Wędrychowicz A, Stec M, Sztefko K, Starzyk J B
Department of Pediatric and Adolescent Endocrinology, Polish-American Pediatric Institute, Jagiellonian University Collegium Medicum, Krakow, Poland.
Department of Clinical Immunology, Chair of Clinical Immunology and Transplantation, Polish-American Pediatric Institute, Jagiellonian University Collegium Medicum, Krakow, Poland.
Exp Clin Endocrinol Diabetes. 2014 Sep;122(8):491-5. doi: 10.1055/s-0034-1375666. Epub 2014 Jun 11.
To investigate the relationship between bone-derived osteocalcin (OC), osteoprotegerin (OPG), Receptor Activator of Nuclear Factor NF-ĸB ligand (RANKL), and fat tissue-derived leptin and adiponectin with a clinical outcome of type 1 diabetes mellitus (T1DM) in children and adolescents.
78 patients (43 girls and 35 boys), aged 11.5±4.3 years with T1DM and 11 age- and BMI-matched controls were included into the study. Patients were divided into 3 groups according to HbA1c level, I - below 7% [53 mmol/mol], II - 7-9% [53-75 mmol/mol] and III - above 9% [75 mmol/mol]. Blood samples for biochemical measurements were drawn at 8.00 AM, when the patients were in a fasting state. HbA1c was measured by the standardized IFCC method. OC, OPG, RANKL, leptin and adiponectin were measured by ELISA. ANOVA, and multiple regression analysis were used for statistical analysis.
Significant differences in leptin and osteocalcin levels between groups with different HbA1c values were observed (p=0.03, p=0.04). Multiple regression analysis adjusted for age showed that serum OC and leptin negatively correlated with HbA1c levels (r=-0.22, p=0.004 and r=-0.27, p=0.0001, respectively). In contrast, serum OPG correlated positively with HbA1c (r=0.26, p=0.02) as well as with adiponectin (r=0.26, p=0.02) and RANKL (r=0.27, p=0.02) levels. The correlation of OC with HbA1c was the strongest in group I - patients with good metabolic control of DM (r=-0.43, p=0.03). In that group, in multiple regression analysis adjusted for age and BMI leptin correlated positively with daily dose of insulin (r=0.52, r=0.009). In group II and III in multiple regression analysis adjusted for age and BMI OC correlated negatively with leptin (r=-0.37, p=0.01).
Our data suggest significant relationships between bone, fat tissue and glucose metabolism in pediatric patients with T1DM. The results can confirm that poor metabolic control is associated with reduced bone formation. On the other hand fat and bone tissue can influence glucose metabolism, potentiality in insulin-dependent manner. From these data leptin or OC may be potentially used as additional therapeutic agents for T1DM.
研究骨源性骨钙素（OC）、骨保护素（OPG）、核因子κB受体活化因子配体（RANKL）以及脂肪组织源性瘦素和脂联素与儿童及青少年1型糖尿病（T1DM）临床结局之间的关系。
本研究纳入了78例11.5±4.3岁的T1DM患者（43例女孩和35例男孩）以及11例年龄和体重指数匹配的对照。根据糖化血红蛋白（HbA1c）水平将患者分为3组：I组-HbA1c低于7%[53 mmol/mol]，II组-HbA1c为7%-9%[53-75 mmol/mol]，III组-HbA1c高于9%[75 mmol/mol]。在上午8:00患者处于空腹状态时采集用于生化检测的血样。采用标准化的国际临床化学和检验医学联合会（IFCC）方法测定HbA1c。通过酶联免疫吸附测定（ELISA）法测定OC、OPG、RANKL、瘦素和脂联素。采用方差分析和多元回归分析进行统计分析。
观察到不同HbA1c值组之间瘦素和骨钙素水平存在显著差异（p=0.03，p=0.04）。经年龄校正的多元回归分析表明，血清OC和瘦素与HbA1c水平呈负相关（r=-0.22，p=0.004；r=-0.27，p=0.0001）。相反，血清OPG与HbA1c（r=0.26，p=0.02）、脂联素（r=0.26，p=0.02）以及RANKL（r=0.27，p=0.02）水平呈正相关。OC与HbA1c的相关性在I组（糖尿病代谢控制良好患者）中最强（r=-0.43，p=0.03）。在该组中，经年龄和体重指数校正的多元回归分析显示，瘦素与每日胰岛素剂量呈正相关（r=0.52，p=0.009）。在II组和III组中，经年龄和体重指数校正的多元回归分析显示，OC与瘦素呈负相关（r=-0.37，p=0.01）。
我们的数据表明，T1DM儿童患者的骨、脂肪组织与糖代谢之间存在显著关系。结果证实，代谢控制不佳与骨形成减少有关。另一方面，脂肪和骨组织可能以胰岛素依赖的方式影响糖代谢。基于这些数据，瘦素或OC可能潜在地用作T1DM的额外治疗药物。
