Monogenic Diabetes with Severe Insulin Resistance Due to INSR Mutation and Acanthosis Nigricans

Clinical scenario

This protocol addresses monogenic diabetes presenting in the context of severe insulin resistance caused by an INSR gene mutation. The defining clinical picture includes moderate to severe acanthosis nigricans together with markedly elevated fasting insulin levels or substantially increased insulin requirements — and notably, this degree of insulin resistance occurs without a corresponding degree of obesity.

Key findings

INSR mutations underlie a group of rare insulin resistance syndromes. The cardinal features are moderate to severe acanthosis nigricans in association with either markedly increased insulin concentrations (fasting insulin >150 pmol/L) or, in the presence of diabetes, increased insulin requirements — usually in the absence of a corresponding degree of obesity.

Management approach

Initial management typically involves an insulin-sensitizing agent. The full structured regimen — including sequencing, additional interventions, and clinical decision points — is outlined in the complete protocol.

Full treatment algorithm available via the link below.

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References

INSR mutations are responsible for a number of rare IR syndromes.
The cardinal features of IR syndromes include moderate to severe acanthosis nigricans in association either with markedly increased insulin concentrations (fasting insulin >150 pmoL/L) or, where there is diabetes, increased insulin requirements, usually in the absence of a corresponding degree of obesity.
Insulin sensitizers such as metformin may be tried initially but most will need extraordinarily high doses of insulin, with limited effect.

DOI: 10.1111/pedi.13426

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