Metabolic dietary patterns, including the Empirical Dietary Index for Hyperinsulinaemia (EDIH) and Empirical Dietary Inflammatory Pattern (EDIP), are known to impact multiple chronic diseases, but the role of the colonic microbiome in mediating such relationships is poorly understood. Among 1,610 adults with faecal 16S rRNA data in the TwinsUK cohort, we identified the microbiome profiles for EDIH and EDIP (from food frequency questionnaires) cross-sectionally using elastic net regression. We assessed the association of the dietary pattern-related microbiome profile scores with circulating biomarkers in multivariable-adjusted linear regression. In addition, we used PICRUSt2 to predict biological pathways associated with the enriched microbiome profiles, and further screened pathways for associations with the dietary scores in linear regression analyses. Microbiome profile scores developed with 32 (EDIH) and 15 (EDIP) genera were associated with higher insulin and homeostatic model assessment of insulin resistance. Six genera were associated with both dietary scores: Ruminococcaceae_UCG-008, Lachnospiraceae_UCG-008, Defluviitaleaceae_UCG-011 Anaeroplasma, inversely and Negativibacillus, Streptococcus, positively. Further, pathways in fatty acid biosynthesis, sugar acid degradation, and mevalonate metabolism were associated with insulinaemic and inflammatory diets. Dietary patterns that exert metabolic effects on insulin and inflammation may influence chronic disease risk by modulating gut microbial composition and function.

Previous studies have reported inconsistent associations between low-carbohydrate diets (LCD) and plasma lipid profile. Also, there is little evidence on the role of the quality and food sources of macronutrients in LCD in cardiometabolic health. We investigated the cross-sectional associations between LCD and plasma cardiometabolic risk markers in a nationwide representative sample of the US population. Diet was measured through two 24-h recalls. Overall, healthy (emphasising unsaturated fat, plant protein and less low-quality carbohydrates) and unhealthy (emphasising saturated fat, animal protein and less high-quality carbohydrate) LCD scores were developed according to the percentage of energy as total and subtypes of carbohydrate, protein and fat. Linear regression was used to estimate the percentage difference of plasma marker concentrations by LCD scores. A total of 34 785 participants aged 18–85 years were included. After adjusting for covariates including BMI, healthy LCD was associated with lower levels of insulin, homoeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP) and TAG, and higher levels of HDL-cholesterol, with the percentage differences (comparing extreme quartile of LCD score) of −5·91, −6·16, −9·13, −9·71 and 7·60 (all P trend < 0·001), respectively. Conversely, unhealthy LCD was associated with higher levels of insulin, HOMA-IR, CRP and LDL-cholesterol (all P trend < 0·001). Our results suggest that healthy LCD may have positive, whereas unhealthy LCD may have negative impacts on CRP and metabolic and lipid profiles. These findings underscore the need to carefully consider the quality and subtypes of macronutrients in future LCD studies.

Millet is a grain high in polyphenols and antioxidants, which are bioactive compounds known to influence blood glucose response. The aim of this study was to compare the effect of finger millet muffin and wheat muffin on glycaemic response (GR), insulin response (IR), gastric emptying (GE) and satiety in healthy individuals and people with prediabetes. In a single-blind randomised controlled crossover trial at Oxford Brookes Centre for Nutrition and Health, fifteen healthy individuals and fourteen individuals with prediabetes were recruited between May and December 2017. The participants’ GR (3 h), IR (3 h), GE (4 h) and satiety (4 h) were measured before and after the consumption of muffins. A mixed method ANOVA was used to compare GE and the incremental AUC (iAUC) for GR and IR between the participant groups and muffins. There was a significant interaction between participants and muffins on IR iAUC at 180 min (P = 0·042). A significant effect of muffins was found on the GR peak (P = 0·013). The millet muffin decreased the GR peak and IR iAUC compared with the wheat muffin in participants with prediabetes. A significant interaction between participants and muffins for GE ascension time Tasc (P = 0·017) was observed, with no effect of muffins on satiety AUC in the participant groups. This study suggested that polyphenol and fibre-rich finger millet may have the potential to influence the management of prediabetes.

Lowering postprandial glucose and insulin responses may have significant beneficial implications for prevention and treatment of metabolic disorders. Bread is a staple food consumed worldwide in a daily basis, and the use of different baking technologies may modify the glucose and insulin response. The aim of this review was to critically record the human studies examining the application of different bread making processes on postprandial glucose and insulin response to bread. Literature is rich of results which show that the use of sourdough fermentation instead of leavening with Saccharomyces cerevisiae is able to modulate glucose response to bread, whereas evidence regarding its efficacy on lowering postprandial insulin response is less clear. The presence of organic acids is possibly involved, but the exact mechanism of action is still to be confirmed. The reviewed data also revealed that the alteration of other processing conditions (method of cooking, proofing period, partial baking freezing technology) can effectively decrease postprandial glucose response to bread, by influencing physical structure and retrogradation of starch. The development of healthier bread products that benefit postprandial metabolic responses is crucial and suggested baking conditions can be used by the bread industry for the promotion of public health.

Increasingly, evidence suggests a role for polyphenols in blood glucose control. The objective of this systematic review was to evaluate the effect of polyphenol-rich sources in combination with carbohydrate sources on resulting postprandial glycaemic and insulin responses. A literature search was conducted using Medline, CINHAL and Web of Science databases. Selected studies included randomised controlled trials in which the association of polyphenol-containing food or beverage consumption with a carbohydrate source and effect on acute postprandial glycaemia and/or insulin was reported. A total of thirteen full articles were included in the review. Polyphenol sources included coffee, black tea, fruit juice, plant extracts, berries and different rye breads, and carbohydrate sources included bread, pancakes and simple sugars such as sucrose, glucose and fructose. Although glycaemic and insulin responses differed depending on the polyphenol–carbohydrate combination, overall, polyphenol sources were shown to reduce the peak and early-phase glycaemic response and maintain the glycaemic response in the later stages of digestion. To a lesser extent, polyphenol sources were also shown to reduce peak insulin response and sustain the insulin response, especially when consumed with bread. This review supports epidemiological data suggesting that polyphenols in foods and beverages may have a beneficial effect on reducing the risk of type 2 diabetes. However, the extent of this effect is variable depending on the polyphenol and carbohydrate source.

Asians typically consume carbohydrate-rich and high-glycaemic-index diets that have been associated with an increased risk of developing type 2 diabetes. Rice is rarely eaten alone such that it is of interest to investigate the effects of co-ingesting different protein-rich meals with rice on insulin and glycaemic response. This study had a randomised, controlled, non-blind, cross-over design in which fifteen healthy Chinese male participants were required to come on non-consecutive days. Five rice-based test meals were served: rice alone (control), rice with fish (RWF), rice with egg white (RWE), rice with soya beancurd (taukwa) (RWT) and rice with chicken (RWC). The control meal consisted of 50 g of available carbohydrate, whereas all other test meals contained additional 25 g of protein. RWT was the only meal that showed significantly lower glucose response when compared with the control (P<0·05). RWF and RWE had significantly higher insulin response, but no significant increase was observed in RWT and RWC when compared with the control (P<0·05). RWT and RWF showed significantly higher glucagon secretion as compared with the control (P<0·05). The four test meals studied showed varying effects, with RWT showing the greatest reduction in glycaemic response. Therefore, the ingestion of soya beancurd with rice may have a direct impact on reducing the risk in Asians transiting from being pre-diabetics to diabetics.

Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP4) which, in turn, associates with another serum protein, transthyretin (TTR), to form a ternary retinol-RBP4-TTR complex. At some tissues, retinol-bound (holo-) RBP4 is recognised by a receptor termed stimulated by retinoic acid 6 (STRA6) which transports retinol into cells. This mini-review summarises evidence demonstrating that, in addition to functioning as a retinol transporter, STRA6 is also a signalling receptor which is activated by holo-RBP4. The data show that STRA6-mediated retinol transport induces receptor phosphorylation, in turn activating a Janus kinases2/signal transducers and activators of transcription (STAT)3/5 cascade that culminates in induction of STAT target genes. STRA6-mediated retinol transport and cell signalling are inter-dependent, and both functions critically rely on intracellular retinol trafficking and metabolism. Hence, STRA6 couples ‘sensing’ of vitamin A homeostasis and metabolism to cell signalling, allowing it to control important biological functions. For example, by inducing the expression of the STAT target gene suppressor of cytokine signalling 3, STRA6 potently suppresses insulin responses. These observations provide a rationale for understanding the reports that elevation in serum levels of RBP4, often observed in obese mice and human subjects, causes insulin resistance. The observations indicate that the holo-RBP4 /STRA6 signalling cascade may comprise an important link through which obesity leads to insulin resistance and suggest that the pathway may be a novel target for treatment of metabolic diseases.

Consumption of high glycaemic index (GI) and glycaemic response (GR) food such as white rice has been implicated in the development of type 2 diabetes. Previous studies have reported the ability of individual amino acids to reduce GR of carbohydrate-rich foods. Because of the bitter flavour of amino acids, they have rarely been used to reduce GR. We now report the use of a palatable, preformed amino acid mixture in the form of essence of chicken. In all, sixteen healthy male Chinese were served 68 or 136 ml amino acid mixture together with rice, or 15 or 30 min before consumption of white rice. Postprandial blood glucose and plasma insulin concentrations were measured at fasting and every 15 min after consumption of the meal until 60 min after the consumption of the white rice. Subsequent blood samples were taken at 30-min intervals until 210 min. The co-ingestion of 68 ml of amino acid mixture with white rice produced the best results in reducing the peak blood glucose and GR of white rice without increasing the insulinaemic response. It is postulated that amino acid mixtures prime β-cell insulin secretion and peripheral tissue uptake of glucose. The use of ready-to-drink amino acid mixtures may be a useful strategy for lowering the high-GI rice diets consumed in Asia.

Asians exhibit larger glycaemic response (GR) and insulin response (IR) than Caucasians, predisposing to an increased risk of type 2 diabetes mellitus (T2DM). We aimed to determine the GR and IR as well as the glycaemic index (GI) and insulinaemic index (II) of two rice varieties among three ethnic groups in Singapore. A total of seventy-five healthy males (twenty-five Chinese, twenty-five Malay and twenty-five Asian-Indians) were served the available equivalent carbohydrate amounts (50 g) of test foods (Jasmine rice and Basmati rice) and a reference food (glucose) on separate occasions. Postprandial blood glucose and plasma insulin concentrations were measured at fasting ( − 5 and 0 min) and at 15, 30, 45, 60, 90 and 120 min after food consumption. Using the trapezoidal rule, GR, IR, GI and II values were determined. The GR did not differ between ethnic groups for Jasmine rice and Basmati rice. The IR was consistently higher for Jasmine rice (P= 0·002) and Basmati rice (P= 0·002) among Asian-Indians, probably due to compensatory hyperinsulinaemia to maintain normoglycaemia. The GI and II of both rice varieties did not differ significantly between ethnicities. The overall mean GI for Jasmine rice and Basmati rice were 91 (sd 21) and 59 (sd 15), respectively. The overall mean II for Jasmine rice was 76 (sd 26) and for Basmati rice was 57 (sd 24). We conclude that the GI values presented for Jasmine rice and Basmati rice were applicable to all three ethnic groups in Singapore. Future studies should include deriving the II for greater clinical utility in the prevention and management of T2DM.

Potatoes, especially mashed potatoes, are known to result in high glycaemic and insulinaemic responses. However, in most meals, potatoes are accompanied by other foods. The objective of the present study was to investigate how glycaemic and insulinaemic responses to a mashed potato meal changed when a high-fat food (rapeseed oil), a high-protein food (chicken breast) and/or salad were added to the meal. Healthy subjects (n 11) ingested the test meals once and the reference food (glucose solution) twice in a random order at 1-week intervals. Capillary blood samples were then drawn for 2 h, and glucose and insulin were analysed. The 2 h glycaemic responses to six mashed potato-containing meals varied more than twofold. The glycaemic index (GI) of pure mashed potato was 108, whereas combined with chicken breast, rapeseed oil and salad, it was only 54. The latter GI also differed considerably from its predicted value of 103, which was based on the individual GI of the components of the meal. The insulinaemic indices of the mashed potato-based meals varied between 94 and 148. Chicken breast in the meal increased the insulinaemic response, and rapeseed oil diminished it. However, the insulinaemic response to mashed potato with chicken breast and rapeseed oil was lower than that to mashed potato alone. In conclusion, the protein, fat and salad contents of a meal exert considerable influence on the glycaemic and insulinaemic responses to mashed potatoes. Furthermore, the estimation of the GI of a mixed meal by calculation is imprecise.

The effects of wheat and rye breads made from whole-wheat grain (WWG), wheat aleurone flour (WAF) or rye aleurone flour (RAF) on net portal absorption of carbohydrate-derived nutrients (glucose, SCFA and lactate) and apparent insulin secretion were studied in a model experiment with catheterised pigs. The breads were similar in dietary fibre (DF, 120–125 g/kg DM) but differed in arabinoxylans (50–62 g/kg), β-glucans (4–9 g/kg) and content of soluble DF (13–29 g/kg). Six pigs in a repeated 3 × 3 crossover design were fitted with catheters in the portal vein and the mesenteric artery and a portal flow probe. Pigs were fed three meals daily (at 09.00, 14.00 and 19.00 hours), and blood profiles were collected repeatedly from 08.30 until 19.00 hours once weekly. Net portal absorption of glucose was similar among breads and between meals. In contrast, insulin secretion was lowest (P < 0·05) in pigs fed RAF bread (3·9 nmol/h), intermediate in pigs fed WAF bread (5·4 nmol/h) and highest in pigs fed WWG bread (5·9 nmol/h), indicating that RAF bread improved insulin economy. Portal concentrations of propionate, butyrate and valerate were high, intermediate and low (P < 0·05) when pigs were fed RAF, WAF and WWG breads, respectively. Insulin secretion was higher (P < 0·001), and portal absorption of SCFA was lower (P < 0·05) after the first daily meal than after the second daily meal (8·8 v. 4·4 nmol/h). A low insulin response was associated with high portal absorption of SCFA. In conclusion, RAF bread was able to improve insulin economy compared to WWG bread.

Streptozotocin-induced diabetes mellitus (STZ-DM) in rats is a model of type 1 diabetes, which is commonly used to study diabetes, but differs from human diabetic pathophysiology in its insulin resistance. An STZ-DM rat can be administered five times the dose of insulin compared to that of a diabetic patient. Thus, attaining normoglycaemia in STZ-DM rats with insulin injections is complicated, and it involves an obvious risk of overdosing before getting a response. This study was designed to investigate whether suboptimal treatment with long-acting insulin restores insulin sensitivity in the STZ-DM rat, and thus an approach to more closely mimic the human condition. Male Sprague-Dawley rats were made diabetic by means of a single intravenous injection of STZ (55 mg/kg body weight (BW)), resulting in an increase in blood glucose (BG) from 6.5 ± 0.2 to 22.5 ± 1.0 mmol/l (P ⩽ 0.05) within 24 h. After treating the STZ-DM rats with vehicle for 14 days, BG was 26.1 ± 1.1 mmol/l, and the response to a single injection of fast-acting insulin (Humalog, 5 IE/kg BW) was a 23% reduction in BG. Thereafter, the rats were treated daily with a suboptimal dose of long-acting insulin for a total of 7 days (Insulatard, 5 IE/kg per day), which resulted in a BG level of 19.4 ± 2.7. The response to fast-acting insulin after the suboptimal treatment was a 61% reduction in BG. Thereafter, the animals were vehicle-treated for another 7 days, which resulted in a response to fast-acting insulin similar to the initial values (−34%). Furthermore, the group treated with suboptimal doses of long-acting insulin had a longer duration of the reduction in BG (150 min, as opposed to 90 min in the vehicle-treated groups). We conclude that the development of a decreased insulin response occurs rapidly within the first 2 weeks after the onset of diabetes in STZ-DM rats. This leads to a brief and significantly reduced decrease in BG when fast-acting insulin is administered. The insulin response is increased by treatment with suboptimal doses of long-acting insulin, but rapidly decreases again when treatment is withdrawn. Regular administration of suboptimal insulin doses may provide an approach to eliminate the effects of a lowered insulin response.

Siraitia grosvenori Swingle (SG) is a traditional Chinese fruit used as a folk medicine. Its extract (SG-ex) contains potent sweet elements with a sweetness several hundred times higher than table sugar. We investigated the antidiabetic effect of SG-ex in the type 2 diabetic Goto–Kakizaki (GK) rat. Diabetic 7-week-old GK rats were fed a diet supplemented with 0·4 % of the SG-ex for 13 weeks, and its antidiabetic effects were evaluated. SG-ex had no effect on food intake or body weight. In oral glucose tolerance tests (OGTT), SG-ex supplementation improved the insulin response at 15 min (control, 63 (sem 6) pm; SG-ex, 107 (sem 20) pm; P < 0·05) and reduced the plasma glucose level at 120 min after the glucose administration (control, 18·5 (sem 0·8) mm; SG-ex, 14·8 (sem 0·7) mm; P < 0·05). The total amount of insulin in whole pancreas taken from fasting rats was higher in the SG-ex-supplemented group, which may explain the greater capacity to secrete insulin during the OGTT. Thiobarbituric acid-reactive substances in both the liver and the plasma were lower in the SG-ex-supplemented group, suggesting that an absorbable component in SG-ex has an antioxidative effect on lipid peroxidation, thereby counteracting the oxidative stress caused by a diabetic state. Excreted urine volume and urinary albumin level for 24 h were both reduced in the SG-ex-supplemented group, suggesting the attenuation of kidney damage that is caused by diabetes. These data indicate that SG-ex supplementation may prevent complications and attenuate pathological conditions for type 2 diabetes, along with its sweet characteristics.