RESUMEN
AIMS/HYPOTHESIS: In patients with type 1 diabetes, there has been concern about the effects of recurrent hypoglycaemia and chronic hyperglycaemia on cognitive function. Because other biomedical factors may also increase the risk of cognitive decline, this study examined whether macrovascular risk factors (hypertension, smoking, hypercholesterolaemia, obesity), sub-clinical macrovascular disease (carotid intima-media thickening, coronary calcification) and microvascular complications (retinopathy, nephropathy) were associated with decrements in cognitive function over an extended time period. METHODS: Type 1 diabetes patients (n = 1,144) who had completed a comprehensive cognitive test battery at entry into the Diabetes Control and Complications Trial were re-assessed at a mean of 18.5 (range: 15-23) years later. Univariate and multivariable models examined the relationship between cognitive change and the presence of micro- and macrovascular complications and risk factors. RESULTS: Univariate modelling showed that smoking history was modestly associated with decrements in learning, memory, spatial information-processing and psychomotor efficiency; hypertension was associated with only psychomotor slowing. Multivariable modelling demonstrated that HbA(1c) level, and retinal and renal complications were each independently associated with decrements in psychomotor efficiency. In contrast, no macrovascular risk factors were significant after correcting for multiple comparisons. No interactions were found between these predictors and sex, severe hypoglycaemic events or presence of the APOE ε4 allele. CONCLUSIONS/INTERPRETATION: In relatively healthy, middle-aged adults with type 1 diabetes who had been followed for an average of 18.5 years, long-term metabolic control and microvascular factors are independently associated with a decline in cognitive function specifically affecting measures of psychomotor efficiency. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360893.
Asunto(s)
Cognición/fisiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/fisiopatología , Adolescente , Adulto , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/fisiopatología , Retinopatía Diabética/complicaciones , Retinopatía Diabética/fisiopatología , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Factores de Riesgo , Fumar/efectos adversos , Adulto JovenRESUMEN
AIMS: Specific polymorphisms of the apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) genes appear to increase risk for Alzheimer's disease and cognitive dysfunction in the general population, yet little research has examined whether genetic factors influence risk of cognitive dysfunction in patients with Type 1 diabetes. The long-term follow-up of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) population provides an opportunity to examine if specific genetic variations in APOE and ACE alter risk for cognitive decline. METHODS: Neurocognitive function in Type 1 diabetic subjects from the DCCT/EDIC study was assessed at DCCT entry and re-assessed approximately 18 years later, using a comprehensive cognitive test battery. Glycated haemoglobin (HbA(1c)) and the frequency of severe hypoglycaemic events leading to coma or seizures were measured over the 18-year follow-up. We determined whether the APO epsilon4 and ACE intron 16 indel genotypes were associated with baseline cognitive function and with change over time, and whether they conferred added risk in those subjects experiencing severe hypoglycaemic events or greater glycaemic exposure. RESULTS: None of the APOE or ACE polymorphisms were associated with either baseline cognitive performance or change in cognition over the 18-year follow-up. Moreover, none of the genotype variations altered the risk of cognitive dysfunction in those subjects with severe hypoglycaemic episodes or high HbA(1c). CONCLUSIONS: In this sample of young and middle-aged adults with Type 1 diabetes, APO epsilon4 and ACE D alleles do not appear to increase risk of cognitive dysfunction.
Asunto(s)
Apolipoproteínas E/genética , Trastornos del Conocimiento/genética , Diabetes Mellitus Tipo 1/genética , Hemoglobina Glucada/genética , Peptidil-Dipeptidasa A/genética , Adolescente , Adulto , Apolipoproteínas E/fisiología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Estudios de Seguimiento , Variación Genética , Genotipo , Hemoglobina Glucada/fisiología , Humanos , Masculino , Pruebas Neuropsicológicas , Peptidil-Dipeptidasa A/fisiología , Polimorfismo Genético , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy of type 1 diabetes mellitus reduces the risk of development and progression of microvascular complications. The Epidemiology of Diabetes Interventions and Complications (EDIC) study assessed whether these benefits persisted after the end of DCCT. Results for the adolescent DCCT cohort are reported here. STUDY DESIGN: Of the DCCT adolescent cohort (n = 195), 175 participated in EDIC, 151 had fundus photography, and 156 had albumin excretion rate measured at year 3 or 4. The odds of progression of retinopathy and albuminuria from closeout of the DCCT until EDIC year 4 were assessed. RESULTS: In contrast to the 7.4 years of the DCCT, during which mean hemoglobin A(1c) levels were significantly lower with intensive therapy than conventional therapy (8.06% vs 9.76%; P <.0001), the subsequent first 4 years of EDIC had mean hemoglobin A(1c) levels that were similar between the former intensive and the former conventional groups (8.38% vs 8.45%). However, the prevalence of worsening of 3 steps or more in retinopathy and of progression to proliferative or severe nonproliferative retinopathy were reduced by 74% (P <.001) and 78% (P <.007), respectively, in the former intensive therapy group compared with the former conventional group. CONCLUSIONS: These findings provide further support for the DCCT recommendation that most adolescents with type 1 diabetes receive intensive therapy aimed at achieving glycemic control as close to normal as possible to reduce the risk of microvascular complications.
Asunto(s)
Albuminuria/prevención & control , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Retinopatía Diabética/prevención & control , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Adolescente , Adulto , Albuminuria/sangre , Albuminuria/etiología , Estudios de Cohortes , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Retinopatía Diabética/sangre , Retinopatía Diabética/etiología , Femenino , Angiografía con Fluoresceína , Hemoglobina Glucada/análisis , Hemoglobina Glucada/efectos de los fármacos , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Oportunidad Relativa , Análisis de Regresión , Factores de Tiempo , Resultado del TratamientoRESUMEN
The relationships between long-term intensive control of glycemia and indicators of skin collagen glycation (furosine), glycoxidation (pentosidine and N(epsilon)-[carboxymethyl]-lysine [CML]), and crosslinking (acid and pepsin solubility) were examined in 216 patients with type 1 diabetes from the primary prevention and secondary intervention cohorts of the Diabetes Control and Complications Trial. By comparison with conventional treatment, 5 years of intensive treatment was associated with 30-32% lower furosine, 9% lower pentosidine, 9-13% lower CML, 24% higher acid-soluble collagen, and 50% higher pepsin-soluble collagen. All of these differences were statistically significant in the subjects of the primary prevention cohort (P < 0.006-0.001) and also of the secondary intervention cohort (P < 0.015-0.001) with the exception of CML and acid-soluble collagen. Age- and duration-adjusted collagen variables were significantly associated with the HbA1c value nearest the biopsy and with cumulative prior HbA1c values. Multiple logistic regression analyses with six nonredundant collagen parameters as independent variables and various expressions of retinopathy, nephropathy, and neuropathy outcomes as dependent variables showed that the complications were significantly associated with the full set of collagen variables. Surprisingly, the percentage of total variance (R2) in complications explained by the collagen variables ranged from 19 to 36% with the intensive treatment and from 14 to 51% with conventional treatment. These associations generally remained significant even after adjustment for HbA1c, and, most unexpectedly, in conventionally treated subjects, glycated collagen was the parameter most consistently associated with diabetic complications. Continued monitoring of these subjects may determine whether glycation products in the skin, and especially the early Amadori product (furosine), have the potential to be predictors of the future risk of developing complications, and perhaps be even better predictors than glycated hemoglobin (HbA1c).
Asunto(s)
Colágeno/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/terapia , Piel/metabolismo , Adolescente , Adulto , Envejecimiento/metabolismo , Biomarcadores , Estudios de Cohortes , Colágeno/fisiología , Nefropatías Diabéticas/metabolismo , Neuropatías Diabéticas/metabolismo , Retinopatía Diabética/metabolismo , Hemoglobina Glucada/análisis , Glicosilación , Humanos , Persona de Mediana Edad , Oxidación-Reducción , Factores de TiempoRESUMEN
OBJECTIVE: To assess the psychosocial functioning of adults who were evaluated as children for short stature and were not treated with human growth hormone. DESIGN: Inception cohort study. SETTING: Hospital-based pediatric endocrinology clinic. PARTICIPANTS: From 1975 to 1980, medical record review indicated that 181 of the children referred to our clinic for concerns about short stature were non-growth hormone deficient. In 1992 and 1993, we were able to recruit 35 of these patients for a follow-up study. Eligible subjects were at least 18 years of age at the time of follow-up. MAIN OUTCOME MEASURES: Standardized self-report questionnaires assessed various domains of psychosocial adjustment. Also, a brief test of intellectual functioning was administered and subjects underwent a semistructured in-person interview to evaluate pragmatic functioning and experiences associated with short stature. RESULTS: Few significant differences between the study sample and standardization samples were found on measures of psychosocial and intellectual functioning. Within-group childhood height during the first evaluation appointment was not significantly associated with most adult measures of psychosocial adjustment. Shorter adult stature was significantly associated with lower educational achievement, lower self-esteem, and greater emotional distress. CONCLUSIONS: The absence of significant psychosocial distress or impairment in these subjects brings into question one basis for hormonal treatment for non-growth hormone deficient short stature; that short stature in childhood is likely to lead to psychological dysfunction in adulthood. The results, however, also suggest that shorter stature in adulthood may constitute a psychosocial stressor, increasing vulnerability across several domains.
Asunto(s)
Estatura , Imagen Corporal , Trastornos del Crecimiento/psicología , Psicología Infantil , Estrés Psicológico/psicología , Adaptación Psicológica , Adolescente , Adulto , Actitud Frente a la Salud , Escolaridad , Femenino , Estudios de Seguimiento , Trastornos del Crecimiento/terapia , Humanos , Pruebas de Inteligencia , Masculino , Autoimagen , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Since synthetic growth hormone became available in the mid-1980s, there has been debate about its use for non-growth-hormone-deficient short children. Justification for this use of growth hormone often is based on a presumed association of short stature with significant psychosocial maladjustment. However, systematic evaluation of psychosocial functioning in short children has been limited, and our understanding of this area is scant. In this study, we have used a combination of interview and self-report measures to examine self-esteem, personality characteristics, affective functioning, coping style, and stature-related stresses in 41 children (5 to 16 years) referred to a pediatric endocrinology service because of short stature. Parent-report and child measures of self-esteem and psychological functioning indicated no evidence of maladjustment in comparison with norms. Furthermore, within the subject sample, the degree of short stature was not related to poor psychological functioning. We found limited evidence linking increased age with increased distress, suggesting that short stature may pose greater difficulties for children as they enter adolescence. Taken as a whole, however, the results do not support the contention that short stature is generally associated with psychosocial maladjustment in children referred for evaluation of their short stature.
Asunto(s)
Adaptación Psicológica , Estatura , Ajuste Social , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Entrevista Psicológica , Masculino , Inventario de Personalidad , Factores Sexuales , Estrés Psicológico/psicologíaRESUMEN
Compared child-rearing behaviors among mothers of children (ages 4-14) with cystic fibrosis (CF) (N = 26), insulin-dependent diabetes mellitus (IDDM) (N = 26), and mothers of physically healthy children (N = 26), on six domains, including involvement, limit setting, responsiveness, reasoning and guidance, free expression, and intimacy using the Iowa Parent Behavior Inventory. Maternal Reports of their child-rearing behavior were comparable across the three groups with one exception: Mothers of children with chronic illnesses (CF and IDDM) were significantly less likely to set limits than mothers of healthy children. The present findings are consistent with those of other studies that have identified few differences in child-rearing practices between mothers of children with chronic illnesses and mothers of healthy children. Future research should identify situation-specific parenting tasks unique to childhood chronic illness.
Asunto(s)
Crianza del Niño/psicología , Fibrosis Quística/psicología , Diabetes Mellitus Tipo 1/psicología , Conducta Materna/psicología , Relaciones Madre-Hijo , Adolescente , Análisis de Varianza , Estudios de Casos y Controles , Niño , Enfermedad Crónica/psicología , Femenino , Humanos , Masculino , Responsabilidad Parental/psicologíaRESUMEN
An 18-year-old man with left-lobe thyroid hemiagenesis underwent isthmectomy for management of a nodule that failed to take up radioactive iodine during a nuclear scan. The resected tissue, which demonstrated nodular hyperplasia, and the remaining right lobe, were black. The association between deep staining and chronic minocycline ingestion was subsequently recognized. Twelve years later, the patient remained asymptomatic, suggesting that complete resection of tetracycline-stained thyroid tissue is unnecessary.
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Minociclina/efectos adversos , Trastornos de la Pigmentación/inducido químicamente , Glándula Tiroides/efectos de los fármacos , Nódulo Tiroideo/complicaciones , Acné Vulgar/tratamiento farmacológico , Adolescente , Hemosiderina/análisis , Humanos , Hiperplasia , Masculino , Microscopía Electrónica , Trastornos de la Pigmentación/complicaciones , Glándula Tiroides/anomalías , Glándula Tiroides/patología , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/cirugíaRESUMEN
Type I diabetes mellitus, also called insulin-dependent diabetes mellitus or IDDM, is a significant chronic condition with implications for dental treatment. Advances in management include intensified therapy, highly purified insulins, and insulin pumps. Periodontal tissues are affected by IDDM, with resultant increases in disease in children affected with IDDM.
Asunto(s)
Diabetes Mellitus Tipo 1 , Enfermedades Periodontales , Adolescente , Niño , Atención Dental para la Persona con Discapacidad , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Humanos , Masculino , Planificación de Atención al Paciente , Enfermedades Periodontales/complicacionesRESUMEN
We measured the effect of human growth hormone (hGH) on urea synthesis, nitrogen retention, and glucose turnover in ten euthyroid growth hormone (GH)-deficient children before and after seven daily injections of 0.1 U/kg hGH. The patients were fed a weight-maintaining diet with 9% of energy derived from protein. Following an overnight fast, urea synthesis and glucose turnover were determined using a primed constant infusion of [15N2] urea and a constant infusion of [6,6-2H2] glucose. Human growth hormone produced a decrease in urea nitrogen synthesis from 6.8 +/- 0.5 to 4.2 +/- 0.4 mg/kg.h; (P less than .01), while plasma urea nitrogen decreased from 13.1 +/- 0.8 to 7.4 +/- 0.8 mg/dL; (P less than .01). The decrease in urea synthesis was reflected in a corresponding decrease in urine urea nitrogen excretion (-2.8 mg/kg.h). There was a significant correlation between plasma urea nitrogen and urea synthesis rate both before (r = 0.85, P less than .01) and after (r = 0.79, P less than .01) hGH treatment. In response to hGH, there was a rise in both plasma glucose (81.4 +/- 2.2 v 89.8 +/- 2.3 mg/dL; P less than .05) and insulin (5.7 +/- 0.8 v 13.1 +/- 3.0 microU/mL; P less than .05), however, glucose turnover remained unchanged (4.7 +/- 0.3 v 4.6 +/- 0.6 mg/kg.min). After seven days of growth hormone treatment, the patients were placed on 0.1 U/kg of hGH three times a week for 6 months, and their growth rate was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Glucosa/metabolismo , Hormona del Crecimiento/deficiencia , Nitrógeno/metabolismo , Urea/biosíntesis , Glucemia/análisis , Nitrógeno de la Urea Sanguínea , Niño , Ayuno , Femenino , Crecimiento/efectos de los fármacos , Hormona del Crecimiento/administración & dosificación , Hormona del Crecimiento/sangre , Humanos , Insulina/sangre , MasculinoAsunto(s)
Neoplasias de Cabeza y Cuello/complicaciones , Hiponatremia/etiología , Linfa , Linfangioma/complicaciones , Trastornos de Deglución/complicaciones , Neoplasias de Cabeza y Cuello/congénito , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Recién Nacido , Linfangioma/congénito , Linfangioma/metabolismo , Linfangioma/cirugía , MasculinoRESUMEN
Forty patients with the Prader-Willi syndrome have been examined. The typical features begin in gestational life with poor fetal vigor and difficulties with birth and post-partum feeding. The classical features of hypotonia, small hands and feet, cryptorchidism can be identified at this time. The delayed milestones, mental retardation and obesity become more prominent later. The average height of the patients in this series who were admitted to the Clinical Study Center was 149 cm and their weight was 114 kg. The weight and height curves show that Prader-Willi individuals are consistently shorter and heavier than normal children. Tests of endocrine function showed normal glucose tolerance. Insulin secretion was increased in relation to obesity. The rise in growth hormone (hGH) after injecting insulin to induce hypoglycemia and after the infusion of arginine was comparable to other obese individuals but was low in comparison to normal weight subjects. There was no rise in growth hormone with L-dopa administration, but there was a rise in hGH with the administration of 2-deoxy-D-glucose. The hypoglycemia produced by insulin was greater in the Prader-Willi patient than in obese controls. The rise in TRH (thyrotropin-releasing hormone) following the injection of TSH (thyrotropin stimulating hormone) was greater in the Prader-Willi patients than in the obese controls. Hypogonadism was routine in this series, and the response to LRH (luteinizing releasing hormone) was absent in all tested subjects. Treatment with clomiphene for 30 to 90 days significantly increased the response to LRH in three adult individuals who had not been treated with gonadal steroids previously and who were hypogonadal. Rectal temperature declined in three of the five Prader-Willi patients during exposure to an ambient temperature of 4 degrees C, but none of the three obese controls showed a decline. Food intake averaged 5167 kcal/d when six patients were given trays containing more food than they could eat. Food intake was not reduced when tryptophan was added to the diet. Salivary secretion was reduced in the Prader-Willi patients. A number of pulmonary function tests were significantly reduced in the study patients compared to obese or normal weight controls. The anatomic findings in four autopsied patients with the Prader-Willi syndrome showed no significant differences from those of obese subjects without this syndrome. The chromosomal pattern showed a deletion or translocation at chromosome 15 in 3 of 12 patients in whom this test was performed. These findings in 40 patients with the Prader-Willi syndrome have been compared with the information contained in 159 reports published in the medical literature.
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Síndrome de Prader-Willi , Estatura , Peso Corporal , Deleción Cromosómica , Cromosomas Humanos 13-15 , Ingestión de Energía , Femenino , Humanos , Pulmón/fisiopatología , Masculino , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/etiología , Síndrome de Prader-Willi/fisiopatología , Embarazo , Pruebas de Función Respiratoria , Translocación GenéticaAsunto(s)
Tejido Adiposo , Composición Corporal , Animales , Peso Corporal , Femenino , Ratas , Ratas Endogámicas , Gravedad EspecíficaRESUMEN
The adrenergic modulation of immunoreactive insulin (IRI) and glucagon (IRG) secretion was studied in 5 massively obese subjects hospitalized ion a metabolic ward. Epinephrine was infused alone or in combination with propranolol, a beta adrenergic blocking drug, or with phentolamine, an alpha adrenergic blocking drug. Epinephrine infusion produced a significant (p less than .02) rise in IRG levels which was blocked by addition of either phentolamine or propranolol. Pure alpha adrenergic stimulation with propranolol-epinephrine infusion inhibited IRG secretion (p less than .02). IRI levels decreased with propranolol-epinephrine infusion (p less than .02), increased with phentolamine-epinephrine infusion, and were not affected by infusion of epinephrine alone. Glucose concentrations rose with all 3 infusions but were less with phentolamine-epinephrine. A control group of 4 lean outpatients on a ad lib diet demonstrated a similar pattern but the changes of IRG secretion were smaller than in the obese subjects and were not statistically significant. We conclude that in obese humans IRI secretion is increased by beta adrenergic stimulation, is decreased by alpha adrenergic stimulation, and is unaffected by combined alpha and beta adrenergic stimulation. In contrast, IRG secretion is stimulated by combined alpha and beta adrenergic stimulation, is inhibited by pure alpha adrenergic stimulation, and is unaffected by pure beta adrenergic stimulation.
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Glucagón/metabolismo , Insulina/metabolismo , Obesidad/fisiopatología , Sistema Nervioso Simpático/fisiología , Adulto , Glucemia/metabolismo , Epinefrina/farmacología , Humanos , Secreción de Insulina , Fentolamina/farmacología , Propranolol/farmacologíaAsunto(s)
Glándulas Endocrinas/fisiopatología , Obesidad/fisiopatología , Corticoesteroides/metabolismo , Glándulas Suprarrenales/fisiopatología , Andrógenos/metabolismo , Estrógenos/metabolismo , Femenino , Hormona Folículo Estimulante/metabolismo , Hormona del Crecimiento/metabolismo , Humanos , Insulina/metabolismo , Islotes Pancreáticos/fisiopatología , Hormona Luteinizante/metabolismo , Masculino , Ovario/fisiopatología , Hipófisis/fisiopatología , Prolactina/metabolismo , Globulina de Unión a Hormona Sexual/metabolismo , Testículo/fisiopatología , Glándula Tiroides/fisiopatología , Hormonas Tiroideas/metabolismoRESUMEN
The activity of lipoprotein lipase (LPL) released from human adipose tissue was measured before and after an oral glucose load in obese (n = 8) and normal (n = 7) weight subjects. The enzymatic activity of LPL release from fat tissue by heparin rose significantly one hour after glucose in the normal subjects. There was no such rise in LPL in adipose tissue from obese subjects. Serum triglyceride, insulin and glycerol were higher in the obese than in the lean subjects.
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Tejido Adiposo/enzimología , Lipoproteína Lipasa/metabolismo , Obesidad/enzimología , Adulto , Femenino , Glucosa/farmacología , Glicerol/sangre , Heparina/farmacología , Humanos , Insulina/sangre , Masculino , Triglicéridos/sangreAsunto(s)
Dieta Reductora , Dieta , Ingestión de Energía , Intestinos/cirugía , Obesidad/terapia , Desoxiglucosa , Ingestión de Alimentos , Retroalimentación , Femenino , Vaciamiento Gástrico , Hormonas/fisiología , Humanos , Masculino , Saciedad , GustoRESUMEN
The present studies were designed to compare physiological and behavioral changes produced by weight loss induced with dieting and the weight loss which follows intestinal bypass. A group of 7 grossly obese individuals were hospitalized in a metabolic unit and studied at their initial weight after 4 weeks on a hypocaloric diet and again following a comparable weight loss after intestinal bypass surgery. The score indicating depression increased after dieting, but returned to initial levels after bypass. A number of other behavioral changes were recorded including a reduction in the time spent thinking about food, the time when the individual felt hungry and a greater percentage of time when they felt "full". After bypass, the patients also selected and ate smaller quantities of food. There were no metabolic differences following the period of dieting. Among the metabolic changes after bypass were an increase in glycerol and a decrease in insulin. The possible relationships between the metabolic and behavioral changes have been reviewed.