Precision treatment of beta-cell monogenic diabetes: a systematic review

Rochelle N. Naylor; Kashyap Amratlal Patel; Jarno L.T. Kettunen; Jonna M.E. Männistö; Julie Støy; Jacques Beltrand; Michel Polak; Tina Vilsbøll; Tiinamaija Tuomi; Andrew T. Hattersley; Siri A.W. Greeley; ADA/EASD PMDI

doi:10.1038/s43856-024-00556-1

Precision treatment of beta-cell monogenic diabetes: a systematic review

Rochelle N. Naylor, Kashyap Amratlal Patel, Jarno L.T. Kettunen, Jonna M.E. Männistö, Julie Støy, Jacques Beltrand, Michel Polak, Tina Vilsbøll, Tiinamaija Tuomi, Andrew T. Hattersley, Siri A.W. Greeley, ADA/EASD PMDI

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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.

Original language	English
Article number	145
Number of pages	17
Journal	Communications Medicine
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/s43856-024-00556-1
Publication status	Published - 18 Jul 2024

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title = "Precision treatment of beta-cell monogenic diabetes: a systematic review",

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{\textquoteright}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.",

author = "Naylor, {Rochelle N.} and Patel, {Kashyap Amratlal} and Kettunen, {Jarno L.T.} and M{\"a}nnist{\"o}, {Jonna M.E.} and Julie St{\o}y and Jacques Beltrand and Michel Polak and Franks, {Paul W.} and Rich, {Stephen S.} and Robert Wagner and Tina Vilsb{\o}ll and Vesco, {Kimberly K.} and Udler, {Miriam S.} and Tiinamaija Tuomi and Arianne Sweeting and Sims, {Emily K.} and Sherr, {Jennifer L.} and Semple, {Robert K.} and Reynolds, {Rebecca M.} and Redondo, {Maria J.} and Redman, {Leanne M.} and Pratley, {Richard E.} and Rodica Pop-Busui and Pollin, {Toni I.} and Wei Perng and Pearson, {Ewan R.} and Ozanne, {Susan E.} and Owen, {Katharine R.} and Richard Oram and Rinki Murphy and Viswanathan Mohan and Shivani Misra and Meigs, {James B.} and Nestoras Mathioudakis and Chantal Mathieu and Ma, {Ronald C.W.} and Loos, {Ruth J.F.} and Lim, {Siew S.} and Laffel, {Lori M.} and Kwak, {Soo Heon} and Josefson, {Jami L.} and Hood, {Korey K.} and Hivert, {Marie France} and Hirsch, {Irl B.} and Hattersley, {Andrew T.} and Kurt Griffin and Greeley, {Siri A.W.} and Gottlieb, {Peter A.} and Gomez, {Maria F.} and Gloyn, {Anna L.} and Florez, {Jose C.} and Dennis, {John M.} and Tina Costacou and Kristen Boyle and Billings, {Liana K.} and Brown, {Rebecca J.} and Philipson, {Louis H.} and Nolan, {John J.} and Eckel, {Robert H.} and Diana Sherifali and Emily Mixter and Mekonnen, {Eskedar Getie} and Chandra Gruber and Fawcett, {Andrea J.} and {de Souza}, Russell and Sungyoung Auh and Yeyi Zhu and Cuilin Zhang and C{\'e}cile Saint-Martin and Michele Provenzano and Hugo Pomares-Millan and Nj{\o}lstad, {P{\aa}l Rasmus} and Mariam Nakabuye and Janne Molnes and Andrew McGovern and Maloney, {Kristin A.} and Flanagan, {Sarah E.} and {de Franco}, Elisa and Ingvild Aukrust and Zhou, {Shao J.} and Yingchai Zhang and Gechang Yu and White, {Sara L.} and Wesley Hannah and Wentworth, {John M.} and Camille Vatier and {Van der Schueren}, Bart and Marzhan Urazbayeva and Ukke, {Gebresilasea Gendisha} and Tye, {Sok Cin} and Rachael Taylor and Julie St{\o}y and Norbert Stefan and Steck, {Andrea K.} and Nele Steenackers and Stanislawski, {Maggie A.} and Cate Speake and Sheu, {Wayne Huey Herng} and Elizabeth Selvin and Scholtens, {Denise M.} and Monaco, {Gabriela S.F.} and Sudipa Sarkar and Sarah Kanbour and Vanessa Santhakumar and Zeb Saeed and Mathias Ried-Larsen and Debashree Ray and Rashmi Jain and Alejandra Quinteros and Powe, {Camille E.} and Petrie, {John R.} and Dianna Perez and Sofia Pazmino and Maleesa Pathirana and Pankow, {James S.} and Suna Onengut-Gumuscu and Motala, {Ayesha A.} and Morton, {Robert W.} and Lowe, {William L.} and Long, {S. Alice} and Kai Liu and Libman, {Ingrid M.} and Leung, {Gloria K.W.} and Aaron Leong and Koivula, {Robert W.} and Jones, {Angus G.} and Johnson, {Randi K.} and Benjamin Hoag and Ismail, {Heba M.} and Arianna Harris-Kawano and Chuiguo Huang and Torben Hansen and Nahal Habibi and Marta Guasch-Ferr{\'e} and Grieger, {Jessica A.} and Goodarzi, {Mark O.} and Gitelman, {Stephen E.} and Fitzpatrick, {Stephanie L.} and Hugo Fitipaldi and Fern{\'a}ndez-Balsells, {Mar{\'i}a Merc{\`e}} and Carmella Evans-Molina and Monika Dudenh{\"o}ffer-Pfeifer and DiMeglio, {Linda A.} and Dickens, {Laura T.} and Deutsch, {Aaron J.} and Dawed, {Adem Y.} and Dana Dabelea and Christoffer Clemmensen and Chivers, {Sian C.} and Tinashe Chikowore and Feifei Cheng and Mingling Chen and Bonham, {Maxine P.} and Andersen, {Mette K.} and Chlo{\'e} Amouyal and Katherine Young and Yamamoto, {Jennifer M.} and Wong, {Jessie J.} and Wang, {Caroline C.} and Wallace, {Amelia S.} and Mustafa Tosur and Thuesen, {Anne Cathrine B.} and Tam, {Claudia Ha ting} and Takele, {Wubet Worku} and Pernille Svalastoga and Magdalena Sevilla-Gonzalez and Zhila Semnani-Azad and Martin Sch{\"o}n and Rooney, {Mary R.} and Sridharan Raghavan and Katsiaryna Prystupa and Pilla, {Scott J.} and Patel, {Kashyap Amratlal} and Bige Ozkan and Jasper Most and Morieri, {Mario Luca} and Miller, {Rachel G.} and Mclennan, {Niamh Maire} and Robert Massey and Lim, {Lee Ling} and Kreienkamp, {Raymond J.} and Kahkoska, {Anna R.} and Jacobsen, {Laura M.} and Ikle, {Jennifer M.} and Alice Hughes and Eram Haider and Romy Gaillard and V{\'e}ronique Gingras and Pieter Gillard and Francis, {Ellen C.} and Felton, {Jamie L.} and Daisy Duan and Cromer, {Sara J.} and Rosa Corcoy and Kevin Colclough and Clark, {Amy L.} and Dhanasekaran Bodhini and Benham, {Jamie L.} and Catherine Aiken and Abrar Ahmad and Jordi Merino and Tobias, {Deirdre K.} and Greeley, {Siri A.W.} and {ADA/EASD PMDI}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = jul,

day = "18",

doi = "10.1038/s43856-024-00556-1",

language = "English",

volume = "4",

journal = "Communications Medicine",

issn = "2730-664X",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Precision treatment of beta-cell monogenic diabetes

T2 - a systematic review

AU - Naylor, Rochelle N.

AU - Patel, Kashyap Amratlal

AU - Kettunen, Jarno L.T.

AU - Männistö, Jonna M.E.

AU - Støy, Julie

AU - Beltrand, Jacques

AU - Polak, Michel

AU - Franks, Paul W.

AU - Rich, Stephen S.

AU - Wagner, Robert

AU - Vilsbøll, Tina

AU - Vesco, Kimberly K.

AU - Udler, Miriam S.

AU - Tuomi, Tiinamaija

AU - Sweeting, Arianne

AU - Sims, Emily K.

AU - Sherr, Jennifer L.

AU - Semple, Robert K.

AU - Reynolds, Rebecca M.

AU - Redondo, Maria J.

AU - Redman, Leanne M.

AU - Pratley, Richard E.

AU - Pop-Busui, Rodica

AU - Pollin, Toni I.

AU - Perng, Wei

AU - Pearson, Ewan R.

AU - Ozanne, Susan E.

AU - Owen, Katharine R.

AU - Oram, Richard

AU - Murphy, Rinki

AU - Mohan, Viswanathan

AU - Misra, Shivani

AU - Meigs, James B.

AU - Mathioudakis, Nestoras

AU - Mathieu, Chantal

AU - Ma, Ronald C.W.

AU - Loos, Ruth J.F.

AU - Lim, Siew S.

AU - Laffel, Lori M.

AU - Kwak, Soo Heon

AU - Josefson, Jami L.

AU - Hood, Korey K.

AU - Hivert, Marie France

AU - Hirsch, Irl B.

AU - Hattersley, Andrew T.

AU - Griffin, Kurt

AU - Greeley, Siri A.W.

AU - Gottlieb, Peter A.

AU - Gomez, Maria F.

AU - Gloyn, Anna L.

AU - Florez, Jose C.

AU - Dennis, John M.

AU - Costacou, Tina

AU - Boyle, Kristen

AU - Billings, Liana K.

AU - Brown, Rebecca J.

AU - Philipson, Louis H.

AU - Nolan, John J.

AU - Eckel, Robert H.

AU - Sherifali, Diana

AU - Mixter, Emily

AU - Mekonnen, Eskedar Getie

AU - Gruber, Chandra

AU - Fawcett, Andrea J.

AU - de Souza, Russell

AU - Auh, Sungyoung

AU - Zhu, Yeyi

AU - Zhang, Cuilin

AU - Saint-Martin, Cécile

AU - Provenzano, Michele

AU - Pomares-Millan, Hugo

AU - Njølstad, Pål Rasmus

AU - Nakabuye, Mariam

AU - Molnes, Janne

AU - McGovern, Andrew

AU - Maloney, Kristin A.

AU - Flanagan, Sarah E.

AU - de Franco, Elisa

AU - Aukrust, Ingvild

AU - Zhou, Shao J.

AU - Zhang, Yingchai

AU - Yu, Gechang

AU - White, Sara L.

AU - Hannah, Wesley

AU - Wentworth, John M.

AU - Vatier, Camille

AU - Van der Schueren, Bart

AU - Urazbayeva, Marzhan

AU - Ukke, Gebresilasea Gendisha

AU - Tye, Sok Cin

AU - Taylor, Rachael

AU - Støy, Julie

AU - Stefan, Norbert

AU - Steck, Andrea K.

AU - Steenackers, Nele

AU - Stanislawski, Maggie A.

AU - Speake, Cate

AU - Sheu, Wayne Huey Herng

AU - Selvin, Elizabeth

AU - Scholtens, Denise M.

AU - Monaco, Gabriela S.F.

AU - Sarkar, Sudipa

AU - Kanbour, Sarah

AU - Santhakumar, Vanessa

AU - Saeed, Zeb

AU - Ried-Larsen, Mathias

AU - Ray, Debashree

AU - Jain, Rashmi

AU - Quinteros, Alejandra

AU - Powe, Camille E.

AU - Petrie, John R.

AU - Perez, Dianna

AU - Pazmino, Sofia

AU - Pathirana, Maleesa

AU - Pankow, James S.

AU - Onengut-Gumuscu, Suna

AU - Motala, Ayesha A.

AU - Morton, Robert W.

AU - Lowe, William L.

AU - Long, S. Alice

AU - Liu, Kai

AU - Libman, Ingrid M.

AU - Leung, Gloria K.W.

AU - Leong, Aaron

AU - Koivula, Robert W.

AU - Jones, Angus G.

AU - Johnson, Randi K.

AU - Hoag, Benjamin

AU - Ismail, Heba M.

AU - Harris-Kawano, Arianna

AU - Huang, Chuiguo

AU - Hansen, Torben

AU - Habibi, Nahal

AU - Guasch-Ferré, Marta

AU - Grieger, Jessica A.

AU - Goodarzi, Mark O.

AU - Gitelman, Stephen E.

AU - Fitzpatrick, Stephanie L.

AU - Fitipaldi, Hugo

AU - Fernández-Balsells, María Mercè

AU - Evans-Molina, Carmella

AU - Dudenhöffer-Pfeifer, Monika

AU - DiMeglio, Linda A.

AU - Dickens, Laura T.

AU - Deutsch, Aaron J.

AU - Dawed, Adem Y.

AU - Dabelea, Dana

AU - Clemmensen, Christoffer

AU - Chivers, Sian C.

AU - Chikowore, Tinashe

AU - Cheng, Feifei

AU - Chen, Mingling

AU - Bonham, Maxine P.

AU - Andersen, Mette K.

AU - Amouyal, Chloé

AU - Young, Katherine

AU - Yamamoto, Jennifer M.

AU - Wong, Jessie J.

AU - Wang, Caroline C.

AU - Wallace, Amelia S.

AU - Tosur, Mustafa

AU - Thuesen, Anne Cathrine B.

AU - Tam, Claudia Ha ting

AU - Takele, Wubet Worku

AU - Svalastoga, Pernille

AU - Sevilla-Gonzalez, Magdalena

AU - Semnani-Azad, Zhila

AU - Schön, Martin

AU - Rooney, Mary R.

AU - Raghavan, Sridharan

AU - Prystupa, Katsiaryna

AU - Pilla, Scott J.

AU - Patel, Kashyap Amratlal

AU - Ozkan, Bige

AU - Most, Jasper

AU - Morieri, Mario Luca

AU - Miller, Rachel G.

AU - Mclennan, Niamh Maire

AU - Massey, Robert

AU - Lim, Lee Ling

AU - Kreienkamp, Raymond J.

AU - Kahkoska, Anna R.

AU - Jacobsen, Laura M.

AU - Ikle, Jennifer M.

AU - Hughes, Alice

AU - Haider, Eram

AU - Gaillard, Romy

AU - Gingras, Véronique

AU - Gillard, Pieter

AU - Francis, Ellen C.

AU - Felton, Jamie L.

AU - Duan, Daisy

AU - Cromer, Sara J.

AU - Corcoy, Rosa

AU - Colclough, Kevin

AU - Clark, Amy L.

AU - Bodhini, Dhanasekaran

AU - Benham, Jamie L.

AU - Aiken, Catherine

AU - Ahmad, Abrar

AU - Merino, Jordi

AU - Tobias, Deirdre K.

AU - Greeley, Siri A.W.

AU - ADA/EASD PMDI

PY - 2024/7/18

Y1 - 2024/7/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85204481256&partnerID=8YFLogxK

U2 - 10.1038/s43856-024-00556-1

DO - 10.1038/s43856-024-00556-1

M3 - Article

C2 - 39025920

AN - SCOPUS:85204481256

SN - 2730-664X

VL - 4

JO - Communications Medicine

JF - Communications Medicine

IS - 1

M1 - 145

ER -

Precision treatment of beta-cell monogenic diabetes: a systematic review

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