In This Issue of Diabetes Care

Early patterns of glycemic control in youth with type 2 diabetes might predict development of complications as much as a decade before their development, according to the latest reporting from the TODAY Study Group (p. 2689). In particular, fasting glucose variability in the first year following diagnosis was highly predictive of decline in glycemic control and the development of complications. This suggests the measure has some promise as a clinical decision-making tool on whether to intensify any treatments earlier to avoid complications later on. The findings come from further analysis of the TODAY study, in which ∼500 individuals with youth-onset type 2 diabetes have been intensively monitored for over a decade. Approximately one-third of the individuals had stable HbA1c over the first 4 years of the study, while about a fifth experienced HbA1c increasing less than 0.5%. The remaining ∼50% of individuals lost glycemic control, with HbA1c rising above 8%. All individuals received regular oral glucose tolerance tests with the prevalence of diabetes complications tracked over 10 years. They found that baseline HbA1c, reduced β-cell function, and a maternal history of diabetes were all associated with loss of glycemic control. Having a failure of glycemic control was also associated with the development of complications. Higher cumulative HbA1c over 4 years and higher fasting glucose variability over a year were also associated with increased prevalence of dyslipidemia and nephropathy and the progression of retinopathy. The authors also estimated a fasting glucose coefficient of variation of 8.3% or above would predict future loss of glycemic control and development of comorbidities. Commenting further, author Janine Higgins said, “This publication provides evidence that assessing the variability of fasting glucose will identify the individuals most likely to benefit from more intensive management early in the disease course. This is a win for both the clinician and the patient. Determining whether data from continuous glucose monitoring could be used similarly to achieve long-term health benefits, beyond glycemic control, is the next logical step.”

Diabetic retinopathy can develop early in the course of dysglycemia, even before a diagnosis of diabetes, according to the latest data from the Diabetes Prevention Program (DPP) (White et al., p. 2653). However, while glycemic parameters, most notably HbA1c, appear to be the strongest risk factors for retinopathy development, there is still no case for screening for retinal changes in people with prediabetes, according to the authors. Based on the findings, they suggest that further studies will be needed to determine whether interventions during the prediabetes phase might alter longer-term complications such as retinopathy. The findings come from further analysis of the DPP study and particularly the follow-up DPP Outcomes Study that has been tracking outcomes in the DPP cohort. The analysis looked at fundus photography used over time in adults at high risk of developing type 2 diabetes to detect retinopathy, including also after they progressed to diabetes. Approximately 20 years after randomization in the DPP, 24% of ∼1,600 individuals who developed type 2 diabetes also developed diabetic retinopathy. In contrast, 14% of 885 individuals who remained without diabetes still developed diabetic retinopathy. Univariate analysis identified American Indian race as being associated with less frequent retinopathy than non-Hispanic White race. Various raised measures of glycemia (including HbA1c) were also associated with more frequent retinopathy along with weight, hypertension, dyslipidemia, and smoking. Nearly all the associations fell away in multivariate analysis, with the exceptions being American Indian race and consistently raised HbA1c. “Since interventions that reduce the development of diabetes have so far not appeared to reduce the subsequent development of long-term diabetes–related retinopathy, and since such retinopathy is mild and does not threaten vision, screening for retinal changes in persons with prediabetes does not seem to be warranted on the basis of currently available data,” the authors conclude.

The American Diabetes Association and the European Association for the Study of Diabetes have published an updated consensus report on the management of hyperglycemia in type 2 diabetes (p. 2753). Although focused on hyperglycemia in diabetes, the report covers a vast range of issues in terms of care, treatments, technology, and patient self-management, mainly because hyperglycemia is so central to diabetes and its complications. Initially outlining the benefits of lowering blood glucose, a clear focal point of the report is on recent developments around glucose-lowering medications such as metformin, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and the rest. A major focus is also given to the large trials that have been conducted over the past few years and the consequences of those findings on the way patients with diabetes are now treated. Attention is also given to recent advances in metabolic surgery and the notion that not all procedures are suitable for or as effective at reducing weight or inducing remission in diabetes. The authors also look at linked but no less important issues, including nutrition, physical exercise, diabetes self-management education and support, and weight reduction, and they even highlight the importance of language use when talking to patients. Two further areas they consider are therapeutic inertia and the growing importance of technology in the wider care model—the latter given a considerable boost in the face of the coronavirus disease 2019 pandemic. As well as making a full series of recommendations, the authors also look to the future and where research should focus to take the field further. Precision medicine, technology, and health care team models will be a particular focus, according to the authors. “We hope the ideas raised in our consensus statement percolate to policy makers, payers, and health care systems in addition to front-line diabetes care professionals,” said author John Buse. “Ensuring equitable access to care and more consistent implementation of what we know works to prevent diabetes and its complications is urgently needed to stem the horrific global burden of diabetes and its comorbidities,” he added.

Rates of diabetes during pregnancy have doubled in the past 30 years, according to Denice Feig (p. 2484), who charts the epidemiology and the development of therapies for women with diabetes who are pregnant. Initially focusing on the changing epidemiology of diabetes in pregnancy, Feig reviews a series of studies that show how rates of pregnancies with type 1 diabetes have increased by 40% in the last 30 years. Meanwhile, type 2 diabetes in pregnancy, which was rarely seen, has doubled and may have even tripled over the same period. This likely reflects rising diabetes rates in the general population in conjunction with increasing rates of obesity, poor diets, sedentary lifestyles, as well as diabetes onset at increasingly younger ages. The same issues may be particularly acute in indigenous populations. For women with type 1 diabetes who are pregnant, outcomes include higher blood glucose levels, more frequent large-for-gestational-age infants, and more preterm births. In comparison, type 2 diabetes during pregnancy more frequently results in hypertension in mothers, perinatal infant mortality, and increasing socioeconomic deprivation. In terms of treatments, Feig illustrates a mixed picture of success during pregnancy with technologies such as continuous glucose monitoring, insulin pumps, and, much more recently, artificial pancreas systems, which are currently undergoing numerous trials. The addition of metformin to insulin in type 2 diabetes during pregnancy is also having notable success in improving pregnancy outcomes with a substantial reduction in insulin doses. Commenting further, author Denice Feig said, “Technological advances have shown great promise in improving pregnancy outcomes in women with type 1 diabetes, but adverse outcomes remain unacceptably high. More research is needed in women with type 1 and type 2 diabetes to determine if we can further reduce complication rates in these women. Concurrently, we need to address the affordability of treatments and technologies, as socioeconomic deprivation remains a significant determinant of pregnancy outcomes.”