Volume 05 · Issue 05 · 2013

On 31 January 2013, a British researcher inJournal of Clinical Endocrinology and MetabolismA retrospective cohort study was published^[1], focusing on the safety of insulin in the treatment of type 2 diabetes. The results of the study show that insulin is associated with an increased risk of diabetes-related complications, cancer and all-cause death in patients with type 2 diabetes. Although the authors of the article pointed out that the differences in baseline characteristics of patients in different treatment groups should be considered when interpreting the results, this study still raised concerns and thinking of doctors and patients about insulin treatment of diabetes. Therefore, it is necessary to analyze this study in depth, and review and examine the application value of insulin in the treatment of type 2 diabetes.

In the natural course of diabetes, both type 1 diabetes (T1DM) and type 2 diabetes (T2DM) have the problem of pancreatic islet β cell failure. The only difference is that the former β cell damage occurs in the early stage and is rapidly progressive, and autoimmune process directly causes its damage; In the latter, β-cell failure occurs in the decompensated phase and is progressive. Insulin resistance and chronic low-grade inflammation state promote β-cell degeneration^[1]。 Therefore, maintaining or reconstructing pancreatic islet function by various means has been a research hotspot in the field of diabetes. The latest progress in the research field of regenerative medicine undoubtedly provides more theoretical basis and possibility for cell therapy of diabetes.

In 1890, Von Mering and Minkowski discovered that removing the canine pancreas could cause diabetes in dogs, thus truly linking the cause of diabetes to the pancreas for the first time. However, in 1898 Zuelzer and other scholars tried to treat diabetes with pancreatic extract but failed, instead causing severe allergies and local suppurative infections. In the next 20 years, a large amount of experimental evidence has gradually been gathered, and it is found that the cause of diabetes lies in the endocrine islets of the pancreas, which can secrete a "factor" that regulates blood sugar homeostasis. In 1920, Banting, a surgeon in Toronto, Canada, and his assistant Best ligated the dog's pancreatic duct to atrophy the pancreatic acin. They extracted the cooling extract from the atrophied pancreas, and then injected it into the dog with diabetes. They found that the dog's blood sugar can indeed drop significantly. With the help of biochemist James Collip, Banting and Best improved the extraction and purification method of pancreatic extract, greatly reducing the toxic side effects of the extract. In January 1922, Banting and Best injected Leonard Thompson, a 14-year-old diabetic at Toronto General Hospital, with pancreatic extract, and the patient's blood sugar dropped to normal levels. They named this extract insulin, and it was publicly reported to the General Assembly at the National Association of Physicians held in Washington, USA on May 3, 1922. It was recognized by everyone and regarded as the greatest achievement in the history of modern medicine. For which Banting won the 1923 Nobel Prize in Medicine.

With the gradual increase of the prevalence of diabetes, people pay more attention to how to screen and diagnose diabetes more conveniently and accurately. At present, the fastest and simplest method in clinic is to measure capillary blood glucose (i.e. fingertip blood glucose). Reference to World Health Organization (WHO) 1999 diagnostic criteria for diabetes mellitus^[1], 2010 edition of Guidelines for the Prevention and Treatment of Type 2 Diabetes in China^[2]The diagnostic criteria of diabetes were defined by the value of venous plasma glucose. A considerable number of diabetic patients are the first to have postprandial blood glucose increase, and the sensitivity of fasting blood glucose to diabetes diagnosis is only 40% ~60%^[3]。 Ideally, both fasting venous plasma glucose and 2 h venous plasma glucose (2 h PG) values after oral glucose tolerance test (OGTT) are checked simultaneously. Due to the reasons of health economics, coupled with the complicated and poor repeatability methods, the application of OGTT in general survey and clinic is also limited. On the premise of meeting the standardization and traceability of the National Glycosylated Hemoglobin (HbA1c) Standardization Program (NGSP), the American Diabetes Association (ADA) promulgated HbA1c ≥6.5% as one of the main criteria for diabetes diagnosis in the guidelines for diabetes diagnosis and treatment in 2010^[4]。 The Diabetes Branch of Chinese Medical Association started to implement the "China HbA1c Promotion Project" in 2010. However, due to many factors such as the lack of common HbA1c detection in China, the lack of standardization of detection methods, and the need to reduce the inter-laboratory and indoor errors, HbA1c cannot be used as a diagnostic standard in China at this stage^[3]。

To compare the efficacy and safety of liraglutide versus biphasic insulin aspart 30(BIAsp30) in overweight and obese type 2 diabetic patients.

A single center, randomized, open-label study was conducted, in which 109 subjects were enrolled (body mass index (BMI)>25 kg/m²). All subjects receiving metformin(1000 mg/d) were randomly assigned to liraglutide group(n=52) or BIAsp30 group(n=57) according to random number table. Fasting plasma glucose(FPG), postprandial plasma glucose(PPG), glycated hemoglobin A1c(HbA1c), weight, waist circumference, blood pressure, triglycolides(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol (LDL-C), C reactive protein(CRP) and 24 hr urine mini albumen (UMA) of each patient were measured 0, 4, 12, 24 weeks after treatment. The t test was used in the data analysis.

Compared to the baseline, the FPG in liraglutide group and BIAsp30 group decreased for (2.9±1.3) mmol/L and (3.5±1.2) mmol/L respectively after 24 weeks treatment(t=-3.2, P<0.01); the PPG decreased for (4.2±3.7) mmol/L and (4.5±2.8)mmol/L(t=-0.83, P>0.05); the HbA1c decreased for (1.7±0.6)% and (1.9±0.8)% (t=-0.6, P>0.05). Weight gain was observed in the BIAsp30 group for (1.2±1.7)kg while weight loss was found in the liraglutide group for (4.2±2.7)kg(t=-3.7, P<0.01). The systolic blood pressure (SBP) decreased for (5.2±4.4) mm Hg(1 mm Hg=0.133 kPa) and (1.8±2.3)mm Hg in liraglutide group and BIAsp30 group respectively(t=4.9, P<0.01). There was no significant difference in diastolic blood pressure between the two groups(P>0.05). The TG, TC, LDL-C were reduced and the HDL-C was improved in both groups, but there was no significant differences in above-mentioned indexes between the two groups(allP>0.05). The incidence rate of hypoglycemic events was higher in BIAsp30 group than that in liraglutide group, but there was no significant differences between the two groups(3.8% vs 14.0%,P>0.05); but much more gastrointestinal side-effects occurred in liraglutide group than in BIAsp30 group(46.2% vs 1.8%,t=2.00, P<0.05).

Liraglutide is superior in control of weight and blood pressure and safety to BIAsp30 but with equivalent glucose-reducing effects for overweight and obese patients with type 2 diabetes mellitus.

To investigate the effect of disease-management programs on glycemic control in type 1 diabetic (T1DM) patients.

T1DM patients registered in the Third Affiliated Hospital of Sun Yat-sen University from August 6, 2010 to January 1, 2013 were enrolled and disease-management programs were implied in those patients, including scheduled follow-up every 3 months, diabetic education, treatment plan adjustment and free glycated hemoglobin A1c (HbA1c) test in each visit. The patients were divided into two groups according to the HbA1c level: those whose HbA1c reached the control standard and those not. Multivariate logistic regression analysis was used to investigate the correlative factors for control effect of HbA1c.

Total of 144 T1DM patients were enrolled, among them 64 were male, 80 were female, the patients aged 29.0 years (interquartile range: 22.0, 38.0, same below) with a T1DM duration of 4.5 years (2.8, 9.0) and a body mass index (BMI) of 19.8 kg/m² (18.9, 22.0). The HbA1c at baseline was 8.2% (6.7%, 9.8%) and 41 patients (28.5%) achieved the age-specific HbA1c targets after the therapy. The number of patients completed the 3-, 6-, 9- and 12-month follow-up was 97, 50, 44 and 36, respectively. And of them, 50.5%, 80%, 77%, 63.9% reached the age-specific glycemic control goals at the 3-, 6-, 9- and 12-month visit, respectively. HbA1c fell from 8.2 (6.7%, 9.8%) at baseline to 7.2% (6.4%, 8.3%) at 3-month, 7.2% (6.6%, 7.9%) at 6-month, 7.0% (6.4%, 7.7%) at 9-month and 7.0% (6.5%, 8.0%) at 12-month (all P<0.05 compared with baseline). Binary logistic regression analysis showed that patients who were older, with lower BMI, more frequent self-monitoring of blood glucose(SMBG) and shorter diabetic duration had better glycemic control.

Disease-management programs has a favorable effect on glycemic control in T1DM patients. Higher frequency of SMBG is beneficial for glycemic improvement.

To investigate the anti-allergic strategy by reporting the desensitization for one case of insulin allergic type 1 diabetes and reviewing relevant literatures.

Sequencing diluted insulin injection for desensitization, continuous subcutaneous insulin infusion (CSII) with Novolin R, or dexamethasone added into CSII were applied to desensitization. Observed the size of erythema and induration, the degree of itching around the site of insulin injection and measured the insulin antibody levels.

The allergic reaction obviously alleviated during CSII, especially when the square mode of bolus was used. The slightest allergic reaction was seen during CSII with Dexamethasone, showing a small induration without erythema or itching. Three months after CSII, the erythema or itching around injection sites disappeared, except occasional small indurations at the thighs. The insulin antibody levels gradually declined to normal as well. However, a local lipoatrophy in the right abdomen turned up.

The allergic reaction is alleviated most when dexamethasone and insulin added into CSII. The square mode of bolus is helpful to alleviate the insulin allergic symptoms.

To investigate the coverage rate of the antidiabetic drugs in national essential medicine list and the status of glycemic control among patients with type 2 diabetes mellitus (T2DM) in Beijing communities.

A total of 904 patients with T2DM were selected from 4 community health service centers of Beijing. They were Pingguoyuan, Yuetan, Huaxiang and Longshan community health service centers, respectively. Questionaires and chemical examination were used among them. Chi-square test was used for data analysis.

(1)The coverage rate of metformin(40.5%, 366/904) was the highest in the 4 national essential antidiabetic drugs, which in Longshan community (48.6%, 121/249) was significantly higher than that of the other 3 communities(χ²=9.86, P<0.05). (2)The coverage rate of glypizide was 3.1%(28/904), which in Huaxiang community(14.3%, 16/112)was the highest (χ²=56.14, P<0.05). (3) The coverage rate of glybenclamide was 0.6%, the difference among the 4 communities had no significance(χ²=0.33, P>0.05). (4) The coverage rate of animal insulin was 0.2%(2/904), which in Huaxiang community(1.8%, 2/112) was more than those of the other communities(0). (5) The proportion of patients reaching the goal of glycated hemoglobin A1c(HbA1c)<7% was 33.2%(300/904), which in Yuetan community(55.1%, 114/207) was more than that in Pingguoyuan(33.0%), Longshan (24.1%, 60/249) and Huaxiang(13.4%, 15/112) communities(χ²=73.79, P<0.05).

The coverage rate of antidiabetic drugs in national essential medicine list is low in Beijing. Though the total proportion of patients reaching the goal of HbA1c<7% is not satisfied, the proportion in Yuetan and Pingguoyuan communities where the two-way referral between community health service centers and general hospitals has been established for a long time are satisfied.

To investigate the expression of placental hypoxia-inducible factor-1α (HIF-1α) and vascular epithelial growth factor (VEGF) in gestational diabetes mellitus (GDM) and its correlation with placental histological abnormalities and GDM pregnancy outcomes.

A case-control study was performed in 44 women with GDM, including 10 cases with not well-controlled glucose level (group A) and 34 cases with well-controlled glucose level (group B), and 37 healthy pregnant women (group C) with 36-41 pregnancy weeks and delivered between October 2010 to October 2011 Placental tissue was histologically examined by HE staining method. The protein expression of HIF-1α and VEGF in placenta was detected by immunohistochemistry. The expression of HIF-1α and VEGF mRNA in placenta was detected by RT-PCR, to compare the differential expression of HIF-1α and VEGF between three groups, and its relationship with pregnancy outcomes.Data was compared using Pearson correlation. P values <0.05 were considered statistically significant.

(1) Women in group A were more likely to develop gestational hypertension, postpartum hemorrhage, polyhydramnios, premature delivery, macrosomia delivery and neonatal hypoglycemia delivery than other groups (P<0.05). (2) The presence of villous immaturity, vascular thickening and intervillous capillary enlargement was significantly increased in the placenta of GDM (P<0.05). (3) The expression of HIF-1α and VEGF mRNA in group A (0.91±0.13 and 0.96±0.23, respectively) and B (0.72±0.12 and 0.75±0.27, respectively) was significantly more than which in group C (0.47±0.11 and 0.43±0.14, respectively, P<0.05). (4) The protein of HIF-1α and VEGF was expressed in all groups. The protein expression of HIF-1α and VEGF in group A (90.0% and 100%, respectively) and group B (82.4% and 88.2%, respectively) was significantly more than which in group C (32.4% and 35.1%, respectively, P<0.05). (5) The protein expression of HIF-1α and VEGF in GDM groups was positively correlated with the presence of villous immaturity (r=0.764, 0.875, respectively, P<0.05), stem villus arteriole thickening (r=0.655, 0.885, respectively, P<0.05) and intervillous capillary congestion (r=0.685, 0.766, respectively, P<0.05).

Over-expression of HIF-1α and VEGF in GDM placenta may be related to the placenta angiogenesis and maturation abnormalities, which is associated with adverse pregnancy outcomes of GDM.

To evaluate the accumulation of advanced glycation end products (AGE) in human skin using the method of skin autofluorescence and compare its sensitivity in diabetes screening with fasting plasma glucose (FPG).

From June 2009 to June 2011, 201 subjects who accepted skin autofluorescence test, FPG test and oral glucose tolerance test(OGTT) in out-patient department of Hefei Institutes of Physical Science's hospital and Anhui Provincial hospital were enrolled, including 111 with normal glucose regulation, 27 with impaired glucose regulation and 63 with type 2 diabetes. The diagnosis of diabetes mellitus and impaired glucose regulation was based on the diagnostic criteria specified in Chinese Type 2 Diabetes Prevention and Treatment Guidelines (2010). FPG was investigated in each group. Oral glucose tolerance test was performed and 2 h post-challenge glycemia (2 h PG) was also measured in the three groups. Skin autofluorescence of right forearm was tested and the intensity was recorded. Statistical analysis was performed by using one way ANOVA, Chi-square test and Spearman correlation analysis.

The levels of FPG in the group with normal glucose regulation, impaired glucose regulation and type 2 diabetes were (4.99±0.45), (6.57±0.27) and (9.45±3.98) mmol/L respectively, there was significant difference among the groups (F=280.88, P<0.05). The levels of skin autofluorescence were (1.88±0.12), (1.92±0.14) and (2.15±0.22) AU respectively in the three groups, and there was significant difference among the groups (F=10.88, P<0.05). According to the receiver-operator characteristics (ROC) for the noninvasive testing and FPG, the sensitivity of the noninvasive testing method and FPG method were 77.8% and 65.1% respectively under the same specificity of 86.2% (FPG=6.1 mmol/L).

The preliminary findings show that skin autofluorescence method has the advantages of non-invasive and rapid testing and also a higher sensitivity.

To investigate the clinical characteristics in outpatients with type 2 diabetes mellitus and coronary heart disease (CHD).

Retrospectively analyzed the clinical data of 528 outpatients with type 2 diabetes mellitus enrolled from January to December in 2007 in outpatients. Patients were divided into two groups according to CHD history: CHD group (n=81, 40 males and 41 females) and non-CHD group (n=447, 249 males and 198 females). The clinical characteristics of the patients were analyzed.Logistic regression analysis was applied to explore independent correlation factor for CHD in patients with type 2 diabetes.

Compared with patients in non-CHD group, patients in CHD group were older((60±12) and (69±8) years, respectively, t=-8.64, P<0.05), with longer duration of diabetes((9±7) and (12±7)years, respectively,t=-4.44, P<0.05), higher glycated hemoglobin A1c (HbA1c)(6.8%±1.1% and 7.4%±1.2%, respectively,t=-3.38, P<0.05), and higher systolic blood pressure ((130±15) and (134±15) mm Hg(1 mm Hg=0.133 kPa), respectively,t=-2.26, P<0.05); And the patients in CHD group had higher incidence of hypertension, dyslipidemia, stroke and positive family history of CHD(χ²=14.29, 9.47, 25.01, 7.56, all P<0.05). The standard-reaching rate of blood pressure and blood lipid in the two groups were similar; but the rate of HbA1c<7.0% was much lower in CHD group than that in non-CHD group(48.1% and 68.2%, respectively, χ²=12.18, P<0.05). Logistic regression analysis showed that age, duration of diabetes, HbA1c, stroke, systolic pressure and the use of statins were correlation factors for CHD(OR=1.08, 1.11, 1.47, 2.72, 1.03 and 2.41, respectively, all P<0.05).

Outpatients with diabetes and CHD are concomitant with multiple risk factors, for these patients, more attention should be paid to the management of blood glucose, blood pressure, blood lipid and the use of statins.

To investigate the expression of genes relevant to insulin synthesis of intrauterine growth retardation(IUGR) rats at 36 weeks.

Twenty healthy female SD rats (250-270 g; 8-10 weeks old) were housed in the SPF animal room. After two weeks acclimatization, male and female rats were placed in same cage overnight for mating. Day 1 of pregnancy was defined as the day on which vaginal plugs were found. Female rats were grouped into normal controls (n=10) and model group (n=10) according to random number table. The IUGR rat model was established by maternal nutrition restriction during mid- to late-gestation. Pregnant rats received 50% of their daily food intake beginning from day 11 through day 21 of gestation, compared with their control counterparts who had free access to rat chow. The birth weights of the offsprings born to semistarvation mothers were more than two times of standard deviation below the mean values of the birth weights of the control group with IUGR. The litter size was randomly reduced to eight at birth to assure uniformity of litter size between IUGR and control litters. Two groups of pups were fostered to their mothers until they were weaned at day 21, and then all the pups were fed with standard rat chow until 36 weeks of life. Male offsprings at 36 weeks of age were selected as research subjects. Intraperitoneal glucose tolerance test (IPGTT) and insulin releasing test (IRT) were performed in IUGR and normal groups. RT-PCR was applied to detect the expression of pancreas genes such as Insulin1, Insulin2 and PDX-1. The t test was used in the comparison between two groups.

At 36 weeks of age, body weight, pancreas weight and pancreas/body weight in IUGR group were much lower than those in normal group ((4971±525) and (5844±398) mg, (0.58±0.05)% and (0.69±0.04)% respectively, t=-2.65 and -3.39, both P<0.05). Glucose levels at 30, 60, 120 and 180 min after glucose load were significantly higher in IUGR group (30 min: (17.9±1.5) vs (16.1±1.1) mmol/L, 60 min: (13.4±1.1) vs (11.7±1.4) mmol/L, 120 min: (10.1±0.8) vs (8.6±1.0) mmol/L, 180 min: (8.9±1.0) vs (7.6±0.9) mmol/L,t=2.31, 2.37, 2.77, 2.34, all P<0.05), indicated glucose tolerance was impaired in IUGR rats. In addition, there was no significant difference in the insulin levels at the time points during glucose tolerance test between normal and IUGR rats (t=1.66, -0.10, -0.65, -0.83, -0.58, P>0.05). In IUGR rats, the expressions ofInsulin1 mRNA were reduced markedly than those in the controls (0.79±0.17 vs 1.25±0.28, t=-2.78, P<0.05). Although no significant differences were observed in gene expression ofInsulin2 mRNA and PDX-1 mRNA (both P>0.05).

The IUGR rats had deteriorated glucose tolerance at 36 weeks of age with decreased gene expression of Insulin1 in pancreas.

Since 1973 Hirata^[1]Since hypoglycemia caused by insulin autoimmune syndrome was first reported, clinical reports have gradually increased, mainly animal insulin and genetically recombinant human insulin caused immune hypoglycemia, but insulin analog insulin aspart 30 injection (NovoRui 30) caused immune hypoglycemia is rare. Because there are few cases, atypical clinical manifestations, and the pathogenesis is not fully understood, the clinical detection indicators are not standardized, which makes it easy to be misdiagnosed. Two patients recently admitted to our hospital are reported and the literature is reviewed to improve the understanding and diagnosis and treatment level of this disease.

It has been established that type 2 diabetes mellitus (T2DM) is a heterogeneous and complex disease caused by many factors, and numerous studies have shown that genes play an important role in its pathogenesis. In recent decades, the related susceptibility genes and regulatory factors have been extensively studied in order to better understand the pathophysiology of this disease, elucidate its pathogenesis, and develop better diagnosis, prevention and treatment strategies. Peroxisome proliferator-activated receptor gamma coactivator 1 α (PGC-1 α) is an important nuclear coactivator recently discovered, which has been closely related to the pathogenesis of type 2 diabetes. PGC-1 gene is involved in various metabolic pathways related to diabetes mellitus pathogenesis. As an important research hotspot, its relationship with mitochondrial morphology and structure in type 2 diabetes mellitus has been described in detail before^[1]。 In this paper, the relationship between PGC-1 gene expression regulation and the pathogenesis of type 2 diabetes mellitus will be described, so as to better clarify its important role in the pathogenesis of diabetes mellitus.

Obesity and diabetes are becoming a global epidemic. The world's obese population has reached 1 billion, and there are 200 million in China alone^[1]。 There were about 366 million people with diabetes worldwide in 2011, and it is expected to reach 552 million by 2030^[2]。 The survey shows that from 2007 to 2008, the prevalence of diabetes in China was as high as 9.7%, and the patients reached 92.4 million^[3]。 Medical treatment of diabetic and obese patients can only relieve and control weight in the short term, but cannot stop the progress of diabetes. However, bariatric surgery is complicated and has related risks, so its application is limited. Duodenojejunal cannula (DJBS) implantation, which can compensate for the shortcomings of drug treatment and surgery, is a less invasive and more cost-effective new technology for the treatment of obesity and diabetes. The mechanism and application of DJBS implantation are reviewed in this paper.

Blood sugar control is the key to diabetes treatment. The results of the UK Diabetes Prospective Study (UKPDS) show that for every 1% decrease in glycosylated hemoglobin (HbA1c), the risk of amputation and death due to microvascular complications of diabetes decreases by 43%, the risk of macrovascular complications decreases by 37%, and the risk of heart failure decreases by 16%^[1]。 Due to the progressive nature of the disease, patients with type 2 diabetes need to start insulin therapy sooner or later in order to effectively control blood sugar^[2]。 Pharmacological studies and clinical trials have confirmed that insulin analogs are currently commonly used insulin preparations in the world. Compared with traditional human insulin, they can better simulate the effects of insulin in physiological conditions, thus bringing more stable and effective hypoglycemic effects to diabetic patients, fewer hypoglycemic events^[3,4,5,6]。 Because clinical trials strictly stipulate patient enrollment conditions and treatment regimens, the efficacy and safety of drugs in actual clinical use often require further evaluation by observational studies. The A1chieve study is a multinational, multicenter, large-scale observational study evaluating the efficacy and safety of premixed insulin analogs (biphasic insulin aspart 30), basal insulin analogs (insulin detemir), and prandial insulin analogs (insulin aspart) alone or in combination with oral hypoglycemic agents in the actual clinical treatment of type 2 diabetes^[7]。 The 24-week study was conducted at 3166 centers in 28 non-European and American countries worldwide. A total of 66,726 patients with type 2 diabetes were included, and 11,020 patients in China participated in the study^[8]。 At present, many academic papers based on A1chieve research have been published in international and domestic academic journals and conferences. These findings provide important information on how insulin analogs can be used in daily clinical practice.

High-intensity exercise can improve the body's metabolic state and may mobilize liver fat. Exercise therapy has long been applied to the lifestyle treatment of diabetic patients. The study aimed to evaluate the level of physical activity in patients with non-alcoholic fatty liver disease (NAFLD) and to observe the relationship between NAFLD and physical activity.

Traditional magnetic resonance imaging (MRI) measurement of hepatic steatosis is often limited by T1 image bias, T2 image decay and interference of fat proton multi-frequency signals. Novel MRI techniques such as proton density fat fraction (PDFF) are able to correct for the above influencing factors, but have not been specifically compared with liver biopsy in adult patients with non-alcoholic fatty liver disease (NAFLD). To examine the relationship between MRI-PDFF and histologically confirmed hepatic steatosis grade and fibrosis, biochemical examination of metabolic characteristics was performed in 51 adult patients with NAFLD confirmed by biopsy. MRI confirmed hepatic steatosis PDFF was used, and liver biopsy grading was performed according to the histological scoring system of Nonalcoholic Steatohepatitis-Clinical Research Network (NASH-CRN).

Nonalcoholic fatty liver disease (NAFLD) encompasses a range of lesions from simple steatosis to nonalcoholic steatohepatitis (NASH). NAFLD can increase the risk of cardiovascular disease, diabetes, and liver-related complications (limited to NASH). The effects of treatment strategies recommended by each guideline on liver disease, glucose metabolism, and cardiovascular risk in patients with NAFLD are unknown.

The prevalence of non-alcoholic fatty liver disease (NAFLD) in children has increased dramatically over the decades, a phenomenon that may not be explained by excessive intake of high-fat foods alone. Recent studies have shown that offspring of high-fat mothers are more likely to develop more severe NAFLD if fed on a high-fat diet after weaning than if fed on a normal diet, suggesting that feedforward cycles may increase the risk of NAFLD in offspring. This study elucidated the above-mentioned feedforward cycle in three consecutive generations of mice fed on a high-fat diet.

Obesity is associated with inflammatory changes in the extracellular matrix. Cytocohesin C (TNC) is an extracellular matrix (ECM) glycoprotein with pro-inflammatory effects. By measuring the level of TNC in adipocytes, the effects of adipocytes and interstitial vascular debris cells (SVFC) on inflammation and ECM regulation were analyzed. At the same time, the stimulating effects of tumor necrosis factor α (TNF-α) and lipopolysaccharide (LPS) on adipocytes and SVFC were analyzed.