PMID- 20307399
OWN - NLM
STAT- MEDLINE
DCOM- 20100810
LR  - 20221207
IS  - 1932-2968 (Electronic)
IS  - 1932-2968 (Linking)
VI  - 4
IP  - 2
DP  - 2010 Mar 1
TI  - Glucose supply and insulin demand dynamics of antidiabetic agents.
PG  - 365-81
AB  - BACKGROUND: For microvascular outcomes, there is compelling historical and 
      contemporary evidence for intensive blood glucose reduction in patients with 
      either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). There 
      is also strong evidence to support macrovascular benefit with intensive blood 
      glucose reduction in T1DM. Similar evidence remains elusive for T2DM. Because 
      cardiovascular outcome trials utilizing conventional algorithms to attain 
      intensive blood glucose reduction have not demonstrated superiority to less 
      aggressive blood glucose reduction (Action to Control Cardiovascular Risk in 
      Diabetes; Action in Diabetes and Vascular Disease: Preterax and Diamicron 
      Modified Release Controlled Evaluation; and Veterans Affairs Diabetes Trial), it 
      should be considered that the means by which the blood glucose is reduced may be 
      as important as the actual blood glucose. METHODS: By identifying quantitative 
      differences between antidiabetic agents on carbohydrate exposure (CE), hepatic 
      glucose uptake (HGU), hepatic gluconeogenesis (GNG), insulin resistance (IR), 
      peripheral glucose uptake (PGU), and peripheral insulin exposure (PIE), we 
      created a pharmacokinetic/pharmacodynamic model to characterize the effect of the 
      agents on the glucose supply and insulin demand dynamic. Glucose supply was 
      defined as the cumulative percentage decrease in CE, increase in HGU, decrease in 
      GNG, and decrease in IR, while insulin demand was defined as the cumulative 
      percentage increase in PIE and PGU. With the glucose supply and insulin demand 
      effects of each antidiabetic agent summated, the glucose supply (numerator) was 
      divided by the insulin demand (denominator) to create a value representative of 
      the glucose supply and insulin demand dynamic (SD ratio). RESULTS: 
      Alpha-glucosidase inhibitors (1.25), metformin (2.20), and thiazolidinediones 
      (TZDs; 1.25-1.32) demonstrate a greater effect on glucose supply (SD ratio >1), 
      while secretagogues (0.69-0.81), basal insulins (0.77-0.79), and bolus insulins 
      (0.62-0.67) demonstrate a greater effect on insulin demand (SD ratio <1). 
      CONCLUSION: Alpha-glucosidase inhibitors, metformin, and TZDs demonstrate a 
      greater effect on glucose supply, while secretagogues, basal insulin, and bolus 
      insulin demonstrate a greater effect on insulin demand. Because T2DM 
      cardiovascular outcome trials have not demonstrated macrovascular benefit with 
      more aggressive blood glucose reduction when using conventional algorithms that 
      predominantly focus on insulin demand, it would appear logical to consider a 
      model that incorporates both the extent of blood glucose lowering (hemoglobin 
      A1c) and the means by which the blood glucose was reduced (SD ratio) when 
      considering macrovascular outcomes.
CI  - (c) 2010 Diabetes Technology Society.
FAU - Monte, Scott V
AU  - Monte SV
AD  - CPL Associates, LLC, Amherst, New York 14226, USA. smonte@cplassociates.com
FAU - Schentag, Jerome J
AU  - Schentag JJ
FAU - Adelman, Martin H
AU  - Adelman MH
FAU - Paladino, Joseph A
AU  - Paladino JA
LA  - eng
PT  - Journal Article
DEP - 20100301
PL  - United States
TA  - J Diabetes Sci Technol
JT  - Journal of diabetes science and technology
JID - 101306166
RN  - 0 (Dietary Carbohydrates)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Thiazolidinediones)
RN  - 0V5436JAQW (miglitol)
RN  - 19130-96-2 (1-Deoxynojirimycin)
RN  - 9100L32L2N (Metformin)
RN  - IY9XDZ35W2 (Glucose)
RN  - T58MSI464G (Acarbose)
SB  - IM
MH  - 1-Deoxynojirimycin/analogs & derivatives/therapeutic use
MH  - Acarbose/therapeutic use
MH  - Cardiovascular Diseases/epidemiology/mortality/prevention & control
MH  - Diabetes Complications/epidemiology/mortality/prevention & control
MH  - Diabetes Mellitus, Type 1/blood/*drug therapy
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Diabetic Angiopathies/epidemiology/prevention & control
MH  - Dietary Carbohydrates
MH  - Energy Intake/drug effects
MH  - Follow-Up Studies
MH  - Gluconeogenesis/drug effects/physiology
MH  - Glucose/*metabolism
MH  - Glycated Hemoglobin/drug effects/metabolism
MH  - Heart Diseases/epidemiology/prevention & control
MH  - Homeostasis
MH  - Humans
MH  - Hypoglycemic Agents/pharmacokinetics/*therapeutic use
MH  - Insulin/pharmacokinetics/*therapeutic use
MH  - Intestinal Absorption/drug effects
MH  - Liver/drug effects/metabolism
MH  - Metformin/therapeutic use
MH  - Myocardial Infarction/epidemiology/prevention & control
MH  - Thiazolidinediones/therapeutic use
PMC - PMC2864174
EDAT- 2010/03/24 06:00
MHDA- 2010/08/11 06:00
PMCR- 2011/03/01
CRDT- 2010/03/24 06:00
PHST- 2010/03/24 06:00 [entrez]
PHST- 2010/03/24 06:00 [pubmed]
PHST- 2010/08/11 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - dst.4.2.0365 [pii]
AID - 10.1177/193229681000400219 [doi]
PST - epublish
SO  - J Diabetes Sci Technol. 2010 Mar 1;4(2):365-81. doi: 10.1177/193229681000400219.