Association of glycemic variability with left ventricular diastolic function in type 2 diabetes mellitus

Background Glycemic variability (GV) confers a risk of cardiovascular events. In this study, we aimed to investigate whether long-term GV has an impact on coronary atherosclerosis progression in patients with type 2 diabetes mellitus (T2DM). Methods A total of 396 patients with T2DM who had coronary computed tomography angiography and laboratory data available at baseline and for follow-up evaluations [median 2.3 (1.8–3.1) years] were included. Fasting plasma glucose (FPG) was measured every 1–3 months, and HbA1c was measured quarterly. The coefficient of variation (CV) of HbA1c and FPG were calculated as measures of GV. Quantitative assessment of coronary plaques was performed by measuring the annual change and progression rate of total plaque volume (TPV). Significant progression was defined as annual TPV progression ≥ 15%. Multivariable regression analyses were used to assess the effects of GV on atherosclerosis progression. Results In the 396 patients, the annual change in TPV was 12.35 ± 14.23 mm3, and annual progression rate was 13.36 ± 12.69%. There were 143 (36.11%) patients with significant progression, and they had a significantly higher CV-HbA1c (P < 0.001) and CV-FPG (P < 0.001) than those without significant progression. In multivariable regression analyses, both CV-HbA1c and CV-FPG were independent predictors of annual change in TPV [CV-HbA1c: β = 0.241 (0.019–0.462), P = 0.034; CV-FPG: β = 0.265 (0.060–0.465), P = 0.012], annual TPV progression [CV-HbA1c: β = 0.214 (0.023–0.405), P = 0.029; CV-FPG: β = 0.218 (0.037–0.399), P = 0.019], and significant atherosclerosis progression [CV-HbA1c: odds ratio [OR] = 1.367 (1.149–1.650), P = 0.010; CV-FPG: OR = 1.321 (1.127–1.634), P = 0.013]. Conclusions Long-term GV is associated with accelerated progression of coronary atherosclerosis independent of conventional risk factors in patients with T2DM. Trial registration ClinicalTrials.gov (NCT02587741), October 27, 2015; retrospectively registered

Section: Discussionmentioning

confidence: 99%

Impact of long-term glucose variability on coronary atherosclerosis progression in patients with type 2 diabetes: a 2.3 year follow-up study

Tang

Luo

et al. 2020

“…In diabetic cardiomyopathy, LV diastolic dysfunction has been suggested as the earliest functional change detectable and is almost always present prior to signs of LV systolic dysfunction [ 27 ]. Hypertension, ageing and diabetes are all associated with an increased risk of developing diastolic dysfunction [ 28 – 30 ], and recently it has been shown that higher glycemic variability may be associated with LV diastolic dysfunction independent of HbA1c [ 31 ]. Recent studies have shown, that treatment with SGLT-2 inhibitors dapagliflozin [ 32 ] or canagliflozin [ 33 ] can improve LV diastolic function in patients with type 2 diabetes, and that SGLT-2 inhibitors may play a future role in prevention and treatment of cardiovascular disease in patients with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor-23 is associated with imaging markers of diabetic cardiomyopathy and anti-diabetic therapeutics

Sørensen

Bojer

Jørgensen

et al. 2020

Background The biomarker fibroblast growth factor-23 (FGF-23) has been associated with increased cardiovascular morbidity and mortality in both patients with and without type 2 diabetes. The aim of this study was to evaluate the relationship between FGF-23 and cardiac structure, function and perfusion in patients with type 2 diabetes and normal or mildly impaired kidney function. Furthermore, to investigate the association between FGF-23, anti-diabetes therapy and the classic complications and risk factors associated with type 2 diabetes. Methods In this cross-sectional study, 246 patients with type 2 diabetes underwent echocardiography and advanced cardiac magnetic resonance imaging to assess left ventricular (LV) structure and function. In addition, myocardial blood flow (MBF) during rest and pharmacological stress (adenosine 140 µg/kg/min) were evaluated in 183 of the patients. Patients with eGFR < 60 ml/min/1.73 m2 were excluded. Results Median (Q1–Q3) FGF-23 was 74 (58–91) ng/L. Patients with FGF-23 above the median had lower MBF during stress (2.3 ± 0.9 vs. 2.7 ± 0.9 ml/min/g, P = 0.001) and lower overall myocardial perfusion reserve (MPR) (2.7 ± 0.8 vs. 3.3 ± 1.1, P < 0.001). LV mass (143 ± 40 vs. 138 ± 36 g, P = 0.04) and E/e* (8.5 ± 3.2 vs. 7.6 ± 2.7, P = 0.04) were higher in patients with FGF-23 above the median. In a linear model adjusted for age, sex, eGFR and hypertension, increasing FGF-23 was associated with decreased MPR (P < 0.01, R2 = 0.11) and increased E/e* (P < 0.01, R2 = 0.07). FGF-23 was lower in patients receiving glucagon like peptide-1 (GLP-1) analogues (71 (57–86) vs. 80 (60–98) ng/L, P = 0.01) than in those who did not receive GLP-1 analogues. Conclusions In patients with type 2 diabetes and normal or mildly impaired kidney function, increased levels of FGF-23 are associated with impaired cardiac diastolic function and decreased MPR, caused by a decrease in maximal MBF during stress. Use of GLP-1 analogues is associated with decreased levels of FGF-23. Clinical trial registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT02684331. Date of registration: February 18, 2016

“…During the past decade, detrimental effects of GV on patients with diabetes have been proposed for various medical conditions [ 7 – 13 ]. GV could not only predict diabetic vascular complications [ 7 , 14 , 15 ], heart failure [ 9 ], and postoperative complications of aortic valve implantation [ 11 ], but also indicate poor prognosis for in-patients with acute lung diseases [ 8 ] and acute coronary syndrome [ 13 ]. Moreover, because GV could modify the correlation between time in range and estimated HbA1c, GV consideration was recommended when setting individualized goals for glycemic control [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Glucose variability and the risks of stroke, myocardial infarction, and all-cause mortality in individuals with diabetes: retrospective cohort study

Lee

Han

Park

et al. 2020

Background Previous research regarding long-term glucose variability over several years which is an emerging indicator of glycemic control in diabetes showed several limitations. We investigated whether variability in long-term fasting plasma glucose (FG) can predict the development of stroke, myocardial infarction (MI), and all-cause mortality in patients with diabetes. Methods This is a retrospective cohort study using the data provided by the Korean National Health Insurance Corporation. A total of 624,237 Koreans ≥ 20 years old with diabetes who had undergone health examinations at least twice from 2005 to 2008 and simultaneously more than once from 2009 to 2010 (baseline) without previous histories of stroke or MI. As a parameter of variability of FG, variability independent of mean (VIM) was calculated using FG levels measured at least three times during the 5 years until the baseline. Study endpoints were incident stroke, MI, and all-cause mortality through December 31, 2017. Results During follow-up, 25,038 cases of stroke, 15,832 cases of MI, and 44,716 deaths were identified. As the quartile of FG VIM increased, the risk of clinical outcomes serially increased after adjustment for confounding factors including duration and medications of diabetes and the mean FG. Adjusted hazard ratios (95% confidence intervals) of FG VIM quartile 4 compared with quartile 1 were 1.20 (1.16–1.24), 1.20 (1.15–1.25), and 1.32 (1.29–1.36) for stroke, MI and all-cause mortality, respectively. The impact of FG variability was higher in the elderly and those with a longer duration of diabetes and lower FG levels. Conclusions In diabetes, long-term glucose variability showed a dose–response relationship with the risk of stroke, MI, and all-cause mortality in this nationwide observational study.