Osteoarthritis, Obesity, and Type 2 Diabetes: Exploring the Interplay and Clinical Implications

Obesity and type 2 diabetes (T2DM) significantly increase the risk of developing arthritic disease. Although two obese or overweight subjects may have the same body mass index (BMI), one may have a metabolic or cardiovascular disorder while the other may only have joint complications. As a consequence, a high BMI is not always sufficient to discriminate between overweight or obese people who are at high risk for health problems.

In 1947, Jean Vague introduced waist circumference measurement to differentiate between abdominal (or central) obesity (visceral, ectopic adipose tissue) and peripheral obesity (subcutaneous, which is the typical location of adipose tissue).

The location of excess fat mass varies between subjects. Imaging (CT and MRI) has revealed differences between subjects in the proportion of adipose tissue housed in the abdominal cavity: certain obese individuals have little visceral adipose tissue, while others with the same total fat mass have a greater amount of adipose tissue. visceral. This visceral adipose tissue is associated with an increased risk of metabolic and cardiovascular diseases and certain cancers, not to mention the risk of non-alcoholic steatohepatitis (NASH).

This visceral adipose tissue induces local and then systemic microinflammation, and is accompanied by accumulation of pericardial and intramuscular fat; This prevents the organs in question, and the entire body, from functioning normally. A recent study in more than 650,000 adults showed that regardless of BMI (normal, overweight, obese; BMI ranging between 20 and 50 kg/m2), an increase in waist circumference leads to a significant and identical increase in risk. of mortality, regardless of BMI.

Relative to a waist circumference of <90 cm for men and <70 cm for women, a 5 cm increase in circumference increases mortality by 7% in men and 9% in women. However, recent studies show that an increase in waist circumference, regardless of BMI, is also a risk factor for osteoarthritis (OA). People with type 2 diabetes (T2D) also have a higher risk of developing arthritic complications.

The primary objective of this review was to explore the links between obesity, type 2 diabetes and OA, with a focus on the effect of ectopic (intra-abdominal) location of fat mass. The second objective was to define the functional consequences of OA in this population, which often has other comorbidities, and how to treat and prevent it.

We conducted a review of the literature on the pathophysiological mechanisms underlying the relationships between obesity, type 2 diabetes, and osteoarthritis (OA).

The pathophysiology of the link between obesity and OA is related to both the direct effect of excessive mechanical loads placed on cartilage and the effect of adipose tissue.

Adipocytes produce and release adipokines (e.g. leptin). They are also the seat of a local inflammatory reaction when adipose tissue is ectopic (visceral adipose tissue vs. subcutaneous adipose tissue), and then systemic effects that further add to a microinflammatory mechanism.

In diabetics, insulin resistance can add to these mechanisms, which can damage cartilage, bone, and synovial tissue. They all act together to reduce mobility in obese subjects and contribute to a vicious cycle centered on OA, especially when obesity is predominantly abdominal and/or associated with type 2 diabetes.

> Direct effect of mechanical loads on cartilage.

Excess weight increases mechanical loads on the hip and knee joint during physical activity, which is the most likely mechanism through which obesity contributes to OA. In fact, each additional kilogram of body weight adds 6 kg of load to each of the two knees. This excess weight can induce cartilage degeneration due to increased mechanical stress on weight-bearing joints.

> Role of adipose tissue independent of location: subcutaneous or ectopic (intra-abdominal)

In combination with these biomechanical factors, cytokines produced by adipose tissue (adipokines, leptin being the best known and studied, but also resistin and adiponectin) can also be implicated. The existence of an association between obesity and OA in non-weight-bearing joints, particularly in the hands and fingers, supports this hypothesis.

> Role of microinflammation: ectopic adipose tissue with and without obesity

Microinflammation depends more on the location of adipose tissue than on the total amount of adipose tissue. Ectopic adipose tissue induces a local and subsequently systemic inflammatory reaction (mild inflammation or microinflammation). For this reason, OA is predominantly found in people with abdominal obesity, including those with normal BMI who have abdominal obesity.

There is abundant published scientific data suggesting that inflammatory mediators of adipose origin play an important role in the initiation and perpetuation of the OA process. These inflammatory mediators are released from adipose tissue (TNFα, IL-6, etc.) into the systemic circulation and reach the joint through the subchondral vascular network. These mediators have deleterious effects on cartilage, bone, and synovial tissue.

The pathophysiology of this association between T2D and OA has not been determined. High blood glucose could trigger inflammation and cartilage degradation through oxidative stress and an accumulation of inflammatory mediators and advanced glycation end products (AGEs). Furthermore, beyond chronic excess glucose, T2DM is characterized by increased insulin resistance, which may be involved in the development of osteophytes and subchondral sclerosis. Prospective studies are needed to determine whether diabetes is a risk factor independent of ectopic obesity for the development of OA or its severity.

Obesity is associated with functional impairment and functional disability in cross-sectional and longitudinal studies, accelerating disability and the need to resort to arthroplasty in subjects with knee OA. However, beyond BMI, the distribution of fat mass is an important element to consider. It is well proven that a predominantly abdominal distribution of fat mass is involved in the pathophysiology of OA.

Muscle mass and physical capacity decrease physiologically with age, but the presence of DM2 accelerates the loss of muscle mass. As a result, diabetics are at high risk for physical disability and more specifically, loss or decline in mobility.

In the Look Ahead Study (5145 subjects with T2DM with a mean age of 59 years and BMI of 36 kg/m2, diabetes duration of 6.8 years, HbA1C 7.3%; 59.8% women), 18 .2% of those with T2DM had severe mobility problems (inability to perform activities of daily living) and the prevalence of this serious limitation increased to 26.4% four years later (note that the subjects were under 65 years of age) .

However, in the diabetic groups that received an intensive lifestyle intervention combining a low-calorie diet and physical activity, the prevalence was reduced to 20.6% four years later.

Notably, this active lifestyle intervention led to a 48% reduction in the severity of mobility inability in overweight or obese type 2 diabetes subjects compared to subjects who did not receive nutrition or physical activity counseling. This effect was related to both weight loss (-4.7% at 4 years, correlated with compliance) and improvement in physical capacity.

A 1% reduction in body weight and a 1% relative increase in physical capacity reduced the risk of mobility loss by 7.3% and 1.4%, respectively. Both factors (weight loss and physical activity) independently contributed to the observed effect.

The care of overweight and obese patients involves reducing their fat mass and significantly reducing their waist circumference (i.e., intra-abdominal fat mass) to reduce excess morbidity. 

The criterion for successful weight loss is maintenance of a weight loss of 10% or more of initial weight after 1 year; This has been shown to be the weight loss threshold for significant improvements in cardiovascular and metabolic parameters. However, it is extremely difficult to maintain this weight loss long term.

Studies have shown that after weight loss induced by calorie restriction, you will regain 33% to 50% of your initial weight over the next 12 to 18 months. Observational studies have shown that regular physical activity initiated during the weight loss phase and maintained during the weight stabilization phase can help maintain weight over the long term.

It is interesting and convenient that abdominal obesity is very sensitive to the effects of regular physical activity. Its management is based on adequate nutrition and physical activity. Visceral adipose tissue is significantly reduced with regular physical activity (following health guidelines for 150 minutes of moderate physical activity per week), even if no weight is lost.

Prevention of obesity-related OA should be the focus of attention in high-risk subjects, such as those who are obese with metabolic syndrome > “metabolically healthy” obese, have type 2 diabetes, and normal weight subjects with abdominal obesity (defined such as waist circumference > 102 cm). for men and 88 cm for women). The main component of this prevention effort is weight loss combined with a balanced diet and regular physical activity.

Physical activity is an element in its own right of the therapeutic management of obesity, type 2 diabetes and metabolic syndrome, along with any disease that has these comorbidities. Interestingly, among the endpoints measured, there is also improvement in mobility, joint pain, and arthritis.

Prevention of obesity-related OA should be the focus of attention in subjects identified as having high "joint and metabolic" risk, such as those who are obese with metabolic syndrome > "metabolically healthy" obese, have type 2 diabetes, and subjects with normal weight with abdominal obesity (defined as waist circumference > 102 cm for men and 88 cm for women).

Finally, symptomatic OA may be a clinical rather than silent entry point (unlike moderately high blood glucose levels) for metabolic disorders. In other words, when a patient presents with symptomatic knee OA, it is an opportunity to measure blood glucose levels and look for type 2 diabetes.