April 2019

OUTSIDE THE OR

Presentation Spotlight
Bird’s eye view of diabetes


by Stefanie Petrou Binder, MD EyeWorld Contributing Writer

More than 400 million individuals worldwide suffer from diabetes, which remains a complex disease with a relatively high disease burden. The years of life lost from the disease, its complications, comorbidities, and treatment side effects are roughly 10 years in people with type 1 and 3 years in type 2 diabetes, despite state-of-the-art care. In a presentation by Coen D.A. Stehouwer, MD, at the 36th Congress of the European Society of Cataract and Refractive Surgeons, a bird’s eye view of diabetes helped update ophthalmologists on the current progress in diabetes treatment.
“Diabetes is a very prevalent disease, with both type 1 and type 2 increasing, owing in part to the increasing patient age. It is still a disease for which we have to improve outcomes,” Dr. Stehouwer said. “The years of life lost and the overall prognosis very much depend on the age of onset and risk factor control. There are important recent developments, such as technologies applied mainly in type 1 diabetes and novel treatments, notably GLP-1 agonists and SGLT-2 inhibitors, applied mostly in type 2, that do appear to improve the prognosis. An important caveat, however, is their price and the fact that their true long-term safety has not been established,” he said.
Dr. Stehouwer explained that even patients with the usual risk factors and less severe classic complications have a considerably low quality of life that is often associated with symptoms such as depression, cognitive decline, heart failure, and shortness of breath, despite receiving the best possible care. Living with diabetes is complicated by cardiovascular disease, microvascular complications, weight gain, and hypoglycemia, among many other serious side effects, which lead to considerable distress among individuals and cause both personal and societal expense.

Toll of diabetes

According to the Swedish National Diabetes Register, the average number of life years lost to individuals with type 1 diabetes is 10 years and 17 years in those with childhood onset, despite the improvement in the available therapeutic options.1 This number is lower in type 2 diabetes, between 2 and 5 years, and largely dependent upon the age of onset.2
A recent study that analyzed the effects of risk factors such as HbA1c, blood pressure, cholesterol, smoking, and albuminuria demonstrated increased mortality with a higher number of risk factors per patient, as well as a graded increase in risk with early onset of disease. Conversely, those with controlled risk factors had an extremely low risk of mortality, suggesting that risk factor control 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 antihypertensive agents revealed that while antihypertensive 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 approach based on variables like patient age, diabetes duration, comorbidities, and of course we try to avoid symptomatic hyper- and hypoglycemia at any cost. But in some people, particularly the elderly, 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 advances surrounding insulin analogues and pumps that improve pharmacokinetics. Sensors allow self-monitoring of blood glucose, as do fully automated closed loop systems that feed information back into the insulin pumps to regulate glycemic levels. “Having said all this, many people with type 1 diabetes struggle to get proper control, 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 metformin, 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/m2 who ceased antihypertensive 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 inhibitors, shown to be safe in cardiovascular trials, that break down incretin hormones, which are responsible for increasing insulin production and decreasing glucagon production, therefore lowering 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 cardiovascular 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 accompanying disease burden can be tempered by new treatment options and a better understanding of the disease.

About the doctor
Coen D.A. Stehouwer, MD
Maastricht University
Maastricht, the Netherlands

Contact information
Stehouwer
: cda.stehouwer@mumc.nl

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-lowering treatment, and associated risks of cardiovascular complications: a nationwide study in Sweden, 2006–2013. Diabetologia. 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, cluster-randomised trial. Lancet. 2018;391:541–551.
6. Wanner C, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–34.

Financial interests
Stehouwer
: None

Bird’s eye view of diabetes Bird’s eye view of diabetes
Ophthalmology News - EyeWorld Magazine
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2019-04-05T09:57:00Z
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