Lower-extremity arterial disease (LEAD) is a major endemic disease with an alarming increased prevalence worldwide. It is a common and severe condition with excess risk of major cardiovascular events ...and death. It also leads to a high rate of lower-limb adverse events and non-traumatic amputation. The American Diabetes Association recommends a widespread medical history and clinical examination to screen for LEAD. The ankle brachial index (ABI) is the first non-invasive tool recommended to diagnose LEAD although its variable performance in patients with diabetes. The performance of ABI is particularly affected by the presence of peripheral neuropathy, medial arterial calcification, and incompressible arteries. There is no strong evidence today to support an alternative test for LEAD diagnosis in these conditions. The management of LEAD requires a strict control of cardiovascular risk factors including diabetes, hypertension, and dyslipidaemia. The benefit of intensive versus standard glucose control on the risk of LEAD has not been clearly established. Antihypertensive, lipid-lowering, and antiplatelet agents are obviously worthfull to reduce major cardiovascular adverse events, but few randomised controlled trials (RCTs) have evaluated the benefits of these treatments in terms of LEAD and its related adverse events. Smoking cessation, physical activity, supervised walking rehabilitation and healthy diet are also crucial in LEAD management. Several advances have been achieved in endovascular and surgical revascularization procedures, with obvious improvement in LEAD management. The revascularization strategy should take into account several factors including anatomical localizations of lesions, medical history of each patients and operator experience. Further studies, especially RCTs, are needed to evaluate the interest of different therapeutic strategies on the occurrence and progression of LEAD and its related adverse events in patients with diabetes.
In a recent meta-analysis of randomized controlled trials of sodium glucose co-transporter 2 inhibitors (SGLT2i) in patients with diabetes, Lin and colleagues showed a positive association between ...SGLT2i-induced blood pressure and weight reduction and the risk of lower limb events. These results support the potential mechanism of a volume depletion effect of SGLT2i to explain the increase risk of amputation observed with this pharmacological class. Since the first result of the CANVAS trial raised a concern regarding the risk of amputation with SGLT2i, this hypothesis emerged from studies showing a higher incidence of amputations in patients with diabetes using diuretics. Furthermore, recent data found that copeptin, a surrogate marker of hydration status was also associated with lower limb outcomes. In conclusion, this assumption of diuretic-induced hypovolemia explanation highlights the fact that medications that induce a contraction of plasma volume, both traditional and novel agents with a diuretic mode of action should be introduced cautiously in patients with diabetes at high risk of diabetic foot events.
Type 2 diabetes is a leading cause of cardiovascular disease (CVD). Observational studies have consistently shown an association between glycaemic level and risk of major adverse cardiovascular ...events (MACE); however, intervention studies have provided limited evidence supporting a reduction in the cardiovascular burden of diabetes through intensive glucose control. In the present review, we aimed to examine the concept of cumulative glycaemic exposure with regard to protection against CVD in diabetes. We address how we can move from a binary approach in trials, to a more quantitative approach based on differences in cumulative glycaemic exposure. We plotted the association between differing glycaemic exposures between study arms and the hazard ratio for MACE in randomized controls trials comparing intensive with conventional glycaemic control in type 2 diabetes. We found a strikingly strong correlation between differential exposure and cardiovascular risk reduction. Similar results were obtained for trials comparing antidiabetes drugs with placebo. The results suggest that a minimum study duration and a minimum gain in glycated haemoglobin (HbA1c) reduction are necessary to drive a relevant risk reduction in CVD risk, and we provide a quantitative perspective in that respect. The present analysis underlines that the duration of the intensification of glycemic control, and the amplitude of the resulting reduction in HbA1c, are important notions for clinical decision‐making.
To investigate the impact of coronavirus disease 2019 lockdown on glycemic control and associated factors in people living with type 1 diabetes.
An observational evaluation from a self-reported ...questionnaire on behavioral changes and glycemic information from flash glucose monitoring (FGM) during the lockdown in 1,378 individuals living with type 1 diabetes who used a French dedicated nationwide web application (CoviDIAB).
The main outcome was the change of the mean glucose level 2 months before and 1 month after the lockdown. We found that mean glucose improved from 9.1 ± 1.7 mmol/L to 8.7 ± 1.7 mmol/L (
< 0.001). Factors associated with better glycemic control were a decrease of alcohol consumption (odds ratio OR 1.75 95% CI 1.04-2.94), an increase in the frequency of FGM scans (OR 1.48 1.04-2.10) and in the number of hypoglycemia events (OR 1.67 1.13-2.46), and an easier diabetes control perception (OR 1.71 1.18-2.49).
Our findings suggest that lockdown has a positive impact on glycemic control in people with type 1 diabetes.
Early in the COVID‐19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both conditions where variations in ...immune responses can mitigate or aggravate disease course. Identifying at‐risk groups based on immunoinflammatory signatures is valuable in directing personalised care and developing potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID‐19 severity in T2D. Broad‐spectrum immunophenotyping quantified 15 leucocyte populations in peripheral circulation from a cohort of 45 hospitalised COVID‐19 patients with and without T2D. Lymphocytopenia and specific loss of cytotoxic CD8+ lymphocytes were associated with severe COVID‐19 and requirement for intensive care in both non‐diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia restricted to classical CD14Hi CD16− monocytes was specifically associated with severe COVID‐19 in patients with T2D requiring intensive care. Increased expression of inflammatory markers reminiscent of the type 1 interferon pathway (IL6, IL8, CCL2, INFB1) underlaid the immunophenotype associated with T2D. These immunophenotypic and hyperinflammatory changes may contribute to increased voracity of COVID‐19 in T2D. These findings allow precise identification of T2D patients with severe COVID‐19 as well as provide evidence that the type 1 interferon pathway may be an actionable therapeutic target for future studies.
Synopsis
The study demonstrates that COVID‐19 affects different circulating immune cells depending on diabetic status. Type‐2 diabetic (T2D) patients with COVID‐19 lose a specific subtype of monocytes, which is associated with changes in cell morphology and highly inflammatory gene expression profile.
Patients with T2D are at higher risk of dying or suffering from severe forms of COVID‐19.
COVID‐19 infection causes a decrease in circulating lymphocyte and monocyte populations associated with severity of disease in patients with T2D.
Monocytes undergo morphological changes and highly express inflammatory markers reminiscent of the type‐1 interferon response in T2D.
Inflammatory and cellular responses to COVID‐19 from patients with T2D are associated with a need for intensive care.
The study demonstrates that COVID‐19 affects different circulating immune cells depending on diabetic status. Type‐2 diabetic (T2D) patients with COVID‐19 lose a specific subtype of monocytes, which is associated with changes in cell morphology and highly inflammatory gene expression profile.
Hydrophobicity/hydrophilicity of aqueous interfaces at the molecular level results from a subtle balance in the water–water and water–surface interactions. This is characterized here via density ...functional theory–molecular dynamics (DFT-MD) coupled with vibrational sum frequency generation (SFG) and THz-IR absorption spectroscopies. We show that water at the interface with a series of weakly interacting materials is organized into a two-dimensional hydrogen-bonded network (2D-HB-network), which is also found above some macroscopically hydrophilic silica and alumina surfaces. These results are rationalized through a descriptor that measures the number of “vertical” and “horizontal” hydrogen bonds formed by interfacial water, quantifying the competition between water–surface and water–water interactions. The 2D-HB-network is directly revealed by THz-IR absorption spectroscopy, while the competition of water–water and water–surface interactions is quantified from SFG markers. The combination of SFG and THz-IR spectroscopies is thus found to be a compelling tool to characterize the finest details of molecular hydrophobicity at aqueous interfaces.
Context:
Experimental data support a role for vasopressin in metabolic disorders.
Objective:
We investigated associations of plasma copeptin, a surrogate of vasopressin, and of allelic variations in ...the arginine vasopressin-neurophysin II gene with insulin secretion, insulin sensitivity, and the risk for impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM).
Design, Setting, and Participants:
We studied 5110 unrelated French men and women from a prospective cohort of the general population (Data from Epidemiological Study on the Insulin Resistance Syndrome cohort, 9-y follow-up). Six single nucleotide polymorphisms were genotyped.
Main Outcome Measure:
Incidence of IFG or T2DM during follow-up.
Results:
The incidence of hyperglycemia (IFG/T2DM) during follow-up by quartiles of baseline plasma copeptin was 11.0% (Q1), 14.5% (Q2), 17.0% (Q3), and 23.5% (Q4), log-rank test P = .003. Participants in the upper quartile of plasma copeptin had significantly lower insulin sensitivity (homeostasis model assessment index) at baseline and during follow-up, as compared with other participants. Cox proportional hazards regression analyses showed significant associations of the CC genotype of rs6084264, the TT genotype of rs2282018, the C-allele of rs2770381, and the CC genotype of rs1410713 with the incidence of hyperglycemia. The genotypes associated with an increased risk of hyperglycemia were also associated with increased plasma copeptin in men but not in women.
Conclusions:
High plasma copeptin was associated with reduced insulin sensitivity and an increased risk for IFG/T2DM diabetes in this community-based cohort. Moreover, in men, allelic associations support a causal role for vasopressin in these disorders.
“High plasma copeptin was associated with reduced insulin sensitivity and with hyperglycemia in a community-based cohort. Allelic associations support a causal role for vasopressin in these disorders.”
Glycemic variability remains frequent in patients with type 1 diabetes treated with insulin pumps. Heterogeneous spreads of insulin infused by pump in the subcutaneous (SC) tissue are suspected but ...were barely studied. We propose a new real-time ex-vivo method built by combining high-precision imaging with simultaneous pressure measurements, to obtain a real-time follow-up of insulin subcutaneous propagation. Human skin explants from post-bariatric surgery are imaged in a micro-computed tomography scanner, with optimised parameters to reach one 3D image every 5 min during 3 h of 1UI/h infusion. Pressure inside the tubing is recorded. A new index of dispersion (IoD) is introduced and computed upon the segmented 3D insulin depot per time-step. Infusions were hypodermal in 58.3% among 24 assays, others being intradermal or extradermal. Several minor bubbles and one occlusion were observed. IoD increases with time for all injections. Inter-assay variability is the smallest for hypodermal infusions. Pressure elevations were observed, synchronised with air bubbles arrivals in the tissue. Results encourage the use of this method to compare infusion parameters such as pump model, basal rate, catheter characteristics, infusion site characteristics or patient phenotype.
OBJECTIVE: Peripheral arterial disease (PAD) is a prognostic marker in cardiovascular disease. The use of Doppler-measured ankle-brachial pressure index (Dop-ABI) for PAD diagnosis is limited because ...of time, required training, and costs. We assessed automated oscillometric measurement of the ankle-brachial pressure index (Osc-ABI) by nurses and clinical staff. RESEARCH DESIGN AND METHODS: Clinical staff obtained Osc-ABI with an automated oscillometric device in 146 patients (83 with diabetes) at the time of Dop-ABI measurement and ultrasound evaluation. RESULTS: Measurements were obtained in most legs (Dop-ABI 98%; Osc-ABI 95.5%). Dop- and Osc-ABI were significantly related in diabetic and nondiabetic patients with good agreement over a wide range of values. When Dop-ABI less-than or equal to0.90 was used as the gold standard for PAD, receiver operating characteristic curve analysis showed that PAD was accurately diagnosed with Osc-ABI in diabetic patients. When ultrasound was used to define PAD, Dop-ABI had better diagnostic performance than Osc-ABI in the whole population and in diabetic patients (P = 0.026). Both methods gave similar results in nondiabetic patients. The cutoff values for the highest sensitivity and specificity for PAD screening were between 1.0 and 1.1. Estimation of cost with the French medical care system fees showed a potential reduction by three of the screening procedures. CONCLUSIONS: PAD screening could be improved by using Osc-ABI measured by clinical staff with the benefit of greater cost-effectiveness but at the risk of lower diagnostic performance in diabetic patients.
End-stage kidney disease (ESKD) is a multifactorial condition influenced by genetic background, but the extent to which a genetic risk score (GRS) improves ESKD prediction is unknown. We built a ...redox GRS on the base of previous association studies (six polymorphisms from six redox genes) and tested its relationship with ESKD in three cohorts of people with type 1 diabetes. Among 1012 participants, ESKD (hemodialysis requirement, kidney transplantation, eGFR < 15 mL/min/1.73 m
) occurred in 105 (10.4%) during a 14-year follow-up. High redox GRS was associated with increased ESKD risk (adjusted HR for the upper versus the lowest GRS tertile: 2.60 (95% CI, 1.51-4.48),
= 0.001). Each additional risk-allele was associated with a 20% increased risk of ESKD (95% CI, 8-33,
< 0.0001). High GRS yielded a relevant population attributable fraction (30%), but only a marginal enhancement in c-statistics index (0.928 0.903-0.954) over clinical factors 0.921 (0.892-0.950),
= 0.04). This is the first report of an independent association between redox GRS and increased risk of ESKD in type 1 diabetes. Our results do not support the use of this GRS in clinical practice but provide new insights into the involvement of oxidative stress genetic factors in ESKD risk in type 1 diabetes.
PDF
