Low-fat cheese ameliorates glucose intolerance and normalizes insulin secretion in a rat model of type 2 diabetes by promoting ß-cell recovery.

We aimed to determine if cheese could reduce glucose intolerance in aged rats with overt type 2 diabetes (T2D). Male Sprague-Dawley rats treated with high-fat diet (HFD) and streptozotocin (STZ) to elicit T2D were hyperglycemic. One week after STZ injection, low-fat (LOW) or regular-fat (REG) cheese was provided for 5 weeks and compared with T2D and low-fat diet reference (REF) groups. Food intake and weight gain were similar in all groups. Oral glucose tolerance tests revealed glucose intolerance in T2D rats that was partially ameliorated by LOW but not REG. Insulin secretion during the oral glucose tolerance test was impaired in T2D and REG at 10 min (p < 0.05) but the iAUC was highly variable in all groups and statistical differences were not detected (p > 0.05). ß-cell mass and pancreatic insulin content in T2D and REG were 50% lower than REF (p < 0.05), whereas LOW was not significantly different. Although isolated islets from all groups responded to glucose, the absolute amount of insulin secreted by T2D and REG was markedly reduced compared with REF, while LOW islets had relatively normal secretion. In conclusion, LOW but not REG cheese enhanced ß-cell recovery from HFD/STZ treatment that led to amelioration of glucose tolerance within 5 weeks.

Both low- and regular-fat cheeses mediate improved insulin sensitivity and modulate serum phospholipid profiles in insulin-resistant rats.

Dietary recommendations for cheese usually promote low (LOW)- over regular (REG)-fat versions due to the saturated fat. Conversely, epidemiological evidence shows that cheese consumption associates with reduced risk of type 2 diabetes. To investigate how cheese influences diabetes-related outcomes, a feeding trial comparing LOW and REG cheese was conducted in high-fat, lard-based diet (HFD)-fed insulin-resistant rats followed by evaluation of potential mechanisms. After 4 weeks of HFD, LOW or REG was added at 7 and 10 g/100 g diet, respectively, for another 8 weeks. Following either an oral glucose or insulin tolerance test to assess glucoregulation, rats were euthanized and serum was collected for metabolomic and lipid analyses. Hepatic tissue was used to measure glucoregulatory enzymes and lipid content. Both LOW and REG improved insulin sensitivity without effect on oral glucose tolerance, insulin secretion or body weight. Serum metabolomics identified 33 metabolites of interest, with 21 being phosphatidylcholines (PCs) or lysophosphatidylcholines (LPCs). HFD rats had significantly reduced LPC C16:1, C17:0, C18:1, C20:3 and C24:0, and these effects were normalized by LOW or REG cheese. Fourteen PC species were lowest in the HFD group and normalized by cheese feeding. Serum choline was elevated sevenfold in HFD- but not cheese-fed rats compared with rats fed low-fat diet. Liver triglyceride was elevated by LOW feeding. In conclusion, inclusion of both LOW and REG cheeses in the diet of insulin-resistant rats improves in vivo glucoregulation. This is associated with altered phospholipid metabolism, including cheese-mediated normalization of species that are decreased by high-fat feeding.

Adherence to Diabetes Dietary Guidelines Assessed Using a Validated Questionnaire Predicts Glucose Control in Adults With Type 2 Diabetes.

OBJECTIVES: The purpose of this study was to determine predominant deviations from Canadian Diabetes Association (CDA) nutrition therapy guidelines for Canadians with type 2 diabetes as a prelude to developing relevant interventions. We hypothesized that lack of adherence to these guidelines would be associated with higher glycated hemoglobin (A1C) levels. METHODS: A cross-sectional trial was conducted to evaluate associations between dietary adherence to CDA and Health Canada guidelines and blood glucose control. Diet was assessed using 3-day diet records and a diabetes-specific validated questionnaire, the Perceived Dietary Adherence Questionnaire (PDAQ). A total of 80 adult participants with type 2 diabetes volunteered. The main outcome measures were A1C levels, adherence to dietary guidelines and food sources of nutrients. Simple and multiple linear regressions that tested the effects of adherence to dietary guidelines concerning A1C levels were conducted; p<0.05 was considered significant. RESULTS: Participants: average age, 61.2±10.4 (standard deviation) years; 48 females and 32 males had A1C levels of 7.3%±1.3% (56±6.3 mmol/mol). Participants' reported mean daily intakes of sodium and saturated fat exceeded CDA nutrition therapy guidelines. Cured meats, fast foods and snack foods were all major contributors to intake of sodium and saturated fat. Saturated fat (r=0.341) and sodium intakes (r=0.296) and total PDAQ scores (r=-0.417) were correlated with A1C levels (p<0.05). CONCLUSIONS: This study population had overall good adherence to several CDA nutrition therapy guidelines; however, sodium and saturated fat intakes exceeded these guidelines and should receive particular attention in interventions with patients who have type 2 diabetes. Adherence to diabetes dietary guidelines as assessed by PDAQ is associated with lower A1C levels.

The impact of low and no-caloric sweeteners on glucose absorption, incretin secretion, and glucose tolerance.

The consumption of non-nutritive, low, or no-calorie sweeteners (LCS) is increasing globally. Previously thought to be physiologically inert, there is a growing body of evidence that LCS not only provide a sweet taste but may also elicit metabolic effects in the gastrointestinal tract. This review provides a brief overview of the chemical and receptor-binding properties and effects on chemosensation of different LCS but focuses on the extent to which LCS stimulates glucose transport, incretin and insulin secretion, and effects on glucose tolerance. Aspartame and sucralose both bind to a similar region of the sweet receptor. For sucralose, the data are contradictory regarding effects on glucose tolerance in humans and may depend on the food or beverage matrix and the duration of administration, as suggested by longer term rodent studies. For aspartame, there are fewer data. On the other hand, acesulfame-potassium (Ace-K) and saccharin have similar binding characteristics to each other but, while Ace-K may increase incretin secretion and glucose responses in humans, there are no data on saccharin except in rats, which show impaired glucose tolerance after chronic administration. Additional research, particularly of the effects of chronic consumption, is needed to provide concrete evidence for beneficial or detrimental effects of LCS on blood glucose regulation in humans.

Dietary Pea Fiber Supplementation Improves Glycemia and Induces Changes in the Composition of Gut Microbiota, Serum Short Chain Fatty Acid Profile and Expression of Mucins in Glucose Intolerant Rats.

Several studies have demonstrated the beneficial impact of dried peas and their components on glucose tolerance; however, the role of gut microbiota as a potential mediator is not fully examined. In this study, we investigated the effect of dietary supplementation with raw and cooked pea seed coats (PSC) on glucose tolerance, microbial composition of the gut, select markers of intestinal barrier function, and short chain fatty acid profile in glucose intolerant rats. Male Sprague Dawley rats were fed high fat diet (HFD) for six weeks to induce glucose intolerance, followed by four weeks of feeding PSC-supplemented diets. Cooked PSC improved glucose tolerance by approximately 30% (p < 0.05), and raw and cooked PSC diets reduced insulin response by 53% and 56% respectively (p < 0.05 and p < 0.01), compared to HFD (containing cellulose as the source of dietary fiber). 16S rRNA gene sequencing on fecal samples showed a significant shift in the overall microbial composition of PSC groups when compared to HFD and low fat diet (LFD) controls. At the family level, PSC increased the abundance of Lachnospiraceae and Prevotellaceae (p < 0.001), and decreased Porphyromonadaceae (p < 0.01) compared with HFD. This was accompanied by increased mRNA expression of mucin genes Muc1, Muc2, and Muc4 in ileal epithelium (p < 0.05). Serum levels of acetate and propionate increased with raw PSC diet (p < 0.01). These results indicate that supplementation of HFD with PSC fractions can improve glycemia and may have a protective role against HFD-induced alterations in gut microbiota and mucus layer.

Cooking enhances beneficial effects of pea seed coat consumption on glucose tolerance, incretin, and pancreatic hormones in high-fat-diet-fed rats.

Pulses, including dried peas, are nutrient- and fibre-rich foods that improve glucose control in diabetic subjects compared with other fibre sources. We hypothesized feeding cooked pea seed coats to insulin-resistant rats would improve glucose tolerance by modifying gut responses to glucose and reducing stress on pancreatic islets. Glucose intolerance induced in male Sprague-Dawley rats with high-fat diet (HFD; 10% cellulose as fibre) was followed by 3 weeks of HFD with fibre (10%) provided by cellulose, raw-pea seed coat (RP), or cooked-pea seed coat (CP). A fourth group consumed low-fat diet with 10% cellulose. Oral and intraperitoneal glucose tolerance tests (oGTT, ipGTT) were done. CP rats had 30% and 50% lower glucose and insulin responses in oGTT, respectively, compared with the HFD group (P < 0.05) but ipGTT was not different. Plasma islet and incretin hormone concentrations were measured. α- and ß-cell areas in the pancreas and density of K- and L-cells in jejunum and ileum were quantified. Jejunal expression of hexose transporters was measured. CP feeding increased fasting glucagon-like peptide 1 and glucose-stimulated gastric inhibitory polypeptide responses (P < 0.05), but K- and L-cells densities were comparable to HFD, as was abundance of SGLT1 and GLUT2 mRNA. No significant difference in ß-cell area between diet groups was observed. α-cell area was significantly smaller in CP compared with RP rats (P < 0.05). Overall, our results demonstrate that CP feeding can reverse adverse effects of HFD on glucose homeostasis and is associated with enhanced incretin secretion and reduced α-cell abundance.

Hydrolysis enhances bioavailability of proanthocyanidin-derived metabolites and improves ß-cell function in glucose intolerant rats.

Proanthocyanidins (PAC) are a highly consumed class of flavonoids and their consumption has been linked to beneficial effects in type 2 diabetes. However, limited gastrointestinal absorption occurs due to the polymeric structure of PAC. We hypothesized that hydrolysis of the PAC polymer would increase bioavailability, thus leading to enhanced beneficial effects on glucose homeostasis and pancreatic ß-cell function. PAC-rich pea seed coats (PSC) were supplemented to a high-fat diet (HFD) either in native (PAC) or hydrolyzed (HPAC) form fed to rats for 4 weeks. HFD or low-fat diet groups were controls. PAC-derived compounds were characterized in both PSC and serum. Glucose and insulin tolerance tests were conducted. Pancreatic α-cell and ß-cell areas and glucose-stimulated insulin secretion (GSIS) from isolated islets were measured. Increased PAC-derived metabolites were detected in the serum of HPAC-fed rats compared to PAC-fed rats, suggesting hydrolysis of PSC-enhanced PAC bioavailability. This was associated with ~18% less (P<.05) weight gain compared to HFD without affecting food intake, as well as improvement in glucose disposal in vivo. There was a 2-fold decrease of α/ß-cell area ratio and a 2.5-fold increase in GSIS from isolated islets of HPAC-fed rats. These results demonstrate that hydrolysis of PSC-derived PAC increased the bioavailability of PAC-derived products, which is critical for enhancing beneficial effects on glucose homeostasis and pancreatic ß-cell function.

Improved glucose tolerance in insulin-resistant rats after pea hull feeding is associated with changes in lipid metabolism-targeted transcriptome.

Understanding of the mechanisms by which pulse grain fractions elicit beneficial effects on glucose tolerance is incomplete. An untargeted metabolomic analysis of serum from insulin-resistant rats was carried out to identify potential metabolic pathways affected by feeding rats the hull fraction of dried peas for 4 weeks. From this, we hypothesized that transcription of hepatic genes involved in lipid metabolism would be altered. cDNA was prepared from total RNA extracted from livers of rats fed a high-fat diet (HFD) or HFD + pea hulls (PH) diet. The liver lipid transcriptome of each cDNA sample was characterized using a PCR-based array of 84 genes. The activity of peroxisome-proliferator-activated receptor alpha (PPAR-α) was measured in hepatocyte nuclei. The predominant findings of the metabolomic analysis revealed a significant increase in the intermediaries of ß-oxidation: C16-OH and C16:1 acylcarnitines (>50%, p < 0.05) and 3-hydroxybutyrate (100%, p < 0.05) in the PH group compared with the HFD group. mRNA of hadha, a gene involved in ß-oxidation, was significantly reduced by 53% (p < 0.005) in the PH group compared with the HFD group, but no differences in PPAR-α activity were detected. 3-Hydroxybutyrate concentrations were associated with insulin sensitivity and reduced demand for insulin. The results indicate that feeding PH alters lipid metabolism in liver, which may contribute to improved glucose tolerance in insulin-resistant rats.