What is the best course of treatment for a patient with uncontrolled diabetes mellitus (DM), presenting with hyperglycemia, glycosuria, and impaired renal function, who recently experienced an episode of severe fatigue and dyspnea?

Management of Uncontrolled Diabetes with Hyperglycemia, Renal Impairment, and Recent Acute Symptoms

This patient requires immediate hospitalization for evaluation and treatment of possible hyperosmolar hyperglycemic state (HHS) or diabetic ketoacidosis, given the severe hyperglycemia with glycosuria, significantly elevated creatinine (300 mg/dL suggesting acute kidney injury or advanced CKD), and recent severe fatigue/dyspnea which may indicate metabolic decompensation or cardiovascular complications. 1

Immediate Assessment and Stabilization

Emergency Evaluation

• Measure arterial blood gas, complete blood count, comprehensive metabolic panel including calculated effective osmolality [2(Na+) + glucose/18], and urinalysis for ketones immediately to differentiate between HHS and DKA 1
• Assess volume status, mental status, vital signs, and respiratory pattern as indicators of severity 1
• Identify precipitating factors: infection (most common), medication non-adherence (confirmed in this case), acute coronary syndrome, or stroke 1
• The recent severe fatigue and dyspnea warrant urgent evaluation for acute heart failure, myocardial infarction, or severe anemia, particularly given the renal dysfunction 2

Initial Fluid Resuscitation

• Begin with 0.9% normal saline at 15-20 mL/kg/hour in the first hour 1
• Target fluid deficit replacement over 24 hours, ensuring osmolality decreases no faster than 3 mOsm/kg/hour to prevent cerebral edema 1
• This aggressive initial fluid therapy is critical as HHS patients typically have profound volume depletion (8-10 liters) 1

Insulin Therapy Initiation

• Start continuous IV regular insulin at 0.1 units/kg/hour ONLY after confirming potassium >3.3 mEq/L 1
• If glucose fails to decrease by at least 50 mg/dL in the first hour, double the insulin infusion rate hourly until achieving 50-75 mg/dL/hour glucose reduction 1
• Target blood glucose of 180-270 mg/dL within 24 hours, not normoglycemia 1
• Monitor blood glucose hourly during acute phase 1

Renal Function Assessment and Management

Determining Kidney Disease Severity

With creatinine at 300 mg/dL, this patient likely has either:

• Acute kidney injury superimposed on chronic kidney disease (most likely given diabetes history and poor adherence)
• Advanced CKD stage 4-5 (eGFR <30 mL/min/1.73m²) 2

Measure urinary albumin-to-creatinine ratio (ACR) and calculate eGFR using MDRD or CKD-EPI formula once stabilized to stage diabetic kidney disease 2, 3

Renal-Specific Considerations

• The presence of glycosuria with creatinine 300 mg/dL indicates the glucose threshold has been exceeded despite severe renal impairment 2
• Discontinue metformin immediately as it is contraindicated with eGFR <30 mL/min/1.73m² due to lactic acidosis risk 2
• Measure lactate levels given the poor adherence history and potential metformin accumulation 2

Transition to Subcutaneous Insulin

When to Transition

• Switch from IV to subcutaneous insulin when the patient is hemodynamically stable, blood glucose <300 mg/dL, able to eat, and mental status has normalized 1, 2
• Administer subcutaneous insulin 1-2 hours before discontinuing IV insulin to prevent rebound hyperglycemia 2

Subcutaneous Insulin Regimen

• Implement basal-bolus regimen at 60-80% of total daily IV insulin dose 2, 1
• Split 50/50 between once-daily basal insulin (glargine or detemir) and rapid-acting insulin (lispro, aspart) divided before meals 1
• For patients with eGFR <30 mL/min/1.73m², insulin is the preferred and often only safe glucose-lowering agent 2, 4

Long-Term Diabetes Management with Advanced CKD

Glycemic Targets

Target HbA1c of 7-8% for this patient with advanced CKD and complications 2, 5

• The 2019 AHA/HFSA statement recommends HbA1c 7-8% for patients with significant comorbidities including advanced kidney disease 2
• Tighter control (<7%) increases hypoglycemia risk without proven benefit in advanced CKD 2, 6
• HbA1c accuracy decreases with eGFR <30 mL/min/1.73m² due to altered red blood cell turnover 7

Medication Selection for eGFR <30 mL/min/1.73m²

Insulin remains the cornerstone of therapy 2, 4, 6:

• Basal-bolus regimen as described above
• Increased hypoglycemia risk due to reduced renal insulin clearance—may require dose reductions of 25-50% 6

SGLT2 inhibitors should NOT be used 2:

• Contraindicated or ineffective with eGFR <30 mL/min/1.73m² 2
• While canagliflozin showed cardiovascular and renal benefits in the CREDENCE trial, this was in patients with eGFR 30-90 mL/min/1.73m² 8

DPP-4 inhibitors may be considered as adjunct therapy 2, 4:

• Can be used with dose adjustment in advanced CKD 4
• Low hypoglycemia risk when used without insulin or sulfonylureas 2
• The Lancet Diabetes and Endocrinology guidelines support their use in hospitalized patients with mild-moderate hyperglycemia 2

Avoid these medications 2:

• Metformin (contraindicated, eGFR <30) 2
• Sulfonylureas (high hypoglycemia risk with renal impairment) 2
• Thiazolidinediones (fluid retention, heart failure risk) 2

Blood Pressure Management

Target systolic BP <140/85 mmHg, with consideration of <130 mmHg if tolerated 2, 5:

• Use ACE inhibitors or ARBs as first-line therapy for nephroprotection 2, 3
• These agents reduce albuminuria and slow CKD progression even in advanced disease 2
• Monitor potassium closely as hyperkalemia risk increases with eGFR <30 2

Cardiovascular Risk Reduction

Given the recent dyspnea/fatigue episode:

• Initiate high-intensity statin therapy targeting LDL <70 mg/dL 2, 5
• Start antiplatelet therapy (aspirin 75-162 mg daily) if not contraindicated 2
• Evaluate for heart failure with echocardiography given symptoms and diabetes/CKD combination 2

Monitoring Strategy

Glucose Monitoring

• Consider continuous glucose monitoring (CGM) rather than relying solely on HbA1c 7
• CGM provides real-time data to prevent hypoglycemia, which is particularly dangerous in advanced CKD 7
• Self-monitored blood glucose at minimum: fasting, pre-meals, bedtime, and 3 AM (to detect nocturnal hypoglycemia) 7

Laboratory Monitoring

• Electrolytes and renal function every 2-4 hours during acute phase 1
• Once stable: electrolytes, creatinine, eGFR, and ACR every 2-4 months 2
• HbA1c every 3 months, but interpret cautiously given renal impairment 7

Addressing Medication Adherence

The poor adherence history is the likely precipitant of this crisis 1:

• Simplify regimen as much as possible—basal insulin alone may be preferable to basal-bolus if patient cannot manage multiple injections 2
• Arrange diabetes education focusing on hypoglycemia recognition and sick-day management 2
• Ensure follow-up within 1-2 weeks of discharge with endocrinology or nephrology 1
• Consider social work evaluation for barriers to medication access 2

Critical Pitfalls to Avoid

• Never correct glucose too rapidly—risk of cerebral edema if glucose falls >100 mg/dL/hour 1
• Never use metformin with creatinine 300 mg/dL—severe lactic acidosis risk 2
• Never target HbA1c <7% in advanced CKD—increases severe hypoglycemia without benefit 2, 6
• Never use sliding-scale insulin alone—associated with worse outcomes 2
• Never discharge without confirming patient can obtain and afford insulin—primary cause of readmission 2