What is the appropriate diagnosis and first-line treatment for a newly diagnosed adult with diabetes mellitus?

Diagnosis and First-Line Treatment of Newly Diagnosed Adult Diabetes Mellitus

For a newly diagnosed adult with diabetes mellitus, confirm the diagnosis with laboratory testing showing A1C ≥6.5%, fasting plasma glucose ≥126 mg/dL, or random plasma glucose ≥200 mg/dL (with symptoms), then initiate metformin as first-line therapy for metabolically stable patients, or insulin for those with marked hyperglycemia (≥250 mg/dL) and symptoms. 1, 2

Diagnostic Criteria

The diagnosis of diabetes requires demonstration of hyperglycemia using one of the following criteria 1:

• A1C ≥6.5% (48 mmol/mol) using an NGSP-certified laboratory method 1
• Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L) 1, 2
• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) in patients with classic symptoms of hyperglycemia (polyuria, polydipsia, weight loss) 1
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during 75-g oral glucose tolerance test 1

Confirmation Requirements

In the absence of unequivocal hyperglycemia or hyperglycemic crisis, results must be confirmed by repeat testing on a separate day. 1 However, if two different tests (such as A1C and fasting plasma glucose) are both above diagnostic thresholds, this confirms the diagnosis without additional testing 1. A single random plasma glucose ≥200 mg/dL with classic symptoms is sufficient for immediate diagnosis 1, 2.

Important Diagnostic Caveats

A1C may be unreliable in certain conditions and should not be used for diagnosis in: 1

• Conditions with increased red blood cell turnover (sickle cell disease, pregnancy second/third trimesters, hemodialysis, recent blood loss or transfusion, erythropoietin therapy) 1
• Hemoglobin variants that interfere with A1C measurement 1
• Marked discrepancies between A1C and plasma glucose levels should prompt consideration of A1C assay unreliability 1

Classification of Diabetes Type

After confirming hyperglycemia, classify the diabetes type to guide treatment using the AABBCC approach: 1

• Age: Consider type 1 diabetes in individuals <35 years old 1
• Autoimmunity: Personal or family history of autoimmune disease 1
• Body habitus: BMI <25 kg/m² suggests type 1 diabetes 1
• Background: Family history of type 1 diabetes 1
• Control: Inability to achieve glycemic goals on noninsulin therapies 1
• Comorbidities: Recent immune checkpoint inhibitor therapy can cause type 1 diabetes 1

Testing for Type 1 Diabetes

For adults with suspected type 1 diabetes, test islet autoantibodies: 1

• Glutamic acid decarboxylase (GAD) should be the primary antibody measured 1
• If GAD is negative, follow with islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) 1
• In autoantibody-negative adults <35 years without features of type 2 diabetes or monogenic diabetes, 5-10% still have type 1 diabetes 1

C-peptide testing helps distinguish diabetes type in insulin-treated patients: 1

• C-peptide <200 pmol/L (<0.6 ng/mL) indicates type 1 diabetes 1
• C-peptide >600 pmol/L (>1.8 ng/mL) suggests type 2 diabetes 1
• Do not test C-peptide within 2 weeks of hyperglycemic emergency 1

First-Line Treatment Algorithm

For Patients with Marked Hyperglycemia and Symptoms

Initiate insulin therapy immediately for patients presenting with: 2

• Blood glucose ≥250 mg/dL (13.9 mmol/L) AND symptoms of polyuria, polydipsia, and weight loss 2
• Check for ketones to rule out diabetic ketoacidosis (DKA), which requires immediate intravenous insulin and fluid resuscitation 2, 3

DKA is confirmed by: 3

• pH <7.3 and bicarbonate <15 mEq/L 3
• Moderate to large ketones in blood or urine 3
• Treatment requires IV fluid replacement (0.9% saline 15-20 mL/kg/h initially) and continuous IV insulin infusion (0.1 unit/kg/h) 3

For Metabolically Stable Patients

For patients with A1C <8.5% (69 mmol/mol) and asymptomatic presentation, initiate metformin as first-line therapy if renal function is normal. 2 This applies to the majority of newly diagnosed type 2 diabetes patients who are not in acute metabolic crisis 1, 2.

Metformin should be started along with lifestyle interventions at the time of diagnosis. 1 Lifestyle modifications include medical nutrition therapy, physical activity, and diabetes self-management education 1.

Critical Treatment Pitfall

Never use only corrective insulin (sliding scale) as monotherapy, as it treats hyperglycemia reactively rather than preventively. 3 Type 1 diabetes patients require basal insulin even when blood glucose is normal to prevent ketoacidosis 3.

Screening Recommendations

Screen for diabetes in asymptomatic adults who are overweight or obese (BMI ≥25 kg/m²) with one or more risk factors: 1

• First-degree relative with diabetes 1
• High-risk race/ethnicity (African American, Latino, Native American, Asian American, Pacific Islander) 1
• History of cardiovascular disease 1
• Hypertension (≥140/90 mmHg or on therapy) 1
• HDL cholesterol <35 mg/dL or triglycerides >250 mg/dL 1
• Women with polycystic ovary syndrome 1
• Physical inactivity 1

For all other patients, begin screening at age 45 years, and if results are normal, repeat testing at minimum 3-year intervals. 1