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Biomedical subjects

Johnny Ludvigsson

Publications and source records attributed to Johnny Ludvigsson.

At least 19 recordsLinked to original sources

Short duration of breast-feeding as a risk-factor for beta-cell autoantibodies in 5-year-old children from the general population.

Breast-feeding has been suggested to have a protective effect against the development of type 1 diabetes. In the present study, we investigated the relation between duration of breast-feeding and beta-cell autoantibodies in 5-year-old non-diabetic children who participated in a prospective population-based follow-up study (the All Babies in Southeast Sweden study). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tryosine phosphatase-like IA-2 (IA-2A) were measured by radiobinding assays. A short duration of total breast-feeding was associated with an increased risk of GADA and/or IAA above the ninety-fifth percentile at 5 years of age (OR 2.09, 95% CI 1.45, 3.02; P<0.000) as well as with an increased risk of IAA above the ninety-fifth percentile at this age (OR 2.89, 95% CI 1.81, 4.62, P<0.000). A short duration of exclusive breast-feeding was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 2.01, 95% CI 1.08, 3.73; P=0.028) as well as with an increased risk of IA-2A above the ninety-ninth percentile (OR 3.50, 95% CI 1.38, 8.92, P=0.009) at 5 years of age. An early introduction of formula was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 1.84, 95% CI 1.01, 3.37; P=0.047) at 5 years of age. The positive association between a short duration of both total and exclusive breast-feeding, as well as an early introduction of formula, and positivity for beta-cell autoantibodies in children from the general population suggest that breast-feeding modifies the risk of beta-cell autoimmunity, even years after finishing breast-feeding.

Animals↗

Predictors and dietary consequences of frequent intake of high-sugar, low-nutrient foods in 1-year-old children participating in the ABIS study.

Foods rich in sugar have been suggested to contribute to the increasing prevalence of obesity in children. The aim of this report is to investigate the dietary pattern in 1-year-old children who frequently receive foods rich in sugar but low in nutrients and to study associated demographic and parental factors. During 1977-9, 21,700 infants were invited to participate in this prospective, population-based, longitudinal cohort study. Screening questionnaires were completed for 16,070 infants after delivery. Follow-up questionnaires from 10,762 children at 1 year of age are included in the analysis. It was found that 24% of the children received sweets/pastries more often than one or two times per week. They had a higher intake of French fries, potato crisps and cream as well as a lower intake of fruit and vegetables. A frequent intake of sugar-rich, low-nutrient foods was significantly associated with several maternal factors (high intake of sweets/pastries during pregnancy, young age, mother living alone) as well as presence of older siblings. Maternal smoking during pregnancy and maternal overweight were of borderline significance. Parental education level was inversely associated with the frequency of intake of sweets/pastries in the child. Children who frequently receive sweets/pastries also have an otherwise unfavourable dietary pattern. Several parental and demographic factors were associated with this feeding pattern, especially high intake of sweets/pastries during pregnancy. Screening of pregnant women for risk predictors like consumption of sweets/pastries, young age and smoking could be possible ways of identifying children at future risk for low dietary quality.

Beverages↗

Coeliac disease and risk of renal disease-a general population cohort study.

BACKGROUND: Coeliac disease (CD) may be a risk factor for renal disease. METHODS: We investigated the risk of any form of glomerulonephritis (GN) (acute, chronic and non-specified), chronic glomerulonephritis (CGN) and renal replacement therapy including dialysis treatment and kidney transplantation (KT) in patients with CD in a general population-based cohort study. We used Cox regression to assess the risk of renal disease in 14,336 patients who had received a diagnosis of CD (1964-2003) and 69,875 reference individuals matched for age, calendar year, sex and county. Patients were identified using the Swedish Hospital Discharge Registry. Follow-up began 1 year after study entry. RESULTS: CD was associated with an increased risk of any form of GN (hazard ratio (HR) = 1.64; 95% confidence intervals (CI) = 1.01-2.66; P = 0.046; 89 events), CGN (HR = 2.65; 95% CI = 1.34-5.24; P = 0.005; 39 events), dialysis (HR = 3.48; 95% CI = 2.26-5.37; P < 0.001; 102 positive events) and KT (HR = 3.15; 95% CI = 1.29-7.71; P = 0.012; 22 events). CONCLUSION: We suggest that immune characteristics associated with CD increase the risk of chronic renal disease. Individuals with CD may also be at a moderately increased risk of any form of GN.

Adolescent↗

Importin beta: a novel autoantigen in human autoimmunity identified by screening random peptide libraries on phage.

By screening random peptide libraries (RPLs) with sera of Type 1 diabetes (T1D) patients, we previously identified 5 disease-specific 'mimotopes' displayed on phages (phagotopes). We already characterised 1 phagotope (CH1p), as an epitope of human osteopontin, an autoantigen expressed within the somatostatin cells of human islets. In this paper, we report the characterization of the second phagotope, 195Dyn, by immunohistochemistry, Western Blotting and screening of a human islet cDNA library using rabbit anti-195Dyn antibodies. The 195Dyn mimotope was detected in human islets. The screening of a lambdagt11 cDNA library from human islets has identified a clone, which corresponded to human importin beta. ELISA detected autoantibodies against this protein in sera of around 60% of TD1 patients and in 30% of patients affected by other autoimmune diseases. In summary, RPLs technology proved again successful in identifying another novel autoantigen (importin beta), whose significance in the autoimmune process remains to be fully elucidated.

Animals↗

Higher prevalence of autoantibodies to insulin and GAD65 in Swedish compared to Lithuanian children with type 1 diabetes.

We compared the prevalence of beta-cell autoantibodies and genetic risk factors in Sweden and Lithuania. Ninety-six patients from Sweden and 96 from Lithuania matched for age and gender (1-15 years old, median age 9.0 years) were included. We analyzed autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase like IA-2 (IA-2A) as well as risk-associated polymorphisms of HLA, insulin and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) genes. The frequency of patients positive for IAA and GADA was higher in Sweden than in Lithuania (p = 0.043 and 0.032). The differences remained even when the patients were matched for HLA, insulin and CTLA-4 risk genotypes. Patients with low levels of IAA had higher levels of HbA1c and ketones at diagnosis. The frequency of the risk haplotype DR4-DQ8 was higher in Swedish than in Lithuanian patients (p = 0.004), as well as the high-risk combination of DR4-DQ8 and DR3-DQ2 haplotypes (p = 0.009). Our results suggest that autoimmune process against insulin and GAD(65) is more common at diagnosis in children in areas with high incidence of type 1 diabetes (T1D), independent of genetic risk markers. Furthermore, the disease in patients with insulin autoantibodies seems to be clinically milder.

Adolescent↗

Dietary risk factors for the emergence of type 1 diabetes-related autoantibodies in 21/2 year-old Swedish children.

We studied dietary risk factors by analysing a questionnaire administered at birth, 1 year and 2(1/2) years of age, as well as the level of glutamic acid decarboxylase autoantibodies (GADA) and tyrosine phosphatase autoantibodies (IA-2A), in 7208 2(1/2)-year-old children from the All Babies in Southeast Sweden cohort, using the 95th percentile cut-off for autoantibodies to identify children at risk of type 1 diabetes. A total of 657 children had either IA-2A (n 360) or GADA (n 335), and thirty-eight children had both GADA and IA-2A. In univariate analysis, male gender and maternal coeliac disease implied a risk of possessing IA-2A. Maternal type 2 diabetes, a high consumption of fresh cows milk at the age of 1 year and a late introduction of gluten were associated with a risk of GADA. Early cessation of breast-feeding (< 2 months of age) was associated with a risk of the simultaneous occurrence of both IA-2A and GADA. In logistic regression analysis, a high consumption of milk at the age of I year (odds ratio 2.6)represented a risk for GADA, and maternal coeliac disease (odds ratio 2.9) represented a risk for IA-2A. The combination of an early introduction of cows milk formula and a late introduction of gluten-containing food gave an odds ratio of 6.0 for positivity for at least one autoantibody at 1 and 21 years of age. The induction of autoantibodies by the age of 2(1/2) years has a male preponderance and is more common in children with maternal type 2 diabetes or maternal coeliac disease. Dietary risk factors for the induction of beta-cell autoantibodies in 21-year-old children are a short duration of breast-feeding, an early introduction of cows milk formula and a late introduction of gluten, as well as a high consumption of milk at the age of I year.

Age Factors↗

Nicotinamide reduces high secretion of IFN-gamma in high-risk relatives even though it does not prevent type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease suggested to be of a T helper (Th)1-like origin. This study aimed to investigate the Th1-like and Th2-like profile in high-risk individuals during the prediabetic phase and the immunologic effect of treatment with nicotinamide. High-risk first-degree relatives of T1D patients participating in the European Nicotinamide Diabetes Intervention Trial (ENDIT) were treated with either nicotinamide or placebo. Peripheral blood mononuclear cells (PBMC) were obtained during the prediabetic phase and close to the onset of manifest T1D and from nondiabetic high-risk individuals. Using the sensitive enzyme-linked immunospot (ELISPOT) technique to distinguish Th1-like from Th2-like lymphocytes, secretion of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was analyzed from PBMCs spontaneously and after in vitro stimulation with the diabetes-associated autoantigens, glutamic acid decarboxylase 65 (GAD65, protein and peptide, aa 247-279), recombinant tyrosine phosphatase (IA-2), and heat shock protein (HSP, aa 437-460). High-risk individuals showed high spontaneous as well as autoantigen-induced IFN-gamma secretion. Secretion of IFN-gamma and the IFN-gamma/IL-4 ratio, induced by autoantigens, decreased in individuals developing T1D (p < 0.05), whereas nondiabetic individuals showed an increased IL-4 response (p < 0.05). Thus, a Th1-dominated cytokine profile observed in high-risk individuals inclined toward a diagnosis of diabetes. Nicotinamide caused decreased spontaneous (p = 0.05) and in vitro autoantigen-induced IFN-gamma secretion (p < 0.05) and may play a role in immune regulation, even though it has not been shown to prevent T1D.

Adolescent↗

Hypoglycemia and ketoacidosis with insulin pump therapy in children and adolescents.

This review deals with the two most serious side effects encountered with insulin pump therapy, severe hypoglycemia and diabetic ketoacidosis (DKA). Although clinical follow-up studies reported decreased rates of severe hypoglycemia, randomized studies have not confirmed this, showing no difference between the pump and injection groups. Less-severe hypoglycemia (mild/moderate/symptomatic hypoglycemia) was found to be more common with pump use. Some patients have inadvertently dosed or overdosed while awake or during sleep, causing fatal outcome in rare cases. Population-based or retrospective clinical studies reported a low rate of DKA in pump users that was still a higher rate than those using injection therapy, at least in some countries. In research settings and for patients with good compliance and adequate family support, the risk of DKA seems lower; many short-term studies report no DKA at all, possibly due to the increased attention given to participants. The use of continuous subcutaneous insulin infusion (CSII) seems to decrease the risk in patients who had recurrent DKA before pump start. Most episodes of DKA occur early after pump start, suggesting a learning curve occurs in all new forms of treatment. Increased teaching and awareness programs are vital to prevent severe hypoglycemia and DKA in children and adolescents using insulin pumps.

3-Hydroxybutyric Acid↗

Probiotics for the prevention of beta cell autoimmunity in children at genetic risk of type 1 diabetes--the PRODIA study.

The final aim of the PRODIA study is to determine whether the use of probiotics during the first 6 months of life decreases the appearance of type 1 diabetes mellitus (T1DM)-associated autoantibodies in children with genetic risk for T1DM. A pilot study including 200 subjects was planned to show whether the use of probiotics during the first 6 months of life is safe and feasible. The prevalence of autoantibodies among the study subjects at 6, 12, and 24 months of age was at levels close to the expected and the clinical follow-up did not either indicate problems in the feasibility of the study.

Autoantibodies↗

Why diabetes incidence increases--a unifying theory.

There is a wide spectrum within the diabetes syndrome. Type 1 diabetes may have a slow progression with good residual insulin secretion and without autoantibodies, while phenotypic type 2 diabetes may have autoantibodies. A single patient may have traits of both types of diabetes. Their incidence increases in parallel. The etiology is mainly unknown, but environmental factors play an important role in genetically predisposed individuals. The search for just one single cause of manifest diabetes may be confusing. Different mechanism may be important in different parts of the world. Furthermore, certain mechanisms may lead to islet inflammation while other/additional mechanisms may increase insulin demand and cause insulin deficiency with manifestation of clinical diabetes. Several hypothesis of etiology may fit different parts of the disease process. Thus, increased hygiene may contribute to an imbalance of the immune system, facilitating autoimmune reactions when virus infections, or proteins like cow's milk or gluten, provoke. Increased insulin demand because of rapid growth, or insulin resistance caused by stress, infections, puberty, etc., lead to beta cell stress, antigen presentation and may cause both an autoimmune reaction in genetically predisposed individuals, and insulin deficiency leading to manifest diabetes in individuals who have lost beta cell function. Vitamins may modulate the immune process, but we know too little to give vitamin substitution. However, we do know that low physical exercise, obesity, and stress, increases insulin demand resulting in insulin deficiency. Now we can therefore intervene to prevent the diabetic syndrome.

Autoimmunity↗

Early diabetic complications in a population of young patients with type 1 diabetes mellitus despite intensive treatment.

AIM: To describe the prevalence of early complications in an unselected population of patients with type 1 diabetes mellitus (DM1) diagnosed in childhood with intensive insulin treatment from diagnosis. METHODS: Eighty children and adolescents with DM1, age 7-22 years and DM1 duration >3 years, were studied. Neuropathy was defined as abnormal nerve conduction finding in > or = 2 of 4 nerves (sural and peroneal nerves), nephropathy as albumin excretion rate > or = 20 microg/min and retinopathy as all grades of retinal changes in fundus photographs. RESULTS: The prevalence of neuropathy was 59%, of retinopathy 27% and of nephropathy 5% after 13 years DM1 duration. Mean (SD) long-term HbA1c was 8.4 (0.9)% (DCCT-corrected value). CONCLUSION: Even in a population with intensive insulin treatment from the beginning and fairly good metabolic control, the prevalence of subclinical neuropathy was high, while other diabetic complications were lower than usually reported.

Adolescent↗

Celiac disease and risk of subsequent type 1 diabetes: a general population cohort study of children and adolescents.

OBJECTIVE: Earlier studies suggest that children with type 1 diabetes are more likely to have a subsequent diagnosis of celiac disease. However, research is sparse on the risk of subsequent type 1 diabetes in individuals with celiac disease. We sought to determine the risk of subsequent type 1 diabetes diagnosed before the age of 20 years in children and adolescents with celiac disease in a national, general population-based cohort. RESEARCH DESIGN AND METHODS: We identified 9,243 children with a diagnosis of celiac disease in the Swedish national inpatient register between 1964 and 2003. We then identified five reference individuals matched at time of diagnosis for age, calendar year, sex, and county (n = 45,680). Only individuals with >1 year of follow-up after study entry (diagnosis of celiac disease) were included in the analyses. RESULTS: Celiac disease was associated with a statistically significantly increased risk of subsequent type 1 diabetes before age 20 years (hazard ratio 2.4 [95% CI 1.9-3.0], P < 0.001). This risk increase was seen regardless of whether celiac disease was first diagnosed between 0 and 2 (2.2 [1.7-2.9], P < 0.001) or 3 and 20 (3.4 [1.9-6.1], P < 0.001) years of age. Individuals with prior celiac disease were also at increased risk of ketoacidosis or diabetic coma before the age of 20 years (2.3 [1.4-3.9], P = 0.001). CONCLUSIONS: Children with celiac disease are at increased risk of subsequent type 1 diabetes. This risk increase is low considering that 95% of individuals with celiac disease are HLA-DQ2 positive.

Adolescent↗

Decreased in vitro type 1 immune response against coxsackie virus B4 in children with type 1 diabetes.

Enteroviruses, particularly Coxsackie virus B4 (CVB4), are considered to be involved in the pathogenesis of type 1 diabetes. We wanted to compare the characteristics of T-cell immune response to CVB4 in children with type 1 diabetes and healthy children with and without HLA risk-associated haplotypes (HLA-DR3-DQ2 or HLA-DR4-DQ8) for type 1 diabetes. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured with CVB4 and analyzed for cytokine and chemokine receptors by flow cytometry and for expression of transcription factors Tbet and GATA-3 by RT-PCR and Western blot. Culture supernatants were analyzed for secretion of gamma-interferon (IFN-gamma). In children with type 1 diabetes, a decreased percentage of T-cells expressed CCR2, CXCR6, interleukin (IL)-18R, and IL-12Rbeta2-chain after in vitro stimulation with CVB4 in comparison with healthy children with or without HLA risk genotype. Moreover, we found that children with type 1 diabetes had decreased IFN-gamma secretion and expression of Tbet, both on mRNA and protein level, in CVB4-stimulated PBMCs. Accordingly, children with type 1 diabetes show an impaired type 1 immune response against CVB4 compared with healthy children. This may lead to a delayed clearance of the virus and, at least partly, explain why children with type 1 diabetes may be more prone to CVB4 infections and related complications, such as beta-cell damage.

Autoantibodies↗

Quality of care from the patient's perspective in pediatric diabetes care.

This study aimed to investigate perceived quality of diabetes care. A geographic population of 400 type 1 diabetes patients <20 years received the validated questionnaire quality of care from the patient's perspective (QPP) including additional context-specific items. Primary endpoints were perceived reality of care by specific items and factors and their subjective importance, respectively. Relations to severe hypoglycemia, HbA1c, insulin dose, BMI, age, duration and sociodemographic factors were also studied. On average, a high perceived quality of care was reported from both parents and adolescents (response rate 285/400 (71%) and 155/237 (65%), respectively); highest regarding possibility to talk to nurse/doctor in privacy, respect, general atmosphere, continuity in patient-physician relationship and patient participation. Lower perceived reality with higher subjective importance was seen for information about results from medical examinations and treatments and information about self-care, access to care and waiting time. While parents' and their adolescents' mean ratings correlated well for reality r=0.95 (p<0.001) and importance r=0.53 (p=0.023), parents rated reality level higher (p=0.012) and importance even higher (p<0.001). The QPP instrument used with additional context-specific items can provide specific information to be used in quality of care development. In our setting, improvements are needed regarding patient information, access to care and waiting time.

Adolescent↗

Information and informed consent in a longitudinal screening involving children: a questionnaire survey.

This empirical study explores participants' perceptions of information and understanding of their children's and their own involvement in a longitudinal screening, the ABIS Study. ABIS (All Babies In Southeast Sweden) is a multicentre, longitudinal research screening for Type 1 diabetes and multifactorial diseases involving 17 005 children and their families. For this study, a random selection of mothers was made, using perinatal questionnaire serial numbers from the ABIS study. In total, 293 of these mothers completed an anonymous questionnaire (response rate 73.3%). Our findings from the questionnaire indicate a marked difference between the reported satisfaction with and understanding of the information provided on the one hand and the significant lack of knowledge of some of the aims and methods of the ABIS screening on the other, namely concerning high-risk identification of involved children, potential prevention and future questionnaires. Two questions evoked by our results are: (1) what information is required for participants in longitudinal studies involving children? and (2) how do we ensure and sustain understanding, and thus in a prolonging, informed consent in these studies? This study underlines the importance of an increased understanding of the ethical issues that longitudinal research on children raise and the need to discuss how information and informed consent strategies should be analysed and designed in longitudinal studies.

Adult↗

Breastfeeding and introduction of solid foods in Swedish infants: the All Babies in Southeast Sweden study.

The aim of this report is to describe breastfeeding duration and introduction of foods in Swedish infants born 1997-9, in relation to current recommendations. A secondary aim is to examine breastfeeding duration and introduction of certain allergenic foods in allergy-risk families (for whom allergy-preventive advice has been issued). Out of 21,700 invited infants, screening questionnaires were completed for 16,070 infants after delivery. Parents to 11,081 infants completed a follow-up questionnaire regarding breastfeeding and introduction of foods and 9849 handed in detailed food diaries at 1 year of age. The percentages of infants who were exclusively breast-fed at 3, 6 and >or=9 months of age were 78.4, 10.1 and 3.9, respectively. The corresponding percentages for partial breastfeeding were 87.8, 68.9 and 43.6. Gluten-containing foods were introduced to 66% of infants between 4 and 6 months, as recommended at the time of the study, and one-quarter had stopped breastfeeding when gluten was introduced. More than 90% of parents introduced the first sample of solid food during months 4-6, as recommended. Fish and eggs had been introduced during the first year in 43% and 29%, respectively, of infants with atopic heredity. Exclusive breastfeeding duration and time of introduction of solid foods, including gluten, seemed to have been in line with Swedish recommendations at the time, although gluten was often introduced late, and not during ongoing breastfeeding as recommended. The adherence to allergy-preventive advice was less than optimal in infants with atopic heredity.

Animals↗

Parental smoking and risk of coeliac disease in offspring.

OBJECTIVE: In adults, smoking seems to give protection against coeliac disease (CD). But, only one study has thus far investigated the association between maternal smoking during pregnancy and risk of CD in offspring. However, that study did not adjust for duration of exclusive breastfeeding, or look at passive smoking after birth. MATERIAL AND METHODS: The current study was part of a prospective cohort study of infants born between 1 October 1997 and 1 October 1999 (the ABIS study; All Babies in Southeast Sweden). Data on smoking and exclusive breastfeeding were obtained through questionnaires distributed at infant birth and at 1 year of age. Coeliac disease was confirmed through small-bowel biopsy. Subgroup analyses were carried out according to maternal body mass index. RESULTS: Nine out of 53 (17%) children with CD as opposed to 1699 out of 15,344 (11.1%) non-coeliac children had mothers who had smoked during pregnancy (p = 0.172). Mothers who had smoked during pregnancy were hence not at increased risk of having a child with CD (OR = 1.64; 95% CI OR =0.80-3.37). Adjusting for duration of exclusive breastfeeding and the sex of infants in some 9585 children with data on exclusive breastfeeding lowered the OR for CD in mothers who smoked (adjusted OR (AOR) =0.89; 95% CI AOR = 0.27-2.93; p =0.843). Parents who smoked during the child's first year of life were not at increased risk of having an offspring with CD (OR = 1.94; 95% CI AOR =0.69-5.47; p =0. 203). CONCLUSIONS: No association was found between CD and parental smoking habits during pregnancy or during the child's first year of life. However, further studies with larger numbers of coeliac children are needed.

Adult↗

Aberrant regulation of interleukin-12 receptor beta2 chain on type 1 cytokine-stimulated T lymphocytes in type 1 diabetes.

An aberrant mitogen-induced polarization of peripheral blood T cells has been associated with type 1 diabetes (T1D). We studied, in T1D, type 1 and 2 cytokine-induced expression of the interleukin-12 receptor beta2 chain (IL-12Rbeta2 chain), which plays a critical role in regulating T-cell polarization. Peripheral blood lymphocytes from children with newly diagnosed T1D (n=10; mean age 10 years), from children with longstanding T1D (n=8; mean age 12.9 years) and from healthy children (n=15; mean age 11.5 years) were stimulated with phytohaemagglutinin (PHA) in a type 1 (IL-12 and anti-IL-4) or a type 2 (IL-4 and anti-IL-12) cytokine environment. Secretion of interferon-gamma (IFN-gamma), IL-5 and IL-13, as detected by enzyme-linked immunosorbent assay (ELISA), and expression of the IL-12Rbeta2 chain on CD4 and CD8 cells by flow cytometry, were analysed. Children with newly diagnosed and longstanding T1D had lower expression levels of the IL-12Rbeta2 chain on IL-12Rbeta2 chain-positive CD4 T cells (for a type 1 or a type 2 cytokine environment: P=0.01 and P=0.002 or P=0.02 and P=0.01, respectively) and on IL-12Rbeta2 chain-positive CD8 T cells (for a type 1 or a type 2 cytokine environment: P=0.007 and P=0.0007 or P=0.003 and P=0.01, respectively) when compared to healthy children. A decreased percentage of IL-12Rbeta2 chain-expressing CD4 T cells (P=0.07 and P=0.03) and CD8 T cells (P=0.004 and P=0.01) and increased secretion of IL-13 (P=0.006 and P=0.04) in a type 1 cytokine environment was seen in both groups of patients. Peripheral blood T cells from patients with both newly diagnosed and longstanding T1D showed poor polarization towards type 1 cells.

CD4-Positive T-Lymphocytes↗