Dataset Information

Association of low fasting C-peptide levels with cardiovascular risk, visit-to-visit glucose variation and severe hypoglycemia in the Veterans Affairs Diabetes Trial (VADT).

ABSTRACT:

Aims

Low C-peptide levels, indicating beta-cell dysfunction, are associated with increased within-day glucose variation and hypoglycemia. In advanced type 2 diabetes, severe hypoglycemia and increased glucose variation predict cardiovascular (CVD) risk. The present study examined the association between C-peptide levels and CVD risk and whether it can be explained by visit-to-visit glucose variation and severe hypoglycemia.

Materials and methods

Fasting C-peptide levels at baseline, composite CVD outcome, severe hypoglycemia, and visit-to-visit fasting glucose coefficient of variation (CV) and average real variability (ARV) were assessed in 1565 Veterans Affairs Diabetes Trial participants.

Results

There was a U-shaped relationship between C-peptide and CVD risk with increased risk with declining levels in the low range (< 0.50 nmol/l, HR 1.30 [95%CI 1.05-1.60], p = 0.02) and with rising levels in the high range (> 1.23 nmol/l, 1.27 [1.00-1.63], p = 0.05). C-peptide levels were inversely associated with the risk of severe hypoglycemia (OR 0.68 [0.60-0.77]) and visit-to-visit glucose variation (CV, standardized beta-estimate - 0.12 [SE 0.01]; ARV, - 0.10 [0.01]) (p < 0.0001 all). The association of low C-peptide levels with CVD risk was independent of cardiometabolic risk factors (1.48 [1.17-1.87, p = 0.001) and remained associated with CVD when tested in the same model with severe hypoglycemia and glucose CV.

Conclusions

Low C-peptide levels were associated with increased CVD risk in advanced type 2 diabetes. The association was independent of increases in glucose variation or severe hypoglycemia. C-peptide levels may predict future glucose control patterns and CVD risk, and identify phenotypes influencing clinical decision making in advanced type 2 diabetes.

SUBMITTER: Koska J

PROVIDER: S-EPMC8656002 | 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.