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ABSTRACT: Infant dietary exposures have been linked to type 1 diabetes (T1D) development. IgG4 antibody responses to food antigens are associated with food intolerances but have not been explored prospectively in the period preceding T1D.
Using a case-cohort design, IgG4 antibodies to ß-lactoglobulin, gluten, and ovalbumin were measured in plasma collected annually from 260 DAISY participants. Of those, 77 developed islet autoimmunity (IA), defined as positive for either insulin, GAD65 or IA-2 autoantibodies on two consecutive visits, and 22 developed T1D.
In mixed model analysis adjusting for HLA-DR status, T1D family history, age and ethnicity, higher ß-lactoglobulin IgG4 concentrations were associated with shorter breastfeeding duration (beta = -0.03, 95% Confidence Interval: -0.05, -0.006) and earlier first cow's milk exposure (beta = -0.04, 95% Confidence Interval: -0.08, 0.00). Higher gluten IgG4 was associated with older age at gluten introduction (beta = 0.06, 95% Confidence Interval: 0.00, 0.13). In proportional hazards analysis adjusting for HLA-DR status, T1D family history and ethnicity, IgG4 against individual or multiple dietary antigens throughout childhood were not associated with IA. In addition, mean antigen-specific IgG4 concentrations in infancy (age <2 years) were not associated with risk of IA nor progression to T1D. Higher ovalbumin IgG4 at first IA positive visit was marginally associated with progression to T1D (Hazard Ratio: 1.39, 95% Confidence Interval: 1.00, 1.92).
We found no association between the IgG4 response to β-lactoglobulin, gluten, and the development of either IA or T1D. The association between higher ovalbumin and progression to T1D in children with IA should be explored in other populations.
PLoS ONE 01/2013; 8(2):e57936. · 4.09 Impact Factor
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ABSTRACT: BACKGROUND: The primary prevention measure for influenza infection has been the use of influenza vaccines. However, even when the vaccine and circulating strains are well-matched, some healthy children do not respond to the vaccine, likely due to a genetic basis for immune hyporesponsiveness. The primary objective of this study was to identify HLA class II genes associated with clinical hyporesponsiveness after trivalent inactivated influenza vaccine (TIV) in children. METHODS: We conducted a case-control study nested within a retrospective cohort of children that were screened at birth for HLA-DR,DQ genotypes by the Diabetes Autoimmunity Study in the Young (DAISY) and were subsequently followed for up to 8 years by Kaiser Permanente, Colorado (KPCO). Hyporesponsiveness was clinically defined as the occurrence of influenza or influenza-like illness (ILI) in peak influenza weeks in children fully vaccinated with TIV. Each child with clinical hyporesponse (n=252) was matched to 4 randomly selected controls (n=1006) by age and season. Children with clinical hyporesponse to TIV were identified using the Kaiser electronic clinical and immunization databases. Fully vaccinated children within the KPCO-DAISY cohort who did not have a diagnosis of ILI during the entire influenza season were eligible to be controls for that season. Class II HLA-DRB1 and HLA-DQB1 genes were the primary exposure variables. We used conditional logistic regression to calculate the matched odds ratios. RESULTS: In non-Hispanic white children, HLA-DR7/4,DQB1*0302 genotype was significantly associated (OR=5.15; 95% CI=1.94, 13.67; p=0.001), while in Hispanic children, HLA-DRB1*15 or 16 allele (OR=0.31; 95% CI=0.14, 0.69; p=0.004) and HLA-DR7/Y (DRB1*11, DRB1*13 and DRB1*14) genotype (OR=5.84; 95% CI=1.68, 20.28; p=0.006) were significantly associated with clinical hyporesponsiveness after TIV. CONCLUSIONS: HLA class II genes are associated with clinical hyporesponsiveness to TIV. This finding is important as it may help identify a group of children who are not protected by the commonly used TIV and may require alternative preventive strategies.
Vaccine 12/2012; · 3.77 Impact Factor
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ABSTRACT: Context:Type 1 diabetes is an insulin-resistant state, but it is less clear which tissues are affected. Our previous report implicated skeletal muscle and liver insulin resistance in people with type 1 diabetes, but this occurred independently of generalized, visceral, or ectopic fat.Objective:The aim of the study was to measure adipose tissue insulin sensitivity and plasma triglyceride composition in individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose.Design, Patients, and Methods:Fifty subjects (25 individuals with type 1 diabetes and 25 controls without) were studied. After 3 d of dietary control and overnight insulin infusion, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) · min. Infusions of [1,1,2,3,3-(2)H(2)]glycerol and [1-(13)C]palmitate were used to quantify lipid metabolism.Results:Basal glycerol and palmitate rates of appearance were similar between groups, decreased more in control subjects during the first two stages of the clamp, and similarly suppressed during the highest insulin dose. The concentration of insulin required for 50% inhibition of lipolysis was twice as high in individuals with type 1 diabetes. Plasma triglyceride saturation was similar between groups, but palmitoleic acid in plasma triglyceride was inversely related to adipocyte insulin sensitivity. Unesterified palmitoleic acid in plasma was positively related to insulin sensitivity in controls, but not in individuals with type 1 diabetes.Conclusions:Adipose tissue insulin resistance is a significant feature of type 1 diabetes. Palmitoleic acid is not related to insulin sensitivity in type 1 diabetes, as it was in controls, suggesting a novel mechanism for insulin resistance in this population.
The Journal of clinical endocrinology and metabolism 11/2012; · 6.50 Impact Factor
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ABSTRACT: OBJECTIVE
Type 1 diabetes is a common chronic childhood disease, and the incidence is increasing globally. Childhood infections are considered a potential environmental trigger of type 1 diabetes. Alternatively, improved hygiene and reduced childhood infections could explain the increase in type 1 diabetes in developed countries. The association of reported illnesses during infancy and later development of islet autoimmunity (IA) were examined in the Diabetes Autoimmunity Study in the Young.RESEARCH DESIGN AND METHODS
Complete illness interviews through 9 months of age were collected for 1,729 children, 1,174 without a family history of type 1 diabetes, and 555 children with a first-degree relative with type 1 diabetes. Persistent IA was defined as positive antibodies to insulin, glutamic acid decarboxylase, or tyrosine phosphatase on at least two consecutive study visits.RESULTSThere were 109 children with persistent IA among the 1,729 children with illness records. A greater number of gastrointestinal illnesses were associated with an increased risk of IA, but only among children who were exposed to gluten-containing grains (wheat or barley) either <4 months of age (hazard ratio 1.37 [95% CI 1.22-1.55]; P < 0.0001) or ≥7 months of age (1.12 [1.05-1.19]; P = 0.0005) compared with 4-6 months of age (P for interaction = 0.02). There were no associations of upper respiratory symptoms, respiratory illnesses, or fevers with IA.CONCLUSIONS
Specific pathogens such as enteroviruses or rotavirus may increase the risk of IA in the presence of existing inflammation induced by diet.
Diabetes care 10/2012; · 8.09 Impact Factor
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ABSTRACT: Herein, we describe recruitment efforts for a trial of lipid-lowering medications in adolescents with type 1 diabetes, age 12-21 years. Based on our experience, future studies will require multiple centers to enroll a sufficient number of participants for adequate data to direct dyslipidemia medication treatment guidelines for adolescents with type 1 diabetes.
International Journal of Pediatric Endocrinology 07/2012; 2012(1):24.
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ABSTRACT: We tested the hypothesis that altered Toll-like receptor (TLR) signaling may be involved in early stages of type 1 diabetes (T1D). To do so, we analyzed TLR-induced interleukin (IL)-1β and IL-6 responses in freshly isolated peripheral blood mononuclear cells (PBMNCs) from seropositive compared with seronegative subjects. Similar frequencies of myeloid dendritic cells (mDCs), plasmacytoid DCs (pDCs), and monocytes were observed in seropositive and seronegative subjects. Subjects with autoantibodies had increased proportions of monocytes expressing IL-1β ex vivo. Activating PBMNCs with TLR3, TLR4, or TLR7/8 agonists in vitro led to increased percentages of IL-1β-expressing monocytes and mDCs from seropositive versus seronegative subjects. TLR ligation also resulted in a diminished IL-6 response in seropositive individuals as lower frequencies of IL-6-expressing monocytes and mDCs were induced. The dysregulated TLR-induced IL-1β and IL-6 pathways were more readily detectable in children aged <11 years and from 11 to <21 years, respectively, and did not involve altered HbA(1c) or the presence of one or more autoantibodies. Finally, subjects with autoantibodies had lower amounts of serum chemokine (C-X-C motif) ligand 10 compared with autoantibody-negative subjects. Our data may imply that alterations in innate immune pathways are detectable in genetically susceptible individuals and could be linked with the early course of T1D.
Diabetes 06/2012; 61(10):2525-33. · 8.29 Impact Factor
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ABSTRACT: To define a panel of novel protein biomarkers of renal disease.
Adults with type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes study who were initially free of renal complications (n = 465) were followed for development of micro- or macroalbuminuria (MA) and early renal function decline (ERFD, annual decline in estimated glomerular filtration rate of ≥3.3%). The label-free proteomic discovery phase was conducted in 13 patients who progressed to MA by the 6-year visit and 11 control subjects, and four proteins (Tamm-Horsfall glycoprotein, α-1 acid glycoprotein, clusterin, and progranulin) identified in the discovery phase were measured by enzyme-linked immunosorbent assay in 74 subjects: group A, normal renal function (n = 35); group B, ERFD without MA (n = 15); group C, MA without ERFD (n = 16); and group D, both ERFD and MA (n = 8).
In the label-free analysis, a model of progression to MA was built using 252 peptides, yielding an area under the curve (AUC) of 84.7 ± 5.3%. In the validation study, ordinal logistic regression was used to predict development of ERFD, MA, or both. A panel including Tamm-Horsfall glycoprotein (odds ratio 2.9, 95% CI 1.3-6.2, P = 0.008), progranulin (1.9, 0.8-4.5, P = 0.16), clusterin (0.6, 0.3-1.1, P = 0.09), and α-1 acid glycoprotein (1.6, 0.7-3.7, P = 0.27) improved the AUC from 0.841 to 0.889.
A panel of four novel protein biomarkers predicted early renal damage in type 1 diabetes. These findings require further validation in other populations for prediction of renal complications and treatment monitoring.
Diabetes care 03/2012; 35(3):549-55. · 8.09 Impact Factor
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ABSTRACT: Type 1 diabetes is known to be a state of insulin resistance; however, the tissues involved in whole-body insulin resistance are less well known. It is unclear whether insulin resistance is due to glucose toxicity in the post-Diabetes Control and Complications Trial era of tighter glucose control.
We performed this study to determine muscle and liver insulin sensitivity individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose concentration.
Fifty subjects [25 controls without and 25 individuals with type 1 diabetes (diabetes duration 22.9 ± 1.7 yr, without known end organ damage] were frequency matched on age and body mass index by group and studied. After 3 d of dietary control and overnight insulin infusion to normalize glucose, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) · min. Glucose metabolism was quantified using an infusion of [6,6-(2)H(2)]glucose. Hepatic insulin sensitivity was measured using the insulin IC(50) for glucose rate of appearance (Ra), whereas muscle insulin sensitivity was measured using the glucose rate of disappearance during the highest insulin dose.
Throughout the study, glucose Ra was significantly greater in individuals compared with those without type 1 diabetes. The concentration of insulin required for 50% suppression of glucose Ra was 2-fold higher in subjects with type 1 diabetes. Glucose rate of disappearance was significantly lower in individuals with type 1 diabetes during the 8- and 40-mU/m(2) · min stages.
Insulin resistance in liver and skeletal muscle was a significant feature in type 1 diabetes. Nevertheless, the etiology of insulin resistance was not explained by body mass index, percentage fat, plasma lipids, visceral fat, and physical activity and was also not fully explained by hyperglycemia.
The Journal of clinical endocrinology and metabolism 02/2012; 97(5):1663-72. · 6.50 Impact Factor
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ABSTRACT: Type 1 diabetes (T1D) is associated with insulin resistance despite elevated levels of the insulin-sensitizing protein adiponectin. Whether the expected positive correlation between adiponectin and insulin sensitivity is preserved in a T1D population is unknown.
We measured the correlation between total and high-molecular-weight (HMW) adiponectin and insulin sensitivity in T1D patients and nondiabetic controls and identified determinants of adiponectin levels in patients with T1D.
Fasting total and HMW adiponectin were measured in 86 subjects from the Coronary Artery Calcification in T1D (CACTI) cohort (39 T1D, 47 nondiabetic; age 45 ± 8 yr; 55% female). The association of adiponectin levels with insulin sensitivity was analyzed.
The study was conducted at an academic research institute.
Fasting total and HMW adiponectin were measured by RIA and ELISA, respectively. Insulin sensitivity was measured by a hyperinsulinemic-euglycemic clamp. Multivariate linear regression was used to identify determinants of adiponectin levels.
Adiponectin levels positively correlated with insulin sensitivity in both subject groups (total adiponectin, r = 0.33 P < 0.05 for T1D, r = 0.29 P < 0.05 controls), but insulin sensitivity was lower in T1D subjects at any given level of total or HMW adiponectin. Adiponectin levels were independently associated with age, gender, and trunk fat, but these variables did not account for increased adiponectin in patients with T1D.
Adiponectin levels are positively correlated with insulin sensitivity in T1D patients. However, T1D patients have decreased insulin sensitivity compared with controls at every level of adiponectin, suggesting an important adaptive change of adiponectin set point.
The Journal of clinical endocrinology and metabolism 01/2012; 97(4):E642-7. · 6.50 Impact Factor
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ABSTRACT: Type I diabetes (T1D) is an autoimmune disease characterized by destruction of insulin-producing β-cells in the pancreas. Although several islet cell autoantigens are known, the breadth and spectrum of autoantibody targets has not been fully explored. Here the luciferase immunoprecipitation systems (LIPS) antibody profiling technology was used to study islet and other organ-specific autoantibody responses in parallel. Examination of an initial cohort of 93 controls and 50 T1D subjects revealed that 16% of the diabetic subjects showed anti-gastric ATPase autoantibodies which did not correlate with autoantibodies against GAD65, IA2, or IA2-β. A more detailed study of a second cohort with 18 potential autoantibody targets revealed marked heterogeneity in autoantibody responses against islet cell autoantigens including two polymorphic variants of ZnT8. A subset of T1D subjects exhibited autoantibodies against several organ-specific targets including gastric ATPase (11%), thyroid peroxidase (14%), and anti-IgA autoantibodies against tissue transglutaminase (12%). Although a few T1D subjects showed autoantibodies against a lung-associated protein KCNRG (6%) and S100-β (8%), no statistically significant autoantibodies were detected against several cytokines. Analysis of the overall autoantibody profiles using a heatmap revealed two major subgroups of approximately similar numbers, consisting of T1D subjects with and without organ-specific autoantibodies. Within the organ-specific subgroup, there was minimal overlap among anti-gastric ATPase, anti-thyroid peroxidase, and anti-transglutaminase seropositivity, and these autoantibodies did not correlate with islet cell autoantibodies. Examination of a third cohort, comprising prospectively collected longitudinal samples from high-risk individuals, revealed that anti-gastric ATPase autoantibodies were present in several individuals prior to detection of islet autoantibodies and before clinical onset of T1D. Taken together, these results suggest that autoantibody portraits derived from islet and organ-specific targets will likely be useful for enhancing the clinical management of T1D.
PLoS ONE 01/2012; 7(9):e45216. · 4.09 Impact Factor
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ABSTRACT: A subset of children develops persistent insulin autoantibodies (IAA; almost always as the only islet autoantibody) without evidence of progression to diabetes. The aim of the current study was the development and characterization of the performance of a nonradioactive fluid phase IAA assay in relation to standard IAA radioassay. We developed a nonradioactive IAA assay where bivalent IAA cross-link two insulin moieties in a fluid phase. The serum samples positive for anti-islet autoantibodies from 150 newly diagnosed patients with diabetes (Barbara Davis Center plus Diabetes Autoantibody Standardization Program [DASP] workshop) and 70 prediabetic subjects who were followed to diabetes were studied. In addition, sequential samples from 64 nondiabetic subjects who were persistently IAA(+) were analyzed. With 99th percentile of specificity, the new assay with the technology from Meso Scale Discovery Company (MSD-IAA) detects as positive 61% (61 of 100) of new-onset patients and 80% (56 of 70) of prediabetic patients compared with our current fluid phase micro-IAA radioassay (mIAA; 44 and 74%, respectively). In addition, MSD-IAA demonstrated better sensitivity than our mIAA from blinded DASP workshop (68 vs. 56% with the same 99% specificity). Of 64 IAA(+) nondiabetic subjects, 25% (8 of 32) who had only IAA and thus the low risk for progression to diabetes were positive with MSD-IAA assay. In contrast, 100% (32 of 32) high-risk children (IAA plus other islet autoantibodies) were positive with MSD-IAA. The IAA detectable by radioassay, but not MSD-IAA, were usually of lower affinity compared with the IAA of the high-risk children. These data suggest that a subset of IAA with current radioassay (not MSD-IAA) represents biologic false positives in terms of autoimmunity leading to diabetes. We hypothesize that factors related to the mechanism of loss of tolerance leading to diabetes determine high affinity and MSD-IAA reactivity.
Diabetes 11/2011; 61(1):179-86. · 8.29 Impact Factor
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ABSTRACT: Does untreated celiac disease associated with type 1 diabetes mellitus worsen microvascular outcomes? Previous studies have concluded that a gluten-free diet offers no major benefit for glycemic control, whereas Leeds and colleagues provide preliminary data to the contrary. The question awaits a long-term prospective study or a clinical trial.
Nature Reviews Endocrinology 11/2011; 8(1):5-6, 7-8. · 9.97 Impact Factor
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Marian Rewers
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ABSTRACT: The "accelerator hypothesis" has made a significant impact on research into the etiology of type 1 diabetes. Some, but not all prospective studies have confirmed a weak association between insulin resistance and faster progression to diabetes among persons with advanced islet autoimmunity. However, there is hardly any evidence that insulin resistance can cause development of islet autoimmunity, thus be responsible for the ongoing pandemic of type 1 diabetes in children.
Pediatric Diabetes 11/2011; 13(4):340-3. · 2.16 Impact Factor
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ABSTRACT: Type 1 diabetes (T1D) is an autoimmune disorder which affects millions around the world. The incidence of T1D in children is increasing worldwide at a rate that cannot be explained by genetics alone. This review explores the recent research regarding possible causes of this epidemic.
Investigation into T1D epidemiology has recently focused on several hypotheses. These theories include the role of infections, early childhood diet, vitamin D exposure, environmental pollutants, increased height velocity, obesity, and insulin resistance in the risk for T1D. Over the past year, the evidence has strengthened for early childhood infections, dietary proteins, and insulin resistance as risk factors for T1D, but not for vitamin D exposure or environmental pollutants.
Investigation into the source of the current epidemic of T1D has shed light on several possible causes, but has not provided definitive answers, yet.
Current opinion in endocrinology, diabetes, and obesity 08/2011; 18(4):248-51.
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ABSTRACT: Cystatin C is used increasingly as a biomarker of renal function; however, cystatin C assays are not standardized. Our objective was to compare cystatin C results within the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study over time and in repeated measures to evaluate for assay drift.
Serum samples were obtained at baseline (visit 1 [V1], 2000 to 2002) and follow-up (visit 2 [V2], 2003 to 2005; visit 3 [V3], 2006 to 2008) and were assayed in 2006 (V1), 2007 to 2008 (V2), and 2010 (V3) in the same laboratory.
Mean cystatin C levels measured using the Dade-Behring assay decreased over time in subjects, with measures at all three visits (V1: 0.80 ± 0.19 [0.42 to 3.41], V2: 0.75 ± 0.22 [0.39 to 3.77], and V3: 0.69 ± 0.22 [0.39 to 3.79]). Cystatin C values were lower in V1 and V2 samples remeasured in 2010 (mean differences -0.13 ± 0.04 and -0.08 ± 0.04, P < 0.0001 for both). Correlations for original and re-run values were strong for V1 (r = 0.99) and V2 (r = 0.99). Deming regression equations and Bland-Altman plots suggest a systematic shift in the values over time.
Systematic shifts in cystatin C levels, which can be corrected by regression adjustment, occurred in our laboratory in samples measured in 2006 and 2007 to 2008 as compared with 2010. Assay standardization and measurement reliability for cystatin C must be addressed.
Clinical Journal of the American Society of Nephrology 08/2011; 6(8):1952-5. · 5.23 Impact Factor
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ABSTRACT: The aim was to examine whether excess weight is associated with coronary artery calcium (CAC), independent of metabolic parameters in adults with type 1 diabetes (T1D).
Subjects between 19 and 56 years of age with T1D (n=621) from the Coronary Artery Calcification in Type 1 Diabetes study were classified as abnormal on four metabolic parameters: blood pressure ≥130/85 mm Hg or on antihypertensive treatment; high-density lipoprotein-cholesterol of <40 mg/dL for men or <50 mg/dL for women; triglycerides of ≥150 mg/dL; or C-reactive protein of ≥3 μg/mL. Study participants with two or more abnormal parameters were classified as metabolically abnormal. Weight categories by body mass index were normal (<25 kg/m(2)), overweight (25 to <30 kg/m(2)), and obese (≥30 kg/m(2)). CAC was measured at two visits 6.0±0.5 years apart. Progression of CAC was defined as an increase in square root transformed CAC volume of ≥2.5 mm(3) or development of clinical coronary artery disease.
Among subjects with T1D, 48% of normal, 61% of overweight, and 73% of obese participants were classified as metabolically abnormal (P<0.0001). Overweight and obesity were independently associated with presence of CAC, independent of presence of metabolically abnormal. Obesity but not overweight was associated with CAC progression, independent of the other cardiovascular risk factors.
Although obesity is known to increase cardiovascular disease risk through inducing metabolic abnormalities such as dyslipidemia, hypertension, and inflammation, it is also a strong predictor of subclinical atherosclerosis progression in adults with T1D independent of these factors.
Diabetes Technology & Therapeutics 07/2011; 13(10):991-6. · 1.93 Impact Factor
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The Journal of pediatrics 07/2011; 159(1):169. · 4.02 Impact Factor
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ABSTRACT: We investigated whether omega-3 fatty acid intake and erythrocyte membrane omega-3 fatty acid levels are associated with conversion to type 1 diabetes in children with islet autoimmunity (IA).
The Diabetes Autoimmunity Study in the Young is following children at increased genetic risk for type 1 diabetes for the development of persistent IA, as defined as being positive for glutamic acid decarboxylase 65, i, or insulin autoantibodies on two consecutive visits, and then for the development of type 1 diabetes, as diagnosed by a physician. One hundred and sixty-seven children with persistent IA were followed for a mean of 4.8 yr, and 45 of these developed type 1 diabetes at a mean age of 8.7 yr. Erythrocyte membrane fatty acids (as a percent of total lipid) and dietary fatty acid intake (estimated via food frequency questionnaire) were analyzed as time-varying covariates in proportional hazards survival analysis, with follow-up time starting at detection of the first autoantibody.
Neither dietary intake of omega-3 fatty acids nor omega-6 fatty acids were associated with conversion to type 1 diabetes, adjusting for human leukocyte antigen (HLA)-DR, family history of type 1 diabetes, age at first IA positivity, maternal age, maternal education, and maternal ethnicity. Adjusting for HLA-DR, family history of type 1 diabetes and age at first IA positivity, omega-3 and omega-6 fatty acid levels of erythrocyte membranes were not associated with conversion to type 1 diabetes.
In this observational study, omega-3 fatty acid intake and status are not associated with conversion to type 1 diabetes in children with IA.
Pediatric Diabetes 03/2011; 12(8):669-75. · 2.16 Impact Factor
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ABSTRACT: To determine the benefits of screening for celiac autoimmunity via immunoglobulin A transglutaminase autoantibodies (TG) in children with type 1 diabetes (T1D).
We followed up 79 screening-identified TG+ and 56 matched TG- children with T1D for 2 years to evaluate growth, bone mineral density, nutritional status, and diabetes control. TG+ subjects self-selected to gluten-free or gluten-containing diet.
Of the initial cohort, 80% were available for reexamination after 2 years. TG+ subjects had consistently lower weight z-scores and higher urine N-telopeptides than TG- subjects, but similar measures of bone density and diabetes outcomes. TG+ children who remained on a gluten-containing diet had lower insulin-like growth factor binding protein 3 z-scores compared with TG+ subjects who reported following a gluten-free diet. Children who continued with high TG index throughout the study had lower bone mineral density z-scores, ferritin, and vitamin D 25OH levels, compared with the TG- group.
No significant adverse outcomes were identified in children with T1D with screening-identified TG+ who delay therapy with a gluten-free diet for 2 years. Children with persistently high levels of TG may be at greater risk. The optimal timing of screening and treatment for celiac disease in children with T1D requires further investigation.
The Journal of pediatrics 02/2011; 158(2):276-81.e1. · 4.02 Impact Factor
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ABSTRACT: Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a lipoprotein-associated enzyme that cleaves oxidized phosphatidylcholines, generating pro-atherosclerotic lysophosphatidylcholine and oxidized free fatty acids. Lp-PLA₂ is independently associated with cardiovascular disease (CVD) in a variety of populations. Coronary calcium is a measure of subclinical CVD, and progression of coronary calcification predicts future CVD events. In type 1 diabetes there is an increase in coronary calcium and CVD despite a favorable lipid profile. Levels of Lp-PLA₂ in type 1 diabetes are not known, nor is the relationship between Lp-PLA₂ and progression of coronary calcification.
The Coronary Artery Calcification in Type 1 Diabetes study measured coronary calcium by electron-beam computed tomography twice over a 2.6 ± 0.3-year interval. Lp-PLA₂ mass and activity were measured at baseline (n = 1,097 subjects, 506 with and 591 without type 1 diabetes).
In type 1 diabetes Lp-PLA₂ mass was marginally higher (285 ± 79 vs. 278 ± 78 ng/mL, P = 0.1), and Lp-PLA₂ activity was significantly lower (137 ± 30 vs. 146 ± 36 nmol/min/mL, P < 0.0001) than in those without diabetes. There was a greater proportion of those with progression of coronary calcification in type 1 diabetes compared with those without diabetes (24% vs. 10%, P < 0.0001). Lp-PLA₂ activity was independently associated with progression of coronary calcification in multivariate analysis (4th quartile verses bottom three quartiles, odds ratio = 1.77 [1.08-2.91], P = 0.02). LpPLA₂ mass was not significantly associated with progression of coronary calcification in this cohort (P = 0.09).
Lp-PLA₂ activity predicts progression of subclinical atherosclerosis in individuals with and without type 1 diabetes.
Diabetes Technology & Therapeutics 02/2011; 13(3):381-7. · 1.93 Impact Factor
