MedNexus
Volume 04 · Issue 04 · 2012
MedNexus
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For a long time, the diagnostic criteria of gestational diabetes mellitus (GDM) have not been agreed at home and abroad, so the incidence of GDM in different regions cannot be compared[
To investigate the effects of gemfibrozil, fenobrate, and bezafibrate on the macrovascular events.
We collected all prospective, randomized control clinical trials comparing the effects of 3 fibrates (fenofibrate, bezafibrate, and gemfibrozil) with placebo or blank controls with macrovascular end points reported from CCTR (Issue 4, 2011), MEDLINE (1950-2011), and EMBASE (1950-2011). Data collection and quality evaluation have been done by two reviewers, independently. Meta Analyst beta 3.13 had been used for statistical analysis.
This study included 11 randomized control clinical trials. Compared with placebo or blank control, none of gemfibrozil, fenofibrate or bezafibrate decreased the risk of all cause mortality or stroke incidence (all cause mortality, RR 0.985, 95%CI 0.830 to 1.169; RR 1.023, 95%CI 0.905 to 1.155; RR 0.948, 95%CI 0.837 to 1.073, respectively; stroke incidence, RR 0.765, 95%CI 0.548 to 1.067; RR 0.865, 95%CI 0.646 to 1.158; RR 1.056, 95%CI 0.772 to 1.081, respectively). All three fibrates could significantly decrease the risk of non-fatal myocardial infarction (RR 0.776, 95%CI 0.646 to 0.931; RR 0.833, 95%CI 0.717 to 0.968; RR 0.752, 95%CI 0.591 to 0.958, respectively). Compared with placebo, gemifibrozil and fenofibrate could significantly decrease 10%-20% risk of all cardiovascular events, and no significant difference was found in cancer incidence and mortality.
Fibrates could reduce the risk of non-fatal myocardial infarction but not all-cause mortality or stroke.
To study phenotype of high-density lipoprotein (HDL) subclasses distribution in coronary heart disease (CHD) patients with diabetes, which might provide useful data in decreasing the incidence of risk among CHD patients with diabetes.
212 patients of coronary heart disease who were dignosed as coronary heart disease by coronary angiography having one or more artery lesion degree>50%. They were divided into two groups: the CHD with diabetic mellitus(DM)group and the CHD without DM group. All the diagnosis of DM including having the history of diabetes and diagnosis of diabetes after hospitalization. Plasma HDL subclasses contents were quantified in patients with CHD by 2-dimensional gel electrophoresis coupled with immunodetection.
Although the particle size of HDL shifted toward smaller, the mean levels of low density lipoprotein (LDL-C) and total cholesterol (TC) have achieved normal or desirable for total CHD patients who received statins treatment. Fasting plasma glucose (FPG), triglyceride (TG), TC, LDL-C concentrations, and HDL3b((170± 21), (142 ± 18) mg/L, respectively) and HDL3a((310 ± 45), (272 ± 38)mg/L, separately) contents along with Gensini Score(54±9, 23±6, respectively) were significantly increased(t=1.061, 0.229, 2.531, P<0.05); but those of HDL-C ((1.0±0.2), (1.3±0.2)mmol/L, respectively), HDL2b((245±32), (334±50)mg/L, respectively), and HDL2a ((190±26), (286±42)mg/L, respectively) were significantly decreased in CHD patients with diabetes(t=1.406, 3.759, 4.012, P<0.05) versus CHD patients with non-diabetes; The changes more marked for CHD patients with diabetes in FPG ≥ 6.1 mmol/L(t=1.674, 1.528, 1.620, 1.537, 3.531, 3.608, P<0.05). Pearson correlation and multiple stepwise regression results revealed that the Gensini Score independently and inversely with large-sized HDL2b(β=-0.598, P<0.01)and HDL2a(β=-0.572, P<0.01).
The abnormality of HDL subpopulations distribution may contribute to CHD risk in diabetic patients. CHD patients with diabetes or without diabetes who using statins therapy, the HDL subclasses profile modification behind the improvement of plasma lipids levels. The HDL subclasses distribution may help in severity of coronary artery and risk stratification, particularly in CHD patients with normal or desirable LDL, TG and HDL levels.
To determine effects on mothers of gestational diabetes on their future anthropometry and metabolic risks.
We conducted a follow-up study of 222 women who delivered in the Department of Obstetrics and Gynecology of First Hospital of Peking University from June 2006 to Dec 2007.The selected cases consisted of 124 women with gestational diabetes mellitus(GDM) and 98 women with normal glucose metabolism(control group). The follow-up study was performed from Nov 2010 to Feb 2011, anthropometry indexes include height, weight, waist circumference, hip circumference, systolic pressure, diastolic pressure and body fat. Laboratory tests include fasting blood glucose, triglyceride, total cholesterol, high density lipoproteins, low density lipoproteins, insulin and C-peptide.
(1)Compared with control mothers, GDM mothers had higher body weight((61±10) vs (59±9) kg, t=2.023, P<0.05), waist circumference(WC)((78±9) vs (76±8) cm,t=2.229, P<0.05)and body fat(34.3% vs 31.4%,t=3.102, P<0.05). Serum fasting glucose((5.3±0.8) vs (4.9±0.3) mmol/L,t=5.369, P<0.001), triglyceride ((1.1±0.6) vs (0.9±0.4) mmol/L,t=2.346, P<0.05)and HOMA-IS(0.077±0.029 vs 0.086±0.029,t=-2.221, P<0.05)level had significant differences between two groups. (2) GDM mothers had higher proportion on WC≥80 cm(37.1% vs 24.5%, χ2=4.03, P<0.05), Fasting glucose ≥6.1 mmol/L(7.4% vs 1.0%, χ2=5.05, P<0.05), DBP≥85 mm Hg(1 mm Hg=0.133 kPa, 16.9% vs 6.1%, χ2=5.991, P<0.05)and metabolic syndrome(13.2% vs 5.2%, χ2=4.026, P<0.05)than control mothers.
GDM pregnancies led to increased conversion to glucose intolerance in mothers, GDM mothers have increased risk of central adiposity, lower insulin sensitivity, impaired glucose intolerance, Hyperlipidemia and metabolic syndrome at 3-4 years after delivery than control mothers.
To establish the reference range of serum 1, 5-anhydroglucitol(1, 5-AG) in healthy people and analyze its correlation with short-term glycemic control.
From March to July in 2010, 281 individuals with normal glucose regulation, 143 men and 138 women aged from 20 to 87 years, were recruited from Gucheng and Pingguoyuan community in Beijing and outpatients of General Hospital of People's Liberation Army(PLA). Serum 1, 5-AG levels were measured with glucose kinase-pyranoid sugars oxidase (GK-PROD) methods in these individuals. Thirty-eight outpatients with type 2 diabetes, 19 men and 19 women aged 37 to 74 years, were selected from General Hospital of PLA and received mixed protamine zinc recombinant human insulin lispro injection (25R) interventions for 12 weeks. The blood glucose levels in the patients were regularly monitored before and 2h after main meals in order to obtain mean blood glucose(MBG); and 1, 5-AG, glycosylated hemoglobin (HbA1c)and serum glycated albumin(GA) were measured at week 0, 2, 4, 8 and 12 with clinic visits. Pearson correlation coefficient was used to measure the relation between 1, 5-AG, HbA1c , GA and MBG.
The normal range of serum 1, 5-AG for healthy population could be suggested at 68-251 μmol/L overall, 80-267 μmol/L for man and 66-206 μmol/L for woman. The level of 1, 5-AG in man was higher than that in woman, but there was no difference in the whole range of age and body mass index(BMI) in subjects. There were significant correlation between 1, 5-AG, HbA1c, GA and MBG( r=-0.491, 0.563, 0.422, all P<0.01). 1, 5-AG was most closely associated with 2-week MBG level(r=-0.675, P<0.01), while the correlation between HbA1c and MBG maintained longer than others. After treatment of 2 weeks, 1, 5-AG increased by 18.8%, but HbA1c and GA decreased by 3.2% and 6.2%. By week 12, 1, 5-AG increased by 65.2%, while the HbA1c and GA decreased by 16.1% and 21.1%. In general, there was satisfactory concordance between longitudinal changes of 1, 5-AG, HbA1c, GA and MBG in patients with type 2 diabetes.
The normal range of serum 1, 5-AG for normal population could be suggested at 68-251 μmol/L overall, 80-267 μmol/L for man and 66-206 μmol/L for woman. 1, 5-AG was a probably better marker than HbA1c and GA in evaluating short-term glycemic control.
To investigate the correlation of serum gamma glutamyl transpeptidase (GGT)level with impaired fasting glucose(IFG)and evaluate the modification effects of age, Body Mass Index(BMI), hypertension and lipids in Chinese adults.
The study samples were from a community-based health examination survey in Xuzhou, Jiangsu province of China. A total of 7309 subjects with biomarkers available were included in the present study. Serum ALT, GGT, triglyceride(TG), total cholesterol (TC), low-density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol (HDL-C)and glucose were measured. IFG was defined from 6.1 mmol/L to 7.0 mmol/L (fasting blood-glucose, FBG). Results are expressed as mean±S.E. The correlation between hepatic markers and other variables were assessed using pearson correlation . Logistic regression model (binary regression) was used to calculate the odds ratio (OR) of IFG with 95% confidence interval (95%CI).
After adjusted for age, sex, BMI, blood pressure, TG, TC, LDL-C and HDL-C, the odds ratios (ORs, 95%CI) of IFG across increasing quintiles of GGT were 1.00, 0.91(0.49-1.72), 1.27(0.68-2.38), 2.31(1.29-4.15) and 2.42(1.32-4.42) (P for trend<0.05). We found significant interactions between GGT and age on IFG risk (P<0.05). When the joint effects were examined, we found an additive effect of BMI level and GGT levels on fasting blood glucose (FBG).
The present data indicate serum GGT is related to the risk of IFG in Chinese adults, and BMI level modified in coordination with the relationship.
To compare the prevalence of metabolic syndrome (MS) and levels of its components between different fasting plasma glucose(FPG) and 2-hour plasma glucose (2 h PG) after 75 g oral glucose tolerance test(OGTT) in a Chinese cohort with normoglycemia.
A diabetes survey was conducted in 2438 individuals aged 25-74 years who lived in Zhanshan Community, Qingdao in 2002. A total of 2109 subjects had complete data on height, weight, blood pressure, waist, body mass index (BMI), FPG, 2 h PG, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and fasting insulin (FINS). 1341 participants with normoglycemia (FPG<6.1 mmol/L and 2 h PG<7.8 mmol/L) were divided into subgroup A (2 h PG≤FPG) and subgroup B (2 h PG>FPG). General linear model and Chi-square test were used for statistics. Logistic regression analysis was used to evaluate the odds ratio of having MS.
The proportion of individuals in subgroup A and B was 42.3% (564/1341) and 57.9% (777/1341), respectively. Compared with individuals in subgroup A, those in subgroup B had higher BMI, waist, systolic blood pressure, diastolic blood pressure, FINS, TG, and Non-HDL-C (P<0.05), after adjusting for age and sex. The prevalence of MS was higher in subgroup B(19.1% (149/777)) than in subgroup A (14.7% (83/564)), the differences were statistically significant(χ2=3.91, P<0.05). Subgroup B was independently associated with increased risk for having MS in a multi-covariate logistic regression model(OR: 1.32, 95% CI: 1.02-1.74). The prevalence of MS was higher in the upper vs bottom quartile of 2 h PG (21.3% vs 11.5%, χ 2=12.8, P<0.05).
Within normoglycemic range, individuals whose 2 h PG levels did not return to below the FPG have higher risk for MS than those did. This should be addressed in identifying high risk population for cardiovascular disease.
To investigate the relationship among serum adipose triglyceride lipase(ATGL) levels and glucose and lipid metabolism in patients with obesity and newly-diagnosed type 2 diabetes mellitus(T2DM).
Sixty-six patients with T2DM(T2DM group) and forty-eight subjects with normal glucose regulation (NGR group) were selected from August 2006 to April 2009 in clinic and Department of Endocrinology of the Affiliated Hospital of Jiangsu University. Each group was divided into obese(OB group) and normal weight(NW group) subgroups according to whether the body mass index (BMI) ≥25 kg/m2. By using enzyme-linked immunosorbent assay(ELISA) methods, the changes of serum levels of ATGL were measured. Meanwhile, fasting blood glucose (FBG), lipids and fasting insulin levels were also measured. BMI and waist-to-hip ratio (WHR) were evaluated and insulin sensitivity was assessed by HOMA-insulin resistance(HOMA-IR). t-test, rectilinear correlation analysis and multiple stepwise regression analysis were used for data analysis.
(1)The serum ATGL levels of obese subjects were lower than the normal weight group in both NGR and T2DM group (T2DM-OB group vs T2DM-NW group: (239±61)vs (355±54)μg/L, NGR-OB group vs NGR-NW group: (242±60)vs (383±58)μg/L), and the differences were statistically significant(t=22.53, 8.23, both P<0.05). (2)Correlation analysis showed that the serum ATGL level was negatively correlated with Fat%, BMI, WHR, triglycerides and HOMA-IR(r value was -0.271, -0.238, -0.375, -0.313, -0.164, respectively, all P<0.05). Multiple stepwise regression analysis showed that WHR, FAT% were independent factors for serum ATGL.
The serum ATGL levels in obese patients are significantly lower than those of normal weight. ATGL is independently associated with WHR and FAT%, but no significant correlation with blood glucose.
To investigate the effect of resveratrol(Res)on the protein expression of reduced form of nicotinamide-adenine dinucleotide phosphate oxidase 4 (NOX4) and glucose-regulated protein 78 (GRP78) and its protective effects on the oxidative stress injuries in the renal cortex of diabetic rats.
Fifteen SD rats were given a single intraperitoneal injection of streptozotocin(STZ) to set up animal models of diabetes. Twelve weeks after STZ injection, 12 rat diabetes models were established successfully and were randomized into diabetes mellitus group (group DM, n=6) and Res intervention group (group DR, n=6). Another 6 untreated healthy SD rats served as normal control (group NC). Rats in DR group were administered intragastricly with Res 10 mg·kg-1·d-1 while those in DM group with equal volume of 0.5% sodium carboxymethylcellulose regularly for 2 weeks. At the end of the experiments, the blood glucose (BG), body weight (BW), serum creatinine (Scr), blood urea nitrogen (BUN), 24 urinary albumin excretion(UAE) of all rats were measured. Renal cortex from the groups were embedded in paraffin and sectioned for morphological studies. The activity of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in the renal cortex was assayed by chromatometry. The expression of NOX4 and GRP78 proteins in the renal cortex were detected by using Western blotting.
Compared with those in group NC, the BW in group DM decreased, while BG, Scr, BUN and 24h UAE increased significantly(t=-52.324, -20.487, -20.724, -55.476, all P<0.0167). It indicated that resveratrol improved the 24 h UAE, Scr and BUN in group DR as compared with those in group DM(t=13.963, 7.849, 8.678, all P<0.0167); but there was no significant differences in BG and BW between the two groups(t=-1.767, 1.876, all P>0.0167). Moreover, the MDA activity in DM group increased while the SOD and CAT activity decreased significantly as compared with those in group NC(t=-10.661, 8.124, 8.222, all P<0.0167). The SOD activity was significantly higher while MDA was significantly lower in group DR than those in DM group (t=-12.309, 4.475, all P<0.0167); no significant differences in CAT activity was observed between the two groups(t=-3.029, P>0.0167). The glomerular basement membrane was intact in NC group, more glomerular mesangial matrix and cell proliferation was observed in group DM and which were attenuated in the group DR. The expression of NOX4 and GRP78 in the blood vessels of group DM were up-regulated than those in group NC (t=-14.255, -25.179, P<0.0167). After the administration of resveratrol, the expression of NOX4 was still up-regulated while GRP48 was down-regulated in group DR as compared with those in group NC (t=-5.125, -28.017, P<0.0167).
Oxidative stress is present in the renal cortex of diabetic rats. It suggests that resveratrol protect the renal cortex of diabetic rats by suppressing the expression of NOX4 and GRP78 to attenuate endoplasmic reticulum stress and subsequent oxidative stress injuries during the early stage of diabetes.
To investigate the relationship between thyroid-stimulating hormone receptor antibody (TRAb), zinc transporter 8 antibody (ZnT8A) and glutamic acid decarboxylase antibody (GADA) in patients with Graves' disease (GD).
A total of 51 GD patients (9 male, 42 female) and 72 type 1 diabetes mellitus(T1DM) patients (30 male, 42 female) were collected from outpatient and inpatient department of our hospital from November 2009 to March 2011, and 70 healthy volunteers(29 male, 41 female)were recruited as control group. The serum levels of TRAb, ZnT8A and GADA were detected by radioimmunoprecipitation and radioimmunoassay methods, respectively. Pearson's correlation coefficient was used to evaluate the correlation between the autoantibodies.
The positive rate of TRAb, ZnT8A and GADA in the GD group was 90.2% (46/51), 15.7% (8/51) and 5.9% (3/51), respectively. The positive rate of TRAb, ZnT8A and GADA in the T1DM group was 4.2% (3/72), 45.8% (33/72) and 41.7% (30/72), respectively. The positive rate of TRAb, ZnT8A and GADA in the health control group was 0, 1.4% (1/70) and 1.4% (1/70), respectively. There was a positive correlation between TRAb and ZnT8A in GD patients, and the correlation was even stronger in TRAb positive GD patients (r=0.537, P<0.01). There also showed a strong positive linear correlation between GADA and ZnT8A in T1DM patients (r=0.892, P<0.01).
TRAb may be related with ZnT8A level in GD patients. ZnT8 and TRAb testing may help to diagnose and predict prognosis of GD.
To investigate the effect of interleukin(IL)-1β and interferon(IFN)-γ on the insulin secretion in mice βTC-6 cells in vitro.
βTC-6 cells were cultured in DMEM for 48 hours then pre-incubated for 30 minutes in Krebs-Ringer bicarbonate-Hepes (KRBH) buffer without glucose. The KRBH was then discarded and replaced with fresh buffer containing 1.38 mmol/L or 5.50 mmol/L or 11.10 mmol/L glucose for 1 hour. Supernatants were collected for insulin assays by an insulin radioimmunoassay (RIA) kit (GSIS). IL-1β (0.15, 1.50 μg/L) and/or IFN-γ (10, 100 U/ml) were added in βTC-6 cells for 24 hours then GSIS was measured as indicated with 1.38 mmol/L glucose stimulation. Data were analyzed by ONE-way ANOVA with correction for multiple comparisons or by Student'st-test for comparison between two groups.
The insulin level reaches a peak in 1.38 mmol/L stimulation group compared with 0 mmol/L glucose stimulation group ((151±14) vs (120±4) mU/L, t=-4.215, P=0.006). The insulin level 5.50 mmol/L and 11.10 mmol/L glucose stimulation groups were significantly lower than that in 1.38 mmol/L glucose stimulation group(all P<0.05). Compared with 1.38 mmol/L glucose stimulation alone group, the insulin level was significantly lower in IL-1β(0.15 μg/L) group ((85.53±5.06) vs (103.11±0.27) mU/L,t=4.897, P=0.039); IL-1β(1.50 μg/L) group ((62.62±0.64) vs (103.11±0.27) mU/L,t=212.66, P<0.001) and IFN-γ(100 U/ml) group ((73.2±1.6) vs (105.2±1.8) mU/L,t=19.52, P=0.003). Compared with IL-1β (0.15 μg/L) and IFN-γ(100 U/ml)groups, the insulin level in 1.38 mmol/L glucose stimulation with IL-1β plus IFN-γ group was significantly lower (F=77.38, P<0.001).
IL-1β or IFN-γ alone can inhibit the glucose-induced insulin secretion in βTC-6 cells or in a synergistic manner.
The epidemiological survey of diabetes mellitus in China from 2007 to 2008 showed that the prevalence of diabetes and pre-diabetes in China was as high as 9.7% and 15.5% respectively[
gestational diabetes mellitus (GDM) refers to the abnormal glucose metabolism occurring during pregnancy. It is one of the most common complications during pregnancy, accounting for 80% to 90% of pregnancy complicated by diabetes. Since the 1960s, with the efforts of medical workers all over the world, the diagnosis, management and treatment measures of GDM have been continuously developed and improved. Many gestational diabetes patients have been well managed during pregnancy, serious complications have been significantly reduced, and maternal and infant outcomes have been significantly improved. However, the research on the long-term outcome of pregnant women with GDM and their fetuses is still in its infancy, and the research shows that the onset of GDM is strongly correlated with the onset of type 2 diabetes mellitus (T2DM) in the future[
The mechanisms of insulin resistance and islet β cell dysfunction in type 2 diabetes mellitus (T2DM) include oxidative stress, endoplasmic reticulum stress, islet amyloidosis, ectopic fat deposition in muscle, liver and pancreas, lipotoxicity and glycotoxicity, etc. All the above mechanisms can be activated by excess nutrition, and can be regarded as some kind of inflammatory reaction or related to inflammation. This paper reviews the mechanism of immune system involvement in the pathogenesis of T2DM and the clinical trials of anti-inflammatory treatment of T2DM.
The International Charcot Joint Working Group was established in January 2011 at the Salpetriere Hospital in Paris, France. The expert group reviewed the literature on the diagnosis and treatment of diabetic Charcot joints, and the discussion formed a consensus of diabetic Charcot foot experts. Although the authors state that the consensus does not represent the official position of the American Academy of Diabetes or the American College of Podiatrists, it is an expert consensus for almost the highest level of Charcot joints and has very important clinical value. The full text of the consensus was published inDiabetes Care(2011, 34:2123-2129), the following are excerpts only.
Glucagon-like peptide (GLP) -1 decreases postprandial blood glucose primarily by inhibiting gastric emptying. This study aimed to investigate whether human tolerance to the effect of GLP-1 on slowing gastric emptying quickly develops.
Glucagon-like peptide (GLP) -1 exerts antidiabetic effects by acting on pancreatic islet beta and alpha cells. Previous studies have mainly focused on the improvement of islet β cell function, while less attention has been paid to the inhibitory effect of α cells. The aim of this study was to quantify the contribution of glucagon inhibition by GLP-1 infusion in lowering blood glucose in patients with type 2 diabetes.
Increasing the activity of glucagon-like peptide (GLP) -1 has become an effective treatment for type 2 diabetes. The effects of GLP-1 on pancreatic islet beta cells, nervous system and digestive system are well known. However, little is known about the role of GLP-1 in adipose tissue. Furthermore, there is no evidence of an association between adipose tissue GLP-1 receptor (GLP-1R) and obesity and insulin resistance.
Glucagon-like peptide (GLP) -1 has the effect of stimulating insulin secretion. However, GLP-1 can also improve vascular endothelial function in diabetic patients.
Serum calcitonin (CT) is a well-recognized marker reflecting C cell proliferation. Chronic use of glucagon-like peptide (GLP) -1 receptor agonists in rodents is associated with elevated serum CT levels and C-cell tumor formation. No researchers have observed changes in CT concentrations in people with no history of medullary thyroid cancer or family history of medullary thyroid cancer. The purpose of this study was to observe the changes of serum CT concentrations in patients with type 2 diabetes or non-diabetic obesity after application of the GLP-1 receptor agonist liraglutide.
When healthy subjects undergo oral glucose tolerance tests, the effect of incretin increases with increasing glucose load, causing blood glucose fluctuations similar to those independent of glucose load. Whether patients with type 2 diabetes mellitus (T2DM) are able to modulate the effects of incretin is currently unknown.
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