Differentials
Impaired glucose tolerance
SIGNS / SYMPTOMS
There may be no differentiating symptoms.
INVESTIGATIONS
Fasting glucose is 100-125 mg/dL (5.6 to 6.9 mmol/L).
Two-hour post-load glucose is 140-199 mg/dL (7.8 to 11.0 mmol/L) on oral glucose tolerance test.
HbA1c of 5.7% to 6.4% (39-47 mmol/mol).
Type 1 diabetes mellitus (T1DM)
SIGNS / SYMPTOMS
Most patients with T1DM do not have obesity (although obesity is increasingly being seen when patients are diagnosed) and have a short duration of symptoms, with recent polyuria, polydipsia, and weight loss, symptoms that are less common in type 2 diabetes mellitus (T2DM).
Typically, there is no family history.
INVESTIGATIONS
Urine ketones are often present in T1DM but observed in only 15% of children with T2DM.
Antibodies to insulin, islet cells, islet antigens, glutamic acid decarboxylase, or zinc transporter 8 are present in 85% to 98% of individuals with T1DM but are typically negative in T2DM.
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.[58]
MODY is caused by mutation of a single gene (i.e., monogenic).
At least 14 gene mutations of MODY are known.[59]
MODY has autosomal dominant inheritance, and should be suspected in those without the typical signs of T1DM or T2DM (e.g., no obesity, negative autoantibodies) and who have a family history of diabetes in successive generations.[1]
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.[60]
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.[1]
INVESTIGATIONS
Genetic testing with majority of mutations in the genes encoding the adenosine triphosphate-sensitive potassium channel and the insulin gene.[61]
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]
Atypical diabetes of African-American youth
SIGNS / SYMPTOMS
Usually presents with ketoacidosis.
No insulin resistance associations (e.g., acanthosis nigricans).
Autosomal-dominant family history.
Intermittent or continuous insulin dependency.
No insulin-resistance comorbidities (e.g., hypertension, dyslipidemia).
Overweight or obesity may be present.
INVESTIGATIONS
No differentiating tests.
Negative for diabetes-specific autoantibodies.
Gestational diabetes
SIGNS / SYMPTOMS
Only occurs in pregnancy.
INVESTIGATIONS
Detected by screening during pregnancy with an oral glucose tolerance test with specific criteria.[1]
Iatrogenic diabetes
SIGNS / SYMPTOMS
History of thalassemia, bone marrow transplants, solid organ transplants, and long-term corticosteroids.
There may be no differentiating symptoms.
INVESTIGATIONS
No differentiating tests.
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