This study was conducted to examine whether glucose in maturation medium containing reduced NaCl could improve oocyte maturation and embryonic development in pigs. The base medium was bovine serum albumin-free porcine zygote medium (PZM)-3 containing 10% (v/v) pig follicular fluid (FPZM) or 0.1% (w/v) polyvinyl alcohol (PPZM). Using each medium, the effects of NaCl concentrations (108 and 61.6 mM) and 5.56 mM glucose supplementation (designated as PZM108N, PZM108G, PZM61N, and PZM61G, respectively) were examined using a 2 × 2 factorial arrangement. When oocytes were matured in FPZM, glucose supplementation improved nuclear maturation compared with no supplementation, regardless of the NaCl concentrations. FPZM61G showed a higher blastocyst formation compared with FPZM108N and FPZM108G after parthenogenesis (PA). Blastocyst formations of somatic cell nuclear transfer (SCNT) embryos derived from FPZM61N and FPZM61G were higher compared with those of oocytes from FPZM108N. When oocytes were matured in PPZM, glucose added to PPZM108 and PPZM61 increased nuclear maturation compared with no supplementation. However, glucose added to PPZM108 did not alter embryonic development after PA. Additionally, oocytes matured in PPZM61G showed a higher blastocyst formation compared with those from PPZM61N. In SCNT, blastocyst formation was not influenced by glucose supplementation of PPZM108, but was increased by maturation in glucose-supplemented PPZM61. In embryonic development of in vitro fertilization (IVF), oocytes matured in medium with reduced NaCl and glucose showed significantly higher blastocyst formation compared with those matured in PPZM108G. Our results demonstrated that glucose in maturation medium containing 61.6 mM NaCl increased oocyte maturation and embryonic development after PA, SCNT, and IVF.

Maternal nutrition status plays an important role in the development of fetal alcohol spectrum disorders (FASD), but its direct evidence is lacking. This study compared a standard chow with a semi-purified energy-dense (E-dense) diet on birth and metabolic outcomes in rats after ethanol (EtOH) consumption during pregnancy. Pregnant Sprague–Dawley rats were randomised into four groups: chow (n 6), chow + EtOH (20 %, v/v) (n 7), E-dense (n 6) and E-dense + EtOH (n 8). Birth outcomes including litter size, body and organ weights were collected. Metabolic parameters were measured in dams and pups at postnatal day (PD) 7. Maternal EtOH consumption decreased body weights (P < 0·0001) and litter sizes (P < 0·05) in chow-fed dams. At PD7, pups born to dams fed the E-dense diet had higher body (P < 0·002) and liver weights (P < 0·0001). These pups also had higher plasma total cholesterol (P < 0·0001), TAG (P < 0·003) and alanine aminotransferase (P < 0·03) compared with those from chow-fed dams. Dams fed the E-dense diet had higher plasma total (P < 0·0001) and HDL-cholesterol (P < 0·0001) and lower glucose (P < 0·0001). EtOH increased total cholesterol (P < 0·03) and glucose (P < 0·05) only in dams fed the E-dense diet. Maternal exposure to the E-dense diet attenuated prenatal EtOH-induced weight loss and produced different metabolic outcomes in both dams and pups. While the long-lasting effects of these outcomes are unknown, this study highlights the importance of maternal diet quality for maternal health and infant growth and suggests that maternal nutrition intervention may be a potential target for alleviating FASD.

Anti-diabetic actions of Camellia sinensis leaves, used traditionally for type 2 diabetes (T2DM) treatment, have been determined. Insulin release, membrane potential and intra-cellular Ca were studied using the pancreatic β-cell line, BRIN-BD11 and primary mouse pancreatic islets. Cellular glucose-uptake/insulin action by 3T3-L1 adipocytes, starch digestion, glucose diffusion, dipeptidyl peptidase-4 (DPP-IV) activity and glycation were determined together with in vivo studies assessing glucose homoeostasis in high-fat-fed (HFF) rats. Active phytoconstituents with insulinotropic activity were isolated using reversed-phase HPLC, LCMS and NMR. A hot water extract of C. sinensis increased insulin secretion in a concentration-dependent manner. Insulinotropic effects were significantly reduced by diazoxide, verapamil and under Ca-free conditions, being associated with membrane depolarisation and increased intra-cellular Ca2+. Insulin-releasing effects were observed in the presence of KCl, tolbutamide and isobutylmethylxanthine, indicating actions beyond K+ and Ca2+ channels. The extract also increased glucose uptake/insulin action in 3T3L1 adipocyte cells and inhibited protein glycation, DPP-IV enzyme activity, starch digestion and glucose diffusion. Oral administration of the extract enhanced glucose tolerance and insulin release in HFF rats. Extended treatment (250 mg/5 ml per kg orally) for 9 d led to improvements of body weight, energy intake, plasma and pancreatic insulin, and corrections of both islet size and β-cell mass. These effects were accompanied by lower glycaemia and significant reduction of plasma DPP-IV activity. Compounds isolated by HPLC/LCMS, isoquercitrin and rutin (464·2 Da and 610·3 Da), stimulated insulin release and improved glucose tolerance. These data indicate that C. sinensis leaves warrant further evaluation as an effective adjunctive therapy for T2DM and source of bioactive compounds.

Lutein is considered as a major biologically active carotenoid, with potential benefits for obesity and cardiometabolic health. This double-blind, randomised controlled trial aimed to assess whether the consumption of lutein along with a low-calorie diet (LCD) can influence anthropometric indices, body composition and metabolic parameters in obese middle-aged individuals. After a 2-week run-in period with an LCD, forty-eight participants aged 45–65 years were randomly assigned to consume 20 mg/d lutein or placebo along with the LCD for 10 weeks. Dietary intake, anthropometric indices, body composition, lipid profile, glucose homoeostasis parameters, NEFA and appetite sensations were assessed at the beginning and end of the study. After 10 weeks, body weight and waist circumference significantly decreased in both groups, although between-group differences were not significant. There was more of a decrease in the percentage of body fat in the lutein group v. the placebo group. Moreover, the placebo group experienced a significant reduction in fat-free mass (FFM), whereas the lutein group preserved FFM during calorie restriction, although the between-group difference did not reach statistical significance. Visceral fat and serum levels of total cholesterol (TC) and LDL-cholesterol were significantly decreased only in the lutein group, with a statistically significant difference between the two arms only for TC. No significant changes were observed in the TAG, HDL-cholesterol, glucose homoeostasis parameters, NEFA and appetite sensations. Lutein supplementation in combination with an LCD could improve body composition and lipid profile in obese middle-aged individuals.

There are few data on the effects on TAG, glucose and uric acid of chronic consumption of a moderate dose of fructose in solid foods. Twenty-eight participants with prediabetes and/or obesity and overweight commenced the study (BMI 32·3 kg/m2, age 44·7 years, fasting glucose 5·3 (sd 0·89) mmol/l and 2-h glucose 6·6 (sd 1·8) mmol/l). Twenty-four men and women who completed the study consumed, in random order, two acute test meals of muffins sweetened with either fructose or sucrose. This was followed by 4-week chronic consumption of 42 g/d of either fructose or sucrose in low-fat muffins after which the two meal tests were repeated. The sugar type in the chronic feeding period was also randomised. Fasting TAG increased after chronic consumption of fructose by 0·31 (sd 0·37) mmol/l compared with sucrose in those participants with impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) (P = 0·004). Total cholesterol (0·33 mmol/l), LDL-cholesterol (0·24 mmol/l) and HDL-cholesterol (0·08 mmol/l) increased significantly over the 1- month feeding period with no differences between muffin types. Fasting glucose was not different after 1 month of muffin consumption. Uric acid response was not different between the two sugar types either baseline or 1 month, and there were no differences between baseline and 1 month. The increase in fasting TAG in participants with IFG/IGT suggests the need for caution in people at increased risk of type 2 diabetes.

Mortality risk is known to be associated with many physiological or biochemical risk factors, and polygenic risk scores (PRSs) may offer an additional or alternative approach to risk stratification. We have compared the predictive value of common biochemical tests, PRSs and information on parental survival in a cohort of twins and their families. Common biochemical test results were available for up to 13,365 apparently healthy men and women, aged 17−93 years (mean 49.0, standard deviation [SD] 13.7) at blood collection. PRSs for longevity were available for 14,169 study participants and reported parental survival for 25,784 participants. A search for information on date and cause of death was conducted through the Australian National Death Index, with median follow-up of 11.3 years. Cox regression was used to evaluate associations with mortality from all causes, cancers, cardiovascular diseases and other causes. Linear relationships with all-cause mortality were strongest for C-reactive protein, gamma-glutamyl transferase, glucose and alkaline phosphatase, with hazard ratios (HRs) of 1.16 (95% CI [1.07, 1.24]), 1.15 (95% CI 1.04–1.21), 1.13 (95% CI [1.08, 1.19]) and 1.11 (95% CI [1.05, 1.88]) per SD difference, respectively. Significant nonlinear effects were found for urea, uric acid and butyrylcholinesterase. Lipid risk factors were not statistically significant for mortality in our cohort. Family history and PRS showed weaker but significant associations with survival, with HR in the range 1.05 to 1.09 per SD difference. In conclusion, biochemical tests currently predict long-term mortality more strongly than genetic scores based on genotyping or on reported parental survival.

We investigated the impact of recent caffeine drinking on glucose and other biomarkers of cardiometabolic function under free-living conditions while also accounting for lifestyle and genetic factors that alter caffeine metabolism and drinking behaviour. Up to 447 794 UK Biobank participants aged 37–73 years in 2006–2010 provided a non-fasting blood sample, for genetic and biomarker measures, and completed questionnaires regarding sociodemographics, medical history and lifestyle. Caffeine drinking (yes/no) about 1 h before blood collection was also recorded. Multivariable regressions were used to examine the association between recent caffeine drinking and serum levels of glycated Hb, glucose, lipids, apo, lipoprotein(a) and C-reactive protein. Men and women reporting recent caffeine drinking had clinically and significantly higher glucose levels than those not recently drinking caffeine (P < 0·0001). Larger effect sizes were observed among those 55+ years of age and with higher adiposity and longer fasting times (P ≤ 0·02 for interactions). Significant CYP1A2 rs2472297×caffeine and MLXIPL rs7800944 × caffeine interactions on glucose levels were observed among women (P = 0·004), with similar but non-significant interactions in men. Larger effect sizes were observed among women with rs2472297 CC or rs7800944 CC genotypes than among rs2472297 T or rs7800944 T carriers, respectively. In summary, men and women drinking caffeine within about 1 h of blood draw had higher glucose levels than those not drinking caffeine. Findings were modified by age, adiposity, fasting time and genetic factors related to caffeine metabolism and drinking behaviour. Implications for clinical and population studies of caffeine-containing beverages and cardiometabolic health are discussed.

Few studies have suggested that long-term adherence to low-carbohydrate diets (LCD) may affect maternal glucose metabolism in Western countries. We aimed to investigate the association between LCD during pregnancy and glucose metabolism in a Chinese population. A total of 1018 women in mid-pregnancy were recruited in 2017–2018. Participants underwent a 75 g oral glucose tolerance test (OGTT). Daily dietary intakes over the past month were accessed using a validated FFQ. The overall, animal and vegetable LCD scores which represent adherence to different low-carbohydrate dietary patterns were calculated. Mixed linear regression and generalised linear mixed regression were conducted to evaluate the associations between LCD scores and maternal glucose metabolism. Of the 1018 subjects, 194 (19·1 %) were diagnosed with gestational diabetes mellitus (GDM). The overall LCD score (β: 0·024, se 0·008, P FDR = 0·02) and animal LCD score (β: 0·023, se 0·008, P FDR = 0·02) were positively associated with OGTT 1-h glucose. No significant associations were found between the three different LCD scores with fasting plasma glucose, OGTT 2-h glucose, or insulin resistance, respectively. Compared with the lowest quartile, the crude OR of GDM for the highest quartile were 1·84 (95 % CI 1·14, 2·95) for overall LCD score (P for trend = 0·02) and 1·56 (95 % CI 1·00, 2·45) for animal LCD score (P for trend = 0·02). However, these associations became non-significant after adjustment for covariates. In conclusion, a low-carbohydrate dietary pattern with high animal protein and fat is associated with higher postprandial 1-h glucose levels in Chinese pregnant women.

Disorder of hepatic glucose metabolism is the characteristic of late-pregnant sows. The purpose of our study was to look into the mechanism of garcinol on the improvement of hepatic gluconeogenic enzyme in late-pregnant sows. Thirty second- and third-parity sows (Duroc × Yorkshire × Landrace, n 10/diet) were fed a basal diet (control) or that diet supplemented with 100 mg/kg (Low Gar) or 500 mg/kg (High Gar) garcinol from day 90 of gestation to the end of farrowing. The livers were processed to measure enzymatic activity. Hepatocytes from pregnant sows were transfected with P300/CBP-associating factor (PCAF) small interfering RNA (siRNA) or treated with garcinol. Dietary garcinol had no effect on average daily feed intake, body weight (BW), backfat and BW gain of late-pregnant sows. Garcinol promoted plasma glucose levels in pregnant sows and newborn piglets. Garcinol up-regulated hepatic gluconeogenic enzyme expression and decreased PCAF activity. Garcinol had no effect on the expression of PPAR-γ co-activator 1α (PGC-1α) and Forkhead box O1 (FOXO1) but significantly increased their activity and decreased their acetylation in late-pregnant sows. Transfection of PCAF siRNA to hepatocytes of pregnant sows increased PGC-1α and FOXO1 activities. Furthermore, in hepatocytes of pregnant sows, garcinol treatment also up-regulated the activities of PGC-1α and FOXO1 and inhibited the acetylation of PGC-1α and FOXO1. Garcinol improves hepatic gluconeogenic enzyme expression in late-pregnant sows, and this may be due to the mechanism of down-regulating the acetylation of PGC-1α and FOXO1 induced by PCAF in isolated hepatocytes.

To investigate the cumulative effects of maternal supplementation with nucleotides in the form of uridine (UR) on fatty acid and amino acid constituents of neonatal piglets, fifty-two sows in late gestation were assigned randomly into the control (CON) group (fed a basal diet) or UR group (fed a basal diet with 150 g/t UR). Samples of neonates were collected during farrowing. Results showed that supplementing with UR in sows’ diet significantly decreased the birth mortality of pigs (P = 0·05), and increased serum total cholesterol, HDL and LDL of neonatal piglets (P < 0·05). Moreover, the amino acid profile of serum and liver of neonatal piglets was affected by the addition of UR in sows’ diets (P < 0·05). Furthermore, an up-regulation of mRNA expression of energy metabolism-related genes, including fatty acid elongase 5, fatty acid desaturase 1, hormone-sensitive lipase and cholesterol-7a-hydroxylase, was observed in the liver of neonates from the UR group. Additionally, a decrease in placental gene expression of excitatory amino acid transporters 2, excitatory amino acid transporter 3 and neutral AA transporter 1 in the UR group was concurrently observed (P < 0·05), and higher protein expression of phosphorylated protein kinase B, raptor, PPARα and PPARγ in placenta from the UR group was also observed (P < 0·05). Together, these results showed that maternal UR supplementation could regulate placental nutrient transport, largely in response to an alteration of mTORC1–PPAR signalling, thus regulating the nutrition metabolism of neonatal piglets and improving reproductive performance.

n-3 Long-chain PUFA (LCPUFA) can improve cardiometabolic blood markers, but studies in children are limited. SNP in the FADS genes, which encode fatty acid desaturases, influence endogenous LCPUFA production. Moreover, SNP in genes that encode PPAR and apoE may modulate the effects of n-3 LCPUFA. We explored whether FADS polymorphisms were associated with blood cholesterol and TAG, insulin and glucose and whether polymorphisms in PPAR and APOE modified associations between FADS or n-3 LCPUFA status and the cardiometabolic blood markers. We measured fasting cholesterol and TAG, insulin, glucose and n-3 LCPUFA in 757 Danish 8–11-year-old children and genotyped SNP in FADS (rs1535 and rs174448), PPARG2 (rs1801282), PPARA (rs1800206) and APOE (rs7412+rs429358). Carriage of two FADS rs174448 major alleles was associated with lower TAG (P = 0·027) and higher HDL-cholesterol (P = 0·047). Blood n-3 LCPUFA was inversely associated with TAG and insulin in PPARG2 minor allele carriers and positively with LDL-cholesterol in major allele homozygotes (Pn-3 LCPUFA × rs180182 < 0·01). Associations between n-3 LCPUFA and cardiometabolic markers were not modified by APOE genotype (Pn-3 LCPUFA × APOE > 0·11), but interaction between FADS rs1535 and APOE showed that rs1535 major allele homozygotes who also carried APOE2 had higher HDL-cholesterol than all other genotype combinations (Prs1535 × APOE = 0·019, pairwise-P < 0·05). This indicates that FADS genotypes, which increase endogenous LCPUFA production, may beneficially affect children’s cardiometabolic profile in a partly APOE-dependent manner. Also, the degree to which children benefit from higher n-3 LCPUFA intake may depend on their PPARG2 genotype.

Resistant maltodextrin (RMD) from various sources of starch has been extensively studied. However, studies which reported the effects of tapioca RMD (TRM) on glucose and insulin response are lacking. This study investigated the effect of TRM on postprandial plasma glucose and serum insulin in healthy subjects. Additionally, satiety and gastrointestinal tolerability were also evaluated. Sixteen healthy participants received five different treatments on five separate days. Participants received 50 g of either: glucose (GL), tapioca maltodextrin (TM), TRM, MIX15% (7⋅5 g TRM + 42⋅5 g TM) or MIX50% (25 g TRM + 25 g TM). Plasma glucose, serum insulin and subjective appetite responses were measured postprandially over 180 min. Gastrointestinal symptoms were evaluated by questionnaire before and after each test day. Results showed that at 30 min after treatment drinks, plasma glucose after TRM was significantly lowest (104⋅60 (sem 2⋅63 mg/dl) than after GL (135⋅87 (sem 4⋅88) mg/dl; P <0⋅001), TM (127⋅93 (sem 4⋅05) mg/dl; P = 0⋅001), MIX15% (124⋅67 (sem 5⋅73) mg/dl; P = 0⋅039) and MIX50% (129⋅33 (sem 5⋅23) mg/dl; P = 0⋅003) (1 mg/dl = 0⋅0555 mmol/l). In addition, TRM also significantly reduced serum insulin (13⋅01 (sem 2⋅12) μIU/ml) compared with GL (47⋅90 (sem 11⋅93) μIU/ml; P = 0⋅013), TM (52⋅96 (sem 17⋅68) μIU/ml; P = 0⋅002) and MIX50% (33⋅16 (sem 4⋅99) μIU/ml; P = 0⋅008). However, there were no significant differences in subjective appetite between treatments (P > 0⋅05). A single high dose of TRM (50 g) caused flatulence (P < 0⋅05). Tapioca resistant maltodextrin has low digestibility in the small intestine and, therefore, reduced incremental plasma glucose and serum insulin, without affecting satiety in healthy subjects over 180 min. Gastrointestinal tolerability of TRM should be considered when consumed in high doses.

Dysregulation in hepatic lipid synthesis by excess dietary carbohydrate intake is often relevant with the occurrence of fatty liver; therefore, the thorough understanding of the regulation of lipid deposition and metabolism seems crucial to search for potential regulatory targets. In the present study, we examined TAG accumulation, lipid metabolism-related gene expression, the enzyme activities of lipogenesis-related enzymes, the protein levels of transcription factors or genes involving lipogenesis in the livers of yellow catfish fed five dietary carbohydrate sources, such as glucose, maize starch, sucrose, potato starch and dextrin, respectively. Generally speaking, compared with other carbohydrate sources, dietary glucose promoted TAG accumulation, up-regulated lipogenic enzyme activities and gene expressions, and down-regulated mRNA expression of genes involved in lipolysis and small ubiquitin-related modifier (SUMO) modification pathways. Further studies found that sterol regulatory element binding protein 1 (SREBP1), a key transcriptional factor relevant to lipogenic regulation, was modified by SUMO1. Mutational analyses found two important sites for SUMOylation modification (K254R and K264R) in SREBP1. Mutant SREBP lacking lysine 264 up-regulated the transactivation capacity on an SREBP-responsive promoter. Glucose reduced the SUMOylation level of SREBP1 and promoted the protein expression of SREBP1 and its target gene stearoyl-CoA desaturase 1 (SCD1), indicating that SUMOylation of SREBP1 mediated glucose-induced hepatic lipid metabolism. Our study elucidated the molecular mechanism of dietary glucose increasing hepatic lipid deposition and found that the SREBP-dependent transactivation was regulated by SUMO1 modification, which served as a new target for the transcriptional programmes governing lipid metabolism.

The farrowing process is one of the most energy-demanding activities for the modern hyperprolific sow. This study evaluated the effects of supply of energy on the expected date of farrowing on the farrowing kinetics and piglets’ performance during the first 24 h after birth. A total of 80 sows were used. The sows and their respective litters were considered as the experimental unit. On the expected day of farrowing, the sows were allocated to one of the following groups: sows that did not have access to feed from farrowing induction until the end of the farrowing process (CON, n = 40); sows fed 500 g of energetic supplement, which consisted of 250 g of the basal lactation diet plus 250 g of cane sugar, 18 h after farrowing induction (SUP, n = 40). The farrowing duration, farrowing assistance, birth interval, number of total born, stillborn and mummified piglets were recorded for each sow. Piglets were weighed individually at birth and 24 h later. The interval from birth to first suckle was evaluated individually for each piglet in 16 randomly selected litters (eight litters per treatment group). Blood glucose concentrations of six sows were measured shortly after expulsion of the first piglet. Farrowing duration, farrowing assistance and stillborn rate tended to be greater (P = 0.06, P = 0.09 and P = 0.07, respectively) in sows from the CON group compared to sows from the SUP group. However, there was no difference (P > 0.05) between the groups for birth interval. Colostrum intake was greater (P < 0.05) for piglets from the SUP group compared to piglets from the CON group. Additionally, BW gain of the piglets suckling the SUP group was greater (P < 0.05) than those suckling the CON group at 24 h after birth. The blood glucose concentrations during the expulsive stage of farrowing were greater (P < 0.05) in the SUP group than for sows from the CON group. In conclusion, supplying modern hyperprolific sows energy on the expected day of farrowing is a valuable nutritional intervention to improve the farrowing kinetics and piglets’ performance in early life.

Spirulina platensis has been found to be useful in the treatment of type 2 diabetes. The present study aims to elucidate the effects of ethanol extract and butanol fraction of S. platensis on insulin release and glucose homoeostasis in type 2 diabetic rats, together with their mechanism of actions. In vitro and in vivo methods were used including cellular studies to determine potential role of ion channels and cAMP in the insulinotropic actions of the extracts. The ethanol extract and butanol fraction stimulated insulin release from mouse islets and pancreatic β-cells in a concentration-dependent manner. The butanol fraction also similarly stimulated insulin release from perfused rat pancreas. The insulin-releasing action was augmented by glucose, isobutylmethylxanthine, tolbutamide and a depolarising concentration of KCl. The insulin secretory effect was attenuated with diazoxide and verapamil and by omission of extracellular Ca2+. Butanol fraction was found to significantly inhibit dipeptidyl peptidase IV enzyme activity. Moreover, butanol fraction improved glucose tolerance following oral glucose administration (2·5 g/kg body weight (b.w.)). The butanol fraction was tested on 24 h starved rats given an oral sucrose load (2·5 g/kg b.w.) to examine possible effects on carbohydrate digestion and absorption. S. platensis substantially decreased postprandial hyperglycaemia after oral sucrose load and increased unabsorbed sucrose content throughout the gut. During in situ intestinal perfusion with glucose, the butanol fraction reduced glucose absorption and promoted gut motility. Finally, chronic oral administration of butanol fraction for 28 d significantly decreased blood glucose, increased plasma insulin, pancreatic insulin stores, liver glycogen and improved lipid profile. The characterisation of active compounds from butanol fraction revealed the presence of p-coumaric acid, β-carotene, catechin and other antioxidant polyphenols. In conclusion, S. platensis could be an adjunctive therapy for the management of type 2 diabetes.

Morning coffee is a common remedy following disrupted sleep, yet each factor can independently impair glucose tolerance and insulin sensitivity in healthy adults. Remarkably, the combined effects of sleep fragmentation and coffee on glucose control upon waking per se have never been investigated. In a randomised crossover design, twenty-nine adults (mean age: 21 (sd 1) years, BMI: 24·4 (sd 3·3) kg/m2) underwent three oral glucose tolerance tests (OGTT). One following a habitual night of sleep (Control; in bed, lights-off trying to sleep approximately 23.00–07.00 hours), the others following a night of sleep fragmentation (as Control but waking hourly for 5 min), with and without morning coffee approximately 1 h after waking (approximately 300 mg caffeine as black coffee 30 min prior to OGTT). Individualised peak plasma glucose and insulin concentrations were unaffected by sleep quality but were higher following coffee consumption (mean (normalised CI) for Control, Fragmented and Fragmented + Coffee, respectively; glucose: 8·20 (normalised CI 7·93, 8·47) mmol/l v. 8·23 (normalised CI 7·96, 8·50) mmol/l v. 8·96 (normalised CI 8·70, 9·22) mmol/l; insulin: 265 (normalised CI 247, 283) pmol/l; and 235 (normalised CI 218, 253) pmol/l; and 310 (normalised CI 284, 337) pmol/l). Likewise, incremental AUC for plasma glucose was higher in the Fragmented + Coffee trial compared with Fragmented. Whilst sleep fragmentation did not alter glycaemic or insulinaemic responses to morning glucose ingestion, if a strong caffeinated coffee is consumed, then a reduction in glucose tolerance can be expected.

The prevalence of Diabetes Mellitus (DM) is becoming a serious public health problem. The use of atypical antipsychotics has been associated with disruption of the glucose metabolism and therefore with causing DM. The underlying mechanisms are unknown, but knowledge of the differences between the pharmacological features of various antipsychotics combined with their diabetogenic profile might help us to understand those mechanisms. This article describes how the binding of various essential receptors or transporters in essential body tissues, adipose tissue, pancreatic tissue and liver and skeletal muscle tissue can cause disruption of the glucose metabolism. With such knowledge in mind one can try to explain the differences between the diabetogenic propensities of various antipsychotics. It is well known that clozapine and olanzapine cause weight gain and DM, whereas aripiprazole and ziprasidone have much less disruptive clinical profiles. The most significant risk factor for adiposity seems to be strong blocking of histaminergic receptors. An agonistic activity on serotonergic-1a receptors, with a very low affinity for muscarinergic-3 receptors, might protect against the development of DM. More data will become available which may help to solve the puzzle.