Differentials

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Patients with prediabetes often have no specific differentiating signs or symptoms.

INVESTIGATIONS

Fasting plasma glucose level is 100-125 mg/dL in prediabetes.

2-hour post-load glucose after 75 g of oral glucose is 140-199 mg/dL in prediabetes.

HbA1c of 5.7% to 6.4% indicates prediabetes and high risk of future diabetes.[2]

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Onset often at age <30 years, but can occur in older individuals.

Many patients are not obese.

More commonly presents with symptoms (polyuria, polydipsia, weight loss, generalized weakness, blurred vision) and ketosis, rather than being detected by screening.[50]

INVESTIGATIONS

Urine ketones are often present in type 1 diabetes, but may be positive in type 2 diabetes if there is severe volume depletion.

Low (<0.6 nanogram/mL) or absent C-peptide level.

One or more autoantibodies (anti-glutamic acid decarboxylase 65 [GAD65] antibodies, islet cell antibodies [ICA], insulin autoantibodies, autoantibodies to the tyrosine phosphatase-related islet antigen-2 [IA-2 and IA-2beta], and zinc-transporter-8 [ZnT8] antibodies) are present in 85% of patients with type 1 at the time of diagnosis, but may disappear within a few years.[53] Type 1 diabetes is defined by the presence of one or more of these autoimmune markers, but testing is usually not required for diagnosis.

Glucose screening criteria cannot be used to differentiate type 1 and type 2 diabetes, as they are identical.

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Typical age of onset of diabetes is over 30 years old. Patients are usually nonobese 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.[57]

LADA is considered a subset of autoimmune type 1 diabetes (immune-mediated diabetes); however, patients with LADA are frequently misclassified as having type 2 diabetes.

INVESTIGATIONS

Positive for at least 1 of the 5 antibodies commonly found in type 1 diabetic patients (islet cell antibodies [ICA], autoantibodies to glutamic acid decarboxylase 65 (GAD65), autoantibodies to the tyrosine phosphatase-related islet antigen-2 [IA-2 and IA-2beta], insulin, and zinc-transporter-8 [ZnT8] antibodies).[54][58]

SIGNS / SYMPTOMS
INVESTIGATIONS
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.[59]

MODY is caused by mutation of a single gene (i.e., monogenic). At least 14 gene mutations of MODY are known.[60]

It has autosomal dominant inheritance and should be suspected in cases of diabetes in nonobese, young patients (adolescence or young adult) with a family history of diabetes in at least one first-degree relative.[60]

Patients are often misclassified as type 1 or type 2 diabetes. Insulin treatment is often not needed.[61]

INVESTIGATIONS

Genetic testing in patients with high index of suspicion (genes encoding glucokinase and transcription factors are identified).[62]

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Presents with unprovoked ketosis or ketoacidosis.[63]

Considered an "idiopathic diabetes," as patients have no evidence of autoimmunity. Often misclassified as type 1 diabetes, as individuals have episodic ketoacidosis and exhibit varying degrees of insulin deficiency between episodes. However, a type 2 diabetes phenotype is common (obesity, insulin resistance, metabolic syndrome).[64]

Patients are usually from a minority ethnic group, and have a positive family history of diabetes.[64]

On discontinuation of insulin therapy, the period of near-normoglycemic remission may last for a few months to several years. However, almost half will be insulin dependent 10 years after diagnosis.[63]

INVESTIGATIONS

Absent islet cell autoantibodies.

C-peptide often low or undetectable during diabetic ketoacidosis; recovery may be used as reliable predictor of insulin discontinuation.[64]

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Only occurs during pregnancy.

INVESTIGATIONS

Guidelines and expert consensus recommend screening for gestational diabetes in pregnant women at both high and usual risk.[2][65] Women with risk factors for diabetes should be screened for type 2 diabetes (or prediabetes) at first prenatal visit.[2] At 24 to 28 weeks' gestation, all women not known to have diabetes (including high-risk women if the initial testing was normal) should undergo screening with glucose tolerance testing.[2] One-step or two-step screening strategies may be used.[2]

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