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Background and aims To compare biventricular and biatrial myocardial strain indices assessed by two-dimensional speckle tracking echocardiography (2D-STE) in women with gestational diabetes mellitus (GDM) and those with uncomplicated pregnancy at the third trimester of pregnancy and in post-partum. Methods and results 30 consecutive GDM women and 30 age-, ethnicity- and gestational week-matched controls without any comorbidity were examined in this prospective case-control study. All women underwent obstetric visit, blood tests and transthoracic echocardiography (TTE) implemented with 2D-STE analysis of all cardiac chambers at 36-38 weeks’ gestation. TTE and 2D-STE were repeated at 6–10 weeks after delivery. At 36-38 weeks’ gestation, GDM women, compared to controls, had significantly higher body mass index (BMI), blood pressure values and inflammatory markers. TTE showed increased left ventricular (LV) mass and impaired LV diastolic function in GDM women, whereas there was no significant difference between the groups in ejection fraction. 2D-STE revealed that biventricular global longitudinal strain (GLS) and biatrial reservoir strain indices were significantly lower in GDM women than controls. Third trimester BMI was inversely correlated with LV-GLS (r=–0.86) and was independently associated with reduced LV-GLS (less negative than –20%) in GDM women in post-partum (OR 1.81, 95%CI 1.14-2.89). A BMI value ≥30 Kg/m2 had 100% sensitivity and 99.5% specificity for identifying GDM women with impaired LV-GLS in post-partum (AUC=0.97). Conclusion Women with GDM, compared to women with uncomplicated pregnancy, have significantly lower biventricular and biatrial myocardial deformation indices. These abnormalities may be persistent in post-partum in GDM women with obesity.

Purpose An observational retrospective study was conducted by 2 diabetes clinics in Italy to assess patterns of use and long-term effectiveness of liraglutide on established and emerging parameters. Methods Data from 261 patients with type 2 diabetes who started treatment with liraglutide between 2010 and 2014 were collected. Hierarchical linear regression models were applied to assess trends over time of clinical parameters. Factors associated with higher likelihood of dropout were identified through multivariate logistic analysis. Findings Liraglutide was initiated as a switch in 42.5% of patients and as an add-on in 49.8%; in 7.7% of the patients initiation of liraglutide was associated with a reduction in the number of pharmacologic agents. A statistically significant reduction after 36 months was found for the following parameters (mean change [95% CIs]): glycosylated hemoglobin (HbA 1c ; –1.01% [1.34% to –0.68%]), fasting blood glucose (–27.5 [–40.6 to –14.4] mg/dL), weight (–2.9 [–4.5 to –1.3] kg), body mass index (–1.13 [–1.76 to –0.50] kg/m 2 ), waist circumference (–1.74 [–3.85 to –0.37] cm), and LDL-C (–24.7 [–36.67 to –12.8] mg/dL). Improvements in systolic (–3.5 mm Hg) and diastolic (–2.3 mm Hg) blood pressures were observed at 24 months. Albuminuria was reduced by –16.6 mg/L during 36 months, although statistical significance was not reached. Glomerular filtration rate and heart rate were unchanged. Reductions in HbA 1c between –0.6% and –1.3% were obtained in specific subgroups. Treatment was effective also in patients with >20 years of diabetes duration, although the likelihood of dropout was 6% higher for each additional year of disease duration (RR = 1.06; 95% CI, 1.01–1.12). The likelihood of dropout was almost four times higher for subjects treated with insulin (RR = 3.82; 95% CI, 1.22–11.96) and more than twice for those treated with sulfonylureas (RR = 2.39; 95% CI, 1.16–4.94) compared with patients not treated with these agents. Implications Liraglutide used in routine clinical conditions maintains its effectiveness on metabolic control and weight after 3 years. Improvements in terms of metabolic control were found when liraglutide was used as both switch and add-on treatment. In addition, improvements were sustained when liraglutide replaced sulfonylureas or insulin. Diabetes duration had no impact on drug efficacy. Long-term benefits relative to blood pressure and LDL-C were also found, which could not be entirely explained by antihypertensive/lipid-lowering treatment intensification. No major effect on renal parameters was documented. Diabetes duration and some concomitant treatments were associated with a higher likelihood of liraglutide discontinuation. These data can contribute to improve appropriateness and cost-effectiveness profile of liraglutide.

AimsTo investigate whether liraglutide improves diastolic function in type 2 diabetes.MethodsThirty-seven patients with type 2 diabetes who began liraglutide therapy between June 2013 and May 2014 were enrolled in this observational, prospective study. 26 patients received liraglutide therapy for at least 6months. The remaining 11 patients withdrew from liraglutide therapy during the first month, were started on other hypoglycaemic therapies and formed the control group. Anthropometric, metabolic and echocardiographic parameters including pulsed wave tissue Doppler imaging were evaluated at baseline and at 6months.ResultsIn the liraglutide group the early diastolic mitral annulus velocity on the lateral (e-lat) and medial (e-med) sides of the mitral annulus increased from 9.2±3.4 to 11.6±4.7cm/s (p

Context Diabetes insipidus (DI) is one of most common complications of Langerhans cell histiocytosis (LCH) but prevalence of anterior pituitary deficiencies and metabolic alterations have not been clearly defined yet. Objectives Evaluate prevalence of endocrine and metabolic manifestations in a cohort of patients affected by Pulmonary LCH. Methods Observational cross-sectional study on 18 adults (7 M/11 F, 42 ± 12 years) studied for complete basal and dynamic endocrine lab tests and glucose metabolism. Results Hypothalamic-pituitary endocrine alterations were found in 9 patients: 9 had DI, 5 Growth Hormone Deficiency (GHD), 5 central hypogonadism, 3 central hypothyroidism and 1 central hypoadrenalism. Hyperprolactinemia and hypothalamic syndrome were found in 2 patients each. All these central endocrine alterations were always associated to DI. Five of the 10 MRI performed showed abnormalities. Prevalence of obesity and glucose alterations (either DM or IFG/IGT) were respectively 39% and 33%, higher than expected basing on epidemiological data on general Italian population. Multi-system-LCH without risk-organ involvement (LCH MS-RO−) seems to have slightly higher prevalence of insulin resistance, glucose alterations and metabolic syndrome than LCH with isolated lung involvement (LCH SS lung+). A papillary BRAFV600E positive thyroid carcinoma was diagnosed in one patient. Conclusions The presence of anterior pituitary deficiencies should be systematically sought in all LCH patients with DI both at diagnosis and during the follow-up by basal and dynamic hormonal assessment. Patients with pulmonary LCH, particularly those with MS disease, have a worse metabolic profile than general population. Occurrence of papillary thyroid carcinoma has been reported.

OBJECTIVE—The presence of an enhanced cortisol secretion in patients with type 2 diabetes is debated. In type 2 diabetic subjects, cortisol secretion was found to be associated with the complications and metabolic control of diabetes. We evaluated cortisol secretion in 170 type 2 diabetic subjects and in 71 sex-, age-, and BMI-matched nondiabetic subjects. RESEARCH DESIGN AND METHODS—In all subjects, we evaluated ACTH at 8:00 a.m. in basal conditions and serum cortisol levels at 12:00 p.m. (F24) and at 9:00 a.m. after a 1-mg overnight dexamethasone suppression test and 24-h urinary free cortisol (UFC). In diabetic patients, we evaluated the presence of chronic complications (incipient nephropathy, asymptomatic neuropathy, background retinopathy, and silent macroangiopathy). Patients were subdivided according to the absence (group 1, n = 53) or presence (group 2, n = 117) of diabetes complications. RESULTS—In group 2, UFC (125.2 ± 4.6 nmol/24 h) and F24 (120.6 ± 4.1 nmol/l) were higher than in group 1 (109.2 ± 6.8 nmol/24 h, P = 0.057, and 99.7 ± 6.1 nmol/l, P = 0.005, respectively) and in nondiabetic patients (101.7 ± 5.9 nmol/24 h, P = 0.002, and 100.3 ± 5.3 nmol/l, P = 0.003, respectively). In diabetic patients, the number of complications was associated with F24 (R = 0.345; P < 0.0001) and diabetes duration (R = 0.39; P < 0.0001). Logistic regression analysis showed that the presence of diabetes complications was significantly associated with F24, sex, duration of diabetes, and glycated hemoglobin. CONCLUSIONS—In type 2 diabetic subjects, hypothalmic-pituitary-adrenal activity is enhanced in patients with diabetes complications and the degree of cortisol secretion is related to the presence and number of diabetes complications.

Background: In patients with primary hyperparathyroidism (pHPT) the therapeutical choice is surgery. In patients with high surgical and anesthetic risks, ultrasound-guided laser ablation (LTA) of parathyroid adenoma has been reported to reduce parathyroid hormone (PTH) hypersecretion without relevant side effects. No data are available from patients followed for >6 months. We report our 3-year follow-up experience with LTA in 3 patients affected by pHPT due to a parathyroid tumor. Methods: LTA was performed under color-Doppler ultrasound guidance with a continuous pulse at 2 W (total treatment duration: 300 s in each session; total energy: 1,200 J in two sessions). Results: In the first patient who refused to undergo the second LTA session, calcium, PTH levels and parathyroid lesion volume showed a slight reduction, returning to baseline values in a month. In the second patient, no modification of parathyroid lesion was obtained even if calcium levels temporarily normalized. In the third patient, LTA led to normalization of calcium and PTH levels and to a 99% reduction of parathyroid volume. Conclusion: After LTA procedures the long-term disease remission of pHPT is achievable in a minority of patients. Data from larger samples are needed to verify the usefulness of this procedure.

The presence of an enhanced cortisol secretion in patients with type 2 diabetes is debated. In type 2 diabetic subjects, cortisol secretion was found to be associated with the complications and metabolic control of diabetes. We evaluated cortisol secretion in 170 type 2 diabetic subjects and in 71 sex-, age-, and BMI-matched nondiabetic subjects.In all subjects, we evaluated ACTH at 8:00 a.m. in basal conditions and serum cortisol levels at 12:00 p.m. (F24) and at 9:00 a.m. after a 1-mg overnight dexamethasone suppression test and 24-h urinary free cortisol (UFC). In diabetic patients, we evaluated the presence of chronic complications (incipient nephropathy, asymptomatic neuropathy, background retinopathy, and silent macroangiopathy). Patients were subdivided according to the absence (group 1, n = 53) or presence (group 2, n = 117) of diabetes complications.In group 2, UFC (125.2 +/- 4.6 nmol/24 h) and F24 (120.6 +/- 4.1 nmol/l) were higher than in group 1 (109.2 +/- 6.8 nmol/24 h, P = 0.057, and 99.7 +/- 6.1 nmol/l, P = 0.005, respectively) and in nondiabetic patients (101.7 +/- 5.9 nmol/24 h, P = 0.002, and 100.3 +/- 5.3 nmol/l, P = 0.003, respectively). In diabetic patients, the number of complications was associated with F24 (R = 0.345; P0.0001) and diabetes duration (R = 0.39; P0.0001). Logistic regression analysis showed that the presence of diabetes complications was significantly associated with F24, sex, duration of diabetes, and glycated hemoglobin.In type 2 diabetic subjects, hypothalamic-pituitary-adrenal activity is enhanced in patients with diabetes complications and the degree of cortisol secretion is related to the presence and number of diabetes complications.

Symptomatic diabetic neuropathy has been found to be associated with hypothalamus-pituitary-adrenal (HPA) axis hyperfunction, but no data are available about HPA activity in diabetic patients with asymptomatic autonomic imbalance. To evaluate HPA axis activity in patients with type 2 diabetes mellitus (T2DM) in relation to the presence or the absence of subclinical parasympathetic or sympathetic neuronal dysfunction, we performed an observational study on 59 consecutive type 2 diabetic patients without chronic complications and/or symptoms of neuropathy or hypercortisolism. The following were measured: serum cortisol at 08:00 am and at midnight (F8 and F24, respectively), post-dexamethasone suppression cortisol, 24-hour urinary free cortisol (UFC), and morning corticotropin (ACTH). Deep-breathing (DB) and LS (LS) autonomic tests were performed to assess the parasympathetic function; postural hypotension test was performed to evaluate sympathetic activity. Patients were subdivided into 4 groups: subjects with parasympathetic failure (group A), sympathetic failure (group B), both para- and sympathetic failure (group C), and without autonomic failure (group D). Hypothalamus-pituitary-adrenal activity was increased in group A compared with group D (UFC, 48.6 +/- 21.4 vs 21.6 +/- 9.8 microg/24 h, P.0001; ACTH, 27.0 +/- 8.6 vs 15.7 +/- 5.7 pg/dL, P.01; F8, 20.4 +/- 4.5 vs 13.6 +/- 3.8 microg/dL, P.05; post-dexamethasone suppression cortisol, 1.2 +/- 0.4 vs 0.8 +/- 0.6 microg/dL, P.05, respectively) and group B (UFC, 26.3 +/- 11.0 microg/24 h, P.0001; ACTH, 19.9 +/- 8.0 pg/dL, P.05). Regression analysis showed that UFC levels were significantly associated with the deep-breathing test (beta = -0.40, P = .004) and tended to be associated with the lying-to-standing test (beta = -0.26, P = .065), whereas body mass index, glycated hemoglobin, and duration of disease were not. Type 2 diabetic patients with asymptomatic parasympathetic derangement have increased activity of HPA axis, related to the degree of the neuronal dysfunction.

Objective: Subclinical hypercortisolism (SH) may play a role in several metabolic disorders, including diabetes. No data are available on the relative prevalence of SH in type 2 diabetes (T2D). In order to compare the prevalence of SH in T2D and matched non-diabetic control individuals, we performed a case-controlled, multicenter, 12-month study, enrolling 294 consecutive T2D inpatients (1.7% dropped out the study) with no evidence of clinical hypercortisolism and 189 consecutive age- and body mass index-matched non-diabetic inpatients (none of whom dropped out). Design and methods: Ascertained SH (ASH) was diagnosed in individuals (i) with plasma cortisol after 1 mg overnight dexamethasone suppression >1.8 μg/dl (50 nmol/l), (ii) with more than one of the following: (a) urinary free cortisol >60.0 μg/24 h (165.6 nmol/24 h), (b) plasma ACTH 7.5 μg/dl (207 nmol/l) at 24:00 h or >1.4 μg/dl (38.6 nmol/l) after dexamethasone-CRH (serum cortisol after corticotrophin-releasing hormone stimulus during dexamethasone administration) test, and (iii) in whom the source of glucocorticoid excess was suggested by imaging and by additional biochemical tests (for ACTH-dependent ASH). Results: Prevalence of ASH was higher in diabetic individuals than in controls (9.4 versus 2.1%; adjusted odds ratio, 4.8; 95% confidence interval, 1.6–14.1; P = 0.004). In our population the proportion of T2D which is statistically attributable to ASH was approx. 7%. Among diabetic patients, the presence of severe diabetes (as defined by the coexistence of hypertension, dyslipidaemia and insulin treatment) was significantly associated with SH (adjusted odds ratio, 3.8; 95% confidence interval, 1.4–10.2; P = 0.017). Conclusions: In hospitalized patients, SH is associated with T2D.

Several papers focused on the possible link between cortisol secretion and physiological and pathological cerebral aging (1,2). The neurological (mainly limbic-hippocampal) degenerative modification during aging has been suggested to be responsible for a hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis, and an age-related decrease of HPA sensitivity to cortisol feedback has been reported (2). In our study (3 …

The ability of acute rosiglitazone administration in influencing ACTH/cortisol secretion in basal conditions and after CRH stimulation was studied in patients with Cushing’s disease. Ten patients (8 women and 2 men, aged 18–65 yr) with Cushing’s disease were enrolled in the study: 6 of them had previously undergone unsuccessful surgery and 4 were untreated. Plasma ACTH and serum cortisol levels were evaluated at serial time points for 3 h during saline infusion and after the administration of rosiglitazone (8 mg, po) and for 1 h after the injection of CRH (1 μg/kg iv) given alone or 30 min following rosiglitazone administration. The 4 tests were performed in all subjects in randomized order on different days. No significant difference was observed between the pattern of hormone secretion during saline alone and after rosiglitazone, as evaluated by two-way analysis of variance (ANOVA). The integrated areas under the curves (AUCs) were also not significantly different (ACTH: 5683±1038 vs 6111±1007 pg/ml/180 min; cortisol: 2333±267 vs 2902±486 μg/dl/180 min). In addition, there was no difference for ACTH and cortisol responses to CRH given either alone or after rosiglitazone, when evaluated as peak, increment or AUC; the pattern of the responses analyzed by two-way ANOVA was also similar. In conclusion: 1) the administration of a single dose of rosiglitazone did not decrease ACTH/cortisol levels or blunt their response after CRH injection; 2) the activation of PPAR-γ receptors by rosiglitazone seems unable to affect ACTH and cortisol secretion, at least in acute conditions, in patients with ACTH-secreting pituitary adenomas.