Associations between continuous glucose monitoring-derived metrics and diabetic retinopathy and albuminuria in patients with type 2 diabetes

Introduction Preventing the development and progression of diabetic microvascular complications through optimal blood glucose control remains an important challenge. Whether metrics based on continuous glucose monitoring are useful for the management of diabetic microvascular complications is not entirely clear. Research design and methods This is an exploratory analysis of an ongoing prospective, multicenter, 5-year follow-up observational study. Study participants included 999 outpatients with type 2 diabetes who underwent continuous glucose monitoring at baseline. Associations between continuous glucose monitoring-derived metrics and the severity of diabetic retinopathy or albuminuria were investigated using multivariable proportional odds models. Results The overall prevalence of diabetic retinopathy was 22.2%. Multivariate analysis with proportional odds models demonstrated that continuous glucose monitoring-derived metrics related to intraday and interday glucose variability are significantly associated with the severity of diabetic retinopathy, even after adjusting for various possible risk factors. However, significant relationships were not observed after adjusting for hemoglobin A1c (HbA1c) levels. The prevalence of microalbuminuria and macroalbuminuria was 20.3% and 6.7%, respectively. Similarly, multivariate analysis demonstrated that those metrics are significantly associated with the severity of albuminuria. These relationships remained significant even after further adjusting for HbA1c levels. Conclusions Continuous glucose monitoring-derived metrics related to intraday and interday glucose variability are significantly associated with the severity of diabetic retinopathy or albuminuria in patients with type 2 diabetes. Thus, evaluating these metrics might possibly be useful for risk assessment of diabetic microvascular complications. Trial registration number UMIN000032325.

[1]  Dongni Zhao,et al.  Association of time in range, as assessed by continuous glucose monitoring, with painful diabetic polyneuropathy , 2020, Journal of diabetes investigation.

[2]  Meng Bian,et al.  Glycemic variability: adverse clinical outcomes and how to improve it? , 2020, Cardiovascular Diabetology.

[3]  A. Goto,et al.  Japanese Clinical Practice Guideline for Diabetes 2019 , 2020, Journal of diabetes investigation.

[4]  G. Umpierrez,et al.  Comparison of the FreeStyle Libre Pro Flash Continuous Glucose Monitoring (CGM) System and Point-of-Care Capillary Glucose Testing in Hospitalized Patients With Type 2 Diabetes Treated With Basal-Bolus Insulin Regimen , 2020, Diabetes Care.

[5]  Sang-Man Jin,et al.  Association Between Continuous Glucose Monitoring-Derived Time in Range, Other Core Metrics, and Albuminuria in Type 2 Diabetes. , 2020, Diabetes technology & therapeutics.

[6]  6. Glycemic Targets: Standards of Medical Care in Diabetes—2020 , 2019, Diabetes Care.

[7]  Yu Xu,et al.  Associations of subclinical atherosclerosis with nonalcoholic fatty liver disease and fibrosis assessed by non‐invasive score , 2019, Liver international : official journal of the International Association for the Study of the Liver.

[8]  I. Shimomura,et al.  Protocol of a Prospective Observational Study on the Relationship Between Glucose Fluctuation and Cardiovascular Events in Patients with Type 2 Diabetes , 2019, Diabetes Therapy.

[9]  F. Doyle,et al.  Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range , 2019, Diabetes Care.

[10]  Shanshan Wang,et al.  Glucose fluctuation increased mesangial cell apoptosis related to AKT signal pathway , 2019, Archives of medical science : AMS.

[11]  Kun-Der Lin,et al.  Severe Hypoglycemia as a Predictor of End-Stage Renal Disease in Type 2 Diabetes: A National Cohort Study , 2019, International journal of environmental research and public health.

[12]  S. Kaneko,et al.  Association of renal arteriosclerosis and hypertension with renal and cardiovascular outcomes in Japanese type 2 diabetes patients with diabetic nephropathy , 2019, Journal of diabetes investigation.

[13]  Y. Bao,et al.  Glycemic variability assessed by continuous glucose monitoring and the risk of diabetic retinopathy in latent autoimmune diabetes of the adult and type 2 diabetes , 2018, Journal of diabetes investigation.

[14]  R. Beck,et al.  Validation of Time in Range as an Outcome Measure for Diabetes Clinical Trials , 2018, Diabetes Care.

[15]  W. Kernan,et al.  Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) , 2018, Diabetologia.

[16]  Geltrude Mingrone,et al.  Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) , 2018, Diabetes Care.

[17]  Y. Bao,et al.  Association of Time in Range, as Assessed by Continuous Glucose Monitoring, With Diabetic Retinopathy in Type 2 Diabetes , 2018, Diabetes Care.

[18]  A. Goto,et al.  Japanese Clinical Practice Guideline for Diabetes 2016 , 2018, Diabetology International.

[19]  Yoshiya Tanaka,et al.  Association Between Diabetic Microangiopathies and Glycemic Variability Assessed by Continuous Glucose Monitoring. , 2018, Journal of UOEH.

[20]  L. Leelarathna,et al.  Accuracy of flash glucose monitoring and continuous glucose monitoring technologies: Implications for clinical practice , 2018, Diabetes & vascular disease research.

[21]  Andrea Facchinetti,et al.  Head-to-head comparison of the accuracy of Abbott FreeStyle Libre and Dexcom G5 mobile. , 2018, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[22]  Eyal Dassau,et al.  International Consensus on Use of Continuous Glucose Monitoring , 2017, Diabetes Care.

[23]  L. Di Paola,et al.  P2X7 receptor antagonism: Implications in diabetic retinopathy , 2017, Biochemical pharmacology.

[24]  L. Ji,et al.  A Multicenter Evaluation of the Performance and Usability of a Novel Glucose Monitoring System in Chinese Adults With Diabetes , 2017, Journal of diabetes science and technology.

[25]  P. Heagerty,et al.  Clinical Manifestations of Kidney Disease Among US Adults With Diabetes, 1988-2014. , 2016, JAMA.

[26]  M. S. Kirkman,et al.  Role of Glycated Proteins in the Diagnosis and Management of Diabetes: Research Gaps and Future Directions , 2016, Diabetes Care.

[27]  J. Joung,et al.  Association between the extent of urinary albumin excretion and glycaemic variability indices measured by continuous glucose monitoring , 2015, Diabetic medicine : a journal of the British Diabetic Association.

[28]  S. Salomone,et al.  Homocysteine Serum Levels in Diabetic Patients with Non Proliferative, Proliferative and without Retinopathy , 2014, BioMed research international.

[29]  Yosuke Okada,et al.  Relationship between fluctuations in glucose levels measured by continuous glucose monitoring and vascular endothelial dysfunction in type 2 diabetes mellitus , 2013, Cardiovascular Diabetology.

[30]  B. Klein,et al.  Global Prevalence and Major Risk Factors of Diabetic Retinopathy , 2012, Diabetes Care.

[31]  Josef Coresh,et al.  Chronic kidney disease , 2012, The Lancet.

[32]  Pratik Choudhary,et al.  Normal reference range for mean tissue glucose and glycemic variability derived from continuous glucose monitoring for subjects without diabetes in different ethnic groups. , 2011, Diabetes technology & therapeutics.

[33]  F. Gueyffier,et al.  Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials , 2011, BMJ : British Medical Journal.

[34]  H. Yamashita,et al.  Incidence and progression of diabetic retinopathy in Japanese adults with type 2 diabetes: 8 year follow-up study of the Japan Diabetes Complications Study (JDCS) , 2011, Diabetologia.

[35]  Z. Li,et al.  Association of glycemic variability and the presence and severity of coronary artery disease in patients with type 2 diabetes , 2011, Cardiovascular Diabetology.

[36]  V. Basevi.  Standards of Medical Care in Diabetes—2010 , 2010, Diabetes Care.

[37]  Yasuhiko Tomino,et al.  Revised equations for estimated GFR from serum creatinine in Japan. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[38]  Grant D. Huang,et al.  Glucose control and vascular complications in veterans with type 2 diabetes. , 2009, The New England journal of medicine.

[39]  R. Testa,et al.  Oscillating Glucose Is More Deleterious to Endothelial Function and Oxidative Stress Than Mean Glucose in Normal and Type 2 Diabetic Patients , 2008, Diabetes.

[40]  B. Klein,et al.  Overview of epidemiologic studies of diabetic retinopathy. , 2007, Ophthalmic epidemiology.

[41]  Antonio Ceriello,et al.  Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. , 2003, Diabetes.

[42]  B. Astor,et al.  Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988-1994). , 2002, Archives of internal medicine.

[43]  R. Holman,et al.  Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study , 2000, BMJ : British Medical Journal.

[44]  R. Holman,et al.  Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. , 1998 .

[45]  The Relationship of Glycemic Exposure (HbA1c) to the Risk of Development and Progression of Retinopathy in the Diabetes Control and Complications Trial , 1995, Diabetes.

[46]  E. Araki,et al.  Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. , 1995, Diabetes research and clinical practice.

[47]  R. Klein,et al.  Relationship of hyperglycemia to the long-term incidence and progression of diabetic retinopathy. , 1994, Archives of internal medicine.

[48]  A Bohle,et al.  The pathogenesis of chronic renal failure in diabetic nephropathy. Investigation of 488 cases of diabetic glomerulosclerosis. , 1991, Pathology, research and practice.

[49]  W. F. Taylor,et al.  Mean Amplitude of Glycemic Excursions, a Measure of Diabetic Instability , 1970, Diabetes.

[50]  Daniel J Cox,et al.  Algorithmic evaluation of metabolic control and risk of severe hypoglycemia in type 1 and type 2 diabetes using self-monitoring blood glucose data. , 2003, Diabetes technology & therapeutics.

[51]  ScienceDirect.  Nutrition, metabolism, and cardiovascular diseases : NMCD. , 1991 .