Dataset Information

The effect of intensive glucose lowering on lipoprotein particle profiles and inflammatory markers in the Veterans Affairs Diabetes Trial (VADT).

ABSTRACT:

Objective

Intensive glucose-lowering therapy (INT) did not reduce macrovascular events in the recent randomized trials, possibly because it did not improve or worsen other traditional or novel cardiovascular risk factors.

Research design and methods

Standard plasma lipids, cholesterol content of lipoprotein subfractions, and plasma inflammatory and prothrombotic markers were determined in a subgroup of the Veterans Affairs Diabetes Trial (VADT) participants (n = 266) at baseline and after 9 months of INT or standard therapy.

Results

INT lowered glycated hemoglobin (by a median of 2% vs. a median of 0.7% by standard treatment; P < 0.0001); increased BMI (4 vs. 1%; P < 0.001), total HDL (9 vs. 4%; P < 0.05), HDL2 (14 vs. 0%; P = 0.009), LDL2 (36 vs. 1%; P < 0.0001), and plasma adiponectin (130 vs. 80%; P < 0.01); and reduced triglycerides (-13 vs. -4%; P = 0.02) and small, dense LDL4 (-39 vs. -13%; P < 0.001), but had no effect on levels of plasma apolipoproteins B-100 and B-48, C-reactive protein, interleukin-6, lipoprotein-associated phospholipase A2, myeloperoxidase, fibrinogen, and plasminogen activator inhibitor 1. Incident macrovascular events were associated with baseline interleukin-6 (hazard ratio per each quartile increase 1.33 [95% CI 1.06-1.66]), total LDL (1.25 [1.01-1.55]), apolipoprotein B-100 (1.29 [1.01-1.65]), and fibrinogen (1.26 [1.01-1.57]) but not changes in any cardiovascular risk factors at 9 months.

Conclusions

INT was associated with improved adiponectin, lipid levels, and a favorable shift in LDL and HDL subfractions after 9 months. These data suggest that the failure of INT to lower cardiovascular outcomes occurred despite generally favorable changes in standard and novel risk factors early in the study.

SUBMITTER: Koska J

PROVIDER: S-EPMC3714508 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AIMS/HYPOTHESIS:We conducted an analysis of data collected during the Veterans Affairs Diabetes Trial (VADT) and the follow-up study (VADT-F) to determine whether intensive (INT) compared with standard (STD) glycaemic control during the VADT resulted in better long-term kidney outcomes. METHODS:VADT randomly assigned 1791 veterans from 20 Veterans Affairs (VA) medical centres who had type 2 diabetes mellitus and a mean HbA1c of 9.4 ± 2% (79.2 mmol/mol) at baseline to receive either INT or STD glucose control for a median of 5.6 years (randomisation December 2000 to May 2003; intervention ending in May 2008). After the trial, participants received routine care through their own physicians within the VA. This is an interim analysis of the VADT-F (June 2008 to December 2013). We collected data using VA and National databases and report renal outcomes based on serum creatinine, eGFR and urine albumin to creatinine ratio (ACR) in 1033 people who provided informed consent to participate in the VADT-F. RESULTS:By the end of the VADT-F, significantly more people who received INT treatment during the VADT maintained an eGFR >60 ml min-1 1.73 m-2 (OR 1.34 [95% CI 1.05, 1.71], p = 0.02). This benefit was most evident in those who were classified as at moderate risk (INT vs STD, RR 1.3, p = 0.03) or high risk (RR 2.3, p = 0.04) of chronic kidney disease on the Kidney Disease Improving Global Outcomes (KDIGO-CKD) at the beginning of VADT. At the end of VADT-F, significantly more people from the INT group improved to a low KDIGO risk category (RR 6.1, p = 0.002). During the VADT-F there were no significant differences between INT and STD for average HbA1c, blood pressure or lipid levels. CONCLUSIONS/INTERPRETATION:After just over 11 years of follow-up, there was a 34% greater odds of maintaining an eGFR of >60 ml min-1 1.73 m-2 and of improving the KDIGO category in individuals with type 2 diabetes who had received INT for a median of 5.6 years. VADT clinical trials.gov number: NCT 00032487.