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; black, Hispanic, or Native American 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. Symptomatic patients may present with: fatigue; polyuria, polydipsia, polyphagia, or weight loss (usually when hyperglycemia is more severe, e.g., >300 mg/dL); blurred vision; paresthesias; unintentional weight loss; nocturia; skin infections (bacterial or candidal); urinary infections; or acanthosis nigricans.
One of four tests can be used to establish a firm diagnosis of diabetes:
Fasting plasma glucose (FPG) >125 mg/dL
Random plasma glucose ≥200 mg/dL with diabetes symptoms such as polyuria, polydipsia, fatigue, or weight loss
2-hour post-load glucose ≥200 mg/dL on a 75 g oral glucose tolerance test
All of these require confirmation with a second test, which may be the same test or a different test. 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. 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, or laboratory variation.
Some individuals cannot be clearly classified as having type 1 or type 2 diabetes at the time of diagnosis. 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 (age <35), thinner patients, and has a more rapid onset and often more severe symptoms. Around one third of patients with newly diagnosed type 1 diabetes present with diabetic ketoacidosis (DKA). However, DKA may also occur in type 2 diabetes, particularly if there is an underlying infection. 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.
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. 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. 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. A GST or non-fasting "random" blood C-peptide level >1 nanomol/L suggests type 2 diabetes. C-peptide results must be interpreted in clinical context of disease duration, comorbidities, and family history.
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. Clinical assessment of cardiac, carotid, and peripheral circulation, with ECG and vascular investigation (e.g., an ankle-brachial index) can be considered at diagnosis. 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. HbA1c, lipid levels, blood pressure, urine albumin excretion, renal function, and clinical assessment are monitored at periodic intervals.
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