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

ADA/EASD PMDI

doi:10.1038/s43856-024-00556-1

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

ADA/EASD PMDI

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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 (US)
Article number	145
Journal	Communications Medicine
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/s43856-024-00556-1
State	Published - Dec 2024

Funding

We acknowledge the contribution of Dr. Rebecca Brown and Dr. Robert Semple in the working group of the Treatment of Monogenic Diabetes of the ADA/EASD Precision Diabetes Medicine Initiative. R.N.N is supported by the following grants: ADA 7-22-ICTSPM-17; R01DK104942; U54DK118612. KAP is supported by Wellcome Trust (219606/Z/19/Z); M.P. is supported by ANR 22-CE17-0025 Neurogli; S.A.W.G is supported by NIH NIDDK R01DK104942 and U54DK118612; T.T. is supported by the Helsinki University Hospital, the Folkhalsan Research Foundation as well as The Academy of Finland (grants no. 336822, 312072 and 336826) and University of Helsinki for the Centre of Excellence of Complex Disease Genetics. The ADA/EASD Precision Diabetes Medicine Initiative, within which this work was conducted, has received the following support: The Covidence license was funded by Lund University (Sweden) for which technical support was provided by Maria Bj\u00F6rklund and Krister Aronsson (Faculty of Medicine Library, Lund University, Sweden). Administrative support was provided by Lund University (Malm\u00F6, Sweden), the University of Chicago (IL, USA), and the American Diabetes Association (Washington D.C., USA). The Novo Nordisk Foundation (Hellerup, Denmark) provided grant support for in-person writing group meetings (PI: L Phillipson, University of Chicago, IL).

ASJC Scopus subject areas

Public Health, Environmental and Occupational Health
Internal Medicine
Epidemiology
Medicine (miscellaneous)
Assessment and Diagnosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s43856-024-00556-1

Cite this

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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 = "{ADA/EASD PMDI} and Naylor, {Rochelle N.} and Patel, {Kashyap A.} 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 Atma W.} and Scholtens, {Denise M.} and Lowe, {William L.} and Katherine Young",

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

year = "2024",

month = dec,

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

language = "English (US)",

volume = "4",

journal = "Communications Medicine",

issn = "2730-664X",

publisher = "Springer Nature",

number = "1",

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TY - JOUR

T1 - Precision treatment of beta-cell monogenic diabetes

T2 - a systematic review

AU - ADA/EASD PMDI

AU - Naylor, Rochelle N.

AU - Patel, Kashyap A.

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 Atma W.

AU - Scholtens, Denise M.

AU - Lowe, William L.

AU - Young, Katherine

PY - 2024/12

Y1 - 2024/12

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.

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

Abstract

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ASJC Scopus subject areas

UN SDGs

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