Insulin-Like Growth Factor-1 and Osteocalcin Are Correlated with Markers of Osteoporosis in Postmenopausal Women with Type-2 Diabetes

Objective: The study was conducted to evaluate the relation between insulin-like growth factor-1 and osteocalcin and markers of bone modulation (osteoprotegerin;OPG, receptor activator nuclear kappa B;RANK and RANK ligand;RANKL) in postmenopausal Type 2 diabetic women with and without osteoporosis. Methods: The study was conducted on 90 female divided into three groups (30 each). Group I included healthy postmenopausal women as a control, Group II included diabetic postmenopausal women without osteoporosis Group III included diabetic postmenopausal women with osteoporosis. Fasting blood samples were obtained for the determination of blood glucose, HbA1c, total and ionized calcium, OPG, RANK and RANKL. Also the levels of IGF-1 and osteocalcin were assessed. Results: In postmenopausal Type 2 diabetic women, the osteoporosis resulted in derangement in OPG/sRANKL system. The serum level of OPG was elevated while sRANKL declines in osteoporotic postmenopausal Type 2 diabetic women. IGF-1 level decreased in diabetic postmenopausal women but those women with osteoporosis showed a great decline by about 60%. IGF-1 level in osteoporotic diabetic postmenopausal women was correlated with BMD and most bone turnover markers (OPG, sRANKL, OPG/sRANKL). Osteocalcin declined significantly only in those women with osteoporosis not without osteoporosis. Conclusions: The circulating levels of OPG and sRANKL were not useful markers for bone status in postmenopausal women while the circulating levels of IGF-1 and osteocalcin might give useful information about bone status in postmenopausal diabetic women.

Effect of Maternal Diabetes on Pre- and Post-Natal Redox Status of F1 Rat Offspring

Background: The oxidative stress and disturbed redox signaling during gestation my play an important role in the fetal programming of adult diabetes. Objective: The study aimed to investigate the effects of maternal diabetes on pre- and post-natal pancreatic and peripheral tissues redox and oxidative status in order to clarify their role in the diabetogenic programming of F1 offspring. Methods: Two groups of female Wistar rats were used (diabetic and control);diabetes was neonatally induced by STZ injection to 5-day old rats. 10 pregnancies of each group were terminated at GD 17 to obtain placentas and fetal pancreas, liver, muscle and adipose tissues for prenatal measurements. The rest of pregnancies were completed to term and the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks 10 male rats were sacrificed and serum and tissues were obtained for assessment of fasting blood glucose, tissues content of 8-oxo-dG, TBARS, GSH, GSSG, antioxidant enzymes and caspase-3. Results: The results indicated that, prenatally redox status of the foetuses of diabetic mothers is shifted toward more oxidizing environment which results from elevated oxidative stress and impaired antioxidants as indicated by elevated fetal tissues content of 8-oxo-dG, TBARS and GSSG and decreased GSH and GSH/GSSG ratio. All of these induce the apoptotic pathway in fetal pancreas. Postnatally, impaired glucose tolerance in the offspring of diabetic mothers is detected at 15th week of age and no hyperglycemia was detected until age of 30 weeks in the offspring under CD while some of offspring under HCD at age 25 weeks and most of them at 30 weeks have developed hyperglycemia. The pancreas of the offspring of diabetic mothers suffers from oxidative stress from the 5th week of age as indicated by elevated levels of nuclear and mitochondrial 8-oxo-dG contents and TBARS. Also, GSH level showed depletion with age and the activity of glutathione reductase was lower in the β-cell and hepatic tissues of the offspring of diabetic mothers. The prenatal shift of redox status persists postnatal and exaggerates with age which may explain the significant induction of the apoptotic pathway in the pancreatic β-cell. Conclusion: Maternal diabetes can crucially affect the redox status in fetal tissues prenatally and these effects can persist postnatal which may play an important role in the programming of the metabolic state of the offspring. Postnatal diet play important role in accelerating development of metabolic derangements and aggravates oxidative stress in the tissues of F1 offspring.