Supplementation with Highly Standardized Cranberry Extract Phytosome Achieved the Modulation of Urinary Tract Infection Episodes in Diabetic Postmenopausal Women Taking SGLT-2 Inhibitors: A RCT Study.

Urinary tract infections (UTIs) are the most common bacterial infections in postmenopausal women, and women with diabetes are possibly at a higher risk. The aim of this study is to evaluate the potential benefit on the prevention of UTI episodes, assessed by urinalysis and urine culture (primary outcome) after two, four and six months, of daily oral dietary supplement (120 mg highly standardized cranberry extract phytosome), compared to placebo, in diabetic postmenopausal women taking SGLT-2 inhibitors. Forty-six subjects (mean age 72.45 ± 1.76) completed the study (23 placebo/23 supplement). Considering UTI episodes, during the six-month supplementation period, an increase of 1.321 (95% CI: -0.322; 2.9650) was observed in the placebo group, while it remained at a steady value of 0.393 (95% CI: -4.230; 5.016) in the supplemented group. Regarding UTI episodes, in both groups, interaction between times for supplementation was statistically significant (p = 0.001). In particular, at follow-up 4, 9% of the placebo group showed infection versus only 3% with cranberry supplementation. Glycaemia and glycated hemoglobin values (secondary outcomes) were not modified at the end of six months with respect to the basal values in both groups, as expected. While in terms of quality of life per the SF-12 health questionnaire, there were no differences between the two groups, an improvement in SF-12 quality of life was observed in both groups (six months vs. basal). In conclusion, highly standardized cranberry extract phytosome supplementation reduced UTI recurrence.

Diabulimia and Type 1 Diabetes: An Unknown and Emerging Problem.

BACKGROUND: T1DM patients have a higher prevalence of eating disorders than the general population, and up to 30-40% of young T1DM patients suffer from an eating disorder, including diabulimia. Eating disorders worsen glycemic control and make insulin therapy management more difficult. Closed loop systems (HCLS) allow major therapeutic flexibility; however, proper carbohydrate (CHO) counting remains a fundamental feature for insulin dose adjustments. CASE REPORT: A 30-year-old female patient affected by T1DM (with a past medical history of drug abuse and depressive syndrome) presented with inadequate glycemic control and prandial boli management. She started a CHO counting course and had a HCLS positioned, with progressive amelioration of glycemic control. During follow-up evaluations, HCLS data showed a progressive reduction and abeyance of prandial boli; the patient also developped an excessive fear of weight gain. An integrated approach between diabetologist, psychiatrist and dietitian allowed a diagnosis of diabulimia, an eating disorder characterized by a progressive reduction and elimination of carbohydrate ingestion and insulin boli, with episodes of uncontrolled binging and purging. A multidisciplinary approach (fortnightly dietetic and psychiatric evaluations, use of bioimpedance, fixed CHO content diet) allowed the patient to reach a better glycometabolic control and disease consciousness. CONCLUSION: T1DM patients need to pay great attention to food quality and quantity; hence, an eating disorder diagnosis may be challenging. Additionally, there are currently no standard screening methods for this purpose. In our experience, an integrated approach is fundamental and may be a valid strategy to face this emerging problem.

Real world effectiveness of subcutaneous semaglutide in type 2 diabetes: A retrospective, cohort study (Sema-MiDiab01).

Introduction: Aim of the present study was to evaluate the real-world impact of once-weekly (OW) subcutaneous semaglutide on different end-points indicative of metabolic control, cardiovascular risk factors, and beta-cell function in type 2 diabetes (T2D). Methods: This was a retrospective, observational study conducted in 5 diabetes clinics in Italy. Changes in HbA1c, fasting blood glucose (FBG), body weight, blood pressure, lipid profile, renal function, and beta-cell function (HOMA-B) during 12 months were evaluated. Results: Overall, 594 patients (97% GLP-1RA naïve) were identified (mean age 63.9 ± 9.5 years, 58.7% men, diabetes duration 11.4 ± 8.0 years). After 6 months of treatment with OW semaglutide, HbA1c levels were reduced by 0.90%, FBG by 26 mg/dl, and body weight by 3.43 kg. Systolic blood pressure, total and LDL-cholesterol significantly improved. Benefits were sustained at 12 months. Renal safety was documented. HOMA-B increased from 40.2% to 57.8% after 6 months (p<0.0001). Discussion: The study highlighted benefits of semaglutide on metabolic control, multiple CV risk factors, and renal safety in the real-world. Semaglutide seems to be an advisable option for preservation of ß-cell function and early evidence suggests it might have a role in modifying insulin resistance (HOMA-IR), the pathogenetic basis of prediabetes and T2D.

Sitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study.

OBJECTIVE: Poor outcomes have been reported in patients with type 2 diabetes and coronavirus disease 2019 (COVID-19); thus, it is mandatory to explore novel therapeutic approaches for this population. RESEARCH DESIGN AND METHODS: In a multicenter, case-control, retrospective, observational study, sitagliptin, an oral and highly selective dipeptidyl peptidase 4 inhibitor, was added to standard of care (e.g., insulin administration) at the time of hospitalization in patients with type 2 diabetes who were hospitalized with COVID-19. Every center also recruited at a 1:1 ratio untreated control subjects matched for age and sex. All patients had pneumonia and exhibited oxygen saturation <95% when breathing ambient air or when receiving oxygen support. The primary end points were discharge from the hospital/death and improvement of clinical outcomes, defined as an increase in at least two points on a seven-category modified ordinal scale. Data were collected retrospectively from patients receiving sitagliptin from 1 March through 30 April 2020. RESULTS: Of the 338 consecutive patients with type 2 diabetes and COVID-19 admitted in Northern Italy hospitals included in this study, 169 were on sitagliptin, while 169 were on standard of care. Treatment with sitagliptin at the time of hospitalization was associated with reduced mortality (18% vs. 37% of deceased patients; hazard ratio 0.44 [95% CI 0.29-0.66]; P = 0.0001), with an improvement in clinical outcomes (60% vs. 38% of improved patients; P = 0.0001) and with a greater number of hospital discharges (120 vs. 89 of discharged patients; P = 0.0008) compared with patients receiving standard of care, respectively. CONCLUSIONS: In this multicenter, case-control, retrospective, observational study of patients with type 2 diabetes admitted to the hospital for COVID-19, sitagliptin treatment at the time of hospitalization was associated with reduced mortality and improved clinical outcomes as compared with standard-of-care treatment. The effects of sitagliptin in patients with type 2 diabetes and COVID-19 should be confirmed in an ongoing randomized, placebo-controlled trial.

Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19.

AIMS: SARS-CoV-2 causes severe respiratory syndrome (COVID-19) with high mortality due to a direct cytotoxic viral effect and a severe systemic inflammation. We are herein discussing a possible novel therapeutic tool for COVID-19. METHODS: Virus binds to the cell surface receptor ACE2; indeed, recent evidences suggested that SARS-CoV-2 may be using as co-receptor, when entering the cells, the same one used by MERS-Co-V, namely the DPP4/CD26 receptor. The aforementioned observation underlined that mechanism of cell entry is supposedly similar among different coronavirus, that the co-expression of ACE2 and DPP4/CD26 could identify those cells targeted by different human coronaviruses and that clinical complications may be similar. RESULTS: The DPP4 family/system was implicated in various physiological processes and diseases of the immune system, and DPP4/CD26 is variously expressed on epithelia and endothelia of the systemic vasculature, lung, kidney, small intestine and heart. In particular, DPP4 distribution in the human respiratory tract may facilitate the entrance of the virus into the airway tract itself and could contribute to the development of cytokine storm and immunopathology in causing fatal COVID-19 pneumonia. CONCLUSIONS: The use of DPP4 inhibitors, such as gliptins, in patients with COVID-19 with, or even without, type 2 diabetes, may offer a simple way to reduce the virus entry and replication into the airways and to hamper the sustained cytokine storm and inflammation within the lung in patients diagnosed with COVID-19 infection.

Mini Nutritional Assessment May Identify a Dual Pattern of Perturbed Plasma Amino Acids in Patients with Alzheimer's Disease: A Window to Metabolic and Physical Rehabilitation?

Conflicting results about alterations of plasma amino acid (AA) levels are reported in subjects with Alzheimer's disease (AD). The current study aimed to provide more homogeneous AA profiles and correlations between AAs and cognitive tests. Venous plasma AAs were measured in 54 fasting patients with AD (37 males, 17 females; 74.63 ± 8.03 yrs; 3.2 ± 1.9 yrs from symptom onset). Seventeen matched subjects without neurodegenerative symptoms (NNDS) served as a control group (C-NNDS). Patients were tested for short-term verbal memory and attention capacity and stratified for nutritional state (Mini Nutritional Assessment, MNA). Compared to C-NNDS, patients exhibited lower plasma levels of aspartic acid and taurine (p < 0.0001) and higher 3-methylhistidine (p < 0.0001), which were independent of patients' MNA. In comparison to normonourished AD, the patients at risk of and with malnutrition showed a tendency towards lower ratios of Essential AAs/Total AAs, Branched-chain AAs/Total AAs, and Branched-chain AAs/Essential AAs. Serine and histidine were positively correlated with verbal memory and attention capacity deficits, respectively. Total AAs negatively correlated with attention capacity deficits. Stratifying patients with AD for MNA may identify a dual pattern of altered AAs, one due to AD per se and the other linked to nutritional state. Significant correlations were observed between several AAs and cognitive tests.

Efficacy of SGLT-2 inhibitors in older adults with diabetes: Systematic review with meta-analysis of cardiovascular outcome trials.

AIMS: Sodium-glucose cotransporter-2 inhibitors (gliflozins) and statins are oral drugs that may have beneficial cardiovascular effects in patients with type 2 diabetes, especially in those with known cardiovascular disease. We planned a systematic review and meta-analysis of cardiovascular outcome trials (CVOTs) that evaluated the effect of gliflozins on MACE risk in patients with T2D stratified by age and by statin use. METHODS: The electronic search was carried out until 20 January 2020. RCTs were included if they were CVOTs performed in adults with T2D, compared add-on therapy with any gliflozin versus placebo, and had major cardiovascular events (MACE) as primary outcome. We limited the evaluation to MACE in order to minimize the statistical impact of post-hoc analyses. We used a random-effect model to calculate hazard ratio (HR) and 95% CI. RESULTS: The hazard ratio for MACE was 0.95 (95% CI, 0.86-1.05) in people <65 years and 0.83 (95% CI, 0.71-0.96) for people ≥65 years, with no subgroup differences (P-value = 0.15), suggesting that the effect was consistent across age categories. The hazard ratio for MACE was 0.87 (95% CI, 0.81-0.94) in people taking a statin and 0.88 (95% CI, 0.77-1.01) for people not taking statin, with no subgroup differences (P-value = 0.90). CONCLUSIONS: The results are reassuring, as they confirm that the efficacy profile of gliflozins is unchanged by age, and may further enhance the CV protection offered by statin.

12-month effects of incretins versus SGLT2-Inhibitors on cognitive performance and metabolic profile. A randomized clinical trial in the elderly with Type-2 diabetes mellitus.

AIM: The aim of the present study is to examine the effects on cognitive performance, anthropometric measures, and metabolic markers in 2 different treatments: Incretins vs sodium-glucose co-transporter-2 inhibitors (SGLT2-I). MATERIALS AND METHODS: A randomized controlled clinical trial was carried out on 39 elderly subjects (23 men and 16 women) with type 2 diabetes mellitus, with a mean age of 77.21±8.07 years. Body mass index (BMI) of 29.92±4.31 kg/m2 and a cognitive status measured by a Mini Mental State Examination (scores >27 points). The subjects were on a 3-month treatment with a maximal dose of metformin as a stable regime, with the addition of incretins (liraglutide at doses of up to 1.8 mg/d; vildagliptin at 100 mg/d; sitagliptin 100 mg/d; and linagliptin 5 mg/d), or SGLT2-I (canagliflozin 300 mg/d; empagliflozin 25 mg/d; and dapagliflozin 10 mg/d). Glucose control was monitored by fasting glucose and glycosylated hemoglobin. Cognitive performance (by way of Verbal Fluency Test, Attentive Matrices Test, and Babcock Story Recall Test), anthropometric measures, and plasma lipids were also evaluated. RESULTS: Cognitive status did not change significantly during the 12 months of treatment in either group: Verbal Fluency Test: (SGLT2-I: P=1.00, incretins: P=0.598); Babcock Story Recall Test (SGLT2-I: P=0.391; incretins: P=0.351); and Attentive Matrices Test (SGLT2-I: P=0.679, incretins: P=0.901). SGLT2-I also resulted in a reduction in weight (-1.95 kg; P<0.05), in BMI (-0.69 kg/m2; P<0.05) and an increase in high-density lipoprotein cholesterol (+5.73 mg/dl; P<0.01). CONCLUSION: Preliminary data show that patients treated with incretins and SGLT2-I have not suffered a reduction in cognitive performance during the 1 year of treatment. Metabolic outcome seemed to benefit, in particular, in patients who were treated with SGLT2-I.

Twenty-four-week effects of liraglutide on body composition, adherence to appetite, and lipid profile in overweight and obese patients with type 2 diabetes mellitus.

BACKGROUND: Liraglutide has well-known effects on glucose patterns. However, its several other metabolic properties are still controversial. Given this background, the aims of the present study are to evaluate the effects of 24-week liraglutide treatment on body composition, appetite, and lipid profile in overweight and obese type 2 diabetes mellitus (T2DM) patients. METHODS: A cohort study was carried out on overweight and obese T2DM patients with glycosylated hemoglobin A1c equal to 6% (42 mmol/mol)-10% (86 mmol/mol), under a 3-month treatment (at least) with maximal dose of metformin as stable regime, by adding liraglutide at doses up to 3 mg/d. Body composition markers were measured by dual-energy X-ray densitometry at baseline and after 24 weeks of liraglutide treatment. Glucose control was monitored by glucose, glycosylated hemoglobin A1c, insulin, and homeostasis model assessment. Finally, the appetite sensation and plasma lipids were also evaluated. RESULTS: Twenty-eight subjects (male/female: 16/12, mean age: 58.75±9.33 years, body mass index: 34.13±5.46 kg/m(2)) were evaluated. Accounting for the adjustment for age, sex, and duration of diabetes, we noted significant decreases in body mass index (-0.86 kg/m(2), P=0.024), fat mass (-2.01 kg, P=0.015), fat mass index (-0.71 kg/m(2), P=0.014), android fat (-1.72%, P=0.022), trunk fat (-1.52%, P=0.016), and waist circumference (-6.86 cm, P<0.001) from the baseline values. Haber score was increased by 3.82 units (P=0.009), and the number of metabolic syndrome risk factors was decreased (-0.69 units, P=0.012). The glucose control variables and total cholesterol/high-density lipoprotein cholesterol ratio also showed significant decreases from baseline values. CONCLUSION: The 24-week liraglutide treatment leads to the reduction of fat mass, android fat, trunk fat, and appetite by improving the lipid profile, glucose control, and insulin sensitivity.

Liraglutide and obesity in elderly: efficacy in fat loss and safety in order to prevent sarcopenia. A perspective case series study.

BACKGROUND: For the growing numbers of obese elderly with diabetes, the glucagon-like peptide-1 (GLP-1) receptor analogue (liraglutide) appears a safe way to promote and maintain substantial weight loss. Given this background, the aim of this study was to assess the effect of the liraglutide treatment, at doses up to 3.0 mg per day, on the body composition, focusing on sarcopenia, in overweight and obese elderly with type 2 diabetes mellitus (T2DM). METHODS: A perspective study was carried out in overweight and obese T2DM patients with HbA1c equal to 7.0 % (53 mmol/mol) ~10.0 % (86), under 3-month treatment (at least) of maximal dose of metformin at stable regime, and additional liraglutide at doses up to 3.0 mg per day. Body composition markers such as skeletal muscle index (SMI), android and gynoid fat mass, and arms and legs fat free mass, was measured by dual-energy X-ray densitometry (DXA) at baseline and after 24 weeks of liraglutide treatment. Glucose control was also carried out by glucose and HbA1c. RESULTS: Nine subjects (male/female 6/3, mean age 68.22 ± 3.86 years, BMI 32.34 ± 4.89 kg/m2) were evaluated. We noted a median decrease in BMI (-0.78 kg/m2), weight (-2000 g), fat mass (-1498 g) and android fat (-0.9 %), and a increase in SMI (+0.03 kg/m2) from baseline. Glycemic control also improved, with a median change HbA1c of -0.80 %. CONCLUSIONS: Twenty-four weeks of liraglutide treatment was associated with reductions in fat mass and android fat. In addition, in order to prevent sarcopenia, it preserved the muscular tropism.

Effects of two-months balanced diet in metabolically healthy obesity: lipid correlations with gender and BMI-related differences.

BACKGROUND: Nowadays no researches has been performed on fatty acid profile (FA) and desaturase activity in metabolically healthy obesity (MHO). The aim of this study was to assessed gender and BMI-related difference in FA, estimated desaturase activities and the efficacy on metabolic changes produced by 2-months well-balance diet in MHO subjects. METHODS: In 103 MHO subjects (30/73 M/F; age:42.2 ± 9.5) FA, estimated desaturase activity, body composition (by DXA), Body Mass Index (BMI), lipid profile, adipokines (leptin, adiponectin, grelin, glucagon-like peptide-1), insulin resistence (by Homestasis metabolic assessment), C-reactive proteine, Atherogenic index of plasma (AIP) and Body Shape Index (ABSI) have been assessed. Gender and BMI related difference have been evaluated and the efficacy produced by 2-months well-balance diet has been considered. RESULTS: At baseline, obese subjects, compared to overweight, show a significantly higher oleic (p <0.050), monounsaturated fatty acids (p <0.040), C18:0 delta-9 desaturase activity (D9D) (p <0.040) and lower linoleic acid (p <0.020), polyunsaturated fatty acids (p <0.020) and n-6 LCPUFA (p <0.010). Concerning gender-related difference, women show a significantly higher arachidonic acid (p <0.001), polyunsaturated fatty acids (p <0.001), n-6 LCPUFA (p <0.002), and lower monounsaturated fatty acids (p <0.001), D6D activity (p <0.030), C18:0 D9D (0.000) and C16:0 D9D (p <0.030). The 2-months diet was associated with a significantly increase in arachidonic acid (p = 0.007), eicosapentaenoic acid (p = 0.030), docosahexaenoic acid (p <0.001), long chain omega 3 polyunsaturated fatty acids (n-3 LCPUFA) (p <0.001), delta-5 desaturase activity (D5D) (p = 0.002), glucagon like peptide-1 (p <0.001) and a significant decrease in palmitoleic acid (p = <0.030), n-6/n-3 LCPUFA (p <0.001), insulin resistance (p = 0.006), leptin (p = 0.006), adiponectin (p <0.001), grelin (p = 0.030), CRP (p = 0.004), BMI (p <0.001) and android fat mass (p <0.001). CONCLUSIONS: The balanced diet intervention was effective in improving metabolic indices.

Acute effect on satiety, resting energy expenditure, respiratory quotient, glucagon-like peptide-1, free fatty acids, and glycerol following consumption of a combination of bioactive food ingredients in overweight subjects.

OBJECTIVE: A combination of bioactive food ingredients (capsaicinoids, epigallocatechin gallate, piperin, and l-carnitine, CBFI) may promote satiety and thermogenesis. The study was conducted in order to assess whether there is any effect on satiety, resting energy expenditure (REE), respiratory quotient, glucagon-like peptide-1 (GLP-1), free fatty acids (FFA) and glycerol release, following a standardized mixed meal with or without single consumption of a CBFI. DESIGN: An 8-week randomized double-blind placebo-controlled trial. SETTING: Dietetic and Metabolic Unit, Azienda di Servizi alla Persona, University of Pavia and "Villa delle Querce" Clinical Rehabilitation Institute, Rome, Italy. PARTICIPANTS: Thirty-seven overweight adults (body mass index [BMI]: 25-35). INTERVENTION: Nineteen overweight subjects were included in the supplemented group (14 women, 5 men; age 46.4 ± 6.4; BMI: 30.5 ± 3.3) and 18 in the placebo group (13 women, 5 men; age 40.8 ± 11.5; BMI: 30.1 ± 2.6). Satiety was assessed using 100-mm visual analogue scales (VAS) and the area under the curve was calculated. RESULTS: All measured parameters increased significantly in comparison with baseline in response to meal, both with CBFI and with placebo. However, throughout the study day, the supplemented group experienced a significantly greater increase than the placebo group in their sensation of satiety following acute administration of the supplement. CONCLUSION: CBFI may therefore be of great value in the treatment of overweight patients by increasing satiety and stimulating thermogenesis.

Improvement in insulin resistance and favourable changes in plasma inflammatory adipokines after weight loss associated with two months' consumption of a combination of bioactive food ingredients in overweight subjects.

This randomized, double blind, placebo-controlled, 8 week trial assessed the efficacy on metabolic changes produced by a consumption of a combination of bioactive food ingredients (epigallocatechin gallate, capsaicins, piperine and L-carnitine) versus a placebo, as part of a therapeutic 'lifestyle change' diet, in 86 overweight subjects. Forty-one patients (2/14 F/M; age 43.7 ± 8.5; BMI 30.3 ± 3.5 kg/m(2)) were randomized to the supplemented group and 45 (29/16; age 40.7 ± 10.2; BMI 30.0 ± 2.7) to the control group. We observed that consumption of the dietary supplement was associated with a significantly greater decrease in insulin resistance, assessed by homostasis model assessment (p < 0.001), leptin/adiponectin ratio (p < 0.04), respiratory quotient (p < 0.008). LDL-cholesterol levels (p < 0.01). Moreover, statistically significant differences were recorded between the two groups in relation to urinary norepinephrine levels (p < 0.001). Leptin, ghrelin, C-reactive protein decreased and resting energy expenditure increased significantly in the supplemented group (p < 0.05, 0.03, 0.02 and 0,02 respectively), but not in the placebo group; adiponectin decreased significantly in the placebo group (0.001) but not in the supplemented group, although no statistical significance between the groups was elicited. BMI, fat mass (assessed by DXA) and vascular endothelial growth factor significantly decreased, whilst the resting energy expenditure/free fat mass significantly increased in both groups. In general, a greater change was recorded in the supplemented group compared to the placebo, although no statistically significant difference between the two groups was recorded. These results suggest that the combination of bioactive food ingredients studied might be useful for the treatment of obesity-related inflammatory metabolic dysfunctions.

Screening for asymptomatic coronary artery disease can reduce cardiovascular mortality and morbidity in type 2 diabetic patients.

The impact of the screening for asymptomatic coronary artery disease (CAD) on the cardiovascular prognosis in diabetes is controversial. The aim of the study was to investigate whether screening for asymptomatic CAD can have an impact on cardiovascular morbidity and mortality in diabetes. In this nonrandomized longitudinal study, 1,189 consecutive type 2 diabetic patients without a history of CAD were evaluated. They were subdivided into two groups according to whether they were screened (screening group, n = 921) or not (no-screening group, n = 268) for asymptomatic CAD. Among the screened patients, 386 had angiographically proven CAD (CAD group) and 535 did not have silent CAD (no-CAD group). During a mean follow-up period of 4.3 ± 1.9 years, 130 patients experienced major adverse cardiac events (MACE). The incidence of MACE was significantly greater in the no-screening than in the screening group (22.0 vs. 7.7%; p = 0.001). The Kaplan-Meier method showed that: (1) the screening was associated with a lower rate of MACE (log-rank test, 3-95; p = 0.047); (2) the no-screening group had a risk profile similar to that of CAD group (log-rank test, 2.02; p = 0.154); and (3) cardiovascular prognosis was significantly better in no-CAD than in no-screening group (log-rank test, 4.27; p = 0.039). Multivariate Cox regression analysis showed that screening for CAD (HR 0.2; 95% CI 0.2-0.3; p = 0.000) was significantly protective against the occurrence of MACE. Our data suggest that screening for asymptomatic CAD can significantly reduce cardiovascular morbidity and mortality in type 2 diabetic patients. This may be due to specific diagnostic and therapeutic interventions in diabetic patients with proven CAD at screening.

Improved glycemic control with weight loss and a low risk of hypoglycemia with insulin detemir: insights from the Italian cohort of the PREDICTIVE study after 6-month observation in type 2 diabetic subjects.

OBJECTIVE: PREDICTIVE (Predictable Results and Experience in Diabetes through Intensification and Control to Target: an International Variability Evaluation) is a large, multinational, open-label, prospective, observational study addressed to assess the efficacy and safety of insulin detemir in clinical practice. This paper reports 26 weeks of follow-up data, from 1298 type 2 diabetes patients from Italy. RESEARCH DESIGN AND METHODS: In this observational study, the primary end point was the incidence of serious adverse drug reactions (SADRs), including major hypoglycemia. Secondary end points were: hemoglobin A1c (HbA1c), mean self-monitored fasting glucose, within-patient fasting glucose variability and body weight change. RESULTS: Insulin detemir significantly improved glycemic control, with a decrease in mean HbA1c, fasting glucose and within-patient fasting glucose variability. Interestingly, the improvements in glycemic control occurred in association with a small, but significant reduction in weight. The safety results of this study showed that 26 weeks of treatment with insulin detemir was associated with a very low rate of SADRs (only 14 events), which mainly consisted of hypoglycemia (78%, of which 42% were major hypoglycemia). CONCLUSIONS: Insulin detemir improves glycemic control, with low risk of hypoglycemia, no weight gain and an excellent safety profile; these data support the overall findings of PREDICTIVE.

Administration of a dietary supplement ( N-oleyl-phosphatidylethanolamine and epigallocatechin-3-gallate formula) enhances compliance with diet in healthy overweight subjects: a randomized controlled trial.

Many studies have found that N-oleyl-ethanolamine (NOE), a metabolite of N-oleyl-phosphatidylethanolamine (NOPE), and epigallocatechin-3-gallate (EGCG) inhibit food intake. The main aim of this study was to evaluate the efficacy of 2 months of administration of an oily NOPE-EGCG complex (85 mg NOPE and 50 mg EGCG per capsule) and its effect on compliance with diet in healthy, overweight people. Secondary end-points of the study were to compare body composition, metabolic parameters, sensation of appetite, depressive symptoms and severity of binge eating. Using a parallel-arm, double-blind, placebo-controlled design, 138 healthy, overweight women (106) and men (thirty-two) were randomly assigned to one of two groups: (1) the treatment group (seventy-one patients: fifty-three females, eighteen males) taking two capsules per day of an oral supplement or (2) the placebo group (sixty-seven patients: fifty-three females, fourteen males). Both groups observed a 3344 kJ/d energy restriction. All parameters were assessed both before onset and after 2 months on the supplement. Dropout was 6 % in the NOPE-EGCG group and 27 % in the placebo group (P < 0.001). The treatment induced a significant weight reduction in both groups ( - 3.28 kg and - 2.67 kg in NOPE-EGCG and placebo, respectively); the weight changes were not significantly different between the groups. NOPE-EGCG treatment improved insulin resistance (P < 0.001), the sensation feelings of fullness (P < 0.05), depressive symptoms (P < 0.004) and severity of binge eating (P < 0.0001).

Defect of a subpopulation of natural killer immune cells in Graves' disease and Hashimoto's thyroiditis: normalizing effect of dehydroepiandrosterone sulfate.

BACKGROUND: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves' disease (GD) and Hashimoto's thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. OBJECTIVE: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. DESIGN: We studied 13 patients with recent onset Graves' disease, 11 patients with Hashimoto's thyroiditis at first diagnosis and 15 age-matched healthy subjects. METHODS: NK cells were concentrated at a density of 7.75x10(6) cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16+/CD56+cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-beta (IFN-beta) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-alpha (TNF-alpha) from NK cells. RESULTS: Lower spontaneous, IL-2- and IFN-beta-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P<0.001). A decrease in spontaneous and IL-2-modulated TNF-alpha release from NK cells was also found in both groups of patients (P<0.001). The co-incubation of NK cells with IL-2/IFN-beta+DHEAS at different molar concentrations (from 10(-8) to 10(-5) M/ml/NK cells) promptly normalized NKCC and TNF-alpha secretion in GD and HT patients. CONCLUSIONS: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.