Volume 04 · Issue 09 · 2012

Medical decision-making is extremely important in clinical work. Medical decision-making must follow the well-known "no harm principle", that is, in addition to considering the possible benefits of treatment options, it is also necessary to be alert to their potential risks. Therefore, physicians must carefully weigh the pros and cons from the patient's perspective when making medical decisions. This is easier to do for those treatment options that already have sufficient clinical evidence, but for new treatment options, it is difficult to do because there is too little evidence. In addition, in today's era of information explosion, people will see the so-called "medical breakthrough" from newspapers, TV and the Internet every day. How to identify truly meaningful information in the "noisy background sound" needs to arouse our thinking.

The American Diabetes Society (ADA) awarded the 2012 Outstanding Scientific Achievement Award to Professor David Altshuler, currently a professor in the departments of medicine and genetics at Harvard Medical School and Massachusetts General Hospital, and associate director of the Broad Research Center at Harvard University and MIT. He is also one of The advocates of several genetic research projects, including The SNP Consortium, The International HapMap Project, and The 1000 Genomes Project. The overall purpose of these international research projects is to more completely identify human disease-related gene polymorphism loci, so as to provide complete data for the correlation analysis of gene variation and disease; Provide more complete nucleotide polymorphism and probe screening data for future genotyping platforms; The perfect database can provide scientists from all over the world with scientific research resources, and can also be used to gain a deeper understanding of the process and mechanism of gene mutation and recombination^[1]。 The winning of the ADA Outstanding Achievement Award is an affirmation of Professor Altshuler's long-term perseverance and fruitful research in the field of diabetes and metabolic disease genetics. At the same time, his research is also deeply inspiring to diabetes workers in China.

Pregnancy is a special and complex physiological process. With the prolongation of gestational age and the increase of weight, the insulin antagonist hormones produced by the placenta, such as prolactin, estrogen, progesterone and corticoids, gradually increase, and the maternal sensitivity to insulin will decrease, thus showing "physiological insulin resistance". At this time, the amount of maternal pancreatic islet beta cells is compensated by expansion, and more insulin is secreted to meet the body's needs. Within 10 days after delivery, the amount of β cells quickly recovered to the level before pregnancy to adapt to the changes of metabolic demand after delivery. This dynamic change of islet β cell mass in peri-pregnancy provides an important observation window for studying the regulation of β cell mass under physiological conditions. In this paper, the current research progress in this field is reviewed.

To assess the accuracy of continuous glucose monitoring system (CGMS) in type 2 diabetic patients by frequent venous blood collection.

A total of 11 patients with type 2 diabetes treated from August to October 2010 were enrolled in this study. The Medtronic GOLD™ CGMS was used to monitor the continuous changes of the blood glucose levels for 3 successive days in all subjects, meanwhile the fingertip blood glucose was tested at least 4 times each day for calibration. The venous blood of the subjects was randomly collected every 15 min per hour for 7 successive hours on one day when the subjects wore the sensor, and was tested using the YSI 2300 STAT Plus™ glucose&lactate analyzer. The accuracy was comprehensively evaluated by using statistical methods including the rate of agreement between the sensor readings and the paired YSI values within ±20% and ±30% of deviations, the error grid analysis, absolute relative difference (ARD), Bland-Altman analysis and trend analysis. Correlation analysis of two variables was done with Pearson correlation analysis.

A total of 319 paired YSI-sensor values were collected from the 11 patients. Total 88.4% of the sensor readings (95%CI: 0.84–0.92) were within ±20% of the YSI values, and 96.9% within ±30% of the YSI values. Clarke error grid analyses showed that the ratios of the YSI-sensor values in region A to region B were 88% and 12%; Consensus error grid analyses showed that the ratios of the YSI-sensor values in region A to region B were 96.2% and 3.8%; Continuous error grid analyses showed that the ratios of the YSI-sensor values in region of accurate reading, benign errors, erroneous reading were 94.4%, 2.8%, 2.8%, respectively. The mean ARD for all subjects was 10.5% and the median ARD was 8.4%. The Bland-Altman analysis detected the mean blood glucose level of 0.47 mmol/L (95%CI: -1.90-3.01 mmol/L). Trend analysis revealed that 82.5% of the difference of the rates of change between the YSI values and sensor readings occurred within the range of 0.06 mmol·L^-1·min^-1, and only 1.7% of the absolute differences of the paired values were more than 0.17 mmol·L^-1·min^-1.

The CGMS has high accuracy both in monitoring the blood glucose at a specific time and reflecting the trend of changes of the blood glucose level. However, actual clinical manifestations should be taken into account for diagnosis of hypoglycemia.

To investigate the characteristics of the daily blood glucose profiles in patients with gestational diabetes mellitus(GDM) by continuous glucose monitoring system(CGMS) so as to guide the clinical treatment.

The glucose level in the subcutaneous tissue was monitored by CGMS for 3 days in 7 patients with GDM and 20 participants with normal glucose tolerance(NGT). The average age was 28 and 41 yrs in GDM and NGT group, respectively. The average body mass index(BMI) was 25 and 24 kg/m² in GDM and NGT group, respectively. After 3-day CGMS, the GDM patients were administrated with multiple daily insulin injections. The mean plasma glucose(MPG), standard deviation of blood glucose (SDBG), mean amplitude of glucose excursions(MAGE), postprandial glucose excursions(PPGE), mean of daily differences (MODD) and difference between maximal and minimal glucose (DMMG) were calculated with the data obtained from CGMS. The insulin dose was recorded when glucose level achieved the target. The t test was used to compare the difference between groups and the difference of postprandial glucose excursions in GDM group.

The MAGE, PPGE and DMMG were significantly higher in GDM group (MAGE (4.3±0.2) vs (1.6±0.3) mmol/L; the breakfast postprandial glucose excursions (BPPGE) (5.5±1.1) vs (1.8±0.4) mmol/L; lunch PPGE(LPPGE) (3.1±0.3) vs (1.3±0.2) mmol/L; dinner PPGE(DPPGE) (3.4±0.4) vs (1.5±0.2) mmol/L and DMMG (6.0±2.7) vs (2.9±0.2) mmol/L; t=4.4, 5.6, 2.3, 2.8, 6.1, all P<0.05). There was no significant difference in MBG, SDBG and MODD between GDM and NGT group. Postprandial glucose excursion was higher at breakfast than those at lunch and dinner in GDM group(t=3.1, 2.6, both P<0.05). The basal insulin requirement accounted for 15% of the total daily insulin usage. Pre-breakfast insulin dosage was higher than pre-lunch and pre-dinner doses. The pre-breakfast insulin dosage accounted for 33.5% of total daily insulin usage.

CGMS is an effective method to assess glycemic excursions in patients with GDM. GDM is characterized by hyper-postprandial glucose and postprandial glucose excursion. Preprandial insulin dose accounts for a majority proportion of total daily dose, within which the pre-breakfast dose is the highest. Insulin dose is consistent with the glucose excursion in GDM patients.

To evaluate cost effectiveness of a school-based intensive self-management education network.

A total of 196 patients with type 2 diabetes mellitus (male 114, female 82, average age (53±10) y) were recruited from a hospital in 2007 and assigned to receive intensive self-management training (treatment group, n=124, male 72, female 52, average age (54±10) y) or conventional education program (control group, n=72, male 42, female 30, average age (51±10) y). The treatment group received diabetes self-management training for 2.5 days and subsequent regular follow-up (website, telephones, short message, etc). In the control group, the subjects received diabetes education lecture once a week for 5 times. The changes of metabolic control and medical expenditure were assessed after 6 or 12 months. Cost-effectiveness was assessed at the end of the study.

Hemoglobin A1c (HbA1c), fasting blood glucose (FBG), 2-h blood glucose were significantly decreased in each group at 6 and 12 months (all P<0.05). At the end of follow-up, PBG (6.1 mmol/L), 2-h blood glucose (8.6 mmol/L) and HbA1c (7.1%) of the treatment group were lower than the control group (6.2 mmol/L, 9.1 mmol/L and 7.6%, respectively; allP<0.05). During 1-year follow-up, to decrease 1% HbA1c, FBG and 2-h blood glucose cost 233.11, 2911.52 and 925.81 RMB in the treatment group. However, the cost was 243.25 and 959.18 RMB to decrease 1% HbA1c or 2-h blood glucose in the control group.

School-based self-management education network may be more effective and economic than conventional education programme in improving glucose control.

To investigate the effectiveness of integrative diabetes management in third-grade class-A hospital.

Three hundred and eighty insulin-naïve type 2 diabetic patients who were going on insulin therapy were enrolled from June 2010 to June 2011.The patients were divided into 2 groups with Excel random sampling, 190 cases in each group: the management group, 91 males and 99 females, aged (54±8) years with a body mass index(BMI)of (25±3)kg/m² and a duration of disease of (8±3) years; the control group, 88 males and 102 females, aged (56±7) years with a BMI of (26±3)kg/m² and a duration of disease of (8±3) years, the baseline information was comparable between the two groups. Patients in management group received intensive integrative diabetic management and those in control group were given routine therapy for 6 months. The therapeutic effects were compared before and after the treatment and between the groups. The data of the two groups were compared with t test or t' test.

Fasting plasma glucose, two-hour postprandial plasma glucose, glycated hemoglobin A1c, satisfaction on life and self-confidence at the end of the treatments were all significantly improved compared with those before the therapy in both groups (t'=-182.81, -27.74,P<0.05). The BMI in control group was significantly higher than that before treatment ((29±4) vs (26±3) kg/m^2,t'=-10.51,P<0.05), while no significant difference was found in BMI in the management group after the treatment ((26±3) vs (26±3) kg/m^2,t=1.65, P>0.05). The BMI in management group was significantly higher than that in control group at the end of the treatment (t'=-9.47,P<0.05). Satisfaction on life and self-confidence of the patients in the management group significantly improved compared with those in the control group (96%±4%, 95%±4% and 62%±10%, 60%±11%, respectively;t'=42.60, 41.69, bothP<0.05). The daily insulin dosage and mean daily expenses in the management group were significantly lower than those in the control group((0.38±0.03) vs (0.55±0.07) U·kg^-1·d^-1 and (11±3) vs (16±6) yuan/d, t'=-30.77, -9.21,P<0.05).

Integrative diabetes management can achieve a better glucose control with less insulin dose, higher self-confidence and less drug expenses with a drop of 27.8%. In the current conditions of excessive medical costs, this practice is worthy to be expanded clinically.

To explore the expressions of Toll-like receptor 4(TLR4) and tumor necrosis factor(TNF)-α on peripheral-blood mononuclear cells(PBMC) and theirs correlation with cardiac function in patients with diabetic cardiomyopathy(DCM).

Patients admitted to Department of Cardiology of Guangdong Medical College from June 2008 to July 2011 were divided into 2 groups: group of type-2 diabetes mellitus(T2DM) (n=36), DCM group (n=48). Forty healthy check-up people were selected as the control group. All the subjects were analyzed by New York Heart Association (NYHA) functional class. To compare the expressions of TLR4, TNF-α, N-terminal -Brain natriuretic peptide(NT-BNP)and left ventricular ejection fraction(LVEF), Left ventricular end diastolic diameter(LVEDd)among three groups. Association between cardiac function and the Level of TLR4, TNF-α were analyzed by Multiple stepwise regression.

(1)Compared with the control and T2DM groups, the expressions of TLR4 and TNF-α were upgraded, the levels of NT-BNP, LVEDd increased, and the level of LVEF decreased in DCM group (P<0.05). (2)The level of TLR4 mRNA on PBMC was significantly increased last in NYHA functional class (class Ⅰ-Ⅳ: 2.1±0.4, 3.1±0.4, 4.1±0.6, 5.1±0.5, respectively,P<0.05); the level of TNF-α was significantly increased last in NYHA functional class (class Ⅰ-Ⅳ: (302±92), (414±102), (658±116), (1035±108)mmol/L); Compared with NYHA functional class Ⅰ-Ⅲ groups, the levels of NT-BNP and LVEDd increased in class Ⅳ group (P<0.05), and Difference was no statistically significant among class Ⅰ-Ⅲ groups; the level of LVEF decreased last in NYHA functional class groups (P<0.05), and Difference was no statistically significant between class Ⅲ and Ⅳ groups.(3)The expression of TLR4, TNF-α were linear correlated positively with NYHA functional class (r=0.61, 0.26, P<0.05), TLR4 had better correlation; and were no correlated positively with NT-BNP, LVEDd, LVEF(P>0.05). (4) The multiple regression analysis may predict that TLR4 was independent related factors of NYHA functional class with DCM(Regression coefficientt=0.371, P=0.000).

The TLR4/TNF-α signaling pathways is correlated positively with the severity of cardiac function in patients with DCM, and plays an important role in the progress of heart failure in DCM patients.

To study the effects of metformin on newly diagnosed type 2 diabetes with diabetic ketoacidosis (DK) and nonalcoholic fatty liver disease(NAFLD).

Sixty newly diagnosed type 2 diabetes patients with DK and NAFLD admitted in our hospital from 2010 January to 2011 December were enrolled in this study. The subjects were randomly divided into 2 groups according to randomized number table: insulin group (INS) and insulin plus metformin group (INS+ MET). The INS group included 24 males and 6 females, with an average age of (37±9) years. The INS+ MET group included 22 males and 8 females, with an average age of (39±10) years. The age, diabetic duration, body mass index(BMI), waist-hip ratio(WHR), blood pressure, glycated hemoglobin A1c(HbA1c), plasma lipid concentration, liver enzyme and insulin dosage at baseline between the two groups were matched. After ketoacidosis was cured and blood glucose was controlled with intensive insulin therapy, the patients in INS group were treated with insulin alone, and the INS+ MET group were treated with metformin 1.5 g/d and insulin. BMI, blood glucose, HbA1c, liver enzyme, plasma lipid concentration, liver sonographic parameters, homeostasis model assessment-insulin resistance(HOMA-IR), the levels of adiponectin and tumor necrosis factor-α(TNF-α) were measured at the beginning and 12, 24 weeks after the therapy. Difference of measurement data was compared witht test and χ ² test was used for ranked data analysis.

After 24-week of therapy, fasting blood glucose, 2 h postprandial blood glucose and HbA1c were decreased in the same extent in both groups. There was no difference in HbA1c compliance rate between the two groups (86.7% vs 82.8% in INS and INS+ MET group, χ ²=0.174, P>0.05). BMI, triglyceride and low density lipoprotein-cholesterol were significantly improved in INS+ MET group compared to those in INS group(t=3.648, 2.883, 2.699, all P<0.05). The level of alanine transaminase(ALT) in INS+ MET group dropped by 13.2% and 32.2% (t=4.264, 4.976, both P<0.05)and γ-glutamyl transferase(γGGT) dropped by 23.1% and 37.5%(t=6.364, 6.315, both P<0.05) after 12- and 24-week of therapy. Ultrasonic scores(2.8±1.3 vs 3.7±1.4,t=2.311, P<0.05) and insulin resistance (HOMA-IR: 2.7±0.8 vs 3.8±1.0,t=0.219, P<0.05) were significantly improved in INS+ MET group than those in INS group. The level of adiponectin ((7.2±1.2) vs (5.5±1.4) μg/L,t=-5.023, P<0.05) was significantly higher and TNF-α((28±9) vs (36±9) ng/L,t=3.110, P<0.05) was significantly lower in INS+ MET than those in INS group.

Metformin could improve insulin resistance, liver enzyme and liver ultrasonic scores when used in newly diagnosed type 2 diabetes with DK and NAFLD. Increased levels of adiponectin as well as decreased plasma TNF-α may involved in the therapeutic effects.

To investigate the effect of rosiglitazone on osteoclastogenesis.

Monocytes from bone marrow were isolated from the C57BL/6 mice and induced to differentiate into osteoclasts. Meanwhile, osteoclasts were incubated in the control group (G1), 0.5 μmol/L rosiglitazone (G2) and 2.0 μmol/L rosiglitazone (G3). Four days after cell culture, tartrate resistant acid phosphatase (TRAP) staining, osteoclast cell counting, real-time PCR analysis and quantitative measurement of TRAP activity were respectively done.

For the number of osteoclastogenesis, the G2 and G3 group were significantly increased compared to the G1 group(G1: 32±5, G2: 54±5, G3: 72±5, F=82.43, P<0.05); for TRAP activity assay, the G2 and G3 group were also increased compared to G1 group(G1: 2.32±0.14, G2: 2.83±0.08, G3: 3.35±0.10,F=108.12, P<0.05). The gene expression in osteoclast, such as peroxisome proliferator activated receptor gamma, cathepsin k, c-fos and c-jun, were increased in rosiglitazone groups compared to the control group(F value was 33.50, 37.46, 53.73, 39.77, respectively, all P<0.05).

Rosiglitazone may increases osteoclastogenesis by cell proliferation.

To establish minipig model of type 2 diabetes mellitus with high-fat and high-sucrose diet and to observe the changes of serum glucagon-like peptide-1(GLP-1) and its relation with blood glucose, insulin and C-peptide.

Twenty 4-month-old Chinese experimental minipigs(weighted (16.9±1.1)kg) were randomly assigned to the control diet group (CD group, n=10) and high-fat and high-sucrose diet (HFSD group, n=10), with 5 females and 5 males in each group, according to the random number table. CD group were fed with basic diet, and HFSD group were fed with high-fat and high-sucrose diet to establish type 2 diabetic minipig model. Fasting blood glucose≥7.0 mmol/L was set as the criterion that the type 2 diabetic minipig model were established successfully. Blood samples for plasma parameters, including blood glucose, insulin, C-peptide and blood lipid, were withdrawn from the animals separately at the end of the 0, 3rd and 6th month following an overnight fasting and 2 hours after feeding, and for detecting the blood GLP-1. The t test was performed to compare the data of the two groups. Pearson's correlation analysis was used to investigate the relationship between GLP-1 and the other variables.

At the end of the 6th month, the average weight of HFSD group was (74±11) kg and that of CD group was (44±4) kg (t=7.93, P<0.01). At the end of the 6th month, the concentrations of fasting blood glucose in HFSD group and CD group were (7.6±1.8) mmol/L and (4.4±0.7) mmol/L, respectively(t=4.32, P<0.01). The results confirmed that type 2 diabetic animal model was established in minipig. The level of triglyceride(TG) and total cholesterol(TC) in HFSD group((0.83±0.29) and (4.0±1.0) mmol/L, respectively)was significantly increased compared with those in CD group ((0.56±0.18) and (2.8±0.5) mmol/L)(t=2.05, 7.11, both P<0.05). The level of GLP-1 in HFSD group had a clear tendency of decreasing, which was negatively correlated with blood glucose (r=-0.81, P<0.01), had a positive association with C-peptide (r=0.73, P<0.01), and had no significant association with insulin(r=0.19, P>0.01).

A 6-month of feeding with high-fat and high-sucrose diet can establish an ideal type 2 diabetes model in minipig, which features weight gain, blood glucose elevation, increased levels of serum TG and TC, and significantly decreased GLP-1 level.

Numerous studies have confirmed that various factors are associated with vascular complications of diabetes, but it is still very difficult to accurately assess their respective roles. Hyperglycemia has been considered to be the most important factor in the macrovascular and microvascular pathogenesis of diabetes. Hyperglycemia leads to chronic complications of diabetes mainly through oxidative stress activation and glycosylation pathways. The Diabetes Complications and Control Test (DCCT) established glycosylated hemoglobin (HbA1c) as the gold standard for glycemic control in diabetes^[1]HbA1c ≤7% is considered an appropriate level to reduce vascular complications in diabetes. Although there was no significant difference in HbA1c between the intensive group and the conventional group, long-term follow-up results showed that diabetic retinopathy was more pronounced in the conventional group, indicating that in addition to HbA1c, blood glucose variability may also be crucial for chronic complications of diabetes^[1]。 Some studies have gradually shown that the occurrence and development of chronic complications of diabetes is not only related to the overall blood glucose level, but also closely related to blood glucose fluctuations^[2,3]。 In this paper, the molecular mechanism of diabetes complications caused by blood glucose fluctuation is reviewed.

Macrovascular disease is the most common chronic complication in diabetic people, and its morbidity and mortality rate are 2~3 times higher than those in non-diabetic people. Various factors are involved in the development of diabetic macrovascular disease, among which vascular endothelial dysfunction plays a crucial role. Numerous studies have confirmed that endothelial dysfunction is an important initiating factor of atherosclerosis and runs through the whole process of atherosclerosis^[1]。 The main biological role of glucagon-like peptide-1 (GLP-1) is to participate in the regulation of blood glucose homeostasis. In addition, GLP-1 not only directly acts on vascular endothelial cells, but also has a wide range of cardiovascular protective effects. The effects of GLP-1 and its analogues on vascular endothelial function are discussed in this paper.

Epidemiological survey results show that the prevalence of hypertension and diabetes in China reached 18.8% and 9.7% respectively^[1,2]。 In the diabetic population, the proportion of patients with combined hypertension reached 56.0%^[3]。 This data indicates that the clustering of blood pressure and blood sugar is very serious. A large number of epidemiological and clinical trials have confirmed that hypertension, dyslipidemia and abnormal glucose metabolism are the main causes of atherosclerosis and cardiovascular disease and death. For example, the UK Prospective Diabetes Study (UKPDS) hypertension subgroup analysis showed that for diabetic patients with hypertension, the risk of any diabetes-related endpoint was reduced by 12% for every 10 mm Hg decrease in blood pressure (1 mm Hg =0.133 kPa)^[4]。 Therefore, the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2010 Edition) regards blood pressure control as a strategy for diabetes management^[5]。

With the rapid development of China's economy, the number of people with diabetes has also increased rapidly, but the blood sugar control standard of type 2 diabetes patients is not optimistic. Asian Diabetes Management China Cooperation Group^[1]The results of the study showed that only 26.9% of patients had glycosylated hemoglobin (HbA1c) below 6.5%, and 41.1% of patients had glycosylated hemoglobin below 7.0%. Recent studies show that^[2]The mean HbA1c at baseline in Chinese patients with type 2 diabetes was 9.5%±2.3%, and 74.5% of patients received no treatment or only oral hypoglycemic drugs, and oral hypoglycemic drugs and insulin initiated treatment late. Recommendation of the 2010 edition of the Guidelines for the Prevention and Treatment of Type 2 Diabetes in China^[3]When oral hypoglycemic drugs do not reach the standard of blood glucose control (HbA1c>7.0%), insulin therapy should be initiated in time, and patients with type 1 diabetes need lifelong insulin replacement therapy.

Visceral fat deposition is a risk factor for type 2 diabetes, metabolic syndrome, cardiovascular disease, and a variety of tumors. In studying the mechanism of early-onset obesity and late-onset insulin resistance induced by sex hormone imbalance using female mice with follicle-stimulating hormone (FSH) receptor gene knockout as a model, the researchers identified mesenteric estrogen-dependent adipogene-4 (MEDA-4), this novel gene is selectively upregulated in mesenteric adipose tissue in a storage site-specific manner. Cloned from human and mouse adipose tissueMEDA-4 genes, all encoding products are cytoplasmic proteins with a relative molecular mass of 34 000, and the homology between them reaches 91%. MouseMEDA-4 mRNA is highest expressed in visceral adipose tissue and is mainly located in adipocytes. Human MEDA-4 is higher in mesenteric fat than in subcutaneous fat in obese patients. In the 3T3-L1 cell line, endogenousMEDA-4 gene expression increases early in cell differentiation,MEDA-4 overexpression can promote pre-adipocyte to adipocyte differentiation and increase glucose uptake; In contrast, short hairpin RNA-mediatedMEDADownregulation of-4 expression reduces the ability to form fat and glucose uptake. In pro-adipogenesis, MEDA-4 upregulates the expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPAR-gamma) 2. MEDA-4 promotes the deposition of lipids in adipocytes and regulates the expression of fatty acid binding protein-2, CD36, lipoprotein lipase, hormone sensitive lipase, acetyl-CoA oxidase-1, perilipin-1 and fatty acid synthetase in adipocytes. 17 β estradiol downregulates MEDA-4 expression levels in mesenteric adipose tissue and 3T3-L1 adipocyte line of ovariectomized mice.

Chronic inflammation exists in obese humans and animals, and it induces insulin resistance to promote the development of type 2 diabetes. Chronic inflammation can promote the degradation of insulin receptor substrate 1 (IRS-1), inhibit the activity of peroxisome proliferator-activated receptor γ (PPAR γ), and impair the insulin signal transduction pathway, thus leading to insulin resistance. Insulin sensitizers (e.g., rosiglitazone, pioglitazone) can reduce free fatty acid levels, inhibit inflammation, and increase insulin sensitivity by activating PPAR γ. Therefore, anti-inflammatory drugs have been considered as a treatment for insulin resistance. However, this treatment has been observed in laboratory and clinical trials for more than a decade, but no significant progress has been made. This leads us to re-evaluate the biological role of chronic inflammation in obese individuals. Current studies suggest that obesity-related inflammation helps the body maintain insulin sensitivity. Inflammation stimulates local adipose tissue remodeling and promotes systemic energy expenditure. The accumulation of energy leads to chronic inflammation, and inflammation can produce negative feedback to promote energy expenditure when there is excess energy. The researchers believe that these beneficial effects of inflammation are a possible mechanism for the ineffectiveness of anti-inflammatory drugs in the treatment of insulin resistance. At present, there are many literatures supporting this view. Since thiazolidinediones have side effects such as weight gain, induction of heart attack and bladder cancer, it is necessary to use a new type of drug to treat insulin resistance. The latest research found that histamine deacetylase inhibitors can reduce lipotoxicity, inhibit inflammation, promote the growth and proliferation of pancreatic islet beta cells, and promote energy consumption. Therefore, histamine deacetylase inhibitors may become a new class of insulin sensitizers.

Obesity-induced diabetes is associated with chronic inflammation and is currently considered a risk factor for neurodegeneration. Recently published inDiabetesA study on the previous study tested a hypothesis through animal experiments: whether resveratrol, as an adenylate-activated protein kinase activator, can attenuate peripheral and central inflammation and improve memory deterioration in mice fed a high-fat diet. In the experiment, the researchers gave C57BL/6J mice a high-fat diet or a high-fat diet plus resveratrol for 20 weeks, evaluated the serum metabolic indexes of the experimental mice, and performed immunoblotting and immunohistochemical detection on peripheral organs and brain. At the same time, the researchers used Morris water maze experiment to test the effect of resveratrol on the improvement of memory function in mice fed a high-fat diet. Resveratrol treatment was found to alleviate the degree of fatty liver, macrophage infiltration in tissues, and insulin resistance in mice fed a high-fat diet. In addition, resveratrol treatment reduced the expression of tumor necrosis factor alpha (TNF-alpha) and Iba-1 protein in the hippocampus of mice fed a high-fat diet. Expression of choline acetyltransferase increased and phosphorylation of Tau protein decreased in the hippocampal gyrus in mice fed a high-fat diet treated with resveratrol. It is worth noting that the researchers found that resveratrol significantly improved memory loss in mice fed a high-fat diet.

APPL1 and APPL2 are two adaptor proteins that bind to adiponectin receptors and can regulate the adiponectin signaling pathway by acting on adiponectin receptors (AdipoR1 and AdipoR2). Both adiponectin and adiponectin receptor gene variants can lead to insulin resistance and increase the risk of obesity.APPL1Genetic variation was associated with body fat distribution, whileAPPL2The association of genetic variants with metabolic diseases such as obesity has not been studied. The purpose of this study was to investigate the normal glucose regulators in the Chinese populationAPPL2Association of genetic variants with obesity.