Fredrik Ahlsson

A high birth weight is associated with increased risk of type 2 diabetes and obesity

The association between low birth weight and adult disease is well known. Less is known on long‐term effects of high birth weight.

Nutrient intakes independently affect growth in extremely preterm infants: results from a population-based study

To explore associations between energy and macronutrient intakes and early growth in extremely low gestational age (ELGA) infants.

Insulin Resistance, a Link between Maternal Overweight and Fetal Macrosomia in Nondiabetic Pregnancies

Background/Aims: During the last decades the number of large for gestational age infants delivered by nondiabetic mothers has increased. Our aim was to investigate to what extent fetal growth in nondiabetic pregnant women can be explained by rates of maternal energy substrate production and resting energy expenditure. Methods: Twenty nonsmoking pregnant women without impaired glucose tolerance and with a wide range of fetal weights (0.2–2.7 SDS) were investigated at 36 weeks of gestation. Maternal lipolysis, glucose production, resting energy expenditure, body composition and insulin resistance were assessed.Results: Median (range) glucose production rate was 805 (653–1,337) µmol/min and that of glycerol, reflecting lipolysis, was 214 (110–576) µmol/min. Multiple linear regression analysis showed that maternal fat mass explained 36% of the variation in insulin resistance, accounting for 62% of the variation in glucose production. Further, glucose production explained 31% of the variation in fetal weight. Resting energy expenditure explained 51% of the variation in estimated fetal weight. Conclusion: Fetal weight is dependent on maternal glucose production, which is in turn determined by the degree of insulin resistance, induced in part by the maternal fat mass. The variation in maternal resting energy expenditure is closely related to fetal weight.

Gestational diabetes and offspring body disproportion

Aim:  It has been demonstrated that females born large for gestational age (LGA) in weight but not length are at increased risk of being obese at childbearing age. We addressed the question whether women with gestational diabetes mellitus (GDM) are at increased risk of giving birth to such infants.

Lipolysis and Insulin Sensitivity at Birth in Infants Who Are Large for Gestational Age

OBJECTIVE. In addition to neonatal hypoglycemia, infants who are born large for gestational age are at risk for developing obesity, cardiovascular disease, and diabetes later in life. The aim of this study was to investigate glucose production, lipolysis, and insulin sensitivity in infants who were born large for gestational age to mothers without diabetes. The effect of glucagon administration on production of energy substrates was also investigated. METHODS. Ten healthy term infants who were born large for gestational age to mothers without diabetes were studied 16 ± 8 hours postnatally after a 3-hour fast. Rates of glucose production and lipolysis were analyzed by gas chromatography–mass spectrometry following constant rate infusion of [6,6-2H2]glucose and [2-13C]glycerol. Insulin sensitivity was assessed by the Homeostasis Assessment Model. In 8 of the infants, the effect of an intravenous injection of 0.2 mg/kg glucagon was also analyzed. RESULTS. Plasma glucose and glycerol averaged 3.8 ± 0.5 mmol/L and 384 ± 183 μmol/L, respectively. The glycerol production rate, reflecting lipolysis, was 12.7 ± 2.9 μmol/kg per min. Mean rate of glucose production was 30.2 ± 4.6 μmol/kg per min. Homeostasis Assessment Model insulin sensitivity corresponded to 82% ± 19%, β-cell function to 221% ± 73%, and insulin resistance to 1.3 ± 0.3. After glucagon administration, rate of glucose production increased by 13.3 ± 8.3 μmol/kg per min and blood glucose by 1.4 ± 0.5 mmol/L. Glycerol production decreased from 12.8 ± 3.0 to 10.7 ± 2.9 μmol/kg per min. Mean insulin concentration increased from 10.9 ± 3.0 to 30.9 ± 10.3 mU/L. There was a strong inverse correlation between the decrease in lipolysis and increase in insulin after glucagon administration. CONCLUSIONS. Infants who are born large for gestational age show increased lipolysis and a propensity for decreased insulin sensitivity already at birth. The simultaneous increase in plasma insulin correlated strongly with the noted decrease in lipolysis, indicating an antilipolytic effect of insulin in these infants.

School Performance After Preterm Birth

Background: An increased risk of poor school performance for children born preterm has been shown in many studies, but whether this increase is attributable to preterm birth per se or to other factors associated with preterm birth has not been resolved. Methods: We used data from the Swedish Medical Birth Register, the Longitudinal Integration Database for Sickness Insurance and Labor Market Study, the Swedish Multigeneration Register, and the National School Register to link records comprising the Swedish birth cohorts from 1974 through 1991. Linear regression was used to assess the association between gestational duration and school performance, both with and without controlling for parental and socioeconomic factors. In a restricted analysis, we compared siblings only with each other. Results: Preterm birth was strongly and negatively correlated with school performance. The distribution of school grades for children born at 31–33 weeks was on average 3.85 (95% confidence interval = −4.36 to −3.35) centiles lower than for children born at 40 weeks. For births at 22–24 weeks, the corresponding figure was −23.15 (−30.32 to −15.97). When taking confounders into account, the association remained. When restricting the analysis to siblings, however, the association between school performance and preterm birth after week 30 vanished completely, whereas it remained, less pronounced, for preterm birth before 30 weeks of gestation. Conclusions: Our study suggests that the association between school performance and preterm birth after 30 gestational weeks is attributable to factors other than preterm birth per se.

Treatment of extreme hyperglycemia monitored with intracerebral microdialysis.

Objective Description of a pediatric patient with hyperosmolar hyperglycemic nonketotic syndrome where the treatment was monitored with intracerebral microdialysis. Design Case report. Setting Intensive care unit at a university hospital. Patient An 11-yr-old boy with new-onset diabetes who presented with a blood glucose concentration of 100 mmol/L (1800 mg/dL) and a serum osmolality of 448 mOsm/kg. Interventions Interventions included intracerebral and subcutaneous microdialysis as well as intracranial pressure monitoring during correction of the hyperosmolar condition. The strategy was to decrease osmolality by 1 mOsm·kg−1·hr−1 and blood glucose by 1.5 mmol·L−1·hr−1 (27 mg/dL). Measurements and Main Results The concentrations of glucose in the subcutaneous dialysates corresponded to the blood glucose concentrations. The brain/subcutaneous glucose ratio varied between 0.20 and 1.28 (mean, 0.43; median, 0.4). When the blood glucose decreased quickly after steady state, the brain/subcutaneous ratio increased sharply, demonstrating that the normalization of glucose in the brain was slower than that in blood. Conclusions Microdialysis can be used to monitor the brain/subcutaneous glucose ratio in patients with extreme hyperglycemia. A rapid decrease in blood glucose increases the brain/subcutaneous glucose ratio, which may be a potential risk factor for osmotic brain edema. Microdialysis may prove to be a valuable tool in treatment management. The child made a full recovery.

Maternal Height and Preterm Birth: A Study on 192,432 Swedish Women

Background There is increasing evidence that lower maternal stature is associated with shorter gestational length in the offspring. We examined the association between maternal height and the likelihood of delivering preterm babies in a large and homogeneous cohort of Swedish women. Methods This study covers antenatal data from the Swedish Medical Birth Register on 192,432 women (aged 26.0 years on average) born at term, from singleton pregnancies, and of Nordic ethnicity. Continuous associations between womens heights and the likelihood of preterm birth in the offspring were evaluated. Stratified analyses were also carried out, separating women into different height categories. Results Every cm decrease in maternal stature was associated with 0.2 days shortening of gestational age in the offspring (p<0.0001) and increasing odds of having a child born preterm (OR 1.03), very preterm (OR 1.03), or extremely preterm (OR 1.04). Besides, odds of all categories of preterm birth were highest among the shortest women but lowest among the tallest mothers. Specifically, women of short stature (≤155 cm or ≤-2.0 SDS below the population mean) had greater odds of having preterm (OR 1.65) or very preterm (OR 1.47) infants than women of average stature (-0.5 to 0.5 SDS). When compared to women of tall stature (≥179 cm), mothers of short stature had even greater odds of giving birth to preterm (OR 2.07) or very preterm (OR 2.16) infants. Conclusions Among Swedish women, decreasing height was associated with a progressive increase in the odds of having an infant born preterm. Maternal short stature is a likely contributing factor to idiopathic preterm births worldwide, possibly due to maternal anatomical constraints.

Obesity rates in two generations of Swedish women entering pregnancy, and associated obesity risk among adult daughters.

We examined changes in obesity rates in two generations of Swedish women entering pregnancy, and assessed the effects of maternal body mass index (BMI) on the risk of overweight or obesity among adult daughters. This study covered an intergenerational retrospective cohort of 26,561 Swedish mothers and their 26,561 first-born daughters. There was a 4-fold increase in obesity rates, which rose from 3.1% among women entering pregnancy in 1982–1988 to 12.3% among their daughters in 2000–2008 (p < 0.0001) when entering pregnancy. The greater the maternal BMI, the greater the odds of overweight and/or obesity among daughters. Underweight mothers had half the odds of having an overweight or obese daughter in comparison to mothers of normal BMI (p < 0.0001). In contrast, the odds ratio of obese mothers having obese daughters was 3.94 (p < 0.0001). This study showed a strong association between maternal obesity and the risk of obesity among their first-born daughters. In addition, we observed a considerable increase in obesity rates across generations in mother-daughter pairs of Swedish women entering pregnancy. Thus, it is important to have preventative strategies in place to halt the worsening intergenerational cycle of obesity.

Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size

OBJECTIVE The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation. STUDY DESIGN Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique. RESULTS Median (range) rate of glucose production was 805 (653-1337) μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576) μmol/min. HOMA insulin resistance averaged 1.5 ± 0.75 and estimated fetal weights ranged between 2670 and 4175 g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2 ± 2.5mg/L and median level of leptin was 47.1 (9.9-58.0) μg/L. Adiponectin concentrations (7.2 ± 2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, p<0.035, r=-0.77, p<0.001, r=-0.67, p<0.002, and r=-0.51, p<0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r=0.76, p<0.001 and r=0.73, p<0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure. CONCLUSION The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy.