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 Table of Contents  
ORIGINAL ARTICLES
Year : 2022  |  Volume : 13  |  Issue : 3  |  Page : 249-254

Fasting serum C-peptide level may not be low in young-onset diabetes


1 Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
2 Department of Physiology, Sheikh Sayera Khatun Medical College, Gopalganj, Bangladesh

Date of Submission27-Jan-2022
Date of Decision04-Apr-2022
Date of Acceptance16-Apr-2022
Date of Web Publication12-Aug-2022

Correspondence Address:
Prof. Muhammad A Hasanat
Room No. 1524, D-Block, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka 1000
Bangladesh
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jod.jod_11_22

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  Abstract 

Background: Diabetes mellitus (DM) is one of the growing health problems among the young population. Secretory defect of insulin is an important cause, and it can be assessed by measuring fasting serum C-peptide level. Aim: The aim of this article is to assess fasting serum C-peptide in young-onset DM individuals. Materials and Methods: This case–control study was conducted in the Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2015 to February 2017. For this purpose, 40 individuals with DM (irrespective of DM type; age range: 11–29 years) were enrolled as case and an equal number of young healthy individuals as control. Demographic profiles, clinical profiles, and serum C-peptide were recorded in a standard and pre-tested structured datasheet. C-peptide was measured by the chemiluminescent immunometric assay. Results: Median fasting C-peptide was 2.67 [interquartile range (IQR) 1.06–4.07, range 0.12–20.0] ng/mL in diabetes individuals, whereas it was 2.19 (IQR 1.36–2.94, range 0.44–9.85) ng/mL in the control group; the difference was insignificant (P = 0.331). Waist circumference (WC) was significantly higher in the young diabetes group in comparison to that of control subjects and so were the plasma glucose values and diastolic blood pressure (P < 0.05 for all). Diabetic participants with low C-peptide group had significantly lower body mass index (BMI) and WC and higher fasting plasma glucose (FPG) and HbA1c in comparison to others (P < 0.05 for all); whereas the high C-peptide group had opposite body indices (higher BMI and WC) and glycemic parameters (lower FPG and HbA1c) (P < 0.05 for all). The classic hyperglycemic symptoms were more common in the low C-peptide group (P = 0.029). In participants with diabetes, C-peptide positively correlated with BMI and WC, whereas it showed a negative correlation with age (P < 0.05 for all). In the control group, C-peptide positively correlated with WC only (P = 0.018). Conclusion: The level of fasting serum C-peptide in diabetic subjects was similar to healthy controls, and it was higher in those subjects who had higher BMI, WC, and lower age.

Keywords: C-peptide, diabetes mellitus, young-onset


How to cite this article:
Hosen M, Sultana N, Hasan M, Jahan S, Jahangir-Alam M, Islam S, Rahman S, Tanvi NE, Fariduddin M, Hasanat MA. Fasting serum C-peptide level may not be low in young-onset diabetes. J Diabetol 2022;13:249-54

How to cite this URL:
Hosen M, Sultana N, Hasan M, Jahan S, Jahangir-Alam M, Islam S, Rahman S, Tanvi NE, Fariduddin M, Hasanat MA. Fasting serum C-peptide level may not be low in young-onset diabetes. J Diabetol [serial online] 2022 [cited 2022 Nov 30];13:249-54. Available from: https://www.journalofdiabetology.org/text.asp?2022/13/3/249/353748




  Introduction Top


The global burden of diabetes mellitus (DM) is rising. In adults aged 20–79 years, the global prevalence of diabetes is 9.3%, which is estimated to reach 10.2% by 2030. It has been reported in 2019 that 83 lacs people in Bangladesh had DM which is expected to be 1.5 crores by 2045.[1] Moreover, DM is progressively affecting more people at an early age and significantly affecting the most productive period of life. Before the 1980s, type 1 diabetes (T1DM) was considered to be the only form of DM prevalent in children and adolescents.[2] However, recent reports show an increasing prevalence of type 2 diabetes (T2DM) in children and adolescents around the world, and it is following the rise of childhood obesity.[3] The prevalence of impaired fasting glucose and diabetes is high among Bangladeshi children (3.4% and 1.8%) and more in urban children with high family income.[4]

The pathophysiologic basis of T2DM demonstrates insulin resistance (IR) resulting in hyperinsulinemia. Diabetes ensues when pancreatic beta cells fail to compensate for IR.[5] The measurement of insulin secretory capacity is being increasingly relevant in clinical practice as there is a rise in the prevalence of T2DM in younger patients. Moreover, the discovery of monogenic subtypes of diabetes requiring specific management and the development of new therapies aimed at preserving insulin secretion further necessitate the assessment of endogenous insulin secretion.[6] Assigning a type of diabetes during the diagnosis is often necessary to help health professionals to choose appropriate treatment. However, newer forms like “hybrid types of diabetes” as included in the new classification of diabetes proposed by the World Health Organization (WHO) make this assignment more challenging.[7]

C-peptide is commonly used in preference to insulin measurement when assessing β-cell function in clinical practice. To assess endogenous insulin secretion in patients on insulin therapy, C-peptide measurement must be used as exogenous insulin will be detected by insulin assays.[8] Insulin produced by the pancreas is extensively metabolized by the liver. Both the extent of this first-pass metabolism and peripheral clearance of insulin are variable; therefore, peripheral insulin levels may not accurately reflect insulin secretory capacity.[9] Even in non-insulin-treated patients, peripheral C-peptide levels more accurately reflect insulin secretion than measurement of peripheral insulin.[10] The physiology of C-peptide makes it appropriate for assessing insulin secretion. C-peptide is produced in equal amounts to insulin and has negligible extraction by the liver and constant peripheral clearance.[11] Its half-life is longer than that of insulin (20–30 vs. 3–5 min) and it, therefore, circulates at concentrations approximately five times higher in the systemic circulation.[12] In addition, current advances in assays and collection techniques have made the assessment of insulin secretion using C-peptide less expensive, more reliable, and widely available.

Assessing beta-cell function may help define subtypes of diabetes and guide treatment decision.[13] So, this study aims to measure the level of C-peptide to assess insulin secretory capacity in young people with diabetes aged <30 years.


  Materials and Methods Top


Study subjects and design

This case–control study was conducted in the Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2015 to February 2017. Forty patients with DM of young onset, diagnosed according to the American Diabetes Association (ADA) criteria[14] (age range: 11–29 years), were enrolled irrespective of DM type as a case by non-probability purposive sampling and an equal number of age-matched healthy individuals as control. Patients with gestational diabetes, chronic liver disease, chronic kidney disease, and on drugs interfering with endogenous insulin and C-peptide concentration were excluded from this study.

Study procedure

A detailed history and thorough examination were done on each individual. Height was measured by using a stadiometer, standing upright on a flat surface without shoes. Weight was measured by a balance on a hard flat surface. Waist circumference (WC) was measured to the nearest centimeter with a flexible steel tape, while the subjects were in a standing position at the end of gentle expiration. The following anatomical landmarks were used: laterally, midway between the lowest portion of the rib cage and iliac crest, and anteriorly, midway between the xiphoid process of the sternum and the umbilicus. Hip circumference was measured at the level of the widest portion of the buttocks. Blood pressure (BP) was measured in millimeters of mercury by a standard sphygmomanometer. The socio-economic condition was assessed by modified Kuppuswamy and Udai Pareekh’s scale.[15]

Clinical diagnosis was established from history and thorough physical examination and was confirmed on laboratory investigations. Patients or eligible attendants were questioned about past and family (parents and siblings) history. Demographic and clinical profiles were recorded in a standard pre-tested structured datasheet. A fasting blood sample (5 mL) was collected from each participant for the measurement of C-peptide and glucose. HbA1c was measured in participants with diabetes.

Analytic method

C-peptide was measured by the chemiluminescent immunometric assay (Siemens 2008, C-peptide, IMMULITE 2000). The reference range of serum fasting C-peptide was 0.9–7.1 ng/mL. Serum glucose was measured by the glucose oxidase (GOD-PAP) method (AUTOLAB Analyzer Medical System, Rome, Italy) and HbA1c by the NGSP-certified Bio-Rad D-10TM Hemoglobin A1c Program 220-0101, USA.

Ethical aspects

Before the commencement of this study, the thesis protocol was approved by the Institutional Review Board, BSMMU, Dhaka, Bangladesh. Before enrollment, informed written consent was taken from the individuals or guardians after a full explanation of the purpose of the study.

Statistical analysis

Quantitative data were expressed as mean±SD or median and interquartile range (IQR), whereas qualitative data were expressed as frequency distribution and percentage. Statistical analyses were performed by using IBM SPSS Statistics for Windows version 22.0 (IBM Corp., Armonk, NY, USA). Association between categorical variables was analyzed by the χ2 test and continuous variable by Student’s t-test and one-way analysis of variance (ANOVA). Continuous variable with skewed distribution was compared with the Mann–Whitney U-test. Correlation was done by Pearson’s correlation test. For all statistical tests, a P-value of less than 0.05 was considered statistically significant.


  Results Top


The participants with diabetes had statistically similar age and gender distribution in comparison to the control group [Table 1]. WC was significantly higher in the young diabetes group in comparison to those of control individuals and so were the plasma glucose values and diastolic BP (P < 0.05 for all). There was a trend of higher body mass index (BMI) and waist–hip ratio (WHR) in participants with diabetes in comparison to the control group, but the difference was not statistically significant. Mean HbA1c was 9.72 ± 3.18% in participants with DM. There were differences in socio-economic distribution and frequency of family history of diabetes between the two groups (P < 0.001 for both). About 40% of the participants with DM were asymptomatic, 48% had classic hyperglycemic symptoms, and 10% had non-specific symptoms. One individual with diabetes had hyperglycemic emergency. More than 50% (22/40) had duration of DM <1 month, 25% between 1 and 12 months, while 20% had it >12 months [Table 2].
Table 1: Characteristics of study participants (n = 80)

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Table 2: Duration of DM and symptoms in participants with DM (n = 40)

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Median fasting C-peptide was 2.67 (IQR 1.06–4.07, range 0.12–20.0) ng/mL in diabetes individuals, whereas it was 2.19 (IQR 1.36–2.94, range 0.44–9.85) ng/mL in the control group (P = 0.331) [Figure 1]. Most of the participants of case and control groups had normal fasting serum C-peptide levels (70% and 85%, respectively). The proportion of participants with low or high C-peptide levels was higher in the case group but statistically insignificant (P = 0.259) [Figure 2]. Comparing the characteristics of the participants with diabetes according to the C-peptide level, it was observed that the low C-peptide group had significantly lower BMI and WC and higher fasting plasma glucose (FPG) and HbA1c in comparison to others (P < 0.05 for all); whereas the high C-peptide group had completely opposite body indices (higher BMI and WC) and glycemic parameters (lower FPG and HbA1c) (P < 0.05 for all). The classic hyperglycemic symptoms were more common in the low C-peptide group (P = 0.029). The age was higher in participants with normal C-peptide, followed by participants with high C-peptide (P < 0.001) [Table 3]. In participants with diabetes, C-peptide positively correlated with BMI and WC, whereas it showed a negative correlation with age (P < 0.05 for all). In the control group, C-peptide positively correlated with WC only (P = 0.018) [Table 4].
Figure 1: Comparison of fasting serum C-peptide level between participants with diabetes in youth (case, n = 40) and normoglycemic control (n = 40)

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Figure 2: Comparison of participants with diabetes in youth (case, n = 40) and normoglycemic control (n = 40) according to the fasting serum C-peptide level. Percentages are over the total number of cases and controls, respectively. The normal value of fasting serum C-peptide was 0.9–7.1 ng/mL

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Table 3: Comparison of characteristics of the participants with diabetes (n = 40) according to fasting C-peptide level

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Table 4: Correlation of fasting C-peptide with age, BMI, WC, FPG, 2-h PG, and HbA1c in participants

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  Discussion Top


The present case–control study encompassed 40 young subjects with diabetes (age 11–29 years) and an equal number of age- and sex-matched healthy controls. It was aimed to see the level of fasting serum C-peptide in participants with young-onset DM and to compare this with the healthy group. It was observed that the median fasting C-peptide level of participants with young-onset diabetes was not significantly different from that of the control group. In participants with young-onset diabetes, the serum C-peptide level increased with the increment of BMI and WC and decreased with increment of age. Low C-peptide level was also associated with higher glycemic excursions reflected by plasma glucose values and HbA1c.

C-peptide is the best measure of endogenous insulin secretion in persons with diabetes. However, hyperglycemia is a result of dynamic interaction between insulin secretion and IR and cannot be explained by the C-peptide level alone. C-peptide levels in persons with diabetes of different etiologies may be widely distributed, which is reflected by the findings of the present study. The reason behind the statistical similarity between the C-peptide levels of the case and control groups in the current study may be the presence of heterogeneous etiology of DM among the young subjects. It signifies the current notion that diabetes in this age group may be of various types including T1DM, T2DM, hybrid form of DM, monogenic forms of diabetes, and disease of the endocrine pancreas. Differentiation of these types needs further genetic and biochemical assessment and needs further studies. It was also notable that few participants with normoglycemia had “low” levels of C-peptide. These might reflect the lack of studies defining reference ranges of fasting C-peptide in our population.

C-peptide significantly varied among the BMI categories in diabetic subjects with a rising trend with an increment of BMI. A positive correlation between BMI and basal serum C-peptide levels was also observed by Park et al.[16] Higher C-peptide in the younger age group with high BMI and WC implies hyperinsulinemia and IR. This finding is in agreement with the results of some other researchers.[17],[18]

The incidence of T2DM in young adults has increased significantly over the past two decades.[19] So, it can be assumed that an important reason behind this is obesity and associated IR. Mean WHR was higher in the cases than that in controls as we expected but not statistically significant. Similar to the present study result, Burns et al.[20] have reported that the WHR is more in DM patients than in the healthy control group and thus it further implies the importance of obesity and IR.

Family history of DM was significantly higher in cases (65.0%) than that of controls (20.0%). Similar to the present study, Annis et al.[21] had reported that a family history of T2DM might be recognized as an important risk factor for the disease. Harrison et al.[22] have reported that family history is directly linked to DM, which is consistent with the present study result. In addition to a high frequency of family history of DM, the higher WC, diastolic BP, asymptomatic presentation in the young diabetes group of the current study indicates more toward IR rather than a secretory failure of beta-cells of the pancreas as the basic pathophysiologic process of DM in this group of individuals. Thereby it may be said that in our young population with diabetes, T2DM might play an important role.

Individuals with higher C-peptide levels would be expected to have lower glucose values and it was found in the present study. A similar result was found in some other studies too.[18] In this study, systolic and diastolic BPs were highest in the high C-peptide group but not statistically significant. Bo et al.[18] observed the highest level of systolic and diastolic BPs in the high C-peptide group. It might be because of the link among hypertension, hyperinsulinemia, and obesity.[23]

The study measured fasting C-peptide which is considered to be a reliable guide of endogenous insulin secretion. Comparison of an equal number of healthy individuals is also a strength of the study. However, the precise etiology of diabetes was not assessed in study participants. A comprehensive evaluation of autoimmune markers, IR, and monogenic abnormalities could have strengthened the evaluation of insulin secretory capacity in different forms of diabetes. Further increasing the sample size may increase the power of the study.


  Conclusion Top


Serum C-peptide level was similar in young diabetic individuals and healthy controls. There was a positive correlation between C-peptide and both BMI and WC, whereas there was an inverse relation with age.

Acknowledgement

The authors kindly acknowledge the contribution of Department of Microbiology, BSMMU for their technical help and Study on Diabetes in Young (SODY) group, BSMMU for their overall support.

Financial support and sponsorship

This work was supported as a research grant by Research and Development, BSMMU, and SODY group, BSMMU, Dhaka, Bangladesh.

Conflicts of interest

There are no conflicts of interest.



 
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Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al; IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 2019;157:107843.  Back to cited text no. 1
    
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Guo C, Zhou Q, Zhang D, Qin P, Li Q, Tian G, et al. Association of total sedentary behaviour and television viewing with risk of overweight/obesity, type 2 diabetes and hypertension: A dose-response meta-analysis. Diabetes Obes Metab 2020;22:79-90.  Back to cited text no. 3
    
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Clark PM Assays for insulin, proinsulin(s) and C-peptide. Ann Clin Biochem 1999;36:541-64.  Back to cited text no. 8
    
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Van Cauter E, Mestrez F, Sturis J, Polonsky KS Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes 1992;41:368-77.  Back to cited text no. 10
    
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Jones AG, Hattersley AT The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med 2013;30:803-17.  Back to cited text no. 11
    
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Polonsky KS, Licinio-Paixao J, Given BD, Pugh W, Rue P, Galloway J, et al. Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. J Clin Invest 1986;77:98-105.  Back to cited text no. 12
    
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Skyler JS, Bakris GL, Bonifacio E, Darsow T, Eckel RH, Groop L, et al. Differentiation of diabetes by pathophysiology, natural history, and prognosis. Diabetes 2017;66:241-55.  Back to cited text no. 13
    
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American Diabetes Association. Standards of medical care in diabetes—2015 abridged for primary care providers. Clin Diabetes 2015;33:97-111. doi:10.2337/diaclin.33.2.97  Back to cited text no. 14
    
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Wani RT Socioeconomic status scales-modified Kuppuswamy and Udai Pareekh’s scale updated for 2019. J Family Med Prim Care 2019;8:1846-9.  Back to cited text no. 15
    
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Park SW, Ihm SH, Yoo HJ, Park JY, Lee KU Differential effects of ambient blood glucose level and degree of obesity on basal serum C-peptide level and the C-peptide response to glucose and glucagon in non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1997;37:165-71.  Back to cited text no. 16
    
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Abdullah BB, Patil BS, Thaseen A Significance of C-peptide in type 2 diabetics: A study in the North Karnataka population of India. Al Ameen J Med Sci 2010;3:65-78.  Back to cited text no. 17
    
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Bo S, Gentile L, Castiglione A, Prandi V, Canil S, Ghigo E, et al. C-peptide and the risk for incident complications and mortality in type 2 diabetic patients: A retrospective cohort study after a 14-year follow-up. Eur J Endocrinol 2012;167:173-80.  Back to cited text no. 18
    
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Burns N, Finucane FM, Hatunic M, Gilman M, Murphy M, Gasparro D, et al. Early-onset type 2 diabetes in obese white subjects is characterised by a marked defect in beta cell insulin secretion, severe insulin resistance and a lack of response to aerobic exercise training. Diabetologia 2007;50:1500-8.  Back to cited text no. 20
    
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Harrison TA, Hindorff LA, Kim H, Wines RC, Bowen DJ, McGrath BB, et al. Family history of diabetes as a potential public health tool. Am J Prev Med 2003;24:152-9.  Back to cited text no. 22
    
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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