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  • 1
    In: Diabetes, American Diabetes Association, Vol. 68, No. 6 ( 2019-06-01), p. 1267-1276
    Abstract: A three-arm, randomized, double-masked, placebo-controlled phase 2b trial performed by the Type 1 Diabetes TrialNet Study Group previously demonstrated that low-dose anti-thymocyte globulin (ATG) (2.5 mg/kg) preserved β-cell function and reduced HbA1c for 1 year in new-onset type 1 diabetes. Subjects (N = 89) were randomized to 1) ATG and pegylated granulocyte colony-stimulating factor (GCSF), 2) ATG alone, or 3) placebo. Herein, we report 2-year area under the curve (AUC) C-peptide and HbA1c, prespecified secondary end points, and potential immunologic correlates. The 2-year mean mixed-meal tolerance test–stimulated AUC C-peptide, analyzed by ANCOVA adjusting for baseline C-peptide, age, and sex (n = 82) with significance defined as one-sided P & lt; 0.025, was significantly higher in subjects treated with ATG versus placebo (P = 0.00005) but not ATG/GCSF versus placebo (P = 0.032). HbA1c was significantly reduced at 2 years in subjects treated with ATG (P = 0.011) and ATG/GCSF (P = 0.022) versus placebo. Flow cytometry analyses demonstrated reduced circulating CD4:CD8 ratio, increased regulatory T-cell:conventional CD4 T-cell ratios, and increased PD-1+CD4+ T cells following low-dose ATG and ATG/GCSF. Low-dose ATG partially preserved β-cell function and reduced HbA1c 2 years after therapy in new-onset type 1 diabetes. Future studies should determine whether low-dose ATG might prevent or delay the onset of type 1 diabetes.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1501252-9
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  • 2
    In: Diabetes Care, American Diabetes Association, Vol. 41, No. 9 ( 2018-09-01), p. 1917-1925
    Abstract: A pilot study suggested that combination therapy with low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) preserves C-peptide in established type 1 diabetes (T1D) (duration 4 months to 2 years). We hypothesized that 1) low-dose ATG/GCSF or 2) low-dose ATG alone would slow the decline of β-cell function in patients with new-onset T1D (duration & lt;100 days). RESEARCH DESIGN AND METHODS A three-arm, randomized, double-masked, placebo-controlled trial was performed by the Type 1 Diabetes TrialNet Study Group in 89 subjects: 29 subjects randomized to ATG (2.5 mg/kg intravenously) followed by pegylated GCSF (6 mg subcutaneously every 2 weeks for 6 doses), 29 to ATG alone (2.5 mg/kg), and 31 to placebo. The primary end point was mean area under the curve (AUC) C-peptide during a 2-h mixed-meal tolerance test 1 year after initiation of therapy. Significance was defined as one-sided P value & lt; 0.025. RESULTS The 1-year mean AUC C-peptide was significantly higher in subjects treated with ATG (0.646 nmol/L) versus placebo (0.406 nmol/L) (P = 0.0003) but not in those treated with ATG/GCSF (0.528 nmol/L) versus placebo (P = 0.031). HbA1c was significantly reduced at 1 year in subjects treated with ATG and ATG/GCSF, P = 0.002 and 0.011, respectively. CONCLUSIONS Low-dose ATG slowed decline of C-peptide and reduced HbA1c in new-onset T1D. Addition of GCSF did not enhance C-peptide preservation afforded by low-dose ATG. Future studies should be considered to determine whether low-dose ATG alone or in combination with other agents may prevent or delay the onset of the disease.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1490520-6
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  • 3
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 12 ( 2020-12-01), p. e4393-e4406
    Abstract: We set forth to compare ethnicities for metabolic and immunological characteristics at the clinical diagnosis of type 1 diabetes (T1D) and assess the effect of ethnicity on beta-cell functional loss within 3 years after clinical diagnosis. Research Methods and Design We studied participants in TrialNet New Onset Intervention Trials (n = 624, median age = 14.4 years, 58% male, 8.7% Hispanic) and followed them prospectively for 3 years. Mixed meal tolerance tests (MMTT) were performed within 6 months following clinical diagnosis and repeated semiannually. Unless otherwise indicated, analyses were adjusted for age, sex, BMI Z-score, and diabetes duration. Results At T1D clinical diagnosis, Hispanics, compared with non-Hispanic whites (NHW), had a higher frequency of diabetic ketoacidosis (DKA) (44.7% vs 25.3%, OR = 2.36, P = 0.01), lower fasting glucose (97 vs 109 mg/dL, P = 0.02) and higher fasting C-peptide (1.23 vs 0.94 ng/mL, P = 0.02) on the first MMTT, and higher frequency of ZnT8 autoantibody positivity (n = 201, 94.1% vs 64%, OR = 7.98, P = 0.05). After exclusion of participants in experimental arms of positive clinical trials, C-peptide area under the curve (AUC) trajectories during the first 3 years after clinical diagnosis were not significantly different between Hispanics and NHW after adjusting for age, sex, BMI-z score, and DKA (n = 413, P = 0.14). Conclusion Despite differences in the metabolic and immunological characteristics at clinical diagnosis of T1D between Hispanics and NHW, C-peptide trajectories did not differ significantly in the first 3 years following clinical diagnosis after adjustment for body mass index and other confounders. These findings may inform the design of observational studies and intervention trials in T1D.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 4
    Online Resource
    Online Resource
    Elsevier BV ; 1992
    In:  Journal of Diabetes and its Complications Vol. 6, No. 3 ( 1992-7), p. 163-165
    In: Journal of Diabetes and its Complications, Elsevier BV, Vol. 6, No. 3 ( 1992-7), p. 163-165
    Type of Medium: Online Resource
    ISSN: 1056-8727
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1992
    detail.hit.zdb_id: 2006763-X
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  • 5
    In: Diabetes Care, American Diabetes Association, Vol. 42, No. 2 ( 2019-02-01), p. 192-199
    Abstract: There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings. RESEARCH DESIGN AND METHODS Subjects from the TrialNet Pathway to Prevention Study (N = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A] , and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years. RESULTS At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all P & lt; 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all P ≤ 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody–positive, 13% for single autoantibody–positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody–positive, 12% for single autoantibody–positive, and 0.5% for initially autoantibody-negative subjects. CONCLUSIONS Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody–positive identical twins and multiple autoantibody–positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1490520-6
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  • 6
    In: Diabetes Care, American Diabetes Association, Vol. 41, No. 9 ( 2018-09-01), p. 1887-1894
    Abstract: We tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression of islet autoimmunity and T1D in at-risk individuals. RESEARCH DESIGN AND METHODS We studied the 1,244 TrialNet Pathway to Prevention study participants (T1D patients’ relatives without diabetes and with one or more positive autoantibodies) who were genotyped with Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2–51.8], 48% male, 80.5% non-Hispanic white, median follow-up 5.4 years). Of 291 participants with a single positive autoantibody at screening, 157 converted to multiple autoantibody positivity and 55 developed diabetes. Of 953 participants with multiple positive autoantibodies at screening, 419 developed diabetes. We calculated the T1D GRS from 30 T1D-associated single nucleotide polymorphisms. We used multivariable Cox regression models, time-dependent receiver operating characteristic curves, and area under the curve (AUC) measures to evaluate prognostic utility of T1D GRS, age, sex, Diabetes Prevention Trial–Type 1 (DPT-1) Risk Score, positive autoantibody number or type, HLA DR3/DR4-DQ8 status, and race/ethnicity. We used recursive partitioning analyses to identify cut points in continuous variables. RESULTS Higher T1D GRS significantly increased the rate of progression to T1D adjusting for DPT-1 Risk Score, age, number of positive autoantibodies, sex, and ethnicity (hazard ratio [HR] 1.29 for a 0.05 increase, 95% CI 1.06–1.6; P = 0.011). Progression to T1D was best predicted by a combined model with GRS, number of positive autoantibodies, DPT-1 Risk Score, and age (7-year time-integrated AUC = 0.79, 5-year AUC = 0.73). Higher GRS was significantly associated with increased progression rate from single to multiple positive autoantibodies after adjusting for age, autoantibody type, ethnicity, and sex (HR 2.27 for GRS & gt;0.295, 95% CI 1.47–3.51; P = 0.0002). CONCLUSIONS The T1D GRS independently predicts progression to T1D and improves prediction along T1D stages in autoantibody-positive relatives.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1490520-6
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  • 7
    Online Resource
    Online Resource
    American Diabetes Association ; 1981
    In:  Diabetes Care Vol. 4, No. 4 ( 1981-07-01), p. 506-506
    In: Diabetes Care, American Diabetes Association, Vol. 4, No. 4 ( 1981-07-01), p. 506-506
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1981
    detail.hit.zdb_id: 1490520-6
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  • 8
    Online Resource
    Online Resource
    American Diabetes Association ; 1980
    In:  Diabetes Care Vol. 3, No. 1 ( 1980-01-01), p. 69-76
    In: Diabetes Care, American Diabetes Association, Vol. 3, No. 1 ( 1980-01-01), p. 69-76
    Abstract: Pregnant diabetic women represent a unique category of patient in whom diabetic control is most desirable, since even minor degrees of hyperglycemia have adverse effects on the conceptus. In 18 insulin-dependent pregnant diabetic women (White Class B, N = 4; C, N = 5; D, N = 7; and R, N =2), we have utilized a therapeutic program consisting of intensive patient education, a multiple-component insulin regimen (two to four injections daily), careful dietary control, and meticulous balancing of food, activity, and insulin dosage, monitoring such balance with patient-determined blood glucose measurements four to seven times daily using the Dextrostix/Eyetone system. Our goals for blood glucose management have been to attain fasting levels of 60–90 mg/dl, preprandial levels less than 105 mg/dl, and postprandial levels less than 120 mg/dl, in the absence of significant hypoglycemia. We have been able to attain these goals for most of the period of monitoring in the majority of these patients, while in the others we have achieved marked improvement in diabetic control, although we did not consistently attain our goals. Despite this, there was not infrequent neonatal morbidity, including a 33% frequency of macrosomia, an 11% frequency of significant hypoglycemia, and a 22% frequency of congenital malformation. Nevertheless, all infants survived and are generally healthy, whereas only 38% of 21 previous pregnancies in these same women have eventuated in living offspring. Thus, although further refinement is clearly indicated, it appears that our approach has resulted in improved pregnancy outcome. Patient self-monitoring of blood glucose is a procedure that is relatively simple, practical, acceptable to patients, and facilitates the attainment of glycemic control.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1980
    detail.hit.zdb_id: 1490520-6
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  • 9
    Online Resource
    Online Resource
    American Diabetes Association ; 1981
    In:  Diabetes Care Vol. 4, No. 2 ( 1981-03-01), p. 311-318
    In: Diabetes Care, American Diabetes Association, Vol. 4, No. 2 ( 1981-03-01), p. 311-318
    Abstract: Patient self-monitoring of blood glucose is a useful adjuvant to diabetes therapy that facilitates improved glycemic control when used as part of an intensive diabetes management program that includes careful balancing of food intake, energy expenditure, and insulin dosage. This paper describes an approach by which patient-determined blood glucose measurements may be used to attain and maintain glycemic control. The patient is provided with a set of algorithms by which minor adjustments in a therapeutic routine may be made to achieve the desired control.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1981
    detail.hit.zdb_id: 1490520-6
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  • 10
    Online Resource
    Online Resource
    American Diabetes Association ; 1978
    In:  Diabetes Care Vol. 1, No. 3 ( 1978-05-01), p. 150-157
    In: Diabetes Care, American Diabetes Association, Vol. 1, No. 3 ( 1978-05-01), p. 150-157
    Abstract: Home blood glucose monitoring, using Dextrostix and an Eyetone meter, has been utilized in several subcategories of patients with insulin-dependent diabetes mellitus. These include pregnant patients, anephric patients, patients undergoing weight reduction, patients with altered renal threshold for glucose reabsorption, and patients in whom diabetic regulation is difficult. Patients monitored home blood glucose continually (on a daily basis), intermittently, or only for particular problems or symptoms. Such monitoring can be practically accomplished in a manner acceptable to patients. Motivation, compliance with protocol, and an understanding of the objectives of the program are essential on the part of the patient. Home blood glucose monitoring, however, can provide an insight diabetes regulation that cannot be attained in any other way and can greatly facilitate regulation of diabetes. Such home blood glucose monitoring may increase the likelihood of achievement of a degree of control approximating euglycemia.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1978
    detail.hit.zdb_id: 1490520-6
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