Phoenix VA Health Care System, 650 E. Indian School Road/CS111E, Phoenix, AZ, 85012-1892, USA.
Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA.
Cardiovasc Diabetol. 2021 Dec 8;20(1):232. doi: 10.1186/s12933-021-01418-z.
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.
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.
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.
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.
低 C 肽水平表明β细胞功能障碍，与日内血糖变化增加和低血糖有关。在 2 型糖尿病晚期，严重低血糖和血糖变化增加预测心血管（CVD）风险。本研究检查了 C 肽水平与 CVD 风险之间的关系，以及它是否可以通过随访血糖变异和严重低血糖来解释。
在 1565 名退伍军人事务部糖尿病试验参与者中评估了基线时的空腹 C 肽水平、复合 CVD 结局、严重低血糖以及随访时空腹血糖变异系数（CV）和平均真实变异性（ARV）。
C 肽与 CVD 风险之间存在 U 形关系，低水平（<0.50 nmol/l，HR 1.30 [95%CI 1.05-1.60]，p=0.02）和高水平（>1.23 nmol/l，1.27 [1.00-1.63]，p=0.05）下降与风险增加相关。C 肽水平与严重低血糖的风险呈负相关（OR 0.68 [0.60-0.77]）和随访时血糖变异（CV，标准化β估计值-0.12 [SE 0.01]；ARV，-0.10 [0.01]）（p<0.0001 所有）。低 C 肽水平与 CVD 风险的关联独立于心血管代谢危险因素（1.48 [1.17-1.87，p=0.001），并且当与严重低血糖和血糖 CV 一起在相同模型中进行测试时，与 CVD 仍然相关。
2 型糖尿病晚期低 C 肽水平与 CVD 风险增加相关。该关联独立于血糖变异或严重低血糖的增加。C 肽水平可能预测未来的血糖控制模式和 CVD 风险，并确定影响 2 型糖尿病晚期临床决策的表型。
