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148 | EYEWORLD | APRIL 2019 O UTSIDE THE OR trol, and adjunctive treatments have been tried but not shown to be completely effective and safe," Dr. Stehouwer said. Glycemic control in type 2 diabetes involves lifestyle changes, as well as known agents like met- formin, sulfonylurea, and insulin. Intensive weight management can effectively induce remission to a non-diabetic state, at least in the short term, according to outcomes of a trial that included 306 type 2 diabetes patients aged 20–65 years with BMIs of 27–45 kg/m 2 who ceased antihyperten- sive drug use and reduced their calorie intake to roughly 850 kcal/day. In the study, the rate of remission was proportional to the amount of weight loss. 5 New agents available over the past 5–10 years for type 2 diabetes include: DDP-4 inhib- itors, shown to be safe in cardiovascular trials, that break down incretin hormones, which are responsible for increasing insulin production and decreasing glucagon production, therefore low- ering blood glucose, decreasing gastric emptying, and allowing early satiety; GLP analogues, a much stronger version than DDP-4 inhibitors with the same mechanism of action, given subcutaneously and associated with improvements in cardiovas- cular and renal outcomes in short-term trials; and sodium glucose co-transporter 2 (SGLT-2) inhibitors that inhibit a transporter in the kidney that reabsorbs glucose, associated with weight loss and a decrease in blood pressure. An important trial involving the SGLT-2 inhibitor empagliflozin in 6,185 type 2 diabetics with high cardiovascular risk receiving either the SGLT-2 inhibitor or placebo showed that in the long term, the agent was associated with a slower progression of kidney disease and lower rates of clinically relevant renal events than placebo. 6 The increasing incidence and prevalence of types 1 and 2 diabetes along with the accompa- nying disease burden can be tempered by new treatment options and a better understanding of the disease. risk with early onset of disease. Conversely, those with controlled risk factors had an extremely low risk of mortality, suggesting that risk factor con- trol was paramount to longer life. 3 Interventions that decrease the incidence of cardiovascular disease and that of retinopathy and nephropathy progression have been the focus of 30 years of research. "Lipid control, blood pressure control, and the use of aspirin have been the subject of intense interest over the years, and it is a sobering thought that what we know today has taken decades and cost us multiple billions in research," he said. Target blood pressure is a controversial issue among diabetes specialists. A meta-analysis of more than 73,000 individuals that were included in randomized controlled trials involving antihy- pertensive agents revealed that while antihyper- tensive treatments reduced the risk of mortality and cardiovascular morbidity in diabetes patients with systolic blood pressures in excess of 140 mm Hg, those with blood pressure below 140 mm Hg who received further treatment, however, were linked to an increased risk of cardiovascular death. 4 Our understanding of glycemic control is much improved. According to Dr. Stehouwer, "The old school says to keep it as low as possible, in all patients. Today, we individualize our ap- proach based on variables like patient age, diabe- tes duration, comorbidities, and of course we try to avoid symptomatic hyper- and hypoglycemia at any cost. But in some people, particularly the el- derly, who have many comorbidities, it is the main goal of treatment, and that is because the benefits of stricter glycemic control can take more than 8–10 years to materialize." Treatment options In type 1 diabetes, insulin remains central, with innovations taking the shape of technological ad- vances surrounding insulin analogues and pumps that improve pharmacokinetics. Sensors allow self-monitoring of blood glucose, as do fully automated closed loop systems that feed infor- mation back into the insulin pumps to regulate glycemic levels. "Having said all this, many people with type 1 diabetes struggle to get proper con- continued from page 146 References 1. Basina M, Maahs DM. Age at type 1 diabetes onset: a new risk factor and call for focused treatment. Lancet. 2018;392:453–454. 2. Norhammar A, et al. Incidence, prevalence and mortality of type 2 diabetes requiring glucose-low- ering treatment, and associated risks of cardiovascular compli- cations: a nationwide study in Sweden, 2006–2013. Diabetolo- gia. 2016;59:1692–701. 3. Rawshani A, et al. Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2018;379:633–644. 4. Brunstrom M, Carlberg B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses. BMJ. 2016;352:i717. 5. Lean ME, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, clus- ter-randomised trial. Lancet. 2018;391:541–551. 6. Wanner C, et al. Empaglifloz- in and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–34. Financial interests Stehouwer: None