The Pathobiology of Diabetic Complications

Brownlee, Michael

doi:10.2337/diabetes.54.6.1615

Cited by 4,645 publications

(3,976 citation statements)

References 62 publications

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“…The development of complications is likely to be caused by the level of glycaemia over a period of many years (i.e. metabolic memory) against the backdrop of genetic disposition and other risk factors 20, 21, 22. The present study showed that HbA 1c levels were associated with incidence of microvascular and macrovascular complications, but that predictability was inversely related to diabetes duration.…”

Section: Discussionmentioning

confidence: 43%

Risk of future microvascular and macrovascular disease in people with Type 1 diabetes of very long duration: a national study with 10‐year follow‐up

et al. 2016

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AimsTo describe factors associated with prevalence or absence of microvascular and macrovascular complications in people with Type 1 diabetes of very long duration and to investigate the risk factors associated with the incidence of such complications.MethodsWe included individuals with Type 1 diabetes who had been entered in the Swedish National Diabetes Register between 2002 and 2004 (n = 18 450). First, risk factor distribution in people with diabetes duration of ≥ 50 years was compared between people with and without complications. Second, the incidence of complications during a 10‐year follow‐up period was studied in all individuals who had no complications at baseline.ResultsAmong people with a diabetes duration of ≥ 50 years (n = 1023), 453 (44%) had macrovascular disease, 534 (52%) had microvascular disease and 319 (31%) did not have either of the diagnoses. Factors that differed significantly between people with and without macrovascular disease were gender, age, HbA1c, BMI, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, albuminuria, antihypertensive medication and lipid‐lowering medication. The same factors differed significantly between people with and without microvascular disease, with the exception of gender and HDL cholesterol. During the follow‐up period, 6.1% of the study cohort were diagnosed with macrovascular disease and 19.6% with microvascular disease. Incidence of macrovascular disease was significantly associated with HbA1c levels. Hazard ratios decreased with longer diabetes duration.ConclusionsPeople with Type 1 diabetes who have survived ≥ 50 years without complications are significantly younger, and have significantly lower HbA1c levels, BMI and triglyceride levels than survivors with complications. HbA1c level is a predictor of macrovascular disease, independently of diabetes duration.

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Section: Discussionmentioning

confidence: 43%

Risk of future microvascular and macrovascular disease in people with Type 1 diabetes of very long duration: a national study with 10‐year follow‐up

et al. 2016

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“…Positive energy balance, which is characterized by hyperglycemia and glycolytic metabolism, activates POMC neurons and generates significant ROS that acts as an endogenous intracellular feedback signal in POMC neurons to control activity. Consistent with this idea, hyperglycemia induces mitochondrial ROS production [48]. In negative energy balance, NPY/AgRP neurons respond to the low levels of glucose and increase neuronal firing rate [49] and potentially use fatty acids as fuel to sustain this firing.…”

Section: Mitochondrial Respiration and Oxidative Stress In The Hypothmentioning

confidence: 98%

Oxidative Stress in the Hypothalamus: the Importance of Calcium Signaling and Mitochondrial ROS in Body Weight Regulation

Gyengési

Paxinos

Andrews³

2012

Current Neuropharmacology

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A considerable amount of evidence shows that reactive oxygen species (ROS) in the mammalian brain are directly responsible for cell and tissue function and dysfunction. Excessive reactive oxygen species contribute to various conditions including inflammation, diabetes mellitus, neurodegenerative diseases, tumor formation, and mental disorders such as depression. Increased intracellular calcium levels have toxic roles leading to cell death. However, the exact connection between reactive oxygen production and high calcium stress is not yet fully understood. In this review, we focus on the role of reactive oxygen species and calcium stress in hypothalamic arcuate neurons controlling feeding. We revisit the role of NPY and POMC neurons in the regulation of appetite and energy homeostasis, and consider how ROS and intracellular calcium levels affect these neurons. These novel insights give a new direction to research on hypothalamic mechanisms regulating energy homeostasis and may offer novel treatment strategies for obesity and type-2 diabetes.

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“…CD36 also interacts with advanced glycation end products (AGE) (Ohgami, et al, 2001), which are generated in diabetes and chronic inflammatory settings such as atherosclerosis (Forbes, Soldatos, & Thomas, 2005,Brownlee, 2005,Basta, Schmidt, & De Caterina, 2004. Advanced glycation end products are protein adducts which are thought to accumulate, and thus may form a repetitive motif recognized by CD36 and other scavenger receptors.…”

Section: Cd36 Ligands and Functionsmentioning

confidence: 99%

CD36: Implications in cardiovascular disease

Febbraio

Silverstein

2007

The International Journal of Biochemistry & Cell Biology

215

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CD36 is a broadly expressed membrane glycoprotein that acts as a facilitator of fatty acid uptake, a signaling molecule, and a receptor for a wide range of ligands, including apoptotic cells, modified forms of low density lipoprotein, thrombospondins, fibrillar beta-amyloid, components of gram positive bacterial walls and malaria infected erythrocytes. CD36 expression on macrophages, dendritic and endothelial cells, and in tissues including muscle, heart, and fat, suggest diverse roles, and indeed, this is truly a multifunctional receptor involved in both homeostatic and pathologic conditions. Despite an impressive increase in our knowledge of CD36 functions, in depth understanding of the mechanistic aspects of this protein remains elusive. This review focuses on CD36 in cardiovascular disease-what we know, and what we have yet to learn.

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The Pathobiology of Diabetic Complications

Cited by 4,645 publications

References 62 publications

Risk of future microvascular and macrovascular disease in people with Type 1 diabetes of very long duration: a national study with 10‐year follow‐up

Risk of future microvascular and macrovascular disease in people with Type 1 diabetes of very long duration: a national study with 10‐year follow‐up

Oxidative Stress in the Hypothalamus: the Importance of Calcium Signaling and Mitochondrial ROS in Body Weight Regulation

CD36: Implications in cardiovascular disease

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