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      Significance of Glycemic Variability in Diabetes Mellitus

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          Abstract

          The goal of diabetes treatment is to maintain good glycemic control, prevent the development and progression of diabetic complications, and ensure the same quality of life and life expectancy as healthy people. Hemoglobin A1c (HbA1c) is used as an index of glycemic control, but strict glycemic control using HbA1c as an index may lead to severe hypoglycemia and cardiovascular death. Glycemic variability (GV), such as excessive hyperglycemia and hypoglycemia, is associated with diabetic vascular complications and has been recognized as an important index of glycemic control. Here, we reviewed the definition and evaluated the clinical usefulness of GV, and its relationship with diabetic complications and therapeutic strategies to reduce GV.

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          Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

          Bernard Zinman, Christoph Wanner, John M. Lachin … (2015)
          The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.
          Article 0 comments Cited 2600 times – based on 0 reviews     Review now
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            Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction

            John J.V. McMurray, Scott D. Solomon, Silvio E Inzucchi … (2020)
            In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.
            Article 0 comments Cited 2082 times – based on 0 reviews     Review now
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              Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

              Bruce Neal, Vlado Perkovic, Kenneth Mahaffey … (2017)
              Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754 , respectively.).
              Article 0 comments Cited 1894 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Intern Med
                Journal ID (iso-abbrev): Intern Med
                Title: Internal Medicine
                Publisher: The Japanese Society of Internal Medicine
                ISSN (Print): 0918-2918
                ISSN (Electronic): 1349-7235
                Publication date (Electronic): 18 September 2021
                Publication date (Print): 1 February 2022
                Volume: 61
                Issue: 3
                Pages: 281-290
                Affiliations
                [1 ]Department of Diabetes, Endocrinology and Clinical Immunology, Hyogo College of Medicine, Japan
                Author notes

                Correspondence to Dr.　Yoshiki Kusunoki, ykusu@ 123456hyo-med.ac.jp

                Article
                DOI: 10.2169/internalmedicine.8424-21
                PMC ID: 8866772
                PubMed ID: 34544956
                SO-VID: 41c312b3-9a4d-4698-a20a-08cec23650a9
                Copyright © Copyright © 2022 by The Japanese Society of Internal Medicine
                License:

                The Internal Medicine is an Open Access journal distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view the details of this license, please visit ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 30 July 2021
                Date accepted : 5 August 2021
                Categories
                Subject: Review Article

                Keywords: glycemic variability,time in range,continuous glucose monitoring,diabetic microvascular complications,diabetic macrovascular complications
                Data availability:
                Keywords: glycemic variability, time in range, continuous glucose monitoring, diabetic microvascular complications, diabetic macrovascular complications

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