What is the recommended workup and treatment for a patient suspected of having diabetes, considering potential complications and comorbidities, including cardiovascular disease?

Workup for Diabetes

For patients suspected of having diabetes, confirm the diagnosis with fasting plasma glucose ≥126 mg/dL, HbA1c ≥6.5%, random plasma glucose ≥200 mg/dL with symptoms, or 2-hour oral glucose tolerance test ≥200 mg/dL, then immediately perform a comprehensive medical evaluation to classify diabetes type, assess for complications, evaluate cardiovascular risk, and initiate treatment. 1, 2

Diagnostic Testing

• Measure fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) as the primary diagnostic test, as this is emphasized over oral glucose tolerance testing for practical reasons 3, 2
• Confirm abnormal results with repeat testing on a subsequent day, unless random plasma glucose is ≥200 mg/dL with classic hyperglycemic symptoms (polyuria, polydipsia, unexplained weight loss), which confirms diabetes without repeat testing 3, 2
• Alternative diagnostic criteria include HbA1c ≥6.5%, random plasma glucose ≥200 mg/dL, or 2-hour plasma glucose ≥200 mg/dL during 75-g oral glucose tolerance test 1, 2

Initial Comprehensive Medical Evaluation

At the initial visit, perform the following assessments to guide treatment: 1

History Components

• Document age at onset, presenting symptoms (polyuria, polydipsia, weight loss, fatigue), and rapidity of symptom development to help classify diabetes type 1
• Assess family history of diabetes in first-degree relatives and autoimmune disorders (suggests type 1 diabetes risk) 1
• Review for symptoms of acute complications: diabetic ketoacidosis (nausea, vomiting, abdominal pain, fruity breath odor) or hyperosmolar hyperglycemic state 1

Physical Examination Findings

• Measure blood pressure at every visit, as hypertension is present in the majority of patients with type 2 diabetes and requires aggressive management 1, 4
• Calculate body mass index and measure waist circumference (abnormal if ≥35 inches in women or ≥40 inches in men) 1, 4
• Perform comprehensive foot examination including inspection for deformities, skin integrity, pulses, and monofilament testing for peripheral neuropathy 1, 4
• Examine skin for acanthosis nigricans (suggests insulin resistance) and lipohypertrophy at injection sites if already using insulin 4

Laboratory Workup at Diagnosis

Obtain the following tests to assess baseline status and screen for complications: 1

• Serum creatinine with estimated glomerular filtration rate (eGFR) calculation to stage chronic kidney disease 1
• Urine albumin-to-creatinine ratio in a random spot collection to screen for diabetic nephropathy (microalbuminuria = 30-300 mg/g; macroalbuminuria >300 mg/g) 1, 3
• Lipid panel including total cholesterol, LDL, HDL, and triglycerides 1
• Liver function tests (ALT, AST) to assess for nonalcoholic fatty liver disease and establish baseline before starting metformin 1, 5
• Thyroid-stimulating hormone (TSH) in patients with type 1 diabetes or symptoms suggesting thyroid dysfunction 1

Cardiovascular Risk Assessment

• Calculate 10-year atherosclerotic cardiovascular disease (ASCVD) risk using the race- and sex-specific Pooled Cohort Equations in patients ≥40 years old 1
• Obtain resting electrocardiogram if patient has cardiovascular symptoms, abnormal cardiac examination, or is ≥40 years with additional cardiovascular risk factors 1
• Assess for cardiovascular risk factors annually: smoking status, family history of premature coronary disease, presence of micro- or macroalbuminuria 1

Screening for Microvascular Complications

Perform the following at diagnosis for type 2 diabetes (or after 5 years duration for type 1 diabetes): 1

• Dilated retinal examination by ophthalmologist or optometrist to screen for diabetic retinopathy 1
• Comprehensive foot examination with 10-g monofilament testing, vibration perception, ankle reflexes, and visual inspection 1
• Annual urine albumin excretion testing as described above 1

Classification of Diabetes Type

Distinguish between type 1 and type 2 diabetes based on clinical presentation: 1, 2

• Type 1 diabetes: younger age at onset (typically <30 years), acute symptom onset, lean body habitus, presence of ketones, absolute insulin requirement 2, 6
• Type 2 diabetes: older age at onset (typically ≥45 years), gradual symptom onset, overweight/obese, strong family history, associated with metabolic syndrome 2, 7
• Additional testing to determine etiology (autoantibodies, C-peptide) is not routinely recommended unless clinical presentation is atypical 2

Immunizations

Administer age-appropriate vaccinations, with special emphasis on: 1

• Annual influenza vaccine for all patients ≥6 months of age 1
• Pneumococcal vaccination: PCV13 for children <2 years; PPSV23 for ages 2-64 years; additional PPSV23 at age ≥65 years regardless of prior vaccination 1
• Hepatitis B vaccine series (2-3 doses depending on vaccine) for unvaccinated adults ages 18-59 years; consider for those ≥60 years 1

Initial Treatment Strategy

For Type 2 Diabetes

Initiate metformin at diagnosis along with comprehensive lifestyle modifications unless contraindicated: 8, 9, 5

• Metformin is contraindicated if eGFR <30 mL/min/1.73 m², hepatic impairment, acute heart failure, or conditions predisposing to lactic acidosis 5
• Verify serum creatinine is <1.5 mg/dL in men or <1.4 mg/dL in women before starting metformin 8
• Start metformin 500 mg once or twice daily with meals to minimize gastrointestinal side effects, titrating up to maximum effective dose of 2000 mg daily 5
• If patient has established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, add GLP-1 receptor agonist or SGLT2 inhibitor at diagnosis for cardiovascular and renal protection 9

Glycemic Targets

• Target HbA1c <7.0% for most adults to reduce microvascular complications 1, 8
• Less stringent targets (HbA1c <8.0%) are appropriate for patients with history of severe hypoglycemia, limited life expectancy, advanced complications, or extensive comorbidities 1
• Recheck HbA1c at 3 months; if target not achieved, add second agent 8

Lifestyle Modifications

All patients must receive: 9

• Diabetes self-management education and support (reduces HbA1c by 0.3-2.0% and mortality risk) 9
• Medical nutrition therapy referral to registered dietitian 1, 9
• ≥150 minutes per week of moderate-intensity aerobic activity spread over at least 3 days, with no more than 2 consecutive days without activity 1, 8, 9
• Resistance training at least 2 days per week 1, 9
• Weight loss of at least 5% for overweight/obese patients 1, 9
• Sodium restriction to <2,300 mg/day 8
• Complete avoidance of sugar-sweetened beverages 8

For Type 1 Diabetes

• Initiate multiple-dose insulin injections (0.25-1.0 U/kg/day) or continuous subcutaneous insulin infusion immediately at diagnosis 9, 6
• Insulin analogues are preferred over regular insulin to reduce hypoglycemia risk 9
• Consider continuous glucose monitoring to reduce severe hypoglycemia risk 9

Cardiovascular Disease Management

For patients ≥40 years with additional cardiovascular risk factors or established cardiovascular disease: 1

• Initiate aspirin 75-162 mg daily unless contraindicated 1
• Start ACE inhibitor or ARB for blood pressure control and nephropathy prevention 1
• Initiate statin therapy regardless of baseline LDL cholesterol (target LDL <100 mg/dL, with <70 mg/dL considered reasonable for very high-risk patients) 1
• Add beta-blocker if prior myocardial infarction 1

Critical Safety Considerations

• Temporarily discontinue metformin before iodinated contrast procedures if eGFR 30-60 mL/min/1.73 m², history of hepatic impairment, alcoholism, heart failure, or intra-arterial contrast administration; restart 48 hours after procedure if renal function stable 5
• Withhold metformin during surgical procedures or when patient has restricted food/fluid intake 5
• Metformin rarely causes hypoglycemia alone but risk increases when combined with insulin or sulfonylureas; lower doses of these agents may be required 5
• Monitor for lactic acidosis symptoms (malaise, myalgias, respiratory distress, abdominal pain) and discontinue metformin immediately if suspected 5
• Measure vitamin B12 levels at 2-3 year intervals as metformin interferes with B12 absorption 5

Follow-up Schedule

• Recheck HbA1c every 3 months until glycemic target achieved, then every 6 months 8, 9
• Measure serum creatinine and urine albumin-to-creatinine ratio annually 1
• Annual dilated eye examination 1
• Annual comprehensive foot examination 1
• Assess cardiovascular risk factors at least annually 1