Objective To estimate the rates of recurrence of pre-eclampsia or gestational hypertension in a subsequent pregnancy and to determine factors predictive of recurrence.Design Retrospective cohort study.Setting St George Public and Private Hospitals, teaching hospitals without neonatal intensive care units.Participants A total of 1515 women with a diagnosis of preeclampsia or gestational hypertension between 1988 and 1998 were identified from the St George Hypertension in Pregnancy database, a system designed initially for ensuring quality outcomes of hypertensive pregnancies. Of these, 1354 women were followed up, and a further 333 records from women coded as having a normal pregnancy during that period were selected randomly as controls.Main outcome measures Likelihood of recurrent pre-eclampsia or gestational hypertension and clinical and routine laboratory factors in the index pregnancy predictive of recurrence of pre-eclampsia or gestational hypertension.Methods The index cases from our unit's database were linked to the matched pregnancy on the State Department of Health database, allowing us to determine whether further pregnancies had occurred at any hospital in the State. The outcome of these pregnancies was determined by review of medical records, using strict criteria for diagnosis of pre-eclampsia or gestational hypertension.Results Almost all women with a normal index pregnancy had a further normotensive pregnancy. One in 50 women hypertensive in their index pregnancy had developed essential hypertension by the time of their next pregnancy. Women with pre-eclampsia in their index pregnancy were equally likely to develop either preeclampsia or gestational hypertension (approximately 14% each), while women with gestational hypertension were more likely to develop gestational hypertension (26%) rather than pre-eclampsia (6%) in their next pregnancy. Multiparous women with gestational hypertension were more likely than primiparous women to develop pre-eclampsia (11 versus 4%) or gestational hypertension (45 versus 22%) in their next pregnancy. Early gestation at diagnosis in the index pregnancy, multiparity, uric acid levels in the index pregnancy and booking blood pressure parameters in the next pregnancy significantly influenced the likelihood of recurrence, predominantly for gestational hypertension and less so for pre-eclampsia. No value for these parameters was significant enough to be clinically useful as a discriminate value predictive of recurrent pre-eclampsia or gestational hypertension.Conclusions Approximately 70% of women with pre-eclampsia or gestational hypertension will have a normotensive next pregnancy. The highest risk group for recurrent hypertension in pregnancy in this study was multiparous women with gestational hypertension. No readily available clinical or laboratory factor in the index pregnancy reliably predicts recurrence of pre-eclampsia.

Diabetes mellitus is a chronic metabolic disease that occurs when the pancreas is not producing enough insulin or when the insulin that it does produce is not able to be used effectively in the body. This results in hyperglycemia and if the blood sugars are not controlled, then it can lead to serious damage of various body systems, especially the nerves and the blood vessels. Uncontrolled diabetes is a major cause of kidney failure, heart attacks, stroke and amputation. One of the most devastating complications for patients is diabetic retinopathy (DR) which represents the leading cause of preventable vision loss in people between 20 and 65 years of age. Sodium glucose transporter 2 (SGLT2) inhibitors have been shown to reduce the risk for cardiovascular and renal events, however literature highlighting their potential role to prevent DR is limited. We therefore used a relevant mouse model (Akimba) to explore the effects of the SGLT2 inhibitor, Empagliflozin (EMPA), on the development of diabetic retinal changes. Here we show that when given in the early stages of type 1 diabetes (T1D), EMPA reduced the weight loss usually associated with T1D, decreased diabetes-associated polydipsia, lowered fasting blood glucose levels, decreased kidney-to-body weight ratios and, most importantly in the current context, substantially reduced retinal abnormalities associated with DR. We show that EMPA reduces vascular leakage indicated by lower albumin staining in the vitreous humor and diminishes expression of the pathogenic factor VEGF in the retina. Additionally, EMPA significantly alters the retinal genetic signature. Our findings suggest that SGLT2 inhibition may be a useful therapeutic approach to prevent the development of DR and its severity if given early in the disease process.

Purpose of Review The moderate glucose-lowering effect of sodium glucose co-transporter 2 (SGLT2) inhibitors is unlikely to explain SGLT2 inhibitor-mediated beneficial outcomes, and unravelling the underlying mechanisms is a high priority in the research community. Given the dominant pathophysiologic role of the sympathetic nervous system activation in conditions such as hypertension and perturbed glucose homeostasis, it is pertinent to postulate that SGLT2 inhibitors may exert their beneficial effects at least in part via sympathetic inhibition. Recent Findings SGLT2 inhibitors have shown enormous potential to improve cardiovascular outcomes in patients with type 2 diabetes, and their therapeutic potential is currently being investigated in a range of associated comorbidities such as heart failure and chronic kidney disease. Indeed, recent experimental data in relevant animal models highlight a bidirectional interaction between sympathetic nervous system activation and SGLT2 expression, and this facilitates several of the features associated with SGLT2 inhibition observed in clinical trials including improved glucose metabolism, weight loss, increased diuresis, and lowering of blood pressure. Summary Currently available data highlight the various levels of interaction between the sympathetic nervous system and SGLT2 expression and explores the potential for SGLT2 inhibition as a therapeutic strategy in conditions commonly characterised by sympathetic activation.

In this review, we focus specifically on the role that the metalloproteinase, A Disintegrin and Metalloproteinase 17 [ADAM17] plays in the development and progression of the metabolic syndrome. There is a well-recognised link between the ADAM17 substrate tumour necrosis factor α (TNF-α) and obesity, inflammation and diabetes. In addition, knocking out ADAM17 in mice leads to an extremely lean phenotype. Importantly, ADAM17-deficient mice exhibit one of the most pronounced examples of hypermetabolism in rodents to date. It is vital to further understand the mechanistic role that ADAM17 plays in the metabolic syndrome. Such studies will demonstrate that ADAM17 is a valuable therapeutic target to treat obesity and diabetes.