Quality of life in Klinefelter patients on testosterone replacement therapy compared to healthy controls: an observational study on the impact of psychological distress, personality traits, and coping strategies.

PURPOSE: We aimed to verify if 1 year-testosterone-replacement therapy could produce a psychopathological recovery and a satisfactory quality of life in Klinefelter syndrome (KS) patients compared to matched healthy controls. Further, we analyzed personality traits and coping strategies, an issue not yet examined in androgen-treated KS patients. We also enquired whether any of the sociodemographic and psychological variables might predict a patient's general and sexual life satisfaction. METHODS: The Quality of Life Enjoyment and Satisfaction Questionnaire and the Temperament and Character Inventory-Revised were administered to both 23 KS patients and matched healthy subjects. Psychopathology was investigated by the Symptom Checklist-90-Revised (SCL-90-R) and the Mini-mental State Examination. The COPE Inventory was used to identify cognitive and behavioral strategies to manage disease-related distress. RESULTS: In testosterone-treated KS patients, when compared with controls, SCL-90-R subscales analysis evidenced high psychological distress, mainly presented as obsessive thoughts, hanger-hostility, phobias, and psychoticism. Self-directedness and self-transcendence, along with the prevalent use of emotion-focused coping strategies, outlined the personality of our KS patients. Depression and somatization proved to be predictors of general life dissatisfaction. Depression, anger-hostility, and paranoid ideation, instead, emerged as predictors of sexual life dissatisfaction. CONCLUSION: Endocrinologists should cooperate with mental health providers to foster a better outcome of the disease in KS patients.

Excisional haemorrhoidectomy: is it safe in patients with an ileal pouch-anal anastomosis?

AIM: Excisional haemorrhoidectomy in patients with ulcerative colitis (UC), especially those undergoing an ileal pouch-anal anastomosis (IPAA), remains controversial. The aim of our study was to determine the safety of excisional haemorrhoidectomy in UC patients with and without an IPAA. METHOD: A retrospective review of all adult UC patients undergoing excisional haemorrhoidectomy between 1 January 1995 and 1 January 2019 at a tertiary inflammatory bowel disease referral centre was performed. Data collected included patient demographics, clinical characteristics of UC, prior surgical intervention for UC (colectomy, IPAA) and complications after haemorrhoidectomy. RESULTS: Forty-one adult patients [50% male; median age 52 (range 25-79) years] with UC underwent excisional haemorrhoidectomy between 1 January 1995 and 1 January 2019. The majority (n = 23) had not previously undergone surgery for UC. However, eight had already undergone construction of an IPAA at the time of haemorrhoidectomy, seven had IPAA at the time of haemorrhoidectomy and three had an IPAA constructed subsequent to haemorrhoidectomy. Two (4.9%) patients need to go back to theatre for postoperative bleeding. There were no further 30-day complications or long-term nonhealing of the surgical site. There were no pouch complications in those who had haemorrhoidectomy at the time of IPAA construction or in the presence of an IPAA. CONCLUSION: Our data suggest that excisional haemorrhoidectomy may be performed safely in carefully selected UC patients with symptomatic haemorrhoids with or without IPAA and even at the time of IPAA construction.

Cardiovascular outcome trials and major cardiovascular events: does glucose matter? A systematic review with meta-analysis.

PURPOSE: We did a meta-analysis with meta-regression to evaluate the relationship between hemoglobin A1c (A1C) reduction and the primary CV outcome of cardiovascular outcome trials (CVOTs). METHODS: We used a random effects meta-analysis of the 12 CVOTs to quantify the effect of A1C reduction on major cardiovascular events (MACE) risk by stratifying the difference in achieved A1C (drug vs placebo) in three strata: A1c < 0.3%, A1c ≥ 0.3% and < 0.5%, and A1c ≥ 0.5%. RESULTS: We found a relation between the reduction in achieved A1C and the hazard ratio reduction for MACE (P = 0.002), explaining almost all (94.1%) the between-study variances: lowering A1C by 0.5% conferred a significant HRR of 20% (95% CI 4-33%) for MACE. CONCLUSIONS: Blood glucose reduction may play a more important role than previously thought in reducing the risk of MACE during treatment with the newer glucose-lowering drugs, including peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors.

Clinical inertia, reverse clinical inertia, and medication non-adherence in type 2 diabetes.

PURPOSE: Clinical inertia and medication non-adherence are thought to contribute largely to the suboptimal glycemic control in many patients with type 2 diabetes. The present review explores the relations between A1C targets, clinical inertia and medication non-adherence in type 2 diabetes. METHODS: We searched PubMed for English-language studies published from 2001 through June 1, 2018. We also manually searched the references of selected articles, reviews, meta-analyses, and practice guidelines. Selected articles were mutually agreed upon by the authors. RESULTS: Clinical inertia is the failure of clinicians to initiate or intensify therapy when indicated, while medication non-adherence is the failure of patients to start or continue therapy that a clinician has recommended. Although clinical inertia may occur at all stages of diabetes treatment, the longest delays were reported for initiation or intensification of insulin. Medication non-adherence to antidiabetic drugs may range from 53 to 65% at 1 year and may be responsible for uncontrolled A1C in about 23% of cases. Reverse clinical inertia can be acknowledged as the failure to reduce or change therapy when no longer needed or indicated. Clinical inertia and medication non-adherence are difficult to address: clinician-and patient-targeted educational programs, more connected communications between clinicians and patients, the help of other health professional figures (nurse, pharmacist) have been explored with mixed results. CONCLUSIONS: Both clinical inertia and medication non-adherence remain significant barriers to optimal glycemic targets in type 2 diabetes. Moreover, part of clinical inertia may be a way through which clinicians face current uncertainty in medicine, including some dissonance among therapeutic guidelines. Scientific associations should find an agreement about how to measure and report clinical inertia in clinical practice and should exhort clinicians to consider reverse clinical inertia as a cause of persisting inappropriate therapy in vulnerable patients.

From inflammation to sexual dysfunctions: a journey through diabetes, obesity, and metabolic syndrome.

Metabolic diseases are associated with chronic low-grade inflammation, which has been indicated as a potential mediator of endothelial dysfunction and cardiovascular disease. Visceral adiposity is thought to be the starting condition of the inflammatory state through the release of inflammatory cytokines, including TNF-alpha, CRP, and IL-6, which in turn promote endothelial dysfunction, endothelial expression of chemokines (IL-1) and adhesion molecules (ICAM-1, VCAM-1, and P-selectin), and the inhibition of anti-atherogenic factors (adiponectin). Obesity, metabolic diseases, and diabetes, all conditions characterized by abdominal fat, are well-recognized risk factors for sexual dysfunction in both sexes. Evidence from randomized-controlled trials supports the association between inflammatory milieau and erectile dysfunction in men suffering from metabolic diseases, whereas, in women, this has to be confirmed in further studies. A healthy lifestyle based on dietary pattern with high content of whole grain, fruit, nuts and seeds, and vegetables and low in sodium and saturated fatty acids plus regular physical activity may help to modulate the pro-inflammatory state associated with metabolic diseases and the related burden of sexual dysfunctions.

TSH oscillations in young patients with type 1 diabetes may be due to glycemic variability.

PURPOSE: A relationship between thyroid dysfunction and diabetes mellitus has been described by several authors but the role of glycemic variability is still unclear. We planned the present study to evaluate the influence of glycemic variability on thyroid hormones and TSH concentrations in patients with type 1 diabetes mellitus (T1DM). METHODS: Seventy-seven young patients with T1DM were enrolled and evaluated for basal glucose concentrations, HbA1c, thyroid hormones and TSH concentrations. Glucose variability was investigated by considering the standard deviation of blood glucose readings and by calculating the mean amplitude of glycemic excursions and continuous overlapping net glycemic action (CONGA). The low (LBGI) and high (HBGI) blood glucose indices were also calculated. The correlations between TSH, thyroid hormones, glycemia and HbA1c were studied in patients and in controls, whereas those between TSH, thyroid hormones and indices of glucose variability only in patients. RESULTS: No correlations were observed in T1DM patients between free thyroid hormones and glycemic values, HbA1c and indices of glucose variability, while an inverse correlation was observed between TSH levels and glycemic values (r = -0.27; p = 0.01), CONGA index (r = -0.35; p = 0.001) and HBGI (r = -0.28; p = 0.01) but not with HbA1c (r = -0.1; p = 0.47). CONCLUSIONS: Our results suggest a direct action of glycemic excursions on TSH secretion, regardless of variations of thyroid hormone concentrations. Thus, the evaluation of thyroid function through the assay of TSH concentrations in these patients should be made, if possible, by multiple samples on patients in euglycemic state to avoid underestimation or overestimation of thyroid dysfunction due to a wrong diagnosis of euthyroidism or dysthyroidism with consequent inappropriate choice of therapeutic options.

Influence of occlusal characteristics, food intake and oral hygiene habits on dental caries in adolescents: a cross-sectional study.

AIM: Dental caries is one of the most common oral diseases affecting children. The complex multifactorial aetiology of caries involves host (saliva composition and tooth enamel characteristics), oral microflora and substrate (oral hygiene quality and dietary habits composition). Occlusal characteristics may be also a factor in dental caries development. The aim of this aepidemiologic study was to verify the association between DMFT (Decayed, Missed, Filled Teeth) index and occlusal characteristics, dietary habits, oral hygiene habits and parents' education level in a sample of 12-year-old schoolchildren from Southern Italy. MATERIALS AND METHODS: A sample of 536 children was examined to detect dental caries status and several occlusal variables (i.e. molar relationship, overjet and overbite, presence of crossbite, scissor bite, crowding, diastemas and/or midline deviation). A questionnaire to retrieve parents' educational level, patient's dietary and oral hygiene habits was administered. The associations among these variables were assessed statistically through the ?2 test. RESULTS: A positive association was found between caries, parents' social status and some occlusal disorders. va specificato, l'abstract non può essere una caccia al tesoro. In relation to occlusal variables, crossbite (?2=3.96, P=0.04) was significantly associated to caries. A significant association was also found between the education level of mothers (?2=7.74, P<0.01) and fathers (?2=6.35, P=0.01) and the presence of caries. Dietary habits, oral hygiene and remaining occlusal characteristics were not associated with caries presence (all P>0.05). CONCLUSIONS: Of the evaluated occlusal characteristics only posterior crossbite was associated with caries prevalence. Education level of the parents was the other factor significantly associated with caries. Dietary habits, oral hygiene frequency and the remaining occlusal characteristics were not associated with dental caries.

Sexual function in young women with type 1 diabetes: the METRO study.

PURPOSE: The aim of this study was to evaluate the prevalence and risk factors associated with female sexual dysfunction (FSD) in young women with type 1 diabetes treated with different intensive insulin regimens. METHODS: Type 1 diabetic women aged 18-35 years were included in this study if they had stable couple relationship and no oral contraceptive use. All women were asked to complete the Female Sexual Function Index (FSFI) and other validated multiple-choice questionnaires assessing sexual-related distress (Female Sexual Distress Scale, FSDS), quality of life (SF-36 Health Survey), physical activity (International Physical Activity Questionnaire), depressive symptoms (Zung Self-Rating Depression Scale, SRDS) and diabetes-related problems (Diabetes Integration Scale ATT-19). FSD was diagnosed according to a FSFI score higher than 26.55 and a FSDS score lower than 15. RESULTS: The overall prevalence of FSD in diabetic and control women was 20 and 15 %, respectively (P = 0.446). Compared with the continuous subcutaneous insulin infusion group and control women, diabetic women on multiple daily injections (MDI) had lower global FSFI score (P = 0.007), FSDS score (P = 0.045) and domains such as arousal (P = 0.006), lubrication and satisfaction scores (P < 0.001 for both). In the multiple regression analysis, only the mental component summary (P = 0.047) and the SRDS score (P = 0.042) were independent predictors of FSFI score in the overall diabetic women. CONCLUSION: Young women with type 1 diabetes wearing an insulin pump show a prevalence of sexual dysfunction similar to that of healthy age-matched women, but sexual function was significantly impaired in diabetic women on MDI therapy. Depression and the mental health status were independent predictors for FSD in diabetic women.

Influence of short-term selenium supplementation on the natural course of Hashimoto's thyroiditis: clinical results of a blinded placebo-controlled randomized prospective trial.

BACKGROUND: The real efficacy of selenium supplementation in Hashimoto's thyroiditis (HT) is still an unresolved issue. OBJECTIVES: We studied the short-term effect of L-selenomethionine on the thyroid function in euthyroid patients with HT. Our primary outcome measures were TSH, thyroid hormones, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) levels and thyroid echogenicity after 6 months of L-selenomethionine treatment. The secondary outcome measure was serum CXCL10 levels. METHODS: In a placebo-controlled randomized prospective study, we have enrolled untreated euthyroid patients with HT. Seventy-six patients were randomly assigned to receive L-selenomethionine 166 µg/die (SE n = 38) or placebo (controls n = 38) for 6 months. TSH, free T4 (FT4), free T3 (FT3), TPOAb and CXCL10 serum levels were assayed at time 0, after 3 and 6 months. An ultrasound examination of the left and right thyroid lobe in transverse and longitudinal sections was performed. A rectangular region, the region of interest, was selected for analysis. RESULTS: TSH, FT4, FT3, TPOAb, thyroid echogenicity and CXCL10 were not statistically different between SE and control groups at time 0, after 3 and 6 months. In the SE group, FT4 levels were significantly decreased (P < 0.03) after 3 months, while FT3 increased (P < 0.04) after 3 and 6 months versus baseline values. In the control group, the FT3 decreased after 3 and 6 months (P < 0.02) compared to baseline. CONCLUSION: The short-term L-selenomethionine supplementation has a limited impact on the natural course in euthyroid HT. Our results tip the balance toward the ineffectiveness of short-term L-selenomethionine supplementation in HT.

Do intraoperative pyloric interventions predict the need for postoperative endoscopic interventions after minimally invasive esophagectomy?

Intraoperative pyloric procedures are often performed during esophagectomies to reduce the rates of gastric conduit dysfunction. They include pyloroplasty (PP), pyloromyotomy (PM), and pylorus botulinum toxin type-A injections (BI). Despite these procedures, patients frequently warrant further endoscopic interventions. The aim of this study is to compare intraoperative pyloric procedures and the rates of postoperative endoscopic interventions following minimally invasive esophagectomy (MIE). We identified patients who underwent MIE for esophageal carcinoma and grouped them as 'None' (no intervention), 'PP', 'PM', or 'BI' based on intraoperative pyloric procedure type. The rates of endoscopic interventions for the first six postoperative months were compared. To adjust for variability due to MIE type, the rates of >1 interventions were compared using a zero-inflated Poisson regression analysis. Significance was established at P < 0.05. There were 146 patients who underwent an MIE for esophageal cancer from 2008 to 2015; 77.4% were three-hole MIE, and 22.6% were Ivor- Lewis MIE. BI was most frequent in Ivor-Lewis patients (63.5%), while PP was most frequent (46.9%) in three-hole patients. Postoperative endoscopic interventions occurred in 38 patients (26.0%). The BI group had the highest percentage of patients requiring a postoperative intervention (n = 13, 31.7%). After adjusting for higher rates of interventions in three-hole MIE patients, the BI and None groups had the lowest rates of >1 postoperative interventions. Our data did not show superiority of any pyloric intervention in preventing endoscopic interventions. The patients who received BI to the pylorus demonstrated a trend toward a greater likelihood of having a postoperative intervention. However when adjusted for type of MIE, the BI and None groups had lower rates of subsequent multiple interventions. Further research is needed to determine if the choice of intraoperative pyloric procedure type significantly affects quality of life, morbidity, and overall prognosis in these patients.

Vitamin D and autoimmunity: what happens in autoimmune polyendocrine syndromes?

PURPOSE: To evaluate the Vitamin D status of patients with a single autoimmune disease and of patients with several autoimmune diseases. METHODS: We enrolled 35 patients with isolated type 1 diabetes mellitus (T1DM), 60 with autoimmune polyendocrine syndromes (APS) including T1DM and 72 control subjects. Among patients with APS, 10 were classified as type 2 (Addison's disease + T1DM), whereas the other 50 as type 3 (autoimmune thyroid disease + T1DM + other autoimmune diseases). Vitamin D (25-OHD) levels were assessed by a chemiluminescent immunoassay in all patients and controls on samples drawn in the morning of the same months. RESULTS: Both groups of APS and T1DM patients showed 25-OHD levels significantly lower than healthy controls (p < 0.001 for both vs controls), without any significant difference between the two groups (p = 0.80). The highest prevalence of vitamin D deficiency (values <20 ng/ml) was observed in APS type 3 subgroup (8 out of 50 patients, 16%). CONCLUSIONS: Patients with APS present reduced vitamin D circulating levels, but the vitamin D status is not different between patients with single or multiple autoimmune diseases. The kind of autoimmune disease, rather than the association of several autoimmune diseases, may influence negatively the levels of vitamin D. Further prospective studies are needed to clarify if impaired vitamin D level is a causal factor in the pathogenesis of autoimmune diseases or a consequence of them.

Characterization of pituitary cells targeted by antipituitary antibodies in patients with isolated autoimmune diseases without pituitary insufficiency may help to foresee the kind of future hypopituitarism.

PURPOSE: Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism. METHODS: Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up. RESULTS: Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism. CONCLUSIONS: The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy.

Effect of metabolic syndrome and its components on prostate cancer risk: meta-analysis.

BACKGROUND: Literature data examining the role of metabolic syndrome and its components in prostate cancer risk are limited and contradictory. AIM: We did a meta-analysis of studies that evaluated the association between metabolic syndrome, its components, and risk of prostate cancer. SUBJECTS AND METHODS: We conducted an electronic search for articles published through September 2012 without restrictions. Every included study was to report risk estimates with 95% confidence intervals for the association between metabolic syndrome and prostate cancer. RESULTS: The final number of papers included in the meta-analysis was 14, all published in English, with 4728 prostate cancer cases. Metabolic syndrome was associated with a 12% increase in prostate cancer risk (p=0.231), that was lower in cohort studies (7 studies, RR=1.04, p=0.791) than other studies (RR=1.23, p=0.125). The association was significant in the 8 European studies (RR=1.30, p=0.034), but not in the 4 U.S. or 2 Asiatic studies. The risk estimates of prostate cancer for higher values of body mass index, dysglycemia or dyslipidemia (high triglycerides, low HDL-cholesterol) were not significant; on the contrary, hypertension and waist circumference >102 cm were associated with a significant 15% (p=0.035) and 56% (p=0.007) greater risk of prostate cancer, respectively. CONCLUSIONS: Metabolic syndrome is weakly and non significantly associated with prostate cancer risk, but associations vary with geography. Among single components of the syndrome, hypertension and higher waist circumference are significantly associated with increased risk of prostate cancer.

Circulating endothelial progenitor cells in acromegaly.

BACKGROUND: Endothelial progenitor cells (EPCs), involved in the repairing mechanisms of vascular damage, are positively correlated to insulin-like growth factor I (IGF-I) concentrations in healthy adults. However, the levels of EPCs and their role in acromegalic patients have never been investigated. AIM: We conducted a cross-sectional study in order to assess the levels of the different phenotypes of circulating EPC in acromegalic patients. SUBJECTS AND METHODS: The study was performed at the Endocrinology Unit of Federico II University and at the Unit of Metabolic Diseases and Endocrinology of the Second University of Naples. Fifty-five acromegalic patients and 65 healthy controls were studied. EPCs were assessed by flow cytometry and IGF-I by immunoradiometric assay. RESULTS: Compared with subjects of the control group, acromegalic patients showed significantly higher levels of EPCs phenotypes expressing KDR antigen [KDR+, cells per 106 events, median and interquartile range, 44 (28-67) vs 23 (13-40), p=0.006; CD34+KDR+ 25 (18-38) vs 12 (8-17), p<0.001; CD133+KDR+ 17 (13-30) vs 8 (6-12), p<0.001; CD34+KDR+CD133+ 16 (12-25) vs 8 (6-10), p<0.001]. There was a positive correlations between CD34+KDR+CD133+ cells count and IGF-I in acromegaly group (r=0.79, p<0.001). CONCLUSIONS: Acromegalic patients show higher circulating EPCs levels expressing KDR, positively correlated with IGF-I, suggesting a role for IGF-I in regulating the expression of this surface marker in the early phase of EPCs differentiation.

Proportion of patients at HbA1c target <7% with eight classes of antidiabetic drugs in type 2 diabetes: systematic review of 218 randomized controlled trials with 78 945 patients.

AIM: We assessed the efficacy of eight classes of diabetes medications used in current clinical practice [metformin, sulphonylureas, α-glucosidase inhibitors, thiazolidinediones, glinides, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 (GLP-1) analogues and insulin analogues] to reach the HbA1c target <7% in type 2 diabetes. METHODS: MEDLINE, EMBASE and the Cochrane CENTRAL were searched from inception through April 2011 for randomized controlled trials (RCTs) involving antidiabetic drugs. RCTs had to report the effect of any diabetes medication on the HbA1c levels, to include at least 30 subjects in every arm of the study, and to report the effect of therapy after a minimum of 12 weeks. Data were summarized across studies using random-effects meta-regression. RESULTS: A total of 218 RCTs (339 arms and 77 950 patients) met the inclusion criteria. The proportion of patients who achieved the HbA1c goal ranged from 25.9% (95% CI 18.5-34.9) with α-glucosidase inhibitors to 63.2% (54.1-71.5) with the long-acting GLP-1 analogue. There was a progressive decrease of the proportion of patients at target for each 0.5% increase in baseline HbA1c, ranging from 57.8% for HbA1c ≤7.5% to 20.8% for HbA1c ≥10% (p for trend <0.0001), with some difference between insulin and non-insulin drugs: for insulin, the proportion of patients at goal reached a plateau for basal HbA1c value >9.0% with no further decrease, whereas for non-insulin drugs the relationship was continuous without any evidence of plateau. CONCLUSIONS: There is a considerable variability with regard to attainment of HbA1c goal of <7% among the different classes of diabetes medications; baseline HbA1c is an important determinant of observed efficacy.

Comparison of insulin lispro protamine suspension versus insulin glargine once daily in basal-bolus therapies with insulin lispro in type 2 diabetes patients: a prospective randomized open-label trial.

AIMS: To compare the efficacy and safety of insulin lispro protamine suspension (ILPS) versus insulin glargine once daily in a basal-bolus regimen in type 2 diabetes mellitus (T2DM) patients. METHODS: Three hundred eighty-three insulin-treated patients were randomized to either ILPS plus lispro or glargine plus lispro in this open-label 24-week European study. Insulin doses were titrated to predefined blood glucose (BG) targets. Non-inferiority of ILPS versus glargine was assessed by comparing the upper limit of the 95% confidence interval (CI) for the change of HbA1c from baseline to week 24 (adjusted for country and baseline HbA1c) with the non-inferiority margin of 0.4%. Secondary endpoints included HbA1c categories, BG profiles, insulin doses, hypoglycaemic episodes, adverse events and vital signs. RESULTS: Non-inferiority of ILPS versus glargine in the change of HbA1c from baseline was shown: least-square mean between-treatment difference (95% CI) was 0.1% (-0.11; 0.31). Mean changes at week 24 were -1.05% (ILPS) and -1.20% (glargine). HbA1c <7.0% was achieved by 21.7 versus 29.4% of patients. Mean basal/mealtime insulin doses at week 24 were 29.6/36.2 IU/day (ILPS) versus 32.8/42.2 IU/day (glargine); the difference was not statistically significant for total dose (p = 0.7). In both groups, 56.1/25.7% versus 63.6/19.3% of patients experienced any/nocturnal hypoglycaemia (p = 0.2 for both). No relevant differences were noted in any other variables. CONCLUSIONS: A basal-bolus regimen with ILPS once daily resulted in non-inferior glycaemic control compared to a similar regimen with glargine, without statistically significant or clinically relevant differences in hypoglycaemia. ILPS-based regimens can be considered an alternative to basal-bolus regimens with glargine for T2DM patients.

Dipeptidyl peptidase-4 inhibitors and HbA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials.

AIM: We assessed the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin, sitagliptin, saxagliptin and alogliptin to reach the haemoglobin HbA1c target of <7% in people with type 2 diabetes. METHODS: We conducted an electronic search for randomized controlled trials (RCTs) involving DPP-4 inhibitors through September 2010. RCTs were included if they lasted at least 12 weeks, included 30 patients or more and reported the proportion of patients reaching the HbA1c target of <7%. RESULTS: A total of 43 RCTs reporting 52 comparisons met the selection criteria, which included 19 101 study participants evaluated for the primary endpoint, 10 467 treated with a DPP-4 inhibitor and 8634 treated with placebo or a comparator drug. DPP-4 inhibitors showed a statistically significant reduction in HbA1c compared to placebo and approximately 40% of participants achieved the HbA1c goal of <7%: this was associated with weight neutrality and no greater hypoglycaemia. The reduction of the HbA1c level and the rate of HbA1c goal attainment was not different from comparator drugs, with similar hypoglycaemia, and different effect on weight owing to the nature of comparator (metformin, sulfonylurea or glitazones). Baseline HbA1c was the best predictor for achievement of A1C target (overall weighted r(2) value = 0.410, p < 0.001). CONCLUSIONS: A greater proportion of type 2 diabetic patients can achieve the HbA1c goal <7% with DPP-4 inhibitors compared to placebo, with no weight gain, and no hypoglycaemic risk when used alone; DPP-4 inhibitors were not different from comparator drugs.

Effects of pioglitazone versus metformin on circulating endothelial microparticles and progenitor cells in patients with newly diagnosed type 2 diabetes--a randomized controlled trial.

AIM: Endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) are markers of endothelial injury and repair. We compared the effects of pioglitazone versus metformin on the circulating numbers of EMPs and EPCs in patients with newly diagnosed type 2 diabetes. METHODS: This was a randomized, double-blind, comparator-controlled, 24-week single-centre trial conducted in a Teaching Hospital in Naples, Italy. One hundred and ten people with newly diagnosed type 2 diabetes who were never treated with antihyperglycaemic drugs and had haemoglobin A1c (HbA1c) levels between 7 and 10% were given pioglitazone hydrochloride (15-45 mg/day) (n = 55) or metformin (1000-2000 mg/day) (n = 55) as an active comparator. Absolute change from baseline to final visit in circulating EMPs and EPCs and their ratio were the main outcomes. RESULTS: Baseline characteristics did not differ between the study groups. The decrease in circulating EMPs CD31+ [intergroup difference, -32 counts/µl (95% CI -51 to -9)] and the increase in EPCs CD34+/KDR+ [intergroup difference, 33 cells/10(6) events (95% CI 13 to 55)] were greater with pioglitazone versus metformin. EMPs/EPCs ratio was reduced with pioglitazone and unchanged with metformin [difference, -1.5 (95% CI -2.6 to -0.5), p < 0.001]. Participants assigned to pioglitazone gained more weight and experienced greater improvements in some coronary risk measures [high-density lipoprotein (HDL)-cholesterol, triglycerides, adiponectin and C-reactive protein (CRP)] than did those assigned to metformin. CONCLUSION: Compared with metformin, pioglitazone treatment improved the imbalance between endothelial damage and repair capacity and led to more favourable changes in coronary risk factors in patients with newly diagnosed type 2 diabetes.

Relationship of baseline HbA1c, HbA1c change and HbA1c target of < 7% with insulin analogues in type 2 diabetes: a meta-analysis of randomised controlled trials.

AIM: We performed a meta-analysis of randomised controlled trials (RCTs) with insulin analogues in type 2 diabetes utilising a least-squared regression model in order to assess the relationship between baseline HbA1c, the magnitude of HbA1c decrease and attainment of HbA1c target of < 7%. METHODS: Randomised controlled trials involving insulin regimens (basal, prandial, biphasic and basal-bolus) were identified through electronic searches (MEDLINE, EMBASE, CINAHL and The Cochrane Library) through September 2010. We included any study arm of RCTs if they were at least 12 weeks in duration; the number of patients in any arm was more than 30 and reported the baseline HbA1c and change from baseline HbA1c. RESULTS: We found 87 studies, with a total of 135 arms, and 38,803 patients. The weighted R(2) values for the overall analysis assessing the association between baseline HbA1c and absolute change in HbA1c or the proportion of patients at target were 0.485 (p < 0.001) and 0.146 (p < 0.001), respectively. Subanalyses of insulin regimens for the association between basal HbA1c and absolute decrease of HbA1c produced weighted R(2), which were significant for all insulin regimens with the highest association for basal-bolus (R(2) = 0.719, p < 0.001). CONCLUSIONS: The strong positive relationship between baseline HbA1c and the magnitude of HbA1c change we found in RCTs using insulin analogues in type 2 diabetes should be considered when assessing the clinical efficacy of insulin therapies.