Doença Aguda , Adolescente , Glicemia/análise , Criança , Cognição/fisiologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/psicologia , Feminino , Glucose/administração & dosagem , Humanos , Hiperglicemia/sangue , Hiperglicemia/psicologia , Hipoglicemia/sangue , Hipoglicemia/fisiopatologia , Hipoglicemia/psicologia , Insulina/administração & dosagem , Insulina/sangue , Masculino , Testes Psicológicos , Tempo de Reação/fisiologiaRESUMO
This study was undertaken (1) to evaluate growth hormone binding protein (GHBP) levels in newly diagnosed patients with Type 1 diabetes before and after insulin therapy and (2) to determine the relationship of GHBP to glycaemic control, C-peptide level and blood pH. GHBP, expressed as a percentage of (125I)GH bound, was determined in 33 patients with Type 1 diabetes (M/F = 19/14, 12.3 +/- 0.4 years) before (day 0), after 5 days (day 5) and after 3 months (month 3) of insulin therapy. At day 0, GHBP was lower in Type 1 diabetes compared with 38 matched healthy control subjects (3.9 +/- 0.4 vs 8.2 +/- 0.4%, p < 0.001). There was no significant improvement in GHBP at day 5 (4.4 +/- 0.3%). At month 3, GHBP increased to (6.0 +/- 0.4%, p < 0.001 vs day 0), but was still lower than controls, p < 0.001. At day 0 GHBP correlated with BMI (r = 0.50, p = 0.001), blood glucose (r = -0.43 p = 0.006) and pH (r = 0.48, p = 0.004), but not HbA1. GHBP at month 3 correlated with day 0 C-peptide (r = 0.41, p = 0.02). Thus, (1) circulating GHBP is low in newly diagnosed patients with Type 1 diabetes, and increases after 3 months of insulin therapy but does not normalize and (2) the severity of biochemical derangement and residual beta-cell function at diagnosis may determine GHBP status and its recovery. We conclude that insulin is an important modulator of GH binding protein in newly diagnosed children with Type 1 diabetes.
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Proteínas de Transporte/sangue , Diabetes Mellitus Tipo 1/sangue , Insulina/uso terapêutico , Adolescente , Índice de Massa Corporal , Peptídeo C/sangue , Proteínas de Transporte/efeitos dos fármacos , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/análise , Hormônio do Crescimento/sangue , Humanos , Masculino , Puberdade , Valores de Referência , Fatores de TempoRESUMO
To assess the effects of mild hypoglycemia on cognitive functioning in diabetic children, we used an insulin glucose clamp technique to induce and maintain a hypoglycemic state. Eleven patients, 11 to 18 years of age, completed a series of cognitive tests during a baseline euglycemic state (100 mg/dl (5.5 mmol/L] and repeated those measures at the beginning and end of a hypoglycemic plateau (55 to 65 mg/dl (3.1 to 3.6 mmol/L], and again at restoration of euglycemia. At plasma glucose levels of 60 to 65 mg/dl (3.3 to 3.6 mmol/L), a significant decline in mental efficiency was found. This was most apparent on measures of mental "flexibility" (Trial Making Test) and on measures that required planning and decision making, attention to detail, and rapid responding. Moreover, complete recovery of cognitive function was not contemporaneous with restoration of euglycemia, particularly on those tests requiring rapid responding and decision making (choice reaction time). Not all subjects showed evidence of cognitive impairment during hypoglycemia. The very high degree of intersubject variability suggests that, in addition to plasma glucose values, unknown physiologic variables are responsible for triggering cognitive impairments in school-aged youngsters with diabetes during an episode of mild hypoglycemia.
Assuntos
Cognição/fisiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Hipoglicemia/psicologia , Adolescente , Atenção , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Técnica Clamp de Glucose , Humanos , Hipoglicemia/fisiopatologia , Insulina/uso terapêutico , Inteligência , Masculino , Tempo de Reação , Teste de Sequência AlfanuméricaRESUMO
To ascertain whether the dawn phenomenon occurs in normal adolescents and, if so, to determine its mechanism, we measured nocturnal plasma glucose, insulin, glucagon, growth hormone, cortisol, and adrenocorticotropic hormone (ACTH) levels between 01.00 and 08.00 h in 10 healthy adolescents. The prehepatic insulin secretion rate was calculated based on C peptide levels. The metabolic clearance rate of insulin (MCRI) was calculated as the ratio of mean insulin secretion rate to mean insulin concentration. There was no change in plasma glucose, insulin, and glucagon between 01.00-04.00 and 05.00-08.00 h (paired t test). The MCRI was higher at 05.00-08.00 h compared to 01.00-04.00 h (9.30 +/- 1.50 vs. 4.87 +/- 1.11 ml.kg-1.min-1; p = 0.008). The prehepatic insulin secretion increased at 05.00-08.00 h relative to 01.00-04.00 h (1.1 +/- 0.2 vs. 0.6 +/- 0.1 pmol.kg-1.min-1; p = 0.013). Similarly, cortisol and ACTH levels were higher at 05.00-08.00 versus 01.00-04.00 h (323 +/- 33 vs. 102 +/- 22 nmol/l, p less than 0.001; 3.6 +/- 0.5 vs. 1.8 +/- 0.4 pmol/l, p = 0.006, respectively). Growth hormone was higher at 01.00-04.00 versus 05.00-08.00 h (7.6 +/- 1.2 and 3.0 +/- 0.9 microgram/l; p = 0.019). ACTH correlated with MCRI (r = 0.66; p = 0.002) and prehepatic insulin secretion (r = 0.75; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)