Diabetic Kidney Disease: Is There a Role for Glycemic Variability?

  • Savitha SubramanianEmail author
  • Irl B. Hirsch
Microvascular Complications—Nephropathy (M Afkarian and B Roshanravan, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Microvascular Complications—Nephropathy


Purpose of Review

Diabetes is the leading cause of kidney disease globally. Diabetic kidney disease (DKD) is a heterogeneous disorder manifested as albuminuria and/or decreasing GFR. Hyperglycemic burden is the major contributor to the development of DKD. In this article, we review the evidence for the contribution of glycemic variability and the pitfalls associated with use of hemoglobin A1c (A1C), the gold standard for assessment of glucose control, in the setting of DKD.

Recent Findings

Glycemic variability, characterized by swings in blood glucose levels, can result in generation of mitochondrial reactive oxygen species, a putative inciting factor for hyperglycemia-induced alterations in intracellular metabolic pathways. While there is indirect evidence supporting the role of glycemic variability in the pathogenesis of DKD, definitive data are lacking. A1C has many limitations and is a particularly suboptimal measure in patients with kidney disease, because its accuracy is compromised by variables affecting RBC survival and other factors. Continuous glucose monitoring (CGM) technology has the potential to enable us to use glucose as a more important clinical tool, for a more definitive understanding of glucose variability and its role in DKD.


Glycemic variability may be a factor in the development of DKD, but definitive evidence is lacking. Currently, all available glycemic biomarkers, including A1C, have limitations and in the setting of DKD and should be used cautiously. Emerging data suggest that personal and professional CGM will play an important role in managing diabetes in patients with DKD, where risk of hypoglycemia is high.


Diabetes Diabetic kidney disease A1C Glycemic variability Continuous glucose monitoring Flash glucose monitoring 


Compliance with Ethical Standards

Conflict of Interest

Savitha Subramanian reports personal fees from Intarcia Pharmaceuticals and Akcea Therapeutics and grants from Ionis Pharmaceuticals.

Irl B. Hirsch reports grants from Medtronic Diabetes and Novo Nordisk and personal fees from Abbott Diabetes Care, Adocia, Intarcia, Roche, and Valeritas.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Authors and Affiliations

  1. 1.Division of Metabolism, Endocrinology, and NutritionUniversity of WashingtonSeattleUSA

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