Repositioning the Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) on the TRAIL to the Development of Diabetes Mellitus: An Update of Experimental and Clinical Evidence.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF protein superfamily, represents a multifaceted cytokine with unique biological features including both proapoptotic and pro-survival effects in different cell types depending on receptor interactions and local stimuli. Beyond its extensively studied anti-tumor and immunomodulatory properties, a growing body of experimental and clinical evidence over the past two decades suggests a protective role of TRAIL in the development of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. This evidence can be briefly summarized by the following observations: (i) acceleration and exacerbation of T1DM and T2DM by TRAIL blockade or genetic deficiency in animal models, (ii) prevention and amelioration of T1DM and T2DM with recombinant TRAIL treatment or systemic TRAIL gene delivery in animal models, (iii) significantly reduced circulating soluble TRAIL levels in patients with T1DM and T2DM both at disease onset and in more advanced stages of diabetes-related complications such as cardiovascular disease and diabetic nephropathy, (iv) increase of serum TRAIL levels in diabetic patients after initiation of antidiabetic treatment and metabolic improvement. To explore the underlying mechanisms and provide mechanistic links between TRAIL and diabetes, a number of animal and in vitro studies have reported direct effects of TRAIL on several tissues involved in diabetes pathophysiology such as pancreatic islets, skeletal muscle, adipose tissue, liver, kidney, and immune and vascular cells. Residual controversy remains regarding the effects of TRAIL on adipose tissue homeostasis. Although the existing evidence is encouraging and paves the way for investigating TRAIL-related interventions in diabetic patients with cardiometabolic abnormalities, caution is warranted in the extrapolation of animal and in vitro data to the clinical setting, and further research in humans is imperative in order to uncover all aspects of the TRAIL-diabetes relationship and delineate its therapeutic implications in metabolic disease.

Comparison of health-related quality of Life (HRQOL) among patients with pre-diabetes, diabetes and normal glucose tolerance, using the 15D-HRQOL questionnaire in Greece: the DEPLAN study.

BACKGROUND: Diabetes mellitus is usually preceded by a pre-diabetic stage before the clinical presentation of the disease, the influence of which on persons' quality of life is not adequately elucidated. The purpose of this study was to compare the Health-Related Quality of Life (HRQOL) of persons with pre-diabetes with that of diabetes or normal glucose tolerance (NGT), using the validated HRQOL-15D questionnaire. METHODS: The HRQOL-15D scores of 172 people with pre-diabetes (108 with Impaired Fasting Glucose [IFG], 64 with Impaired Glucose Tolerance [IGT], aged 58.3 ± 10.3 years) and 198 with NGT (aged 54.4 ± 10.1 years) from the Greek part of the DEPLAN study (Diabetes in Europe - Prevention using Lifestyle, Physical Activity and Nutritional Intervention), were compared to 100 diabetes patients' scores (aged 60.9 ± 12.5 years, diabetes duration 17.0 ± 10.0 years, HbA1c 7.2 ± 1.2%), derived from the outpatient Diabetes Clinic of a University Hospital. RESULTS: The diabetes patients' HRQOL-15D score (0.8605) was significantly lower than the pre-diabetes' (0.9008) and the controls' (0.9092) (p < 0.001). There were no differences in the total score between the controls and the group with pre-diabetes. However, examination of individual parameters of the score showed that people with IGT had lower scores compared to the control group, as related to the parameters of "mobility" and "psychological distress". No differences were found in any component of the HRQOL-15D score between the control group and the IFG group, nor between the two groups with pre-diabetes (IFG vs. IGT). CONCLUSIONS: Persons with pre-diabetes had a similar HRQOL score with healthy individuals, and a higher score than persons with diabetes. Specific components of the score, however, were lower in the IGT group compared to the controls. These findings help clarify the issue of HRQOL of persons with pre-diabetes and its possible impact on prevention.

A randomized, controlled trial on the effect of non-surgical periodontal therapy in patients with type 2 diabetes. Part I: effect on periodontal status and glycaemic control.

AIM: the purpose of the present study was to assess the effect of non-surgical periodontal therapy on glycaemic control of type 2 diabetes patients with moderate-to-severe periodontitis. MATERIALS AND METHODS: this was a randomized, controlled clinical trial of patients with type 2 diabetes. A total of 60 patients with moderate-to-severe periodontal disease were assigned to either a periodontal treatment arm, consisting of scaling and root planing (intervention group [IG]), or a delayed treatment arm that received periodontal care after 6 months (control group [CG]). Periodontal parameters and glycosylated haemoglobin (A1C) were evaluated at 1, 3 and 6 months. RESULTS: all periodontal parameters improved significantly in the IG. A1C levels decreased statistically significantly more in the IG versus the CG (0.72%versus 0.13%; p<0.01) independently of other confounders. CONCLUSIONS: this study provides evidence that periodontal treatment contributes to improved glycaemic control in type 2 diabetes mellitus patients. Larger controlled trials are needed to confirm if this finding is generalizable to other populations of patients with type 2 diabetes.

Intermittent Energy Restriction, Weight Loss and Cardiometabolic Risk: A Critical Appraisal of Evidence in Humans.

Dietary patterns with intermittent energy restriction (IER) have been proposed as an attractive alternative to continuous energy restriction (CER) for the management of obesity and its associated comorbidities. The most widely studied regimens of IER comprise energy restriction on two days per week (5:2), alternate-day energy restriction by 60-70% (ADF), and timely restriction of energy intake during a specific time window within the day (TRF; time-restricted feeding). Although there is some evidence to suggest that IER can exert beneficial effects on human cardiometabolic health, yet is apparently not superior compared to CER, there are still some critical issues/questions that warrant further investigation: (i) high-quality robust scientific evidence regarding the long-term effects of IER (safety, efficacy, compliance) is limited since the vast majority of intervention studies had a duration of less than 6 months; (ii) whether the positive effects of IER are independent of or actually mediated by weight loss remains elusive; (iii) it remains unknown whether IER protocols are a safe recommendation for the general population; (iv) data concerning the impact of IER on ectopic fat stores, fat-free mass, insulin resistance and metabolic flexibility are inconclusive; (v) the cost-effectiveness of IER dietary regimens has not been adequately addressed; (vi) direct head-to-head studies comparing different IER patterns with variable macronutrient composition in terms of safety and efficacy are scarce; and (vii) evidence is limited with regard to the efficacy of IER in specific populations, including males, the elderly and patients with morbid obesity and diabetes mellitus. Until more solid evidence is available, individualization and critical perspective are definitely warranted to determine which patients might benefit the most from an IER intervention, depending on their personality traits and most importantly comorbid health conditions.

The impact of metabolic syndrome on left ventricular myocardial performance.

BACKGROUND: Metabolic syndrome (MetS) is common and is associated with increased cardiovascular morbidity and mortality. Recent prospective studies suggested that MetS is associated with increased risk of heart failure. In the present cross-sectional study, we examined the association between left ventricular myocardial performance with MetS. MATERIALS AND METHODS: A total of 550 non-diabetic subjects, 275 without MetS and 275 with MetS, matched for gender, age and body mass index and free of clinically apparent macrovascular disease were studied. MetS was diagnosed using the NCEP-ATP III criteria. Left ventricular myocardial performance was assessed using the Tei index. RESULTS: Both men and women with MetS had higher values of the Tei index, indicating worse myocardial performance, in comparison with those without MetS (p < 0.001). Participants with a cluster of more components of the MetS had higher Tei index values than those with fewer components of the MetS. In addition, among normotensive subjects, those with MetS had significantly higher Tei index values than subjects without MetS. Multivariate linear regression analysis, after adjustment for age and body mass index, demonstrated that MetS status and from the individual components of the MetS, high fasting blood glucose levels, higher blood pressure, low high density lipoprotein levels and high waist circumference were associated with worse myocardial performance. CONCLUSION: MetS is associated with subclinical myocardial dysfunction in both men and women. Strategies to reduce the cardiovascular burden and the risk of heart failure associated with MetS should aim at prevention of the MetS and its related conditions.

Important Considerations for the Treatment of Patients with Diabetes Mellitus and Heart Failure from a Diabetologist's Perspective: Lessons Learned from Cardiovascular Outcome Trials.

Heart failure (HF) represents an important cardiovascular complication of type 2 diabetes mellitus (T2DM) associated with substantial morbidity and mortality, and is emphasized in recent cardiovascular outcome trials (CVOTs) as a critical outcome for patients with T2DM. Treatment of T2DM in patients with HF can be challenging, considering that these patients are usually elderly, frail and have extensive comorbidities, most importantly chronic kidney disease. The complexity of medical regimens, the high risk clinical characteristics of patients and the potential of HF therapies to interfere with glucose metabolism, and conversely the emerging potential of some antidiabetic agents to modulate HF outcomes, are only some of the challenges that need to be addressed in the framework of a team-based personalized approach. The presence of established HF or the high risk of developing HF in the future has influenced recent guideline recommendations and can guide therapeutic decision making. Metformin remains first-line treatment for overweight T2DM patients at moderate cardiovascular risk. Although not contraindicated, metformin is no longer considered as first-line therapy for patients with established HF or at risk for HF, since there is robust scientific evidence that treatment with other glucose-lowering agents such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) should be prioritized in this population due to their strong and remarkably consistent beneficial effects on HF outcomes.

The Effect of the Oral Administration of Leucine on Endothelial Function, Glucose and Insulin Concentrations in Healthy Subjects.

OBJECTIVE: The aim of our study was to investigate the potential differential effect of hyperglycaemia and hyperinsulinaemia induced by glucose infusion alone and in combination with leucine consumption on endothelial function in healthy individuals. METHODS: Ten male volunteers were examined in random order twice. In one visit, they consumed 250 ml water (baseline) and 30 min later glucose was infused iv. In the other visit, they consumed 250 ml water with 25 g of leucine and 30 min later the same amount of glucose was infused. Serum glucose and insulin were measured at baseline and every 10 min after glucose infusion for 1 h. Endothelial function was evaluated by measurement of flow mediated vasodilatation (FMD) at baseline, 10 and 60 min after glucose infusion. RESULTS: In both visits, glucose levels increased to the same degree, whereas insulin response was significantly higher after leucine administration. FMD values declined significantly compared to baseline 10 min after glucose infusion in the control visit (6.9±2.7 vs. 3.2±3.5%, respectively, p=0.006), while no significant change was observed when glucose infusion was followed by leucine consumption. CONCLUSIONS: Acute hyperglycaemia impairs endothelial function in healthy male individuals. Leucine administration prevents hyperglycaemia-mediated endothelial dysfunction probably due to enhanced insulin secretion.

Experimental hypogonadism: insulin resistance, biochemical changes and effect of testosterone substitution.

Background We sought to clarify the role of testosterone substitution in terms of insulin resistance and metabolic profile dysregulation in hypogonadism. Methods Twenty-nine male Wistar rats aged 11-12 weeks were divided in three groups: control (C, n = 10), sham operation; orchiectomy (ORX, n = 9); and orchiectomy + testosterone substitution (ORX+T, n = 10). Blood samples were obtained at day 1 (operation), after 10 days (intramuscular T injection 100 µg/100 g b.w.), 25 days (second T injection) and 40 days (sacrifice). Results Hormonal replacement significantly attenuated the negative effect of orchiectomy on insulin resistance as indicated by the successive changes in both insulin levels (1.44 ± 2.94 vs. 4.10 ± 2.47 vs. 1.78 ± 0.68 ng/mL, for D1, D10 and D40, respectively; p = 0.028 and p = 0.022, respectively) and HOMA-IR index (1.36 ± 2.75 vs. 3.68 ± 1.87 vs. 1.74 ± 0.69 ng/mL, for D1, D10 and D40, respectively; p = 0.024 and p = 0.026, respectively) in the ORX+T group. Irisin levels peaked at the 10th postoperative day and were decreased at the end of the experiment (0.27 ± 0.11 vs. 0.85 ± 0.54 vs. 0.02 ± 0.07 ng/mL for D1, D10 and D40, respectively; p = 0.028 in both cases), whereas resistin levels did not differ. Experimental hypogonadism results in an unfavorable lipid profile and insulin resistance, which is not observed when the ORX animals are substituted for T.

Metabolic syndrome is not associated with reduction in aortic distensibility in subjects with type 2 diabetes mellitus.

BACKGROUND: Aortic distensibility (AD) is a marker of the elastic properties of the aorta. Reduction of AD occurs early in subjects with type 2 diabetes mellitus (T2DM) and it is associated with subclinical generalized atherosclerosis. Metabolic syndrome (MetS) is common in subjects with T2DM and predicts cardiovascular morbidity and mortality. This study examined the potential relationship between MetS and AD in a cohort of subjects with T2DM. METHODS AND RESULTS: A total of 210 subjects with T2DM were studied. MetS was diagnosed using the NCEP/ATP-III criteria. AD was assessed non-invasively by ultrasonography. The prevalence of MetS was 64.8%. AD was not significantly different between subjects with and without MetS (1.80 +/- 0.54 vs. 1.84 +/- 0.53 10-6 dyn-1 cm2, p = 0.55). Univariate linear regression analysis showed that AD was associated positively with male sex (p = 0.02) as well as glomerular filtration rate (p < 0.001), and negatively with age (p = 0.04), history of hypertension (p = 0.001), as well as duration of diabetes (p < 0.001). After multivariate adjustment, AD was associated independently and significantly only with age (p = 0.02), duration of diabetes p < 0.001), and history of hypertension (p = 0.004); no significant relationship was found with MetS status, the sum of the components of the MetS or the individual components-besides hypertension-of the MetS. CONCLUSION: In subjects with T2DM, MetS status per se is not associated with reduction of AD. In addition, it was shown that besides ageing, duration of glycemia was a strong predictor of AD. From the components of the MetS only hypertension was associated with reduction of the elastic properties of the aorta.

Diet-induced thermogenesis and substrate oxidation are not different between lean and obese women after two different isocaloric meals, one rich in protein and one rich in fat.

Reduction in diet-induced thermogenesis (DIT) may promote weight gain and maintenance. Data on differences in DIT and macronutrient oxidation between lean and obese subjects are conflicting. In this study, we sought for differences in DIT and macronutrient oxidation between lean and obese women after consumption of 2 different isocaloric meals, one rich in protein and one rich in fat. Fifteen lean and 15 obese women were studied on 2 occasions, 1 week apart. In one visit, they consumed a protein-rich meal; in the other visit, a fat-rich meal. The 2 meals were isocaloric ( approximately 2026 kJ each), of equal volume, and given in random order. Resting energy expenditure and macronutrient oxidation rates were measured and calculated in the fasting state and every 1 hour for 3 hours after meal consumption. Diet-induced thermogenesis was not significantly different between lean and obese subjects after consumption of either the protein-rich (P = .59) or the fat-rich meal (P = .68). Diet-induced thermogenesis was significantly higher (by almost 3-fold) after consumption of the protein-rich meal in comparison with the fat-rich meal in both study groups. In addition, no significant differences in macronutrient oxidation rates were found between lean and obese women after the test meals. The results indicate that DIT is higher after protein intake than after fat intake in both lean and obese participants; however, DIT and macronutrient oxidation rate are not different between lean and obese subjects after consumption of either a protein-rich or a fat-rich meal. Over the long term, a low DIT after regular or frequent fat intake may contribute to the development and maintenance of obesity.

High rates of comorbid conditions in patients with type 2 diabetes and foot ulcers.

UNLABELLED:   Background/Aim. Foot ulceration is one of the most important diabetic complications that results in major medical, social, and economic consequences for patients, their families, and society as a whole. Previous studies have shown increased mortality in patients with diabetes with foot ulcers; however, the reason for the high mortality in this group of patients is not known. The aim of this cross-sectional study was to investigate prevalence rates of comorbid conditions in patients with diabetes and foot ulcers. METHODS: A total of 742 patients with type 2 diabetes (234 with foot ulcers and 508 without ulcers), consecutively attending the outpatient diabetes and diabetic foot clinics of the authors' hospital were reviewed. Clinical examination was performed to classify ulcers as neuropathic or neuroischemic, microvascular and macrovascular complications, as well as laboratory tests that were reviewed from medical records. RESULTS: Patients with diabetes with and without foot ulcers did not differ significantly in terms of age, sex, smoking habits, glycemic control, and prevalence rates of hypertension, dyslipidemia, and cerebrovascular disease. Known duration of diabetes was longer (P < 0.001), while the values of body mass index (P = 0.03) and creatinine clearance (P = 0.003) were lower in the patients with foot ulcers than in those without ulcers. In addition, prevalence rates of coronary artery disease (P = 0.005), lower extremity arterial disease (P < 0.001), retinopathy (P < 0.001), and nephropathy (P = 0.04), were higher in the patients with foot ulcers compared to those without ulcers. Additionally, duration of diabetes was longer and the prevalence rates of microvascular and macrovascular complications as well as hypertension, dyslipidemia, and smoking were much higher in the patients with neuroischemic ulcers in comparison to those with neuropathic ulcers. CONCLUSION: The high mortality rates in patients with diabetes and foot ulcers may be due to the high prevalence rates of comorbid conditions, especially coronary artery disease and nephropathy.

Roux-en-Y Gastric Bypass Is More Effective than Sleeve Gastrectomy in Improving Postprandial Glycaemia and Lipaemia in Non-diabetic Morbidly Obese Patients: a Short-term Follow-up Analysis.

PURPOSE: We aimed to compare the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on postprandial glucose and lipid metabolism in addition to weight loss and fasting metabolic profile, in non-diabetic patients undergoing bariatric surgery. METHODS: Seventy-one patients were consecutively recruited and studied preoperatively, 3 and 6 months after surgery. Of these, 28 underwent RYGB (7 males, age 38 ± 9 years, BMI 46.9 ± 5.0 kg/m2), and 43 SG (9 males, age 38 ± 9 years, BMI 50.2 ± 7.0 kg/m2). A semi-liquid mixed meal was consumed, and blood samples were taken before, and every 30 min after meal ingestion up to 180 min postprandially, for measurement of glucose, insulin, and lipids. The overall postprandial response was assessed as area under the concentration-time curve (AUC). RESULTS: Baseline metabolic parameters were similar between RYGB and SG. Both groups experienced comparable weight loss, and a similar improvement in fasting glucose, insulin, and insulin resistance. Total and LDL cholesterol levels were lower at 6 months after RYGB compared to SG, while there was no difference in HDL cholesterol or triglycerides. Glucose AUC was lower after RYGB compared to SG at both 3 (p = 0.008) and 6 months (p = 0.016), without any difference in postprandial insulin response. Triglyceride AUC was also lower in RYGB vs. SG at 3 and 6 months (p ≤ 0.001). CONCLUSIONS: RYGB is superior to SG in improving postprandial glycaemia and lipaemia and cholesterol profile 6 months postoperatively in non-diabetic, severely obese patients. These findings imply procedure-specific effects, such as the malabsorptive nature of RYGB, and less likely a different incretin postoperative response.

Defining the Optimal Dietary Approach for Safe, Effective and Sustainable Weight Loss in Overweight and Obese Adults.

Various dietary approaches with different caloric content and macronutrient composition have been recommended to treat obesity in adults. Although their safety and efficacy profile has been assessed in numerous randomized clinical trials, reviews and meta-analyses, the characteristics of the optimal dietary weight loss strategy remain controversial. This mini-review will provide general principles and practical recommendations for the dietary management of obesity and will further explore the components of the optimal dietary intervention. To this end, various dietary plans are critically discussed, including low-fat diets, low-carbohydrate diets, high-protein diets, very low-calorie diets with meal replacements, Mediterranean diet, and diets with intermittent energy restriction. As a general principle, the optimal diet to treat obesity should be safe, efficacious, healthy and nutritionally adequate, culturally acceptable and economically affordable, and should ensure long-term compliance and maintenance of weight loss. Setting realistic goals for weight loss and pursuing a balanced dietary plan tailored to individual needs, preferences, and medical conditions, are the key principles to facilitate weight loss in obese patients and most importantly reduce their overall cardiometabolic risk and other obesity-related comorbidities.

Differentiation in the short- and long-term effects of smoking on plasma total ghrelin concentrations between male nonsmokers and habitual smokers.

To explore the association between the anorexigenic effects of nicotine and the orexigenic properties of ghrelin, plasma total ghrelin levels were measured in nonsmokers and habitual smokers before and after short-term exposure to cigarette smoke. Thirty-one male smokers and 23 nonsmoking volunteers were matched for age and body mass index. After an overnight fast and abstinence from smoking, they all smoked 2 cigarettes consecutively (same brand, rate of inhalation, and duration of smoking). Total ghrelin concentrations were measured by radioimmunoassay before smoking (baseline), immediately afterward, and 30, 60, and 90 minutes after the second cigarette. Baseline ghrelin levels were not different between smokers and nonsmokers. Smoking did not have an immediate influence on ghrelin concentrations in smokers (analysis of variance for repeated measurements, P=0.74), whereas there was a progressive decline in nonsmokers, reaching statistical significance at 30 minutes (P=.04) and a nadir at 60 minutes (P=.04) after smoking. Moreover, the area under the curve for the changes of ghrelin over time after smoking was lower in nonsmokers than in smokers (-287.2+/-167.1 vs 29.2+/-125.3 ng.min/L, P=.03). In conclusion, fasting plasma total ghrelin concentrations are not different between male smokers and nonsmokers. Smoking does not provoke any short-term change in ghrelin levels in smokers, but induces a decline in nonsmokers. If the anorectic effect of smoking is ghrelin induced, this effect may be present only in people not habituated to smoke exposure. In habitual smokers, ghrelin suppression by short-term smoking could be blunted as a result of desensitization due to prolonged nicotine exposure.

Components of the metabolic syndrome, but not the metabolic syndrome per se, are associated with aortic distensibility.

BACKGROUND AND AIM: Reduction in aortic distensibility occurs early in the atherosclerosis process and carries a poor prognosis. Metabolic syndrome is common and it is associated with increased cardiovascular mortality. The aim of this cross-sectional study was to investigate the association between metabolic syndrome and aortic distensibility. METHODS AND RESULTS: A total of 135 subjects without diabetes were studied. Metabolic syndrome was diagnosed using the NCEP-ATP-III criteria. Aortic distensibility was assessed non-invasively by ultrasonography. Multivariate analysis, after controlling for the components of the metabolic syndrome, and, additionally, for body mass index, pulse pressure, presence of coronary artery disease, use of statins and use of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, demonstrated an independent association between aortic distensibility and age (p<0.001), systolic blood pressure, (p=0.02), diastolic blood pressure (p=0.005), and history of hypertension (p<0.001), but not metabolic syndrome status. Moreover, there was a suggestive association with albumin-to-creatinine ratio (p=0.06). CONCLUSIONS: Metabolic syndrome per se is not associated with reduction in aortic distensibility. From the components of the metabolic syndrome, only blood pressure is a strong predictor of aortic distensibility. In addition, ageing and higher values of albumin-to-creatinine ratio are also associated with low aortic distensibility.

A review of nateglinide in the management of patients with type 2 diabetes.

Impaired insulin secretion occurs early in the pathogenesis of type 2 diabetes mellitus (T2DM) and is chronic and progressive, resulting initially in impaired glucose tolerance (IGT) and eventually in T2DM. As most patients with T2DM have both insulin resistance and insulin deficiency, therapy for T2DM should aim to control not only fasting, but also postprandial plasma glucose levels. While oral glucose-lowering treatment with metformin and thiazolidinediones corrects fasting plasma glucose, these agents do not address the problem of mealtime glucose spikes that have been shown to trigger atherogenic processes. Nateglinide is a derivative of the amino acid D-phenylalanine, which acts directly on the pancreatic beta-cells to stimulate insulin secretion. Nateglinide monotherapy controls significantly mealtime hyperglycemia and results in improved overall glycemic control in patients with T2DM by reducing glycosylated hemoglobin (HbA1c) levels. The combination of nateglinide with insulin-sensitising agents, such as metformin and thiazolidinediones, targets both insulin deficiency and insulin resistance and results in reductions in HbA1c that could not be achieved by monotherapy with other antidiabetic agents. In prediabetic subjects with IGT, nateglinide restores early insulin secretion and reduces postprandial hyperglycemia. Nateglinide has an excellent safety and tolerability profile and provides a lifetime flexibility that other antidiabetic agents could not accomplish. The aim of this review is to identify nateglinide as an effective "gate-keeper" in T2DM, since it restores early-phase insulin secretion and prevents mealtime glucose spikes throughout the day and to evaluate the results of ongoing research into its potential role in delaying the progression to overt diabetes and reducing its complications and mortality.

Association of plasma fetuin-a levels with peripheral arterial disease and lower extremity arterial calcification in subjects with type 2 diabetes mellitus.

AIMS: Fetuin-A is a hepatic glycoprotein that is involved in insulin resistance and atherosclerosis. Herein we examined the association of plasma fetuin-A levels with peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: A total of 71 patients with T2DM and 57 non-diabetic individuals were recruited. Diagnosis of PAD was based on the absence of triphasic waveform at pedal arteries, while ankle-brachial index (ABI) was calculated. Radiographs of both feet and ankles were taken for the assessment of lower extremity arterial calcification (LEAC). Plasma fetuin-A levels were measured using ELISA. RESULTS: Patients with T2DM had higher fetuin-A levels than non-diabetic participants. Participants with diabetes and PAD had lower fetuin-A levels than non-PAD diabetic patients. In subjects with T2DM fetuin-A levels were associated with ABI. Multivariate analysis demonstrated that in patients with T2DM the odds of PAD increased with long diabetes duration, smoking, presence of arterial hypertension and dyslipidemia, as well as with lower fetuin-A levels. A trend towards higher fetuin-A levels in subjects with less severe LEAC was found. CONCLUSION: Plasma fetuin-A levels are lower in patients with T2DM and PAD and are associated with PAD, irrespective of traditional cardiovascular risk factors. Moreover, fetuin-A may be involved in arterial calcification.

Metabolic effects of Crocus sativus and protective action against non-alcoholic fatty liver disease in diabetic rats.

Non-alcoholic fatty liver disease (NAFLD) is the result of the accumulation of adipose tissue deposits in the liver and it is associated with type 2 diabetes. Crocus sativus (saffron) is known for its antioxidant and its potential hypoglycemic effects. We investigated the role of saffron on NAFLD in diabetic rats. Thirty adult male rats were allocated into three groups; control (n=10), which received normal diet; streptozotocin (STZ) group (n=10), which received normal chow diet, 10% fructose in their drinking water and STZ (40 mg/kg body weight; STZ-saffron group (n=10), which followed the same dietary and pharmacological pattern as STZ group and were additionally supplemented with saffron (100 mg/kg/day). Metabolic profile was measured and histopathological examination of the liver was evaluated. STZ group exhibited the highest glucose levels at the end of the experiment (P<0.05), while there was no difference between control and STZ-saffron group (584 vs. 213 mg/dl vs. 209 mg/dl, respectively). STZ group revealed higher percentage of steatosis (5-33%) when compared to the other two groups (P<0.005). Saffron exhibits both hypoglycemic and hepatoprotective actions. Yet, further studies enlightening the exact mechanisms of saffron's mode of actions are required.

QT dispersion: comparison between participants with Type 1 and 2 diabetes and association with microalbuminuria in diabetes.

BACKGROUND AND AIMS: The interlead variation of QT duration in surface electrocardiogram [ECG; QT dispersion (QTd)] has been shown to predict mortality in both diabetic and general population. Diabetic cardiac autonomic neuropathy (CAN) is a common complication of diabetes, and it is also associated with worse prognosis among the diabetic population. In this study, we investigated the association between QTd duration and CAN, as well as other complications of diabetes in participants with Types 1 and 2 diabetes. METHODS: A total of 184 patients with either Type 1 (n=63) or 2 (n=121) diabetes, as well as 100 control participants, matched for age and sex with the diabetic individuals, were studied. QT and RR intervals were measured on 12 leads of resting ECG tracing. QTd was calculated semiautomatically using a computer program as the difference between the maximum and the minimum QT in any of the 12 leads. CAN was diagnosed when two out of the four classical tests were abnormal. RESULTS: QTd was not significantly different between controls and patients with either Type 1 or 2 diabetes. Age-adjusted QTd intervals were not significantly different between patients with Types 1 and 2 diabetes (P=.86). For both types of diabetes, no significant differences were found in QTd between patients with and without CAN. Multivariable linear regression analysis, after adjustment for a number of confounding factors, demonstrated a positive association between QTd and duration of diabetes (P=.02) in the group of the patients with Type 1 diabetes. In those with Type 2 diabetes, QTd was associated with age (P=.006) and presence of microalbuminuria (P=.001). In addition, no significant association was found with retinopathy or blood pressure levels. CONCLUSIONS: Age-adjusted QTd interval was not different between patients with Types 1 and 2 diabetes. CAN is not associated with QTd interval in both types of diabetes. Furthermore, microalbuminuria was found to be the strongest predictor of QTd in patients with Type 2 diabetes. Because long QTd interval predicts cardiac mortality in participants with diabetes, it is suggested that it may be a useful adjuvant index in the evaluation of cardiovascular risk in participants with Type 2 diabetes and microalbuminuria.

Critical review of the international guidelines: what is agreed upon--what is not?

The nutrition recommendations of 6 major scientific organizations (the American Diabetes Association, the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, the Canadian Diabetes Association, the Joslin Diabetes Center and Joslin Clinic, the American Association of Clinical Endocrinologists and Diabetes UK) are reviewed. They all agree that weight loss (with reduction in energy intake and increase in physical activity) is an important therapeutic strategy in all overweight/obese individuals who have or are at risk of type-2 diabetes. Very low carbohydrate diets are not considered appropriate. The recommended proportion varies slightly (from 40 to 65%). The concept of the glycemic index is stressed as important in nearly all guidelines. Fiber intake is advised, up to 50 g/day, if tolerated. Protein intake (for normal kidney function) is advised to range from 10 to 20% of total energy. A low fat diet (<30-35%) is recommended by all. Saturated fat and trans-fatty acids should be restricted to <10% and dietary cholesterol to <300 mg/day. Monounsaturated fatty acids are generally considered beneficial and should replace saturated fat or carbohydrates in low-fat diets. Polyunsaturated fatty acids (PUFAs) should comprise about 10%, with the n-3 PUFAs being more beneficial, especially for high triglyceride levels. Alcohol intake has cardioprotective effects when used in moderation. Routine supplementation of the diet with antioxidants and vitamins is not necessary.