The Insulin reistent
triggered by high proinsulin to insulin ratio which is associated with NIDDM( 1
). Elevated intact proinsulin seems to indicate an advanced stage of β-cell
exhaustion and is a highly specific marker for insulin resistance. It might be
used as arbitrary marker for the therapeutic decision between secretagogue,
sensitizer, or insulin therapy in type 2 diabetes( 2 ). In DM2, insulin
processing deficient. There is an increased proinsulin:insulin ratio( 3 ).
Changes in proinsulin levels are associated with diabetes.
Random proinsulin levels and
the proinsulin-to-C-peptide ratio represent dynamic markers of the state of β-cell
function that complement immune markers in identifying relatives who are at
high risk of contracting type 1 diabetes( 4 ). Proinsulin is a very sensitive
marker of beta cell exhaustion and may therefore be useful for therapeutic
decision-making in type 2 diabetes ( 5 ). IDDM in humans and in non-obese
diabetic (NOD) mice is a T-cell–dependent autoimmune disease in which the β-cells
of the pancreatic islets are destroyed.
Several putative β-cell auto
antigens have been identified, but insulin and its precursor, proinsulin, are
the only ones that are β-cell specific.(6), his assay allows for a
pathophysiological staging of type 2 diabetes based on beta-cell secretion. It
could be confirmed by a large epidemiological study (IRIS-2, 4,265 patients)
that intact proinsulin is a highly specific marker for insulin resistance. It
could also be shown in other studies that successful resistance treatment with
insulin or glitazones led to a decrease in elevated proinsulin levels and,
thus, to a decrease of cardiovascular risk, while the levels remained high
during sulfonylurea therapy.
Therefore, patients with
increased fasting intact proinsulin values should be treated with a therapy
focusing on insulin resistance. Assessment of beta-cell function by
determination of intact proinsulin may facilitate the selection of the most
promising therapy and may also serve to monitor treatment success in the
further course of the disease.( 7).
[1.] Michelle, B. French (1997). Transgenic Expression of
Mouse Proinsulin II Prevents Diabetes in Nonobese Diabetic Mice, Diabetes
January vol. 46 no. 1 34-39,Retrieved from,
[2.] Mykkänen, L.(1997). The relation of proinsulin,
insulin, and proinsulin-to-insulin ratio to insulin sensitivity and acute
insulin response in normoglycemic subjects. Diabetes. Dec;46(12):1990-5.Retrieved
[3.] Pfützner, A.(2004). Fasting intact proinsulin is a
highly specific predictor of insulin resistance in type 2 diabetes.Diabetes
[4.] Pfützner, A.( 2004), Role of intact proinsulin in
diagnosis and treatment of type 2 diabetes mellitus, Diabetes Technol Ther.
Jun;6(3):405-12.Retrieved by http://www.ncbi.nlm.nih.gov/pubmed/15198846