Fish oil supplemented for 9 months does not improve glycaemic control or insulin sensitivity in subjects with impaired glucose regulation: a parallel randomised controlled trial.

The effects of fish oil (FO) supplementation on glycaemic control are unclear, and positive effects may occur only when the phospholipid content of tissue membranes exceeds 14% as n-3 PUFA. Subjects (n 36, thirty-three completed) were paired based on metabolic parameters and allocated into a parallel double-blind randomised trial with one of each pair offered daily either 6 g of FO (3·9 g n-3 PUFA) or 6 g of maize oil (MO) for 9 months. Hyperinsulinaemic-euglycaemic-euaminoacidaemic (HIEGEAA) clamps (with [6,6 2H2 glucose]) were performed at the start and end of the intervention. Endogenous glucose production (EGP) and whole-body protein turnover (WBPT) were each measured after an overnight fast. The primary outcome involved the effect of oil type on insulin sensitivity related to glycaemic control. The secondary outcome involved the effect of oil type on WBPT. Subjects on FO (n 16) had increased erythrocyte n-3 PUFA concentrations >14%, whereas subjects on MO (n 17) had unaltered n-3 PUFA concentrations at 9%. Type of oil had no effect on fasting EGP, insulin sensitivity or total glucose disposal during the HIEGEAA clamp. In contrast, under insulin-stimulated conditions, total protein disposal (P=0·007) and endogenous WBPT (P=0·001) were both increased with FO. In an associated pilot study (n 4, three completed), although n-3 PUFA in erythrocyte membranes increased to >14% with the FO supplement, the enrichment in muscle membranes remained lower (8%; P<0·001). In conclusion, long-term supplementation with FO, at amounts near the safety limits set by regulatory authorities in Europe and the USA, did not alter glycaemic control but did have an impact on WBPT.

Imposed rate and extent of weight loss in obese men and adaptive changes in resting and total energy expenditure.

OBJECTIVES: Weight loss (WL) is associated with a decrease in total and resting energy expenditure (EE). We aimed to investigate whether (1) diets with different rate and extent of WL determined different changes in total and resting EE and if (2) they influenced the level of adaptive thermogenesis, defined as the decline in total or resting EE not accounted by changes in body composition. METHODS: Three groups of six, obese men participated in a total fast for 6 days to achieve a 5% WL and a very low calorie (VLCD, 2.5 MJ/day) for 3 weeks or a low calorie (LCD, 5.2 MJ/day) diet for 6 weeks to achieve a 10% WL. A four-component model was used to measure body composition. Indirect calorimetry was used to measure resting EE. Total EE was measured by doubly labelled water (VLCD, LCD) and 24-hour whole-body calorimetry (fasting). RESULTS: VLCD and LCD showed a similar degree of metabolic adaptation for total EE (VLCD = -6.2%; LCD = -6.8%). Metabolic adaptation for resting EE was greater in the LCD (-0.4 MJ/day, -5.3%) compared to the VLCD (-0.1 MJ/day, -1.4%) group. Resting EE did not decrease after short-term fasting and no evidence of adaptive thermogenesis (+0.4 MJ/day) was found after 5% WL. The rate of WL was inversely associated with changes in resting EE (n = 30, r = 0.-42, p=0.01). CONCLUSIONS: The rate of WL did not appear to influence the decline in total EE in obese men after 10% WL. Approximately 6% of this decline in total EE was explained by mechanisms of adaptive thermogenesis.

Responses in gut hormones and hunger to diets with either high protein or a mixture of protein plus free amino acids supplied under weight-loss conditions.

High-protein diets are an effective means for weight loss (WL), but the mechanisms are unclear. One hypothesis relates to the release of gut hormones by either protein or amino acids (AA). The present study involved overweight and obese male volunteers (n 18, mean BMI 36·8 kg/m2) who consumed a maintenance diet for 7 d followed by fully randomised 10 d treatments with three iso-energetic WL diets, i.e. with either normal protein (NP, 15% of energy) or high protein (HP, 30%) or with a combination of protein and free AA, each 15% of energy (NPAA). Psychometric ratings of appetite were recorded hourly. On day 10, plasma samples were taken at 30 min intervals over two consecutive 5 h periods (covering post-breakfast and post-lunch) and analysed for AA, glucose and hormones (insulin, total glucose-dependent insulinotropic peptide, active ghrelin and total peptide YY (PYY)) plus leucine kinetics (first 5 h only). Composite hunger was 16% lower for the HP diet than for the NP diet (P<0·01) in the 5 h period after both meals. Plasma essential AA concentrations were greatest within 60 min of each meal for the NPAA diet, but remained elevated for 3-5 h after the HP diet. The three WL diets showed no difference for either fasting concentrations or the postprandial net incremental AUC (net AUCi) for insulin, ghrelin or PYY. No strong correlations were observed between composite hunger scores and net AUCi for either AA or gut peptides. Regulation of hunger may involve subtle interactions, and a range of signals may need to be integrated to produce the overall response.

Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men.

There is growing interest in understanding how diet affects the intestinal microbiota, including its possible associations with systemic diseases such as metabolic syndrome. Here we report a comprehensive and deep microbiota analysis of 14 obese males consuming fully controlled diets supplemented with resistant starch (RS) or non-starch polysaccharides (NSPs) and a weight-loss (WL) diet. We analyzed the composition, diversity and dynamics of the fecal microbiota on each dietary regime by phylogenetic microarray and quantitative PCR (qPCR) analysis. In addition, we analyzed fecal short chain fatty acids (SCFAs) as a proxy of colonic fermentation, and indices of insulin sensitivity from blood samples. The diet explained around 10% of the total variance in microbiota composition, which was substantially less than the inter-individual variance. Yet, each of the study diets induced clear and distinct changes in the microbiota. Multiple Ruminococcaceae phylotypes increased on the RS diet, whereas mostly Lachnospiraceae phylotypes increased on the NSP diet. Bifidobacteria decreased significantly on the WL diet. The RS diet decreased the diversity of the microbiota significantly. The total 16S ribosomal RNA gene signal estimated by qPCR correlated positively with the three major SCFAs, while the amount of propionate specifically correlated with the Bacteroidetes. The dietary responsiveness of the individual's microbiota varied substantially and associated inversely with its diversity, suggesting that individuals can be stratified into responders and non-responders based on the features of their intestinal microbiota.

Oat-enriched diet reduces inflammatory status assessed by circulating cell-derived microparticle concentrations in type 2 diabetes.

SCOPE: Inflammatory status can increase the risk of adverse cardiovascular events linked to platelet activity and involvement of microparticles (MP) released from platelets (PMP), leukocytes (LMP), and monocytes (MMP). These MP carry host cell-derived antigens that may act as markers of metabolic health. Subjects newly diagnosed with type 2 diabetes are offered appropriate standard dietary advice (SDA) but this may not be optimal as specific inclusion of other nutrients, such as oats, may add benefit. The effectiveness of such interventions can be tested by examination of MP activation markers. METHODS AND RESULTS: Subjects (n = 22) with type 2 diabetes participated in a randomized cross-over trial involving 8 wk interventions with either an oat-enriched diet (OAT) or following reinforced SDA. Responses were also compared with preintervention habitual (HAB) intake. OAT reduced the concentrations and proportions of fibrinogen- and tissue factor-related PMP and MMP_11b. The main effect of SDA was to reduce fibrinogen-activated PMP. Regardless of chronic intake, a healthy test meal led to postprandial declines in total PMP as well as tissue factor-, fibrinogen-, and P-selectin-positive PMP. CONCLUSION: OAT improved risk factors assessed by MP status, even in subjects with type 2 diabetes already well-controlled by diet and life-style alone.

Glucose uptake by the brain on chronic high-protein weight-loss diets with either moderate or low amounts of carbohydrate.

Previous work has shown that hunger and food intake are lower in individuals on high-protein (HP) diets when combined with low carbohydrate (LC) intakes rather than with moderate carbohydrate (MC) intakes and where a more ketogenic state occurs. The aim of the present study was to investigate whether the difference between HPLC and HPMC diets was associated with changes in glucose and ketone body metabolism, particularly within key areas of the brain involved in appetite control. A total of twelve men, mean BMI 34·9 kg/m², took part in a randomised cross-over trial, with two 4-week periods when isoenergetic fixed-intake diets (8·3 MJ/d) were given, with 30% of the energy being given as protein and either (1) a very LC (22 g/d; HPLC) or (2) a MC (182 g/d; HPMC) intake. An ¹8fluoro-deoxyglucose positron emission tomography scan of the brain was conducted at the end of each dietary intervention period, following an overnight fast (n 4) or 4 h after consumption of a test meal (n 8). On the next day, whole-body ketone and glucose metabolism was quantified using [1,2,3,4-¹³C]acetoacetate, [2,4-¹³C]3-hydroxybutyrate and [6,6-²H2]glucose. The composite hunger score was 14% lower (P= 0·013) for the HPLC dietary intervention than for the HPMC diet. Whole-body ketone flux was approximately 4-fold greater for the HPLC dietary intervention than for the HPMC diet (P< 0·001). The 9-fold difference in carbohydrate intakes between the HPLC and HPMC dietary interventions led to a 5% lower supply of glucose to the brain. Despite this, the uptake of glucose by the fifty-four regions of the brain analysed remained similar for the two dietary interventions. In conclusion, differences in the composite hunger score observed for the two dietary interventions are not associated with the use of alternative fuels by the brain.

Measurement of body composition changes during weight loss in obese men using multi-frequency bioelectrical impedance analysis and multi-compartment models.

BACKGROUND: The accurate measurement of changes in body composition is important to assess the contribution of fat and fat free mass to total body mass change as a measure of the effectiveness of weight loss programmes. Bioelectrical impedance spectroscopy (BIS) is a rapid and non-invasive technique which could be applied to assess body composition changes. The aim of the study was to evaluate the accuracy of the BIS for the measurement of fat mass (FM), total body water (TBW) and extracellular water (ECW) changes induced by different degrees of caloric deficit in obese men. METHODS: Three groups of six, obese men participated in either (i) a total fast (for 6 days); (ii) a VLCD (2.5 MJ/day for 3 weeks); or (iii) LCD (5.2 MJ/day for 6 weeks). FM was measured using a 4-compartment (4-C) model. TBW and ECW were determined by dilution methods, respectively. TBW, ECW and FM were also assessed with BIS. RESULTS: Body weight loss in the fasting group was 6.0 ± 1.3 kg over 6 days; the VLCD group lost 9.2 ± 1.2 kg over 21 days and the LCD group lost 12.6 ± 2.4 kg over 42 days. BIS underestimated FM changes (bias = -3.3 ± 3.8 kg) and overestimated changes in TBW and ECW by +1.8 ± 4.8 kg and +2.3 ± 6.4 kg, respectively. The measurement error was consistently larger in the fasting group and the magnitude of the bias interacted significantly with the rate of weight loss. CONCLUSION: Rapid weight loss affects the accuracy of the BIS in detecting changes in body composition. A careful interpretation of the results is needed when sizable changes in body water compartments occurs.

Platelet-derived microparticle count and surface molecule expression differ between subjects with and without type 2 diabetes, independently of obesity status.

This study investigated the impact of either type 2 diabetes or obesity, separately or in combination, on the absolute amounts of microparticles (MP) and the pathways by which these are associated with either condition. The concentrations of circulating MP derived from platelets (PMP), leukocytes (LMP) and monocytes (MMP), together with their specific activation markers, were compared in 30 subjects who were characterised across 4 cohorts as obese or type 2 diabetes. The subjects with type 2 diabetes had elevated concentrations of total PMP (P = 0.003), and PMP that were fibrinogen-positive (P = 0.04), tissue factor-positive (P < 0.001), P-selectin-positive (P = 0.03). Type 2 diabetes did not alter either total or activated LMP or MMP. Obesity per se did not impact on any MP measurement. Elevated concentrations of plasma PMP occurred in subjects with type 2 diabetes, whether they were obese or non-obese. In contrast, obesity in the absence of type 2 diabetes had no effect. The increased concentrations of specific marker-positive PMP in the subjects with diabetes might reflect potential pathways by which PMP may contribute to the pathogenesis of atherosclerosis and type 2 diabetes.

Impact of short term consumption of diets high in either non-starch polysaccharides or resistant starch in comparison with moderate weight loss on indices of insulin sensitivity in subjects with metabolic syndrome.

This study investigated if additional non-starch polysaccharide (NSP) or resistant starch (RS), above that currently recommended, leads to better improvement in insulin sensitivity (IS) than observed with modest weight loss (WL). Obese male volunteers (n = 14) were given an energy-maintenance (M) diet containing 27 g NSP and 5 g RS daily for one week. They then received, in a cross-over design, energy-maintenance intakes of either an NSP-enriched diet (42 g NSP, 2.5 g RS) or an RS-enriched diet (16 g NSP, 25 g RS), each for three weeks. Finally, a high protein (30% calories) WL diet was provided at 8 MJ/day for three weeks. During each dietary intervention, endogenous glucose production (EGP) and IS were assessed. Fasting glycaemia was unaltered by diet, but plasma insulin and C-peptide both decreased with the WL diet (p < 0.001), as did EGP (-11%, p = 0.006). Homeostatis model assessment of insulin resistance improved following both WL (p < 0.001) and RS (p < 0.05) diets. Peripheral tissue IS improved only with WL (57%-83%, p < 0.005). Inclusion of additional RS or NSP above amounts currently recommended resulted in little or no improvement in glycaemic control, whereas moderate WL (approximately 3 kg fat) improved IS.

Effects of methyl-deficient diets on methionine and homocysteine metabolism in the pregnant rat.

Although the importance of methyl metabolism in fetal development is well recognized, there is limited information on the dynamics of methionine flow through maternal and fetal tissues and on how this is related to circulating total homocysteine concentrations. Rates of homocysteine remethylation in maternal and fetal tissues on days 11, 19, and 21 of gestation were measured in pregnant rats fed diets with limiting or surplus amounts of folic acid and choline at two levels of methionine and then infused with L-[1-(13)C,(2)H(3)-methyl]methionine. The rate of homocysteine remethylation was highest in maternal liver and declined as gestation progressed. Diets deficient in folic acid and choline reduced the production of methionine from homocysteine in maternal liver only in the animals fed a methionine-limited diet. Throughout gestation, the pancreas exported homocysteine for methylation within other tissues. Little or no methionine cycle activity was detected in the placenta at days 19 and 21 of gestation, but, during this period, fetal tissues, especially the liver, synthesized methionine from homocysteine. Greater enrichment of homocysteine in maternal plasma than placenta, even in animals fed the most-deficient diets, shows that the placenta did not contribute homocysteine to maternal plasma. Methionine synthesis from homocysteine in fetal tissues was maintained or increased when the dams were fed folate- and choline-deficient methionine-restricted diets. This study shows that methyl-deficient diets decrease the remethylation of homocysteine within maternal tissues but that these rates are protected to some extent within fetal tissues.

Phylogenetic distribution of genes encoding ß-glucuronidase activity in human colonic bacteria and the impact of diet on faecal glycosidase activities.

Bacterial ß-glucuronidase in the human colon plays an important role in cleaving liver conjugates of dietary compounds and xenobiotics, while other glycosidase activities are involved in the conversion of dietary plant glycosides. Here we detected an increase in ß-glucuronidase activity in faecal samples from obese volunteers following a high-protein moderate carbohydrate weight-loss diet, compared with a weight maintenance diet, but little or no changes were observed when the type of fermentable carbohydrate was varied. Other faecal glycosidase activities showed little or no change over a fivefold range of dietary NSP intake, although α-glucosidase increased on a resistant starch-enriched diet. Two distinct groups of gene, gus and BG, have been reported to encode ß-glucuronidase activity among human colonic bacteria. Degenerate primers were designed against these genes. Overall, Firmicutes were found to account for 96% of amplified gus sequences, with three operational taxonomic units particularly abundant, whereas 59% of amplified BG sequences belonged to Bacteroidetes and 41% to Firmicutes. A similar distribution of operational taxonomic units was found in a published metagenome dataset involving a larger number of volunteers. Seven cultured isolates of human colonic bacteria that carried only the BG gene gave relatively low ß-glucuronidase activity that was not induced by 4-nitrophenyl-ß-D-glucuronide. By comparison, in three of five isolates that possessed only the gus gene, ß-glucuronidase activity was induced.

Anabolic signaling and protein deposition are enhanced by intermittent compared with continuous feeding in skeletal muscle of neonates.

Orogastric tube feeding is indicated for neonates with impaired ability to ingest and can be administered by intermittent bolus or continuous schedule. Our aim was to determine whether feeding modalities affect muscle protein deposition and to identify mechanisms involved. Neonatal pigs were overnight fasted (FAS) or fed the same amount of food continuously (CON) or intermittently (INT; 7 × 4 h meals) for 29 h. For 8 h, between hours 20 and 28, pigs were infused with [(2)H(5)]phenylalanine and [(2)H(2)]tyrosine, and amino acid (AA) net balances were measured across the hindquarters. Insulin, branched-chain AA, phenylalanine, and tyrosine arterial concentrations and whole body phenylalanine and tyrosine fluxes were greater for INT after the meal than for CON or FAS. The activation of signaling proteins leading to initiation of mRNA translation, including eukaryotic initiation factor (eIF)4E·eIF4G complex formation in muscle, was enhanced by INT compared with CON feeding or FAS. Signaling proteins of protein degradation were not affected by feeding modalities except for microtubule-associated protein light chain 3-II, which was highest in the FAS. Across the hindquarters, AA net removal increased for INT but not for CON or FAS, with protein deposition greater for INT. This was because protein synthesis increased following feeding for INT but remained unchanged for CON and FAS, whereas there was no change in protein degradation across any dietary treatment. These results suggest that muscle protein accretion in neonates is enhanced with intermittent bolus to a greater extent than continuous feeding, mainly by increased protein synthesis.

Effects of a high-protein, low-carbohydrate v. high-protein, moderate-carbohydrate weight-loss diet on antioxidant status, endothelial markers and plasma indices of the cardiometabolic profile.

There are concerns that weight-loss (WL) diets based on very low carbohydrate (LC) intake have a negative impact on antioxidant status and biomarkers of cardiovascular and metabolic health. Obese men (n 16) participated in a randomised, cross-over design diet trial, with food provided daily, at approximately 8.3 MJ/d (approximately 70 % of energy maintenance requirements). They were provided with two high-protein diets (30 % of energy), each for a 4-week period, involving a LC (4 % carbohydrate) and a moderate carbohydrate (MC, 35 % carbohydrate) content. Body weight was measured daily, and weekly blood samples were collected. On average, subjects lost 6.75 and 4.32 kg of weight on the LC and MC diets, respectively (P < 0.001, SED 0.350). Although the LC and MC diets were associated with a small reduction in plasma concentrations of retinol, vitamin E (α-tocopherol) and ß-cryptoxanthin (P < 0.005), these were still above the values indicative of deficiency. Interestingly, plasma vitamin C concentrations increased on consumption of the LC diet (P < 0.05). Plasma markers of insulin resistance (P < 0.001), lipaemia and inflammation (P < 0.05, TNF-α and IL-10) improved similarly on both diets. There was no change in other cardiovascular markers with WL. The present data suggest that a LC WL diet does not impair plasma indices of cardiometabolic health, at least within 4 weeks, in otherwise healthy obese subjects. In general, improvements in metabolic health associated with WL were similar between the LC and MC diets. Antioxidant supplements may be warranted if LC WL diets are consumed for a prolonged period.

High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health.

BACKGROUND: Diets that are high in protein but reduced in carbohydrate contents provide a common approach for achieving weight loss in obese humans. However, the effect of such diets on microbiota-derived metabolites that influence colonic health has not been established. OBJECTIVE: We designed this study to assess the effect of diets with reduced carbohydrate and increased protein contents on metabolites considered to influence long-term colonic health, in particular the risk of colorectal disease. DESIGN: We provided 17 obese men with a defined weight-maintenance diet (85 g protein, 116 g fat, and 360 g carbohydrate/d) for 7 d followed by 4 wk each of a high-protein and moderate-carbohydrate (HPMC; 139 g protein, 82 g fat, and 181 g carbohydrate/d) diet and a high-protein and low-carbohydrate (HPLC; 137 g protein, 143 g fat, and 22 g carbohydrate/d) diet in a crossover design. Fecal samples were analyzed to determine concentrations of phenolic metabolites, short-chain fatty acids, and nitrogenous compounds of dietary and microbial origin. RESULTS: Compared with the maintenance diet, the HPMC and HPLC diets resulted in increased proportions of branched-chain fatty acids and concentrations of phenylacetic acid and N-nitroso compounds. The HPLC diet also decreased the proportion of butyrate in fecal short-chain fatty acid concentrations, which was concomitant with a reduction in the Roseburia/Eubacterium rectale group of bacteria, and greatly reduced concentrations of fiber-derived, antioxidant phenolic acids such as ferulate and its derivatives. CONCLUSIONS: After 4 wk, weight-loss diets that were high in protein but reduced in total carbohydrates and fiber resulted in a significant decrease in fecal cancer-protective metabolites and increased concentrations of hazardous metabolites. Long-term adherence to such diets may increase risk of colonic disease.

Rates of production and utilization of lactate by microbial communities from the human colon.

Lactate metabolism was studied in mixed bacterial communities using single-stage continuous flow fermentors inoculated with faecal slurries from four different volunteers and run for 6 days at pH 5.5 and 6.0, using carbohydrates, mainly starch, as substrates. A continuous infusion of [U-(13) C]starch and l-[3-(13) C]lactate was performed on day 5 and a bolus injection of l-[3-(13) C]lactate plus dl-lactate on day 6. Short-chain fatty acids and lactate concentrations plus enrichments and numbers of lactate-producing and -utilizing bacteria on day 5 were measured. Faecal samples were also collected weekly over a 3-month period to inoculate 24-h batch culture incubation at pH 5.9 and 6.5 with carbohydrates alone or with 35 mmol L(-1) lactate. In the fermentors, the potential lactate disposal rates were more than double the formation rates, and lactate concentrations usually remained below detection. Lactate formation was greater (P<0.05) at the lower pH, with a similar tendency for utilization. Up to 20% of butyrate production was derived from lactate. In batch cultures, lactate was also efficiently used at both pH values, especially at 6.5, although volunteer and temporal variability existed. Under healthy gut environmental conditions, bacterial lactate disposal seems to exceed production markedly.

Dominant and diet-responsive groups of bacteria within the human colonic microbiota.

The populations of dominant species within the human colonic microbiota can potentially be modified by dietary intake with consequences for health. Here we examined the influence of precisely controlled diets in 14 overweight men. Volunteers were provided successively with a control diet, diets high in resistant starch (RS) or non-starch polysaccharides (NSPs) and a reduced carbohydrate weight loss (WL) diet, over 10 weeks. Analysis of 16S rRNA sequences in stool samples of six volunteers detected 320 phylotypes (defined at >98% identity) of which 26, including 19 cultured species, each accounted for >1% of sequences. Although samples clustered more strongly by individual than by diet, time courses obtained by targeted qPCR revealed that 'blooms' in specific bacterial groups occurred rapidly after a dietary change. These were rapidly reversed by the subsequent diet. Relatives of Ruminococcus bromii (R-ruminococci) increased in most volunteers on the RS diet, accounting for a mean of 17% of total bacteria compared with 3.8% on the NSP diet, whereas the uncultured Oscillibacter group increased on the RS and WL diets. Relatives of Eubacterium rectale increased on RS (to mean 10.1%) but decreased, along with Collinsella aerofaciens, on WL. Inter-individual variation was marked, however, with >60% of RS remaining unfermented in two volunteers on the RS diet, compared to <4% in the other 12 volunteers; these two individuals also showed low numbers of R-ruminococci (<1%). Dietary non-digestible carbohydrate can produce marked changes in the gut microbiota, but these depend on the initial composition of an individual's gut microbiota.

Food intake and dietary glycaemic index in free-living adults with and without type 2 diabetes mellitus.

UNLABELLED: A recent Cochrane review concluded that low glycaemic index (GI) diets are beneficial in glycaemic control for patients with type 2 diabetes mellitus (T2DM). There are limited UK data regarding the dietary GI in free-living adults with and without T2DM. We measured the energy and macronutrient intake and the dietary GI in a group (n = 19) of individuals with diet controlled T2DM and a group (n = 19) without diabetes, matched for age, BMI and gender. Subjects completed a three-day weighed dietary record. Patients with T2DM consumed more daily portions of wholegrains (2.3 vs. 1.1, P = 0.003), more dietary fibre (32.1 vs. 20.9 g, P < 0.001) and had a lower diet GI (53.5 vs. 57.7, P = 0.009) than subjects without T2DM. Both groups had elevated fat and salt intake and low fruit and vegetable intake, relative to current UK recommendations. CONCLUSIONS: Patients with T2DM may already consume a lower GI diet than the general population but further efforts are needed to reduce dietary GI and achieve other nutrient targets.

Effects of proportions of dietary macronutrients on glucocorticoid metabolism in diet-induced obesity in rats.

Tissue glucocorticoid levels in the liver and adipose tissue are regulated by regeneration of inactive glucocorticoid by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and inactivation by 5alpha- and 5beta-reductases. A low carbohydrate diet increases hepatic 11beta-HSD1 and reduces glucocorticoid metabolism during weight loss in obese humans. We hypothesized that similar variations in macronutrient proportions regulate glucocorticoid metabolism in obese rats. Male Lister Hooded rats were fed an obesity-inducing ad libitum 'Western' diet (37% fat, n = 36) for 22 weeks, then randomised to continue this diet (n = 12) or to switch to either a low carbohydrate (n = 12) or a moderate carbohydrate (n = 12) diet for the final 8 weeks. A parallel lean control group were fed an ad libitum control diet (10% fat, n = 12) throughout. The low and moderate carbohydrate diets decreased hepatic 11beta-HSD1 mRNA compared with the Western diet (both 0.7+/-0.0 vs 0.9+/-0.1 AU; p<0.01), but did not alter 11beta-HSD1 in adipose tissue. 5Alpha-reductase mRNA was increased on the low carbohydrate compared with the moderate carbohydrate diet. Compared with lean controls, the Western diet decreased 11beta-HSD1 activity (1.6+/-0.1 vs 2.8+/-0.1 nmol/mcg protein/hr; p<0.001) and increased 5alpha-reductase and 5beta-reductase mRNAs (1.9+/-0.3 vs 1.0+/-0.2 and 1.6+/-0.1 vs 1.0+/-0.1 AU respectively; p<0.01) in the liver, and reduced 11beta-HSD1 mRNA and activity (both p<0.01) in adipose tissue. Although an obesity-inducing high fat diet in rats recapitulates the abnormal glucocorticoid metabolism associated with human obesity in liver (but not in adipose tissue), a low carbohydrate diet does not increase hepatic 11beta-HSD1 in obese rats as occurs in humans.

Tissue methionine cycle activity and homocysteine metabolism in female rats: impact of dietary methionine and folate plus choline.

Impaired transfer of methyl groups via the methionine cycle leads to plasma hyperhomocysteinemia. The tissue sources of plasma homocysteine in vivo have not been quantified nor whether hyperhomocysteinemia is due to increased entry or decreased removal. These issues were addressed in female rats offered diets with either adequate or excess methionine (additional methyl groups) with or without folate and choline (impaired methyl group transfer) for 5 wk. Whole body and tissue metabolism was measured based on isotopomer analysis following infusion with either [1-(13)C,methyl-(2)H3]methionine or [U-(13)C]methionine plus [1-(13)C]homocysteine. Although the fraction of intracellular methionine derived from methylation of homocysteine was highest in liver (0.18-0.21), most was retained. In contrast, the pancreas exported to plasma more of methionine synthesized de novo. The pancreas also exported homocysteine to plasma, and this matched the contribution from liver. Synthesis of methionine from homocysteine was reduced in most tissues with excess methionine supply and was also lowered in liver (P<0.01) with diets devoid of folate and choline. Plasma homocysteine concentration (P<0.001) and flux (P=0.001) increased with folate plus choline deficiency, although the latter still represented <12% of estimated tissue production. Hyperhomocysteinemia also increased (P<0.01) the inflow of homocysteine into most tissues, including heart. These findings indicate that a full understanding of hyperhomocysteinemia needs to include metabolism in a variety of organs, rather than an exclusive focus on the liver. Furthermore, the high influx of homocysteine into cardiac tissue may relate to the known association between homocysteinemia and hypertension.