Aspects of carbohydrate quality and their relevance for risk markers of type 2 diabetes and related health outcomes

Concern has been raised that the commonly advocated low-fat, high-carbohydrate diet might be actually detrimental for the growing number of people with impaired IR since it favors postprandial rises in glucose and insulin, which are associated with an increased risk of type 2 diabetes mellitus (T2D). Successful prevention strategies to fight the increasing prevalence rates of obesity, T2D and related chronic diseases are urgently needed. Since insulin-resistant individuals are particularly prone to glycemic excursions, this might also extend to puberty, a period characterized by physiological IR. A further age group, which to date has not been addressed, are elderly people, who represent a growing proportion of our population and for whom specialized prevention strategies might be necessary. Therefore, the overall aim of the present thesis was to investigate the relevance of different aspects of carbohydrate quality for selected risk markers of T2D. In this regard, prospective associations between puberty and young adulthood as well as 5-year longitudinal relations in older age were examined. Major data source was the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study, which includes data on dietary intake, anthropometry, and health from birth until adulthood. Moreover, data from the Blue Mountains Eye Study (BMES) was used, where information on nutritional status and markers of liver function was repeatedly collected from an older Australian cohort. Additionally, a systematic literature search was conducted on the association between carbohydrate quality and chronic low-grade inflammation in adults. Four analyses (Study I, II, III, and V) and one systematic review (Study IV) were performed. Study I, including 262 participants of the DONALD Study, showed that a higher habitual dietary insulin index, but not a higher glycemic index (GI), during puberty was related to a higher percentage body fat in young adulthood. Study II revealed that a habitually higher dietary GI during puberty was the only aspect of carbohydrate nutrition which was consistently related to the analyzed T2D risk markers i.e. homeostasis model assessment IR (HOMA-IR), alanine-aminotransferase (ALT), and gamma-glutamyltransferase (GGT) in a subsample of the DONALD Study (n=226 and n=214, respectively). In Study III, again based on data from the DONALD Study (n=205), a higher habitual pubertal intake of carbohydrates from higher GI food sources and a lower intake of whole grains was associated with higher levels of the pro-inflammatory cytokine interleukin-6 in younger adulthood. In this regard, Study IV showed that the observational evidence in adults is less consistent for a beneficial role of a lower GI or GL compared to dietary fiber/whole grain. However, there is less consistent evidence from intervention studies for anti-inflammatory benefits of higher fiber or whole grain diets than there is for low-GI/GL diets (60 studies were included in the systematic review). Benefits of higher fiber and whole grain intakes suggested by observational studies may hence reflect confounding. Finally, in Study V, including 866 older people from the BMES, no longitudinal relation was observed between the different aspects of carbohydrate quality and liver enzymes and serum lipids. In conclusion, our results suggest a particular relevance of postprandial glycemic – and also insulinemic – excursions during puberty for risk markers of T2D during adulthood. Overall, efforts to improve carbohydrate quality should not focus solely on a high whole grain intake, but needs to be complemented by an advice for a preferred selection of low-GI foods.Aspekte der Kohlenhydratqualität und ihre Relevanz in Bezug auf Risikomarker für Typ 2 Diabetes und assoziierte Erkrankungen Zunehmend werden Bedenken laut, dass die derzeitige Empfehlung, sich fettarm und kohlenhydratreich zu ernähren, ungünstig für die steigende Zahl an Menschen mit gestörter Insulinresistenz ist, da sie zu postprandialen Blutglukose- und Insulinanstiegen führt, welche wiederum mit einem erhöhtem Risiko für Typ 2 Diabetes mellitus (T2D) verbunden sind. Daher sind vor dem Hintergrund der steigenden Prävalenz von Übergewicht, T2D und weiteren chronischen Erkrankungen erfolgreiche Präventionskonzepte dringend notwendig. Da insbesondere insulinresistente Personen sehr empfindlich auf Blutzuckeranstiege reagieren, könnte dies auch auf die Phase der Pubertät zutreffen, die durch eine physiologische Insulinresistenz gekennzeichnet ist. Eine weitere, bisher kaum berücksichtigte Altersgruppe sind ältere Menschen, die einen immer größeren Anteil in unserer Gesellschaft ausmachen, und für die möglicherweise speziell zugeschnittene Präventionskonzepte erforderlich sind. Das übergeordnete Ziel dieser Arbeit war, die Relevanz verschiedener Aspekte der Kohlenhydratzufuhr für Risikomarker von T2D zu untersuchen. Von Interesse waren hierbei prospektive Assoziationen zwischen der Pubertät und dem Erwachsenenalter sowie 5-Jahres-Veränderungen bei älteren Personen. Daten für diese Untersuchungen lieferte die DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study, in der Informationen zur Ernährung, Anthropometrie und dem Gesundheitsstatus von der Geburt bis ins Erwachsenenalter erhoben werden. Außerdem wurden Daten aus der Blue Mountains Eye Study (BMES) herangezogen, in der wiederholt Informationen zur Ernährung und zu Markern der Leberfunktion in einer älteren australischen Kohorte erfasst wurden. Zusätzlich wurde eine systematische Literaturrecherche zum Zusammenhang zwischen der Kohlenhydratqualität und chronisch geringgradiger Entzündungsneigung im Erwachsenenalter durchgeführt. Vier Auswertungen (Studie I, II, III, V) und eine systematische Literaturrecherche wurden durchgeführt (Studie IV). Studie I, in der 262 Probanden aus der DONALD Studie eingeschlossen wurden, zeigte, dass ein gewohnheitsmäßig höherer Insulin Index, jedoch nicht ein höherer glykämischer Index (GI), in der Pubertät mit einem höheren Körperfettanteil im jungen Erwachsenenalter assoziiert war. In Studie II war ein habituell höherer GI in der Pubertät der einzige Aspekt der Kohlenhydratqualität, der in einer Untergruppe der DONALD Studie (n=226 bzw. n=214) konsistent mit den untersuchten T2D Risikomarkern (Homeostasis model assessment IR (HOMA-IR), Alanin-Aminotransferase (ALT) und Gamma-Glutamyltransferase (GGT)) zusammenhing. Studie III basierte ebenfalls auf Daten der DONALD Studie (n=205) und konnte zeigen, dass eine gewohnheitsmäßig hohe Zufuhr von Kohlenhydraten aus Lebensmitteln mit einem höheren GI sowie eine niedrigere Aufnahme von Vollkorn während der Pubertät mit höheren Werten des proinflammatorischen Cytokins Interleukin 6 assoziiert war. In diesem Zusammenhang wurde aus Studie IV ersichtlich, dass die vorhandene Evidenz aus Beobachtungsstudien weniger eindeutig für den günstigen Einfluss eines niedrigen GI ist als für die Ballaststoff- und Vollkornzufuhr. Im Gegensatz dazu ist die Evidenz aus Interventionstudien weniger konsistent, dass eine ballaststoff- und vollkornreichen Kost verglichen mit einer Kost mit niedrigem GI/GL anti-inflammatorische Effekte hat (60 Studien wurden im systhematischen Review eingeschlossen). Günstige Effekte eines hohen Ballaststoff- und Vollkornverzehrs aus Beobachtungsstudien lassen Confounding vermuten. Schließlich deutete Studie V, basierend auf Daten von 866 Probanden aus der BMES, darauf hin, dass kein longitudinaler Zusammenhang zwischen den verschiedenen Aspekten der Kohlenhydratqualität und den Leberenzymen oder Serumlipiden besteht. Zusammenfassend lässt sich festhalten, dass unsere Ergebnisse auf eine besondere Relevanz von postprandialen Blutglukose-, sowie Insulinanstiegen während der Pubertät für verschiedene Risikomarker von T2D im jungen Erwachsenenalter hinweisen. Insgesamt sollten Bemühungen, die Kohlenhydratqualität zu steigern, sich nicht ausschließlich auf Vollkornprodukte fokussieren, sondern um den Hinweis für eine bevorzugte Auswahl von Lebensmitteln mit einem niedrigen GI erweitert werden

Lower glycemic load meals reduce diurnal glycemic oscillations in women with risk factors for gestational diabetes

Objective Maternal glycemia plays a key role in fetal growth. We hypothesized that lower glycemic load (GL) meals (lower glycemic index, modestly lower carbohydrate) would substantially reduce day-long glucose variability in women at risk of gestational diabetes mellitus (GDM). Research design and methods A crossover study of 17 women (mean±SD age 34.8±4 years; gestational weeks 29.3±1.3; body mass index 23.8±4.7 kg/m2) who consumed a low GL or a high GL diet in random order, 1-day each, over 2 consecutive days. Diets were energy-matched and fiber-matched with 5 meals per 24 hours. All food was provided. Continuous glucose monitoring was used to assess diurnal glycemia. Results Maternal glucose levels were 51% lower on the low GL day with lower incremental area under the curve (iAUC±SEM 549±109 vs 1120±198 mmol/L min, p=0.015). Glycemic variability was significantly lower on the low GL day, as demonstrated by a lower average SD (0.7±0.1 vs 0.9±0.1, p<0.001) and lower mean amplitude of glycemic excursions (2.1±0.2 vs 2.7±0.2 mmol/L, p<0.001). Conclusions A lower GL meal plan in pregnancy acutely halves day-long maternal glucose levels and reduces glucose variability, providing further evidence to support the utility of a low GL diet in pregnancy

Effect of a Nutrient-Rich, Food-Based Supplement Given to Rural Vietnamese Mothers Prior to or during Pregnancy on the Trajectories of Nutrient Biomarkers

Nutrient interventions initiated after conception tend to have modest effects on maternal nutritional status and pregnancy outcomes. Thus, we compared the association between micronutrient intakes and the trajectories of their biomarkers before and during pregnancy. Data from a randomized trial of the effect of a nutrient-rich, food-based supplement given to 317 Vietnamese women prior to or during pregnancy on birth outcomes were used to assess nutrient intakes with biomarker trajectories of zinc, iron, folate, cobalamin, and vitamin A using linear mixed regression models. The circulating plasma or serum trajectories of all five micronutrients were associated to their baseline levels (p &lt; 0.0001). Plasma zinc trajectories were also related to farm work (p = 0.024). Cobalamin and vitamin A trajectories were associated with gestational weight gain (p = 0.003 and p = &minus;0.037, respectively). In this population of rural Vietnamese women, nutrient intakes during pregnancy did not affect biomarker trajectories. The primary determinant of each nutrient biomarker trajectory was its respective baseline level prior to conception

Longitudinal adrenal gland measurements and growth trajectories as risk markers for late preterm delivery

Background!#!The fetal adrenal gland receives rising awareness as a predictor of spontaneous preterm birth. We hereby provide longitudinal growth assessments of the fetal adrenal gland in a low risk population with an additional focus on trajectories in fetuses born preterm.!##!Methods!#!Fetal adrenal gland was assessed via transabdominal ultrasound at gestational weeks (gw) 24-26, 28-30, and 34-36 in a low-risk pregnancy cohort. Longitudinal trajectories of the total gland and the mark (so called fetal zone) as well as ratio of fetal zone width/ total widths (w/W) were analyzed using repeated ANOVA analyses. To compare trajectories of the ratio w/W for preterm and term fetuses respectively, as well as women with and without clinical signs of preterm labor, the propensity score method was applied.!##!Results!#!Fetal zone width increased over the course of pregnancy (p &amp;lt; 0.0001), while the ratio w/W decreased (p &amp;lt; 0.0001) (n = 327). Comparing the trajectories of the ratio w/W in fetuses born preterm (n = 11) with propensity-score matched term born fetuses (n = 22), a decrease between gw 24-26 and 28-30 was observed in both groups, which continued to decrease for the term born fetuses. However, in preterm born fetuses, the ratio increased above the term born values at gw 34-36.!##!Conclusion!#!Our study provides for the first time longitudinal growth data on the fetal adrenal gland and supports the hypothesis that fetal zone enlargement is associated with preterm birth which could play an important role in risk-prediction

Effect of a Nutrient-Rich, Food-Based Supplement Given to Rural Vietnamese Mothers Prior to or during Pregnancy on the Trajectories of Nutrient Biomarkers.

Nutrient interventions initiated after conception tend to have modest effects on maternal nutritional status and pregnancy outcomes. Thus, we compared the association between micronutrient intakes and the trajectories of their biomarkers before and during pregnancy. Data from a randomized trial of the effect of a nutrient-rich, food-based supplement given to 317 Vietnamese women prior to or during pregnancy on birth outcomes were used to assess nutrient intakes with biomarker trajectories of zinc, iron, folate, cobalamin, and vitamin A using linear mixed regression models. The circulating plasma or serum trajectories of all five micronutrients were associated to their baseline levels (p &lt; 0.0001). Plasma zinc trajectories were also related to farm work (p = 0.024). Cobalamin and vitamin A trajectories were associated with gestational weight gain (p = 0.003 and p = -0.037, respectively). In this population of rural Vietnamese women, nutrient intakes during pregnancy did not affect biomarker trajectories. The primary determinant of each nutrient biomarker trajectory was its respective baseline level prior to conception

Effect of a Nutrient-Rich, Food-Based Supplement Given to Rural Vietnamese Mothers Prior to or during Pregnancy on the Trajectories of Nutrient Biomarkers.

Nutrient interventions initiated after conception tend to have modest effects on maternal nutritional status and pregnancy outcomes. Thus, we compared the association between micronutrient intakes and the trajectories of their biomarkers before and during pregnancy. Data from a randomized trial of the effect of a nutrient-rich, food-based supplement given to 317 Vietnamese women prior to or during pregnancy on birth outcomes were used to assess nutrient intakes with biomarker trajectories of zinc, iron, folate, cobalamin, and vitamin A using linear mixed regression models. The circulating plasma or serum trajectories of all five micronutrients were associated to their baseline levels (p &lt; 0.0001). Plasma zinc trajectories were also related to farm work (p = 0.024). Cobalamin and vitamin A trajectories were associated with gestational weight gain (p = 0.003 and p = -0.037, respectively). In this population of rural Vietnamese women, nutrient intakes during pregnancy did not affect biomarker trajectories. The primary determinant of each nutrient biomarker trajectory was its respective baseline level prior to conception

Dietary micronutrient intake during pregnancy is a function of carbohydrate quality

Background: Despite normal gestational weight gain, dietary studies in pregnant women show intakes below the recommendations for energy and micronutrients. Objective: This study compared changes in dietary intake from the second to third trimester with emphasis on energy intake and carbohydrate quality. Design: These post hoc analyses were based on 566 women participating in the Pregnancy and Glycemic Index Outcomes study, a randomized controlled trial comparing the effect of low-glycemic index (GI) dietary advice with healthy eating advice on selected pregnancy outcomes. With the use of multilevel mixed-regression analysis, changes in total energy intake, starch, sugar, fiber intake, GI, and glycemic load (GL) were correlated with intake of different micronutrients. Results: Energy intake decreased in the third trimester, and most women did not meet the national recommended amounts for iron, folate, and dietary fiber from food sources alone. After adjustment for age, ethnicity, prepregnancy body mass index, and intervention group, change in energy intake was positively related to change in intake of all micronutrients (P \u3c 0.001). GI, GL, and starch intake were inversely related to micronutrient intake (P \u3c 0.001), whereas higher total sugars predicted higher intake (P \u3c 0.001). Associations with dietary fiber were inconsistent. Conclusions: Normal pregnancy can be associated with a decline in energy and micronutrient intake from diet. Low dietary GI and GL were the best predictors of a favorable micronutrient profile. This trial was registered at www.anzctr.org.au as ACTRN12610000174088

Effect of a Low-Glycemic Load Diet Intervention on Maternal and Pregnancy Outcomes in Obese Pregnant Women.

The increased prevalence of obese, pregnant women who have a higher risk of glucose intolerance warrants the need for nutritional interventions to improve maternal glucose homeostasis. In this study, the effect of a low-glycemic load (GL) (n = 28) was compared to a high-GL (n = 34) dietary intervention during the second half of pregnancy in obese women (body mass index (BMI) &gt; 30 or a body fat &gt;35%). Anthropometric and metabolic parameters were assessed at baseline (20 week) and at 28 and 34 weeks gestation. For the primary outcome 3h-glucose-iAUC (3h-incremental area under the curve), mean between-group differences were non-significant at every study timepoint (p = 0.6, 0.3, and 0.8 at 20, 28, and 34 weeks, respectively) and also assessing the mean change over the study period (p = 0.6). Furthermore, there was no statistically significant difference between the two intervention groups for any of the other examined outcomes (p ≥ 0.07). In the pooled cohort, there was no significant effect of dietary GL on any metabolic or anthropometric outcome (p ≥ 0.2). A post hoc analysis comparing the study women to a cohort of overweight or obese pregnant women who received only routine care showed that the non-study women were more likely to gain excess weight (p = 0.046) and to deliver large-for-gestational-age (LGA) (p = 0.01) or macrosomic (p = 0.006) infants. Thus, a low-GL diet consumed during the last half of pregnancy did not improve pregnancy outcomes in obese women, but in comparison to non-study women, dietary counseling reduced the risk of adverse outcomes

Paracetamol Medication During Pregnancy: Insights on Intake Frequencies, Dosages and Effects on Hematopoietic Stem Cell Populations in Cord Blood From a Longitudinal Prospective Pregnancy Cohort

Background: Paracetamol is the first choice for antipyretic or analgesic treatment throughout pregnancy. Products with Paracetamol are readily available over the counter and therefore easily accessible for self-medication. Epidemiological data on Paracetamol intake pattern during pregnancy and its potential immunological effects are sparse. We aimed to analyze a possible association between Paracetamol medication and numbers of hematopoietic stem cells (HSC) in cord blood. Methods: The objective was addressed in the PRINCE (PRENATAL DETERMINANTS OF CHILDREN'S HEALTH) study, a population-based prospective pregnancy cohort study initiated in 2011 at the University Medical Center in Hamburg, Germany. 518 healthy pregnant women with singleton pregnancies were recruited during the first trimester. Three examinations were scheduled at the end of the 1st (gestational week 12–14), the 2nd (gestational week 22–24) and the 3rd trimester (gestational week 34–36). For 146 of these women, cord blood flow cytometry data were available. Paracetamol intake was assessed for each trimester of pregnancy. Findings: Among the 518 enrolled women, 40% took Paracetamol as main analgesic treatment during pregnancy. The intake frequency and dosage of Paracetamol varied between the women and was overall low with a tendency towards higher frequencies and higher dosages in the third trimester. Paracetamol intake, particularly during the third trimester, resulted in decreased relative numbers of HSCs in cord blood, independent of maternal age, first-trimester BMI, parity, gestational age and birth weight (−0.286 (95% CI −0.592, 0.021), p = 0.068). Interpretation: Prenatal Paracetamol intake, especially during the third trimester, may be causally involved in decreasing HSCs in cord blood