Increased fasting serum glucose concentration is associated with adverse knee structural changes in adults with no knee symptoms and diabetes
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, VIC 3004, Australia. Maturitas
(Impact Factor: 2.94).
06/2012; 72(4):373-8. DOI: 10.1016/j.maturitas.2012.05.013
There is evidence to suggest that elevated glucose concentration and clinical diabetes are associated with osteoarthritis (OA). However, the association may be confounded by knee symptoms, concomitant treatment for OA or diabetes. We performed a longitudinal cohort study to examine the relationship between serum glucose concentration and knee structure in adults with no knee symptoms or diabetes.
179 participants who had fasting serum glucose measurements at 1990-4, with no knee symptoms or diabetes (physician-diagnosed or fasting serum glucose ≥7 mmol/L), underwent knee MRI in 2003-4 and 2 years later. Body mass index was measured at 1990-4 and 2003-4. Cartilage volume and bone marrow lesions were determined from MRI at 2003-4 and 2006-7.
Fasting serum glucose concentration was positively associated with the rate of tibial cartilage volume loss over 2 years in women (B=44.2mm(3), 95% CI 4.6, 83.8) but not in men (B=6.0mm(3), 95% CI -68.5, 80.6). Fasting serum glucose concentration was positively associated with incident bone marrow lesions in women (OR=5.76, 95% CI 1.06, 31.21) but not in men (OR=0.11, 95% CI 0.01, 1.79) with significant gender difference (p=0.001 for interaction).
Increased fasting serum glucose concentration in a non-diabetic population was associated with adverse structural changes at the knee in women but not in men, suggesting that there may be susceptibility to knee structural change even below the arbitrary "diabetic range" of serum glucose levels. The sex differences warrant further investigation as this may be one mechanism underlying the sex difference in knee OA.
Available from: Sultana Monira Hussain
- "Differences in body composition may account for these discrepancies, as increased fat mass is associated with increased dyslipidaemia ; none of these studies accounted for body composition. IFG has been found to be associated with adverse structural changes (increased cartilage volume loss and incident BMLs) over 2 years in the knee for healthy women without knee OA or diabetes . Cross-sectional studies showed conflicting findings for the association between blood glucose levels and OA, as some Table 3 Incidence of total hip replacement due to osteoarthritis in relation to components of the metabolic syndrome "
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ABSTRACT: To examine whether components of metabolic syndrome (MetS), either singly or additively, were associated with the incidence of severe knee and hip OA, and whether these associations were independent of obesity assessed by body mass index (BMI).
Twenty thousand, four hundred and thirty participants who had blood lipids, anthropometric and blood pressure measurements during 2003-2007 were selected from the Melbourne Collaborative Cohort Study. MetS was defined as central obesity assessed by waist circumference and any two of raised triglyceride level, reduced HDL cholesterol level, hypertension or impaired fasting glycaemia. The incidence of total knee and hip replacement was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry.
Six hundred and sixty participants had knee OA and 562 had hip OA. After adjustment for age, gender, country of birth, education, physical activity and BMI, central obesity [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.25-2.01] and hypertension (1.24, 1.05-1.48) were associated with increased risk of knee OA. The accumulation of MetS components was associated with knee OA risk, independent of BMI: one component, 2.12 (1.15-3.91); two components, 2.92 (1.60-5.33) and three or more components, 3.09 (1.68-5.69). No statistically significant associations were observed for hip OA.
Cumulative number of MetS components and central obesity and hypertension were associated with increased risk of severe knee OA, independent of BMI. No associations were observed with severe hip OA. These findings suggest that the pathogenesis of knee and hip OA differ and that targeting the management of MetS may reduce the risk of knee OA.
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Effective induction of human mesenchymal stem cell (hMSC) differentiation for regenerative medicine applications remains a great challenge. While much research has studied hMSC activity during differentiation, it is unclear whether pre-differentiation culture can modulate differentiation capacity. We investigate the effect of glucose concentration in pre-differentiation/expansion culture on modulating chondrogenic capacity of hMSCs, and explore the underlying molecular mechanism.
The extent of chondrogenesis of hMSCs previously cultured with different concentrations of glucose was evaluated. Transforming growth factor-beta (TGF-β) signaling molecules and protein kinase C (PKC) were analyzed to identify the role of these molecules in the regulation of glucose on chondrogenesis. In addition, hMSCs in high-glucose expansion culture were treated with the PKC inhibitor to modulate the activity of PKC and TGF-β signaling molecules.
High-glucose maintained hMSCs were less chondrogenic than low-glucose maintained cells upon receiving differentiation signals. Interestingly, we found that high-glucose culture increased the phosphorylation of PKC and expression of type II TGF-β receptor (TGFβRII) in pre-differentiation hMSCs. However, low-glucose maintained hMSCs became more responsive to chondrogenic induction with increased PKC activation and TGFβRII expression than high-glucose maintained hMSCs during differentiation. Inhibiting the PKC activity of high-glucose maintained hMSCs during expansion culture upregulated the TGFβRII expression of chondrogenic cell pellets, and enhanced chondrogenesis.
Our findings demonstrate the effect of glucose concentration on regulating the chondrogenic capability of pre-differentiation hMSCs, and provide insight into the mechanism of how glucose concentration regulates PKC and TGF-β signaling molecules to prime pre-differentiation hMSCs for subsequent chondrogenesis.
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ABSTRACT: Diabetes mellitus is an enormous menace to public health globally. This chronic disease of metabolism will adversely affect the skeleton if not controlled. Both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are associated with an increased risk of osteoporosis and fragility fractures. Bone mineral density is reduced in T1DM, whereas patients with T2DM have normal or slightly higher bone density, suggesting impaired bone quality is involved. Detrimental effects of T1DM on the skeleton are more severe than T2DM, probably because of the lack of osteo-anabolic effects of insulin and other pancreatic hormones. In both T1DM and T2DM, low bone quality could be caused by various means, including but not limited to hyperglycemia, accumulation of advanced glycosylation end products (AGEs), decreased serum levels of osteocalcin and parathyroid hormone. Risk for osteoarthritis is also elevated in diabetic population. How diabetes accelerates the deterioration of cartilage remains largely unknown. Hyperglycemia and glucose derived AGEs could contribute to the development of osteoarthritis. Moreover, it is recognized that oral antidiabetic medicines affect bone metabolism and turnover as well. Insulin is shown to have anabolic effects on bone and hyperinsulinemia may help to explain the slightly higher bone density in patients with T2DM. Thiazolidinediones can promote bone loss and osteoporotic fractures by suppressing osteoblastogenesis and enhancing osteoclastogenesis. Metformin favors bone formation by stimulating osteoblast differentiation and protecting them against diabetic conditions such as hyperglycemia. Better knowledge of how diabetic conditions and its treatments influence skeletal tissues is in great need in view of the growing and aging population of patients with diabetes mellitus.
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