Charlotta Nilsson

Increased risk for overweight among Swedish children born to mothers with gestational diabetes mellitus.

Investigate the effects of maternal gestational diabetes mellitus (GDM) on height, weight, and body mass index (BMI) in offspring compared both to their siblings and to age‐specific BMI reference values in Sweden. Their parents present BMI was also investigated.

Prevalence of zinc transporter 8 antibodies in gestational diabetes mellitus.

Diabet. Med. 29, e436–e439 (2012)

Outcomes of women with gestational diabetes mellitus in Sweden.

OBJECTIVE The number of women with gestational diabetes mellitus (GDM) during pregnancy is increasing around the world and in our region in the south Sweden 1.2% of all pregnant women received the GDM diagnosis in the 90s and now it is about 2.2%. The aim of this study was to compare women with GDM 1995-99 against women with GDM 2012-13 regarding eventual differences in demographics and pregnancy outcome. STUDY DESIGN In our region in Sweden, all pregnant women are tested for GDM with a 2-h 75g oral glucose tolerance test and the 2-h cut off value for GDM is ≥10.0mmol/l in capillary plasma glucose. 1995-99 there were 131 women with GDM and their medical journals were compared against the 210 women with GDM during 2012-13. The same screening and diagnostic method was uses during the whole time period. RESULTS In the 2012-13 GDM pregnancies there were more non-Scandinavian women, more women with insulin treatment during pregnancy and a higher frequency of cesarean deliveries compared to 1995. First weight of the women during GDM pregnancy 2012-13 was significantly higher than the weight of women with GDM 1995-99, 71kg (43-138; n=201) and 65kg (43-133; n=125) (p=0.008) respectively. However, there was no significant difference in weight of the mother at delivery. Birth weight of the child in GDM pregnancies 1995-99 was 3722.4g±578.2 (n=109; p=0.009), and in GDM pregnancies 2012-13 3555.6g±465.8 (n=162). CONCLUSION Even though women with GDM 2012-13 weigh more when they start the pregnancy there is no difference in weight at delivery compared to women with GDM 1995-99. This is also reflected on the newborn, that 2012-13 had significantly lower birth weight but with the same gestational length as 1995-1999. We believe that this is due to a more active and intense treatment of women with GDM during pregnancy together with higher frequency of cesarean delivery. Prevention of large infants is crucial to avoid complications during delivery.

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.

Towards normalized birthweight in gestational diabetes mellitus.

The objective was to describe pregnancy outcomes in gestational diabetes mellitus (GDM) in comparison with general population in Sweden.

Clinical use of C-peptide and β-cell specific autoantibodies during gestational diabetes mellitus

Gestational diabetes mellitus (GDM) confers a risk for developing type 2 diabetes later in life, but the risk of developing type 1 diabetes is also increased. In this study we have evaluated the clinical use of C‐peptide and β‐cell specific autoantibodies during pregnancy with GDM as predictors for later development of diabetes.

HbA1c levels in children with type 1 diabetes and correlation to diabetic retinopathy

Abstract Background: Type 1 diabetes mellitus (T1D) is a metabolic disease causing hyperglycemia due to β-cell destruction. Despite adequate treatment, complications such as diabetic retinopathy (DR) are common. The first aim was to investigate if acute onset of type 1 diabetes differed between those who had developed retinopathy and who had not after 15 years from diagnosis. The second aim was to investigate if mean glycosylated hemoglobin (HbA1c) levels affect the time to development of DR. Methods: The medical records of all children and adolescents diagnosed with type 1 diabetes during 1993–2001 in our area in Sweden were studied retrospectively and the mean HbA1c each year until the development of retinopathy was investigated. In total 72 patients were included and the follow-up time was between 15 and 23 years. Gender, p-glucose, age and HbA1c at diagnosis were analyzed for possible correlations to years to retinopathy. Results: HbA1c was significantly higher among those who had developed DR after 15 years from diagnosis, 98±9.2 (n=25) vs. 86±9.2 (n=46; p=0.025). A negative correlation was found between age at diagnosis and years to DR (rs=−0.376; p=0.026). Mean HbA1c levels at years 6–10 after diabetes diagnosis correlated significantly (rs=−0.354, p=0.037) to years until retinopathy. Mean HbA1c levels at years 1–15 after diabetes diagnosis were significantly higher at years 2–3 and years 5–8 for those who had developed retinopathy after 15 years from diagnosis. Conclusions: Higher HbA1c levels shortened the time to development of retinopathy. It is therefore important to keep HbA1c as close to normal as possible.

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.