Risk Of Insulin-dependent Diabetes Mellitus Research Articles

Risk factors of Hemorrhagic Stroke- a Case-Control Study in Bangladesh

Background: Spontaneous intracerebral hemorrhage is one of the leading causes of mortality and morbidity. Genetic factors play an important role in this disease. Among the non-genetic causes Hypertension (HTN), IDDM (insulin dependent diabetes mellitus), NIDDM (non-insulin dependent diabetes mellitus), family history of hemorrhagic stroke, smoking, previous history of ischemic stroke, alcohol intake and education level are important. Methods: The aim of the study was to evaluate the association between ICH and non-genetic risk factors. This was a case-control study with 120 participants. The place of the study was in the Neurosurgery department of Sylhet Women’s Medical College Hospital (SWMCH) and the study period was 2 years. Result: Alcohol consumption (RR=3, Odd=3.11) showed highest risk for ICH. Other risk factors of ICH were smoking (RR=2, Odd=2.36), family history (F/H) of ICH (RR=1.3, Odd=1.38), Hypertension (RR=1.1, Odd=1.39) and below 12 class education status (RR=1.08, Odd=1.63). The relative risk of IDDM, NIDDM, previous history (P/H) of ischemic stroke were less than 1. Conclusion: There are few controllable risk factors of hemorrhagic stroke apart from genetic risk factors.

Association of Diabetes Mellitus With Postoperative Complications and Mortality After Non-Cardiac Surgery: A Meta-Analysis and Systematic Review.

BackgroundAlthough a variety of data showing that diabetes mellitus (DM) (Type 1 or Type 2) is associated with postoperative complication, there is still a lack of detailed studies that go through the specific diabetic subgroups. The goal of this meta-analysis is to assess the relationship between DM and various complications after non-cardiac surgery.MethodsWe searched articles published in three mainstream electronic databases (PubMed, EMBASE, Web of science) before November, 2020. A random effects model was conducted since heterogeneity always exist when comparing results between different types of surgery.ResultsThis paper included 125 studies with a total sample size of 3,208,776 participants. DM was a risk factor for any postoperative complication (Odds ratio (OR)=1.653 [1.487, 1.839]). The risk of insulin-dependent DM (OR=1.895 [1.331, 2.698]) was higher than that of non-insulin-dependent DM (OR=1.554 [1.061, 2.277]) for any postoperative complication. DM had a higher risk of infections (OR=1.537 [1.322, 1.787]), wound healing disorders (OR=2.010 [1.326, 3.046]), hematoma (OR=1.369 [1.120, 1.673]), renal insufficiency (OR=1.987 [1.311, 3.013]), myocardial infarction (OR=1.372 [0.574, 3.278]). Meanwhile, DM was a risk factor for postoperative reoperation (OR=1.568 [1.124, 2.188]), readmission (OR=1.404 [1.274, 1.548]) and death (OR=1.606 [1.178, 2.191]).ConclusionsDM is a risk factor for any postoperative complications, hospitalization and death after non-cardiac surgery. These findings underscore the importance of preoperative risk factor assessment of DM for the safe outcome of surgical patients.

Hemoglobin A1c Is a Predictor of New Insulin Dependence After Partial Pancreatectomy: A Multi-Institutional Analysis

BackgroundPancreatic diseases have long been associated with impaired glucose control. This study sought to identify the incidence of new insulin-dependent diabetes mellitus (IDDM) after pancreatectomy and the predictive accuracy of hemoglobin A1c (HbA1c) or blood glucose. MethodsPatients who underwent partial pancreatectomy and had preoperative HbA1c available at two academic institutions were assessed for new IDDM on discharge in relation to complication rates and survival. ResultsOf the 267 patients analyzed, 67% had abnormal HbA1c levels prior to surgery (mean 6.8%, glucose 135 mg/dL). Two hundred eight (77.9%) were not insulin-dependent prior to surgery, and 35 (16.8%) developed new IDDM after resection. On multivariable regression, increasing HbA1c and preoperative glucose were the only significant predictors for new IDDM. Optimal predictive cutoffs (HbA1c of 6.25% and glucose of 121 mg/dL) were determined in a discovery group (n = 143) and confirmed in a validation group (n = 124) with a diagnostic sensitivity of 72.7% and specificity of 84.8%. Patients with new IDDM after resection had higher rates of severe complications (OR 3.39), increased TPN at discharge (OR 4.32), and increased rates of discharge to nursing facilities (OR 2.57) (all P < 0.05). New IDDM was also associated with a decreased cancer-specific survival. ConclusionPreoperative HbA1c ≥ 6.25% and blood glucose ≥ 121 mg/dL can accurately identify patients at increased risk of IDDM. These diagnostics may help identify patients in a preoperative setting that may benefit from interventions such as diabetes education or enhanced glucose control preoperatively.

Autoimmune Diabetes After Initiation of Nivolumab in a Patient With Hepatocellular Carcinoma

Abstract Background: Immune checkpoint inhibitors have become an integral part of oncologic treatment, and their role is rapidly evolving. Nivolumab is an immune checkpoint inhibitor to anti-programmed cell death protein-1 (PD-1), which blocks PD-L1 from binding to PD-1, allowing the T cell to activate. While nivolumab has been shown to improve outcomes in certain malignancies, anti-PD-1 therapy can cause multiple endocrinopathies, including autoimmune diabetes (AD). Case: Here we present a 60-year-old male with a past medical history of end-stage liver disease secondary to hepatitis C and hepatocellular carcinoma (HCC). After undergoing transarterial chemoembolization for HCC, nivolumab was initiated. The patient initially tolerated the immunotherapy well. However, after three cycles, the patient acutely developed nausea, vomiting, lethargy and confusion. On presentation, he was afebrile, blood pressure of 85/46 mmHg, and a heart rate of 92 bpm. Exam was significant for abnormal mentation, and diffuse guarding of the abdomen. Laboratory workup showed hyperglycemia (1,178 mg/dL), positive serum ketones (beta-hydroxybutyrate 11.4 mmol/L), anion gap metabolic acidosis (AG 31, CO2 7 mmol/L), anemia, thrombocytopenia, acute kidney injury, leukocytosis, and elevated lipase. He was admitted to the intensive care unit, and further workup for acute pancreatitis was unrevealing. C-peptide was low (0.8 ng/mL) with corresponding hyperglycemia (1,055 mg/dL). GAD-65, islet cell, and insulin antibodies were undetectable. Hemoglobin A1c was 8.0%. Blood sugars from the previous one and a half years were in normal range. The patient was ultimately diagnosed with DKA and AD secondary to anti-PD-1 therapy. Discussion: This case is representative of AD secondary to nivolumab. While there have been many cases of AD reported after nivolumab, this is the fifth case that has been reported in a patient being treated for HCC. Our patient presented acutely in DKA with no prior diagnosis of diabetes. His antibody testing was undetectable, C-peptide was low in the context of hyperglycemia, and he continued to require insulin therapy until his passing. Prior case reports have demonstrated that the majority of patients with AD related to anti-PD-1 therapy present in DKA, while less than half have detectable diabetes autoantibodies. Specific haplotypes and diabetes autoantibodies have been postulated as risk factors for AD secondary to anti-PD-1 therapy. However, this does not explain the pathology behind a number of patients who have neither of these risk factors. While AD is a rare complication of nivolumab (&amp;lt;1%), this case identifies the need for patients and clinicians to be aware of and discuss the risk of AD after starting nivolumab. Future research is needed to identify risk factors for patients at highest risk of developing AD related to anti-PD-1 therapy and reporting every case encountered is the first step.

Risk of insulin-dependent diabetes mellitus in patients undergoing carotid endarterectomy

ObjectiveThere is conflicting evidence regarding the association of diabetes mellitus (DM) and insulin use with outcomes after carotid endarterectomy (CEA). Therefore, we sought to evaluate the risk of insulin-dependent DM (IDDM) and noninsulin-dependent DM (NIDDM) on 30-day outcomes after CEA. MethodsWe identified patients undergoing CEA from the Targeted Vascular module of the National Surgical Quality Improvement Program (2011-2015) and stratified patients on the basis of their preprocedural symptom status. We compared 30-day outcomes between nondiabetics and patients with NIDDM or IDDM, with 30-day stroke/death as the primary end point. ResultsOf 16,739 CEA patients, 9784 (58%) were asymptomatic, of whom 6720 (69%) had no diagnosis of DM, 1109 (11%) had IDDM, and 1955 (20%) had NIDDM. Of the 6955 symptomatic patients, 4982 (72%) had no diagnosis of DM, 810 (12%) had IDDM, and 1163 (17%) had NIDDM. Among asymptomatic patients, patients with IDDM experienced higher rates of 30-day stroke/death compared with those without DM (3.4% vs 1.5%; P < .001), whereas those with NIDDM experienced rates similar to those of patients without DM (2.1% vs 1.5%; P = .1). Moreover, asymptomatic patients with IDDM and an anatomic high-risk criterion experienced a 30-day stroke/death rate of 6.6%. After adjustment, IDDM was associated with 30-day stroke/death in asymptomatic patients compared with patients without DM (odds ratio, 2.3; 95% confidence interval, 1.5-3.4; P < .001), but NIDDM was not (odds ratio, 1.4; 95% confidence interval, 1.0-2.1; P = .1). In comparison, among symptomatic patients, those with IDDM and NIDDM experienced similar rates of 30-day stroke/death as patients without DM (4.9% vs 3.6% and 4.0% vs 3.6%; both P > .1). After adjustment, neither IDDM nor NIDDM was associated with 30-day stroke/death in symptomatic patients compared with symptomatic patients without DM. ConclusionsRates of 30-day stroke/death after CEA in asymptomatic patients with IDDM exceed international vascular societies' guideline thresholds for acceptable outcomes in asymptomatic patients, especially those with anatomic high-risk criteria. Thus, asymptomatic patients with IDDM may not benefit from CEA, although more data are needed about the natural history of carotid disease in this population.

High Levels of Education Are Associated With an Increased Risk of Latent Autoimmune Diabetes in Adults

OBJECTIVETo investigate whether the risk for autoimmune diabetes in adults differs between socioeconomic groups and to compare such risk with that for type 2 diabetes.RESEARCH DESIGN AND METHODSThe inhabitants of the Norwegian county of Nord-Trøndelag were investigated by questionnaires and clinical examinations on three occasions during 1984–2008. We used information from a subset consisting of 56,296 subjects (participating in at least two surveys), including 122 incident cases of autoimmune diabetes in adults (aged ≥35 and anti-GAD positive) and 1,555 cases of type 2 diabetes (aged ≥35 and anti-GAD negative). Hazard ratios (HRs) of diabetes associated with self-reported education and occupation were estimated by Cox proportional hazards models.RESULTSHigh levels of education (university versus primary school) were associated with an increased risk of autoimmune diabetes (HR 1.98 [95% CI 1.21–3.26]), after adjustment for BMI, lifestyle factors, and family history of diabetes. Case subjects with high levels of education had lower levels of C-peptide, tended to have higher levels of anti-GAD, and were more often treated with insulin. Conversely, these subjects had a reduced risk of type 2 diabetes (HR 0.69 [95% CI 0.57–0.82]), a risk that was partly explained by lower BMI and more physical activity (adjusted HR 0.89 [95% CI 0.74–1.06]).CONCLUSIONSHigh levels of education are associated with an increased risk of autoimmune diabetes in adults, a finding that may be mediated by effects on autoimmune activity. Because the association is not explained by traditional risk factors, other, currently unidentified, environmental factors are likely to be involved.

Risk of autoimmune diabetes in APECED: association with short alleles of the 5′insulin VNTR

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disease causing a wide spectrum of autoimmune dysfunction potentially including diabetes of an autoimmune etiology. We have previously described a pair of discordant APECED siblings and pointed to a possible role of 5'insulin variable number of tandem repeats (VNTR) locus IDDM2 in the appearance of diabetes within this disease. In vitro studies have previously suggested that class I VNTR alleles were associated with decreased fetal thymic insulin expression. We genotyped the 5'INS VNTR locus and several flanking 11p15.5 markers in 50 Finnish APECED subjects and explored the possible contribution of IDDM2 in the development of diabetes. The shorter 5'INS VNTR class I alleles (<35 repeats) were more prevalent in the diabetic Finnish APECED subjects than in non-diabetic APECED subjects. Logistic regression analysis revealed that having 1 short (<35) VNTR allele did not increase the risk of developing diabetes (95% CI 0.6-27.0), whereas having 2 short alleles conferred a 43.5-fold increased risk (95% CI 3.0-634.6). We conclude that short 5'INS VNTR class I alleles play a role in susceptibility to autoimmune diabetes in the context of APECED.

Transient insulin-dependent diabetes mellitus in children with steroid-dependent idiopathic nephrotic syndrome during tacrolimus treatment

Despite the availability of immunosuppressive drugs such as prednisone, cyclophosphamide, cyclosporine A (CyA) and mycophenolate mofetil for the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS), medication-free remission is not achieved in a number of patients. To avoid excessive steroid toxicity, the use of tacrolimus (Tac) has been discussed. We report on five children diagnosed with SDNS on the histological basis of minimal change glomerulopathy or focal segmental glomerulosclerosis. Following the failure of other medications to achieve sustained remission, Tac was administered to these patients who varied in age from 10.5 to 13.5 years. Only one patient showed a substantial reduction in the number of relapses with the Tac treatment. Two boys, after 9 and 44 months on therapy, respectively, developed insulin-dependent diabetes mellitus (IDDM), necessitating the withdrawal of Tac and the daily use of insulin for 3 and 6 months. In both patients hyperglycemia had occurred during prednisone-based relapse therapy of SDNS. The patients had low serum protein concentrations, presumably increasing the free active Tac fraction, while trough levels of the drug remained unchanged. Both of the affected patients had additional risk factors for impaired glucose tolerance, such as morbid obesity (patient 1; BMI: 41.6 kg/m(2)) and African American origin (patient 2). Our case reports demonstrate that the use of Tac in patients with SDNS may be associated with an increased risk for IDDM, especially during relapse of NS, and particularly if additional risk factors are present. Moreover, Tac does not appear to substantially increase the success of treatment.

Functional variants in SUMO4, TAB2, and NFκB and the risk of type 1 diabetes

Several functional genetic variants that can potentially modulate the activity of NFkappaB have been recently described. As reduced NFkappaB activity has been implicated in risk for autoimmune diabetes in the NOD mouse, these variants were tested for allelic association with type 1 diabetes (T1D) in a family based study. Alleles at markers in the TAB2/SUMO4 locus on chromosome 6q had been previously reported to be associated with T1D in two separate studies, but these studies disagreed on the identity of the risk allele. The current study failed to confirm either of these results. No significant evidence of association with T1D was obtained for three SNP markers in the TAB2/SUMO4 region. An additional functional variant in the promoter of the NFKB1 gene that has been shown to directly affect the expression of NFkappaB was also tested.

Association of class II HLA antigens and insulin-dependent diabetes mellitus in the population of Vojvodina

Class II HLA antigens were investigated in a group of 28 patients with insulin-dependent diabetes mellitus (IDDM) and 218 healthy unrelated persons (control group) from Vojvodina. We used a modified two-colour immunofluorescence method (serologic technique) to determine the phenotype of DR and DQ locus HlA antigens. Phenotype frequencies of class II HLA antigens were determined in both investigated groups and were used for calculating relative risk (RR). If RR was higher than 1, we calculated the population attributable risk (EF), and if RR was lower than 1, we calculated the preventive fraction (PF). Investigation of statistically significant differences in frequencies of class II HLA antigens in patients and control group was performed by using chi 2 test. Results of investigation showed that values of RR were higher than 1 for HLA DR4 (2,808), DR10 (1,116) and DQ3 (1,386), while we noticed a statistically significant difference in frequencies of HLA DR4 (chi 2 test: 4,805) in patients regarding control group. HLA DQ1 antigen has a preventive role in development of IDDM due to highest value of PF (0,314). Results of our investigation confirm that there is an association of HLA DR4 with IDDM in population of Vojvodina. High values of relative risk of IDDM, noticed in persons with HLA-DR4 antigen, point to the degree of risk of IDDM, which is a disease with great socioeconomic importance in Vojvodina.

Bayesian analysis of case control polygenic etiology studies with missing data.

Many genetic studies are based on analysing multiple DNA regions of cases and controls. Usually each is tested separately for association with disease. However, some diseases may require interacting polymorphisms at several regions, and most disease susceptibility is polygenic. In this paper, we develop new methods for determining combinations of polymorphisms that affect the risk of disease. For example, two different genes might produce normal proteins, but these proteins improperly function when they occur together. We consider a Bayesian approach to analyse studies where DNA data from cases and controls have been analysed for polymorphisms at multiple regions and a polygenic etiology is suspected. The method of Gibbs sampling is used to incorporate data from individuals who have not had every region analysed at the DNA sequence or amino acid level. The Gibbs sampling algorithm alternatively generates a sample from the posterior distribution of the sequence of combinations of polymorphisms in cases and controls and then uses this sample to impute the data that are missing. After convergence the algorithm is used to generate a sample from the posterior distribution for the probability of each combination in order to identify groups of polymorphisms that best discriminate cases from controls. We apply the methods to a genetic study of type I diabetes. The protein encoded by the TAP2 gene is important in T cell function, and thus may affect the development of autoimmune diseases such as insulin dependent diabetes mellitus (IDDM). We determine pairs of polymorphisms of genetic fragments in the coding regions of linked HLA genes that may impact the risk of IDDM.

Association between atopic dermatitis and insulin-dependent diabetes mellitus: a case-control study

Up to two-thirds of children with atopic dermatitis have IgE-mediated allergic reactions and a Th2 immune reactivity pattern with low production of interferon gamma and high production of interleukin 4 after allergen stimulation of T lymphocytes. Insulin-dependent diabetes mellitus (IDDM) seems to be associated with a Th1 immune reactivity pattern. We therefore postulated that these diseases may be inversely associated. We designed a case-control study including 920 children with IDDM, registered in the Danish Registry for Childhood Diabetes, and a sample of 9732 non-diabetic children registered in the Danish Medical Birth Registry. The children were aged 3-15 years. Information on atopic dermatitis was obtained by questionnaires. The cumulative incidence of atopic dermatitis up to age 15 years was 13.1% among children with IDDM and 19.8% in non-diabetic children (p<0.0001). Among children who developed IDDM, the incidence of atopic dermatitis was significantly lower than in the controls before onset of IDDM (73 cases in 5314 person-months vs 1375 in 57432 person-months; odds ratio 0.49 [0.39-0.63]). After onset of IDDM, diabetic and non-diabetic groups did not differ in incidence of atopic dermatitis (1.36 [0.89-2.07]). Our findings may be explained by different acquired or inherited reactivity patterns associated with atopic dermatitis (Th2) and IDDM (Th1). The results do not allow us to find out whether early development of atopic dermatitis reduces the risk of IDDM, or a propensity for IDDM reduces the risk of early-onset atopic dermatitis.

IDDM and early exposure of infant to cow's milk and solid food.

Associations studies were attempted between the type of feeding, duration, and time of starting of solid foods in infancy and the incidence of insulin-dependent diabetes mellitus (IDDM). The study subjects comprised 52 IDDM patients and 52 control subjects matched for sex, age, social status, country, geographical location and selected from pediatric departments of different hospitals in Tehran. Diabetic children (21 boys, 31 girls) were of the ages of 1.5 to 14 years. Information about the pattern of their feeding at the first two years of life were collected through questionnaires administered to the mothers. The questionnaire was designed to evaluate the duration of complete or partial breast-feeding and the age at which dietary products containing cow's milk were introduced into the diet. A large proportion of the diabetic children rather than the control children had been breast-fed, and the risk of IDDM among children who had not been breast-fed was below unity. No significant difference in the duration of breast-feeding was observed between diabetic and control group. Our data do not support the existence of a protective effect of breast-feeding on the risk of IDDM, nor do the data indicate that early exposure to cow's milk and dairy products has any influence on the development of IDDM.

Screening for the IDDM high-risk genotype. A rapid microtitre plate method using serum as source of DNA.

Norwegian babies born with the HLA-DRB1*0401-DQA1*03-DQB1*0302/DRB1*03-DQA1+ ++*05-DQB1*0201 genotype have an estimated 17% lifetime risk of developing insulin-dependent diabetes mellitus (IDDM). Identifying these children is important for future prevention, and for studies of the non-genetic factors involved in IDDM. The aim of the study was to develop a rapid screening method for this high-risk genotype. DNA was extracted from serum collected during routine newborn screening for phenylketonuria and hypothyreosis. The second exons of HLA-DQA1 and DQB1 were co-amplified using biotinylated primers, amplicons were hybridized to a set of seven probes immobilized on a microtitre plate using a single hybridisation temperature, and detected colorimetrically by streptavidin-HRP conjugate and tetramethylbenzidine substrate. The DRB1*04 subtyping was performed using six different probes at identical conditions. The prevalence of the DRB1*0401-DQA1*03-DQB1*0302/DRB1*03-DQA1*0 5-DQB1*0201 genotype among 1,026 Norwegian babies was 2.7% (CI 95%: 1.7-3.7%). The new high-throughput genetic screening method for IDDM risk can easily be automated and included in newborn screening programs.

No alteration in T lymphocyte expression of CD40 ligand (CD154) in individuals with or at increased risk for insulin-dependent diabetes mellitus.

CD40 ligand (CD40L) regulates multiple phases of the humoral and cellular immune response through binding to CD40. Previous investigations have suggested that insulin-dependent diabetes (IDDM) in both humans and nonobese diabetic mice may be strongly influenced by similar immunoregulatory molecules. As persons with or at increased risk for the disease are characterized by a number of immunological abnormalities, including that of self-reactive autoantibody production (e.g. islet cell cytoplasmic autoantibodies), we analyzed the expression of CD40L on T lymphocytes (CD3+ cells) in a series of individuals with newly diagnosed IDDM (n = 11), nondiabetic relatives of IDDM probands at increased risk for the disease (n = 21; islet cell cytoplasmic autoantibodies positive; Juvenile Diabetes Foundation titer, > or = 20), and healthy controls (n = 13). Both phorbol myristate acetate (PMA)-stimulated and unstimulated peripheral blood mononuclear cells from study subjects were analyzed by flow cytometry with a series of phenotypic antibody markers (CD3, CD40L, and isotype controls). The kinetics of CD3 and CD40L expression on peripheral blood mononuclear cells under PMA-stimulated and unstimulated conditions were similar in the three study groups (6, 24, and 48 h; all P = NS). Similarly, unstimulated and PMA stimulated CD40L expressions (percentage of positive cells and level) on CD3+ cells from newly diagnosed IDDM patients and persons at increased risk for the disease were similar to those in healthy controls (6, 24, and 48 h; all P = NS). These findings do not support abnormal CD40L expression as the mechanism underlying the functional defect(s) in communication between T lymphocytes and antigen-presenting cells that allows for autoantibody production or the inability of individuals to regulate antiself immunity in IDDM.

No Alteration in T Lymphocyte Expression of CD40 Ligand (CD154) in Individuals with or at Increased Risk for Insulin-Dependent Diabetes Mellitus

No Alteration in T Lymphocyte Expression of CD40 Ligand (CD154) in Individuals with or at Increased Risk for Insulin-Dependent Diabetes Mellitus

T-cell response to proinsulin and insulin in type 1 and pretype 1 diabetes.

Insulin-dependent diabetes mellitus (IDDM) results from the selective destruction of pancreatic beta cells by a T cell-mediated autoimmune process. Insulin and proinsulin are the only known beta cell-specific autoantigens. Using short-term cultures of freshly isolated peripheral blood mononuclear cells, we evaluated T-cell responses to proinsulin and to insulin in IDDM patients and individuals at risk for IDDM. A proliferative T-cell response to proinsulin was observed in only 2 of 26 recent-onset IDDM subjects and 2 of 12 long-standing IDDM subjects and was associated with a proliferative response to insulin. In contrast, 5 of 13 islet cell autoantibody-positive first-degree relatives of IDDM patients showed a proliferative response to proinsulin alone, 3 of 13 to insulin alone, and 1 of 13 to both insulin and proinsulin. Overall, 9 of 13 ICA-positive first-degree relatives responded to either proinsulin or insulin. We observed an inverse relationship between antiinsulin antibodies and T-cell responses to insulin in ICA-positive first-degree relatives but not in long-standing IDDM patients. Our data indicate that proinsulin is a major antigen in IDDM and, further, illustrate the difference between the autoimmune response to insulin and the immune response to exogenous insulin.

Low vitamin E status is a potential risk factor for insulin-dependent diabetes mellitus.

To study the association of vitamin E status with occurrence of insulin-dependent diabetes mellitus (IDDM). A case-control study nested within a 21-year follow-up study. Nineteen incident IDDM patients with an average age of 28 years and three individually matched controls per patient. Serum concentrations of alpha-tocopherol. Serum alpha-tocopherol concentration at the baseline examination was inversely associated with IDDM occurring 4-14 years later. The cholesterol-adjusted relative risk of IDDM between the highest and lowest thirds of the vitamin concentration was 0.12 (95% confidence interval = 0.02-0.85). The finding corroborates the hypothesis of a protective effect of vitamin E against development of IDDM. Because of the relatively old age of the patients in the present population, further epidemiological studies on the topic are warranted.

Distribution of insulin-dependent diabetes mellitus (IDDM)-related HLA alleles correlates with the difference in IDDM incidence in four populations of the Eastern Baltic region.

The high incidence of insulin-dependent diabetes mellitus (IDDM) in Finland contrasts strikingly with the low rates in the neighbouring populations of countries in the Eastern Baltic region: Estonia, Latvia and Russia. To evaluate the possible contribution of genetic factors to these differences, the frequencies of HLA-DQB1 alleles and relevant DQB1-DQA1 or DQB1-DRB1 haplotypes associated with IDDM risk or protection were analysed among IDDM patients and control subjects from these four populations. An increased frequency of HLA-DQB1*0302, DQB1*02-DQA1*05 and DQB1*0302-DRB1*0401 was observed in subjects with IDDM in all studied populations, whereas the prevalence of DQB1*0301 and DQB1*0602 and/or *0603 was decreased among patients. The degree of IDDM risk associated with HLA alleles analysed here did not differ significantly between the populations. Comparisons of the distribution of IDDM-related HLA alleles and haplotypes in the background populations revealed its consonance with IDDM incidence. The combined frequency of high risk genotypes was significantly higher among Finns than in other populations studied. Our data support the hypothesis that variance in the dispersion of HLA alleles is the genetic basis of variation of IDDM incidence observed in the Eastern Baltic region.

Patient and Family Reflections on the Use of Subcutaneous Insulin to Prevent Diabetes: A Retrospective Evaluation from a Pilot Prevention Trial

A retrospective, semi-structured telephone interview was used to collect data from 28 of 31 families who participated in a pilot study testing subcutaneous insulin as a means to prevent or delay insulin-dependent diabetes mellitus (IDDM) onset. Interviews were conducted an average of 3 years after the initiation of the subcutaneous insulin protocol. Both the high-risk person (if ⩾ 8 years of age) and a family member (spouse or parent) were interviewed. Most participants reported that they were distressed to learn that they or a family member were at risk for IDDM, and families readily agreed to initiate subcutaneous insulin therapy. More children than adults reported insulin injections and blood glucose tests were “hard” or “very hard,” but noncompliance was more common in adults. Of the high-risk participants interviewed, 58% of children and 100% of adults reported experiencing hypoglycemia, although episodes requiring someone else’s assistance were rare, occurring in 38% of the children and 27% of the adults. Participants remained enthusiastic about trial participation; most favored screening programs to identify those at risk for IDDM, believed screening should be conducted regardless of age, believed subcutaneous insulin prevented or delayed IDDM onset, and would recommend subcutaneous insulin therapy to another high-risk individual. In addition, more than 40% of children, parents, and spouses reported that they would have benefited from access to a mental health professional at some point during the trial.