C-peptide levels measured during an oral glucose tolerance test at 16 to 18 weeks of pregnancy predicted which patients later developed gestational diabetes mellitus at 24 to 28 weeks, according to researchers in the United Kingdom. C-peptide at 30 and 60 minutes discriminated between patients who progressed to gestational diabetes mellitus and those who remained normal glucose tolerant. Insulin and proinsulin did not show predictive value.

The prospective study included 83 pregnant patients with at least one gestational diabetes mellitus (GDM) risk factor. These risk factors included body mass index greater than 30 kg/m², prior GDM, a history of a macrosomic baby, or a first-degree relative with type 2 diabetes. Participants completed a 75-g oral glucose tolerance test (OGTT) at 16 to 18 weeks and again at 24 to 28 weeks. Diagnosis of GDM at the second visit followed United Kingdom National Institute for Health and Care Excellence criteria: fasting plasma glucose ≥5.6 mmol/L or 2-hour plasma glucose ≥7.8 mmol/L.

Twelve patients met diagnostic thresholds for GDM at the first visit and were excluded, while five did not return for the second test. Of the 66 patients who completed follow-up, 15 developed GDM and 51 remained normal glucose tolerant. Patients who progressed were older at baseline, averaging 34 years compared with 30 years in the normal group. At 16 to 18 weeks, fasting, 30-minute, and 120-minute glucose values were similar, but 60-minute glucose was higher among patients who later developed GDM. Only C-peptide at 30 and 60 minutes predicted progression.

“Pregnancy is initially associated with a decrease in insulin resistance which promotes glucose uptake in preparation for the rapid fetus growth phase in late pregnancy,” said Gareth Dunseath, PhD, of Swansea University Faculty of Medicine, Health and Life Science. He noted that when pancreatic beta cells fail to compensate later in gestation, hyperglycemia develops.

Researchers had planned to enroll 200 patients to ensure adequate statistical power, assuming a 30% prevalence of GDM in this high-risk group. Recruitment ended early because of the COVID-19 pandemic, which reduced the use of OGTT in local practice. This smaller sample size limited statistical power and was cited as the main limitation. Other limitations included the single-center design and lack of ethnic diversity. In addition, “further studies in a larger cohort will be needed to validate these findings,” Dr. Dunseath said.

The researchers concluded that early C-peptide measurement could help identify patients at risk of developing GDM prior to the conventional diagnostic window, though larger studies are needed to confirm these findings.

The authors reported no conflicts of interest.

Source: BMJ Open