Jonatan Dereke

Prevalence of zinc transporter 8 antibodies in gestational diabetes mellitus.

Diabet. Med. 29, e436–e439 (2012)

Plasma levels of relaxin-2 are higher and correlated to C-peptide levels in early gestational diabetes mellitus

Relaxin-2 is an important gestational hormone in shaping the endometrium in early pregnancy and its secretion peaks during the first trimester [1]. The relaxin family of peptides are structurally found to be similar to insulin and insulinlike growth factors with A-chains and B-chains making up the bioactive molecule [2, 3] and a C-peptide connecting the pre-molecule [4]. A study investigating relaxin levels in women with type 2 diabetes found a correlation between relaxin and insulin sensitivity. Contrarily, a negative correlation between relaxin and beta cell function has been suggested [5]. Another study reported lower levels of relaxin-2 but not of relaxin-3 in patients with recent onset type 2 diabetes. This data combined would suggest that relaxin-2 could be involved in the pathophysiology of type 2 diabetes and beneficial in increasing insulin sensitivity in patients with insulin resistance [6]. Pregnancy is a normal state of insulin resistance which ensures continuous glucose transport to the fetus. Women are however not normally hyperglycemic during pregnancy. If hyperglycemic, the women are diagnosed with gestational diabetes mellitus [7]. There are currently no reports on levels of relaxin-2 in gestational diabetes mellitus. The aim of this study was to investigate plasma levels of relaxin-2 in patients with gestational diabetes mellitus, in comparison to pregnant controls without diabetes.

The significance of biomarkers such as FABP4 in gestational diabetes mellitus and the importance of rigorous peer review

performed in the statistical software Graph Pad Prism, but the ROC curve analysis is apparently made using another statistical software clearly indicating that this section has not been carefully evaluated. All data in the study are presented as mean ± standard deviation with comparisons performed with the Students’ T test although soluble biomarkers are rarely normally distributed and any parametric tests performed for non-normally distributed data will be skewed. A clear presentation of the sample handling and preparation is essential if the reader is to draw any conclusion from the results of a study. This is, however, poorly described in the paper where the authors do not describe the collection process, the time and temperature regarding the sample storage nor time from sample collection to analysis. This could affect the stability and level of cytokines and possibly other biomarkers [2]. It is also unclear whether FABP4 has been analysed in serum or plasma as the title states plasma, while the results state serum. It is important to clearly state in which type of sample the analysis has been made in order to be able to confirm the results of the study. Further there are clear discrepancies between Table 1 and the first paragraph on page 894 regarding LGA and Apgar score. This is of particular importance since Table 1 states statistically significant differences for these variables. The authors mention that serum levels of FABP4 have previously been observed in a small study made on patients with GDM [3], while other and more comprehensive studies also have investigated circulating FABP4 levels in GDM without being discussed [4, 5]. Relating and discussing the findings in this study to the other previous studies would give the reader a better understanding of the merit and addition made by the present study regarding FABP4 in GDM. Dear Editor-in-chief We appreciate that biomarkers in gestational diabetes mellitus (GDM) recently have gained increased interest. Diagnostic criteria for GDM are still debated. It is important to find reliable diagnostic tools to complement blood glucose measurement in early GDM since diabetes during pregnancy is associated with adverse outcome for both mother and child. In their case–control study, Dr Ning et al. [1] suggested plasma fatty acid-binding protein 4 (FABP4) to be elevated in women with GDM. By performing a receiver operating characteristics (ROC) curve analysis, they have identified FABP4 as a potential novel predictor of GDM. Even though the reported results are credible, there are several issues that need to be addressed which should have been acknowledged already during the peer review process. In order to properly evaluate the scientific conclusions from a study, the scientific and statistical methods should be clearly presented to the reader. Sometimes the reviewers seem to underestimate the value of correct statistical methods, and in this case, the section describing the statistical analysis seems to have been overlooked in the review process. First of all, serum calprotectin concentrations are mentioned despite the fact that they have not been analysed in this study. Secondly, the authors state that ANOVA has been performed for multiple comparisons despite the fact that ANOVA has not been used in the study. Thirdly, the authors claim that all statistical analyses have been

Depression in type 1 diabetes was associated with high levels of circulating galectin-3

Objective Neuroinflammatory responses are implicated in depression. The aim was to explore whether depression in patients with type 1 diabetes (T1D) was associated with high circulating galectin-3, controlling for metabolic variables, s-creatinine, life style factors, medication and cardiovascular complications. Design Cross-sectional. Methods Participants were T1D patients (n = 283, 56% men, age 18–59 years, diabetes duration ≥1 year). Depression was assessed by Hospital Anxiety and Depression Scale-depression subscale. Blood samples, anthropometrics and blood pressure were collected, and supplemented with data from medical records and the Swedish National Diabetes Registry. Galectin-3 ≥2.562 µg/l, corresponding to the 85th percentile, was defined as high galectin-3. Results Median (quartile1, quartile3) galectin-3 (µg/l) was 1.3 (0.8, 2.9) for the 30 depressed patients, and 0.9 (0.5, 1.6) for the 253 non-depressed, P = 0.009. Depression was associated with high galectin-3 in all the 283 patients (adjusted odds ratio (AOR) 3.5), in the 161 men (AOR 3.4), and in the 122 women (AOR 3.9). HbA1c, s-lipids, s-creatinine, blood pressure, obesity, smoking, physical inactivity, cardiovascular complications and drugs (antihypertensive, lipid lowering, oral antidiabetic drugs and antidepressants) were not associated with high galectin-3. Conclusions This is the first study to show an association between depression and galectin-3. Depression was the only explored parameter associated with high circulating galectin-3 levels in 283 T1D patients. High galectin-3 levels might contribute to the increased risk for Alzheimer’s disease, cardiovascular and all-cause mortality observed in persons with depression. Potentially, in the future, treatment targeting galactin-3 might improve the prognosis for patients with high galectin-3 levels.

Plasma levels of the interleukin-1-receptor antagonist are lower in women with gestational diabetes mellitus and are particularly associated with postpartum development of type 2 diabetes

Diabetes mellitus is a group of diseases characterized by chronic hyperglycemia. Women who develops hyperglycemia for the first time during pregnancy receive the diagnosis gestational diabetes mellitus (GDM). Presently, there is no consensus about the diagnostic criteria for GDM. A majority of these women subsequently develop postpartum overt diabetes making it important to identify these patients as early as possible. In this study we investigated if plasma levels of the interleukin-1 receptor antagonist (IL-1Ra), an endogenous inhibitor of IL-1 signaling, can be used as a complementary biomarker for diagnosing GDM and predicting postpartum development of overt diabetes mellitus. Patients participating in this study (n = 227) were diagnosed with their first GDM 2004–2013 at Lund University Hospital, Lund, Sweden. Healthy pregnant volunteers (n = 156) were recruited from women’s welfare centers in the same region 2014–2015. Levels of IL-1Ra and C-peptide were analyzed in ethylenediaminetetraacetic acid (EDTA)-plasma or serum using enzyme linked immunosorbent assay (ELISA). GDM patients had significantly lower levels of IL-1Ra than the control group (p = 0.012). In addition, GDM patients that had developed impaired glucose tolerance (IGT) or type 2 diabetes mellitus postpartum had significantly lower levels of IL-1Ra, and significantly higher levels of C-peptide than GDM patients that had not developed diabetes mellitus postpartum (p = 0.023) and (p = 0.0011) respectively. An inverse correlation was found between IL-1Ra and serum C-peptide levels in the control group (rs = -0.31 p = 0.0001). Our results show that IL-1Ra might be included in a future panel of biomarkers, both for diagnosing GDM to complement blood glucose, and also identifying GDM patients that are at risk of developing type 2 diabetes mellitus postpartum. However, the ROC curve analysis provided a sensitivity of 52.2% and specificity of 67.1%, which nonetheless may not be sufficient enough to use IL-1Ra as a sole biomarker.

IgG4 subclass glutamic acid decarboxylase antibodies (GADA) are associated with a reduced risk of developing type 1 diabetes as well as increased C-peptide levels in GADA positive gestational diabetes.

Some women with gestational diabetes (GDM) present with autoantibodies associated with type 1 diabetes. These are usually directed against glutamic acid decarboxylase (GADA) and suggested to predict development of type 1 diabetes. The primary aim of this study was to investigate if GADA IgG subclasses at onset of GDM could assist in predicting postpartum development. Of 1225 women diagnosed with first-time GDM only 51 were GADA-positive. Total GADA was determined using ELISA. GADA subclasses were determined with radioimmunoassay. Approximately 25% of GADA-positive women developed type 1 diabetes postpartum. Titers of total GADA were higher in women that developed type 1 diabetes (142.1 vs 74.2u/mL; p=0.04) and they also had lower titers of GADA IgG4 (index=0.01 vs 0.04; p=0.03). In conclusion we found that that women with high titers of total GADA but low titers of GADA IgG4 were more prone to develop type 1 diabetes postpartum.