In This Issue of Diabetes Care

The global prevalence of prediabetes is substantial and forecast to grow in the next two decades, according to Rooney et al. (p. 1388). Using estimates of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) as measures for prediabetes, they found that 464 million adults (9.1%) had IGT and 298 million adults (5.8%) had IFG in 2021. By 2045, the same figures are expected to increase to 638 million (10.0%) for IGT and 414 million (6.5%) for IFG. In addition to 2021 prevalence figures, the authors used extensive statistical analyses to project estimates out to 2045. Just over 7,000 articles relating to 215 countries and territories were screened in the analyses. Despite the volume of studies originally included, they found that only about a fifth of countries had high-quality data relating to either IFG or IGT, and only ∼5% had estimates for both. They found that North America and the Caribbean had the highest IGT prevalence in 2021, while Southeast Asia had the lowest prevalence. Conversely, Southeast Asia had the highest IFG prevalence and the Western Pacific region the lowest in 2021. Prevalence was also predicted to increase across most age-groups. Higher income was linked to increased prevalence, but a striking 120–130% increase is also predicted in lower-income countries for both measures up to 2045. The authors note that the availability and quality of data were generally poor and that their definition of prediabetes is only one of many available. Based on the findings, they conclude that effective prevention measures are now needed, especially in low-income settings, but agreement is needed on what exactly defines prediabetes. “The global burden of prediabetes is substantial and projected to grow,” said author Mary R. Rooney. “Our findings highlight the urgent need for more effective diabetes prevention policies and interventions worldwide.”

Routinely available clinical test parameters can help to identify patients with high-risk type 2 diabetes who require further liver assessments, according to Castera et al. (p. 1354). Specifically, they found that the parameters could identify factors associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis (AF) in patients with suspected nonalcoholic fatty liver disease (NAFLD). Currently, the prevalence of NASH and AF among patients with type 2 diabetes is poorly characterized, with invasive liver biopsy being the only definitive method of diagnosis. The findings come from a nested, prospective, cross-sectional, multicenter study that included just over 700 patients with type 2 diabetes who were screened for NAFLD. A liver biopsy was proposed when ALT levels were persistently >20 IU/L for women and >30 IU/L for men (i.e., much lower than recommendations). In the 330 liver biopsy samples included in the analysis, the authors found that 58% had NASH, 38% had AF, and 10% had cirrhosis. They also found that liver lesions were independently associated with components of metabolic syndrome but not with micro- and macrovascular complications of type 2 diabetes. One of the noninvasive tests currently but not widely used for diagnosing NAFLD is a technique called vibration-controlled transient elastography (VCTE). Due to the limited availability of VCTE, the authors used modeling based on routinely available clinical data and biological data (age, waist circumference, HDL cholesterol, and platelet count) with and without the technique included, and they found that both model versions had good accuracy for AF and NASH. “Until now, the burden and severity of NAFLD in outpatients with type 2 diabetes attending diabetes clinics have been overlooked by most endocrinologists,” said author Laurent Castera. “We hope that our findings showing a high prevalence of AF and NASH, despite mild liver test abnormalities, in patients with type 2 diabetes and NAFLD will help put the liver on the radar for endocrinologists. Importantly, simple and widely available parameters can be used to identify these patients.”

Fluctuations in overnight glucose levels appear to influence various dimensions of functioning the following day, according to Pyatak et al. (p. 1345). In the context of type 1 diabetes, glucose variations and hyperglycemia appear to affect physical, cognitive, and self-reported functioning. Although effect sizes tended to be small, the authors note that these will still likely have a cumulative impact over a lifetime, and that means individualized treatments should result in improved functioning in type 1 diabetes. In particular, they highlight how diabetes technologies will likely help minimize overnight glucose fluctuations. The findings come from an observational study that enrolled just under 200 individuals with type 1 diabetes and involved an intensive investigation of the effects of continuous glucose monitoring, physical activity, and cognitive function monitoring. They found that overall next-day functioning could be predicted by examining overnight glucose variability and percent time above >250 mg/dL blood glucose levels (i.e., hyperglycemia). More specifically, they found that higher variability was associated with poorer sustained attention and lower engagement in demanding activities. Overnight hypoglycemia also was associated with poorer attention, which in turn predicted illness levels and quality of life, while hyperglycemia was associated with increased sedentary time. Despite the existence of such associations, the authors note that the effect sizes tended to be small—e.g., spending 10% more time overnight with hyperglycemia resulted in ∼2 min more sedentary time the next day. Previous studies in this area have tended to look at the longer-term effects of glycemic variability on functioning in terms of type 1 diabetes. Few studies have looked at the overnight effects. Commenting further, author Elizabeth A. Pyatak said, “Because automated insulin delivery systems are particularly good at controlling glucose levels overnight, these technologies could support better quality of life for people with type 1 diabetes by minimizing overnight glucose fluctuations. Further research is also needed to investigate how daytime glucose fluctuations impact function and activity engagement in the moment.”

A closed-loop automated insulin delivery system customized for use during pregnancy appears to be feasible and effective, according to Levy et al. (p. 1425). While using the system, the participants experienced improved glycemic control compared with their glucose control at baseline and showed improved time in range and reduced time with hyperglycemia and hypoglycemia. The feasibility study included 10 pregnant women with type 1 diabetes and is the first to explore extended home use outcomes during pregnancy in the U.S. Participants who were in the second or early third trimester at enrollment initially completed a run-in period to collect baseline data, followed by 2 days of supervised outpatient system use. In the third study phase, they used the system, called CLC-P, at home until delivery. Of the 10 participants, 9 exceeded the goal of >70% time in range (63–140 mg/dL) during system use, and time in range increased by 14.1% compared with baseline, equivalent to 3.4 extra hours per day. Baseline time in range was approximately 65%, compared with nearly 79% while using the system over 24-h periods, and time in range overnight reached nearly 85%. Likewise, there were significant reductions in the time above (i.e., hyperglycemia) and below (i.e., hypoglycemia) range. The authors note that there were still several maternal and neonatal events, but none were serious in terms of maternal hypoglycemia or ketoacidosis or infant outcomes attributable to the system. They also note several expected limitations but point out that 9 out of 10 participants achieved the consensus recommendations for time in range during pregnancy by using the system. Commenting further, author Eyal Dassau said, “Our study, inspired by Lois Jovanovic, MD, demonstrates that advanced hybrid closed-loop systems customized to the tighter glycemic targets required during pregnancy are feasible and effective. We look forward to larger studies focusing on this underserved community of people with diabetes.”