Janene B. Biggs

Olive (Olea europaea L.) Leaf Polyphenols Improve Insulin Sensitivity in Middle-Aged Overweight Men: A Randomized, Placebo-Controlled, Crossover Trial

Background Olive plant leaves (Olea europaea L.) have been used for centuries in folk medicine to treat diabetes, but there are very limited data examining the effects of olive polyphenols on glucose homeostasis in humans. Objective To assess the effects of supplementation with olive leaf polyphenols (51.1 mg oleuropein, 9.7 mg hydroxytyrosol per day) on insulin action and cardiovascular risk factors in middle-aged overweight men. Design Randomized, double-blinded, placebo-controlled, crossover trial in New Zealand. 46 participants (aged 46.4±5.5 years and BMI 28.0±2.0 kg/m2) were randomized to receive capsules with olive leaf extract (OLE) or placebo for 12 weeks, crossing over to other treatment after a 6-week washout. Primary outcome was insulin sensitivity (Matsuda method). Secondary outcomes included glucose and insulin profiles, cytokines, lipid profile, body composition, 24-hour ambulatory blood pressure, and carotid intima-media thickness. Results Treatment evaluations were based on the intention-to-treat principle. All participants took >96% of prescribed capsules. OLE supplementation was associated with a 15% improvement in insulin sensitivity (p = 0.024) compared to placebo. There was also a 28% improvement in pancreatic β-cell responsiveness (p = 0.013). OLE supplementation also led to increased fasting interleukin-6 (p = 0.014), IGFBP-1 (p = 0.024), and IGFBP-2 (p = 0.015) concentrations. There were however, no effects on interleukin-8, TNF-α, ultra-sensitive CRP, lipid profile, ambulatory blood pressure, body composition, carotid intima-media thickness, or liver function. Conclusions Supplementation with olive leaf polyphenols for 12 weeks significantly improved insulin sensitivity and pancreatic β-cell secretory capacity in overweight middle-aged men at risk of developing the metabolic syndrome. Trial Registration Australian New Zealand Clinical Trials Registry #336317.

Increased Adiposity in Adults Born Preterm and Their Children

Background Preterm birth is associated with abnormalities in growth, body composition, and metabolism during childhood, but adult data are scarce and none exist for their offspring. We therefore aimed to examine body composition and cardiovascular risk factors in adults born preterm and their children. Methods A cohort of 52 adults (aged 35.7 years, 54% female, 31 born preterm) and their term-born children (n=61, aged 8.0 years, 54% female, 60% from a preterm parent) were studied. Auxology and body composition (whole-body dual-energy X-ray absorptiometry) were measured, and fasting blood samples taken for metabolic and hormonal assessments. Results Adults born preterm had greater abdominal adiposity, displaying more truncal fat (p=0.006) and higher android to gynoid fat ratio (p=0.004). Although women born preterm and at term were of similar weight and BMI, men born preterm (n=8) were on average 20 kg heavier (p=0.010) and of greater BMI (34.2 vs 28.4 kg/m2; p=0.021) than men born at term (n=16). Adults born preterm also displayed a less favourable lipid profile, including lower HDL-C concentrations (p=0.007) and greater total cholesterol to HDL-C ratio (p=0.047). Children of parents born preterm tended to have more body fat than the children of parents born at term (21.3 vs 17.6%; p=0.055). Even after adjustment for mean parental BMI, children of parents born preterm had altered fat distribution, with more truncal fat (p=0.048) and greater android to gynoid fat ratio (p=0.009). Conclusions Adults born preterm, particularly men, have markedly increased fat mass and altered fat distribution. A similar increase in abdominal adiposity was observed in the term born offspring of parents born preterm, indicating that adverse outcomes associated with preterm birth may extend to the next generation.

Higher omega-3 index is associated with increased insulin sensitivity and more favourable metabolic profile in middle-aged overweight men

We assessed whether omega-3 index (red blood cell concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) was associated with insulin sensitivity and other metabolic outcomes in 47 overweight men aged 46.5 ± 5.1 years. Participants were assessed twice, 16 weeks apart. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test. Linear associations were examined; stratified analyses were carried out with participants separated according to the omega-3 index: lower tertiles (LOI; n = 31) and highest tertile (HOI; n = 16). Increasing omega-3 index was correlated with higher insulin sensitivity (r = 0.23; p = 0.025), higher disposition index (r = 0.20; p = 0.054), and lower CRP concentrations (r = −0.39; p < 0.0001). Insulin sensitivity was 43% higher in HOI than in LOI men (Matsuda index 6.83 vs 4.78; p = 0.009). Similarly, HOI men had disposition index that was 70% higher (p = 0.013) and fasting insulin concentrations 25% lower (p = 0.038). HOI men displayed lower nocturnal systolic blood pressure (−6.0 mmHg; p = 0.025) and greater systolic blood pressure dip (14.7 vs 10.8%; p = 0.039). Men in the HOI group also had lower concentrations of CRP (41% lower; p = 0.033) and free fatty acids (21% lower, p = 0.024). In conclusion, higher omega-3 index is associated with increased insulin sensitivity and a more favourable metabolic profile in middle-aged overweight men.

Effects of antenatal exercise in overweight and obese pregnant women on maternal and perinatal outcomes: a randomised controlled trial

To assess whether antenatal exercise in overweight/obese women would improve maternal and perinatal outcomes.

Psyllium supplementation in adolescents improves fat distribution & lipid profile: a randomized, participant-blinded, placebo-controlled, crossover trial.

Aims We aimed to assess the effects of psyllium supplementation on insulin sensitivity and other parameters of the metabolic syndrome in an at risk adolescent population. Methods This study encompassed a participant-blinded, randomized, placebo-controlled, crossover trial. Subjects were 47 healthy adolescent males aged 15–16 years, recruited from secondary schools in lower socio-economic areas with high rates of obesity. Participants received 6 g/day of psyllium or placebo for 6 weeks, with a two-week washout before crossing over. Fasting lipid profiles, ambulatory blood pressure, auxological data, body composition, activity levels, and three-day food records were collected at baseline and after each 6-week intervention. Insulin sensitivity was measured by the Matsuda method using glucose and insulin values from an oral glucose tolerance test. Results 45 subjects completed the study, and compliance was very high: 87% of participants took >80% of prescribed capsules. At baseline, 44% of subjects were overweight or obese. 28% had decreased insulin sensitivity, but none had impaired glucose tolerance. Fibre supplementation led to a 4% reduction in android fat to gynoid fat ratio (p = 0.019), as well as a 0.12 mmol/l (6%) reduction in LDL cholesterol (p = 0.042). No associated adverse events were recorded. Conclusions Dietary supplementation with 6 g/day of psyllium over 6 weeks improves fat distribution and lipid profile (parameters of the metabolic syndrome) in an at risk population of adolescent males. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000888268

Severe Hyperemesis Gravidarum Is Associated With Reduced Insulin Sensitivity in the Offspring in Childhood

BACKGROUND Hyperemesis gravidarum alters maternal (and possibly fetal) nutrition throughout pregnancy, but there are no data on long-term effects on offspring metabolism. Thus, we aimed to assess whether severe hyperemesis gravidarum (SHG) affects glucose homeostasis and body composition in the offspring in childhood. METHODS Healthy prepubertal children (aged 4-11 years) born at term were studied: offspring of mothers who were admitted to hospital with SHG (n = 36) and offspring of mothers from control pregnancies (n = 42). Primary outcome was insulin sensitivity measured using iv glucose tolerance tests and Bergmans minimal model. Other assessments included lipid and hormonal profiles and body composition using whole-body dual-energy x-ray absorptiometry. RESULTS Insulin sensitivity in SHG children was 20% lower than in controls (8.49 vs 10.60 × 10(-4)·min(-1)·(mU/L); P = .014). SHG children also had higher fasting insulin (6.88 vs 5.04 mIU/L; P = .024) and lower IGF binding protein 1 (11.8 vs 19.0 ng/mL; P = .004) concentrations than controls. Baseline cortisol concentrations were 22% higher in SHG offspring (256 vs 210 nmol/L; P = .021). Children in both groups were anthropometrically similar. CONCLUSION Children born to mothers who experienced SHG have lower insulin sensitivity, which may increase their long-term risk of developing diabetes mellitus. Follow-up of SHG offspring is essential to determine later risk of metabolic disease.

Supplementation with a blend of krill and salmon oil is associated with increased metabolic risk in overweight men

BACKGROUND Krill is an increasingly popular source of marine n-3 (ω-3) PUFA that is seen as a premium product. However, to our knowledge, the effect of krill-oil supplementation on insulin sensitivity in humans has not been reported. OBJECTIVE We assessed whether supplementation with a blend of krill and salmon (KS) oil [which is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] affects insulin sensitivity in overweight men. DESIGN The design was a randomized, double-blind, controlled crossover trial. A total of 47 men with a mean ± SD age of 46.5 ± 5.1 y, who were overweight [body mass index (in kg/m(2)) from 25 to 30] but otherwise healthy, received 5 1-g capsules of KS oil or a control (canola oil) for 8 wk and crossed over to another treatment after an 8-wk washout period. The primary outcome was insulin sensitivity assessed by using the Matsuda method from an oral-glucose-tolerance test. Secondary outcomes included lipid profiles, inflammatory markers, 24-h ambulatory blood pressure, and carotid artery intimamedia thickness. RESULTS Unexpectedly, insulin sensitivity (per the Matsuda index) was 14% lower with the KS oil than with the control oil (P = 0.049). A mediation analysis showed that, after controlling for the likely positive effects of blood EPA and DHA (i.e., the omega-3 index), the reduction in insulin sensitivity after KS-oil supplementation was more marked [27% lower than with the control oil (P = 0.009)]. CONCLUSIONS Supplementation with a blend of KS oil is associated with decreased insulin sensitivity. Thus, krill-oil supplementation in overweight adults could exacerbate risk of diabetes and cardiovascular disease. This trial was prospectively registered at the Australian New Zealand Clinical Trials Registry as ACTRN12611000602921.

Pre-Pubertal Children Born Post-Term Have Reduced Insulin Sensitivity and Other Markers of the Metabolic Syndrome

Background There are no data on the metabolic consequences of post-term birth (≥42 weeks gestation). We hypothesized that post-term birth would adversely affect insulin sensitivity, as well as other metabolic parameters and body composition in childhood. Methods 77 healthy pre-pubertal children, born appropriate-for-gestational-age were studied in Auckland, New Zealand: 36 born post-term (18 boys) and 41 (27 boys) born at term (38–40 weeks gestation). Primary outcome was insulin sensitivity measured using intravenous glucose tolerance tests and Bergman’s minimal model. Other assessments included fasting hormone concentrations and lipid profiles, body composition from whole-body dual-energy X-ray absorptiometry, 24-hour ambulatory blood pressure monitoring, and inflammatory markers. Results Insulin sensitivity was 34% lower in post-term than in term children (7.7 vs. 11.6 x10-4·min-1·(mU/l); p<0.0001). There was a compensatory increase in acute insulin response among post-term children (418 vs 304 mU/l; p=0.037), who also displayed lower glucose effectiveness than those born at term (2.25 vs 3.11 x10-2·min-1; p=0.047). Post-term children not only had more body fat (p=0.014) and less fat-free mass (p=0.014), but also had increased central adiposity with more truncal fat (p=0.017) and greater android to gynoid fat ratio (p=0.007) compared to term controls. Further, post-term children displayed other markers of the metabolic syndrome: lower normal nocturnal systolic blood pressure dipping (p=0.027), lower adiponectin concentrations (p=0.005), as well as higher leptin (p=0.008) and uric acid (p=0.033) concentrations. Post-term boys (but not girls) also displayed a less favourable lipid profile, with higher total cholesterol (p=0.018) and LDL-C (p=0.006) concentrations, and total cholesterol to HDL-C ratio (p=0.048). Conclusions Post-term children have reduced insulin sensitivity and display a number of early markers of the metabolic syndrome. These findings could have important implications for the management of prolonged pregnancies. Future studies need to examine potential impacts later in life, as well as possible underlying mechanisms.

Effects of whole-body vibration training on physical function, bone and muscle mass in adolescents and young adults with cerebral palsy

We performed a clinical trial on the effects of whole-body vibration training (WBVT) on muscle function and bone health of adolescents and young adults with cerebral palsy. Forty participants (11.3–20.8 years) with mild to moderate cerebral palsy (GMFCS II–III) underwent 20-week WBVT on a vibration plate for 9 minutes/day 4 times/week at 20 Hz (without controls). Assessments included 6-minute walk test, whole-body DXA, lower leg pQCT scans, and muscle function (force plate). Twenty weeks of WBVT were associated with increased lean mass in the total body (+770 g; p = 0.0003), trunk (+410 g; p = 0.004), and lower limbs (+240 g; p = 0.012). Bone mineral content increased in total body (+48 g; p = 0.0001), lumbar spine (+2.7 g; p = 0.0003), and lower limbs (+13 g; p < 0.0001). Similarly, bone mineral density increased in total body (+0.008 g/cm2; p = 0.013), lumbar spine (+0.014 g/cm2; p = 0.003), and lower limbs (+0.023 g/cm2; p < 0.0001). Participants reduced the time taken to perform the chair test, and improved the distance walked in the 6-minute walk test by 11% and 35% for those with GMFCS II and III, respectively. WBVT was associated with increases in muscle mass and bone mass and density, and improved mobility of adolescents and young adults with cerebral palsy.

Among overweight middle-aged men, first-borns have lower insulin sensitivity than second-borns

We aimed to assess whether birth order affects metabolism and body composition in overweight middle-aged men. We studied 50 men aged 45.6 ± 5.5 years, who were overweight (BMI 27.5 ± 1.7 kg/m2) but otherwise healthy in Auckland, New Zealand. These included 26 first-borns and 24 second-borns. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test. Other assessments included DXA-derived body composition, lipid profiles, 24-hour ambulatory blood pressure, and carotid intima-media thickness. First-born men were 6.9 kg heavier (p = 0.013) and had greater BMI (29.1 vs 27.5 kg/m2; p = 0.004) than second-borns. Insulin sensitivity in first-born men was 33% lower than in second-borns (4.38 vs 6.51; p = 0.014), despite adjustment for fat mass. There were no significant differences in ambulatory blood pressure, lipid profile or carotid intima-media thickness between first- and second-borns. Thus, first-born adults may be at a greater risk of metabolic and cardiovascular diseases.