Proton Shell Gaps in N=28 Nuclei from the First Complete Spectroscopy Study with FRIB Decay Station Initiator.

The first complete measurement of the ß-decay strength distribution of _{17}^{45}Cl_{28} was performed at the Facility for Rare Isotope Beams (FRIB) with the FRIB Decay Station Initiator during the second FRIB experiment. The measurement involved the detection of neutrons and γ rays in two focal planes of the FRIB Decay Station Initiator in a single experiment for the first time. This enabled an analytical consistency in extracting the ß-decay strength distribution over the large range of excitation energies, including neutron unbound states. We observe a rapid increase in the ß-decay strength distribution above the neutron separation energy in _{18}^{45}Ar_{27}. This was interpreted to be caused by the transitioning of neutrons into protons excited across the Z=20 shell gap. The SDPF-MU interaction with reduced shell gap best reproduced the data. The measurement demonstrates a new approach that is sensitive to the proton shell gap in neutron rich nuclei according to SDPF-MU calculations.

Patient preferences in geriatric wards, a survey of health care professionals' practice, experience and attitudes.

PURPOSE: We aimed to identify whether health care professionals (HCP) examine their patient and next-of-kin preferences, and to study whether medical decisions follow these preferences. METHOD: A cross-sectional web-based survey was conducted with multidisciplinary HCP from 12 geriatric wards in the South-Eastern Norway Regional Health Authority. RESULTS: Of the 289 HCPs responding (response rate 61%), mean age 37.8 years (SD 11.3), 235 (81.3%) women, 12.4 (SD 9.6) years of experience and 67 (23.2%) medical doctors, only half report clarifying patients' preferences. The majority reported that they did not inform, involve and treat in line with such preferences. However, 53% believe that HCP, patients and next-of-kin should make clinical decisions together. DISCUSSION: Our findings indicate a lack of engagement in conversation and inclusion of patient preferences when providing health interventions in geriatric wards. Measures for change of culture are needed.

Dietary medium-chain saturated fatty acids induce gene expression of energy metabolism-related pathways in adipose tissue of abdominally obese subjects.

BACKGROUND: Dietary medium-chain saturated fatty acids (MC-SFAs) have been shown to reduce total body fat. Previously, we showed that MC-SFAs prevent body fat accumulation, despite weight gain. Here, we aim to explore potential molecular mechanisms underlying the protective effect of MC-SFAs on body fat gain. METHODS: The DairyHealth study examined the long-term effects of milk protein and milk fat with a low or high content of MC-SFA. In this 12 week, randomized, double-blind, diet intervention study, participants consumed 60 g milk protein (whey or casein) and 63 g milk fat (high MC-SFA or low MC-SFA) daily in a two by two factorial design. We used microarrays to measure whole genome gene expression changes in subcutaneous adipose tissue in a subpopulation of 12 participants, 6 in the low MC-SFA+casein group and 6 in the high MC-SFA+casein group. Gene expression of several genes that were found to be changed by MC-SFAs was confirmed in the full study population using qPCR. RESULTS: High MC-SFA resulted in an upregulation of gene expression related to citric acid cycle and oxidative phosphorylation, and a downregulation of gene expression related to complement system and inflammation. CONCLUSIONS: We hypothesize that the beneficial effects of MC-SFAs on prevention of fat accumulation are mediated via increased gene expression related to energy metabolism in the adipose tissue. Decreases in inflammation-related gene expression may have beneficial effects in relation to cardiometabolic diseases.

Safety and efficacy of insulin degludec/insulin aspart with bolus mealtime insulin aspart compared with standard basal-bolus treatment in people with Type 1 diabetes: 1-year results from a randomized clinical trial (BOOST® T1).

AIMS: To evaluate the long-term safety and efficacy of a simplified basal-bolus regimen of once-daily insulin degludec/insulin aspart (IDegAsp) with additional IAsp vs. a standard basal-bolus insulin regimen of insulin detemir (IDet) with IAsp in adults with Type 1 diabetes. METHODS: This was an open-label trial comprising a 26-week core phase followed by a 26-week extension phase. Participants were randomized to IDegAsp once daily at the main meal and IAsp at remaining meals (IDegAsp+IAsp), or IDet (once or twice daily) and IAsp at all meals (IDet+IAsp). Insulins were titrated to target plasma glucose of < 5 mmol/l (< 90 mg/dl) at pre-breakfast (IDegAsp and IDet) and at pre-meal (IAsp). RESULTS: After 52 weeks, the overall confirmed hypoglycaemia rate was 31.8 episodes/patient-years of exposure (PYE) with IDegAsp+Asp and 36.7 episodes/PYE with IDet+IAsp, and the rate of nocturnal confirmed hypoglycaemia was significantly lower with IDegAsp+Asp than with IDet+IAsp (3.1 vs. 5.4 episodes/PYE, respectively; P < 0.05). Adverse event rates were comparable between groups. Mean HbA1c decreased from baseline by 0.7% (IDegAsp+IAsp) and 0.6% (IDet+IAsp), achieving 60 or 61 mmol/mol (7.6% or 7.7%, respectively), at Week 52. The mean total daily insulin dose was lower with IDegAsp+IAsp than with IDet+IAsp (ratio: 0.87; 95% CI 0.79-0.95; P = 0.0026). CONCLUSIONS: Once-daily treatment with IDegAsp and IAsp as bolus insulin for remaining meals was associated with significantly lower risk of nocturnal confirmed hypoglycaemia, improved glycaemic control and showed non-inferiority compared with IDet+IAsp, the standard of care in Type 1 diabetes.

The effects of proteins and medium-chain fatty acids from milk on body composition, insulin sensitivity and blood pressure in abdominally obese adults.

BACKGROUND/OBJECTIVES: To investigate whether intake of whey protein and butter naturally enriched in medium-chain fatty acids (MC-SFAs) (C6-C12) affected body composition, insulin sensitivity, blood pressure (BP) and plasma cholesterol concentrations. SUBJECTS/METHODS: A 12-week randomised, double-blinded, intervention study was completed in 52 abdominally obese adults. Subjects were assigned to one of four dietary supplementations: 63 g per day of milk fat with either high- (8.5 g per day) or low-MC-SFA (6.9 g per day) content combined with 60 g per day of whey or casein.We examined changes in the body composition by dual-energy X-ray absorption scan, insulin sensitivity using homoeostatic model assessment of insulin resistance (HOMA-IR) and Matsuda index, and diurnal BP and plasma cholesterol concentrations. Two-factor analysis of variance was used to examine the impact of MC-SFA content and protein type. RESULTS: We observed that lean body mass increased by 981 g (95% confidence interval (CI): 248-1713; P=0.010) after high-MC-SFA compared with low-MC-SFA supplementation. Concomitantly, total body-fat percentage increased by 0.70 percentage points (95% CI: 0.10-1.31; P=0.024) after intake of low-MC-SFA butter compared with intake of high-MC-SFA butter. Both changes were independent of protein type (P=0.96 and P=0.99, respectively). We found no difference in HOMA-IR, Matsuda index, diurnal BP or plasma cholesterol concentrations related to MC-SFA content or protein type. CONCLUSIONS: Enhanced intake of MC-SFA increased the lean body mass and caused a significantly lower total body-fat percentage compared with lower intake of MC-SFA. Consequently, the composition of dairy fat should be considered when evaluating the impact of dairy products on body composition.

Weight-sparing effect of insulin detemir: a consequence of central nervous system-mediated reduced energy intake?

Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight-sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter-regulatory response to insulin through restoration of the hepatic-peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight-sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.

Acute effects of monounsaturated fat on postprandial lipemia and gene expression in first-degree relatives of subjects with type 2 diabetes.

BACKGROUND/OBJECTIVES: Subjects with type 2 diabetes (T2D) and their nondiabetic first-degree relatives (REL) have increased risk of cardiovascular disease (CVD). Postprandial triglyceridemia (PPL), influenced by diet, is an independent risk factor for CVD. Dietary fat elicits increased PPL in T2D compared with nondiabetic controls, but our knowledge of PPL responses to fat in REL is sparse. Our aim was to test the hypothesis that REL respond to a monounsaturated fatty acid (MUFA) challenge with a higher PPL response compared with controls who have no family history of T2D (CON) and that MUFAs exert a differential impact on incretin responses and on the expression of genes involved in carbohydrate and lipid metabolism in muscle and adipose tissues of REL and CON. SUBJECTS/METHODS: A total of 17 REL and 17 CON consumed a meal with 72 energy percent derived from MUFAs (macadamia nut oil). Plasma triglycerides, free fatty acids, insulin, glucose, glucagon-like peptide 1, glucose-dependent insulintropic peptide and ghrelin were measured at baseline and regular intervals until 4 h postprandially. Muscle and adipose tissue biopsies were collected at baseline and at 210 min after the meal. RESULTS: The MUFA-rich meal did not elicit different responses (P>0.05) in PPL, insulin, glucose, incretins or ghrelin in REL and CON. Several genes were differentially regulated in muscle and adipose tissues of REL and CON. CONCLUSIONS: A MUFA-rich meal elicits similar PPL, insulin and incretin responses in REL and CON. MUFAs have a differential impact on gene expression in muscle and adipose tissues in a pattern pointing toward early defects in lipid metabolism in REL.

Postprandial effects of test meals including concentrated arabinoxylan and whole grain rye in subjects with the metabolic syndrome: a randomised study.

BACKGROUND/OBJECTIVES: Prospective studies have shown an inverse relationship between whole grain consumption and the risk of type 2 diabetes, where short chain fatty acids (SCFA) may be involved. Our objective was to determine the effect of isolated arabinoxylan alone or in combination with whole grain rye kernels on postprandial glucose, insulin, free fatty acids (FFA), gut hormones, SCFA and appetite in subjects with the metabolic syndrome (MetS). SUBJECTS/METHODS: Fifteen subjects with MetS participated in this acute, randomised, cross-over study. The test meals each providing 50 g of digestible carbohydrate were as follows: semolina porridge added concentrated arabinoxylan (AX), rye kernels (RK) or concentrated arabinoxylan combined with rye kernels (AXRK) and semolina porridge as control (SE). A standard lunch was served 4 h after the test meals. Blood samples were drawn during a 6-h period, and appetite scores and breath hydrogen were assessed every 30 min. RESULTS: The AXRK meal reduced the acute glucose (P=0.005) and insulin responses (P<0.001) and the feeling of hunger (P=0.005; 0-360 min) compared with the control meal. The AX and AXRK meals increased butyrate and acetate concentrations after 6 h. No significant differences were found for the second meal responses of glucose, insulin, FFA, glucagon-like peptide-1 or ghrelin. CONCLUSIONS: Our results indicate a stimulatory effect of arabinoxylan on butyrate and acetate production, however, with no detectable effect on the second meal glucose response. It remains to be tested in a long-term study if a beneficial effect on the glucose response of the isolated arabinoxylan will be related to the SCFA production.

Plasma alkylresorcinols C17:0/C21:0 ratio, a biomarker of relative whole-grain rye intake, is associated to insulin sensitivity: a randomized study.

BACKGROUND/OBJECTIVES: Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism. We aimed to investigate the association between plasma alkylresorcinols (AR), a biomarker of whole-grain rye and wheat intake, and glucose metabolism in individuals with metabolic syndrome (MetS). SUBJECTS/METHODS: Participants were 30-65 years of age, with body mass index 27-40 kg/m(2) and had MetS without diabetes. Individuals were recruited through six centers in the Nordic countries and randomized to a healthy Nordic diet (ND, n=96), rich in whole-grain rye and wheat, or a control diet (n=70), for 18-24 weeks. In addition, associations between total plasma AR concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake, and glucose metabolism measures from oral glucose tolerance tests were investigated in pooled (ND+control) regression analyses at 18/24 weeks. RESULTS: ND did not improve glucose metabolism compared with control diet, but the AR C17:0/C21:0 ratio was inversely associated with fasting insulin concentrations (P=0.002) and positively associated with the insulin sensitivity indices Matsuda ISI (P=0.026) and disposition index (P=0.022) in pooled analyses at 18/24 weeks, even after adjustment for confounders. The AR C17:0/C21:0 ratio was not significantly associated with insulin secretion indices. Total plasma AR concentration was not related to fasting plasma glucose or fasting insulin at 18/24 weeks. CONCLUSIONS: The AR C17:0/C21:0 ratio, an indicator of relative whole-grain rye intake, is associated with increased insulin sensitivity in a population with MetS.

Effects of concentrated arabinoxylan and ß-glucan compared with refined wheat and whole grain rye on glucose and appetite in subjects with the metabolic syndrome: a randomized study.

BACKGROUND/OBJECTIVES: Several studies emphasise that arabinoxylan and ß-glucan have more beneficial effects on glucose metabolism than low-dietary fibre (DF) meals. Less attention has been paid to the effects of concentrated DF compared with whole grain. We compared the effects of DF and whole grain on glucose, hormone responses and appetite in subjects with the metabolic syndrome (MetS). SUBJECTS/METHODS: Fifteen subjects with MetS participated in this acute, randomised, cross-over intervention study. The test breads provided 50 g of digestible carbohydrate: wheat bread with concentrated arabinoxylan (AX) or ß-glucan (BG), rye bread with kernels (RK) and wheat bread (WB) as control. Blood samples were drawn for 270 min to determine glucose, insulin, glucagon-like peptide-1, glucose-dependent insulinotropic peptide (GIP) and ghrelin. Appetite score was addressed every 30 min. Ad libitum energy intake (EI) was measured 270 min after test meals. RESULTS: Compared with WB, BG and RK induced lower initial glycaemic responses (P<0.001), whereas AX only reduced the glucose peak value (P<0.001). RK reduced insulin (P<0.001) and GIP responses (P<0.001) compared with the other breads. BG lowered insulin responses more than AX (P<0.001). AX, BG and RK increased satiety feeling (P<0.001) more than WB, but did not differ significantly in terms of subsequent EI (P=0.089). CONCLUSION: BG and RK had beneficial impact on the glucose response, whereas AX had only effect on the postprandial glucose peak. The impact of the AX bread was influenced by higher protein content. Whether the metabolic effects of the breads are still present to mixed meals remains to be tested.

Effects of an isocaloric healthy Nordic diet on ambulatory blood pressure in metabolic syndrome: a randomized SYSDIET sub-study.

BACKGROUND/OBJECTIVES: Dietary pattern is central in the prevention of hypertension and blood pressure (BP)-related diseases. A diet based on healthy Nordic foods may have a favourable impact on BP. The objective was to clarify whether a Nordic alternative for a healthy food pattern would have beneficial effects on ambulatory BP in subjects with metabolic syndrome (MetS). SUBJECTS/METHODS: In total, 37 subjects were randomized to either a healthy Nordic diet or a control diet. A healthy Nordic diet embraced whole grains, rapeseed oil, berries, fruits, vegetables, fish, nuts and low-fat dairy products of Nordic origin. The mean nutrient intake in the Nordic countries formed the control diet, embracing wheat products, dairy fat-based spread and a lower intake of fruits, vegetables and fish. Diets were isoenergetic. Ambulatory BP was monitored and 24-h urine was collected before and after 12 weeks of intervention. RESULTS: After 12 weeks, ambulatory diastolic BP (-4.4 mm Hg; P=0.001) and mean arterial pressure (-4.2 mm Hg; P=0.006) were lowered by the healthy Nordic diet compared with the control diet, whereas changes in ambulatory systolic BP did not differ significantly between diets (-3.5 mm Hg; P=0.122). Heart rate tended to be lower in those on the healthy Nordic diet (P=0.057). Urinary sodium and potassium excretions were unaffected by diets and consequently not associated with the healthy Nordic diet-induced lowering of BP. CONCLUSIONS: Consumption of Nordic varieties of health-enhancing foods for 12 weeks decreased diastolic ambulatory BP and mean arterial pressure in subjects with features of MetS during weight-stable condition, suggesting beneficial effects of a healthy Nordic dietary pattern on ambulatory BP.

Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial.

AIMS: Postprandial triglyceridaemia is a risk factor for cardiovascular disease (CVD). This study investigated the effects of steady-state liraglutide 1.8 mg versus placebo on postprandial plasma lipid concentrations after 3 weeks of treatment in patients with type 2 diabetes mellitus (T2DM). METHODS: In a cross-over trial, patients with T2DM (n = 20, 18-75 years, BMI 18.5-40 kg/m²) were randomized to once-daily subcutaneous liraglutide (weekly dose escalation from 0.6 to 1.8 mg) and placebo. After each 3-week period, a standardized fat-rich meal was provided, and the effects of liraglutide on triglyceride (primary endpoint AUC(0-8h)), apolipoprotein B48, non-esterified fatty acids, glycaemic responses and gastric emptying were assessed. ClinicalTrials.gov ID: NCT00993304. FUNDING: Novo Nordisk A/S. RESULTS: After 3 weeks, mean postprandial triglyceride (AUC(0-8h) liraglutide/placebo treatment-ratio 0.72, 95% CI [0.62-0.83], p = 0.0004) and apolipoprotein B48 (AUC(0-8h) ratio 0.65 [0.58-0.73], p < 0.0001) significantly decreased with liraglutide 1.8 mg versus placebo, as did iAUC(0-8h) and C(max) (p < 0.001). No significant treatment differences were observed for non-esterified fatty acids. Mean postprandial glucose and glucagon AUC(0-8h) and C(max) were significantly reduced with liraglutide versus placebo. Postprandial gastric emptying rate [assessed by paracetamol absorption (liquid phase) and the ¹³C-octanoate breath test (solid phase)] displayed no treatment differences. Mean low-density lipoprotein and total cholesterol decreased significantly with liraglutide versus placebo. CONCLUSIONS: Liraglutide treatment in patients with T2DM significantly reduced postprandial excursions of triglyceride and apolipoprotein B48 after a fat-rich meal, independently of gastric emptying. Results indicate liraglutide's potential to reduce CVD risk via improvement of postprandial lipaemia.

Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome -- a randomized study (SYSDIET).

BACKGROUND: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. METHODS: We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. RESULTS: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra. CONCLUSIONS: Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study.

AIMS: To investigate efficacy and safety of dual therapy with liraglutide and metformin in comparison to glimepiride and metformin, and metformin monotherapy over 2 years in patients with type 2 diabetes. METHODS: In the 26-week the Liraglutide Effect and Action in Diabetes (LEAD)-2 core trial, patients (n = 1091) were randomized (2 : 2 : 2 : 1: 2) to liraglutide (0.6, 1.2 or 1.8 mg once-daily), placebo or glimepiride; all with metformin. Patients were enrolled if they were 18-80 years old with HbA1c 7.0-11.0% (previous monotherapy ≥3 months), or 7.0-10.0% (previous combination therapy ≥3 months), and body mass index ≤40 kg/m(2) . Patients completing the 26-week double-blinded phase could enter an 18-month open-label extension. RESULTS: HbA1c decreased significantly with liraglutide (0.4% with 0.6 mg, 0.6% with 1.2 and 1.8 mg) versus 0.3% increase with metformin monotherapy (p < 0.0001). HbA1c decrease with liraglutide was non-inferior versus 0.5% decrease with glimepiride. Liraglutide groups experienced significant weight loss (2.1, 3.0 and 2.9 kg with 0.6, 1.2 and 1.8 mg, respectively) compared to weight gain (0.7 kg) with glimepiride (p < 0.0001). Weight loss with liraglutide 1.2 and 1.8 mg was significantly greater than with metformin monotherapy (1.8 kg; p = 0.0185 and p = 0.0378 for 1.2 and 1.8 mg, respectively). The occurrence of minor hypoglycaemia was <5.0% in all liraglutide groups, significantly less than with glimepiride (24.0%; p < 0.0001). Liraglutide was well tolerated overall: gastrointestinal events were more common than with glimepiride or metformin monotherapy, but occurrence decreased with time. CONCLUSIONS: Liraglutide provided sustained glycaemic control over 2 years comparable to that provided by glimepiride. Liraglutide was well tolerated, and was associated with weight loss and a low rate of hypoglycaemia.

Impact of glucagon-like peptide-1 (7-36) amide, isosteviol and 5-aminoimidazole-4-carboxamide 1-ß-d-ribofuranoside on leucine-mediated α-cell dysfunction.

AIM: To investigate the acute and chronic effects of l-leucine on pancreatic α-cell function in vitro. Furthermore, we wanted to explore if glucagon-like peptide-1 (GLP-1), isosteviol (ISV) and 5-aminoimidazole-4-carboxamide 1-ß-d-ribofuranoside (AICAR) counteract changes in α-cell function induced by chronic exposure to leucine. METHODS: Isolated mice islets were incubated with 10 mM leucine for 2 or 72 h. We investigated glucagon and insulin secretion at 2 mM and 16.7 mM glucose. In addition, we cultured clonal α-TC1-6 cells with 5 mM leucine, 5 mM leucine plus GLP-1 (10(-6) M), or ISV (10(-6) M) or AICAR (10(-5) M) at high glucose for 72 h. We measured the glucagon secretion, cholesterol (CHO) and triglyceride (TG) content, cell proliferation as well as gene expression. RESULTS: Ten millimolar of leucine for 2 h significantly stimulated glucagon and insulin secretion both at 2 and 16.7 mM glucose in mice islets. After 72 h incubation with 10 mM leucine the glucagon secretion was enhanced at both 2 and 16.7 mM glucose, whereas the glucose-stimulated insulin secretion (16.7 mM glucose) was inhibited. Chronic exposure to 5 mM leucine increased glucagon secretion, CHO and TG content, cell proliferation and Pcsk2 (p < 0.001), MafB (p < 0.05), Gcg (p < 0.001), Prkaa1 (p < 0.01), Hmgcr (p < 0.001), Srebf2 (p < 0.001), Acaca (p < 0.001), Mtor (p < 0.05) mRNA expression in clonal α-TC1-6 cells. While GLP-1 was cable of reducing glucagon hypersecretion and Pcsk2 (p < 0.05) mRNA expression. ISV and AICAR had no effect on leucine-induced glucagon hypersecretion. CONCLUSIONS: Long-term exposure to leucine induces hypersecretion of glucagon secretion, that is, aminoacidotoxicity and influences some key genes of pancreatic α-cells. Interestingly, GLP-1 counteracts the leucine-induced α-cell dysfunction.

Effects of different fractions of whey protein on postprandial lipid and hormone responses in type 2 diabetes.

BACKGROUND/OBJECTIVES: Exacerbated postprandial lipid responses are associated with an increased cardiovascular risk. Dietary proteins influence postprandial lipemia differently, and whey protein has a preferential lipid-lowering effect. We compared the effects of different whey protein fractions on postprandial lipid and hormone responses added to a high-fat meal in type 2 diabetic subjects. SUBJECTS/METHODS: A total of 12 type 2 diabetic subjects ingested four isocaloric test meals in randomized order. The test meals contained 100 g of butter and 45 g of carbohydrate in combination with 45 g of whey isolate (iso-meal), whey hydrolysate (hydro-meal), α-lactalbumin enhanced whey (lac-meal) or caseinoglycomacropeptide enhanced whey (CGMP-meal). Plasma concentrations of triglyceride, retinyl palmitate, free fatty acid, insulin, glucose, glucagon, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide were measured before and at regular intervals until 8-h postprandially. RESULTS: We found no statistical significant differences between meals on our primary variable triglyceride. The retinyl palmitate response was higher after the hydro-meal than after the iso- and lac-meal in the chylomicron-rich fraction (P=0.008) while no significant differences were found in the chylomicron-poor fraction. The hydro- and iso-meal produced a higher insulin response compared with the lac- and CGMP-meal (P<0.001). Otherwise no significant differences in the hormone responses were found in the incremental area under the curve over the 480-min period. CONCLUSIONS: A supplement of four different whey protein fractions to a fat-rich meal had similar effects on postprandial triglyceride responses in type 2 diabetic subjects. Whey isolate and whey hydrolysate caused a higher insulin response.

Acute differential effects of milk-derived dietary proteins on postprandial lipaemia in obese non-diabetic subjects.

BACKGROUND/OBJECTIVES: Postprandial lipaemia is an established risk factor for atherosclerosis. To investigate the acute effect of four milk-derived dietary proteins (alpha-lactalbumin, whey isolate, caseinoglycomacropeptide and whey hydrolysate) on postprandial lipaemia, we have conducted a randomized, acute, single-blinded clinical intervention study with crossover design. SUBJECTS/METHODS: A total of 11 obese non-diabetic subjects (age: 44-74, BMI: 30-41.4 kg m(-2)) were included. On 4 different days the subjects ingested a high-fat meal with the following energy distribution: 66% energy from fat (100 g of butter), 15% of energy from carbohydrate (90 g of white wheat bread) and 19% of energy from protein (45 g of pure protein). Our primary variable was plasma triglyceride measured in the 8-h postprandial period. Secondarily, retinyl palmitate, non-esterified free fatty acids, glucose, insulin, glucagon, GLP-1 and GIP, active and total grehlin and cholecystokinin were measured. RESULTS: We observed no statistically significant (P=0.8) differences between meals on our primary variable that is, triglycerides. Whey hydrolysate was associated with a significantly (P=0.02) smaller postprandial suppression of non-esterified free fatty acids compared with the other dietary proteins. CONCLUSION: We did not observe significant differences in postprandial lipaemia to the four milk-derived dietary proteins. Whey hydrolysate caused less postprandial suppression of free fatty acids.

Alcohol and type 2 diabetes. A review.

AIMS: To describe a) the association between alcohol consumption and the risk of type 2 diabetes (T2D) and b) the impact of alcohol on the glycemic control with and without anti-diabetic drugs. DATA SYNTHESIS: We searched MEDLINE and the Cochrane Library data base with the key words "Diabetes Mellitus, type 2" and "Alcohol Drinking" in English-language studies in adults. For the first part of the review we selected meta-analyses, review articles and observational studies more recent than year 1990 including at least 1000 participants. For the second part of the review we included all articles more recent than year 1990. Most observational studies find a J-shaped association between alcohol intake and incidence of T2D. Interestingly, drinking pattern plays a role, i.e. binge drinking increases the risk of T2D. Opposing information exists about the influence of beverage type. In T2D the acute effects on plasma glucose, insulin, fatty acids and triglyceride vary, in part depending on concomitant intake of food. Acute alcohol intake does not induce hypoglycemia in diet treated T2D, but increases the risk of hypoglycemia in sulphonylurea treated patients. In most studies, long-term alcohol use is associated with improved glycemic control in T2D. CONCLUSIONS: Alcohol consumption reduces the incidence of T2D, however, binge drinking seems to increase the incidence. Acute intake of alcohol does not increase risk of hypoglycemia in diet treated subjects with T2D, only when sulphonylurea is co-administered. Long-term alcohol use seems to be associated with improved glycemic control in T2D probably due to improved insulin sensitivity.

Obesity does not influence the unique pharmacological properties of different biphasic insulin aspart preparations in patients with type 2 diabetes.

AIM: To investigate the influence of obesity in type 2 diabetic patients upon pharmacological properties of different biphasic preparations of insulin aspart. METHODS: A total of 75 type 2 diabetic patients were stratified according to their body mass index (BMI) into 40 non-obese (BMI 23-28 kg/m(2)) and 35 obese (BMI 30-35 kg/m(2)) subjects. The trial was a double-blinded crossover study. In two periods of 4 weeks each the patients received subcutaneous injections of biphasic insulin aspart 50 (BIAsp 50) or biphasic insulin aspart 70 (BIAsp 70) thrice daily in random order. Insulin doses were titrated individually. At the end of each period 24-h serum profiles of insulin aspart, C-peptide and glucose were recorded. The primary endpoint was the area under the curve of serum glucose concentration during 24 h (AUC(Glu)(0-24 h)). RESULTS: The insulin concentration profiles of BIAsp 50 and 70 were as expected according to the content of protamine-bound insulin aspart (50 and 30% respectively). AUC(Glu(0-24 h)) BIAsp 50/BIAsp 70 ratios were 0.97 (95% CI: 0.90-1.05, p = 0.49) for non-obese and 0.98 (95% CI: 0.92-1.05, p = 0.55) for obese. Fasting serum glucose (FSG) BIAsp 50/BIAsp 70 ratios were 0.90 (95% CI: 0.84-0.96, p = 0.002) for non-obese and 0.90 (95% CI: 0.84-0.97, p = 0.006) for obese. During both treatment regimens the frequency of minor hypoglycaemic episodes was highest for the non-obese group. CONCLUSIONS: The pharmacokinetic and pharmacodynamic characteristics of the two preparations of biphasic insulin aspart were different; however, they were not influenced by the degree of obesity in type 2 diabetic patients.

Acute effects of casein on postprandial lipemia and incretin responses in type 2 diabetic subjects.

BACKGROUND AND AIMS: Exaggerated and prolonged postprandial lipemia is potentially atherogenic and associated with type 2 diabetes. Limited data exist regarding the influence of dietary protein on postprandial lipemia in type 2 diabetes. We investigated, over 8-h, the acute effects of casein alone or in combination with carbohydrate on postprandial lipid and incretin responses to a fat-rich meal in type 2 diabetes. METHODS AND RESULTS: Eleven type 2 diabetic subjects ingested four test meals in random order: an energy-free soup plus 80 g of fat (control-meal); control-meal plus 45 g carbohydrates (CHO-meal); control-meal plus 45 g of casein (PRO-meal); and PRO-meal plus 45 g carbohydrates (CHO+PRO-meal). Triglyceride and retinyl palmitate responses were measured in plasma and in a chylomicron-rich and chylomicron-poor fraction. We found no significant differences in triglyceride responses to PRO- and CHO+PRO-meal compared to the control-meal. However, the addition of casein to the CHO-meal reduced the raised triglyceride response in the chylomicron-rich fraction. Retinyl palmitate responses did not differ significantly between meals in the chylomicron-rich fraction, whereas the PRO-meal increased retinyl palmitate in the chylomicron-poor fraction. PRO- and PRO+CHO-meal increased insulin and glucagon compared to the control-meal. PRO+CHO-meal increased the glucose-dependent insulinotropic peptide response while no change in glucagon-like peptide-1 responses was detected. CONCLUSIONS: The data presented suggest that casein per se did not modulate the postprandial triglyceride response in type 2 diabetes. When added to carbohydrate, casein suppressed the triglyceride response in the chylomicron-rich fraction, increased insulin and glucagon but did not affect the incretin responses.