Time in range, as measured by continuous glucose monitor, as a predictor of microvascular complications in type 2 diabetes: a systematic review

Continuous glucose monitoring (CGM)-derived time in range (TIR) correlates with hemoglobin A1c (A1c) among patients with type 2 diabetes mellitus (T2DM); however, there is a paucity of data evaluating its association with microvascular complications. We conducted this systematic review to examine the association between TIR and microvascular complications of diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN). We conducted a comprehensive literature search on PubMed, Scopus, and Web of Science online databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Full-text original articles that evaluated the association between CGM-derived TIR and risk of microvascular complications and were published between 2010 and June 2021 were included in our systematic review. The quality of the included studies was evaluated using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Data were analyzed using qualitative synthesis. Eleven studies on a total of 13 987 patients were included in the systematic review. The median sample size, baseline A1c, and diabetes duration were 466 patients (range: 105–5901), 8.2% (SD 0.5%), and 11.3 years (1.0), respectively. Majority of the studies were conducted in Asia (10 out of 11). Four studies evaluated the relationship between CGM-derived TIR and DR and CGM-derived TIR and DN, while seven studies evaluated the relationship between CGM-derived TIR and DPN. A 10% increase in TIR was associated with a reduction in albuminuria, severity of DR, and prevalence of DPN and cardiac autonomic neuropathy. In addition, an association was observed between urinary albumin to creatinine ratio but not with estimated glomerular filtration rate. This review summarizes recent evidence supporting an association between CGM-derived TIR and microvascular complications among patients with T2DM. A larger-scale multicenter investigation that includes more diverse participants is warranted to further validate the utility of TIR as a predictor of diabetic microvascular complications.

Diabetic Cardiovascular Autonomic Neuropathy: Effects of Simvastatin and Omega-3 Polyunsaturated Fatty Acids on Insulin Resistance and Lipid Profile Parameters

Introduction. Currently, there is no unified treatment algorithm of cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). The aim of the study was to investigate the effects of simvastatin (SIM) and -3 polyunsaturated fatty acids (-3 PUFAs) on blood lipid profile and insulin resistance (IR) in patients with type 2 diabetes mellitus and definite cardiac autonomic neuropathy. Materials and methods. The study involved 72 patients with T2DM and definite CAN. Patients were divided into four groups: 1st - received standard hypoglycemic therapy - control (n = 15); 2nd (n = 22) – in addition simvastatin (SIM) 20.0 mg/q.d.; 3rd (n = 18) - in addition 1 capsule/q.d. of the ω-3 PUFAs; 4th (n = 17) - in addition SIM 10.0 mg/q.d and 1 capsule/q.d of the ω-3 PUFAs for three months. The concentration of glucose, glycated hemoglobin A1c, immunoreactive insulin (IRI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) in the blood were determined. Homeostasis model assessment IR (HOMA-IR), atherogenic coefficient (AC), TG/LDL-C, TG/TC, TG/LDL-C and TG and glucose index (TyG) were calculated. Results. Prescription of SIM was accompanied by a statistically significant decrease in TC, LDL-C, TG concentrations. In parallel, SIM induced a decrease of AC, TG/HDL-C, increase in HDL-C, and does not affect the IRI, HOMA-IR, TG/LDL-C, TG/TC, TC/LDL-C/HDL-C, TyG. The use of ω-3 PUFAs has contributed to a significant reduction in TG, AC, TG/LDL-C, TG/TC, TG/HDL-C, TyG index, increase in HDL-C, and was not accompanied by changes in IRI content, HOMA-IR, TC, LDL-C, and TC/LDL-C/HDL-C. The combined prescription of SIM and -3 PUFAs was accompanied by more pronounced, statistically significant changes in the blood lipid spectrum, as well as a decrease in the IRI and HOMA-IR. Conclusions. Obtained results justify the appropriateness of combined simvastatin and -3 polyunsaturated fatty acids prescription to patients with type 2 diabetes mellitus and definite cardiac autonomic neuropathy. Keywords: diabetes mellitus, cardiac autonomic neuropathy, treatment.

Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and type 2 diabetes: a meta-analysis

We aimed to determine the prognostic association between cardiac autonomic neuropathy (CAN) and cardiovascular disease events (CVE) and mortality in type 1 and type 2 diabetes through a systematic review and meta-analysis. This systematic review and meta-analysis was registered with PROSPERO (CRD42020216305) and was conducted with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodological criteria. CAN was defined on the basis of 1 (early/possible CAN) or ≥2 (definite CAN) positive autonomic function tests as per the Toronto Consensus guidelines. Studies included those with prospective CVE or mortality data. Methodological variables/risk of bias were assessed using ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) and RoB-2 (Risk-Of-Bias tool for randomized trials) appraisal tools. Electronic database searches yielded 18 467 articles; 84 articles were screened full-text, 26 articles fulfilled the inclusion criteria for quantitative synthesis. Sixteen studies from patients with (n=2875) and without (n=11 722) CAN demonstrated a pooled relative risk (RR) of 3.16 (95%CI 2.42 to 4.13; p<0.0001) of future CVE in favour of CAN. Nineteen studies provided all-cause mortality data from patients with (n=3679) and without (n=12 420) CAN, with a pooled RR of 3.17 (95%CI 2.11 to 4.78; p<0.0001) in favour of CAN. The risk of both future CVE and mortality was higher in type 1 compared with type 2 diabetes and with a definite CAN (vs possible CAN) diagnosis. Three studies were considered to have risk of serious bias. This study confirms the significant association between CAN and CVE and all-cause mortality. The implementation of population-based CAN screening will identify a subgroup with disproportionately higher cardiovascular and mortality risk that will allow for earlier targeted intervention.

A model for early diagnosis of Cardiac Autonomic Neuropathy (CAN)

Convolutional Neural Networks (CNN) are widely used as prediction models in medical diagnosis in the recent research. Remodelling the CNN architecture to make it more reliable for classification is the core of each finding. Cardiac Autonomic Neuropathy (CAN) is a severity amongst the diabetic population, who are subject to diabetes for long duration. The aim of this work is to provide a predictive mechanism that is designed for more reliable diagnostics by studying the ECG physiology and enhancing the diagnostics by artificial technique, like using a remodelled CNN architecture. Results of CNN show 95.42 % efficiency in classifying between groups of CAN+ and CAN-groups..

Study of sympathetic and parasympathetic control of haemodynamics in mid pregnancy by cardiac autonomic neuropathy analyzer

Pregnancy is associated with substantial changes in cardiovascular system. The action of autonomic nervous system is essential for circulatory adaptations in pregnancy and nourishing growing fetus. The study was conducted to assess the significance of autonomic function tests amongst women of mid pregnancy and non pregnant women. A comparative study was caried out amongst pregnant and non pregnant women in Department of Physiology. A total of 60 women (30 pregnant as study group and 30 non pregnant healthy women as control group) aged between 18- 30 years were included in study. The results indicated that there was statistically significant change in resting heart and highly statistically significant change to deep breathing in mid pregnancy reflecting higher parasympathetic activity in study group (pregnant female) as compared to control group (non pregnant female) while sympathetic activity assessed by isometric hand grip test didn’t show any statistically significant change among pregnant as compared to non pregnant. Our study showed role of parasympathetic activity in controlling haemodynamics in mid pregnancy and it may help to return the arterial pressure to non pregnant level by causing haemodilution, although when the increase in activity is excessive, hypertension may ensue.

Effect of alpha-lipoic acid on arterial stiffness parameters in type 2 diabetes mellitus patients with cardiac autonomic neuropathy

Objective. Significantly underdiagnosed, diabetes-associated cardiac autonomic neuropathy (CAN) causes a wide range of cardiac disorders that may cause life-threatening outcomes. This study investigated the effects of alpha-lipoic acid (ALA) on arterial stiffness and insulin resistance (IR) parameters in type 2 diabetes mellitus (T2D) patients and definite CAN. Methods. A total of 36 patients with T2D and a definite stage of CAN were recruited. This investigation was carried out on two separate arms: traditional hypoglycemic therapy (n=18, control) and ALA (n=18) 600 mg in film-coated tablets/q.d. in addition to traditional hypoglycemic therapy. The duration of the study was three months. Results. In subjects with T2D and definite stage of СAN, treatment with ALA resulted in a significant decrease of glucose, immunoreactive insulin concentration, and Homeostasis Model Assessment (HOMA)-IR (HOMA-IR) parameters; pulse wave velocity (PWV), aorta augmentation index (AIxao) during the active period of the day and decrease of PWV, AIxao, and brachial augmentation index during the passive period of the day compared with the results, obtained in the control group. Therefore, the administration of ALA to patients with T2D for three months promotes the improvement of glucose metabolism and arterial stiffness parameters. Conclusions. In patients with T2D and definite stage of СAN treatment with ALA improved HOMA-IR and arterial stiffness parameters. These findings can be of clinical significance for the complex treatment of diabetes-associated CAN.