Association of Insulin Glargine Treatment with Bone Mineral Density in Patients with Type 2 Diabetes Mellitus.

PURPOSE: To assess the association of type 2 diabetes mellitus (T2DM) and insulin glargine treatment with bone mineral density (BMD) in Chinese people. METHODS: This retrospective study included 50 subjects with T2DM: 25 received oral glucose-lowering medication (ORL group), and 25 received oral glucose-lowering medication in combination with insulin glargine injection (CGI group). Thirty non-diabetic control subjects were also included. BMD was measured at lumbar vertebrae 1-4 (L1-L4), spine bone mineral density (sBMD) results summary (L2-L4), femoral neck and trochanter by dual-energy x-ray absorptiometry. RESULTS: Compared with non-diabetic controls, people with T2DM had significantly lower mean BMD at L2 (1.073±0.120 vs 0.984±0.158), L3 (1.094±0.129 vs 0.991±0.163) and L4 (1.089±0.130 vs 0.982±0.165) (all P<0.05), significantly lower levels of serum calcium (2.02±0.22 vs 2.27±0.17 mmol/L, P<0.05), PTH (24.19±9.71 vs 31.52±8.96 pg/mL, P<0.05), and higher serum phosphate levels (1.43±0.37 vs 1.20±0.15 mmol/L, P<0.05). The CGI group had higher L2, L3 and L4 BMD and sBMD (L2-L4) (P<0.05), higher serum calcium levels (2.19±0.11 vs 1.98±0.20 mmol/L, P<0.05) and lower serum phosphate levels (1.28±0.20 vs 1.58±0.43 mmol/L, P<0.05) versus the ORL group. BMD and serum calcium levels were associated with the application of insulin glargine. CONCLUSION: These results suggest that insulin glargine may affect bone metabolism in patients diagnosed with T2DM. The study has implications for the selection of hypoglycemic agents for diabetic patients at risk of osteoporosis.

Novel Double Endobutton Technique Combined with Three-Dimensional Printing: A Biomechanical Study of Reconstruction in Acromioclavicular Joint Dislocation.

OBJECTIVE: To reconstruct the acromioclavicular (AC) joint using an adjusted closed-loop double Endobutton technique via a guiding locator that was applied using three-dimensional (3D) printing technology. At the same time, the reliability and safety of the novel double Endobutton (NDE) were tested by comparing the biomechanics of this technique with the TightRope (TR) approach. METHODS: This retrospective study was conducted between January 2017 and January 2019. The Department of Anatomy at Southern Medical University obtained 18 fresh-frozen specimens (8 left and 10 right; 12 men and 6 women). First, the guiding locators were applied using 3D printing technology. After preparation of materials, specimens were divided into an NDE group, a TR group, and a normal group. In the NDE and TR groups, the navigation module was used to locate and establish the bone tunnels; after that, the NDE or TR was implanted. However, the Endobuttons were fixed while pressing the distal clavicle downwards and the length of the loop could be adjusted by changing the upper Endobutton in the NDE group while the suture button construct was tensioned and knotted after pressing down the distal clavicle in the TR. Finally, load testing in anterior-posterior (AP), superior-inferior (SI), and medial-lateral (ML) directions as well as load-to-failure testing in the SI direction were undertaken to verify whether the NDE or TR had better biomechanics. RESULTS: In the load testing, the displacements of the NDE and TR groups in the AP, SI, and ML direction were significantly shorter than those of the normal group (P < 0.05). In the load-to-failure testing, the ultimate load of the NDE and TR groups had significantly higher increases than the normal group (722.16 ± 92.04 vs 564.63 ± 63.05, P < 0.05; 680.20 ± 110.29 vs 564.63 ± 63.05, P < 0.05). However, there was no statistically significant difference between the two techniques for these two tests (P > 0.05). In the NDE group, four of six failures were a result of tunnel fractures of the coracoid, while two of six were due to suture breakage. In the TR, three failures were due to coracoid tunnel fractures, one was a result of a clavicle tunnel fracture, and the rest were due to suture breakage. In the normal group, half of the failures were a result of avulsion fractures of the conical ligament at the point of the coracoid process, and the other three were due to rupture of the conical ligament, fracture of the distal clavicle, and fracture of the scapular body. CONCLUSION: As for the TR technique, the stability and strength of the AC joint were better in patients who underwent reconstruction using the NDE technique than in the intact state.

The source of circulating selenoprotein S and its association with type 2 diabetes mellitus and atherosclerosis: a preliminary study.

BACKGROUND: Selenoprotein S (SelS) is a transmembrane protein that is expressed in the liver, skeletal muscle, adipose tissue, pancreatic islets, kidney, and blood vessels. In addition to its transmembrane localization, SelS is also secreted from hepatoma HepG2 cells (but not L6 skeletal muscle cells, 3T3-L1 adipocytes, Min6 pancreatic ß cells and human embryonic kidney 293 cells) and has been detected in the serum of some human subjects, with a detection rate of 31.1 %. These findings prove that serum SelS is secreted by hepatocytes. However, whether vascularly expressed SelS can be secreted has not been reported. Transmembrane SelS has been suggested to play different roles in the pathogenesis and progression of diabetes mellitus (DM) and atherosclerosis (AS), but the association of secreted SelS with DM and macroangiopathy remains unclear. RESEARCH DESIGN AND METHODS: Supernatants were collected from human umbilical vein endothelial cells (HUVECs), human aortic vascular smooth muscle cells (HA/VSMCs) and human hepatoma HepG2 cells that were untransfected or transfected with the indicated plasmid and concentrated for western blotting. Serum samples were collected from 158 human subjects with or without type 2 DM (T2DM) and/or AS. Serum SelS levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Secreted SelS was only detected in the supernatants of hepatoma HepG2 cells. The SelS detection rate among the 158 human serum samples was 100 %, and the average SelS level was 64.81 ng/dl. The serum SelS level in the isolated DM subjects was lower than the level in the healthy control subjects (52.66 ± 20.53 vs 70.40 ± 21.38 ng/dl). The serum SelS levels in the DM complicated with SAS subjects (67.73 ± 21.41 ng/dl) and AS subjects (71.69 ± 27.00 ng/dl) were significantly increased compared with the serum SelS level in the isolated DM subjects. There was a positive interaction effect between T2DM and AS on the serum SelS level (P = 0.002). Spearman correlation analysis showed that the serum SelS level was negatively correlated with fasting plasma glucose. CONCLUSIONS: Vascular endothelial and vascular smooth muscle cells could not secrete SelS. Serum SelS was primarily secreted by hepatocytes. SelS was universally detected in human serum samples, and the serum SelS level was associated with T2DM and its macrovascular complications. Thus, regulating liver and serum SelS levels might become a new strategy for the prevention and treatment of DM and its macrovascular complications.

Efficacy of switching from premixed insulin to insulin glargine regimen in Type 2 diabetes mellitus patients with different islet functions.

The present study evaluated the efficacy of switching from premixed insulin or an insulin analogue to insulin glargine plus oral antidiabetic drugs (OADs) in patients with type 2 diabetes mellitus (T2DM). The feasibility and suitability of the regimen to the patients was examined based on islet function. Patients with T2DM (n=30) treated with stable doses of premixed insulin or an insulin analogue for eight weeks were divided into two groups according to islet function. Group A had a 2 h of C peptide (2hCP)/fasting C peptide (FCP) ratio ≤3, whereas group B had a 2hCP/FCP ratio >3. Eight weeks following the switch to insulin glargine plus OADs, a significant decrease in fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPBG) and glycosylated­haemoglobin (HbA1c) were observed in the two groups, with effective rates of 75, 42.9 and 39.3%, respectively. A distinct reduction in the insulin dose was particularly evident in group B. There was a marked decrease in FBG in group A, more so than that observed in group B. By contrast, the decrease in HbA1c was more evident in group B following the switch. A larger number of patients in group B had HbA1c≤7.0%, compared with group A. No difference in the incidence of hypoglycaemia and change of body weight were observed. Following the switch to insulin glargine plus OADs, patients with T2DM demonstrated improved blood glucose control and reduced insulin dosage. The results revealed that this switch in regimen is more suitable for patients with T2DM with 2hCP/FCP>3 and that administration of insulin glargine plus OADs is more efficacious for patients with T2DM with increased FBG levels.

Effects of selenoprotein S on oxidative injury in human endothelial cells.

BACKGROUND: Selenoprotein S (SelS) is an important endoplasmic reticulum and plasma membrane-located selenoprotein implicated in inflammatory responses and insulin resistance. However, the effects of SelS on endothelial cells (ECs) have not been reported. In the present study, the role of SelS in oxidative stress and the underlying mechanism were investigated in human ECs. METHODS: A SelS over-expression plasmid (pc-SelS) and a SelS-siRNA plasmid were transfected into human umbilical vein endothelial cells (American Type Culture Collection, USA). The cells were divided into four groups: control, SelS over-expression (transfected with pc-SelS), vector control, and SelS knockdown (transfected with siRNA-SelS). After treating the cells with H2O2, the effects of oxidative stress and the expression of caveolin-1 (Cav-1) and protein kinase Cα (PKCα) were investigated. RESULTS: Following treatment with H2O2, over-expression of SelS significantly increased cell viability and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) production and Cav-1 gene and protein expression. However, no effects on PKCα were observed. In contrast, knockdown of SelS significantly decreased cell viability, SOD activity, and PKCα gene and protein expression, and increased MDA production and Cav-1 gene and protein expression. CONCLUSIONS: SelS protects ECs from oxidative stress by inhibiting the expression of Cav-1 and PKCα.

Primary prevention of macroangiopathy in patients with short-duration type 2 diabetes by intensified multifactorial intervention: seven-year follow-up of diabetes complications in Chinese.

OBJECTIVE: To explore whether intensified, multifactorial intervention could prevent macrovascular disease in patients with recently diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 150 type 2 diabetic patients, with disease duration of <1 year and without clinical arteriosclerotic disease or subclinical atherosclerotic signs confirmed by ultrasonographic scanning of three conducting arteries, were randomized into an intensive intervention group and a conventional intervention group. They then received intensive, multifactorial intervention or conventional intervention over 7 years of follow-up. The patients' common carotid intima-media thicknesses (CC-IMTs) were measured every year. The primary outcome was the time to the first occurrence of CC-IMTs ≥1.0 mm and/or development of atherosclerosis plaques in the carotid artery. The secondary outcome was clinical evidence of cardiovascular disease. RESULTS: A total of 70 patients in the intensive group and 68 patients in the conventional group completed the 7-year follow-up. Subclinical macrovascular (primary) outcomes occurred in seven cases in the intensive group and 22 cases in the conventional group for a cumulative prevalence of 10.00 and 32.35%, respectively (P < 0.05). No significant differences between the two groups were observed regarding the secondary outcome. CONCLUSIONS: Primary prevention of macrovascular diseases can be achieved through intensified, multifactorial intervention in patients with short-duration type 2 diabetes. Type 2 diabetic patients should undergo intensive multifactorial interventions with individual targets for the prevention of macrovascular diseases.

Effects of five-year intensive multifactorial intervention on the serum amyloid A and macroangiopathy in patients with short-duration type 2 diabetes mellitus.

BACKGROUND: A five-year follow-up study of intensive multifactorial intervention was undertaken to assess the changes of circulating serum amyloid A (SAA) levels and the incidence of atherosclerosis (AS) in patients with short-duration type 2 diabetes mellitus (T2DM) without macroangiopathy, and whether intensive multifactorial intervention could prevent or at least postpone the occurrence of macroangiopathy. METHODS: Among 150 patients with short-duration T2DM, 75 were assigned to receive conventional outpatient treatment (conventional group) and the others underwent intensive multifactorial integrated therapy targeting hyperglycemia, hypertension, dyslipidemia and received aspirin simultaneously (intensive group). RESULTS: Plasma SAA levels were higher in diabetic patients than those in healthy control subjects, and decreased obviously after intensive multifactorial intervention. The levels of SAA were positively correlated with body mass index (BMI), waist hip ratio (WHR), triglyceride (TG), high sensitive C-reactive protein (hs-CRP) and common carotid intima-media thickness (CC-IMT). The standard-reaching rates of glycemia, blood pressure and lipidemia were significantly higher in intensive group than those of conventional group. The incidence of macroangiopathy decreased by 58.96% in intensive group compared with conventional group. CONCLUSIONS: Intensive multifactorial intervention may significantly reduce the SAA levels and prevent the occurrence of AS in short-duration patients with T2DM. SAA might be one of the risk factors of T2DM combined with AS.

Association of SelS mRNA expression in omental adipose tissue with Homa-IR and serum amyloid A in patients with type 2 diabetes mellitus.

BACKGROUND: Tanis was reported as a putative receptor for serum amyloid A (SAA) involving glucose regulated protein in insulin regulated resistance. It was found to be dysregulated in diabetic rats (Psammomys obesus, Israeli sand rat) and its homologue for humans is SelS/AD-015. The present study analyzed mRNA expression of SelS in omental adipose tissue biopsies from patients with type 2 diabetes mellitus (T2DM), and age- and weight-matched nondiabetic patients, the relationship of SelS mRNA with Homa-IR and serum SAA level. METHODS: Human omental adipose tissues from ten cases of type 2 diabetic patients and twelve cases of nondiabetic individuals were analyzed for the expression level of SelS mRNA by semiquantitative polymerase chain reaction (PCR), Homa-IR estimated by standard formula and SAA level by enzyme-linked immunosorbent assay (ELISA). RESULTS: SelS mRNA expression, Homa-IR and serum SAA were higher in T2DM sufferers than in nondiabetic control group. SelS mRNA level was positively correlated with Homa-IR and SAA level in each group. CONCLUSIONS: SelS protein may be involved in insulin resistance in Chinese with T2DM by acting as the SAA receptor, thus playing an important role in the development of T2DM and atherosclerosis.