Can you have type 2 diabetes with insulinopenia?

Type 2 Diabetes with Insulinopenia

Yes, type 2 diabetes can present with insulinopenia, particularly as the disease progresses or in certain subtypes of the condition. While type 2 diabetes is traditionally characterized by insulin resistance with relative insulin deficiency, some patients develop significant insulin deficiency (insulinopenia) over time or as part of their disease presentation.

Pathophysiology of Insulinopenia in Type 2 Diabetes

• Type 2 diabetes involves both impaired insulin secretion and insulin resistance, with their relative contributions varying due to the heterogeneity of the disease 1
• While patients with type 2 diabetes initially have insulin levels that appear normal or elevated, there is a progressive decline in beta-cell function and insulin secretion over time 2
• As the disease progresses, insulin secretion becomes increasingly defective and insufficient to compensate for insulin resistance 2
• Recent evidence suggests several subtypes of type 2 diabetes may coexist, including a specific subtype characterized by insulinopenia (generally severe) 3

Clinical Manifestations of Insulinopenia in Type 2 Diabetes

• Approximately one-third of all hyperinsulinemic diabetic patients eventually develop insulinopenia 4
• Progressive beta-cell dysfunction leads to worsening insulin secretory capacity over time 5
• Chronic hyperglycemia can result in further deterioration of insulin sensitivity and secretion (glucotoxicity), which is aggravated by elevated free fatty acids (lipotoxicity) 1
• Marked reduction in beta-cell mass has been reported in post-mortem examinations of pancreases from patients with type 2 diabetes, with increased beta-cell apoptosis not compensated by neogenesis 5

Diagnostic Considerations

• Fasting plasma insulin levels can help identify insulinopenia, with normal levels being <15 mU/L 6
• Measuring C-peptide alongside insulin can help differentiate between endogenous insulin production and exogenous insulin administration 6
• In patients without traditional risk factors for type 2 diabetes and/or of younger age, consider islet autoantibody testing to exclude type 1 diabetes 7
• Patients with insulinopenia may require insulin therapy despite having type 2 diabetes, known as "insulin-requiring type 2 diabetes" 2

Treatment Implications

• Treatment combining long-acting and short-acting insulins may become compulsory in type 2 diabetes cases with insulinopenia 8
• Patients with insulinopenia may be at higher risk for diabetic ketoacidosis (DKA) during stress, though it seldom occurs spontaneously in type 2 diabetes 2
• When DKA occurs in type 2 diabetes, it usually arises in association with the stress of another illness such as infection, myocardial infarction, or with the use of certain drugs 2

Distinguishing from Other Types of Diabetes

• Unlike type 1 diabetes, autoimmune destruction of beta-cells does not occur in type 2 diabetes with insulinopenia 2
• Pancreatic diabetes (secondary to pancreatic diseases) also features severe insulinopenia but with an increased risk of hypoglycemia due to simultaneous decrease in glucagon secretion 2
• Idiopathic type 1 diabetes presents with permanent insulinopenia and proneness to DKA but without evidence of beta-cell autoimmunity 2

Clinical Implications and Management

• Patients with type 2 diabetes and significant insulinopenia may require insulin therapy earlier in their disease course 8
• The presence of insulinopenia in type 2 diabetes may indicate a more advanced disease state with greater beta-cell dysfunction 5
• Newer classification systems for diabetes are being developed that may better account for the heterogeneity of the disease, including insulinopenic subtypes 3
• Recognizing insulinopenia in type 2 diabetes is important for appropriate treatment selection and management of complications 8

Common Pitfalls

• Failing to recognize that type 2 diabetes frequently goes undiagnosed for many years because hyperglycemia develops gradually 7
• Not considering the possibility of insulinopenia in patients with longstanding type 2 diabetes who are becoming increasingly difficult to control with oral medications 1
• Overlooking the progressive nature of beta-cell dysfunction in type 2 diabetes, which can eventually lead to significant insulin deficiency 5
• Misclassifying patients with insulinopenia as having type 1 diabetes when they may actually have a subtype of type 2 diabetes with severe insulin deficiency 3