More Like this

1. Association of Both Short-term and Long-term Glycemic Variability With the Development of Microalbuminuria in the ACCORD Trial

   https://doi.org/10.2337/db23-0374  

   Okuno, Tomoki ; Vansomphone, Arin ; Zhang, Elyse ; Zhou, Hua ; Koska, Juraj ; Reaven, Peter ; Zhou, Jin J. ( September 2023 , Diabetes)

   Both long- and short-term glycemic variability have been associated with incident diabetes complications. We evaluated their relative and potential additive effects on incident renal complications in the Action to Control Cardiovascular Risk in Diabetes trial. A marker of short-term glycemic variability, 1,5-anhydroglucitol (1,5-AG), was measured in 4,000 random 12-month postrandomization plasma samples (when hemoglobin A1c [HbA1c] was stable). Visit-to-visit fasting plasma glucose coefficient of variation (CV-FPG) was determined from 4 months postrandomization until the end point of microalbuminuria or macroalbuminuria. Using Cox proportional hazards models, high CV-FPG and low 1,5-AG were independently associated with microalbuminuria after adjusting for clinical risk factors. However, only the CV-FPG association remained after additional adjustment for average HbA1c. Only CV-FPG was a significant risk factor for macroalbuminuria. This post hoc analysis indicates that long-term rather than short-term glycemic variability better predicts the risk of renal disease in type 2 diabetes.

   The relative and potential additive effects of long- and short-term glycemic variability on the development of diabetic complications are unknown. We aimed to assess the individual and combined relationships of long-term visit-to-visit glycemic variability, measured as the coefficient of variation of fasting plasma glucose, and short-term glucose fluctuation, estimated by the biomarker 1,5-anhydroglucitol, with the development of proteinuria. Both estimates of glycemic variability were independently associated with microalbuminuria, but only long-term glycemic variability remained significant after adjusting for average hemoglobin A1c. Our findings suggest that longer-term visit-to-visit glucose variability improves renal disease prediction in type 2 diabetes.

    

   more » « less
2. Heterogeneous treatment effects of intensive glycemic control on major adverse cardiovascular events in the ACCORD and VADT trials: a machine-learning analysis

   https://doi.org/10.1186/s12933-022-01496-7  

   Edward, Justin A. ; Josey, Kevin ; Bahn, Gideon ; Caplan, Liron ; Reusch, Jane E. ; Reaven, Peter ; Ghosh, Debashis ; Raghavan, Sridharan ( December 2022 , Cardiovascular Diabetology)

   Abstract Background Evidence to guide type 2 diabetes treatment individualization is limited. We evaluated heterogeneous treatment effects (HTE) of intensive glycemic control in type 2 diabetes patients on major adverse cardiovascular events (MACE) in the Action to Control Cardiovascular Risk in Diabetes Study (ACCORD) and the Veterans Affairs Diabetes Trial (VADT). Methods Causal forests machine learning analysis was performed using pooled individual data from two randomized trials (n = 12,042) to identify HTE of intensive versus standard glycemic control on MACE in patients with type 2 diabetes. We used variable prioritization from causal forests to build a summary decision tree and examined the risk difference of MACE between treatment arms in the resulting subgroups. Results A summary decision tree used five variables (hemoglobin glycation index, estimated glomerular filtration rate, fasting glucose, age, and body mass index) to define eight subgroups in which risk differences of MACE ranged from − 5.1% (95% CI − 8.7, − 1.5) to 3.1% (95% CI 0.2, 6.0) (negative values represent lower MACE associated with intensive glycemic control). Intensive glycemic control was associated with lower MACE in pooled study data in subgroups with low (− 4.2% [95% CI − 8.1, − 1.0]), intermediate (− 5.1% [95% CI − 8.7, − 1.5]), and high (− 4.3% [95% CI − 7.7, − 1.0]) MACE rates with consistent directions of effect in ACCORD and VADT alone. Conclusions This data-driven analysis provides evidence supporting the diabetes treatment guideline recommendation of intensive glucose lowering in diabetes patients with low cardiovascular risk and additionally suggests potential benefits of intensive glycemic control in some individuals at higher cardiovascular risk. 

   more » « less
3. Systematic Heritability and Heritability Enrichment Analysis for Diabetes Complications in UK Biobank and ACCORD Studies

   https://doi.org/10.2337/db21-0839  

   Kim, Juhyun ; Jensen, Aubrey ; Ko, Seyoon ; Raghavan, Sridharan ; Phillips, Lawrence S. ; Hung, Adriana ; Sun, Yan ; Zhou, Hua ; Reaven, Peter ; Zhou, Jin J. ( February 2022 , Diabetes)

   Diabetes-related complications reflect longstanding damage to small and large vessels throughout the body. In addition to the duration of diabetes and poor glycemic control, genetic factors are important contributors to the variability in the development of vascular complications. Early heritability studies found strong familial clustering of both macrovascular and microvascular complications. However, they were limited by small sample sizes and large phenotypic heterogeneity, leading to less accurate estimates. We take advantage of two independent studies—UK Biobank and the Action to Control Cardiovascular Risk in Diabetes trial—to survey the single nucleotide polymorphism heritability for diabetes microvascular (diabetic kidney disease and diabetic retinopathy) and macrovascular (cardiovascular events) complications. Heritability for diabetic kidney disease was estimated at 29%. The heritability estimate for microalbuminuria ranged from 24 to 60% and was 41% for macroalbuminuria. Heritability estimates of diabetic retinopathy ranged from 6 to 33%, depending on the phenotype definition. More severe diabetes retinopathy possessed higher genetic contributions. We show, for the first time, that rare variants account for much of the heritability of diabetic retinopathy. This study suggests that a large portion of the genetic risk of diabetes complications is yet to be discovered and emphasizes the need for additional genetic studies of diabetes complications. 

   more » « less
4. Understanding temporal changes and seasonal variations in glycemic trends using wearable data

   https://doi.org/10.1126/sciadv.adg2132  

   Belsare, Prajakta ; Bartolome, Abigail ; Stanger, Catherine ; Prioleau, Temiloluwa ( September 2023 , Science Advances)

   Seasonal variations in glycemic trends remain largely unstudied despite the growing prevalence of diabetes. To address this gap, our objective is to investigate temporal changes in glycemic trends by analyzing intensively sampled blood glucose data from 137 patients (ages 2 to 76, primarily type 1 diabetes) over the course of 9 months to 4.5 years. From over 91,000 days of continuous glucose monitor data, we found that glycemic control decreases significantly around the holidays, with the largest decline observed on New Year’s Day among the patients with already poor glycemic control (i.e., <55% time in the target range). We also observed seasonal variations in glycemic trends, with patients having worse glycemic control in the months of November to February (i.e., mid-fall and winter, in the United States), and better control in the months of April to August (i.e., mid-spring and summer). These insights are critical to inform targeted interventions that can improve diabetes outcomes.

    

   more » « less
5. Initiation of Continuous Glucose Monitoring Is Linked to Improved Glycemic Control and Fewer Clinical Events in Type 1 and Type 2 Diabetes in the Veterans Health Administration

   https://doi.org/10.2337/dc22-2189  

   Reaven, Peter D. ; Newell, Michelle ; Rivas, Salvador ; Zhou, Xinkai ; Norman, Gregory J. ; Zhou, Jin J. ( February 2023 , Diabetes Care)

   To determine the benefit of starting continuous glucose monitoring (CGM) in adult-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) with regard to longer-term glucose control and serious clinical events.

   A retrospective observational cohort study within the Veterans Affairs Health Care System was used to compare glucose control and hypoglycemia- or hyperglycemia-related admission to an emergency room or hospital and all-cause hospitalization between propensity score overlap weighted initiators of CGM and nonusers over 12 months.

   CGM users receiving insulin (n = 5,015 with T1D and n = 15,706 with T2D) and similar numbers of nonusers were identified from 1 January 2015 to 31 December 2020. Declines in HbA1c were significantly greater in CGM users with T1D (−0.26%; 95% CI −0.33, −0.19%) and T2D (−0.35%; 95% CI −0.40, −0.31%) than in nonusers at 12 months. Percentages of patients achieving HbA1c <8 and <9% after 12 months were greater in CGM users. In T1D, CGM initiation was associated with significantly reduced risk of hypoglycemia (hazard ratio [HR] 0.69; 95% CI 0.48, 0.98) and all-cause hospitalization (HR 0.75; 95% CI 0.63, 0.90). In patients with T2D, there was a reduction in risk of hyperglycemia in CGM users (HR 0.87; 95% CI 0.77, 0.99) and all-cause hospitalization (HR 0.89; 95% CI 0.83, 0.97). Several subgroups (based on baseline age, HbA1c, hypoglycemic risk, or follow-up CGM use) had even greater responses.

   In a large national cohort, initiation of CGM was associated with sustained improvement in HbA1c in patients with later-onset T1D and patients with T2D using insulin. This was accompanied by a clear pattern of reduced risk of admission to an emergency room or hospital for hypoglycemia or hyperglycemia and of all-cause hospitalization.

    

   more » « less