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BackgroundPatients with type 1 diabetes (T1D) have higher mortality risk compared to the general population; this is largely due to increased rates of cardiovascular disease (CVD). As accurate CVD risk stratification is essential for an appropriate preventive strategy, we aimed to evaluate the concordance between 2019 European Society of Cardiology (ESC) CVD risk classification and the 10-year CVD risk prediction according to the Steno Type 1 Risk Engine (ST1RE) in adults with T1D.MethodsA cohort of 575 adults with T1D (272F/303M, mean age 36 ± 12 years) were studied. Patients were stratified in different CVD risk categories according to ESC criteria and the 10-year CVD risk prediction was estimated with ST1RE within each category.ResultsMen had higher BMI, WC, SBP than women, while no difference was found in HbA1c levels between genders. According to the ESC classification, 92.5% of patients aged 20 years) alone identified few patients (ConclusionsUsing ESC criteria, a large proportion (45%) of T1D patients without CVD are classified at very high CVD risk; however, among them, none of those

Aims: Hypoglycemia is a serious complication of bariatric surgery. The aim of the present meta-analysis was to evaluate the rate and the timing of post-bariatric hypoglycemia (PBH) with different bariatric procedures using reliable data from continuous glucose monitoring (CGM). Data synthesis: Studies were systematically searched in the Web of Science, Scopus and PubMed databases according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The prevalence of PBH was expressed as weighted mean prevalence (WMP) with pertinent 95% confidence intervals (95%CI). A total of 8 studies (16 datasets) enrolling 280 bariatric subjects were identified. The total WMP of PBH was 54.3% (95%CI: 44.5%–63.8%) while the WMP of nocturnal PBH was 16.4% (95%CI: 7.0%–34%). We found a comparable rate of PBH after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) (OR 1.62, 95%CI: 0.71–3.7; P = 0.248); likewise, the percent time spent in hypoglycemia was similar with the two procedures (mean difference 5.3%, 95%CI: −1.4%–12.0%; P = 0.122); however, RYGB was characterized by a higher glycemic variability than SG. Regression models showed that the time elapsed from surgical intervention was positively associated with a higher rate of both total PBH (Z-value: 3.32, P < 0.001) and nocturnal PBH (Z-value: 2.15, P = 0.013). Conclusions: PBH, both post-prandial and nocturnal, is more prevalent than currently believed. The rate of PBH increases at increasing time from surgery and is comparable after RYGB and SG with a higher glucose variability after RYGB.

Introduction: gut microbiota (GM) seems to be involved in the pathophysiology and progression of both metabolic syndrome (MS) and obesity. The aim was to investigate GM's composition in patients with severe obesity, candidates for bariatric/metabolic surgery BMS. Materials and Methods: Multicentre, prospective, cohort study, enrolling 84 patients with BMI 40–55 kg/m2, divided by metabolic status (MS) in healthy (group A), pre-MS (B), or MS (C). Results: No differences were found regarding anthropometric, nutritional parameters, except for vitamin D. As a whole the alpha and beta diversity examinations showed no statistical differences in GM profile. A total of 5/7 phyla with relative frequencies were identified above 0.1% (Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia). Fusobacteria and Patescibacteria represented the less abundant. There were no significant differences in the top ten genera. Data on Bacteroidetes (inversely related to triglycerides and LDL and directly related to HDL levels) and on Firmicutes (opposite trend) relative abundances suggest no differences among the three conditions. No correlation between the relative abundance of the main phyla and plasmatic glucose levels was observed. Conclusions: In a selected cohort of patients with obesity, MS did not affect the preoperative GM's profile. Severe obesity, per se, seems to be an independent condition affecting GM.

BACKGROUND The usefulness of adapted small-sided games (SSGs) in improving cardiac function in subjects with T2DM is still debated. Here we evaluated the effects of 18 weeks indoor muscular activation training (6 weeks; IMA) followed by adapted SSGs football training (12 weeks) on cardiac function, muscular fitness, body composition and adiponectin expression in sedentary T2DM volunteers. METHODS Six T2DM patients underwent IMA protocol of 6 weeks, twice a week followed by 12 weeks SSGs (5-a-side, once a week) training. Glucose, lipid profile and serum homocysteine concentration, body composition (BC), bone mineral density (DEXA), were determined at baseline and after 18 weeks (IMA+SSGs). VO 2max and muscular fitness were recorded at baseline and after IMA (6 weeks) and SSGs (12 weeks), respectively. RESULTS No significant differences were found for VO 2max and muscular fitness after 6weeks of IMA. After 18 weeks (6 weeks IMA + 12 weeks SSGs) of training, significant improvements were found in the following parameters: work capacity, VO 2peak , Ventilation (VE peak ), breathing reserve consumption and oxygen uptake efficiency slope (P

Background and aims: Although the use of Continuous Glucose Monitoring (CGM) is rapidly extending, little evidence is currently available on daily glycemic excursions after different bariatric procedures. We assessed glycemic patterns after sleeve gastrectomy (SG) and roux-en-Y gastric bypass (RYGB) using CGM. Methods and results: Cross-sectional study in subjects who had undergone RYGB (n = 22) or SG (n = 29) since at least 1 year, without pre-surgery or in current diabetes (T2DM) remission. All subjects underwent 7 day-CGM (Dexcom G4 PLATINUM), which provides glucose variability (GV), number and time spent in hypoglycemia, hypoglycemia patterns (postprandial, nocturnal or mixed). All indexes of GV were higher after RYGB than after SG (p < 0.001). Twenty-eight (55%) subjects experienced hypoglycemia. The number of events was higher after RYGB than SG (p = 0.017) while it did not differ in subjects with or without pre-surgery T2DM (p = 0.129). Overall, 9 (32%) subjects presented hypoglycemia exclusively during the postprandial period, 8 (29%) an exclusively nocturnal pattern and 11 (39%) a mixed pattern. The nocturnal pattern was more frequent after SG than RYGB (53.8% vs 6.7%, p = 0.036) while no difference was observed in subjects with or without pre-surgery T2DM (p = 0.697). Hypoglycemia symptoms were more frequent in subjects with postprandial than in those with nocturnal pattern (77.8% vs 12.5%, p = 0.015). Conclusions: RYGB is characterized by a greater GV and a higher number of hypoglycemia events mostly post-prandial and symptomatic, while SG is associated with nocturnal and often asymptomatic hypoglycemia. These findings suggest that post-bariatric hypoglycemia is a more complex, not exclusively, postprandial phenomenon.

Hypoglycemia is a pathological condition characterized by a low plasma glucose concentration associated with typical autonomic and/or neuroglycopenic symptoms, and resolution of these symptoms with carbohydrate consumption. Hypoglycemia is quite common in clinical practice, particularly in insulin-treated patients with diabetes and in other inherited or acquired conditions involving the regulation of glucose metabolism. Beyond symptoms that might strongly affect the quality of life, hypoglycemia can lead to short- and long-term detrimental consequences for health. Hypoglycemia can be prevented by appropriate changes in dietary habits or by relevant modifications of the drug treatment. Several dietary approaches based on the intake of various carbohydrate foods have been tested for hypoglycemia prevention; among them uncooked cornstarch (UCS) has demonstrated a great efficacy. In this narrative review, we have summarized the current evidence on the UCS usefulness in some conditions characterized by high hypoglycemic risk, focusing on some inherited diseases −i.e. glycogen storage diseases and other rare disorders − and acquired conditions such as type 1 diabetes, postprandial hypoglycemia consequent to esophageal-gastric or bariatric surgery, and insulin autoimmune syndrome. We also considered the possible role of UCS during endurance exercise performance. Lastly, we have discussed the dose requirement, the side effects, the limitations of UCS use, and the plausible mechanisms by which UCS could prevent hypoglycemia.

Background: Growing evidence shows that grape polyphenols can improve cardiovascular risk factors. Although there are clear data supporting a beneficial effect of grape supplementation on blood pressure and glucose metabolism, the effects of grape polyphenols on lipid metabolism are still controversial. Objective: We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effect of grape products on lipid profile. Design: A systematic search was performed in the PubMed, Web of Science, Scopus, and EMBASE databases without any language or publication year restriction. The reference lists of all retrieved articles were manually reviewed. RCTs evaluating the impact of grape products/juice/extracts on lipid profile were included. Difference in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), oxidized low-density lipoprotein cholesterol (oxLDL-C), apolipoprotein (apo) A, apo B before and after administration of grape products or placebo were expressed as mean differences (MD) with pertinent 95% confidence intervals (95% CI). The impact of clinical and demographic features on effect size was assessed by meta-regression. Results: The administration of grape products is associated with a significant improvement of lipid profile, as evidenced by changes in TC (MD: &minus, 7.6 mg/dL (&minus, 0.2 mmol/L), 95% CI: &minus, 10.8, &minus, 4.4, p &lt, 0.001), HDL-C (MD: 1.4 mg/dL (0.04 mmol/L), 95% CI: 0.8, 1.9, 0.001, I2 = 74.7%, p &lt, 0.001), LDL-C (&minus, 6.3 mg/dL (&minus, 0.16 mmol/L), 9.5, &minus, 3.0, 0.001), oxLDL-C (MD: &minus, 4.5 U/L, 7.5, &minus, 1.5, p = 0.003, I2 = 90.6%, p &lt, 0.001), apo B (MD: &minus, 2.4 mg/dL (&minus, 0.05 &micro, mol/L), 4.5, &minus, 0.3, p = 0.026), and TG (MD: &minus, 14.5 mg/dL (&minus, 17.7, &minus, 11.2, 0.001) levels in subjects receiving grape products compared to placebo. With regard to the extent of the lipid-lowering effect, compared to baseline values, the highest reduction was reported for LDL-C (MD: &minus, 5.6 mg/dL (&minus, 0.14 mmol/L), 1.7, p = 0.005) and for oxLDL-C (MD: &minus, 5.0 U/L, 8.8, &minus, 1.2, p = 0.010, I2 = 0%, p = 0.470). Conclusions: Grape polyphenols exert a favorable effect on lipid profile in humans by significantly reducing plasma levels of LDL-C and oxLDL-C.

To prevent the spread of COVID-19, lockdown was imposed in many countries with rigid restrictions on all outdoor activities, also limiting attendance at diabetes clinics. In patients with diabetes, lockdown implies lifestyle changes related to physical activity, stress, and nutrition that are likely to adversely affect glycemic control (1). Conversely, during lockdown, individuals with type 1 diabetes (T1D) are to be expected to have a more regular lifestyle, more closely respecting time schedules and insulin administration timing. We evaluated the impact of lockdown on glucose control in 207 Italian adults with T1D attending the Diabetes Outpatient Clinic of the Federico II University Hospital, Naples: 96 females/111 males, mean ± SD age 38.4 ± 12.7 years, 104 on multiple daily insulin injections (MDI), and 103 on insulin pump (continuous subcutaneous insulin infusion [CSII]). Inclusion criteria were continuous glucose monitoring (CGM) for at least 6 months, including a 2-week period with CGM use >70% before (January–February) and during (March–April 2020) lockdown, while maintaining the same device: FreeStyle ( n = 130), Guardian 3 ( n = 47), Dexcom G6 ( n = 18), and Eversense ( n = 12). Each participant gave informed consent for the use of her or his data. No participant reported …

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

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 postmeal 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.

Aims To investigate whether in type 1 diabetes (T1DM) patients the concomitance of long-lasting celiac disease (CD) treated with a gluten free diet (GFD) impacts glycaemic control and the prevalence/severity of microvascular complications. Methods A case-control, observational study was performed in 34 patients with T1DM and GFD-treated CD and 66 patients with T1DM alone matched for age, gender, and T1DM duration. Anthropometric parameters, glucose control (HbA1c), status of chronic complications and concomitant autoimmune diseases were evaluated. Results HbA1c level was similar in T1DM + CD and T1DM alone (7.8 ± 1.0 vs 7.7 ± 1.1%, P = 0.57); insulin requirement was significantly higher in T1DM + CD compared with T1DM (P = 0.04). There were no differences in systolic blood pressure while diastolic blood pressure was significantly lower in T1DM + CD (P = 0.003). The prevalence/severity of microvascular complications was similar between the two groups. Glomerular filtration rate (eGFR) was significantly lower in T1DM + CD (100 ± 20 vs 110 ± 16 ml/min/1.73 m2, P = 0.007). Conclusions In patients with T1DM, the co-occurrence of long-term GFD-treated CD neither worsens glycemic control nor negatively impacts chronic microvascular complications. However, patients with T1DM + CD have lower eGFR values than those with T1DM alone.

Type 2 diabetes (T2DM) has become an important public health priority because of its rapidly increasing prevalence driven by an increasing prevalence of overweight/obesity. Given the primary role of obesity in the aetiology of T2DM, weight loss is considered by far the most essential means of controlling the disease. Indeed, growing evidence demonstrates that weight loss achieved either by bariatric surgery (BS) or very-low-calorie diet (VLCD) can lead to reversal of T2DM, at least in patients with short duration of disease. Indeed, a negative energy balance reduces fat content in the liver, in the pancreas as well as in skeletal muscle thus improving insulin action and insulin secretion; this translates into normalization of glucose control. These findings raised great interest regarding the feasibility and the implementation of these therapeutic options in clinical practice.

Context Diabetes mellitus is associated with gastrointestinal (GI) motility dysfunction, ranging from delayed to accelerated gastric emptying (GE). Objective To evaluate GE in patients with type 1 diabetes mellitus (T1DM) without chronic complications and to investigate its relation with postprandial glucose and GI hormone responses. Design Cross-sectional study. Setting/Participants Forty-two patients with T1DM free of chronic complications referred to Federico II University and 31 healthy controls similar for age, sex, and body mass index. Interventions/Main Outcome Measures GE was assessed by using the 13C-octanoate breath test with a standardized solid meal. During the meal, plasma glucose, ghrelin, and glucagon-like peptide 1 (GLP-1) responses were assessed, and GI symptoms were evaluated by a specific questionnaire. Results Patients with T1DM showed a significantly slower GE half-emptying time (GE t1/2) (113 ± 34 minutes) than did controls (89 ± 17 minutes; P < 0.001). Thirty-six percent of T1DM showed a delayed GE (t1/2 > 120 minutes), whereas all controls showed a normal GE. When patients with T1DM were stratified according to GE t1/2, postmeal glucose response was significantly different between those with delayed and those with normal GE (P = 0.013). In particular, patients with T1DM and delayed GE showed a significantly longer mean time to peak glucose than did patients with normal GE (P = 0.004). In addition, GE t1/2 was an independent predictor of the time to peak glucose (β = 0.329; P = 0.025). GLP-1 and ghrelin responses to the test meal, as well as the prevalence of GI symptoms, were similar between patients with T1DM and controls and between patients with T1DM with normal GE and those with delayed GE. Conclusions Delayed GE time is associated with a longer time to peak glucose. GE evaluation could be useful for individualizing the timing of preprandial insulin bolus in patients with T1DM.

Post-bariatric hypoglycemia (PBH) is an increasingly recognized long-term complication of bariatric surgery. The nutritional treatment of PBH includes a high-fiber diet and the restriction of soluble and high-glycemic index carbohydrates; however, these measures are not always enough to prevent hypoglycemia. We evaluated the efficacy of uncooked cornstarch, a low-glycemic index carbohydrate characterized by slow intestinal degradation and absorption, in addition to a high-fiber diet, for the treatment of PBH. We report the cases of two young women suffering from severe postprandial and fasting hypoglycemia following Roux-en-Y gastric bypass (RYGB). The patients underwent Continuous Glucose Monitoring (CGM) before and 12–16 weeks after the administration of uncooked cornstarch (respectively 1.25 g/kg b.w. and 1.8 g/kg b.w.) in addition to a high-fiber diet. In both patients, CGM showed more stable glucose levels throughout monitoring, a remarkable reduction of the time spent in hypoglycemia (

Idiopathic reactive hypoglycemia (IRH) is characterized by recurrent episodes of symptomatic hypoglycemia occurring within 4 hours after meals. The underlying mechanisms remain obscure.This study aimed to investigate the response of the glucoregulatory and gastrointestinal hormones to an oral glucose load (OGTT) in individuals with documented IRH.This was a cross-sectional study composed of outpatients referred to "Federico II" University of Naples.We enrolled subjects with IRH documented by a mixed meal under ordinary life conditions and healthy subjects as controls.We measured plasma glucose, insulin, glucagon-like peptide 1 (GLP-1), GIP, and glucagon response to a 75-g OGTT in cases and controls.Ten IRH and eight control subjects were enrolled. During the OGTT, mean plasma glucose tended to be lower in IRH than in control subjects, reaching a statistically significant difference at 240 minutes (T240) (43 ± 1.6 vs 72 ± 0.3 mg/dL; P = .001). Accordingly, the insulin response was higher in IRH than in control subjects (P.019) with a statistically significant difference (46%) at T90 (P = .045) and was associated with significantly lower glucagon levels in the late phase of the OGTT: at T120 (P = .031) and T180 (P = .048) in IRH than in control subjects. A greater GLP-1 response was found among IRH compared with control subjects (P = .005); GLP-1 peak was 2-fold higher in IRH individuals (9.77 ± 2.52 pmol/L) than in the control group (4.19 ± 0.53 pmol/L; P = .041). In the IRH group, GLP-1 peak inversely correlated with the nadir of plasma glucose (r = -0.66; P = .039). A multivariate analysis confirmed that GLP-1 peak independently predicted the plasma glucose nadir (β = -0.593; P = .026).GLP-1 may play a significant role in the pathogenesis of idiopathic IRH.

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.

Multiple acyl-CoA dehydrogenation deficiency (MADD) is an inborn disorder of fatty acid oxidation due to a defect in electron transfer to the respiratory chain. We describe the medical/nutritional management of a successful pregnancy in a 19-year-old woman with a known diagnosis of MADD. A high-carbohydrate, low-fat, six-meal diet supplemented with protein was prescribed to meet the nutritional needs during pregnancy. L-Carnitine supplementation was also progressively increased over the weeks. Serum acyl-carnitine profile revealed raised levels of chain-length C6-C14, which remained substantially unchanged during pregnancy. Serum amino acid profile was in the normal range indicating an adequate nutritional support. Pregnancy progressed uneventful and the patient gave birth to a healthy boy without any complication.A careful clinical monitoring associated with an adequate medical/nutritional management may improve pregnancy outcome in women with MADD.

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. 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. The two groups had similar pre-intervention characteristics. After the intervention, mean body weight decreased significantly in both groups (p

Bariatric surgery is recognized as a highly effective therapy for obesity since it accomplishes sustained weight loss, reduction of obesity-related comorbidities and mortality, and improvement of quality of life. Overall, bariatric surgery is associated with a 42% reduction of the cardiovascular risk and 30% reduction of all-cause mortality. This review focuses on some nutritional consequences that can occur in bariatric patients that could potentially hinder the clinical benefits of this therapeutic option. All bariatric procedures, to variable degrees, alter the anatomy and physiology of the gastrointestinal tract; this alteration makes these patients more susceptible to developing nutritional complications, namely, deficiencies of macro- and micro-nutrients, which could lead to disabling diseases such as anemia, osteoporosis, protein malnutrition. Of note is the evidence that most obese patients present a number of nutritional deficits already prior to surgery, the most important being vitamin D and iron deficiencies. This finding prompts the need for a complete nutritional assessment and, eventually, an adequate correction of pre-existing deficits before surgery. Another critical issue that follows bariatric surgery is post-operative weight regain, which is commonly associated with the relapse of obesity-related co-morbidities. Nu-tritional complications associated with bariatric surgery can be prevented by life-long nutritional monitoring with the administration of multi-vitamins and mineral supplements according to the patient's needs.

To investigate the anthropometric and metabolic correlates of different patterns of left ventricular (LV) geometry in a cohort of outpatient children with high prevalence of obesity.Anthropometric measures, lipid profile, blood pressure (BP), fasting plasma glucose (FPG), and echocardiographic variables were evaluated in 281 white children (6-16 years), of whom 105 were obese and 105 were morbidly obese. Patterns of LV geometry were defined as follows: normal geometry, eccentric LV hypertrophy (LVH), concentric LV remodeling, and concentric LVH.One hundred forty-eight children exhibited normal LV geometry, 53 eccentric LVH, 36 concentric LV remodeling, and 44 concentric LVH. The 4 groups differed in body mass index, waist circumference, waist-to-height ratio, triglycerides/high-density lipoprotein cholesterol ratio (Tg/HDL-C), and BP (P.05-.0001). A statistically significant impairment of diastolic function (expressed as greater E/E', P.002) was observed across patterns of LV geometry. Among anthropometric measures, waist-to-height ratio showed better performance in relation to LVH, with an optimal cut-point of 0.58, compared with body mass index and waist circumference. Children with concentric LVH exhibited the worst metabolic risk profile, with greater prevalence of visceral obesity, high Tg/HDL-C, high BP, and high-normal FPG, than children with normal LV geometry.In children with high levels of obesity, an unfavorable "cardiometabolic phenotype" can be identified, which includes concentric LVH, visceral obesity, high BP, high Tg/HDL-C, and high-normal FPG.

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. 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. Age was 47 ± 8 years (mean ± SD) in bariatric surgery and 56 ± 9 years in medical treatment group (p

The achievement of optimal post-prandial (PP) glucose control in patients with type 1 diabetes (T1DM) remains a great challenge. This review summarizes the main factors contributing to PP glucose response and discusses the likely reasons why PP glucose control is rarely achieved in T1DM patients. The macronutrient composition of the meal, the rate of gastric emptying and premeal insulin administration are key factors affecting the PP glucose response in T1DM. Although the use of continuous insulin infusion systems has improved PP glucose control compared to conventional insulin therapy, there is still need for further ameliorations. T1DM patients frequently present a delayed gastric emptying (GE) that produces a lower but more prolonged PP hyperglycemia. In addition, delayed GE is associated with a longer time to reach the glycemic peak, with a consequent mismatch between PP glucose elevation and the timing of premeal insulin action. On this basis, including GE time and meal composition in the algorithms for insulin bolus calculation of the insulin delivery systems could be an important step forward for optimization of PP glucose control in T1DM.

Objective To evaluate the relationship between estimated glomerular filtration rate (eGFR) and cardiometabolic risk factors (CMRF) in an outpatient pediatric population with high prevalence of obesity. Design and Methods eGFR was evaluated in 901 children unselected for chronic kidney disease of whom 694 were overweight/obese (6-16 years) and 207 were age- and sex-matched normal weight (NW). We generated three categories of eGFR: mild-low eGFR ( 80th percentile) and intermediate eGFR (20-80th percentile), considered as the reference category Results Children with either mild-low or high eGFR category showed a 2-4 fold higher Odds ratio of high blood pressure, left ventricular hypertrophy, and microalbuminuria compared with children of the intermediate eGFR category. In addition, children with mild-low eGFR levels showed a 1.5-2 fold higher Odds ratio of impaired fasting glucose and high white blood cell count compared with children with intermediate eGFR levels. Conclusions In outpatient children with high prevalence of obesity, children with either mildly reduced or high eGFR have an increased burden of CMRF. Children with eGFR < 97 mL/min/1.73 m2 show a worse CMR profile. This finding supports the usefulness to assess eGFR to identify children with unfavorable CMR profile.

OBJECTIVE To evaluate whether impaired fasting glucose (IFG) or the combination of IFG and impaired glucose tolerance (IGT) is associated with progressive abnormalities of cardiac geometry and function. RESEARCH DESIGN AND METHODS We studied 562 nondiabetic (311 women), nonhypertensive participants of the second Strong Heart Study exam, without prevalent cardiovascular (CV) disease and with estimated glomerular filtration rate ≥60 mL/min/1.73 m2 (age 46–65 years, 198 with isolated IFG [35%], and 132 with combined IFG and IGT [23%]). Anthropometric parameters, insulin resistance, fibrinogen, C-reactive protein (CRP), lipid profile, blood pressure (BP), and echocardiographic parameters were compared with 232 participants with normal glucose tolerance (NGT). RESULTS BMI, prevalence of central obesity, homeostatic model assessment index of insulin resistance, plasma triglycerides, fibrinogen, and CRP increased progressively across categories of glucose intolerance (P < 0.0001), with the IFG+IGT group having higher values than those with isolated IFG (0.05 < P < 0.0001). Compared with NGT, both IFG and IFG+IGT exhibited greater left ventricular (LV) mass (P < 0.0001) and lower Doppler early peak rapid filling velocity to peak atrial filling velocity ratio (P < 0.005), without differences in LV systolic function. The odds of LV hypertrophy (LV mass index >46.7 in women or >49.2 g/m2.7 in men) was 3.5 in IFG participants (95% CI 0.68–17.76; P = NS) and 9.76 (2.03–46.79; P = 0.004) in IFG+IGT, compared with NGT, after adjustment for age, sex, heart rate, systolic BP, and waist circumference (WC). In the overall sample, LV mass index was associated with WC (P = 0.033), CRP (P = 0.027), and 2-h oral glucose tolerance test (P = 0.001) independently of confounders. CONCLUSIONS Cardiometabolic profile and markers of inflammation are more severely altered in men and women with both IFG and IGT compared with those with IFG alone. These individuals, in the absence of hypertension, have a 10-fold greater probability of preclinical CV disease (LV hypertrophy).

To evaluate whether the pediatric metabolic syndrome (MetS) or its factors are useful to detect subclinical abnormalities of cardiac, liver, and glomerular damage in an outpatient population.The population study included 799 children (age 10 ± 3 years, mean ± SD), 24% of whom were normalweight, 25% overweight, and 51% obese. Alanine-aminotransferase (ALT) levels, estimated glomerular filtration rate (eGFR) and HOMA-IR were analyzed in all children. Microalbuminuria (MA) and left ventricular (LV) geometry and function were evaluated in 501 and 247 children, respectively. MetS was defined using Cook's criteria.MetS was diagnosed in 131 children (16%). Children with MetS+ and MetS- were similar for age, gender and Tanner stage distribution. Children with MetS+ showed higher ALT levels (31 ± 19 vs 21 ± 11 IU/L, p0.0001), LV mass (39 ± 10 vs 34 ± 10 g/h(2.7), p0.001) and relative wall thickness (0.37 ± 0.06 vs 0.35 ± 0.05, p0.01) than MetS-. The two groups were similar for MA and eGFR. At multiple logistic regression analysis, children MetS+ showed a higher risk (OR, 95% Cl) adjusted for confounding factors, of high ALT levels (1.71, 1.12-2.59, p=0.012) and concentric LV hypertrophy (2.17, 1.01-4.66, p=0.047) than children MetS-. The risk of preclinical liver and cardiac damage associated with the MetS phenotype was not higher than predicted by its single components.Children with MetS show a 2-fold greater risk of having high ALT levels and concentric LV hypertrophy. However, the risk of subclinical manifestations of liver and cardiac damage can be predicted equally well by the single components of the syndrome.

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.

The aim of the study was to analyze the prevalence of prehypertension (PH) in obese (OB) children and its relation with estimated glomerular filtration rate (eGFR) and left ventricular (LV) function.The study included 447 OB and 131 normal-weight children. PH was defined according to the criteria proposed by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. Insulin sensitivity was evaluated by HOMA(IR), and eGFR was calculated by Schwartz's formula. LV function was analyzed by echocardiography in 165 OB children.PH was observed in 79 OB children (17.7%) and in 2 (1.5%) controls. Among OB children, those with PH had greater percentage of males (P0.05), higher level of body mass index (BMI) (P0.001), waist circumference (WC) (P0.005), and HOMA(IR) (P0.001), compared to PH- children. The two groups did not differ for eGFR and LV function. At logistic regression analysis, PH was independently associated with male gender (P0.025) and HOMA(IR) (P0.002). Gender analysis showed that boys with PH presented higher levels of BMI (P0.005), WC (P0.01), HOMA(IR) (P0.001), and triglycerides (P0.005) compared to PH- boys. Females with PH were older and in more advanced postpubertal stage, had higher BMI, WC (P0.05, for all), and HOMA(IR) (P0.025), compared to PH- girls.In a population of outpatient OB children, the prevalence of PH was 17.7% and boys were more likely than girls to have PH. This condition is characterized by insulin resistance in both sexes but no impairment in glomerular and LV function.

Alanine aminotransferase (ALT) elevations are considered a surrogate marker of nonalcoholic liver disease and predict later development of diabetes and metabolic syndrome in adults. The aim of the present study is to evaluate the prevalence of high ALT levels in obese children using updated and sex-related cutoff ALT value (ALT >30 IU/L for boys and >19 IU/L for girls). We also analyzed the association between ALT levels and metabolic factors in the 2 sexes. Three-hundred fifty-eight obese children (168 boys and 190 girls; age range, 6-16 years) were studied. Inclusion criteria were as follows: obesity, defined by an individual body mass index (BMI) greater than or equal to the 95th percentile for age and sex; negativity of markers for viral hepatitis; and no alcohol consumption. Two hundred six nonobese children (92 boys and 114 girls; age range, 6-16 years) served as a control group for ALT levels. The percentage of obese children with elevated ALT was 36% in boys and 55% in girls. Obese boys with ALT greater than 30 IU/L showed higher mother's BMI (P < .025), BMI, waist circumference, insulin resistance evaluated with homeostasis model assessment (HOMA-IR) index (P < .0001, for all), and systolic and diastolic blood pressure (P < .025, for both) compared with those with ALT not exceeding 30 IU/L. The ALT levels correlated positively with mother's BMI, BMI, waist circumference, HOMA-IR, triglycerides, and blood pressure. In linear regression analysis, waist circumference was the only independent factor associated with ALT level (beta = 0.370, t = 3,905, P < .0001). Obese girls with ALT greater than 19 IU/L exhibited lower age (P < .025) and higher triglycerides (P < .0001) than girls with ALT not exceeding 19 IU/L. The ALT levels correlated positively with triglycerides and HOMA-IR and negatively with age and Tanner stage. In linear regression analysis, ALT levels were independently associated only with triglycerides (beta = 0.330, t = 4.588, P < .0001). Our study shows that a high proportion of obese children present elevated ALT levels. This abnormality is associated in boys, more than in girls, with preclinical traits of the metabolic syndrome. The adoption of sex-related cutoff of ALT levels is desirable also for the pediatric population.

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.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), p0.0001). 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), p0.0001) and LVM(i) (32.1+/-6.5 vs 37.1+/-8.5 g/h(2.7), p0.01). Among obese children a positive correlation (standardized for age and gender) was found between LVM(i) and BMI (r=0.282, p0.01) and WHtR (r=0.334, p0.0001). 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).Obese children show an increased LVM(i) and a preserved LV function. Central adiposity is the major determinant of left ventricular mass.

Left ventricular (LV) diastolic dysfunction is considered the earliest manifestation of diabetic cardiomyopathy. Whether LV abnormalities identified at rest by echocardiography predict peak exercise LV performance in uncomplicated type 1 diabetes mellitus (DM1) is largely unknown.We evaluated LV size, mass, and functions and peak exercise LV performance in 25 subjects with uncomplicated DM1 (median disease duration 13.5 years, 1-30 years) and in 56 non-DM subjects (24 hypertensive (HT) and 32 normotensive (NT)). Overt coronary heart disease, significant microangiopathy and central autonomic neuropathy were minimized by exclusion criteria. Peak exercise LV stroke index (SVi), cardiac index (COi), LV ejection fraction (EF), LV end-diastolic and end-systolic volumes were assessed noninvasively. No subject was on cardiovascular medications at the time of evaluation.In our study, DM1 did not show LV hypertrophy or impaired LV systolic function at rest. Prevalence of diastolic dysfunction was 8% among DM1, 18% among NT and 50% among HT. Pre-exercise heart rate, SVi, COi, and peak exercise blood pressure (BP) and heart rate were comparable among the three groups, but peak exercise LV EF, SVi and COi were lower in DM1 than in HT and NT independent to covariates (p0.05). In separate analyses, DM1 predicted lower peak exercise SVi (B=-6.2) and COi (B=-1.6, both p0.05) independently. Within DM1, glycated haemoglobin (HbA1c) and disease duration did not predict peak exercise LV systolic function.Our study suggests that uncomplicated DM1 may be associated with subnormal LV contractility reserve, which might not be predicted by LV dysfunction evaluated at rest.

Coronary flow reserve (CFR) may be reduced even in the absence of coronary artery disease. We investigated the determinants of CFR impairment in Type 2 diabetes mellitus (DM2) and in arterial hypertension (HTN) without epicardial coronary artery stenosis.Twenty-eight patients with DM2 and 27 with HTN, both with normal coronary angiography, and 18 healthy controls underwent transthoracic echocardiography, including Doppler recording of the distal left anterior descending artery, at rest as well as after high-dose dipyridamole. Coronary flow reserve was calculated as the hyperemic to resting coronary diastolic peak velocities ratio.The three groups were comparable for sex, age, and heart rate. Systolic and mean blood pressures were higher in DM2 and HTN patients than in control subjects. Diabetic and hypertensive patients had a higher left-ventricular mass index (LVMi) and relative wall thickness, impaired diastolic indexes, and lower CFR compared with control subjects (P = .02 and P = .03, respectively) because of lower hyperemic coronary velocity (P = .005 and P = .004, respectively). After a multilinear regression analysis (using age, sex, HTN status, DM2 status, smoking, total cholesterol/HDL-cholesterol ratio, and LVMi as potential determinants), the LVMi increase was the main predictor of the reduction of CFR, adjusted for mean BP (P.0001), in the pooled population, with a minor contribution of age (P = .03), HTN status (P = .02), and DM2 status (P = .03).In Type 2 DM and HTN without epicardial coronary stenosis, an impairment of CFR is demonstrable. This is partly explained by an increased left-ventricular mass, able to condition the hyperemic stimulation of myocardial blood flow.

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. 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. 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

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.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.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; P0.001), 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, P0.001), FMD (Z=-4.26, P0.001) and NMD (Z=-3.81, P0.001).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.

Background Phenylketonuria (PKU) is an autosomal recessive disorder caused by the deficiency of phenylalanine hydroxylase that catalyzes the conversion of phenylalanine to tyrosine, using tetrahydrobiopterin (BH4) as coenzyme. Besides dietary phenylalanine restriction, new therapeutic options are emerging, such as the treatment with BH4 in subgroups of PKU patients responding to a loading test with BH4. Methods A no-profit open-label interventional trial with long-term oral BH4 therapy, sponsored by the Italian Medicines Agency (AIFA), was performed in a group of 17 PKU patients resulted as BH4 responders among 46 subjects analyzed for BH4-responsiveness (prot. FARM5MATC7). We report on efficacy and safety data of BH4 therapy and analyze factors predicting BH4-responsiveness and long-term response to BH4. A BH4-withdrawal test was used as a proof of the efficacy of long-term therapy with BH4. Results Forty-four percent of the patients responded to the 48 h-long loading test with BH4. All the phenotypic classes were represented. Genotype was the best predictor of responsiveness, along with lower phenylalanine levels at diagnosis, higher tolerance and lower phenylalanine/tyrosine ratio before the test. In BH4 responder patients, long-term BH4 therapy resulted safe and effective in increasing tolerance while maintaining a good metabolic control. The BH4 withdrawal test, performed in a subset of patients, showed that improved tolerance was directly dependent on BH4 assumption. Tolerance to phenylalanine was re-evaluated in 43.5% of patients and was longitudinally analyzed in 5 patients. Conclusions Long-term treatment with BH4 is safe and effective in increasing tolerance to phenylalanine. There is real need to assess the actual tolerance to phenylalanine in PKU patients to ameliorate quality of life, improve nutritional status, avoiding unnecessarily restricted diets, and interpret the effects of new therapies for PKU. Electronic supplementary material The online version of this article (doi:10.1186/s13023-015-0227-8) contains supplementary material, which is available to authorized users.

The aim of this article is to evaluate food properties able to influence specific physiological targets that may be helpful for the prevention and management of overweight and diabetes.Observational and intervention studies have clearly shown that type 2 diabetes can be prevented by lifestyle measures, including reduced energy intake to induce a modest but sustained weight reduction, together with changes in diet composition.Foods can be regarded as functional if proven to affect beneficially one or more target functions in the body, beyond adequate nutritional effects, in a way relevant to improved state of health and well-being, reduction of risk of diseases, or both. Functional foods might have a particularly high impact for prevention or treatment of overweight and diabetes for which, more than in many other fields, the link between nutrition, biological responses and diseases is clearly established. Functional foods for obesity should be able to influence the energy balance equation regulated by the control of energy intake or of energy dissipated as heat (thermogenesis). For prevention of type 2 diabetes, several unmodified foods with functional properties have already been identified (low saturated fat products, vegetables, fruit, wholegrain foods, low glycemic index starchy foods). Overall, the available evidence on functional foods so far identified in this field is incomplete: the major gap is the lack of diet-based intervention trials of sufficient duration to be relevant for the natural history of diseases like overweight and diabetes.

The effect of known diabetes on in-hospital mortality from ischemic stroke is still debated whereas the role of unknown diabetes is virtually unexplored. This study evaluates the impact of known and unknown diabetes on in-hospital mortality from ischemic stroke.We have retrospectively evaluated the records of 286 consecutive cases of ischemic stroke hospitalized from January 1998 to December 2000 at the Department of Internal Medicine of the General Hospital located in the western area of Naples. Fasting plasma glucose level7 mmol/L identified non diabetic subjects. Known diabetes mellitus was diagnosed by history of diabetes and/or hypoglycemic therapy, unknown diabetes was defined as a random plasma glucose levelor = 11 mmol/L and/or in-hospital fasting glucoseor = 7 mmol/L on two or more occasions. Severity of stroke was defined using the Canadian Neurological Score (CNS). According to these criteria, 144 subjects were non diabetics, 99 had known diabetes and 43 had unknown diabetes. Subjects with known diabetes showed a higher prevalence of female sex, hypertension and increased triglyceride levels as compared with non diabetic subjects (p0.01). Subjects with unknown diabetes were older (p0.01) and showed a more severe CNS (3.4 +/- 2.7) than non diabetic and diabetic subjects (5.8 +/- 2.6 and 5.8 +/- 2.6, respectively; p0.01). In-hospital mortality was significantly higher in the unknown diabetic group (44%) as compared with known diabetic (15%) and non diabetic groups (12%) (p0.001). This finding was independent of neurological deficit, age, atrial fibrillation and history of previous stroke.Our study shows that unknown diabetes, more than known diabetes, is a strong risk factor for in-hospital mortality in subjects with acute ischemic stroke.

Diabet. Med. 28, 227–229 (2011) Abstract 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), HbA1c 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

BACKGROUND: Insulin resistance was found in some but not in all previous studies of non-diabetic first degree relatives of Type 2 diabetic patients. Small study groups, ethnic differences and/or non-optimal techniques may explain the conflicting results. AIM: To study the impact of a family history of Type 2 diabetes on insulin action in a large group of non-diabetic Europeans using the 'gold standard' euglycaemic hyperinsulinaemic clamp technique. METHODS: Non-diabetic subjects (n = 235) with a positive family history of Type 2 diabetes (FH+) and 564 subjects with no family history of diabetes (FH-) were recruited from The European Group of Insulin Resistance (EGIR) database. This database includes measurements of insulin action using the insulin clamp technique (1 mU/kg per min) in normal glucose-tolerant individuals from 20 different European centres. In a subset of subjects the measurements were performed in combination with indirect calorimetry (n = 80 vs. 213 with and without family history of Type 2 diabetes). RESULTS: The body mass index (BMI) was slightly higher in FH+ compared with FH- (26.7 +/- 4.6 vs. 25.1 +/- 4.7 kg/m(2); P < 0.02). After correction for covariates according to differences between investigators and subject characteristics including BMI (multiple regression analysis), insulin-stimulated glucose disposal was lower in FH+ compared with FH- (P < 0.00001). Insulin-stimulated glucose oxidation was slightly increased in FH+ compared with FH-, and insulin-stimulated non-oxidative glucose metabolism was consequently markedly reduced in FH+ compared with FH- (P < 0.0005). CONCLUSION: Insulin resistance is present in European non-diabetic relatives of Type 2 diabetic patients. The insulin resistance is independent of degree of obesity and is restricted solely to the pathway of non-oxidative glucose metabolism. (Less)

It is controversial whether transport adaptation takes place in chronic or acute hyperglycemia. Blood-brain barrier glucose permeability and regional brain glucose metabolism (CMRglc) was studied in acute hyperglycemia in six normal human subjects (mean age, 23 yr) using the double indicator method and positron emission tomography and[ 18F]fluorodeoxyglucose as tracer. The Kety-Schmidt technique was used for measurement of cerebral blood flow (CBF). After 2 h of hyperglycemia (15.7 ± 0.7 mmol/L), the glucose permeability-surface area product from blood to brain remained unchanged (0.050 ± 0.008 vs. 0.059 ± 0.031 mL/100 g·min). The unidirectional clearance of[ 18F]fluorodeoxyglucose (K1*) was reduced from 0.108 ± 0.011 to 0.061 ± 0.005 mL/100 g·min (P < 0.0004). During hyperglycemia, global CMRglc remained constant (21.4 ± 1.2 vs. 23.1 ± 2.2 μmol/100 g·min, normo- and hyperglycemia, respectively). Except for a significant increase in white matter CMRglc, no regional difference in CMRglc was found. Likewise, CBF remained unchanged. The reduction in K1* was compatible with Michaelis-Menten kinetics for facilitated transport. Our findings indicate no major adaptational changes in the maximal transport velocity or affinity to the blood-brain barrier glucose transporter. Finally, hyperglycemia did not change global CBF or CMRglc.

Aims We examined the effects of growth hormone administration on the sympathetic nervous system in patients with idiopathic dilated cardiomyopathy. Background Growth factor therapy is emerging as a new potential option in the treatment of heart failure. Although growth hormone provides functional benefit in the short term, it is unknown whether it affects the sympathetic nervous system, which plays a role in the progression of heart failure. Methods Seven patients with idiopathic cardiomyopathy received 3 months treatment with recombinant human growth hormone (0·15–0·20 IU.kg−1.week−1). Standard medical therapy was unchanged. Myocardial norepinephrine release, both at rest and during submaximal physical exercise, plasma aldosterone, and plasma volume were measured before and after growth hormone treatment. Myocardial norepinephrine release was assessed from arterial and coronary venous plasma concentrations of unlabelled and tritiated norepinephrine and coronary plasma flow (thermodilution). Results Growth hormone induced a significant fall in myocardial norepinephrine release in response to physical exercise (from 180±64 to 99±34ng.min−1; P

Abstract In population surveys, blood pressure and plasma insulin concentration are related variables, but the association is confounded by age and obesity. Whether insulin resistance is independently associated with higher blood pressure in normal subjects is debated. We analyzed the database of the European Group for the Study of Insulin Resistance, made up of nondiabetic men and women from 20 centers, in whom insulin sensitivity was measured by the euglycemic insulin clamp. After excluding subjects aged ≥70 years, those with severe obesity (body mass index [BMI] >40 kg · m −2 ), and those with abnormal blood pressure values (≥140/90 mm Hg), 333 cases (ages 18 to 70 years; BMI, 18.4 to 39.8 kg · m −2 ) were available for analysis. In univariate analysis, both systolic and diastolic blood pressures were inversely related to insulin sensitivity, with r values of 0.18 ( P P r , 0.15 and 0.19; P −1 · kg −1 was +1.4 mm Hg, similar to that associated with a 10-year difference in age. Although insulin levels and insulin action were reciprocally interrelated, diastolic blood pressure varied as a simultaneous function of both. In normotensive, nondiabetic Europeans, insulin sensitivity and age are significant, mutually independent correlates of blood pressure, whereas body mass is not. The relation of blood pressure to both insulin action and circulating insulin levels is compatible with distinct influences on blood pressure by insulin resistance and compensatory hyperinsulinemia.

Very little is known about the atherosclerotic risk in patients with childhood-onset growth hormone deficiency (GHD). Such data may be relevant to reconstructing the natural course of the cardiovascular abnormalities associated with GHD. To this end, the intima-media thickness (IMT) of the carotid arteries and the vascular risk factors were evaluated in 14 childhood-onset GHD patients (age 25 +/- 1 yr, BMI 22 +/- 0.6 Kg/m2) and in 14 age-, sex-, and BMI-matched control subjects. IMT was greater in GHD patients (0.83 +/- 0.06 and 0.81 +/- 0.06 mmol/L for the right and left carotid artery) than in controls (0.64 +/- 0.03 and 0.64 +/- 0.04 mmol/L, P < 0.01 and P < 0.02, respectively). Serum total and lipoprotein cholesterol, and serum total triglycerides did not differ between the two groups. However, a significant increase in low density lipid triglycerides was present in GHD patients (0.27 +/- 0.02 mmol/L) compared with controls (0.19 +/- 0.01; P = 0.007). No difference was found in plasma fibrinogen and serum Lp(a) levels. Plasma glucose and insulin concentrations were similar in GHD and control subjects both in the fasted state and after an oral glucose load. In conclusion, young patients with childhood-onset GHD show an increased IMT in the absence of clear-cut abnormalities of the classic vascular risk factors. This suggests a role for GH deficiency per se in increasing the atherosclerotic risk.

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. 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. After BS, there was a significant reduction in body weight (p

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.Overweight/obese American Indians from the Strong Heart Study population, without diabetes and with FBG ≤ 110 mg/dL and with GFR60 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 p0.001); they also had a greater prevalence of hypertension, impaired glucose tolerance (IGT) or OGTT-diabetes than participants with normal FFM (all p0.003) and a near 2-fold greater probability of significant proteinuria (p0.01). RFFMD was more frequent in women than in men: significant sex-RFFMD interactions were found for BMI and waist circumference (both p0.0001).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.

To evaluate the predictive factors of insulin requirement in newly diagnosed patients with unclassifiable diabetes, 54 consecutive patients, aged less than 35 years, were prospectively followed for 3 years or more. At entry, haemoglobin HbA1c, basal and stimulated C-peptide concentrations, HLA phenotype, islet cell antibodies (ICA) status, and serum levels of soluble CD8 antigen (sCD8) were evaluated. After a median time of 9 (range 2-32) months, 31 patients (group 1) required insulin therapy, whereas 23 patients (group 2) remained non-insulin-requiring after 36 months. Group 1 patients were younger (P0.05) and had higher HbA1c and sCD8 serum levels (P0.0001), respectively), a higher frequency of ICA positivity and of HLA DR3 and/or DR4 phenotype (P0.005 and P0.0001, respectively), and lower C-peptide concentrations (P0.005 and P0.0001, basal and stimulated, respectively) than group 2. The sensitivity, specificity, positive and negative predictive value, and overall accuracy for the subsequent insulin requirement were: sCD8 serum levels (737 U/ml), 100%, 65%, 79%, 100% and 85%, respectively; stimulated C-peptide (0.60 nmol/l), 71%, 96%, 96%, 74% and 81%, respectively; and ICA positivity (20 JDFU), 45%, 91%, 87%, 55% and 65%, respectively. Thus, higher sCD8 serum levels, low stimulated C-peptide concentrations and ICA positivity are the most powerful predictors of subsequent recourse to insulin therapy in young, newly detected patients with unclassifiable diabetes.

with the control group (p

Cardiac hypertrophy is a physiologic response that allows the heart to adapt to an excess hemodynamic load. We hypothesized that inducing cardiac hypertrophy with recombinant human growth hormone might be an effective approach to the treatment of idiopathic dilated cardiomyopathy, a condition in which compensatory cardiac hypertrophy is believed to be deficient.Seven patients with idiopathic dilated cardiomyopathy and moderate-to-severe heart failure were studied at base line, after three months of therapy with human growth hormone, and three months after the discontinuation of growth hormone. Standard therapy for heart failure was continued throughout the study. Cardiac function was evaluated with Doppler echocardiography, right-heart catheterization, and exercise testing.When administered at a dose of 14 IU per week, growth hormone doubled the serum concentrations of insulin-like growth factor I. Growth hormone increased left-ventricular-wall thickness and reduced chamber size significantly. Consequently, end-systolic wall stress (a function of both wall thickness and chamber size) fell markedly (from a mean [+/-SE] of 144+/-11 to 85+/-8 dyn per square centimeter, P0.001). Growth hormone improved cardiac output, particularly during exercise (from 7.4+/-0.7 to 9.7+/-0.9 liters per minute, P=0.003), and enhanced ventricular work, despite reductions in myocardial oxygen consumption (from 56+/-6 to 39+/-5 ml per minute, P=0.005) and energy production (from 1014+/-100 to 701+/-80 J per minute, P=0.002). Thus, ventricular mechanical efficiency rose from 9+/-2 to 21+/-5 percent (P=0.006). Growth hormone also improved clinical symptoms, exercise capacity, and the patients' quality of life. The changes in cardiac size and shape, systolic function, and exercise tolerance were partially reversed three months after growth hormone was discontinued.Recombinant human growth hormone administered for three months to patients with idiopathic dilated cardiomyopathy increased myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement in hemodynamics, myocardial energy metabolism, and clinical status.

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.

To determine the role of insulin and free fatty acid (FFA) concentration in the regulation of FFA metabolism, forearm FFA fluxes were quantified in 16 healthy volunteers by combining the forearm perfusion technique with the infusion of [3H]palmitate. Three groups of studies were performed. In study 1 (n = 6), a systemic insulin infusion (1.2 mU/kg.min) was performed for 120 min while euglycemia was maintained by a variable glucose infusion. In Study 2 (n = 5), insulin (0.05 mU/kg.min) was infused into the brachial artery to expose the forearm tissues to the same insulin level as in study 1. In study 3 (n = 5), heparin was infused to raise plasma FFA concentration to 1-1.5 mmol/L. At 60 min, an intrabrachial insulin infusion was added as in study 2 and maintained for 60 min. During systemic insulin infusion, plasma FFA concentration fell to 0.09 +/- 0.02 mmol/L. Forearm FFA uptake (FFA-U) decreased from the basal value of 2.54 +/- 0.52 to 0.95 +/- 0.10 mumol/L.min (P < 0.05). Likewise, forearm FFA release (FFA-R) fell to 1.0 +/- 0.31 mumol/L.min (P < 0.05). With local insulin administration, both FFA levels and FFA-U remained unchanged, whereas FFA-R was markedly inhibited (from 1.78 +/- 0.23 to 1.04 +/- 0.24 mumol/L.min; P < 0.05). In study 3 (heparin infusion), FFA levels rose to 1.17 +/- 0.12 mmol/L due to a 4-fold increase in FFA-R (from 1.18 +/- 0.36 to 6.92 +/- 2.40 mumol/L.min; P < 0.05). FFA-U rose from the basal value of 2.50 +/- 0.82 to 6.92 +/- 1.95 mumol/L.min (P < 0.05). Addition of intrabrachial insulin did not modify FFA-U, whereas heparin activation of FFA-R was only partially antagonized (4.53 +/- 2.40 mumol/L.min; 0.01 < P < 0.05 vs. heparin alone). The data demonstrate that plasma FFA concentration is the main determinant of forearm FFA transport. Insulin exerts a direct inhibitory effect on FFA release and affects tissue FFA transport only indirectly through the fall in circulating FFA.

OBJECTIVE To evaluate whether the high triglyceride-to-HDL cholesterol (TG-to-HDL-C) ratio is associated with cardiometabolic risk (CMR) factors and preclinical signs of organ damage in an outpatient population of white children and adolescents. RESEARCH DESIGN AND METHODS The study population included 884 subjects (aged 6–16 years), of whom 206 (23%) were normal weight, 135 (15%) were overweight, and 543 (61%) were obese. Biochemical variables were analyzed in the whole sample, whereas homocysteine and left ventricular (LV) geometry and function were evaluated in 536 and 258 children, respectively. RESULTS The percentage of pubertal children (P < 0.001), as well as measurements of BMI, waist circumference, homeostasis model assessment of insulin resistance, white blood cell count, alanine aminotransferase (ALT), systolic blood pressure (P < 0.0001, for all), creatinine (P < 0.001), and diastolic blood pressure (P < 0.02), increased from the lowest to the highest tertile of the TG-to-HDL-C ratio. Age, sex, homocysteine, and glomerular filtration rate did not change. Moreover, interventricular septum thickness, relative wall thickness, and LV mass index (P = 0.01 to P < 0.0001) increased across tertiles of the TG-to-HDL-C ratio. Children with a TG-to-HDL-C ratio ≥2.0 showed a two- to threefold higher risk of elevated ALT levels and concentric LV hypertrophy than those with a TG-to-HDL-C ratio CONCLUSIONS The high TG-to-HDL-C ratio is associated with several CMR factors and preclinical signs of liver and cardiac abnormalities in the outpatient, white pediatric population. Thus, a TG-to-HDL-C ratio ≥2.0 may be useful in clinical practice to detect children with a worsened CMR profile who need monitoring to prevent cardiovascular disease in adulthood.