Volume 05 · Issue 09 · 2013

This issue of Metabolic Inflammation and Diabetes collects two expert written talks, a review and several treatises. The authors introduce the relationship between metabolic inflammation and diabetes in detail, evaluate the effect of anti-inflammatory treatment, and also preliminarily explore the merits and disadvantages of inflammatory factors, and also put forward the idea of pro-inflammatory treatment of obesity. After reading each article, I benefited a lot and provoked thought, and some issues deserve attention and discussion.

In obesity, inflammation has a negative effect on glucose and lipid metabolism. This is the theoretical basis of anti-inflammatory therapy for insulin resistance. Although anti-inflammatory therapy has some efficacy in animal experiments, the clinical effect has been poor. This phenomenon has plagued us for many years, and the reason for it is still unknown. This article reviews the results of clinical and animal studies in recent years, and expounds the role of inflammation in regulating insulin sensitivity and energy balance from a new perspective, which provides a new perspective for the treatment of obesity and type 2 diabetes.

Diabetes mellitus is a systemic metabolic disease that seriously endangers human health, but the etiology has not been elucidated so far. 1999 Schmidt et al.^[1]It was proposed for the first time that inflammatory mediators can predict the occurrence of type 2 diabetes, and subsequent basic and clinical studies further supported the theory of inflammatory etiology of diabetes, forming the inflammatory theory of type 2 diabetes onset. This theory believes that diabetes mellitus is a chronic low-grade inflammatory disease mediated by inflammatory factors, which is a chronic, subclinical and non-specific immune-mediated inflammation, including non-specific inflammatory cells, inflammatory factors secreted by inflammatory cells and acute reaction substances produced by the liver. This chronic inflammation is different from the inflammatory response under the action of infection, injury and other stress factors, and belongs to the broad innate immune response (IIS). In recent years, the above-mentioned inflammation theory has attracted increasing attention. This paper analyzes and introduces the research progress of low-grade chronic inflammation and type 2 diabetes in recent years.

To evaluate whether the level of serum vascular endothelial growth factor(VEGF)and platelet-derived growth factor(PDGF-BB)correlates with the glucose fluctuation and microangiopathy, and to explore the mechanism of interaction in type 2 diabetic patients with normal glycosylated hemoglobin values.

A total of 100 type 2 diabetic patients with HbA1c less than 7% treated in the Heilongjiang Province Hospital were enrolled in the study with 52 males and 48 famales, aged 40-66 years old. According to the existing diabetic microangiopathy, the subjects were divided into the following three groups: the T2DM group without documented microangiopathy (n=30, 14 males and 16 females, aged (50±11) years old); the diabetic nephropathy (DN) group (n=38, 20 males and 18 females, aged (52±10) years old); the diabetic retinopathy (DR) group (n=32, 18 males and 14 females, aged (53±13) years old). The healthy control group consisted of 25 subjects with 12 males and 13 famales aged (48±9) years old, who carried out routine health examination in the same hospital during the same enrollment period. All the patients went through the laboratory examination and the following parameters were taken: fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein (HDL-C), 2 h postprandial plasma glucose (2 h PG), 24 h urine albumin (24 h urine ALB) and glycosylated hemoglobin (HbA1c). The continuous glucose monitoring system was used to detect mean blood glucose(MBG), standard deviation of mean blood glucose(SDBG), mean amplitude of glucose excursions(MAGE), largest amplitude of glucose excursions(LAGE), absolute means of daily differences (MODD) and area under curve (AUC). The level of serum VEGF and PDGF-BB were measured by the enzyme-linked immunosorbent assay (ELISA). SPSS 19.0 was used for the statistical analysis with the data shown as (±s). The t test, was used to compare difference between the groups and the single factor analysis of variance was used to investigate the correlation among the groups. The logistic regression analysis was used to explore the correlation factors for the diabetic microvascular complications, while the multiple linear regression analysis was adopted to investigate the correlation factors for the level of VEGF and PDGF-BB, Statistical difference was accepted at P<0.05.

The level of PDGF-BB was significantly increased in the DN group than that of the T2DM group without documented microangiopathy and the normal control group ((53±12), (31±6), (26±4) μg/ml, respectively with F=9.56 and P<0.05). The level of VEGF was significantly increased in the DR group than that of the T2DM group without documented microangiopathy and the normal control group ((217±57), (105±12), (74±10)μg/ml, respectively withF=8.13 and P<0.05). Compared with the T2DM group without documented microangiopathy, the DN group showed significantly higher SDBG, MAGE, LAGE, MODD and AUC ((2.41±0.34), (7.9±0.4), (8.1±0.4), (2.51±0.3), (8.0±0.7)mmol/L, respectively witht=2.57, 3.46, 5.75, 3.59, 4.28 and P<0.05), while the DR group showed significantly higher SDBG, MAGE, LAGE, MODD and AUC((2.4±1.7), (7.9±0.4), (8.1±0.4), (3.1±1.6), (8.2±0.6)mmol /L, respectively witht=3.29, 3.77, 5.38, 4.54, 3.16 and P<0.05). The level of PDGF-BB, VEGF and the blood glucose fluctuation were the independent risk factors for the diabetic microangiopathy revealed by the logistic regression analysis. Taken the level of PDGF-BB and VEGF as the dependent variables, and the blood glucose fluctuation index of SDBG, LAGF, MAGE, MODD, AUC and 2 h PG as the independent variables, the multiple linear regression analysis showed the greatest impact of MAGE, SDBG and 2 h PG on the level of PDGF-BB and VEGF.

Blood glucose fluctuation significantly correlates with the development and progression of the microangiopathy in type 2 diabetics. The level of VEGF and PDGF-BB could be increased by the blood glucose fluctuation, which may involve in the in the progression of the diabetic retinopathy and nephropathy.

To investigate the protective role of curcumin in the dysfunctional vascular endothelial cells induced by inflammation.

THP-1 cells were pretreated with 20 μmol/L curcumin under the condition of 25 mmol/L glucose and 500 μmol/L palmitic acid, while other groups received 25 mmol/L glucose and 500 μmol/L palmitic acid and dimethyl sulfoxide (DMSO), seperately. After 24 h treatment, the real time Polymerase Chain Reaction(PCR) was explored to detect the mRNA expression of receptor interaction protein 140(RIP140), tumor necrosis factor-α (TNF-α) and interleukin- 6 (IL-6), while the concentration of TNF-α and IL-6 in the supernatant was detected by the enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were incubated with the supernatant from the THP-1 in each group. The methodology of 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and western-blot was applied to investigate the proliferation, apoptosis and the protein expression of phosphorylated extracellular regulated protein kinases (ERK) and B-cell lymphoma 2 (Bcl-2).

The mRNA expression of RIP140, TNF-α and IL-6 in the THP-1 cells and the concentration of TNF-α and IL-6 in the supernatant were significantly higher when treated with 25 mmol/L glucose and 500 μmol/L palmitic acid, than those in the control group (t= 8.55, 9.44, 9.73, 16.01, 19.22 with all P<0.05). In the groups treated with 25 mmol/L glucose and 500 μmol/L palmitic acid, the pretreatment with curcumin significantly decreased the mRNA expression of RIP140, TNF-α and IL-6 in the THP-1 cells and the concentration of TNF-α and IL-6 in the supernatant(t=3.59, 5.96, 5.59, 6.95, 23.91 with all P<0.05). At 24 h and 48 h treatment, compared with the control group, the supertant from the groups treated with 25 mmol/L glucose and 500 μmol/L palmitic acid significantly suppressed the proliferation of HUVECs (24 h: 1.22±0.07 vs 1.85±0.14,t=6.58, P<0.05; 48 h: 1.72±0.02 vs 2.49±0.09,t=10.08, P<0.05), while the proliferation of HUVECs could be improved by the pretreatment with 20 μmol/L curcumin (24 h: 1.22±0.07 vs 1.72±0.11,t=2.13, P<0.05; 48 h: 1.72±0.02 vs 2.33±0.11,t=6.92, P<0.05). Compared with the control group, the incubation with the supertant from the groups treated with 25 mmol/L glucose and 500 μmol/L palmitic acid significantly increased the apoptosis rate and the level of phosphated ERK, while decreased the Bcl-2 protein expression (t=9.82, 9.69, 4.61, all P<0.05). Such effect could be reserved by the pretreatment with 20 μmol/L curcumin (t=6.35, 7.17, 3.26, all P<0.05).

Curcumin could protect the vascular endothelial cells from the dysfunction induced by inflammation.

To investigate the anti-proteinuria and anti-inflammatory effect of the different dosages of tripterygium wilfordii polyglucosides (TWP) in rats with diabetic nephropathy.

A total of 68 male SD rats aged 5-6 weeks and weighed (190±15)g were divided into the normal control group (NC, n=8) and the high glucose fatty diet group (HGFD, n=60) by the randomized table method. After feeding with high glucose fatty diet for 4 weeks, rats in the HGFD group were induced into the diabetics by Streptozotocin (STZ) and further divided into the diabetic model group (DM group), TWP low-dose group (TL group, 6 mg/kg), TWP middle-dose group (TM group, 12 mg/kg) and TWP high-dose group (TH group, 24 mg/kg), with 15 rats in each. At week 5, after the induction of DN in the HGFD group, the intervention was given by gavage and all rats were sacrificed at the end of the week 8. The following parameters were tested in all rats: blood glucose and blood lipid after HGFD, UMA at week 0, 4 and 8, liver and kidney function and the expression of tumor necrosis factor-α, interleukin-4 in the renal tissue at the the end of week 8. Difference was compared by the single factor analysis and the independent-samplest test of variance. The multivariate analysis of covariance was applied to control the baseline difference between the groups and the effect of weight, triglycerides and total cholesterol on the expression of TNF-α and IL-4.

(1)The levels of blood glucose (t=4.404, 3.393, 2.699, 2.940, all P<0.05), TG and TC(t=13.546, 15.251, all P<0.05)in the HGFD group were significantly higher than those in the NC Group. The UMA levels were higher in the HGFD group than that in the NC group (t=11.588, 23.452, 16.033, 19.992, all P<0.05). (2)At the end of the week 8, the levels of UMA and Kidney Weight/Body Weight (KW/BW) were higher in the HGFD group than those in the NC group(t=17.276, 10.477, all P<0.05). Compared with the DM group, all the three TWP groups showed decreased UMA and KW/BW with the most reduction observed in the TM group (t=13.274, 15.877, 10.480, 3.588, 4.794, 3.134, all P<0.05). No statistical difference was found in the liver and kidney function among the groups (F=0.610, 1.263, 1.032, 0.278, respectively, P>0.05). (3) Significant difference was showed in the mRNA and protein expression of TNF-α and IL-4 among the 5 groups(F=87.415, 15.623, 152.196, 11.377, respectively, P<0.05). Compared with the NC group, the DM group manifested increased ex-pression of TNF-α(t=19.961, 8.888, all P<0.05), while not the expression of IL-4 (P>0.05). Compared with the DM group, the mRNA and protein expression of TNF-α were dramatically decreased in the three TWP groups (t=5.233, 8.397, 4.021, 4.765, 5.977, 2.727, all P<0.05), while those of IL-4 were significantly increased (t=31.509, 36.532, 6.540, 7.761, 9.621, 5.387, all P<0.05), with the highest effect observed in the TM group and followed by the TL group and the TH group.

TWP can enhance the expression of the anti-inflammatory cytokines, such as IL-4, and inhibit that of the pro-inflammatory cytokines, such as TNF-α. Thus, TWP could alleviate the local inflammation in kidney, which may be the key mechanism of its anti-proteinuria effect.

To analyze and compare the difference between the finger capillary blood glucose (CBG), capillary plasma glucose (CPG), venous blood glucose (VBG) and venous plasma glucose (VPG) in fasting or 2-hour postprandial state.

One hundred and forty patients with type 1 or type 2 Diabetes Mellitus patients (56 males and 84 females with mean age(54±10)years and 82 patients with fasting and 58 with 2-hour postprandial glucose) were included in this study. Four different blood samples were measured for each patient simultaneously. CBG and VBG was measured using One Touch Verio blood glucose monitoring system. CPG and VPG was measured using YSI 2300 glucose analyzer as a reference method. A clinical evaluation of accuracy of One Touch Verio glucose monitoring system was conducted.

The accuracy of Verio blood glucose monitoring system met the requirements of ISO 15197 (2003) standard. In fasting state, CBG and VBG which detected by blood glucose monitoring system was (6.7±2.4) mmol/L and (6.7±2.3) mmol/L, respectively. The relative error was 0.40%(t=0.62, P>0.05). CPG and VPG which detected by YSI was (6.4±2.5) mmol/L and (6.4±2.4) mmol/L, respectively. The relative error was 0.25%(t=0.39, P>0.05). CBG were slightly higher than VPG. The relative error was 5.89%(P<0.05). In 2-hour postprandial state, CBG and VBG were (8.5±3.6) mmol/L and (7.9±3.6) mmol/L, respectively. The relative error was 7.58%(t=9.55, P<0.05). CPG and VPG was (8.1±3.8) mmol/L and (7.6±3.8) mmol/L, respectively. The relative error was 6.08%(t=10.9, P<0.05). CBG was obviously higher than VPG. The relative error was 11.6%,P<0.01.

One Touch Verio glucose monitoring system is suitable for clinical monitoring of blood glucose and also for SMBG, the fasting CBG values are close to those of the VPG. The postprandial CBG values are higher than those of the VPG.

To explore the effect of oral alpha-lipoic acid(ALA)supplement on the function of islet β cell and level of oxidative stress in overweight/obese subjects.

This was a clinical trial using the randomized, double blind, placebo controlled, cross-over design. In Physical Examine Department of People's Hospital of Kelamay City in Xinjiang between May 2009 and October 2009, 103 overweight/obese Han subjects( 63 males and 40 females ) who met the inclusion and excluded criteria were randomly assigned to group A(n=52) or group B(n=51) using blocked randomization. Group A received 8-week ALA(1200 mg/d)followed by placebo for 8 weeks, while group B received 8-week placebo(1200 mg/d)followed by ALA for 8 weeks. A washout period of 4-week followed completion of the ALA/ placebo study period. Questionare, plasma oxidized low density lipoprotein(Ox-LDL) and 8-iso-prostaglandin F(8-iso-PGF), fasting and postprandial 2-hour plasma glucose, fasting and postprandial 2-hour plasma insulin, blood pressure, anthropometrics and biochemical parameters were measured at baseline. The methods of examine and inspectors were same through the whole trial. Data were analyzed by mixed-effect statistical model using STATA 11.0.

Compared with placebo group, except for HOMA-β(3.96(-28.95-36.93)vs 0.03(-17.11-17.17)), the value of HOMA-IR(0.27(-3.13-3.56) vs 0.23(-1.14-1.60)), 8-iso-PGF (36.91(-3.22-76.42) ng/L vs 32.15 (-2.72-67.06) ng/L), Ox-LDL(-3.52(-5.48-1.52) μg/L vs -6.49(-8.22-4.78)μg/L) was not reduced in the intervention group after 8 weeks. There was no significant difference between the two groups (t=1.0443, 0.848, 1.247, respectively, all P>0.05). But the mix-effect models showed ALA had no significant effect on HOMA-β, HOMA-IR, 8-iso-PGF and Ox-LDL after adjusting for baseline values, sex, age, treatment order or period.

Oral ALA supplement, 1200 mg/d for 8-week may not reduce the level of oxidative stress and insulin-resistant or improve the function of islet β cell for the short time in overweight/obese subjects.

To investigate the association of serum sex hormone-binding globulin (SHBG) with metabolic variables in type 2 diabetic patients, and to evaluate whether serum SHBG could be a biomarker of nonalcoholic fatty liver disease (NAFLD).

Total of 281 type 2 diabetic patients treated in Nanjing Drum Tower Hospital from September 2009 to August 2012 were included in the study.The patients were assigned to the NAFLD group and non-NAFLD group according to the result of liver ultrasound.Fasting blood draw were taken to detect liver enzymes, lipids, insulin levels, thyroid function and sex hormones.The correlations between serum SHBG levels and metabolic parameters as well as the prevalence of NAFLD were analyzed by using multiple linear regression or unconditional multinomial logistic regression analysis.

There were 125 subjects in NAFLD group (male 85, female 40, age (57 ± 12) yrs) and 156 in non-NAFLD group (male 85, female 71, age (61 ± 13) yrs), respectively.Serum SHBG levels in NAFLD group were significantly lower than that in non-NAFLD group ((26 ± 9) vs (44 ± 6) nmol/L, t=-10.42, P<0.05). In the multiple linear regression model with SHBG as the dependent variable, age and high density lipoprotein cholesterol (HDL-C) were positively associated with SHBG (β=0.316, 0.200, allP<0.05), while waist circumference, triglycerides (TG), homeostasis model assessment of insulin resistance (HOMA-IR) and thyrotropin were inversely associated with SHBG (β=-0.175, -0.243, -0.163, -0.205, allP<0.05). The patients were divided into 4 groups according to SHBG quartiles.With the increased quartiles of serum SHBG, the age and HDL-C in the patients increased (allP for trend <0.05), while the body mass index (BMI), waist circumference, alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), TG, fasting plasma glucose (FPG), fasting insulin (FIns) and HOMA-IR changed in a decreased trend (all P for trend < 0.05). Besides, the proportion of NAFLD also decreased significantly with increased quartiles of SHBG ( P for trend <0.05). In the fully adjusted model, when compared with the first quartile of SHBG (reference, 1.00), the odds ratio ( OR) and 95% confidence interval (CI) for NAFLD across increasing quartiles of SHBG were 0.39 (0.14-0.88), 0.20 (0.07-0.57) and 0.08 (0.02-0.26), respectively (P for trend <0.05).

Serum SHBG level in type 2 diabetic patients is significantly associated with age, waist circumference, HDL-C, TG and HOMA-IR.Low serum SHBG is an independent risk factor for the presence of NAFLD and might be an important bio-marker of NAFLD in type 2 diabetic patients.

To investigate effect of radix hedysari polysaccharide (HPS) on secretion of nitric oxide (NO) and endothelin-1 (ET-1) on human umbilical vein endothelial cells(HUVECs) induced by high glucose and its mechanism.

HUVECs were isolated from umbilical vein, and cultured cells were divided into normal control group, high glucose group, HPS group, MTT assay were used to analyze the effect of HPS on HUVECs viability under high glucose. The levels of NO, nitric oxide synthase (NOS) and inducible nitric oxide synthase (iNOS) were measured by colorimetric analysis. The content of ET-1 in clear supernatant were detected by enzyme linked immunosorbent assay (ELISA). The expression of endothelial nitric oxide synthase (eNOS), ET-1 mRNA, c-Jun kinase-1(JNK1) mRNA were examined by real-time quantitative RT-PCR.

The cells viability were markedly decreased when HUVECs were treated with 30 mmol/L-glucose for 6 h((82.4±3.5)%), 24 h((68.2±1.4)%), 48 h((63.0±2.9)%), HPS could efficiently prevented cells viability lost(P<0.05), especially in 50 mg/L((85.3±4.6)%), 100 mg/L ((89.6±1.1)%), 200 mg/L ((88.8±3.6)%),P<0.05. In high glucose group, the levels of NO ((24.84±1.34)μmol/L)and NOS((0.54±0.06) U/ml) were increased at early stage and decreased at advanced stage compared with normal control group (P<0.05). The contents of iNOS((0.08±0.020) U/ml) and ET-1 ((0.710±0.030) ng/ml) were upgraded under high glucose at any time, nevertheless, HPS could balanced the levels of NO((23.20±0.55)μmol/L), NOS((0.46±0.10) U/ml), iNOS((0.08±0.020) U/ml) and ET-1((0.710±0.030) μg/L),P<0.05. At equal pace, the expressions of eNOS mRNA was up-regulated and ET-1 mRNA was down-regulated in HPS group compared with high glucose group(0.33±0.02 vs 0.23±0.04, 2.28±0.31 vs 2.79±0.29). The contents of JNK1 mRNA in HUVECs were shown to increased after exposure to high glucose(2.95±0.05),P<0.05, which were markedly prevented by HPS(1.45±0.05),P<0.05.

HPS can protect the injury of HUVECs induced by high glucose in vitro. The mechanism of protection may be associated with blocked JNK signaling pathway.

We reported three cases of POEMS syndrome with diabetes mellitus. All of the patients had the first symptom of peripheral neuropathy, as combined with diabetes mellitus. They were diagnosed initially as diabetic peripheral neuropathy. However, they were finally diagnosed as POEMS syndrome through related examinations. POEMS syndrome is a rare plasma cell clonal disorder and most of the patients come on with peripheral neuropathy. We summarize the features of differential diagnosis between polyneuropathy of the POEMS syndrome and diabetic peripheral neuropathy.

Diabetes is one of the most important epidemics in the world. According to WHO data, there are currently 347 million diabetic patients in the world, with a prevalence rate of 9.5% in adults^[1]。 Chronic complications of diabetes mellitus are the main causes of death and disability in diabetic patients. The causes of chronic complications of diabetes are not well understood at present, but they are at least partly caused by vascular damage caused by long-term hyperglycemia, hypertension and lipid metabolism disorders.

In recent years, the incidence of obesity has increased rapidly in the world. It is closely related to diabetes, cardiovascular and cerebrovascular diseases, infection and tumor, which has caused a huge economic and psychological burden to human society. At present, the research on obesity has gone deep into the molecular level, and the results suggest that insulin resistance caused by obesity is the central link in the occurrence and development of the above complications, while low-grade and chronic inflammatory reactions in visceral adipose tissue under obesity are considered to be an important pathophysiological mechanism leading to insulin resistance^[1]。 Studies have shown that both natural immunity and acquired immunity play an important role in this process. Among them, T cell immunity including regulatory T lymphoid (Treg) cells is attracting more and more attention from domestic and foreign scholars^[2]。 This paper briefly summarizes the research progress in the above aspects.

Nonalcoholic fatty liver disease (NAFLD) refers to a clinicopathological syndrome characterized by diffuse hepatocellular steatosis and fat storage in addition to alcohol and other definite hepatic damage factors. The pathological changes varied with the course of the disease, including simple fatty liver, steatohepatitis (NASH) and its associated liver fibrosis, cirrhosis and hepatocellular carcinoma^[1]。 NAFLD is strongly associated with metabolic syndrome, especially insulin resistance (IR), obesity, and type 2 diabetes^[2]With the acceleration of global urbanization and the change of lifestyle, its incidence is increasing day by day, and it has become one of the three major liver diseases that endanger human health. Although the harm of NAFLD is increasingly serious, the pathogenesis of the disease is still unclear. So far, one theory that has been widely accepted by scholars is the "second strike" theory^[3], the first blow refers to insulin resistance causing peripheral lipolysis and hyperinsulinemia, resulting in hepatocyte steatosis; On this basis, the second "strike" factors such as inflammatory factors, free fatty acids (FFA), oxidative stress, and inflammatory response initiated by endoplasmic reticulum stress have direct toxic effects on hepatocytes through various signaling pathways, resulting in liver pathological damage. It can be seen that insulin resistance and inflammatory response are key factors in the occurrence and development of NAFLD. The relationship between insulin resistance and inflammation is also very close. Many studies have found that in the state of insulin resistance, the level of inflammatory factors in the body is significantly increased, and these inflammatory factors are involved in the pathophysiological mechanism of insulin resistance. Therefore, inflammatory response runs throughout the occurrence and development of NAFLD, and plays an important role in the pathogenesis of NAFLD. Therefore, this article reviews the relationship between inflammation and non-alcoholic fatty liver disease and its role in the pathogenesis of non-alcoholic fatty liver disease.

Dipeptidyl peptidase-IV (DPP-4) inhibitors increase the concentration of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) in vivo by inhibiting the activity of DPP-4 enzyme, and exert glucose-dependent insulinotropic and anti-glucagon effects, thereby lowering blood sugar. Since its launch in 2006, DPP-4 inhibitors have become one of the ideal hypoglycemic drugs for patients with type 2 diabetes because of their good hypoglycemic efficacy, few adverse reactions (low risk of hypoglycemia, neutral weight impact), and convenient administration.

Study on the impact of diabetes based on a large national population-based screening study in China to estimate the use and expenditure of medical resources for diabetes in China and to clarify the use of major basic drugs and treatments. From 2009 to 2010, this study surveyed 1482 adult diabetic patients and 1553 adults with normal glucose tolerance through population-based random sampling at 12 survey sites in China, with a response rate of 67%.

Macrovascular disease can increase the risk of accelerated cognitive decline in patients with type 2 diabetes. The Edinburgh Type 2 Diabetes Study (ET2DS) aims to clarify the association of macrovascular disease indicators with cognitive changes in cognitively normal elderly patients with type 2 diabetes. The study examined baseline clinical and subclinical macrovascular disease, including cardiovascular history, carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and serum amino-terminal brain natriuretic peptide (NT-proBNP) levels, in 831 men and women (aged 60 to 75 years). Subjects were subjected to 7 neuropsychological tests at baseline and 4 years later; Cognitive scores were combined with a standardized general competence factor (g). Follow-up period g was adjusted for baseline g to assess cognitive change over 4 years. Adjusting vocabulary (estimating pre-onset ability) was used to estimate cognitive changes over survival.

Studies on metabolic status of metabolically normal obese (MHO) people have always attracted more attention and curiosity. The North West Adelaide Health Study aimed to determine whether metabolically normal obesity (MHO) is associated with long-term diabetes and the occurrence of cardiovascular events/stroke. The study randomly selected 4056 adults aged ≥18 years. No cardiovascular disease (CVD) /stroke or underweight according to body mass index (BMI) level and metabolic status (n=3743) were grouped. Metabolic status is determined according to the diagnostic criteria of metabolic syndrome (except waist circumference) established by the International Diabetes Federation (IDF), and those who meet more than 2 of them are metabolic abnormalities. It was found that MHO [n=454 (12.1%)] associated factors included smoking, socioeconomic disadvantage, lack of physical activity, etc. With metabolically normal normal body weight [n=1172 (31.3%)] compared with MHO, who were more susceptible to metabolic abnormalities during follow-up of 5.5 to 10.3 years (incidence of 15.5% and 33.1%, respectively,P<0.001) and diabetes [odds ratioOR=2.09, 95% CI (CI): 0.87-5.03] but no CVD/stroke (OR＝1.16，95%CI：0.58～2.29)。 MHO study subjects who can maintain metabolic normality [n=188 (67.0%)] did not present these risks. In obese participants, the reason why they were able to maintain a metabolic normal state was related to factors such as age ≤40 years and smaller waist circumference. MHO women exhibited significantly higher (mean [standard error]) proportions of leg fat (49.9 [0.5] vs. 53.2 [0.7]) and smaller waist circumference (104 cm [0.6] and 101 cm [0.8]) compared to metabolically dangerous obesity, although there was no significant difference in overall obesity.

Some studies suggest that type 2 diabetes may increase the risk of amnestic mild cognitive impairment (aMCI) through Alzheimer's disease (AD) -related lesions and vascular lesions, and non-amnestic mild cognitive impairment (naMCI) through vascular lesion mechanisms. To this end, the Mayo Clinic has conducted a prospective study aimed at investigating the association of type 2 diabetes with MCI and its subtypes in the overall population and among different genders.

Studies have found that gestational diabetes mellitus (GDM) increases the risk of fetal birth injury, shoulder dystocia, neonatal hypoglycemia, respiratory distress syndrome, childhood obesity, and maternal caesarean section, hypertension, and type 2 diabetes. Therefore, it is extremely important to reduce the incidence of GDM. To this end, a research team from the Department of Obstetrics and Gynecology of the University of Messina, Italy, conducted a prospective, randomized, placebo-controlled study to test a hypothesis: whether inositol supplementation can reduce the risk of GDM in pregnant women with a family history of type 2 diabetes.