What is insulin resistant diabetes?

Insulin Resistant Diabetes: Understanding Type 2 Diabetes

Insulin resistant diabetes, commonly known as type 2 diabetes, is a metabolic disorder characterized by high blood glucose levels due to the body's cells not responding properly to insulin, resulting in relative insulin deficiency despite normal or elevated insulin levels. 1

Definition and Pathophysiology

Type 2 diabetes accounts for 90-95% of all diabetes cases and is characterized by:

• Insulin resistance: Decreased biological response to insulin in target tissues (muscle, liver, fat)
• Relative insulin deficiency: Unlike type 1 diabetes (which has absolute insulin deficiency), people with type 2 diabetes have insulin levels that may appear normal or elevated 1
• Defective insulin secretion: Despite having insulin, it's insufficient to overcome the resistance and normalize blood glucose 1

The key pathophysiological sequence involves:

1. Development of insulin resistance in peripheral tissues
2. Initial compensation by increased insulin production (hyperinsulinemia)
3. Eventual beta-cell dysfunction leading to inadequate insulin secretion
4. Progressive hyperglycemia as the disease advances

Causes and Risk Factors

Multiple factors contribute to insulin resistant diabetes:

• Obesity: Most patients have overweight or obesity, which directly causes insulin resistance 1
• Visceral adiposity: Even those without clinical obesity may have increased abdominal fat distribution 1
• Genetic predisposition: Strong familial association, more so than type 1 diabetes 1
• Age: Risk increases with advancing age 1
• Physical inactivity: Sedentary lifestyle contributes to insulin resistance 2
• Race/ethnicity: Higher prevalence in certain populations (African American, Native American, Hispanic/Latino, Asian American) 1
• Medical history: Prior gestational diabetes, polycystic ovary syndrome, hypertension, or dyslipidemia 1

Clinical Presentation

Type 2 diabetes often develops gradually and may go undiagnosed for years because:

• Early hyperglycemia may not be severe enough to cause noticeable symptoms 1
• The disease develops insidiously, unlike the more acute presentation of type 1 diabetes
• Ketoacidosis is rare and typically only occurs with significant stress or illness 1

Despite being asymptomatic, patients are still at risk for developing macrovascular and microvascular complications 1.

Diagnostic Criteria

Diagnosis is based on one of the following criteria:

• Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L)
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during OGTT
• A1C ≥6.5% (48 mmol/mol)
• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) with symptoms of hyperglycemia

Prediabetes, which often precedes type 2 diabetes, is defined as:

• Fasting glucose 100-125 mg/dL (IFG)
• 2-hour glucose 140-199 mg/dL during OGTT (IGT)
• A1C 5.7-6.4% 1

Hyperinsulinemia and Insulin Resistance

A key feature of early type 2 diabetes is hyperinsulinemia, which:

• Often precedes clinical hyperglycemia by years 3
• Represents the body's attempt to overcome insulin resistance
• Is associated with increased cardiovascular risk, hypertension, and dyslipidemia 3, 4
• May contribute to weight gain, further worsening insulin resistance

Importantly, while insulin levels may be normal or high, they are inadequate relative to the degree of insulin resistance 5. The failure to normalize blood glucose reflects a relative defect in glucose-stimulated insulin secretion that is insufficient to compensate for insulin resistance 1.

Management Considerations

Management focuses on:

1. Lifestyle modifications: Weight reduction, physical activity, and dietary changes 3
2. Pharmacological therapy: Often starting with insulin sensitizers like metformin
3. Regular monitoring: Blood glucose, A1C, and cardiovascular risk factors

Important Clinical Distinctions

• Unlike type 1 diabetes, patients with type 2 diabetes don't typically need insulin to survive, at least initially 1
• Insulin resistance may improve with weight reduction and exercise but is seldom restored to normal 1
• Recent interventions with intensive diet and exercise, newer pharmacological agents, or surgical weight loss have led to diabetes remission in some cases 1

Common Pitfalls

1. Assuming normal insulin levels mean normal function: Even "normal" insulin levels may be inadequate for the degree of resistance
2. Focusing only on glucose control: Addressing insulin resistance is crucial for reducing cardiovascular risk
3. Overlooking hyperinsulinemia risks: Chronic hyperinsulinemia itself carries health risks beyond hyperglycemia 4
4. Delayed diagnosis: The gradual onset often leads to years of undiagnosed disease and complications

Understanding insulin resistant diabetes as a dual problem of insulin resistance and relative insulin deficiency is essential for effective management and prevention of complications.