Type 2 diabetes mellitus increases the risk of cardiovascular morbidity and mortality and that of microvascular complications such as nephropathy, retinopathy and neuropathy. Its global prevalence is rising and leads to an enormous economic burden. Treatment of hyperglycaemia has been proven to decrease microvascular and macrovascular complications and to improve patients' quality of life. Prevention and primary treatment of diabetes consists of lifestyle intervention in order to reduce obesity by diet and exercise. As diabetes is a progressive disease, pharmacotherapy needs to be introduced at some point of time to achieve the individualized glycaemic targets. In addition to established medications such as metformin, sulfonylureas and glitazones, recent developments targeting the incretin system or renal glucose absorption offer novel approaches for diabetes treatment. This review attempts to provide an overview about the current and future aspects of the pharmaceutical treatment of type 2 diabetes mellitus.

The most common form of diabetes mellitus, type 2 diabetes mellitus (T2DM), is characterized by impaired insulin sensitivity of skeletal muscle, liver and adipose tissue, termed insulin resistance (IR), and by inadequate insulin secretion by pancreatic β cells, termed β-cell dysfunction. Recent studies propose that the brain may also contribute to IR and to the pathogenesis of T2DM. There is growing evidence that IR is the earliest detectable abnormality, whereas β-cell exhaustion is mandatory for manifesting overt T2DM. The current concepts of possible mechanisms underlying IR are lipid overflow (lipotoxicity), abnormal energy balance and mitochondrial function, subclinical inflammation, and central neuronal mechanisms. Here we review the relative roles of these mechanisms for the development of T2DM.

The global burden of type 2 diabetes mellitus is increasing rapidly. The Gulf region, especially the United Arab Emirates, is one of the most severely affected regions. Traditionally, diabetes has been diagnosed on the basis of plasma glucose levels. However, more recently, haemoglobin A_1c has been added to recommended criteria as an alternative tool for diagnosis. This review highlights some of the arguments for and against the use of haemoglobin A_1c as a diagnostic measure.

Dietary factors and insufficient exercise levels are now presumed to be the leading cause of chronic disease worldwide. Insulin resistance due to chronic energy-dense food intake combined with lack of physical activity has been proposed as the strongest single predictor for the development of type 2 diabetes mellitus (T2DM). Conversely, a healthy diet in conjunction with exercise causes weight loss and reduces abdominal fat mass and insulin resistance. Furthermore, modulating the macronutrient composition of isoenergetic foods appears to have additional important effects on insulin sensitivity and diabetes risk, concepts that are of particular interest given that long-term sustained weight loss is difficult to achieve. We here provide an update of the current literature regarding the role of nutrition and exercise in the prevention and treatment of T2DM, with a focus on currently used concepts and controversies regarding modulation of glucose metabolism and diabetes risk using lifestyle measures.

With two randomised prospective studies, ‘Bariatric surgery versus conventional medical therapy for type 2 diabetes’ by Geltrude Mingrone et al.¹ and ‘Bariatric surgery versus intensive medical therapy in obese patients with diabetes’ by Philip Schauer et al.,² published in 2012 in the New England Journal of Medicine, bariatric and metabolic surgery highlights its potential benefit in the treatment of type 2 diabetes mellitus in obese patients.

Healing of diabetic foot ulcers is limited by multiple factors and therefore therapeutic strategies require a multifactorial approach. Reduction of the amputation rates is one of the primary goals. Up to 70% of all lower-leg amputations are performed on people with diabetes, and more >1 million people undergo a lower-limb amputation as a consequence of diabetic foot syndrome (DFS) every year. Lifelong observation and continuity of care of people with a foot at risk are essential in both prevention and management. The important principles are regular inspection, cleansing, removal of debris and/or regular debridement with a scalpel. The principles of care of diabetic foot ulcer are (1) treatment of any associated infection, (2) revascularization if feasible, (3) off-loading, and (4) management of the wound bed in order to promote healing. Adequate pressure relief is an essential component of successful and consistent healing for the majority of neuropathic diabetic foot ulcers. Every diabetic foot wound should be assessed routinely for the presence of infection. The diagnosis of infection in DFS is based on clinical findings of inflammation. Infected diabetic foot ulcers often require surgical therapy and hospital stay. In DFS, the rate of ulcer recurrence are 27% in the first year and 100% after 4 years.

Diabetes mellitus and its complications is a serious global health problem and the total number of people with this disease is projected to rise from 171 million in 2000 to 366 million in 2030. A recent study among Emirati citizens reported age-standardized rates for diabetes mellitus (diagnosed and undiagnosed) and pre-diabetes in those 30–64 years old as 29.0% and 24.2%, respectively. The association between type 2 diabetes mellitus and obesity is very strong and cardiovascular disease is the leading cause of morbidity and mortality among diabetic patients. The changes in ventricular myocyte contraction, intracellular calcium and the expression of genes encoding cardiac muscle proteins that take place in young (9–13 weeks) and ageing (30–34 weeks) Zucker diabetic fatty (ZDF) rat heart have been reviewed. Diabetes mellitus was associated with a fourfold elevation in non-fasting blood glucose in young and ageing ZDF rat compared with age-matched Zucker lean controls. Amplitude of shortening was unaltered in myocytes from young and ageing ZDF rats. Time to peak and time to half relaxation of shortening was prolonged in myocytes from young ZDF rats and was unaltered in myocytes from ageing ZDF rats compared with controls. Amplitude of the Ca²⁺ transient was unaltered in myocytes from young and ageing ZDF rats. Time to peak Ca²⁺ transient was prolonged in myocytes from young and ageing ZDF rats. L-type Ca²⁺ current was significantly reduced in myocytes from young and ageing ZDF rats. Sarcoplasmic reticulum Ca²⁺ transport did not appear to be altered in myocytes from young or ageing ZDF rats. Expression of genes encoding L-type Ca²⁺ channel proteins, plasma membrane transporters, sarcoplasmic reticulum Ca²⁺ and regulatory proteins and cardiac muscle proteins were variously up-regulated, down-regulated or unaltered in ventricles from young and ageing ZDF rats. Up-regulated genes in young ZDF rat heart included CACNA1C, CACNA1G, CACNA1H, ATP1A1 and MYH7, whereas down-regulated genes in young ZDF rat heart included ATP1B1, SLC9A1, ATP2A2, CALM1, MYH6, MYL2, ACTC1, TNNI3, TNNT2 and TNNC1. Up-regulated genes in ageing ZDF rat heart included CACNA1G, CACNA1H, ATP2A1 and MYL2, whereas down-regulated genes in ageing ZDF rat heart included CACNA2D3, SLC9A1, ATP2A2, MYH6 and TNNT2. Subtle changes in expression of genes encoding various cardiac muscle proteins may underlie functional changes in hearts of young and ageing ZDF rats compared with age-matched controls.

Massive penetrating trauma by impalement is a rare form of injury. As this report presents two new cases of thoracoabdominal impalement, the description of the clinical courses of these two patients, who had both been hit by iron rods falling from a great height, is used to analyse the available literature as well. There is uniform agreement that the penetrating object needs to stay in situ until management at a tertiary trauma centre can be started. The possibility of multiple lesions with the need to be treated by different surgical specialities needs to be taken into account. Damage to cardiovascular structure is the highest risk factor for a poor outcome. However, in all other situations, qualified treatment can lead to a favourable outcome, as was seen for the two patients described in this report.

The evolution of cancer cells in clinical metastases depends on antimetastatic immune activity and the ability of the tumour to proliferate and generate new blood vessels (neoangiogenesis). Surgery by itself can depress cellular immunity and functions of cytotoxic T lymphocytes and natural killer (NK) cells. The perioperative stress response releases tumour cells into the circulation and anaesthesia further reduces immune functions, including the functions of neutrophils, macrophages, dendritic cells, T lymphocytes and NK cells. Effective treatment of postoperative pain could play an important role in limiting the metastatic migration following oncology surgery. Opioids used intraoperatively and postoperatively inhibit cellular and humoral immune functions in humans and have natural pro-angiogenic properties. In a retrospective analysis, paravertebral anaesthesia and analgesia for breast cancer surgery reduced the risk of recurrence or metastasis by four during the first years of follow-up. Similarly, following epidural anaesthesia for resection of the prostate, biochemical recurrence of prostate cancer was reduced by 65% and, following colon surgery, the oncological prognosis was enhanced in the first two years. To date there are only retrospective clinical studies available. A prospective, randomized, large-size study focused on cancers with high risk of recurrence is needed to determine if regional anaesthesia and analgesia could have potential for clinically reducing cancer recurrence after oncology surgery.

The additional application of low-dose rivaroxaban twice daily to standard therapy showed improved efficacy in patients with acute coronary syndrome (ACS) in the ATLAS ACS 2-TIMI 51 (anti-Xa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome thrombolysis in myocardial infarction) study. All-cause mortality was even reduced with 2×2.5 mg rivaroxaban. However, increased efficacy was associated with worse safety with, most importantly, an increased rate of intracranial bleeding.