Differentials
Monogenic diabetes: maturity onset diabetes of the young
SIGNS / SYMPTOMS
Monogenic diabetes is caused by a mutation in a single gene. Maturity-onset diabetes of the young (MODY) is the most common form of monogenic diabetes and affects 1% to 2% of people with diabetes.[76]
At least 14 gene mutations of MODY are known.[77][78] It has autosomal dominant inheritance but de novo mutations have been reported.[78] It should be suspected in cases of diabetes in adolescent or young adult patients who do not have obesity and who have multiple family members with diabetes not characteristic of type 1 or type 2 diabetes.[1]
Presents with nonketotic, noninsulin-dependent diabetes that responds to oral glucose lowering drugs.[79][80]
INVESTIGATIONS
C-peptide present (>0.6 ng/mL [>200 pmol/L]).
Autoantibodies absent.
Genetic testing in patients with high index of suspicion identifies mutations most commonly in genes encoding glucokinase and transcription factors.[79]
Monogenic diabetes: neonatal diabetes mellitus
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.[1] Neonatal diabetes occurs much less often after 6 months of age, whereas autoimmune type 1 diabetes rarely occurs before 6 months of age.[1]
May be transient (resolution by 12 months of age) or permanent.[1] Transient diabetes is most often due to overexpression of genes on chromosome 6q24, is recurrent in about half of cases, and may be treatable with drugs other than insulin. Permanent neonatal diabetes is most commonly due to autosomal dominant mutations in the genes encoding the Kir6.2 subunit (KCNJ11) and SUR1 subunit (ABCC8) of the beta-cell ATP-sensitive potassium channel (which affects the link between sensing of glucose levels and release of insulin from the pancreatic beta-cell).[1]
Usually manifests as isolated diabetes in an autosomal dominant pattern of inheritance but some monogenic causes are characterized by a variety of syndromic features.[1][81]
INVESTIGATIONS
Genetic testing with majority of mutations in the genes encoding the adenosine triphosphate-sensitive potassium channel and the insulin gene.[81] 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]
Type 2 diabetes
SIGNS / SYMPTOMS
Older age (most patients >35 years; greater likelihood with increasing age) and slow onset of illness, obesity, a strong family history, absence of ketoacidosis, and initial response to oral antihyperglycemic drugs are typical of type 2 diabetes.
Clinical signs of insulin resistance (such as acanthosis nigricans) may be present.
Signs of more marked insulin deficiency (for example, glycemic lability as well as susceptibility to ketosis) are more suggestive of type 1 diabetes.
INVESTIGATIONS
C-peptide present (>0.6 ng/mL [>200 pmol/L]).
Autoantibodies absent.
Testing for C-peptide and autoantibodies usually not required.
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