Initiating Characteristics of Early-onset Type 2 Diabetes Mellitus in Chinese Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Type 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly; however, the age at diagnosis has gradually reduced in recent years. Although the incidence of young-onset T2DM is increasing, it is still not fully clear the onset characteristics and risk factors of early-onset T2DM. The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus.</p><p><b>METHODS</b>This cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China. A total of 1545 patients with T2DM with an age at onset of <40 years were included, and the control group consisted of subjects aged <40 years with normal blood glucose level.</p><p><b>RESULTS</b>In patients with young-onset T2DM, the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 ± 5.40 years and 9.59 ± 2.71%, respectively. Most of the patients were obese, followed irregular diet pattern and sedentary lifestyle, had life or work pressure, and had a family history of diabetes mellitus. Compared with subjects with normal blood glucose level, logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99, 95% confidence interval [CI] 42.37-4714.87), family history of diabetes mellitus (OR 23.46, CI 14.47-38.03), dyslipidemia (OR 2.65, CI 1.54-4.56), diastolic blood pressure (OR 1.02, CI 1.00-1.04), and body mass index (OR 0.95, CI 0.92-0.99) are independent factors for early-onset T2DM.</p><p><b>CONCLUSIONS</b>We observed that abdominal obesity, family history of diabetes mellitus, and medical history of hypertension and dyslipidemia are independent risk factors for early-onset T2DM. It is, therefore, necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus.</p>

Liraglutide protects against nonalcoholic fatty liver disease in ApoE knockout mice with high-fat diet and silenced Acrp30 by increasing AMPK / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of liraglutide-mediated protection against nonalcoholic fatty liver disease (NAFLD) using aApoE knockout (KO) mouse with high-fat diet (HFD) and Acrp30 knockdown.</p><p><b>METHODS</b>Fifty-six male ApoE KO mice were divided into the following six modeling and experimental groups:regular chow fed (ApoE KO, n=10), HFD fed (HF, n=10), HFD+Adenovirus (Ad)-small hairpin (sh) Acrp30 (Ad-shAcrp30, n=10), HFD+Ad-shGreen Fluorescent Protein (GFP) (Ad-shGFP, n=6), HFD+Ad-shAcrp30+liraglutide (liraglutide, n=10), and HFD+Ad-shAcrp30+saline (saline, n=10). Weight-matched C57BL/6 mice on the regular chow diet were used as the control group (WT control, n=10).All mice were fed their assigned diet for 16 weeks.The Ad-shGFP or Ad-shAcrp30 was injected by tail vein at the end of 14 and 15 weeks.Mice in the liraglutide group received 1 mg/kg of the drug, twice daily, intraperitoneally for a total of 8 weeks (from the 9th to 16th week).Fasting blood samples were collected for testing levels of fasting plasma glucose (FPG), triglycerides (TGs), total cholesterol (TC), free fatty acid (FFA), alanine aminotransferase (ALT), Acrp30 and insulin.Liver tissue was procured for histological examination.Expression of mRNA was detected by real-time RT-PC and of protein was detected by western blot analysis.</p><p><b>RESULTS</b>The Ad-shAcrp30 treated mice had reduced expression of Acrp30 at both the mRNA and protein levels in adipose tissues and plasma, as compared with the AdshGFP treated mice (all P < 0.01).Compared to the WT and ApoE KO groups, the HF group showed higher levels of FPG, FFA, TGs and TC (all P < 0.01); furthermore, the Ad-shAcrp30 treatment compounded these changes.The Ad-shAcrp30 treated group had markedly higher hepatic TC and TGs than the HF group (P < 0.01 and P < 0.05).Oil Red O staining showed that there was more lipid droplets in the liver tissue of the Ad-shAcrp30 treated group than in that of the HF group (P < 0.01), and hematoxylin-eosin staining confirmed these results.Liraglutide treatment prevented the increase in body weight, FPG, FFA, TGs, TC and ALT levels, as compared to the saline controls (all P < 0.01), but the plasma Acrp30 levels and the Acrp30 mRNA and protein expression in adipose tissues were elevated (all P < 0.01).Oil-Red O staining indicated that the liraglutide group had a significantly lower hepatic lipid content than the saline group, and total hepatic TG and TC were reduced in the former group (P < 0.01 and P < 0.05).The liraglutide treatment significantly attenuated the mRNA expression of ACC and FAS (both P < 0.01) but increased AMPK phosphorylation (P < 0.01).</p><p><b>CONCLUSION</b>Administration of liraglutide prevented the development of HFD-and hypoadiponectinemia-induced metabolic disturbance and accumulation of hepatic lipids in this mouse model system of NAFLD.</p>

Comparison of parathyroid hormone (1-34) and elcatonin in postmenopausal women with osteoporosis: an 18-month randomized, multicenter controlled trial in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH (1-34) in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China.</p><p><b>METHODS</b>A total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 µg (200 U) daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded.</p><p><b>RESULTS</b>rhPTH (1-34) increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment (4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P < 0.01). There was only a small but significant increase of femoral neck BMD after 18 months (2.6%, P < 0.01) in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH (1-34) group than those in the elcatonin group after 6, 12, and 18 months (serum bone-specific alkaline phosphatase (BSAP) 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P < 0.01; urinary C-telopeptide/creatinine (CTX/Cr) 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P < 0.01). rhPTH (1-34) showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% (6/112) in elcatonin group and 3.2% (11/341) in rhPTH (1-34) group (P = 0.303). Both treatments were well tolerated. Hypercaluria (9.4%) and hypercalcemia (7.0%) in rhPTH (1-34) group were transient and caused no clinical symptoms. Pruritus (8.2% vs. 2.7%, P = 0.044) and redness of injection site (4.4% vs. 0, P = 0.024) were more frequent in rhPTH (1-34). Nausea/vomiting (16.1% vs. 6.2%, P = 0.001) and hot flushes (7.1% vs. 0.6%, P < 0.001) were more common in elcatonin group.</p><p><b>CONCLUSIONS</b>rhPTH (1-34) was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months of treatment. rhPTH could improve back pain effectively. The results of the present study indicate that rhPTH (1-34) is an effective, safe agent in treating Chinese postmenopausal women with osteoporosis.</p>

A randomized, multicenter controlled trial to compare the efficacy of recombinant human parathyroid hormone (1-34) with elcatonin in postmenopausal women with osteoporosis in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) given by injection is a new seventh class drug of biological products, which is prepared by adopting gene recombination technique. rhPTH (1-34) is mainly used to treat osteoporosis, especially for postmenopausal women. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China.</p><p><b>METHODS</b>Two hundred and five women with osteoporosis were enrolled in a 6-month, multicenter, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 microg (200 U) daily or elcatonin 20 U weekly. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), as well as biochemical markers of bone turnover were measured. Adverse events were recorded.</p><p><b>RESULTS</b>rhPTH (1-34) increased lumbar BMD significantly more than did elcatonin at 3 months and 6 months (2.38% vs 0.59%, P < 0.05; 5.51% vs 1.55%, P < 0.01), but there were no significant increases of BMD in these two groups at femoral neck. There were larger mean increases in bone markers in the rhPTH (1-34) group than in the elcatonin group at 3 months and 6 months (serum bone-specific alkaline phosphatase (BSAP) 36.79% vs 0.31%; 92.42% vs -0.17%; urinary N-telopeptide/creatinine (NTX/Cr) 48.91% vs -5.32%; 68.82% vs -10.86%). Both treatments were well tolerated and there were no significant differences detected between the two groups in the proportion of any adverse events and any serious adverse events (67.0% vs 59.0%; 0 vs 0).</p><p><b>CONCLUSIONS</b>rhPTH (1-34) has more positive effects on bone formation, as shown by the larger increments of lumbar BMD and bone formation markers, than elcatonin, with only mild adverse events and no significant change in the liver, kidney or hematological indices.</p>

Reduction of plasma obestatin levels in patients with impaired glucose regulation and type 2 diabetes / 中华内分泌代谢杂志

Plasma obestatin level was determined in patients with impaired glucose regulation and type 2 diabetes mellitus.The plasma obestatin levels in patients of both groups were significantly decreased as compared with that in controls.Plasma obestatin level was negatively correlated with body mass index,HbA_(1C),waist-to-hip ratio,plasma insulin and HOMA-IR.Obestatin level seems to be related with metabolic disorder.

Change of plasma visfatin level in the population with different glucose tolerances / 中华内分泌代谢杂志

Objective To investigate the change of plasma visfatin level and the relationship of plasma visfatin level to body mass index(BMI),waist hip ratio(WHR),blood glucose,plasma insulin levels as well as other factors in the subjects with different glucose tolerances.Methods Fasting and glucose loading 2 h plasma visfatin levels were assayed by ELISA in patients with type 2 diabetes and impaired glucose tolerance(IGT),and controls.The relationship of plasma visfatin level with BMI,HOMA-IR,blood lipids,plasma glucose,plasma insulin,free fatty acids(FFA)levels were also analyzed.Results Fasting and glucose loading 2 h plasma visfatin levels in the type 2 diabetic patients were significantly reduced compared with controls[(11.63?7.48)?g/L vs (16.82?6.06)?g/L and (12.02?6.86)?g/L vs (16.26?7.78)?g/L,both P＜0.05],and the level of plasma visfatin in IGT was lower than that in diabetics and higher than controls.The level of visfatin in obese subjects was modestly higher than that in non-obese subjects,but the difference is not significant.Plasma visfatin level was positively correlated with WHR(r=0.42,P＜0.01),and negatively with 2 h plasma glucose after glucose loading(2hPG)and HbA_(1C)(r=-0.33,P＜0.01 and r=-0.25,both P＜0.05).Multiple regression analysis showed that fasting plasma glucose,WHR,2hPG,high density lipoprotein cholesterol and HbA_(1C) were independent related factors in influencing plasma visfatin levels.Conclusion The change of visfatin level is associated with glucose metabolism,which may contribute,in part,to the pathogenesis of diabetes and obesity.

Effects of pioglitazone on lipid-induced insulin resistance in rats / 中华内分泌代谢杂志

Objective To investigate the effects of pioglitazone on glucose metabolism,circulating resistin and adiponectin concentrations,and tissue resistin levels in rats with insulin resistance induced by free fatty acid (FFA).Methods A hyperinsulinaemic-euglycaemic clamp and[3-~3H]-glucose tracing technique were used in awake rats.Insulin-mediated peripheral and hepatic glucose metabolism,plasma resistin and adipenectin levels, resistin levels in tissues were assessed by hyperinsulinaemic-euglycaemic clamp with elevation of FFA by lipid infusion over 4 h in rats pretreated with or without pioglitazone.Results During steady-state of clamp,there was a significant increase in plasma FFA in lipid-infused group(L group)and pioglitazone-pretreated lipid-infused group(P/L group)compared to control rats(P＜0.01).The glucose infusion rate(GIR)in P/L group was significantly reduced as compared with controls[(20.6?0.9 vs 33.6?1.5)mg?kg~(-1)?min~(-1),P＜0.01], whereas the GIR was lower in L group than in P/L group[(12.6?0.8 vs 20.6?0.9)mg?kg~(-1)?min~(-1),P＜0.01].As compared with baseline,the hepatic glucose production(HGP)was significantly suppressed by 85% [(18.3?2.1 vs 2.7+2.4)mg?kg~(-1)?min~(-1) and (17.5?2.6 vs 2.6?1.0)mg?kg~(-1)?min~(-1),both P＜0.01]during the hyperinsulinaemic clamp in control and P/L groups.The suppressive effect of insulin on HGP was significantly blunted in L group[(17.3?2.1 vs 15.8?1.5]mg?kg~(-1)?min~(-1)].The rate of glucose disappearance(G_(Rd))was reduced in L group and P/L group compared with controls(P＜0.01).Baseline plasma resistin level was lower in P/L group than that in the controls[(7.8?1.3 vs 29.1?3.1)?g/L,P＜0.01].After lipid infusion,plasma resistin levels significantly increased in P/L group,but remained lower than that of L group [(18.1?3.8 vs 47.0?2.2)?g/L,P＜0.01].Baseline adiponectin level was higher in P/L group than those in the controls and L groups[(3.9?0.2 vs 2.8?0.1 and 2.6?0.2)mg/L,P＜0.01].After clamp,plasma adiponectin levels were decreased in L group and L/P group compared with baseline(both P＜0.05).In addition, the resistin level in the liver of P/L group decreased compared with the controls and L groups(both P＜0.05), whereas significantly increased in the muscle of L group.Conclusion Lipid infusion induces an acute insulin- resistance in vivo.Pioglitazone pretreatment partly prevents FFA-induced insulin resistance possibly by changing resistin and adiponectin levels.