Korean J Med.  2005 Feb;68(2):168-177.

Relationships between serum osteoprotegerin levels and insulin resistance, cardiovascular risk factors and bone metabolism in type 2 diabetic patients

• Oh SY
• Rhee EJ
• Lee WY
• Chun HB
• Yoo TW
• Kang JM
• Hwang ST
• Kim YC
• Oh KW
• Oh ES
• Baek KH
• Kang MI
• Kim SW

Abstract

BACKGROUND: Osteoprotegerin (OPG) is a soluble glycoprotein which inhibits osteoclastogenesis through binding to receptor activator of nuclear factor-kappaB ligand (RANKL). OPG-knockout mice develop early-onset osteoporosis and arterial calcification. Recent studies report that serum OPG levels are elevated in diabetic patients with cardiovascular disease and are associated with the presence and severity of coronary artery disease. We examined the relationships between serum OPG levels and insulin resistance, bone metabolism and cardiovascular risk factors in diabetic patients.
METHODS
In 84 diabetic patients (33 men, 51 women, mean age 56.7 years old) were studied. Blood pressure, body mass index (BMI), fasting blood glucose, postprandial 2-hour blood glucose, fasting insulin and lipid profiles were measured. Serum OPG levels were measured with sandwich ELISA method. Bone mineral density (BMD)s were checked and serum osteocalcin and urine deoxypyridinoline levels were checked as bone turnover markers. 24-hour urine microalbumin were checked and left ventricular mass index (LVMI) were evaluated with echocardiography. From simple chest X-ray, the presence of aortic calcification were confirmed by a trained radiologist. Homeostatic model assessment (HOMA)-insulin resistance (IR), quantitative insulin sensitivity check index (QUICKI) were calculated as insulin resistance indices.
RESULTS
Serum OPG levels were positively correlated with age, LVMI, HOMA and negatively correlated with lumbar spine BMD and QUICKI. After adjustment for age, only LVMI showed persistent correlation with serum OPG levels and when multiple regression analysis was performed with LVMI as the dependent variable, BMI and OPG were the significant predictors of LVMI (R2=0.054, p=0.012). Dividing the subjects into 3 groups according to 24-hour urine microalbumin levels, mean values for serum OPG levels increased as 24-hours urine microalbumin levels increased, but without statistical significance. Mean serum OPG levels were higher in patients with aortic calcification, without statistical significance.
CONCLUSION
Serum OPG levels were positively correlated with insulin resistance indices and negatively correlated with lumbar spine BMD in diabetic patients, suggesting a compensatory mechanism to counteract bone loss progression. Serum OPG levels were independent predictor for LVMI in diabetic patients, warranting further research on OPG as the marker for future cardiovascular mortality in diabetic patients.

Keyword

Osteoprotegerin; Osteoporosis; Diabetes mellitus; Insulin resistance; Left ventricular hypertrophy

MeSH Terms

Animals
Blood Glucose
Blood Pressure
Body Mass Index
Bone Density
Cardiovascular Diseases
Coronary Artery Disease
Diabetes Mellitus
Echocardiography
Enzyme-Linked Immunosorbent Assay
Fasting
Female
Glycoproteins
Humans
Hypertrophy, Left Ventricular
Insulin Resistance*
Insulin*
Male
Metabolism*
Mice
Mortality
Osteocalcin
Osteoporosis
Osteoprotegerin*
RANK Ligand
Risk Factors*
Spine
Thorax
Blood Glucose
Glycoproteins
Insulin
Osteocalcin
Osteoprotegerin
RANK Ligand