Monogenic diabetes
ICD-10 E13.9 · ICD-11 5A13.6

Monogenic Diabetes with Lipodystrophy: Managing Insulin Resistance and Hypertriglyceridemia

Clinical Scenario

Condition

This protocol addresses diabetes and insulin resistance arising from monogenic lipodystrophy — a genetic condition characterised by partial or complete reduction in adipose tissue. The consequent loss of adipose tissue drives decreased adipokine levels and significant hypertriglyceridemia, compounding glycaemic dysregulation.

Key Clinical Features

Lipodystrophies result in markedly reduced adipokine levels and severe insulin resistance. Congenital generalised forms (such as Berardinelli–Seip syndrome) account for a substantial share of cases, with identified mutations explaining the majority of presentations. Both generalised and partial forms can present with the metabolic triad relevant here: adipose deficiency, adipokine insufficiency, and hypertriglyceridaemia.

Treatment Approach

Management in this setting includes an adjunctive therapy approach involving recombinant leptin. Evidence supports that this intervention has shown sustained improvements in hypertriglyceridaemia and glycaemic management — but the full protocol, including specific criteria for use, additional therapeutic components, and monitoring, is detailed in the complete structured regimen.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1111/pedi.13426

Lipodystrophies are characterized by a partial or complete reduction in adipose tissue, which results in decreased adipokine levels and IR.

Mutations in either AGPAT2 or BSCL account for 80% of cases of congenital generalized lipodystrophy (Berardinelli–Seip syndrome).

More recently, therapy with recombinant leptin, given by daily subcutaneous injection, has been shown to be well tolerated, with sustained improvements in hypertriglyceridemia, glycemic management, and liver volume.

Efficacy in the partial forms of lipodystrophy is less clear, but where conventional therapy for diabetes and hypertriglyceridemia has not been successful, adjunctive therapy with metreleptin should be considered.

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