In This Issue of Diabetes Care

Although there is compelling evidence supporting the safety and efficacy of metformin as a first-line agent for diabetes treatment, there is no consensus about the choice of a second-line agent when metformin fails to meet or maintain glycemic goals. Given that there are currently 11 classes of approved glucose-lowering drugs on the market, the absence of empirical evidence supporting use of one second-line agent over another leaves many clinicians uncertain about appropriate strategies for treatment intensification. A report in this issue of Diabetes Care (p. 1338) addresses this basic issue with a new computer model that uses data from more than 37,000 diabetic individuals aged ≥40 years. The new study examined intensification of metformin monotherapy with four regimens: 1) addition of insulin, 2) sulfonylurea then insulin, 3) DPP-4 inhibitors then insulin, and 4) GLP-1 agonists then insulin. The report focused on a number of outcomes including life-years (LYs), quality-adjusted LYs (QALYs), cost, time to initiation of insulin, and a variety of complications, such as heart disease and renal failure. The results of the new study indicated that although none of the four treatment intensification regimens performed better than the others in terms of LYs or QALYs, relative to an HbA_1c treatment goal of 8%, a goal of 7% was associated with higher QALYs regardless of which treatment regimen was used. Perhaps the most striking finding was that the treatment intensification regimen including sulfonylurea was associated with the lowest cost and the longest delay to insulin initiation. Although the authors acknowledge that these results are based on computer modeling, the profound differences in cost and time to insulin initiation between the sulfonylurea regimen and the more expensive regimens involving DPP-4 inhibitors and GLP-1 agonists address the interests of clinicians, payers, and patients alike. The new approach provides these diverse stakeholders with the ability to make direct comparisons among competing regimens in a manner that has not been available in the past. — Helaine E. Resnick, PhD, MPH

Zhang et al. Second-line agents for glycemic control for type 2 diabetes: Are newer agents better? Diabetes Care 2014;37:1338–1345

Findings from a case-control study in this issue of Diabetes Care (p. 1296) suggest that, even years before a pregnancy occurs, low levels of sex hormone–binding globulin (SHBG) may predict development of gestational diabetes mellitus (GDM). The new report used data from 256 nondiabetic women who were examined between 1984 and 1996 and who had a subsequent GDM pregnancy between 1984 and 2009. Each of the GDM cases was matched to two control women who were also examined between 1984 and 1996 and who were similar to GDM cases on a number of features including age at pregnancy. All women had stored blood samples from the 1984–1996 examination, and these specimens were used to measure SHBG for both cases and controls. SHBG levels were then related to the odds of developing GDM. The investigators divided SHBG levels into quartiles, with the highest analyzed as the reference group. Relative to the highest quartile of SHBG, there was a striking trend toward increased odds of GDM as quartile of SHBG decreased. Even when adjusted for numerous potential confounding factors, the odds of GDM were 1.06 (95% CI 0.44–2.52), 2.33 (1.07–5.09), and 4.06 (1.90–8.65) in the 3rd, 2nd, and 1st quartiles of SHBG, respectively, relative to the highest quartile. Notably, the blood samples from which SHBG was measured for these women were collected an average of 6 years prior to pregnancy, suggesting that an androgenic hormone profile may be present long before a GDM pregnancy occurs. If true, these findings raise the intriguing possibility that SHBG could be developed as a novel strategy for GDM screening and prevention many years prior to pregnancy. — Helaine E. Resnick, PhD, MPH

Hedderson et al. Prepregnancy SHBG concentrations and risk for subsequently developing gestational diabetes mellitus. Diabetes Care 2014;37:1296–1303

Findings in this issue of Diabetes Care (p. 1204) may help address a basic challenge for people with type 1 diabetes and their caregivers: How to achieve recommended pediatric glucose targets without the accompanying fear of severe nocturnal hypoglycemia. The new report shows that automated, overnight insulin delivery in adolescents is both safe and feasible—findings that support the importance of larger studies to further explore this control strategy. The new report details a randomized, crossover study of 16 adolescents with type 1 diabetes who used sensor-augmented pumps with or without supplementation with an overnight closed-loop system. The closed-loop system is based on an algorithm that is housed on a laptop that is connected to the sensor receiver and controls the pump wirelessly. The primary end point of the study was the amount of time between 2300 h and 0700 h when participants’ glucose was in the target range of 3.9–8.0 mmol/L. Secondary end points included mean glucose levels, hypoglycemia, hyperglycemia, and amount of insulin delivery. The closed-loop system was used on 93% of all available nights, and the system had no interruptions in 74% of all nights when the system was used. Apart from the acceptability of the closed-loop system, the most notable finding of the new report is that time spent in the target glucose range was increased by 15% among patients using closed loop. Further, average overnight glucose decreased significantly on closed loop, and the frequency with which participants’ glucose was <63 mg/dL was also significantly lower with closed loop, as was the frequency of hyperglycemia. Although the lower nighttime glucose levels were achieved with higher nocturnal insulin delivery with closed loop, daytime insulin delivery was reduced in this group. The net effect was a reduction in overall insulin delivery with closed loop. This report provides promising data that support further exploration of closed-loop approaches for overnight glucose control in youth. — Helaine E. Resnick, PhD, MPH

Hovorka et al. Overnight closed-loop insulin delivery in young people with type 1 diabetes: a free-living, randomized clinical trial. Diabetes Care 2014;37:1204–1211

A new report in this issue of Diabetes Care (p. 1353) suggests that moderate alcohol consumption, particularly wine, is associated with reduced risk of both cardiovascular disease (CVD) and all-cause mortality. The new report examined data from the ADVANCE trial, an international study of more than 11,000 people with type 2 diabetes and a history of a major cardiovascular event or microvascular disease with an additional CVD risk factor. Unlike previous studies with homogenous populations and limited detail on alcohol subtypes, the new report contains large numbers of men and women from diverse ethnic backgrounds, as well as detailed information on consumption of wine, beer, and spirits. While 30% of study participants reported alcohol consumption at baseline, only 4% reported heavy consumption. Results in the new report are based on median follow-up time of 5 years and show that relative to participants who did not report any alcohol consumption, those who reported moderate consumption had significantly lower rates of cardiovascular events (17% reduction), microvascular complications (15% reduction), and all-cause mortality (13% reduction). By contrast, diabetic people who reported high alcohol consumption had higher rates of cardiovascular events and all-cause mortality relative to nondrinkers. Additional analyses that focused on alcohol types showed that wine drinkers had particularly low risk of unfavorable end points: Compared to diabetic people who did not drink, those who drank wine had a 22% reduction in cardiovascular events and a 23% reduction in all-cause mortality. Beer and spirits consumption did not have an impact on any study outcomes. Although the authors stress that the associations were robust after adjustment for multiple risk factors, they caution that these results do not demonstrate causality. They also point out that any inferences regarding the potential benefits of alcohol consumption among diabetic people must be weighed against potential drawbacks such as hypoglycemia and liver problems. — Helaine E. Resnick, PhD, MPH

Blomster et al. The relationship between alcohol consumption and vascular complications and mortality in individuals with type 2 diabetes. Diabetes Care 2014;37:1353–1359