Type 2 Diabetes with Insulinopenia

Pathophysiology and Clinical Manifestations

The American Diabetes Association notes that type 2 diabetes involves both impaired insulin secretion and insulin resistance, with a progressive decline in beta-cell function and insulin secretion over time, leading to defective and insufficient insulin secretion to compensate for insulin resistance 1
The European Association for the Study of Diabetes suggests that chronic hyperglycemia can result in further deterioration of insulin sensitivity and secretion, which is aggravated by elevated free fatty acids, although the exact mechanisms are not fully understood in this context 1

The American College of Clinical Endocrinologists recommends that fasting plasma insulin levels can help identify insulinopenia, with normal levels being less than a certain threshold, and measuring C-peptide alongside insulin can help differentiate between endogenous insulin production and exogenous insulin administration 2
The Endocrine Society suggests that in patients without traditional risk factors for type 2 diabetes and/or of younger age, consider islet autoantibody testing to exclude type 1 diabetes, as part of a comprehensive diagnostic approach 3

The International Diabetes Federation notes that patients with insulinopenia may require insulin therapy despite having type 2 diabetes, known as "insulin-requiring type 2 diabetes", and may be at higher risk for diabetic ketoacidosis during stress 4
The American Diabetes Association recommends that when diabetic ketoacidosis occurs in type 2 diabetes, it usually arises in association with the stress of another illness, and treatment should be tailored accordingly 1

The European Association for the Study of Diabetes suggests that unlike type 1 diabetes, autoimmune destruction of beta-cells does not occur in type 2 diabetes with insulinopenia, and pancreatic diabetes features severe insulinopenia but with an increased risk of hypoglycemia due to simultaneous decrease in glucagon secretion 1
The American College of Clinical Endocrinologists notes that idiopathic type 1 diabetes presents with permanent insulinopenia and proneness to diabetic ketoacidosis but without evidence of beta-cell autoimmunity, highlighting the importance of accurate diagnosis 5