Browsing by Author "Haller, Michael J."

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    Clinical trial data validate the C-peptide estimate model in type 1 diabetes
    (SpringerLink, 2020-04) Wentworth, John M.; Bediaga, Naiara G.; Gitelman, Stephen E.; Evans-Molina, Carmela; Gottlieb, Peter A.; Colman, Peter G.; Haller, Michael J.; Harrison, Leonard C.; Medicine, School of Medicine
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    Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes
    (Springer, 2024-09) Phillip, Moshe; Achenbach, Peter; Addala, Ananta; Albanese-O'Neill, Anastasia; Battelino, Tadej; Bell, Kirstine J.; Besser, Rachel E. J.; Bonifacio, Ezio; Colhoun, Helen M.; Couper, Jennifer J.; Craig, Maria E.; Danne, Thomas; de Beaufort, Carine; Dovc, Klemen; Driscoll, Kimberly A.; Dutta, Sanjoy; Ebekozien, Osagie; Elding Larsson, Helena; Feiten, Daniel J.; Frohnert, Brigitte I.; Gabbay, Robert A.; Gallagher, Mary P.; Greenbaum, Carla J.; Griffin, Kurt J.; Hagopian, William; Haller, Michael J.; Hendrieckx, Christel; Hendriks, Emile; Holt, Richard I. G.; Hughes, Lucille; Ismail, Heba M.; Jacobsen, Laura M.; Johnson, Suzanne B.; Kolb, Leslie E.; Kordonouri, Olga; Lange, Karin; Lash, Robert W.; Lernmark, Åke; Libman, Ingrid; Lundgren, Markus; Maahs, David M.; Marcovecchio, M. Loredana; Mathieu, Chantal; Miller, Kellee M.; O'Donnell, Holly K.; Oron, Tal; Patil, Shivajirao P.; Pop-Busui, Rodica; Rewers, Marian J.; Rich, Stephen S.; Schatz, Desmond A.; Schulman-Rosenbaum, Rifka; Simmons, Kimber M.; Sims, Emily K.; Skyler, Jay S.; Smith, Laura B.; Speake, Cate; Steck, Andrea K.; Thomas, Nicholas P. B.; Tonyushkina, Ksenia N.; Veijola, Riitta; Wentworth, John M.; Wherrett, Diane K.; Wood, Jamie R.; Ziegler, Anette-Gabriele; DiMeglio, Linda A.; Pediatrics, School of Medicine
    Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk of (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb+; (2) when people who are IAb+ are initially identified there is a need for confirmation using a second sample; (3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.
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    Correction to: Consensus guidance for monitoring individuals with islet autoantibody‑positive pre‑stage 3 type 1 diabetes
    (Springer, 2024) Phillip, Moshe; Achenbach, Peter; Addala, Ananta; Albanese-O'Neill, Anastasia; Battelino, Tadej; Bell, Kirstine J.; Besser, Rachel E. J.; Bonifacio, Ezio; Colhoun, Helen M.; Couper, Jennifer J.; Craig, Maria E.; Danne, Thomas; de Beaufort, Carine; Dovc, Klemen; Driscoll, Kimberly A.; Dutta, Sanjoy; Ebekozien, Osagie; Elding Larsson, Helena; Feiten, Daniel J.; Frohnert, Brigitte I.; Gabbay, Robert A.; Gallagher, Mary P.; Greenbaum, Carla J.; Griffin, Kurt J.; Hagopian, William; Haller, Michael J.; Hendrieckx, Christel; Hendriks, Emile; Holt, Richard I. G.; Hughes, Lucille; Ismail, Heba M.; Jacobsen, Laura M.; Johnson, Suzanne B.; Kolb, Leslie E.; Kordonouri, Olga; Lange, Karin; Lash, Robert W.; Lernmark, Åke; Libman, Ingrid; Lundgren, Markus; Maahs, David M.; Marcovecchio, M. Loredana; Mathieu, Chantal; Miller, Kellee M.; O'Donnell, Holly K.; Oron, Tal; Patil, Shivajirao P.; Pop-Busui, Rodica; Rewers, Marian J.; Rich, Stephen S.; Schatz, Desmond A.; Schulman-Rosenbaum, Rifka; Simmons, Kimber M.; Sims, Emily K.; Skyler, Jay S.; Smith, Laura B.; Speake, Cate; Steck, Andrea K.; Thomas, Nicholas P. B.; Tonyushkina, Ksenia N.; Veijola, Riitta; Wentworth, John M.; Wherrett, Diane K.; Wood, Jamie R.; Ziegler, Anette-Gabriele; DiMeglio, Linda A.; Pediatrics, School of Medicine
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    Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial
    (AMA, 2015-12) Libman, Ingrid M.; Miller, Kellee M.; DiMeglio, Linda A.; Bethin, Kathleen E.; Katz, Michelle L.; Shah, Avni; Simmons, Jill H.; Haller, Michael J.; Raman, Sripriya; Tamborlane, William V.; Coffey, Julie K.; Saenz, Ashleigh M.; Beck, Roy W.; Nadeau, Kristen J.; Department of Pediatrics, IU School of Medicine
    Importance Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results. Objective To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes. Design, Setting, and Participants Multicenter (26 pediatric endocrinology clinics), double-blind, placebo-controlled randomized clinical trial involving 140 adolescents aged 12.1 to 19.6 years (mean [SD] 15.3 [1.7] years) with mean type 1 diabetes duration 7.0 (3.3) years, mean body mass index (BMI) 94th (4) percentile, mean total daily insulin 1.1 (0.2) U/kg, and mean HbA1c 8.8% (0.7%). Interventions Randomization to receive metformin (n = 71) (≤2000 mg/d) or placebo (n = 69). Main Outcomes and Measures Primary outcome was change in HbA1c from baseline to 26 weeks adjusted for baseline HbA1c. Secondary outcomes included change in blinded continuous glucose monitor indices, total daily insulin, BMI, waist circumference, body composition, blood pressure, and lipids. Results Between October 2013 and February 2014, 140 participants were enrolled. Baseline HbA1c was 8.8% in each group. At 13-week follow-up, reduction in HbA1c was greater with metformin (−0.2%) than placebo (0.1%; mean difference, −0.3% [95% CI, −0.6% to 0.0%]; P = .02). However, this differential effect was not sustained at 26-week follow up when mean change in HbA1c from baseline was 0.2% in each group (mean difference, 0% [95% CI, −0.3% to 0.3%]; P = .92). At 26-week follow-up, total daily insulin per kg of body weight was reduced by at least 25% from baseline among 23% (16) of participants in the metformin group vs 1% (1) of participants in the placebo group (mean difference, 21% [95% CI, 11% to 32%]; P = .003), and 24% (17) of participants in the metformin group and 7% (5) of participants in the placebo group had a reduction in BMI z score of 10% or greater from baseline to 26 weeks (mean difference, 17% [95% CI, 5% to 29%]; P = .01). Gastrointestinal adverse events were reported by more participants in the metformin group than in the placebo group (mean difference, 36% [95% CI, 19% to 51%]; P < .001). Conclusions and Relevance Among overweight adolescents with type 1 diabetes, the addition of metformin to insulin did not improve glycemic control after 6 months. Of multiple secondary end points, findings favored metformin only for insulin dose and measures of adiposity; conversely, use of metformin resulted in an increased risk for gastrointestinal adverse events. These results do not support prescribing metformin to overweight adolescents with type 1 diabetes to improve glycemic control.
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    Simplifying prediction of disease progression in pre-symptomatic type 1 diabetes using a single blood sample
    (SpringerLink, 2021-11) Bediaga, Naiara G.; Li-Wai-Suen, Connie S.N.; Haller, Michael J.; Gitelman, Stephen E.; Evans-Molina, Carmella; Gottlieb, Peter A.; Hippich, Markus; Ziegler, Anette-Gabriele; Lernmark, Ake; DiMeglio, Linda A.; Wherrett, Diane K.; Colman, Peter G.; Harrison, Leonard C.; Wentworth, John M.; Pediatrics, School of Medicine
    Aims/hypothesis: Accurate prediction of disease progression in individuals with pre-symptomatic type 1 diabetes has potential to prevent ketoacidosis and accelerate development of disease-modifying therapies. Current tools for predicting risk require multiple blood samples taken during an OGTT. Our aim was to develop and validate a simpler tool based on a single blood draw. Methods: Models to predict disease progression using a single OGTT time point (0, 30, 60, 90 or 120 min) were developed using TrialNet data collected from relatives with type 1 diabetes and validated in independent populations at high genetic risk of type 1 diabetes (TrialNet, Diabetes Prevention Trial-Type 1, The Environmental Determinants of Diabetes in the Young [1]) and in a general population of Bavarian children who participated in Fr1da. Results: Cox proportional hazards models combining plasma glucose, C-peptide, sex, age, BMI, HbA1c and insulinoma antigen-2 autoantibody status predicted disease progression in all populations. In TrialNet, the AUC for receiver operating characteristic curves for models named M60, M90 and M120, based on sampling at 60, 90 and 120 min, was 0.760, 0.761 and 0.745, respectively. These were not significantly different from the AUC of 0.760 for the gold standard Diabetes Prevention Trial Risk Score, which requires five OGTT blood samples. In TEDDY, where only 120 min blood sampling had been performed, the M120 AUC was 0.865. In Fr1da, the M120 AUC of 0.742 was significantly greater than the M60 AUC of 0.615. Conclusions/interpretation: Prediction models based on a single OGTT blood draw accurately predict disease progression from stage 1 or 2 to stage 3 type 1 diabetes. The operational simplicity of M120, its validity across different at-risk populations and the requirement for 120 min sampling to stage type 1 diabetes suggest M120 could be readily applied to decrease the cost and complexity of risk stratification.
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    The Influence of Pubertal Development on Autoantibody Appearance and Progression to Type 1 Diabetes in the TEDDY Study
    (Oxford University Press, 2024-05-24) Warncke, Katharina; Tamura, Roy; Schatz, Desmond A.; Veijola, Riitta; Steck, Andrea K.; Akolkar, Beena; Hagopian, William; Krischer, Jeffrey P.; Lernmark, Åke; Rewers, Marian J.; Toppari, Jorma; McIndoe, Richard; Ziegler, Anette-G.; Vehik, Kendra; Haller, Michael J.; Elding Larsson, Helena; Pediatrics, School of Medicine
    Context: The 2 peaks of type 1 diabetes incidence occur during early childhood and puberty. Objective: We sought to better understand the relationship between puberty, islet autoimmunity, and type 1 diabetes. Methods: The relationships between puberty, islet autoimmunity, and progression to type 1 diabetes were investigated prospectively in children followed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Onset of puberty was determined by subject self-assessment of Tanner stages. Associations between speed of pubertal progression, pubertal growth, weight gain, homeostasis model assessment of insulin resistance (HOMA-IR), islet autoimmunity, and progression to type 1 diabetes were assessed. The influence of individual factors was analyzed using Cox proportional hazard ratios. Results: Out of 5677 children who were still in the study at age 8 years, 95% reported at least 1 Tanner Stage score and were included in the study. Children at puberty (Tanner Stage ≥2) had a lower risk (HR 0.65, 95% CI 0.45-0.93; P = .019) for incident autoimmunity than prepubertal children (Tanner Stage 1). An increase of body mass index Z-score was associated with a higher risk (HR 2.88, 95% CI 1.61-5.15; P < .001) of incident insulin autoantibodies. In children with multiple autoantibodies, neither HOMA-IR nor rate of progression to Tanner Stage 4 were associated with progression to type 1 diabetes. Conclusion: Rapid weight gain during puberty is associated with development of islet autoimmunity. Puberty itself had no significant influence on the appearance of autoantibodies or type 1 diabetes. Further studies are needed to better understand the underlying mechanisms.