Differentials
Impaired glucose tolerance
SIGNS / SYMPTOMS
There may be no differentiating symptoms.
INVESTIGATIONS
Fasting glucose is between 5.6 and 6.9 mmol/L (100-125 mg/dL).
Two-hour post-load glucose is 7.8 to 11.0 mmol/L (140-199 mg/dL) on oral glucose tolerance test.
HbA1c of 38 mmol/mol to 47 mmol/mol (5.7% to 6.4%).
Type 1 diabetes mellitus (T1DM)
SIGNS / SYMPTOMS
Body weight: most patients with typeT1DM do not have obesity (although obesity is increasingly being seen when patients are diagnosed)
Symptoms: most patients with T1DM have a short duration of symptoms, with recent polyuria, polydipsia, and weight loss. These symptoms are less common in type 2 diabetes mellitus (T2DM). Patients with T2DM often present with features of insulin resistance and metabolic syndrome, such as acanthosis nigricans, hypertension, dyslipidaemia, and polycystic ovary syndrome, whereas such findings are rarely encountered in youth diagnosed with T1DM.[65]
Family history: a reported 75% to 90% of patients with T2DM have an affected first- or second-degree relative, while the corresponding percentage for patients with T1DM is less than 10%.[65]
Age: almost half of patients with T1DM present before aged 10 years.[65] By contrast, patients with T2DM usually present after the onset of puberty, at a mean age of 14 years.[36]
Ethnic group: youth belonging to minority groups such as American-Indian, African-American, Hispanic, and Pacific Islander run a much higher risk of developing T2DM compared with white youth.[65]
INVESTIGATIONS
Urine ketones: since patients with T1DM are more likely to present with ketoacidosis at the time of diagnosis, measurement of venous pH and urinary ketones can help differentiate between T2DM and T1DM, especially in the presence of typical symptoms (e.g., polydipsia, polyuria, and signs of dehydration). It should be remembered, however, that diabetic ketoacidosis may be present in 5% to 25% of children with T2DM at presentation.[4]
Pancreatic autoantibodies: antibodies to insulin, glutamic acid decarboxylase, islet antigen 2, or zinc transporter 8 are present in 85% to 100% of individuals with T1DM but are typically negative in T2DM.[65]
C-peptide: a low C-peptide level (<200 picomol/L [<0.6 nanogram/mL]) detected in newly diagnosed children with diabetes strongly suggests T1DM.[65]
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.[70]
MODY is caused by mutation of a single gene (i.e., monogenic). It is characterised by noninsulin-dependent diabetes together with lack of pancreatic autoimmunity.[65]
At least 14 gene mutations of MODY are known.[71]
MODY has autosomal dominant inheritance, and should be suspected in those without the typical signs of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (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.[72]
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.[1]
Usually isolated diabetes in an autosomal dominant pattern of inheritance.[1]
Some monogenic causes are characterised by a variety of syndromic features.[1][73]
INVESTIGATIONS
Genetic testing with majority of mutations in the genes encoding the adenosine triphosphate-sensitive potassium channel and the insulin gene.[73]
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 black 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, dyslipidaemia). 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 thalassaemia, bone marrow transplants, solid organ transplants, or long-term corticosteroids.
There may be no differentiating symptoms.
INVESTIGATIONS
No differentiating tests.
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