Maternal serum androgens in human pregnancy: early increases within the cycle of conception

Previous studies have demonstrated elevations in testosterone and androstenedione initiated within the cycle of conception in pregnant non-human primates, and minimal data in the human support the same picture. In the present study we have investigated a group of patients scheduled for artificial insemination with regular menstrual cycles. For this study all patients provided blood samples at 5 days after the luteinizing hormone (LH) surges and daily through the luteal phase and into early pregnancy (n = 12). Patients who did not become pregnant served as normal controls (n = 9). We have measured 17- hydroxyprogesterone (17-OHP) as a marker of luteal activity not obscured by progesterone within the cycle of conception and testosterone and androstenedione as the major androgens. There were no significant changes in testosterone and androstenedione in the non- pregnant controls, but both testosterone and androstenedione were significantly elevated in the pregnant luteal phase, with the first increases occurring at 15 and 14 days respectively after the LH surge. Three of 12 pregnant patients did not demonstrate a dramatic increase in either testosterone or androstenedione and when examined more carefully a corresponding lack of increase in 17-OHP in those same subjects indicated less than optimal luteal activity, suggesting that these androgens were products of the corpus luteum. In three subjects in which consecutive non-pregnant and pregnant cycles were followed there was a dramatic increase from the non-pregnant luteal phase to the pregnant luteal phase indicating that the more important observation may be the concentrations of androgens in the conceptive luteal phase compared to some baseline, either previous luteal phase or even follicular phase. We have also studied changes in dehydroepiandrosterone sulphate and found that there was no significant contribution to this increase in androgens in early conception. These studies demonstrate a significant increase in both testosterone and androstenedione presumably of ovarian, specifically luteal, origin and that adrenal androgen production is not a factor in these changes.      

16-year excess all-cause mortality of newly diagnosed type 2 diabetic patients: a cohort study

Background  

Studies have shown that type 2 diabetic patients have higher all-cause mortality than people without diabetes, but it is less clear how diabetes affects mortality in elderly patients and to what degree mortality differs between diabetic men and women. The aim of the present study is to investigate the age- and sex-specific all-cause mortality pattern in patients with type 2 diabetes in comparison with the Danish background population.     

The relationship between HbA1c level, symptoms and self-rated health in type 2 diabetic patients

Objective

Improving glycaemic control is generally supposed to reduce symptoms experienced by type 2 diabetic patients, but the relationships between glycated haemoglobin (HbA_1c), diabetes-related symptoms, and self-rated health (SRH) are unclarified. This study explored the relationships between these aspects of diabetes control.

Design

A cross-sectional study one year after diagnosis of type 2 diabetes.

Subjects

A population-based sample of 606 type 2 diabetic patients, median age 65.6 years at diagnosis, regularly reviewed in primary care.

Main outcome measures

The relationships between HbA_1c, diabetes-related symptoms, and SRH.

Results

The patients’ median HbA_1c was 7.8 (reference interval: 5.4–7.4 % at the time of the study). 270 (45.2%) reported diabetes-related symptoms within the past 14 days. SRH was associated with symptom score (γ = 0.30, p < 0.001) and HbA_1c (γ = 0.17, p = 0.038) after correction for covariates. The relation between HbA_1c and symptom score was explained by SRH together with other confounders, e.g. hypertension (γ = 0.02, p = 0.40). The relation between the symptom fatigue and SRH was not explained by symptom score and significantly modified the direct association between symptom score and SRH.

Conclusions

Symptom relief may not occur even when HbA_1c level is at its lowest average level in the natural history of diabetes, and symptoms and SRH are closely linked. Monitoring symptoms in the clinical encounter to extend information on disease severity, as measured e.g. by HbA_1c, may help general practitioners and patients to understand the possible impact of treatments and of disease manifestations in order to obtain optimum disease control.Key Words: Family practice, glycosylated haemoglobin A, health status, signs and symptoms, type 2 diabetes mellitusTo reduce complications, lowering of HbA1c is a primary objective in diabetes care.

• Many patients experience diabetes-related symptoms in spite of acceptable glycaemic control.
• These symptoms are closely related to poor SRH while the association with HbA_1c is weak.

Patients with type 2 diabetes mellitus (T2DM) are commonly treated in general practice where treatment typically aims to improve glycaemic control in order to prevent complications [1], reduce symptom burden, and improve perceived health [2]. Moreover, the experience of obtaining these goals may improve patients’ motivation for treatment adherence, e.g. lifestyle changes and medication [3,4].Poor glycaemic control is related to symptoms such as frequent urination, genital itching, and unintended weight loss [5,6]. The association between glycated haemoglobin (HbA_1c) levels and specific symptoms is not necessarily close [7,8] except among dysregulated patients, e.g. at the time of diagnosis [5] or in patients with longstanding diabetes [2,6]. Despite the central role of symptom amelioration in treatment, few studies have looked into the relation between HbA_1c level and symptoms when HbA_1c is supposed to be at its lowest average level in the natural history of diabetes [7,9].General practitioners (GPs) and patients may evaluate the patient''s health differently [10]. The association between the patient''s HbA_1c level and perceived health is weak [2], or non-existent [1,11]. The patients’ perceived health gauged by a single question, known as perceived health, self-assessed health, or self-rated health (SRH), has been shown to vary with other factors than HbA_1c such as symptoms [12,13], sociodemographic factors [14], comorbidities [14–16], and functional ability [12,14]. Recent research has shown that SRH predicts which patients have a higher risk of diabetic complications even after accounting for established risk factors such as HbA_1c, but this predictive value may be mediated by presence of symptoms which were not accounted for [16]. Yet the relationships between HbA_1c and symptoms, both of which are important treatment targets, and SRH, which is a motivational factor for treatment adherence [2,3], are unclarified. A better insight into these relationships may help GPs to tailor treatments such as to maintain or improve patients’ health, which may include motivating the patient for treatment adherence.In a population-based sample of patients with T2DM seen in general practice one year after diabetes diagnosis we examined the relationships between HbA_1c, symptoms, and SRH primarily to see whether high HbA_1c levels are associated with many symptoms and low SRH ratings, and whether many symptoms are associated with low SRH ratings.     

Similar cardiovascular risk factor profile in screen-detected and known type 2 diabetic subjects

OBJECTIVE. To compare the cardiovascular disease (CVD) risk factor profile in subjects with screen-detected type 2 diabetes (SDM) and subjects with known type 2 diabetes (KDM). DESIGN. Population-based, cross-sectional survey. SETTING AND SUBJECTS. In a single, semi-rural general practice 2082 subjects were between 20 and 69 years. Of those, 1970 subjects were invited, and a total of 1374 (69.7%) subjects were examined by blood tests, anthropometric measures, and self-administered questionnaires. RESULTS. Before the survey 19 persons were known to have type 2 diabetes. The screening revealed another 31 individuals with type 2 diabetes, diagnosed according to the 1999 World Health Organization criteria. Age, levels of blood pressure, BMI, and dyslipidaemia, and markers of haemostasis and inflammation were comparable in the two groups. Median age in the KDM group was 58 vs. 57 years in the SDM group, p = 0.82, 79% were male vs. 61%, p = 0.23. In both groups 74% had blood pressure ≥ 130/85 mmHg, p = 1.00. In both groups 90% had BMI ≥ 25, p = 1.00, and about half in both groups had BMI ≥ 30, p = 0.56. In the KDM group 63% had dyslipidaemia (low HDL cholesterol or elevated triglycerides) vs. 80% in the SDM group, p = 0.32. Median levels of plasminogen-activator-inhibitor (PAI-1), tissue plasminogen activator (t-PA), as well as fibrinogen and C-reactive protein (CRP) were without statistically significant differences in the two groups, p > 0.1. In contrast, in markers of glycaemic regulation statistically significant differences were found between groups. Median HbA1 was 8.0 vs. 6.5, p < 0.001. Median fasting whole blood glucose level was 8.8 mmol/L vs. 6.3 mmol/L, p < 0.001, and glucose at two hours during OGTT was 16.9 mmol/L vs. 11.2 mmol/L, p < 0.001. Median fasting serum insulin level was 52 pmol/L vs. 80 pmol/L, p = 0.039 and at two hours 127 pmol/L vs. 479 pmol/L, p < 0.001. CONCLUSIONS. The CVD risk-factor profile of SDM patients was similar to the expected adverse profile of patients with KDM. This indicates an already increased risk of cardiovascular disease in diabetic patients before the diabetes becomes clinically manifest, supporting the need for early diagnosis.     

A comparative study of whole body DWIBS MRI versus bone scan for evaluating skeletal metastases

Background

Skeletal metastases in oncology patients are identified by Bone scan and/Positron Emission Tomography (PET) scan. But developing countries in the world still lack adequate numbers of these imaging facilities.

Aims

Since Magnetic Resonance Imaging (MRI) is widely available as compared to bone scan or PET scan; a double blind study was undertaken to see if whole body imaging with MRI can give an idea of skeletal metastases.

Method

Diffusion weighted whole body Magnetic Resonance Imaging with background body signal suppression (DWIBS) was performed using 1.5 Tesla (T) MRI on histopathologically proven cases of carcinoma of breast within two months of mastectomy and followed up after a year of surgery. Similarly bone scan was also performed in these patients.

Results

DWIBS MRI demonstrated the presence and extent of bone metastases in 10 out of a total 18 patients included in study while bone scan could demonstrate them in only three cases. A highly significant difference between proportions of the skeletal metastases detected by whole body DWIBS-MRI than that by bone scan at one year follow-up. (i.e. p<0.01, z=2.66) was seen.

Conclusion

DWIBS MRI scores high in demonstrating skeletal metastases. Further comparative studies are necessary to evaluate if DWIBS can replace bone scan or PET scan.     

Non‐medically supervised treatment interruptions among participants in a universally accessible antiretroviral therapy programme

Background

We examined clinical outcomes, patient characteristics and trends over time of non‐medically supervised treatment interruptions (TIs) from a free‐of‐charge antiretroviral therapy (ART) programme in British Columbia (BC), Canada.

Methods

Data from ART‐naïve individuals ≥18 years old who initiated triple combination highly active antiretroviral therapy (HAART) between January 2000 and June 2006 were analysed. Participants having ≥3 month gap in HAART coverage were defined as having a TI. Cox proportional hazards modelling was used to examine factors associated with TIs and to examine factors associated with resumption of treatment.

Results

A total of 1707 participants were study eligible and 643 (37.7%) experienced TIs. TIs within 1 year of ART initiation decreased from 29% of individuals in 2000 to 19% in 2006 (P<0.001). TIs were independently associated with a history of injection drug use (IDU) (P=0.02), higher baseline CD4 cell counts (P<0.001), hepatitis C co‐infection (P<0.001) and the use of nelfinavir (NFV) (P=0.04) or zidovudine (ZDV)/lamivudine (3TC) (P=0.009) in the primary HAART regimen. Male gender (P<0.001), older age (P<0.001), AIDS at baseline (P=0.008) and having a physician who had prescribed HAART to fewer patients (P=0.03) were protective against TIs. Four hundred and eighty‐eight (71.9%) participants eventually restarted ART with male patients and those who developed an AIDS‐defining illness prior to their TI more likely to restart therapy. Higher CD4 cell counts at the time of TI and unknown hepatitis C status were associated with a reduced likelihood of restarting ART.

Conclusion

Treatment interruptions were associated with younger, less ill, female and IDU participants. Most participants with interruptions eventually restarted therapy. Interruptions occurred less frequently in recent years.