Detection,management,and prevention of diabetes-related foot disease in the Australian context

Diabetes-related foot disease(DFD)is a widely feared complication among people who live with diabetes.In Australia and globally,rates of disability,cardiovascular disease,lower extremity amputation,and mortality are significantly increased in patients with DFD.In order to understand and prevent these outcomes,we analyse the common pathogenetic processes of neuropathy,arterial disease,and infection.The review then summarises important management considerations through the interdisciplinary lens.Using Australian and international guidelines,we offer a stepwise,evidence-based practical approach to the care of patients with DFD.

Structural and functional damage to the hippocampal neurovascular unit in diabetes-related depression

Previous studies have shown that models of depression exhibit structural and functional changes to the neurovascular unit. Thus, we hypothesized that diabetes-related depression might be associated with damage to the hippocampal neurovascular unit. To test this hypothesis, neurons, astrocytes and endothelial cells were isolated from the brain tissues of rat embryos and newborn rats. Hippocampal neurovascular unit co-cultures were produced using the Transwell chamber co-culture system. A model of diabetes-related depression was generated by adding 150 mM glucose and 200 μM corticosterone to the culture system and compared with the neuron + astrocyte and astrocyte + endothelial cell co-culture systems. Western blot assay was used to measure levels of structural proteins in the hippocampal neurovascular unit co-culture system. Levels of basic fibroblast growth factor, angiogenic factor 1, glial cell line–derived neurotrophic factor, transforming growth factor β1, leukemia inhibitory factor and 5-hydroxytryptamine in the hippocampal neurovascular unit co-culture system were measured by enzyme-linked immunosorbent assay. Flow cytometry and terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling staining was used to assess neuronal apoptosis in the hippocampal neurovascular unit. The neurovascular unit triple cell co-culture system had better barrier function and higher levels of structural and secretory proteins than the double cell co-culture systems. In comparison, in the model of diabetes-related depression, the neurovascular unit was damaged with decreased barrier function, poor structural integrity and impaired secretory function. Moreover, neuronal apoptosis was markedly increased, and 5-hydroxytryptamine levels were reduced. These results suggest that diabetes-related depression is associated with structural and functional damage to the neurovascular unit. Our findings provide a foundation for further studies on the pathogenesis of diabetes-related depression.

Psychological status and diabetes-related distress of Chinese type 1 diabetes patients in Jiangsu province, China

We sought to assess the psychological status and diabetes-related distress of Chinese type 1 diabetes patients in Jiangsu province, China. According to the World Health Organization criteria, 42 patients with type 1 diabetes were enrolled in the study and assessed with the Self-Rating Anxiety Scale （SAS）, Self-Rating Depression Scale （SDS） and Diabetes Distress Scale （DDS）. All data were tabulated and statistical analyses were performed. The study summarized cases of 42 patients with type 1 diabetes, including 17 males and 25 females with a mean age of 23- 12 years and a mean duration of diabetes of 7_ 6 years. Compared to the Chinese normative data, the SAS standard score was significantly higher, whereas SDS standard score had no statistical significance. The SAS standard score was most highly correlated with diabetes duration （y = 0.547, P = 0.011）. Additionally, 19.5% of the patients had moderate or even severe diabetes-related distress and 21.4% had moderate or even severe emo- tional burden while 26.2% had regimen-related distress. Multiple stepwise regression analysis showed that the mean correlation between DDS and the four domains was high, particularly the emotional burden domain （esti- mated D = 0.363, P 〈 0.001） and regimen-related distress domain （estimated 13 = 0.356, P 〈 0.001）. The correlation between SAS and DDS was positive （estimated 13 = 0.039, P = 0.027）. In conclusion, the results showed the im- portance of psychological aspects in Chinese individuals with type 1 diabetes. Screening and treatment of psycho- logical aspects may result in better adherence and increased quality of life for patients with diabetes.

Does parity worsen diabetes-related chronic complications in women with type 1 diabetes?

AIM: To determine the relationship between parity, glycemic control, cardiovascular risk factors and diabetesrelated chronic complications in women with type 1 diabetes.METHODS: This was a multicenter cross-sectional study conducted between December 2008 and December 2010 in 28 public clinics in 20 cities from the 4 Brazilian geographic regions. Data were obtained from 1532 female patients, 59.2% Caucasians, and aged 25.2 ± 10.6 years. Diabetes duration was of 11.5 ± 8.2 years. Patient's information was obtained through a questionnaire and a chart review. Parity was stratified in five groups: Group 0(nulliparous), group 1(1 pregnancy), group 2(2 pregnancies), group 3(3 pregnancies), group 4(≥ 4 pregnancies). Test for trend and multivariate random intercept logistic and linear regression models were used to evaluate the effect of parity upon glycemic control, cardiovascular risk factors and diabetes-related complications. RESULTS: Parity was not related with glycemic control and nephropathy. Moreover, the effect of parity upon hypertension, retinopathy and macrovascular disease did not persist after adjustments for demographic and clinical variables in multivariate analysis. For retinopathy, the duration of diabetes and hypertension were the most important independent variables and for macrovascular disease, these variables were age and hypertension. Overweight or obesity was noted in a total of 538 patients(35.1%). A linear association was found between the frequency of overweight or obesity and parity(P = 0.004). Using a random intercept multivariate linear regression model with body mass index(BMI) as dependent variable a borderline effect for parity(P = 0.06) was noted after adjustment for clinical and demographic data. The observed variability of BMI was not attributable to differences between centers.CONCLUSION: Our results suggest that parity has a borderline effect on body mass index but does not have an important effect upon hypertension and micro or macrovascular chronic complications. Future prospective evaluations must be conducted to clarify the relationship between parity, appearance or worsening of diabetesrelated chronic complications.

Research progress of RhoA/ROCK pathway in diabetes-related diseases

RhoA is a small GTPase protein.Its downstream effector protein Rho kinase(ROCK)regulates a variety of cell functions,including cell growth,gene expression and cytoskeleton recombination.Studies have demonstrated that this pathway plays an important pathophysiological role in diabetic nephropathy and other complications,hypertension,stroke,tumor,osteoarthritis,acute lung injury and other diseases.The occurrence and development of diabetes-related disease is closely related to the activation or up-regulation of RhoA/ROCK pathway.As a key target of drug development,ROCK inhibitors have been widely concerned by scholars.This article reviews the relationship between RhoA/ROCK pathway and diabetesrelated disease,and offers a new and effective strategy for the prevention and treatment of this series of diseases.

Abnormal Glu/mGluR2/3/PI3K pathway in the hippocampal neurovascular unit leads to diabetesrelated depression

Our previous studies have shown that glutamate and hippocampal neuron apoptosis are key signals and direct factors associated with diabetes-related depression,and structural and functional damage to the hippocampal neurovascular unit has been associated with diabetesrelated depression.However,the underlying mechanism remains unclear.We hypothesized that diabetes-related depression might be associated with the glutamate(Glu)/metabotropic glutamate receptor2/3(mGluR2/3)/phosphoinositide 3-kinase(PI3K)pathway,activated by glucocorticoid receptors in the hippocampal neurovascular unit.To test this hypothesis,rat hippocampal neurovascular unit models,containing hippocampal neurons,astrocytes,and brain microvascular endothelial cells,were treated with 150 mM glucose and 200μM corticosterone,to induce diabetes-related depression.Our results showed that under conditions of diabetes complicated by depression,hippocampal neurovascular units were damaged,leading to decreased barrier function;elevated Glu levels;upregulated glucocorticoid receptor,vesicular glutamate transporter 3(VGLUT-3),and metabotropic glutamate receptor 2/3(mGluR2/3)expression;downregulated excitatory amino acid transporter 1(EAAT-1)expression;and alteration of the balance of key proteins associated with the extracellular signal-regulated kinase(ERK)/glial cell-derived neurotrophic factor(GDNF)/PI3K signaling pathway.Moreover,the viability of neurons was dramatically reduced in the model of diabetes-related depression,and neuronal apoptosis,and caspase-3 and caspase-9 expression levels,were increased.Our results suggest that the Glu/mGluR2/3/PI3K pathway,induced by glucocorticoid receptor activation in the hippocampal neurovascular unit,may be associated with diabetes-related depression.This study was approved by the Laboratory Animal Ethics Committee of The First Hospital of Hunan University of Chinese Medicine,China(approval No.HN-ZYFY-2019-11-12)on November 12,2019.

Long-term case study of a Wuzhishan miniature pig with diabetes

Background:Miniature pigs are attractive animal models for exploring diabetes because they are similar to humans in terms of physiological structure and metabolism.However,little is known about the complications of diabetes in pigs.Methods:In this study,a 28-month observation of a Wuzhishan miniature pig with streptozotocin(STZ)-induced(120 mg/kg)diabetes was conducted,to investigate diabetes-related complications and the possibility of self-recovery in miniature pigs.Blood glucose,serum and urinary biochemistry was measured,and histopathologic examinations of eyes,kidney and pancreas were made.Results:During the observation,diabetic complications of eyes and kidney were observed.The eye complications included bilateral cataracts in the 15th month and degeneration of inner retina and microaneurysm in the 28th month.Kidney complications included glomerular mesangial expansion,focal segmental glomerular sclerosis,and renal tubular epithelial degeneration,but no proteinuria was observed.By 28 months after the application of STZ,with no treatment given,blood glucose had recovered and the number of pancreatic islet beta-cells had increased significantly.Conclusions:We showed that the STZ-induced diabetes model in miniature pigs could accurately mimic the pathological changes of human diabetes,and that pancreatic islet beta-cell regeneration did occur in an adult miniature pig,providing a new means for exploring diabetic complications and pancreatic islet beta-cell regeneration.

Advances in the Study of Exosomal miRNAs in Diabetes and Its Complications

Diabetes mellitus is a group of metabolism-related diseases characterized by elevated plasma glucose levels, and the course of diabetes mellitus is closely linked to the development of diabetes-related complications, which can be life-threatening due to poor glycemic control. Exosomes are small vesicles that encapsulate intracellular molecules and are composed of a variety of bioactive proteins, lipids and nucleic acids (including microRNAs, lncRNAs, and circ-RNAs), and recent studies have increasingly shown that miRNAs in exosomes are an important mode of intercellular and intertissued communication and play a key role in the development and progression of various diseases. This review presents the progress of the application of exosomal miRNAs in type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and diabetes-related complications.