Clinica Applications

HbA1c

Hemoglobin (Hb) is the red-pigmented, iron-containing protein, located in the erythrocytes. Its main function is to transport oxygen and carbon dioxide in blood. Hb consists of a variety of variants (such as adult HbA and fetal HbF) and derivatives (e.g. acetylated, glycated). HbA makes up the largest fraction (> 95 %) of Hb in adult subjects and consists of 4 protein chains (2 alpha, 2 beta chains). HbA1c is one of the glycated hemoglobins, a subfraction formed by the attachment of various sugars to the HbA molecule. HbA1c is formed in two steps by the nonenzymatic reaction of glucose with the Nterminal amino group of the beta- chain of normal adult Hb (HbA). The first step is reversible and yields labile HbA1c. This is rearranged to form stable HbA1c in a second reaction step. In the erythrocytes, the relative amount of HbA converted to stable HbA1c increases with the average concentration of glucose in the blood. The conversion to stable HbA1c is limited by the erythrocyte’s life span of approximately 100 to 120 days. As a result, HbA1c reflects the average blood glucose level during the preceding 2 to 3 months rather than daily variations in blood glucose levels. HbA1c is thus suitable to monitor long-term blood glucose control in individuals with diabetes mellitus.

Insulin

A single protein (monomer) of human insulin is composed of 51 amino acids, and has a molecular mass of 5808 Da. It is a combination of two peptide chains (dimer) named an A-chain and a B-chain, which are linked together by two disulfide bonds. Decreased or absent insulin activity results in diabetes mellitus, a condition of high blood sugar level (hyperglycaemia). There are two types of the disease. In diabetes mellitus type 1, the beta cells are destroyed by an autoimmune reaction so that insulin can no longer be synthesized or be secreted into the blood. In diabetes mellitus type 2, the destruction of beta cells is less pronounced than in type 1, and is not due to an autoimmune process. Instead, there is an accumulation of amyloid in the pancreatic islets, which likely disrupts their anatomy and physiology. The pathogenesis of type 2 diabetes is not well understood but reduced population of islet beta-cells, reduced secretory function of islet beta-cells that survive, and peripheral tissue insulin resistance are known to be involved. Type 2 diabetes is characterized by increased glucagon secretion which is unaffected by, and unresponsive to the concentration of blood glucose.​​​​​​​

C-peptide

C-peptide is a short 31-amino-acid polypeptide that connects insulin's A-chain to its B- chain in the proinsulin molecule. The proteolytic cleavage of the precursor proinsulin results in the two molecules insulin and C-peptide. Both are secreted in equimolar amounts and released into circulation via the portal vein.
Patients with diabetes may have their C-peptide levels measured as a means of distinguishing type 1 diabetes from type 2 diabetes or maturity-onset diabetes of the young (MODY). Measuring C-peptide can help to determine how much of their own natural insulin a person is producing as C-peptide is secreted in equimolar amounts to insulin. C-peptide levels are measured instead of insulin levels because C-peptide can assess a person's own insulin secretion even if they receive insulin injections, and because the liver metabolizes a large and variable amount of insulin secreted into the portal vein but does not metabolise C-peptide, meaning blood C-peptide may be a better measure of portal insulin secretion than insulin itself. A very low C-peptide confirms Type 1 diabetes and insulin dependence and is associated with high glucose variability, hyperglycaemia and increased complications. The test may be less helpful close to diagnosis, particularly where a patient is overweight and insulin resistant, as levels close to diagnosis in Type 1 diabetes may be high and overlap with those seen in type 2 diabetes.