Volume 07 · Issue 02 · 2015

In recent decades, the number of diabetic patients worldwide has increased at an alarming rate. About 246 million people worldwide had diabetes in 2007, and it is estimated that by 2030, there will be 380 million people with diabetes, most of which will be concentrated in developing countries. The Diabetes Branch of the Chinese Medical Association screened 48,431 people over the age of 20 in 14 provinces, municipalities and autonomous regions in China for diabetes from 2007 to 2008. The results showed that the prevalence of diabetes and pre-diabetes were 9.7% and 15.5%, respectively, and it is estimated that the number of people affected by diabetes in China will reach 92.4 million^[1]。 According to the 2013 Journal of the American Medical Association (JAMA), the prevalence of diabetes among Chinese adults has reached 11.6%^[2]Diabetes has become a major public health problem that seriously affects the physical and mental health of Chinese people.

Diet has been regarded as an important factor in inducing diabetes and is key to diabetes management. Studies over the past decades have demonstrated the importance of interventions with nutrients such as carbohydrates and fats for diabetes prevention and management. However, in real life, the food intake by individuals is diverse and there are synergistic or antagonistic effects between foods, emphasizing that single foods or individual nutrients do not reflect the overall effect of the meal. In recent years, researchers have paid more and more attention to the influence of dietary structure on diabetes prevention and treatment, in order to seek the "best" dietary pattern for diabetes.

Due to stress and inflammatory reactions, serious glucose metabolism disorders mainly caused by insulin resistance often occur in critically ill patients, which is manifested as elevated blood sugar, which is called stress hyperglycemia. Since 1990, a number of clinical studies have found that stress hyperglycemia is a common pathophysiological disorder in critically ill patients in surgery, internal medicine and pediatrics, which can cause serious adverse effects on clinical outcomes, including increasing mortality, increasing the risk of organ dysfunction, etc^[1]。

In recent decades, the number of diabetic patients worldwide has increased at an alarming rate, and it is expected that by 2030, the number of diabetic patients will grow to 380 million, with the majority concentrated in developing countries^[1]。 In 2013, it was reported that the prevalence of diabetes among adults in China has reached 11.6%^[2]Diabetes has become a major public health problem that seriously affects the physical and mental health of Chinese people.

To investigate the molecular pathogenesis of misfolded proinsulin induced β-cell failure.

293T cells were transfected with vector expressing preproinsulin wild type (normal control group) or preproinsulin missense mutants C (A7) Y, G (B8) S, G (C28) R. At 72 h posttransfection, cells were collected and divided into 2 groups. In one group, the expression of spliced XBP-1 mRNA and unspliced XBP-1 mRNA in cell were detected with semi-quantitive RT -PCR. In another group, Western blotting chest protein BiP, eukaryotic initiation factor 2α (eIF2α) and phosphorylation eIF2α (peIF2α). Data were analyzed with one-way ANOVA andt test.

Compared with WT-mouse proinsulin, C (A7), G (B8) S mutant increased XBP-1s/XBP-1u in 293T cell, and the difference was statistically significant (0.52±0.16 vs 0.84±0.17, 0.52±0.16 vs 0.70±0.16, t=3.17, 2.35, both P<0.01). While mutant G (C28) S didn't up-regulate the level of XBP-1s/XBP-1u (0.52±0.16 vs 0.55±0.14,t=0.30, P>0.05). Compared with wild type, mutant C (A7) Y and G (B8) S increased p-eIF2α/eIF2α (0.10±0.01 vs 0.35±0.03, 0.10±0.01 vs 0.27±0.02,t=13.57, 9.37, both P<0.01). Mutant proinsulin G (C28) R didn't up-regulate the level of p-eIF2α/eIF2α (0.10±0.01 vs 0.08±0.01,t=1.09, P>0.05).

Expression of MIDY mutants C (A7) Y and G (B8) S could lead endoplasmic reticulum stress and unfolded protein response, which may be through the activation of IRE1-XBP1 and PERK-eIF2α-ATF4 pathway.

To determine the role and possible mechanisms of 1,25-dihydroxy vitamin D₃ and vitamin D receptor (VDR) in anti-fibrosis of diabetic nephropathy (DN).

DN rats (n=24) were randomly divided into 4 groups as blow: (1) over-expression with arachis oil group (group A, n=6); (2) over-expression with vitamin D group (group D, n=6); (3) virus vector with arachis oil group (group B,n=6); (4) virus vector with vitamin D group (group E, n=6). Six normal rats was resigned as control group with arachis oil (group C, n=6). DN rats were injected different lentivirus with transforming growth factor beta 1 (TGF-β₁) to establish the model. After a 37 days gavage of 1,25-dihydroxy vitamin D₃ or arachis oil, the kidney was taken out as samples. The structure and morphology change in kidney tissues was observed by electron microscope and Masson staining; the expressions of mRNA and protein of TGF-β₁, VDR, moynocte chemoattractant protein-1 (MCP-1), collagen-1 (Col-1) in kidney tissues were measured by immunohistochemistry, Western blotting and real-time PCR. Variance analysis was used to compare among multigroups, and t test was used to compare two groups.

(1) Glomerular fibrosis was correlated with TGF-β₁ level. (2) MCP-1, Col-1 mRNA and protein expressions were all decreased (all P<0.05), while VDR was increased in group A (0.65±0.44, 2.01±0.70), B (1.17±0.59, 3.19±1.01) and C (3.93±1.17, 5.38±0.48) with the reducing level of TGF-β₁ (F=19.28, 19.11, all P<0.01). (3) After the intervention of 1,25-dihydroxy vitamin D₃ in group D, TGF-β₁, MCP-1 and Col-1 mRNA and protein expressions are decreased (all P< 0.05); while VDR mRNA and protein expressions was increased (t=5.61, 2.95; all P<0.05), compared with group A. In group E, TGF-β₁, MCP-1 and Col-1 expressions were decreased (all P<0.05); while VDR was increased (t=5.42, 3.33; all P<0.05), compared with group B. (4) The severity of renal fibrosis is improved after vitamin D treatment in electron microscope, Masson staining.

1,25-dihydroxy vitamin D₃ may have anti-fibrosis effects in DN by down-regulating the expression of renal fibrosis factors, such as TGF-β₁, MCP- 1 and Col- 1, and increasing the expression of VDR. Under different expression of TGF-β₁ in kidney, 1,25-dihydroxy vitamin D₃ may also plays a protective role in diabetic nephropathy via the pathway above.

To investigate the effect of C-peptide on advanced glycation end products (AGE)-induced oxidative stress in rat mesangial cells and its mechanism.

Rat mesangial cells were cultured in the normal medium (Control group), or medium with 200 mg/L AGEs (AGEs group), or medium with 200 mg/L AGEs and 5 μmol/L C-peptide (AGEs+C-peptide group) or medium with 10 μmol/L H89 (added in advance, and incubated for 30 min) and 200 mg/L AGEs and 5 μmol/L C-peptide (AGEs+C-peptide + H89 group). The intracellular reactive oxygen species (ROS) was detected with fluorescence method, and the supernatant nitric oxide (NO) level was detected by Griess reaction. Real-time PCR and Western blotting were used to detect the expression of the receptor for advanced glycation endproducts (RAGE), protein kinase A (PKA), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and inducible nitric oxide synthase (iNOS). Non-parametric Kruskal-Wallis H test and Mann-Whitney U test were used to compare data between groups, and two groups, respectively.

Compared with control group, the level of ROS and NO increased in AGEs group (193.7±6.4 vs 136.1±4.9; and 27.2±4.7 vs 15.5±0.7, respectively, all U=0, P<0.05). C-peptide could suppress the production of ROS and NO. In AGEs+C-peptide group, ROS and NO reduced than AGEs group (136.9±14.3 vs 193.7±6.4 and 16.0±2.1 vs 27.2±4.7 respectively, all U=0, P<0.05). Compared with control group, AGEs could up-regulate the expression of RAGE (0.565±0.027 vs 0.148±0.006,0=0,P<0.05) but down-regulate PKA (0.085±0.035 vs 0.518±0.019, U=0, P<0.05). And AGEs increased the expression of NOX4 and iNOS (0.912±0.055 vs 0.105±0.012, and 0.279±0.003 vs 0.126±0.004 respectively, all U=0, P<0.05). Compared with AGEs group, C-peptide down-regulated RAGE (0.159±0.003 vs 0.565±0.027,0=0,P<0.05), up-regulated PKA (0.594±0.079 vs 0.085±0.035, U=0, P<0.05), and down-regulated NOX4 and iNOS (0.085±0.005 vs 0.912±0.055, and 0.071±0.016 vs 0.279±0.003 respectively, all U=0, P<0.05) Compared with C-peptide group, H89 groupinhibited the activation of PKA, increased the production of ROS and NO (195.7±9.3 vs 149.7±11.7 and 22.2±1.1 vs 16.4±2.1, all U=0, P<0.05). Moreover, compared with C-peptide group, the expression of NOX4 and iNOS in H89 group was increased (0.455±0.018 vs 0.085±0.005 and 0.296±0.013 vs 0.071±0.016 respectively, all U=0, P<0.05).

C-peptide inhibited oxidative stress in mesangial cells through PKA signaling pathway.

To explore the effects of β2- glycoprotein I (β2- GP1) on renal tissue pathologic change and transforming growth factor β1 (TGF-β1) expression in streptozotocin (STZ) induced diabetic mice.

Forty-eight female BALB/c mice were fed with high fat chow diet for 8 weeks. Then the mice were injected intraperitoneally with STZ (80 mg/kg). Diabetic mice were confirmed by the criterion that plasma glucose concentration was higher than 16.7 mmol/L after 1 week from injection date. The mice were randomly divided into a diabetes mellitus (DM) group (n=12), treatment with β2-GP1 (20 μg) groups (treated for 3 weeks or 6 weeks, each n=12) and a normal control group (n=12). The changes of glomerular structure and expression of TGF-β1 in renal cortical were detected by immunohistochemical techniques, quantitative real-time PCR and Western blotting. Single factor analysis of variance (ANOVA) was applied to perform the homogeneity of variance test among the groups, and SNK-q test were used to analyze the difference between two groups.

β2- GP1 improved renal dysfunction and kidney structure damage, and decreased TGF-β1 mRNA expression (3.14±0.14, 1.98±0.11 vs 6.07±0.22,q=18.037, 28.454, respectively, all P<0.05) and protein expression (0.66±0.07, 0.40±0.05 vs 1.44±0.08, q=12.757, 16.454, respectively, all P<0.05) in STZ- induced diabetic.

β2- GP1 plays a role of renal protecting by inhibiting the expression of TGF-β1 in renal tissues of the STZ-diabetic mice, may in time-dependent way.

To investigate the impact of dietary factors on metabolic syndrome (MS) in the rural population in Beijing city.

From April 2008 to March 2009, using the method of PPS random sampling cross-sectional survey for 8 189 permanent resident families in Beijing Pinggu district, in every family, use KISH table method to pick 1 person randomly (18-76 years old). The consent of each subjects for questionnaire, physical examination and blood tests were collected. Semi-quantitative food frequency method was used to understand common 10 kind of food intake. In the end, a total of 6 925 people completed the survey, of which 6 272 (male 3 132, female 3 140) effective questionnaires were included in this study. MS was diagnosed with the national cholesterol education program adult treatment report the third (NCEP ATP III-2005). Measurement data was compared by using t test. The influence factors of MS were analyzed by mul Stivariate logistic regression analysis.

The total incidence of MS was 24.69% in this population, and was significantly higher in females than that in males (32.23% vs 17.18%, χ ²=190.93, P<0.05). There were significant differences in daily frequencies of eating fruit, animal offal, livestock meat, aquatic food seafood between MS and non-MS group every day (χ²=21.18, 32.06, 9.40, 10.98, all P<0.05). People who ate fruit and livestock meat every day had a lower prevalence of MS than that in those who did not eat fruit and meat. People who ate animal offal and aquaculture seafood 0-1 time/day had a lower prevalence of MS than those who did not eat or ate more than 1 time daily. It was found by multivariate logistic regression analysis that the prevalence of MS was lower in male than in female (OR=0.42, 95%CI=0.37-0.48), and increased with age (OR=1.32, 95%CI=1.21-1.43); the dietary factors that associated with MS morbidity was not to eat fruit (OR= 1.72, 95%CI=1.33-2.21), eating livestock meat for ≥1 times daily on average (OR=1.23, 95%CI=1.07-1.42), eating animal innards for ≥1 times daily (OR=3.93, 95%CI=1.45-10.65). There was no significant differences in macro nutrients proportion (lipid, carbohydrate and protein) between the MS non-MS groups (χ²=1.01, 3.53, 7.82, all P≥0.05).

The factors associated with increased risk for MS are female, age, not to eat fruit, livestock meat eating ≥1 times daily, eating animal innards ≥1 times daily. No significant differences in macro nutrients proportion (lipid, carbohydrate and protein) between the MS non-MS groups.

To investigate the relationship between dietary intake and body composition in elderly type 2 diabetes (T2DM).

Retrospectively analyzing the differences of body composition between age (older group: ≥60 years and younger group: <60 years), and further analyzing the differences between genders and overweight or not in older group. The related dietary factors of physical makeup in the elderly patients were investigated with multiple linear regression analysis, included the intake of energy and macronutrients.

Compared with younger group, older group had lower body mass index, grip strength, and muscle mass, and hemoglobin, albumin, fasting blood glucose levels (t=-3.309 to -1.983, all P<0.05). There was no significant differences in waist-hip ratio, percentage of body fat, visceral fat area and the intake of total energy, quantity and proportion of macronutrients between the age groups (t=-1.435 to 0.316, all P>0.05). In elderly group, female had higher percentage of body fat, and lower grip strength, muscle mass (t=-3.911, -2.207, -2.825, 13.921, all P<0.05). However, the adjusted energy intake by body weight was lower in non-overweight patients in older group (t=3.239, P<0.05). The detection rates of sarcopenia and muscle mass reducing were 6.3% and 34.0% in older group, respectively. Multiple linear regression analysis showed that insufficient intake of energy (B=-1.4000, P=0.045, 95%CI:-2.770 to -0.029), protein (B=-0.0095, P=0.013, 95%CI:-0.168 to -0.021), and excessive visceral fat accumulation (B=0.019,P=0.007, 95%CI: 0.006 to 0.033) were the independent risk factors of muscle mass reducing in elderly T2DM patients.

The decrease of muscle mass in elderly diabetic patients relates to insufficient intake of energy and protein, and excessive visceral fat accumulation. Individual nutrition evaluation and support is necessary especially in elderly diabetic patients.

Recently, more and more attention has been paid to the relationship between intestinal flora and human health and disease. With the extensive application of various molecular biology techniques in the study of intestinal microbial community, it has been found that intestinal microbial flora can not only degrade indigestible nutrients in food, provide host vitamins and other nutrients, but also promote the differentiation and maturation of intestinal epithelial cells, activate intestinal immune system, resist the invasion of exogenous microorganisms, maintain the intestinal barrier function, and regulate host energy storage and metabolism. A large number of studies have also shown that the disorder of intestinal flora structure and function is closely related to various metabolic diseases^[1,2]。 Type 1 diabetes mellitus (T1DM) is a metabolic disease commonly occurring in children and adolescents. It was previously believed that its pathogenesis is related to autoimmune defects, genetic defects or viral infections. In recent years, some studies have found that intestinal flora is closely related to T1DM. In this paper, the research progress of the relationship between intestinal flora and T1DM is reviewed.

In the process of diagnosis and treatment of diabetic foot disease, bacterial infection is easy to be paid attention by clinicians, but fungal infection is not paid enough attention. Clinically, the cases of diabetic foot ulceration caused by fungal infection are common, but they are often ignored. By reviewing the relevant literature at home and abroad, this paper introduces and expounds the types, epidemiological investigation, clinical manifestations and experience of diagnosis and treatment of diabetic foot complicated with foot fungal infection.

According to data from the International Diabetes Federation (IDF) in 2013, the prevalence of diabetes among adults aged 20 to 79 in the world is 8.3%, and the number of patients has reached 382 million. Chinese patients account for about a quarter, making it the country with the largest number of diabetes patients in the world^[1]。 IDF reports that the treatment of diabetes and its complications cost about $471 billion in 2012^[1]。 The rapid growth of diabetes has brought a heavy burden to social and economic development, and also put tremendous pressure on patients and families.