Search

Aims/hypothesis: Numerous adaptations of the maternal immune system are necessary during pregnancy to maintain immunological tolerance to the semi-allogeneic fetus. Several complications of pregnancy have been associated with dysregulation of these adaptive mechanisms. While gestational diabetes mellitus (GDM) has been associated with upregulation of circulating inflammatory factors linked to innate immunity, polarisation of the adaptive immune system has not been extensively characterised in this condition. We aimed to characterise pro- and anti-inflammatory CD4+ (T helper [Th]) T cell subsets in women with GDM vs women without GDM (of similar BMI), during and after pregnancy, and examine the relationship between CD4+ subsets and severity of GDM.Methods: This is a prospective longitudinal case-control study of 55 women with GDM (cases) and 65 women without GDM (controls) at a tertiary maternity hospital. Quantification of proinflammatory (Th17, Th17.1, Th1) and anti-inflammatory (regulatory T cell [Treg]) CD4+ T cell subsets was performed on peripheral blood at 37 weeks gestation and 7 weeks postpartum, and correlated with clinical characteristics and measures of blood glucose.Results: Women with GDM had a significantly greater percentage of Th17 (median 2.49% [interquartile range 1.62-4.60] vs 1.85% [1.13-2.98], p = 0.012) and Th17.1 (3.06% [1.30-4.33] vs 1.55% [0.65-3.13], p = 0.006) cells compared with the control group of women without GDM. Women with GDM also had higher proinflammatory cell ratios (Th17:Treg, Th17.1:Treg and Th1:Treg) in pregnancy compared with the control group of women without GDM. In the control group, there was a statistically significant independent association between 1 h glucose levels in the GTT and Th17 cell percentages, and also between 2 h glucose levels and percentage of Th17 cells. The percentage of Th17 cells and the Th17:Treg ratio declined significantly after delivery in women with GDM, whereas this was not the case with the control group of women. Nevertheless, a milder inflammatory phenotype persisted after delivery (higher Th17:Treg ratio) in women with GDM vs women without.Conclusions/interpretation: Dysregulation of adaptive immunity supports a novel paradigm of GDM that extends beyond hyperglycaemia and altered innate immunity. [ABSTRACT FROM AUTHOR]

Secondary osteoporosis is less common than primary osteoporosis. It may be suspected in patients who present with a fragility fracture despite having no risk factors for osteoporosis. In addition, secondary osteoporosis should be considered if the bone density Z-score is -2.5 or less. Consider the fracture site and presence of other clinical clues to guide investigations for an underlying cause. The tests to use are those that are indicated for the suspected cause. Baseline investigations include tests for bone and mineral metabolism (calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone), liver and kidney function, full blood count and thyroid-stimulating hormone. More detailed testing may be required in patients with severe osteoporosis. [ABSTRACT FROM AUTHOR]

Primary osteoporosis is related to bone loss from ageing. Secondary osteoporosis results from specific conditions that may be reversible. A thoracolumbar X-ray is useful in identifying vertebral fractures, and dual energy X-ray absorptiometry is the preferred method of calculating bone mineral density. The density of the total hip is the best predictor for a hip fracture, while the lumbar spine is the best site for monitoring the effect of treatment. The T-score is a comparison of the patient's bone density with healthy, young individuals of the same sex. A negative T-score of -2.5 or less at the femoral neck defines osteoporosis. The Z-score is a comparison with the bone density of people of the same age and sex as the patient. A negative Z-score of -2.5 or less should raise suspicion of a secondary cause of osteoporosis. Clinical risk calculators can be used to predict the 10-year probability of a hip or major osteoporotic fracture. A probability of more than 5% for the hip or more than 20% for any fracture is abnormal and treatment may be warranted.