Gamma heavy-chain disease accompanied with follicular lymphoma: a case report.

Heavy chain diseases (HCD) are B-cell lymphoprolipherative disorders characterized by the production of monoclonal heavy chains without associated light chains. Some cases of gamma-HCD (γ-HCD) are concurrent with other lymphoid neoplasm. The monoclonal component is not always detectable by serum electrophoresis, and often an immunofixation procedure is necessary to detect this component. Prognosis is variable, and no established guidelines for follow-up are available. We describe a case of a challenging diagnosis of γ-HCD due to the absence of clinical signs frequently reported in the disease (anaemia and palatal oedema among others). Haematological malignancy was the first suspicion but bone marrow examination was negative. In addition, the presence of an autoimmune bicytopenia and a Klinefelter syndrome complicated the clinical context of the patient. A thoracoabdominal computed tomography reported many small adenopathies whose pathological and immunohystochemical study revealed a follicular lymphoma. Shortly after, serum inmunofixation secondary to an abnormal electrophoretic pattern revealed a gamma paraprotein without light chains. Eventually, γ-HCD in association with follicular lymphoma was the final diagnosis. This is the first case reporting this association.

Type 1 diabetes: Developing the first risk-estimation model for predicting silent myocardial ischemia. The potential role of insulin resistance.

OBJECTIVES: The aim of the study was to develop a novel risk estimation model for predicting silent myocardial ischemia (SMI) in patients with type 1 diabetes (T1DM) and no clinical cardiovascular disease, evaluating the potential role of insulin resistance in such a model. Additionally, the accuracy of this model was compared with currently available models for predicting clinical coronary artery disease (CAD) in general and diabetic populations. RESEARCH, DESIGN AND METHODS: Patients with T1DM (35-65years, >10-year duration) and no clinical cardiovascular disease were consecutively evaluated for: 1) clinical and anthropometric data (including classical cardiovascular risk factors), 2) insulin sensitivity (estimate of glucose disposal rate (eGDR)), and 3) SMI diagnosed by stress myocardial perfusion gated SPECTs. RESULTS: Eighty-four T1DM patients were evaluated [50.1±9.3 years, 50% men, 36.9% active smokers, T1DM duration: 19.0(15.9-27.5) years and eGDR 7.8(5.5-9.4)mg·kg-1·min-1]. Of these, ten were diagnosed with SMI (11.9%). Multivariate logistic regression models showed that only eGDR (OR = -0.593, p = 0.005) and active smoking (OR = 7.964, p = 0.018) were independently associated with SMI. The AUC of the ROC curve of this risk estimation model for predicting SMI was 0.833 (95%CI:0.692-0.974), higher than those obtained with the use of currently available models for predicting clinical CAD (Framingham Risk Equation: 0.833 vs. 0.688, p = 0.122; UKPDS Risk Engine (0.833 vs. 0.559; p = 0.001) and EDC equation: 0.833 vs. 0.558, p = 0.027). CONCLUSION: This study provides the first ever reported risk-estimation model for predicting SMI in T1DM. The model only includes insulin resistance and active smoking as main predictors of SMI.

FGF-23/Vitamin D Axis in Type 1 Diabetes: The Potential Role of Mineral Metabolism in Arterial Stiffness.

OBJECTIVE: To investigate the usefulness of Fibroblast Growth Factor 23 (FGF-23) and vitamin D as possible biomarkers of pre-clinical atherosclerosis, assessed as arterial stiffness (AS), in a group of subjects with type 1 diabetes (T1DM) and no previous cardiovascular events. RESEARCH DESIGN AND METHODS: 68 T1DM patients and 68 age- and sex-matched controls were evaluated for 1) age, sex, diabetes duration, physical activity, smoking, alcohol intake, BMI, blood pressure, fasting plasma glucose, HbA1c, estimated glomerular filtration rate (eGFR) and lipid profile; 2) microvascular complications; 3) blood concentrations of FGF-23 and mineral metabolism parameters (calcium, phosphate, parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25(OH)D)); 4) AS, assessed as aortic pulse wave velocity (aPWV); and 5) low-grade inflammation (hsCRP, IL-6, sTNFαR1, sTNFαR2) and endothelial dysfunction (ED) markers (ICAM-1, VCAM-1, E-Selectin). RESULTS: Patients with T1DM had higher aPWV compared with controls (p<0.001), but they did not present differences in 25(OH)D (70.3(50.4-86.2)nmol/L vs. 70.7(59.7-83.0)nmol/L; p = 0.462) and in FGF-23 plasma concentrations (70.1(38.4-151.9)RU/mL vs. 77.6(51.8-113.9)RU/mL; p = 0.329). In T1DM patients, higher concentrations of FGF-23 were positively associated with aPWV after adjusting for eGFR and classical cardiovascular risk factors (model 1: ß = 0.202, p = 0.026), other mineral metabolism parameters (model 2: ß = 0.214, p = 0.015), microvascular complications, low-grade inflammation and ED markers (model 3: ß = 0.170, p = 0.045). Lower 25(OH)D concentrations were also associated with higher aPWV after adjusting for all the above-mentioned factors (model 3: ß = -0.241, p = 0.015). CONCLUSIONS: We conclude that both FGF-23 plasma concentrations (positively) and 25(OH)D serum concentrations (negatively) are associated with AS in patients with T1DM and no previous cardiovascular events.

Men with hyperferritinemia and diabetes in the Mediterranean area do not have a higher iron overload than those without diabetes.

AIM: To assess the role of iron overload in type 2 diabetic men with hyperferritinemia. METHODS: 150 men were recruited from a genetic screening programme for hereditary hemocromatosis (HH) and were tested for type 2 diabetes, other components of the metabolic syndrome, beta cell function (BCF), insulin sensitivity, high-sensitivity C-reactive protein and iron overload. RESULTS: Fifty-one men had type 2 diabetes. They were older (p=0.017) and 99 had lower BCF (p<0.001) than non-diabetic men. None of the iron overload indexes was associated with diabetes. CONCLUSIONS: Our findings dispute a role of iron overload in the pathogenesis of type 2 diabetes.

A lesser postprandial suppression of plasma ghrelin in Prader-Willi syndrome is associated with low fasting and a blunted postprandial PYY response.

OBJECTIVE: Ghrelin and polipeptide YY (PYY) are involved in the regulation of food intake. We evaluated these two peptides and their possible relationship in adult patients with Prader-Willi syndrome (PWS). PATIENTS: Seven patients with PWS, 16 age-sex-BMI matched obese and 42 age-sex matched lean subjects. DESIGN AND MEASUREMENTS: Fasting plasma PYY and ghrelin levels were measured in all subjects and, postprandially until 6 h, in seven matched subjects of each group. RESULTS: Fasting ghrelin levels were higher in PWS than in the other two groups. Fasting PYY levels were lower in patients with PWS than in lean subjects but similar to those in obese subjects. The postprandial decrease in ghrelin concentrations was lower in PWS as compared to the other two groups and therefore the 6-h-postprandial area under the curve (AUC) for ghrelin was higher in PWS than in obese subjects. PYY response after the meal was blunted in patients with PWS, but not in the other two groups that showed a peak at 60 min The AUC for PYY was lower in PWS as compared to the other two groups. Fasting PYY levels correlated negatively with fasting ghrelin levels and with ghrelin AUC and they were the only predictor for ghrelin AUC (beta = -0.464, P = 0.034). The increase in PYY correlated negatively with the decrease in ghrelin at times 60 min and 120 min in PWS. CONCLUSIONS: In PWS, the low decrease in postprandial ghrelin levels could be related to the low fasting PYY concentrations and their blunted postprandial response.

Circulating ghrelin in thyroid dysfunction is related to insulin resistance and not to hunger, food intake or anthropometric changes.

OBJECTIVE: Ghrelin is a gastric peptide that plays a role in appetite stimulation, energy balance and possibly in insulin resistance. Hyperthyroidism is a situation where negative energy balance and insulin resistance coexist, while in hypothyroidism a positive energy balance and normal insulin sensitivity predominate. We investigated ghrelin levels and their relationship with hunger, food intake and both anthropometric and insulin resistance parameters in patients with thyroid dysfunction. DESIGN AND METHODS: We studied 24 hyperthyroid and 17 hypothyroid patients before and after normalisation of thyroid hormone levels and their respective body mass index (BMI)-matched control group. We measured plasma ghrelin levels, homeostasis model assessment of insulin resistance (HOMA-IR) index, a hunger score, mean three-day calorie intake and anthropometric parameters. RESULTS: In hyperthyroidism, HOMA-IR index was higher (3.21 +/- 0.60 vs 1.67 +/- 0.15 mMmU/l; P = 0.014, t test for independent data) and ghrelin levels were lower (463.6 +/- 36.4 vs 561.1 +/- 32.1 pg/ml; P = 0.041, Mann-Whitney U-test) than in its control group and both normalised after treatment (HOMA-IR: 2.28 +/- 0.38 mMmU/l; P = 0.106, t test for independent data, and ghrelin: 539.7 +/- 45.4 pg/ml; P = 0.549, Mann-Whitney U-test). Glucose, as a component of HOMA-IR index was the only predictor for ghrelin levels (beta = -0.415, P = 0.044, stepwise multiple regression analysis). In hypothyroidism, HOMA-IR index and ghrelin levels were similar to those in its control group both before and after treatment. In both thyroid dysfunction states, no correlations were observed between changes in ghrelin levels and in free T4, free T3, anthropometric parameters, total calorie intake and hunger score. CONCLUSIONS: In thyroid dysfunction states, ghrelin levels seemed to be in relation to insulin resistance and not to energy balance and food intake regulation, as seen in other physiological and pathological states.