Diabetes Paradox Research Articles

Diabetes associates with mortality in critically ill patients with SARS-CoV-2 pneumonia: No diabetes paradox in COVID-19

BackgroundDiabetes mellitus (DM) is not associated with increased mortality in critically ill patients, a phenomenon known as the “diabetes paradox”. However, DM is a risk factor for increased mortality in patients with COVID-19. This study aims to investigate the association of DM and stress-induced hyperglycemia at intensive care unit (ICU) with mortality in this population. MethodsThis is a retrospective study. Electronic medical records from patients admitted from March 2020 to September 2020 were reviewed. Primary outcome was mortality. Secondary outcomes were ICU and hospital mortality and stay, and need for mechanical ventilation and renal replacement therapy. Results187 patients were included. Overall mortality was 43.2%, higher in patients with DM (55.7% vs. 34%; p = 0.007), even after adjustment for age, hypertension, and disease severity. When patients were separated into groups, named normoglycemia (without DM and glycemia ≤140 mg/dL), stress-induced hyperglycemia (without DM and glycemia >140 mg/dL), and DM (previous diagnosis or HbA1c ≥ 6.5%), the mortality rate was 25.8%, 37.3%, and 55.7%, respectively (p = 0.021). Mortality was higher in patients with higher glycemic variability. No statistical difference related to secondary outcomes was observed. ConclusionsDM, hyperglycemia, and glycemic variability associated with increased mortality in critically ill patients with severe COVID-19, but did not increase the rates of other clinical outcomes. More than stress-induced hyperglycemia, DM was associated with mortality.

Takotsubo syndrome: Does “Diabetes Paradox” exist?

BackgroundPrevious small-scale studies have reported conflicting findings regarding the prevalence of diabetes mellitus (DM) and its association with outcomes in patients with takotsubo syndrome (TTS) ObjectiveWe sought to assess the prevalence of DM and its association with outcomes in TTS patients. MethodsNationwide inpatient sample (NIS) was queried to extract patient information from January 1, 2009 to September 30, 2015. Propensity score matching (PSM) was done to compare mortality and other in-hospital outcomes. ResultsA total of 40,327 hospitalizations for TTS were included. The prevalence of DM in TTS was 19.3% vs 23.1% (p-value < 0.01) in patients without TTS in the NIS from 2009 to 2015. In the PSM cohort, there was no difference in in-hospital mortality (1.1% vs 1.4%; p = 0.76), stroke (1.2% vs 0.9%; p = 0.09), cardiogenic shock (3.7% vs 3.9%; p = 0.61), cardiac arrest (1.2% vs 1.2%; p = 0.94), ventricular arrhythmias (3.7% vs 3.3%; p = 0.23), circulatory support (2.1% vs 1.8%; p = 0.17), and invasive mechanical ventilation (4.9% vs 4.7%; p = 0.54) in TTS patients with versus without diabetes. In sub-group analysis, diabetes with chronic complications patients were found to have lower mortality (0.7% vs 2.0%; p = 0.04) compared to patients without diabetes and those with uncomplicated diabetes (0.6% vs 2.6%; p = 0.002). ConclusionsPrevalence of DM was lower in TTS in comparison to patients without TTS. In addition, complicated DM patients were found to have lower in-hospital mortality. Further studies are needed to assess the mid and long-term outcomes of DM with and without chronic complications in TTS

Dysglycemia in the critically ill patient: current evidence and future perspectives.

Dysglycemia in critically ill patients (hyperglycemia, hypoglycemia, glycemic variability and time in range) is a biomarker of disease severity and is associated with higher mortality. However, this impact appears to be weakened in patients with previous diabetes mellitus, particularly in those with poor premorbid glycemic control; this phenomenon has been called "diabetes paradox". This phenomenon determines that glycated hemoglobin (HbA1c) values should be considered in choosing glycemic control protocols on admission to an intensive care unit and that patients' target blood glucose ranges should be adjusted according to their HbA1c values. Therefore, HbA1c emerges as a simple tool that allows information that has therapeutic utility and prognostic value to be obtained in the intensive care unit.

The diabetic paradox: Bone mineral density and fracture in type 2 diabetes

Type 2 diabetes mellitus prevalence and morbidity are increasing. Osteoporotic fractures are among the ‘non-classical’ complications of diabetes and been overlooked for a long time, maybe because of their complex diagnostic and therapeutic approach. The usual tools for preventing fragility fractures (such as the fracture risk assessment tool and bone densitometry) underestimate risk of fractures in type 2 diabetic patients. New techniques, such as trabecular bone score or bone turnover markers, could be useful, but greater scientific evidence is required to recommend their use in clinical practice. The special characteristics of their pathophysiology result in decreased bone remodeling with normal or even increased bone mineral density, but with low quality. These changes lead to the occurrence of osteoporotic fractures without evidence of densitometric changes, which could be called ‘the diabetic paradox’.

La paradoja diabética: densidad mineral ósea y fractura en la diabetes tipo 2

Type 2 diabetes mellitus prevalence and morbidity are increasing. Osteoporotic fractures are among the ‘non-classical’ complications of diabetes and been overlooked for a long time, maybe because of their complex diagnostic and therapeutic approach. The usual tools for preventing fragility fractures (such as the fracture risk assessment tool and bone densitometry) underestimate risk of fractures in type2 diabetic patients. New techniques, such as trabecular bone score or bone turnover markers, could be useful, but greater scientific evidence is required to recommend their use in clinical practice. The special characteristics of their pathophysiology result in decreased bone remodeling with normal or even increased bone mineral density, but with low quality. These changes lead to the occurrence of osteoporotic fractures without evidence of densitometric changes, which could be called ‘the diabetic paradox’.

“Diabetes paradox” in Takotsubo Cardiomyopathy

“Diabetes paradox” in Takotsubo Cardiomyopathy

Hypoxia in vascular networks: a complex system approach to unravel the diabetic paradox.

In this work we model the extent of hypoxia in the diabetic retina as a function of the area affected by vessel disruption. We find two regimes that differ on the ratio between the area of disrupted vasculature and the area of tissue in hypoxia. In the first regime the hypoxia is localized in the vicinity of the vascular disruption, while in the second regime there is a generalized hypoxia in the affected tissue. The transition between these two regimes occurs when the tissue area affected by individual sites of vessel damage is on the order of the square of the characteristic irrigation length in the tissue (the maximum distance that an irrigated point in the tissue is from an existing vessel). We observe that very high levels of hypoxia are correlated with the rupture of larger vessels in the retina, and with smaller radii of individual sites of vessel damage. Based on this property of vascular networks, we propose a novel mechanism for the transition between the nonproliferative and the proliferative stages in diabetic retinopathy.

The diabetes conundrum: despite increasing incidences of coronary disease in diabetic type II patients, their first cathlab presentation is later than expected

This editorial refers to ‘Severity of coronary atherosclerosis in patients with a first acute coronary event: a diabetes paradox’[†][1], by M. Niccoli et al. , on page 729 Niccoli et al . assessed the severity of coronary artery disease (CAD) in the culprit vessels of diabetic type II as well as non-diabetic patients ( n = 167) at the time of their first coronary event employing standard coronary angiography and intracoronary optical coherence tomography (OCT) imaging ( n = 72).1 To assess the severity of CAD, they applied the Bogarty, Gensini, and Sullivan scores, and to evaluate the development of collaterals they used the Rentrop score, all based on coronary angiography. Intracoronary imaging by OCT was performed to study coronary plaque morphology, more particularly to quantify the amount of lipids and calcification present in the plaques. This was assessed at the site of the minimal lumen area (MLA) and at the cross-section showing the largest arc of calcium in the culprit vessel. Furthermore, the OCT images were inspected for the presence of calcified nodules.2 The findings of the authors are: more collateral development towards the culprit vessel, less lipids at the MLA site, more severe calcified segments, and more superficial calcified nodules in diabetic type II patients as compared with non-diabetics at the time of their first event. As the author's state: despite more severe coronary calcification, including calcified nodules, potent pro-inflammatory, pro-oxidant, and pro-thrombotic stimuli in diabetic type II patients, these patients seem to experience their first event at a later stage in the process of CAD as compared with non-diabetic patients. This finding is seemingly at odds with general convention, i.e. that the first event for all patients happens at the same stage of CAD. The authors hypothesized that there might be, besides an increased presence … [1]: #fn-2

Severity of coronary atherosclerosis in patients with a first acute coronary event: a diabetes paradox

We aimed to compare coronary artery disease (CAD) at the time of a first acute coronary syndrome (ACS) in type II diabetic and non-diabetic patients by coronary angiography and by optical coherence tomography (OCT). Two different patient populations with a first ACS were enrolled for the angiographic (167 patients) and the OCT (72 patients) substudy. Angiographic CAD severity was assessed by Bogaty, Gensini, and Sullivan scores, whereas collateral development towards the culprit vessel was assessed by the Rentrop score. Optical coherence tomography plaque features were evaluated at the site of the minimum lumen area (MLA) and of culprit segment. In the angiographic substudy, at multivariate analysis, diabetes was associated with both the stenosis score and the extent index (P = 0.001). Furthermore, well-developed collateral circulation (Rentrop 2-3) towards the culprit vessel was more frequent in diabetic than in non-diabetic patients (73% vs. 16%, P = 0.001). In the OCT substudy, at MLA site lipid quadrants were less and the lipid arc was smaller in diabetic than in non-diabetic patients (2.3 ± 1.3 vs. 3.0 ± 1.2; P = 0.03 and 198° ± 121° vs. 260° ± 118°; P = 0.03). Furthermore, the most calcified cross-section along the culprit segment had a greater number of calcified quadrants and a wider calcified arc in diabetic than in non-diabetic patients (1.7 ± 1.0 vs. 1.2 ± 0.9; P = 0.03 and 126° ± 95° vs. 81° ± 80°; P = 0.03). Superficial calcified nodules were more frequently found in diabetic than in non-diabetic patients (79 vs. 54%, P = 0.04). In spite of potent pro-inflammatory, pro-oxidant and pro-thrombotic stimuli operating in type II diabetes, diabetic patients exhibit substantially more severe coronary atherosclerosis than non-diabetic patients at the time of a first acute coronary event. Better collateral development towards the culprit vessel, a predominantly calcific plaque phenotype and, probably, yet unknown protective factors operating in diabetic patients may explain these intriguing paradoxical findings.

The Diabetes Paradox: Diabetes is Not Independently Associated with Mortality in Critically Ill Patients

Intensive monitoring of blood glucose levels and treatment of hyperglycemia in critically ill patients has become a standard of care over the past decade. Although diabetes is associated with a large burden of illness in outpatients, the “diabetes paradox” suggests that in patients admitted to intensive care units, the presence of diabetes as a comorbidity is not independently associated with increased risk of mortality. This review article 1) describes prospective trial and observational cohort literature addressing this issue, 2) addresses the potential mechanisms underlying the diabetes paradox, and 3) discusses implications for patient care and future research.

Endothelial Progenitor Cells and the Diabetic Paradox Current Knowledge and Therapeutic Perspectives

Endothelial Progenitor Cells and the Diabetic Paradox Current Knowledge and Therapeutic Perspectives

Endothelial Progenitor Cells and the Diabetic Paradox Current Knowledge and Therapeutic Perspectives

The discovery of postnatal vasculogenesis and of the important roles played by bone marrow-derived Endothelial Progenitor Cells was a landmark in vascular biology that forever has changed the concept of neovascularization. Diabetes associated vascular complications involve distinct modifications in neovascular formation, which is reduced in cardiovascular disease and increased in diabetic retinopathy, defining the diabetic paradox. The vasculogenic process seems to play a central dual role in these alterations: by one side dysfunctional EPCs impair endothelial regeneration in peripheral vasculopathy and on the other hand alterations in EPCs are involved in increased retinal vessel growth in diabetic retinopathy. Although still under investigation, these divergent features seem related to a differential response of progenitor cells to ischemic-induced depletion/induction of angiogenic factors. Due to the importance of vasculogenesis, therapeutic interventions targeting EPCs in diabetic vascular complications arose as a potential tool. However, scarce information has been disclosed regarding the safety and harmful side effects of these therapies. Future research is mandatory in order to further elucidate the complex mechanisms governing the diabetic- vasculogenic paradigm, bringing also novel insights into the potential therapeutic usefulness of EPCs.

Using Shiffman's political priority model for future diabetes advocacy

Securing political priority for diabetes has long been an issue for the global diabetes community. We have seen a ‘diabetes paradox’ on the international agenda; while the disease is epidemic in scale, constitutes a vast economic burden and leads to more deaths than AIDs and malaria combined, it has not commanded political attention or sufficient resources on the global stage. However, the recent focus on Non-Communicable Diseases (NCDs) has meant global health priorities are finally realigning with the reality of the burden of disease. IDF has led the campaign to address the chronic neglect of diabetes; after gaining political recognition that diabetes is a “chronic, debilitating and costly disease” with the 2006 UN Resolution on diabetes [ [1] UN General Assembly Resolution A/RES/61/225, World Diabetes Day, 2006. Google Scholar ], IDF secured international political action with the UN Summit on NCDs in 2011. Despite taking diabetes to the highest global forum, however, political prioritisation of diabetes has yet to be fully realised – the disease remains underfunded and there is no widespread outrage about the extent of diabetes and the suffering caused. The complexity and idiosyncrasy of the global health agenda has attracted academic attention. To better assess the diabetes position and frame IDF's post-Summit advocacy priorities, this editorial looks at Shiffman's analysis of the features of a health issue that attract political priority on the global health agenda [ [2] Shiffman J. Smith S. Generation of political priority for global health initiatives: a framework and case study of maternal mortality. Lancet. 2007; 370: 1370-1379 Abstract Full Text Full Text PDF PubMed Scopus (429) Google Scholar ].

Endothelial Progenitor Cells and the Diabetic Paradox Current Knowledge and Therapeutic Perspectives~!2009-10-25~!2009-11-07~!2010-03-04~!

Endothelial Progenitor Cells and the Diabetic Paradox Current Knowledge and Therapeutic Perspectives~!2009-10-25~!2009-11-07~!2010-03-04~!

Endothelial Progenitor Cells and the Diabetic Paradox

An unexplained paradox puzzles diabetologists: diabetic patients must face both poor vessel growth in ischemic heart and limbs and increased angiogenesis in retinal complications (1,2). Endothelial progenitor cells (EPCs) are marrow-derived cells involved in adult neovascularization and endothelial homeostasis (3,4). It has been postulated that low EPCs in peripheral blood may have a role in cardiovascular disease, and we have demonstrated that EPCs are reduced in macrovascular diabetes complications (5,6). On the other hand, an excess of EPCs may be involved in pathologic neoangiogenesis of cancer and proliferative retinopathy (7,8). Therefore, diabetes complications may be associated with both decreased and increased EPCs. Recently, novel therapeutic approaches have been directed to enrich the EPC pool in ischemic diseases and to block EPC function in proliferative diseases (9,10). These approaches in diabetic subjects require cautious evaluation of the implications carried by the paradox and new studies to unravel its causes (11,12). This study was carried out to investigate the contemporaneous effects of retinal and peripheral vascular complications on circulating progenitor cells. Ethics committee approval was obtained, and after giving informed consent, 60 type 2 diabetic patients were prospectively included. Patients were characterized in terms of peripheral arterial disease (PAD) and diabetic retinopathy (DR) as the most representative complications at the two extremities of the diabetic paradox. PAD was diagnosed by minimal criteria (including history of claudication or rest pain, pulse examination, ankle-brachial indexes, and ultrasonography) and eventually confirmed by angiography. Diabetic retinopathy (severe nonproliferative or proliferative) was defined by a dilated and comprehensive eye examination and acquisition of high-quality stereoscopic photographs by …

Autologous Transplantation of Granulocyte Colony–Stimulating Factor–Mobilized Peripheral Blood Mononuclear Cells Improves Critical Limb Ischemia in Diabetes

Huang et al. (1), in their small seminal clinical trial of cellular therapy for critical limb ischemia in diabetic patients, did not include presence of diabetic retinopathy among their exclusion criteria. It is known that individuals with diabetes are subjected to poor blood vessel growth in ischemic hearts and limbs and increased angiogenesis in retinal complications. This so-called “diabetic paradox” has been attributed …