By Max Bingham, PhD
Dyslipidemia in Youth With Type 1 Diabetes: Prospective Longitudinal Study Data
Higher blood glucose levels (HbA1c) and higher waist-to-height ratio (a measure of central obesity) are likely modifiable risk factors for unfavorable changes in blood cholesterol levels and consequently cardiovascular disease risk in youth with type 1 diabetes. The multicenter longitudinal prospective cohort SEARCH for Diabetes in Youth (SEARCH) study by Shah et al. (p. 607) examined blood lipids at baseline and then again at 7 years in approximately 1,500 youths with type 1 diabetes. Progression to dyslipidemia was defined as “normal” blood levels of non–HDL cholesterol or HDL cholesterol at baseline and then abnormal levels (>130 mg/dL non–HDL cholesterol or <35 mg/dL HDL cholesterol) after 7 years. The authors report that approximately 25% of the patients either progressed to dyslipidemia or maintained already unfavorable levels over the period of follow-up. Subsequent analysis then identified HbA1c and waist-to-height ratio as independent factors associated with the unfavorable progression of dyslipidemia. The authors suggest that their data might point to a delicate balance between needing to maintain optimal body weight and achieving glycemic control. They go on to suggest the relationship is complex as higher insulin doses are needed to achieve adequate glucose control but this also promotes weight gain. Nevertheless, they state that until this relationship is further investigated, their data suggest that both are likely modifiable risk factors and therefore potential opportunities for intervention. Commenting more widely on the study, author Amy S. Shah told Diabetes Care: “We have identified two risk factors that appear to influence abnormal cholesterol levels in youth with type 1 diabetes: glucose control and central obesity. There are other risk factors that are also likely to be important such as diet, exercise, and smoking, which we did not evaluate. Future studies should consider these additional risk factors and importantly, whether treatments such as weight loss or weight maintenance are able to improve blood cholesterol levels in this population.”
Out-of-Range HbA1c Proposed to Improve Quality of Diabetes Care for Older Adults
Diabetes Care features a special section this month that covers the emerging science and concepts for the management of diabetes and aging. In this special section is an article by Pogach et al. (p. 518) that proposes a new out-of-range (OOR) HbA1c measurement concept for older populations receiving insulin or hypoglycemic-prone oral agents. More specifically, the authors argue that both over- and undertreatment of glycemic control should be assessed rather than the single "less than" target HbA1c that is currently used for all patients. The current measurement standard, HbA1c <8%, is based upon the assumption that achieving lower values will reduce major complications for most patients 65–75 years of age. However, the measure does not assess how many patients are overtreated, thus increasing the risk for hypoglycemia, which now exceeds hyperglycemia as a cause for hospitalization in older adults in the U.S. To assess the potential impact of their proposal, the authors report an evaluation of HbA1c control in nearly 200,000 older (aged >65 years) veterans with diabetes and at least one significant comorbid condition. Using the current standard, approximately two-thirds would be considered to have appropriate control. In contrast, about half would be considered at-risk (HbA1c <7 or >9%) using an OOR approach. Moreover, overtreatment (i.e., HbA1c <7%) was 2.4-fold greater than undertreatment (i.e., HbA1c >9%). Additionally, only 28% of patients had an HbA1c value in a target range between 7.5–8.5%. As a result, the authors recommend the OOR approach as a medication safety accountability measure that addresses a gap in population health risk surveillance. They suggest the target range as a quality improvement measure to further focus the goal of glycemic management in older adults as the avoidance of extreme HbA1c values that could result in imminent harms. According to author Leonard Pogach: "Many older adults will continue to need or benefit from insulin as well as other medications with potentially significant side effects. Guidelines recommend that targets be individualized based upon patient preferences through a process of shared decision making that presents both treatment benefits and risks. Our measure would incentivize this approach."
Continuous Glucose Monitoring Is Likely Equivalent to Standard Glucose Monitoring Methods: Randomized Controlled Trial Data
A noninferiority randomized multicenter clinical trial of a continuous glucose monitoring (CGM) device alone versus the technology with regular calibration with standard fingerstick blood glucose monitoring (BGM) suggests that CGM is as safe alone as it is with the standard approach. The result will likely be a major boost to patients with type 1 diabetes as well as the manufacturers of the devices. The trial, authored by Aleppo et al. (p. 538), who are part of the T1D Exchange Clinic Network, suggests that alone the CGM technology is likely to be as effective as when it is combined with the fingerstick approach. The 26-week trial assessed the outcomes of 226 adult patients with well-controlled type 1 diabetes assigned 2:1 to CGM alone or to the technology plus standard daily assessments of blood glucose. The result: there were no differences in outcomes. Reportedly, the primary outcome was “time in range” for blood glucose of 70–180 mg/dL over the trial period. A number of secondary outcomes were also included. Both the CGM alone and CGM+BGM groups achieved a within-range time result of about 65%. There was little influence on the outcome if the patients were male, female, old, or young. Racial background or income level made no difference either. The U.S. Food and Drug Administration (FDA) previously has steered away from recommending CGM devices alone as a method for monitoring blood glucose. However, the technology is rapidly developing and in December 2016, the FDA approved the use of one particular CGM device as a replacement for fingerstick blood glucose testing for diabetes treatment decisions. The results of this study are consistent with that decision. Commenting on the outcomes of the study, author Tonya D. Riddlesworth stated: “The study results are important in showing that CGM can be used safely for dosing insulin without the need for blood glucose meter testing.”
Improved Glycemic Control in Type 1 Diabetes With Insulin Glargine 300 Units/mL
An exploratory study on the use of insulin glargine 300 units/mL (Gla-300) in type 1 diabetes suggests improved glucose control over 24 h is possible in comparison to insulin glargine 100 units/mL (Gla-100) and that much less fluctuation in glucose levels can be expected, irrespective of the time of day injections are made. The study also highlights (again) the potential of continuous glucose monitoring (CGM) to provide higher resolution information on glucose profiles to guide insulin delivery in a more accurate manner. The study by Bergenstal et al. (p. 554) compared the effects of Gla-300 and Gla-100 given in the morning or in the evening to 59 adults with well-controlled type 1 diabetes in a parallel group crossover design with CGM used to assess a range of blood glucose end points. While there was no difference between the treatments in terms of time spent in the target range (around 30%, the primary outcome), many other measures pointed toward a much smoother blood glucose profile resulting from treatment with Gla-300 than from Gla-100. For example, Gla-300 resulted in much narrower excursions in blood glucose, and there was very little variation when Gla-300 was given in the morning or in the evening. This was not the case with Gla-100, where excursions were much more evident. Hypoglycemic events were also reduced in the Gla-300 group, particularly at night, with the suggestion of a risk reduction in comparison to using Gla-100. Study author Richard M. Bergenstal suggests there are two key aspects of their study to consider: “First, I think CGM is rapidly emerging as the gold standard for comparing the ability of new drugs to optimize glucose control beyond just the average glucose level that HbA1c provides. Second, patients and clinicians want a background insulin that really lasts 24 h, works the same way each day regardless of the time it is injected, and can help minimize the glucose variability and often associated hypoglycemia. Using CGM, we were able to show U300 glargine (Gla-300) fits this description better than U100 glargine (Gla-100).”
