Disease In First-degree Relatives Research Articles

Familial prevalence among first-degree relatives of celiac disease in North India

Background and objectives Prevalence of celiac disease is increased in first-degree relatives with reported prevalence rates in the west between 2.8 and 10%. Paucity of similar data from Asia and the Indian subcontinent prompted us to determine the familial prevalence of celiac disease in first-degree relatives of patients diagnosed with this disorder in Northern India. Methods One hundred sixty-nine first-degree relatives (66 parents, 71 siblings and 32 children) of 53 probands were screened by using anti tissue transglutaminase antibodies. Duodenal biopsy was performed in all seropositive relatives and graded as per Marsh classification. Patients with both positive serology and biopsy suggestive of celiac disease were classified as typical celiac disease whereas those with only positive serology were classified as potential celiacs. Results The prevalence of celiac disease among first-degree relatives was 8.2% (14/169). The prevalence of celiac disease among siblings (15.6%) was much higher as compared to that in parents (3.5%) and offspring (3%). More than one family member was affected in 23% (12/53) of families. Of 14 new cases detected by targeted screening, 11 (78%) were overtly symptomatic with either chronic diarrhoea (8) or easy fatiguability (3). Growth retardation was seen in all six newly diagnosed children, three of whom (22%) were otherwise asymptomatic. Eight members detected to be seropositive had minimal changes on duodenal biopsy (Marsh I and II) suggesting that they have potential celiac disease. Conclusion Familial prevalence of celiac disease in North India is similar to the data from the West. However unlike the situation in the West, the overwhelming majority of first-degree relatives in India are overtly symptomatic with majority having chronic diarrhoea. Since gluten restriction is a highly effective treatment modality, early detection of these patients would result in significant improvement in quality of life as manifested by cessation of diarrhoea and improvement in growth and lab parameters. Our data strongly supports the targeted screening of all first-degree relatives of celiac disease patients in north India.

Familial risks of hospitalization for Parkinson’s disease in first-degree relatives: a nationwide follow-up study from Sweden

The aim of this study was to estimate familial risks of Parkinson's disease (PD) in first-degree relatives of probands with PD compared with first-degree relatives of control probands. Standardized incidence ratios (SIRs) of PD were estimated in the total Swedish population for the period January 1, 1987 to December 31, 2001. SIRs were calculated by age, sex, occupation, geographic region, family size, and type of related proband on the basis of first hospital diagnoses of PD during the study period. Results showed that during the study period, there were 65 cases of first-degree relatives who were hospitalized for PD out of the total 13,276 events (first hospital diagnoses of PD) between 1987 and 2001. Age-specific analyses of familial PD revealed that there was no apparent difference in SIRs by age category. Overall, significant SIRs for PD in first-degree relatives were 3.1 (95% CI 2.1-4.3) for men and 4.0 (95% CI 2.8-5.7) for women. When the related PD proband was a sibling, the SIR was significantly higher (8.7) than when the related proband was a parent (SIR=2.9, p=0.01) or a child (SIR=3.6, p=0.04). For spouses, no increased risks were found. In conclusion, the findings of the present study suggest that genetic factors are important in early- (age < or =50 years) and later (age >50 years) onset PD, and that shared environmental factors during childhood or recessive effects may partly be important for familial aggregation of the disease.

Polycystic Ovary Syndrome: The influence of environmental and genetic factors

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder characterized by hyperandrogenemia, hyperinsulinemia, insulin resistance, and chronic anovulation. It is the most common endocrine disorder in women of reproductive age with an enigmatic pathophysiologic and molecular basis. The high prevalence of affected individuals and the wide range of phenotypic expression can be explained by the interaction of a number of key genes with environmental factors. Heritability of PCOS has been inferred from studies of the syndrome in various population groups (ethnic groups, twins, and PCOS families). Although evidence of familial segregation and clustering of the disease in first-degree relatives of women diagnosed with PCOS has been presented, no particular pattern of inheritance has emerged. Some of the problems in genetic studies have been the lack of uniform criteria for diagnosis, heterogeneity of phenotypic features, and the fact that the disorder is only expressed clinically in women during their reproductive years. Even within affected families and between sisters with polycystic ovaries, there is heterogeneity in presentation. However, regardless of diagnostic criteria used to identify the propositus and to determine affected status in the kindred, the genetic studies available suggest a strong familial component. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants and environmental factors, during either prenatal or postnatal life.

Creatine as a Potential Treatment for Amyotrophic Lateral Sclerosis

Key words: Creatine; amyotrophic lateral sclerosis; clinical trials; neurotherapeutics; transgenic mouse models; ALS functional rating scale. Introduction Amyotrophic lateral sclerosis (ALS) is a rare degenerative disorder of large motor neurons that results in progressive wasting and paralysis of voluntary muscles of the extremities, bulbar regions and respiratory apparatus (Rowland, 1994; Mulder, 1982). The incidence of ALS is currently approximately 2/100 000/year (Chio & Silani, 2001; Haverkamp et al ., 1995) with a prevalence of approximately 5/100 000. The lifetime ALS risk is 1 in 600 to 1 in 1000. Fifty percent of ALS cases die within 3 years of onset of symptoms and 90% die within 5 years (Shefner, 1996; Kurtzke & Kurland, 1989). The median age of onset is 55 years. In sporadic disease, males are at slightly greater risk, while the male/female ratio is 1 : 1 in most cases of familial disease. Ten Percent of patients have a history of the disease in first degree relatives; about 20% of these patients have a mutation in the gene encoding cytosolic copper–zinc superoxide dismutase (SOD1) have been robustly identified as causing typical familial ALS (fALS) (Rosen et al ., 1993). Patients with ALS typically present with focal weakness of an arm, a leg, or of facial and bulbar muscles. The weakness typically progresses regionally and ultimately involves all muscles of voluntary movement. Both lower motor neurons (spinal) and upper (cortical) motor neurons are involved, so that patients display signs of atrophy, fasciculations, cramps and weakness in combination with spasticity, increased stretch reflexes and incoordination. Although there is sometimes pathologic evidence of sensory neuron loss, clinically, sensory signs are sparse or absent (Shefner et al ., 1991).

Nicotinamide protected first-phase insulin response (FPIR) and prevented clinical disease in first-degree relatives of type-1 diabetics

Background After a study of ICA prevalence among relatives of Type-1 diabetics (DM1) in Santiago, Chile, parents of those who tested positive asked us to go on forward with an intervention study. Methods We had screened 1021 relatives, of which 30 had shown ICA ≥ 20 JDF units (2.9%). Among the 26/30 who participated in the intervention study, the baseline screening showed normal glucose tolerance in all, and the first-phase insulin response (FPIR) was normal in 24/26 individuals, which were randomized into Nicotinamide ( n = 12; oral Nicotinamide, 1200 mg m −2 day −1) and Placebo ( n = 12) groups. The FPIRs and ICAs were monitored yearly. Compliance was monitored by urine Nicotinamide. Results The 1.5, 3.0 and 5-year life-table estimates of keeping the FPIR ≥ 10th centile were, for Nicotinamide group 100% in all time points, and for Placebo these were 90.0% (c.i. = 100–71.4), 72.0% (c.i. = 100–37.1) and 0.0% (c.i. = 0.0–0.0) ( p = 0.0091). The 5-year life-table estimates of remaining diabetes-free were 100% for Nicotinamide and 62.5% for Placebo ( p = 0.0483). No adverse effects were observed. Conclusions Oral Nicotinamide protected beta-cell function and prevented clinical disease in ICA-positive first-degree relatives of type-1 diabetes.

Identification of mildly oxidized low-density lipoprotein (electronegative LDL) and its auto-antibodies IgG in children and adolescents hypercholesterolemic offsprings

Background Oxidative modification of low-density lipoproteins (LDL) is an essential step in atherogenesis, generating minimally oxidized LDL, also called electronegative LDL [LDL(−)], which has chemotactic, cytotoxic and immunogenic properties. Methods and results Serum LDL(−) and anti-LDL(−) auto-antibodies (IgG) were evaluated in 28 children and adolescents with familial hypercholesterolemia (FH) antecedents, with or without early coronary artery disease in first-degree relatives (eCAD), hypercholesterolemic (hc) or normocholesterolemic (nc) versus a control group of normocholesterolemic children without pathologic antecedents (C). ELISA method was used for detection of LDL(−) and anti-LDL(−) IgG. LDL(−) serum levels did not differ among the four groups (FH-eCAD-hc 41.4 ± 24.9 μg/dl; FH-hc 38.3 ± 11.2 μg/dl; FH-nc 47.3 ± 17.0 μg/dl and C 44.2 ± 28.8 μg/dl, p = 0.659). However, IgG anti-LDL(−) auto-antibodies were significantly higher in the control group in comparison to the FH groups with or without eCAD, independent of hypercholesterolemia or normocholesterolemia (FH-eCAD-hc 0.825 ± 0.289 μg/dl; FH-hc 0.667 ± 0.307 μg/dl; FH-nc 0.763 ± 0.204 μg/dl and C 1.105 ± 0.233 μg/dl, p = 0.006). When the auto-antibodies of groups with FH, with or without eCAD and with or without hypercholesterolemia were compared, no differences were found ( p = 0.509). Conclusion These results showed that FH and/or eCAD children and adolescents have lower titers of auto-antibodies anti-LDL(−) than children from normal families, independent of serum LDL-cholesterol or serum LDL(−).

Clinical presentation of celiac disease in the pediatric population

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains (including wheat, rye, and barley) in genetically susceptible individuals. CD is associated with HLA molecules DQ2 (90%-95%) and DQ8 (5%-10%), and in the continued presence of gluten the disease is self-perpetuating. CD is one of the most common lifelong disorders worldwide and is characterized by a variety of clinical presentations. These include the typical malabsorption syndrome (classic symptoms) and a spectrum of symptoms potentially affecting any organ or body system (nonclassic symptoms). Because CD often is atypical or even clinically silent, many cases go undiagnosed and are exposed to the risk of long-term complications. There is growing interest in the social aspects of CD because the burden of illness related to this condition is doubtless higher than previously thought.

Prevalence of gallstone disease in first-degree relatives of patients with cholelithiasis

To evaluate the influence of familiality on the prevalence of gallstone disease (GD) in Italy. Families of 79 subjects with gallstones (cases) and of 79 subjects without gallstones (controls) were investigated for the presence of gallstones by ultrasonography. Index cases and index controls were matched for age, sex, and operative unit. Sixty-three and sixty-two husbands and wives of index cases and index controls, respectively, were also studied. Overall, the prevalence of GD was significantly higher (c2=14.52, P<0.001) in the 202 first-degree relatives of subjects with gallstones than that in the 201 first-degree relatives of subjects without gallstones (28.6% vs 12.4%, relative risk (RR) 1.80, 95% confidence interval (CI) 1.29-2.63). In particular, prevalence of GD was significantly higher in mothers, fathers, and sisters of index cases than that in the respective family members of index controls. The highest RR was observed in mothers (RR=2.35, 95%CI 1.38-4.3). Prevalence of GD was not obviously different in brothers and also in husbands and wives of index cases and index controls. Family members of index cases did not differ from family members of control cases with respect to the most important risk factors for gallstones (age, diabetes, BMI, and number of pregnancies) with an exception of a higher prevalence of diabetes in fathers of index controls than in fathers of index cases. This study confirms that familiality plays a very important role in the pathogenesis of gallstones.

Familial clustering of autoimmune diseases in patients with dilated cardiomyopathy

In this study, we examined the hypothesis that dilated cardiomyopathy (DCM) shares genetic risk factors with other diseases of presumed autoimmune etiology, and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases. In accordance with this hypothesis, we showed an increased prevalence of autoimmune diseases in first-degree relatives of patients with DCM. Also, T-cell activation, as reflected in high levels of the soluble interleukin-2 receptor, appears to identify patients with DCM with a clustering of autoimmune diseases.

Increased Prevalence of Autoimmune Diseases in First-Degree Relatives of Patients With Celiac Disease

The prevalence of autoimmune disorders is increased in patients with celiac disease (CD), and it is unknown whether their first-degree relatives also have a high risk of autoimmune disorders. To assess the prevalence of autoimmune diseases in first-degree relatives of CD patients, the authors looked for autoimmune disorders in 225 first-degree relatives of 66 children with CD (group A) and in 232 first-degree relatives of 68 healthy children (group B). For both groups, serologic screening for CD was performed through antiendomysium (EMA) and tissue transglutaminase autoantibodies (tTGAA). EMA- and tTGAA-positive subjects were offered an intestinal biopsy. The age at onset of autoimmune diseases was also recorded in group A. The prevalence of autoimmune disorders was significantly (P = 0.028) higher in group A (11 of 225, 4.8%) than in group B (2 of 232, 0.86%). In relatives of CD patients, the prevalence increased with age (chi2 for trend, 43.5; P < 0.0001). Serologic screening for CD was only positive in group A (15 of 225 subjects). An intestinal biopsy was performed in 13 of these 15 relatives (2 refused biopsy). Eleven of 13 had flat mucosa, with subclinical or silent forms of CD. The prevalence of autoimmune diseases in the EMA- and tTGAA-positive relatives of CD patients was significantly higher (3 of 15, 20%; P = 0.028; odds ratio, 6.3; 95% CI, 1/0.21-1/0.11, 4.9-7.6) than in those who were EMA and tTGAA negative (8/210, 3.8%). The first-degree relatives of CD patients have an increased risk of autoimmune diseases, most likely connected with unrecognized subclinical or silent forms of CD.

Echogenicity of the substantia nigra in relatives of patients with sporadic Parkinson’s disease

Increased echogenicity of the substantia nigra (SN) on ultrasound is a typical sonographic finding in Parkinson’s disease (PD). Sonographic signal intensity of the SN is related to tissue iron content with higher iron level being associated with increased echogenicity. Recent findings indicate that hyperechogenicity of the SN represents an important susceptibility factor for nigrostriatal degeneration. In this study we determined the prevalence of a characteristic ultrasound sign of Parkinson’s disease in first-degree relatives of PD patients. Fourteen patients with sporadic PD and 58 of their relatives underwent neurological, neuropsychological, and ultrasound examination. In addition, four pairs of relatives (one member of each pair exhibiting increased echogenicity of the SN and the other with regular SN echogenicity) underwent 18F-Dopa PET examination. On transcranial sonography, 26 of the 58 relatives exhibited SN hyperechogenicity. Twenty-four relatives showed minor signs of motor slowing. Relatives with SN hyperechogenicity more often showed signs of hypokinesia (16 v 8 relatives; U test, P = 0.01) and impaired executive functions (Tower of London task, problems solved with the minimum number of moves; U test, P = 0.012) than relatives without this echo pattern. In addition, 18F-Dopa uptake (influx constants) at the putamen was reduced in subjects with SN hyperechogenicity compared to their relatives without this ultrasound sign (Wilcoxon, P = 0.03). In conclusion, approximately 45% of relatives of PD patients exhibited an increased echogenicity of the SN. This sign is associated with clinical findings and objective measurements, indicating some degree of impaired nigrostriatal function.

Targeted Screening For Prostate Cancer In High Risk Families: Early Onset Is A Significant Risk Factor For Disease In First Degree Relatives

Targeted screening for prostate cancer in high risk families is generally suggested by ages 40 to 45 years in first degree relatives. We support this concept by reporting higher risk and earlier onset of the disease in these families. We proposed serum prostate specific antigen (PSA) testing in 40 to 70-year-old first degree relatives of 435 patients with prostate cancer treated between July 1994 and June 1997. A previous systematic genealogical analysis allowed us to define the familial prostate cancer status of each patient as sporadic or familial. Of the 747 potential candidates 442 (59%) accepted into the study have been screened, including 240 who were 40 to 49 years old (mean age 44.8) and 202 who were 50 to 70 years old (mean age 57.4). Two of the 240 subjects (0.8%) had PSA greater than 4 ng./ml. in the 40 to 49-year-old group. Prostate biopsies were negative in 1 relative but diagnostic for prostate cancer in the other. In the 50 to 70-year-old group 25 of 202 subjects (12.4%) had a PSA of greater than 4 ng./ml. Prostate cancer was diagnosed in 9 individuals (4.5%), 9 had negative biopsy results, 1 died before biopsy and 6 refused biopsy. The proportion of relatives with PSA greater than 4 ng./ml. and prostate cancer detection was not different according to familial status (sporadic or familial) but it was significantly higher in first degree relatives with early onset prostate cancer in the family at ages younger than 65 years (p = 0.037 and 0.012, respectively). Our results emphasize the usefulness of PSA screening in high risk families, including those without obvious hereditary features. Furthermore, early onset prostate cancer is a significant risk factor for prostate cancer in first degree relatives.

Lifestyle and Other Risk Factors for Thyroid Cancer in Los Angeles County Females

PURPOSE AND METHODS: We conducted a population-based case-control study of thyroid cancer. Cases were 292 women, aged 15–54 when diagnosed between the years 1980 and 1983 (145 diagnosed in 1980–81 and 147 diagnosed in 1982–83). Female neighborhood controls ( n = 292) were matched to each case on birth-year and race. RESULTS: Among women < 35 years, thyroid disease in first-degree relatives increased thyroid cancer risk [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.1–3.7]. Risk was not associated with fish consumption, although high childhood consumption of shellfish decreased thyroid cancer risk (OR = 0.2, 95% CI = 0.05–0.7 for consumption at least a few times weekly). Among papillary thyroid cancers (82% of cases), frequent adult consumption of saltwater fish decreased risk. Cancer risk was reduced with consumption of certain vegetables, wine, and tea. Other dietary variables, including milk, beer and hard liquor, and coffee were not related to thyroid cancer risk. Among the papillary sample, risk increased with longer use of multivitamins (OR = 2.9, 95% CI = 1.2–7.4 for > 10 years of use). Smoking and body mass were not associated with thyroid cancer risk. CONCLUSIONS: These results suggest a role of family history of thyroid disease and certain dietary variables in the etiology of thyroid cancer in adult females.

Review: breast cancer is associated with a family history of the disease in first degree relatives

Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986...

Gallstones: genetics versus environment.

The aim of this study was to determine if a significant genetic component contributes to the pathogenesis of symptomatic gallstones. Gallstones represent a polygenic disorder that affects more than 30,000,000 Americans and results in more than 750,000 cholecystectomies in the United States annually. Risk factors include age, gender, race, parity, obesity, and diabetes. A family history of gallstones also has been identified as a risk factor suggesting that genetics play a role in gallstone formation. However, the role of genetics in the pathogenesis of gallstone formation has not been determined. A gallbladder disease-specific questionnaire was administered to 904 healthy unrelated adult volunteers (association study). The questionnaire ascertained a history of cholecystectomy and gallstone disease in first-degree relatives, as well as medical history, demographic, and anthropometric data. A logistic regression model was used to identify risk factors for symptomatic gallstone disease in a multivariate analysis. A maximum likelihood based variance decomposition approach was then used in 1,038 individuals from 358 families (family study) to estimate the additive genetic heritability of symptomatic gallstone disease. In the association study significant risk factors for symptomatic gallstone disease were female gender (relative risk 8.8, P <.003), obesity (BMI > 30, relative risk 3.7, P <.001), age > 50 (relative risk 2.5, P <.001), and a positive family history of previous cholecystectomy in a first-degree family member (relative risk 2.2, P <.01). In the family study the additive genetic heritability of symptomatic gallstones was 29% (P <.02), age and gender were significant covariates and explained 9.3% of the phenotypic variation in gallbladder disease. These data suggest that genetic factors are responsible for at least 30% of symptomatic gallstone disease. However, the true role of heredity in gallstone pathogenesis is probably higher because data based on symptomatic gallbladder disease underestimates the true prevalence in the population.

Factores de riesgo relacionados con lupus eritematoso sistémico en población mexicana

To assess risk factors associated with systemic lupus erythematosus (SLE) in the Mexican population. A case-control study was conducted on June 1996, at the Reumathology Clinic of Hospital de Especialidades del Centro Médico Nacional Siglo XXI (HE CMN), Instituto Mexicano del Seguro Social, in Mexico City. Cases were one hundred thirty subjects with four or more SLE criteria and disease evolution of +/- 5 years. Controls were hospitalized patients with acute diseases but without autoimmune diseases. Cases and controls were matched 1:1 by age and gender; both groups were evaluated by direct interview through a structured questionnaire. The following risk factors were assessed: genetic family history of SLE and connective tissue disease; socioedemographic (ethnicity, geographic distribution, education, monthly income); hormonal (use of oral contraceptives, replacement therapy and gynecoobstetric background); environmental (use of hair products, living with dogs, bacterial/viral infections, and allergies). Statistical analysis consisted of odd ratios (OR) with 95% confidence intervals (CI) and multivariate analysis using logistic regression. The multivariate model showed association with family history of SLE (OR 4.2, CI 95% 1.17-15.2), family history of connective tissue disorder (OR 2.6, CI 95% 1.15-4.5), use of oral contraceptives for more than one year (OR 2.1, CI 95% 1.13-4.3), repetitive pharyngitis (OR 2.1, CI 95% 1.18-3.6), and use of medications (OR 5.0 IC 95% 1.62-21.6). No association was found with socieconomic status, hair dye products, asthma, or allergies. Genetic factors, such as family history of SLE and connective tissue disease in first-degree relatives, persist as important factors in the development of SLE. Other factors, such as use of some drugs, oral contraceptives, and repetitive pharyngitis, may also favor the onset of disease in genetically susceptible hosts. The English version of this paper is available at: http://www.insp.mx/salud/index.html.

Review: breast cancer is associated with a family history of the disease in first degree relatives

Review: breast cancer is associated with a family history of the disease in first degree relatives

Colonoscopy: Evaluating Indications and Diagnostic Yield

Colonoscopic procedure is an accepted modality for the evaluation of colonic disease. Open-access versus restricted-access colonoscopy has been argued over in the recent literature. The aim of this retrospective analysis is to identify the yield of the major indications for the procedure, and the pattern of colon pathology in our community. We retrospectively analyzed our experience in 3000 colonoscopies over a five-year period. The patients comprised 1145 females (38%) and 1855 males (62%), and their ages ranged from 9 months to 95 years (mean 39.2). There were 2283 patients (76%) who were aged less than 55 years. Complete examination to the cecum was possible in 2850 cases (95%). Pathological findings were identified in 640 patients (21%). The diagnostic yield of patients referred for lower abdominal pain and surveillance was low, at 7% and 17%, respectively. The yield was high for those with lower gastrointestinal bleeding (47%), non-bloody diarrhea (35%), iron deficiency anemia (30%), mass lesions identified by radiology (53%), and polyps identified by radiology (70%). Inflammatory bowel disease was diagnosed in 220 patients, carcinoma in 64 patients, and colonic polyps in 139 patients. Colonic diseases are not uncommon in our part of the world. Colonoscopy is a rewarding procedure in those patients referred with lower gastrointestinal bleeding, mass lesions, polyps and diarrhea. The procedure is less rewarding in patients with lower abdominal pain and in those undergoing surveillance colonoscopy. Patient selection on the basis of the presenting complaint may help to utilize the limited resources available to gastroenterologists. About 63% of the procedures were done for indications found to have a low yield. Inflammatory bowel disease is seen with increasing frequency in our population.

Hypertrophic Cardiomyopathy

ypertrophic cardiomyopathy (HCM) is a fascinatingdisease that has intrigued and challenged cardiolo-gists for decades. Initially a diagnosis made bymaster clinicians adept at translating bedside dynamic aus-cultation into hemodynamic pathophysiology, HCM contin-ues to challenge the frontiers of diagnosis and technology.The development of 2D and Doppler echocardiography pro-vided the greatest increment in understanding the complexityof HCM. While clinicians at large became skilled at thebedside detection of dynamic left ventricular outflow obstruc-tion, echocardiography revealed that many more patients hadunexplained left ventricular hypertrophy (LVH) consistentwith HCM but without evidence of obstruction. In fact, thenonobstructive, “silent” forms are more frequent than theobstructive, “noisy” variants. The pattern and severity ofLVH are now appreciated as heterogeneous and diastolicdysfunction as highly prevalent.

Factores de riesgo y prevención en diabetes mellitus tipo I: Actualización

Insulin dependent diabetes mellitus (IDDM) or type 1 is the result of a long immunological process resulting in destruction of pancreatic islet beta cells. Inspite of medical advances a cure for the disease has not been achieved. This prompts the importance of attempts to prevent the disease in first degree relatives whose risk of developing IDDM is 20 times greater than the general population. Any attempt to modify the immune system that may alter the disease´s natural history must first identify susceptibles individuals. To this end the presence of anti-islet antibodies is determined. In those who tested positive (35%) it is measured the first phase of insulin secretion in response to an iv glucose load. Individuals with a greater risk of developing IDDM are those who are antibody positive and a FPIR of less than the 10th centile of the reference population. This protocol has been applied to first degree relatives of patients with IDDM in 2 controlled prospective multicentre clinical trials taking place at this moment. The European trial (ENDIT) is using nicotinamide and has recluted more than 40,000 subjects, while the American protocol, the Diabetes Prevention trail of DM type 1 (DPT-1) use oral or subcutaneous insulin according to the risk of developing IDDM. In this trial are participating more than 80,000 subjects, the results of which are expected in 2003-4. There are hopes that the results of this trials help to answer the question, if it is possible to alter the biological destiny of a person, and prevent or retard the development of IDDM in susceptible individuals.