Grape pomace polyphenols improve insulin response to a standard meal in healthy individuals: A pilot study.

BACKGROUND & AIMS: Dietary polyphenols have beneficial effects on glucose/lipid metabolism in subjects at high risk to develop type 2 diabetes; however, the underlying mechanisms are not clear. We aimed to evaluate: 1) the acute effects of the consumption of a drink rich in polyphenols from red grape pomace (RGPD) on glucose/insulin and triglyceride responses to a standard meal in healthy individuals, and, 2) the relationship between plasma levels of phenolic metabolites and metabolic parameters. METHODS: Twelve healthy men, aged 20-40 years participated in a randomized, controlled study according to a cross-over design. After a 3-day low-polyphenol diet, all participants consumed, on two different days and separated by a one week interval, after an overnight fast, a drink rich in polyphenols (1.562 g gallic acid equivalents (GAE)) or a control drink (CD, no polyphenols), followed after 3 h by a standard meal (960 kcal, 18% protein, 30% fat, 52% CHO). Blood samples were taken at fasting, 3 h after the drink, over 5 h after the standard meal and at fasting on the next day to measure plasma concentrations of glucose, insulin, triglyceride and phenolic metabolites. RESULTS: Glycemic and triglyceride post-meal responses were similar after both the RGPD and the control drink. In contrast, postprandial insulin incremental area (iAUC0-5h) was 31% lower (p < 0.05), insulin secretion index was 18% lower (p < 0.016) and insulin sensitivity (SI) index was 36% higher (p = 0.037) after the RGPD compared to CD. Among phenolic metabolites, gallic acid correlated inversely with the insulin response (r = -0.604; p = 0.032) and positively with the SI index (r = 0.588, p = 0.037). CONCLUSIONS: RGPD consumption acutely reduced postprandial insulin levels and improved insulin sensitivity. This effect could be likely related to the increase in gallic acid levels. This drink, added to usual diet, could contribute to increase the daily intake of polyphenols, with potential health benefits. CLINICALTRIALS. GOV IDENTIFIER: NCT02865278.

Intensive dietary intervention promoting the Mediterranean diet in people with high cardiometabolic risk: a non-randomized study.

AIMS: Mediterranean diet (MD) is acknowledged to exert a number of beneficial health effects. We assessed the efficacy and the durability of a 3-month intensive dietary intervention aimed at implementing the MD on body weight and cardiometabolic risk factors in subjects at high risk. METHODS: One hundred and sixteen subjects participated in the study (71 assigned to the intensive intervention and 45 to the conventional intervention). The intensive intervention consisted of 12 weekly group educational meetings and a free-of-charge supply of meals prepared according to the MD model. The conventional intervention consisted of an individual education session along with monthly reinforcements of nutritional messages by the general practitioner. All participants were followed up for 9 months. RESULTS: The two groups had similar pre-intervention characteristics. After the intervention, mean body weight decreased significantly in both groups (p < 0.001). However, the intervention group lost more weight (6.8 ± 4.0 vs. 0.7 ± 1.3, p < 0.0001) and showed a greater reduction in plasma glucose, triglycerides, blood pressure and an increase in HDL cholesterol than the control group (p < 0.01-p < 0.002). In the subgroup of participants with type 2 diabetes, there was a significant reduction in HbA1c level following the intensive (p < 0.0001) but not the conventional intervention. At follow-up, weight loss still persisted in the intervention group (p < 0.0001), while it was lost in the control group. Both interventions significantly reduced blood pressure in the long term (p < 0.001). A significant reduction in daily total energy intake was observed in both groups with a greater reduction in saturated fat and a higher increase in fibre intake in the intervention than in the control group (p < 0.009 and p < 0.001, respectively). CONCLUSIONS: A 3-month intensive dietary intervention inspired to the traditional MD produced greater and more durable weight loss and improvement in cardiometabolic risk profile than the conventional intervention.

Diabetes remission after bariatric surgery is characterized by high glycemic variability and high oxidative stress.

BACKGROUND AND AIM: To evaluate glycemic variability (GV) and oxidative stress in patients who achieved type 2 diabetes (T2DM) remission after bariatric surgery (BS). METHODS AND RESULTS: Twenty-two patients (M/F10/12, age 50 ± 9 years, BMI 31 ± 6 kg/m2) who were in remission of T2DM (T2DM remitters) after BS since at least 1 year and 22 age-, sex- and BMI-matched control subjects were studied. Of the BS group, eleven subjects had undergone Roux-en-Y gastric bypass (RYGB) and eleven subjects sleeve gastrectomy (SG). Oral glucose tolerance test (OGTT), 7 days-continuous glucose monitoring, 24-h urinary excretion of 8-isoprostaglandin F2α (8-isoPGF2α) and dietary intake evaluation were performed. According to general linear model for repeated measures, glucose and insulin response during OGTT were significantly different in T2DM remitter than in control subjects (p < 0.001, for both). All measures of GV (standard deviation, coefficient of variation and mean amplitude of glucose excursions) were significantly higher in T2DM remitters than in controls, (p < 0.001 for all). These indexes were higher among RYGB than SG patients (p < 0.05). The time spent out of the 60-160 mg/dl range was significantly longer in T2DM remitters undergoing RYGB than in controls (p < 0.02). Mean 24-h urinary 8-isoPGF2α excretion was significantly higher in T2DM remitters than that of control subjects (p = 0.04). All GV indexes were directly correlated with blood glucose levels at 30 and 60 min during OGTT (p < 0.05-0.001). CONCLUSION: Remission of T2DM after BS is characterized by high GV and high oxidative stress in the face of fasting blood glucose and HbA1c within the normal range.

Comparative Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Glucose Homeostasis and Incretin Hormones in Obese Type 2 Diabetic Patients: A One-Year Prospective Study.

The aim of the work was to compare the hormonal and the metabolic mechanisms involved in weight loss and remission of T2DM one year after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) in morbidly obese type 2 diabetic (T2DM) patients. Insulin sensitivity, insulin secretion, and the gastrointestinal (GI) hormone response to a mixed meal test (MMT) were evaluated before and one year after BS (14 RYGB and 19 VSG). RYGB and VSG groups had similar characteristics at baseline. Weight loss at one year was similar in the 2 groups (ΔBMI%: - 32±10 and - 30±7%, p=0.546). Insulin sensitivity and insulin secretion improved similarly after either procedures with a similar rate in T2DM remission (86% in RYGB and 76% in VSG). Meal-stimulated GLP-1 levels increased after both procedures reaching significantly higher levels after RYGB (p=0.0001). GIP response to MMT decreased to a similar extent after the 2 interventions (p=0.977). Both fasting and post-meal ghrelin concentrations were markedly suppressed after VSG and significantly lower than RYGB (p=0.013 to p=0.035). The improvement of insulin sensitivity and beta-cell function was significantly associated with weight loss (p=0.014 to p=0.035), while no relation was found with the changes in GI hormones. In conclusion, in morbidly obese T2DM patients, RYGB and VSG result in similar improvements of the glucose status in the face of different GI hormonal pattern. Weight loss is the key determinant of diabetes remission one year after surgery.

Effects of bariatric surgery on markers of subclinical atherosclerosis and endothelial function: a meta-analysis of literature studies.

BACKGROUND/OBJECTIVES: Several studies confirmed a significantly increased carotid intima-media thickness (IMT) and impaired flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) in obese subjects, but few data are available on the effects of bariatric surgery on these markers of cardiovascular (CV) risk. We performed a meta-analysis of studies evaluating changes in IMT, FMD and NMD in obese patients after bariatric surgery. METHODS: A systematic search was performed in the PubMed, Web of Science, Scopus and EMBASE databases without any language or publication year restriction. The last search was performed in January 2015. In addition, the reference lists of all retrieved articles were manually reviewed. Prospective studies evaluating the impact of bariatric surgery on the markers of CV risk were included. Changes in IMT, FMD and NMD after bariatric surgery were expressed as mean differences (MD) with pertinent 95% confidence intervals (95% CIs). IMT has been expressed in millimeters (mm); FMD and NMD as percentage (%). Impact of clinical and demographic features on effect size was assessed by meta-regression. RESULTS: Ten articles (314 obese patients) were included in the analysis. Six studies contained data on IMT (7 data sets; 206 patients), 8 studies on FMD (9 data sets; 269 patients) and 4 on NMD (4 data sets; 149 patients). After bariatric surgery, there was a significant reduction of IMT (MD: -0.17 mm; 95% CI: -0.290, -0.049; P=0.006) and a significant improvement in FMD (MD: 5.65%; 95% CI: 2.87, 8.03; P<0.001), whereas NMD did not change (MD: 2.173%; 95% CI: -0.796, 5.142; P=0.151). Interestingly, percentage of changes in the body mass index were associated with changes in IMT (Z=11.52, P<0.001), FMD (Z=-4.26, P<0.001) and NMD (Z=-3.81, P<0.001). CONCLUSIONS: Despite heterogeneity among studies, bariatric surgery is associated with improvement of subclinical atherosclerosis and endothelial function. These effects may significantly contribute to the reduction of the CV risk after bariatric surgery.

Effects of Sleeve Gastrectomy and Gastric Bypass on Postprandial Lipid Profile in Obese Type 2 Diabetic Patients: a 2-Year Follow-up.

BACKGROUND: Bariatric surgery (BS) is known to favorably impact fasting lipid profile. Fasting and postprandial lipids were evaluated before and 2 years after BS in obese type 2 diabetic (T2DM) patients. METHODS: A prospective study was conducted in 19 obese T2DM patients: ten undergoing sleeve gastrectomy (SG) and nine undergoing Roux-en-Y gastric bypass (RYGB). Before and 2 years after BS, clinical parameters and the response of lipid and incretin hormones to a mixed meal (MM) were assessed. RESULTS: The two groups had similar characteristics at baseline. After BS, weight loss was similar in the two groups (p ≤ 0.01). Fasting glucose, insulin, and triglycerides decreased while HDL cholesterol increased in a similar way (p < 0.05); in contrast, fasting LDL cholesterol decreased only after RYGB (p < 0.05). Post-meal glucose concentrations decreased while early insulin response significantly improved after both procedures (p < 0.001 for both). Postprandial triglycerides decreased after both procedures (p < 0.05) while postprandial LDL cholesterol decreased only after RYGB (p < 0.05). Meal-GLP-1 increased postoperatively in both groups although to a greater extent after RYGB (p < 0.001 vs. SG). GIP decreased after both procedures, especially after RYGB (p = 0.003). At multivariate analysis, GLP-1 peak was the best predictor of LDL reduction (ß = -0.552, p = 0.039) while the improvement of HOMA-IR (ß = 0.574, p = 0.014) and weight loss (ß = 0.418, p = 0.036) predicted triglycerides reduction. CONCLUSIONS: Both surgical procedures markedly reduce fasting and postprandial triglycerides and increase HDL cholesterol levels. LDL cholesterol decreases only after RYGB through a mechanism likely mediated by the restoration of GLP-1.

Clinical efficacy of bariatric surgery versus liraglutide in patients with type 2 diabetes and severe obesity: a 12-month retrospective evaluation.

AIMS: To evaluate the clinical efficacy of bariatric surgery vs medical therapy with liraglutide on weight loss, glycemic control and cardiovascular risk profile in patients with type 2 diabetes and severe obesity. METHODS: A retrospective evaluation was conducted in 31 patients with type 2 diabetes and severe obesity who had undergone bariatric surgery and in 31 patients with type 2 diabetes and comparable body weight who had added liraglutide to their background medical treatment in the period 2009-2013. Anthropometric parameters, glycemic control, treatment of diabetes and other comorbidities, safety and side effects before and 12 months after treatment were assessed. RESULTS: Age was 47 ± 8 years (mean ± SD) in bariatric surgery and 56 ± 9 years in medical treatment group (p < 0.001); body mass index before treatment was 44 ± 7 and 40 ± 4 kg/m(2) in bariatric surgery and medical treatment, respectively (p = 0.03). Twelve months after treatment, average weight loss was 38 ± 15 kg among bariatric surgery patients, and 5 ± 8 kg in medical treatment group (p < 0.001). Glycemic control improved in both groups with greater improvement in bariatric surgery patients. The UKPDS risk score decreased in both groups, although it remained higher in medical treatment than in bariatric surgery patients (p < 0.001). Of note, almost 60 % of patients on liraglutide met the target of glycated hemoglobin <7 % (53 mmol/mol) and lost ≥5 % of body weight. CONCLUSIONS: In severely obese type 2 diabetic patients, bariatric surgery reduced body weight and improved overall metabolic control to a greater extent than medical treatment. Randomized clinical studies are necessary.

Cardiometabolic risk in overweight subjects with or without relative fat-free mass deficiency: the Strong Heart Study.

BACKGROUND AND AIM: Sarcopenia is a condition mainly due to loss of fat-free mass (FFM) in elderly individuals. RFFMD, however, is also frequent in obese subjects due to abnormal body composition. Objective of this study was to evaluate the impact of relative fat-free mass deficiency (RFFMD) on cardiometabolic (CM) risk in obese normoglycemic individuals. METHODS AND RESULTS: Overweight/obese American Indians from the Strong Heart Study population, without diabetes and with FBG ≤ 110 mg/dL and with GFR >60 mg/mL/1.73 m(2) were selected for this analysis (n = 742). RFFMD was defined on the basis of a multivariable equation previously reported. Fasting glucose and 2 h-OGTT were measured together with urine albumin/creatinine excretion, laboratory and anthropometric parameters. In addition to lower FFM and greater adipose mass, participants with RFFMD had higher body mass index, waist circumference, C-reactive protein, fibrinogen, insulin resistance and urinary albumin/creatinine than participants with normal FFM (all p < 0.001); they also had a greater prevalence of hypertension, impaired glucose tolerance (IGT) or OGTT-diabetes than participants with normal FFM (all p < 0.003) and a near 2-fold greater probability of significant proteinuria (p < 0.01). RFFMD was more frequent in women than in men: significant sex-RFFMD interactions were found for BMI and waist circumference (both p < 0.0001). CONCLUSIONS: RFFMD in overweight/obese normoglycemic individuals is associated with greater probability of hypertension, abnormalities of glucose tolerance and proteinuria. Assessment of RFFRMD might, therefore, help stratifying cardiometabolic risk among normoglycemic individuals with overweight/obesity.

Dietary fat differentially modulate the mRNA expression levels of oxidative mitochondrial genes in skeletal muscle of healthy subjects.

BACKGROUND AND AIMS: Different types of dietary fats exert differential effects on glucose and lipid metabolism. Our aim was to evaluate the impact of different dietary fats on the expression of skeletal muscle genes regulating mitochondrial replication and function in healthy subjects. METHODS AND RESULTS: Ten healthy subjects (age 29 ± 3 years; BMI 25.0 ± 3 kg/m(2)) received in a random order a test meal with the same energy content but different composition in macronutrients and quality of fat: Mediterranean (MED) meal, SAFA meal (Lipid 66%, saturated 36%) and MUFA meal (Lipid 63%, monounsaturated 37%). At fast and after 180 min, a fine needle aspiration was performed from the vastus lateralis for determination of mitochondrial gene expression by quantitative PCR. No difference in glucose and triglyceride response was observed between the three meals, while NEFA levels were significantly higher following fat-rich meals compared to MED meal (p < 0.002-0.0001). MED meal was associated with an increased expression, albeit not statistically significant, of some genes regulating both replication and function. Following MUFA meal, a significant increase in the expression of PGC1ß (p = 0.02) and a reduction in the transcription factor PPARδ (p = 0.006) occurred with no change in the expression of COX and GLUT4 genes. In contrast, SAFA meal was associated with a marked reduction in the expression of COX (p < 0.001) PFK (p < 0.003), LPL (p = 0.002) and GLUT4 (p = 0.009) genes. CONCLUSION: Dietary fats differentially modulate gene transcriptional profile since saturated, but not monounsaturated fat, downregulate the expression of genes regulating muscle glucose transport and oxidation.

Early improvement of postprandial lipemia after bariatric surgery in obese type 2 diabetic patients.

BACKGROUND: Bariatric surgery (BS) is able to positively influence fasting lipid profile in obese type 2 diabetic patients (T2DM), but no data is available on the impact of BS on postprandial lipid metabolism neither on its relation with incretin hormones. We evaluated the short-term (2 weeks) effects of BS on fasting and postprandial lipid metabolism in obese T2DM patients and the contribution of changes in active GLP-1. METHODS: We studied 25 obese T2DM patients (age = 46 ± 8 years, BMI = 44 ± 7 kg/m2), of which 15 underwent sleeve gastrectomy and 10 underwent gastric bypass. Lipid and incretin hormone concentrations were evaluated for 3 h after ingestion of a liquid meal before and 2 weeks after BS. RESULTS: After BS, there was a significant reduction in body weight (p < 0.001), fasting plasma glucose (p < 0.001), fasting plasma insulin (p < 0.05), HOMA-IR (p < 0.001), and fasting plasma lipids (p < 0.05). The meal response of plasma triglycerides, total cholesterol, and HDL cholesterol was significantly lower compared to pre-intervention (p < 0.05, p < 0.001). In particular, the incremental area under the curve (IAUC) of plasma triglycerides decreased by 60% (p < 0.005). The meal-stimulated response of active GLP-1 increased, reaching a statistical significance (p < 0.001). CONCLUSIONS: BS leads to an early improvement of fasting and postprandial lipemia. The fall in fasting triglycerides is associated with an improvement of insulin resistance, while the reduction of postprandial lipemia is likely related to reduced intestinal lipid absorption consequent to bariatric surgery.

Clinical efficacy of laparoscopic sleeve gastrectomy vs laparoscopic gastric bypass in obese type 2 diabetic patients: a retrospective comparison.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are performed in patients with obesity and type 2 diabetes mellitus (T2DM). The aim of this study is to evaluate retrospectively the clinical efficacy of RYGB and SG in two groups of obese T2DM patients. METHODS: From the hospital database, we extracted the clinical records of 31 obese T2DM patients, of whom 15 (7 F/8 M) had undergone laparoscopic SG (LSG) and 16 (7 F/9 M) laparoscopic RYGB (LRYGB) in the period 2005-2008. The groups were comparable for age (range 33-59 years) and BMI (range 38-57 kg/m(2)). LRYGB alimentary limb was 150 cm, and biliopancreatic limb was 150 cm from the Treitz ligament. LSG vertical transection was calibrated on a 40-Fr orogastric bougie. Data were analysed at 6, 12 and 18-24 months with reference to weight loss and remission of comorbidities. RESULTS: The reduction in body weight was comparable in the two groups. At 18-24 months the percent BMI reduction was 29 ± 8 and 33 ± 11 % in LSG and LRYGB, respectively. Percent excess weight loss was 53 ± 16 and 52 ± 19 % in LSG and LRYGB, respectively. Thirteen patients in LSG and 14 patients in LRYGB discontinued their hypoglycaemic medications. Five (55 %) patients in LSG and eight (89 %) in LRYGB discontinued antihypertensive drugs. Three out of five patients in LSG and one out of two patients in LRYGB withdrew lipid-lowering agents. CONCLUSIONS: LSG and LRYGB are equally effective in terms of weight loss and remission of obesity-related comorbidities. Controlled long-term comparisons are needed to establish the optimal procedure in relation to patients' characteristics.

Impact of sleeve gastrectomy on weight loss, glucose homeostasis, and comorbidities in severely obese type 2 diabetic subjects.

This study was undertaken to assess medium-term effects of laparoscopic sleeve gastrectomy (LSG) on body weight and glucose homeostasis in severely obese type 2 diabetic (T2DM) subjects. Twenty-five obese T2DM subjects (10 M/15 F, age 45 ± 9 years, BMI 48 ± 8 kg/m(2), M ± SD) underwent evaluation of anthropometric/clinical parameters and glucose homeostasis before, 3 and 9-15 months after LSG. Mean BMI decreased from 48 ± 8 kg/m(2) to 40 ± 9 kg/m(2) (P < .001) at 3 months and 34 ± 6 kg/m(2) (P < .001) at 9-15 months after surgery. Remission of T2DM (fasting plasma glucose < 126 mg/dL and HbA1c < 6.5% in the absence of hypoglycemic treatment) occurred in all patients but one. There was a remarkable reduction in the percentage of patients requiring antihypertensive and hypolipidemic drugs. Our study shows that LSG is effective in producing a significant and sustained weight loss and improving glucose homeostasis in severely obese T2DM patients.

Effects of meals with different glycaemic index on postprandial blood glucose response in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion.

OBJECTIVE: To evaluate the impact of high-glycaemic index and low-glycaemic index meals on postprandial blood glucose in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion. METHODS: Sixteen patients with Type 1 diabetes under continuous subcutaneous insulin infusion treatment, age 36±0.5 years (mean±sem), HbA(1c) 7.6±0.2% (56±1.1 mmol/mol), consumed two test meals with an identical macronutrient composition, but with a different glycaemic index: 59 vs. 90. Blood glucose was checked before the test meal and every 30 min thereafter for 180 min. The same preprandial insulin dose was administered on the two occasions. RESULTS: Blood glucose concentrations following the low-glycaemic index meal were significantly lower than those of the high-glycaemic index meal (P<0.05 to P<0.01). The blood glucose area under the curve after the low-glycaemic index meal was 20% lower than after the high-glycaemic meal (P=0.006). CONCLUSIONS: Our data show that meals with the same carbohydrate content but a different glycaemic index produce clinically significant differences in postprandial blood glucose.

Prevalence of the metabolic syndrome using ATP-derived definitions and its relation to insulin-resistance in a cohort of Italian outpatient children.

OBJECTIVE: To analyze the prevalence of the metabolic syndrome (MetS) defined by three sets of Adult Treatment Panel III (ATPIII)-derived criteria, and the ability of each definition to identify insulin-resistance (IR) in a wide cohort of outpatient children. SUBJECTS AND METHODS: Seven hundred and twenty-four children consecutively observed in the Outpatient Pediatric Clinic of Pozzuoli Hospital during the period 2004-2009 were included in the study. Diagnosis of the MetS was made using three definitions: Cook, Jolliffe (which adopt age- and gender-specific cut-points) and de Ferranti. Insulin sensitivity was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR). IR was defined by the 90th percentile of HOMA-IR in healthy non-obese Italian children grouped by gender and Tanner stage. The ability of each definition to identify IR was evaluated in terms of sensitivity and specificity. RESULTS: The prevalence of the MetS in the overall cohort was 11, 12 and 24% using Cook, Jolliffe and de Ferranti criteria, respectively. Sensitivity and specificity in relation to IR were 19 and 94% with Cook criteria, 21 and 92% with Jolliffe criteria, and 39 and 84% with de Ferranti criteria. CONCLUSIONS: The prevalence of the MetS in children increases with increasing body weight. Among the three definitions analyzed, de Ferranti identifies a larger number of children with the MetS. The prediction of IR is weak with all definitions; on the contrary, the absence of MetS identifies fairly well children with low degree of IR.

Coronary vasoreactivity is not altered in young people with type 1 diabetes.

BACKGROUND AND AIM: Abnormal coronary microvascular circulation has been demonstrated in diabetes and is associated with increased rate of cardiovascular events. Our objective was to evaluate coronary vasoreactivity in young people with type 1 diabetes with and without microvascular complications. METHODS AND RESULTS: Twenty-five type 1 diabetic patients without microvascular complications (DC-), 23 with microvascular complications (DC+), and 18 control subjects (C) were studied. Coronary vasoreactivity was assessed by means of coronary flow reserve (CFR). Blood flow velocity in the left anterior descending coronary artery was measured at rest and after high-dose dipyridamole using transthoracic color-guided pulsed Doppler echocardiography. CFR was defined as the ratio of hyperaemic to resting diastolic peak flow velocities. The three groups had similar cardiac function parameters, and also systolic and diastolic blood pressure at rest, which remained unchanged during dipyridamole infusion. Resting coronary flow velocity was comparable in C, DC-, and DC+ (p=ns). Dipyridamole infusion produced a threefold increase in coronary diastolic peak velocity, which reached similar values in C (0.69±0.16 m/s), DC- (0.69±0.18 m/s), and DC+ (0.66±0.11 m/s). Mean CFR ratio was similar in C (3.33±0.66), DC- (3.30±0.51), and DC+ (3.24±0.60). At multiple linear regression analysis, no association was found between CFR and age, sex, HbA(1c), duration of diabetes, and complications. CONCLUSION: Coronary vasodilatory function is preserved in young D patients, even those with early microvascular complications, suggesting that coronary vasoreactivity deteriorates at more advanced stages of microvascular complications and/or in the presence of other cardiovascular risk factors.

Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders?

Glycogen storage disease type Ib (GSD Ib, OMIM 232220) is an inborn disorder of glucose metabolism, caused by mutations in the G6PT gene, encoding a glucose 6-phosphate transporter (G6PT). GSD Ib is mainly associated with fasting hypoglycaemia and hepatomegaly. Most GSD Ib patients also show neutropenia and neutrophil dysfunction and therefore are at risk of developing severe infections and inflammatory bowel disease (IBD). An increased risk for autoimmune disorders, such as thyroid autoimmunity and Crohn-like disease, has also been demonstrated, but no systematic study on the prevalence of autoimmune disorders in GSD Ib patients has ever been performed. We describe a 25-year-old patient affected by GSD Ib who developed 'seronegative' myasthenia gravis (MG), presenting with bilateral eyelid ptosis, diplopia, dysarthria, severe dysphagia, dyspnoea and fatigue. The repetitive stimulation of peripheral nerves test showed signs of exhaustion of neuromuscular transmission, particularly evident in the cranial area. Even in the absence of identifiable anti-acetylcholine receptor antibodies, seronegative MG is considered an autoimmune disorder and may be related to the disturbed immune function observed in GSD Ib patients.

Prevalence of elevated liver enzymes in Type 2 diabetes mellitus and its association with the metabolic syndrome.

The occurrence of liver disease and raised liver enzymes is common in Type 2 diabetes, and may be multifactorial in origin. Very few studies are available on the exact prevalence of the phenomenon, however. We carried out an observational point-prevalence study of elevated liver enzymes in eight hospital-based Italian diabetes units. Data of 9621 consecutive Type 2 diabetes patients (males, 52.4%; median age, 65 yr) were analyzed, and alanine and aspartate aminotransferase (ALT, AST) and gamma-glutamyltransferase (GGT) levels were related to body mass index (BMI), metabolic control and the presence of the metabolic syndrome. ALT, AST, and GGT levels exceeding the upper limit of normal were present in 16.0%, 8.8%, 23.1%, respectively, the prevalence being higher in males, increasing with obesity class and poor metabolic control, and decreasing with age. Elevated enzymes were systematically associated with most parameters of the metabolic syndrome. After correction for age, gender, BMI, and differences across centers, elevated triglyceride levels/fibrate treatment [odds ratio (OR), 1.57; 95% confidence interval (CI), 1.34- 1.84] and an enlarged waist circumference (OR, 1.47; 95% CI, 1.17-1.85) were the only parameters independently associated with high ALT. In a separate analysis, the presence of metabolic syndrome (Adult Treatment Panel III criteria) was highly predictive of raised liver enzymes. After exclusion of hepatitis B and C positive cases, tested in 2 centers, the prevalence of raised enzymes decreased by approximately 4%, but the association with the metabolic syndrome did not change significantly. In conclusion, the high prevalence of elevated liver enzymes in Type 2 diabetes is in keeping with the well-demonstrated risk of progressive liver disease. A large amount of diabetes patients may require a thorough clinical, laboratory and histological investigation.

Central adiposity and left ventricular mass in obese children.

AIM: The impact of central adiposity on left ventricular (LV) mass in childhood obesity has been little explored. This study evaluates whether central obesity influences LV mass and function in obese children. METHODS AND RESULTS: Biochemical, anthropometric and echocardiographic measurements were taken in obese (n=111, mean age 10.6+/-2.5 years) and non-obese children (n=30, mean age 10.8+/-3.0 years). Left ventricular function was analyzed by conventional and tissue Doppler echocardiography. LV mass was calculated according to the Penn convention and indexed for height(2.7) (LVM(i)). The obese group showed increased levels of LVM(i) as compared to the non-obese group (35.7+/-8.5 vs 23.5+/-2.8 g/h(2.7), p<0.0001). Among obese children, we observed a significant increase of LVM(i) across tertile of waist-height ratio (WHtR). The subjects identified by the highest tertile of WHtR, as compared to subjects identified by the lowest tertile, showed higher levels of BMI (29.5+/-5.4 vs 31.0+/-5.0 kg/m(2), p<0.0001) and LVM(i) (32.1+/-6.5 vs 37.1+/-8.5 g/h(2.7), p<0.01). Among obese children a positive correlation (standardized for age and gender) was found between LVM(i) and BMI (r=0.282, p<0.01) and WHtR (r=0.334, p<0.0001). To analyze the independent predictors of LVM(i), a stepwise linear regression analysis was performed using age, gender, BMI, blood pressure, heart rate, HOMA-IR and WHtR as independent variables. LVM(i) was independently associated only with WHtR (beta=0.309, t=3.238, p=0.002). CONCLUSION: Obese children show an increased LVM(i) and a preserved LV function. Central adiposity is the major determinant of left ventricular mass.

Upper airway obstructive disease in mucopolysaccharidoses: polysomnography, computed tomography and nasal endoscopy findings.

In mucopolysaccharidoses, upper airway obstruction has multiple causative factors and progressive respiratory disease may severely affect morbidity and mortality. In a cross-sectional study over 2 years we evaluated upper airway obstructive disease through overnight polysomnography, upper airway computed tomography and nasal endoscopy in 5 children and 6 adults with mucopolysaccharidoses of various types. Measurements of apnoea and apnoea-hypopnoea index, arousal index, and sleep efficiency were obtained through polysomnography. Retropalatal and retroglossal spaces were calculated through computed tomography, and the degree of adenoid hypertrophy was assessed through endoscopy. Apnoea index and apnoea-hypopnoea index were significantly higher in children than in adults with mucopolysaccharidoses (p = 0.03 and p = 0.03, respectively). Compared to healthy controls, retropalatal and retroglossal spaces were significantly smaller in children (p = 0.03 and p = 0.004, respectively) or adults with mucopolysaccharidoses (p = 0.004 and p = 0.004, respectively). All subjects had adenoid hypertrophy causing first-degree (36%) or second-degree (64%) obstruction at endoscopy. Overnight polysomnography, upper airway computed tomography and nasal endoscopy are useful tools for diagnosing obstructive sleep apnoea syndrome in mucopolysaccharidoses, and identifying the site and severity of airway obstruction.

Impact of impaired fasting glucose and other metabolic factors on cognitive function in elderly people.

AIM: The present study was undertaken to evaluate the impact of impaired fasting glucose (IFG), insulin resistance (IR) and hyperhomocysteinaemia (Hhcy) on cognitive function (CF) in a sample of non-diabetic elderly subjects. METHODS AND RESULTS: One hundred and eighty-two non-diabetic subjects, aged > or = 65 years, without signs of previous stroke were included in the study. CF was evaluated by the Mini Mental State Examination (MMSE) score, corrected for age and education. Since diagnostic criteria for IFG have been recently lowered from 110 to 100 mg/dl, subjects were categorized according to old (IFG1997) and new (IFG2003) criteria. IR and Hhcy were defined by the upper quartile of insulin (11.0 UI/L) and Hcy (18.6 micromol/L) distribution, respectively. The frequency of IFG1997, Hhcy, and IR, but not of IFG2003, showed a linear trend across tertiles of MMSE (p<0.001). The odds ratio (95% CI) for impaired CF (MMSE<24.3) was 9.08 (2.97-27.74) for IFG1997, 3.66 (1.28-10.45) for Hhcy, 2.83 (1.25-6.37) for IR and 1.32 (0.61-2.89) for IFG2003. CONCLUSIONS: Our study shows that IFG1997, Hhcy and IR are powerful metabolic markers of impaired CF among elderly people.