Association of C- peptide Levels and Type 1 Diabetes in Urban and Rural areas of South India

Introduction

Type 1 diabetes (T1D) is a significant global health concern, affecting 5-10% of all diabetes cases but posing a disproportionate challenge due to its lifelong management needs.¹ Unlike type 2 diabetes (T2D), which often develops later in life, T1D manifests as a severe, chronic autoimmune condition that typically arises in childhood or adolescence.¹ This distinction highlights the crucial role of insulin production in maintaining healthy blood sugar levels and the devastating consequences of its deficiency in T1D patients. Despite being categorised as a single disease entity, T1D encompasses a spectrum of clinical presentations. The most common form, type 1a diabetes, involves a well-defined autoimmune attack mediated by T cells that progressively destroy insulin producing pancreatic beta cells.² This immunological assault ultimately leads to absolute insulin deficiency, necessitating lifelong exogenous insulin administration to manage blood sugar levels.  A less prevalent subtype, type 1b diabetes, arises from idiopathic (unknown cause) dysfunction or destruction of beta cells.² Although the exact mechanisms remain unclear, this subtype shares similar clinical features with type 1a diabetes, requiring the same treatment approach. Traditionally diagnosed in children and adolescents, T1D has increasingly been identified in adults. The reasons for this trend are not fully understood, but they underscore the evolving nature of the disease and the potential role of environmental factors.³ This broadening of the age of onset necessitates heightened awareness of T1D symptoms across all age groups, ensuring timely diagnosis and prompt intervention.  Following a T1D diagnosis, individuals typically experience a rapid decline in beta cell function within the first five years. This rapid loss is primarily attributed to the ongoing T-cell-mediated destruction of insulin-producing cells.⁴ Studies in pediatric populations have documented lower C-peptide levels than in adults, often followed by a swift decrease in C-peptide production rate within six months of diagnosis.⁵ C-peptide, a byproduct of insulin synthesis, serves as a reliable indicator of the remaining beta cell function. The rate of T1D progression can vary considerably, with some individuals experiencing a more fulminant course leading to complete beta cell destruction within months, while others may retain some residual function for several years.⁶ This variability highlights the complex interplay between genetic and environmental factors in T1D pathogenesis. Interestingly, the presence of some residual beta cell function can offer potential benefits, such as a reduced risk of complications, fewer hypoglycaemic episodes, and improved overall metabolic control.⁷ Optimizing treatment strategies to preserve any remaining beta cell function is a crucial aspect of T1D management. Researchers are actively exploring ways to prevent or slow down autoimmune attacks and preserve beta cell function, offering a ray of hope for future T1D therapies. C-peptide is a reliable indicator of remaining beta cell function, particularly when measured after glucagon stimulation or a mixed meal.⁸ C-peptide levels directly reflect beta-cell activity as a byproduct of insulin synthesis. While it has no inherent hormonal effect itself, C-peptide measurement provides valuable information for healthcare professionals to assess the severity of T1D, guide treatment decisions (such as insulin dosage adjustments), and monitor treatment efficacy.^8,9 This study aimed to investigate the relationship between disease duration, age at onset, and gender with C-peptide levels in individuals diagnosed with Type 1 Diabetes (T1D).

Materials and Methods

This prospective study was conducted on thirty-one individuals diagnosed with T1D who sought treatment at the KLES Diabetes Centre, Belagavi, Karnataka, India, and were invited to participate. The study adhered to ethical standards and informed consent procedures. All procedures and outcomes of the study were explained to the patients and their relatives in vernacular language.

Inclusion criteria

1. Patients diagnosed with T1D according to existing criteria.
2. Willing to provide informed consent and participate in all the study procedures. 
3. Available for follow-up examination and investigations 

Exclusion criteria

1. Any co-existing medical conditions that could significantly affect C-peptide levels, such as hypoglycaemia of non-diabetic origin, pancreatic diseases, liver disease, and renal failure.
2. Pregnancy or breastfeeding.

Demographic information (age and sex) and age at T1D diagnosis were collected using a self-report questionnaire. Disease Duration: The duration of T1D for each participant was calculated by subtracting the age at diagnosis from the current age. A single fasting blood sample (approximately 10 mL) was collected from each participant via a peripheral venipuncture. C-peptide Estimation: Serum C-peptide levels were measured in all samples using a validated chemiluminescent immunoassay (CLIA) kit according to the manufacturer's instructions.

Statistical Analysis

Descriptive statistics were used to summarize participant demographics, disease duration, and C-peptide levels. Fisher's exact test was used to analyze the association between sex and T1D characteristics (presence/absence of symptoms at diagnosis). Pearson’s correlation coefficient was used to assess the relationships between C-peptide levels and disease duration, as well as age at onset.

Results

The present study investigated the relationship between C-peptide levels and the duration of type 1 diabetes in children. A sample of 31 participants was drawn, consisting of 17 (54.84%) males and 14 (45.16%) females, with a male-to-female ratio of 1.2:1. The mean C-peptide levels at enrolment were 0.72 ng/mL for males and 0.74 ng/mL for females. The age range of the participants was 5–22 years, with a mean age of 16.8 years. The onset of the disease ranged from 1 to 18 years, with a mean age of 9.2 years, and occurred in 8 (25.8%) children between 1 and 6 years, 8 (25.8%) children between 7 and 12 years, and 15 (48.4%) children between 13 and 18 years (Figure 1).

At enrolment, the initial C-peptide levels ranged from 0.2 ng/mL to 1.7 ng/mL, with a mean level of 0.90 ng/ mL. The decline in C-peptide levels was observed over 5 to 15 years, with a decrease of 0.54 ng/mL for males and 0.19 ng/mL for females. However, the decline was not statistically significant, with a P-value of 0.247 (Figure 2).

The mean C-peptide levels were significantly higher (1.12 ng/mL) in participants with disease onset between 11 and 15 years than in those with onset between 0 and 5 years (0.57 ng/mL). The participants had a mean disease duration of 6.93 years, ranging from 3 to 15 years, with 14 (45.1%) having a disease duration of 0–5 years, 7 (22.8%) with 6–10 years, and 10 (32.2%) with 11–15 years of type 1 diabetes.

The average C-peptide level seen in 14 out of 31 subjects at disease onset was 1.58 ng/mL, decreasing to 0.7 ng/ mL over 5–15 years, with an insignificant P-value of 0.287 compared to children with low levels. The decline in C-peptide levels was observed from 0.86 ng/mL to 0.61 ng/mL over five years, from 0.87 ng/mL to 0.41 ng/mL over ten years, and from 1.23 ng/mL to 0.31 ng/ mL over 15 years of disease duration. However, the mean C-peptide level changes and duration were not statistically significant (P=0.329). The study found a weak positive Pearson correlation coefficient between C-peptide levels and diabetes duration (r=0.150).

Discussion

In children with type 1 diabetes mellitus (T1DM), this study evaluated the correlation between C-peptide levels and several clinical and laboratory markers at three-month intervals after diagnosis. Furthermore, in those with type 1 diabetes (T1D), there is a connection between C-peptide levels and the duration of the condition. An essential component of insulin production is C-peptide. C-peptide is co-secreted into the portal circulation with insulin when proinsulin is broken down inside pancreatic beta cells.¹⁰ When evaluating endogenous insulin secretion and beta-cell activity, measuring C-peptide levels under controlled circumstances is thought to be the gold standard.¹⁰ In T1D patients, higher C-peptide levels are often correlated with better clinical results.^11,12 The use of post stimulation C-peptide levels as a proven technique for assessing endogenous insulin production has been made easier by the development of sensitive and repeatable C-peptide assays.¹⁰ The beta cell secretory function of a particular ethnic group in Belagavi, Karnataka State, is clarified by this study. Due to possible ethnic differences in T1D presentation and development, the generalizability of results from earlier research done in primarily Caucasian populations may be restricted.^13,14 This study offers insightful data that advances our understanding of T1D across a wider range of demographics.

This study provides important insights for a deeper understanding of T1D in various populations. We observed mean C-peptide levels of 0.72 ng/mL in males and 0.74 ng/mL in females, which is consistent with the gender distribution in our cohort and falls within the typical range for T1D patients reported by other similar studies.¹⁵ However, similar studies with larger cohorts are necessary to make definitive population-specific comparisons. Over a disease duration of 5-15 years, we noted a decline in C-peptide levels to 0.54 ng/mL in males and 0.19 ng/mL in females, corroborating prior studies that have documented a gradual loss of beta cell function over time.¹¹ Although the P-value (0.247) indicated no statistically significant gender-based differences in this decline, a study with a more extensive sample size might provide clearer evidence.

The current study found a statistically significant link (P=0.045) between the age of commencement of the illness and its progression, suggesting that those with T1D who are identified earlier in life may have a faster decline in C-peptide levels, which may indicate a more severe course for their condition.¹⁶ To clarify the processes behind this association, more in-depth investigations are necessary to fully understand the f indings of our work. More significantly, the study's f indings establish the value of C-peptide measurements as a crucial and reliable method for assessing beta cell activity in T1D patients and provide crucial details on the course of the illness and the effectiveness of treatment. Peptide C is becoming more widely acknowledged as a crucial metric in therapeutic settings as it is necessary for the body to produce insulin naturally.

Limitation of the current study

1. The study has a relatively small sample size, necessitated by stringent inclusion criteria, which might have limited the strength of the observed correlation between C-peptide levels and disease duration. 
2. Younger participants with T1D diagnosis have a rapid reduction of C-peptide levels; the details of the mechanism have not been elucidated in this study.
3. Future research with larger and more diverse populations could further solidify these findings.

Conclusion

This study investigated the relationship between C-peptide levels, disease duration, and age at onset in individuals with Type 1 Diabetes (T1D). Our findings suggest a potential link between later disease onset (10-15 years) and higher C-peptide levels, which might indicate a slower progression in older individuals diagnosed with T1D. However, a longer disease duration was positively correlated with a gradual decline in C-peptide levels. However, this study finds a slower rate of C-peptide decline, and nearly 45% of the participants had no C-peptide levels at the onset of the disease, highlighting the potential for initial preservation of beta cell function in some T1D patients.

Source of Support

Nil

Ethical Permission

Obtained

Conflict of Interest

None

Acknowledgement

The authors express their sincere gratitude to Dr Jali and the dedicated staff of the KLES Dr Prabhakar Kore Hospital for their invaluable support throughout the study.  Special thanks are extended to Dr. M.V. Jali, former medical director and Chief Executive of the hospital, for his crucial support. We also acknowledge the invaluable assistance provided by the clinical staff of the hospital's Diabetes Centre.