Plasma levels of soluble urokinase plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein after Roux-en-Y gastric bypass or sleeve gastrectomy: a 1-year prospective observational study.

PURPOSE: Low-grade inflammation in obesity contributes to the development of cardiovascular disease, diabetes mellitus and cancer, and is associated with increased mortality. The purpose of this 1-year prospective observational study was to examine the weight loss effect of bariatric surgery on plasma concentrations of two inflammatory markers, namely high-sensitivity C-reactive protein (hsCRP) and soluble urokinase-type plasminogen activator receptor (suPAR), in patients with obesity. METHODS: Sixteen subjects without obesity and 32 patients with obesity class III, who had already settled upon Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were included in the study. Subjects without obesity were examined once, at baseline; patients with obesity were examined preoperatively (baseline) and 3, 6 and 12 months postoperatively. RESULTS: Plasma suPAR and hsCRP concentrations at baseline were higher in patients with obesity than in lean participants (2.68 ± 0.86 vs 1.86 ± 0.34 ng/mL, p < 0.001 and 9.83 ± 9.55 vs 1.36 ± 1.95 mg/dL, p < 0.001). Levels of suPAR following bariatric surgery increased significantly 3 months after either RYGB or SG (3.58 ± 1.58 vs 3.26 ± 0.7 ng/mL, respectively) and declined at 6 (3.19 ± 1.75 vs 2.8 ± 0.84 ng/mL, respectively) and 12 months (2.6 ± 1.5 vs 2.22 ± 0.49 ng/mL, respectively; p < 0.05 for the effect of time on suPAR levels during the study), whereas those of hsCRP declined consistently after bariatric surgery (3 months: 5.44 ± 3.99 vs 9.47 ± 11.98 mg/dL, respectively; 6 months; 5.39 ± 5.6 vs 10.25 ± 17.22 mg/dL, respectively; and 12 months: 2.23 ± 2.5 vs 3.07 ± 3.63 mg/dL, respectively; p < 0.001 for the effect of time on hsCRP levels during the study). 1-year change in BMI was negatively associated with suPAR levels at 12 months. CONCLUSION: Our findings support an association between obesity and low-grade inflammation. Weight loss following bariatric surgery is associated with a consistent decline in plasma hsCRP, while plasma suPAR levels increase at 3 months and decline by 12 months.

Clinical benefits of switching to insulin degludec irrespective of previous basal insulin therapy in people with Type 1 or Type 2 diabetes: evidence from a European, multicentre, retrospective, non-interventional study (EU-TREAT).

AIMS: To investigate whether the benefits of switching to insulin degludec observed in the European retrospective chart review study EU-TREAT were dependent on the previous basal insulin used. METHODS: People with Type 1 or Type 2 diabetes were switched to insulin degludec from other basal insulins ≥6 months before data collection. Participants were stratified into three groups based on their previous basal insulin: insulin glargine 100 units/ml (Type 1: n=888; Type 2: n=259); insulin detemir (Type 1: n=726; Type 2: n=415); and neutral protamine Hagedorn (Type 1: n=53; Type 2: n=95). Their glycaemic control and hypoglycaemia incidence at 6 and 12 months post-switch vs pre-switch was then evaluated. RESULTS: Significant HbA1c reductions were achieved in all previous basal insulin groups for participants with Type 1 diabetes [insulin glargine 100 units/ml: -2.08 mmol/mol (-0.19%); insulin detemir: -2.40 mmol/mol (-0.22%)] and those with Type 2 diabetes [insulin glargine 100 units/ml: -5.90 mmol/mol (-0.54%); insulin detemir: -6.01 mmol/mol (-0.55%); neutral protamine Hagedorn: -2.73 mmol/mol (-0.25%)] at 6 months, except for the relatively small neutral protamine Hagedorn group in those with Type 1 diabetes [-1.75 mmol/mol (-0.16%)], where statistical significance was not reached. At 6 months in the Type 1 diabetes group, switching to insulin degludec from insulin glargine 100 units/ml resulted in significantly lower hypoglycaemia rates across all hypoglycaemia categories; for the insulin detemir group, this significance was also observed for severe and nocturnal non-severe hypoglycaemia, while the low number of people in the neutral protamine Hagedorn group resulted in nonsignificant reductions in hypoglycaemia rates. At 6 months in the people with Type 2 diabetes, switching to insulin degludec resulted in significantly lower rates of hypoglycaemia across all categories for all groups. Similar outcomes were observed at 12 months. CONCLUSIONS: Switching to insulin degludec from other basal insulins can improve glycaemic control and/or reduce hypoglycaemia risk in people with diabetes (although there was a nonsignificant reduction in HbA1c and hypoglycaemia rates for the neutral protamine Hagedorn group in Type 1 diabetes) under routine care.

A simple new non-invasive sweat indicator test for the diagnosis of diabetic neuropathy.

A simple non-invasive indicator test (Neuropad(®)) has been developed for the assessment of sweating and, hence, cholinergic innervation in the diabetic foot. The present review summarizes current knowledge on this diagnostic test. The diagnostic ability of this test is based on a colour change from blue to pink at 10 min, with excellent reproducibility, which lends itself to patient self-examination. It has a high sensitivity (65.1-100%) and negative predictive value (63-100%), with moderate specificity (32-78.5%) and positive predictive value (23.3-93.2%) for the diagnosis of diabetic peripheral neuropathy. It also has moderate to high sensitivity (59.1-89%) and negative predictive value (64.7-91%), but low to moderate specificity (27-78%) and positive predictive value (24-48.6%) for the diagnosis of diabetic cardiac autonomic neuropathy. There are some data to suggest that Neuropad can detect early diabetic neuropathy, but this needs further evaluation. It remains to be established whether this test can predict foot ulceration and amputation, thereby contributing to the identification of high-risk patients.

Peripheral arterial disease in diabetes--a review.

Diabetic patients are at high risk for peripheral arterial disease (PAD) characterized by symptoms of intermittent claudication or critical limb ischaemia. Given the inconsistencies of clinical findings in the diagnosis of PAD in the diabetic patient, measurement of ankle-brachial pressure index (ABI) has emerged as the relatively simple, non-invasive and inexpensive diagnostic tool of choice. An ABI < 0.9 is not only diagnostic of PAD even in the asymptomatic patient, but is also an independent marker of increased morbidity and mortality from cardiovascular diseases. With better understanding of the process of atherosclerosis, avenues for treatment have increased. Modification of lifestyle and effective management of the established risk factors such as smoking, dyslipidaemia, hyperglycaemia and hypertension retard the progression of the disease and reduce cardiovascular events in these patients. Newer risk factors such as insulin resistance, hyperfibrinogenaemia, hyperhomocysteinaemia and low-grade inflammation have been identified, but the advantages of modifying them in patients with PAD are yet to be proven. Therapeutic angiogenesis, on the other hand, represents a promising therapeutic adjunct in the management of PAD in these patients. Outcomes after revascularization procedures, such as percutaneous transluminal angioplasty and surgical bypasses in diabetic patients, are poorer, with increased perioperative morbidity and mortality compared with that in non-diabetic patients. Amputation rates are higher due to the distal nature of the disease. Efforts towards increasing awareness and intensive treatment of the risk factors will help to reduce morbidity and mortality in diabetic patients with PAD.

The association between the spatial QRS-T angle with cardiac autonomic neuropathy in subjects with Type 2 diabetes mellitus.

AIMS: To examine differences in the spatial QRS-T angle in patients with Type 2 diabetes mellitus with and without cardiac autonomic neuropathy. METHODS: Two hundred and thirty-two patients with diabetes mellitus (105 with cardiac autonomic neuropathy and 127 without cardiac autonomic neuropathy) and 232 control subjects, matched by gender and age, were studied. Diagnosis of cardiac autonomic neuropathy was based on the classic autonomic function tests. All subjects underwent a digital electrocardiographic recording. Electrocardiographic parameters were measured using the Modular Electrocardiographic Analysis (MEANS) program. Left ventricular mass index (LVMi) and global myocardial performance index (Tei index) of the left ventricle were assessed by ultrasonography. RESULTS: The spatial QRS-T angle was higher in the patients with diabetes in comparison with the control subjects (24.5 ± 10.7 vs. 9.7 ± 4.5°, P < 0.001) and in the patients with diabetes and cardiac autonomic neuropathy than in those without cardiac autonomic neuropathy (30.1 ± 11.3 vs. 19.5 ± 7.1, P < 0.001). No differences were found in the QT interval between the studied groups. Multivariate linear regression analysis in subjects with diabetes after controlling for age, gender, BMI, blood pressure, diabetes duration, HbA(1c) , lipids, microalbuminuria and insulin resistance, demonstrated significant and independent associations between the spatial QRS-T angle with presence and severity of cardiac autonomic neuropathy, all parameters of heart rate variability, LVMi and Tei index. CONCLUSIONS: The spatial QRS-T angle is increased in patients with Type 2 diabetes who have cardiac autonomic neuropathy, suggesting increased ventricular arrhythmogenicity, and is associated with the structural and functional properties of the myocardium. Further research is warranted to evaluate its role in cardiovascular risk stratification of patients with diabetes.

The effects of medications used for the management of dyslipidemia on postprandial lipemia.

Postprandial lipemia has emerged as an independent risk factor for coronary artery disease. In this systematic review we examined the effect of the medications used for the management of dyslipidemia on postprandial lipemia. Statins, beyond their effects on fasting lipid levels, reduce also postprandial lipemia mainly by inhibiting the production of apoB containing lipoproteins from the liver and thus increasing the clearance of triglyceride-rich lipoproteins of either liver or intestinal origin. Fibrates decrease fasting triglyceride and increase high density lipoprotein cholesterol levels. Besides, fibrates are particularly potent drugs in the reduction of postprandial lipemia; they decrease the production or triglyceride-rich lipoproteins and increase their clearance by enhancing the activity of lipoprotein lipase.

Sudomotor dysfunction is associated with foot ulceration in diabetes.

AIM: To examine the relationship between sudomotor dysfunction and foot ulceration (FU) in patients with diabetes. METHODS: Ninety patients with either Type 1 or Type 2 diabetes [30 without peripheral sensorimotor neuropathy (PN), 30 with PN but without FU and 30 with FU] were recruited in this cross-sectional study. Assessment of PN was based on neuropathy symptom score (NSS), neuropathy disability score (NDS) and vibration perception threshold (VPT). Sudomotor dysfunction was assessed using the sympathetic skin response (SSR). Cardiac autonomic nervous system activity was assessed by the battery of the classical autonomic function tests. RESULTS: Patients with foot ulcers had longer duration of diabetes, higher values of VPT and NDS and lower values of the autonomic functions tests in comparison with the other study groups. Sudomotor dysfunction and cardiac autonomic neuropathy were significantly more common in the FU group. Multivariate logistic regression analysis after adjustment for gender, body mass index, duration of diabetes and glycated haemoglobin (HbA(1c)) demonstrated that the odds ratio (95% confidence intervals) of FU increased with measures of neuropathy such as NDS >or= 6 (10.2, 6.2-17.3) and VPT >or= 25 volts (19.8, 9.9-47.5), but was also significantly increased with absent SSR (15.3, 5.3-38.4). CONCLUSIONS: Sudomotor dysfunction is associated with increased risk of FU and should be included in the screening tests for identification of diabetic patients at risk of ulceration.

Impaired aortic elastic properties in patients with systemic sarcoidosis.

BACKGROUND: Systemic sarcoidosis (Sar) is a granulomatous disorder involving multiple organs. Widespread vascular involvement and microangiopathy are common in patients with Sar. In addition, subclinical cardiac involvement is increasingly recognized in patients with Sar. However, data on the effect of Sar on the elastic properties of the arteries and myocardial performance are limited. In this study we looked for differences in aortic distensibility (AoD) which is an index of aortic elasticity, and myocardial performance of the ventricles, between patients with Sar and healthy subjects. In addition, we examined potential associations between AoD and clinical, respiratory and echocardiographic findings in patients with Sar. MATERIALS AND METHODS: A total of 83 consecutive patients (26 male/57 female, mean age 51.1 +/- 13.3 years) with Sar, without cardiac symptoms, were included. All patients underwent echocardiographic and respiratory evaluation including lung function tests. Additionally, 83 age- and sex-matched healthy subjects served as controls. AoD was determined non-invasively by ultrasonography. RESULTS: AoD was lower in the Sar compared to the control group (2.29 +/- 0.26 vs. 2.45 +/- 0.20 .10(-) (6) cm2 x dyn(-1), P < 0.01), while left ventricular mass (LVM) was higher in the Sar group (221.3 +/- 50.2 vs. 195.6 +/- 31.3 g, P = 0.007). Furthermore, myocardial performance of both ventricles was impaired in the Sar group. Multivariate linear regression analysis in the total sample population demonstrated a significant and independent inverse relationship between AoD and the presence of Sar (P < 0.001). The same analysis in the Sar patients showed that AoD was associated significantly and independently with the stage of Sar, age, systolic blood pressure, LVM and myocardial performance of both ventricles. No significant relationship was found between AoD and disease duration, pulmonary artery pressure or lung function tests. CONCLUSIONS: Presence and severity of Sar are associated with reduced aortic distensibility, irrespective of the disease duration, pulmonary artery pressure and lung function. In addition, patients with Sar have increased LVM and impaired myocardial performance.

Schizophrenia and type 2 diabetes mellitus.

Schizophrenia is associated with increased risk for type 2 diabetes mellitus, resulting in elevated cardiovascular risk and limited life expectancy, translated into a weighted average of 14.5 years of potential life lost and an overall weighted average life expectancy of 64.7 years. The exact prevalence of type 2 diabetes among people with schizophrenia varies across studies and ranges 2-5fold higher than in the general population, whereas the aetiology is complex and multifactorial. Besides common diabetogenic factors, applied similarly in the general population, such as obesity, hyperlipidemia, smoking, hypertension, poor diet and limited physical activity, the co-occurrence of schizophrenia and diabetes is also attributed to unique conditions. Specifically, excessive sedentary lifestyle, social determinants, adverse effects of antipsychotic drugs and limited access to medical care are considered aggravating factors for diabetes onset and low quality of diabetes management. Schizophrenia itself is further proposed as causal factor for diabetes, given the observed higher prevalence of diabetes in young patients, newly diagnosed with schizophrenia and unexposed to antipsychotics. Furthermore, studies support genetic predisposition to diabetes among people with schizophrenia, suggesting shared genetic risk and disclosing a number of overlapped risk loci. Therefore, special attention should be paid in preventing diabetes in people with schizophrenia, through intervention in all possible modifiable risk factors. Implementation of careful antipsychotic prescription, provision of adequate motivation for balanced diet and physical activity and facilitating access to primary health care, could serve in reducing diabetes prevalence. On the other hand, increasing calls are made for early diagnosis of diabetes, application of the appropriate anti-diabetic therapy and strict inspection of therapy adherence, to limit the excess mortality due to cardiovascular events in people with schizophrenia. Moreover, population health programs could help counseling and preventing diabetes risk, additionally to early screening and diagnosis set, aiming to reduce disparities in populations. Finally, mental health-care providers might greatly promote offered health services to patients with schizophrenia, through a holistic individualized approach, considering additionally the physical health of the patients and working closely, preventively and therapeutically, in collaboration with the physicians and diabetologists.

Sympathetic system activity in obesity and metabolic syndrome.

Obesity is a very common disease worldwide, resulting from a disturbance in the energy balance. The metabolic syndrome is also a cluster of abnormalities with basic characteristics being insulin resistance and visceral obesity. The major concerns of obesity and metabolic syndrome are the comorbidities, such as type 2 diabetes, cardiovascular disease, stroke, and certain types of cancers. Sympathetic nervous system (SNS) activity is associated with both energy balance and metabolic syndrome. Sympathomimetic medications decrease food intake, increase resting metabolic rate (RMR), and thermogenic responses, whereas blockage of the SNS exerts opposite effects. The contribution of the SNS to the daily energy expenditure, however, is small ( approximately 5%) in normal subjects consuming a weight maintenance diet. Fasting suppresses, whereas meal ingestion induces SNS activity. Most of the data agree that obesity is characterized by SNS predominance in the basal state and reduced SNS responsiveness after various sympathetic stimuli. Weight loss reduces SNS overactivity in obesity. Metabolic syndrome is characterized by enhanced SNS activity. Most of the indices used for the assessment of its activity are better associated with visceral fat than with total fat mass. Visceral fat is prone to lipolysis: this effect is mediated by catecholamine action on the sensitive beta(3)-adrenoceptors found in the intraabdominal fat. In addition, central fat distribution is associated with disturbances in the hypothalamo-pituitary-adrenal axis, suggesting that a disturbed axis may be implicated in the development of the metabolic syndrome. Furthermore, SNS activity induces a proinflammatory state by IL-6 production, which in turn results in an acute phase response. The increased levels of inflammatory markers seen in the metabolic syndrome may be elicited, at least in part, by SNS overactivity. Intervention studies showed that the disturbances of the autonomic nervous system seen in the metabolic syndrome are reversible.

Prevalence of methicillin-resistant Staphylococcus aureus in infected and uninfected diabetic foot ulcers.

This study investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in infected and uninfected diabetic foot ulcers of 84 patients with the two types of diabetes. S. aureus was the most common pathogen among the Gram-positive bacteria isolated from ulcers, and almost 50% of S. aureus isolates were MRSA. The prevalence of MRSA was significantly higher in patients with infected foot ulcers. MRSA infection or colonisation was not associated with factors (previous hospitalisation, use of antibiotics, etc.) known to predispose to MRSA colonisation or infection. The high prevalence of MRSA in patients with foot ulcers may reflect the increased prevalence of MRSA in the community.

Relationship between antidiabetic treatment with QT dispersion during acute coronary syndromes in type 2 diabetes: comparison between patients receiving sulfonylureas and insulin.

Patients with acute coronary syndromes (ACS) show prolongation of QT interval duration and its dispersion (QTd). Prolongation of QTd has been associated with inhomogeneity of ventricular recovery times and high arrhythmyogenic potential. Previous studies have shown that preservation of the ischaemic preconditioning is associated with shorter QTd. Sulfonylureas may inhibit cardiac ischaemic preconditioning. The effect, however, of the previous treatment with sulfonylureas on QTd in patients with ACS has not been studied so far. This cross-sectional study examined the effect of the previous antidiabetic treatment on QTd in patients with type 2 diabetes during ACS. A total of 150 patients with ACS (myocardial infarction: n = 120; unstable angina: n = 30) admitted to the coronary care unit of our hospital were studied. Three groups of patients were examined: patients without diabetes (n = 60); patients with type 2 diabetes treated with sulfonylureas alone or in combination with metformin (n = 50); and patients treated with insulin alone or in combination with metformin (n = 40). Standard 12-lead ECG recordings at admission to the coronary care unit were obtained. QT interval duration and QTd were measured using ECG analysis software. At admission, QTd was not different between diabetic and non-diabetic patients (72.1 +/- 21.7 vs. 78.4 +/- 21.3 msec, p = 0.13, respectively). Similarly, the values of the above interval were also not different between patients with type 2 diabetes treated with sulfonylureas and insulin (73.8 +/- 23.9 vs. 70.1 +/- 18.5 msec, p = 0.55, respectively). It is concluded that the previous treatment with either sulfonylureas or insulin does not affect QTd in patients with type 2 diabetes and ACS.

Differential effects of high-fat and high-carbohydrate isoenergetic meals on cardiac autonomic nervous system activity in lean and obese women.

Food ingestion can influence autonomic nervous system activity. This study compares the effects of 2 different isoenergetic meals on sympathetic nervous system (SNS) activity, assessed by heart rate variability (HRV) and plasma norepinephrine (NE) levels, in lean and obese women. Fifteen lean and 15 obese healthy women were examined on 2 occasions: after a carbohydrate (CHO)-rich and after a fat-rich test meal. Measurements of blood pressure, heart rate, resting energy expenditure, plasma glucose, lipids, insulin, leptin, and NE, as well as spectral analysis of the HRV, were performed at baseline and every 1 hour for 3 hours after meals. At baseline, obese women had higher SNS activity than lean controls (higher values of low-to-high frequency ratio [LF/HF], 1.52 +/- 0.31 v 0.78 +/- 0.13, P=.04; and plasma NE levels, 405.6 +/- 197.9 v 240.5 +/- 95.8 pg/mL, P<.0001). After the CHO-rich meal a greater increase in LF/HF and in plasma NE levels was observed in lean, compared to obese women (1.21 +/- 0.6 v 0.32 +/- 0.06, P=.04; and 102.9 +/- 35.4 v 38.7 +/- 12.3 pg/mL, P=.01, respectively), while no differences were observed after the fat-rich meal. Meal-induced thermogenesis was higher after the CHO-rich as compared to the fat-rich meal and was comparable between lean and obese women. Changes in HRV were not associated with the thermogenic response to the test meals. In conclusion, consumption of a CHO-rich meal causes greater cardiac SNS activation in lean than in obese women, while fat ingestion does not result in any appreciable change in either group. SNS activation does not appear to influence the thermic effect of the food in either lean or obese women.

Natural history and prognostic factors of diabetic nephropathy in type 2 diabetes.

BACKGROUND: The causes and mechanisms of increased mortality of patients with diabetic nephropathy are unclear, and its natural history is poorly understood. AIM: To evaluate risk factors for mortality in type 2 diabetic patients with nephropathy. DESIGN: Retrospective study of clinical and biochemical parameters in diabetic nephropathic patients and controls sampled from a secondary care register. METHODS: We studied 170 type 2 diabetic patients (from 1987 to 1995) with nephropathy (proteinuria >0.5 g/24 h) and 170 non-nephropathic patients. Follow-up was until death or December 1997. Details of demographics, clinical and treatment history were obtained from medical records. RESULTS: Mean follow-up was 5.3 years. Of the patients with nephropathy at baseline, 63 (37%) died compared with 14 (8%) non-nephropathic patients (chi(2)=53.8, p<0.0001). Age- and sex-adjusted all-cause mortality rates were 8.1 (6.4, 9.8) and 1.4 (0.5, 2.2) deaths per 100 person-years, respectively (rate ratio 5.8). Forty-four patients (57%) died from cardiovascular causes (rate ratio 5.4). Mortality was directly proportional to degree of proteinuria: 0.5-2 g/24 h, 4.6 (2.9-7.1); >2 g/24 h, 9.9 (7.3-13.5) per 100 patient-years. A 36% (5-78%) excess risk of mortality was observed for each log unit increase in proteinuria. Multivariate Cox regression analyses confirmed a five-fold excess risk for all-cause and cardiovascular mortality in patients with nephropathy compared with those without. This was independent of other risk factors including baseline age [5% (1-8%)/year], creatinine [2.5 (1.12-5.6)/10 micromol/l] and glycaemic control (HbA(1c)) [15% (1-31%) per 1% rise]. CONCLUSIONS: Proteinuria is a potentially preventable and reversible risk factor associated with high mortality in type 2 diabetic patients. Prevention of the development of overt nephropathy and improvement in diabetes control may reduce mortality in these patients.

Impact of body mass on autonomic function in persons with type 2 diabetes.

The aim of this study was to investigate the influence of body mass on autonomic nerve function in persons with type 2 diabetes. Towards this aim we studied two groups of diabetic persons. Group 1: n = 30 lean (mean age 57.2+/-12.5 years, body mass index (BMI) 22.5+/-1.8 kg/m2]. Group 2: n = 35 overweight and obese (age 52.3+/-10.3 years, BMI 28.8 + 3.2 kg/m2). Autonomic neuropathy (DAN) was assessed using the battery of the five classical tests. DAN was diagnosed when at least two of the five tests were abnormal. Abnormalities of the heart rate based tests were considered as indication of parasympathetic and of blood pressure changes as indication of sympathetic dysfunction. The prevalence rates of DAN were not different between group 2 and group 1 (54.2 and 53.3%, respectively, P = 0.54). The same was valid for the rates of parasympathetic and sympathetic dysfunction in the studied groups (51.4 and 53.3% (P = 0.87) in group 2 and 34.2 and 33.3% (P = 0.93) in group 1, respectively). When the values of the arithmetic expression of each single autonomic function test were compared, no significant difference could be shown between the studied groups. In addition, no significant correlation was found between BMI and indices of DAN. These data indicate that moderate increase of body mass does not affect autonomic function in persons with type 2 diabetes.

Lack of effect of acute repaglinide administration on postprandial lipaemia in patients with type 2 diabetes mellitus.

The effect of acute repaglinide administration (2 mg) on postprandial glycaemia and lipaemia has been examined in 20 subjects with type 2 diabetes mellitus. Each subject received in the morning, after a 12 to 14 h fast, a standard mixed meal (total energy 783 kcal), preceded by one tablet of 2 mg repaglinide or placebo. Chylomicrons and chylomicron-deficient plasma were prepared by ultracentrifugation. Triglyceride levels in CM fraction (CM-triglycerides) in total plasma as well as in CM-deficient plasma (non-CM-triglycerides) were determined. A significant reduction in postprandial glycaemia was observed after repaglinide administration compared to placebo ( p < 0.001). Plasma concentrations of total triglycerides, CM-triglycerides, non-CM-triglycerides, free fatty acids and the other plasma lipids measured, were not significantly different between the two phases of the study. It is concluded that, in contrast to sulphonylureas, acute repaglinide administration does not improve postprandial lipaemia in patients with type 2 diabetes.

A pilot, randomized controlled trial to examine the health outcomes of raisin consumption in patients with diabetes.

OBJECTIVES: Dried fruits, like their fresh homologues, contain relatively high concentrations of antioxidants. The aim of this study was to determine the health outcomes of raisin consumption on patients with diabetes. METHODS: We examined the effects of dried grapes (Vitis vinifera) cultivated in Greece, namely Corinthian Raisins (CR) on blood pressure, fasting glucose, glucated hemoglobin (HbA1c), lipid peroxidation, high-sensitivity C-reactive protein, antioxidant status, and cytokines in patients with type 2 diabetes mellitus (T2DM). Forty-eight well-controlled patients with T2DM from the diabetes outpatient clinic of our hospital were recruited to a two-armed, randomized, controlled, 24-wk prospective intervention trial in order to examine the health outcomes of CR consumption. All participants were reported to consume less fruits and vegetables than the recommended amount of five servings daily. Participants in the intervention were instructed to consume CR equal to two fruit servings (36 g/d), replacing snacks with similar energy density twice during the day. Anthropometric and blood pressure measurements, assessment of dietary intake, and fasting blood draws were conducted at baseline and at week 24. Also, phenolic compounds present in CR were analyzed in plasma of the patients. t Test for parametric data and Mann-Whitney test or Wilcoxon test for non-parametric data were performed. Significance was set at P < 0.05. RESULTS: Body weight, glycemic control, and lipid profile were not affected in either arm. Patients in the CR arm reduced their diastolic blood pressure and increased their total antioxidant potential significantly compared with baseline. The differences between the two groups at week 24 were significant. No change in high-sensitivity C-reactive protein was observed. A significant difference in plasma circulating p-hydroxybenzoic acid was observed between groups at the end of the trial. CONCLUSIONS: Our study shows that naturally CR may improve health features in patients with well-controlled T2DM.

Advances in the topical treatment of diabetic foot ulcers.

The diabetic foot remains a major cause of morbidity worldwide. Even though considerable progress has been achieved over the past years, there is still an urgent need for improvement. While established therapeutic modalities (revascularization, casting and debridement) remain the mainstay of management, there is, therefore, continuous development of new treatment options. This review provides an outlook of advances in topical treatment, including bioengineered skin substitutes (such as Dermagraft, Apligraf, HYAFF, OASIS and Graftjacket), extracellular matrix proteins (such as Hyalofill and E-matrix), as well as miscellaneous further therapeutic adjuncts. Although promising, new therapies should not, for the time being, constitute the basis of management, since clinical experience has not yet confirmed their effectiveness in hard-to-heal diabetic foot ulcers. Furthermore, their cost-effectiveness merits further investigation. Instead, they should only be considered in combination with established treatments or be attempted when these have not been successful. Moreover, we should not be oblivious to the fact that established and emerging treatments need to be practised in the setting of multidisciplinary foot clinics to reduce the number of amputations.