NASH more likely, liver fibrosis less likely with increasing C-peptide levels in type 2 diabetes

Adults with type 2 diabetes and higher C-peptide levels are more likely to develop simple nonalcoholic fatty liver disease and nonalcoholic steatohepatitis compared with those with lower levels, according to findings published in Diabetes Metabolism Research and Reviews. In contrast, those with higher C-peptide levels are less likely to have advanced fibrosis.

“There were significant but opposite associations between C-peptide level and the inflammatory and fibrotic progression of NAFLD,” Yingli Lu, MD, PhD, of the department of endocrinology and metabolism at Shanghai Ninth Hospital and Shanghai Jiao Tong University School of Medicine in Shanghai, and colleagues wrote. “In patients with type 2 diabetes, Cpeptide may play different roles in these two processes.”

Lu and colleagues conducted a cross-sectional study with 4,120 adults with type 2 diabetes from the Huangpu and Pudong Districts in Shanghai (mean age, 67 years; 56.5% women). C-peptide, total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, fasting plasma glucose, alanine aminotransferase and aspartate aminotransferase were measured from blood samples. The researchers also recorded waist circumference and blood pressure to establish the presence of metabolic syndrome and used ultrasound to evaluate steatosis.

Participants with metabolic syndrome and NAFLD were considered to have probable NASH (n = 2,345) while those with NAFLD alone had simple NAFLD (n = 537). Compared with those with C-peptide levels of 1.12 ng/mL or less, probable NASH was more likely to be identified in participants with C-peptide levels of at least 2.06 ng/mL (OR = 5.28; 95% CI, 3.94-7.09) and those with levels between 1.53 and 2.05 ng/mL (OR = 3.95; 95% CI, 3.06-5.12) and 1.13 and 1.52 ng/mL (OR = 1.91; 95% CI, 1.5-2.44). According to the researchers, the odds of presenting with probable NASH were higher with every standard deviation increase in C-peptide (OR = 1.97; 95% CI, 1.76-2.2).

Simple NAFLD was more likely to be identified in those with C-peptide levels of at least 2.06 ng/mL (OR = 4.55; 95% CI, 3.16-6.), between 1.53 and 2.05 ng/mL (OR = 3.21; 95% CI, 2.34-4.39) and between 1.13 and 1.52 ng/mL (OR = 2.08; 95% CI, 1.57-2.75) compared with those with lower levels. The odds of presenting with simple NAFLD were heightened with each standard deviation increase in C-peptide (OR = 1.78; 95 CI, 1.56-2.04).

Inflammatory progression was also more likely to occur for those with C-peptide levels of 2.06 ng/mL or more (OR = 2.2; 95 CI, 1.-.5) as well as those with levels between 1.53 and 2.05 ng/mL (OR = 1.92; 95% CI, 1.7-2.16) and those with levels between 1.13 and 1.52 ng/mL (OR = 1.36; 95% CI, 1.21-1.52) compared with those with lower levels. The odds of inflammatory progression were 1.34 times higher for every standard deviation increase in C-peptide (OR = 1.34; 95% CI, 1.2-1.41).

 

Fibrosis status was evaluated using the NAFLD fibrosis score, which identified 485 participants with “a probable presence of advanced fibrosis.” The odds of were lower for those with C-peptide levels of at least 2.23 ng/mL (OR = 0.59; 95 CI, 0.36-0.97), between 1.72 and 2.22 ng/mL (OR = 0.6; 95% CI, 0.38-0.96) and between 1.3 and 1.71 ng/mL (OR = 0.56; 95% CI, 0.35-0.9) compared with those with lower levels. The odds of presenting with advanced fibrosis were 20% lower for every standard deviation increase in C-peptide (OR = 0.8; 95% CI, 0.65-0.98).

The researchers also found that fibrotic progression odds were lower for those with C-peptide levels of at least 2.23 ng/mL (OR = 0.74; 95 CI, 0.57-0.97), between 1.72 and 2.22 ng/mL (OR = 0.77; 95% CI, 0.6-0.99) and between 1.3 and 1.71 ng/mL (OR = 0.74; 95 CI, 0.58-0.94) compared with those with lower levels. The odds of fibrotic progression were 12% lower for every standard deviation increase in C-peptide (OR = 0.88; 95% CI, 0.79-0.98).

“Our results indicated that islet function might significantly interact with the progression of NAFLD, including inflammation and fibrosis, in diabetic adults,” the researchers wrote. “Further understanding of the relationship between [beta] islet cells and liver tissue may help to personalize treatment strategies of NAFLD patients with type 2 diabetes.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.