Background: As insulin resistance frequently precedes overt diabetes, its early detection is crucial for preventing disease progression and associated complications such as cardiovascular disease. Elevated fasting C-peptide levels often indicate increased insulin secretion, usually as a compensatory mechanism for insulin resistance. Understanding the association between fasting C-peptide levels, insulin resistance, and anthropometric measures in diabetic patients helps in assessing disease severity and tailoring therapeutic interventions. Methods: This was an observational cross-sectional study conducted over a period of one year involving 216 patients above 18 years of age. 5000 patients were screened using random blood sugar and 216 patients were diagnosed as diabetics. Anthropometric measurements (weight, height, body mass index and waist-to-hip ratio) were recorded. Laboratory investigations including complete blood count, renal function test, serum electrolytes, HbA1c, fasting blood sugar, fasting C-peptide levels and lipid profile were performed. Results: The association between C-peptide and age was significant (p-value =0.001). A significant association was observed between C-peptide levels and BMI categories (X2: 51.355, df: 8, p=0.001). High C-peptide levels were associated with a high waist-to-hip ratio of >0.80 in both sexes. The relationship between C-peptide and peripheral signs of resistance was found to be significantly associated (p-value-0.001). The relationship between C-peptide and HbA1c levels was found to be significantly associated (P value-0.001) with a bidirectional effect wherein fasting C-peptide levels in the normal range actually had lower HbA1c levels with an increase as we move away from this group. There was a statistically significant difference in serum triglyceride levels among different fasting C-peptide levels with a p-value of 0.014. Serum VLDL levels and C-peptide levels had a significant association (p-value<0.05), whereas fasting C-peptide had no significant association with serum cholesterol, HDL and S. LDL levels (p-0.117, 0.102, 0.622 respectively). Conclusion: Fasting C-peptide level is strongly associated with insulin resistance and key anthropometric measures in patients with type 2 diabetes mellitus.
Type 2 diabetes mellitus is a complex metabolic disorder characterized by insulin resistance and impaired insulin secretion. Insulin resistance, a condition in which the body's cells become less responsive to insulin, is a key pathogenic factor leading to elevated blood glucose levels and subsequent diabetes. As insulin resistance frequently precedes overt diabetes, its early identification is crucial for preventing disease progression and associated complications such as cardiovascular disease. C-peptide, a cleavage product of proinsulin, is secreted in equimolar amounts as insulin from pancreatic beta cells and serves as an important marker of endogenous insulin secretion. Unlike insulin, which has a short half-life and fluctuates rapidly, C-peptide has a longer half-life and reflects pancreatic beta-cell function more reliably. Elevated fasting C-peptide levels often indicate increased insulin secretion, usually as a compensatory mechanism for insulin resistance. Understanding the association between fasting C-peptide levels, insulin resistance, and anthropometric measures in diabetic patients helps in assessing disease severity and tailoring therapeutic interventions.[1] Research has shown that increased fasting C-peptide levels correlate strongly with insulin resistance indices such as HOMA-IR. In type 2 diabetic patients, high fasting C-peptide reflects enhanced beta-cell activity compensating for peripheral insulin resistance. Since insulin and C-peptide are released equimolarly, higher C-peptide levels mirror increased beta-cell secretory activity in response to insulin resistance. This makes C-peptide a useful clinical marker for quantifying beta-cell function and indirectly insulin resistance.[2]
Anthropometric measures provide an estimation of body fat distribution and overall adiposity, critical risk factors for insulin resistance and type 2 diabetes. Common anthropometric indices include BMI (Body Mass Index), WC (Waist Circumference), waist-to-hip ratio, and measurements of abdominal adipose tissue volumes through imaging.[3] Studies have consistently shown that fasting C-peptide levels correlate positively with anthropometric indices. Higher BMI and waist circumference in diabetic patients correspond with increased fasting C-peptide levels, indicating amplified insulin secretion to overcome peripheral resistance. Patients with central or abdominal obesity tend to exhibit increased C-peptide levels compared to lean individuals.[4]
Fasting C-peptide thus provides a combined indicator of both beta-cell function and metabolic risk due to obesity. Due to the equimolar secretion of C-peptide and longer half-life, C-peptide can be used to evaluate the beta cell function as well as a marker for insulin resistance. The plasma concentration of C-peptide in a fasted state is 0.9 to 1.8 ng/ml. It is now possible to detect C-peptide levels as low as 0.0045 ng/ml.[5] The advantage of C-peptide levels over insulin levels is the accurate depiction of pancreatic function while undergoing almost no degradation by the liver. This study was conducted to assess the relationship between fasting C-peptide levels and insulin resistance, their correlation with anthropometric indices, and the clinical significance of these associations.
This was an observational cross-sectional study conducted over a period of one year involving 216 patients above 18 years of age. 5000 patients were screened using random blood sugar and 216 patients were diagnosed as diabetics. They were enrolled in the study. Those diagnosed with malignancy, gestational diabetes mellitus, cirrhosis of liver, chronic kidney disease on maintenance haemodialysis; and patients taking drugs that cause hyperglycaemia/hypoglycaemia in the last 3 months were excluded from the study.
The newly diagnosed diabetics as per the ADA (American Diabetes Association) were recruited in the study after taking written and informed consent in vernacular language and then subjected to detailed history taking, anthropometric measurements (weight, height, body mass index and waist-to-hip ratio) and clinical examination (including fundus examination).Laboratory investigations (complete blood count, renal function test, serum electrolytes, HbA1c, fasting blood sugar, fasting C-peptide levels, lipid profile and ECG) were performed. Data thus obtained was analyzed statistically.
The recorded data was compiled and entered in a spreadsheet computer program (Microsoft Excel 2010) and then exported to the editor page of SPSS version 23. (SPSS Inc., Chicago, Illinois, USA). Descriptive statistics including computations of percentages, means and standard deviations were calculated. Statistical tests such as the Pearson chi-square test, the student t-test, the Kruskal-Wallis test for nonparametric data, and Pearson correlation coefficient were applied. The level of confidence interval and p-value were set at 95% and 5%.
5000 people presenting to the OPD/IPD were screened using random blood sugar levels out of which 216 patients were diagnosed as suffering from newly diagnosed diabetes giving an incidence of 4.32 percent in the general population.
The majority belonged to the age group of 51-60 years (24.1%). The extreme age groups had the least number of diabetics with a measly 3.2 percent of all patients in these age groups. Out of the total 216 cases, 101 (46.8%) were female while 115 (53.2%) were males.
The mean ages of patients in the low, normal and high C-peptide groups were 47.340±16.7848, 58.810±11.2366 and 59.3311±3.0285 years, respectively. The association between C-peptide and age was significant (p value =0.001).
Fasting C-Peptide (ng/ml) |
Age (in Years) |
|
Mean |
SD |
|
<0.90 (Low) |
47.340 |
16.7848 |
0.90-1.80 (Normal) |
58.810 |
11.2366 |
>1.80 (High) |
59.331 |
13.0285 |
Total |
56.338 |
14.7538 |
p-value (Kruskal-Wallis Test) |
0.001 |
|
Table 1: Fasting C-peptide and Distribution by Mean Age |
With respect to the waist-to-hip ratio, among females, 24 cases, accounting for 11.1%, were in the <0.80 (normal) category, while in the >0.80 (high) category there were 77 cases, 35.6% of the total. Waist-to-hip ratio in males showed that 33 cases, representing 15.3%, fell into the <0.95 (normal) category, while 82 cases, accounting for 38.0%, were in the >0.95 (high) category.
166 patients (76.9%) had the presence of peripheral signs of insulin resistance on physical examination. Among the peripheral signs of insulin resistance, skin tags were seen in 59.7%, acanthosis nigricans in 68.5% and truncal obesity in 51.4%.
For individuals with low C-peptide levels (<0.90), the mean BMI was 25.89 with an SD of 4.45, for those with normal C-peptide levels (0.90-1.80), the mean BMI was 25.74 with an SD of 3.54, and for those with high C-peptide levels (>1.80), the mean BMI was significantly higher at 28.42 with an SD of 4.41. The overall mean BMI across all categories was 27.54 with an SD of 4.49. The Kruskal-Wallis test yielded a p-value of 0.001, indicating that there was a statistically significant difference in BMI across the different C-peptide level groups. This suggests that higher C-peptide levels are associated with higher BMI.
The table below displays the mean and standard deviation of waist-to-hip ratios across different C-peptide level categories. The p-value from the Kruskal-Wallis test was 0.020 and 0.001 for female and male categories respectively, indicating a statistically significant difference in waist-to-hip ratios.
Fasting C-Peptide (ng/ml) |
Waist-to-Hip Ratio (Female) |
Waist-to-Hip Ratio (Male) |
||
Mean |
Mean |
Mean |
SD |
|
<0.90 (Low) |
0.9113 |
0.9200 |
0.9200 |
0.17746 |
0.90-1.80 (Normal) |
0.9000 |
1.0279 |
1.0279 |
0.23544 |
>1.80 (High) |
1.0169 |
1.0968 |
1.0968 |
0.13817 |
Total |
0.9774 |
1.0530 |
1.0530 |
0.17393 |
p-value (Kruskal-Wallis Test) |
0.020 |
0.001 |
||
Table 2: Fasting C-Peptide versus Mean Waist-Hip Ratio |
The table below displays the distribution of individuals based on C-peptide levels and the presence of peripheral signs of insulin resistance. For individuals without peripheral signs of insulin resistance, there were 50 cases, accounting for 23.14% of the total, while for those with signs, there were 166 cases, making up 76.8% of the total, across different C-peptide categories of <0.90 (low), 0.90-1.80 (normal), and >1.80 (high). The statistical analysis shows a p-value of 0.001, indicating a significant association between C-peptide levels and the presence of peripheral signs of insulin resistance.
Fasting C-Peptide (ng/ml) |
Peripheral Signs of Insulin Resistance |
Total |
||||
No |
Yes |
No. |
%age |
|||
No. |
% |
No. |
% |
|
|
|
<0.90 (Low) |
27 |
12.50 |
26 |
12.04 |
53 |
24.54 |
0.90-1.80 (Normal) |
11 |
5.09 |
10 |
4.63 |
21 |
9.72 |
>1.80 (High) |
12 |
5.56 |
130 |
60.19 |
142 |
65.74 |
Total |
50 |
23.14 |
166 |
576.8 |
216 |
100.00 |
p-value |
X2: 50.347; df: 2; p=0.001 |
|||||
Table 3: Fasting C-Peptide versus Peripheral Signs of Insulin Resistance |
Figure 1: Fasting C-Peptide versus Peripheral Signs of Insulin Resistance |
The table below displays the mean and standard deviation of HbA1c levels across different C-peptide categories. For low C-peptide levels (<0.90), the mean HbA1c was approximately 8.857. For normal C-peptide levels (0.90-1.80), the mean HbA1c decreased to around 6.971. For high C-peptide levels (>1.80), the mean HbA1c increases again to about 8.549. The p-value from the Kruskal-Wallis test was 0.001, indicating a statistically significant difference in HbA1c levels among the C-peptide groups.
Fasting C-Peptide (ng/ml) |
HbA1c |
|
Mean |
SD |
|
<0.90 (Low) |
8.857 |
2.440 |
0.90-1.80 (Normal) |
6.971 |
1.622 |
>1.80 (High) |
8.549 |
2.509 |
Total |
8.471 |
2.464 |
p-value (Kruskal-Wallis Test) |
0.001 |
|
Table 4: Fasting C-Peptide versus mean HbA1c (Mean) |
The figure below presents the distribution of participants based on their C-peptide levels and HbA1c categories. The majority of participants, 65.74% of the total sample, fell into the high C-peptide category (>1.80). Among them, 9.72% had HbA1c levels in the 0.90-1.80 range, and 18.52% had HbA1c levels in the 7.5-10.0 range. In contrast, participants with low C-peptide levels had a lower percentage in the high HbA1c category, with 9.26% having HbA1c levels below 7.5 and 7.41% having HbA1c levels in the 7.5-10.0 range.
Figure 2: Fasting C-Peptide versus HBA1C |
The table below shows the relationship between mean serum cholesterol levels and different C-peptide categories: low (<0.90), normal (0.90-1.80), and high (>1.80). The data shows that individuals with low C-peptide levels have a mean serum cholesterol level of approximately 190 mg/dl. This level slightly decreased to around 170 mg/dl in the normal C-peptide group, indicating a dip in cholesterol levels. However, in the high C-peptide group, the mean serum cholesterol level was higher again, at about 200 mg/dl. This suggests a possible association between fasting C-peptide and serum cholesterol.
Fasting C-Peptide (ng/ml) |
Serum Cholesterol |
|
Mean |
SD |
|
<0.90 (Low) |
179.143 |
82.105 |
0.90-1.80 (Normal) |
160.300 |
54.344 |
>1.80 (High) |
190.565 |
67.940 |
Total |
184.824 |
70.857 |
p-value (Kruskal-Wallis Test) |
0.117 |
|
Table 5: Fasting C-Peptide versus Mean Serum Cholesterol |
The figure below shows the distribution of individuals with different C-peptide levels across two categories of serum cholesterol: less than 200 mg/dl and greater than 200 mg/dl. It also provides the total number and percentage of individuals in each category. For low C-peptide levels (<0.90), 32 individuals (14.81%) had serum cholesterol <200 mg/dl, and 21 individuals (9.72%) had serum cholesterol >200 mg/dl, totalling 53 individuals (24.54%). For normal C-peptide levels (0.90-1.80), 14 individuals (6.48%) had serum cholesterol <200 mg/dl, and 7 individuals (3.24%) had serum cholesterol >200 mg/dl, totalling 21 individuals (9.72%). For high C-peptide levels (>1.80), 86 individuals (39.81%) had serum cholesterol <200 mg/dl, and 56 individuals (25.93%) had serum cholesterol >200 mg/dl, totalling 142 individuals (65.74%).
Overall, 132 individuals (61.11%) had serum cholesterol <200 mg/dl, while 84 individuals (38.89%) had serum cholesterol >200 mg/dl, out of a total of 216 individuals (100%). The data indicate that a higher percentage of individuals with high C-peptide levels also tend to have higher serum cholesterol levels.
Figure 3: C-peptide Levels across Two Categories of Serum Cholesterol |
The table below illustrates the relationship between mean serum triglyceride levels and different C-peptide categories: low (<0.90), normal (0.90-1.80), and high (>1.80). The data shows that individuals with low C-peptide levels have a mean serum triglyceride level of approximately 209.719 mg/dl. This level decreased to around 139.181 mg/dl in the normal C-peptide group, indicating a dip in triglyceride levels. However, in the high C-peptide group, the mean serum triglyceride level increased again to about 218.647 mg/dl. This trend suggests a potential correlation where both low and high C-peptide levels are associated with higher mean serum triglyceride, while normal C-peptide levels correspond to lower mean serum triglyceride. The Kruskal-Walli’s test indicates that these differences are statistically significant with a p-value of 0.014.
Fasting C-Peptide (ng/ml) |
Serum Triglyceride |
|
Mean |
SD |
|
<0.90 (Low) |
209.719 |
151.349 |
0.90-1.80 (Normal) |
139.181 |
70.976 |
>1.80 (High) |
218.647 |
137.058 |
Total |
208.731 |
137.353 |
p-value (Kruskal-Wallis Test) |
0.014 |
|
Table 6: Fasting C-Peptide versus Mean Serum Triglyceride |
The figure below represents the distribution of individuals based on C-peptide levels (<0.90, 0.90-1.80, >1.80) and their corresponding triglyceride levels (<150, >150). Among the total 216 participants, the majority (65.74%) fell into the high C-peptide category (>1.80), with 44.91% having triglyceride levels >150. In contrast, the low C-peptide group (<0.90) had 12.50% with triglyceride levels >150. This data suggests a potential association between higher C-peptide levels and elevated triglyceride levels in the study population.
Figure 4: Fasting C-Peptide versus Serum Triglyceride |
The table below displays the mean and standard deviation of RBS levels across different C-peptide categories. The p-value from the Kruskal-Wallis Test, 0.006, indicates a statistically significant difference in RBS levels among the C-peptide groups. The majority of participants, 65.74% of the total sample, fell into the high C-peptide category (>1.80). Among them, 9.72% have RBS levels in the 0.90-1.80 range, and 50.00% had RBS levels above 200. In contrast, participants with low C-peptide levels had a lower percentage in the high RBS category, with 3.24% having RBS levels below 200 and 21.30% having RBS levels above 200. However, when the mean and standard deviation of FBS levels across different C-peptide categories were considered, the p-value from the Kruskal-Wallis test was 0.112, indicating no statistically significant difference in FBS levels among the C-peptide groups.
Fasting C-Peptide (ng/ml) |
RBS |
|
Mean |
SD |
|
<0.90 (Low) |
266.604 |
81.404 |
0.90-1.80 (Normal) |
212.905 |
55.761 |
>1.80 (High) |
262.424 |
90.492 |
Total |
258.618 |
86.535 |
p-value (Kruskal-Wallis Test) |
0.006 |
|
Table 7: Fasting C-Peptide versus Mean Random Blood Sugar Levels |
The fasting C-peptide level in diabetic patients is significantly associated with insulin resistance and anthropometric measures. Anthropometric measures like BMI, waist circumference, and waist-to-hip ratio correlate with fasting C-peptide, linking obesity and insulin resistance. This study aimed to establish this association and involved 216 patients who were diagnosed as suffering from newly diagnosed diabetes. The data showed the maximum number of newly diagnosed diabetics in the 51-60 years (24.1%) and 61-70 years (22.2%) groups. The study by Sosale A. similarly gave the bulk of newly diagnosed type 2 diabetics as 40% in the age group of 41-50 years.[6] Other studies also provided data analysis supporting the bulk of newly diagnosed type 2 diabetics in age groups of 41-60 years, while for type 1 diabetics it was found to be significantly lower at 20-30 years.
Our study measured fasting C-peptide levels (in ng/ml) and categorized cases into three groups: <0.9 (low) with 53 cases (24.5%), 0.9-1.8 (normal) with 21 cases (9.7%), and >1.8 (high) with 142 cases (65.7%). The mean C-peptide value across all cases is calculated to be 3.802.
On evaluating the relationship of fasting C-peptide and age, it was found out that the mean ages of patients in the low, normal, and high C-peptide groups were 47.340±16.7848, 58.810±11.2366, and 59.3311±3.0285 years, respectively. As the C-peptide levels increase from low to high, there is a corresponding increase in mean age. Individuals with low C-peptide levels had a mean age above 50, those with normal C-peptide levels had a mean age above 60, and those with high C-peptide had a mean age close to 60. This trend suggests that higher C-peptide levels are associated with an older age. The association between C-peptide and age was significant (p-value = 0.001). In comparison with prior studies by Iweka FK and Sosale A., it also provided a similar distribution seen in the study population.[6,7]
It was found that C-peptide was directly associated with the body mass index of the patients. The majority (65.74%) of individuals had high C-peptide levels, with the highest prevalence (30.09%) found in the BMI range of 25.0-29.90. Low C-peptide levels were most common in the 25.0-29.90 BMI range (9.72%), while normal levels were least common overall (9.72%), with a fairly even distribution across BMI categories. For individuals with high C-peptide levels (>1.80), the mean BMI was significantly higher at 28.42 with an SD of 4.41. The overall mean BMI across all categories is 27.54 with an SD of 4.49. The chi-square test indicated a significant association between C-peptide levels and BMI categories (X²: 51.355, df: 8, p=0.001).
A study conducted by Nagaratnam S et al. studied 113 participants with recently diagnosed young-onset T2DM and found a significant association between higher C-peptide levels and obesity/BMI.[8] Similarly, another study by Shaomin Shi in type 2 diabetics noted that obesity was a risk factor for DKD, and the effect may be attributable to C-peptide, which represents insulin resistance. Contrasting with these studies, the study by Majaliwa ES et al. investigated the correlation of type 1 diabetes mellitus (T1DM) complications with C-peptide levels in Tanzania and found out that patients with lower C-peptide levels were underweight, but this difference was not significant.[9]
It was found that fasting C-peptide levels were directly associated with higher waist-to-hip ratios (WTH ratios) in both males and females. The majority of females with high C-peptide levels tend to have a waist-to-hip ratio >0.80, indicating a higher prevalence of central obesity in this group. The p-value from the Kruskal-Wallis test was 0.020, indicating that the differences in waist-to-hip ratios among the C-peptide groups were statistically significant. Similarly in males, higher C-peptide levels were associated with a higher waist-to-hip ratio. The p-value from the Kruskal-Wallis test is 0.001, indicating that the differences in waist-to-hip ratios among the C-peptide groups were statistically significant.
Multiple studies have found a significant positive correlation between fasting C-peptide levels and waist-to-hip ratio, indicating that higher WHR-which suggests greater central (abdominal) obesity-is associated with elevated C-peptide levels. This reflects increased insulin secretion in response to insulin resistance linked to central fat accumulation. For example, a study in a Mexican population with metabolic syndrome (MetS) found C-peptide correlated better than insulin with anthropometric measures including WHR, supporting its role as a sensitive marker of metabolic dysregulation.[10]
In the study by Gilsa E S et al,[4] all three anthropometric measurements of obesity-BMI, waist circumference, and waist-to-hip ratio-showed a positive correlation with C-peptide levels. This aligns with a study conducted among Arab females by A. Abdulla et al.[11] and similar reports from other researchers among diabetic patients.[12,13] The present study also reveals a significant positive correlation between the subjects' age and C-peptide levels, consistent with findings by others. In a large Chinese population study, fasting C-peptide was positively associated with waist-to-hip ratio alongside other metabolic syndrome variables.[14]
Studies consistently demonstrate WHR as an important predictor for the development of type 2 diabetes and correlate with poor glycemic parameters, paralleling the association between C-peptide and insulin resistance.[3] WHR is acknowledged as a better marker than BMI for central obesity and is strongly associated with insulin resistance, a key driver of elevated C-peptide secretion. Elevated WHR typically reflects increased visceral adiposity, which exacerbates insulin resistance and thus stimulates greater insulin and C-peptide release from pancreatic beta cells.[15]
Individuals with high C-peptide levels in the present study had higher serum cholesterol and triglyceride levels. In a similar study by Gilsa E S et al,[4] only LDL-C correlates with C-peptide among lipid parameters despite significantly elevated TC and TG levels in the overweight group. Kim et al. and Cho et al. reported a significant association of C-peptide with TG and HDL,[14,16] Banu et al., in their study on patients with metabolic syndrome, demonstrated a significant correlation of TG with C-peptide levels and a progressive increase in insulin resistance with an increase in C-peptide levels, supporting the usefulness of C-peptide in monitoring insulin resistance.[17] A study from central Mexico also identified C-peptide as a sensitive indicator for insulin resistance.[10] However, the multiple linear regression models do not include anthropometric measurements of obesity like BMI and WC as predictors of C-peptide levels, possibly due to the multicollinearity of independent predictors such as age, BMI, WC, and lipid parameters, along with a small sample size. Mariyam et al. report obesity as a significant predictor of C-peptide.[18] The impact of weight gain or reduction on C-peptide levels requires further investigation, and interventions through lifestyle modifications may prove beneficial in reversing metabolic abnormalities associated with insulin resistance.
Our study also compared the association between fasting C-peptide and HbA1c levels across the three groups of fasting C-peptide (low, normal, and high). It was observed that for low C-peptide levels (<0.90), the mean HbA1c was approximately 8.857, compared to 6.971 in the normal group while it showed an increase to about 8.549 in the high C-peptide levels. The p-value from the Kruskal-Wallis test is 0.001, indicating that the differences in HbA1c levels among the C-peptide groups are statistically significant. Several studies demonstrate a significant negative correlation between fasting C-peptide levels and HbA1c in diabetic patients, especially in type 2 diabetes mellitus (T2DM). Lower C-peptide levels (indicating diminished endogenous insulin secretion) tend to correspond with higher HbA1c values, representing poorer glycemic control. This relationship highlights the progressive decline in beta-cell function as diabetes worsens.[19,20]
A study by Kavita Priyadarshani et al.,[19] involving T2DM patients showed fasting C-peptide negatively correlates with HbA1c (r = -0.42, p < 0.001), and postprandial C-peptide also correlates inversely with HbA1c (r = -0.48, p < 0.001).
Similarly, investigation by Ismail HM et al.[21] found that HbA1c correlated inversely with various C-peptide measures including peak and AUC (Area Under the Curve) C-peptide responses, which reflect beta-cell function dynamics during OGTT (Oral Glucose Tolerance Tests). Patients showing a later peak C-peptide response had better (lower) HbA1c levels.
In early- or recent-onset diabetes, higher C-peptide levels might coexist with moderately elevated HbA1c due to insulin resistance. In contrast, long-standing diabetes often shows lower C-peptide with higher HbA1c due to beta-cell exhaustion. In type 1 diabetes, preserved C-peptide secretion correlates with better glycemic control and lower HbA1c, also linked with decreased risks of complications.[22]
Our study also tried to find out the relationship between the serum lipid profile and fasting C-peptide levels. Individuals with high C-peptide levels had higher serum triglyceride levels compared to those with normal and low C-peptide levels. According to the results of the Kruskal-Wallis test in the study, there was a statistically significant difference in serum triglyceride levels among different C-peptide levels, as indicated by the p-value of 0.014. Similarly, the relation between serum VLDL levels and C-peptide levels was significant (p-value<0.05). However, there was no significant association with total cholesterol, HDL and S. LDL levels.
Studies demonstrate that fasting C-peptide levels positively correlate with dyslipidemia characteristics often seen in T2DM (Type 2 Diabetes Mellitus), such as elevated total cholesterol (TC), triglycerides (TG), and LDL-C (Low-Density Lipoprotein Cholesterol). Conversely, similar to our observation, the relationship with HDL-C (High-Density Lipoprotein Cholesterol) is less consistent or insignificant in many observations. For instance, a meta-analysis showed that diabetic patients with low serum C-peptide had significantly higher TC, TG, HbA1c, and LDL-C levels compared to those with normal C-peptide levels, indicating more atherogenic lipid profiles and poorer glycemic control.[23]
Elevated fasting C-peptide reflects hyperinsulinemia secondary to insulin resistance, which influences lipid metabolism by promoting hepatic VLDL (Very-Low-Density Lipoprotein) synthesis and impairing lipoprotein lipase activity, contributing to hypertriglyceridemia and enriching circulating LDL particles. These changes increase cardiovascular risk. C-peptide levels thus indirectly reflect lipid abnormalities associated with insulin resistance.[24]
C-peptide was found to be significantly associated with random blood sugar levels (p-value 0.006) but not with fasting blood sugar levels (p-value- 0.112). Several studies report a positive correlation between fasting C-peptide levels and random blood sugar levels, particularly in T2DM. Elevated random sugar levels often coincide with elevated C-peptide as beta cells increase insulin (and thus C-peptide) secretion to compensate for hyperglycemia and insulin resistance. For example, a cross-sectional study of newly diagnosed T2DM patients found mean FBS and postprandial blood sugar (RBS equivalent) to be elevated alongside high mean C-peptide levels, demonstrating that poor glycemic control is associated with higher endogenous insulin secretion. High random sugar combined with high fasting C-peptide may indicate insulin resistance and retained beta-cell function, guiding treatment towards insulin sensitizers or secretagogues.[25]
Our study also compared the presence of peripheral signs of insulin resistance with fasting C-peptide levels. The statistical analysis shows a p-value of 0.001, indicating a significant association between C-peptide levels and the presence of peripheral signs of insulin resistance. This means that higher levels of C-peptide had higher chances of having peripheral signs of insulin resistance. On the other hand, HbA1c levels didn’t correlate well with the peripheral signs of insulin resistance (p-value >0.05).
Studies show that higher fasting C-peptide levels correlate with the presence and severity of acanthosis nigricans, indicating that elevated endogenous insulin activity (reflected by C-peptide) is linked to this skin manifestation. For example, a research demonstrated that AN severity positively correlated with fasting insulin and C-peptide levels, suggesting that C-peptide can serve as an indirect marker of peripheral insulin resistance manifesting as AN. AN severity also correlates with insulin resistance indices like HOMA-IR, supporting the link between C-peptide, insulin resistance, and peripheral clinical signs.[26] Skin tags (acrochordons), androgenetic alopecia, acne, and hirsutism may also reflect insulin resistance states and elevated insulin and C-peptide levels. These skin changes offer visible indicators that complement biochemical markers like C-peptide.[27]
When observed together, elevated C-peptide levels and peripheral signs suggest a compensatory hyperinsulinemic state secondary to insulin resistance, which may guide early intervention to improve metabolic outcomes. While contributing to a better understanding of the association of fasting C-peptide levels and insulin resistance, our study was not without limitations. While fasting C-peptide is a valuable marker, it should be interpreted alongside clinical parameters, glucose levels, and other metabolic indices for comprehensive assessment. Renal dysfunction affects C-peptide clearance and could confound results. Ethnic and population-specific variations in C-peptide levels and their association with insulin resistance necessitate local validation of cutoffs. Insulin treatment and exogenous insulin use can influence endogenous insulin and C-peptide secretion dynamics. Further studies involving larger, diverse groups of patients addressing these short falls are warranted.
Fasting C-peptide level is strongly associated with insulin resistance and key anthropometric measures in patients with type 2 diabetes mellitus. Elevated C-peptide reflects compensatory hyperinsulinemia in response to peripheral insulin resistance, especially central obesity. Its measurement is clinically useful in assessing beta-cell reserve, insulin resistance, and metabolic risk, helping guide diabetes management and preventive interventions. Integrating fasting C-peptide with anthropometric assessments provides a practical approach to understanding and monitoring diabetic patients' metabolic status.