Abstract
Objective
To explore the relationship between C-peptide secretion and time in range (TIR) in adult patients with type 1 diabetes.
Methods
From December 2018 to December 2020, 76 type 1 diabetes participants were enrolled from the Department of Endocrinology and Metabolism of Peking University People’s Hospital. All participants wore intermittently scanned continuous glucose monitoring (isCGM), and insulin dosage was adjusted according to standardized clinical procedures. Subjects were divided into low C-peptide group (<10 pmol/L) and preserved C-peptide group (10–200 pmol/L) based on fasting serum C-peptide levels. Differences of TIR, metrics related to glucose variability and hypoglycemic events were compared.
Results
A total of 94,846 isCGM values obtained from 39 male and 37 female participants were analyzed. Individuals with preserved C-peptide secretion had shorter diabetes duration (2.0 (0.5, 10.0) vs 10.0 (3.0, 18.3) years, P = 0.002). TIR was higher in the individuals with preserved C-peptide than those with decreased C-peptide (67.1% (54.2, 75.8) vs 45.5% (33.9, 56.1), P < 0.001), and time above range was significantly lower in those with preserved C-peptide (28.0% (15.6, 42.4) vs 49.4% (39.1, 64.2), P < 0.001). Preserved C-peptide was associated with lower glucose variability, as defined by s.d. (3.0 mmol/L (2.6, 3.4) vs 3.8 mmol/L (3.2, 4.3), P < 0.001) and interquartile range (4.3 mmol/L (3.1, 4.8) vs 5.3 mmol/L (4.5, 6.3), P < 0.001). Metrics related to hypoglycemia were not different between the two groups.
Conclusion
Preserved C-peptide secretion was associated with higher TIR and lower glucose variability in Chinese type 1 diabetes adults.
Introduction
Measurement of serum C-peptide is important in clinical practice since differences in intrinsic insulin secretion are fundamental to diabetes classification and treatment strategy (1). In clinically diagnosed type 1 diabetes, serum C-peptide testing could help to identify monogenetic diabetes and type 2 diabetes (2), which required treatment different from type 1 diabetes.
Even in confirmed type 1 diabetes, C-peptide measurement still had clinical significance. Preserved C-peptide secretion is more common in those diagnosed in adulthood and with shorter diabetes duration. A previous study suggested that C-peptide was detectable in 36% of patients diagnosed with type 1 diabetes for less than 10 years, while the proportion decreased to 22% in those after 20 years of diagnosis (3). Another study revealed that the level of C-peptide secretion decreased rapidly in the first 7 years after diagnosis (4). Although it was believed that type 1 diabetes was caused by absolute insulin deficiency, recent studies on long-duration type 1 diabetes showed that even in those with type 1 diabetes for more than 50 years, a large proportion of them still had detectable serum C-peptide (5, 6, 7). The Diabetes Control and Complications Trial showed that intensive treatment was associated with better preservation of C-peptide secretion (8). Moreover, higher C-peptide level was further related to lower severe hypoglycemia incidence (9), better glycosylated hemoglobin (HbA1c) control and lower insulin requirement in the intensive therapy group (10). Meanwhile, some observational studies suggested that higher serum C-peptide level was associated with lower incidence of self-reported symptomatic, asymptomatic and severe hypoglycemia (11, 12, 13). Kuhtreiber et al. showed that serum C-peptide level > 10 pmol/L was independently associated with lower risk of diabetic complications (11). In children with newly diagnosed type 1 diabetes wearing continuous glucose monitoring (CGM), preserved C-peptide secretion function was related to increased time in range (TIR) (14). And in individuals with type 2 diabetes, higher random serum C-peptide level was associated with shorter duration of hypoglycemia events and less glucose variability (12).
Recently, some studies have focused on the clinical significance of residual C-peptide reflected by CGM recorded metrics relating to glucose control and glucose variability. Gibb et al. showed that in adult type 1 diabetes patients, preserved C-peptide secretion was associated with less hypoglycemia events and lower glucose variability, but not with TIR (15). In another study, Michael et al. suggested that high level of residual C-peptide was associated with lower mean glucose and better TIR, but not with hypoglycemia or glucose variability (16). In a smaller study in Japanese type 1 diabetes patients, stable glycemic control with minimal hypoglycemia was related to preserved C-peptide secretion (17). It is important to notice that in most of the above studies, CGM was worn under free-living conditions. And not enough information about socioeconomic factors, diabetes self-management ability or other indicators related to blood glucose control was collected; thus, the impact of these factors on blood glucose control could not be excluded.
The incidence of type 1 diabetes in China is significantly lower than that in the Caucasian population, and there is no study focusing on the relationship between preserved C-peptide level and glucose recorded by CGM in China. In this study, Chinese type 1 diabetes participants were enrolled to explore the association between preserved C-peptide secretion and CGM recorded glucose metrics including glucose control, hypoglycemia and glucose variability. To better control underlying confounders, standard medical nutrition management and insulin dosage adjustment were conducted.
Methods
Participants
All participants were hospitalized type 1 diabetes patients recruited from the Department of Endocrinology and Metabolism of Peking University People’s Hospital from December 2018 to December 2020. The diagnosis of type 1 diabetes was confirmed according to the following criteria: diabetic ketoacidosis at onset; relying on insulin therapy; at least one positive diabetes autoantibody (anti-glutamic acid decarboxylase autoantibody, islet cell antibodies and insulin antibody). Meanwhile, in order to confirm the diagnosis of type 1 diabetes, for the participants with less than 1 year of duration, only those with serum C-peptide level less than 10 pmol/L were included. Inclusion criteria were: (i) age ≥ 18 years; (ii) no contraindication of wearing intermittently scanned CGM (isCGM) and (iii) isCGM was worn for 10–14 days, and the proportion of glucose data captured ≥75%. Exclusion criteria included: (i) fasting C peptide > 200 pmol/L; (ii) receiving glucocorticoid treatment; (iii) pregnancy or lactation and (iv) history of severe cardiovascular diseases, cerebrovascular diseases, severe liver diseases or kidney diseases. All the participants were CGM naïve and they were not blinded to CGM readings. Since they were inpatients and insulin dosage was adjusted according to standardized protocol (Supplementary Table 1, see section on supplementary materials given at the end of this article) by endocrinologists, their subjective behaviors on glucose control were minimized.
Food intake was managed by nutritionists based on the patient’s age, sex, BMI and physical activity. Insulin dosage was adjusted according to the standardized strategy by two endocrinologists during hospitalization (Supplementary Table 1) based on isCGM (Freestyle Libre H, Abbott, Witney, UK) readings. A total of 76 type 1 diabetic participants were continuously recruited. The study was approved by the Ethics Committee of Peking University People’s Hospital. Informed consent was acquired from all participants.
Data collection
The clinical information including age, gender, weight, height, blood pressure, age of onset and disease duration was collected. HbA1c was measured (Primus Ultra 2, Trinity Biotech, Bray, Co-Wicklow, Ireland), along with lipid profile, fasting glucose, fasting insulin and fasting C peptide (Hitachi Automatic Biochemical Analyzer, 7600-120, Hitachi).
Statistical analysis
Subjects were divided into low C-peptide group (<10 pmol/L) and preserved C-peptide group (10–50 pmol/L) based on fasting serum C-peptide levels. Additionally, patients with fasting C-peptide level between 10 and 50 pmol/L were recognized as less preserved C-peptide group. The primary comparison of the study was the difference in glucose data recorded by isCGM between low C-peptide group and preserved C-peptide group. And differences between low C-peptide group and less preserved C-peptide group were also compared. Glucose metrics included mean glucose, s.d., coefficient of variation (CV), mean times of hypoglycemia per day, time below range (TBR, <3.9 mmol/L), TIR (3.9–10.0 mmol/L), time above range (TAR, >10.0 mmol/L), mean duration of hypoglycemia and interquartile range (IQR) were calculated in all participants.
Qualitative data were described by percentage and frequency, and non-normal distribution of data was presented as median and IQR. χ2 or Mann–Whitney U test was used for intergroup comparison. Spearman analysis was used for correlation analysis. Analyses were conducted with SPSS version 23.0. All P values were double-sided. P < 0 .05 was considered significant for the analysis.
Results
A total of 76 participants, including 39 males, with an average age of 47 ± 19 years and an average diabetes duration of 9 ± 4.7 years were included. C-peptide level was negatively correlated with diabetes duration (r = −0.293, P < 0.010). The clinical characteristics of participants in low C-peptide group (<10 pmol/L), preserved C-peptide group (10–200 pmol/L) and less preserved C-peptide group (10–50 pmol/L) are shown in Table 1. The median C-peptide levels in the three groups were 0.3, 21.1 and 19.7 pmol/L, respectively.
Demographic and clinical characteristics of the participants.
| Low C-peptide <10 pmol/L (N = 48) | Preserved C-peptide 10–200 pmol/L (N = 30) | P valuea | Less preserved C-peptide 10–50 pmol/L (N = 26) | P valueb | |
|---|---|---|---|---|---|
| Age, years | 54 (31, 66) | 42 (24, 61) | 0.082 | 43 (28, 61) | 0.178 |
| Male sex, n (%) | 23 (47.9) | 16 (53.3) | 0.816 | 15 (57.7) | 0.472 |
| Age at diagnosis, years | 38 (26, 51) | 38 (21, 52) | 0.857 | 40 (27, 52) | 0.703 |
| Duration of type 1 diabetes, years | 10.0 (3.0, 18.3) | 2.0 (0.5, 10.0) | 0.002 | 3.0 (0.6, 10.3) | 0.008 |
| Body mass index, kg/m2 | 23.8 (21.3, 25.9) | 22.4 (20.0, 24.6) | 0.127 | 22.6 (20.8, 24.6) | 0.206 |
| Glycated hemoglobin, % | 8.1 (7.8, 9.7) | 10.1 (8.6, 11.0) | 0.027 | 10.0 (8.5, 10.9) | 0.030 |
| SBP, mmHg | 126 (114, 143) | 122 (113, 140) | 0.594 | 121 (113, 136) | 0.461 |
| DBP, mmHg | 72 (62, 78) | 71 (65, 79) | 0.814 | 71 (65, 79) | 0.791 |
| HDL-C, mmol/L | 1.31 (1.16, 1.70) | 1.13 (1.00, 1.32) | 0.022 | 1.13 (1.00, 1.31) | 0.016 |
| TG, mmol/L | 0.88 (0.62, 1.19) | 0.95 (0.63, 1.09) | 0.984 | 1.00 (0.63, 1.09) | 0.988 |
| LDL-C, mmol/L | 2.39 (1.94, 2.93) | 2.26 (1.92, 2.69) | 0.606 | 2.34 (2.04, 2.86) | 0.963 |
| FPG, mmol/L | 10.5 (7.0, 15.3) | 7.91 (6.00, 10.02) | 0.006 | 8.34 (5.87, 10.02) | 0.011 |
| Usage of insulin pump, n (%) | 7 (14.9) | 1 (3.3) | 0.140 | 1 (3.8) | 0.245 |
| Diabetic retinopathy, n (%) | 12 (25.5) | 2 (6.7) | 0.066 | 2 (7.7) | 0.118 |
| Diabetic nephropathy, n (%) | 5 (10.6) | 2 (6.9) | 0.702 | 1 (4.0) | 0.658 |
| Daily insulin dosage, U/kg/d | 0.50 (0.39, 0.71) | 0.51 (0.36, 0.79) | 0.903 | 0.52 (0.39, 0.79) | 0.961 |
Data are median (IQR) or n (%).
a Intergroup comparison between low C-peptide group and preserved C-peptide group; b Intergroup comparison between low C-peptide group and less preserved C-peptide group.
DBP, diastolic blood pressure; FPG, fasting plasma glucose; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure; TG, triglycerides.
TIR, which reflected blood glucose control, was higher in those with preserved C-peptide than those with low C-peptide (67.1% (54.2, 75.8) vs 45.5% (33.9, 56.1), P < 0.001). Correspondingly, mean glucose (8.6 mmol/L (6.9, 9.7) vs 10.1 mmol/L (9.3, 11.8), P < 0.001) and TAR (28.0% (15.6, 42.4) vs 49.4% (39.1, 64.2), P < 0.001) were lower in the preserved C-peptide group (Fig. 1 and Table 2).
Differences of isCGM metrics between low C-peptide (fasting serum C-peptide < 10 pmol/L) and preserved C-peptide (fasting serum C-peptide 10–200 pmol/L): (A) mean glucose; (B) s.d.; (C) interquartile range (IQR); (D) time in range (TIR, 3.9–10.0 mmol/L); (E) time above range (TAR, >10.0 mmol/L).
Citation: Endocrine Connections 11, 11; 10.1530/EC-22-0244
isCGM metrics in low C-peptide, preserved C-peptide and less preserved C-peptide groups.
| Low C-peptide <10 pmol/L (N = 48) | Preserved C-peptide 10–200 pmol/L (N = 30) | P valuea | Less preserved C-peptide 10–50 pmol/L (N = 26) | P value b | |
|---|---|---|---|---|---|
| Mean glucose, mmol/L | 10.1 (9.3, 11.8) | 8.6 (6.9, 9.7) | <0.001 | 8.6 (7.2, 9.7) | <0.001 |
| s.d., mmol/L | 3.8 (3.2, 4.3) | 3.0 (2.6, 3.4) | <0.001 | 3.0 (2.7, 3.3) | <0.001 |
| CV, % | 36.3 (34.3, 39.8) | 34.3 (30.9, 38.1) | 0.062 | 34.7 (30.9, 38.5) | 0.140 |
| Daily hypoglycemic events, n | 0.5 (0.3, 0.8) | 0.5 (0.4, 0.8) | 0.436 | 0.6 (0.4, 0.8) | 0.501 |
| TBR, % | 3.2 (1.4, 4.7) | 2.5 (1.5, 3.9) | 0.868 | 2.7 (1.5, 3.9) | <0.001 |
| TIR, % | 45.5 (33.9, 56.1) | 67.1 (54.2, 75.8) | <0.001 | 67.8 (57.7, 75.8) | <0.001 |
| TAR, % | 49.4 (39.1, 64.2) | 28.0 (15.6, 42.4) | <0.001 | 28.0 (18.8, 40.4) | <0.001 |
| Duration of hypoglycemic events, min | 52 (30, 74) | 46 (27, 62) | 0.904 | 45 (24, 60) | 0.569 |
| IQR, mmol/L | 5.3 (4.5, 6.3) | 4.3 (3.1, 4.8) | <0.001 | 4.3 (3.3, 4.6) | <0.001 |
Data are median (IQR) or n (%).
aIntergroup comparison between low C-peptide group and preserved C-peptide group; bIntergroup comparison between low C-peptide group and less preserved C-peptide group.
CV, coefficient of variation; isCGM, intermittently scanned continuous glucose monitoring; IQR, interquartile range; TAR, time above range (>10.0 mmol/L); TBR, time below range (<3.9 mmol/L); TIR, time in range (3.9–10.0 mmol/L).
Metrics related to glucose variability, s.d. (3.0 mmol/L (2.6, 3.4) vs 3.8 mmol/L (3.2, 4.3), P < 0.001) and IQR (4.3 mmol/L (3.1, 4.8) vs 5.3 mmol/L (4.5, 6.3), P < 0.001) in the preserved C-peptide group were lower than those in the decreased C-peptide group. s.d. (3.0 mmol/L (2.6, 3.4) vs 3.0 mmol/L (2.7, 3.3), P < 0.001) and IQR (4.3 mmol/L (3.1, 4.8) vs 4.3 mmol/L (3.3, 4.6), P < 0.001) were also lower in less preserved C-peptide group than in low C-peptide group.
Hypoglycemia events per day, TBR and duration of hypoglycemia among all three groups were not significantly different between groups (Fig. 1 and Table 2).
Discussion
The present study was performed to investigate the association between residual C-peptide secretion and glucose profile in Chinese type 1 diabetes. Our study suggested that under well-controlled carbohydrate intake and standard insulin adjustment procedure, preserved C-peptide level was still associated with better TIR and lower glucose variability.
Similar to our findings, Buckingham et al. found that higher serum C-peptide level was associated with higher TIR and less blood glucose fluctuation recorded by CGM in children and adolescents with type 1 diabetes less than 2 years, but not with hypoglycemia (14). In another study conducted on adult type 1 diabetes participants, Gibb et al. found that preserved C-peptide was associated with shorter hypoglycemia period and lower glucose variability, but not with TIR (15). In this study, individuals with preserved C-peptide were defined by detectable random serum C-peptide level. Although some studies have suggested a close relationship between random C-peptides, fasting C-peptides and mixed meal-stimulated C-peptide (18), differences in the definition of ‘preserved C-peptide secretion’ may contribute to the inconsistent results among studies. Michael et al. used mixed meal-stimulated C-peptide to classify type 1 diabetes participants as negative, low, intermittent and high C-peptide groups, and they demonstrated that higher stimulated C-peptide level likely contributed to better TIR and lower incidence of hypoglycemia (16). In newly diagnosed adult type 1 diabetes, Alice et al. showed that stimulated C-peptide level was related to better TIR and less hyperglycemia, but not to hypoglycemia. Meanwhile, with every 100 pmol/L increase in C-peptide after stimulation, TIR increased 2.4% (19).
The importance and originality of this study is that the insulin dosage adjustment for all participants was based on standardized insulin adjustment strategy, which could eliminate other external factors related to glucose control but focus on the impact of intrinsic pathophysiological features. The results of the study indicate that even under standard medical conditions, the positive role of preserved C-peptide level in glucose control was still important. This further highlighted the importance of monitoring the change of C-peptide level in type 1 diabetes, and an emerging trend in C-peptide protection treatment of type 1 diabetes is also of great clinical importance.
Due to absolute insulin deficiency, type 1 diabetes is marked by obvious glucose variability. CGM metrics reflecting glucose variability including s.d., IQR and CV were adopted in the study. Among them, s.d. and IQR were lower in preserved C-peptide group. A previous study suggested that preserved C-peptide secretion is associated with less blood glucose variability (1) and is associated with microvascular complications (20). Some studies showed that glucose variability is an important risk factor for hypoglycemia and chronic complications (21). Therefore, setting individualized glucose management goals based on intrinsic insulin production should be considered in clinical practice. Meanwhile, clinical interventions aiming to preserve β-cell function may also be an important direction for future research.
Our study showed that HbA1c in preserved C-peptide group was higher than that in the low C-peptide group. The underlying reason was that diabetes duration was obviously shorter in the preserved C-peptide group, and other factors like lack of diabetes management skills might contribute to higher HbA1c level in the preserved C-peptide group.
This study had certain limitations. First, it was conducted in a single center and bias might exist. At the same time, the relatively small sample size made it difficult to elucidate the relationship between the C-peptide levels and diabetes complications. Moreover, continuously following the changes of the CGM metrics in different C-peptide groups may reveal more information about the clinical significance of residual β-cell function.
In summary, our study confirmed the association between preserved C-peptide secretion and better TIR and less glucose variation in adult type 1 diabetes patients in China. This finding suggested that routine measurement of serum C-peptide level in type 1 diabetes could reflect the risk of high glucose variability and may further assist the development of personalized glucose management goals. Since preserving a small amount of β cell function likely confers clinical benefits compared with absolute loss, future treatment strategies aiming to protect intrinsic insulin production in newly diagnosed type 1 diabetes will be of great clinical importance.
Supplementary materials
This is linked to the online version of the paper at https://doi.org/10.1530/EC-22-0244.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding
This work was supported by Peking University People’s Hospital Scientific Research Development Funds (RDY2019-05); Peking University Medical Research Fund (2158000040); National Natural Science Foundation of China (81700722, 61973030).
Acknowledgements
We thank the doctors, nurses and technicians for their practical during the study at Department of Endocrinology and Metabolism in Peking University People’s Hospital.
References
- 1↑
Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabetic Medicine 2013 30 803–817. (https://doi.org/10.1111/dme.12159)
- 2↑
Shields BM, Shepherd M, Hudson M, McDonald TJ, Colclough K, Peters J, Knight B, Hyde C, Ellard S & Pearson ER et al.Population-based assessment of a biomarker-based screening pathway to aid diagnosis of monogenic diabetes in young-onset patients. Diabetes Care 2017 40 1017–1025. (https://doi.org/10.2337/dc17-0224)
- 3↑
Davis AK, DuBose SN, Haller MJ, Miller KM, DiMeglio LA, Bethin KE, Goland RS, Greenberg EM, Liljenquist DR & Ahmann AJ et al.Prevalence of detectable C-peptide according to age at diagnosis and duration of type 1 diabetes. Diabetes Care 2015 38 476–481. (https://doi.org/10.2337/dc14-1952)
- 4↑
Shields BM, McDonald TJ, Oram R, Hill A, Hudson M, Leete P, Pearson ER, Richardson SJ, Morgan NG & Hattersley AT et al.C-peptide decline in type 1 diabetes has two phases: an initial exponential fall and a subsequent stable phase. Diabetes Care 2018 41 1486–1492. (https://doi.org/10.2337/dc18-0465)
- 5↑
Keenan HA, Sun JK, Levine J, Doria A, Aiello LP, Eisenbarth G, Bonner-Weir S, King GL. Residual insulin production and pancreatic β-cell turnover after 50 years of diabetes: Joslin Medalist study. Diabetes 2010 59 2846–2853. (https://doi.org/10.2337/db10-0676)
- 6↑
Liu W, Han X, Wang Y, Gong S, Ma Y, Zhang S, Gao X, Ji L. Characteristics and ongoing autoimmunity of patients with long-standing type 1 diabetes living in China. Diabetes Care 2018 41 e97–e98. (https://doi.org/10.2337/dc18-0046)
- 7↑
Yu MG, Keenan HA, Shah HS, Frodsham SG, Pober D, He Z, Wolfson EA, D’Eon S, Tinsley LJ & Bonner-Weir S et al.Residual β cell function and monogenic variants in long-duration type 1 diabetes patients. Journal of Clinical Investigation 2019 129 3252–3263. (https://doi.org/10.1172/JCI127397)
- 8↑
The Diabetes Control and Complications Trial Research Group. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group. Annals of Internal Medicine 1998 128 517–523. (https://doi.org/10.7326/0003-4819-128-7-199804010-00001)
- 9↑
Steffes MW, Sibley S, Jackson M, Thomas W. β-Cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 2003 26 832–836. (https://doi.org/10.2337/diacare.26.3.832)
- 10↑
Lachin JM, McGee P, Palmer JP & DCCT/EDIC Research Group. Impact of C-peptide preservation on metabolic and clinical outcomes in the diabetes control and complications trial. Diabetes 2014 63 739–748. (https://doi.org/10.2337/db13-0881)
- 11↑
Kuhtreiber WM, Washer SL, Hsu E, Zhao M, Reinhold 3rd P, Burger D, Zheng H, Faustman DL. Low levels of C-peptide have clinical significance for established type 1 diabetes. Diabetic Medicine 2015 32 1346–1353. (https://doi.org/10.1111/dme.12850)
- 12↑
Hope SV, Knight BA, Shields BM, Hill AV, Choudhary P, Strain WD, McDonald TJ, Jones AG. Random non-fasting C-peptide testing can identify patients with insulin-treated type 2 diabetes at high risk of hypoglycaemia. Diabetologia 2018 61 66–74. (https://doi.org/10.1007/s00125-017-4449-2)
- 13↑
Marren SM, Hammersley S, McDonald TJ, Shields BM, Knight BA, Hill A, Bolt R, Tree TI, Roep BO & Hattersley AT et al.Persistent C-peptide is associated with reduced hypoglycaemia but not HbA(1c) in adults with longstanding type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice? Diabetic Medicine 2019 36 1092–1099. (https://doi.org/10.1111/dme.13960)
- 14↑
Buckingham B, Cheng P, Beck RW, Kollman C, Ruedy KJ, Weinzimer SA, Slover R, Bremer AA, Fuqua J & Tamborlane W et al.CGM-measured glucose values have a strong correlation with C-peptide, HbA1c and IDAAC, but do poorly in predicting C-peptide levels in the two years following onset of diabetes. Diabetologia 2015 58 1167–1174. (https://doi.org/10.1007/s00125-015-3559-y)
- 15↑
Gibb FW, McKnight JA, Clarke C, Strachan MWJ. Preserved C-peptide secretion is associated with fewer low-glucose events and lower glucose variability on flash glucose monitoring in adults with type 1 diabetes. Diabetologia 2020 63 906–914. (https://doi.org/10.1007/s00125-020-05099-3)
- 16↑
Rickels MR, Evans-Molina C, Bahnson HT, Ylescupidez A, Nadeau KJ, Hao W, Clements MA, Sherr JL, Pratley RE & Hannon TS et al.High residual C-peptide likely contributes to glycemic control in type 1 diabetes. Journal of Clinical Investigation 2020 130 1850–1862. (https://doi.org/10.1172/JCI134057)
- 17↑
Babaya N, Noso S, Hiromine Y, Taketomo Y, Niwano F, Yoshida S, Yasutake S, Kawabata Y, Ikegami H. Relationship of continuous glucose monitoring-related metrics with HbA1c and residual β-cell function in Japanese patients with type 1 diabetes. Scientific Reports 2021 11 4006. (https://doi.org/10.1038/s41598-021-83599-x)
- 18↑
Hope SV, Knight BA, Shields BM, Hattersley AT, McDonald TJ, Jones AG. Random non-fasting C-peptide: bringing robust assessment of endogenous insulin secretion to the clinic. Diabetic Medicine 2016 33 1554–1558. (https://doi.org/10.1111/dme.13142)
- 19↑
Carr ALJ, Oram RA, Marren SM, McDonald TJ, Narendran P, Andrews RC. Measurement of peak C-peptide at diagnosis informs glycemic control but not hypoglycemia in adults with type 1 diabetes. Journal of the Endocrine Society 2021 5 bvab127. (https://doi.org/10.1210/jendso/bvab127)
- 20↑
Johansson BL, Borg K, Fernqvist-Forbes E, Kernell A, Odergren T, Wahren J. Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with type 1 diabetes mellitus. Diabetic Medicine 2000 17 181–189. (https://doi.org/10.1046/j.1464-5491.2000.00274.x)
- 21↑
Kovatchev B Glycemic variability: risk factors, assessment, and control. Journal of Diabetes Science and Technology 2019 13 627–635. (https://doi.org/10.1177/1932296819826111)
