title: Elevated intact proinsulin levels are indicative of Beta-cell dysfunction, insulin resistance, and cardiovascular risk: impact of the antidiabetic agent pioglitazone.
abstract: BACKGROUND
  Insulin resistance (IR) and deterioration of beta-cell secretion are main features in the development of type 2 diabetes, which is reflected in increasing serum intact proinsulin levels in later disease stage. Introduction of stable assays that are able to distinguish between intact proinsulin and its specific and unspecific cleavage products has resulted in the finding that serum intact proinsulin values can serve as a direct marker for beta-cell dysfunction, are a highly specific indicator of IR, and can predict cardiovascular risk.
  
  
  METHODS
  Determination of fasting intact proinsulin may be used to monitor and optimize antidiabetic therapeutic approaches. Our study group has been involved in a variety of clinical studies investigating drug effects on beta-cell secretory capacity, IR, and intact proinsulin levels. One focus was on the impact of insulin-sensitizing therapy with pioglitazone on the pancreatic beta-cell load.
  
  
  RESULTS
  Treatment with pioglitazone resulted in significant decreases in elevated proinsulin levels in type 2 diabetes patients. This effect was independent from glycemic control.
  
  
  CONCLUSIONS
  Measurement of fasting intact proinsulin values allows a staging of beta-cell dysfunction and evaluation of IR, thus providing an interesting diagnostic tool for both selection of appropriate therapy and monitoring of treatment success.
authors: IKFE, Institute for Clinical Research and Development, Mainz, Germany. andreasp@ikfe.de
authors: Andreas
authors: A
authors: Pfützner
authors: Thomas
authors: T
authors: Forst
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications*; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D018450:Disease Progression; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology*; D000077205:Pioglitazone; D011384:Proinsulin / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D011384:Proinsulin; D000077205:Pioglitazone