Associations of hypoglycemia, glycemic variability and risk of cardiac arrhythmias in insulin-treated patients with type 2 diabetes: a prospective, observational study

Abstract Background Insulin-treated patients with type 2 diabetes (T2D) are at risk of hypoglycemia, which is associated with an increased risk of cardiovascular disease and mortality. Using a long-term monitoring approach, we investigated the association between episodes of hypoglycemia, glycemic variability and cardiac arrhythmias in a real-life setting. Methods Insulin-treated patients with T2D (N = 21, [mean ± SD] age 66.8 ± 9.6 years, BMI 30.1 ± 4.5 kg/m2, HbA1c 6.8 ± 0.4% [51.0 ± 4.8 mmol/mol]) were included for a one-year observational study. Patients were monitored with continuous glucose monitoring ([mean ± SD] 118 ± 6 days) and an implantable cardiac monitor (ICM) during the study period. Results Time spend in hypoglycemia was higher during nighttime than during daytime ([median and interquartile range] 0.7% [0.7–2.7] vs. 0.4% [0.2–0.8]). The ICMs detected 724 episodes of potentially clinically significant arrhythmias in 12 (57%) participants, with atrial fibrillation and pauses accounting for 99% of the episodes. No association between hypoglycemia and cardiac arrhythmia was found during daytime. During nighttime, subject-specific hourly incidence of cardiac arrhythmias tended to increase with the occurrence of hypoglycemia (incident rate ratio [IRR] 1.70 [95% CI 0.36–8.01]) but only slightly with increasing time in hypoglycemia (IRR 1.04 [95% CI 0.89–1.22] per 5 min). Subject-specific incidence of cardiac arrhythmias during nighttime increased with increasing glycemic variability as estimated by coefficient of variation whereas it decreased during daytime (IRR 1.33 [95% CI 1.05–1.67] and IRR 0.77 [95% CI 0.59–0.99] per 5% absolute increase, respectively). Conclusions Cardiac arrhythmias were common in insulin-treated patients with T2D and were associated with glycemic variability, whereas arrhythmias were not strongly associated with hypoglycemia. Trial registration: NCT03150030, ClinicalTrials.gov, registered May 11, 2017. https://clinicaltrials.gov/ct2/show/NCT03150030

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Glycemic variability and cardiovascular disease in patients with type 2 diabetes

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-002032 ◽

2021 ◽

Vol 9 (1) ◽

pp. e002032

Author(s):

Marcela Martinez ◽

Jimena Santamarina ◽

Adrian Pavesi ◽

Carla Musso ◽

Guillermo E Umpierrez

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Glycated Hemoglobin ◽

Glucose Monitoring ◽

Glycemic Variability ◽

Cardiovascular Complications ◽

Glucose Levels ◽

Increased Risk ◽

Patients With Diabetes

Glycated hemoglobin is currently the gold standard for assessment of long-term glycemic control and response to medical treatment in patients with diabetes. Glycated hemoglobin, however, does not address fluctuations in blood glucose. Glycemic variability (GV) refers to fluctuations in blood glucose levels. Recent clinical data indicate that GV is associated with increased risk of hypoglycemia, microvascular and macrovascular complications, and mortality in patients with diabetes, independently of glycated hemoglobin level. The use of continuous glucose monitoring devices has markedly improved the assessment of GV in clinical practice and facilitated the assessment of GV as well as hypoglycemia and hyperglycemia events in patients with diabetes. We review current concepts on the definition and assessment of GV and its association with cardiovascular complications in patients with type 2 diabetes.

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The association between hypoglycemia and glycemic variability in elderly patients with type 2 diabetes: a prospective observational study

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00656-1 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Takahisa Handa ◽

Akinobu Nakamura ◽

Aika Miya ◽

Hiroshi Nomoto ◽

Hiraku Kameda ◽

...

Keyword(s):

Type 2 Diabetes ◽

Logistic Regression ◽

Regression Analysis ◽

Observational Study ◽

Elderly Patients ◽

Prospective Observational Study ◽

Multivariate Logistic Regression Analysis ◽

Glycemic Variability ◽

Multivariate Logistic Regression

Abstract Background This study aimed to explore predictive factors of time below target glucose range (TBR) ≥ 1% among patients’ characteristics and glycemic variability (GV) indices using continuous glucose monitoring data in elderly patients with type 2 diabetes. Methods We conducted a prospective observational study on 179 (71 female) Japanese outpatients with type 2 diabetes aged ≥ 65 years. The characteristics of the participants with TBR ≥ 1% were evaluated by multivariate logistic regression analysis. Receiver-operating characteristic (ROC) curve analyses of GV indices, comprising coefficient of variation (CV), standard deviation, and mean amplitude of glycemic excursions, were performed to identify the optimal index for the identification of patients with TBR ≥ 1%. Results In the multivariate logistic regression analysis, none of the clinical characteristics, including HbA1c and C-peptide index, were independent markers for TBR ≥ 1%, while all three GV indices showed significant associations with TBR ≥ 1%. Among the three GV indices, CV showed the best performance based on the area under the curve in the ROC curve analyses. Conclusions Among elderly patients with type 2 diabetes, CV reflected TBR ≥ 1% most appropriately among the GV indices examined. Trial registration UMIN-CTR: UMIN000029993. Registered 16 November 2017

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New-onset type 2 diabetes in heart failure: impact of heart failure and death versus ischemic events – a Danish nationwide cohort study

European Heart Journal ◽

10.1093/ehjci/ehaa946.1145 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

B Zareini ◽

P.B Blanche ◽

A.H Holt ◽

M.M Malik ◽

D.P Rajan ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Risk Ratio ◽

Real Life ◽

Ischemic Event ◽

Increased Risk ◽

The Absolute ◽

Ischemic Events ◽

New Onset

Abstract Background Development of type 2 diabetes (T2D) is common in patients with heart failure (HF), but knowledge of future cardiovascular events is lacking. Purpose We compared risk of heart failure hospitalization (HFH) or death versus ischemic events in real-life HF patients with new-onset T2D, prevalent T2D and no T2D. Methods Using the Danish nationwide registers, we identified all patients with HF between 1998–2016. The patients were separated in two different HF cohorts based on the status of T2D. One cohort consisted of HF patients with either prevalent or absent T2D at the time of HF diagnosis. The other cohort consisted of HF patients, who developed new-onset T2D, included at time of diagnosis. The two HF cohorts were analyzed separately. Outcomes for both cohorts were analyzed as time-to-first event as either an ischemic event (i.e. composite outcome of fatal and non-fatal myocardial infarction, stroke, and peripheral artery disease), HFH, or event-free death (not related to HFH or the ischemic event). For each cohort, we estimated the five-year absolute risk of ischemic event, HFH and event-free death, along with five-year risk ratio of HFH or event-free death versus ischemic events. Effects among subgroups were investigated by stratifying both cohorts based on age, gender and comorbidities present at inclusion. Results A total of 139,264 HF patients were included between 1998 and 2016, of which 29,078 (21%) patients had prevalent T2D at baseline. A total of 11,819 (8%) developed new-onset T2D and were included in the second cohort. The median duration of time between HF diagnosis and new-onset T2D diagnosis was: 4.1 years (IQR:1.5; 5.8). The absolute five-year risk of an ischemic event in patients with new-onset T2D, prevalent T2D and no T2D was: 17.9% (95% confidence interval (CI): 17.2; 18.6), 26.1% (95% CI: 25.6; 26.7), and 18.8% (95% CI:18.6; 19.0). Corresponding estimates for HFH were: 31.5% (95% CI: 30.6; 32.3), 33.6% (95% CI: 33.0; 34.2), and 30,7% (95% CI: 30.5; 31.0). The absolute five-year risk of event-free death among patients with new-onset T2D, prevalent T2D and no T2D was: 20.9% (95% CI: 20.2; 21.7), 18.9% (95% CI:18.4; 19.3), and 18.6% (95% CI: 18.4; 18.8) (see Figure). The five-year risk ratio of experiencing HFH or event-free death versus an ischemic event was: 2.9 (95% CI: 2.8; 3.1), 2.0 (95% CI:2.0; 2.1), and 2.6 (95% CI: 2.6; 2.7) for patients with new-onset T2D, prevalent T2D and no T2D, respectively. Similar results of absolute and relative risk were present across all subgroups. Conclusion In our population of HF patients, 8% developed new-onset diabetes. Development of T2D in patients with HF increases the risk of HFH and mortality three-fold. The increased risk of new-onset T2D is higher than the importance of prevalent T2D in patients with HF. Funding Acknowledgement Type of funding source: None

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The Association Between Continuous Glucose Monitoring-derived Metrics, Including Time in Range, and Cardiovascular Autonomic Neuropathy in Outpatients With Type 2 Diabetes

10.21203/rs.3.rs-101449/v1 ◽

2020 ◽

Author(s):

Min Young Kim ◽

Gyuri Kim ◽

Ji Yun Park ◽

Min Sun Choi ◽

Ji Eun Jun ◽

...

Keyword(s):

Type 2 Diabetes ◽

Autonomic Neuropathy ◽

Autonomic Function ◽

Glucose Monitoring ◽

Glycemic Variability ◽

Cardiovascular Autonomic Neuropathy ◽

Inverse Association ◽

International Consensus ◽

Time In Range

Abstract BackgroundContinuous glucose monitoring (CGM)-derived metrics including time in range (TIR) are attracting attention as new indicators of glycemic control and diabetes complications beyond hemoglobin A1c. This study investigated the association between CGM-derived TIR, hyperglycemia, hypoglycemia metrics, and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes.MethodsA total of 284 patients with type 2 diabetes who underwent CGM for three days and autonomic function tests within three months based on outpatient data were recruited. The definition of CGM-derived metrics was subject to the most recent international consensus. CAN was defined as an abnormal case in two or more parasympathetic and the severity of CAN was estimated as the sum of the scores of the five cardiovascular autonomic function tests.ResultsMultiple logistic regression analysis revealed that the odds ratio of definite CAN was 0.876 [95% confidence interval (CI): 0.79–0.98] per 10% increase in the TIR of 70 to 180 mg/dL, after adjusting for age, sex, diabetes duration, any medications, and glycemic variability. A 10% increase in TIR was significantly inversely associated with the presence of advanced CAN (OR: 0.89, 95% CI: 0.81–0.98). In addition, there was a strong inverse association between a 10% increase in the TIR and the total CAN score (p for trend = 0.001). Among the metrics of hyperglycemia, a time above range (TAR) of greater than 180 mg/dL was also independently correlated with the presence of definite CAN (OR: 1.013, 95% CI: 1.00–1.02) and advanced CAN (OR: 1.01, 95% CI: 1.00–1.02).ConclusionsA TIR value of 70 to 180 mg/dL and a TAR value of greater than 180 mg/dL were significantly associated with cardiovascular autonomic neuropathy in outpatients with type 2 diabetes.

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