The American Heart Hospital Journal
Higher circulating levels of adiponectin are present with oxidative stress and coronary artery calcification (adjusting for weight and insulin resistance). This may indicate an enhanced adiponectin secretory response of adipose tissue to the metabolic environment present in the early development of macrovascular disease, thus suggesting that the elevated levels of adiponectin may comprise an attempt to alleviate risk for additional development and progression of macrovascular disease in an at-risk environment. Table 2 summarizes the effects of these adipokines.
Presented in Table 3 are observational data from the participants of a program that involved six months of exercise training and dietary changes to impact the BMI of the participants at the end.
As individuals lost weight via lifestyle modification, adiponectin levels were seen to increase and leptin levels decrease, thus also affecting the related cardiometabolic factors as described previously.
Tuomilehto et al. in 200117 provided evidence that type 2
diabetes mellitus can be prevented by changes in lifestyles of high-risk individuals. Some individuals have high baseline adiponectin levels that, as they lose weight, become higher and provide further protection against cardiometabolic risk. It is interesting to review the above presented data in the light of this knowledge.
The woman presented in Table 4 has a BMI of 113.5, which relates well with her high blood pressure as the relationship between obesity and hypertension is well established, as described by Theodore. The relationship between diabetes mellitus and obesity has also been very well established. While 85 % of patients with type 2 diabetes mellitus are obese, only 15 % of obese individuals have type 2 diabetes mellitus.
A striking feature in this observation is that despite carrying such a large burden of adipocytes, the patient has not yet developed diabetes mellitus. This may be due to the fact that her adiponectin levels are relatively high, thus providing her with relative protection against diabetes mellitus. Not every individual is genetically endowed with the same capacity to produce adiponectin and thus not every individual has the same cardiovascular and metabolic risk associated with obesity.
Of further interest in regards to the role of these biomarkers of obesity, leptin, and adiponectin, are the effects that medications used in managing cardiovascular disease have on their circulating levels. Krysiak has shown
Summer 2011
Table 4: Data Obtained from a Woman who Weighs 700 lbs BMI
113.5
Blood pressure IL-6 level TGF-alpha Total LDL Total HDL Total VLDL
Total cholesterol Triglycerides CRP
Fasting glucose HbA1C
Leptin
Adiponectin Insulin
Glucose/insulin ratio 180/100 mmHg
11 pg/ml (<12 pg/ml) 73 pg/ml (<30 pg/ml) 81 mg/dl (<130 mg/dl) 64 mg/dl (>40 mg/dl) 14 mg/dl (<30 mg/dl) 160 mg/dl (<200 mg/dl) 68 mg/dl (<150 mg/dl) >15 µg/ml (<1 µg/ml)
104 mg/dl (65–100 mg/dl) 5.9 (4.0–5.6 %)
111 ng/ml (<20 ng/ml) 5.2 µg/ml (>2.7 µg/ml) 5.6 µIU/ml (<5.4 µIU/ml) 4.1 (>4.5)
BMI = body mass index, CRP = C-reactive protein, HDL = high-density lipoprotein, IL-6 = interleukin-6, LDL = low-density lipoprotein, TGF-alpha = transforming growth factor alpha, VLDL = very-low-density lipoprotein.
Review
that certain angiotensin-converting enzyme (ACE) inhibitors result in decreased levels of leptin and an increase in the level of adiponectin.18
Ohashi19 and Suglyama20 have also independently
demonstrated that lipid lowering therapy increases the concentrations of adiponectin in patients with coronary artery disease and impaired glucose tolerance. In addition, pioglitazone, an anti-diabetic medication, has been shown to increase adiponectin levels in diabetics as well as non-diabetic individuals.21
The measurement of these unique adipokines as biomarkers is key. The US is facing an epidemic of obesity with limited resources to care for these individuals. It is paramount that we use these powerful tools to determine who is at greatest risk for developing insulin resistance and type 2 diabetes mellitus and focus our greatest efforts on them. These biomarkers can also be used to guide our interventions as patients lose weight and decrease their risk.
Understanding the adipocyte and recognizing these adipokines as biomarkers has the potential to change the way physicians manage high-risk individuals. Management options for those individuals with an unfavorable biomarker profile in addition to being obese may prompt more aggressive measures such as bariatric surgery. Gastric bypass surgery has been shown to produce considerable improvement in the prevalence of metabolic syndrome, as demonstrated by Batsis et al. at the Mayo Clinic in 2008.22 The risks of such interventions may seem minor compared with the overall detriments that adipose tissue poses to the body. n
Biomarkers Associated with Cardiometabolic Risk in Obesity 31
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