AI(I)DA Acarbose and the Subclinical Inflammation
Condition: Type 2 Diabetes Mellitus; Subclinical Inflammation
MeSH terms: Diabetes Mellitus, Type 2; Inflammation
Study type: Interventional
Phase: Phase 3

Summary: 
      Acarbose an alphaglucosidase inhibitor changes in a complex way the transport, the digestion
      and the place of glucose release and absorption. As a result the intestinal milieu, the
      intestinal flora and the provision of enzymes in the lower small destine are changed. This
      should modify immune response of intestinal wall on food and its proinflammatory effects. The
      small intestine is the biggest immune organ of the organism. The postprandial glucose
      increase could have a direct effect on low-grade inflammation. Toxic effects (glucotoxicity),
      activation of the immune system and low grad inflammation could be reasons of developing
      endothelial dysfunction and affect plaque stability. The activity of the lymphocyte immune
      system in the intestine would be a further component, by which acarbose could take influence
      on diabetogenesis and atherogenesis. The question of an enterovasal axis is one of the new
      research concepts. As indicators of this axis considered: leucocytes, high sensitive
      C-reactive protein, plasminogen activator inhibitor antigen and lymphocytes sub-populations.
      The effect of acarbose on these parameters in the postprandial phase are not known yet.
    

Detailed description: 
      Acarbose, an alpha-glucosidase-inhibitor, delays the release of glucose out of complex
      carbohydrates in the upper small intestine. The digestion of carbohydrates after acarbose
      intake therefore mainly takes place in the lower small intestine and colon. Through this
      innovative mode of action the postprandial hyperglycemia is specifically delayed and
      flattened. Acarbose is used for more of 15 years for the therapy of type 2 diabetes.
      Efficiency and safety in treating diabetes were proved in extensive studies. Until today no
      serious side effects under acarbose were reported, the reduction of HbA1c is 0.7-1 %. Three
      large prospective studies and metaanalysis resp., could prove that acarbose has a highly
      significant positive effect on the incidence and progression of cardiovascular disease in
      people with prediabetes and type 2 diabetes resp. In the STOP-NIDDM-trail in persons with
      prediabetes as well as in the meta-analysis in type 2 diabetes (MERIA) the event rate in the
      acarbose group was ~ 50 % lower. In a substudy of the STOP-NIDDM intervention study a ca. 50
      % lower progression of the intima-media-thickness of the A. carotis communis was documented
      under acarbose in comparison with placebo. In multivariate analysis acarbose was always the
      most important independent determinant of vasoprotective effects. Epidemiological
      investigations, even as controlled prospective studies, cannot establish causal
      relationships. Thus the question rises wether acarbose has - besides the known therapeutic
      effect on postprandial hyperglycemia pleiotropic effects, which lead to the documented
      preventive effects on cardiovascular complications. This would be of principal importance for
      the use of acarbose in patients with prediabetes / type 2 diabetes and increased vascular
      risk. So far acarbose is the only cardiovascular oral antidiabetic drug in people with IGT.

      Working hypothesis:

      Acarbose changes in a complex way the transport, the digestion and the place of glucose
      release and absorption. As a result the intestinal milieu, the intestinal flora and the
      provision of enzymes in the lower small intestine are changed. This should modify immune
      response of intestinal wall on food and its proinflammatory effects. The small intestine is
      the biggest immune organ of the organism. The postprandial glucose increase could have a
      direct effect on low-grade inflammation. Toxic effects (glucotoxicity), activation of the
      immune system and low-grade inflammation could be reasons of developing endothelial
      dysfunction and affect plaque stability. The activity of the lymphocyte immune system in the
      intestine would be a further component, by which acarbose could take influence on
      diabetogenesis and atherogenesis. The question after an enterovasal axis is now one of the
      most fascinating new research concepts and basis of incretin-related drug treatment of
      diabetes resp. As intravasal indicator for low-grade inflammation are considered: leucocytes,
      high sensitive C-reactive protein (hsCRP) and plasminogen activator inhibitor active antigen
      (PAI1) as well as lymphocytes subpopulations. The effects of acarbose on these parameters in
      the postprandial phase are not known yet.
    

Intervention name(s): acarbose
Intervention type(s): Drug
Intervention description(s): oral application
Intervention MeSH terms: Acarbose
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment