Soichi Kurioka

Serum Osteocalcin Level Is Associated with Glucose Metabolism and Atherosclerosis Parameters in Type 2 Diabetes Mellitus

CONTEXT Recent animal studies showed that osteocalcin action is related to not only bone metabolism but also glucose metabolism and fat mass. We investigated the relationship between two bone formation markers, serum osteocalcin and bone-specific alkaline phosphatase, and glucose metabolism, serum adiponectin, and the amount of fat mass as well as atherosclerosis parameters in men and postmenopausal women with type 2 diabetes. METHODS A total of 179 men and 149 postmenopausal women were recruited consecutively, and radiographic and biochemical characteristics were collected. Brachial-ankle pulse wave velocity (baPWV) and intima-media thickness (IMT) were evaluated as the parameters of atherosclerosis. RESULTS Multiple regression analysis adjusted for age, duration of diabetes, body mass index, and serum creatinine showed that osteocalcin negatively correlated with fasting plasma glucose and hemoglobin A(1c) in both men and postmenopausal women (P < 0.05) and with percent fat, baPWV, and IMT in men (P < 0.05). Osteocalcin positively correlated with total adiponectin in postmenopausal women (P < 0.001). After additional adjustments for systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, hemoglobin A(1c), and Brinkmann index, osteocalcin still significantly and negatively correlated with baPWV and IMT in men. In contrast, osteocalcin did not correlate with fasting C-peptide, and bone-specific alkaline phosphatase did not correlate with any variable in either men or postmenopausal women. CONCLUSIONS Serum osteocalcin is associated with glucose and total adiponectin levels, fat mass, and atherosclerosis parameters in patients with type 2 diabetes, suggesting that osteocalcin is important for not only bone metabolism but also glucose and fat metabolism.

Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus

SummaryAlthough recent animal studies have shown that undercarboxylated osteocalcin acts as a hormone regulating glucose metabolism and fat mass, little is known about the relationships in humans. We reported here for the first time that undercarboxylated osteocalcin were associated with glucose/fat metabolism in patients with type 2 diabetes.IntroductionRecent studies have shown that undercarboxylated osteocalcin (ucOC) acts as a hormone regulating glucose metabolism and fat mass. We investigated the relationship between ucOC as well as other bone turnover markers [serum OC, bone-specific alkaline phosphatase (BAP), and urinary N-terminal cross-linked telopeptide of type-I collagen] versus serum levels of glucose, fasting serum C-peptide, and adiponectin as well as the amount of fat mass in type 2 diabetes.MethodsA total of 180 men and 109 postmenopausal women were consecutively recruited, and radiographic and biochemical characteristics were collected. Fat mass was measured by dual X-ray absorptiometry (DXA) and computed tomography (CT).ResultsIn men, ucOC negatively correlated with percent trunk fat (%trunk fat; by DXA) and visceral/subcutaneous fat ratio (by CT) as well as fasting plasma glucose and HbA1c (at least p < 0.05). Multiple regression analysis showed that these associations were still significant independent of age, duration of diabetes, body stature, and renal function as well as glucose or fat metabolism, whereas BAP, another bone formation marker, did not correlate with any variable. On the other hand, although ucOC also negatively correlated with %fat and %trunk fat as well as HbA1c (at least p < 0.05) in postmenopausal women, we found no significant association in multiple regression analysis.ConclusionsThese findings suggest that ucOC is associated with plasma glucose level and fat mass in men with type 2 diabetes.

Associations between components of the metabolic syndrome versus bone mineral density and vertebral fractures in patients with type 2 diabetes

The association of bone with the metabolic syndrome and its features, visceral fat accumulation or insulin resistance, remains unclear. We determined visceral and subcutaneous fat areas (V and S) by computed tomography on 187 men (28-83 years) and 125 postmenopausal women (46-82 years) with type 2 diabetes. Men whose V was 100 cm(2) or more had significantly lower urinary N-terminal cross-linked telopeptide of type-I collagen (p=0.005), higher femoral neck bone mineral density (FN-BMD) (p=0.004), and lower prevalence of vertebral fractures (VFs) (p=0.04) than controls. Fat mass, V, S, and lean body mass positively correlated with FN-BMD in men and with lumbar (L) and FN-BMD in women. When adjusted for weight, these correlations became negative. Urinary C-peptide positively correlated with FN-BMD in both genders. Multivariate logistic regression analysis adjusted for age, height, weight, L-BMD, duration of diabetes, and diabetes therapies identified V in men and urinary C-peptide in women as factors inversely associated with the presence of VFs [odds ratio (OR)=0.61 per SD increase, p=0.04, and OR=0.32, p=0.01, respectively]. These findings suggest that, of the components of the metabolic syndrome, body fat in gravity and hyperinsulinemia could increase FN-BMD in diabetic subjects. Visceral fat in men and hyperinsulinemia in women may protect against VFs independent of weight, L-BMD, diabetes duration, or therapies.

Adiponectin Is Associated with Changes in Bone Markers during Glycemic Control in Type 2 Diabetes Mellitus

OBJECTIVE Although several experiments show that adiponectin is associated with bone metabolism, a relationship between adiponectin and bone markers is still unclear. We monitored chronological changes in hyperglycemia, serum adiponectin, and bone markers during glycemic control in type 2 diabetes and analyzed relationships among these parameters. SUBJECTS AND RESULTS A total of 50 Japanese patients with poorly controlled type 2 diabetes [initial hemoglobin A(1c) (HbA(1c)) = 10.0 +/- 2.5%] were recruited, and biochemical data were collected before and after glycemic control for a month. Of bone formation markers, bone-specific alkaline phosphatase was decreased with a mean change of -3.11 [95% confidence interval (CI), -5.03 to -1.20; P < 0.01], whereas osteocalcin (OC) was increased with a mean change of 1.94 (95% CI, 1.45-2.42; P < 0.001) and undercarboxylated OC (ucOC)/OC ratio was decreased with a mean change of -0.15 (95% CI, -0.27 to -0.03; P < 0.01). Although adiponectin level was not significantly different before and after glycemic control, baseline adiponectin level, but not HbA(1c), was positively correlated with changes in OC, ucOC, and urinary N-terminal cross-linked telopeptide of type I collagen (uNTX) (r = 0.30, P =0.04; r = 0.32, P = 0.03; and r = 0.36, P = 0.01, respectively). Changes in adiponectin were also negatively correlated with changes in OC and uNTX (r = -0.42, P < 0.01; and r = -0.38, P < 0.01, respectively). Changes in HbA(1c) were negatively correlated with changes in OC (r = -0.30, P = 0.03). CONCLUSION These findings show that treatments for hyperglycemia enhance OC level and suggest that serum adiponectin level before starting to compensate poorly controlled diabetics could predict the subsequent improvement of bone remodeling markers during glycemic control.

Association of cognitive dysfunction with hippocampal atrophy in elderly Japanese people with type 2 diabetes

This study aimed to examine the associations of cognitive function with hippocampal and whole brain atrophies, age, education, and diabetes-related parameters in patients with type 2 diabetes. Sixty-one patients over 65 years of age with type 2 diabetes and 53 age- and sex-matched non-diabetic controls were enrolled. Hippocampal and whole brain atrophies were assessed by quantifying hippocampal and brain volumes by brain magnetic resonance imaging. Cognitive function was evaluated by Mini-Mental State Examination (MMSE) and the Revised Hasegawa Dementia Scale (HDS-R). Compared with the non-diabetic group, patients with type 2 diabetes showed significant increases in hippocampal and whole brain atrophies. The MMSE and HDS-R scores in type 2 diabetic patients showed significant negative correlations with age and significant positive correlations with years of education. These scores were also significantly negatively correlated with hippocampal atrophy, but not whole brain atrophy. Hippocampal atrophy in diabetic patients did not, however, correlate with age, years of education, or diabetes-related parameters. We showed hippocampal and whole brain atrophies to be more frequent in elderly patients with type 2 diabetes than in non-diabetic controls. Their cognitive functions were significantly and negatively associated with hippocampal atrophy.

Close relationship between serum hyaluronan levels and vascular function in patients with type 2 diabetes

Abstract Objective: To clarify the relationship between serum hyaluronan levels and vascular function in type 2 diabetic patients. Methods: A cross-sectional cohort study. Results: In multivariate regression analysis, endothelium-dependent flow-mediated dilation was associated with age and duration of diabetes, but not with serum hyaluronan level, while endothelium-independent nitroglycerine-mediated dilation (NMD) was only associated with serum hyaluronan level (standardized estimate = −0.401, p = 0.003). NMD in the lowest tertile of hyaluronan level was significantly higher than the other tertiles (15.9% versus 12.5% and 10.4%, p = 0.047 and p = 0.002, respectively). Conclusions: Serum hyaluronan level may be useful as a surrogate marker for early changes in the vascular function, which often occurs in patients with diabetes mellitus.