Precision treatment of beta-cell monogenic diabetes: a systematic review
Rochelle N. Naylor, Kashyap Patel, Jarno L. T. Kettunen, Jonna M. E. Männistö, Julie Støy, Jacques Beltrand, Michel Polak, ADA/EASD PMDI, Deirdre K. Tobias, Jordi Merino, Abrar Ahmad, Catherine Aiken, Jamie L. Benham, Dhanasekaran Bodhini, Amy L. Clark, Kevin Colclough, Rosa Corcoy, Sara J. Cromer, Daisy Duan, Jamie L. Felton, Ellen C. Francis, Pieter Gillard, Véronique Gingras, Romy Gaillard, Eram Haider, Alice E. Hughes, Jennifer M. Iklé, Laura M. Jacobsen, Anna R. Kahkoska, Raymond J. Kreienkamp, Lee‐Ling Lim, Robert Massey, Niamh‐Maire Mclennan, Rachel G. Miller, Mario Luca Morieri, Jasper Most, Bige Ozkan, Kashyap Patel, Scott J. Pilla, Katsiaryna Prystupa, Sridharan Raghavan, Mary R. Rooney, Martin Schön, Zhila Semnani‐Azad, Magdalena Sevilla-González, Pernille Svalastoga, Wubet Worku Takele, Claudia H.T. Tam, Anne Cathrine B. Thuesen, Mustafa Tosur, Amelia S. Wallace, Caroline C. Wang, Jessie J. Wong, Jennifer M. Yamamoto, Katherine Young, Chloé Amouyal, Mette K. Andersen, Maxine P. Bonham, Mingling Chen, Feifei Cheng, Tinashe Chikowore, Sian C. Chivers, Christoffer Clemmensen, Dana Dabelea, Adem Y. Dawed, Aaron J. Deutsch, Laura T. Dickens, Linda A. DiMeglio, Monika Dudenhöffer‐Pfeifer, Carmella Evans‐Molina, María Mercè Fernández-Balsells, Hugo Fitipaldi, Stephanie L. Fitzpatrick, Stephen E. Gitelman, Mark O. Goodarzi, Jessica A. Grieger, Marta Guasch‐Ferré, Nahal Habibi, Torben Hansen, Chuiguo Huang, Arianna Harris-Kawano, Heba M. Ismail, Benjamin Hoag, Randi K. Johnson, Angus G. Jones, Robert W. Koivula, Aaron Leong, Gloria K. W. Leung, Ingrid Libman, Kai Liu, S. Alice Long, William L. Lowe, Robert W. Morton, Ayesha A. Motala, Suna Önengüt-Gümüşcü, James S. Pankow, Maleesa Pathirana, Sofia Pazmiño, Dianna Perez, John R. Petrie
Abstract
BACKGROUND: Beta-cell monogenic forms of diabetes have strong support for precision medicine. We systematically analyzed evidence for precision treatments for GCK-related hyperglycemia, HNF1A-, HNF4A- and HNF1B-diabetes, and mitochondrial diabetes (MD) due to m.3243 A > G variant, 6q24-transient neonatal diabetes mellitus (TND) and SLC19A2-diabetes. METHODS: The search of PubMed, MEDLINE, and Embase for individual and group level data for glycemic outcomes using inclusion (English, original articles written after 1992) and exclusion (VUS, multiple diabetes types, absent/aggregated treatment effect measures) criteria. The risk of bias was assessed using NHLBI study-quality assessment tools. Data extracted from Covidence were summarized and presented as descriptive statistics in tables and text. RESULTS: There are 146 studies included, with only six being experimental studies. For GCK-related hyperglycemia, the six studies (35 individuals) assessing therapy discontinuation show no HbA1c deterioration. A randomized trial (18 individuals per group) shows that sulfonylureas (SU) were more effective in HNF1A-diabetes than in type 2 diabetes. Cohort and case studies support SU's effectiveness in lowering HbA1c. Two cross-over trials (each with 15-16 individuals) suggest glinides and GLP-1 receptor agonists might be used in place of SU. Evidence for HNF4A-diabetes is limited. Most reported patients with HNF1B-diabetes (N = 293) and MD (N = 233) are on insulin without treatment studies. Limited data support oral agents after relapse in 6q24-TND and for thiamine improving glycemic control and reducing/eliminating insulin requirement in SLC19A2-diabetes. CONCLUSION: There is limited evidence, and with moderate or serious risk of bias, to guide monogenic diabetes treatment. Further evidence is needed to examine the optimum treatment in monogenic subtypes.