Differentials
Monogenic diabetes: maturity onset diabetes of the young
SIGNS / SYMPTOMS
Maturity-onset diabetes of the young (MODY) is the most common form of monogenic diabetes and affects 1% to 2% of people with diabetes.[48]
MODY is caused by mutation of a single gene (i.e., monogenic). At least 14 gene mutations of MODY are known.[49] It has autosomal dominant inheritance and should be suspected in cases of diabetes in young patients who do not have obesity (adolescent or young adult) with family history of diabetes in at least one first-degree relative.[49]
Presents with nonketotic, noninsulin-dependent diabetes that responds to oral glucose lowering drugs.[50][51]
INVESTIGATIONS
C-peptide present.
Autoantibodies absent.
Genetic testing in patients with high index of suspicion identifies mutations most commonly in genes encoding glucokinase and transcription factors.[50]
Monogenic diabetes: neonatal diabetes
SIGNS / SYMPTOMS
Diabetes occurring under 6 months of age is termed “neonatal” or “congenital” diabetes, and about 80% to 85% of cases can be found to have an underlying monogenic cause. Neonatal diabetes occurs much less often after 6 months of age, whereas autoimmune type 1 diabetes rarely occurs before 6 months of age.[1]
Usually isolated diabetes in an autosomal dominant pattern of inheritance.[1]
Some monogenic causes are characterized by a variety of syndromic features.[52]
INVESTIGATIONS
Genetic testing with majority of mutations in the genes encoding the adenosine triphosphate-sensitive potassium channel and the insulin gene.[52] Regardless of current age, all people diagnosed with diabetes in the first 6 months of life should have immediate genetic testing for neonatal diabetes.[1]
Latent autoimmune diabetes in adults (LADA)
SIGNS / SYMPTOMS
Typical age of onset of diabetes is over 30 years old. Patients do not usually have obesity and respond initially to lifestyle modifications and oral agents. Production of insulin gradually decreases (between 6 months and 5 years), such that treatment with insulin is required.[44]
LADA is considered a subset of type 1 diabetes; however, patients with LADA are frequently misclassified as having type 2 diabetes.
INVESTIGATIONS
Low to normal initial C-peptide level.
Can be positive for at least 1 of the 4 antibodies commonly found in type 1 diabetic patients.[44]
Type 2 diabetes
SIGNS / SYMPTOMS
Typically, signs of insulin resistance (such as acanthosis nigricans) should be sought and in their absence clinical suspicion of type 1 diabetes is greater.
Signs of more marked insulin deficiency (for example, glycemic lability as well as susceptibility to ketosis) raise suspicion of type 1 diabetes.
Older age and slow onset, obesity, a strong family history, absence of ketoacidosis, and initial response to oral antihyperglycemic drugs are typical of type 2 diabetes.
INVESTIGATIONS
C-peptide present.
Autoantibodies absent.
Testing for C-peptide and autoantibodies usually not required.
Use of this content is subject to our disclaimer