Longitudinal plasma protein profiling of newly diagnosed type 2 diabetes

Abstract

Background Comprehensive proteomics profiling may offer new insights into the dysregulated metabolic milieu of type 2 diabetes, and in the future, serve as a useful tool for personalized medicine. This calls for a better understanding of circulating protein patterns at the early stage of type 2 diabetes as well as the dynamics of protein patterns during changes in metabolic status. Methods To elucidate the systemic alterations in early-stage diabetes and to investigate the effects on the proteome during metabolic improvement, we measured 974 circulating proteins in 52 newly diagnosed, treatment-naïve type 2 diabetes subjects at baseline and after 1 and 3 months of guideline-based diabetes treatment, while comparing their protein profiles to that of 94 subjects without diabetes. Findings Early stage type 2 diabetes was associated with distinct protein patterns, reflecting key metabolic syndrome features including insulin resistance, adiposity, hyperglycemia and liver steatosis. The protein profiles at baseline were attenuated during guideline-based diabetes treatment and several plasma proteins associated with metformin medication independently of metabolic variables, such as circulating EPCAM. Interpretation The results advance our knowledge about the biochemical manifestations of type 2 diabetes and suggest that comprehensive protein profiling may serve as a useful tool for metabolic phenotyping and for elucidating the biological effects of diabetes treatments. Funding This work was supported by the Swedish Heart and Lung Foundation, the Swedish Research Council, the Erling Persson Foundation, the Knut and Alice Wallenberg Foundation, and the Swedish state under the agreement between the Swedish government and the county councils (ALF-agreement).

Next generation plasma proteome profiling to monitor health and disease

“…The characteristics of T2D and its association with the epidemic of obesity have been extensively studied, but relatively little is known about the incidence of lean diabetes and the progression of disease during treatment 28 . The results presented here support the notion that broad biochemical alterations are present already at the onset of type 2 diabetes and that protein profiling could deliver individualized health assessments of cardiometabolic diseases 4 , 17 . The anthropometrical parameters of the T2D cohort allowed us to stratify the patients into two distinct groups based on BMI and an analysis of the protein profiles between the health individuals and the T2D patients at base line (visit 1) revealed several proteins, that could be useful for early detection of disease based solely on protein profiles.…”

“…The complete list of assessed clinical variables is available in Supplementary Data 2 . The second cohort (type 2 diabetes) consisted of 48 individuals also recruited from the SCAPIS study, with no history of diabetes, and who were diagnosed during the population-based screening 17 . The sample collection in combination with clinical chemistry analysis of 30 parameters as described in the wellness study, anthropometric measurements as well as analysis of insulin, C-peptide, and the homeostatic model assessment of insulin resistance (HOMA-IR) were conducted at the start of the trial (visit 1) and after approximately 1 month (visit 2) and 3 months (visit 3) of treatment (Fig.…”

“…The T2D study is an extension of the S3WP study with the aim to perform molecular phenotyping of T2D before and after diabetes treatment 17 . Fifty-two subjects at age between 50 and 65 years with no history of diabetes and diagnosed during population-based screening examinations were enrolled from the Sahlgrenska University Hospital, Gothenburg, from 2016 to 2018.…”

Periodontitis is associated to increased systemic inflammation in postmyocardial infarction patients

“… 30 Similarly, plasma expression of HGF, IL-6, FGF-21, CDCP1 and IL-18R1 have been identified among the top 30 proteins associated with newly diagnosed type 2 diabetes. 31 It is interesting to note that four of the proteins increased in diabetes were also increased in patients with MI deep periodontal pockets. We have previously reported in the PAROKRANK cohort that undetected diabetes was more frequent among participants with severe periodontitis.…”

Next generation plasma proteome profiling of COVID-19 patients with mild to moderate symptoms

“…An important effort to understand the biology of the host-virus response is to move towards comprehensive proteome profiling of host proteins in blood in response to viral infections, not only to understand the basis for disease, but also to facilitate precision medicine efforts aimed at stratification and monitoring of patients before and during therapeutic interventions (Gummesson et al , 2021; Zhong et al , 2021; Zhong et al , 2020). The objective is thus to probe the circulating plasma proteome of individuals with sensitive and specific assays that can allow massive sample throughput.…”