Caterina Policola

25-Hydroxyvitamin D Concentration Correlates With Insulin-Sensitivity and BMI in Obesity

The prevalence of hypovitaminosis D is high among obese subjects. Further, low 25‐hydroxyvitamin D (25(OH)D) concentration has been postulated to be a risk factor for type 2 diabetes, although its relation with insulin‐sensitivity is not well investigated. Thus, we aimed to investigate the relationship between 25(OH)D concentration and insulin‐sensitivity, using the glucose clamp technique. In total, 39 subjects with no known history of diabetes mellitus were recruited. The association of 25(OH)D concentration with insulin‐sensitivity was evaluated by hyperinsulinemic euglycemic clamp. Subjects with low 25(OH)D (<50 nmol/l) had higher BMI (P = 0.048), parathyroid hormone (PTH) (P = 0.040), total cholesterol (P = 0.012), low‐density lipoprotein (LDL) cholesterol (P = 0.044), triglycerides (P = 0.048), and lower insulin‐sensitivity as evaluated by clamp study (P = 0.047). There was significant correlation between 25(OH)D and BMI (r = −0.58; P = 0.01), PTH (r = −0.44; P < 0.01), insulin‐sensitivity (r = 0.43; P < 0.01), total (r = −0.34; P = 0.030) and LDL (r = −0.40; P = 0.023) (but not high‐density lipoprotein (HDL)) cholesterol, and triglycerides (r = 0.45; P = 0.01). Multivariate analysis using 25(OH)D concentration, BMI, insulin‐sensitivity, HDL cholesterol, LDL cholesterol, total cholesterol, and triglycerides, as the cofactors was performed. BMI was found to be the most powerful predictor of 25(OH)D concentration (r = −0.52; P < 0.01), whereas insulin‐sensitivity was not significant. Our study suggested that there is no cause–effect relationship between vitamin D and insulin‐sensitivity. In obesity, both low 25(OH)D concentration and insulin‐resistance appear to be dependent on the increased body size.

Long-term follow-up in adrenal incidentalomas: an Italian multicenter study

CONTEXT The long-term consequences of subclinical hypercortisolism (SH) in patients with adrenal incidentalomas (AIs) are unknown. SETTING AND PATIENTS In this retrospective multicentric study, 206 AI patients with a ≥5-year follow-up (median, 72.3 mo; range, 60-186 mo) were enrolled. INTERVENTION AND MAIN OUTCOME MEASURES Adrenocortical function, adenoma size, metabolic changes, and incident cardiovascular events (CVEs) were assessed. We diagnosed SH in 11.6% of patients in the presence of cortisol after a 1 mg-dexamethasone suppression test >5 μg/dL (138 nmol/L) or at least two of the following: low ACTH, increased urinary free cortisol, and 1 mg-dexamethasone suppression test >3 μg/dL (83 nmol/L). RESULTS At baseline, age and the prevalence of CVEs and type 2 diabetes mellitus were higher in patients with SH than in patients without SH (62.2 ± 11 y vs 58.5 ± 10 y; 20.5 vs 6%; and 33.3 vs 16.8%, respectively; P < .05). SH and type 2 diabetes mellitus were associated with prevalent CVEs (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-9.0; and OR, 2.0; 95% CI, 1.2-3.3, respectively), regardless of age. At the end of the follow-up, SH was diagnosed in 15 patients who were without SH at baseline. An adenoma size >2.4 cm was associated with the risk of developing SH (sensitivity, 73.3%; specificity, 60.5%; P = .014). Weight, glycemic, lipidic, and blood pressure control worsened in 26, 25, 13, and 34% of patients, respectively. A new CVE occurred in 22 patients. SH was associated with the worsening of at least two metabolic parameters (OR, 3.32; 95% CI, 1.6-6.9) and with incident CVEs (OR, 2.7; 95% CI, 1.0-7.1), regardless of age and follow-up. CONCLUSION SH is associated with the risk of incident CVEs. Besides the clinical follow-up, in patients with an AI >2.4 cm, a long-term biochemical follow-up is also required because of the risk of SH development.

Low levels of 25(OH)D and insulin-resistance: 2 unrelated features or a cause-effect in PCOS?

BACKGROUND & AIMS Recent investigations have identified low vitamin D status as a hypothetical mechanism of insulin-resistance in Polycystic Ovary Syndrome (PCOS). Instead, some authors supported the hypothesis that low vitamin D levels and insulin-resistance are 2 unrelated features of body size in PCOS. Hence, we aimed to explore the association of 25-hydroxyvitamin D (25(OH)D) with anthropometric, metabolic and hormonal features in PCOS. METHODS We assessed the association of low 25(OH)D levels with endocrine parameters, insulin-sensitivity evaluated by hyperinsulinemic euglycemic clamp (HEC) and body composition measured by DEXA in 38 women affected by PCOS. RESULTS Low 25(OH)D (25(OH)D < 50 nmo/L) was detected in 37% of the entire cohort of patients. Body Mass Index (BMI), in particular total fat mass (p < 0.001), resulted to be the most predictor factor of 25(OH)D levels whereas Sex Hormone Binding Globulin (SHBG), Free Androgen Index (FAI), glucose uptake and fat free mass were not. CONCLUSIONS Our data demonstrated that in PCOS low 25(OH)D levels are significantly determined by the degree of adiposity.

Assessment of insulin resistance in lean women with polycystic ovary syndrome.

OBJECTIVE To develop and validate a specific simple measure of insulin sensitivity using oral glucose tolerance test (OGTT) values for lean polycystic ovary syndrome (PCOS) women. DESIGN Retrospective study. SETTING Gynecologic Outpatient Clinic of University Hospital, affiliated with Unit of Gynecologic Endocrinology. PATIENT(S) Totals of 201 lean and 198 overweight/obese (ov-ob) nondiabetic PCOS patients were retrospectively selected. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) All patients underwent OGTT, euglycemic-hyperinsulinemic clamp, and androgenic and biochemical assays. The predictive performance of each insulin resistance (IR) index was analyzed with the use of receiver operating characteristic (ROC) curves. RESULT(S) Higher correlation coefficients with clamp studies were obtained with the Belfiore Area (RS=0.579) and the homeostasis-model assessment (HOMA)-M120 (RS=-0.576) in lean PCOS patients and with the Sib (RS=0.697) in ov-ob PCOS patients. The best predictive index of IR in lean PCOS was a HOMA-M120 value of ≥12.8 or more (area under the ROC curve [AUC] 92.4%). In the ov-ob PCOS population, the best predictive performance was obtained by a Sib of ≤10.2 or less (AUC 85.7%). CONCLUSION(S) IR should be assessed in all PCOS women, both lean and ov-ob subjects. The HOMA-M120 resulted as a very simple tool, validated specifically for the lean PCOS woman whose cardiometabolic impairment is more frequently misunderstood.

In anorexia nervosa, even a small increase in abdominal fat is responsible for the appearance of insulin resistance

Context  The aim of treatment in patients affected by anorexia nervosa (AN) is weight recovery. However, during weight gain, anorectic patients’ body composition is changed, with an increase in abdominal fat, particularly in the visceral compartment.

Association of Vitamin D With Insulin Resistance and β-Cell Dysfunction in Subjects at Risk for Type 2 Diabetes Comment to Kayaniyil et al.

We read with interest the article by Kayaniyil et al. (1) that supplied elegant data suggesting that 25-hydroxyvitamin D [25(OH)D] is related to insulin resistance and β-cell function in a large population at high risk for type 2 diabetes and/or metabolic syndrome, thus concluding that 25(OH)D may be an independent risk factor for diabetes. We have, however, some concerns. First, the studied population was mainly composed of obese subjects (the mean BMI was 30.5 kg/m2). Clearly, within a …

Early postoperative continuous glucose monitoring in pancreas transplant recipients

Continuous glucose monitoring (CGM) is used in people with type 1 diabetes to help with insulin treatment regimens. Its value in whole‐organ pancreas transplantation (PT) is largely unknown. This study aimed to use CGM to assess the metabolic profile of pancreas transplant recipients in the early post‐transplant period. We studied CGM data in 30 PT recipients and related findings to an early oral glucose tolerance test (OGTT). Complete data were available for 26 recipients. Seven days after a PT, normoglycaemia was present 77.9% of the time. Hypoglycaemic events (glucose <3.9 mmol/l) occurred in 10 of 26 (38.5%) of the cohort, but were infrequent (present 1.4% of the time). Hyperglycaemia (glucose >7.8 mmol/l) was present for 20.7% of the study period and correlated with a diagnosis of abnormal glucose tolerance. Whilst normoglycaemia is successfully achieved for the majority of the time after PT, hypoglycaemia can occur. Hyperglycaemia is more common and correlates well with the early postoperative OGTT, which is associated with graft failure. CGM is easier to perform and provides 24‐h data that could inform clinical decision‐making in patients in the postoperative period.

Myoinositol combined with alpha-lipoic acid may improve the clinical and endocrine features of polycystic ovary syndrome through an insulin-independent action

Abstract The aim of our study was to investigate the effects of a combined treatment with alpha-lipoic acid (ALA) and myoinositol (MYO) on clinical, endocrine and metabolic features of women affected by polycystic ovary syndrome (PCOS). In this pilot cohort study, forty women with PCOS were enrolled and clinical, hormonal and metabolic parameters were evaluated before and after a six-months combined treatment with ALA and MYO daily. Studied patients experienced a significant increase in the number of cycles in six months (p < 0.01). The free androgen index (FAI), the mean androstenedione and DHEAS levels significantly decreased after treatment (p < 0.05). Mean SHBG levels significantly raised (p < 0.01). A significant improvement in mean Ferriman–Gallwey (F–G) score (p < 0.01) and a significant reduction of BMI (p < 0.01) were also observed. A significant reduction of AMH levels, ovarian volume and total antral follicular count were observed in our studied women (p< 0.05). No significant changes occurred in gluco-insulinaemic and lipid parameters after treatment. The combined treatment of ALA and MYO is able to restore the menstrual pattern and to improve the hormonal milieu of PCOS women, even in the absence of apparent changes in insulin metabolism.

Hypovitaminosis D Is Associated with Liver Insulin Resistance in Obese Subjects

1738-P Sustained Action of Ceramide on Insulin Signaling in Muscle Cells: Implication of the Double-Stranded RNA Activated Protein Kinase RIMA HAGE HASSAN, ISABELLE HAINAULT, AGNIESZKA BLACHNIO-ZABIELSKA, RANA MAHFOUZ, OLIVIER BOURRON, PASCAL FERRÉ, FABIENNE FOUFELLE, ERIC HAJDUCH, Paris, France, Białystok, Poland Intramyocellular accumulation of fatty acid derivatives like ceramide plays a crucial role in altering the insulin message. If short-term action of ceramide inhibits the protein kinase B (PKB/Akt), long-term action of ceramide on insulin signaling is less documented. Short-term treatment of either the C2C12 cell line or human myotubes with palmitate (ceramide precursor, 16h) or directly with ceramide (2h) induces a loss of the insulin signal through the inhibition of PKB/Akt. Extended periods of treatment with palmitate (48h) or ceramide (16h), however, shows an inhibition of insulin signaling through increased-IRS1 serine 307 phosphorylation. The double-stranded RNA-dependent protein kinase (PKR) could play a central role to mediate long-term ceramide effects on IRS1, as recent studies showed that PKR acts as a key modulator of metabolic infl ammation, insulin sensitivity and glucose homeostasis in obesity. Here, we show that both PKR mRNA and PKR phosphorylation are increased in muscle of high fat diet fed mice compared to control mice as well as in myotubes from diabetic patients compared to human control myotubes. These results are confi rmed in vitro in both human and C2C12 myotubes in response to either palmitate or ceramide. Pre-treatment of C2C12 or human myotubes with PKR inhibitors prevents the inhibitory effect of either palmitate or ceramide on IRS1. Finally, we show that c-Jun kinase (JNK) mediates ceramide-activated PKR inhibitory action on IRS1. Altogether, our data show that ceramide inhibits effi ciently insulin signalling by targeting in a time dependent manner two important actors, e.g. PKB/Akt and IRS1 in myotubes. Supported By: Société Francophone du Diabète

Long-term follow-up in adrenal incidentalomas: an Italian Multicentre Study

Department of Clinical Sciences and Community Health (V.M., S.P., A.D., M.A., P.B.-P., I.C.), University of Milan, 20122 Milan, Italy; Unit of Endocrinology and Diabetology (V.M., S.P., P.B.-P., I.C.), Fondazione IRCCS Ca Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy; Division of Internal Medicine I (G.R., M.T.), Ospedale San Luigi, 10043 Orbassano, Italy; Department of Biological and Clinical Sciences (G.R., R.G., M.T.), University of Turin, 10124 Turin, Italy; Catholic University (S.D.C., C.P.), Unit of Endocrinology and Metabolism, 00168 Rome, Italy; Unit of Endocrinology (A.S.S., A.S.), Ospedale “Casa Sollievo della Sofferenza,” IRCCS, 71013 San Giovanni Rotondo, Foggia, Italy; Unit of Endocrine Diseases and Diabetology (A.D., M.A.), Ospedale San Giuseppe, Gruppo Multimedica, 20123 Milan, Italy; Department of Biomedical Sciences for Health (M.M., B.A.), University of Milan, Unit of Endocrinology and Diabetology, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Milan, Italy; and Division of Endocrinology, Diabetology, and Metabolism (E.G.), Department of Medical Sciences, University of Turin, 10124 Turin, Italy