Early combination versus initial metformin monotherapy in the management of newly diagnosed type 2 diabetes: An East Asian perspective

Type 2 diabetes (T2D) in the East Asian population is characterized by phenotypes such as low body mass index, an index of β-cell dysfunction, and higher percentage of body fat, an index of insulin resistance. These phenotypes/pathologies may predispose people to early onset of diabetes with increased risk of stroke and renal disease. Less than 50% of patients with T2D in East Asia achieve glycaemic targets recommended by national or regional guidelines, which may be attributable to knowledge and/or implementation gaps. Herein, we review the latest evidence with special reference to East Asian patients with T2D and present arguments for the need to use early combination therapy to intensify glycaemic control. This strategy is supported by the 5-year worldwide VERIFY study, which reported better glycaemic durability in newly diagnosed patients with T2D with a mean HbA1c of 6.9% treated with early combination therapy of vildagliptin plus metformin versus those treated with initial metformin monotherapy followed by addition of vildagliptin only with worsening glycaemic control. This paradigm shift of early intensified treatment is now recommended by the American Diabetes Association and the European Association for the Study of Diabetes. In order to translate these evidence to practice, increased awareness and strengthening of the healthcare system are needed to diagnose and manage patients with T2D early for combination therapy.     

Life-threatening heat-related illness with severe hyponatremia in an aluminum smelter worker

Heat stress is a recognized occupational hazard in aluminum smelter pot rooms. This is the report of an unusual and complex case of heat-related illness in an aluminum smelter worker. The 34-year-old male US worker developed life-threatening heat-related illness in August 2018, on his first day back at work after a 7-day absence. The worker initially presented with bilateral hand then all-extremity cramping followed some hours later by a generalized seizure and acute mental status changes, including combativeness. Emergency room evaluation identified a serum sodium level of 114 mmol/L. Acute liver and kidney injury ensued along with profound rhabdomyolysis, with peak total creatinine phosphokinase level reaching over 125 000 units/L at 3 days post incident. Initial ventilatory support, careful fluid resuscitation, and electrolyte management were provided. Metabolic encephalopathy resolved. Complications included sepsis. After 5 days in the intensive care unit and eight additional days of inpatient management, observation, and the initiation of rehabilitation, the worker was discharged. Residual effects include polyneuropathy of upper and lower extremities and the postdischarge magnetic resonance imaging finding of a cerebellar lesion. Prevailing considerations in the differential diagnosis included exertional heat stroke and/or exertion-associated hyponatremia with encephalopathy.     

Mechanical circulatory support devices for bridge to heart transplantation, bridge to recovery, or destination therapy

Both the ventricular assist device (VAD) and the total artificial heart (TAH) have been effective in supporting circulation of end-stage cardiac patients and in bridging to heart transplantation. However, because of a shortage of donor hearts and age limitations, destination therapy with the completely implantable VAD has also been started. The totally implantable TAH in the United States is in the final stage of development and will go into preclinical trials in 2004. In Japan, heart transplantation has been re-instituted since last year, but because of shortages of donor hearts the waiting time prior to transplantation is fairly long. To date, six heart transplantations have been carried out, of which four have been bridged transplantations, using extracorporeal or implantable VADs. With the extracorporeal VADs, patients cannot be discharge home, which increases the hospital expenses. With the implantable VADs such as Novacor and HeartMate imported from the USA, patients can be discharged home, but major threats with these devices are thromboembolic, complications and infection. These devices are also fairly large, being designed for 80-kg patients, and are thus difficult to implant in patients of 50 to 60 kg, including women. Because of these limitations, there is a strong clinical demand for a compact, high-performance, implantable, permanent-use VAD. This paper addresses the current status of the artificial heart research and development program at the Tokyo Medical and Dental University, which was started in May 1999.     

Early combination therapy delayed treatment escalation in newly diagnosed young-onset type 2 diabetes: A subanalysis of the VERIFY study

We analysed glycaemic durability (sustained glycaemic control) with early combination therapy (metformin plus vildagliptin) versus metformin monotherapy, among patients with type 2 diabetes diagnosed before (young-onset [YOD]) and after (late-onset [LOD]) the age of 40 years, enrolled in the VERIFY trial. The primary endpoint was time to initial treatment failure (TF), defined as HbA1c of 7.0% or higher at two consecutive scheduled visits after randomization. The time to secondary TF was assessed when both groups were receiving and failing on the combination. A total of 186 (9.3%) patients had YOD and 1815 (90.7%) had LOD with a mean age difference of 20.4 years. Compared with metformin monotherapy, early combination reduced the risk of time to initial TF for both YOD (48%, P < .0006) and LOD (46%, P < .0001). With early combination, risk for time to secondary TF was reduced by 48% (P < .0035) in YOD and 24% (P < .0009) in LOD. Both treatment approaches were well tolerated with no unexpected safety concerns. In treatment-naïve patients with YOD (HbA1c 6.5%-7.5%), an early combination strategy improved attainment of the glycaemic target with durability and delayed treatment escalation compared with initial metformin monotherapy.     

Segmented polyurethane modified by photopolymerization and cross-linking with 2-methacryloyloxyethyl phosphorylcholine polymer for blood-contacting surfaces of ventricular assist devices

To improve the biocompatibility of pulsatile ventricular assist devices (VADs), the blood-contacting surface of the segmented polyurethane (SPU) diaphragm employed in an electromechanical VAD was modified by introducing 2-methacryloyloxyethyl phosphorylcholine (MPC) units into its surface and forming an interpenetrating polymer network (IPN) structure, which contained independently cross-linked MPC polymer and SPU. The SPU diaphragm modified with an IPN structure was then assembled into a target test pump and underwent continuous pump operation at 37°C for 2 weeks in a simulated systemic circulation using a mock circulatory loop. The surface characteristics of the pump diaphragm after 2 weeks of pump operation were then analyzed with an X-ray photoelectron spectroscope (XPS) and gold-colloid-labeled immunoassay. The XPS surface analysis of the IPN-modified SPU indicated the firm anchoring of MPC units even after 2 weeks of pump operation (the phosphor : carbon ratio was reduced by only 0.09%). The IPN-modified diaphragm prevented protein adsorption as well as cell adhesion in comparison to the unmodified SPU surface. This result thus validated that (1) the IPN structure could firmly secure MPC units to the SPU surface even in a high-mechanical-stress and high-shear environment, (2) the antithrombogenic power of MPC units remained unchanged after 2 weeks of continuous exposure to a high-shear environment, and (3) the IPN modified SPU cross-linked with MPC could be a powerful antithrombogenic surface for blood pumps used for chronic circulatory support of cardiac patients.