What causes darkening of the gums and skin creases in a 45-year-old with Type 1 Diabetes Mellitus (Type 1 DM) on insulin lispro (Humalog) and glargine (Lantus)?

Darkening of Gums and Skin Creases in Type 1 Diabetes: Acanthosis Nigricans

The darkening of gums and skin creases in a 45-year-old with Type 1 diabetes on insulin therapy is most likely acanthosis nigricans, a condition associated with insulin resistance that can develop at sites of repetitive insulin injections or as a systemic manifestation of insulin resistance even in Type 1 diabetes patients. 1

Pathophysiology and Causes

Acanthosis nigricans is characterized by:

• Hyperpigmented, velvety skin plaques
• Thickening of the keratin layer of the skin
• Commonly found in skin folds and intertriginous areas
• Can also affect the gums (oral manifestation)

In patients with Type 1 diabetes, acanthosis nigricans can develop through several mechanisms:

1. Insulin resistance development:

   • Despite having Type 1 diabetes (an insulin deficiency condition), patients can develop insulin resistance over time, especially with exogenous insulin administration 1
   • This insulin resistance exhibits a unique phenotype in Type 1 diabetes that can occur regardless of body weight 1

2. Local insulin injection effects:

   • High-dose or repetitive insulin injections at the same sites can cause localized acanthosis nigricans 2
   • Both insulin lispro and glargine have been implicated in this phenomenon

3. Systemic insulin effects:

   • Hyperinsulinemia from exogenous insulin therapy can promote acanthosis nigricans development 3
   • The high circulating insulin levels required to manage blood glucose in insulin-resistant states can trigger skin changes

Clinical Significance

The presence of acanthosis nigricans in a Type 1 diabetes patient has important clinical implications:

• Marker of insulin resistance: Indicates the development of insulin resistance in a patient who already has Type 1 diabetes 3
• Increased cardiovascular risk: Associated with metabolic syndrome components and increased cardiovascular risk 4
• Need for insulin regimen adjustment: May indicate need for insulin dose optimization or injection site rotation 2
• Potential for additional metabolic complications: May signal risk for other metabolic abnormalities 4

Management Approach

1. Evaluate insulin injection technique:

   • Assess current injection sites and rotation practices
   • Look for localized acanthosis nigricans at injection sites

2. Optimize insulin regimen:

   • Ensure proper insulin dosing based on carbohydrate intake and blood glucose levels
   • Consider adjusting the ratio of basal to bolus insulin 5

3. Implement proper site rotation:

   • Advise rotating injection sites systematically
   • Avoid injecting into areas already showing signs of acanthosis nigricans 2

4. Address insulin resistance:

   • Consider lifestyle modifications (physical activity, dietary changes)
   • Evaluate for potential addition of insulin-sensitizing agents in consultation with endocrinology

5. Topical treatments:

   • Consider topical retinoids (0.1% retinoic acid cream) for cosmetic improvement 2

Monitoring and Follow-up

• Regular skin examinations to monitor progression or improvement
• Periodic assessment of glycemic control and insulin requirements
• Evaluation for other manifestations of insulin resistance or metabolic syndrome

Important Considerations

• Acanthosis nigricans can occur in Type 1 diabetes despite it being primarily associated with Type 2 diabetes and insulin resistance 6
• The presence of acanthosis nigricans should prompt evaluation for optimal insulin delivery methods and dosing
• While rare in Type 1 diabetes compared to Type 2, its appearance signals important metabolic changes that warrant attention

By addressing the underlying insulin resistance and optimizing insulin delivery, the appearance of acanthosis nigricans may improve over time, though complete resolution may not always be achievable.