Does in vitro fertilisation increase type 2 diabetes and cardiovascular risk?

Since the first in-vitro fertilisation (IVF) birth in 1978, the number of children born by assisted reproductive technologies (ART) continues to increase worldwide. However, the safety issues surrounding these procedures remain controversial, and the long term impact on human health is unknown. There is emerging evidence to indicate that IVF may predispose individuals to increased incidence of obesity, elevated blood pressure, fasting glucose and triglycerides and subclinical hypothyroidism. However, few studies have been conducted to date and the underlying mechanisms are unclear. This review will summarize the existing evidence in animal models and in humans, and will discuss epigenetic alterations, which may link manipulation of the pre-implantation embryo with increased risk of the later development of obesity, insulin resistance, type 2 diabetes and cardiovascular disease in offspring. Since these diseases are the leading cause of mortality and can be delayed or prevented by lifestyle modification, prospective follow up studies in IVF born adults are now urgently required to determine the degree of risks utilizing gold standard measures in human and animal models.     

Does calcium supplementation increase cardiovascular risk?

Calcium supplementation is widely used for the prevention of osteoporosis in postmenopausal women and in men. While there has been ongoing debate regarding its effectiveness in fracture prevention, the underlying assumption has been that, even if it was not particularly effective, at least it was safe. The recent finding of the Auckland Calcium Study that myocardial infarctions were more common in women randomised to calcium calls this assumption into question, and consideration of vascular event data from other calcium trials does not refute the Auckland findings. Meta‐analyses of these data will be necessary to settle this matter. It is already accepted that calcium supplements increase vascular risk in patients with renal compromise, even in those not yet requiring dialysis. Also, there is substantial epidemiological evidence that serum calcium levels in the upper part of the normal range are a risk factor for vascular disease, and that calcium supplements acutely elevate serum calcium – a combination of findings that lends plausibility to supplementation increasing vascular risk. As there are reasonable grounds for doubting the safety of calcium supplements, and as the evidence for their efficacy in fracture prevention remains marginal, we suggest that there should be a reappraisal of their role in the management of osteoporosis, with a greater emphasis on agents known to prevent fractures.     

Should patients with type 2 diabetes focus on glycemic control to reduce their cardiovascular risk?

3 very large randomized trials have recently announced their results, massively expanding the evidence base for the efficacy and safety of intensive glycemic control in patients with type 2 diabetes. Taken together, these trials indicate that tight glycemic control is potentially harmful (one of the trials was stopped earlier than planned because of an increased risk of death in patients assigned to the intensive glycemic control arm) while offering potential benefits of unclear importance to patients. In this commentary, we review these trials, their methods, results, and implications for practice. We finish by formulating a recommended approach to the contemporary evidence-based management of patients with type 2 diabetes.     

Do patients with type 2 diabetes mellitus have an increased prevalence of Cushing's syndrome?

Many clinical features are common for patients with type 2 diabetes mellitus (T2DM) and Cushing's syndrome (CS) such as central obesity, hypertension and dyslipidaemia. Patients with CS often have T2DM. Because T2DM is much more frequent than CS, it is possible that some patients with T2DM have increased production of cortisol and thus represent patients with CS. The aim of this review was to evaluate the prevalence of CS in patients with T2DM. A search was performed in PubMed and Medline. We found seven prospective studies, two case-control studies and two cross-sectional studies. The difficulties in diagnosing subclinical CS is discussed. The most frequent tests for diagnosing CS, late-night salivary cortisol, 1-mg dexamethasone suppression test and urinary free cortisol are discussed and put in relation to the results of the literature found. The observed prevalence of CS in patients with T2DM varies widely between the different studies, ranging from 0-9.4%. This may be due to patient selection, differences in test methodology (including choice of test), cutoff values and different cortisol assays. The true prevalence of CS in T2DM has not been determined. We need more studies investigating the prevalence of CS in T2DM patients. There is a need for developing more specific tests for diagnosing CS in patients with only slightly elevated cortisol secretion and subclinical CS. We suggest that examination for hypercortisolism should only be performed in T2DM patients with a cushingoid appearance and hypertension or truncal obesity or dyslipidaemia.     

Does androgen excess contribute to the cardiovascular risk profile in postmenopausal women with type 2 diabetes?

The purpose of this study was to determine if postmenopausal women with type 2 diabetes have clinical and biochemical evidence of androgen excess as a potential contributor to an increase in risk for coronary heart disease when compared with women without diabetes. Fasting glucose, insulin, lipids, sex hormone-binding globulin (SHBG), and sex steroids (from pooled samples) (total testosterone and free testosterone [non-SHBG-T], androstenedione [A-dione], total estrogens) were measured at baseline in 16 postmenopausal women with type 2 diabetes treated with diet or a sulfonylurea and 17 age-matched controls. Measurements of glucose, insulin, and sex steroids were repeated at hourly intervals for 3 hours after oral glucose administration. Hirsutism scores and insulin sensitivity (homeotasis model assessment [HOMA] insulin [SI]) were obtained. Women with type 2 diabetes were more hyperglycemic, hyperinsulinemic, and insulin-resistant (HOMA SI, 46.7 +/- 7.0 vs 12.9 +/- 2.0, P < .001), and had higher total to high-density lipoprotein cholesterol (TC/HDL) ratios, lower SHBG (20.8 +/- 3.5 vs 59.3 +/- 14.4 nmol/L, P < .05), higher non-SHBG-T (0.225 +/- 0.025 vs 0.135 +/- 0.021 nmol/L, P < .05), and higher hirsutism scores (1.1 +/- 0.3 vs 0.3 +/- 0.2, P = .004) than those without diabetes. No changes in sex steroids occurred after the oral glucose challenge. HOMA SI and area under the curve for glucose correlated significantly with SHBG (r = -0.42), non-SHBG-T (r = 0.40), and TC/HDL (r = 0.41) (all P < .05) in the combined groups. Postmenopausal women with type 2 diabetes have both clinical and biochemical evidence of androgen excess that may contribute to more adverse cardiovascular risk profiles.     

Does altered glucocorticoid homeostasis increase cardiovascular risk?

The hypothalamic-pituitary-adrenal (HPA) axis, like the sympathetic nervous system and the renin-angiotensin-aldosterone (RAA) system, sustains life in stressful situations by increasing vascular tone and ensuring fuel availability. It also modulates inflammation and tissue repair processes. Untoward cardiovascular effects of chronic sympathetic and RAA activation are well recognized, illustrating that the short-term benefit of the physiologic stress response can be detrimental in the long term. Similarly, chronic tissue exposure to glucocorticoids may lead to metabolic and vascular changes that accelerate vascular senescence. Specific situations associated with chronic activation of the HPA axis-such as major depression, inflammatory disease and perhaps the metabolic syndrome-may derive some of their associated cardiovascular risk from untoward glucocorticoid effects. Since there are no definitive clinical studies directly addressing the relationship between the HPA axis and cardiovascular disease, we present indirect evidence from two types of studies: (1) studies that examine the cardiovascular effects of exogenous glucocorticoids, and (2) studies demonstrating that endogenous glucocorticoid activity varies between individuals. The effects of physiologic increases in endogenous glucocorticoid activity may not always mirror the effects of supraphysiologic glucocorticoids. Nevertheless, the known effects of exogenous glucocorticoids provide important insights into the putative effects of endogenous glucocorticoids.