Metabolic response to dietary fibre composition in horses

The hypothesis for this study was that a higher dietary proportion of soluble fibre would result in stable and constant plasma metabolite and regulatory hormone concentrations. The study was a 4×4 Latin Square design with a sequence of 17 days adaptation to the ration followed by 8 sampling days. The feed rations consisted of only timothy hay (H), hay plus molassed sugar beet pulp combined with either whole oats (OB) or barley (BB) and hay plus a loose chaff-based concentrate (M). Four horses were fitted with permanent caecal cannulas and liquid caecal content was withdrawn manually and blood was drawn from the jugular vein at 0, 3 and 9 h postprandial. The horses were exercised daily at medium level for about 1 h. Samples were analysed for short-chain fatty acids (SCFA) and metabolic traits. Caecal SCFA and propionic acid concentrations increased with increased dietary starch and soluble fibre. The diet highest in soluble fibre (M) resulted in the highest plasma glucose and insulin concentrations in the morning, which then remained stable and constant throughout the day. A strong interaction (P<0.01) between time and diet was measured for plasma urea, glucose, insulin and leptin. The greatest variations in plasma glycaemic and insulinaemic responses were associated with the cereal grain diets (OB and BB). There were indications of a negative energy balance, which was reflected in a significantly higher plasma β-hydroxybutyrate concentration and a numerically higher non-esterified fatty acid concentration. In conclusion, this study found that inclusion of soluble fibre resulted in increased total caecal SCFA and propionic acid concentrations. This consequently resulted in stable and constant plasma glycaemic and insulinaemic responses. Diets with a high content of soluble fibre provided enough energy for horses at medium work level.     

Influence of salt on glycaemic response to carbohydrate loading.

The effect of dietary salt on glycaemic responses to different test meals was investigated. Eight healthy male volunteers ate four test meals on consecutive mornings and in random order; the meals were 50 g carbohydrate taken as a 20% glucose solution or as boiled macaroni with and without supplementation with 6 g salt. In contrast with other reports, no significant differences in peak plasma glucose concentrations or areas under the plasma glucose curves could be established. These findings do not support a beneficial effect of salt restriction on glycaemic control in diabetes.     

Supplementation with a combination of antioxidants does not affect glycaemic control,oxidative stress or inflammation in type 2 diabetes subjects

Abstract

The present clinical trial examined the influence of a supplement, containing a combination of antioxidants extracted from fruit, berries and vegetables, on levels of plasma antioxidants (tocopherols, carotenoids and ascorbate), glycaemic control (blood glucose, HbA1c, insulin), oxidative stress biomarkers (F₂-isoprostane, malondialdehyd, nitrotyrosine, 8-oxo-7, 8-dihydro-2′-deoxyguanosine, formamidopyrimidine glycosylase sites, frequency of micronucleated erythrocytes) and inflammatory markers (interleukin-6, C-reactive protein, prostaglandin F_2α-metabolite) in type 2 diabetes. Forty subjects were randomly assigned to control, single or double dose group and completed the study. In summary, 12 weeks of antioxidant supplementation did neither affect glycaemic control nor the levels of biomarkers of oxidative stress or inflammation, despite substantially increased plasma concentrations of antioxidants. The absence of an effect may be explained by the selected study subjects with relatively well-controlled diabetes, a high intake of fruit and vegetable and levels of plasma antioxidants, biomarkers of oxidative stress and inflammatory markers comparable to those found in healthy subjects.     

Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial

ObjectiveTo compare perinatal outcome and glycaemic control in two groups of pregnant diabetic patients receiving two insulin regimens.DesignRandomised controlled open label study.SettingUniversity affiliated hospital, Israel.Participants138 patients with gestational diabetes mellitus and 58 patients with pregestational diabetes mellitus received insulin four times daily, and 136 patients with gestational diabetes and 60 patients with pregestational diabetes received insulin twice daily.InterventionThree doses of regular insulin before meals and an intermediate insulin dose before bedtime (four times daily regimen), and a combination of regular and intermediate insulin in the morning and evening (twice daily regimen).ResultsMean daily insulin concentration before birth was higher in the women receiving insulin four times daily compared with twice daily: by 22 units (95% confidence interval 12 to 32) in patients with gestational diabetes and by 28 units (15 to 41) in patients with pregestational diabetes. Glycaemic control was better with the four times daily regimen than with the twice daily regimen: in patients with gestational diabetes mean blood glucose concentrations decreased by 0.19 mmol/l (0.13 to 0.25), HbA_1c by 0.3% (0.2% to 0.4%), and fructosamine by 41 μmol/l (37 to 45), and adequate glycaemic control (mean blood glucose concentration <5.8 mmol/l) was achieved in 17% (8% to 26%) more women; in patients with pregestational diabetes mean blood glucose concentration decreased by 0.44 mmol/l (0.28 to 0.60), HbA_1c by 0.5% (0.2% to 0.8%), and fructosamine by 51 μmol/l (45 to 57), and adequate glycaemic control was achieved in 31% (15% to 47%) more women. Maternal severe hypoglycaemic events, caesarean section, preterm birth, macrosomia, and low Apgar scores were similar in both dose groups. In women with gestational diabetes the four times daily regimen resulted in a lower rate of overall neonatal morbidity than the twice daily regimen (relative risk 0.59, 0.38 to 0.92), and the relative risk for hyperbilirubinaemia and hypoglycaemia was lower (0.51, 0.29 to 0.91 and 0.12, 0.02 to 0.97 respectively). The relative risk of hypoglycaemia in newborn infants to mothers with pregestational diabetes was 0.17 (0.04 to 0.74).ConclusionsGiving insulin four times rather than twice daily in pregnancy improved glycaemic control and perinatal outcome without further risking the mother.

Key messages

• Improving maternal glycaemic control during pregnancy is the key to better perinatal outcome
• In pregnant diabetic women insulin four times daily achieved better glycaemic control and lower rate of perinatal complications (hypoglycaemia, hyperbilirubinaemia) than insulin twice daily
• Better glycaemic control resulted from a larger total daily insulin dose
• The intensified regimen did not lead to higher rate of severe maternal hypoglycaemia

     

A modified oral sugar test for evaluation of insulin and glucose dynamics in horses

Background

An oral sugar test (OST) using Karo^® Light Corn Syrup has been developed in the USA as a field test for the assessment of insulin dysregulation in horses but the syrup is not available in Scandinavian grocery stores. The aim of the study was to compare the results of a modified OST between horses with equine metabolic syndrome (EMS) and healthy horses using a Scandinavian commercially available glucose syrup (Dansukker glykossirap). In addition, the effect of breed and the repeatability of the test were evaluated. In the present study, clinically healthy horses (7 Shetland ponies, 8 Icelandic horses, 8 Standardbred horses) and 20 horses of various breeds with EMS underwent the modified OST test. The Icelandic horses and Shetland ponies underwent the OST twice. Insulin and glucose data from the OST were used to calculate peak insulin concentration (Peak_INS), time to peak insulin concentration (T-peak_INS), area under the curve for insulin (AUC_INS) and glucose (AUC_GLU) as well as whole body insulin sensitivity index (ISI_COMP).

Results

Compared to the healthy group, the EMS group had 6–7 times higher geometric mean for Peak_INS and AUC_INS and 8 times lower geometric mean for ISI_COMP. The EMS group had a delayed T-peak_INS compared to the healthy group. There was no effect of breed in the group of healthy horses on Peak_INS, T-peak_INS, AUC_INS, AUC_GLU and ISI_COMP. Coefficient of variation for repeated tests was 19.8, 19.0 and 17.6 % for Peak_INS, AUC_INS and ISI_COMP respectively.

Conclusions

The results of the present study demonstrate that the modified OST appears to be a practical and useful diagnostic tool for assessment of insulin dysregulation in the horse. However, to make it possible to establish the most appropriate sampling interval and to evaluate the accuracy of the modified OST, further studies in horses with a variable degree of insulin resistance are needed, where results from the modified OST are compared with quantitative measurements for IS.

     

Blood pressure in Warmblood horses before and during a euglycemic-hyperinsulinemic clamp

Background

Insulin resistance (IR) in humans is related to hypertension and impaired vasodilation. Insulin administration has been shown to lower blood pressure both in insulin resistant as well as in insulin sensitive individuals. The aim of the study was to investigate the association between insulin sensitivity and alterations in blood pressure in healthy horses before and after a euglycemic-hyperinsulinemic clamp (EHC). A 3-h EHC was performed in 13 healthy horses (11 mares, 2 geldings). Blood samples for measurement of plasma glucose and insulin were collected before the start of the EHC, every 10 min during the EHC and immediately after the EHC. Mean, systolic- and diastolic blood pressure was measured before and during the final 10 min of the EHC using an indirect high-definition oscillometric monitor (HDO, horse model) applied to the middle of the coccygeal artery. Five consecutive measurements were made in each horse and on each occasion. Insulin and glucose data from the EHC were used to calculate the mean rate of glucose disposal per unit of insulin during steady state (M/I ratio). Insulin resistance was defined as a M/I ratio <5 mg/kg/min/mUL (Lindåse et al. in Am J Vet Res 77:300–309, 2016).

Results

Insulin administration decreased systolic, diastolic and mean arterial pressure in all horses. The M/I ratio for all horses was negatively correlated with the decrease in systolic blood pressure (r² = 0.55, P = 0.004) and mean arterial pressure (r² = 0.31, P = 0.048) but not diastolic blood pressure (r² = 0.12, P = 0.26). Eight horses were defined as insulin resistant (IR) and five horses had normal insulin sensitivity. The five horses with normal insulin sensitivity showed a greater decrease in systolic blood pressure (−17.0 ± 7.4 vs. −3.4 ± 4.6 mmHg, P = 0.001) and MAP (19.2 ± 14.7 vs. 6.9 ± 8.7 mmHg, P = 0.04) than IR horses. There was no difference in the decrease in diastolic blood pressure between groups (16 ± 12.8 vs. 8.9 ± 12.1 mmHg, P = 0.17).

Conclusions

This study indicates that there is a relationship between insulin sensitivity and systolic and MAP in horses. However, studies on a larger number of horses are needed to confirm this association.

     

A forage-only diet alters the metabolic response of horses in training

Most athletic horses are fed a high-starch diet despite the risk of health problems. Replacing starch concentrate with high-energy forage would alleviate these health problems, but could result in a shift in major substrates for muscle energy supply from glucose to short-chain fatty acids (SCFA) due to more hindgut fermentation of fibre. Dietary fat inclusion has previously been shown to promote aerobic energy supply during exercise, but the contribution of SCFA to exercise metabolism has received little attention. This study compared metabolic response with exercise and lactate threshold (V_La4) in horses fed a forage-only diet (F) and a more traditional high-starch, low-energy forage diet (forage–concentrate diet - FC). The hypothesis was that diet F would increase plasma acetate concentration and increase V_La4 compared with diet FC. Six Standardbred geldings in race training were used in a 29-day change-over experiment. Plasma acetate, non-esterified fatty acids (NEFA), lactate, glucose and insulin concentrations and venous pH were measured in samples collected before, during and after a treadmill exercise test (ET, day 25) and muscle glycogen concentrations before and after ET. Plasma acetate concentration was higher before and after exercise in horses on diet F compared with diet FC, and there was a tendency (P = 0.09) for increased V_La4 on diet F. Venous pH and plasma glucose concentrations during exercise were higher in horses on diet F than diet FC, as was plasma NEFA on the day after ET. Plasma insulin and muscle glycogen concentrations were lower for diet F, but glycogen utilisation was similar for the two diets. The results show that a high-energy, forage-only diet alters the metabolic response to exercise and, with the exception of lowered glycogen stores, appears to have positive rather than negative effects on performance traits.     

Effect of dietary medium chain triacylglycerols on plasma triacylglycerol levels in horses

The hypothesis tested was that the feeding of medium chain triacylglycerols (MCT) to horses would raise the level of plasma triacylglycerols by increasing the availability of glucose as lipogenic substrate, implying that the MCT effect would be greater with glucose in the diet instead of cellulose. A Latin square experiment was carried out with 4 horses and 4 dietary treatments. The experimental periods lasted 21 d. Blood samples were taken 16 h after feeding. The diets consisted of hay and experimental concentrates, differing in fat source (MCT or soybean oil) and carbohydrate source (corn starch plus glucose or cellulose). The dietary variables, MCT or soybean oil, provided on average 27% of total dietary net energy, while glucose plus cornstarch or cellulose provided 33%. The feeding of MCT versus soybean oil raised the level of plasma triacylglycerols significantly from 196.7 ± 30.2 to 427.3 ± 85.7 mmol/1 and that of VLDL cholesterol from 0.028 ± 0.01 to 0.069 ± 0.01 mmol/ml. As based on analysis of variance, for the four experimental diets there was no significant effect of carbohydrate source and no fat‐carbohydrate interaction. Thus, the hypothesis was rejected. When the diets contained soybean oil, cellulose versus starch plus glucose produced significantly greater increase plasma triacylglycerols. This carbohydrate effect was not seen when horses were fed the MCT diets. The experimental concentrates did not differently influence the concentrations of plasma glucose, total serum cholesterol, phospholipids, insulin, free fatty acids and the activity of post‐heparin lipoprotein lipase. We suggest that the MCT‐induced increase in plasma triacylglycerols is related to an increase in hepatic VLDL secretion, with the extra substrate for increased synthesis of triacylglycerols being the acetyl‐CoA derived from the hepatic oxidation of medium chain fatty acids.     

Postprandial glucose, insulin and glucagon responses to meals with different nutrient compositions in non-insulin-dependent diabetes mellitus

Postprandial glycaemic and hormone responses to meals with different nutrient compositions and their heterogeneity were evaluated in 16 non-insulin-dependent diabetic patients and 5 healthy volunteers. Five kinds of nutrient stimulation--75 g glucose, a Japanese mixed meal (400 kcal, carbohydrate 60%, protein 14%, fat 26%), a high protein meal (300 kcal, C 26%, P 64%, F 10%), a high fat meal (300 kcal, C 23%, P 5%, F 72%) and 20 g iv glucose--was given to each subject. On the average, in both normal and diabetic subjects, the increases in plasma glucose (PG) and insulin (IRI) were the largest with the oral glucose load and the smallest with the high protein meal. The ratio of increase in IRI and PG (sigma delta IRI/sigma delta PG) was the highest with the high protein meal and the lowest with the oral glucose load. sigma delta IRI with the high protein meal and the high fat meal were the same in normal and diabetic subjects. However, each of the 16 NIDDM patients and 5 normal volunteers exhibited a different pattern of response to the nutrient stimuli and no definite subgroup could be classified. There was no correlation between metabolic responses and family history of diabetes mellitus, duration of diabetes, body mass index and fasting plasma glucose. The present results suggest the nearly intact capacity of insulin secretion in NIDDM in response to a high protein or high fat meal and the difficulty of subclassification in NIDDM according to the glycaemic and hormone responses to the different nutrient stimuli.     

Successful treatment of prediabetes in clinical practice: targeting insulin resistance and β-cell dysfunction

ObjectiveTo determine the effectiveness of targeted pharmacologic interventions to reverse documented pathophysiologic abnormalities in prediabetes.MethodsPatients with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) were treated with insulin sensitizers (pioglitazone + metformin) or insulin sensitizers + exenatide on the basis of oral glucose tolerance testing-derived indices of insulin resistance and impaired b-cell function. Patients who declined pharmacologic therapy received lifestyle modification only.ResultsOne hundred five patients with IGT and/or IFG were treated with insulin sensitizers (pioglitazone + metformin) (n = 40), insulin sensitizers + exenatide (n = 47), or lifestyle modification only (n = 18). After a mean follow-up period of 8.9 months, the lifestyle modification group demonstrated no significant changes in fasting plasma glucose, plasma glucose area under the curve during oral glucose tolerance testing, insulin sensitivity, or b-cell function. In the pioglitazone + metformin group (24 hours off medication), fasting plasma glucose fell from 109 to 102 mg/dL; plasma glucose area under the curve decreased by 12.0%; insulin sensitivity and b-cell function improved by 42% and 50%, respectively (all P < .001); 14.3% converted to normal glucose tolerance; and no patient developed diabetes. In the pioglitazone + metformin + exenatide group (24 hours off medication), fasting plasma glucose fell from 109 to 98 mg/dL; plasma glucose area under the curve decreased by 21.2%; insulin sensitivity and b-cell function improved by 52% and 109%, respectively (all P < .001); 59.1% of patients with IGT reverted to normal glucose tolerance; and no patient developed diabetes.ConclusionsTargeted pathophysiologic therapy based on oral glucose tolerance test-derived measures of insulin sensitivity and b-cell function can be implemented in general internal medicine and endocrine practice and is associated with marked improvement in glucose tolerance and reversion of prediabetes to normal glucose tolerance in more than 50% of patients. (Endocr Pract. 2012;18: 342-350)     

Effects of cefaclor on gastric emptying and cholecystokinin release in healthy humans

Background and aimsIn rodents, cephalosporin antibiotics can mimic peptones and stimulate release of cholecystokinin (CCK), a hormone that slows gastric emptying. The rate of gastric emptying is a major determinant of postprandial blood glucose and insulin concentrations. We therefore evaluated the effect of orally administered cefaclor on plasma CCK and gastric emptying, as well as postprandial glycemic and insulinemic responses, in healthy humans.Materials and methodsWe studied 8 healthy subjects on two days in double-blind, randomized order. On each day, subjects consumed 1000 mg cefaclor or placebo 30 min before a mashed potato meal labeled with ¹³C octanoic acid. Blood and breath samples were collected for 4 h after the meal.ResultsBlood glucose, serum insulin and plasma CCK increased in response to the carbohydrate meal on both study days, and cefaclor had no effect on these responses. Similarly, the gastric half-emptying time (measured by breath test) did not differ (placebo: 137.5 ± 6.0 min vs. cefaclor: 143.1 ± 8.0 min).ConclusionCefaclor, when given before a meal in the form of a capsule, does not stimulate CCK release or slow gastric emptying in healthy humans.     

Glucose tolerance, lipids, and GLP-1 secretion in JCR:LA-cp rats fed a high protein fiber diet

Background: We have shown that individually, dietary fiber and protein increase secretion of the anorexigenic and insulinotropic hormone, glucagon‐like peptide‐1 (GLP‐1). Objective: Our objective was to combine, in one diet, high levels of fiber and protein to maximize GLP‐1 secretion, improve glucose tolerance, and reduce weight gain. Methods and Procedures: Lean (+/?) and obese (cp/cp) male James C Russell corpulent (JCR:LA‐cp) rats lacking a functional leptin receptor were fed one of four experimental diets (control, high protein (HP), high fiber (HF, prebiotic fiber inulin), or combination (CB)) for 3 weeks. An oral glucose tolerance test (OGTT) was performed to evaluate plasma GLP‐1, insulin and glucose. Plasma lipids and intestinal proglucagon mRNA expression were determined. Results: Energy intake was lower with the HF diet in lean and obese rats. Weight gain did not differ between diets. Higher colonic proglucagon mRNA in lean rats fed a CB diet was associated with higher GLP‐1 secretion during OGTT. The HP diet significantly reduced plasma glucose area under the curve (AUC) during OGTT in obese rats, which reflected both an increased GLP‐1 AUC and higher fasting insulin. Diets containing inulin resulted in the lowest plasma triglyceride and total cholesterol levels. Discussion: Overall, combining HP with HF in the diet increased GLP‐1 secretion in response to oral glucose, but did not improve glucose tolerance or lipid profiles more than the HF diet alone did. We also suggest that glycemic and insulinemic response to prebiotics differ among rat models and future research work should examine their role in improving glucose tolerance in diet‐induced vs. genetic obesity with overt hyperleptinemia.     

Equine pre-caecal and total tract digestibility of individual carbohydrate fractions and their effect on caecal pH response

The working hypothesis was that a minor postprandial caecal pH decline would affect apparent total tract digestibility (ATTD) of the fibre fraction in horses and, hence, that soluble fibre would amplify fermentation and consequently increase ATTD of fibre. This study was a 4 × 4 Latin Square design with a sequence of 17 days adaptation to the ration followed by 8 sampling days. The feed rations consisted of only timothy hay (Group H), hay plus molassed sugar beet pulp combined with either whole oats (Group OB) or barley (Group BB) and hay plus loose chaff based concentrate (Group M). Four horses fitted with permanent caecal cannulas and collection harnesses were used. A pH electrode with logger was inserted through the cannula and caecal pH was recorded at 1 min intervals for 8 h. The mobile nylon bag technique was used to quantify pre-caecal loss (PCL) of individual feedstuffs. Fibre was analysed as dietary fibre (DF), non-starch polysaccharides, soluble non-cellulosic polysaccharides (S-NCP), insoluble non-cellulosic polysaccharide (I-NCP) and neutral detergent fibre. The ATTD of the S-NCP fraction was above 0.8, which was 60% higher than for the I-NCP fraction. The PCL of starch were 0.98 (oats) and 0.75 (barley). The BB diet lowered (p < 0.001) postprandial caecal pH more than the other diets and a significant correlation was found between the lowest pH and ATTD of I-NCP (r = ?0.66; p = 0.005). In conclusion, this study successfully measured the in vivo digestibility of individual fibre fractions and found that S-NCP was more digestible than the I-NCP, and that a single meal of unprocessed barley was sufficient to decrease caecal pH to such an extent that the fibre digestibility of the whole diet was negatively affected.     

Amino acid requirement of growing pigs depending on amino acid efficiency and level of protein deposition. 2nd communication: threonine

Forty Swiss Large White pigs (barrows with 31.7 kg initial to 103.7 kg final BW) were equally and randomly assigned to one of four treatments (H0, H200, L0, L200) involving a combination of chromium supplementation (0 or 200 μg/kg) and glycemic index (high GI (H) or low GI (L)). Growth performance, energy and protein digestibility, carcass composition, and some plasma traits were investigated.

The data indicated, that the substitution of dietary carbohydrates with fat and crude fibre (low GI) resulted in lower growth performance due to impaired energy digestibility. Moreover, the strong stimulation of insulin secretion due to the high and rapid availability of carbohydrates of the diets HO and H200 caused increased carcass fat deposition. Chromium supplementation also affected plasma insulin and glucagon concentrations. Depending on glycemic index, chromium affected the growth performance. Daily gain was reduced in pigs of the L200 treatment compared to the L0 group. This finding indicated that the energy availability expressed as GI is one of several nutritional factors, which determine the efficacy of dietary chromium. We could not corroborate evidences that dietary chromium modifies the chemical composition of the whole carcass, but depending on GI, chemical composition of the longissimus muscle was affected.     

Effect of Feeding Inorganic Chromium on Growth Performance, Endocrine Variables, and Energy Metabolites in Winter-Exposed Buffalo Calves (Bubalus bubalis)

We investigated the effect of chromium (Cr) supplementation on the growth performance, energy metabolites, and hormonal variation in winter-exposed buffalo calves. Twenty-four female buffalo calves were randomly allotted to four dietary treatments (n?=?6) for a period of 120 days. Feeding regimen was the same in all the groups, except the animals in the four respective groups were additionally supplemented with 0.0, 0.5, 1.0, and 1.5 mg of Cr/kg DM in the form of CrCl₃.6H₂O. Calves were monitored daily for physiological variables and dry matter intake (DMI). Blood samples were collected at fortnightly intervals from each buffalo calves to measure concentrations of hormones (insulin, cortisol, and growth hormone), energy metabolites (glucose and non-esterified fatty acids), and plasma mineral levels. After 120 days of feeding trial, buffalo calves fed with Cr had lower (P?<?0.05) circulating plasma concentrations of glucose, insulin, and cortisol hormones, whereas plasma thyroid hormone and non-esterified fatty acids concentrations were found similar (P?>?0.05) among all the treatments. The results suggested that dietary Cr supplementation influenced plasma Cr levels without affecting the plasma concentrations of other trace minerals. However, physiological variables, nutrient intake, and growth performance of buffalo calves did not differ among all treatments (P?>?005). In summary, the current study showed that supplementation of Cr at the level of 1.0 and 1.5 mg of Cr/kg DMI was more effective in improving glucose utilization by increasing potency of insulin hormone and reducing concentration of cortisol hormone. Results also suggested that supplemental Cr also improves blood plasma Cr levels.     

Associations of iron status with breast cancer risk factors in adult women: Findings from National Health and Nutrition Examination Survey 2017–2018

ObjectiveThis study examined the association between iron status and a set of breast cancer risk factors among U.S. adult women aged 20–80 years.MethodsData from National Health and Nutrition Examination Survey (2017–2018) were used to examine the relation between serum ferritin, serum iron and transferrin saturation with a set of breast cancer risk factors [body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), fasting plasma glucose, insulin and HOMA-IR]. The multivariable linear regressions were used controlling for age, race/ethnicity, menopause status, education level, smoking status, alcohol consumption, physical activity, high-sensitivity C-reactive protein (hsCRP) and total energy intake.ResultsHbA1c, BMI and waist circumference data were available for 1902 women with a fasting sample (n = 913) for fasting plasma glucose, insulin and HOMA-IR. Transferrin saturation had significant, inverse associations with BMI, waist circumference and HbA1c. The size of difference observed were that participants in the fourth quartile of transferrin saturation had a 4.50 kg/m² smaller BMI, a 9.36 cm smaller waist circumference and a 0.1 % lower HbA1c level than participants in the first quartile. Similarly, serum iron concentrations were inversely associated with BMI and waist circumference. In addition, serum iron had significant, inverse associations with insulin and HOMA-IR. Sensitivity analyses among men gave similar results. For serum ferritin, there was a trend towards a positive association between waist circumference, HbA1c and fasting plasma glucose with serum ferritin. However, the associations did not reach statistical significance among women.ConclusionsIron status may impact breast cancer risk via effects on adiposity or glucose metabolism. The findings should be confirmed with further prospective data.     

Repeated post-exercise administration with a mixture of leucine and glucose alters the plasma amino acid profile in Standardbred trotters

Background  

The branched chain amino acid leucine is a potent stimulator of insulin secretion. Used in combination with glucose it can increase the insulin response and the post exercise re-synthesis of glycogen in man. Decreased plasma amino acid concentrations have been reported after intravenous or per oral administration of leucine in man as well as after a single per oral dose in horses. In man, a negative correlation between the insulin response and the concentrations of isoleucine, valine and methionine have been shown but results from horses are lacking. This study aims to determine the effect of repeated per oral administration with a mixture of glucose and leucine on the free amino acid profile and the insulin response in horses after glycogen-depleting exercise.     

How should we monitor the cardiovascular benefit of sodium–glucose cotransporter 2 inhibition?

Background

High N-terminal pro-brain-type natriuretic peptide levels have been associated with a lower risk of type 2 diabetes mellitus (T2D). However, less is known about other cardiac stress biomarkers in this context. Here we evaluated the association of mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-arginine vasopressin (copeptin), C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM) with incident T2D and changes in glucose metabolism.

Methods

We performed a prospective cohort study using data from the population-based KORA F4/FF4 study. 1773 participants (52.3% women) with MR-proANP measurements and 960 (52.7% women) with copeptin, CT-proET-1 and MR-proADM measurements were included. We examined associations of circulating plasma levels of MR-proANP, copeptin, CT-proET-1 and MR-proADM with incident T2D, the combined endpoint of incident prediabetes/T2D and with fasting and 2 h-glucose, fasting insulin, HOMA-IR, HOMA-B and HbA1c at follow-up. Logistic and linear regression models adjusted for age, sex, waist circumference, height, hypertension, total/HDL cholesterol ratio, triglycerides, smoking, physical activity and parental history of diabetes were used to compute effect estimates.

Results

During a median follow-up time of 6.4 years (25th and 75th percentiles: 6.0 and 6.6, respectively), 119 out of the 1773 participants and 72 out of the 960 participants developed T2D. MR-proANP was inversely associated with incident T2D (odds ratio [95% confidence interval]: 0.75 [0.58; 0.96] per 1-SD increase of log MR-proANP). Copeptin was positively associated with incident prediabetes/T2D (1.29 [1.02; 1.63] per 1-SD increase of log copeptin). Elevated levels of CT-proET-1 were associated with increased HOMA-B at follow-up, while elevated MR-proADM levels were associated with increased fasting insulin, HOMA-IR and HOMA-B at follow-up. These associations were independent of previously described diabetes risk factors.

Conclusions

High plasma concentrations of MR-proANP contributed to a lower risk of incident T2D, whereas high plasma concentrations of copeptin were associated with an increased risk of incident prediabetes/T2D. Furthermore, high plasma concentrations of CT-proET-1 and MR-proADM were associated with increased insulin resistance. Our study provides evidence that biomarkers implicated in cardiac stress are associated with incident T2D and changes in glucose metabolism.

     

Comparison of high fibre diets,basal insulin supplements,and flexible insulin treatment for non-insulin dependent (type II) diabetics poorly controlled with sulphonylureas.

OBJECTIVE--To compare high fibre diet, basal insulin supplements and a regimen of insulin four times daily in non-insulin dependent (type II) diabetic patients who were poorly controlled with sulphonylureas. DESIGN--Run in period lasting 2-3 months during which self monitoring of glucose concentration was taught, followed by six months on a high fibre diet, followed by six months'' treatment with insulin in those patients who did not respond to the high fibre diet. SETTING--Teaching hospital diabetic clinics. PATIENTS--33 patients who had had diabetes for at least two years and had haemoglobin A1 concentrations over 10% despite receiving nearly maximum doses of oral hypoglycaemic agents. No absolute indications for treatment with insulin. INTERVENTIONS--During the high fibre diet daily fibre intake was increased by a mean of 16 g (95% confidence interval 12 to 20 g.) Twenty five patients were then started on once daily insulin. After three months 14 patients were started on four injections of insulin daily. ENDPOINT--Control of diabetes (haemoglobin A1 concentration less than or equal to 10% and fasting plasma glucose concentration less than or equal to 6 mmol/l) or completion of six months on insulin treatment. MEASUREMENTS AND MAIN RESULTS-- No change in weight, diet, or concentrations of fasting glucose or haemoglobin A1 occurred during run in period. During high fibre diet there were no changes in haemoglobin A1 concentrations, but mean fasting glucose concentrations rose by 1.7 mmol/l (95% confidence interval 0.9 to 2.5, p less than 0.01). With once daily insulin mean concentrations of fasting plasma glucose fell from 12.6 to 7.6 mmol/l (p less than 0.001) and haemoglobin A1 from 14.6% to 11.2% (p less than 0.001). With insulin four times daily concentrations of haemoglobin A1 fell from 11.5% to 9.6% (p less than 0.02). Lipid concentrations were unchanged by high fibre diet. In patients receiving insulin the mean cholesterol concentrations fell from 7.1 to 6.4 mmol/l (p less than 0.0001), high density lipoprotein concentrations rose from 1.1 to 1.29 mmol/l (p less than 0.01), and triglyceride concentrations fell from 2.67 to 1.86 mmol/l (p less than 0.05). Patients taking insulin gained weight and those taking it four times daily gained an average of 4.2 kg. CONCLUSIONS--High fibre diets worsen control of diabetes in patients who are poorly controlled with oral hypoglycaemic agents. Maximum improvements in control of diabetes were achieved by taking insulin four times daily.     

Dietary fibres,fibre analogues,and glucose tolerance: importance of viscosity.

To define the type of dietary fibre of fibre analogue with the greatest potential use in diabetic treatment, groups of four to six volunteers underwent 50-g glucose tolerance tests (GTT) with and without the addition of either guar, pectin, gum tragacanth, methylcellulose, wheat bran, or cholestyramine equivalent to 12 g fibre. The addition of each substance significantly reduced blood glucose concentration at one or more points during the GTT and generally reduced serum insulin concentrations. The greatest flattening of the glucose response was seen with guar, but this effect was abolished when hydrolysed non-viscous guar was used. The reduction in the mean peak rise in blood glucose concentration for each substance correlated positively with its viscosity (r = 0.926; P less than 0.01), as did delay in mouth-to-caecum transit time (r = 0.885; P less than 0.02). Viscous types of dietary fibre are therefore most likely to be therapeutically useful in modifying postprandial hyperglycaemia.