According to the World Health Organization (WHO), in 2014, there were estimated to be a total of 422 million adult individuals with diabetes mellitus (8.5% of the world's population) [1]. In Portugal, the prevalence of diabetes mellitus was estimated to be 13.6% in 2018 by the National Diabetes Observatory (OND) [2].
Diabetes mellitus includes a set of metabolic alterations characterized by the presence of sustained hyperglycemia in the absence of hypoglycemic therapy. The etiopathogenesis of the disease includes an impairment of insulin secretion and/or action, which leads to changes in the metabolism of the different macronutrients: carbohydrates, lipids, and proteins. There are several types of diabetes, the most common being type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM). On the one hand, T1DM destruction of β-cell takes place through an immune-mediated process, with the presence of autoantibodies in 70 to 90% of the cases [3, 4]. On the other hand, in T2DM there is an initial insulin resistance followed by pancreatic β dysfunction, subsequently compromising insulin secretion [5].
T1DM is one of the most common endocrine and metabolic conditions occurring in childhood. The pathogenesis of T1DM can be divided into stages that relate to the detection of autoantibodies and progress to β-cell destruction, dysglycemia, and, finally, symptoms associated with hyperglycemia [6].
The ultimate goal of insulin therapy is to mimic normal insulin secretion. Intensive insulin replacement therapy is currently the mainstream therapy in T1DM. In most people with T1DM, β cells are destroyed after a short honeymoon period, between 1 and 2 years after diagnosis. However, the pancreatic β cell may still retain some functional viability decades after the beginning of the diagnosis of T1DM [7].
C-peptide is secreted in an equimolar ratio of 1:1 for an insulin molecule, representing an indirect measure of endogenous insulin secretion. C-peptide, compared to insulin, has a longer half-life and negligible hepatic metabolization, which translates into systemic circulating levels about 5 times higher. Its measurement in clinical practice has a great interest in the diagnosis and classification of diabetes, being an economically accessible, widely available, and reliable method. In recent years, the usefulness of measuring C-peptide in patients with T1DM has been investigated, since its residual secretion may have clinical implications in the course of the disease, particularly in the therapeutic strategies to be adopted during follow-up [8].
Significant residual secretion of C-peptide is more frequent in adult patients, ranging from 36% in the first 5 years to 22% 20 years after diagnosis [9]. During the first 7 years of diagnosis, there is an abrupt drop in C-peptide values, with further stabilization in subsequent years [10].
Intensive insulin therapy, based on data from the Diabetes Control and Complications Trial (DCCT), seems to prolong the duration of the persistence of C-peptide in people with T1DM. This preserved C-peptide secretion was associated with a lower number of severe hypoglycemia, a lower number of microvascular complications, lower absolute HbA1c value, and lower insulin requirements [11, 12]. Regarding new glucose metrics, such as glycemic variability, data are scarcer although they point to lower glycemic variability in patients with preserved C-peptide secretion [13].
The proposed work aims to study the effect of the persistence of measurable C-peptide values on new glucose metrics obtained through interstitial glucose monitoring, namely on glycemic variability, as well as on the development of acute and chronic complications in adult patients with T1DM.