Both glycaemic control and insulin dose during pregnancy in women with type 1 diabetes are associated with neonatal anthropometric measures and placental weight.

BACKGROUND: To investigate longitudinal associations of maternal glucose/HbA1c and insulin dose with birthweight-related outcomes in women with type 1 diabetes. METHODS: We performed a cohort study including 473 pregnant women with type 1 diabetes with singleton pregnancies. We investigated maternal self-monitored blood glucose (SMBG, mmol/L), HbA1c (%, mmol/mol) and insulin dose (IU/kg/day) in the three trimesters as potential independent variables, while adjusting for potential confounders. Outcomes of interest were birthweight, birthweight SD score, neonatal length, weight/length index, ponderal index and placental weight. Multiple linear regression analysis was performed with separate analyses for SMBG and HbA1c . RESULTS: Maternal glucose and insulin dose were independently associated with birthweight-related outcomes. In the main analysis, in the first trimester most associations were positive for insulin dose, in the second the associations were positive for glucose and inverse for insulin while in the third there were no associations. Most sensitivity analyses produced consistent results. In a sensitivity analysis splitting the first trimester in two periods, positive associations of maternal insulin with birthweight-related outcomes were observed in weeks 0+ to 6+. CONCLUSIONS: Early in pregnancy in women with type 1 diabetes, maternal insulin dose is positively associated with birthweight-related outcomes, whereas in the second trimester, a positive association with SMBG emerges and the association with maternal insulin becomes inverse. If confirmed in other cohorts, these results would have implications in the management of women with type 1 diabetes.

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.

Latent autoimmune diabetes in adults (LADA) in Asian and European populations.

Diabetes mellitus is a chronic disorder caused by relative or absolute insulin deficiency and characterized by chronic hyperglycaemia. It is expected that by year 2025, 80% of all type 2 diabetic patients will be living in developing or low- and middle-income countries. Among Asians, there has been an overall increase in abdominal obesity; however, the risk of diabetes in these populations starts at much lower body mass index as compared to Caucasians. A significant proportion of diabetic patients with adult-onset, initially nonrequiring insulin treatment, have diabetes-associated autoantibodies in their sera. A new subclass of diabetes with the designation of latent autoimmune diabetes of adult-onset (LADA) has been proposed for this category of subjects. Studies have demonstrated that patients with autoimmune diabetes, characterized by the presence of glutamic decarboxylase autoantibodies display a different clinical phenotype from classical type 2 diabetes without glutamic decarboxylase autoantibodies. This subset of phenotypic type 2 diabetes subjects with islet autoantibodies tend to have sulphonylurea failure and need insulin treatment earlier in the disease process. Diagnosing LADA at an initial stage will be important so that insulin can be initiated earlier, facilitating improved glycemic control sooner as well as the preservation of residual beta-cell function in adult-onset autoimmune diabetes. Because of differences in dietary habits, environmental factors, and phenotypic characteristics between European and Asian populations, there may be heterogeneity in the prevalence and other characteristics of LADA in these two populations.

CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol.

BACKGROUND: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy. METHODS/DESIGN: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes. DISCUSSION: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012.

Insulin secretion in patients with latent autoimmune diabetes (LADA): half way between type 1 and type 2 diabetes: action LADA 9.

BACKGROUND: The study of endogenous insulin secretion may provide relevant insight into the comparison of the natural history of adult onset latent autoimmune diabetes (LADA) with types 1 and 2 diabetes mellitus. The aim of this study was to compare the results of the C-peptide response to mixed-meal stimulation in LADA patients with different disease durations and subjects with type 2 and adult-onset type 1 diabetes. METHODS: Stimulated C-peptide secretion was assessed using the mixed-meal tolerance test in patients with LADA (n = 32), type 1 diabetes mellitus (n = 33) and type 2 diabetes mellitus (n = 30). All patients were 30 to 70 years old at disease onset. The duration of diabetes in all groups ranged from 6 months to 10 years. The recruitment strategy was predefined to include at least 10 subjects in the following 3 disease onset categories for each group: 6 to 18 months, 19 months to 5 years and 5 to 10 years. RESULTS: At all time-points of the mixed-meal tolerance test, patients with LADA had a lower stimulated C-peptide response than the type 2 diabetes group and a higher response than the type 1 diabetes group. The same results were found when the peak or area under the C-peptide curve was measured. When the results were stratified by time since disease onset, a similar pattern of residual insulin secretory capacity was observed. CONCLUSIONS: The present study shows that the magnitude of stimulated insulin secretion in LADA is intermediate between that of type 1 and type 2 diabetes mellitus.

Hypovitaminosis D in type 2 diabetes: relation with features of the metabolic syndrome and glycemic control.

AIM: To assess the association of hypovitaminosis D with clinical and biochemical characteristics of type 2 diabetic patients and to determine the effect of glycemic control optimization on 25-hydroxyvitamin D (25(OH)D) concentrations. METHODS: Cross-sectional study of 63 patients with type 2 diabetes (mean age 60 ± 9.8 years, 69.8% men). Twenty of the 63 patients were also studied before and after glycemic control optimization. RESULTS: Mean 25(OH)D concentrations were 63.64 ± 25.51 nmol/L and 74.6% of patients had hypovitaminosis D. Compared with patients with vitamin D sufficiency, patients with hypovitaminosis D had higher prevalence of overweight or obesity (72.3% versus 37.5%; p = 0.012) and higher VLDL cholesterol (VLDL-c) (0.71 (0.24-3.59) versus 0.45 (0.13-1.6) mmol/L; p = 0.011) and C-reactive protein (3.28 (0.36-17.69) versus 1.87 (0.18-17.47) mg/L; p = 0.033) concentrations. The composition of HDL particles also differed in both groups, with higher relative content of triglycerides and lower of cholesterol in patients with hypovitaminosis D. After adjustment for age, seasonality and BMI, differences remained significant for VLDL-c and triglyceride content of HDL. No differences were found regarding other diabetes characteristics. Improvement of glycemic control (HbA1c 9.4 (7.6-14.8) versus 7.3 (6.2-8.7)%; p = 0.000) was accompanied by a decrease in 25(OH)D concentrations (72.7 ± 33.3 to 59.0 ± 21.0 nmol/L; p = 0.035). Correlation analysis revealed that changes in 25(OH)D concentrations were negatively associated to changes in HbA1c (r - 0.482; p = 0.032). CONCLUSION: Hypovitaminosis D is associated with features of the metabolic syndrome in type 2 diabetes and improvement of glycemic control decreases 25(OH)D concentrations.

Thyroglobulin as early prognostic marker to predict remission at 18-24 months in differentiated thyroid carcinoma.

INTRODUCTION: Thyroglobulin (Tg), the most common marker to determine remission of differentiated thyroid carcinoma (DTC), can take 18 months or longer to be undetectable. We hypothesized that Tg stimulated after surgery and immediately before radioiodine treatment (baseline-stimulated Tg) could be a good predictor of remission at 18-24 months. The aim of this study was to evaluate the role of baseline-stimulated Tg as early prognostic marker of DTC. PATIENTS AND METHODS: Retrospective study of 133 patients with DTC from 1998 to 2010 (age at diagnosis 47·4 ± 16·8, follow-up 5·09 ± 3·2 years). Initial subset analysis was performed after excluding patients with positive TgAb, who were later included in the second. Baseline-stimulated Tg was divided into tertiles. Multivariate logistic regression analysis included baseline Tg and other known prognostic markers and receiver operating characteristic (ROC) curve to identify the best cut-off level of baseline Tg were performed. RESULTS: Baseline-stimulated Tg in the highest tertile was the only predictive variable of persistence of disease at 18-24 months in the initial analysis (OR 45·3, P < 0·01). In the second analysis, the predictive variables were baseline-stimulated Tg (OR 39·6, P < 0·001), presence of TgAb (OR 23·4, P < 0·005) and uptake outside of the thyroid bed post-treatment whole body scan (WBS; OR 5·3, P < 0·05) were predictive of persistence of disease. The ROC curve showed that baseline-stimulated Tg below 8·55 µg/l identified 95% of disease-free patients at 18-24 months after initial treatment. CONCLUSIONS: Baseline-stimulated Tg is a good predictor of remission of disease at 18-24 months after initial treatment and could be a useful marker to stratify risk immediately after surgery.

Inflammatory biomarkers in type 2 diabetic patients: effect of glycemic control and impact of LDL subfraction phenotype.

BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with higher cardiovascular risk partly related to an increase in inflammatory parameters. The aim of this study was to determine the association of inflammatory biomarkers with low-density lipoprotein (LDL) subfraction phenotype and glycemic control in subjects with T2D and poor glycemic control. METHODS: A cross-sectional study was performed comparing 122 subjects with T2D (59 ± 11 years old, body mass index 30.2 ± 5.6 kg/m2) with 54 control subjects. Patients with T2D were classified according to their LDL subfraction phenotype and inflammatory biomarkers (C-reactive protein, Interleukin-6, Interleukin-8, Transforming growth factor ß1, Monocyte chemotactic protein 1, Leptin, Adiponectin) were evaluated according to the degree of glycemic control, LDL phenotype and other clinical characteristics. Forty-two subjects with T2D were studied before and after 3 months of improving glycemic control by different strategies. RESULTS: Patients with T2D had higher C-reactive protein (CRP) and monocyte chemotactic protein-1 (MCP1) levels and lower adiponectin concentration, compared to controls. T2D subjects with body mass index ≥ 30 kg/m2 had higher CRP levels (5.2 ± 4.8 mg/l vs 3.7 ± 4.3 mg/l; p < 0.05). The presence of LDL phenotype B was related to higher levels of transforming growth factor-ß1 (TGF-ß1) (53.92 ± 52.82 ng/l vs 31.35 ± 33.74 ng/l; p < 0.05) and lower levels of adiponectin (3663 ± 3044 ng/l vs 2723 ± 1776 ng/l; p < 0.05). The reduction of HbA1c from 9.5 ± 1.8% at baseline to 7.4 ± 0.8% was associated with a significant reduction of TGF-ß1 (41.86 ± 32.84 ng/l vs 26.64 ± 26.91 ng/l; p = 0.02). CONCLUSIONS: Subjects with T2D, especially those with LDL phenotype B and obesity, have higher levels of inflammatory biomarkers. Improvement of glycemic control reduces TGF-ß1 levels, which may contribute partly to its renoprotective role.

Latent autoimmune diabetes in adults is perched between type 1 and type 2: evidence from adults in one region of Spain.

BACKGROUND: The aim of this study was to characterize the clinical characteristics and insulin secretion in adults with latent autoimmune diabetes in adults (LADA). We also compared these characteristics in subjects with antibody-negative type 2 diabetes (T2DM) or adult-onset type 1 diabetes (T1DM) to subjects with LADA. METHODS: In this cross-sectional study, 82 patients with LADA, 78 with T1DM and 485 with T2DM were studied. Clinical and metabolic data, in particular those that related to metabolic syndrome, fasting C-peptide and islet-cell autoantibodies [glutamic acid decarboxylase (GADAb) and IA2 (IA2Ab)] were measured. RESULTS: The frequency of metabolic syndrome in patients with LADA (37.3%) was higher than in those with T1DM (15.5%; p = 0.005) and lower than in patients with T2DM (67.2%; p < 0.001). During the first 36 months of the disease, the C-peptide concentration in LADA patients was higher than in subjects with T1DM but was lower than in T2DM patients (p < 0.01 for comparisons). Glycemic control in LADA patients (HbA1c 8.1%) was worse than in patients with T2DM (HbA1c 7.6%; p =0.007). An inverse association between GADAb titers and C-peptide concentrations was found in subjects with LADA (p < 0.001). Finally, LADA patients rapidly progressed to insulin treatment. CONCLUSIONS: As in other European populations, patients with LADA in Spain have a distinct metabolic profile compared with patients with T1DM or T2DM. LADA is also associated with higher impairment of beta-cell function and has worse glycemic control than in T2DM. Beta cell function is related to GADAb titers in patients with LADA.

Breastfeeding is associated with a delayed decrease in postprandial maternal glucose concentration.

BACKGROUND: Breastfeeding has long-term benefits in reducing the risk of diabetes; however, information about the acute influence on maternal glucose profile is scarce. Thus, the aim of the study was to assess maternal glucose fluctuations associated with breastfeeding episodes in women with normal glucose status. METHODS: We performed an observational study of glucose fluctuations with breastfeeding episodes in 26 women with normal glucose status in fasting and postprandial state. Continuous glucose monitoring was performed using CGMS MiniMed Gold®/iPro2® (Medtronic, Dublin, Ireland) three months after delivery under real-life conditions. We compared fasting and postprandial periods of 150 minutes affected or not by a breastfeeding episode. RESULTS: Mean glucose concentration of postprandial periods affected by breastfeeding was lower than not affected (-6.31 mg/dL [95% CI: -11.17, -1.62] P<0.01). Glucose concentration was significantly lower between 50 and 105 minutes after meal initiation (maximum difference -9.19 mg/dL [95% CI: -16.03, -2.16] at 91-95 min). Mean glucose concentrations of fasting periods affected by breastfeeding were similar to those not affected (-0.18 mg/dL [95% CI: -2.7, 0] P=0.831). CONCLUSIONS: In women with normal glucose status, breastfeeding episodes are associated with a lower glucose concentration in the postprandial but not in the fasting state.

Cholesterol and 27-hydroxycholesterol promote thyroid carcinoma aggressiveness.

Cholesterol mediates its proliferative and metastatic effects via the metabolite 27-hydroxycholesterol (27-HC), at least in breast and endometrial cancer. We determined the serum lipoprotein profile, intratumoral cholesterol and 27-HC levels in a cohort of patients with well-differentiated papillary thyroid carcinoma (PTC; low/intermediate and high risk), advanced thyroid cancers (poorly differentiated, PDTC and anaplastic thyroid carcinoma, ATC) and benign thyroid tumors, as well as the expression of genes involved in cholesterol metabolism. We investigated the gene expression profile, cellular proliferation, and migration in Nthy-ori 3.1 and CAL-62 cell lines loaded with human low-density lipoprotein (LDL). Patients with more aggressive tumors (high-risk PTC and PDTC/ATC) showed a decrease in blood LDL cholesterol and apolipoprotein B. These changes were associated with an increase in the expression of the thyroid's LDL receptor, whereas 3-hydroxy-3-methylglutaryl-CoA reductase and 25-hydroxycholesterol 7-alpha-hydroxylase were downregulated, with an intratumoral increase of the 27-HC metabolite. Furthermore, LDL promoted proliferation in both the Nthy-ori 3.1 and CAL-62 thyroid cellular models, but only in ATC cells was its cellular migration increased significantly. We conclude that cholesterol and intratumoral accumulation of 27-HC promote the aggressive behavior process of PTC. Targeting cholesterol metabolism could be a new therapeutic strategy in thyroid tumors with poor prognosis.

Real-time continuous glucose monitoring together with telemedical assistance improves glycemic control and glucose stability in pump-treated patients.

BACKGROUND: Real-time continuous glucose monitoring (CGM) has recently been incorporated into routine diabetes management because of the potential advantages it offers for glycemic control. The aim of our study was to evaluate the impact of the use of real-time CGM together with a telemedicine system in hemoglobin A1c and glucose variability in patients with type 1 diabetes treated with insulin pumps. METHODS: Ten patients (five women, 41.2 [range, 21-62] years old, duration of diabetes 14.9 [range, 3-52] years) were included in this randomized crossover study. Patients used the DIABTel telemedicine system throughout the study, and real-time CGM was used for 3 days every week during the intervention phase. At the end of the control phase, a blind 3-day CGM was performed. Glucose variability was evaluated using the Glucose Risk Index (GRI), a comparative analysis of continuous glucose values over two consecutive hours. RESULTS: Hemoglobin A1c decreased significantly (8.1 +/- 1.1% vs. 7.3 +/- 0.8%; P = 0.007) after the intervention phase, while no changes were observed during the control phase. The mean number of daily capillary glucose readings was higher during the intervention phase (4.7 +/- 1.1 vs. 3.8 +/- 1.0; P < 0.01), because of an increase in random analyses (1.22 +/- 0.3 vs. 0.58 +/- 0.1; P < 0.01), and there was also a significant increase in the mean number of bolus doses per day (5.23 +/- 1.1 vs. 4.4 +/- 0.8; P < 0.05). The GRI was higher during the control phase than during the experimental phase (9.6 vs. 6.25; P < 0.05). CONCLUSIONS: Real-time CGM in conjunction with the DIABTel system improves glycemic control and glucose stability in pump-treated patients with type 1 diabetes.

Web Support for Weight-Loss Interventions: PREDIRCAM2 Clinical Trial Baseline Characteristics and Preliminary Results.

An ongoing clinical trial is testing the efficacy of web telematic support in a structured program for obesity treatment and diabetes prevention. Participants were recruited from two tertiary-care hospitals and randomized to receive either a telematic intervention (TI) supported by PREDIRCAM2 web platform or a non-telematic intervention (NTI). All receive 1-year follow-up. Both interventions consist of tailored dietary and exercise prescriptions, based on a Mediterranean dietary pattern and general WHO exercise recommendations for adults. At 6 months, both groups have received 7 contacts, 3 exclusively telematic for the TI group. This is a preliminary result intention-to-treat analysis. One hundred eighty-three participants were recruited, with a mean body mass index of 34.75 ± 2.75 kg/m2. General dropout rate at 6 months was 26.8%. Weight changes were statistically significant at months 3 and 6 compared to baseline, -2.915 ± 0.24 kg, -3.29 ± 0.36 kg, respectively (P < 0.001), but not statistically significant between the 3- and 6-month time points -0.37 ± 0.21 kg (P = 0.24). Mean group differences showed that the TI group lost 1.61 ± 1.88 kg more than the NTI group (P = 0.39). Waist, waist/hip ratio, resting heart rate, blood pressure, HbA1c, and low-density lipoprotein cholesterol also showed statistically significant changes at 6 months, with no significant differences between groups. Weight loss in the TI group shows similar results as the usual care NTI group for weight loss and control of obesity comorbidities. At completion of the clinical trial, these results will be reevaluated to assess the potential role of web support in weight-loss maintenance and its cost-effectiveness.

Latent Autoimmune Diabetes in Adults in North Indian Region: Assessment of ß-Cell Function, Metabolic and Immunological Features.

BACKGROUND: We undertook a study to assess ß-cell function, metabolic and immunological features of patients with latent autoimmune diabetes in adults (LADA) and investigate heterogeneity within LADA based on low and high glutamic acid decarboxylase autoantibodies (GADA) titers. METHODS: A total of 139 patients with adult-onset diabetes were examined cross-sectionally in the National capital region of Northern India. Medical history of all subjects was reviewed with the aim of collecting clinical data. Glucose, glycosylated hemoglobin, lipid profile, creatinine, C-peptide, and GADA were measured in 10-12 hrs fasting blood sample. RESULTS: Assessment of metabolic features revealed lower mean systolic blood pressure in subjects with LADA than in those with type 2 diabetes (DM2). Mean triglyceride levels were lower in LADA subjects compared to DM2 subjects. Compared to DM2 subjects, prevalence of metabolic syndrome (MS) was also lower in LADA subjects. Compared to GADA-low, all GADA-high patients were male, had lower waist circumference, fasting C-peptide (FCP), and prevalence of MS. Compared to DM2 patients, GADA-high patients were younger, had lower age at onset, body mass index, waist circumference, systolic blood pressure, triglycerides, FCP, and prevalence of MS. The rate of patients on insulin was higher in GADA-high compared to DM2. There were no significant differences between characteristics of DM2 and GADA-low patients. CONCLUSIONS: Our results indicate that LADA patients have distinct metabolic features with lower residual ß-cell function than DM2 patients. GADA titer is important parameter in defining the severity of the disease as patients with high GADA titer tend to have significant ß-cell impairment.

Postprandial thrombin activatable fibrinolysis inhibitor and markers of endothelial dysfunction in type 2 diabetic patients.

The aim of this study was to assess postprandial changes in thrombin activatable fibrinolysis inhibitor (TAFI) antigen, a thrombin-dependent fibrinolysis inhibitor with anti-inflammatory properties, and soluble markers of endothelial dysfunction in normotriglyceridemic type 2 diabetic patients. Fasting and postprandial TAFI antigen, thrombomodulin, tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor 1 were assessed in 12 normotriglyceridemic type 2 diabetic patients treated with diet (hemoglobin A1c, 6.80% +/- 0.67%) and 14 controls. Fasting low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, free fatty acids and apolipoprotein B, and fasting and postprandial triglyceride, glucose, and insulin were also measured. Fasting TAFI was higher in the control group (102% +/- 16.9% vs 72.9% +/- 15.9%; P < .0005) and was inversely correlated with glycemic control. It decreased 4 hours after the meal (31.8% reduction [P < .005] for controls and 12.6% [P < .05] for diabetic patients) and returned to fasting levels after 8 hours. This decrement was correlated with fasting TAFI, glucose and hemoglobin A1c, and the area under the curve of glucose. Thrombomodulin, TFPI, and plasminogen activator inhibitor 1 were similar in both groups, with thrombomodulin and TFPI showing a transient postprandial increase. A fat-rich meal produces a transient increase in markers of endothelial dysfunction and a temporary reduction in TAFI, an anti-inflammatory molecule whose concentration is low in type 2 diabetes mellitus.

PTEN promoter methylation in sporadic thyroid carcinomas.

The tumor-suppressor gene PTEN/MMAC1, on chromosome 10q23.3, has been implicated in an important number of human tumors, such as thyroid carcinomas. PTEN somatic mutations occur in sporadic tumors of the endometrium, brain, prostate, or melanomas, while germline mutations predispose to development of the multiple hamartoma syndromes (i.e., Cowden's disease and Bannayan-Zonana syndrome). Activation of the two alleles of PTEN is required for its tumor-suppression role. Because the frequency of PTEN suppression in thyroid tumors exceeds that of PTEN mutations or deletions, it is very likely that epigenetic mechanisms, such as promoter hypermethylation, may account for its inactivation in a subset of tumors. The main aim of this study was to assess the frequency of promoter hypermethylation of PTEN in thyroid tumors. We studied frozen tissue samples from 46 papillary carcinomas, 7 follicular carcinomas, 6 follicular adenomas as well as 39 normal thyroid tissue samples. Methylation-specific polymerase-chain reaction (PCR) with three different sets of primers was used. Two of the primer sets were designed to avoid any interference with PTEN pseudogene promoter. PTEN promoter hypermethylation was detected in 21 of 46 (45.7%) papillary carcinomas, 6 of 7 follicular carcinomas, and 5 of 6 follicular adenomas. It was negative in all normal tissues. Negative immunohistochemical staining for PTEN was significantly associated with the presence of promoter hypermethylation (p < 0.001). These results show a high frequency of PTEN promoter hypermethylation, especially in follicular tumors, suggesting its possible role in thyroid tumorigenesis.

Sex ratio at birth is associated with type 1 diabetes characteristics.

AIMS: To assess the association between maternal diabetes characteristics and sex ratio at birth (SRB) in women with type 1 diabetes mellitus. METHODS: We performed a case-control study. The study subjects were infants born alive to women with type 1 diabetes and singleton pregnancies. Cases and controls were defined as male and female newborns, respectively. SRB was analysed according to diabetes-related characteristics adjusting in a logistic regression analysis for maternal characteristics known to affect SRB in the general population. RESULTS: The observed SRB (238 males/468 live births = 0.509) did not differ from the expected. In the logistic regression analysis, SRB was significantly associated with three diabetes characteristics: (1) diabetes duration, with odds ratios (ORs) for a live male newborn = 1.22 (95 % confidence interval (CI), 0.66-2.24 for ≤5 years, OR 2.79 (95 % CI 1.36-5.74) for >20 years; (2) mean first-trimester glycated haemoglobin, with OR 1.98 (95 % CI 1.09-3.62) for ≤6.7 % (50 mmol/mol) and OR 2.61 (95 % CI 1.16-5.85) for >8.2 % (66 mmol/mol) and (3) mean first-trimester insulin dose, with OR 0.70 (95 % CI 0.36-1.38) for ≤0.5 IU/kg/day and OR 0.18 (95 % CI 0.05-0.59) for >1.0 IU/kg/day. CONCLUSIONS: We conclude that SRB in this cohort is independently associated with three diabetes characteristics. These associations are to be confirmed.

Effects of bariatric surgery on vitamin D status and secondary hyperparathyroidism: a prospective study.

BACKGROUND: Morbidly obese patients have been reported to present with vitamin D insufficiency and secondary hyperparathyroidism. Scattered data are available regarding the effects of bariatric surgery on vitamin D status. We studied calcium metabolism and vitamin D status before and after bariatric surgery. METHODS: In this prospective study, 64 patients (M5/F59) fulfilled the inclusion criteria (i.e. 2 calcidiol serum determinations in the winter season) among 457 morbidly obese individuals who underwent Roux-en-Y gastric bypass (RYGBP) a mean of 36 months previously. Laboratory data (serum calcium, phosphorus, creatinine, alkaline phosphatase, albumin, calcidiol, albumin and iPTH) were determined before and after RYGBP. Pre- and postoperative calcidiol levels were categorized as being normal (>50 nmol/L), insufficient (25-50 nmol/L), and deficient (<25 nmol/L). Pre- and postoperative mild secondary hyperparathyroidism was defined as iPTH >7.3 pmol/L with simultaneous normal values for creatinine, calcium and phosphorus. RESULTS: RYGBP produced a significant weight loss coupled with a simultaneous increase in calcidiol (+28%, P<0.0005) and decrements in total alkaline phosphatase (-53%, P<0.0005) and iPTH (-74%, P=0.001). Corrected serum calcium, phosphorus, and creatinine levels were indistinguishable before and after RYGBP. Additionally, 37.5% of the patients maintained their calcidiol category, while 42.2 % improved it and 20.3% lost one category. CONCLUSIONS: RYGBP does not completely correct pre-existing vitamin D deficient states with secondary hyperparathyroidism. Low calcidiol bioavailability and or insufficient sunlight exposure do probably persist after bariatric surgery. While randomized controlled studies are warranted, it seems advisable to support vitamin D supplementation as well as increasing sunlight exposure in the morbidly obese population.

Unchanged hypovitaminosis D and secondary hyperparathyroidism in morbid obesity after bariatric surgery.

BACKGROUND: Morbidly obese patients have been reported to present with vitamin D insufficiency and secondary hyperparathyroidism. We assessed whether bariatric surgery alters the 25-hydroxyvitamin D (calcidiol) and intact parathyroid hormone (iPTH) levels in patients presenting with morbid obesity. METHODS: A cross-sectional survey was conducted on 144 patients of whom 80 had not undergone bariatric surgery, while 64 had bariatric surgery at a mean of 36 months previously. Calcidiol levels were defined as being normal (>50 nmol/L), insufficient (2550 nmol/L) and deficient (<25 nmol/L). Mild secondary hyperparathyroidism was defined as iPTH >7.3 pmol/L with simultaneous normal values for creatinine, calcium and phosphorus. RESULTS: 80% of the patients presented low vitamin D levels and mild secondary hyperparathyroidism. Previous surgery or the presence of diabetes did not influence calcidiol levels. Corrected serum calcium, phosphorus, alkaline phosphatase, iPTH and Calcidiol were similar between subjects with and without surgery. CONCLUSIONS: Vitamin D deficient states with secondary hyperparathyroidism in the morbidly obese precede and are not significantly affected by bariatric surgery. Hypovitaminosis D with secondary hyperparathyroidism due to low calcidiol bio-availability should be added to the crowded list of sequelae of morbid obesity. While further studies are warranted, it seems advisable to support vitamin D supplementation in the morbidly obese population.