Concerns have been raised about the health and development of children conceived by assisted reproductive technologies (ART) since 1978. Controversially, ART has been linked with adverse obstetric ...and perinatal outcomes, an increased risk of birth defects, cancers, and growth and development disorders. Emerging evidence suggests that ART treatment may also predispose individuals to an increased risk of chronic ageing related diseases such as obesity, type 2 diabetes and cardiovascular disease. This review will summarize the available evidence on the short-term and long-term health outcomes of ART singletons, as multiple pregnancies after multiple embryos transfer, are associated with low birth weight and preterm delivery, which can separately increase risk of adverse postnatal outcomes, and impact long-term health. We will also examine the potential factors that may contribute to these health risks, and discuss underlying mechanisms, including epigenetic changes that may occur during the preimplantation period and reprogram development in utero, and adult health, later in life. Lastly, this review will consider the future directions with the view to optimize the long-term health of ART children.
Early reports suggested that resistin is associated with obesity and insulin resistance in rodents. However, subsequent studies have not supported these findings. To our knowledge, the present study ...is the first assessment in human subjects of serum resistin and insulin sensitivity by the insulin clamp technique. Thirty-eight nonobese subjects age, 23 ± 4 yr; body mass index (BMI), 25.4 ± 4.3 kg/m2, 12 obese subjects (age, 54 ± 8 yr; BMI, 33.0 ± 2.5 kg/m2), and 22 obese subjects with type 2 diabetes (age, 59 ± 7 yr; BMI, 34.0 ± 2.4 kg/m2) were studied. Serum resistin concentrations were not different among nonobese (4.1 ± 1.7 ng/ml), obese (4.2 ± 1.6 ng/ml), and obese diabetic subjects (3.7 ± 1.2 ng/ml), and were not significantly correlated to glucose disposal rate during a hyperinsulinemic glucose clamp across groups. Serum resistin was, however, inversely related to insulin sensitivity in nonobese subjects only (r = −0.35; P = 0.05), although this association was lost after adjusting for percent body fat. Serum resistin was not related to percent fat, BMI, or fat cell size. A strong correlation was observed between serum resistin and resistin mRNA expression from abdominal sc adipose tissue in a separate group of obese subjects (r = 0.62; P < 0.01; n = 56). Although the exact function of resistin is unknown, we demonstrated only a weak relationship between resistin and insulin sensitivity in nonobese subjects, indicating that resistin is unlikely to be a major link between obesity and insulin resistance in humans.
It is widely accepted that increasing adiposity is associated with insulin resistance and increased risk of type II diabetes. The predominant paradigm used to explain this link is the portal/visceral ...hypothesis. This hypothesis proposes that increased adiposity, particularly in the visceral depots, leads to increased free-fatty acid flux and inhibition of insulin-action via Randle's effect in insulin-sensitive tissues.
In this review, limitations of this paradigm will be discussed and two other paradigms that may explain established links between adiposity and insulin resistance/diabetes will be presented. (A) Ectopic fat storage syndrome. Three lines of evidence support this concept. Firstly, failure to develop adequate adipose tissue mass (also known as 'lipodystrophy') results in severe insulin resistance and diabetes. This is thought to be the result of ectopic storage of lipid into liver, skeletal muscle and the pancreatic insulin-secreting beta cell. Secondly, most obese patients also shunt lipid into the skeletal muscle, the liver and probably the beta cell. The importance of this finding is exemplified by several studies demonstrating that the degree of lipid infiltration into skeletal muscle and liver highly correlates with insulin resistance. Thirdly, increased fat cell size is highly associated with insulin resistance and the development of diabetes. Increased fat cell size may represent the failure of the adipose tissue mass to expand and therefore to accommodate an increased energy influx. Taken together, these observations support the 'acquired lipodystrophy' hypothesis as a link between adiposity and insulin resistance. Ectopic fat deposition is therefore the result of additive or synergistic effects including increased dietary intake, decreased fat oxidation and impaired adipogenesis. (B) Endocrine paradigm. This concept was developed in parallel with the 'ectopic fat storage syndrome' hypothesis. Adipose tissue secretes a variety of endocrine hormones such as leptin, interleukin-6, angiotensin II, adiponectin and resistin. From this viewpoint, adipose tissue plays a critical role as an endocrine gland, secreting numerous factors with potent effects on the metabolism of distant tissues.
The novel paradigms of ectopic fat and fat cell as an endocrine organ probably will constitute a new framework for the study of the links between our obesigenic environment and the risk of developing diabetes.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
C-reactive protein (CRP) is an inflammatory-response protein that is a strong, independent predictor of cardiovascular mortality. CRP is positively associated with body mass index (BMI). In this ...study, we investigated the effects of dynamic weight loss on CRP in 83 healthy, obese women (mean BMI, 33.8±0.4 kg/m; range, 28.2 to 43.8 kg/m). Subjects were placed on very-low-fat, energy-restricted diets (5700 kJ, 15% fat) for 12 weeks. Weight, waist and hip circumferences, plasma lipids, glucose, and CRP were measured at baseline and after 12 weeks. CRP was positively associated with BMI (r =0.281, P =0.01) and waist circumference (r =0.278, P =0.01) but was not related to other atherosclerosis risk factors. BMI was significantly different between groups split above or below the median for CRP (34.8±0.6 kg/m vs 33.0±0.5 kg/m, P =0.02). After 12 weeks, weight loss was 7.9±0.3 kg. CRP was significantly decreased by 26% (P < 0.001), and a correlation was observed between weight loss and the change in CRP (r =0.309, P =0.005). The variance in the change in CRP was partly explained by initial CRP (13.6%), energy intake (5.4%), and percentage weight loss (4.6%, P =0.001). This study confirms recent observations that BMI is associated with CRP, a marker for low-grade systemic inflammation. Furthermore, we observed that CRP was lowered in proportion to weight loss.
Diabet. Med. 29, 986–989 (2012)
Aim Hyperbaric oxygen therapy is known to reduce fasting blood glucose in individuals with Type 2 diabetes. However, the mechanisms of this effect are not clear. The ...aim of this study was to determine whether peripheral insulin sensitivity by hyperinsulinaemic euglycaemic clamp is increased in patients presenting for hyperbaric oxygen therapy.
Methods Participants were non‐obese individuals without Type 2 diabetes (n = 5) or obese patients with Type 2 diabetes (n = 5). Patients were given 100% oxygen at 2.0 absolute atmospheres for 2 h, six sessions per week for 5 weeks.
Results Peripheral insulin sensitivity was increased in the whole cohort (P = 0.04). Subsequent analysis revealed that this was significant at both treatment 3 (+37.3 ± 12.7%, P = 0.02) and treatment 30 (+40.6 ± 12.6%, P = 0.009). HbA1c was significantly reduced in subjects without diabetes only (P < 0.05).
Conclusion Insulin sensitivity increased within 3 days of hyperbaric oxygen treatment and this was maintained for 30 sessions. This increase in insulin sensitivity is equivalent to that observed following moderate weight loss. The mechanisms underlying the insulin‐sensitizing effect of hyperbaric oxygen require further elucidation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
An unexplained >4σ discrepancy persists between "beam" and "bottle" measurements of the neutron lifetime. A new model proposed that conversions of neutrons n into mirror neutrons n^{'}, part of a ...dark mirror sector, can increase the apparent neutron lifetime by 1% via a small mass splitting Δm between n and n^{'} inside the 4.6 T magnetic field of the National Institute of Standards and Technology Beam Lifetime experiment. A search for neutron conversions in a 6.6 T magnetic field was performed at the Spallation Neutron Source which excludes this explanation for the neutron lifetime discrepancy.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Aims/hypothesis The purpose of the study was to test prospectively whether healthy individuals with a family history of type 2 diabetes are more susceptible to adverse metabolic effects during ...experimental overfeeding. Methods We studied the effects of 3 and 28 days of overfeeding by 5,200 kJ/day in 41 sedentary individuals with and without a family history of type 2 diabetes (FH+ and FH− respectively). Measures included body weight, fat distribution (computed tomography) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp). Results Body weight was increased compared with baseline at 3 and 28 days in both groups (p < 0.001), FH+ individuals having gained significantly more weight than FH− individuals at 28 days (3.4 ± 1.6 vs 2.2 ± 1.4 kg, p < 0.05). Fasting serum insulin and C-peptide were increased at 3 and 28 days compared with baseline in both groups, with greater increases in FH+ than in FH− for insulin at +3 and +28 days (p < 0.01) and C-peptide at +28 days (p < 0.05). Fasting glucose also increased at both time points, but without a significant group effect (p = 0.1). Peripheral insulin sensitivity decreased in the whole cohort at +28 days (54.8 ± 17.7 to 50.3 ± 15.6 µmol min⁻¹ kg fat-free mass⁻¹, p = 0.03), and insulin sensitivity by HOMA-IR decreased at both time points (p < 0.001) and to a greater extent in FH+ than in FH− (p = 0.008). Liver fat, subcutaneous and visceral fat increased similarly in the two groups (p < 0.001). Conclusions Overfeeding induced weight and fat gain, insulin resistance and hepatic fat deposition in healthy individuals. However, individuals with a family history of type 2 diabetes gained more weight and greater insulin resistance by HOMA-IR. The results of this study suggest that healthy individuals with a family history of type 2 diabetes are predisposed to adverse effects of overfeeding. Trial registration: ClinicalTrials.gov NCT00562393 Funding: The study was funded by the National Health and Medical Research Council (NHMRC), Australia (no. #427639).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The postprandial state is hypothesised to be proinflammatory and prooxidative, but the relative contributions of fat versus carbohydrate are unclear. Therefore, we examined inflammation and oxidative ...stress responses in serum and skeletal muscle before and after 1000 kcal meals, which were high in either fat or carbohydrate in 15 healthy individuals. Serum and muscle expression of IL6 was elevated 3 hours after each meal, independently of macronutrient composition (P<0.01). Serum IL18 was decreased after high-fat meal only (P<0.01). Plasma total antioxidative status and muscle Cu/Zn-superoxide dismutase were decreased after high-carbohydrate meal only (P<0.05). We conclude that a high-carbohydrate meal may evoke a greater postprandial oxidative stress response, whereas both fat and carbohydrate increased IL6. We speculate that the observed increases in postprandial IL6, without increases in any other markers of inflammation, may indicate a normal IL6 response to enhance glucose uptake, similar to its role postexercise.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Aims/hypothesis A hallmark feature of the metabolic syndrome is abnormal glucose metabolism which can be improved by exercise. Recently the orphan nuclear receptor subfamily 4, group A, member 1 ...(NUR77) was found to be induced by exercise in muscle and was linked to transcriptional control of genes involved in lipid and glucose metabolism. Here we investigated if overexpression of Nur77 (also known as Nr4a1) in skeletal muscle has functional consequences for lipid and/or glucose metabolism. Methods L6 rat skeletal muscle myotubes were infected with a Nur77-coding adenovirus and lipid and glucose oxidation was measured. Nur77 was also overexpressed in skeletal muscle of chow- and fat-fed rats and the effects on glucose and lipid metabolism evaluated. Results Nur77 overexpression had no effect on lipid oxidation in L6 cells or rat muscle, but did increase glucose oxidation and glycogen synthesis in L6 cells. In chow- and high-fat-fed rats, Nur77 overexpression by electrotransfer significantly increased basal glucose uptake and glycogen synthesis, but no increase in insulin-stimulated glucose metabolism was observed. Nur77 electrotransfer was associated with increased production of GLUT4 and glycogenin and increased hexokinase and phosphofructokinase activity. Interestingly, Nur77 expression in muscle biopsies from obese men was significantly lower than in those from lean men and was closely correlated with body-fat content and insulin sensitivity. Conclusions/interpretation Our data provide compelling evidence that NUR77 is a functional regulator of glucose metabolism in skeletal muscle in vivo. Importantly, the diminished content in muscle of obese insulin-resistant men suggests that it might be a potential therapeutic target for the treatment of dysregulated glucose metabolism.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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