The Impact of an 8-Week Supplementation with Fermented and Non-Fermented Aronia Berry Pulp on Cardiovascular Risk Factors in Individuals with Type 2 Diabetes.

Aronia berries contain antioxidants that may be health-promoting, e.g., demonstrated positive effects on hypertension and dyslipidaemia. There is a close link between cardiovascular diseases and hypertension and dyslipidaemia, and cardiovascular events are the leading cause of death among subjects with type 2 diabetes (T2D). Thus, we investigated the effect of an 8-week supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE), and placebo on cardiovascular risk factors. Snack bars were produced containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-crossover design. We examined the effects of aronia extracts on blood pressure, adiponectin, and high-sensitive C-reactive protein, and found no effects. After supplementation with placebo, there were significantly higher blood concentrations of total cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total cholesterol and LDL-cholesterol than the AE group. Furthermore, we observed an increase in HDL-cholesterol in the FAE group and an increase in triglyceride in the AE group. Thus, we assume that the raisins may have increased the participants' cholesterol levels, with both AE and FAE having the potential to prevent this increase.

Aronia in the Type 2 Diabetes Treatment Regimen.

Aronia melanocarpa berries are rich in antioxidants and possess a high antioxidant capacity. Aronia berries have shown potential in type 2 diabetes mellitus (T2DM) treatment, and previous studies indicate improvements in glycemia after supplementation. Unfortunately, the effectiveness of aronia berries is limited by the low bioavailability of aronia, which fermentation could potentially overcome. The objective of this study was to compare the effects of fermented or non-fermented aronia pulp with placebo in subjects with T2DM. This study was a triple-blinded, triple-crossover study with eight-week intervention periods with fermented aronia extract (FAE), non-fermented aronia extract (AE), and placebo. Extracts were incorporated in snack bars with 37% aronia (FAE or AE) or wheat bran (placebo) and 63% raisins and coconut oil. Pre- and post-treatment period, we did fasting blood samples, including hemoglobin A1c, fructosamine, insulin, glucose, glucagon-like peptide-1, glucose-dependent insulinotropic peptide (GIP) and glucagon, oral glucose tolerance tests, and anthropometric measurements. Of 36 randomized participants, 23 completed the trial. Aside from a higher increase in GIP after FAE supplementation compared to after placebo supplementation, aronia extracts had no effect. The increase in GIP levels after FAE supplementation may hold potential benefits, but the overall clinical impact remains unclear.

The Effects of 12-Weeks Whey Protein Supplements on Markers of Bone Turnover in Adults With Abdominal Obesity - A Post Hoc Analysis.

Background: While osteoporosis is characterized by skeletal fragility due to increased bone turnover and low bone mineral density (BMD), subjects with abdominal obesity and type-2 diabetes have increased risk of bone fractures despite low bone turnover and increased BMD. Diets with increased protein content are reported to increase bone turnover in healthy adults and may be a point of interest in preserving bone strength in subjects with abdominal obesity and/or type-2 diabetes. Methods: We examined the effect of 12-weeks dietary intervention on bone turnover in 64 adults with abdominal obesity using data from the MERITS trial. The trial was a randomized, controlled, double blinded study in which participants were allocated to receive either 60 g/d of whey protein hydrolysate or maltodextrin in combination with either high (30 g/d) or low dietary fiber intake (10 g/d). Primarily, we assessed changes in plasma markers of bone turnover Procollagen type 1 N-terminal propeptide (p1NP), C-terminal telopeptide type-1 collagen (CTX), and parathyroid hormone (PTH) within the four intervention groups. In addition, we measured u-calcium and u-carbamide excretion, 25(OH)D, and BMD by whole body DXA scans. Finally, we compared changes in insulin resistance (Homeostasis-model assessment of insulin resistance, HOMA-IR) with changes in bone turnover markers.The trial was registered at www.clinicaltrials.gov as NCT02931630. Results: Sixty-four subjects were included in the study. We did not find any effect of twelve weeks of high protein or high fiber intake on plasma levels of P1NP or CTX. There was a nonsignificant positive association between protein intake and PTH levels (p=0.06). U-calcium and u-carbamide increased in both protein groups. There was a positive association between change in HOMA-IR and PTH (p=0.042), while changes in P1NP and CTX did not associate to changes in HOMA-IR. Conclusion: Twelve weeks of increased whey protein intake in subjects with abdominal obesity did not affect markers of bone turnover significantly, although tended to increase PTH levels. Dietary fiber intake did not affect bone turnover. We report a positive association between change in HOMA-IR and PTH supporting a hypothesis of insulin resistance as a potential key factor in the expanding field of bone fragility in T2D subjects.

Steviol glucuronide, a metabolite of steviol glycosides, potently stimulates insulin secretion from isolated mouse islets: Studies in vitro.

AIMS: Steviol glycosides are the sweet components extracted from medicinal plant Stevia rebaudiana Bertoni, which have antihyperglycaemic effects. Steviol glucuronide (SVG) is the metabolite excreted in human urine after oral administration of steviol glycosides. We aimed to clarify whether SVG exerts direct insulin stimulation from pancreatic islets and to explore its mode of action. MATERIALS AND METHODS: Insulin secretion was measured after 60 minutes static incubation of isolated mouse islets with (a) 10-9-10-5 mol/L SVG at 16.7 mmol/L glucose and (b) 10-7 mol/L SVG at 3.3-16.7 mmol/L glucose. Islets were perifused with 3.3 or 16.7 mmol/L glucose in the presence or absence of 10-7 mol/L SVG. Gene transcription was measured after 72 hours incubation in the presence or absence of 10-7 mol/L SVG. RESULTS: SVG dose-dependently increased insulin secretion from mouse islets with 10-7 mol/L exerting the maximum effect in the presence of 16.7 mmol/L glucose (P < .001). The insulinotropic effect of SVG was critically dependent on the prevailing glucose concentration, and SVG (10-7 mol/L) enhanced insulin secretion at or above 11.1 mmol/L glucose (P < .001) and showed no effect at lower glucose concentrations. During perifusion of islets, SVG (10-7 mol/L) had a long-acting and apparently reversible insulinotropic effect in the presence of 16.7 mmol/L glucose (P < .05). Gene-transcript levels of B2m and Gcgr were markedly altered. CONCLUSION: This is the first report to demonstrate that SVG stimulates insulin secretion in a dose- and glucose-dependent manner from isolated mouse islets of Langerhans. SVG may be the main active metabolite after oral intake of steviol glycosides.

Efficacy of Arabica Versus Robusta Coffee in Improving Weight, Insulin Resistance, and Liver Steatosis in a Rat Model of Type-2 Diabetes.

The effects of chronic coffee exposure in models of type 2 diabetes mellitus (T2D) models is scarcely studied, and the efficacy of the main coffee species has never been compared. We tested the hypothesis that long-term consumption of arabica and robusta coffee may differentially delay and affect T2D development in Zucker diabetic fatty rats. Three study groups received either chow mixed with arabica or robusta instant coffee (1.8% w/w) or unsupplemented chow food for 10 weeks. Both coffee species reduced liver triglyceride content and area under the curve of fasting and postprandial insulin. At study end, plasma adiponectin, total cholesterol and high density lipoprotein levels were higher in the robust group compared with both arabica and control groups. The liver gene expression of Glucose-6-phosphatase, catalytic subunit (G6pc) and Mechanistic target of rapamycin (mTOR) in robusta and Cpt1a in both coffee groups was downregulated. In conclusion, long-term consumption of both coffee species reduced weight gain and liver steatosis and improved insulin sensitivity in a rat model of T2D. Robusta coffee was seemingly superior to arabica coffee with respect to effects on lipid profile, adiponectin level and hepatic gene expression.

Nordic Seaweed and Diabetes Prevention: Exploratory Studies in KK-Ay Mice.

BACKGROUND: The global epidemic of type 2 diabetes (T2D) is a challenging health problem. Lifestyle changes, including nutrition therapy, areimportant for the prevention and management of T2D. Seaweeds contain several bioactive substances with potential health properties and may be a low-cost alternative functional food in the prevention of T2D. OBJECTIVE: The aim of this study was to explore the preventive effects of dried Nordic seaweed species on diabetes in an animal model of T2D. METHOD: Fiftymale KK-Ay mice were randomly assigned to one of four diets: control diet (chow) or diets supplemented with Alaria esculenta (AE), Saccharina latissima (SL), or Palmaria palmata (PP). The effect of the interventions on the progression of T2D was monitored over 10 weeks and evaluated by circulating glucose, glycated hemoglobin (HbA1c), insulin, glucagon, and lipid levels. RESULTS: The SL group had significantly lower bodyweight, lower HbA1c and insulin levels, as well as higher high density lipoprotein (HDL) cholesterol levels after the 10-week intervention than the control group. At the end of the study, the control group had significantly higher HbA1c (p < 0.001) than all of the seaweed groups. CONCLUSION: All seaweed groups improved HbA1C compared to control and Saccharinalatissima seaweed had concomitantly beneficial effects on glycemic control and lipid levels in KK-Ay diabetic mice.

Effects of Unfiltered Coffee and Bioactive Coffee Compounds on the Development of Metabolic Syndrome Components in a High-Fat-/High-Fructose-Fed Rat Model.

The literature is inconsistent as to how coffee affects metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. This study aimed to evaluate the effects of unfiltered coffee on diet-induced MetS and investigate whether or not phenolic acids and trigonelline are the main bioactive compounds in coffee. Twenty-four male Sprague‒Dawley rats were fed a high-fat (35% W/W) diet plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water at a dosage equal to 4 cups/day in a human. Compared to the controls, total food intake (p = 0.023) and mean body weight at endpoint (p = 0.016) and estimated average plasma glucose (p = 0.041) were lower only in the coffee group. Surrogate measures of insulin resistance including the overall fasting insulin (p = 0.010), endpoint HOMA-IR (p = 0.022), and oral glucose tolerance (p = 0.029) were improved in the coffee group. Circulating triglyceride levels were lower (p = 0.010), and histopathological and quantitative (p = 0.010) measurements indicated lower grades of liver steatosis compared to controls after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

A Combination of Coffee Compounds Shows Insulin-Sensitizing and Hepatoprotective Effects in a Rat Model of Diet-Induced Metabolic Syndrome.

Since coffee may help to prevent the development of metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. In this study, 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high-fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control, but improved fed hyperinsulinemia (mean difference = 30.80 mU/L, p = 0.044) and homeostatic model assessment-insulin resistance (HOMA-IR) (mean difference = 15.29, p = 0.033), and plasma adiponectin levels (mean difference = -0.99 µg/mL, p = 0.048). The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating (mean difference = 4.75 U/L, p = 0.014) and intrahepatocellular alanine transaminase activity was assessed by hyperpolarized-13C nuclear magnetic resonance NMR spectroscopy and found to be reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

Cafestol, a Bioactive Substance in Coffee, Has Antidiabetic Properties in KKAy Mice.

Daily coffee consumption is inversely associated with risk of type-2 diabetes (T2D). Cafestol, a bioactive substance in coffee, increases glucose-stimulated insulin secretion in vitro and increases glucose uptake in human skeletal muscle cells. We hypothesized that cafestol can postpone development of T2D in KKAy mice. Forty-seven male KKAy mice were randomized to consume chow supplemented daily with either 1.1 (high), 0.4 (low), or 0 (control) mg of cafestol for 10 weeks. We collected blood samples for fasting glucose, glucagon, and insulin as well as liver, muscle, and fat tissues for gene expression analysis. We isolated islets of Langerhans and measured insulin secretory capacity. After 10 weeks of intervention, fasting plasma glucose was 28-30% lower in cafestol groups compared with the control group (p < 0.01). Fasting glucagon was 20% lower and insulin sensitivity improved by 42% in the high-cafestol group (p < 0.05). Cafestol increased insulin secretion from isolated islets by 75-87% compared to the control group (p < 0.001). Our results show that cafestol possesses antidiabetic properties in KKAy mice. Consequently, cafestol may contribute to the reduced risk of developing T2D in coffee consumers and has a potential role as an antidiabetic drug.

Whey and Casein Proteins and Medium-Chain Saturated Fatty Acids from Milk Do Not Increase Low-Grade Inflammation in Abdominally Obese Adults.

BACKGROUND: Low-grade inflammation is involved in the development of diabetes and cardiovascular disease (CVD). Inflammation can be modulated by dietary factors. Dairy products are rich in saturated fatty acids (SFA), which are known to possess pro-inflammatory properties. However, different fatty acid compositions may exert different effects. Other components such as milk proteins may exert anti-inflammatory properties which may compensate for the potential negative effects of SFAs. Generally, the available data suggest a neutral role of dairy product consumption on inflammation. AIM: To investigate the effects of, and potential interaction between, a dietary supplementation with whey protein and milk fat, naturally enriched in medium-chain SFA (MC-SFA), on inflammatory markers in abdominal obese adults. METHODS: The study was a 12-week, randomized, double-blinded, intervention study. Sixty-three adults were equally allocated to one of four groups which received a supplement of either 60 g/day whey or 60 g/day casein plus 63 g/day milk fat either high or low in MC-SFA content. Fifty-two subjects completed the study. Before and after the intervention, changes in plasma interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1RA), high-sensitive C-reactive protein (hsCRP), adiponectin, and monocyte chemoattractant protein-1 (MCP-1) were measured. Changes in inflammatory genes in the subcutaneous adipose tissue were also documented. RESULTS: There were no differences in circulating inflammatory markers between protein types or fatty acid compositions in abdominally obese subjects, with the exception of an increase in adiponectin in response to high compared to low MC-SFA consumption in women. We found that combined dairy proteins and MC-SFAs influenced inflammatory gene expression in adipose tissue, while no effect was detected by dairy proteins or MC-SFA per se. CONCLUSION: Whey protein compared with casein and MC-SFA-enriched milk fat did not alter circulating markers of low-grade inflammation in abdominally obese subjects, except for an increase in circulating adiponectin in response to high MC-SFA in abdominally obese women.

Cafestol, a Bioactive Substance in Coffee, Stimulates Insulin Secretion and Increases Glucose Uptake in Muscle Cells: Studies in Vitro.

Diet and exercise intervention can delay or prevent development of type-2-diabetes (T2D), and high habitual coffee consumption is associated with reduced risk of developing T2D. This study aimed to test whether selected bioactive substances in coffee acutely and/or chronically increase insulin secretion from ß-cells and improve insulin sensitivity in skeletal muscle cells. Insulin secretion from INS-1E rat insulinoma cells was measured after acute (1-h) and long-term (72-h) incubation with bioactive substances from coffee. Additionally, we measured uptake of radioactive glucose in human skeletal muscle cells (SkMC) after incubation with cafestol. Cafestol at 10(-8) and 10(-6) M acutely increased insulin secretion by 12% (p < 0.05) and 16% (p < 0.001), respectively. Long-term exposure to 10(-10) and 10(-8) M cafestol increased insulin secretion by 34% (p < 0.001) and 68% (p < 0.001), respectively. Caffeic acid also increased insulin secretion acutely and chronically. Chlorogenic acid, trigonelline, oxokahweol, and secoisolariciresinol did not significantly alter insulin secretion acutely. Glucose uptake in SkMC was significantly enhanced by 8% (p < 0.001) in the presence of 10(-8) M cafestol. This newly demonstrated dual action of cafestol suggests that cafestol may contribute to the preventive effects on T2D in coffee drinkers and be of therapeutic interest.

Dairy proteins, dairy lipids, and postprandial lipemia in persons with abdominal obesity (DairyHealth): a 12-wk, randomized, parallel-controlled, double-blinded, diet intervention study.

BACKGROUND: Abdominal obesity and exaggerated postprandial lipemia are independent risk factors for cardiovascular disease (CVD) and mortality, and both are affected by dietary behavior. OBJECTIVE: We investigated whether dietary supplementation with whey protein and medium-chain saturated fatty acids (MC-SFAs) improved postprandial lipid metabolism in humans with abdominal obesity. DESIGN: We conducted a 12-wk, randomized, double-blinded, diet intervention study. Sixty-three adults were randomly allocated to one of 4 diets in a 2 × 2 factorial design. Participants consumed 60 g milk protein (whey or casein) and 63 g milk fat (with high or low MC-SFA content) daily. Before and after the intervention, a high-fat meal test was performed. We measured changes from baseline in fasting and postprandial triacylglycerol, apolipoprotein B-48 (apoB-48; reflecting chylomicrons of intestinal origin), free fatty acids (FFAs), insulin, glucose, glucagon, glucagon-like peptide 1 (GLP-1), and gastric inhibitory polypeptide (GIP). Furthermore, changes in the expression of adipose tissue genes involved in lipid metabolism were investigated. Two-factor ANOVA was used to examine the difference between protein types and fatty acid compositions, as well as any interaction between the two. RESULTS: Fifty-two participants completed the study. We found that the postprandial apoB-48 response decreased significantly after whey compared with casein (P = 0.025) independently of fatty acid composition. Furthermore, supplementation with casein resulted in a significant increase in the postprandial GLP-1 response compared with whey (P = 0.003). We found no difference in postprandial triacylglycerol, FFA, insulin, glucose, glucagon, or GIP related to protein type or MC-SFA content. We observed no interaction between milk protein and milk fat on postprandial lipemia. CONCLUSION: We found that a whey protein supplement decreased the postprandial chylomicron response compared with casein in persons with abdominal obesity, thereby indicating a beneficial impact on CVD risk. This trial was registered at clinicaltrials.gov as NCT01472666.

Chronic exposure to leucine in vitro induces ß-cell dysfunction in INS-1E cells and mouse islets.

Chronic hyperglycemia and hyperlipidemia cause deleterious effects on ß-cell function. Interestingly, increased circulating amino acid (AA) levels are also a characteristic of the prediabetic and diabetic state. The chronic effects of AAs on ß-cell function remain to be determined. Isolated mouse islets and INS-1E cells were incubated with or without excess leucine. After 72 h, leucine increased basal insulin secretion and impaired glucose-stimulated insulin secretion in both mouse islets and INS-1E cells, corroborating the existence of aminoacidotoxicity-induced ß-cell dysfunction. This took place concomitantly with alterations in proteins and genes involved in insulin granule transport, trafficking (e.g. collapsin response mediator protein 2 and GTP-binding nuclear protein Ran), insulin signal transduction (proteasome subunit α type 6), and the oxidative phosphorylation pathway (cytochrome c oxidase). Leucine downregulated insulin 1 gene expression but upregulated pancreas duodenum homeobox 1 and insulin 2 mRNA expressions. Importantly, cholesterol (CH) accumulated in INS-1E cells concomitantly with upregulation of enzymes involved in CH biosynthesis (e.g. 3-hydroxy-3-methylglutaryl-CoA reductase, mevalonate (diphospho) decarboxylase, and squalene epoxidase) and LDL receptor, whereas triglyceride content was decreased. Our findings indicate that chronic exposure to elevated levels of leucine may have detrimental effects on both ß-cell function and insulin sensitivity. Aminoacidotoxicity may play a pathogenic role in the development of type 2 diabetes.

Antihyperglycemic effects of stevioside in type 2 diabetic subjects.

Stevioside is present in the plant Stevia rebaudiana Bertoni (SrB). Extracts of SrB have been used for the treatment of diabetes in, for example, Brazil, although a positive effect on glucose metabolism has not been unequivocally demonstrated. We studied the acute effects of stevioside in type 2 diabetic patients. We hypothesize that supplementation with stevioside to a test meal causes a reduction in postprandial blood glucose. Twelve type 2 diabetic patients were included in an acute, paired cross-over study. A standard test meal was supplemented with either 1 g of stevioside or 1 g of maize starch (control). Blood samples were drawn at 30 minutes before and for 240 minutes after ingestion of the test meal. Compared to control, stevioside reduced the incremental area under the glucose response curve by 18% (P =.013). The insulinogenic index (AUC(i,insulin)/AUC(i,glucose)) was increased by approximately 40% by stevioside compared to control (P <.001). Stevioside tended to decrease glucagon levels, while it did not significantly alter the area under the insulin, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide curves. In conclusion, stevioside reduces postprandial blood glucose levels in type 2 diabetic patients, indicating beneficial effects on the glucose metabolism. Stevioside may be advantageous in the treatment of type 2 diabetes.