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Monogenic Diabetes: A Diagnostic Algorithm for Clinicians

Richard W. Carroll, Rinki Murphy · 2013 · 31 citationsRead the paper

Monogenic forms of beta cell diabetes account for approximately 1%-2% of all cases of diabetes, yet remain underdiagnosed. Overlapping clinical features with common forms of diabetes, make diagnosis challenging. A genetic diagnosis of monogenic diabetes in many cases alters therapy, affects prognosis, enables genetic counseling, and has implications for cascade screening of extended family members. We describe those types of monogenic beta cell diabetes which are recognisable by distinct clinical features and have implications for altered management; the cost effectiveness of making a genetic diagnosis in this setting; the use of complementary diagnostic tests to increase the yield among the vast majority of patients who will have commoner types of diabetes which are summarised in a clinical algorithm; and the vital role of cascade genetic testing to enhance case finding.

What the full text shows

Working prototype
  • Monogenic beta cell diabetes prevalence among all diabetes cases. — 1%-2%
  • K ATP channel mutations in Permanent Neonatal Diabetes Mellitus (PNDM) and Transient Neonatal Diabetes Mellitus (TNDM). — 50% of PNDM and 20% of TNDM
  • Glucokinase (GCK) monogenic diabetes prevalence among all monogenic diabetes cases. — 20%-30%
  • Maternally inherited diabetes and deafness (MIDD) prevalence among all monogenic diabetes cases. — up to 50%
  • Conversion from insulin to sulphonylurea therapy in children with KCNJ11 or ABCC8 mutations. — >90%
  • Islet cell autoantibody prevalence in HNF1A, GCK, or HNF4A patients. — 1%
Setup
Literature review and simulation models based on UKPDS data for a hypothetical population aged 20-40 years.
How
The authors developed a clinical diagnostic algorithm based on a review of recognizable phenotypes, biochemical markers (C-peptide, hsCRP, HDL), and cost-effectiveness simulation models. They proposed a process of exclusion starting with the most common genetic subtypes and the use of cascade genetic testing for family members.
Limitations
Cost-effectiveness evidence is predominantly based on simulation models with inherent assumptions. · MODY probability calculator validated on a predominantly Caucasian, UK-based population. · hsCRP test performance is modest (79% sensitivity, 70% specificity).

Summarized by Gemma 4 from the open-access full text · 8 Oct 2026. Read it