Fasting is related to glucose intolerance and insulin resistance, but it is unknown whether the duration of fasting influences these factors. We explored whether prolonged fasting increases norepinephrine and ketone concentrations and decreases core temperature to a greater extent than short-term fasting; if so, this should lead to improved glucose tolerance. Forty-three healthy young adult males were randomly assigned to undergo a 2-d fast, 6-d fast or the usual diet. Changes in rectal temperature (TR), ketone and catecholamine concentrations, glucose tolerance and insulin release in response to an oral glucose tolerance test were assessed. Both fasting trials increased ketone concentration, and the effect was larger after the 6-d fast (P < 0·05). TR and epinephrine concentration increased only after the 2-d fast (P < 0·05). Both fasting trials increased the glucose area under the curve (AUC) (P < 0·05), but the AUC remained higher than the baseline value after participants returned to their usual diet in the 2-d fast group (P < 0·05). Neither fasting had an immediate effect on the insulin AUC, although it increased after return to their usual diet in the 6-d fast group (P < 0·05). These data suggest that the 2-d fast elicited residual impaired glucose tolerance, which may be linked to greater perceived stress during short-term fasting, as shown by the epinephrine response and change in core temperature. By contrast, prolonged fasting seemed to evoke an adaptive residual mechanism that is related to improved insulin release and maintained glucose tolerance.

This study investigated whether long-chain n-3 PUFA (LC n-3 PUFA) given to pregnant rats fed a high-fat (HF) diet may prevent fetal programming in male offspring at adulthood. Six weeks before mating, and throughout gestation and lactation, female nulliparous Sprague–Dawley rats were given a chow (C) diet, HF (60·6 % fat from maize, rapeseed oils and lard) or HF in which one-third of fat was replaced by fish oil (HF n-3). At weaning, the three offspring groups were randomly separated in two groups fed C diet, or HF without LC n-3 PUFA, for 7 weeks until adulthood. Glucose tolerance and insulin sensitivity were assessed by an oral glucose tolerance test both at weaning and at adulthood. Insulin signalling was determined in liver, muscle and adipose tissue by quantification of the phosphorylation of Akt on Ser 473 at adulthood. At weaning, as at adulthood, offspring from HF-fed dams were obese and displayed glucose intolerance (GI) and insulin resistance (IR), but not those from HFn-3 fed dams. Following the post-weaning C diet, phosphorylation of Akt was strongly reduced in all tissues of offspring from HF dams, but to a lesser extent in liver and muscle of offspring from HFn-3 dams. However, it was abolished in all tissues of all offspring groups fed the HF post-weaning diet. Thus, LC n-3 PUFA introduced in a HF in dams partially prevented the transmission of GI and IR in adult offspring even though they were fed without LC n-3 PUFA from weaning.

As rates of obesity, diabetes, and related comorbidities have increased, the consumption of artificial sweeteners (ASs) as sugar substitutes has also risen in popularity as they are perceived as a healthier alternative to sugar sweetened products. However, there is conflicting evidence regarding the impact of AS intake on metabolic and reproductive health. Glucose intolerance during pregnancy due to intake of sugar sweetened foods can result in an increased risk for the development of type 2 diabetes post-pregnancy. However, limited information exists on the impact of AS intake during pregnancy and lactation on the mother’s health in later life. We hypothesised both AS and fructose would impair metabolic health post-partum (PP) following maternal consumption during pregnancy and lactation. Female C57Bl/6 mice received a standard control diet ad libitum with either water (CD), fructose (Fr; 34.7 mm intake), or AS (AS;12.5 mm Acesulfame-K) throughout pregnancy and lactation. Post-weaning, AS and Fr dams were fed the CD diet for the remainder of the experiment. Oral glucose tolerance tests were undertaken 8 weeks PP and dams were humanely killed at 9 weeks PP, with adipose tissue and ovaries collected for analysis. Experimental diets did not influence maternal bodyweight. At 8 weeks PP, increased glucose intolerance was evident in both AS and Fr dams. Adipocyte size was significantly increased in both the AS and Fr groups PP. Further, in the ovary, AS increased expression of genes associated with follicular development and ovulation. Therefore, ASs may not represent beneficial substitutes to fructose during pregnancy, with the potential to increase the risk of T2DM in later life in mothers.

Glucagon-like peptide-1 (GLP-1) is postprandially secreted from enteroendocrine L-cells and enhances insulin secretion. Currently, it is still controversial whether postprandial GLP-1 responses are altered in obesity and diabetes. To address the issue and to find out possible factors related, we compared postprandial GLP-1 responses in normal rats and in diabetic rats chronically fed an obesogenic diet. Male Wistar rats and diabetic Goto-Kakizaki (GK) rats were fed either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose) diet for 26 weeks. Meal tolerance tests were performed for monitoring postprandial responses after a liquid diet administration (62·76 kJ/kg body weight) every 4 or 8 weeks. Postprandial glucose, GLP-1 and insulin responses in Wistar rats fed the HFS diet (WH) were higher than Wistar rats fed the control diet (WC). Although GK rats fed the HFS diet (GH) had higher glycaemic responses than GK rats fed the control diet (GC), these groups had similar postprandial GLP-1 and insulin responses throughout the study. Jejunal and ileal GLP-1 contents were increased by the HFS diet only in Wistar rats. Furthermore, mRNA expression levels of fatty acid receptors (Ffar1) in the jejunum were mildly (P = 0·053) increased by the HFS diet in Wistar rats, but not in GK rats. These results demonstrate that postprandial GLP-1 responses are enhanced under an obesogenic status in normal rats, but not in diabetic rats. Failure of adaptive enhancement of GLP-1 response in GK rats could be partly responsible for the development of glucose intolerance.

Glucose intolerance during pregnancy – a major driver of gestational diabetes mellitus (GDM) – has significant short- and long-term health consequences for both the mother and child. As GDM prevalence continues to escalate, there is growing need for preventative strategies. There is limited but suggestive evidence that myo-inositol (MI) and probiotics (PB) could improve glucose tolerance during pregnancy. The present study tested the hypothesis that MI and/or PB supplementation would reduce the risk of glucose intolerance during pregnancy. Female C57BL/6 mice were randomised to receive either no treatment, MI, PB (Lactobacillus rhamnosus and Bifidobacterium lactis) or both (MIPB) for 5 weeks. They were then provided with a high-fat diet for 1 week before mating commenced and throughout mating/gestation, while remaining on their respective treatments. An oral glucose tolerance test occurred at gestational day (GD) 16·5 and tissue collection at GD 18·5. Neither MI nor PB, separately or combined, improved glucose tolerance. However, MI and PB both independently increased adipose tissue expression of Ir, Irs1, Akt2 and Pck1, and PB also increased Pparγ. MI was associated with reduced gestational weight gain, whilst PB was associated with increased maternal fasting glucose, total cholesterol and pancreas weight. These results suggest that MI and PB may improve insulin intracellular signalling in adipose tissue but this did not translate to meaningful differences in glucose tolerance. The absence of fasting hyperglycaemia or insulin resistance suggests this is a very mild model of GDM, which may have affected our ability to assess the impact of these nutrients.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates postprandial glycaemic response by enhancing insulin secretion. We previously demonstrated that the postprandial GLP-1 response was enhanced during the development of diet-induced obesity in rats. However, the physiological relevance of the enhanced GLP-1 response remained unclear. We aimed to determine the role of endogenous GLP-1 during obesity development. Male Sprague–Dawley rats were given either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose, weight basis) diet with or without continuous administration of the GLP-1 receptor antagonist, exendin (9–39) (Ex9, 100 µg/d), for 5 weeks. Meal tolerance tests (MTT) were performed to assess postprandial glucose, insulin and GLP-1 responses to a liquid diet administration (15 kcal (63 kJ)/10 ml per kg body weight) every 2 weeks. The AUC of postprandial glucose in the HFS group was similar to the control group in both MTT (P = 0·9665 and P = 0·3475, respectively), whereas AUC of postprandial GLP-1 (after 4 weeks,P = 0·0457) and of insulin (after 2 and 4 weeks, P = 0·0486 and P = 0·0110) was higher in the HFS group compared with the control group. In the Ex9 group, AUC of postprandial glucose (P = 0·0297 and P = 0·0486) was higher along with a lower insulin response compared with the HFS group (P = 0·0564 and P = 0·0281). These results suggest that enhancement of the postprandial GLP-1 response during obesity development has a role in maintaining a normal postprandial glycaemic response. Hence, enhancing endogenous GLP-1 secretion by certain materials could be a potential target for prevention of glucose intolerance.

The exact mechanism of ethanol's effects on glucose tolerance has not been well determined. The present study focuses for the first time on hypoxia and low-grade inflammation in adipose tissue (AT). In the in vivo experiments, twenty-four male Wistar rats were randomly allocated into control and ethanol feeding groups. Ethanol-treated rats received edible ethanol once a day at a total dosage of 5 g/kg per d, and the controls received distilled water. Ethanol volumes were adjusted every week. At the end of 8 weeks, we carried out an oral glucose tolerance test. Blood and AT were collected for measuring hypoxia-inducible factor-1α (HIF-1α), GLUT1, TNF-α, IL-6, leptin and vascular endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9 adipocytes were incubated with 100 mm of ethanol for 48 h; the media and cells were then collected for measuring HIF-1α, GLUT1, TNF-α and IL-6. The results showed that long-term ethanol consumption impaired glucose tolerance in rats. Ethanol consumption had little influence on body weight, but both epididymal and perirenal AT were markedly enlarged in the ethanol-treated rats as compared to the controls. Visceral adipose tissue (VAT) had accumulated, and the protein levels of HIF-1α and GLUT1, the indicators of hypoxia in rat epididymal AT and OP9 adipocytes, were elevated. Secondary to the AT hypoxia, the levels of inflammation-related adipokines, such as TNF-α, IL-6, leptin and VEGF, were increased. Based on these findings, we conclude that VAT hypoxia and low-grade inflammation might be a new mechanism in the treatment of ethanol-related diabetes.

The present study is a secondary analysis of the ROLO study, a randomised control trial of a low-glycaemic index (GI) diet in pregnancy to prevent the recurrence of fetal macrosomia. The objectives of the present study were to identify which women are most likely to respond to a low-GI dietary intervention in pregnancy with respect to three outcome measures: birth weight; maternal glucose intolerance; gestational weight gain (GWG). In early pregnancy, 372 women had their mid-upper arm circumference recorded and BMI calculated. Concentrations of glucose, insulin and leptin were measured in early pregnancy and at 28 weeks. At delivery, infant birth weight was recorded and fetal glucose, C-peptide and leptin concentrations were measured in the cord blood. Women who benefited in terms of infant birth weight were shorter, with a lower education level. Those who maintained weight gain within the GWG guidelines were less overweight in both their first and second pregnancies, with no difference being observed in maternal height. Women who at 28 weeks of gestation developed glucose intolerance, despite the low-GI diet, had a higher BMI and higher glucose concentrations in early pregnancy with more insulin resistance. They also had significantly higher-interval pregnancy weight gain. For each analysis, women who responded to the intervention had lower leptin concentrations in early pregnancy than those who did not. These findings suggest that the maternal metabolic environment in early pregnancy is important in determining later risks of excessive weight gain and metabolic disturbance, whereas birth weight is mediated more by genetic factors. It highlights key areas, which warrant further interrogation before future pregnancy intervention studies, in particular, maternal education level and inter-pregnancy weight gain.

Glucose intolerance and dyslipidaemia are independent risk factors for endothelium dysfunction and CVD. The aim of the present study was to analyse the preventive effect of n-3 PUFA (EPA and DHA) on lipid and carbohydrate disturbances and endothelial dysfunction. Three groups of adult hamsters were studied for 20 weeks: (1) control diet (Control); (2) high-fat diet (HF); (3) high-fat diet enriched with n-3 PUFA (HFn-3) groups. The increase in body weight and fat mass in the HF compared to the Control group (P < 0·05) was not found in the HFn-3 group. Muscle TAG content was similar in the Control and HF groups, but significantly lower in the HFn-3 group (P = 0·008). Glucose tolerance was impaired in the HF compared to the Control group, but this impairment was prevented by n-3 PUFA in the HFn-3 group (P < 0·001). Plasma TAG and cholesterol were higher in the HF group compared to the Control group (P < 0·001), but lower in the HFn-3 group compared to the HF group (P < 0·001). HDL-cholesterol was lower in the HFn-3 group compared to the Control and HF groups (P < 0·0005). Hepatic secretion of TAG was lower in the HFn-3 group compared to the HF group (P < 0·005), but did not differ from the Control group. Hepatic gene expression of sterol regulatory element-binding protein-1c, diacylglycerol O-acyltransferase 2 and stearyl CoA desaturase 1 was lower in the HFn-3 group, whereas carnitine palmitoyl transferase 1 and scavenger receptor class B type 1 expression was higher (P < 0·05). In adipocytes and adipose macrophages, PPARγ and TNFα expression was higher in the HF and HFn-3 groups compared to the Control group. Endothelium relaxation was higher in the HFn-3 (P < 0·001) than in the HF and Control groups, and was correlated with glucose intolerance (P = 0·03) and cholesterol (P = 0·0003). In conclusion, n-3 PUFA prevent some metabolic disturbances induced by high-fat diet and improve endothelial function in hamsters.

Both high and low maternal dietary intakes adversely affect fetal nutrient supply in adolescent sheep pregnancies. Aims were: (a) to assess the impact of prenatal nutrition on pregnancy outcome, offspring growth and offspring glucose metabolism and (b) to determine whether the offspring metabolic phenotype could then be altered by modifying postnatal nutrition. Dams carrying a single fetus were offered either an optimal control (C) intake to maintain adiposity throughout pregnancy, undernourished to maintain weight at conception but deplete maternal reserves (UN), or overnourished to promote rapid maternal growth and adiposity (ON). Placental weight and gestation length were reduced in ON dams and lamb birth weights were C>UN>ON (P < 0·001). All offspring were fed ad libitum from weaning to 6 months of age. ON offspring exhibited rapid catch-up growth and had increased fasting glucose and relative glucose intolerance compared with C offspring (P < 0·05). Irrespective of prenatal diet and sex, birth weight correlated negatively with these indices of glucose metabolism. From 7 to 12 months offspring either had continued ad libitum diet (ADLIB; to induce an obesogenic state) or a decreased ration appropriate for normal growth (NORM). At 12 months, the negative relationship between birth weight and indices of glucose metabolism persisted in ADLIB females (for example, fasting glucose, r − 0·632; P < 0·03) but was absent in NORM females and in both male groups. Therefore, low-birth-weight offspring from differentially achieved prenatal malnutrition exhibit an early adverse metabolic phenotype, and this can apparently be ameliorated by postnatal nutrition in females but not in males.

Oxidised frying oil (OFO) and fish oil have been shown to be peroxisome proliferator-activated receptor (PPAR)α activators and their ingestion results in pleotropic peroxisome proliferator responses in rats. To examine the effect of dietary OFO on adiposity, four groups of weanling Sprague–Dawley rats were fed isoenergetically with, respectively, a low fat basal diet containing 5 g/100 g of fresh soybean oil (LSB) or a high fat diet containing 20 g/100 g of fresh soybean oil (HSB), OFO (HO) or fish oil (HF). The tissue mass, cell size and lipid/DNA ratio in the retroperitoneal fat pad and serum leptin levels were lowest in the HO group (P < 0·05), indicating that dietary OFO has a greater anti-adipogenic action than dietary fish oil. However, a tendency to hyperglycaemia was observed in the HO group (P = 0·0528). To examine the effect of dietary OFO on glucose tolerance, three groups of rats and three groups of mice were fed, respectively, the LSB, HSB or HO diet, and an oral glucose tolerance test was performed. After oral glucose load, the area under the curve for blood glucose (AUCglu) over 2 h was significantly higher, and that for serum insulin (AUCins) over 90 min was significantly lower, in the HO group than in the other two groups (P < 0·05). These results demonstrate that, in rats and mice, a high OFO diet is less adipogenic, but induces glucose intolerance.

Objectives: The Finnish Diabetes Prevention Study (DPS) was a randomized intervention program that evaluated the effect of intensive lifestyle modification on the development of diabetes mellitus type 2 in patients with impaired glucose tolerance. As such, a program is demanding in terms of resources; it is necessary to assess whether it would be money well spent. This determination was the purpose of this study.

Methods: We developed a simulation model to assess the economic consequences of an intervention like the one studied in DPS in a Swedish setting. The model used data from the trial itself to assess the effect of intervention on the risk of diabetes and on risk factors for cardiovascular disease. Results from the United Kingdom Prospective Diabetes Study were used to estimate the risk of cardiovascular disease and stroke. Cost data were derived from Swedish studies. The intervention was assumed to be applied to eligible patients from a population-based screening program of 60-year-olds in the County of Stockholm from which the baseline characteristics of the patients was used.

Results: The model predicted that implementing the program would be cost-saving from the healthcare payers' perspective. Furthermore, it was associated with an increase in estimated survival of .18 years. Taking into consideration the increased consumption by patients due to their longer survival, the predicted cost-effectiveness ratio was 2,363€ per quality-adjusted life-year gained.

Conclusions: Lifestyle intervention directed toward high-risk subjects would be cost-saving for the healthcare payer and highly cost-effective for society as a whole.

Glucose intolerance represents a spectrum of abnormalities, including impaired fasting glucose, impaired glucose tolerance and type 2 diabetes. It is a major public health challenge worldwide, with rapidly increasing prevalence rates in both developed and developing countries. This global epidemic of diabetes is largely driven by the globalisation of Western culture and lifestyles. Specifically, there is now evidence from large-scale observational studies, and from intervention studies, of powerful synergistic interactions between diet, obesity, exercise, smoking and alcohol in the development of glucose intolerance. It is estimated that > 90 % of cases of type 2 diabetes in the population could be prevented with the adoption of a prudent diet (high in cereal fibre and polyunsaturated fatty acids and low in trans-fatty acids and glycaemic load), avoidance of overweight and obesity (BMI < 25 kg/m2), engagement in moderate to vigorous physical activity for at least 05 h/d, non-smoking and moderate alcohol consumption. These findings are biologically plausible and have major public health implications. They form the basis for a clear, simple and coherent message for health promotion and public policy. However, to make progress on these issues health will need to be placed at the centre of public policy and relevant vested interests tackled, notably in the food, entertainment, tobacco and automobile industries.

The clustering of cardiovascular risk factors such as abdominal obesity, hypertension, dyslipidaemia and glucose intolerance in the same persons has been called the metabolic or insulin-resistance syndrome. In 1998 WHO proposed a unifying definition for the syndrome and chose to call it the metabolic syndrome rather than the insulin-resistance syndrome. Although insulin resistance has been considered as a common denominator for the different components of the syndrome, there is still debate as to whether it is pathogenically involved in all of the different components of the syndrome. Clustering of the syndrome in families suggests a genetic component. It is plausible that so-called thrifty genes, which have ensured optimal storage of energy during periods of fasting, could contribute to the phenotype of the metabolic syndrome. Common variants in a number of candidate genes influencing fat and glucose metabolism can probably, together with environmental triggers, increase susceptibility to the syndrome. Among these, the genes for β3-adrenergic receptor, hormone-sensitive lipase, lipoprotein lipase, IRS-1, PC-1, skeletal muscle glycogen synthase, etc. appear to increase the risk of the metabolic syndrome. In addition, novel genes may be identified by genome-wide searches.