Dietary glycemic index during pregnancy is associated with biomarkers of the metabolic syndrome in offspring at age 20 years.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Growing evidence indicates that metabolic syndrome is rooted in fetal life with a potential key role of nutrition during pregnancy. The objective of the study was to assess the possible associations between the dietary glycemic index (GI) and glycemic load (GL) during pregnancy and biomarkers of the metabolic syndrome in young adult offspring.Dietary GI and GL were assessed by questionnaires and interviews in gestation week 30 and offspring were clinically examined at the age of 20 years. Analyses based on 428 mother-offspring dyads were adjusted for maternal smoking during pregnancy, height, pre-pregnancy body mass index (BMI), education, energy intake, and the offspring's ambient level of physical activity. In addition, possible confounding by gestational diabetes mellitus was taken into account.Waist circumference, blood pressure, HOMA insulin resistance (HOMA-IR) and plasma levels of fasting glucose, triglycerides, HDL cholesterol, LDL cholesterol, total cholesterol, insulin, and leptin were measured in the offspring.Significant associations were found between dietary GI in pregnancy and HOMA-IR (the relative increase in HOMA-IR per 10 units' GI increase was 1.09 [95% CI: 1.01, 1.16], p = 0.02), insulin (1.09 [95% CI: 1.02, 1.16], p = 0.01) and leptin (1.21 [95% CI: 1.06, 1.38], p = 0.01) in the offspring; whereas no associations were detected for GL.Our data suggests that high dietary GI in pregnancy may affect levels of markers for the metabolic syndrome in young adult offspring in a potentially harmful direction.Danish Council for Strategic Research/ 09-067124 09-063072 2101-06-000

Criterion validity and reliability of a smartphone delivered sub-maximal fitness test for people with type 2 diabetes

BACKGROUND: Prevention of multi-morbidities following non-communicable diseases requires a systematic registration of adverse modifiable risk factors, including low physical fitness. The aim of the study was to establish criterion validity and reliability of a smartphone app (InterWalk) delivered fitness test in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes (N = 27, mean (SD) age 64.2 (5.9) years, BMI 30.0 (5.1) kg/m(2), (30 % male)) completed a 7-min progressive walking protocol twice (with and without encouragement). VO(2) during the test was assessed using indirect calorimetry and the acceleration (vector magnitude) from the smartphone was obtained. The vector magnitude was used to predict VO(2peak) along with the co-variates weight, height and sex. The validity of the algorithm was tested when the smartphone was placed in the right pocket of the pants or jacket. The algorithm was validated using leave-one-out cross validation. Test-retest reliability was tested in a subset of participants (N = 10). RESULTS: The overall VO(2peak) prediction of the algorithm (R(2)) was 0.60 and 0.45 when the smartphone was placed in the pockets of the pants and jacket, respectively (p < 0.001). The mean bias (limits of agreement) in the cross validation was−0.4 (38) % (pants) and−0.1 (46) % (jacket). When the smartphone was placed in the jacket a significant intensity dependent bias (r = 0.5, p = 0.02) was observed. The test-retest intraclass correlations were 0.85 and 0.86 (p < 0.001), for the pants and jacket, respectively. No effects of encouragement were observed on test performance. CONCLUSION: In conclusion, the InterWalk Fitness Test is accurate and reliable for persons with type 2 diabetes when the smartphone is placed in the side pocket of the pants for. The test could give a fair estimate of the CRF in absence of a progressive maximal test during standardized conditions with the appropriate equipment. TRIAL REGISTRATION: www.clinicaltrials.org (NCT02089477), first registered (prospectively) on March 14th 201

DNA Methylation and Gene Expression in Blood and Adipose Tissue of Adult Offspring of Women with Diabetes in Pregnancy—A Validation Study of DNA Methylation Changes Identified in Adolescent Offspring

Maternal gestational diabetes and obesity are associated with adverse outcomes in offspring, including increased risk of diabetes and cardiovascular diseases. Previously, we identified a lower DNA methylation degree at genomic sites near the genes ESM1, MS4A3, and TSPAN14 in the blood cells of adolescent offspring exposed to gestational diabetes and/or maternal obesity in utero. In the present study, we aimed to investigate if altered methylation and expression of these genes were detectable in blood, as well in the metabolically relevant subcutaneous adipose tissue, in a separate cohort of adult offspring exposed to gestational diabetes and obesity (O-GDM) or type 1 diabetes (O-T1D) in utero, compared with the offspring of women from the background population (O-BP). We did not replicate the findings of lower methylation of ESM1, MS4A3, and TSPAN14 in blood from adults, either in O-GDM or O-T1D. In contrast, in adipose tissue of O-T1D, we found higher MS4A3 DNA methylation, which will require further validation. The adipose tissue ESM1 expression was lower in O-GDM compared to O-BP, which in turn was not associated with maternal pre-pregnancy BMI nor the offspring’s own adiposity. Adipose tissue TSPAN14 expression was slightly lower in O-GDM compared with O-BP, but also positively associated with maternal pre-pregnancy BMI, as well as offspring’s own adiposity and HbA1c levels. In conclusion, the lower DNA methylation in blood from adolescent offspring exposed to GDM could not be confirmed in the present cohort of adult offspring, potentially due to methylation remodeling with increased aging. In offspring adipose tissue, ESM1 expression was associated with maternal GDM, and TSPAN14 expression was associated with both maternal GDM, as well as pre-pregnancy BMI. These altered expression patterns are potentially relevant to the concept of developmental programming of cardiometabolic diseases and require further studies

Effect of Adjunct Metformin Treatment in Patients with Type-1 Diabetes and Persistent Inadequate Glycaemic Control. A Randomized Study

Despite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control.One hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA(1c) (HbA(1c)) > or = 8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA(1c) after one year of treatment. At enrolment, mean (standard deviation) HbA(1c) was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA(1c), 0.13% (-0.19; 0.44), p = 0.422; Total daily insulin dose, -5.7 U/day (-8.6; -2.9), p<0.001; body weight, -1.74 kg (-3.32; -0.17), p = 0.030. Minor and overall major hypoglycaemia was not significantly different between treatments. Treatments were well tolerated.In patients with poorly controlled T1DM, adjunct metformin therapy did not provide any improvement of glycaemic control after one year. Nevertheless, adjunct metformin treatment was associated with sustained reductions of insulin dose and body weight. Further investigations into the potential cardiovascular-protective effects of metformin therapy in patients with T1DM are warranted.ClinicalTrials.gov NCT00118937

Microchimerism of male origin in a cohort of Danish girls

Male microchimerism, the presence of a small number of male cells, in women has been attributed to prior pregnancies. However, male microchimerism has also been reported in women with only daughters, in nulliparous women and prepubertal girls suggesting that other sources of male microchimerism must exist. The aim of the present study was to examine the presence of male microchimerism in a cohort of healthy nulliparous Danish girls aged 10–15 y using DNA extracted from cells from whole blood (buffy coats) and report the association with potential sources of male cells. A total of 154 girls were studied of which 21 (13.6%) tested positive for male microchimerism. There was a tendency that girls were more likely to test positive for male microchimerism if their mothers previously had received transfusion, had given birth to a son or had had a spontaneous abortion. Furthermore, the oldest girls were more likely to test positive for male microchimerism. However, less than half of microchimerism positivity was attributable to these factors. In conclusion, data suggest that male microchimerism in young girls may originate from an older brother either full born or from a discontinued pregnancy or from transfusion during pregnancy. We speculate that sexual intercourse may be important but other sources of male cells likely exist in young girls

Impact of intensive lifestyle intervention on gut microbiota composition in type 2 diabetes:a <i>post-hoc</i> analysis of a randomized clinical trial

Type 2 diabetes (T2D) management is based on combined pharmacological and lifestyle intervention approaches. While their clinical benefits are well studied, less is known about their effects on the gut microbiota. We aimed to investigate if an intensive lifestyle intervention combined with conventional standard care leads to a different gut microbiota composition compared to standard care alone treatment in individuals with T2D, and if gut microbiota is associated with the clinical benefits of the treatments. Ninety-eight individuals with T2D were randomized to either an intensive lifestyle intervention combined with standard care group (N = 64), or standard care alone group (N = 34) for 12 months. All individuals received standardized, blinded, target-driven medical therapy, and individual counseling. The lifestyle intervention group moreover received intensified physical training and dietary plans. Clinical characteristics and fecal samples were collected at baseline, 3-, 6-, 9-, and 12-month follow-up. The gut microbiota was profiled with 16S rRNA gene amplicon sequencing. There were no statistical differences in the change of gut microbiota composition between treatments after 12 months, except minor and transient differences at month 3. The shift in gut microbiota alpha diversity at all time windows did not correlate with the change in clinical characteristics, and the gut microbiota did not mediate the treatment effect on clinical characteristics. The clinical benefits of intensive lifestyle and/or pharmacological interventions in T2D are unlikely to be explained by, or causally related to, changes in the gut microbiota composition