RESUMEN
AIMS: To examine the association between islet autoantibody positivity and clinical characteristics, residual ß-cell function (C-peptide) and prevalence of complications in a childhood-onset (age <17 years), long-duration (≥32 years) type 1 diabetes cohort. METHODS: Islet autoantibodies (glutamic acid decarboxylase, insulinoma-associated protein 2 and zinc transporter-8 antibodies) were measured in the serum of participants who attended the 2011-2013 Pittsburgh Epidemiology of Diabetes Complications study follow-up examination (n=177, mean age 51 years, diabetes duration 43 years). RESULTS: Prevalences of islet autoantibodies were: glutamic acid decarboxylase, 32%; insulinoma-associated protein 2, 22%; and zinc transporter-8, 4%. Positivity for each islet autoantibody was associated with older age at diabetes onset (glutamic acid decarboxylase antibodies, P=0.03; insulinoma-associated protein 2 antibodies, P=0.001; zinc transporter-8 antibodies, P<0.0001). Older age at onset was also associated with an increasing number of autoantibodies (P = 0.001). Glutamic acid decarboxylase antibody positivity was also associated with lower HbA1c (P = 0.02), insulinoma-associated protein 2 antibody positivity was associated with lower prevalence of severe hypoglycaemic episodes (P=0.02) and both distal and autonomic neuropathy (P=0.04 for both), and zinc transporter-8 antibody positivity was associated with higher total and LDL cholesterol (P=0.01). No association between autoantibody positivity and C-peptide was observed. CONCLUSIONS: The strong association between islet autoantibody positivity and older age at type 1 diabetes onset supports the hypothesis of a less aggressive, and thus more persistent, immune process in those with older age at onset. This observation suggests that there may be long-term persistence of heterogeneity in the underlying autoimmune process.
Asunto(s)
Autoanticuerpos/inmunología , Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus Tipo 1/inmunología , Transportador 8 de Zinc/inmunología , Adulto , Edad de Inicio , Anciano , Péptido C/metabolismo , Colesterol/metabolismo , LDL-Colesterol/metabolismo , Complicaciones de la Diabetes/etiología , Complicaciones de la Diabetes/inmunología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Pathogen spillover from wildlife to humans or domestic animals requires a series of conditions to align with space and time. Comparing these conditions between times and locations where spillover does and does not occur presents opportunities to understand the factors that shape spillover risk. Bovine rabies transmitted by vampire bats was first confirmed in 1911 and has since been detected across the distribution of vampire bats. However, Uruguay is an exception. Uruguay was free of bovine rabies until 2007, despite high-cattle densities, the presence of vampire bats and a strong surveillance system. To explore why Uruguay was free of bovine rabies until recently, we review the historic literature and reconstruct the conditions that would allow rabies invasion into Uruguay. We used available historical records on the abundance of livestock and wildlife, the vampire bat distribution and occurrence of rabies outbreaks, as well as environmental modifications, to propose four alternative hypotheses to explain rabies virus emergence and spillover: bat movement, viral invasion, surveillance failure and environmental changes. While future statistical modelling efforts will be required to disentangle these hypotheses, we here show how a detailed historical analysis can be used to generate testable predictions for the conditions leading to pathogen spillover.
Asunto(s)
Migración Animal , Enfermedades de los Bovinos/embriología , Quirópteros , Monitoreo Epidemiológico/veterinaria , Virus de la Rabia/fisiología , Rabia/veterinaria , Animales , Bovinos , Vigilancia de la Población , Rabia/epidemiología , UruguayRESUMEN
Bats (Order: Chiroptera) have been widely studied as reservoir hosts for viruses of concern for human and animal health. However, whether bats are equally competent hosts of non-viral pathogens such as bacteria remains an important open question. Here, we surveyed blood and saliva samples of vampire bats from Peru and Belize for hemotropic Mycoplasma spp. (hemoplasmas), bacteria that can cause inapparent infection or anemia in hosts. 16S rRNA gene amplification of blood showed 67% (150/223) of common vampire bats (Desmodus rotundus) were infected by hemoplasmas. Sequencing of the 16S rRNA gene amplicons revealed three novel genotypes that were phylogenetically related but not identical to hemoplasmas described from other (non-vampire) bat species, rodents, humans, and non-human primates. Hemoplasma prevalence in vampire bats was highest in non-reproductive and young individuals, did not differ by country, and was relatively stable over time (i.e., endemic). Metagenomics from pooled D. rotundus saliva from Peru detected non-hemotropic Mycoplasma species and hemoplasma genotypes phylogenetically similar to those identified in blood, providing indirect evidence for potential direct transmission of hemoplasmas through biting or social contacts. This study demonstrates vampire bats host several novel hemoplasmas and sheds light on risk factors for infection and basic transmission routes. Given the high frequency of direct contacts that arise when vampire bats feed on humans, domestic animals, and wildlife, the potential of these bacteria to be transmitted between species should be investigated in future work.
Asunto(s)
Quirópteros/microbiología , Infecciones por Mycoplasma/veterinaria , Mycoplasma/genética , Animales , Belice , ADN Bacteriano/genética , Reservorios de Enfermedades/microbiología , Variación Genética/genética , Infecciones por Mycoplasma/microbiología , Infecciones por Mycoplasma/transmisión , Perú , Filogenia , Reacción en Cadena de la Polimerasa/veterinaria , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND/AIMS: There are few studies about gastrointestinal abnormalities in patients with juvenile rheumatoid arthritis-probably due to the fact that this association is not frequently recognized. The aim of our study was to observe the prevalence of endoscopic gastroduodenal lesions in these patients. METHODOLOGY: Fourteen patients with juvenile rheumatoid arthritis, all of them using non-steroidal anti-inflammatory drugs associated or not with methotrexate, were assessed clinically and by endoscopy. Gastric antrum biopsy and Helicobacter pylori search were also performed. RESULTS: The mean age of the patients was 10.6 years (7 boys). Abdominal pain was observed in 27% of them. Macroscopic endoscopic lesions were found in 43% and infection by Helicobacter pylori in 57%. The correlation between anemia and endoscopic abnormalities was statistically significant (p < 0.05). CONCLUSIONS: Our data show that patients with juvenile rheumatoid arthritis have considerable susceptibility to gastroduodenal lesions, especially if they are using any drug association and present anemia.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Antirreumáticos/efectos adversos , Artritis Juvenil/tratamiento farmacológico , Úlcera Péptica/inducido químicamente , Adolescente , Antiinflamatorios no Esteroideos/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/patología , Biopsia , Niño , Endoscopía Gastrointestinal , Femenino , Mucosa Gástrica/patología , Infecciones por Helicobacter/patología , Helicobacter pylori , Humanos , Masculino , Úlcera Péptica/patología , Factores de RiesgoRESUMEN
The objective of this study was to examine whether fasting serum insulin is a predictor of coronary heart disease in high-risk US men, and whether any such predictive role explains the enhanced cardiovascular risk seen in subjects with the apolipoprotein (Apo) E 3/2 phenotype. This was a nested case-control study of participants in the Multiple Risk Factor Intervention Trial. Ninety-four subjects who died from coronary heart disease (post-trial follow-up) and 114 case patients with myocardial infarction (during trial) were compared to control subjects (n = 414) matched (1:2) by age, center, randomization date, and intervention group. Overall, fasting serum insulin at baseline was not associated with case-control status. (Means for cases versus controls: 16.8 and 16.6 microU/mL), although serum insulin showed significant correlations with low-density-lipoprotein cholesterol, triglycerides, and uric acid. When stratified by the three Apo E phenotypes, 3/2, 3/3, 3/4, a significant association of fasting insulin with case-control status was seen for Apo E 3/2 individuals (19.9 versus 14.5 microU/mL; P = 0.02) but not for those with the other two phenotypes. Though fasting insulin is not a risk factor overall in this high-risk male population, it appears to contribute to cardiovascular risk in those with the Apo E 3/2 phenotype but does not explain the increased risk seen in these subjects. This new finding, if confirmed, may throw further light on the role of insulin in atherosclerosis.
Asunto(s)
Apolipoproteínas E/análisis , Enfermedad Coronaria/sangre , Enfermedad Coronaria/mortalidad , Insulina/sangre , Infarto del Miocardio/sangre , Infarto del Miocardio/mortalidad , Adulto , Apolipoproteína E2 , Apolipoproteína E3 , Apolipoproteína E4 , Apolipoproteínas E/genética , Estudios de Casos y Controles , LDL-Colesterol/sangre , Enfermedad Coronaria/genética , Ayuno , Humanos , Modelos Logísticos , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Infarto del Miocardio/genética , Fenotipo , Valor Predictivo de las Pruebas , Factores de Riesgo , Triglicéridos/sangreRESUMEN
Maximal red blood cell (RBC) sodium-lithium countertransport activity has been consistently related to essential hypertension and may be a marker for risk of developing hypertension. Although there is strong evidence for genetic control of sodium-lithium countertransport, increasing evidence suggests that obesity and insulin-glucose metabolism are related to countertransport activity. This study was performed to determine whether countertransport activity decreases with weight loss in healthy obese adults. Forty-five healthy, white, obese adults were studied at baseline and after 6 months of behavioral dietary intervention. Weight loss was 11.5 kg (25.4 lb) in 24 men and 8.1 kg (17.8 lb) in 21 women. Sodium-lithium countertransport activity decreased 55.0 mumol Li/L RBC/h in men (P < .001, paired t test) and 14.6 mumol Li/L RBC/h in women (NS). Change in countertransport activity was correlated with change in body mass index (BMI) in men (r = .52, P < .01) and women (r = .27, NS) and was also strongly correlated with change in fasting glucose levels in both men and women (r = .50 and r = .56, respectively; P < .01) and with change in fasting insulin levels in men (r = .42, P = .04). Change in countertransport activity was not significantly related to change in physical exercise or serum lipid levels. There was a large decrease in systolic blood pressure in men (10.0 mm Hg, P < .001) and a smaller decrease in women (4.1 mm Hg, P < .05). These changes were significantly correlated with change in weight, but not with change in countertransport or baseline countertransport activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Antiportadores , Proteínas Portadoras/fisiología , Obesidad/fisiopatología , Pérdida de Peso/fisiología , Adulto , Análisis de Varianza , Glucemia/análisis , Presión Sanguínea/fisiología , Índice de Masa Corporal , Femenino , Glucosa/metabolismo , Humanos , Insulina/metabolismo , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
The beneficial effect of physical activity in the general population is well known, but, to the authors' knowledge, has not been reported for persons with insulin-dependent diabetes mellitus. In a cohort of 548 diabetes patients followed as part of the Pittsburgh Insulin-dependent Diabetes Mellitus Morbidity and Mortality Study, physical activity was ascertained by survey in 1981, and mortality was ascertained through January 1, 1988. Cases were also compared with non-diabetic sibling controls. Activity level among cases varied inversely with the occurrence of diabetic complications. Overall activity level was inversely related to mortality risk. Sedentary males (< 1,000 kcal/week) were three times more likely to die than active males (> 2,000 kcal/week). A similar, but statistically nonsignificant, relation was seen in females. Cox proportional hazards analysis controlling for potential confounders (age, body mass index, insulin dose, reported diabetes complications, cigarette smoking, and current alcohol drinking) similarly revealed that activity level was inversely associated with mortality risk. Comparison of cases with non-diabetic sibling controls identified similar activity levels for the two groups. The results suggest that activity is not detrimental with regard to mortality, and may in fact provide a beneficial effect in terms of longevity in diabetes patients.
Asunto(s)
Diabetes Mellitus Tipo 1/mortalidad , Ejercicio Físico , Adolescente , Adulto , Femenino , Humanos , Estilo de Vida , Masculino , Pennsylvania/epidemiología , Estudios Prospectivos , Análisis de Regresión , Encuestas y CuestionariosRESUMEN
The risk for insulin-dependent diabetes mellitus (IDDM) associated with genetic susceptibility markers at the human leukocyte antigen (HLA) DQA1 and DQB1 loci was evaluated among individuals with and those without islet cell antibodies. A total of 108 antibody-positive parents and siblings of IDDM patients from the Pittsburgh registry were identified among 1,592 who were screened. HLA-DQ molecular typing was performed on 79 of these individuals and on 78 antibody-negative relatives. There were similar proportions of homozygotes for both of the diabetogenic alleles DQA1 arginine-52 (R/R) and DQB1 non-aspartate-57 (nD/nD) among the antibody-positive and antibody-negative relatives (19.0 and 15.4%, respectively). However, subsequent development of IDDM was restricted to individuals who were both antibody positive and carried the potential to make at least one diabetogenic DQ heterodimer. A dose-response effect was observed among the antibody-positive relatives, in which two of 18 capable of generating one diabetogenic heterodimer and six of 29 generating two heterodimers became insulin requiring. Nine of 15 who were homozygous for both R/R and nD/nD, coding exclusively for diabetogenic variants, became diabetic over the course of the follow-up. With a multivariate model, the relative risk for IDDM among those with islet cell antibodies who were also R/R and nD/nD was estimated to be 229.3 compared with those lacking both, after age and sex were controlled for. The data suggest that while autoimmunity, indicated by the presence of cytoplasmic islet cell antibodies may be relatively common, it progresses only in those with variant HLA-DQ molecules.
Asunto(s)
Anticuerpos/sangre , Enfermedades Autoinmunes/epidemiología , Diabetes Mellitus Tipo 1/epidemiología , Marcadores Genéticos/genética , Antígenos HLA-DQ/inmunología , Islotes Pancreáticos/inmunología , Adolescente , Adulto , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Femenino , Pruebas Genéticas/normas , Prueba de Histocompatibilidad/normas , Humanos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Análisis Multivariante , Pennsylvania/epidemiología , Valor Predictivo de las Pruebas , Sistema de Registros , Factores de RiesgoRESUMEN
The apolipoprotein (apo) E polymorphism has been related to differences in lipoprotein metabolism and lipid/lipoprotein concentrations in a number of studies. Whether these associations are seen in insulin-dependent diabetes mellitus (IDDM), which itself affects many of the same aspects of lipoprotein metabolism as does the apo E polymorphism, is unknown. The present study is an investigation into the influence of apo E phenotype on lipoprotein concentrations in a large group of IDDM patients (n = 433) participating in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. The frequency of the three apo E alleles 2, 3, and 4 did not differ in this population from that reported in general white populations. Although the diabetic subjects show the same trends as seen in the general population, ie, apo E-2 is associated with lower and apo E-4 with higher low-density lipoprotein cholesterol (LDLc) compared with apo E3 (P less than .03), they also show relationships with glycemic control that influence the relative levels of lipid measures with respect to apo E phenotype. Results also raise the possibility that lipoprotein composition varies according to apo E phenotype in IDDM.
Asunto(s)
Apolipoproteínas E/genética , Diabetes Mellitus Tipo 1/sangre , Lipoproteínas/sangre , Adulto , Alelos , Apolipoproteínas E/sangre , Diabetes Mellitus Tipo 1/genética , Femenino , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Caracteres SexualesAsunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Dieta para Diabéticos , Sacarosa/metabolismo , Niño , HumanosRESUMEN
Cardiovascular disease is a frequent complication of insulin-dependent diabetes mellitus (IDDM), but the prevalence, interrelations, and risk factors of its principal components (coronary, cerebrovascular, and lower-extremity arterial disease) and of medial arterial wall calcification are not well understood. To address these issues, data from the Epidemiology of Diabetes Complications Study (n = 657) baseline examination were examined. The term coronary heart disease (CHD) was applied to those with myocardial infarction or angina, whereas lower-extremity arterial disease (LEAD) was applied to those who had undergone amputation of a lower limb or who had an ankle to arm blood pressure ratio less than 0.8 at rest or after exercise. Calcification of the lower-extremity arteries was considered to be present if ankle pressure was more than 100 mm Hg higher than brachial pressure. Although the prevalence of CHD was low, LEAD was significantly more common in women than in men (p less than 0.01), whereas calcification was more frequent in men than in women (p less than 0.01). Ten percent of those with LEAD also had CHD, and 8% with LEAD had calcification. Modeling of potential risk factors (e.g., diabetes duration and glycosylated hemoglobin) revealed that duration, female gender, fibrinogen, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and high density lipoprotein cholesterol to apolipoprotein A-I ratio were independent predictors of LEAD, whereas for CHD only, diabetes duration and hypertension contributed to CHD. Calcification revealed a mixed pattern, with duration, hypertension, and triglyceride to apolipoprotein A-I ratio being the statistically significant associated factors. The results suggest that although LEAD, CHD, and calcification often coexist, their risk factor profiles differ.
Asunto(s)
Calcinosis/epidemiología , Enfermedad Coronaria/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Angiopatías Diabéticas/epidemiología , Adulto , Calcinosis/sangre , Calcinosis/etiología , Enfermedad Coronaria/sangre , Enfermedad Coronaria/etiología , Diabetes Mellitus Tipo 1/sangre , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/etiología , Femenino , Humanos , Lípidos/sangre , Masculino , Pennsylvania/epidemiología , Prevalencia , Análisis de Regresión , Factores de RiesgoRESUMEN
Recently, concern has arisen that human (as opposed to beef or pork) insulin may cause more frequent and/or severe hypoglycaemia in association with reduced warning symptoms. This question was examined from questionnaire data of 628 Type 1 diabetic patients (mean age 28 years and duration of diabetes 19 years) participating in the baseline examination of a follow-up study of diabetes complications. Those using human insulin (n = 73) reported an insignificantly higher frequency of hypoglycaemic reactions in the last year than those using animal insulin (66 vs 55% with reactions at least monthly) and only a weak trend was seen overall for the prevalence of human insulin use to increase with increasing frequency of hypoglycaemia (p = 0.06). Hypoglycaemic reactions resulting in unconsciousness were too rare to permit analysis by type of insulin used. The prevalence of reduced awareness of hypoglycaemia was similar among human insulin users to that seen in animal insulin users (25 vs 19%, NS). However, prevalence of reduced awareness showed a strong relationship to current blood glucose in the animal (r = -0.18, p less than 0.001) but not human (r = -0.06, NS) insulin users. Excluding patients with autonomic symptoms or neuropathy did not alter the results, nor did excluding the 34 individuals taking more than three insulin injections per day. It is concluded that human insulin use is not associated with either any substantial increased frequency of hypoglycaemia or reduction in awareness of hypoglycaemia. However, human insulin use does appear to be associated with reduced awareness of hypoglycaemia in those whose blood glucose control is relatively poor.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemia/diagnóstico , Insulina/efectos adversos , Adulto , Animales , Concienciación , Bovinos , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/complicaciones , Insulina/uso terapéutico , Masculino , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Encuestas y Cuestionarios , PorcinosRESUMEN
We report results from 120 (25- to 34-year-old) participants in a neuropathy substudy of subjects with insulin-dependent diabetes mellitus (IDDM) taking part in a cohort follow-up study. Diabetic neuropathy was evaluated by quantitative sensory testing, nerve conduction studies, and clinical examination. Mean quantitative sensory thresholds differed significantly by clinical category of abnormal sensation and ankle reflex activity. Mean sural and peroneal amplitudes and conduction velocities were also significantly lower for subjects classified as having abnormal ankle reflex activity. Modeling potential correlates in logistic analyses showed glycemic control, triglyceride levels, and hypertension status to be independently associated with clinically overt neuropathy. Similar lipid and hemodynamic parameters were associated with abnormality by any single assessment method used to define neuropathy. Although follow-up is needed to resolve the best assessment methods for determining neuropathy, these results suggest that good glycemic control as well as control of blood pressure and lipids is advisible.
Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Neuropatías Diabéticas/diagnóstico , Adulto , Diabetes Mellitus Tipo 1/sangre , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Lípidos/sangre , Masculino , Conducción Nerviosa , Examen Neurológico , Factores de Riesgo , Umbral SensorialRESUMEN
The prevalence of and interrelationships among all four major complications of insulin-dependent diabetes mellitus (IDDM) and their risk factors are being examined in a large epidemiologic study of IDDM subjects diagnosed in childhood. This article focuses on the baseline prevalence of complications in the 657 subjects diagnosed between 1950 and 1980 and currently aged 8-48 yr, with a mean duration of 20 yr. In addition to background retinopathy being virtually universal after 20 yr of diabetes, proliferative retinopathy affects 70% of IDDM subjects after 30 yr duration. As with overt nephropathy, prevalence of proliferative retinopathy is marginally higher in females than in males at short durations; the previously reported male excess is limited to the subjects with IDDM of longer duration (greater than or equal to 25 yr). Somewhat different patterns of microalbuminuria are also seen by sex. Males show a threefold increase in prevalence from 10 to 25 yr duration, whereas females show a more constant prevalence across these durations. A further rise in microalbuminuria is seen in males but not females at greater than or equal to 30 yr duration, giving a combined prevalence of microalbuminuria and overt nephropathy at greater than or equal to 30 yr duration of 84% (males) and 59% (females). Distal symmetrical polyneuropathy shows a constant rise with duration and is only marginally higher in men. Prevalence of cardiovascular (coronary and cerebral) disease shows no sex difference, whereas peripheral vascular disease is particularly common in women after 30 yr duration (greater than 30%) compared with men (11%) when determined by ankle/arm blood pressure ratio less than 0.8 at rest or after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Adulto , Albuminuria/epidemiología , Presión Sanguínea , Trastornos Cerebrovasculares/epidemiología , Niño , Enfermedad Coronaria/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/fisiopatología , Angiopatías Diabéticas/epidemiología , Nefropatías Diabéticas/epidemiología , Retinopatía Diabética/epidemiología , Femenino , Humanos , Masculino , Pennsylvania/epidemiología , Prevalencia , Factores de Riesgo , Factores Sexuales , Factores de TiempoRESUMEN
Diabetic autonomic neuropathy (DAN) has been shown to confer a high risk of mortality. The association between DAN and cardiovascular risk factors was examined in a well-defined cohort of 25- to 34-year-old insulin-dependent diabetes mellitus subjects (n = 168) with and without DAN as evaluated by heart rate response to deep breathing, standing, and the Valsalva maneuver. The autonomic tests were performed using both an office-based procedure and a method employed by the Diabetes Control and Complications Trial with analyses performed by the Diabetes Research and Analysis Association, Lexington, Ky. Good agreement was found between the procedures for the assessment modalities of heart rate response to deep breathing. Modeling potential correlates in logistic analyses, where heart rate response to deep breathing was the dependent variable, revealed hypertension status, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and gender (female) to be independent determinants of DAN. These results suggest that traditional cardiovascular risk factors are important correlates of DAN and may relate to both its cause and poor prognosis. Since these results are from a cross-sectional study, prospective follow-up of this cohort will be needed for confirmation.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades Cardiovasculares/complicaciones , Neuropatías Diabéticas/fisiopatología , Adulto , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Colesterol/metabolismo , Estudios de Cohortes , Estudios Transversales , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/fisiopatología , Neuropatías Diabéticas/epidemiología , Femenino , Frecuencia Cardíaca , Humanos , Hipertensión/complicaciones , Incidencia , Masculino , Análisis Multivariante , Análisis de Regresión , Reproducibilidad de los Resultados , Factores de Riesgo , Maniobra de Valsalva/fisiologíaRESUMEN
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)
Asunto(s)
Glucemia/metabolismo , Ritmo Circadiano , Hormonas/sangre , Insulina/sangre , Adolescente , Hormona Adrenocorticotrópica/sangre , Péptido C/sangre , Péptido C/metabolismo , Femenino , Glucagón/sangre , Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/sangre , Insulina/metabolismo , Secreción de Insulina , Masculino , Pubertad/fisiología , Valores de ReferenciaRESUMEN
The natural history of diabetic neuropathy and its risk factors are not well understood, apart from the recognition that prevalence increases with duration and, in many studies, degree of glycemia. The role of potential risk factors was therefore evaluated in a cross-sectional analysis from the baseline examination of the Pittsburgh Epidemiology of Diabetes Complications Study. We present results from the first 400 subjects seen at baseline examination. Neuropathy was determined by a trained internist with a standardized examination and was defined as the presence of at least two of three criteria: abnormal sensory or motor signs, symptoms consistent with neuropathy, and decreased tendon reflexes. The prevalence of neuropathy in this cohort was 34% (18%, 18-29 yr old, 58% greater than or equal to 30 yr old) with no difference by sex. By focusing on subjects greater than or equal to 18 yr old, all significant univariate variables (e.g., duration, glycosylated hemoglobin [HbA1]) were analyzed in 3 multiple logistic regression models: all subjects greater than or equal to 18 yr old and separating the same subjects into two groups based on age (18-29 and greater than or equal to 30 yr). Duration, HbA1, smoking status, and high-density lipoprotein cholesterol were found to be associated with neuropathy in the models for the greater than or equal to 18-yr-old group and the greater than or equal to 30-yr-old group. In the 18- to 29-yr-old group, duration, HbA1, and hypertension status were found to be significantly associated with neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Neuropatías Diabéticas/epidemiología , Adulto , HDL-Colesterol/sangre , Estudios Transversales , Retinopatía Diabética/epidemiología , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Pennsylvania/epidemiología , Prevalencia , Análisis de Regresión , FumarRESUMEN
Higher levels of physical activity have been related to higher concentrations of high density lipoprotein (HDL) cholesterol and lower concentrations of triglycerides. To test the hypothesis that the association between physical activity and the lipoprotein profile is mediated at least in part through increased insulin sensitivity, the authors measured fasting serum levels of HDL cholesterol, triglycerides, insulin, and glucose in 87 men and 83 women (aged 20-24 years) from a population-based survey in Beaver County, Pennsylvania, in 1981-1982. An insulin sensitivity index was calculated as the reciprocal of the insulin and glucose product multiplied by 10,000. Univariate analysis among men indicates that HDL cholesterol was positively related to insulin sensitivity (r = 0.24, p less than 0.05) and to the physical activity score as assessed with Paffenbarger's questionnaire (r = 0.21, p less than 0.05). Insulin sensitivity and physical activity score were positively related (r = 0.14), although not significantly (p = 0.21). Triglycerides were inversely related to both physical activity (r = -0.22, p less than 0.05) and insulin sensitivity (r = -0.19, p = 0.07). No significant findings among women were noted. Multivariate results indicate that the relation between physical activity and the male lipoprotein profile is reduced after controlling for the effects of insulin sensitivity (p greater than 0.10). The authors conclude that in these young men the beneficial effect of physical activity is likely to be partially mediated by increased insulin sensitivity. The lack of findings among women suggests that sex hormones may influence the association between insulin sensitivity and lipoprotein lipids.
Asunto(s)
Glucemia/análisis , HDL-Colesterol/sangre , Insulina/sangre , Esfuerzo Físico , Triglicéridos/sangre , Adulto , Estatura , Peso Corporal , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pennsylvania , Análisis de Regresión , Factores SexualesRESUMEN
The relationship of early retinal changes and subclinical proteinuria to duration and metabolic regulation of insulin-dependent diabetes was studied in 67 children. Retinopathy was found in 25 patients and occurred almost exclusively (96%) in those with duration of disease longer than five years. Glomerular filtration rate was normal or increased in all patients. Urinary excretion of beta 2-microglobulin, albumin, transferrin, and IgG was significantly increased in patients, as compared with controls, whereas serum concentrations of these proteins were generally normal. The mechanisms responsible for the hyperexcretion of both large and small proteins are unclear but probably involve both glomerular and tubular dysfunction. Increased urinary protein excretion occurred independently of duration of disease. Retinopathy but not microproteinuria was more common in patients with glycosylated hemoglobin greater than 11% and in those with duration of disease longer than five years. Although a significant association was found between retinopathy and the hyperexcretion of one or more of the large molecular weight proteins, the weight of the evidence suggests that these two sequelae of diabetes differ in their pathogenesis. Long-term follow-up of these patients may provide insight as to their risk of developing more serious retinopathy or nephropathy, and whether good glycemic control may protect against these complications of insulin-dependent diabetes.