Pregnancy-associated plasma protein-A is related to gender and to adipocytokine levels: results of the Health Survey of Catalonia.

OBJECTIVE: Pregnancy-associated plasma protein-A (PAPP-A) is a protease promoting IGF1 tissue availability and considered as a new biomarker of cardiovascular disease. AIM: To evaluate the relationship between PAPP-A concentrations and anthropometric variables, physical activity, smoking status, glucose homoeostasis and adipocytokines in healthy adults. DESIGN AND METHODS: One hundred and forty-nine subjects (77 women; mean age 39·7 ± 14 years; mean BMI 23·7 ± 1·9 kg/m(2) ) were randomly selected from 8000 adults of The Health Survey of Catalonia. Possible effects of gender, age, body composition, smoking status, physical activity, glucose homoeostasis and adipocytokines on PAPP-A concentrations were assessed. RESULTS: Pregnancy-associated plasma protein-A was significantly higher in men than in women [1·04 (0·61-0·44) vs 0·61 (0·41-0·90) µIU/ml; P < 0·0001]; there were no differences in relation to physical activity or smoking status. PAPP-A showed a negative correlation with leptin in men (P = 0·01) and women (P = 0·05), and a positive correlation with adiponectin (P = 0·006) in women and a trend (P = 0·073) in men. Homoeostasis model assessment of insulin resistance (HOMA-IR) showed a negative correlation with PAPP-A only in women (P = 0·019). No association was found with blood pressure, IGF1, lipids or glucose in either gender. When a multiple regression analysis was performed including gender, age, BMI, waist-hip ratio, HOMA-IR, adiponectin and leptin as confounders, PAPP-A was independently correlated with adiponectin (ß = 0·23; P = 0·02) and leptin (ß = -0·33; P = 0·04). CONCLUSIONS: Our study shows a sexual dimorphism of PAPP-A, and a possible influence of leptin and adiponectin on its concentrations in healthy subjects. The mechanisms responsible for this relationship remain to be determined.

Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment.

CONTEXT: One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined. OBJECTIVE: Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT. DESIGN, PATIENTS AND METHODS: From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT). RESULTS: Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) γδ(+) , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3(+) percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001). CONCLUSIONS: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT.

A prospective study of lymphocyte subpopulations and regulatory T cells in patients with chronic hepatitis C virus infection developing interferon-induced thyroiditis.

OBJECTIVE: One of the side effects of interferon-alpha (IFN-α) therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT remains to be defined. The aim of this study was to assess different peripheral blood lymphocyte subpopulations, mainly CD4(+) CD25(+) CD127low/-FoxP3(+) regulatory T cells (Tregs), in patients with chronic hepatitis C virus (HCV) infection who developed IIT. DESIGN, PATIENTS AND METHODS: From 120 patients with chronic HCV who started antiviral treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-HCV). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment (PT) and at appearance of IIT (TT). RESULTS: Eleven patients developed IIT: three Hashimoto's thyroiditis, one Graves'disease, one positive antithyroidal antibodies, one nonautoimmune hypothyroidism and five destructive thyroiditis. During antiviral treatment, an increase in CD8(+) and in Tregs was observed in both groups. A decrease in CD3(+) , CD19(+) and NKT lymphocyte subpopulations was also observed (all P < 0·05). However, no changes were observed in the percentage of CD4(+) , CD3(+) γδ(+) and iNKT lymphocytes, Th1/Th2 balance and Bcl2 expression on B cells when BT was compared with ET. At the appearance of IIT (TT), IIT patients had a higher Th1 response (CCR5(+) CCR7(-) ) (P < 0·01) and a higher Tregs percentage (P < 0·05) than Co-HCV. CONCLUSIONS: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Th1 response and Tregs in patients with HCV who developed IIT.

[Usefulness of pulse oximetry in screening of carotid atherosclerosis in patients with type 2 diabetes mellitus]. / Utilidad de la pulsioximetría en el cribado de la aterosclerosis carotídea en pacientes con diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: Pulse oximetry of the toes has been suggested in the screening of peripheral arterial disease. We studied the uselfuness of pulse oximetry in detection of type 2 diabetic patients with carotid atherosclerosis. SUBJECTS AND METHODS: 105 patients with type 2 diabetes mellitus (DM) without previous clinical peripheral arterial disease were enrolled. All patients had (1) ankle-brachial index (ABI) measurement, (2) pulse oximetry to measure SaO(2) of their index fingers and big toes in the supine position and at elevated 30cm and (3) a carotid ultrasound [carotid artery intima-media thickness (IMT) and carotid plaques (CP) measurements]. The ABI was considered abnormal when it was <0.9 and when the pulse oximetry showed a decrease in SaO(2) of >2% of the finger compared to foot or to 30cm foot elevation. RESULTS: 60 patients were men (age of 62+/-7 years, HbA(1c) of 6.9+/-1.0); 58.1% had CP. There were no differences in anthropometric and biochemical results between patients with or without CP. The ABI was <0.9 in 49% and 25% of patients with and without CP, respectively. Neither were there differences in pulse oximetry in patients with CP or in those with ABI <0.9. The IMT did not change in relation to pulse oximetry, but it was higher in patients with CP and with ABI <0.9 than in patients without alterations. These results were independent of the presence of previous clinical macroangiopathy. CONCLUSION: Pulse oximetry is not a useful screening method of carotid atherosclerosis in type 2 DM.

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. OBJECTIVE: To validate the use of serum IGF-I concentrations measured by four immunoassays in the diagnosis of adult GH deficiency and acromegaly. DESIGN: Cross-sectional study. PATIENTS: Fifty GH-deficient (GHD) patients, 41 acromegaly patients and 405 controls. MEASUREMENTS: Serum IGF-I concentrations were measured by four commercial immunoassays: (1) RIA-NICHOLS; (2) ICMA-IMMULITE; (3) IRMA-IMMUNOTECH; and (4) non-extraction-IRMA-DSL. Reference values were established from the control population in six age groups. Individual results were transformed to standard deviation score (SD score) from the age-related reference population and reference data provided by each assay manufacturer. Diagnostic sensitivity for GH deficiency was calculated. RESULTS: IGF-I measured by the four assays differed significantly. In controls, assay 2 yielded the lowest results, followed by assays 1, 3 and 4 (P < 0.0001 for all comparisons). IGF-I declined with age, but no sex-related differences were observed. When IGF-I was standardized with respect to reference data obtained from the manufacturers, it showed better sensitivity in assays 1 and 2, than with our controls (65%vs. 77.5% and 58%vs. 70%, respectively) for GHD diagnosis. With assays 3 and 4, higher sensitivity was obtained when standardized with our controls (62%vs. 52% and 56%vs. 36%, respectively). In acromegaly, IGF-I was > 2 SD score with all assays. CONCLUSIONS: IGF-I SD score for GHD diagnosis differed according to the normative data used. All assays proved to be useful for active acromegaly diagnosis.

Ghrelin, glucose homeostasis, and carotid intima media thickness in kidney transplantation.

BACKGROUND: Abnormalities in glucose homeostasis (AGH) frequently occur in kidney transplantation and favor vascular lesions. The purpose of this study was to analyze whether C-reactive protein (CRP), adiponectin, and ghrelin are markers of AGH and indicators of carotid atherosclerosis in kidney transplant patients with fasting plasma glucose below 126 mg/dL. METHODS: This was a cross-sectional study of 85 kidney transplant patients (59 men; mean age: 52.4 +/- 11.6 years; median posttransplant follow-up 31 (range 3-61) months). All patients underwent an oral glucose tolerance test. Abnormalities in glucose homeostasis were diagnosed following American Diabetes Association criteria. CRP, adiponectin, and ghrelin levels were determined. Doppler ultrasound of the carotid artery was performed to determine intima media thickness (IMT) and atheromatous plaque. RESULTS: A total of 50.5% of patients had AGH (12.9% were diagnosed with new-onset diabetes mellitus after transplantation and 37.7% had impaired glucose tolerance or impaired fasting glucose), whereas 49.4% were normoglycemic. Patients with AGH were older (P=0.002), had greater carotid IMT (P=0.022), and lower ghrelin concentrations (P=0.017) than normoglycemic patients. Logistic regression analyses showed ghrelin to be an independent marker for AGH (P=0.012) and AGH to be related to greater IMT (P=0.041). No differences in adiponectin or CRP were found in relation to AGH or atherosclerosis; however, there was a positive correlation between adiponectin levels and prednisone dose (r=0.240; P=0.044). CONCLUSIONS: A total of 50.5% of the study patients had abnormalities in glucose homeostasis. Patients with AGH had a higher percentage of preclinical atherosclerosis (greater carotid IMT). Ghrelin is an independent marker for abnormalities in glucose homeostasis.

Early intensive treatment improves outcomes in patients with glomerular hyperfiltration and type 2 diabetes.

BACKGROUND AND OBJECTIVE: Approximately 24-40% of patients with type 2 diabetes mellitus (T2DM) develop kidney damage. Our objective was to evaluate the long-term evolution of renal function using isotopic determination of GFR and urinary albumin excretion (UAE) in patients with T2DM undergoing intensive treatment for renal and cardiovascular risk factors. PATIENTS AND METHODS: This was a single-center, prospective study of 201 patients with T2DM and UAE who initiated intensive treatment. They were followed for 17.2±6.5 years. Patients were divided into three groups, according to renal function: 167(85.6%) had stable renal function, 16(8.2%) had creatinine levels that doubled and 12(6.2%) began renal replacement therapy (RRT). We performed periodic isotopic determinations of GFR using (125)I-iothalamate. RESULTS: There were significant differences between the three groups with respect to age, duration of T2DM at baseline, years of follow-up in the study and systolic blood pressure, serum creatinine, isotopic GFR, and UAE at baseline. Renal function evolution slopes were -1.55mL/min/1.73m(2)/year in patients with stable creatinine, -2.49mL/min/1.73m(2)/year in those with doubled creatinine, and -8.16mL/min/1.73m(2)/year in those requiring RRT. We also found that differences in renal events were determined by delayed initiation of intensive treatment. CONCLUSION: Patients with glomerular hyperfiltration who were undergoing treatment with renin angiotensin aldosterone system blockers exhibited a better evolution in renal function, possibly because these patients initiated intensive treatment earlier. Although diabetic nephropathy is associated with classic risk factors, early initiation of intensive treatment should be a priority in order to prevent worsening renal function.

Postpartum thyroiditis: long-term follow-up.

OBJECTIVE: To determine the incidence of persistent hypothyroidism (PH) after a long follow-up in 45 patients with postpartum thyroiditis (PPT) from a nonselected population of 641 pregnant women (PPT incidence 7.8%) and the clinical and biochemical factors associated with PPT evolution. DESIGN AND PATIENTS: The 45 women who developed PPT were followed for 8.1 +/- 2.2 years after delivery. MEASUREMENTS: Age at delivery, family and personal history, smoking, newborn gender, breast-feeding, and PPT course were recorded. Thyrotropin (TSH) and free thyroxine (T(4)) concentrations and antithyroid antibodies were evaluated at each visit. PH was considered when it persisted one year after being diagnosed. RESULTS: Fourteen of 45 patients with PPT developed PH with a probability of 56% after a PPT episode with hypothyroidism. None of the patients who developed hyperthyroidism alone during PPT evolved to PH. PH risk was higher if the newborn was a girl (relative risk [RR] 3.88) and increased for each additional TSH unit during PPT and for every additional year of the mother's age. CONCLUSIONS: The probability of developing PH after a PPT with hypothyroidism episode is 56%. PPT screening in all women permits us to establish levothyroxine treatment, if necessary, before a new pregnancy.

Frozen section in a cytological diagnosis of thyroid follicular neoplasm.

OBJECTIVE/HYPOTHESIS: Fine-needle aspiration biopsy is the most accurate diagnostic test for thyroid nodules, its only limitation being the diagnosis of follicular neoplasm that does not distinguish between benign and malignant follicular lesions. STUDY DESIGN: To determine the utility of intraoperative frozen-section analysis in cases of a cytological diagnosis of follicular neoplasm, a retrospective review of 66 patients with a solitary thyroid nodule and follicular neoplasm who underwent thyroid surgery was carried out. METHODS: Fine-needle aspiration was classified following the Papanicolaou Society of Cytopathology Classification, and frozen section was defined as malignant or "deferred." If a malignant diagnosis was made by frozen-section analysis, a total thyroidectomy was carried out. The extension of thyroid surgery in the deferred cases was based on the definitive histological diagnosis. RESULTS: Sixty-four cases were classified as deferred, and two as suspect for malignancy. Among the 64 deferred cases, 15 were malignant in the final pathological findings, and 49 were benign. The two suspect cases were papillary carcinoma. Frozen-section analysis classified 2 of 17 (11.7%) cases as follicular variant of papillary carcinoma that could not be diagnosed by cytological study. However, these two cases had a strong clinical evidence of malignancy. CONCLUSION: The routine use of frozen-section analysis is useless in cases of cytological diagnosis of follicular neoplasm on fine-needle aspiration biopsy, because of the low probability of achieving the diagnosis of follicular carcinoma and the inability to provide additional information apart from the clinical and the cytological data.

[Healthcare impact of introduction of thyroid ultrasound in a thyroid nodule pathology unit]. / Impacto asistencial tras la introducción de la ecografía tiroidea en una unidad monográfica de atención al nódulo tiroideo.

INTRODUCTION: Worldwide incidence of thyroid cancer has increased in recent decades. OBJECTIVE: To provide evidence of the diagnostic and care efficiency of a monographic thyroid nodule clinic integrating clinical examination, ultrasound examination, and cytology with on site evaluation. PATIENTS AND METHODS: Patients attending the monographic thyroid nodule clinic from January 2004 to June 2010. Two periods may be distinguished based on availability of ultrasound equipment at the time of the visit: a first period (P1: 01/2004-09/2007) where no ultrasound equipment was available at the clinic and FNA by palpation was performed, and a second period (P2: 10/2007-06/2010) where this equipment was available and ultrasound-guided FNA was performed. RESULTS: A total of 1036 patients [P1: 537 (52%), P2: 499 (48%)] were seen and enrolled. Diagnostic efficiency (P1 vs P2): 143 vs 181 patients were seen annually, p<0.001; FNA number/nodule: 1.68 vs 1.17, p<0.001; percent FNAs with inadequate material: 26% vs 5.3%, p<0.001; mean (SD) nodule size: 23.6 (12.4) vs 21.7 (11.7) mm, p 0.040; proportion of nodules examined less than 10mm in size: 9.9% vs 13.7%, p 0.030. Care efficiency: mean time (range) from the first visit to surgery indication: 332 (0-2177) vs 108 (0-596) days, p<0.001; proportion of patients referred for surgery due to suspect cytology/other reasons: 1.06 vs 2.21, p<0.001; and operated benign neoplasm/pathology: 0.47 vs 0.93, p=0.002. CONCLUSION: A monographic thyroid nodule clinic integrating clinical examination, ultrasound, and cytology evaluated on site increases diagnostic and care efficiency in patients with thyroid nodules.

Non-detectable Chlamydophila pneumoniae DNA in peripheral leukocytes in type 2 diabetes mellitus patients with and without carotid atherosclerosis.

BACKGROUND AND OBJECTIVE: To study Chlamydophila pneumoniae DNA (CP-DNA) in leukocytes measured by real-time polymerase chain reaction (PCR) in patients with type 2 diabetes mellitus (DM2) with different degrees of atherosclerosis, a cross-sectional protocol was performed. PATIENTS AND METHODS: We included 135 patients with DM2. Clinical, metabolic and inflammatory variables were measured. Previous clinical macrovascular disease was recorded and carotid ultrasound and real-time PCR for CP-DNA were performed. RESULTS: Mean age was 62 (7) years and mean diabetes duration 16 (9) years; 40.7% of patients presented clinical atherosclerosis, 32.5% subclinical atherosclerosis and 26.6% no evidence of atherosclerosis. Anthropometric data were homogeneous in the three groups. Patients with clinical atherosclerosis had greater carotid intima-media thickness compared to the other two groups. No CP-DNA was detected in any patient. CONCLUSIONS: The lack of detection of CP-DNA in blood leukocytes suggests that C. pneumoniae plays no active, systemic role in the pathogenesis of atherosclerosis in DM2 patients and is not a reliable marker of atherosclerosis in high-risk patients.

[Comparative study of historical series of differentiated thyroid carcinoma in two tertiary hospitals in Spain versus North American series]. / Estudio comparativo de las series históricas de carcinoma diferenciado de tiroides en dos centros hospitalarios de tercer nivel españoles en relación a series norteamericanas.

BACKGROUND AND OBJECTIVE: There is little national literature on descriptive series of patients with differentiated thyroid carcinoma (DTC) and long-term monitoring in Spain. The aim of our study was to describe the DTC series in two tertiary hospitals [Hospital Clínic de Barcelona (HC) and Hospital Germans Trias i Pujol (HGTiP)] and compare these series with those described in the National Cancer Data Base (NCDB) and the Mayo Clinic, the leading international series by number of patients and length of follow-up. MATERIAL AND METHODS: We performed a retrospective review of the medical records of patients diagnosed with DTC in two tertiary hospitals in the Barcelona area. The results were compared with those published by the NCDB and the Mayo Clinic. RESULTS: We reviewed 480 medical records of patients with DTC diagnosed between 1973 and 2006, with a mean follow-up of 16±8 years. No significant differences were observed in clinical characteristics, risk factors or the most frequent form of presentation between the joint HC/HGTiP group and the NCDB series. The most commonly used diagnostic methods were ultrasound and cytology in all series and the main type of surgery was total or nearly total thyroidectomy, with no differences between groups. Postoperative I-131 was administered more often in the HC/HGTiP series (83.9%) than in the NCDB series (55.1%) and in the Mayo Clinic (46%). In the HC/HGTiP group tumor recurrence was 9.3% and mortality 1.8%. CONCLUSIONS: The HC and HGTiP series were comparable and the various diagnostic and therapeutic techniques used were similar. This study highlights historical trends in the use of imaging techniques, as well as differences with large American series in some procedures (such as laryngoscopy) and the use of radioiodine therapy.

[Clinical endocrinologists' perception of the deleterious effects of TSH suppressive therapy in patients with differentiated thyroid carcinoma]. / Percepción de los endocrinólogos clínicos sobre los potenciales efectos perjudiciales del tratamiento supresor de la TSH en el carcinoma diferenciado de tiroides.

OBJECTIVE: To explore the opinion of clinical endocrinologists as to the deleterious effects of thyrotropin (TSH) suppressive therapy in patients with differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: A self-administered survey was sent by e-mail to a group of endocrinologists with expertise in the treatment of patients with differentiated thyroid carcinoma. The questionnaire consisted of three questions related to: 1) the possible adverse effects of this therapy on different organ systems, 2) the clinical significance of these effects and 3) the usefulness of treatment guidelines for DTC. RESULTS: A total of 91 endocrinologists responded with a wide divergence of opinions. No question had more than 80% of answers in a particular option. Of the possible side effects of suppressive therapy, a high degree of ignorance to three of them (increased left ventricular mass, reentrant tachycardia and diastolic dysfunction). Most respondents felt that the seven items, dementia and Alzheimer, decreased quality of life, decreased bone mineral density (BMD) in premenopausal women and men, thromboembolic disease, signs and symptoms of hyperthyroidism and increased risk of fractures were not affected by suppressive therapy, while most responded positively to two items (increased heart rate and decreased BMD in postmenopausal women). Eighty percent of the respondents felt that in any case these effects were not clinically significant and 33% considered that treatment guidelines should be reviewed. CONCLUSIONS: Clinical endocrinologists seem to have a very heterogeneous opinion regarding the potential harmful effects of TSH-suppressive therapy for DTC.

Bone mineral density and bone fracture in male patients receiving long-term suppressive levothyroxine treatment for differentiated thyroid carcinoma.

Studies on the effect of exogenous subclinical thyrotoxicosis on bone mineral density (BMD) in male patients treated with suppressive doses of levothyroxine for differentiated thyroid carcinoma (DTC) are not conclusive. In order to evaluate BMD (in femoral neck, lumbar spine, and distal radius) and bone fractures in men under long-term suppressive treatment with levothyroxine for DTC, we conducted a cross-sectional, retrospective study in 33 Caucasian men (mean ± SD age: 56 ± 14 years) under treatment for DTC. The control group comprised 33 healthy age- and body mass index-matched male volunteers. BMD was assessed by dual-energy X-ray absorptiometry (DXA). Bone turnover biomarkers (calcium, phosphate, alkaline phosphatase, PTH, vitamin D, urinary calcium, and N-Telopeptide/creatinine index) and testosterone were determined. Previous bone fractures were evaluated with a questionnaire and X-ray images of thoracic and lumbar vertebrae. Patients were treated for a mean duration of 15 ± 5 years. No differences were found between patients and controls in bone turnover biomarkers or areal BMD, T-scores or Z-scores in all sites evaluated. No earlier fractures or pain episodes were registered in either group and the incidence of asymptomatic vertebral fractures did not differ significantly between patient (18.8%) and control groups (16.7%), (P = 0.9). In conclusion, long-term suppressive treatment with levothyroxine in men with DTC does not appear to exert deleterious effects on bone mineral density or increase the prevalence of fracture.

Polymorphisms in platelet glycoproteins Ia and IIIa are associated with arterial thrombosis and carotid atherosclerosis in type 2 diabetes.

To determine the genotype distributions of the polymorphisms in platelet glycoproteins (GP) Ib-alpha, Ia/IIa and IIb/IIIa and their association with clinical arterial thrombosis and preclinical carotid atherosclerosis in type 2 diabetes we studied 229 patients with type 2 diabetes and 229 controls matched by age, gender and ethnicity. Biochemical and haemostasis analyses were performed. The GP Ib-alpha VNTR, GP Ia 807 C/T and GP IIIa Pl(A) polymorphisms were determined by PCR. Thrombotic events were registered and carotid atherosclerosis was evaluated by ultrasound examination. A total of 107 patients had clinical atherothrombosis (CA), 65 subclinical atherosclerosis (SA), and 57 had no evidence of atherosclerosis (NA). There were no differences in allele frequencies and the genotype distribution of platelet GP polymorphisms between diabetic patients and controls. The VNTR Ib-alpha polymorphism was not associated with CA. We found a significant association between CA and the 807T (odds ratio [OR]: 2.86, confidence interval [CI]: 1.65-4.93; p<0.001) and PlA2 (OR: 2.03, CI: 1.13-3.65; p=0.03) alleles (in GP Ia and GP IIIa, respectively) in comparison to SA and NA group. Diabetic patients with the coexistence of the 807T and PlA2 alleles presented the highest risk of CA (OR: 3.59, CI: 1.64-7.8; p<0.001). The coexistence of both 807T and PlA2 alleles was also associated with the presence of SA (OR: 9.00, CI: 1.10-73.42; p=0.04). In conclusion, the 807T allele of GP Ia and the PlA2 allele of GP IIIa, and specially its combination, may confer an additional risk for development of carotid atherosclerosis and arterial thrombosis in type 2 diabetes.

Regulatory T cells in diabetes and gastritis.

Patients with Type 1 diabetes mellitus (T1D) have an increased prevalence of associated organ-specific autoimmune diseases such as pernicious anemia whose histological substrate is a chronic atrophic gastritis (CAG). Latent pernicious anemia precedes clinically-manifest pernicious anemia and may be difficult to detect solely on simple analytical grounds. We recently described an increased prevalence of clinically-latent pernicious anemia in T1D using low concentrations of pepsinogen I, a zymogen of pepsin present in gastric mucosa, as a useful additional diagnostic marker, besides parietal cell antibodies, for screening latent pernicious anemia in T1D. The failure of peripheral tolerance mechanisms such as regulatory T cells (Treg) might be involved in CAG development in T1D patients. Indeed, functional defects in Tregs have been described in T1D patients. To this end, the percentage of Tregs in peripheral blood of T1D-CAG patients was analyzed and compared with those of a group of T1D without associated autoantibodies and a healthy control group. Tregs levels were also analyzed in gastric biopsies of T1D-CAG patients. The results obtained have led to new questions regarding the pathogenic mechanisms implicated in the development of associated autoimmune diseases in T1D.

Association of the IGF1/pregnancy-associated plasma protein-A system and adipocytokine levels with the presence and the morphology of carotid plaques in type 2 diabetes mellitus patients with stable glycaemic control.

OBJECTIVE: Pregnancy-associated plasma protein-A (PAPP-A) has been implicated in the atherosclerotic process through regulation of local expression of IGF1. In type 2 diabetes mellitus, glycaemic control has been involved in PAPP-A expression. We compared PAPP-A, IGF1, inflammatory markers and adiponectin concentrations in type 2 diabetic patients with and without carotid plaques and evaluated the relationship between these serum parameters and ultrasound carotid markers of atherosclerosis. METHODS: We studied 125 consecutive type 2 diabetic patients. Clinical data, metabolic variables, hemostatic factors (plasma type-1 plasminogen activator inhibitor, fibrinogen), high-ultrasensitive C reactive protein (hsCRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, adiponectin, IGF1 and PAPP-A were determined. Patients were classified into two groups according to the presence of carotid plaques on ultrasound. Carotid intima-media thickness (IMT) and morphology of carotid plaques were evaluated. RESULTS: The mean age was 61.5+/-7.3 years and the mean glycated hemoglobin of 6.8+/-0.9%. A total of 60% presented carotid plaques. Both groups were homogeneous in anthropometric data, biochemical determinations and hemostatic factors. Adiponectin, hsCRP, TNF-alpha and IL-6 were similar in both groups. No differences were observed in serum PAPP-A (0.46 (0.22-0.86) vs 0.38 (0.18-0.66) mIU/l and in SDS IGF1 (-0.34+/-1.38 vs -0.67+/-1.35)) in patients with and without carotid plaques respectively. PAPP-A and IGF1 were not correlated with IMT. CONCLUSIONS: Serum PAPP-A and IGF1 do not appear to be useful serum biomarkers for carotid atherosclerosis in type 2 diabetic patients with stable glycemic control, despite scientific evidence of their local role in atherosclerosis.

Regulatory T cells in type 1 diabetic patients with autoimmune chronic atrophic gastritis.

Type A chronic atrophic gastritis (CAG) is increased in type 1 diabetic patients (DM1). To address this issue, we determined and analyzed the number of peripheral blood regulatory T cells (Tregs) in 15 DM1-CAG patients, 15 DM1 patients without associated autoantibodies (DM1) and 15 healthy controls by flow cytometry and compared gastric Tregs expression (CD4+Foxp3+/CD4+) in DM1-CAG patients with that observed in 10 control Helicobacter pylori CAG-infected biopsies. The percentage of peripheral Tregs was higher in DM1-CAG patients compared to DM1 and controls (CD4+Foxp3+: 7.67 +/- 1.91% vs. 5.38 +/- 1.57% and 5.65 +/- 1.76%, P < 0.001, respectively), with no differences between DM1 and controls. Gastric mucosal Tregs were higher in H. pylori CAG than in DM1-CAG patients (31.31 +/- 5.52% vs. 7.68 +/- 3.70%; P < 0.001). Data suggest that Tregs are stimulated in patients with more than one autoimmune disease (DM1 + CAG) in an ineffectual attempt to control autoimmune response and that the number of Tregs in gastric mucosa implicated in the chronification of gastritis differs according to the etiology.