By Max Bingham, PhD

An updated ADA position statement in this month’s issue of Diabetes Care on diabetic retinopathy is refocusing the original statement of 2002 to take into account the many diagnostic and treatment options that have emerged in recent years. Technological advances that are considered in the position statement include the use of optical coherence tomography and wide-field fundus photography for screening and diagnosis, as well as the widespread use of anti–vascular endothelial growth factor (anti-VEGF) agents for the treatment of diabetic macular edema and proliferative diabetic retinopathy. Authored by Solomon et al. (p. 412), the position statement considers the background of diabetic retinopathy as well as the natural history, screening, and treatment of the disease. The recommendations that are made take into account many published reports that have appeared since the original statement was made and, in particular, focus on the outcomes from major trials such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD), the Diabetes Control and Complications Trial (DCCT), the UK Prospective Diabetes Study (UKPDS), and the Diabetic Retinopathy Clinical Research Network (DRCRN). In terms of the natural history of the disease, the recommendations focus very much on the optimization of glycemic control, blood pressure, and serum lipids to reduce risk and to slow progression of any sight loss. In line with diabetes complications in general, the authors point out that the duration of diabetes and the degree of poor glycemic and blood pressure control are all risk factors for diabetic retinopathy and should be considered in terms of managing the disease. The position statement also includes recommendations for screening and suggests that both initial and comprehensive eye examinations involving modern techniques should be used depending on the level of progression of the disease. Of course, treatments are still needed should diabetic retinopathy complications develop. The authors detail procedures involving both laser photocoagulation therapy and intravitreous injections of anti-VEGF agents as possible courses of intervention and consider their success rates as well as their cost-effectiveness. Author Thomas W. Gardner noted that: “The diagnostic and therapeutic options for diabetic retinopathy continue to improve and more people with diabetes are retaining good vision. This work lays the groundwork for continued progress.”

Solomon et al. Diabetic retinopathy: a position statement by the American Diabetes Association. Diabetes Care 2017;40:412–418

Marked ethnic differences may exist in terms of life expectancy and type 2 diabetes with white men and women in England experiencing the greatest loss of estimated life expectancy (5–6 years) when compared with people without diabetes. In comparison, a loss of 1–2 years of life expectancy may occur for South Asians and blacks when type 2 diabetes is present at 40 years of age but conversely, type 2 diabetes may confer up to 1.1 years of extra life expectancy in South Asians that are older than 65 years of age. The outcomes are the result of a large cohort study by Wright et al. (p. 338). The research is based on anonymized hospitalization and mortality records of ∼188,000 patients with type 2 diabetes and ∼908,000 control patients from 383 general practices in England. Apart from highlighting apparent differences in life expectancy according to ethnic origin, the authors highlight lower adjusted risks for mortality from both cardiovascular and respiratory diseases in South Asian and black ethnic groups with type 2 diabetes in comparison to whites with the disease. On that basis, the authors suggest further work is needed to understand why such marked ethnic differences exist and suggest that the findings should be used to optimize cardiovascular disease risk factor management, especially in whites with type 2 diabetes. They add that screening for type 2 diabetes in South Asian and black ethnic groups may also be warranted as the data could suggest that there is some underdiagnosis in these ethnic groups. Commenting more widely on the study, author Martin K. Rutter told Diabetes Care: “Type 2 diabetes was associated with more years of life lost among white people than South Asians or black people. The leading cause of death was cardiovascular disease and therefore this underlines the need for optimized cardiovascular disease risk factor management, especially in white people with type 2 diabetes.”

Wright et al. Life expectancy and cause-specific mortality in type 2 diabetes: a population-based cohort study quantifying relationships in ethnic subgroups. Diabetes Care 2017;40:338–345

Hydrolyzed infant formula likely does not reduce risk of islet autoimmunity in infants with increased genetic risk for type 1 diabetes and indeed may increase risk if fed the infant formula during the first 7 days after birth. The findings, which will likely add to the questions relating to such formula and allergies in general, suggest that very early decisions relating to infant formula feeding may turn out to be important, especially in relation to infants at risk of type 1 diabetes. The study by Hummel et al. (p. 398) prospectively followed 8,676 children with increased genetic risk of type 1 diabetes, regularly measuring islet autoantibodies associated with type 1 diabetes risk and also assessing infant formula feeding habits. After adjusting for a range of potential confounders, the authors report that there was no significant association between hydrolyzed formula intake during the first 3 months after birth and later islet autoantibody development. Equally, using no formula or nonhydrolyzed or partially hydrolyzed formula was also not associated with risk of islet autoimmunity development. However, using extensively hydrolyzed formula during the first 7 days after birth was associated with increased risk of islet autoimmunity development. According to author Sandra Hummel: “Various infant feeding policies suggest a type 1 diabetes protective effect by delayed introduction of cow’s milk. As a result, health care professionals and mothers are uncertain regarding the choice of infant formula if breast-feeding is not possible or if additional milk feeding is needed. Our study adds to the existing evidence that there is no benefit for infants at increased risk for type 1 diabetes to be fed hydrolyzed infant formula as a first formula if breast-feeding is not possible and that consumption of extensively hydrolyzed formula as a first formula may even increase islet autoimmunity risk. This information, which will be of particular interest to mothers with type 1 diabetes who experience difficulties with exclusive breast-feeding and have to introduce infant formula in the early postpartum period, should be added to recommendations on infant feeding.”

Hummel et al. First infant formula type and risk of islet autoimmunity in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Diabetes Care 2017;40:398–404

A combination of exenatide and pioglitazone appears to be effective in reducing HbA1c over a year in patients with poorly controlled type 2 diabetes who are also on metformin and sulfonylurea. The conclusion comes from an interim analysis by Abdul-Ghani et al. (p. 325) of The Qatar Study that is currently investigating the therapy as a potential option to fundamentally correct the underlying metabolic defects of type 2 diabetes and its progressive hyperglycemia. The open-label study involved 231 patients with type 2 diabetes and with HbA1c higher than 7.5% who were also taking metformin and sulfonylurea. They were then randomized to receive either the combination of exenatide (a glucagon-like peptide 1 agonist) and pioglitazone (a potent insulin sensitizer) or a combination of basal/bolus insulin (as control subjects) with the specific aim of reducing HbA1c to less than 7.0%. According to the article, while HbA1c was 10.1% in both groups at baseline, those taking the combination therapy experienced a fall to 6.1%, while those receiving insulin therapy fell to 7.1%—a difference that was reportedly statistically significant. The study, which is ongoing, aims to examine the long-term durability of the combination therapy benefits obtained at 1 year. While both therapies did result in reductions in HbA1c, the gap between therapies appeared to widen with time. On top of this, subjects in the insulin therapy group also reported significantly higher weight gain and a higher rate of hypoglycemia than those receiving the combination therapy. Author Muhammad Abdul-Ghani commented on the study: “The findings of The Qatar Study should foster larger, multicenter, and multiethnic studies to examine the generalizability of its findings. If these findings are confirmed in a large multiethnic study, they should mandate a change in the treatment algorithm of type 2 diabetes from focusing on a glucose-lowering approach to correcting the underlying defects present in type 2 diabetes and that are responsible for the development of hyperglycemia.”

Abdul-Ghani et al. Combination therapy with exenatide plus pioglitazone versus basal/bolus insulin in patients with poorly controlled type 2 diabetes on sulfonylurea plus metformin: The Qatar Study. Diabetes Care 2017;40:325–331

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