Do patients with type 2 diabetes mellitus (T2DM) typically have insulin resistance?

Type 2 Diabetes and Insulin Resistance

Yes, most patients with type 2 diabetes mellitus (T2DM) have insulin resistance as a core pathophysiological feature, though the degree varies and is accompanied by progressive beta-cell dysfunction. 1

Prevalence and Pathophysiology

Insulin resistance is present in the vast majority of T2DM patients, with over 90% having some degree of peripheral insulin resistance. 1 Type 2 diabetes accounts for 90-95% of all diabetes cases and encompasses individuals who have relative (rather than absolute) insulin deficiency combined with peripheral insulin resistance—meaning a decreased biological response to insulin. 1

The pathophysiology involves:

• Dual defect mechanism: T2DM is characterized by both insulin resistance and impaired insulin secretion, with neither defect alone being sufficient to cause diabetes. 1, 2, 3
• Progressive beta-cell failure: While insulin levels may appear normal or even elevated early in the disease, these levels are insufficient to compensate for the degree of insulin resistance present. 1
• Adipose tissue dysfunction: More than 90% of people with T2DM have obesity, and the release of free fatty acids and cytokines from adipose tissue directly impairs insulin sensitivity. 1

Clinical Manifestations of Insulin Resistance

The presence of insulin resistance in T2DM is evidenced by the fact that patients often have normal or elevated insulin levels, yet these levels fail to normalize blood glucose—reflecting a relative defect in glucose-stimulated insulin secretion that is insufficient to overcome the resistance. 1

Key clinical indicators include:

• Compensatory hyperinsulinemia: Early in the disease course, the pancreas secretes excess insulin to overcome peripheral resistance. 1
• Central obesity: Most patients have increased body fat distributed predominantly in the abdominal region, even if not meeting traditional obesity criteria. 1
• Associated metabolic abnormalities: Insulin resistance is typically accompanied by hypertension, dyslipidemia (low HDL, elevated triglycerides), and other features of metabolic syndrome. 1

Important Clinical Distinctions

A critical pitfall is assuming all T2DM patients have the same degree of insulin resistance—the phenotype varies considerably. Some patients, particularly those without obesity or of certain ethnic backgrounds (Asian populations), may have relatively less insulin resistance and more prominent beta-cell dysfunction. 1

• Insulin resistance can improve with weight reduction, physical activity, and pharmacologic treatment of hyperglycemia, but is seldom restored to normal. 1
• Progressive nature: The disease involves a continuum from insulin resistance with compensatory hyperinsulinemia, through impaired glucose tolerance, to overt diabetes with declining insulin secretion. 1
• Not absolute insulin deficiency: Unlike type 1 diabetes, T2DM patients retain some endogenous insulin production and do not have autoimmune beta-cell destruction. 1

Therapeutic Implications

The presence of insulin resistance in T2DM directly informs treatment strategy, with insulin sensitizers like metformin serving as first-line therapy. 4, 2

Treatment targeting insulin resistance includes:

• Lifestyle modification: Weight loss of 5-7% of initial body weight through calorie reduction and at least 150 minutes weekly of moderate-intensity aerobic activity significantly improves insulin resistance. 4
• Metformin as first-line pharmacotherapy: This agent enhances insulin sensitivity and is the preferred initial medication when lifestyle changes are insufficient. 4, 2
• Thiazolidinediones: Agents like pioglitazone directly improve insulin sensitivity by enhancing cellular responsiveness to insulin and increasing insulin-dependent glucose disposal. 5

Diagnostic Considerations

While insulin resistance is nearly universal in T2DM, it can be present with normal glucose levels (prediabetes) or even without meeting diabetes diagnostic criteria. 6

• Fasting insulin >15 mU/L directly confirms insulin resistance. 6
• Physical examination findings such as acanthosis nigricans, central adiposity, and skin tags indicate insulin resistance. 6
• Normal glucose does not exclude insulin resistance, as hyperinsulinemia can maintain euglycemia in early stages. 6