Fetal restriction (FR) alters insulin sensitivity, but it is unknown how the metabolic profile associated with restriction affects development of the dopamine (DA) system and DA-related behaviors. The Netrin-1/DCC guidance cue system participates in maturation of the mesocorticolimbic DA circuitry. Therefore, our objective was to identify if FR modifies Netrin-1/DCC receptor protein expression in the prefrontal cortex (PFC) at birth and mRNA in adulthood in rodent males. We used cultured HEK293 cells to assess if levels of miR-218, microRNA regulator of DCC, are sensitive to insulin. To assess this, pregnant dams were subjected to a 50% FR diet from gestational day 10 until birth. Medial PFC (mPFC) DCC/Netrin-1 protein expression was measured at P0 at baseline and Dcc/Netrin-1 mRNA levels were quantified in adults 15 min after a saline/insulin injection. miR-218 levels in HEK-293 cells were measured in response to insulin exposure. At P0, Netrin-1 levels are downregulated in FR animals in comparison to controls. In adult rodents, insulin administration results in an increase in Dcc mRNA levels in control but not FR rats. In HEK293 cells, there is a positive correlation between insulin concentration and miR-218 levels. Since miR-218 is a Dcc gene expression regulator and our in vitro results show that insulin regulates miR-218 levels, we suggest that FR-induced changes in insulin sensitivity could be affecting Dcc expression via miR-218, impacting DA system maturation and organization. As fetal adversity is linked to nonadaptive behaviors later in life, this may contribute to early identification of vulnerability to chronic diseases associated with fetal adversity.

We previously reported that the addition of a specified mulberry fruit extract (MFE) to rice consistently reduces post-prandial glycaemic (PPG) and post-prandial insulinemic (PPI) responses. This research tested whether this effect generalises to a broad range of rice types, reflecting the wide variation in rice characteristics known to influence glycaemic responses. In a randomised, balanced, partial factorial crossover design, Sona Masoori (SM), Bora Saul (BS), Gobindobogh (Gb) and Banskati (Bn) rices were tested with and without 0·37 g MFE. Healthy, normal-weight Indian adults (N 120) each consumed four of the eight possible boiled rice meals, all containing about 50 g available carbohydrate. The primary outcome was the effect of MFE on PPG, expressed as the percentage change in the positive, incremental AUC over 2 h. The mean effect of MFE on PPG for all rice types combined was −11·4 % (P < 0·003). The reduction in PPG was in a qualitatively similar range for all rice types (–9·8 to −15·1 %), and this was statistically significant for Bn. MFE also reduced the corresponding PPI response to all rice types combined by a mean of 10·1 % (P < 0·001; range −6·1 to −13·4 %), and the reduction in PPI was statistically significant for SM, Gb and BS. In conclusion, addition of 0·37 g MFE modestly reduced PPG and PPI responses to rices in general, and the effects were statistically significant for specific rice types.

To evaluate the effects of pistachio consumption on the glucoregulatory status in individuals with a high risk of CVD, a systematic review and meta-analysis of randomised controlled trials (RCT) were conducted. Online databases including PubMed, Scopus, Web of Science and Cochrane Library were searched from inception until June 2019. Human trials that reported data for fasting blood sugar (FBS), fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were included. Data were pooled using the random effect models and expressed as weighted mean difference (WMD) with 95 % CI. Eight RCTs were included in the analyses. Pistachio consumption, exchanged isocalorically for other foods, decreased FBS (WMD: −5·32 mg/dl, 95 % CI (−7·80, −2·64), P < 0·001) and insulin (WMD: −1·86 µIU/ml, 95 % CI (−3·13, −0·59), P < 0·01) concentrations in individuals with a high risk of CVD. However, no changes were observed in the levels of HOMA-IR between the groups (WMD: −0·66, 95 % CI (−1·89, 0·58), P = 0·30). Pistachio consumption may improve glucoregulatory status in individuals at risk for CVD, as evidenced by reduced FBS and insulin concentrations. However, due to the limited availability of studies with diabetic cases and relatively small sample sizes of available studies, well-designed trials with adequate sample sizes aimed at diabetic populations are recommended.

Complete nutrition drinks with a low glycemic index (GI) provide nutritional support and prevent hyperglycaemia. The present study identified GI and factors predicting individual glucose response to a new complete nutrition drink. A randomised cross-over controlled trial was conducted in eighteen healthy volunteers (FPG < 100 mg/dl). Complete nutrition drinks containing retrograded starch, glucose solution and white bread were assigned in a random sequence with 14-day wash-out intervals. Plasma glucose and insulin levels were measured from baseline to 180 min after consuming each food. Results show the adjusted GIs of the drink was 48.2 ± 10.4 and 46.7 ± 12.7 with glucose and white bread as the reference, respectively. While the drink has low GI (<55), the individual glucose responses varied (GI: 7–149). Comparing characters in individual GI < 55 (n = 12) and GI ≥ 55 (n = 6) groups revealed significantly higher baseline insulin in the low GI group (14.86 ± 16.51 μIU/ml v. 4.9 ± 3.4 μIU/ml, P < 0·05). The correlation matrix confirms only two predictive factors for having individual GI <55 were baseline insulin (r = 0·5, P = 0·03) and HOMA-IR (r = 0·55, P = 0·02). ROC curve reveals fasting insulin above 1.6 μIU/ml and HOMA-IR above 1.05 as the cut-off values. The findings suggest that the complete nutrition drink has a low GI, but there was wide variability in individual responses partly explained by fasting insulin levels and HOMA-IR. Screening for fasting insulin and HOMA-IR may be encouraged to maximise the functional benefit of the drink.

Extracts of mulberry have been shown to reduce post-prandial glucose (PPG) and insulin (PPI) responses, but reliability of these effects and required doses and specifications are unclear. We previously found that 1·5 g of a specified mulberry fruit extract (MFE) significantly reduced PPG and PPI responses to 50 g carbohydrate as rice porridge, with no indications of intolerance. The trials reported here aimed to replicate that work and assess the efficacy of lower MFE doses, using boiled rice as the carbohydrate source. Two separate randomised controlled intervention studies were carried out with healthy Indian males and females aged 20–50 years (n 84 per trial), with PPG area under the curve over 2 h as the primary outcome. Trial 1 used doses of 0, 0·37, 0·75, 1·12 and 1·5 g MFE in boiled rice and 0 or 1·5 g MFE in rice porridge. Trial 2 used doses of 0, 0·04, 0·12, 0·37 g MFE in boiled rice. In trial 1, relative to control, all MFE doses significantly decreased PPG (–27·2 to −22·9 %; all P ≤ 0·02) and PPI (–34·6 to −14·0 %, all P < 0·01). Breath hydrogen was significantly increased only at 1·5 g MFE (in rice porridge), and self-reported gastrointestinal symptoms were uniformly low. In trial 2, only 0·37 g MFE significantly affected PPG (–20·4 %, P = 0·002) and PPI (–17·0 %, P < 0·001). Together, these trials show that MFE in doses as low as 0·37 g can reliably reduce PPG and PPI responses to a carbohydrate-rich meal, with no apparent adverse effects.

This study aimed to evaluate the cardiovascular health-related effects of consuming ghee in the usual diet. Thirty healthy men and women were studied in a free-living outpatient regimen. The participants were instructed for the isoenergetic inclusion of ghee or olive oil in their diets for 4 weeks using a randomised crossover design. At the end of run-in (baseline), 2-week wash-out and interventions, fasting blood samples were drawn. In addition, 2-h postprandial blood samples were collected after ingestion of a meal containing olive oil or ghee at week 4 of each dietary intervention. Body weight was not different between the two interventions. Compared with the olive oil, the diet with ghee increased fasting plasma apo-B (apo B) (0·09, 95 % CI 0·02, 0·17 g/l, P = 0·018), non-HDL-cholesterol (non-HDL-cholesterol) (0·53, 95 % CI 0·01, 1·05 mmol/l, P = 0·046) and LDL-cholesterol did not differ significantly between diet groups (0·29, 95 % CI –0·05, 0·63 mmol/l, P = 0·092), but had no significant effect on total cholesterol:HDL-cholesterol ratio (0·75, 95 % CI − 0·24 to 1·74 mmol/l, P = 0·118). No significant difference was observed in fasting as well as 2-h postprandial plasma TAG, glucose, insulin and plasminogen activator inhibitor-1 concentrations. This study showed that ghee that is predominantly saturated fats had an increasing effect on plasma apo B and non-HDL-cholesterol compared with olive oil, adding further evidence to the existing recommendations to replace dietary fats high in SFA with dietary fats high in unsaturated fats to reduce CVD risk.

Dietary interventions to delay carbohydrate digestion or absorption can effectively prevent hyperglycaemia in the early postprandial phase. L-arabinose can specifically inhibit sucrase. It remains to be assessed whether co-ingestion of L-arabinose with sucrose delays sucrose digestion, attenuates subsequent glucose absorption and impacts hepatic glucose output. In this double-blind, randomised crossover study, we assessed blood glucose kinetics following ingestion of a 200-ml drink containing 50 g of sucrose with 7·5 g of L-arabinose (L-ARA) or without L-arabinose (CONT) in twelve young, healthy participants (24 ± 1 years; BMI: 22·2 ± 0·5 kg/m2). Plasma glucose kinetics were determined by a dual stable isotope methodology involving ingestion of (U-13C6)-glucose-enriched sucrose, and continuous intravenous infusion of (6,6–2H2)-glucose. Peak glucose concentrations reached 8·18 ± 0·29 mmol/l for CONT 30 min after ingestion. In contrast, the postprandial rise in plasma glucose was attenuated for L-ARA, because peak glucose concentrations reached 6·62 ± 0·18 mmol/l only 60 min after ingestion. The rate of exogenous glucose appearance for L-ARA was 67 and 57 % lower compared with CONT at t = 15 min and 30 min, respectively, whereas it was 214 % higher at t = 150 min, indicating a more stable absorption of exogenous glucose for L-ARA compared with CONT. Total glucose disappearance during the first hour was lower for L-ARA compared with CONT (11 ± 1 v. 17 ± 1 g, P < 0·0001). Endogenous glucose production was not differentially affected at any time point (P = 0·27). Co-ingestion of L-arabinose with sucrose delays sucrose digestion, resulting in a slower absorption of sucrose-derived glucose without causing adverse effects in young, healthy adults.

The double burden of malnutrition (DBM) has been described in many low-/middle-income countries. We investigated food addiction, thyroid hormones, leptin, the lipid/glucose profile and body composition in DBM children/adolescents. Subjects were allocated into groups according to nutritional status: control (C, n 28), weight excess (WE, n 23) and DBM (WE plus mild stunting, n 22). Both the DBM and WE groups showed higher mean insulin concentrations than the control (DBM = 57·95 (95 % CI 47·88, 70·14) pmol/l, WE = 74·41 (95 % CI 61·72, 89·80) pmol/l, C = 40·03 (95 % CI 34·04, 47·83) pmol/l, P < 0·001). WE and DBM showed more food addiction symptoms than the control (3·11 (95 % CI 2·33, 3·89), 3·41 (95 % CI 2·61, 4·20) and 1·66 (95 % CI 0·95, 2·37)). In DBM individuals, addiction symptoms were correlated with higher body fat and higher insulin and leptin levels. These data provide preliminary evidence consistent with the suggestion that DBM individuals have a persistent desire to eat, but further studies are required to confirm these results in a larger study. These hormonal changes and high body fat contribute to the development of diabetes in long term.

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.

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.