The relationship between the metabolic syndrome and energy-utilization deficit in the pathogenesis of obesity-induced osteoarthritis
Introduction
Osteoarthritis (OA) is the most common rheumatic disease and the first cause of disability derived from chronic musculoskeletal disease in people aged 50 years or more worldwide [1]. Despite its high frequency and health costs, the pathogenesis of OA remains unclear. We studied the possible involvement of muscle insulin resistance in the pathogenesis of OA and searched for the presence of systemic (non-rheumatic) clinical manifestations of insulin resistance in patients with different musculoskeletal diseases and osteoarthritis. Osteoarthritis is characterized by pain related to use and structural abnormalities of all tissues in the synovial joint, including cartilage, subchondral bone, synovium, capsule and ligaments [2].
Epidemiological and clinical studies have proven the coexistence of obesity and OA of the knee and interphalangeal (IP) joints of the hand. Numerous clinical conditions associated with obesity and a sedentary lifestyle, such as hypertension and type 2 diabetes, are also frequently observed in OA patients [3], [4].
According to the International Diabetes Federation (IDF) definition [5], for a person to be defined as having the metabolic syndrome they must have: central obesity (defined as waist circumference ⩾94 cm for European men and ⩾80 cm for European woman, ⩾102 for USA men and ⩾88 for USA women). Plus, any two of the following factors: raised triglyceride (TG) levels: >150 mg/dl (1.7 mmol/L) or specific treatment for this lipid abnormality, reduced HDL cholesterol: <40 mg/dl (0.9 mmol/L) in males and <50 mg/dl (1.1 mmol/L) in females or specific treatment for this lipid abnormality, raised blood pressure: systolic BP ⩾130 or diastolic BP ⩾85 or treatment for previously diagnosed hypertension, raised fasting plasma glucose ⩾100 mg/dl (5.6 mmol/L) or previously diagnosed type 2 diabetes.
Section snippets
Hypothesis
We propose that the pathogenesis of obesity-induced osteoarthritis may be explained by the metabolic changes in the striated muscle induced by the interaction of insulin resistance and systemic inflammation in obese individuals with metabolic syndrome being osteoarthritis the latest consequence by the physiological changes seen in the metabolic syndrome.
Increased levels of TH1 cytokines are produced by activated macrophages in the presence of an acute or chronic infectious disease and suppress
Insulin resistance
Cross-sectional studies have shown that plasma nitric oxide concentrations are raised in insulin-resistant healthy subjects and that individuals with the greatest insulin response also have a significantly higher plasma glucose response to oral glucose, faster heart rate, higher blood pressure, and the combination of higher triglyceride and lower high-density lipoprotein (HDL) cholesterol plasma levels [6].
Longitudinal studies have shown that muscle insulin resistance precedes the onset of type
Glucose metabolism
Glucose is the main source of energy for various cells and tissues and adequate glucose supply is an essential condition for normal physiology and cell survival. The free access of glucose into distinct cells is prevented by the structural arrangement of an electrically charged double layer of lipids on the cell membrane. With the exception of the brain, human tissues need insulin to activate the glucose transporter system into the cell; in physiological conditions, serum glucose levels are
The role of muscular weakness in the pathogenesis of osteoarthritis
It is known that articular damage produces pain and effusion that can be relieved by rest or reduced articular movement, but this therapeutic approach increases the weakness. The weak muscle fatigue easily and their motor and reflex control is slower than well trained muscles. This motor dysfunction compromises neuromuscular protective mechanisms producing excessive articular movement and instability which causes an overload of the innervated tissues with pain and rapid, excessive articular
Muscle metabolism and the muscle insulin resistance
Muscle chronically deprived of glycogen is impelled to obtain the energy necessary for contractile function from other sources and therefore alternative pathways of energy expenditure are activated in the muscle of MIR individuals.
Patients with MIR might require an additional amount of insulin to match increasing insulin resistance determined by physiological or pathological conditions such as pregnancy or systemic inflammation.
The role of inflammation in insulin resistance and the pathogenesis of obesity-induced osteoarthritis
Acute inflammation is characterized by intense activity of mononuclear macrophage lineage cells and the presence of Th-1 cytokines. It has been shown that tumor necrosis factor alpha (TNFα) suppresses the sensitivity of membrane muscle insulin receptors, reducing tyrosine kinase phosphorylation and insulin induced IRS-1 autophosphorylation. Thus, this cytokine down regulates muscle glucose uptake during acute or chronic inflammation. Additionally, TNFα may contribute significantly to insulin
Acknowledgements
We thank David Buss for his editorial assistance.
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