Management of Hyperinsulinemia in a Patient with CKD Stage 3b, Psoriatic Arthritis, and Prediabetes
For patients with hyperinsulinemia, CKD stage 3b, psoriatic arthritis, and prediabetes, first-line treatment should include lifestyle modifications combined with metformin and a sodium-glucose cotransporter-2 inhibitor (SGLT2i) if eGFR ≥30 ml/min/1.73m².
Glycemic Monitoring and Targets
- HbA1c remains the primary tool for monitoring glycemic control in CKD stage 3b (eGFR 30-44 ml/min/1.73m²) as its accuracy is not significantly affected at this level of kidney function 1
- For patients with CKD stage 3b and prediabetes, an individualized HbA1c target ranging from <6.5% to <8.0% should be established based on hypoglycemia risk and comorbidities 1
- Consider continuous glucose monitoring (CGM) as it is not affected by kidney function and may be particularly useful in patients with discordance between HbA1c and clinical symptoms 1
Pharmacological Management
Metformin is recommended as first-line therapy for patients with CKD stage 3b (eGFR ≥30 ml/min/1.73m²) 1
SGLT2 inhibitors are recommended as first-line therapy alongside metformin for patients with eGFR ≥30 ml/min/1.73m² 1
- These agents provide cardiorenal protection independent of their glucose-lowering effects 1
If glycemic targets are not achieved with metformin and SGLT2i, or if these medications cannot be used, add a GLP-1 receptor agonist 1
- GLP-1 receptor agonists are preferred over other agents due to their cardiovascular benefits and low hypoglycemia risk 1
Avoid first-generation sulfonylureas in CKD stage 3b due to increased risk of hypoglycemia 1
- If a sulfonylurea is needed, prefer glipizide or gliclazide as they don't have active metabolites that accumulate in CKD 1
Lifestyle Interventions
Dietary recommendations:
- Maintain protein intake at 0.8 g/kg body weight/day for CKD patients not on dialysis 1
- Limit sodium intake to <2 g/day (or <5 g sodium chloride/day) 1
- Focus on a balanced diet high in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts 1
- Reduce consumption of processed meats, refined carbohydrates, and sweetened beverages 1
Physical activity:
Weight management:
- For patients with obesity, encourage weight loss which may improve both insulin sensitivity and kidney function 1
Special Considerations for Psoriatic Arthritis
- Severe psoriasis is an independent risk factor for CKD progression and ESRD (adjusted hazard ratio 1.90 for CKD and 2.97 for ESRD) 2
- Psoriatic arthritis acts as an effect modifier for CKD progression 2
- Avoid long-term use of nephrotoxic drugs, including NSAIDs commonly used for arthritis management 2
- Consider the impact of anti-inflammatory treatments for psoriatic arthritis on insulin sensitivity and kidney function 2
Monitoring and Follow-up
- Monitor eGFR more frequently when <60 ml/min/1.73m² 1
- Assess for medication side effects, particularly hypoglycemia with insulin-sensitizing agents 1
- Screen for cardiovascular complications as patients with CKD, prediabetes, and hyperinsulinemia have increased cardiovascular risk 1, 3
- Evaluate for progression of both CKD and conversion from prediabetes to diabetes 4, 5
Mechanisms and Pathophysiology
- CKD-induced insulin resistance involves multiple mechanisms including inflammation, oxidative stress, elevations in aldosterone, angiotensin II, uremic toxins, and metabolic acidosis 3
- These mechanisms lead to degradation of insulin receptor substrate 1 (IRS1), impairing intracellular insulin signaling 3
- Hyperinsulinemia in CKD may worsen cardiovascular outcomes, highlighting the importance of addressing insulin resistance 3