Incretins in Impaired Fasting Glucose
Condition: Pre-diabetes
MeSH terms: Prediabetic State
Study type: Interventional
Phase: Phase 4

Summary: 
      People with high fasting glucose can develop type 2 diabetes with the passage of time. This
      study is being done to determine the effect of a novel medication in people with this
      elevated fasting glucose. Sitagliptin is a substance that raises levels of a hormone normally
      found in the blood. This hormone, called glucagon-like peptide-1 (GLP-1), is normally
      released by the intestine in response to the presence of food. This hormone acts like a
      messenger between the intestine and the pancreas to raise insulin levels, and therefore,
      lower blood sugars. Sitagliptin is effective in people with diabetes, however, this study is
      being done to determine if Sitagliptin is effective in people with high fasting glucose who
      do not yet have diabetes.
    

Detailed description: 
      Impaired fasting glucose (IFG) confers a high risk of progression to diabetes. Its
      pathogenesis has been an area of active investigation, with defects in insulin and glucagon
      secretion as well as insulin action likely to play a role. Several studies have suggested
      that the prediabetic and diabetic state are associated with alterations in circulating
      incretin concentrations. More recently, a large study of non-diabetic individuals
      demonstrated decreased GLP-1 concentrations after a glucose challenge in individuals with
      prediabetes but concluded that defects in GLP-1 secretion were unrelated to insulin
      secretion. In impaired glucose tolerance (IGT), defects in incretin-induced insulin secretion
      coexist with defects in glucose induced insulin secretion.

      Worsening degrees of glucose tolerance are associated with decreased insulin secretion for
      the prevailing insulin action. Moreover early glucagon suppression is impaired in IGT. Since
      GLP-1 is an insulin secretagogue and suppresses glucagon, it is conceivable that defects in
      GLP-1 secretion could contribute to the pathogenesis of pre-diabetes. Inhibition of
      Dipeptidyl Peptidase-4 (DPP-4), an enzyme which rapidly degrades the incretin hormones, has
      been shown to be a useful therapeutic strategy in type 2 diabetes. DPP-4 inhibitors increase
      (model-calculated) insulin secretion and decrease glucagon concentrations resulting in a
      lowering of fasting (and postprandial) glucose concentrations in people with type 2 diabetes.
      Their effects in people with IFG are less certain. However, DPP-4 inhibitors provide an
      opportunity to directly examine the contribution of abnormal incretin concentrations to the
      pathogenesis of IFG, by raising concentrations of endogenous incretin hormones.

      The current experiments tested this hypothesis by measuring insulin secretion and action and
      fasting and postprandial glucose turnover before and after 8 weeks of therapy with a DPP-4
      inhibitor.
    

Intervention name(s): Sitagliptin; Placebo
Intervention type(s): Drug; Other
Intervention description(s): 100 mg once daily; once daily for duration of the study
Other intervention name(s): Januvia
Intervention MeSH terms: Sitagliptin Phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment