Approach

For updates on the diagnosis and management of coexisting conditions during the coronavirus disease 2019 (COVID-19) pandemic, please see our topic "Management of coexisting conditions in the context of COVID-19".

Type 2 diabetes is most often diagnosed on routine screening. Strong risk factors, which also indicate the need for screening, include: older age; overweight/obesity; African-American, Latino, Native American, Asian-American, or Pacific Islander ancestry; family history of type 2 diabetes; history of gestational diabetes; presence of prediabetes; physical inactivity; polycystic ovary syndrome; hypertension; dyslipidemia; or known cardiovascular disease.[2] Symptomatic patients may present with: polyuria, polydipsia, polyphagia, or unintentional weight loss (usually when hyperglycemia is more severe, e.g., >300 mg/dL); fatigue; blurred vision; paresthesias; nocturia; skin infections (bacterial or candidal); urinary infections; or acanthosis nigricans. com.bmj.content.model.Caption@7944a9d5[Figure caption and citation for the preceding image starts]: Acanthosis nigricans involving the axillaFrom the collection of Melvin Chiu, MD; used with permission [Citation ends].

Because type 2 diabetes can often be present without diagnosis for many years, it is sometimes diagnosed at the time of presentation with microvascular complications of peripheral neuropathy, retinopathy, or nephropathy.

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) may be the initial presentation of type 2 diabetes, particularly if there is an underlying infection.[3][46][47] Patients are symptomatic of hyperglycemia (polyuria, polydipsia, weakness) and significant volume depletion (dry mucous membranes, poor skin turgor, tachycardia, hypotension, and, in severe cases, shock). This is a life-threatening emergency, which requires early diagnosis and management.[48] Compared with the acute presentation of DKA, people with HHS have an insidious onset (over days or weeks) of symptoms and are usually older than 60 years.[3] Certain medications, particularly antipsychotic agents, may precipitate HHS.[48] For further information, please see our topics "Diabetic ketoacidosis" and "Hyperosmolar hyperglycemic state". 

Diagnosis

One of four tests can be used to establish a firm diagnosis of diabetes:[2]

  • Fasting plasma glucose (FPG) >125 mg/dL

  • HbA1c ≥6.5%

  • 2-hour post-load glucose ≥200 mg/dL on a 75 g oral glucose tolerance test

  • Random plasma glucose ≥200 mg/dL with diabetes symptoms such as polyuria, polydipsia, fatigue, weight loss, or hyperglycemic crisis.

In the absence of unequivocal hyperglycemia, diagnosis requires confirmation with a second test, which may be the same test or a different test.[2] Some variability in HbA1c results is possible as a result of such factors as increased red blood cell turnover (e.g., sickle cell anemia), factors related to ancestry. This means a single blood sample is sufficient to establish a diabetes diagnosis if assays of both HbA1c and fasting plasma glucose meet criteria for diabetes diagnosis.[2] Some variability in HbA1c results is possible as a result of such factors as increased red blood cell turnover (e.g., sickle cell anemia), factors related to ancestry,[49] or laboratory variation.

Some individuals cannot be clearly classified as having type 1 or type 2 diabetes at the time of diagnosis.[2] However, at initial diagnosis of diabetes, it is important to determine if immediate treatment with insulin is required. Type 1 diabetes can occur at any age, but usually is diagnosed in younger patients (age <30 years), and has a more rapid onset and often more severe symptoms. Around one third of patients with newly diagnosed type 1 diabetes present with DKA.[50] However, DKA may also occur in type 2 diabetes, particularly if there is an underlying infection.[46][47] Urine ketones should be checked if patients are symptomatic of hyperglycemia (polyuria, polydipsia, weakness) and volume depletion (dry mucous membranes, poor skin turgor, tachycardia, hypotension, and, in severe cases, shock) at diagnosis or throughout course of disease. Although by definition HHS is characterized by negative ketone bodies, mild-to-moderate ketonemia may be present.[48]

C-peptide is produced in equal amounts to insulin and is the best measure of endogenous insulin secretion in patients with diabetes. There is no role for routine testing for C-peptide for diagnosis of diabetes, but measuring C-peptide may be useful in differentiating type 1 and type 2 diabetes.[51] The best evidenced C-peptide test is the glucagon stimulation test (GST), but non-fasting "random" blood C-peptide has been shown to correlate with fasting C-peptide and post-GST samples in subjects with well-defined type 1 or type 2 diabetes.[52] Development of absolute insulin deficiency is a key feature of type 1 diabetes, which results in low (<0.2 nanomol/L) or undetectable levels of plasma C-peptide.[2][51] A GST or non-fasting "random" blood C-peptide level >1 nanomol/L suggests type 2 diabetes.[51] C-peptide results must be interpreted in clinical context of disease duration, comorbidities, and family history.[52]

Although C-peptide can be helpful in evaluating the endogenous production of insulin, both type 1 and type 2 diabetes can be associated with insulinopenia, and endogenous insulin production can be detected in some individuals with type 1 diabetes for prolonged periods of time after diagnosis, especially in individuals diagnosed in adulthood. Testing for autoimmunity can therefore often be more helpful in identifying immune-mediated diabetes, the most prevalent form of type 1 diabetes. Autoantibodies to glutamic acid decarboxylase 65 (GAD65), islet cell antibodies (ICA), insulin antibodies, antibodies to tyrosine phosphatase-related islet antigen-2 (IA-2 and IA-2beta), and zinc-transporter-8 (ZnT8) antibodies can help to identify individuals with immune-mediated diabetes, although these antibodies fade with time after the onset of illness.[2][53][54]

Evaluation of disease and risks of macrovascular/microvascular complications

Blood pressure, smoking status, and fasting lipid levels should be assessed. Baseline urine albumin/creatinine ratio and serum creatinine with estimated glomerular filtration rate (eGFR) are also indicated, as signs of chronic kidney disease may be present at diagnosis.[2] Clinical assessment of cardiac, carotid, and peripheral circulation, with ECG and vascular investigation (e.g., an ankle-brachial index [ABI]) can be considered at diagnosis.[2][44] Due to the potential for calcification of the arteries from atherosclerotic peripheral vascular disease (which falsely elevates the ABI), toe pressure testing is often done as an adjunct to ABI testing.[55] A normal ABI value is 1.0; a normal toe pressure value is over 0.7. Values below these levels are considered abnormal and are evidence of macrovascular arterial disease. Examination of the feet, including assessment of ankle reflexes, pulses, vibratory sensation, and monofilament touch sensation, and a dilated retinal exam, should be part of the evaluation.[2] A comprehensive dilated eye exam is recommended at diagnosis of type 2 diabetes, as patients may have had years of undiagnosed diabetes and some manifestation of diabetic retinopathy is present in about 30% of patients.[2][56] HbA1c, lipid levels, blood pressure, urine albumin excretion, renal function, and clinical assessment are monitored at periodic intervals.

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