Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Childhood obesity is prevalent and linked to the development of Type 2 diabetes mellitus (DM) and poor bone health. Some PUFA enhance bone mass and thus may improve bone health in obese children. The study objective was to determine the effects of dietary (n-6) compared with (n-3) essential PUFA and long-chain PUFA (LCPUFA) on bone in an obese and insulin-resistant state. Male fa/fa (n = 48) and lean Zucker rats (n = 48) were fed diets containing safflower oil [SO, high (n-6) PUFA], flaxseed oil [FXO, high (n-3) PUFA], or menhaden oil [MO, high (n-3) LCPUFA] for 9 wk. Measurements included the following: femur bone area (BA), mineral content (BMC), density (BMD), morphometry and ex vivo release of prostaglandin E(2) (PGE(2)); plasma osteocalcin and C-terminal telopeptides of type I collagen. Differences among groups were detected using 2-way ANOVA. Genotype effects in the fa/fa rats included lower femoral weight, length, BA, and BMC, as well as femoral head and proximal epiphysis widths compared with the lean rats, but BMD was not affected. Femur BA, BMC, and BMD did not differ among the dietary groups, but diaphysis width was elevated in the MO group and PGE(2) release was reduced by the FXO and MO diets. No genotype x diet interactions were observed. These data indicate that the fa/fa Zucker rat is at risk for low bone mass and that dietary (n-3) FA effectively reduce PGE(2) release. Whether reduced PGE(2) will support optimal peak bone mass during childhood and conserve bone mass with aging warrants investigation.
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PMID:(n-3) fatty acids reduce the release of prostaglandin E2 from bone but do not affect bone mass in obese (fa/fa) and lean Zucker rats. 1573 84

Few reports are available on bone turnover in type 2 diabetes. Impaired bone turnover in type 2 diabetes appears to result from decreased bone formation. Studies also suggest that poor glycaemic control in type 2 diabetes may contribute to osteopaenia. The aim of this study was to investigate biochemical markers of bone turnover in males with poorly controlled type 2 diabetes and look for correlations with glycaemic control and gonadal and hypophyseal hormonal axis. Consecutive male patients with poorly controlled type 2 diabetes and attending the internal medicine department during a period of 6 months were enrolled. The patients were receiving oral hypoglycaemic agents (metformin or sulphonylureas or both). None of the patients had any evidence of macroangiopathy, nephropathy or neuropathy. Only two patients had proliferative retinopathy. Serum osteocalcin, crosslaps (C-telopeptide, CTx), parathyroid hormone (PTH), testosterone, oestrogen, prolactin, follicle-stimulating hormone (FSH) and luteinising hormone (LH) were measured in 35 patients and 35 controls. The mean age of the study population was 53.7 (10.3) years (range: 50.2-57.3) and the mean disease duration was 8.6 (6.0) years (range: 6.5-10.7). No differences between patients and controls were observed in serum calcium, phosphorus, creatinine, albumin, PTH, CTx, oestrogen, testosterone, LH, FSH, prolactin and urinary calcium. Patients had lower serum levels of osteocalcin than controls with a significant statistical difference [15.3 (4.1) vs 18.3 (5.3), p=0.012]. There was a negative significant statistical correlation between CTx levels and HbA1c (r=-0.41, p< 0.05). Our study suggested that bone formation is altered in type 2 diabetes and that bone turnover is affected by glycaemic control status.
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PMID:Bone metabolism in male patients with type 2 diabetes. 1574 54

We assessed the effect of chronic hyperglycemia on bone mineral density (BMD) and bone remodeling in patients with type 2 diabetes mellitus. We investigated 42 patients with type 2 diabetes under stable control for at least 1 year, 22 of them with good metabolic control (GMC: mean age = 48.8 +/- 1.5 years, 11 females) and 20 with poor metabolic control (PMC: mean age = 50.2 +/- 1.2 years, 8 females), and 24 normal control individuals (CG: mean age = 46.5 +/- 1.1 years, 14 females). We determined BMD in the femoral neck and at the L2-L4 level (DEXA) and serum levels of glucose, total glycated hemoglobin (HbA1), total and ionic calcium, phosphorus, alkaline phosphatase, follicle-stimulating hormone, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OH-D), insulin-like growth factor I (IGFI), osteocalcin, procollagen type I C propeptide, as well as urinary levels of deoxypyridinoline and creatinine. HbA1 levels were significantly higher in PMC patients (12.5 +/- 0.6 vs 7.45 +/- 0.2% for GMC and 6.3 +/- 0.9% for CG; P < 0.05). There was no difference in 25-OH-D, iPTH or IGFI levels between the three groups. BMD values at L2-L4 (CG = 1.068 +/- 0.02 vs GMC = 1.170 +/- 0.03 vs PMC = 1.084 +/- 0.02 g/cm(2)) and in the femoral neck (CG = 0.898 +/- 0.03 vs GMC = 0.929 +/- 0.03 vs PMC = 0.914 +/- 0.03 g/cm(2)) were similar for all groups. PMC presented significantly lower osteocalcin levels than the other two groups, whereas no significant difference in urinary deoxypyridine was observed between groups. The present results demonstrate that hyperglycemia is not associated with increased bone resorption in type 2 diabetes mellitus and that BMD is not altered in type 2 diabetes mellitus.
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PMID:Lack of relationship between glycemic control and bone mineral density in type 2 diabetes mellitus. 1727 58

Visfatin (also known as pre-B cell colony-enhancing factor or PBEF) is a novel adipocytokine that is highly expressed in visceral fat and upregulated in obesity and type 2 diabetes mellitus. Visfatin binds to and activates the insulin receptor (IR), thereby exerting insulin-mimetic effects in various cell lines. IR has been detected in osteoblasts, which is consistent with the role of insulin as an important osteotropic hormone. This study investigated the actions of visfatin on human primary osteoblasts. The expression and tyrosine phosphorylation of IR, IR substrate-1 (IRS-1), and IRS-2 were determined by immunoprecipitation and immunoblotting. Cell proliferation was determined by measuring [(3)H]thymidine incorporation and cell number. Glucose uptake was determined by measuring 2-[(3)H]deoxyglucose incorporation. Real-time quantitative reverse-transcription polymerase chain reaction (PCR) was used for determining alkaline phosphatase (ALP), osteocalcin, and type I collagen mRNA expression. Enzyme-linked immunosorbent assay and radioimmunoassay were used for measuring ALP activity, osteocalcin secretion, and type I collagen production. We found that visfatin induced tyrosine phosphorylation of IR, IRS-1, and IRS-2. Moreover, the effects of visfatin - glucose uptake, proliferation, and type I collagen enhancement of cultured human osteoblast-like cells - bore a close resemblance to those of insulin and were inhibited by hydroxy-2-naphthalenylmethylphosphonic acid tris-acetoxymethyl ester, a specific inhibitor of IR tyrosine kinase activity. We also unexpectedly found that visfatin downregulated osteocalcin secretion from human osteoblast-like cells. These data indicate that the regulation of glucose uptake, proliferation, and type I collagen production by visfatin in human osteoblasts involves IR phosphorylation, the same signal-transduction pathway used by insulin.
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PMID:Insulin-like effects of visfatin on human osteoblasts. 1734 Feb 25

There have been several reports about associations of serum leptin or adiponectin with bone mineral density and biochemical markers of bone turnover. However, the precise roles of adipocytokines in bone metabolism have not been fully elucidated. We investigated the associations of serum level of leptin or adiponectin with bone mineral density, serum osteocalcin, and urinary N-terminal telopeptide of type I collagen (NTX) in 40 Japanese patients with type 2 diabetes mellitus. Bone mineral density was measured by using dual-energy x-ray absorptiometry at different sites (distal radius, femoral neck, and lumbar spine) and was expressed as z score. Multiple regression analysis revealed that there were significant positive correlations between serum leptin or adiponectin level and z score at the distal radius, but not at the femoral neck or the lumbar spine. Although no correlation was observed between serum leptin and serum osteocalcin, there was a significant negative correlation between serum leptin and urinary NTX, a marker of bone resorption. No correlation was observed between serum adiponectin and serum osteocalcin or urinary NTX. These results indicate that leptin and adiponectin may have a protective effect on bone metabolism in patients with type 2 diabetes mellitus.
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PMID:Serum leptin and adiponectin are positively associated with bone mineral density at the distal radius in patients with type 2 diabetes mellitus. 1744 36

It is well known that patients with type 1 diabetes mellitus exhibit bone abnormalities as one of the complications of the disease. Whether this occurs in type 2 diabetes is controversial. This uncertainty could be because type 2 diabetes includes several pathological types such as obese and non-obese. To examine the bone abnormalities in non-obese type 2 diabetes, we used Spontaneously Diabetic Torii (SDT) rats, which is a newly established model of non-obese type 2 diabetes. Sprague-Dawley (SD) rats were used as a control group (n=17). SDT rats were divided into two groups: the diabetic (DM) group (n=18) and the DM+insulin (INS) group (n=18) at 20 weeks of age. The DM+INS group received subcutaneously implanted insulin pellets every 2 weeks. At 36 weeks of age, the rats were killed, and we evaluated bone formation and the effect of insulin on bone formation, blood and urine analyses, bone mineral density (BMD), histomorphometry, and mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN). Despite renal function not being impaired, BMD and bone strength were significantly lower in the DM group than in the control group. Osteoid volume per bone volume, osteoblast surface per bone surface, eroded surface per bone surface, osteoclast surface per bone surface, the mineral apposition rate, and the bone formation rate per bone surface were significantly lower in the DM group than in the control and DM+INS groups. The mRNA expression of ALP and OCN was significantly lower in the DM group than in the control group. Furthermore, 8-hydroxydeoxyguanosine, which is an oxidative stress marker, was remarkably elevated in the DM group. These abnormalities were recovered by insulin therapy. Our data support the notion that non-obese type 2 diabetes is associated with a low turnover of bone and that the abnormalities are ameliorated by insulin. The SDT rat may be a useful animal model for examining the mechanisms of bone abnormalities in non-obese type 2 diabetes.
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PMID:Bone formation in spontaneously diabetic Torii-newly established model of non-obese type 2 diabetes rats. 1803 64

It is unclear whether metformin, one of the anti-hyperglycemic agents commonly used for type 2 diabetes, could affect bone formation through activation of AMP-activated protein kinase (AMPK). In order to clarify this issue, we investigated the effects of metformin on the differentiation and mineralization of osteoblastic MC3T3-E1 cells as well as intracellular signal transduction. Metformin (50 microM) significantly increased collagen-I and osteocalcin mRNA expression, stimulated alkaline phosphatase activity, and enhanced cell mineralization. Moreover, metformin significantly activated AMPK in dose- and time-dependent manners, and induced endothelial nitric oxide synthase (eNOS) and bone morphogenetic protein-2 (BMP-2) expressions. Supplementation of Ara-A (0.1mM), a specific AMPK inhibitor, significantly reversed the metformin-induced eNOS and BMP-2 expressions. Our findings suggest that metformin can induce the differentiation and mineralization of osteoblasts via activation of the AMPK signaling pathway, and that this drug might be beneficial for not only diabetes but also osteoporosis by promoting bone formation.
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PMID:Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression. 1872 96

In order to investigate the underlying mechanism of alterations in bone mineral metabolism in patients with type 2 diabetes, we determined circulating levels of bone functional markers along with urinary excretion of sorbitol (SOR) and bone mineral density (BMD), and also examined their mutual interrelationship. A total of 151 male type 2 diabetic patients were examined in this study. Forty-eight age-matched male healthy subjects were also studied as the controls. A significant reduction of serum intact osteocalcin (i-OC) was found in the diabetic groups (p<0.01). On the other hand, circulating levels of tartrate resistant acid phosphatase (TRAP) in the diabetic patients were significantly higher than those in the controls (p<0.01). Interestingly, a significantly negative relationship was observed between BMD and serum TRAP (p<0.01), although no significant relationship was noted between BMD and serum i-OC in diabetic patients. Urinary excretion of SOR was significantly elevated in the diabetic patients when compared with the controls (p<0.01). In addition, a significantly positive correlation was observed between serum TRAP and urinary SOR (p<0.01), but not between serum i-OC and urinary SOR. Elevated serum TRAP in diabetes was reduced after the administration of aldose reductase inhibitor (p<0.05). It seems most likely that the increase in osteoclastic function probably due to accelerated polyol pathway plays a crucial role in the pathogenesis of decreased bone mineral content in male patients with type 2 diabetes.
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PMID:Increased bone resorption may play a crucial role in the occurrence of osteopenia in patients with type 2 diabetes: Possible involvement of accelerated polyol pathway in its pathogenesis. 1877 97

Although patients with type 2 diabetes show no bone mineral density (BMD) reduction, fracture risks are known to increase. It is unclear why the patients have an increased risk of fracture despite sufficient BMD. We investigated the relationships of body mass index (BMI), HbA(1c), and urinary C-peptide (uC-peptide) versus BMD, bone metabolic markers, serum adiponectin, and prevalent vertebral fracture (VF). A total of 163 Japanese type 2 diabetic men were consecutively recruited, and radiographic and biochemical data were collected. BMI was positively correlated with BMD at the whole body, lumbar spine, and femoral neck (P < 0.05) and negatively correlated with osteocalcin and urinary N-terminal cross-linked telopeptide of type-I collagen (uNTX) (P < 0.01). HbA(1c) was negatively correlated with osteocalcin (P < 0.01) but not BMD at any site. Subjects were classified into four groups based on BMI and HbA(1c) (group LL BMI < 24 and HbA(1c) < 9, group LH BMI < 24 and HbA(1c) > or = 9, group HL BMI > or = 24 and HbA(1c) < 9, group HH BMI > or = 24 and HbA(1c) > or = 9). Serum adiponectin, osteocalcin, and uNTX were lower and the incidence of VF was higher despite sufficient BMD in the HH group. Multivariate logistic regression analysis adjusted for age, duration of diabetes, uC-peptide, and estimated glomerular filtration rate showed that the HH group was associated with the presence of a VF and multiple VFs (odds ratio [OR] = 3.056, 95% confidence interval [CI] 1.031-9.056, P = 0.0439, and OR = 5.415, 95% CI 1.126-26.040, P = 0.0350, respectively). Combination of obesity with hyperglycemia was a risk factor for VF despite sufficient BMD in diabetic men.
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PMID:Combination of obesity with hyperglycemia is a risk factor for the presence of vertebral fractures in type 2 diabetic men. 1894 27

It has been suggested that hormones released after nutrient absorption, such as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 2 (GLP-2), could be responsible for changes in bone resorption. However, information about the role of GLP-1 in this regard is scanty. Diabetes-related bone loss occurs as a consequence of poor control of glucose homeostasis, but the relationship between osteoporosis and type 2 diabetes remains unclear. Since GLP-1 is decreased in the latter condition, we evaluated some bone characteristics in streptozotocin-induced type 2 diabetic (T2D) and fructose-induced insulin-resistant (IR) rat models compared to normal (N) and the effect of GLP-1 or saline (control) treatment (3 days by osmotic pump). Blood was taken before and after treatment for plasma measurements; tibiae and femora were collected for gene expression of bone markers (RT-PCR) and structure (microCT) analysis. Compared to N, plasma glucose and insulin were, respectively, higher and lower in T2D; osteocalcin (OC) and tartrate-resistant alkaline phosphatase 5b were lower; phosphate in IR showed a tendency to be higher; PTH was not different in T2D and IR; all parameters were unchanged after GLP-1 infusion. Bone OC, osteoprotegerin (OPG) and RANKL mRNA were lower in T2D and IR; GLP-1 increased OC and OPG in all groups and RANKL in T2D. Compared to N, trabecular bone parameters showed an increased degree of anisotropy in T2D and IR, which was reduced after GLP-1. These findings show an insulin-independent anabolic effect of GLP-1 and suggest that GLP-1 could be a useful therapeutic agent for improving the deficient bone formation and bone structure associated with glucose intolerance.
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PMID:Effect of GLP-1 treatment on bone turnover in normal, type 2 diabetic, and insulin-resistant states. 1921 81


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