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)

To investigate the frequency and etiology of diabetic osteopenia, we measured spinal bone mineral density (SBMD), total body bone mineral density (TBBMD), total body fat and lean body mass in 69 female diabetic patients (14 IDDMs and 55 NIDDMs). SBMD decreased with age in both IDDM and NIDDM, but when expressed as a percentage of age-matched normal Japanese females, some had lower SEMD, but others had normal or increased SBMD. Postmenopausal IDDM patients had lower SBMD than postmenopausal NIDDM patients. Thirteen out of 69 (18.8%) had an SBMD lower than 90% of age-matched controls. SBMD correlated positively with TBBMD. Those with lower SBMD had poor glycemic control, but there was no relation between SBMD and either duration of diabetes or presence of retinopathy and/or nephropathy. IDDM patients had lower 1.25 (OH)2D, osteocalcin than NIDDMs. SBMD correlated negatively with urinary pyridinoline and deoxypyridinoline excretion. SBMD correlated positively with body weight, and those with lower SBMD had significantly lower body mass index, body weight, fat weight and lean body mass than those with normal or increased SBMD. These results suggest that IDDM patients may be at higher risk of losing bone postmenopausally, and diabetic patients with lower SBMD have characteristics of poor diabetic control, lean habitus, low serum 1.25 (OH)2D.
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PMID:[Spinal bone mineral density in the female diabetic patients]. 149 83

The goal of this study was to evaluate in 98 diabetic patients the serum levels of osteocalcin (OC) and their relationship with glycosylated hemoglobin levels and with the duration, calculated in years, of the disease. Patients were divided in 3 groups: 17 IDDM patients, 62 NIDDM patients treated with oral hypoglycaemic agents, and 19 NIDDM patients treated with insulin. Results were compared to 2 different control groups. In IDDM patients OC serum levels were significantly lower if compared either to control group and to NIDDM patients. The 2 groups of NIDDM patients showed significantly higher OC values than controls. No significant relationship resulted between OC levels, the duration of diabetes and the glycosylated hemoglobin values. The results of the study indicate a direct correlation between pancreatic function and osteoblastic activity: insulin lack is associated with reduced OC serum levels.
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PMID:[Serum osteocalcin and diabetes mellitus. A study of 98 patients]. 155 61

Recent studies indicate that serum levels of osteocalcin, a 49-aminoacid bone matrix protein, are a biochemical marker of bone formation. In order to study bone metabolism in diabetes mellitus, in 28 patients with Type 1 (insulin-dependent) diabetes mellitus, in 38 patients with Type 2 (non-insulin-dependent) diabetes mellitus and two control groups, matched for Type 1 and Type 2 diabetic patients, respectively, serum levels of osteocalcin, parathyroid hormone and 25 hydroxy vitamin D were measured by radioimmunoassay. Whereas in Type 1 diabetic patients and control subjects serum levels of osteocalcin and 25 hydroxy vitamin D were not statistically different, serum osteocalcin and 25 hydroxy vitamin D levels were significantly decreased in Type 2 diabetic patients when compared with corresponding control subjects (p less than 0.03 and p less than 0.001, respectively). Independent of the type of diabetes, serum parathyroid hormone levels were comparable in diabetic patients and matched control subjects. Serum osteocalcin levels were significantly lower in Type 1 diabetic patients with retinopathy and/or proteinuria than in Type 1 diabetic patients without microangiopathy (p less than 0.05). Whereas serum parathyroid hormone levels in Type 2 diabetic patients with retinopathy and/or proteinuria were significantly increased (p less than 0.02), 25 hydroxy vitamin D levels were decreased (p less than 0.02) when compared with Type 2 diabetic patients without microangiopathy. Our data give evidence of a vitamin D deficiency and a decreased bone formation in patients with Type 2 diabetes mellitus. In Type 1 diabetes mellitus bone formation as reflected by serum osteocalcin levels is influenced by the presence or absence of microangiopathic complications.
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PMID:Serum osteocalcin levels in diabetes mellitus: analysis of the type of diabetes and microvascular complications. 326 86

Patients with poorly controlled noninsulin dependent diabetes mellitus (NIDDM) are shown to have higher bone mass. However, the influence of changes in glycemic control on bone turnover is not known. To clarify whether metabolic improvement of poorly controlled NIDDM affects bone turnover, markers for glucose, mineral, and bone metabolism were assessed before and after glycemic control for 3 weeks in 78 poorly controlled NIDDM patients with initial hemoglobin A1c over 8%. Metabolic improvement caused a reduction in urinary calcium (Ca) and phosphate (Pi) and serum 1,25(OH)2D levels, and an increase in serum Pi without changes in serum Ca or parathyroid hormone levels. Bone resorption markers, urinary deoxypyridinoline (Dpd) and type I collagen carboxy-terminal telopeptide (CTx), as well as a bone formation marker, serum bone type alkaline phosphatase (BALP), were reduced. However, another bone formation marker, serum osteocalcin (OC), was low before treatment and was elevated after treatment. The decrease in Dpd, CTx and BALP, but not the increase in OC, correlated with each other and with the improvement in glycemic indices. In conclusion, metabolic improvement of poorly controlled NIDDM decreases bone turnover within a short period. Thus, glycemic control may protect NIDDM patients from bone loss. It is possible that serum OC is affected by hyperglycemia per se, and may not correctly reflect bone turnover.
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PMID:Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover. 928 19

Osteoblast deficit plays a principal role in the development of diabetic osteopenia. We have previously reported that high glucose conditions impair the function of osteoblast-like MG-63 cells. This study was performed to assess the sensitivity of osteoblasts to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in patients with type 2 diabetes without insulin deficiency or overt diabetic complications. During stimulation with 1,25(OH)2D3 at 2.0 micrograms/day for 6 consecutive days in 9 type 2 diabetic patients, serum levels of bone alkaline phosphatase (BALP), osteocalcin (OC) and the carboxyterminal propeptide of type 1 procollagen, and the urinary excretion of pyridinoline and deoxypyridinoline (DPYR), were monitored. As parameters of glycemic control, the mean level of fasting plasma glucose (mFPG) throughout the 1,25(OH)2D3 stimulation test and the level of HbA1C were used. 1,25(OH)2D3 increased serum 1,25(OH)2D significantly by day 2, which was followed by a significant reduction in the serum level of intact parathyroid hormone. The maximal increment of serum OC adjusted for that of 1,25(OH)2D was negatively correlated with both mFPG and HbA1C levels (p < 0.05). Furthermore, the magnitude of 1,25(OH)2D3-induced bone resorption, as reflected by the maximal increase in urinary DPYR excretion, was negatively correlated with the mFPG level (p < 0.05). Basal BALP tended to be negatively correlated with HbA1C, although not to a significant extent. In conclusion, our findings would indicate that poor glycemic control impairs the responses of osteoblasts and osteoclasts to 1,25(OH)2D3 in normo-insulinemic type 2 diabetic patients.
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PMID:Poor glycemic control impairs the response of biochemical parameters of bone formation and resorption to exogenous 1,25-dihydroxyvitamin D3 in patients with type 2 diabetes. 1062 60

Poorly controlled type 2 or non-insulin dependent diabetes mellitus (NIDDM) patients exhibit high bone turnover, which decelerate with treatment according to the degree of improvement in glycemic control. In adults, higher bone turnover results in rapid bone loss. Therefore, deceleration of bone turnover is beneficial for bone. Troglitazone (Tro), a new anti-diabetic drug, is a thiazolidinedione (TZD) which promotes adipocyte differentiation by activating peroxisome proliferator activated receptor gamma (PPARgamma). Because, in the bone marrow, adipocytes and osteoblasts originate in common mesenchymal stem cells that are also essential for osteoclastogenesis, TZDs may directly affect bone metabolism. Thus, we examined the effects of Tro on metabolic bone markers in type 2 DM patients. Tro (400 mg/day) was administered to 33 type 2 DM patients for four weeks. The day before and four weeks after starting Tro, serum and urine samples were collected after overnight fasting. Metabolic bone markers and glycemic indices were assessed. As bone resorption markers, urinary free and total deoxypyridinoline as well as urinary collagen type I C-terminal telopeptide were measured; as bone formation markers, serum bone type and total alkaline phosphatase (BALP and ALP) levels along with osteocalcin (OC) were used. No significant changes in fasting plasma glucose or HbA1c levels were observed in our short-term treatment with Tro. All the bone resorption markers, BALP and ALP were significantly decreased. OC was not significantly changed. The discrepant changes of OC from all the other metabolic bone markers suggest limitation of the use of OC as a reliable bone formation marker in diabetics. Our results that Tro decreased metabolic bone markers before significantly improving glucose metabolism suggest that it has direct effects on bone and decreased bone turnover. TZDs may spare bone mass in NIDDM subjects through its dual effects on glucose and bone metabolism.
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PMID:Short-term treatment with troglitazone decreases bone turnover in patients with type 2 diabetes mellitus. 1072 55

The most common cause of inflammatory bone loss is periodontal disease. After bacterial insult, inflammation induces bone resorption, which is followed by new reparative bone formation. Because diabetics have a higher incidence and more severe periodontitis, we examined mechanisms by which diabetes alters the response of bone to bacterial challenge. This was accomplished with db/db mice, which naturally develop type 2 diabetes. After inoculation of bacteria osteoclastogenesis and bone resorption was measured. Both parameters were decreased in the diabetic group. Diabetes also suppressed reparative bone formation measured histologically and by the expression of osteocalcin. The impact of diabetes on new bone formation coincided with the effect of diabetes on apoptosis of bone-lining cells. Within 5 d of bacterial challenge, apoptosis declined in the wild-type animals yet remained significantly higher in the diabetic group. Thus, diabetes may cause a net loss of bone because the suppression of bone formation is greater than the suppression of bone resorption. The uncoupling of bone formation and resorption may be due in part to prolonged apoptosis of bone lining cells.
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PMID:Diabetes causes decreased osteoclastogenesis, reduced bone formation, and enhanced apoptosis of osteoblastic cells in bacteria stimulated bone loss. 1452 17

We conducted a cross-sectional examination of the role of serum vitamin K levels as they relate to bone metabolism in elderly women with type II diabetes mellitus (DM). Eighty-five elderly women with type II DM were enrolled. Three fractions of vitamin K, phylloquinone (PK), menaquinone 4 (menatetrenone; MK 4), and menaquinone 7 (MK 7), along with undercarboxylated osteocalcin (UcOC), intact osteocalcin (IOC), urinary deoxypyridinoline (udpd), urinary type I collagen N-telopeptide (NTx), and intact parathyroid hormone (IPTH) were measured. Bone mineral density was measured in the lumbar spine (LSBMD) by dual-energy X-ray absorptiometry (DXA), and T scores or Z scores were calculated. The patients were divided into two groups by T score, under -2.5 (osteoporotic group) and over -2.5 (non-osteoporotic group). UcOC levels in osteoporotics patients were significantly higher than those in the non-osteoporotic group (3.09 +/- 3.94 vs 1.82 +/- 1.76 ng/ml, P = 0.02). The correlation between Z score and logarithmic UcOC/IOC levels in type II DM showed a negative trend ( P = 0.07) and a significantly and negatively association with logarithmic NTx ( r = -0.38; P = 0.001). In osteoporotic DM, the UcOC/IOC ratio was significantly correlated with the Z score ( r = -0.61; P << 0.05). Furthermore, logarithmic UcOC/IOC showed a negative correlation with logarithmic MK 7 ( r = -0.50; P = 0.001). In conclusion, the reduction in LSBMD in elderly women with type II DM may be associated, in part, with a defect in Gamma-glutamylcarboxylation by vitamin K.
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PMID:Impaired gamma carboxylation of osteocalcin in elderly women with type II diabetes mellitus: relationship between increase in undercarboxylated osteocalcin levels and low bone mineral density. 1510 65

Retrospective and uncontrolled studies suggest that the lipid-lowering statin class of drugs has either no or beneficial effects on bone density and may reduce fracture risk. We have examined the effects of atorvastatin on serum and plasma markers of bone turnover in 25 patients (age 56 +/- 8 years) with type 2 diabetes (duration: 4.7 +/- 5.0 years, 16 female, 2 insulin-treated, 4 diet alone, and 19 on oral hypoglycemic agents) and baseline hypercholesterolemia (cholesterol 6.6 +/- 0.8 mmol/l) in a double-blind, placebo-controlled, crossover study of 12 weeks of placebo/40 mg of atorvastatin with an 8-week wash-out period. Atorvastatin resulted in a fall in total cholesterol of 2.3 +/- 0.9 mmol/l. There were no effects of active or placebo therapy on total alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin, or beta C-telopeptide of type 1 collagen (beta-CTX). We conclude that atorvastatin (40 mg/day) has no significant effect on bone turnover in man.
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PMID:The effect of atorvastatin on markers of bone turnover in patients with type 2 diabetes. 1533 14

Thiazolidinediones (TZDs) increase peripheral tissue insulin sensitivity in patients with type 2 diabetes mellitus by activating the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). In bone marrow stromal cell cultures and in vivo, activation of PPARgamma by high doses (20 mg/kg/day) of TZDs has been reported to alter stem cell differentiation by promoting commitment of progenitor cells to the adipocytic lineage while inhibiting osteoblastogenesis. Here, we have examined the in vivo effects of low-dose rosiglitazone (3 mg/kg/day) on bone, administered to mice by gavage for 90 days. Rosiglitazone-treated mice had increased weight when compared with controls, with no significant alterations in serum levels of glucose, calcium or parathyroid hormone (PTH). Bone mineral density (BMD) at the lumbar vertebrae (L1-L4), ilium/sacrum, and total body was diminished by rosiglitazone treatment. Histologically, bone was characterized by decreased trabecular bone volume and increased marrow space with no significant change in bone marrow adipocity. Decreased osteoblast number and activity due to increased apoptotic death of osteoblasts and osteocytes was apparent while osteoclast parameters and serum levels of osteocalcin, alkaline phosphatase activity, and leptin were unaltered by rosiglitazone treatment. Therefore, the imbalance in bone remodeling that follows rosiglitazone administration arises from increased apoptotic death of osteogenic cells and diminished bone formation leading to the observed decrease in trabecular bone volume and BMD. These novel in vivo effects of TZDs on bone are of clinical relevance as patients with type 2 diabetes mellitus and other insulin resistant states treated with these agents may potentially be at increased risk of osteoporosis.
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PMID:Rosiglitazone impacts negatively on bone by promoting osteoblast/osteocyte apoptosis. 1552 88


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