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Biomedical subjects

F Santeusanio

Publications and source records attributed to F Santeusanio.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cerebrovascular reactivity and hypercapnic respiratory drive in diabetic autonomic neuropathy.

Because abnormalities in cerebrovascular reactivity (CVR) in subjects with long-term diabetes could partly be ascribed to autonomic neuropathy and related to central chemosensitivity, CVR and the respiratory drive output during progressive hypercapnia were studied in 15 diabetic patients without (DAN-) and 30 with autonomic neuropathy (DAN+), of whom 15 had postural hypotension (PH) (DAN+PH+) and 15 did not (DAN+PH-), and in 15 control (C) subjects. During CO(2) rebreathing, changes in occlusion pressure and minute ventilation were assessed, and seven subjects in each group had simultaneous measurements of the middle cerebral artery mean blood velocity (MCAV) by transcranial Doppler. The respiratory output to CO(2) was greater in DAN+PH+ than in DAN+PH- and DAN- (P < 0.01), whereas a reduced chemosensitivity was found in DAN+PH- (P < 0.05 vs. C). MCAV increased linearly with the end-tidal PCO(2) (PET(CO(2))) in DAN+PH- but less than in C and DAN- (P < 0.01). In contrast, DAN+PH+ showed an exponential increment in MCAV with PET(CO(2)) mainly >55 Torr. Thus CVR was lower in DAN+ than in C at PET(CO(2)) <55 Torr (P < 0.01), whereas it was greater in DAN+PH+ than in DAN+PH- (P < 0.01) and DAN- (P < 0.05) at PET(CO(2)) >55 Torr. CVR and occlusion pressure during hypercapnia were correlated only in DAN+ (r = 0.91, P < 0.001). We conclude that, in diabetic patients with autonomic neuropathy, CVR to CO(2) is reduced or increased according to the severity of dysautonomy and intensity of stimulus and appears to modulate the hypercapnic respiratory drive.

Adult↗
PubMed2001

Cigarette smoking: a risk factor for erectile dysfunction in diabetics.

OBJECTIVES: Diabetes is one of the systemic disorders most frequently associated with erectile dysfunction (ED). An extensive literature documents well the relationship between ED and several factors related to diabetic pathology, but the role of risk factors mainly related to life-style, e.g. cigarette smoking, is still not defined. METHODS: Eligible for the study were men aged 20-70 years with a diagnosis of insulin-dependent (type 1---IDDM) or non-insulin-dependent (type 2--NIDDM) diabetes who were observed on randomly selected days in 178 diabetes centers in Italy. ED was defined as a failure to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: The study population consisted of 9,670 diabetic men. Of these 2,962 (30%) were never smokers, 2,877 (30%) current smokers and 3,831 (40%) ex-smokers. After taking into account the effect of age, the odds ratios of ED in comparison with never smokers was 1.4 (95% confidence interval 1.3-1.6) for smokers and 1.5 (95% confidence interval 1.3-1.6) for ex-smokers. Duration and intensity of the smoking habit was associated with an increased risk of ED. Among ex-smokers, the risk of ED significantly decreased; with increase in the number of years since the patient quit smoking. CONCLUSION: The study offers an assessment of the association between smoking habit and ED and its potential interaction with other risk factors in diabetic men.

Adult↗
PubMed2001

Two distinct MICA gene markers discriminate major autoimmune diabetes types.

The polymorphism of the major histocompatibility complex class I chain-related A gene is associated with type 1 diabetes mellitus. The major histocompatibility complex class I chain-related A gene 5 allele is significantly more frequent in Caucasian type 1 diabetes mellitus children than in healthy subjects, but no information is available on the association with adult-onset type 1 diabetes mellitus or with the so-called slowly progressive latent autoimmune diabetes of the adult in the same ethnic group. In this study we estimated the frequency of major histocompatibility complex class I chain- related A gene alleles and human leukocyte antigen-DRB1*03-DQA1*0501-DQB1*0201 and human leukocyte antigen-DRB1*04- DQA1*0301-DQB1*0302 in 195 type 1 diabetes mellitus subjects, in 80 latent autoimmune diabetes of the adult subjects, and in 158 healthy subjects from central Italy. Major histocompatibility complex class I chain-related A gene 5 was significantly associated with type 1 diabetes mellitus only in the 1-25 yr age group at diagnosis, and the odds ratio of the simultaneous presence of both major histocompatibility complex class I chain-related A gene 5 and human leukocyte antigen-DRB1*03- DQA1*0501-DQB1*0201 and/or human leukocyte antigen-DRB1*04-DQA1*0301-DQB1*0302 was as high as 54 and higher than 388 when compared with double negative individuals. Adult-onset type 1 diabetes mellitus (age at diagnosis, >25 yr) and latent autoimmune diabetes of the adult were significantly associated with major histocompatibility complex class I chain-related A gene 5.1, which was not significantly increased among diabetic children. Only the combination of major histocompatibility complex class I chain-related A gene 5.1 and human leukocyte antigen-DRB1*03-DQA1*0501-DQB1*0201 and/or human leukocyte antigen-DRB1*04-DQA1*0301-DQB1*0302 conferred increased risk for adult-onset type 1 diabetes mellitus or for latent autoimmune diabetes of the adult. Our study provides demonstration of the existence of distinct genetic markers for childhood/young-onset type 1 diabetes mellitus and for adult-onset type 1 diabetes mellitus/latent autoimmune diabetes of the adult, namely major histocompatibility complex class I chain-related A gene 5 and major histocompatibility complex class I chain-related A gene 5.1, respectively.

Adolescent↗
PubMed2001

Incidence of erectile dysfunction in Italian men with diabetes.

PURPOSE: We determined the incidence of erectile dysfunction in Italian men with diabetes. MATERIALS AND METHODS: We estimated the incidence of erectile dysfunction, defined as failure to achieve and maintain erection sufficient for satisfactory sexual performance, after 2.8 years of followup in 1,010 men enrolled for a prevalence study of erectile dysfunction in diabetes. RESULTS: Of the 1,010 men 192 (19%) complained of erectile dysfunction. The crude incidence rate of erectile dysfunction was 68 cases per 1,000 person-years (95% confidence interval 59 to 77). The incidence of erectile dysfunction increased with increasing age (10-fold higher for ages 70 to 79 than for 19 to 29 years), duration of diabetes (1.6-fold higher a history of 11 years or greater than for less than 5) and deteriorating metabolic control (1.7-fold higher for hemoglobin A1c greater than 9% than less than 7.5%). Moreover, it was higher in type 2 than in type 1 diabetes (74 versus 45 cases per 1,000 person-years). The relative risk was 1.75, 2.02, 1.97, 1.16, 1.86, 3.79 and 1.52 for associated obliterative arterial disease of the lower legs, ischemic heart disease, renal disease, autonomic neuropathy, sensitive and motor neuropathy, diabetic foot and retinal disease, respectively. Of the characteristics at study enrollment patient age, duration of diabetes, renal disease and hypertension were multivariate predictors of the erectile dysfunction 2.8 years later. CONCLUSIONS: The incidence of erectile dysfunction in Italian men with diabetes at a mean followup of 2.8 years was 68 cases per 1,000 person-years, more than 2-fold that in the Massachusetts Male Aging Study of the general population. The knowledge of this incidence should promote specific preventive and therapeutic interventions for erectile dysfunction in men with diabetes.

Adult↗
PubMed2001

Management of erectile dysfunction in diabetic subjects: results from a survey of 400 diabetes centres in Italy.

We report the results of a survey on erectile dysfunction (ED) conducted in 400 Italian Diabetes Centres in 1998. A questionnaire consisting of 10 items was sent to the Centres recorded by the Italian Association of Diabetologists and the Italian Society of Diabetology; 400 Centres returned the completed questionnaire (58%). Forty-nine percent of the Centres declared that they investigated ED systematically but less than half of them (46%) had done it autonomously. The percentage of Centres performing intracavernous injection (ICI) was 84%. This maneuvre was most commonly performed by diabetologists (61%), followed by urologists (29%) and andrologists (18%) (categories are not mutually exclusive). ICI was also the most common type of treatment (85%), followed by oral (32%) and topic (7%) therapies (categories are not mutually exclusive). Slightly more than half of the interviewed Centres (51%) did not investigate ED routinely, attributing this to structural problems, lack of specific training and the availability of more specialised Centres as the main reasons for this. However, the majority of Centres expressed interest in managing ED. Among the available tests for ED, ICI was the most frequently employed. While most Centres seek the collaboration of external specialists to diagnose ED, the diabetologist is the physician who most frequently performs ICI. We conclude that Italian diabetologists need specific training to reach a greater degree of autonomy in the management of ED in their patients.

Community Health Centers↗
PubMed2000

Administration of recombinant human growth hormone on alternate days is sufficient to increase whole body protein synthesis and lipolysis in growth hormone deficient adults.

OBJECTIVE: At present, the duration of the effect of recombinant human growth hormone (rhGH) on the rates of protein synthesis and lipolysis in GH deficient (GHD) adults is unknown. This study was designed to establish the frequency of rhGH administration necessary to provide the beneficial metabolic effects of the hormone in GHD adults. DESIGN AND PATIENTS: Two different studies (A and B) were performed in two groups of five GHD men. In study A, whole body protein and lipid kinetics was determined in the basal state (Bas), 12 (GH12h) and 36 (GH36h) h after the last of seven injections of rhGH (3.3 microg/kg), given at bedtime on alternate days. In study B, the same parameters were determined in the basal state (Bas), 60 (GH60h) and 84 (GH84h) h after the last of seven injections of rhGH (3.3 microg/kg), given at bedtime at 3 day intervals. MEASUREMENTS: The rates of protein metabolism were estimated by infusing [1-13C]leucine, and those of lipolysis by infusing [1,1,2,3, 3-D5]glycerol. RESULTS: Leucine oxidation decreased (P < 0.01) by approximately 30% after GH12h and GH36h but did not change after GH60h and GH84h. Non-oxidative leucine disposal increased after GH12h and GH36h by approximately 13% (P < 0.05) whereas it did not change after GH60h and GH84h. Glycerol appearance increased (P < 0. 01) by approximately 45% after GH12h and GH36h but did not change after GH60h and GH84h. CONCLUSIONS: The effects on protein and lipid metabolism following the injection of rhGH last longer than 36 and less than 60 h. In fact, rhGH administration on alternate days induced a sustained increase in the rates of protein synthesis and lipolysis of GHD adults, whereas a longer interval of administration (3 days) had no effect by 60 h.

Adult↗
PubMed2000

Increased risk for endocrine autoimmunity in Italian type 2 diabetic patients with GAD65 autoantibodies.

OBJECTIVE: Glutamic acid decarboxylase (GAD)65 autoantibodies (GAD65Ab) in type 2 diabetic subjects with secondary failure to sulphonylurea treatment identify the so-called latent autoimmune diabetes of the adult (LADA). The aim of our study was to estimate the risk for endocrine autoimmunity in type 2 diabetic subjects with GAD65Ab. DESIGN AND PATIENTS: We analysed serum samples from 600 adult subjects with a clinical diagnosis of type 2 diabetes mellitus for the presence and levels of GAD65Ab and antibodies directed against the islet autoantigen IA-2/ICA512 (IA-2/ICA512Ab). All the patients had been treated initially with hypoglycaemic agents and/or diet for at least 1 year. GAD65Ab+ subjects were studied for the presence of thyroid peroxidase autoantibodies (TPOAb), 21 hydroxylase autoantibodies (21OHAb) and frequency of HLA class II haplotypes. RESULTS: GAD65Ab were found in 67/600 (11%) and IA-2/ICA512Ab in 12/600 (2%) subjects (P < 0.0001). The presence of GAD65Ab, but not that of IA-2/ICA512Ab, was significantly associated with insulin therapy, low BMI (P < 0.0001) and low basal C-peptide (P < 0.01). Islet-cell antibodies (ICA) were detected in 43/67 (64%) GAD65Ab+ and in 10/12 (83%) IA-2/ICA512Ab + subjects. TPOAb occurred more frequently in GAD65Ab+ (16/67, 24%) than in GAD65Ab-subjects (9/174, 5%) (P < 0.0001). 21OHAb were detected only in GAD65Ab+ subjects (3/67, 4.5%) (P = 0.03 vs. GAD65Ab-subjects). None of the 21OHAb+ subjects had metabolic or clinical signs of adrenal dysfunction. HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) was significantly more frequent in GAD65Ab+ subjects than in healthy controls (OR = 5.42, corrected P < 0.0026). The presence of TPOAb was significantly associated with DR3-DQ2 (P = 0.024). CONCLUSIONS: Our study demonstrates that the presence of GAD65Ab identifies a subgroup of type 2 diabetic patients with high risk for thyroid and adrenal autoimmunity, and that both GAD65Ab and TPOAb are associated with the presence of HLA-DR3-DQ2, in these patients.

Adult↗
PubMed2000

Low dose (1 microg) ACTH test in the evaluation of adrenal dysfunction in pre-clinical Addison's disease.

OBJECTIVE: The presence of 21-hydroxylase autoantibodies (21OHAb) is a marker of adrenal autoimmunity and can be used to identify subjects with pre-clinical Addison's disease. The low-dose (1 microg) ACTH test (LDT) is more sensitive than the high-dose (250 microg) test (HDT) for the diagnosis of pituitary adrenal insufficiency, but no information is available on the use of a LDT in subjects with autoimmune adrenalitis and primary adrenal insufficiency. The aim of our study was to evaluate the clinical use of the LDT in the diagnosis of early adrenocortical dysfunction in patients with adrenal autoantibodies. DESIGN AND METHODS: Firstly, we evaluated the cortisol responses to both a LDT and a HDT in a group of 12 healthy volunteers. We then performed a LDT in 11 subjects positive for 21OHAb, but without clinical signs of Addison's disease identified by screening 920 patients with one or more organ-specific autoimmune diseases. In all cases, the LDT was followed by a sequential HDT which was used as a control test of the sensitivity and specificity of the LDT. RESULTS: In healthy subjects, the peak cortisol levels after the LDT were similar to those after the classical HDT. In 21OHAb-positive subjects, the LDT showed a pathological response in five out of 11 (45%) cases and the diagnostic concordance between the results of the LDT and those of the HDT was 100%. All the five cases with pathological LDT were also positive for adrenal cortex autoantibodies (ACA) and 4/5 had high levels of basal ACTH. One subject with pathological LDT developed clinical Addison's disease 4 months after the test had been performed. CONCLUSIONS: Our study demonstrates that the low dose ACTH test has a high diagnostic sensitivity and specificity for primary adrenal insufficiency and suggests that it can accurately identify subjects with pre-clinical adrenal dysfunction.

Addison Disease↗
PubMed2000

Carbohydrate sources and glycaemic control in Type 1 diabetes mellitus. EURODIAB IDDM Complications Study Group.

AIMS: Little information is available on the relationship between glycated haemoglobin levels and the source or amount of dietary carbohydrate. The present study compares the association of carbohydrate intake with HbA1c between European individuals with Type 1 diabetes mellitus injecting insulin once or twice per day and those with > or = 3 daily injections. METHODS: The relation of carbohydrate intake (total, cereal, fruit, vegetable, milk, and potato carbohydrate assessed by a 3-day dietary record) to HbA1c was examined in 2084 patients (age 32.6 +/- 10.2 years, duration of diabetes 14.8 +/- 9.5 years) included in the EURODIAB Complications Study. RESULTS: In both insulin injection regimens, an increased intake of total carbohydrate (% of energy) and a higher consumption of potato carbohydrates (g) were associated with higher levels of HbA1c, whereas an increased intake of vegetable carbohydrate (g) was inversely related to HbA1c. These tendencies were all more pronounced in persons with one or two daily insulin injections. Consumption of cereal and fruit carbohydrates (g) was not related to HbA1c, irrespective of the insulin injection regimen. A trend of HbA1c to increase with higher intakes of milk carbohydrate was confined to those with one or two insulin injections per day (test for interaction: P = 0.01). CONCLUSIONS: In particular, subjects with only 1 or 2 daily insulin injections per day should receive specific advice to correctly consider milk and potato carbohydrates. On the other hand, people with Type 1 diabetes may profit from a higher consumption of vegetable carbohydrates for their levels of HbA1c.

Adult↗
PubMed2000

Relation between serum uric acid and risk of cardiovascular disease in essential hypertension. The PIUMA study.

The question of serum uric acid as an independent risk factor in subjects with essential hypertension remains controversial. For up to 12 years (mean, 4.0) we followed 1720 subjects with essential hypertension. At entry, all subjects were untreated and all were carefully screened for absence of cardiovascular disease, renal disease, cancer, and other important disease. Outcome measures included total cardiovascular events, fatal cardiovascular events, and all-cause mortality. During 6841 person-years of follow-up there were 184 cardiovascular events (42 fatal) and 80 deaths from all causes. In the 4 quartiles of serum uric acid (division points: 0.268, 0.309, and 0.369 mmol/L [4.5, 5.2, and 6.2 mg/dL] in men; 0.190, 0.232, and 0.274 mmol/L [3.2, 3.9, and 4.6 mg/dL] in women), the rate (per 100 person-years) of cardiovascular events was 2.51, 1.48, 2.66, and 4.27, that of fatal cardiovascular events was 0.41, 0.33, 0.38, and 1.23, and that of all-cause deaths was 1.01, 0.55, 0.93, and 2.01, respectively. The relation between uric acid and event rate was J-shaped in both genders. After adjustment for age, gender, diabetes, total cholesterol/HDL cholesterol ratio, serum creatinine, left ventricular hypertrophy, ambulatory blood pressure, and use of diuretics during follow-up, uric acid levels in the highest quartile were associated with increased risk for cardiovascular events (relative risk, 1.73; 95% CI, 1.01 to 3.00), fatal cardiovascular events (relative risk, 1.96; 95% CI, 1.02 to 3.79), and all-cause mortality (relative risk, 1.63; 95% CI, 1.02 to 2.57) in relation to the second quartile. In untreated subjects with essential hypertension, raised uric acid is a powerful risk marker for subsequent cardiovascular disease and all-cause mortality.

Antihypertensive Agents↗
PubMed2000

Erectile dysfunction in type 1 and type 2 diabetics in Italy. On behalf of Gruppo Italiano Studio Deficit Erettile nei Diabetici.

BACKGROUND: Several studies reported data on the increased risk of erectile dysfunction (ED) in populations of diabetic men, but few presented data separately for Type 1 and Type 2 subjects. No comparison data for these diabetic subgroups are available with regard to risk factors for ED. METHODS: Eligible for the study were men aged 20-69 years with a diagnosis of insulin-dependent (Type 1) or non-insulin-dependent (Type 2) diabetes who were observed on randomly selected days in 178 diabetes centres in Italy. Erectile dysfunction was defined as a failure to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: The study population consisted of 1383 Type 1 and 8373 Type 2 men. The prevalence of ED increased with age for both groups. After taking into account the effect of age Type 2 men (37/100 men) tend to report ED less frequently than Type 1 men (51/100 men). A significant positive relationship was reported between ED and poor metabolic control and smoking for both Type 1 and Type 2 men, whereas high body mass index (BMI) increased only the risk of ED in Type 1 cases. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of ED and its main risk factors in Type 1 and Type 2 diabetic subgroups.

Adult↗
PubMed2000

Impairment of the respiratory system in diabetic autonomic neuropathy.

Diabetic autonomic neuropathy (DAN) may affect up to 30% of the diabetic population. Sometimes DAN becomes clinically manifest causing specific symptoms and signs; more often, however, DAN is responsible for subtle alterations detectable only by functional tests, as in the case of the respiratory system. At first, abnormalities both in the bronchomotor tone and aspecific airway responsiveness to different stimuli were recognised in diabetic patients with DAN, indicating a defective control of mechanisms which regulate the bronchial calibre in these subjects. Subsequently, peculiar changes in breathing pattern and greater ventilatory requirements have been observed during incremental exercise in diabetics with DAN, suggesting an altered control of breathing in stressful conditions. Alterations in either peripheral or central chemosensitivity have been repeatedly shown in these patients, with marked differences related to the severity of DAN, concerning the neuro-muscular and ventilatory responsiveness to CO2. Following anecdotal reports, respiratory disturbances during sleep have been more carefully investigated in diabetic subjects and greater prevalence of sleep apnea, mainly in the obstructive form, has been found in the presence of DAN. The underlying mechanisms of sleep disordered breathing, however, are poorly understood in DAN and further studies are needed to elucidate them.

Autonomic Nervous System Diseases↗
PubMed1999

Circulating insulin and insulin growth factor-1 are independent determinants of left ventricular mass and geometry in essential hypertension.

BACKGROUND: It is unclear whether insulin and insulin-like growth factor-1 (IGF-1) are independent determinants of left ventricular (LV) mass in essential hypertension. METHODS AND RESULTS: We studied 101 never-treated nondiabetic subjects with essential hypertension. All had 24-hour noninvasive ambulatory blood pressure (ABP) monitoring and a 75-g oral glucose tolerance test. We determined fasting glucose, insulin, and IGF-1 and postload glucose and insulin 2 hours after glucose. Insulin resistance was estimated by the homeostasis model assessment (HOMA(IR)) formula. LV mass showed an association with body mass index (BMI) (r=0.47; P<0.01), postload insulin (r=0.54; P<0.01), HOMA(IR) (r=0.39; P<0.01), and IGF-1 (r=0. 43; P<0.01) and a weaker association with average 24-hour systolic and diastolic ABPs (r=0.29 and r=0.26; P<0.05) and basal insulin (r=0.31; P<0.05). Relative wall thickness was positively related to IGF-1 (r=0.39; P<0.01) but not to fasting or 2-hour postload insulin, HOMA(IR), and glucose. In a multiple regression analysis, the final LV mass model (R(2)=0.64) included IGF-1, postload insulin, average 24-hour systolic ABP, sex, and BMI. IGF-1 and postload insulin accounted for >40% of variability of LV mass. The final model (R(2)=0.36) for relative wall thickness included IGF-1 (16% total explained variability), average 24-hour systolic ABP, sex, BMI, and age but not insulin and HOMA(IR). CONCLUSIONS: These data indicate that insulin and IGF-1 are powerful independent determinants of LV mass and geometry in untreated subjects with essential hypertension and normal glucose tolerance.

Adult↗
PubMed1999

Efficacy and safety of acarbose in the treatment of Type 1 diabetes mellitus: a placebo-controlled, double-blind, multicentre study.

AIMS: The aim of the study was to evaluate the efficacy and safety of acarbose in patients with Type 1 diabetes mellitus (DM). METHODS: A multicentre double-blind, randomized, placebo-controlled study was performed. After a 6-week run-in, 121 patients were randomized to acarbose or placebo and to high- or low-fibre diet for 24 weeks. Acarbose dose was 50 mg t.d.s. for the first 2 weeks and 100 mg t.d.s. for the subsequent weeks. RESULTS: At the end of 24 weeks of treatment the intention to treat analysis showed that acarbose compared with placebo decreased 2 h postprandial plasma glucose levels (12.23 +/- 0.83 vs. 14.93 +/- 0.87 mmol/l; F = 6.1, P < 0.02) (least square means +/- SEM). No significant effect of acarbose was recorded on HbA1c or on the number of hypoglycaemic episodes. The effect of acarbose on blood glucose control was not influenced by the amount of carbohydrate and/or fibre intake. The incidence of adverse events were 75% and 39% in acarbose and placebo groups, respectively; they were mild and confined to the gastrointestinal tract. CONCLUSIONS: The use of acarbose in combination with insulin reduces postprandial plasma glucose levels in Type 1 diabetic patients who are not satisfactorily controlled with insulin alone but without significant effect on HbA1c.

Acarbose↗
PubMed1999

Microsatellite polymorphism of the MHC class I chain-related (MIC-A and MIC-B) genes marks the risk for autoimmune Addison's disease.

The major histocompatibility complex class I chain-related MIC-A and MIC-B genes are located on chromosome 6 between the histocompatibility leucocyte antigen (HLA)-B and the B-associated transcript genes. The presence of 21-hydroxylase autoantibodies is a sensitive and specific marker of autoimmune Addison's disease. We studied the polymorphism of exon 5 of the MIC-A gene, of intron 1 of the MIC-B gene, and of HLA-DRB1, -DQA1, and -DQB1 genes in 28 autoimmune (21-hydroxylase autoantibody positive) Addison's disease patients and in 75 healthy subjects from central Italy. The MIC-A5.1 allele was significantly more frequent in Addison's disease patients (79%) than in healthy subjects (36%) [odds ratio (OR) = 6.52, corrected P (Pc) = 0.0015], whereas MIC-A6 was significantly reduced in affected subjects (15% vs. 56%, OR = 0.13, Pc = 0.002). The A5.1/A5.1 genotype had an OR for autoimmune Addison's disease as high as 18.0 and an absolute risk of 1 per 1131. In the presence of MIC-A5.1, MICB-CA-25 was significantly increased in Addison's disease patients (25% vs. 4%, OR = 8.0, P = 0.0039, Pc = 0.047). The MICB-CA-17 allele was absent in Addison's disease patients, but present in more than 25% healthy individuals (OR = 0.10, P = 0.0025, Pc = 0.03). Among HLA-DR and -DQ haplotypes, only DRB1*03-DQA1*0501-DQB1*0201 (DR3/DQ2) was significantly more frequent in Addison's disease patients than in healthy subjects, but only in the presence of MIC-A5.1. The frequency of MIC-A5.1 was significantly increased in Addison's disease patients only in the presence of HLA-DR3-DQ2. Our study demonstrates that susceptibility to autoimmune Addison's disease is linked to the MIC-A microsatellite allele 5.1 and that both MIC-A5.1 and HLA-DR3/DQ2 are necessary to confer increased genetic risk for Addison's disease.

Addison Disease↗