Anna Sanmartí

Calculated Low-Density Lipoprotein Cholesterol Should Not Be Used for Management of Lipoprotein Abnormalities in Patients With Diabetes Mellitus

OBJECTIVE To assess the validity of calculated low-density lipoprotein cholesterol by the Friedewald formula for management of lipoprotein abnormalities in patients with diabetes mellitus. RESEARCH DESIGN AND METHODS Calculated LDL cholesterol by the Friedewald formula was compared with measured LDL cholesterol after separation by ultracentrifugation in 61 patients with type I diabetes, 50 patients with type II diabetes, and 116 healthy control subjects. RESULTS Calculated LDL cholesterol coincided with measured LDL cholesterol, with < 10% error, in 54 (49%) patients with diabetes mellitus, and 85 (73%) control subjects. Calculated LDL cholesterol was overestimated, with an error of > or = 10% of measured LDL cholesterol in 39% of patients and 26% of control subjects, and underestimated in 13 and 1%, respectively. Despite a good correlation between calculated and measured LDL cholesterol, the intraclass correlation coefficients demonstrated a poor concordance between calculated and measured LDL cholesterol, both in patients and control subjects. When comparing the mean differences of calculated and measured LDL cholesterol for diabetic subjects versus control subjects, significantly greater differences in type II (but not type I) diabetic subjects were seen. CONCLUSIONS Calculation of LDL cholesterol by the Friedewald formula may be inaccurate for assessment of cardiovascular risk in patients with type II diabetes and may not be appropriate for management of lipoprotein abnormalities in those diabetic patients.

Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults

objective To investigate the GH response to glucagon in adult patients with GH deficiency and in controls compared with the GH response to the insulin tolerance test (ITT) in patients with GH deficiency and to determine whether the use of glucagon results in a diagnostic utility test.

Suppressive therapy with levothyroxine for solitary thyroid nodules

objective To evaluate the effect of treatment with TSH suppressive dose of levothyroxine In patients with benig nthyroid nodules.

Endotoxin contamination may be responsible for the unexplained failure of human pancreatic islet transplantation.

Clinical transplantation of human islets has a disappointingly low rate of success. We report here the identification of a possible causative factor: endotoxin present in the collagenase preparations used to disperse the pancreatic tissue before islet purification and transplantation. Supporting evidence includes (1) detection of unexpectedly high levels of endotoxin in most collagenase solutions currently used to digest human pancreases; (2) demonstration that supernatants generated during islet separation are able to induce the inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in macrophages; and (3) induction of IL-1, IL-6, and TNF-alpha in the islets during the separation procedure. Cytokine expression was assessed by reverse transcription-polymerase chain reaction and, for TNF-alpha, confirmed by enzyme-linked immunoabsorbent assay. It is proposed that endotoxin and locally induced cytokines carried over with the graft activate the endothelium and promote lymphomonocytic infiltration of grafted islets and surrounding liver tissue favoring primary nonfunction and early rejection. These results also have implications for the numerous experimental procedures that use collagenase, and they point to possible ways to improve islet preparation and transplantation protocols.

Thrombomodulin and induced tissue factor expression on monocytes as markers of diabetic microangiopathy: A prospective study on hemostasis and lipoproteins in insulin-dependent diabetes mellitus

Vascular complications are the main cause of morbidity in diabetes mellitus. To evaluate lipoprotein and hemostatic parameters and their relationship with clinically detectable microangiopathy, we studied 58 insulin‐dependent diabetes mellitus patients and 60 controls matched for age, sex, and body mass index. Thirteen patients presented clinically detectable microangiopathy (8 retinopathy and 5 both retinopathy and microalbuminuria). A cross‐sectional study of lipid profile, coagulation parameters, and a flow‐cytometric evaluation of tissue factor expression in normal monocytes induced by patient plasma were performed. Patients were re‐evaluated for microangiopathy in a 3‐year median follow‐up. Patients showed triglyceride enrichment in low (P = 0.00002) and high density lipoproteins (P = 0.004) and increased levels of D‐dimer (P < 0.00001), prothrombin fragment 1 + 2 (P < 0.00001), and thrombin‐antithrombin III complex (P = 0.0001). Patients with clinically detectable microangiopathy had increased type 1 plasminogen activator inhibitor (P = 0.00001), thrombomodulin (P = 0.02), and induced monocyte tissue factor expression (P < 0.00001). Nine patients developed clinically detectable microangiopathy in the follow‐up and the only predictive variable was increased induced tissue factor expression. In conclusion, in these patients elevated thrombin and fibrin generation reflects a hypercoagulable state but clinically detectable microangiopathy seems related to endothelial cell injury markers and to increased induced tissue factor expression on monocytes. Am. J. Hematol. 56:93–99, 1997.

Postpartum thyroid dysfunction and postpartum depression: are they two linked disorders?

OBJECTIVE Postpartum has been considered as a period of risk for developing postpartum depression (PD) by some but not all authors, and this PD has been linked with postpartum thyroid dysfunction (PPTD). The major aim of this study was to evaluate the relation between the presence of PPTD and PD.

Assay-dependent results of immunoassayable spontaneous 24-hour growth hormone secretion in short children.

ABSTRACT. Forty‐eight children, referred for evaluation of short stature, underwent 24‐hour spontaneous growth hormone (GH) secretion studies. The GH level in pooled sera was assessed for each child, using up to 11 commercial immunoassays. In a group of 15 children, the mean GH values obtained by nine of the assays were compared with the mean value given by a polyclonal radioimmunoassay (RIA) from Sorin: four gave higher results (p < 0.0001), three gave comparable results and two gave lower results (p < 0.001). The assay yielding the highest results (Nichols: 5.9 ± 2.3 ng/ml, mean ± SD) gave values that were approximately triple those obtained by the assay yielding the lowest results (Hybritech: 1.8 ± 0.8 ng/ml; p < 0.0001); both of these are monoclonal immunoradiometric assays (IRMAs). The GH concentrations measured in 24‐hour pools from 32 children using a monoclonal IRMA from Biomerieux were similar to those obtained using a polyclonal RIA from Farmos (2.8 ± 1.1 ng/ml and 2.9 ± 1.4 ng/ml, respectively) but significantly lower than those measured by another polyclonal RIA from Sorin (3.5 ±1.5 ng/ml). Two polyclonal assays (Biomérieux and Sorin) were then used to measure the GH levels in all of the 30‐minute samples and in the day, night and 24‐hour pools from the secretion studies of 22 children. The ratio of the results of the two assays remained fairly constant for a given child (although the GH levels in different 30‐minute samples differed considerably). However, the ratios between different children showed quite wide variation (from 2.03 to 1.04). It was concluded that the GH assay must be taken into account when evaluating data from GH secretion studies, and the disparity in the GH level measured by two or more assays may differ from child to child.

One-year follow-up of quality of life in adults with untreated growth hormone deficiency

The aim of the study was to evaluate the impact on health‐related quality of life (HRQoL) in untreated GHD patients using the disease‐specific Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire.

Serum IGF-I measured by four different immunoassays in patients with adult GH deficiency or acromegaly and in a control population

Background  IGF‐I is a useful tool in GH disorders diagnosis, however, the use of commercially available kits needs to be validated.

Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A.

OBJECTIVE GH deficiency (GHD) in adults is associated with adverse effects on metabolism and increased cardiovascular risk. Pregnancy-associated plasma protein-A (PAPP-A) is a protease that promotes IGF-I availability in vascular tissues. PAPP-A levels appear to correlate with carotid intima-media thickness and have been proposed as an early predictor of cardiac events. The aim of our study was to evaluate PAPP-A levels in GHD adults at baseline and after GH replacement and correlate them with changes in body composition, lipid profile, glucose homeostasis, inflammatory markers and in leptin and adiponectin. PATIENTS AND METHODS Fourteen GHD adults were evaluated at baseline and after 1 year of GH therapy. All patients were compared at baseline with 28 age-, sex- and body mass index (BMI)-matched control subjects. RESULTS At baseline, GHD adults showed higher PAPP-A levels (P=0.03) and higher leptin (P=0.04), fibrinogen (P=0.002) and highly sensitive C-reactive protein (P=0.01) values than controls. Therapy with GH reduced PAPP-A (P=0.03) and fibrinogen levels (P=0.002) while increased BMI (P=0.01) and reduced waist-hip ratio (WHR; P=0.05) were observed. Insulin and homeostasis model assessment of insulin resistance index increased after treatment (P<0.004/P=0.007), without changes in leptin or adiponectin levels. PAPP-A values correlated positively with BMI and WHR and negatively with adiponectin before and after treatment, with no correlation with glucose homeostasis parameters, lipid profile or leptin. CONCLUSIONS Our study suggests that PAPP-A expression is increased in GHD adults, and that 1 year of GH replacement therapy is able to reduce PAPP-A levels in this population. However, further studies are required to determine whether this decrease correlates with an improvement in atherosclerosis.