[Clinical parameters for molecular testing of Maturity Onset Diabetes of the Young (MODY)]

Dtsch Med Wochenschr. 2011 May;136(21):1111-5. doi: 10.1055/s-0031-1280519. Epub 2011 May 17.
[Article in German]

Abstract

Background: Monogenic forms of diabetes are often diagnosed by chance, due to the variety of clinical presentation and limited experience of the diabetologists with this kind of diabetes. Aim of this study was to evaluate clinical parameters for an efficient screening.

Methods: Clinical parameters were: negative diabetes-specific antibodies at onset of diabetes, positive family history of diabetes, and low to moderate insulin requirements after one year of diabetes treatment. Molecular testing was performed through sequencing of the programming regions of HNF-4alpha (MODY 1), glucokinase (MODY 2) and HNF-1alpha/TCF1 (MODY 3) and in one patient the HNF-1beta/TCF2 region (MODY 5). 39 of 292 patients treated with insulin were negative for GADA and IA2A, and 8 (20.5%) patients fulfilled both other criteria.

Results: Positive molecular results were found in five (63%) patients (two with MODY 2, two with MODY 3, one with MODY 5). At diabetes onset, the mean age of the 5 patients with MODY was 10.6 ± 5.3 yrs (range 2.6-15 yrs), HbA(1c) was 8.4 ± 3.1 % (6.5-13.9%), mean diabetes duration until diagnosis of MODY was 3.3 ± 3.6 yrs (0.8-9.6 yrs) with insulin requirements of 0.44 ± 0.17 U/kg/d (0.2-0.6 U/kg/d). Patients with MODY 3 were changed from insulin to repaglinide, those with MODY 2 were recommended discontinuing insulin treatment.

Conclusion: In patients with negative diabetes-specific antibodies at onset of diabetes, with a positive family history, and low to moderate insulin needs a genetic screening for MODY is indicated. Watchful consideration of these clinical parameters may lead to an early genetic testing, and to an adequate treatment.

MeSH terms

  • Adolescent
  • Autoantibodies / blood
  • Blood Glucose / metabolism
  • Child
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / immunology
  • Diagnosis, Differential
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing*
  • Glucokinase / genetics
  • Glycated Hemoglobin / metabolism
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 1-beta / genetics
  • Hepatocyte Nuclear Factor 4 / genetics
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Male
  • Phenotype
  • Prognosis
  • Sequence Analysis, DNA

Substances

  • Autoantibodies
  • Blood Glucose
  • Glycated Hemoglobin A
  • HNF1B protein, human
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 4
  • Hypoglycemic Agents
  • Insulin
  • hemoglobin A1c protein, human
  • Hepatocyte Nuclear Factor 1-beta
  • Glucokinase