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.
|Original language||English (US)|
|State||Published - Dec 2021|
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Cardiology and Cardiovascular Medicine
FingerprintDive into the research topics of '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)'. Together they form a unique fingerprint.
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)
Koska, J. (Creator), Nuyujukian, D. S. (Creator), Bahn, G. D. (Creator), Zhou, J. J. (Creator) & Reaven, P. D. (Creator), figshare, 2021
DOI: 10.6084/m9.figshare.c.5743477.v1, https://springernature.figshare.com/collections/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_/5743477/1