ABSTRACT
Of 957 patients with type 1 diabetes without known Addison's disease 1.6% (n = 15) were positive for 21-hydroxylase autoantibodies. Among DQ8/DQ2 heterozygous patients, the percentage expressing 21-hydroxylase autoantibodies was 5% (10 of 208) vs. less than 0.5% of patients with neither DQ8 nor DQ2. Three of the diabetic patients found to have 21-hydroxylase autoantibodies on screening were subsequently diagnosed with Addison's disease. Overall, the genotype DQ8/DQ2, consisting of DRB1*0404/DQ8 with DRB1*0301/DQ2, was present in 14 of 21 patients with Addison's disease (8 of 12 with diabetes and 6 of 9 without diabetes or antiislet autoantibodies) vs. 0.7% of the general population (109 of 15,547; P < 10(-6)) and 11% of patients with DM without Addison's disease (62 of 578; P < 10(-6)). Among patients with diabetes with DQ8, Addison's disease was strongly associated with the specific DRB1 subtype, DRB1*0404 (8 of 9 patients from 8 families, in contrast to only 109 of 408 DQ8 DM patients with diabetes without Addison's disease having DRB1*0404; P < 0.001). Among 21-hydroxylase autoantibody-positive DQ8 patients, 80% with DRB1*0404 (12 of 15) had Addison's disease, in contrast to 1 of 10 autoantibody-positive patients with DRB1*0401 or DRB1*0402 (P < 0.001). We conclude that patients with DRB1*0404 and 21-hydroxylase autoantibodies are at high risk for Addison's disease. Patients with DRB1*0401 and DRB1*0402 have more limited progression to Addison's disease despite the presence of 21-hydroxylase autoantibodies.
Subject(s)
Addison Disease/etiology , Alleles , Autoantibodies/blood , Diabetes Mellitus, Type 1/immunology , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Steroid 21-Hydroxylase/immunology , Addison Disease/genetics , Adolescent , Adult , Child , Child, Preschool , Diabetes Mellitus, Type 1/genetics , HLA-DRB1 Chains , Humans , Infant , Middle Aged , RiskABSTRACT
OBJECTIVE: The purpose of this study was to define the correlation between HbA1c values and the percentage of home blood glucose (HBG) measurements within given ranges in a pie chart in three age-groups of subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: HbA1c values were compared with HBG measurements in subjects who did at least three blood glucose tests per day over 30 days in three age groups: 5-11, 12-16, and 17-35 years. The blood glucose values were arbitrarily divided into three groups, defined as the percentage of HBG measurements within, above, and below target range. Each range was then compared with the corresponding HbA1c value. Longitudinal data were also collected for 279 of the subjects after a mean of 139 days. RESULTS: A strong correlation (P = 0.001) was found between HbA1c values and the average blood glucose, and also with the percentage of HBG measurements within, above, and below target range in each of the three age-groups (P < 0.001). Analyses of longitudinal data showed a strong correlation of the changes in HbA1c values to the changes in blood glucose values. CONCLUSIONS: These data showed that a pie-shaped graph of the HBG data can be useful as a clinical parameter in helping patients and families attain desired HbA1c values.
Subject(s)
Blood Glucose/metabolism , Glycated Hemoglobin/metabolism , Adolescent , Adult , Blood Glucose Self-Monitoring , Child , Child, Preschool , Data Interpretation, Statistical , Diabetes Mellitus, Type 1/blood , Female , Humans , MaleSubject(s)
Cocaine/antagonists & inhibitors , Neuropeptides/pharmacology , Peptides, Cyclic/pharmacology , Animals , Body Temperature/drug effects , Catalepsy/chemically induced , Cocaine/pharmacology , Haloperidol/pharmacology , Motor Activity/drug effects , Rats , Stereotyped Behavior/drug effectsABSTRACT
Ethanol withdrawal symptoms in clinical populations are observed to occur in unique clusters which differ in time of onset relative to the time of withdrawal and in their duration. Since periods of mild symptoms are sometimes observed between these clusters of more severe symptoms, the symptom clusters may reflect separate periods of hyperexcitability during which times different neuronal mechanisms are involved. To investigate this possibility in an animal model of ethanol withdrawal, rats were chronically exposed to ethanol in vapor inhalation chambers. Upon withdrawal from this exposure regimen, the time course of spontaneous seizure activity was observed for a period of 84 hr and compared to sensitivity to seizures elicited by audiogenic stimuli or by the convulsant drug picrotoxin. Spontaneous seizure events were observed to occur in clusters, and these clusters were differentially correlated with periods of increased sensitivity to induced seizure activity. These results further support the suggestion that seizure sensitivity during ethanol withdrawal may indicate the involvement of multiple, independent, neuronal mechanisms.