Source: Medicine, by Khalid Siddiqui; Salini S Joy; Shaik Sarfaraz Nawaz; Teena P George; Satish Kumar David; Muhammad Mujammami; Assim A Alfadda; Mohamed Rafiullah (August 21, 2026). AI-generated summary by biochip.com, published . Not independently reviewed.
Key takeaways
- Among 91 adults with type 2 diabetes, 58 with complications had significantly higher C-peptide levels than 33 without complications.
- Participants with complications also had higher body mass index, triglycerides, resistin, TNF alpha, TyG index, and triglyceride-to-HDL cholesterol ratio.
- The cross-sectional study cannot determine whether higher C-peptide precedes, causes, or results from diabetic complications.
Researchers at King Saud University examined whether fasting C-peptide, a molecule released when the pancreas makes insulin, tracks with insulin resistance in adults with type 2 diabetes. Their cross-sectional study included 91 people, 58 with diabetic complications and 33 without them. Participants with complications had higher C-peptide levels than those without complications, alongside higher body mass index, triglycerides, resistin, tumor necrosis factor alpha, and two surrogate measures of insulin resistance. The team measured blood markers after an overnight fast using a Randox Evidence biochip analyzer and calculated insulin-resistance and beta-cell-function estimates with the HOMA 2 calculator. Type 2 diabetes develops through a mix of insulin resistance, in which body tissues respond poorly to insulin, and beta-cell dysfunction, in which pancreatic cells cannot produce enough insulin. C-peptide may help clarify where a person sits in that changing balance because it is released in equal amounts with the body's own insulin. The work therefore connects a routinely measurable marker of insulin production with the metabolic and inflammatory changes seen in people who already have diabetes-related complications. It does not establish that elevated C-peptide causes those complications, but it identifies an association worth testing in larger, longer studies.
A companion signal to insulin
Think of insulin and C-peptide as two items that leave the same factory in the same package. Pancreatic beta cells first make proinsulin, then split it into active insulin and C-peptide before releasing both into the bloodstream. Measuring C-peptide can therefore indicate how much insulin the body itself is producing, rather than measuring injected insulin used as a medication.
That distinction matters in type 2 diabetes. Early in the disease, the pancreas may compensate for insulin resistance by producing more insulin. Over time, beta cells can lose their ability to keep pace, leaving blood glucose high even when the body needs more insulin.
Comparing people with and without complications
The study enrolled 91 participants with type 2 diabetes and divided them according to whether they had diabetic complications. Thirty-three participants had no complications, while 58 had complications. The researchers collected clinical information, routine biochemical measurements, and fasting serum samples after participants had fasted overnight.
The group with complications had significantly higher body mass index and triglycerides, a type of blood fat. It also had higher concentrations of C-peptide, resistin, and tumor necrosis factor alpha, often shortened to TNF alpha. Resistin is a signaling protein linked to metabolic regulation, while TNF alpha is an inflammatory signaling protein that can interfere with insulin action.
Looking at insulin resistance from several angles
Insulin resistance is not usually measured directly in routine care because the most precise tests are labor-intensive. Instead, the team used calculated indicators, including the homeostatic model assessment, or HOMA 2, which estimates insulin resistance and beta-cell function from fasting glucose and insulin-related measurements. It is a bit like estimating a car's fuel efficiency from distance and fuel used, rather than taking apart the engine.
They also calculated the triglyceride-glucose, or TyG, index and the triglyceride-to-high-density-lipoprotein cholesterol ratio. Both are indirect metabolic signals that combine blood-fat and glucose measurements. The complication group had higher TyG values and higher triglyceride-to-HDL cholesterol ratios, reinforcing the pattern of greater metabolic disturbance in that group.
Accounting for factors that can blur the picture
Diabetes biology is rarely explained by one blood marker. To examine the relationship between C-peptide and insulin-resistance indicators, the investigators used multiple linear regression, a statistical approach that assesses a relationship while accounting for other variables that may influence it. Their adjustment models included age, sex, diabetes duration, body mass index, systolic blood pressure, low-density-lipoprotein cholesterol, glycated hemoglobin, TNF alpha, and use of metformin or sulfonylurea medications.
Glycated hemoglobin, known as HbA1c, reflects average blood glucose over roughly the preceding two to three months. Including it is important because long-term glucose exposure could be related both to diabetes complications and to how hard beta cells must work. Medication use also matters, since glucose-lowering therapies can change insulin secretion and blood glucose levels.
What the association can and cannot tell us
The findings fit a plausible picture of type 2 diabetes in which people with complications show higher fasting C-peptide together with markers associated with insulin resistance, unfavorable blood fats, and inflammation. Higher C-peptide in this setting may reflect beta cells working harder to compensate for tissues that have become less responsive to insulin. But C-peptide is not a simple scorecard of health because its meaning can depend on disease stage, glucose levels, medication use, and residual beta-cell capacity.
The study used a cross-sectional design, meaning measurements were taken at one point in time. That design can reveal patterns between groups but cannot show which change came first. A high C-peptide result might precede complications, accompany them, or result from metabolic changes connected to them.
Why This Matters
Diabetes complications are often discussed as consequences of high glucose alone, yet this study highlights a broader metabolic pattern involving insulin production, insulin resistance, circulating fats, and inflammatory signals. C-peptide is particularly interesting because it is already measurable in blood and offers a window into endogenous insulin secretion. Pairing it with established clinical measures could help researchers better characterize the different metabolic profiles hidden under the broad diagnosis of type 2 diabetes.
The next step is to follow people over time and determine whether C-peptide levels, alone or combined with insulin-resistance measures, predict who develops complications or whose beta-cell function declines. Studies that include larger and more diverse patient groups could also test how medications and disease duration alter these relationships. For now, the King Saud University team's results support treating C-peptide as a useful research signal within the complex biology of type 2 diabetes, rather than as a stand-alone answer.