PMID- 20307400
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  - Characterization of cardiovascular outcomes in a type 2 diabetes glucose supply 
      and insulin demand model.
PG  - 382-90
AB  - BACKGROUND: The nonsignificant reduction in macrovascular outcomes observed in 
      Action to Control Cardiovascular Risk in Diabetes; Action in Diabetes and 
      Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; 
      and the Veterans Affairs Diabetes Trial have collectively created uncertainty 
      with respect toward the proper extent of blood glucose reduction and also the 
      optimal therapeutic choice to attain the reduction. In the article entitled 
      "Glucose Supply and Insulin Demand Dynamics of Antidiabetic Agents" in this issue 
      of Journal of Diabetes Science and Technology, we presented data for a 
      pharmacokinetic/pharmacodynamic model that characterizes the effect of 
      conventional antidiabetic therapies on the glucose supply and insulin demand 
      dynamic. Here, it is our objective to test the hypothesis that, in conjunction 
      with hemoglobin A1c (HbA1c), patients managed on the glucose supply side of the 
      model would have fewer cardiovascular events versus those managed on the insulin 
      demand side. METHODS: To test this hypothesis, the electronic medical records of 
      a group model health maintenance organization were queried to compile a 
      population of patients meeting the following inclusion criteria: (1) type 2 
      diabetes mellitus (T2DM), (2) known date of T2DM diagnosis; (3) ICD-9 or CPT code 
      identification and chart review confirmation of a first major cardiovascular 
      event (myocardial infarction, coronary artery bypass graft, or angioplasty),(4) 
      five years of continuous eligibility, and (5) on antidiabetic therapy at the 
      beginning of the 5-year observation period. These patients were subsequently 
      matched (1:1) to T2DM patients meeting the same criteria who had not experienced 
      an event and were analyzed for differences in glucose control (HbA1C), the 
      glucose supply:insulin demand dynamic (SD ratio), and categorical combinations of 
      both parameters. RESULTS: Fifty cardiovascular event patients met inclusion 
      criteria and were matched to controls. No difference was observed for the average 
      HbA1c or SD ratio between patients experiencing an event and controls (7.5 +/- 
      1.0% versus 7.3 +/- 0.9%, p = .275, and 1.2 +/- 0.3 versus 1.3 +/- 0.3, p = .205, 
      respectively). Likewise, for categorical representations, there were no 
      differences in event rate at the pre-identified breakpoints (HbA1c >or=7% versus 
      <7%; 72% versus 64%, p = .391, and SD ratio >or=1 versus <1; 68% versus 76%, p = 
      .373, >or=1.25 versus <1.25; 42% versus 56%, p = .161, >or=1.5 versus <1.5; 22% 
      versus 30%, p = .362, respectively). Analyzing the combined effect of glucose 
      control and the SD dynamic, patients managed at higher glucose values and on the 
      insulin demand side of the model (HbA1c >or=7% and SD ratio <1.25) tended to have 
      greater cardiovascular risk than those managed at an HbA1c <7%, or HbA1c >or=7% 
      with an SD ratio >or=1.25 (61% versus 39%; p = .096). CONCLUSION: Independently, 
      more aggressive HbA1c reduction and higher SD ratio values were not independently 
      associated with a reduction in cardiovascular outcomes. Combining the parameters, 
      it would appear that patients managed at higher glucose values and on the insulin 
      demand side of the model may have increased cardiovascular risk. Based on these 
      findings, it is pertinent to conduct subsequent works to refine SD ratio 
      estimates and apply the model to larger, long-term T2DM cardiovascular outcome 
      trials. J Diabetes Sci Technol 2010;4(2):382-390.
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 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Lipoproteins, LDL)
SB  - IM
MH  - Administration, Oral
MH  - Aged
MH  - Blood Glucose/drug effects/*metabolism
MH  - Blood Pressure
MH  - Diabetes Mellitus, Type 2/blood/complications/*drug therapy
MH  - Diabetic Angiopathies/*epidemiology/etiology
MH  - Female
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/therapeutic use
MH  - Insulin/*therapeutic use
MH  - Intestinal Absorption
MH  - Lipoproteins, HDL/blood
MH  - Lipoproteins, LDL/blood
MH  - Male
MH  - Middle Aged
MH  - Models, Biological
MH  - Reference Values
MH  - Treatment Outcome
PMC - PMC2864175
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.4.2.0382 [pii]
AID - 10.1177/193229681000400220 [doi]
PST - epublish
SO  - J Diabetes Sci Technol. 2010 Mar 1;4(2):382-90. doi: 10.1177/193229681000400220.