Background: The proinsulin-to-C-peptide (PI:C) ratio is thought to be an index of pancreatic β-cell dysfunction, and in subjects with prediabetes and type 2 diabetes (T2DM), abnormally high PI:C ratios have been identified. In the present study, we investigated the relationships of the duration of diabetes and glucose variability in subjects with T2DM with the PI:C ratio.

Methods: We performed a prospective observational study of 272 Japanese outpatients with T2DM who underwent blinded professional continuous glucose monitoring (CGM) and fasting blood sample collection. Their fasting PI:C ratio and CGM-related indices were calculated. After placing all the participants into four groups on the basis of quartile (Q) of diabetes duration (Q1 <8 years, Q2 8-13 years, Q3 14-21 years, Q4 ≥22 years), the characteristics associated with PI:C ratio were identified. All of the statistical tests were two-sided and P<0.05 was considered to indicate statistical significance.

Results: The mean age of the cohort was 68.0 years, their mean HbA1c 7.1%, and their mean body mass index (BMI) 24.9 kg/m2. High PI:C ratio was associated with a short duration of diabetes (P<0.001). In each group, there was a positive correlation between PI:C ratio and the time above the target glucose range (TAR; >180 mg/dL) in Q1, Q2, and Q3. The closest correlation between PI:C ratio and TAR was found for Q1 but there was no significant correlation for Q4 (Q1: ρ=0.38, P=0.003; Q2: ρ=0.28, P=0.019; Q3: ρ=0.24, P=0.045; Q4: ρ=0.03, P=0.811).

Conclusions: We have shown that the PI:C ratio was positively associated with TAR in subjects with a short duration of T2DM. Given that insufficient pancreatic β-cell function and hyperglycemia is closely related, the PI:C ratio may play a role as the index of pancreatic β-cell dysfunction in subjects with a short duration of T2DM, but not in those with long-standing T2DM.

Disclosure

A.Miya: None. A.Nakamura: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim Japan, Inc., Daiichi Sankyo, Taisho Pharmaceutical Holdings Co., Ltd., Teijin Pharma Limited, Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation. H.Nomoto: Speaker's Bureau; Novo Nordisk, Sumitomo Pharma, Co., Ltd. H.Kameda: None. T.Atsumi: Speaker's Bureau; Eli Lilly Japan K.K., Kowa Company, Ltd.

Funding

Japan Society for the Promotion of Science (22K17766)

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