Classification of Type 1 and Type 2 Diabetes Mellitus from Studies of ICA, HLA and Insulin Secretory Capacity

We studied ICA, HLA and insulin secretory capacity in 87 children with positive urinary screening and more than 2 points in the oral glucose tolerance test in order to establish criteria by which they could be classified into type 1 or type 2 diabetes mellitus. Fifty-five non-obese, ketosis-prone insulin dependent diabetic children were used as controls for type 1 diabetes mellitus. Our conclusions were as follows: 1. Type 1 diabetics were non-obese (on insulin therapy), ICA positive, ketosis-prone, had an insulin secretory capacity (Z IRI) of less than 100/nU/ml, and most of them possessed HLA-Bw54-DR4 or DRw9, DRw53 but did not possess Bw52-DR2 haplotype. 2. In the patients who were treated by dietary regimens alone for certain periods, however, insulin secretory capacities gradually deteriorated and they finally became insulin dependent. The children of this group who were not obese during insulin therapy and possessed an HLA haplotype identical to that in type 1 diabetes, regardless of ICA, might be classified as having slowly progressive type 1 diabetes. 3. The major difference between type 1 and slowly progressive type 1 diabetes was a family history of diabetes. Genetic factors might modify the clinical course of type 1 diabetes mellitus. 4. If the sensitivity of ICA or related autoantibodies to islet cells can be detected more readily, it should become easier to distinguish between type 1 and 2 diabetes.     

HLA in Japanese Insulin-Dependent Diabetes Mellitus

Ninety-four Japanese patients with insulin-dependent diabetes mellitus (IDDM) and 388 healthy randomly selected Japanese were HLA typed. Significantly increased frequencies of Bw54, Cwl, DR4, B17 (Bw58), DR3 and DRw9 were observed. Simultaneously, the frequencies of Bw52 and DR2 in the patients were found to be significantly low as compared with those in helathy Japanese controls. It was suggested that one of the susceptibility genes to IDDM, which is associated with B8, DR3 haplotypes in Caucasoids, might be associated with B17 (Bw58), DR3 haplotypes in Japanese and in Chinese. Another susceptibility gene to IDDM associated with DR4 in Caucasoids might be associated with both DR4 and DRw9 in Japanese. A very rare variant of properdin factor B allotypes (BF*FT or BF*F075) was shown to be associated significantly with Japanese IDDM and with Bw52, DRw9 haplotypes.     

Diabetes mellitus-related autoantibodies in childhood autoimmune hepatitis

OBJECTIVE: To determine the frequency and significance of diabetes mellitus (DM)-related autoantibodies in children with autoimmune hepatitis (AIH). RESEARCH DESIGN AND METHODS: Anti-islet cell antibodies (ICA), insulin autoantibodies (IAA), and anti-glutamic acid decarboxylase (GAD65) antibodies were assessed in 28 children (25 female) with AIH before and after 3-9 years of therapy with azathioprine and prednisone. RESULTS: There was biochemical and clinical remission of AIH activity in 76% of the children after 1 year of immunosuppressive therapy. Positive ICA and IAA were found in 60.7% and 18.5% of the patients, decreasing to 38.5% and 12% after 3-9 years of therapy. Anti-GAD autoantibodies were present in only one patient who had Graves' disease, high ICA titer, and developed type 1 DM after 3 years. After 3-9 years of follow up, all had normal fasting glycemia, glycosylated hemoglobin (HbA1c), and, with a single exception, normal responses to oral glucose tolerance testing. No increase in the frequencies of HLA antigens was observed in ICA- and IAA-positive patients compared to antibody-negative patients or a control population. The majority of the patients with HLA-DRB1*03 or DRB1*04, however, were positive for ICA (7/10), and three of them had IAA. The frequency of high risk HLA DQB1*0302 or DQB1*02 alleles was low and similar to control frequencies, indicating low-risk for DM despite the presence of DM-related autoimmunity markers. CONCLUSIONS: AIH in childhood is associated with high frequency of ICA and IAA, with less than expected rates of progression to DM. Immunosuppression reduced ICA and IAA frequency and titers.     

Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies

Delli AJ, Lindblad B, Carlsson A, Forsander G, Ivarsson S‐A, Ludvigsson J, Marcus C, Lernmark Å; for the Better Diabetes Diagnosis (BDD) Study Group. Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies. Aim: To determine whether type 1 diabetes mellitus (T1DM) patients, having parents who immigrated to Sweden, have increased T1DM risk before 18 yr compared with countries of origin. We also determined whether they have different human leukocyte antigen (HLA) genetic markers and islet autoantibodies at diagnosis compared with Swedish patients. Methods: A total of 1988 (53% males) newly diagnosed and confirmed T1DM patients <18 yr registered within the Better Diabetes Diagnosis (BDD) study (May 2005 to September 2008) were included. Participants were classified into three groups: Swedish, non‐Swedish, and Mixed‐origin patients according to country of origin of two generations (parents and grandparents). These groups were compared with respect to T1DM HLA markers and islet autoantibodies [glutamic acid decarboxylase autoantibodies (GAD65Ab), insulin autoantibodies (IAA), and islet antigen‐2 autoantibodies (IA‐2Ab)]. Results: Only 30 (1.5%) patients were born outside Sweden. Swedish patients constituted 66%, non‐Swedish patients 8%, Mixed origins 17%, and 9% were of uncertain origin. Confirmed T1DM in patients within the study was 22 (95% CI: 21–23) patients/10⁵/yr rate for Swedish patients compared with 14 (95% CI: 13–15) among non‐Swedish patients. The HLA‐DQ8 haplotype (p < 0.0001) and DQ2/8 genotype (p < 0.02) predominated among Swedish compared with non‐Swedish patients. In contrast, DQ2 was the most frequent haplotype among non‐Swedish patients [OR = 1.5 (95% CI: 1.0–2.0), p < 0.04]. Multiple (≥2) autoantibodies (p < 0.04) and specifically IA‐2Ab (p < 0.001) were most prevalent among the Swedish patients. Multiple autoantibodies were associated with DQ8 among the Swedish patients only (p < 0.001). Conclusion: Patients born to parents who had immigrated to the high T1DM incidence environment of Sweden have, compared with Swedish patients, more frequent HLA‐DQ2 genetic markers and are diagnosed more often with GAD65Ab.     

Twins with moyamoya disease

Moyamoya disease is a progressive disease which involves the internal carotid arteries and its branches bilaterally. The disease is reported both in adults and in children. Moyamoya disease is frequently seen in Japanese patients having certain human leucocyte antigen (HLA) haplotypes including HLA-Aw24, Bw46 and Bw54. Twin cases are rarely reported in the literature. We hereby present the first Turkish monozygotic twins with moyamoya disease whose HLA haplotypes are A2, A9, B21, Bw22, Bw4, Bw6, Cw3, and DR2, DR4, DRw52, DRw53, Dq7. The patients with advanced disease were given nifedipine and intravenous immunoglobulin (400mg/kg/d for 5 days). During the 11 months of follow-up, the patients were attack free.     

Latent autoimmune diabetes mellitus in children (LADC) with autoimmune thyroiditis and Celiac disease

Latent autoimmune diabetes mellitus in adults (LADA) is characterized by clinical presentation as type 2 diabetes mellitus after 25 years of age, initial control achieved with oral hypoglycemic agents for at least 6 months, presence of autoantibodies and some immunogenetic features of type 1 diabetes mellitus. An 8.3 year-old girl was referred to our pediatric endocrinology department because of incidental glucosuria. She did not complain of polyuria, polydipsia, or weight loss. Her body mass index (BMI) was at the 80th percentile. Fasting glucose was 126 mg/dl, and OGTT glucose level at 120 min was 307 mg/dl. Although C-peptide levels were normal, her first phase insulin response (FIR) was lower than the 1st percentile. Anti-insulin antibody (AIA), islet cell antibody (ICA), and anti-glutamic acid decarboxylase (antiGAD) were negative. According to the clinical and laboratory findings, she was diagnosed as having type 2 diabetes mellitus. She was started with oral anti-diabetic treatment for a period of 1 year. Insulin had to be initiated for worsening of HbA1c levels. In the fourth year of follow-up, she was admitted to our hospital with diabetic ketoacidosis although she was on an intensive insulin regimen. At this time, C-peptide levels were low, antiGAD and AIA were positive with HLA DR3/DQ2 haplotype. In addition, her thyroid peroxidase antibody and endomysium antibody were found to be high at follow-up. Small intestinal biopsy revealed celiac disease. This patient may represent the first case of latent autoimmune diabetes mellitus in children (LADC) with autoimmune thyroiditis and celiac disease.     

HLA A Class II (DR, DQ) in Japanese Patients with Type 1 Diabetes Mellitus

DNA restriction fragment length polymorphism (RFLP) typing of HLA-DR and DQ alleles of 60 Japanese type 1 (insulin dependent) diabetic patients and 115 controls was performed. RFLP typing of DRB1 showed increased frequency of DR9 and decreased frequencies of DR2 and DRW6 among patients compared to controls. In the RFLP typing of BamHI- digested DNA to DQ β probe (BamHI-DQB1), the incidence of the 10.26 kb fragment, which represents either DQW4, DQW8 or DQW9, was markedly elevated in the patients, whereas the incidence of DQW6 was reduced. The predicted DR-DQ haplotype study revealed that DR4-DQW4 or DQW8, DRW8-DQW4 or DQW8 and DR9-DQW9 may contribute to susceptibility to type 1 diabetes. When serological typing of the 13 DRW8 patients was performed, all the 11 DRW8 patients carrying DQW4 or DQW8 (BamHI-10.26 kb) were positive for DQW3.
These results indicated that the HLA-DQ locus may play an important role in the development of type 1 diabetes in the Japanese as well as other ethnic groups and that the DRW8- DQW8 haplotype may predispose to the disease in Japan.     

Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study

Background:  Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children.
Methods:  T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study.
Results:  GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6–7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies.
Conclusions:  The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response.     

Slowly progressing form of type 1 diabetes mellitus in children: genetic analysis compared with other forms of diabetes mellitus in Japanese children

AIMS: Slowly progressing insulin-dependent diabetes mellitus (SPIDDM, hereafter referred to as IDDMS in this article) is a unique subtype of type 1 diabetes in Japanese children. To clarify the genetic background of IDDMS, we analyzed HLA-DRB1, -DQB1 and -DQA1 alleles, phenotypes, and genotypes and compared them with acute-onset type 1 diabetes, non-insulin-dependent diabetes mellitus (NIDDM), and control subjects. METHODS: HLA-DRB1, -DQA1, and -DQB1 types were defined by DNA analysis using polymerase chain reaction (PCR), and typing for human leukocyte antigen (HLA) was performed by the sequencing-based typing (SBT) method using Match Maker and MT Navigator in combination. HLA-A24 was determined by the PCR-sequence-specific oligo-nucleotide probe (PCR-SSOP) method. The 234 patients with type 1 diabetes were divided into three groups: 32 cases of IDDMS, 137 cases of acute-onset form aged more than 5 yr (IDDMA), and 65 cases of acute-onset form less than 5 yr of age at onset (IDDME). In addition, we studied 55 children with type 2 diabetes (NIDDM) and 97 normal controls. RESULTS: The patients with IDDMS were older at diagnosis and had a greater body mass index (BMI) than those with IDDM (A + E). The prevalence of islet autoantbodies was not significantly different from IDDMA. The allele frequencies of DRB1*0405, DQA1*0302, and DQB1*0401 were significantly increased; however, DRB1*0901, DQA1*03, DQB1*0303, and HLA-A24 were low and not significantly different from control subjects. CONCLUSIONS: HLA phenotypes and genotypes in patients with IDDMS were different from those in NIDDM and control subjects and were closer to those of IDDMA. Together with a low prevalence of HLA-A24, the genetic features are similar to those of SPIDDM and latent autoimmune diabetes in adults (LADA) in adults. In our series, the clinical features such as lack of obesity and lack of responsiveness to oral hypoglycemic agents were most different from those of adults' onset.     

Autoimmunity of Insulin-Dependent Diabetes in Japan

In this paper some findings concerning autoimmunity have been studied in young Japanese patients with diabetes. Patients diagnosed before 30 years old were classified carefully into new categories recommended by WHO in 1980: insulin-dependent (IDDM), non-insulin-dependent (NIDDM) and other types of diabetes. HLA antigen types, islet cell antibodies (ICA) and islet cell surface antibodies (ICSA) were checked in the sera. HLA-Bw54 and -DR4 were found in a significantly high percentage of IDDM patients, especially in those with Insulin-Dependent Diabetes Mellitus with Special Reference to acute onset of the disease. Positivity of ICA was remarkably high in IDDM Viral Infections patients within one year after the onset, and then decreased very rapidly. ICSA had the same tendency, but the rate of decrease of positivity seemed slower than that of ICA Apparent autoimmune diseases were rare among our patients, and persistent positivity of ICA was found only in a few cases. At this time we have notenough evidence concerning autoimmunity as a major cause of IDDM.     

Screening for preclinical type 1 diabetes in a discrete population with an apparent increased disease incidence

Environmental agents are proposed to play a role in triggering or exacerbating pancreatic islet autoimmunity in people genetically predisposed to type 1 diabetes. However, with few exceptions, these agents remain enigmatic. Clues to environmental agents may be found by investigating population/geographic clusters or 'hotspots' of high disease incidence. We were alerted to a small community where the incidence of type 1 diabetes appeared to be five-fold higher than expected. Because type 1 diabetes is now recognized to have a subclinical phase during which anti-islet antibodies can be detected, we aimed to identify and characterize a reservoir of children with subclinical disease in this community. Venous blood samples were collected from 1906/2347 (81%) local school children during one week. Islet cell antibodies (ICAs) were detected in 122 (6.4%) children, 18 (0.9%) being high titer (> or = 20 Juvenile Diabetes Foundation units (JDFu)). On retest, 15 months later, the majority of low titer ICAs were undetectable, whereas high-titer ICAs persisted. The latter were found in two distinct age-related, ethnically similar groups. The younger group, aged 6-9 yr, had antibodies to insulin (IAAs), glutamic acid decarboxylase (GAD) and tyrosine phosphatase IA2 in addition to ICA, human leukocyte antigen (HLA) genes associated with susceptibility to type 1 diabetes, and lower first-phase insulin responses (FPIRs) to intravenous glucose. The older group, aged 13-16 yr, the age cohort of the index clinical cases, had few antibodies other than ICA, non-susceptibility HLA genes and normal FPIRs. During follow-up, three children, all from the younger group with multiple antibodies and FPIRs less than the first percentile, developed diabetes 4, 6 and 7 yr after screening. The finding of two age groups of subclinical disease suggests that if environmental agents triggered islet autoimmunity they did not act constantly on the community. Furthermore, the absence of multiple autoantibodies and/or HLA susceptibility genes in the older group, the source of index clinical cases, implies they are a residual subgroup with slow or absent progressive beta-cell destruction. This study illustrates that the natural history of type 1 diabetes may be elucidated by analyzing age-related subclinical disease in the general population.     

Contrasting Features of Insulin Dependent Diabetes Mellitus Associated with Neuroectodermal Defects and Classical Insulin Dependent Diabetes Mellitus

ABSTRACT. The Wolfram, or DIDMOAD, syndrome is a rare congenital disease that is associated with diabetes insipidus, insulin dependent diabetes mellitus of an early onset, bilateral optic atrophy and deafness. Urological disorders are usually present as well. We have studied nine patients belonging to five different families. All of the family members were HLA typed (including DR), and islet cell as well as antinuclear antibody determinations were carried out. Although individuals with insulin dependent diabetes mellitus are very prone to have either HLA-DR3 or -DR4 antigens, none of our patients had DR3 antigens and only one was DR4 positive. On the other hand, three of our patients were typed as HLA-DR2 positive. This antigen is uncommon in classical insulin dependent diabetes. In one of the families, the affected siblings did not share the same HLA haplotype. Islet cell and antinuclear antibodies were not found in any of the cases and six of the patients had a small, but significant, insulin secretory reserve. On the basis of some of the clinical features it was also possible to further distinguish between the DIDMOAD syndrome and the classical insulin dependent diabetes mellitus. The differences encountered between classical and DIDMOAD insulin dependent diabetes mellitus—the presence/absence of HLA linkage, HLA-DR2, -DR3 and -DR4 associations, islet cell or antinuclear antibodies, the tendency to ketosis and diabetic retinopathy—indicate that their etiopathogenies are triggered by distinct mechanisms.     

The challenge of childhood diabetes mellitus in India

The prevalence of DM is about 0.4/1000 children with a lower incidence in the rural areas. Children comprise 3–5% of the total diabetics. A study of 55 pediatrie cases of DM (1980-84) showed that only 22 (40%) had ketoacidosis on admission. Ten (18.2%) had onset of illness before 4 years of age. HLA antigen studies in childhood IDDM have shown a positive linkage disequilibrium with Bw21 (RR-12.7), and DR3 (RR=16.6). Prevalence of islet cell antibodies (ICA) was 30.9% (n = 110) as compared with 0.8% in controls. Antibodies against Coxasckie B2 virus were increased (75.5% vs 46.4% in controls). The C-peptide content was substantially low. Malnutrition related DM occurs in adolescents in some parts of India. It is characterized by moderate hyperglycemia, low serum glycerol, relative insulin insensitivity, and pancreatic malformation/calcification in about 1/4 of subjects. There is no association with HLA antigens or ICA, and the precise etiology is unclear. Mortality was 3.6% in patients admitted in our hospital but is higher in other regions due to poverty and relative lack of health care facilities.     

Contrasting features of insulin dependent diabetes mellitus associated with neuroectodermal defects and classical insulin dependent diabetes mellitus

The Wolfram, or DIDMOAD, syndrome is a rare congenital disease that is associated with diabetes insipidus, insulin dependent diabetes mellitus of an early onset, bilateral optic atrophy and deafness. Urological disorders are usually present as well. We have studied nine patients belonging to five different families. All of the family members were HLA typed (including DR), and islet cell as well as antinuclear antibody determinations were carried out. Although individuals with insulin dependent diabetes mellitus are very prone to have either HLA-DR3 or -DR4 antigens, none of our patients had DR3 antigens and only one was DR4 positive. On the other hand, three of our patients were typed as HLA-DR2 positive. This antigen is uncommon in classical insulin dependent diabetes. In one of the families, the affected siblings did not share the same HLA haplotype. Islet cell and antinuclear antibodies were not found in any of the cases and six of the patients had a small, but significant, insulin secretory reserve. On the basis of some of the clinical features it was also possible to further distinguish between the DIDMOAD syndrome and the classical insulin dependent diabetes mellitus. The differences encountered between classical and DIDMOAD insulin dependent diabetes mellitus--the presence/absence of HLA linkage, HLA-DR2, -DR3 and -DR4 associations, islet cell or antinuclear antibodies, the tendency to ketosis and diabetic retinopathy--indicate that their etiopathogenies are triggered by distinct mechanisms.     

Diabetes-related autoantibodies do appear in children with coeliac disease

Humoral immune factors related to type 1 diabetes have been investigated in children with coeliac disease. Anti-insulin (IAAb), immunoglobulin (alpha IgAb), islet cell (ICA) and glucagon autoantibodies were examined in 15 children with coeliac disease at diagnosis (group 1), in 15 children with coeliac disease following a gluten-free diet (group 2) and in 30 control patients (groups 3 and 4). IAAb were present in 27% of group 1 and in 20% of group 2 patients and alpha IgAb were significantly increased in group 1 and 2 patients; two patients in group 2 were positive for ICA; none of the coeliac disease patients were positive for anti-glucagon antibodies. The levels of anti-gliadin antibodies in group 1 were positively correlated with those of alpha IgAb. Coeliac disease-related HLA antigens were not correlated with antibody presence. The presence of diabetes-related humoral immune factors in coeliac disease raises the question as to whether or not they are predictive of subclinical pancreatic damage or whether they are simply indicators of a more general autoimmune diathesis.     

HLA-DRB1*08 allele may help to distinguish between type 1 diabetes mellitus and type 2 diabetes mellitus in Mexican children

BACKGROUND: It may be difficult to distinguish type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus (T2DM) in the pediatric population. Autoantibodies may help to differentiate both types of diabetes, but sometimes these are positive in patients with T2DM and negative in patients with T1DM. The human leukocyte antigen (HLA)-DR genotype has been associated with T1DM and with T2DM only in adults and in determined cases. AIM: To determine the differences in HLA class II allele frequencies in Mexican children with T1DM and T2DM. METHODS: We included 72 children with T1DM, 28 children with T2DM, and 99 healthy controls. All were Mexican, and diabetes was diagnosed according to the clinical and laboratory criteria established by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. The HLA-DRB1 typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probe and polymerase chain reaction sequence-specific primers. RESULTS: We found an increased frequency of HLA-DRB1*08 and a decreased frequency of HLA-DRB1*04 in the group with T2DM vs. T1DM [p = 0.0001, odds ratio (OR) = 10.58, 95% confidence interval (CI) = 3-40.8 and p = 0.0006, OR = 0.24, 95% CI = 0.11-0.53, respectively]. No significant differences were found between HLA-DRB1 alleles in T2DM vs. controls. In the group with T1DM, there was a significantly increased frequency of the HLA-DR4 and HLA-DR3 alleles relative to controls (p = 0.0000001, OR = 3.59, 95% CI = 2.2-5.8 and p = 0.00009, OR = 4.66, 95% CI = 2.1-10.3, respectively). CONCLUSION: There are significant differences in the HLA profile in Mexican children with T1DM and T2DM. HLA typing could play a role in the differentiation between both types of diabetes in this population.     

A Study of HLA in Japanese Patients with Rheumatic Fever

HLA was analysed to study an aspect of genetic background of susceptibility to rheumatic fever. The frequency of HLA was determined in 66 Japanese patients with rheumatic fever and compared with 95 healthy Japanese controls by chi-square method with Yates' correction. The frequency of Bw35 was increased significantly in rheumatic fever group compared with control group (Pc < 0.01). An association between Bw35 and rheumatic fever may imply that rheumatic fever is an autoimmune disease. And the susceptibility to rheumatic fever may be controlled by immune response genes, which have a linkage disequilibrium with Bw35 as an immunogenetic background.     

Changes in lymphocyte subsets in children with newly diagnosed type 1 diabetes mellitus

The aim of this study was to assess changes in selected peripheral blood lymphocyte subsets in children and adolescents with newly diagnosed type 1 diabetes mellitus (DM) and determine the correlation between these changes and other immunological markers. The study involved a group of 39 patients aged 2-14 years and a control group. The number of T- and B-lymphocytes and the number of CD4, CD8, CD4/HLA-DR, CD8/HLA-DR, CD5/CD20 subsets were measured by flow-cytometry using monoclonal antibodies. Islet cell antibodies (ICA) and antibodies to glutamic acid decarboxylase (GADA) were assessed. In both the diabetic and control groups the number of T-and B-lymphocytes were within normal limits. In patients with DM, the percentage of CD5+/CD20+ cells was significantly increased compared with the control group (p < 0.0001). ICA were positive in 80% of patients and GADA in nearly 65%. A positive correlation between the CD5/CD20 subset and ICA and GADA was found. In patients with a high percentage of CD5+/CD20+ lymphocytes, a higher percentage of activated subsets (CD4/HLA DR and CD8/ HLA DR) was detected. In conclusion: CD5/ CD20 lymphocyte subsets are a good additional marker of autoimmunological processes in DM.     

儿童1型糖尿病并甲状腺自身抗体异常的意义

目的 探讨儿童1型糖尿病(DM)并甲状腺自身抗体异常的临床意义。方法 应用酶联免疫吸附法(ELISA)及放射免疫法(RIA)测定11例1型DM患儿血清谷氨酸脱羧酶抗体(GADA)、胰岛素自身抗体(IAA)、胰岛细胞抗体(ICA)、甲状腺球蛋白抗体(TgAb)、甲状腺微粒体抗体(TMA)及甲状腺功能。结果 11例1型DM患儿中GADA、IAA、ICA阳性率分别为27.3％、63.6％、18.2％;TgAb、TMA阳性率分别为0％、27.3％,其中亚临床甲状腺功能低下(甲低)2例,发生率为18.2％。伴与不伴甲状腺自身抗体阳性两组1型DM患儿GADA、IAA、ICA阳性率分别为66.7％和12.5％、100％和50％、33.3％和12.5％,但无统计学差异(P>0.05)。结论 1型DM有相当高TMA阳性检出率和自身免疫性甲状腺疾病(AITD)发生率,并可能演变为自身免疫性多内分泌腺综合征(PAS),并甲状腺自身抗体异常的1型DM确实存在胰岛自身抗体高企。     

Maternal diet during pregnancy and islet autoimmunity in offspring

Background:  Recent studies on the etiology of type 1 diabetes mellitus (T1DM) suggest that the components of the infant diet are associated with islet autoimmunity (IA), a precursor of T1DM. The role of prenatal nutritional exposures has not been thoroughly investigated.
Methods:  The Diabetes Autoimmunity Study in the Young has enrolled newborns from 1993 to 2004 at increased risk for T1DM based on human leukocyte antigen (HLA) genotype and family history of T1DM. The child is tested for islet autoantibodies at 9 and 15 months, 2 yr, and annually thereafter. We conducted a cohort study of 642 subjects for whom a Willett food frequency questionnaire for the mother's third trimester diet was completed. A case is defined as a subject who tests positive for islet autoantibodies at two consecutive blood draws and is still positive (or diabetic) at last follow-up (n = 27).
Maternal consumption frequencies of potatoes, other root vegetables, gluten-containing foods, non-gluten cereal grains, cow's milk and cow's milk products, fruits, vegetables, meat and poultry, and fish were analyzed in a survival analysis.
Results:  Adjusting for breast-feeding duration, age at first cereal introduction, ethnicity, HLA genotype, family history of T1DM, and total caloric intake, higher maternal intake of potatoes (hazard ratio for one standard deviation difference: 0.49, 95% confidence interval: 0.28–0.86) was associated with a delayed time to IA onset. No other food groups ingested during pregnancy were associated with IA in the child.
Conclusions:  The composition of the maternal diet during pregnancy may play a role in the offspring's risk of development of IA and potentially T1DM.