Mitochondrial heteroplasmy-phenotype correlation and response to glucose lowering therapy in subjects with m.3243A>G mutations
Authors' conclusion
β-cell dysfunction and insulin resistance contribute to mitochondrial diabetes development. 65 % of subjects required insulin to improve glycaemic control. Early insulin initiation may be necessary to improve glycaemic control in the long term.
Study context
- Population
- Subjects with a confirmed m.3243A>G mutation, phenotyped in detail with 2 hr OGTT, heteroplasmy measurement and bi-annual clinical follow-up
- Participants
- 49 subjects
- Exposure
- Diabetes mellitus (DM) vs normal glucose tolerance (NGT) in m.3243A>G carriers
- DMn = 34
- Impaired glucose tolerance or impaired fasting glucosen = 7
- NGTn = 8reference
- Outcome
- Insulin secretion (AUC C-peptide)
- Follow-up
- 2 hr OGTT
Main finding
As reported in the abstract
P = 0.002
Observational data: associations, not effects.
Further findings
| Outcome | DM | NGT | P value |
|---|---|---|---|
| Insulin sensitivity (OGIS)DM vs NGT · reduced with DM | 283.0 (range 209.0–324.0) ml min-1m-2 | 437.0 (range 416.0–524.0) ml min-1m-2 | P < 0.001 |
| HeteroplasmyDM vs NGT · higher with DM | 20 (range 11–26) % | 6 (range 5–10) % | P = 0.014 |
- DM onset age
- 38 · range 31–44 · years
Response to glucose lowering therapy
- Required insulin to improve glycaemic control
- 65 %
- Transitioned from insulin to Sulphonylurea (SU)
- 1/6
- Subjects on SGLT2i and GLP-1 agonists progressed to insulin
- 2
Safety
- Subjects on metformin with raised lactate
- 5 of 8
Original publication
Mitochondrial heteroplasmy-phenotype correlation and response to glucose lowering therapy in subjects with m.3243A>G mutations. Diabetes Metab. Published 18 June 2025. doi:10.
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