Continuous Glucose Monitoring: A Brief Review for Primary Care Practitioners

Glycated hemoglobin A1c (HbA1c) is routinely used as a marker of average glycemic control, but it fails to provide data on hypoglycemia and glycemic variability, both of which are associated with adverse clinical outcomes. Self-monitoring of blood glucose (SMBG), particularly in insulin-treated patients, is a cornerstone in the management of patients with diabetes. SMBG helps with treatment decisions that aim to reduce high glucose levels while avoiding hypoglycemia and limiting glucose variability. However, repeated SMBG can be inconvenient to patients and difficult to maintain in the long term. By contrast, continuous glucose monitoring (CGM) provides a convenient, comprehensive assessment of blood glucose levels, allowing the identification of high and low glucose levels, in addition to evaluating glycemic variability. CGM using newer detection and visualization systems can overcome many of the limitations of an HbA1c-based approach while addressing the inconvenience and fragmented glucose data associated with SMBG. When used together with HbA1c monitoring, CGM provides complementary information on glucose levels, thus facilitating the optimization of diabetes therapy while reducing the fear and risk of hypoglycemia. Here we review the capabilities and benefits of CGM, including cost-effectiveness data, and discuss the potential limitations of this glucose-monitoring strategy for the management of patients with diabetes

Vascular Structure and Functional Responses to Consecutive High-Fat Feeding between Insulin Treatment Regimens in Adults with Type 1 Diabetes and Matched Controls.

Background Impaired vascular health is prevalent in type 1 diabetes (T1D); however, it remains unknown whether di!erent insulin treatment regimens mediate indices of vascular structure or function. Methods Sixteen individuals with T1D receiving either multiple daily injection therapy (MDI; n=8; age: 32±13years; BMI:26.0±5.9kg.m2; HbA1c:53.7±11.2mmol/mol [7.1±3.2%]) or continuous subcutaneous insulin infusion (CSII; n=8; age:35±18years; BMI:26.3±4.6kg.m2; HbA1c: 58.6±9.7mmol/mol [7.5±3.0%]) and ten matched controls (CON; age:31±13years; BMI: 24.3±2.9kg.m2) consumed two high fat (HF) meals at 4-hour intervals. Carotid artery intima-media thickness (CIMT) and flow mediated dilation (FMD) was assessed at baseline, with further FMD assessment at 3-hrs following the ingestion of each meal using high resolution B-mode ultrasound. Bolus insulin dose was standardised using the carbohydrate-counting method. Results CIMT was significantly higher in individuals with T1D compared to controls (p=0.039); treatment stratification within T1D revealed MDI mediated this e!ect (MDI vs. CON: p=0.049; CSII vs. CON: p=0.112). FMD remained unchanged following the first meal (p=0.204) but was significantly impaired following the second meal (p=<0.001); post- hoc analysis revealed MDI mediated this e!ect of impaired FMD after the second meal (MDI vs. CON: p=0.048; CSII vs. CON: p=0.416). Conclusions Our findings indicate that patients treated with MDI therapy have higher CIMT (a structural marker of subclinical atherosclerosis) compared to controls but not CSII therapy. FMD was impaired following a second HF meal irrespective of a diabetes status. Considering the pre-existing heightened cardiovascular disease risk in T1D therapeutic strategies to reduce postprandial risk warrants further research

PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target

Hypofibrinolysis is a key abnormality in diabetes and contributes to the adverse vascular outcome in this population. Plasminogen activator inhibitor (PAI)-1 is an important regulator of the fibrinolytic process and levels of this antifibrinolytic protein are elevated in diabetes and insulin resistant states. This review describes both the physiological and pathological role of PAI-1 in health and disease, focusing on the mechanism of action as well as protein abnormalities in vascular disease with special focus on diabetes. Attempts at inhibiting protein function, using different techniques, are also discussed including direct and indirect interference with production as well as inhibition of protein function. Developing PAI-1 inhibitors represents an alternative approach to managing hypofibrinolysis by targeting the pathological abnormality rather than current practice that relies on profound inhibition of the cellular and/or acellular arms of coagulation, and which can be associated with increased bleeding events. The review offers up-to-date knowledge on the mechanisms of action of PAI-1 together with the role of altering protein function to improve hypofirbinolysis. Developing PAI-1 inhibitors may form for the basis of future new class of antithrombotic agents that reduce vascular complications in diabetes

Estimated glucose disposal rate demographics and clinical characteristics of young adults with type 1 diabetes mellitus: A cross-sectional pilot study

Background: Estimated glucose disposal rate (eGDR) is a practical measure of Insulin Resistance (IR) which can be easily incorporated into clinical practice. We profiled eGDR in younger adults with type 1 diabetes mellitus (T1DM) by their demographic and clinical characteristics. Methods: In this single centre study, medical records of TIDM were assessed and eGDR tertiles correlated with demographic and clinical variables. Results: Of 175 T1DM individuals, 108 (61.7%) were males. Mean age (±SD) was 22.0 ± 1.6 years and median time from diagnosis 11.0 years (range 1–23). Individuals were predominantly Caucasian (81.7%), with 27.4% being overweight (BMI: 25–30 kg/m2) and 13.7% obese (BMI > 30 kg/m2). Mean total cholesterol (TC) levels were significantly lower in high and middle eGDR tertiles (4.4 ± 1 and 4.3 ± 0.8 mmol/l, respectively) compared with low eGDR tertile (4.8 ± 1, p < 0.05 for both). Triglyceride (TG) levels showed a similar trend at 1.1 ± 0.5 and 1.1 ± 0.5 mmol/l for high and middle eGDR tertile compared to low eGDR tertile (1.5 ± 1 mmol/l, p < 0.05 for both). Renal function was similar across eGDR tertiles and no difference in retinopathy was detected. Conclusion: TC and TG are altered in individuals with T1DM and low eGDR, suggesting that this subgroup requires optimal lipid management to ameliorate their vascular risk

Can vitamin D deficiency cause diabetes and cardiovascular diseases? Present evidence and future perspectives

Several studies have shown that vitamin D may play a role in many biochemical mechanisms in addition to bone and calcium metabolism. Recently, vitamin D has sparked widespread interest because of its involvement in the homeostasis of the cardiovascular system. Hypovitaminosis D has been associated with obesity, related to trapping in adipose tissue due to its lipophilic structure. In addition, vitamin D deficiency is associated with increased risk of cardiovascular disease (CVD) and this may be due to the relationship between low vitamin D levels and obesity, diabetes mellitus, dyslipidaemia, endothelial dysfunction and hypertension. However, although vitamin D has been identified as a potentially important marker of CVD, the mechanisms through which it might modulate cardiovascular risk are not fully understood. Given this background, in this work we summarise clinical retrospective and prospective observational studies linking vitamin D levels with cardio-metabolic risk factors and vascular outcome. Moreover, we review various randomised controlled trials (RCTs) investigating the effects of vitamin D supplementation on surrogate markers of cardiovascular risk. Considering the high prevalence of hypovitaminosis D among patients with high cardiovascular risk, vitamin D replacement therapy in this population may be warranted; however, further RCTs are urgently needed to establish when to begin vitamin D therapy, as well as to determine the dose and route and duration of administration. © 2011 Elsevier B.V

Coronary artery disease-associated genetic variants and biomarkers of inflammation

Introduction: Genetic constitution and inflammation both contribute to development of coronary artery disease (CAD). Several CAD-associated single-nucleotide polymorphisms (SNPs) have recently been identified, but their functions are largely unknown. We investigated the associations between CAD-associated SNPs and five CAD-related inflammatory biomarkers. Methods: We genotyped 45 CAD-associated SNPs in 701 stable CAD patients in whom levels of high-sensitivity C-reactive protein (hsRCP), interleukin-6, calprotectin, fibrinogen and complement component 3 levels had previously been measured. A genetic risk score was calculated to assess the combined risk associated with all the genetic variants. A multiple linear regression model was used to assess associations between the genetic risk score, single SNPs, and the five inflammatory biomarkers. Results: The minor allele (G) (CAD risk allele) of rs2075650 (TOMM40/APOE) was associated with lower levels of high-sensitivity C-reactive protein (effect per risk allele: -0.37 mg/l [95%CI -0.56 to -0.18 mg/l]). The inflammatory markers tested showed no association with the remaining 44 SNPs or with the genetic risk score. Conclusions: In stable CAD patients, the risk allele of a common CAD-associated marker at the TOMM40/APOE locus was associated with lower hsCRP levels. No other genetic variants or the combined effect of all variants were associated with the five inflammatory biomarkers

Automated quantification of 3D wound morphology by machine learning and optical coherence tomography in type 2 diabetes

Background: Driven by increased prevalence of type 2 diabetes and ageing populations, wounds affect millions of people each year, but monitoring and treatment remain limited. Glucocorticoid (stress hormones) activation by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) also impairs healing. We recently reported that 11β-HSD1 inhibition with oral AZD4017 improves acute wound healing by manual 2D optical coherence tomography (OCT), although this method is subjective and labour-intensive. Objectives: Here, we aimed to develop an automated method of 3D OCT for rapid identification and quantification of multiple wound morphologies. Methods: We analysed 204 3D OCT scans of 3 mm punch biopsies representing 24 480 2D wound image frames. A u-net method was used for image segmentation into 4 key wound morphologies: early granulation tissue, late granulation tissue, neo-epidermis, and blood clot. U-net training was conducted with 0.2% of available frames, with a mini-batch accuracy of 86%. The trained model was applied to compare segment area (per frame) and volume (per scan) at days 2 and 7 post-wounding and in AZD4017 compared to placebo. Results: Automated OCT distinguished wound tissue morphologies, quantifying their volumetric transition during healing, and correlating with corresponding manual measurements. Further, AZD4017 improved epidermal re-epithelialisation (by manual OCT) with a corresponding trend towards increased neo-epidermis volume (by automated OCT). Conclusion: Machine learning and OCT can quantify wound healing for automated, non-invasive monitoring in real-time. This sensitive and reproducible new approach offers a step-change in wound healing research, paving the way for further development in chronic wounds

Body mass index, estimated glucose disposal rate and vascular complications in type 1 diabetes: Beyond glycated haemoglobin

Aims To understand the relationship between insulin resistance (IR), assessed as estimated glucose disposal rate (eGDR), and microvascular/macrovascular complications in people with type 1 diabetes. Materials and methods Individuals with a confirmed diagnosis of type 1 diabetes were included in this cross-sectional study. BMI was categorised into normal weight (18.0–24.9 kg m−2), overweight (25.0–29.9 kg m−2) and obese groups (≥30.0 kg m−2). We categorised eGDR into four groups: eGDR >8, 6–7.9, 4–5.9 and <4 mg kg−1 min−1. Multiple logistic regression was used to identify associations with vascular complications, after adjusting for relevant confounders. Results A total of 2151 individuals with type 1 diabetes were studied. Median [interquartile range (IQR)] age was 41.0 [29.0, 55.0] with diabetes duration of 20.0 [11, 31] years. Odds ratio (OR) for retinopathy and nephropathy in obese compared with normal weight individuals was 1.64 (95% CI: 1.24–2.19; p = 0.001) and 1.62 (95% CI: 1.10–2.39; p = 0.015), while the association with cardiovascular disease just failed to reach statistical significance (OR 1.66 [95% CI: 0.97–2.86; p = 0.066]). Comparing individuals with eGDR ≥8 mg kg−1 min−1 and <4 mg kg−1 min−1 showed OR for retinopathy, nephropathy and macrovascular disease of 4.84 (95% CI: 3.36–6.97; p < 0.001), 8.35 (95% CI: 4.86–14.34; p < 0.001) and 13.22 (95% CI: 3.10–56.38; p < 0.001), respectively. Individuals with the highest eGDR category (≥8 mg kg−1 min−1) had the lowest complication rates irrespective of HbA1c levels. Conclusions Obesity is prevalent in type 1 diabetes and diabetes complications are not only related to glucose control. IR, assessed as eGDR, is strongly associated with both microvascular and macrovascular complications, regardless of HbA1c levels