Sarit Polsky

OBJECTIVE: The value of adding continuous glucose monitoring (CGM) to blood glucose monitoring (BGM) during pregnancy is unclear. PURPOSE: To clarify CGM's role in pregnancy using meta-analysis, Grading of Recommendations Assessment, Development and Evaluation (GRADE) ratings, harmonized neonate size definitions, and trial sequential analysis (TSA). DATA SOURCES: We performed bibliographic database and hand searches. We selected clinically relevant randomized controlled trials (RCTs) comparing CGM and BGM in pregnancy. DATA EXTRACTION: Neonate size measures were primary; additional maternal, obstetric, and neonatal outcomes data were also extracted. DATA SYNTHESIS: Seventeen RCTs (n = 2,672 participants) met inclusion criteria. Incidence of macrosomia was reduced overall (risk ratio [RR] 0.67 [95% CI 0.48, 0.94]; strength of evidence [SOE], moderate) and for gestational diabetes mellitus (GDM) (RR 0.55 [95% CI 0.35, 0.86]; SOE, high); incidence of large for gestational age was also reduced overall (RR 0.77 [95% CI 0.61, 0.98]; SOE, very low) and for GDM (RR 0.65 [95% CI 0.45, 0.96]; SOE, very low). Incidence of small for gestational age (SGA) was elevated with CGM but not statistically significant (RR 1.37 [95% CI 0.96, 1.95]; SOE, moderate). The TSA showed no neonate size outcome met the required information size (RIS) to draw firm conclusions, and no cumulative Z curve crossed the adjusted monitoring boundary. Summary statistical significance may fluctuate with the publication of new studies. CONCLUSIONS: CGM benefits mothers with preexisting diabetes and GDM and their neonates for varying outcomes, including reducing large size at birth. Our TSA found that the RIS for neonate size outcomes has not been reached. Literature should be monitored particularly for RCTs reporting SGA in GDM, which the TSA shows cannot be conclusively ruled out as a risk.

Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like polypeptide-1 receptor agonist, has significantly increased in use in overweight (OW)/obese people with type 1 diabetes (T1D). It is not known if tirzepatide affects the incidence and/or progression of diabetic retinopathy (DR), including diabetic macular edema (DME), in individuals with T1D. We performed a retrospective chart review of OW/obese people with T1D using adjunctive tirzepatide treatment continuously for at least 1 year ± 2 months (cases, n = 106). Eighty-five controls with T1D not using tirzepatide were matched by age, sex, and body mass index. Retinal eye examination results were collected at baseline and follow-up (6-24 months). Cases were eligible if temporary drug discontinuations were ≤1 month. For individuals without baseline eye disease, the incidence rates of DR and DME were analyzed. For individuals with baseline DR and/or DME, progression and regression of eye diseases were evaluated. Mean diabetes duration was 26.2 years (cases) and 28.0 years (controls). Baseline DR and/or DME rates were high in both groups (63.2% cases vs. 71.8% controls). Most people in both groups were using an automated insulin delivery system. Mean glycated hemoglobin A1C (HbA1c) improved within 6 months (P < 0.001) and remained stable for cases, but was unchanged for controls. New-onset DR developed in 10/39 (25.6%) of cases and 7/24 (29.2%) of controls over a mean follow-up of 11.7 and 15.3 months, respectively. Incident DR occurred more frequently in individuals (cases and controls) with a rapid HbA1c decline (≥0.5% within 6 months) compared with those without it (11/28 [39.3%] vs. 6/35 [17.1%], P = 0.048). Among cases and controls with baseline DR, eye disease remained stable at follow-up for most individuals. OW/obese individuals with T1D treated with off-label tirzepatide developed DR similar to controls. Randomized controlled trials are needed to confirm these findings.

Among the most impactful therapeutic advances in the management of diabetes over the past two decades has been the development of incretin-based therapies, specifically glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and in combination with glucose-dependent insulinotropic polypeptide (GIP) RAs. Since the introduction of exenatide in 2005, a growing number of these drugs has transformed the management of type 2 diabetes (T2D). Their pleiotropic effects include weight loss, reduced insulin resistance, improved glucose regulation, and reductions in known risk markers for diabetic kidney disease and cardiovascular disease. To date, these important noninsulin glucose-lowering therapies have only received regulatory approval for use in T2D, obesity, sleep apnea, and metabolic dysfunction-associated steatohepatitis with moderate-advanced fibrosis, supported by randomized controlled trials (RCTs) and real-world data that demonstrate efficacy and safety. Regulatory approval for use of weekly GLP-1 and GLP-1/GIP RAs in type 1 diabetes (T1D) has not yet been achieved, in part because of the limited number of inconsistent, small-scale, RCTs and real-world studies for glycemic impacts of these agents in T1D. Larger RCTs are ongoing or planned in participants with T1D. Potential safety risks include hypoglycemia and hyperglycemia-related ketosis in T1D after initiation of GLP-1/GIP RA drugs. While RCTs are ongoing to further investigate GLP-1 and GLP-1/GIP RA agents as adjunct therapy for people with T1D, access to these drugs is already possible, based on their use to treat overweight and obesity. However, without regulatory approval for the T1D indication, access and opportunities for people with T1D to engage with important education regarding the safety of GLP-1 and GLP-1/GIP RA therapy may be limited. This precludes support from diabetes health care professionals to optimize diabetes management of these agents alongside expected insulin dose changes. The purpose of this consensus report is to review the current literature and provide guidelines for diabetes clinicians and people with T1D to facilitate the safe use of GLP-1/GIP RAs in the management of T1D. This consensus statement has been endorsed by the following professional associations: Advanced Technologies & Treatments for Diabetes (ATTD), International Diabetes Federation–Europe, American Association of Clinical Endocrinologists (AACE), Breakthrough T1D, International Society for Pediatric and Adolescent Diabetes (ISPAD), Association of Diabetes Care and Education Specialists (ADCES).

OBJECTIVE: Adult-onset type 1 diabetes is not well characterized, especially after 40 years of age, and is commonly misdiagnosed as type 2 diabetes. We evaluated the differences in clinical presentation, islet autoantibodies, and HLA genetics between pediatric- and adult-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: Individuals who were newly diagnosed with type 1 diabetes were tested for islet autoantibodies within 1 year of diagnosis in this retrospective study. Islet autoantibodies against GAD, insulin, islet antigen 2, and zinc transporter 8 were measured using fluid-phase radiobinding assays. High-resolution HLA class I (n = 655) and II (n = 1,196) typing was performed in a subset of participants. RESULTS: In total, 414 adults (aged ≥20 years) and 2,000 children were included. Adults were aged 20–76 years and had a mean BMI of 23.5 ± 4.7 kg/m2 at onset. Compared with children, adults presented with diabetic ketoacidosis (DKA) less frequently (32.6% vs. 56.0%; P < 0.001) and with slightly lower HbA1c values (11.3% ± 2.6% vs. 12.0% ± 2.4%; P < 0.001). Notably, adults older than 40 years (n = 84) presented with DKA only 13.1% of the time. Adults more often presented with zero or one islet autoantibodies compared with children (43.0% vs. 20.2%; P < 0.001). There were no differences in high-risk HLA haplotypes between adults and children (DR4-DQ8: 57.1% vs. 63.7%; P = 0.060; DR3-DQ2: 43.6% vs. 46.1%; P = 0.482). CONCLUSIONS: Adult-onset type 1 diabetes is characterized by a reduced frequency of DKA and by fewer total islet autoantibodies. Our findings can help in the accurate diagnosis of type 1 diabetes in adults.

OBJECTIVE: Multiple states have passed legislation limiting out-of-pocket insulin costs for individuals on private insurance, including Colorado in 2020. Because disruptions in insulin access are life-threatening for people with type 1 diabetes, this study examined the real-world impact of Colorado’s law on patient/parent-reported outcomes. RESEARCH DESIGN AND METHODS: Patient/parent-reported frequency of insulin insecurity (insulin rationing, running out early, or finding alternative sources of insulin), cost concerns, and most recent insulin out-of-pocket cost were assessed by a clinic-developed survey. Demographics, A1C, and glycemic time in range (TIR; 70–180 mg/dL) were obtained from medical record review. Linear regression models were fit to compare out-of-pocket costs, A1C, and TIR, adjusting for sex, diabetes duration, race/ethnicity, insurance, and age. RESULTS: Of 184 enrolled participants, 149 responded to insulin insecurity questions, with 34% reporting at least one insulin insecurity behavior. Insulin insecurity was associated with higher monthly insulin costs ($77.60 vs. $19.30, P = 0.004) and A1C (+0.69 ± 0.23%, P = 0.003) and lower TIR (−9.78 ± 4.03%, P = 0.02) compared with insulin security. Similar rates of insecurity were seen in emerging adults (46%, n = 18/39) and those publicly insured (43.5%, n = 10/23). There was no difference in mean copayments between those on public versus private insurance ($39.40 vs. $38.00). CONCLUSION: Despite costs falling below the out-of-pocket cap, insulin insecurity remains common among emerging adults and families of youth with type 1 diabetes and is associated with worse glycemia. Further research into root causes of insecurity, such as limitations on early refills, is required.

Diabetic ketoacidosis (DKA) occurring during pregnancy is an obstetric emergency that can result in significant adverse outcomes for both the pregnant person and the fetus. While DKA generally presents with glucose levels >250 mg/dL, up to 30% of DKA cases involve euglycemic DKA (euDKA) wherein glucose levels <200 mg/dL have been reported. However, detection and prevention of DKA in pregnancy can be challenging for both the pregnant individual and health care providers due to variable clinical presentations of the disease and the limitations of current ketone monitoring technologies. Abbott Diabetes Care (Alameda, CA) is developing a dual monitoring system that utilizes a single sensor to enable continuous monitoring of interstitial glucose and β-hydroxybutyrate, the primary metabolic product of blood ketones. This article reviews the challenges of monitoring ketones during pregnancy and discusses how continuous ketone monitoring could be considered for use in clinical practice once it becomes commercially available.

Since the discovery of the life-saving hormone insulin in 1921 by Dr. Frederick Banting in 1921, there have been many critical discoveries and technical breakthroughs that have enabled people living with type 1 diabetes (T1D) to live longer, healthier lives. The development of insulin pumps, continuous glucose monitoring systems, and automated insulin delivery (AID) systems has enabled people living with T1D to safely manage their glucose, reduce their HbA1c, and improve their overall health and quality of life. Nevertheless, AID systems are not yet designed for all people with T1D, and they perform best during the overnight period when meals and exercise are not occurring. AID systems are not fully automated in that they require the person using the system to announce meals and exercise to the system to avoid dangerous hyper- or hypoglycemia, respectively. In this review, which is one of a collection of articles to commemorate the 75th anniversary of the National Institute for Diabetes and Digestive and Kidney Diseases, we celebrate the commercialization of the AID and discuss the major challenges and research gaps that remain to be solved to enable single- and multihormone AID systems to more fully support glucose management in people living with T1D. More research is required to design and evaluate more intelligent AID systems that do not require accurate carbohydrate estimations or announcements for meals and exercise. Current AID systems are also not designed to be used by older adults or pregnant people. Results are presented on new AID systems that can automatically respond to meals and exercise. Results are also presented on evaluations of AID systems in older adults and pregnant people. Next-generation AID systems will need to support all people, including older adults, people during pregnancy, athletes, and people who may be too busy to announce carbohydrates or exercise to the system. Solutions are now becoming available that will enable AID systems to support a broader range of people living with T1D by leveraging the latest technologies in artificial intelligence and adaptive control.

Data on the cost implications of continuous glucose monitoring (CGM) use in type 1 diabetes (T1D) pregnancies in the United States are sparse. Drawing on associations identified in real-world evidence from a retrospective chart review at the Barbara Davis Center for Diabetes, we conducted a cost-consequences analysis of CGM use versus self-monitoring of blood glucose (SMBG), inclusive of neonatal intensive care unit (NICU) spending. In the base-case analysis assuming per-label CGM use and per-guideline finger-stick frequency, the per-person cost was $16,254 for CGM versus $15,182 for SMBG. In a real-world scenario analysis, the per-person cost was $13,708 for CGM versus $14,524 for SMBG. In both analyses, there was a cost savings for NICU admissions of $2,903 with CGM use. In the probabilistic sensitivity analysis, CGM was cost saving in 25% of base-case model iterations and 46% of real-world model iterations. This study adds to the growing evidence base that the increased costs of CGM use versus SMBG to manage T1D pregnancies are likely offset by better neonatal health outcomes.

Automated insulin delivery (AID) systems adapt insulin delivery via a predictive algorithm integrated with continuous glucose monitoring and an insulin pump. Automated insulin delivery has become standard of care for glycemic management of people with type 1 diabetes (T1D) outside pregnancy, leading to improvements in time in range, with lower risk for hypoglycemia and improved treatment satisfaction. The use of AID facilitates optimal preconception care, thus more women of reproductive age are becoming pregnant while using AID. The effectiveness and safety in pregnant populations of using AID systems with algorithms for non-pregnant populations may be impacted by requirements for lower glucose targets and existence of increased insulin resistance during gestation. The CamAPS FX is the only AID system approved for use in pregnancy. A large randomized controlled trial (RCT) with this AID system demonstrated a 10.5% increase in time in pregnancy range (an additional 2.5 hours/day) compared with standard insulin therapy in pregnant women with T1D with a baseline glycated hemoglobin A1c (HbA _1c ) ≥48 mmol/mol (6.5%). A RCT of AID not approved for use in pregnancy (MiniMed 780G) has also demonstrated some benefits of AID compared with standard insulin therapy with improved time in pregnancy range overnight (24 minutes), less hypoglycemia, and improved treatment satisfaction. There is also increasing evidence that AID can be safely continued during delivery and postpartum, while maintaining glycemic goals with lower risk for hypoglycemia. More AID systems are needed with flexible glucose targets in the pregnancy range and possibly with algorithms that better adapt to changing insulin requirements. More evidence is needed on the impact of AID on maternal and neonatal outcomes. We review the current evidence on the use of AID in pregnancy and postpartum.