Claes Ignell

Trends in the prevalence of gestational diabetes mellitus in southern Sweden, 2003-2012.

There is accumulating evidence that gestational diabetes is a growing problem. The lack of internationally standardized diagnostic procedures prevents consistent diagnosis and the burden of gestational diabetes must be determined in country‐specific studies. In southern Sweden, gestational diabetes is defined as a 2‐h capillary plasma glucose concentration of ≥10.0 mmol/L during a universal 75‐g oral glucose tolerance test. We report the crude prevalence of gestational diabetes during the years 2003–2012. Of 156 144 women who gave birth, 2.2% were diagnosed with gestational diabetes. When the effect of time on the prevalence of gestational diabetes was assessed in a log‐linear Poisson model, an overall increase in prevalence of 35% was predicted, corresponding to an average annual increase of 3.4%. Predicted prevalence was 1.9 (95% CI 1.8–2.0) in 2003 and 2.6 (95% CI 2.4–2.7) in 2012 (p < 0.0001). Due to a simultaneous rise in birth rate, the number of women diagnosed with gestational diabetes increased by 64%.

Evaluation of the relationship between capillary and venous plasma glucose concentrations obtained by the HemoCue Glucose 201+ system during an oral glucose tolerance test

Abstract In 55 women with previous gestational diabetes mellitus, simultaneous capillary and venous plasma glucose concentrations were measured at 0, 30 and 120 min during a 75 g oral glucose tolerance test (OGTT). The aims of the study were to examine the relationship between capillary and venous glucose measurements, and to establish equations for the conversion of capillary and venous glucose concentrations using the HemoCue Glucose 201+ system. Additionally, the correlation between the capillary and venous glucose concentrations with the diagnostic cut-off limits proposed by the World Health Organization (WHO) in 1999 was evaluated. Capillary glucose concentrations were consistently higher than venous glucose concentrations at all time points of the OGTT (p < 0.001), and the correlations between the measurements were statistically highly significant (p < 0.001). The differences between the samples were greatest in the non-fasting state as revealed by the 95% prediction intervals (mmol/L) in Bland-Altman plots; ± 0.54 at 0 min, ± 2.01 at 30 min, and ± 1.35 at 120 min. Equivalence values for capillary plasma glucose concentrations derived from this study tended to be higher than those proposed by the WHO as diagnostic cut-off limits. Stratifying subjects by glucose tolerance status according to the WHO criteria revealed disagreements related to glucose values close to the diagnostic cut-off points. The study findings highlight the uncertainty associated with derived equivalence values. However, capillary plasma glucose measurements could be suitable for diagnostic purposes in epidemiological studies and when translating results on a group basis.

HbA1c as a predictor of diabetes after gestational diabetes mellitus

AIM We wanted to investigate third-trimester HbA1c as a predictor of diabetes after gestational diabetes mellitus (GDM). METHODS Women with GDM were followed up prospectively for five years from pregnancy to detect the development of diabetes. The ability of HbA1c to predict diabetes was evaluated with receiver-operating characteristic (ROC) curves and logistic regression analysis. RESULTS By five years, 73 of 196 women had been diagnosed with diabetes. An optimal cut-off point for HbA1c of 36mmol/mol (5.4%) could predict diabetes with 45% sensitivity and 92% specificity. For HbA1c ≥39mmol/mol (≥5.7%), sensitivity, specificity, and positive predictive value were 30%, 97%, and 91%, respectively. In logistic regression analysis, adjusting for the diagnostic glucose concentration during pregnancy, HbA1c levels in the upper quartile (≥36mmol/mol) were associated with a 5.5-fold increased risk of diabetes. CONCLUSION Third-trimester HbA1c levels in the pre-diabetes range revealed women with post-partum diabetes with high specificity and high positive predictive value. HbA1c testing could be used as a strategy to select high-risk women for lifestyle interventions aimed at prevention of diabetes starting during pregnancy. The results should encourage further validation in other populations using new diagnostic criteria for GDM.

Seasonal Pattern in the Diagnosis of Gestational Diabetes Mellitus in Southern Sweden

Aim. The aim of this study was to examine seasonal patterns in glucose tolerance and in the diagnosis of gestational diabetes mellitus (GDM). Methods. Altogether, 11 538 women underwent a 75-g oral glucose tolerance test (OGTT) in the twenty-eighth week of pregnancy during the years 2003–2005 in southern Sweden. GDM was defined by the 2-h capillary glucose concentration in the OGTT (≥8.9 mmol/L). Chi-squared test, analysis of variance, and regression analyses were used for statistical evaluations. Results. The seasonal frequency of GDM ranged from 3.3% in spring to 5.5% in summer (p < 0.0001). Mean 2-h glucose concentrations followed the same seasonal trend, with a difference of 0.15 mmol/L between winter and summer (p < 0.0001). The 2-h glucose level increased by 0.009 mmol/L for every degree increase in temperature (p < 0.0001). In regression analysis, summer (June–August) was associated with increased 2-h glucose level (p < 0.001) and increased frequency of GDM compared to the other seasons (odds ratio 1.51, 95% confidence interval 1.24–1.83, and p < 0.001). Conclusions. Our findings suggest seasonal variation in the 2-h glucose concentration in the OGTT and in the proportion of women diagnosed with GDM, with a peak in the summer.

Role of HbA1c in post-partum screening of women with gestational diabetes mellitus

Aim To compare the performance of HbA1c with established glucose criteria during an oral glucose tolerance test (OGTT) and to assess HbA1c as a screening test for undiagnosed diabetes and pre-diabetes after gestational diabetes mellitus (GDM). Methods Glucose homeostasis was re-evaluated 1–5 years after delivery in 140 women with previous GDM, by means of OGTT and simultaneous HbA1c measurement. Glucose tolerance was defined according to World Health Organisation criteria. HbA1c ≥6.5% (≥48 mmol/mol) was used for diabetes diagnosis and HbA1c ≥5.7% (≥39 mmol/mol) to define abnormal glucose homeostasis. Results HbA1c had low sensitivity (14.3%) and high specificity (99.1%) in diabetes diagnosis. Sensitivity and specificity of HbA1c to detect abnormal glucose tolerance were 29.5% and 95.2%, respectively. The consistency in classifying abnormal glucose tolerance between HbA1c and OGTT criteria was 59% (κ = 0.227) and the area under the receiver operating characteristic curve was 0.708. The combined use of HbA1c and fasting glucose criteria showed similar performance to that of fasting glucose criteria alone. The latter identified 63% of the women with pre-diabetes or diabetes in the study cohort. However, by lowering the cut-point of HbA1c to ≥5.0% (≥31 mmol/mol), an additional proportion (27%) with isolated post-glucose load hyperglycaemia was identified. Conclusion Proposed thresholds of HbA1c had low diagnostic sensitivity. Combined with a fasting glucose test, the performance was no better than with using a fasting glucose test alone. Combining a fasting glucose test with a lower HbA1c cut-point may be an alternative approach for selection of women for an OGTT.

Health consequences of premature birth revisited – what have we learned?

The survival of prematurely born babies is, to a large extent, a modern phenomenon over the last 20–30 years, and it reflects improvements in obstetric routines and neonatal care. A growing number of children now survive into early adulthood, and this has been the focus of a number of follow-up analyses on somatic and mental health outcomes, as well as psychological scoring. As the incidence of prematurity in a country such as Sweden is 6%, according to the Swedish Medical Birth Register (accessed 4 May 2017), an accumulation of survivors has now reached early adulthood. Previous fears for poor health conditions in general following premature birth have not been supported, as documented by systematic reviews. In this issue of Acta Paediatrica, Raju et al. summarised the updated evidence on prematurity and health, based on a number of reports and systematic reviews (1). They concluded that even if the risk of some adverse health consequences had increased following premature birth, the general impression was that the prognosis had improved for each extra gestational week and that this was a reflection of the better standards of medical care that are now offered. It is also of special interest to elucidate on the mechanisms behind the link between prematurity and, for example, increased cardiovascular risk. Studies by Bonamy, later Edstedt Bonamy et al. investigated the vascular structure and arterial wall morphology in prematurely born children and compared them to children born at term (2,3). They reported that carotid artery elasticity and structure were not altered after preterm birth (2). A further finding was that very preterm birth, as well as exposure to maternal smoking in foetal life, was independent and strong risk factors for general aortic narrowing 15 years after birth (3). Other authors have found that children born preterm were characterised by decreased elastic properties of the descending abdominal aorta, which were potentially attributable to the impaired viscoelastic properties of the aorta and lipid damage (4). A Canadian group reported that transient neonatal high oxygen exposure led to vascular wall alterations, namely a decreased elastin/collagen ratio and a shift in the balance towards increased deposition of collagen, which were associated with increased rigidity. It is important to note that such changes are present before the elevation of blood pressure and vascular dysfunction (5), and this could increase the risk of arterial stiffness and vascular ageing in adult life. Regarding blood pressure regulation, prematurity has been linked to increased blood pressure and to reduced capillary function, which was linked to specific biomarker profiles (6). This could contribute to an increased cardiovascular risk in prematurely born infants and would remain invisible until they reached middle age. Taken all together, these findings could be of importance for longterm cardiovascular risk increases. So what should be done, based on the facts and their implications from the present systematic review? First of all, these prematurely born children and their parents should know that the prognosis has improved considerably over recent years and that previous interventions that imposed risk, such as too much oxygen in premature newborns with the risk of retinal damage, have now been abandoned. Furthermore, it has been suggested that the increased cardiometabolic risk of young adults born either prematurely or small for gestational age (SGA) could encourage clinicians to provide structured follow-up appointments at polyclinics, offering cardiovascular risk factor screening and treatment starting in young adulthood. This could prove to be important on an individual level for controlling risk, but also provide a way to strengthen the links between paediatrics and adult medicine. The previous grim prognosis for babies born prematurely has now improved substantially, with better survival and less immediate health hazards, even if these should not to be disregarded or overlooked (7). Well-designed clinical cohorts not only warrant follow-up periods that last decades, but they should also be repeated as neonatal medical care improves. Similarly, studies to identify and treat some of the important causes of preterm deliveries, such as pre-eclampsia, also warrant long-term follow-up studies to elucidate lifelong results and safety for the mother and child (8–10). National registers on healthrelated factors that add data to previous studies might be cost-effective tools to complement these clinical studies. On the other hand, the improved survival into adult life that has already been achieved for preterm born children is an impetus for establishing routines to screen and treat cardiovascular risk factors in this group, by applying a life course perspective from early life to adulthood.

Glucose homeostasis, beta cell function, and insulin resistance in relation to vitamin D status after gestational diabetes mellitus

We wanted to determine vitamin D status after gestational diabetes mellitus (GDM) and to evaluate whether levels of 25‐hydroxyvitamin D3 (25OHD3) are associated with beta cell function, insulin resistance or a diagnosis of diabetes after GDM.