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Background: The recommended protein intake for the elderly is 25–30 g at main meals, with at least 2500–2800 mg of leucine at each meal. There is still little evidence regarding the amount and distribution of protein and leucine intake with meals in the elderly with type 2 diabetes (T2D). In this cross-sectional study, we evaluated protein and leucine intake at each meal in elderly patients with T2D. Methods: A total of 138 patients (91 men and 47 women) with T2D, aged 65 years or older, were included. Participants performed three 24-h dietary recalls for the evaluation of their dietary habits and protein and leucine intake at meals. Results: The average protein intake was 0.9 ± 0.2 g/kg body weight/day, and only 23% of patients complied with the recommendations. The average protein intake was 6.9 g at breakfast, 29 g at lunch, and 21 g at dinner. None of the patients reached the recommended protein intake at breakfast; 59% of patients complied with the recommendations at lunch; and 32% at dinner. The average leucine intake was 579 mg at breakfast, 2195 g at lunch, and 1583 mg at dinner. The recommended leucine intake was not reached by any patient at breakfast, by 29% of patients at lunch, and by 13% at dinner. Conclusions: Our data show that, in elderly patients with T2D, the average protein intake is low, particularly at breakfast and dinner, and that leucine intake is remarkably lower than the recommended levels. These data raise the need to implement nutritional strategies capable of increasing protein and leucine intake in the elderly with T2D.

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

Exposure to artificial light at night (ALAN) has been associated with disruption of the circadian system, which has been pointed out to have detrimental effects on health. Exposure to outdoor ALAN is very frequent in industrialised countries due to nocturnal light pollution and the relevant involvement of the total workforce in shift work and night work. Ecological and epidemiologic studies highlight the association between exposure to ALAN and several diseases, mainly obesity and cancer. More recently, also indoor ALAN exposure has been investigated. Among several multifactorial mechanisms linking ALAN exposure and health risks, suppression of melatonin secretion plays a pivotal role leading to alterations in circadian rhythm patterns, that are detrimental in terms of appetite regulation, and dysfunctions in metabolic signalling and cell growth in cancer. In addition, gut dysbiosis, inflammation, hypovitaminosis D, imbalance in cytokine secretion and levels are responsible for the multiple relationship linking circadian dysregulation due to ALAN exposure and obesity, and cancer. Therefore, the current manuscript summarises human and basic studies pointing out the impact of ALAN exposure on health, mostly focusing on obesity and cancer. Based on extant evidence, prevention strategies for obesity and cancer should be prompted, targeting exposure to ALAN. (C) 2022 Published by Elsevier Ltd.

The study compares the performance of the European Society of Cardiology (ESC) risk criteria and the Steno Type 1 Risk Engine (ST1RE) in the prediction of cardiovascular (CV) events.456 adults with type 1 diabetes (T1D) were retrospectively studied. During 8.5 ± 5.5 years of observation, twenty-four patients (5.2%) experienced a CV event. The predictive performance of the two risk models was evaluated by classical metrics and the event-free survival analysis.The ESC criteria show excellent sensitivity (91.7%) and suboptimal specificity (64.4 %) in predicting CV events in the very high CV risk group, but a poor performance in the high/moderate risk groups. The ST1RE algorithm shows a good predictive performance in all CV risk categories. Using ESC classification, the event-free survival analysis shows a significantly higher event rate in the very high CV risk group compared to the high/moderate risk group (p 0.0019). Using the ST1RE algorithm, a significant difference in the event-free survival curve was found between the three CV risk categories (p 0.0001).In T1D the ESC classification has a good performance in predicting CV events only in those at very high CV risk, whereas the ST1RE algorithm has a good performance in all risk categories.

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.

Background: The usefulness of adapted small-side games (SSGs) in improving cardiac function in subjects with T2DM is still debated. Here we evaluated the effects of 18weeks Indoor Muscular Activation training (6 wks; IMA) followed by adapted SSGs football training (12wks) on cardiac function, muscular fitness, Body Composition and adiponectin expression in sedentary T2DM volunteers. Methods: 6 T2DM patients underwent IMA protocol of 6 wks, 2/wk followed by 12 wks SSGs (5vs5; once a wk) training. Glucose, lipid profile and serum homocysteine concentration, Body Composition (BC), bone mineral density (DEXA), were determined at baseline and after 18wks (IMA+SSGs). VO2max and muscular fitness were recorded at baseline and after IMA (6wks) and SSGs (12 wks), respectively. Results: No significant differences were found for VO2max and muscular fitness after 6wks of IMA. After 18wks (6 wks IMA+ 12 wks SSGs) of training, significant improvements were found in the following parameters: work capacity, VO2peack, Ventilation (VEpeack), breathing reserve consumption and oxygen uptake efficiency (OUES) (p

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.

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

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 (

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.

On the basis of the recommendation of the American Diabetes Association’s Panel on Ethical Scientific Programs (ESP), the American Diabetes Association, the publisher of Diabetes, is issuing this expression of concern to alert readers to questions about the reliability of the data in the above-cited article. After readers of the journal contacted Diabetes about potentially duplicated images in the article, the ESP reviewed the following issues

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.

BACKGROUND: Sleeve gastrectomy (SG) was pioneered as a two-stage intervention for super and super-super obesity to minimize morbidity and mortality; it is employed increasingly as a primary procedure. Early outcomes and integrity of laparoscopic SG (LSG) against leak using a technique incorporating gastric transection-line reinforcement were studied. METHODS: Between 2003 and 2009, 121 patients underwent LSG (16, two-stage; 105, primary). Of the patients, 66% were women, mean age 38.8 ± 10.9 (15.0-64.0), and body mass index (BMI, kg/m(2)) 48.7 ± 9.3 (33.7-74.8). Bovine pericardium (Peri-Strips Dry [PSD]) was used to reinforce the staple line. Parametric and nonparametric tests were used, as appropriate. The paired t test was used to assess change from baseline; bivariate analyses and logistic regression were used to identify preoperative patient characteristics predictive of suboptimal weight loss. RESULTS: Mean operative time was 105 min (95-180), and mean hospitalization was 5.6 days (1-14). There was no mortality. There were 6 (5.0%) complications: 1 intraoperative leak, 1 stricture, 1 trocar-site bleed, 1 renal failure, and 2 wound infections. There were no postoperative staple-line leaks. Following 15 concomitant hiatal hernia operations, 3 (20%) recurred: 1 revised to RYGB and 2 in standby. Two post-LSG hiatal hernias of the two-stage series required revisions because of symptoms. BMI decreased 24.7% at 6 months (n = 55) to 37.5 ± 9.3 (22.2-58.1); %EWL was 48.1 ± 19.3 (15.5-98.9). Twelve-month BMI (n = 41) was 38.4 ± 10.5 (19.3-62.3); %EWL was 51.7 ± 25.0 (8.9-123.3). Forty-eight-month BMI (n = 13) was 35.6 ± 6.8 (24.9-47.5); %EWL was 61.1 ± 12.2 (43.9-82.1) (p 70% of patients who experienced

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, age45±9years, BMI48±8 kg/m2, M ± SD) underwent evaluation of anthropometric/clinical parameters and glucose homeostasis before, 3 and 9–15 months after LSG. Mean BMI decreased from48±8 kg/m2to40±9 kg/m2(P<.001) at 3 months and34±6 kg/m2(P<.001) at 9–15 months after surgery. Remission of T2DM (fasting plasma glucose < 126 mg/dL andHbA1c<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.

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 complica- tions (DCe), 23 with microvascular complications (DCþ), 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 coro- nary flow velocity was comparable in C, DCe ,a nd DC þ (p Zns). Dipyridamole infusion produced a threefold increase in coronary diastolic peak velocity, which reached similar values in C (0.69 � 0.16 m/s), DCe (0.69 � 0.18 m/s), and DCþ (0.66 � 0.11 m/s). Mean CFR ratio was similar in C (3.33 � 0.66), DCe (3.30 � 0.51), and DCþ (3.24 � 0.60). At multiple linear regres- sion analysis, no association was found between CFR and age, sex, HbA1c, 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 cardio- vascular risk factors.

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.

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.

Objective: There is some evidence that acute hyperglycemia (H) may cause vascular dysfunction in normal subjects. This study investigates whether acute, short-term H affects coronary vasodilatory function in healthy subjects. Design: Diastolic peak flow velocity in the left anterior descending coronary artery was measured at rest and after dipyridamole (0.56 mg/kg over 4 min) using transthoracic color Doppler echocardiography in 13 healthy men. Coronary flow reserve (CFR) was defined as the ratio of dipyridamole-induced coronary peak diastolic to resting peak diastolic flow velocity. CFR was measured both in euglycemia (E) and after 3 h H (∼14 mmol/liter) by a variable infusion of glucose and octreotide (0.4 mg/h) to prevent increase in insulin concentration. Results: Fasting plasma glucose increased to 14.3 ± 0.33 mmol/liter during the study and maintained variability within less than 10%. Plasma insulin remained nearly stable during H. Resting diastolic flow velocity was 18.5 ± 0.6 cm/sec in E and increased to 20.0 ± 0.7 cm/sec during H (P < 0.005). Dipyridamole infusion produced a marked increase in coronary flow velocity, which reached values of 50.8 ± 2.9 cm/sec in E and 51.8 ± 2.1 cm/sec in H (P = not significant). CFR was 2.78 ± 0.16 in E and 2.59 ± 0.12 in H (P = not significant). Conclusion: Our study indicates that short-term hyperglycemia does not affect the vasodilatory response of coronary microcirculation in healthy subjects.

We report the case of a 20-yr-old girl with thiamine-responsive megaloblastic anemia (TRMA) associated with diabetes mellitus and bilateral sensorineural deafness (1, 2). Megaloblastic anemia was diagnosed at 7 months and was successfully treated with multiple vitamin preparations. Diabetes was diagnosed at age 2 yr and was treated with insulin for 6 months at a dose of 0.5 IU/kg BW. The diagnosis of TRMA syndrome was clinically confirmed when bilateral sensorineural deafness was detected. Thereafter, thiamine treatment was started (50 mg/day), and insulin was discontinued because of frequent episodes of hypoglycemia. At age 9 yr, due to reoccurrence of hyperglycemia, the patient underwent glibenclamide treatment (2.5 mg/day), which was replaced by insulin at menarche. Glycemic control was satisfactory, as evidenced by hemoglobin A1c (HbA1c) values between 7.5–8%. Laboratory parameters, including coagulation factors, were in the normal range. At age 17 yr, because of secondary amenorrhea and echographic findings of small ovarian cysts, the patient was diagnosed as having polycystic ovary syndrome and was treated with estro-progestins (12 cycles/yr of ciproterone, ethinyl estradiol). One year later, at age 18 yr, the patient developed motor seizures initially involving the left leg, then rapidly extending to the whole body, followed by unconsciousness. On admission, left hemiplegia was observed. Arterial blood pressure and plasma lipid concentrations were normal (100/60 mm Hg; total cholesterol, 147 mg/dL; total triglycerides, 84 mg/dL). The patient was receiving insulin therapy (30–35 IU/24 h), and the average HbA1c levels had been between 7.1–7.3% during the previous year. A computed tomography scanning revealed a small area of edema at the right cerebral hemisphere; 24 h later an ischemic area involving the territory of the right middle cerebral artery became manifest. One month later, during antiepileptic and ticlopidine therapy, the patient developed clonic movements of the left leg followed by generalized coreic movements and unconsciousness. Brain magnetic resonance (MR) imaging and angiography showed severely reduced blood flow in the right middle cerebral artery, with a large ischemic area in the corresponding territory, absence of flow in the distal internal carotid arteries, and slight compensatory hypertrophy of the basilar artery (Fig. 1). X-Ray digital arteriography confirmed MR findings and showed narrowing of the left superficial femoral and popliteas arteries. Hemostasis tests revealed high fibrinogen levels (612 mg/dL), whereas prothrombin, APTT, antithrombin III, and protein S were normal. Anticardiolipin (IgG and IgM) and lupus anticoagulant antibodies were also normal. In contrast, a low activity of protein C (60% vs. 98 6 15%) was found, which reverted to normal after a year. Further investigation for a hypercoagulable state showed negative factor V Leiden and a homocysteine concentration in the normal range. In addition, screening for prothrombin gene G20210A mutation and mutations of two enzymes involved in homocysteine metabolism, i.e. C677T in the coding region for N,N-methylenetetrahydrofolate reductase and cystathionine b-synthase 844INS68, gave negative results. On hospital discharge, the patient had left-sided hemiparesis. Oral anticoagulant and antiepileptic drugs were prescribed together with insulin and thiamine, which induced satisfactory glycemic control and resumption of menses. During the 1-yr follow-up the patient progressively recovered upper limb motility and is now independent with regard to everyday life needs.

To determine the contribution of skeletal muscle to the insulin resistance of essential hypertension, insulin-stimulated forearm glucose uptake was quantitated in 12 control (age, 32 +/- 3 years) and 12 hypertensive subjects (age, 36 +/- 2 years) using the forearm perfusion technique. Peripheral insulin levels were raised acutely (approximately 60 microU/mL), while blood glucose concentration was clamped at its basal value (90 mg/dL) by a variable glucose infusion. During insulin stimulation, whole body glucose uptake was lower in hypertensive (4.5 +/- .3 mg.kg-1.min-1) than in normal subjects (5.8 +/- .4 mg.kg-1.min-1, P less than .05). Similarly, the amount of glucose taken up by the forearm was markedly reduced in the hypertensive (5.3 +/- .91 mg.L-1.min-1) compared with the control group (8.7 +/- 1.1 mg.L-1.min-1). No appreciable difference was observed as to forearm blood flow (39 +/- 4 mL.L-1.min-1 and 37 +/- 5 mL.L-1.min-1) in hypertensive patients. These results indicate that skeletal muscle is a major site of insulin resistance in essential hypertension and that this defect is independent of muscle perfusion.

This study attempts to evaluate whether the putative excess risk of cardiovascular disease in individuals with impaired glucose tolerance (IGT) can be explained by the clustering of other major cardiovascular risk factors after controlling for obesity. The study population was 1376 male and female employees of a Naples telephone company who had participated in a health survey in which an oral glucose tolerance test (OGTT) was given. After excluding treated hypertensives, we recruited all 65 individuals with IGT and 125 euglycemic controls matched for gender, age, and weight. Systolic and diastolic blood pressure was significantly higher in individuals with IGT (134 +/- 16 vs 127 +/- 15 mm Hg, p less than 0.001; 87 +/- 10 vs 84 +/- 8 mm Hg, p less than 0.05 (M +/- SD). Blood lipids were similar in the two groups (total cholesterol was 214 +/- 34 vs 218 +/- 40 mg/dl; HDL cholesterol was 39 +/- 9 vs 40 +/- 10 mg/dl; total triglyceride was 145 +/- 58 vs 135 +/- 63 mg/dl). Serum insulin values (fasting or at 1 or 2 hours after 75 g of oral glucose) were also similar. The number of persons currently smoking was significantly lower among individuals with IGT (30% vs 47%, p less than 0.025) but the percentage of exsmokers was identical in the two groups. We conclude that, among the possible cardiovascular risk factors investigated, blood pressure is the only one significantly associated with IGT independent of matched variables and antihypertensive treatment.