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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. [ABSTRACT FROM AUTHOR]

Introduction: The term empty sella refers to a shrunken or displaced (by a subarachnoid diverticulum) pituitary gland. It can be primary (genetically determined) or secondary (due to trauma/surgery/radiation). It has been reported that 50% of patients are asymptomatic, and others experience symptoms, such as headache, hypertension, or visual field defects. Few cases have an empty sella syndrome, i.e., lacking functional pituitary hormones. Diagnosis is made through NMR or CT. If asymptomatic, this condition requires no treatment; otherwise, empty sella syndrome needs hormonal replacement therapy. We examined the case of asymptomatic empty sella syndrome., Case Report: A 67-year-old female patient was admitted for dilatative cardiomyopathy. She had a past medical history of arterial hypertension and right ICA endovascular repair. Blood tests demonstrated hypothyroidism, hypoadrenalism, and GH deficiency, without any signs or symptoms. NRM confirmed an empty sella, hence replacement therapy with levothyroxine and cortisone acetate was started. During a follow-up evaluation, we discovered that this biochemical profile of the patient had been known for more than a decade and never treated. Despite being exposed to stress conditions, vascular surgery and angiography, she never developed an adrenal crisis, nor has she ever been symptomatic for severe hypothyroidism. Hormonal replacement therapy was performed., Conclusion: The described clinical scenario is rare, as usually, empty sella syndrome presents with signs of hormone deficiency, even if asymptomatic cases have been described. Some authors suggest considering it as a hypothalamic dysfunction requiring treatment; others identify it as a paraphysiological variant. However, more cases are needed to establish a correct therapeutic strategy for these patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Chopart amputation is the consequence of severe diabetes-related foot complications. A new interim orthosis allowing the patient a greater degree of mobility after Chopart surgery than currently used systems is now available. The aim of this study was to evaluate the effectiveness of the new orthosis compared with traditional treatment. Safety and level of patient acceptance of the device were also investigated. We performed a retrospective case-control observational study involving people with diabetes who underwent Chopart amputation between January 2016 and January 2018. The sample of subjects treated with the innovative orthosis was compared with consecutive patients, who were treated with traditional management. The main study outcomes include major amputation occurrence, ulcer recurrence, healing time, and patient acceptance of the orthosis. Patient satisfaction was evaluated using the Italian validated version of the Orthotic Prosthetic User's Survey (OPUS) questionnaire. Overall, 27 subjects were enrolled using the new device (mean age 68.7 ± 8.4 years, 70.4% males, mean diabetes duration 22.7 ± 15 years). Clinical baseline characteristics were comparable between the cases and the controls. There was no difference between the groups in the healed wound rate (81.5% vs 80.0% for cases and the control group, respectively, P  = .53). The ulcer recurrence rate was higher in the control group compared with subjects using the new orthosis (62.5% vs 24.0%, respectively, P  = .04). The use of the innovative orthosis was associated with an 81% lower probability to have ulcer recurrence (odds ratio 0.19, 95% confidence interval 0.04-1.04). No between groups difference was detected for a major amputation rate. The wound healing time was faster for cases compared with controls (160.4 ± 114.1 vs 256.5 ± 112.9 days, P  = .05). No adverse events related to the use of the new orthosis were recorded. Patient acceptance of the new orthosis was high. This orthosis can be recommended as an efficient, safe, and well-accepted device after Chopart amputation.

Osteomyelitis represents a challenging condition in the diabetic foot with an associated high risk of major amputation. S53P4 Bioactive Glass (BG) has bacterial inhibiting properties on the market and indicated to be used in osteomyelitis. The objective of the study was to test the efficacy and safety of BG in treating diabetic foot osteomyelitis. This was an observational, retrospective, single-centre study involving subjects with diabetes affected by osteomyelitis of the foot who underwent surgical debridement from 01/2016 to 10/2018. Overall, 44 diabetic patients (14 [31.8%] female, aged 68.0 ± 10.2 years, diabetes duration 26.8 ± 11.9 years) were studied: 22 (50%) treated with surgical debridement and a local application of BG; 22 (50%) treated by means of surgical debridement. The primary outcome was the osteomyelitis resolution. Revascularization was performed before surgical procedure in 31 (70.5%) of patients. Systemic antibiotics were used in both groups. The osteomyelitis resolution rate was significantly higher in subjects treated with BG than in subjects treated with traditional procedure (18 [90%] vs 13 [61.9%], respectively p = .03). The odds of BG to reach osteomyelitis resolution was 5.54 times greater than for traditional treatment (odds ratio 5.54, 95% confidence interval 1.10-30.5). The use of BG was associated with an 81% lower probability to need additional antibiotic therapy compared to subjects treated with traditional procedure (odds ratio 0.19, 95% confidence interval 0.04-0.87). The debridement of osteomyelitis followed by application of BG could be an effective and safe option in the treatment of osteomyelitis of the diabetic foot., (Copyright © 2020. Published by Elsevier Inc.)

Context: In type 2 diabetes (T2D), the vertebral fracture (VFx) prevalence and cortisol secretion are increased., Objective: The objective of this study was to evaluate the role of glucocorticoid secretion and sensitivity in T2D-related osteoporosis., Design and Setting: This was a case-control study in an outpatient setting., Patients: The patients were ninety-nine well-compensated T2D postmenopausal women (age, 65.7 ± 7.3 y) and 107 controls (age, 64.5 ± 8.2 y)., Main Outcome Measures: We assessed osteocalcin, C-terminal telopeptide of type I collagen, ACTH, cortisol after the dexamethasone suppression test (F-1mgDST), BclI and N363S single-nucleotide polymorphisms (SNPs) of glucocorticoid receptor, lumbar spine and femoral neck bone mineral density by dual x-ray absorptiometry, and VFx by radiography., Results: Compared with controls, T2D subjects had increased VFx prevalence (20 vs 34.3%, respectively; P = .031), bone mineral density (Z-scores, lumbar spine, 0.16 ± 1.28 vs 0.78 ± 1.43, P = .001; femoral neck, -0.03 ± 0.87 vs 0.32 ± 0.98, P = .008, respectively), and F-1mgDST (1.06 ± 0.42 vs 1.21 ± 0.44 μg/dL, 29.2 ± 1.2 vs 33.3 ± 1.2 nmol/L, respectively; P = .01), and decreased osteocalcin (10.6 ± 6.4 vs 4.9 ± 3.2 ng/mL, 10.6 ± 6.4 vs 4.9 ± 3.2 μg/L, respectively; P < .0001) and C-terminal telopeptide of type I collagen (0.28 ± 0.12 vs 0.14 ± 0.08 ng/mL, 0.28 ± 0.12 vs 0.14 ± 0.08 mcg/L, respectively; P < .0001). Fractured controls or T2D patients had increased sensitizing N363S SNP prevalence (20 and 17.6%, respectively) compared to non-fractured subjects (3.4 and 3.1%, respectively; P = .02 for both comparisons), and similar BclI SNP prevalence. The VFx presence was associated with the sensitizing variant of N363S SNPs in controls (odds ratio [OR] = 10.6; 95% confidence interval [CI], 1.8-63.3; P = .01) and in T2D patients (OR = 12.5; 95% CI, 1.8-88.7; P = .01), and with the F-1mgDST levels (OR = 2.1; 95% CI, 1.1-4.1; P = .03) only in T2D patients., Conclusions: In postmenopausal T2D women, VFx are associated with cortisol secretion and the sensitizing variant of N363S SNPs.

Background: The metabolic syndrome is a common condition among liver transplanted patients and contributes to morbidity and mortality by favouring the development of cardiovascular diseases., Aims: This prospective study assessed the prevalence of metabolic syndrome in the first year after orthotopic liver transplantation, the associated pre-operative and post-operative risk factors and the influence of nutritional factors., Methods: 84 cirrhotic patients (75% male, mean age 53.9±9.3 years) were evaluated at baseline and after liver transplantation. Metabolic syndrome was defined according to 2004 Adult Treatment Panel-III criteria. Nutritional habits were assessed using 3-day food records., Results: Prevalence of metabolic syndrome before orthotopic liver transplantation was 14/84 (16.6%); at 3, 6 and 12 months post-orthotopic liver transplantation it was 27/84 (32.1%), 30/84 (35.7%), and 32/81 (39.5%), respectively. Diabetes, family history of diabetes, and excess body weight at baseline independently correlated with incidence of metabolic syndrome. After orthotopic liver transplantation, patients with metabolic syndrome showed a higher increase in the intake of total energy and saturated fats and a higher prevalence of complications, especially cardiovascular events, than subjects without metabolic syndrome., Conclusion: Occurrence of metabolic syndrome is an early phenomenon after liver transplantation. Pre-operative and post-operative factors predispose patients to metabolic syndrome, which may be reduced by controlling modifiable risk factors, such as body weight and dietary intake., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Williams syndrome (WS) is a rare, multisystemic genomic disorder showing a high prevalence of impaired glucose metabolism in adulthood. The reason for this association is unknown, though hemizygosity for genes mapping to the WS chromosome region has been implicated. Twenty-two Italian young adults with WS (13 females, 9 males) were studied. A 75 g oral glucose tolerance test (OGTT) was performed and β-cell function was estimated with Homeostasis Model Assessment (HOMA)-B%, Insulinogenic Index, and corrected insulin response whereas insulin sensitivity was assessed with HOMA-Insulin Resistance Index, Quantitative Insulin Check Index, and composite Insulin Sensitivity Index. One patient had known diabetes mellitus (DM), whereas impaired glucose tolerance (IGT) was diagnosed in 12 patients and DM in one (63.6% prevalence of impaired glucose metabolism). IGT patients were more insulin resistant than those with normal glucose tolerance (NGT), whereas β-cell function was unchanged or increased. Islet autoimmunity was absent. Logistic regression showed that impaired glucose metabolism was not associated with age, body mass index (BMI), or family history of DM. β-cell function, insulin sensitivity, and post-load insulin levels did not differ between WS patients with NGT and healthy controls comparable for gender, age, and BMI, though WS-NGT patients had higher post-load glucose values. These data confirm the high prevalence of impaired glucose metabolism in WS young adults, thus suggesting the need for screening these patients with OGTT. IGT is associated with reduced insulin sensitivity, but not with impaired β-cell function, islet autoimmunity, and traditional risk factors for type 2 DM., (Copyright © 2013 Wiley Periodicals, Inc.)

Context: In patients with adrenal incidentalomas and subclinical hypercortisolism (SH), the factors influencing bone and the prevalence of vertebral fractures are debated. Spinal deformity index (SDI), which reflects bone quality, has never been evaluated., Objective: The objective of the study was to investigate in these patients SDI and factors influencing the prevalence of fractures., Design: This was a retrospective, multicenter study., Setting: The study was conducted on an in- and outpatient basis., Patients: Patients included 287 adrenal incidentaloma patients (111 eugonadal males, 31 premenopausal, 145 postmenopausal females) and 194 controls (90 eugonadal males, 29 premenopausal, 75 postmenopausal females)., Main Outcome Measure: Bone mineral density (BMD) was measured by dual X-ray absorptiometry at lumbar spine and femoral neck. By radiograph each vertebra was assessed as intact (grade 0) or grade 1 (20-25%), 2 (25-40%), or 3 (>40%) deformity; SDI was calculated by summing the grade of deformity for each vertebra. SH was diagnosed in the presence of at least two of the following: urinary free cortisol greater than 70 microg per 24 h (193.1 nmol/liter), cortisol after 1-mg dexamethasone test greater than 3.0 microg/dl (>82.8 nmol/liter), ACTH less than 10 pg/ml (<2.2 pmol/liter)., Results: BMD was significantly lower in SH+ than SH- patients and controls (lumbar spine -0.73 +/- 1.43, 0.17 +/- 1.33, 0.12 +/- 1.21, respectively; femoral neck -0.37 +/- 1.06, 0.07 +/- 1.09, 0.17 +/- 1.02). Patients with SH had higher fracture prevalence and SDI than those without SH and controls (70.6, 22.2, 21.8%, respectively, P < 0.0001; 0.31 +/- 0.68, 0.39 +/- 0.93, 1.35 +/- 1.27, respectively, P < 0.0001). Fractures and SDI were associated with SH (odds ratio 7.27, 95% confidence interval 3.94-13.41, P = 0.0001; beta = 0.352, t = 6.241, P = 0.0001, respectively) regardless of age, BMD, menopause, and gender., Conclusion: SH is associated with low BMD, high fracture prevalence, and reduced bone quality as measured by SDI.

Objective: The criteria for defining subclinical hypercortisolism (SH) are debated and a real gold standard test or combination of tests is lacking. Recently, late-night salivary cortisol (MSC) has been described as a sensitive and easy-to-perform marker for diagnosing overt hypercortisolism. No data are available on the role of MSC in the diagnosis of SH. The aim of this study was to evaluate the sensitivity and specificity of MSC levels in the diagnosis of SH in patients with adrenal incidentalomas (AI)., Methods: In 103 (females/males, 69/34) patients with AI, MSC levels were studied. One milligram overnight dexamethasone suppression test (DST), urinary-free cortisol (UFC), and ACTH plasma levels were also evaluated. Patients were defined as affected by SH if they showed two of the following criteria: DST>83 nmol/l, ACTH <2.2 pmol/l, and UFC >193 nmol/24 h., Results: No difference in MSC levels in patients with SH (3.1+/-3.1 nmol/l) compared with patients without SH (2.2+/-2.8 nmol/l) was observed. In patients with SH, MSC levels were significantly correlated with DST (r=0.4, P<0.05). Using the cut-off of 5.1 nmol/l, the sensitivity and specificity of MSC levels for diagnosis of SH is 22.7 and 87.7% respectively., Conclusion: In patients with AI, normal levels of MSC do not exclude SH, whereas high levels may suggest the presence of SH identified by conventional tests. Thus, MSC is not suitable as a screening test, although it may be used in conjunction with other tests as the confirming test in selected patients.

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.