Any features of the clinical picture that suggest end-organ insensitivity to insulin, such as visceral obesity, must be identified. The family history should document not only the incidence of diabetes in other members of the family but also the age at onset, whether it was associated with obesity, and whether insulin was required. An attempt should be made to characterize the diabetes as type 1 or type 2, based on the clinical features present and on whether or not ketonuria accompanies the glycosuria. For the occasional patient, measurement of islet cell, glutamic acid decarboxylase (GAD65), insulin antibodies, and ICA 512 antibodies can help distinguish between type 1 and type 2 diabetes.

Many patients in whom type 1 diabetes is newly diagnosed still have significant endogenous insulin production, and C peptide levels may not reliably distinguish between type 1 and type 2 diabetes. Other factors that increase cardiac risk, such as smoking history, presence of hypertension or hyperlipidemia, or oral contraceptive pill use, should be recorded.

Laboratory diagnosis should document fasting plasma glucose levels above 126 mg/dL or postprandial values consistently above 200 mg/dL and whether ketonuria accompanies the glycosuria. A glycohemoglobin measurement is useful for assessing the effectiveness of future therapy. Some flexibility of clinical judgment is appropriate when diagnosing diabetes mellitus in the elderly patient with borderline hyperglycemia.

Baseline values include fasting plasma triglycerides, total cholesterol and HDL-cholesterol, electrocardiography, renal function studies, peripheral pulses, and neurologic, podiatric, and ophthalmologic examinations to help guide future assessments.