Endocrinology News
Yale researchers use uterine stem cells to treat diabetes
Controlling diabetes may someday involve mining stem cells from the lining of the uterus, Yale School of Medicine researchers report in a new study published in the journal Molecular Therapy. The team treated diabetes in mice by converting cells from the uterine lining into insulin-producing cells.
Led by Yale Professor Hugh S. Taylor, M.D., the researchers bathed endometrial stem cells in cultures containing special nutrients and growth factors. Responding to these substances, the endometrial stem cells adopted the characteristics of beta cells in the pancreas that produce insulin. Over the course of a three-week incubation process, the endometrial stem cells took on the shape of beta cells and began to make proteins typically made by beta cells. Some of these cells also produced insulin.
Serum gamma-glutamyltransferase is associated with arterial stiffness in healthy individuals
Gamma-glutamyltransferase (GGT) has been reported to be useful in predicting cardiovascular disease. Arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) is not only a marker of vascular damage but a significant predictor of cardiovascular events. Gender difference has been reported in the association between GGT and baPWV. This article assessed the association between GGT and baPWV in a large population and determined whether there was gender difference and the results suggest that GGT is independently associated with the increased level of arterial stiffness both in men and in women and the association between them appears to be stronger in men compared to women.
Early Metformin Therapy (Age 8–12 Years) in Girls with Precocious Pubarche to Reduce Hirsutism, Androgen Excess, and Oligomenorrhea in Adolescence
Girls with a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP) are at high risk to develop polycystic ovary syndrome (PCOS).
The objective of the study was to compare the capacity of early vs. late metformin treatment to prevent adolescent PCOS.
This was a randomized, open-label study over 7 yr of early metformin (study yr 1–4; age 8–12 yr) vs. late metformin (yr 6; age 13–14 yr).
This article foundt that in LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea, and PCOS more effectively than late metformin. The time window of late childhood and early puberty may be more critical for the development, and thus for the prevention, of adolescent PCOS than the first years beyond menarche.
Are arterial and venous samples clinically equivalent for the estimation of pH, serum bicarbonate and potassium concentration in critically ill patients?
The authors of this article sought to assess the comparability of venous and arterial samples for pH, bicarbonate and potassium measurements in critically ill patients.
Simultaneous arterial and venous samples from 206 critically ill patients were analysed in duplicate. Coefficients of variation and 95% limits of agreement were calculated for arterial and venous samples. Bland-Altman plots were constructed to assess agreement between sampling sites. The authors found that a venous blood sample, analysed on a blood gas machine, is sufficiently reliable to assess pH, bicarbonate and potassium concentrations in critically ill patients, suggesting that venous sampling alone is appropriate in the management of diabetic ketoacidosis.
Cut-off values of fasting and post-load plasma glucose and HbA1c for predicting Type 2 diabetes
This study examined the optimal cut-off values of fasting plasma glucose, 2-h post-load glucose and HbA1c for predicting Type 2 diabetes in community-dwelling Japanese subjects. A total of 1982 subjects without diabetes aged 40–79 years who underwent a 75-g oral glucose tolerance test were followed prospectively for 14 years by annual health examination. The study findings suggest that the cut-off value for predicting Type 2 diabetes in the Japanese population is 5.6 mmol/l (101 mg/dl) for fasting plasma glucose and 37 mmol/mol (5.5%) for HbA1c, while the 2-h post-load glucose cut-off value is lower than the diagnostic criterion for impaired glucose tolerance.
HbA1c Plus Fasting Glucose More Accurately Identifies Prediabetes
Having a hemoglobin A1c level of 5.7%-6.4% or impaired fasting glucose each predicted a sixfold higher risk for developing diabetes among individuals screened for the disease, and people who meet both criteria are at a 32-fold increased risk for diabetes, compared with normoglycemic individuals, a large longitudinal study found.
Oxidative DNA damage and obesity in type 2 diabetes mellitus
This study illustrates the relationship between oxidative DNA damage and obesity in patients with prediabetes and type 2 diabetes compared with controls.
A total of 162 participants (35 type 2 diabetic patients; eight prediabetic subjects; and 119 age-, gender-, and weight-matched controls) were investigated. All patients were selected on clinical grounds. Serum 8-hydroxy 2′-deoxy-guanosine (8-OHdG) level was significantly greater in the prediabetic subjects (671.3±140 pg/ml) compared with controls (210.1±166 pg/ml; P<0.01). The diabetic group (1979.6±1209 pg/ml) had the highest level of 8-OHdG. There was a significant increase in serum 8-OHdG in obese subjects (848.5±103 pg/ml; P<0.001) and overweight subjects (724±102 pg/ml; P=0.005) compared with the lean subjects (196.5±327 pg/ml). These results indicate that serum 8-OHdG is increased already in prediabetes suggesting oxidative DNA damage to be present with minor elevation of blood glucose levels (BGLs). The statistically significant positive correlation between serum 8-OHdG and body mass index in the diabetic group indicates that obesity has an additive effect to increased BGL contributing to oxidative DNA damage.
Prognostic impact of electrocardiographic signs in patients with Type 2 diabetes and cardiovascular disease
Although a resting electrocardiograph is broadly applied in clinical practice for evaluating patients with Type 2 diabetes and cardiovascular disease, the independent prognostic relevance of electrocardiographic signs has not thoroughly been examined. Baseline 12-lead electrocardiographs available in 5231 of the 5238 participants of the PROactive trial were analysed for heart rate, heart rate corrected QT-interval, presence of atrial fibrillation/flutter, left axis deviation, right and left bundle branch block. The association of ecectrocardiographic signs with total mortality, the principal secondary composite endpoint (death, myocardial infarction and stroke) and serious adverse heart failure events was examined by Cox-regression analysis. Overall, two hundred and twenty-three (4.3%) patients showed atrial fibrillation/flutter, 213 (4.1%) patients had right bundle branch block, 111 (2.1%) patients had left bundle branch block and 706 (13.5%) patients had left axis deviation. Mean cQT-interval was 418 ms (± 25 ms) and mean heart rate was 72/min (± 14/min). In multivariate adjusted analyses, heart rate and cQT-interval were significantly associated with mortality, the composite secondary endpoint and heart failure, whereas right and left bundle branch blocks were significantly associated with heart failure only. Left axis deviation was associated with heart failure and atrial fibrillation/flutter was associated with mortality and heart failure in univariate but not multivariate analyses.
Influence of spironolactone treatment on endothelial function in non-obese women with polycystic ovary syndrome
Accumulating evidence connects polycystic ovary syndrome (PCOS) with increased risk of cardiovascular disease. Endothelial dysfunction is present in PCOS and represents an early, reversible marker of cardiovascular damage. As androgens and renin–angiotensin–aldosterone system are implicated in the atherogenesis process of PCOS, we tested the hypothesis that treatment with spironolactone, an androgen and mineralocorticoid receptor blocking drug, might reverse endothelial dysfunction in PCOS.
A total of 30 non-obese PCOS patients, compared with 20 body mass index matched control subjects, were evaluated. PCOS patientswere given spironolactone 100 mg daily in 21-day long intervals followed by a 7-day pause, for 6 months. This article found that treatment with spironolactone normalized endothelial function and improved cholesterol levels in non-obese PCOS patients.
External validation of the QDScore for predicting the 10-year risk of developing Type 2 diabetes
A small number of risk scores for the risk of developing diabetes have been produced but none has yet been widely used in clinical practice in the UK. The aim of this study is to independently evaluate the performance of the QDScore for predicting the 10-year risk of developing diagnosed Type 2 diabetes in a large independent UK cohort of patients from general practice. A prospective cohort study of 2.4 million patients (13.6 million person years) aged between 25 and 79 years from 364 practices from the UK contributing to The Health Improvement Network (THIN) database between 1 January 1993 and 20 June 2008. The QDScore showed good performance data when evaluated on a large external data set. The score is well calibrated with reasonable agreement between observed and predicted outcomes. There is a slight underestimation of risk in both men and women aged 60 years and above, although the magnitude of underestimation is small. The ability of the score to differentiate between those who develop diabetes and those who do not is good, with values for the area under the receiver operating characteristic curve exceeding 0.8 for both men and women.
Diabetes, metformin and lactic acidosis
Metformin has long been thought to cause lactic acidosis (LA) but evidence from various sources has led researchers to question a direct causative relationship. We assessed the relationship of metformin prescription and other factors to the incidence of LA. This article found that Diabetes rather than metformin therapy is the major risk factor for the development of LA. Lactic acidosis occurs in association with acute illness particularly in diabetes. Current guidance for the prevention of lactic acidosis may overemphasize the role of metformin.
Infection with Helicobacter pylori increases insulin resistance
Study results show that Helicobacter pylori infection increases insulin resistance through elevation of fetuin A, which could indicate a link with diabetes."Among the various factors capable of inducing insulin resistance, the upregulation of α2-Heremans Schmid glycoprotein, also known as human fetuin A, has been linked with impaired insulin sensitivity, glucose metabolism and, subsequently, the onset of diabetes mellitus," explain Spyros Potamianos (University of Thessaly, Larissa, Greece) and colleagues.
Effect of subsequent pregnancies on the risk of developing diabetes following a first pregnancy complicated by gestational diabetes
Women with gestational diabetes mellitus have a high risk of developing Type 2 diabetes, secondary to post-partum progression of the chronic pancreatic ß-cell defect that underlies their presenting with dysglycaemia in pregnancy. Insulin-sensitizing therapy can decrease this risk of Type 2 diabetes, partly by offloading the secretory demand placed on the ß-cells. Conversely, however, it is not known whether the considerable secretory demands posed by the physiologic insulin resistance of a subsequent pregnancy could accelerate the progression to Type 2 diabetes. Thus, we sought to determine whether subsequent pregnancies are associated with the risk of developing diabetes following gestational diabetes. This article found that a subsequent pregnancy is not necessarily associated with an increased risk of Type 2 diabetes following gestational diabetes. Instead, the absence of recurrent gestational diabetes in a subsequent pregnancy may identify a lessened risk of developing Type 2 diabetes in this high-risk patient population.
Gender differences in the association of C-reactive protein with coronary artery calcium in Type-2 diabetes
Plasma C-reactive protein (CRP) is associated with cardiovascular disease (CVD), but effects may vary by gender and degree of CVD risk. Whether CRP has value as a CVD risk marker in type-2 diabetes (T2DM) is unclear.This article examined whether CRP has gender differences in association with coronary artery calcium (CAC) in diabetic and nondiabetic samples without clinical CVD.
Female gender was associated with higher plasma CRP in diabetic and nondiabetic samples after adjustment for covariates. In diabetic women, CRP was associated with higher CAC even after further adjustment for age, race, medications, metabolic syndrome, Framingham risk score and body mass index. Although this relationship was attenuated in nondiabetic women, the combined sample maintained this association in fully adjusted models. There was no association of CRP with CAC in either diabetic or nondiabetic men.
Effects of Evening vs Morning Levothyroxine Intake
Levothyroxine sodium is widely prescribed to treat primary hypothyroidism. There is consensus that levothyroxine should be taken in the morning on an empty stomach. A pilot study showed that levothyroxine intake at bedtime significantly decreased thyrotropin levels and increased free thyroxine and total triiodothyronine levels. To date, no large randomized trial investigating the best time of levothyroxine intake, including quality-of-life evaluation, has been performed. Compared with morning intake, direct treatment effects when levothyroxine was taken at bedtime were a decrease in thyrotropin level of 1.25 mIU/L, an increase in free thyroxine level of 0.07 ng/dL, and an increase in total triiodothyronine level of 6.5. Overall this study shows that levothyroxine taken at bedtime significantly improved thyroid hormone levels. Quality-of-life variables and plasma lipid levels showed no significant changes with bedtimevs morning intake. Clinicians should consider prescribing levothyroxine intake at bedtime.
Long-Term Effects of Dihydrotestosterone Treatment on Prostate Growth in Healthy, Middle-Aged Men Without Prostate Disease
Benign prostatic hypertrophy increases with age and can result in substantially decreased quality of life for older men. Surgery is often required to control symptoms. It has been hypothesized that long-term administration of a nonamplifiable pure androgen might decrease prostate growth, thereby decreasing or delaying the need for surgical intervention.
A Randomized, placebo-controlled tested this hypothesis in which patients recieved transdermal DHT (70 mg) or placebo gel daily for 2 years. Overall it was found that dihydrotestosterone treatment for 24 months has no beneficial or adverse effect on prostate growth but causes a decrease in spinal but not hip BMD. These findings have important implications for the wider use of nonsteroidal pure androgens in older men.
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