Appetite-regulating hormones in early life and relationships with type of feeding and body composition in healthy term infants

Introduction: Body composition in early life influences development of obesity during childhood and beyond. Appetite-regulating hormones (ARH) play a role in regulation of food intake and might thus influence body composition in later life. Studies on associations between ARH and body composition in early life are limited. Methods: In 197 healthy term infants, we measured serum fasting levels of ghrelin, leptin, insulin, glucose-dependent insulinotropic peptide (GIP), pancreatic polypeptide (PP) and peptide YY (PYY) at 3 months and in 41 infants also at 6 months and their associations with type of feeding and longitudinal fat mass percentage (FM%) measured by air displacement plethysmography at 1, 3 and 6 months and abdominal visceral and subcutaneous fat, measured by ultrasound, at 3 and 6 months. Results: Infants with formula feeding for 3 months had significantly higher serum levels of ghrelin, leptin, insulin, GIP and PP (p = 0.026, p = 0.018, p = 0.002, p < 0.001, resp.) and lower serum levels of PYY (p = 0.002) at 3 months than breastfed infants. Leptin and ghrelin correlated positively with FM% at 3 months and insulin with change in FM% between 1 and 3 months (r = 0.40, p < 0.001, r = 0.23, p < 0.05, r = 0.22, p < 0.01, resp.). Leptin at 3 months correlated with subcutaneous fat at 3 months (r = 0.23, p < 0.001), but not with visceral fat. Other ARH did not correlate with body composition. Conclusion: Formula-fed infants had a different profile of ARH than breastfed infants, suggesting that lower levels of ghrelin, leptin and insulin in breastfed infants contribute to the protective role of breastfeeding against obesity development. Leptin, ghrelin and insulin were associated with fat mass percentage or its changes

Appetite-regulating hormone trajectories and relationships with fat mass development in term-born infants during the first 6 months of life

BACKGROUND: The first 6 months of life are a critical window for adiposity programming. Appetite-regulating hormones (ARH) are involved in food intake regulation and might, therefore, play a role in adiposity programming. Studies examining ARH in early life are limited. PURPOSE: To investigate ghrelin, peptide YY (PYY) and leptin until 6 months and associations with fat mass percentage (FM%), infant feeding and human milk macronutrients. PROCEDURES: In 297 term-born infants (Sophia Pluto Cohort), ghrelin (acylated), PYY and leptin were determined at 3 and 6 months, with FM% measurement by PEAPOD. Exclusive breastfeeding (BF) was classified as BF ≥ 3 months. Human milk macronutrients were analyzed (MIRIS Human Milk Analyzer). MAIN FINDINGS: Ghrelin increased from 3 to 6 months (p < 0.001), while PYY decreased (p < 0.001), resulting in increasing ghrelin/PYY ratio. Leptin decreased. Leptin at 3 months was higher in girls, other ARH were similar between sexes. Leptin at 3 and 6 months correlated with FM% at both ages(R ≥ 0.321, p ≤ 0.001) and gain in FM% from 1 to 6 months(R ≥ 0.204, p = 0.001). In BF infants, also ghrelin and ghrelin/PYY ratio correlated with this gain in FM%. Exclusively BF infants had lower ghrelin and higher PYY compared to formula fed infants at 3 months (p ≤ 0.039). ARH did not correlate with macronutrients. CONCLUSIONS: Increasing ghrelin and decreasing PYY, thus increasing ghrelin/PYY ratio, suggests an increasing orexigenic drive until 6 months. ARH were different between BF and FF infants at 3 months, but did not correlate with human milk macronutrients. Ghrelin and leptin, but not PYY, correlated with more FM development during the first 6 months, suggesting that they might be involved in adiposity programming. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00394-021-02533-z

A placebo-controlled proof-of-concept study of alirocumab on postprandial lipids and vascular elasticity in insulin-treated patients with type 2 diabetes mellitus

Aim: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidaemia, particularly in the postprandial situation, are less clear. Material and Methods: Twelve male patients with T2DM on an intensive insulin regimen completed a 6-week randomized, double-blind, placebo-controlled, proof-of-concept study. Participants received three biweekly dosages of subcutaneous alirocumab (150 mg) or placebo. Before and after the intervention, fasting and postprandial triglyceride (TG) plasma levels, apolipoprotein (apo) B48, lipoprotein composition isolated by ultracentrifugation, vascular function and markers of inflammation were evaluated. Results: Alirocumab treatment reduced fasting plasma TG levels (between group median change −24.7%; P = 0.018) and fasting apoB48 serum levels (−35.9%; P = 0.039) compared with placebo. Alirocumab reduced the plasma TG area under the curve (AUC) (−26.4%; P = 0.006) and apoB48 AUC (−55.7%; P = 0.046), as well as plasma TG incremental AUC (−21.4%; P = 0.04) and apoB48 incremental AUC (−26.8%; P = 0.02). In addition, alirocumab reduced fasting and postprandial TG levels in very low-density lipoprotein (VLDL) and LDL. Alirocumab improved fasting pulse wave velocity, but no changes in postprandial markers of inflammation were observed. Conclusions: In addition to the well-known LDL-C-reducing effects, 6 weeks of alirocumab treatment lowered both fasting and postprandial plasma TG levels by reducing the TG levels in VLDL and LDL and the concentration of intestinal remnants

Variation in Coronary Atherosclerosis Severity Related to a Distinct LDL (Low-Density Lipoprotein) Profile Findings From a Familial Hypercholesterolemia Pig Model

OBJECTIVE: In an adult porcine model of familial hypercholesterolemia (FH), coronary plaque development was characterized. \nTo elucidate the underlying mechanisms of the observed inter-individual variation in disease severity, detailed lipoprotein \nprofiles were determined. \nAPPROACH AND RESULTS: FH pigs (3 years old, homozygous LDLR R84C mutation) received an atherogenic diet for 12 months. \nCoronary atherosclerosis development was monitored using serial invasive imaging and histology. A pronounced difference \nwas observed between mildly diseased pigs which exclusively developed early lesions (maximal plaque burden, 25% [23%\xe2\x80\x93 \n34%]; n=5) and advanced-diseased pigs (n=5) which developed human-like, lumen intruding plaques (maximal plaque burden, \n69% [57%\xe2\x80\x9377%]) with large necrotic cores, intraplaque hemorrhage, and calcifications. Advanced-diseased pigs and mildly \ndiseased pigs displayed no differences in conventional risk factors. Additional plasma lipoprotein profiling by size-exclusion \nchromatography revealed 2 different LDL (low-density lipoprotein) subtypes: regular and larger LDL. Cholesterol, sphingosine1-phosphate, ceramide, and sphingomyelin levels were determined in these LDL-subfractions using standard laboratory \ntechniques and high-pressure liquid chromatography mass-spectrometry analyses, respectively. At 3 months of diet, regular \nLDL of advanced-diseased pigs contained relatively more cholesterol (LDL-C; regular/larger LDL-C ratio 1.7 [1.3\xe2\x80\x931.9] versus \n0.8 [0.6\xe2\x80\x930.9]; P=0.008) than mildly diseased pigs, while larger LDL contained more sphingosine-1-phosphate, ceramides, and \nsphingomyelins. Larger and regular LDL was also found in plasma of 3 patients with homozygous FH with varying LDL-C ratios. \nCONCLUSIONS: In our adult FH pig model, inter-individual differences in atherosclerotic disease severity were directly related to \nthe distribution of cholesterol and sphingolipids over a distinct LDL profile with regular and larger LDL shortly after the diet \nstart. A similar LDL profile was detected in patients with homozygous FH

Statin treatment increases lipoprotein(a) levels in subjects with low molecular weight apolipoprotein(a) phenotype

Background and aims: We aimed to evaluate the effect of statin treatment initiation on lipoprotein(a) [Lp(a)] levels in patients with dyslipidemia, and the interactions with the apolipoprotein(a) [apo(a)] phenotype, LPA single nucleotide polymorphisms (SNPs) and change in LDL cholesterol. Methods: The study population consisted of patients with dyslipidemia, predominantly familial hypercholesterolemia, who first initiated statin treatment (initiation group; n = 39) or were already on stable statin treatment for at least 4 months (control group; n = 42). Plasma Lp(a) levels were determined with a particle-enhanced immunoturbidimetric assay before and at least 2 months after start of statin treatment in individuals of the initiation group, and at two time points with an interval of at least 2 months in the control group. High and low molecular weight (HMW and LMW, respectively) apo(a) phenotype was determined by immunoblotting, and the common LPA SNPs rs10455872, rs3798220 and rs41272110 by Taqman assay. Results: Plasma Lp(a) levels did not increase significantly in the initiation group (median 20.5 (IQR 10.9–80.7) to 23.3 (10.8–71.8) mg/dL; p = 0.09) nor in the control group (30.9 (IQR 9.2–147.0) to 31.7 (IQR 10.9–164.0) mg/dL; p = 0.61). In patients with the LMW apo(a) phenotype, Lp(a) levels increased significantly from 66.4 (IQR 23.5–148.3) to 97.4 (IQR 24.9–160.4) mg/dL (p = 0.026) in the initiation group, but not in the control group and not in patients characterized by the HMW apo(a) phenotype. Interactions with common LPA SNPs and change in LDL cholesterol were not significant. Conclusions: Statins affect Lp(a) levels differently in patients with dyslipidemia depending on the apo(a) phenotype. Statins increase Lp(a) levels exclusively in patients with the LMW apo(a) phenotype

Cerebral Accumulation of Dietary Derivable Plant Sterols does not Interfere with Memory and Anxiety Related Behavior in Abcg5−/− Mice

Plant sterols such as sitosterol and campesterol are frequently applied as functional food in the prevention of atherosclerosis. Recently, it became clear that plasma derived plant sterols accumulate in murine brains. We questioned whether plant sterols in the brain are associated with alterations in brain cholesterol homeostasis and subsequently with brain functions. ATP binding cassette (Abc)g5−/− mice, a phytosterolemia model, were compared to Abcg5+/+ mice for serum and brain plant sterol accumulation and behavioral and cognitive performance. Serum and brain plant sterol concentrations were respectively 35–70-fold and 5–12-fold increased in Abcg5−/− mice (P < 0.001). Plant sterol accumulation resulted in decreased levels of desmosterol (P < 0.01) and 24(S)-hydroxycholesterol (P < 0.01) in the hippocampus, the brain region important for learning and memory functions, and increased lanosterol levels (P < 0.01) in the cortex. However, Abcg5−/− and Abcg5+/+ displayed no differences in memory functions or in anxiety and mood related behavior. The swimming speed of the Abcg5−/− mice was slightly higher compared to Abcg5+/+ mice (P < 0.001). In conclusion, plant sterols in the brains of Abcg5−/− mice did have consequences for brain cholesterol metabolism, but did not lead to an overt phenotype of memory or anxiety related behavior. Thus, our data provide no contra-indication for nutritional intake of plant sterol enriched nutrition

Perceived wellbeing of patients one year post stroke in general practice - recommendations for quality aftercare

<p>Abstract</p> <p>Background</p> <p>Annually, 41,000 people in the Netherlands have strokes. This has multiple physical and psychosocial consequences. Most patients return home after discharge from hospital. Quality aftercare by general practitioners is important to support patients at home. The purpose of this study is to examine the wellbeing of patients who returned home immediately after discharge from hospital, one year post stroke, in comparison with the general Dutch population of the same age and to determine factors that could influence wellbeing.</p> <p>Methods</p> <p>All the stroke patients from the Department of Neurology, Martini Hospital Groningen in the period November 2006 to October 2007 were included. People aged under 65 years or with haemorrhaging were excluded. All the patients (N = 57) were interviewed at home using the following questionnaires: Barthel Index, SF-36, HADS, CSI and a questionnaire about their way of life.</p> <p>Results</p> <p>31% of the patients in this study experienced a decrease in functional status after one year. Nevertheless, there was no significant difference between the median Barthel Index value at discharge from hospital and one year post stroke. ADL independence correlated with a better quality of life. The health-related quality of life was high. Stroke patients have almost the same quality of life as the 'average' Dutch elderly population. Where patients can no longer fully participate in society, their perceived quality of life is also lower. In this study there is an indication of a high prevalence of depression and anxiety disorders in stroke patients. This negatively affects the quality of life a year after stroke. Although caregiver strain was low for the partners of stroke patients, a reduced quality of life is correlated to greater burden.</p> <p>Conclusions</p> <p>This study provides valuable insight into the wellbeing of patients living at home one year post stroke. Physical functioning and quality of life are comparable to the general population of the same age, but improvements in mental functioning can be envisaged. In addition, more attention should be paid to maintaining the patients' activities. The wellbeing of these stroke patients could be increased further if greater attention is paid to these aspects of life. This seems to be applicable to general practice.</p