Dietary Blueberry Ameliorates Vascular Complications in Diabetic Mice Possibly through NOX4 and Modulates Composition and Functional Diversity of Gut Microbes.

SCOPE: In diabetes, endothelial inflammation and dysfunction play a pivotal role in the development of vascular disease. This study investigates the effect of dietary blueberries on vascular complications and gut microbiome in diabetic mice. METHODS AND RESULTS: Seven-week-old diabetic db/db mice consume a standard diet (db/db) or a diet supplemented with 3.8% freeze-dried blueberry (db/db+BB) for 10 weeks. Control db/+ mice are fed a standard diet (db/+). Vascular inflammation is assessed by measuring monocyte binding to vasculature and inflammatory markers. Isometric tension procedures are used to assess mesenteric artery function. db/db mice exhibit enhanced vascular inflammation and reduced endothelial-dependent vasorelaxation as compared to db/+ mice, but these are improved in db/db+BB mice. Blueberry supplementation reduces the expression of NOX4 and IκKß in the aortic vessel and vascular endothelial cells (ECs) isolated from db/db+BB compared to db/db mice. The blueberry metabolites serum reduces glucose and palmitate induced endothelial inflammation in mouse aortic ECs. Further, blueberry supplementation increases commensal microbes and modulates the functional potential of gut microbes in diabetic mice. CONCLUSION: Dietary blueberry suppresses vascular inflammation, attenuates arterial endothelial dysfunction, and supports the growth of commensal microbes in diabetic mice. The endothelial-specific vascular benefits of blueberries are mediated through NOX4 signaling.

Effect of Early and Late Interventions with Dietary Oils on Vascular and Neural Complications in a Type 2 Diabetic Rat Model.

AIMS: Determine the effect of dietary oils enriched in different mono- or polyunsaturated fatty acids, i.e., olive oil (18 : 1, oleic acid), safflower oil (18 : 2 n-6, linoleic acid), flaxseed oil (18 : 3 n-3, alpha linolenic acid), evening primrose oil (18 : 3 n-6, gamma linolenic acid), or menhaden oil (20:5/22 : 6 n-3 eicosapentaenoic/docosahexaenoic acids), on vascular and neural complications in high-fat-fed low-dose streptozotocin-treated Sprague-Dawley rats, an animal model for late-stage type 2 diabetes. MATERIALS AND METHODS: Rats were fed a high-fat diet (45% kcal as fat primarily derived from lard) for 8 weeks and then treated with a low dose of streptozotocin (30 mg/kg) in order to induce hyperglycemia. After an additional 8 (early intervention) or 20 (late intervention) weeks, the different groups of rats were fed diets with 1/2 of the kcal of fat derived from lard replaced by the different dietary oils. In addition, a control group fed a standard diet (4.25% kcal as fat) and a diabetic group maintained on the high-fat diet were maintained. The treatment period was approximately 16 weeks. The endpoints evaluated included vascular reactivity of epineurial arterioles, motor and sensory nerve conduction velocity, thermal and corneal sensitivity, and innervation of sensory nerves in the cornea and skin. RESULTS: Our findings show that menhaden and flaxseed oil provided the greatest benefit for correcting peripheral nerve damage caused by diabetes, whereas enriching the high-fat diet with menhaden oil provided the most benefit to acetylcholine-mediated vascular relaxation of epineurial arterioles of the sciatic nerve. Enriching the diets with fatty acids derived from the other oils provided none to partial improvements. CONCLUSIONS: These studies imply that long-chain n-6 and n-3 polyunsaturated fatty acids could be an effective treatment for diabetic peripheral neuropathy with n-3 polyunsaturated fatty acids derived from fish oil being the most effective.

Inhibition of vascular smooth muscle cells premature senescence with rutin attenuates and stabilizes diabetic atherosclerosis.

Atherosclerosis is an age-associated disease; however, diabetic atherosclerosis has higher severity beyond age range for accumulative premature senescent cells in diabetes. Recent findings suggest that rutin, a flavonoid, has potential benefits for diabetic individuals. This study was designed to evaluate the effects of rutin on premature senescence and atherosclerosis. Apolipoprotein E knockout mice exhibiting insulin resistance after 6 weeks of high-fat diet were administered with a low dose of streptozotocin (STZ) to induce diabetes. After 8 weeks of STZ administration, rutin (40 mg/kg/d) was supplemented by gavage for the last 6 weeks. We evaluated the prosperity of the plaque and diabetes using serial echocardiography, histopathologic and metabolite analysis. Premature senescence induced by hydrogen peroxide in primary vascular smooth muscle cells (VSMCs) was used to analyze the underlying mechanism. Mice with diabetes showed more severe plaque burden on aortic arteries and less smooth muscle cells but larger senescent cell ratio in plaque compared with mice with control diets. Rutin significantly improves glucose and lipid metabolic disturbance in diabetes. Moreover, rutin decreased the atherosclerotic burden and senescent cell number and increased the VSMC ratio in aortic root plaque. In vitro, we demonstrated that rutin ameliorated premature senescence induced by oxidative stress, and the protective function may be mediated by inhibiting oxidative stress and protecting telomere. Rutin administration attenuates atherosclerosis burden and stabilizes plaque by improving metabolic disturbance and alleviating premature senescence of VSMCs. Inhibition of VSMCs premature senescence with rutin may be an effective therapy for diabetic atherosclerosis.

Short-term effects of a low carbohydrate diet on glycaemic variables and cardiovascular risk markers in patients with type 1 diabetes: A randomized open-label crossover trial.

The aim of the present study was to assess the effects of a high carbohydrate diet (HCD) vs a low carbohydrate diet (LCD) on glycaemic variables and cardiovascular risk markers in patients with type 1 diabetes. Ten patients (4 women, insulin pump-treated, median ± standard deviation [s.d.] age 48 ± 10 years, glycated haemoglobin [HbA1c] 53 ± 6 mmol/mol [7.0% ± 0.6%]) followed an isocaloric HCD (≥250 g/d) for 1 week and an isocaloric LCD (≤50 g/d) for 1 week in random order. After each week, we downloaded pump and sensor data and collected fasting blood and urine samples. Diet adherence was high (225 ± 30 vs 47 ± 10 g carbohydrates/d; P < .0001). Mean sensor glucose levels were similar in the two diets (7.3 ± 1.1 vs 7.4 ± 0.6 mmol/L; P = .99). The LCD resulted in more time with glucose values in the range of 3.9 to 10.0 mmol/L (83% ± 9% vs 72% ± 11%; P = .02), less time with values ≤3.9 mmol/L (3.3% ± 2.8% vs 8.0% ± 6.3%; P = .03), and less glucose variability (s.d. 1.9 ± 0.4 vs 2.6 ± 0.4 mmol/L; P = .02) than the HCD. Cardiovascular markers were unaffected, while fasting glucagon, ketone and free fatty acid levels were higher at end of the LCD week than the HCD week. In conclusion, the LCD resulted in more time in euglycaemia, less time in hypoglycaemia and less glucose variability than the HCD, without altering mean glucose levels.

Dietary glutamine supplementation enhances endothelial progenitor cell mobilization in streptozotocin-induced diabetic mice subjected to limb ischemia.

Diabetes is a metabolic disorder with increased risk of vascular diseases. Tissue ischemia may occur with diabetic vascular complications. Bone marrow-derived endothelial progenitor cells (EPCs) constitute a reparative response to ischemic injury. This study investigated the effects of oral glutamine (GLN) supplementation on circulating EPC mobilization and expression of tissue EPC-releasing markers in diabetic mice subjected to limb ischemia. Diabetes was induced by a daily intraperitoneal injection of streptozotocin for 5 days. Diabetic mice were divided into 2 nonischemic groups and 6 ischemic groups. One of the nonischemic and 3 ischemic groups were fed the control diet, while the remaining 4 groups received diets with identical components except that part of the casein was replaced by GLN. The respective diets were fed to the mice for 3 weeks, and then the nonischemic mice were sacrificed. Unilateral hindlimb ischemia was created in the ischemic groups, and mice were sacrificed at 1, 7 or 21 days after ischemia. Their blood and ischemic muscle tissues were collected for further analyses. Results showed that plasma matrix metallopeptidase (MMP)-9 and the circulating EPC percentage increased after limb ischemia in a diabetic condition. Compared to groups without GLN, GLN supplementation up-regulated plasma stromal cell-derived factor (SDF)-1 and muscle MMP-9, SDF-1, hypoxia-inducible factor-1 and vascular endothelial growth factor gene expression. The CD31-immunoreactive intensities were also higher in the ischemic limb. These findings suggest that GLN supplementation enhanced circulating EPC mobilization that may promote endothelium repair at ischemic tissue in diabetic mice subjected to limb ischemia.

Potential of Dietary Non-Provitamin A Carotenoids in the Prevention and Treatment of Diabetic Microvascular Complications.

Diabetes is a chronic metabolic disease that affects a substantial part of the population around the world. Whether type I or type II, this disease has serious macro- and microvascular complications that constitute the primary cause of death in diabetic patients. Microvascular complications include diabetic retinopathy, nephropathy, and neuropathy. Although these complications are clinically and etiologically diverse, they share a common factor: glucose-induced damage. In the progression of diabetic complications, oxidative stress, inflammation, and the formation of glycation end products play an important role. Previous studies have shown that a healthy diet is vital in preventing these complications; in particular, the intake of antioxidants has been studied for their potential effect in ameliorating hyperglycemic injuries. Carotenoids are lipid-soluble pigments synthesized by plants, bacteria, and some kinds of algae that are responsible for the yellow, red, and orange colors in food. These compounds are part of the antioxidant machinery in plants and have also shown their efficacy in quenching free radicals, scavenging reactive oxygen species, modulating gene expression, and reducing inflammation in vitro and in vivo, showing that they can potentially be used as part of a preventive strategy for metabolic disorders, including diabetes and its related complications. This review highlights the potential protective effects of 4 non-provitamin A carotenoids--lutein, zeaxanthin, lycopene, and astaxanthin--in the development and progression of diabetic microvascular complications.

Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials.

BACKGROUND: The effects of nuts on major cardiovascular disease (CVD) risk factors, including dose-responses and potential heterogeneity by nut type or phytosterol content, are not well established. OBJECTIVES: We examined the effects of tree nuts (walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, and Brazil nuts) on blood lipids [total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein, and triglycerides], lipoproteins [apolipoprotein A1, apolipoprotein B (ApoB), and apolipoprotein B100], blood pressure, and inflammation (C-reactive protein) in adults aged ≥18 y without prevalent CVD. DESIGN: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two investigators screened 1301 potentially eligible PubMed articles in duplicate. We calculated mean differences between nut intervention and control arms, dose-standardized to one 1-oz (28.4 g) serving/d, by using inverse-variance fixed-effects meta-analysis. Dose-response for nut intake was examined by using linear regression and fractional polynomial modeling. Heterogeneity by age, sex, background diet, baseline risk factors, nut type, disease condition, duration, and quality score was assessed with meta-regression. Publication bias was evaluated by using funnel plots and Egger's and Begg's tests. RESULTS: Sixty-one trials met eligibility criteria (n = 2582). Interventions ranged from 3 to 26 wk. Nut intake (per serving/d) lowered total cholesterol (-4.7 mg/dL; 95% CI: -5.3, -4.0 mg/dL), LDL cholesterol (-4.8 mg/dL; 95% CI: -5.5, -4.2 mg/dL), ApoB (-3.7 mg/dL; 95% CI: -5.2, -2.3 mg/dL), and triglycerides (-2.2 mg/dL; 95% CI: -3.8, -0.5 mg/dL) with no statistically significant effects on other outcomes. The dose-response between nut intake and total cholesterol and LDL cholesterol was nonlinear (P-nonlinearity < 0.001 each); stronger effects were observed for ≥60 g nuts/d. Significant heterogeneity was not observed by nut type or other factors. For ApoB, stronger effects were observed in populations with type 2 diabetes (-11.5 mg/dL; 95% CI: -16.2, -6.8 mg/dL) than in healthy populations (-2.5 mg/dL; 95% CI: -4.7, -0.3 mg/dL) (P-heterogeneity = 0.015). Little evidence of publication bias was found. CONCLUSIONS: Tree nut intake lowers total cholesterol, LDL cholesterol, ApoB, and triglycerides. The major determinant of cholesterol lowering appears to be nut dose rather than nut type. Our findings also highlight the need for investigation of possible stronger effects at high nut doses and among diabetic populations.

Mediterranean Diet, Retinopathy, Nephropathy, and Microvascular Diabetes Complications: A Post Hoc Analysis of a Randomized Trial.

OBJECTIVE: To date no clinical trials have evaluated the role of dietary patterns on the incidence of microvascular diabetes complications. We hypothesized that a nutritional intervention based on the Mediterranean diet (MedDiet) would have greater protective effect on diabetic retinopathy and nephropathy than a low-fat control diet. RESEARCH DESIGN AND METHODS: This was a post hoc analysis of a cohort of patients with type 2 diabetes participating in the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter randomized nutritional intervention trial conducted in a population at high cardiovascular risk. Individuals with type 2 diabetes who were free of microvascular complications at enrollment (n = 3,614, aged 55-80 years) were randomly assigned to one of three dietary interventions: MedDiet supplemented with extravirgin olive oil (MedDiet+EVOO), MedDiet supplemented with mixed nuts (MedDiet+Nuts), or a low-fat control diet. Two independent outcomes were considered: new onset of diabetic retinopathy and nephropathy. Hazard ratios (HRs) were calculated using multivariable-adjusted Cox regression. RESULTS: During a median follow-up of 6.0 years, we identified 74 new cases of retinopathy and 168 of nephropathy. Compared with the control diet, multivariable-adjusted HRs for diabetic retinopathy were 0.56 (95% CI 0.32-0.97) for the MedDiet+EVOO and 0.63 (0.35-1.11) for the MedDiet+Nuts. No between-group differences were found for nephropathy. When the yearly updated information on adherence to the MedDiet was considered, the HR for retinopathy in the highest versus the lowest quintile was 0.34 (0.13-0.89; P = 0.001 for trend). No significant associations were found for nephropathy. CONCLUSIONS: A MedDiet enriched with EVOO may protect against diabetic retinopathy but not diabetic nephropathy.

Vascular endothelial dysfunction and nutritional compounds in early type 1 diabetes.

Cardiovascular disease is the major cause of death in patients with type 1 diabetes. Vascular endothelial dysfunction is an early pathophysiological precursor of cardiovascular disease. There is extensive evidence that hyperglycemia causes acute perturbations in endothelial function likely due to increases in oxidative damage. Interestingly, oscillating hyperglycemia may cause more damage than persistent hyperglycemia. Many, but not all, studies indicate that vascular endothelial dysfunction occurs early in the course of type 1 diabetes and is present even in adolescents. Ascorbic acid has been shown to diminish the acute effects of hyperglycemia on endothelial function in type 1 diabetes and in conjunction with euglycemia to restore endothelial function to normal values in adults with well-controlled diabetes. In vitro and in vivo animal evidence suggests potential benefit from two other small molecule antioxidants, nicotinamide and taurine. Early studies suggested that folate supplementation may improve endothelial function in adolescents with type 1 diabetes but this has not been confirmed by more recent studies. Epidemiological evidence suggests a possible role for vitamin D therapy although intervention studies in type 2 diabetes have yielded varying results and have not been done in type 1 diabetes. Further exploration of these and other compounds is clearly appropriate if we are to reduce cardiovascular risk in type 1 diabetes.

The effect of green tea and sour tea on blood pressure of patients with type 2 diabetes: a randomized clinical trial.

INTRODUCTION: The use of herbal medicines including different types of tea is among the different strategies for preventing and controlling the side-effects of diabetes. The aim of the present study was to compare the effect of sour tea and green tea on mildly hypertensive patients with diabetes. METHODS: The present study was a randomized clinical trial in which 100 mildly hypertensive patients with diabetes were randomly assigned into sour tea group (ST) and green tea group (GT). They were instructed to drink sour tea and green tea infusion, respectively, three times a day 2 hr after each meal for 4 weeks. The participants' blood pressure was measured at days 1, 15, and at the end of study. RESULTS: The systolic pressure of both groups statistically decreased at the end of the study; it decreased from 123.1 ± 15.5 to 116.8 ± 16.3 mmHg in the ST and from 119.4 ± 15.1 to 114.8 ± 15.9 mmHg in the GT. The diastolic pressure of both groups statistically decreased by the end of the study; it decreased from 79.4 ± 11.1 to 74.5 ± 9.3 mmHg in the ST and from 78.9 ± 8.3 to 75.3 ± 7.7 mmHg in the GT. The therapeutic effectiveness of tea drinking by the end of intervention was 43.5% in the ST and 39.6% in the GT compared to the beginning. CONCLUSIONS: The present study revealed that mildly hypertensive type 2 diabetic individuals who drink three glasses of green or sour tea daily for 4 weeks show significant decreased systolic and diastolic blood pressures.

Transcultural diabetes nutrition therapy algorithm: the Asian Indian application.

India and other countries in Asia are experiencing rapidly escalating epidemics of type 2 diabetes (T2D) and cardiovascular disease. The dramatic rise in the prevalence of these illnesses has been attributed to rapid changes in demographic, socioeconomic, and nutritional factors. The rapid transition in dietary patterns in India-coupled with a sedentary lifestyle and specific socioeconomic pressures-has led to an increase in obesity and other diet-related noncommunicable diseases. Studies have shown that nutritional interventions significantly enhance metabolic control and weight loss. Current clinical practice guidelines (CPGs) are not portable to diverse cultures, constraining the applicability of this type of practical educational instrument. Therefore, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed and then customized per regional variations in India. The resultant India-specific tDNA reflects differences in epidemiologic, physiologic, and nutritional aspects of disease, anthropometric cutoff points, and lifestyle interventions unique to this region of the world. Specific features of this transculturalization process for India include characteristics of a transitional economy with a persistently high poverty rate in a majority of people; higher percentage of body fat and lower muscle mass for a given body mass index; higher rate of sedentary lifestyle; elements of the thrifty phenotype; impact of festivals and holidays on adherence with clinic appointments; and the role of a systems or holistic approach to the problem that must involve politics, policy, and government. This Asian Indian tDNA promises to help guide physicians in the management of prediabetes and T2D in India in a more structured, systematic, and effective way compared with previous methods and currently available CPGs.

CA 72-4 levels in patients with type 2 diabetes mellitus.

OBJECTIVE: CA 72-4 is one of the blood group carbohydrate antigens which can be used as a tumour marker in ovarian, pancreatic and gastrointestinal carcinomas. It can also be elevated in various benign conditions including pancreatitis. Diabetes mellitus is a chronic disorder related with the pancreas. In this study, we investigated CA 72-4 levels in patients with type 2 diabetes and its relation to the metabolic status. METHODS: Sixty-nine patients with type 2 diabetes mellitus (female/male = 40/29) and 60 healthy subjects (female/male = 35/25) participated in this study. The levels of serum CA 72-4 were measured and faecal occult blood tests (following 3 days of white diet were obtained for three consecutive days) were performed in all patients. Patients had a pathological finding for any of these two parameters were further investigated with upper gastrointestinal endoscopy, colonoscopy and computerised tomography. RESULTS: The mean levels of CA 72-4 was 1.89 +/- 2.61 U/ml in the study group and 1.4 +/- 0.98 U/ml in the control group (p > 0.05). There was no association between CA 72-4 levels and age and sex of the patients, duration of diabetes, body mass index, biochemical indicators of metabolic control (the levels of HbA(1c), fasting and postprandial glucose, serum lipids), the presence of microvascular complications (retinopathy, nephropathy, neuropathy) or treatment modalities. CONCLUSIONS: Elevated levels of CA 72-4 in diabetic patients are not related to diabetes and it should be interpreted as evaluated in a non-diabetic patient.

[Critical analysis of the American Diabetes Association dietary recommendations for cardiovascular disease in diabetes mellitus]. / Análise crítica das recomendações da Associação Americana de Diabetes para doença cardiovascular no diabetes melito.

Cardiovascular disease (CVD) is the main cause of mortality among patients with diabetes mellitus (DM), and dietary intervention is an essential measure to prevent and treat this complication. The aim of this manuscript was to review scientific evidence that underlies the dietetic recommendations of the American Diabetes Association (ADA) for prevention and treatment of CVD in patients with DM. The ADA guidelines are mostly based on studies performed on patients with CVD and without DM. The evidence-based dietary recommendations for patients with DM are to increase the intake of fish and soluble fibers. Although DM has been considered as an equivalent of established CVD, the adoption of the same dietary recommendations for patients without DM and with CVD for all patients with DM is still questionable -- especially considering the peculiarities of CVD in DM. Randomized clinical trials including patients with DM should provide further information regarding the benefits of these dietary interventions for CVD.

Análise crítica das recomendações da Associação Americana de Diabetes para doença cardiovascular no diabetes melito: [revisão] / Critical analysis of the American Diabetes Association dietary recommendations for cardiovascular disease in diabetes mellitus: [review]

A doença cardiovascular (DCV) é a principal causa de mortalidade em pacientes com diabetes melito (DM), sendo essencial a intervenção dietética no manejo dessa complicação. O objetivo deste manuscrito foi revisar as evidências científicas que fundamentam as recomendações dietéticas da American Diabetes Association (ADA) para prevenção e tratamento da DCV nos pacientes com DM. As diretrizes da ADA baseiam-se, em sua maioria, em estudos com pacientes com DCV, porém sem DM. Nos pacientes com DM, um aumento na ingestão de peixe e de fibras solúveis são as recomendações dietéticas com benefício comprovado. Embora o DM possa ser considerado um equivalente de DCV estabelecida, a adoção das recomendações dietéticas de pacientes sem DM e com DCV para todos pacientes com DM é questionável - em especial quando são consideradas as peculiaridades da DCV no DM. Ensaios clínicos aleatorizados em pacientes com DM deverão fundamentar melhor os benefícios das intervenções dietéticas sobre a DCV.

Cardiovascular disease (CVD) is the main cause of mortality among patients with diabetes mellitus (DM), and dietary intervention is an essential measure to prevent and treat this complication. The aim of this manuscript was to review scientific evidence that underlies the dietetic recommendations of the American Diabetes Association (ADA) for prevention and treatment of CVD in patients with DM. The ADA guidelines are mostly based on studies performed on patients with CVD and without DM. The evidence-based dietary recommendations for patients with DM are to increase the intake of fish and soluble fibers. Although DM has been considered as an equivalent of established CVD, the adoption of the same dietary recommendations for patients without DM and with CVD for all patients with DM is still questionable - especially considering the peculiarities of CVD in DM. Randomized clinical trials including patients with DM should provide further information regarding the benefits of these dietary interventions for CVD.

The effect of a low-fat, high-protein or high-carbohydrate ad libitum diet on weight loss maintenance and metabolic risk factors.

BACKGROUND: High-protein (HP) diets are often advocated for weight reduction and weight loss maintenance. OBJECTIVE: The aim was to compare the effect of low-fat, high-carbohydrate (HC) and low-fat, HP ad libitum diets on weight maintenance after weight loss induced by a very low-calorie diet, and on metabolic and cardiovascular risk factors in healthy obese subjects. DESIGN: Forty-eight subjects completed the study that consisted of an energy restriction period of 5-6 weeks followed by a weight maintenance period of 12 weeks. During weight maintenance subjects received maltodextrin (HC group) or protein (HP group) (casein (HPC subgroup) or whey (HPW subgroup)) supplements (2 x 25 g per day), respectively and consumed a low-fat diet. RESULTS: Subjects in the HP diet group showed significantly better weight maintenance after weight loss (2.3 kg difference, P=0.04) and fat mass reduction (2.2 kg difference, P=0.02) than subjects in the HC group. Triglyceride (0.6 mM difference, P=0.01) and glucagon (9.6 pg ml(-1) difference, P=0.02) concentrations increased more in the HC diet group, while glucose (0.3 mM difference, P=0.02) concentration increased more in the HP diet group. Changes in total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, insulin, HOMAir index, HbA1c, leptin and adiponectin concentrations did not differ between the diets. No differences were found between the casein- or whey-supplemented HP groups. CONCLUSIONS: These results show that low-fat, high-casein or whey protein weight maintenance diets are more effective for weight control than low-fat, HC diets and do not adversely affect metabolic and cardiovascular risk factors in weight-reduced moderately obese subjects without metabolic or cardiovascular complications.

Glucose control in the UKPDS: what did we learn?

The UK Prospective Diabetes Study (UKPDS) set out to establish whether improved glucose control could alleviate the macrovascular and microvascular complications of diabetes and to compare the relative merits of diet, oral glucose-lowering agents or insulin in achieving this objective. The study broke many of the rules of trial design, not least by constant addition of further interventions and analyses, but this flexibility would, paradoxically, prove to be one of its greatest strengths. The UKPDS taught us that glucose control must be tackled aggressively in Type 2 diabetes. It taught us that treatment must be escalated in parallel with the evolution of pancreatic B-cell failure. It also taught us that glucose control is not enough: the central objective of therapy is to reduce vascular risk by any means available. This commentary looks back along the winding road that led to these conclusions.

A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease.

AIMS/HYPOTHESIS: Most studies of diet in glucose intolerance and type 2 diabetes have focused on intakes of fat, carbohydrate, fibre, fruits and vegetables. Instead, we aimed to compare diets that were available during human evolution with more recently introduced ones. METHODS: Twenty-nine patients with ischaemic heart disease plus either glucose intolerance or type 2 diabetes were randomised to receive (1) a Palaeolithic ('Old Stone Age') diet (n = 14), based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; or (2) a Consensus (Mediterranean-like) diet (n = 15), based on whole grains, low-fat dairy products, vegetables, fruits, fish, oils and margarines. Primary outcome variables were changes in weight, waist circumference and plasma glucose AUC (AUC Glucose(0-120)) and plasma insulin AUC (AUC Insulin(0-120)) in OGTTs. RESULTS: Over 12 weeks, there was a 26% decrease of AUC Glucose(0-120) (p = 0.0001) in the Palaeolithic group and a 7% decrease (p = 0.08) in the Consensus group. The larger (p = 0.001) improvement in the Palaeolithic group was independent (p = 0.0008) of change in waist circumference (-5.6 cm in the Palaeolithic group, -2.9 cm in the Consensus group; p = 0.03). In the study population as a whole, there was no relationship between change in AUC Glucose(0-120) and changes in weight (r = -0.06, p = 0.9) or waist circumference (r = 0.01, p = 1.0). There was a tendency for a larger decrease of AUC Insulin(0-120) in the Palaeolithic group, but because of the strong association between change in AUC Insulin(0-120) and change in waist circumference (r = 0.64, p = 0.0003), this did not remain after multivariate analysis. CONCLUSIONS/INTERPRETATION: A Palaeolithic diet may improve glucose tolerance independently of decreased waist circumference.

Effect of moderate red wine intake on cardiac prognosis after recent acute myocardial infarction of subjects with Type 2 diabetes mellitus.

BACKGROUND: Oxidative stress and increased inflammation have been reported to be increased in subjects with diabetes and to be involved in the pathogenesis of cardiovascular complications after myocardial infarction (MI). It is well recognized that red wine has antioxidant and anti-inflammatory activities. We examined the effects of moderate red wine intake on echocardiographic parameters of functional cardiac outcome in addition to inflammatory cytokines and nitrotyrosine (oxidative stress marker), in subjects with diabetes after a first uncomplicated MI. METHODS: One hundred and fifteen subjects with diabetes who had sustained a first non-fatal MI were randomized to receive a moderate daily amount of red wine (intervention group) or not (control group). Echocardiographic parameters of ventricular dys-synchrony, circulating levels of nitrotyrosine, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP) were investigated at baseline and 12 months after randomization. RESULTS: After 1 year of diet intervention, concentrations of nitrotyrosine (P < 0.01), CRP (P < 0.01), TNF-alpha (P < 0.01), IL-6 (P < 0.01) and IL-18 (P < 0.01) were increased in the control group compared with the intervention group. In addition, myocardial performance index (P < 0.02) was higher, and transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P < 0.02) and ejection fraction (P < 0.05) were lower in the control group, indicating ventricular dys-synchrony. The concentrations of nitrotyrosine, CRP, TNF-alpha and IL-6 were related to echocardiographic parameters of ventricular dys-synchrony. CONCLUSIONS: In subjects with diabetes, red wine consumption, taken with meals, significantly reduces oxidative stress and pro-inflammatory cytokines as well as improving cardiac function after MI. Moderate red wine intake with meals may have a beneficial effect in the prevention of cardiovascular complications after MI in subjects with diabetes.