Development of diabetic complications and influencing factors among 32653 type 2 diabetes patients:retrospective cohort study using a multi-state Markov

Background:Patients with type 2 diabetes are at high risk for developing multiple chronic complications.However,there is a lack of studies of the cumulative number of diabetic complications in China.Methods:A retrospective cohort study was performed from 2009 to 2021.Type 2 diabetes patients who were first diagnosed after the age of 35 years between January 1,2009,and December 31,2017,were included.Five states were defined according to the number of chronic complications:no(S0),one(S1),two(S2),three(S3),and four or more complications(S4).A multi-state Markov model was constructed to estimate transition probability,transition intensity,mean sojourn time,and the possible factors for each state.Results:The study included 32653 type 2 diabetes patients(mean age,59.59 years;15929(48.8%)male),and mean follow-up time of 7.75 years.In all,4375 transitions were observed.The 12-year transition probability of from state S0 to S1 was the lowest at 16.4%,while that from S2 to S3 was the highest,at 45.6%.Higher fasting blood glucose,lower high-density lipoprotein cholesterol,higher total cholesterol,and an unhealthy diet were associated with higher risk of progression from S0 to S1.Being female,less than 60 years old,weekly physical activity,and vegetarian diet decreased this risk.Being female and less than 60 years old reduced the likelihood of transition from S1 to S2,whereas lower high-density lipoprotein cholesterol increased this likelihood.Conclusions:Following the occurrence of two complications in type 2 diabetes patients,the risk for accumulating a third complication within a short time is significantly increased.It is important to take advantage of the stable window period when patients have fewer than two complications,strengthen the monitoring of blood glucose and blood lipids,and encourage patients to maintain good living habits to prevent further deterioration.

Sitagliptin in treatment of diabetes complicated by chronic hepatitis C

To the Editor: A high prevalence of glucose intolerance in patients with chronic hepatitis C has been reported, [1] and there is a significant association of chronic hepatitis C with diabetes mellitus (DM). [2] But DM has been suggested to be associated with the onset of hepatocellular carcinoma

Effects of Lipoprotein(a) on Elderly Diabetes Mellitus

In order to explore clinical relationship between Lipoprotein(a) and elderly diabetes, the level of plasma Lp(a) in 78 elderly patients with diabetes mellitus and 60 healthy controls was assayed. The results showed that there was significant difference in the percentage of high Lp(a) level between diabetis and healthy subjects (P<0.01); that the percentages of high Lp(a) level with fasting Lp(a)200 mg/L, 300 mg/L in complication group were all significantly higher than those in noncomplication group (P<0.02); that there was significant difference in the percentage of high Lp(a) level with fasting and postprandial 2 hours Lp(a)200 mg/L in 30 patients without complication, the former was also significantly higher as compared with controls. These suggested that fasting blood sample was better for measurement of plasma Lp(a) level, and that fasting plasma Lp(a)200 mg/L might be useful for diabetes epidemiological investigation; that there was high plasma Lp(a) level in diabetics, especially in diabet

THERAPEUTIC EFFECT OF NON-SURGICAL TREATMENT OF CHRONIC PERIODONTITIS IN DIABETIC CHINESE

Objective To observe the therapeutic effect of non-surgical treatment on diabetic Chinese withchronic periodontitis. Methods Moderate to advanced chronic periodontitis ( CP) was studied in 36 diabetes mellitus (DM) patients classified as 20 with high and fluctuating blood glucose level (DM-H) and 16 with relatively low and stable blood glucose level (DM-L). 28 non-DM CP patients acted as controls (Non-DM). Plaque index (PlI) , gingival index (GI) , bleeding on probing (BOP) , probing depth (PD) and clinical attachment loss (AL) of all patients were recorded at 6 sites on each tooth at the baseline and 1, 3 and 6 months after oral hygiene instruction (OHI), scaling and root planing. Results It was found that the short-term effect of non-surgical periodon-tal procedure had resulted in significant resolution of gingival inflammation and pronounced reduction in pocket depth and gain of attachment loss in both DM and Non-DM CP patients. Conclusion The pilot study suggested that non-surgical periodontal treatment allowed for favorable treatment responses in a group of Chinese diabetic subjects with chronic periodontitis and that their various profiles of blood glucose did not influence the short-term healing response to OHI, scaling and root planning.

Exosome/metformin-loaded self-healing conductive hydrogel rescues microvascular dysfunction and promotes chronic diabetic wound healing by inhibiting mitochondrial fission

Chronic diabetic wounds remain a globally recognized clinical challenge.They occur due to high concentrations of reactive oxygen species and vascular function disorders.A promising strategy for diabetic wound healing is the delivery of exosomes,comprising bioactive dressings.Metformin activates the vascular endothelial growth factor pathway,thereby improving angiogenesis in hyperglycemic states.However,multifunctional hydrogels loaded with drugs and bioactive substances synergistically promote wound repair has been rarely reported,and the mechanism of their combinatorial effect of exosome and metformin in wound healing remains unclear.Here,we engineered dual-loaded hydrogels possessing tissue adhesive,antioxidant,self-healing and electrical conductivity properties,wherein 4-armed SH-PEG cross-links with Ag^(+),which minimizes damage to the loaded goods and investigated their mechanism of promotion effect for wound repair.Multiwalled carbon nanotubes exhibiting good conductivity were also incorporated into the hydrogels to generate hydrogen bonds with the thiol group,creating a stable three-dimensional structure for exosome and metformin loading.The diabetic wound model of the present study suggests that the PEG/Ag/CNT-M+E hydrogel promotes wound healing by triggering cell proliferation and angiogenesis and relieving peritraumatic inflammation and vascular injury.The mechanism of the dual-loaded hydrogel involves reducing the level of reactive oxygen species by interfering with mitochondrial fission,thereby protecting F-actin homeostasis and alleviating microvascular dysfunction.Hence,we propose a drug-bioactive substance combination therapy and provide a potential mechanism for developing vascular function-associated strategies for treating chronic diabetic wounds.

Gene-activated dermal equivalents to accelerate healing of diabetic chronic wounds by regulating inflammation and promoting angiogenesis

Diabetic chronic wound,characterized by prolonged inflammation and impaired angiogenesis,has become one of the most serious challenges in clinic and pose a significant healthcare burden worldwide.Although a great variety of wound dressings have been developed,few of encouraged achievements were obtained so far.In this study,the gene-activated strategy was applied to enhance sustained expression of vascular endothelial growth factor(VEGF)and achieve better healing outcomes by regulating inflammation and promoting angiogenesis.The gene-activated bilayer dermal equivalents(Ga-BDEs),which has good biocompatibility,were fabricated by loading the nano-sized complexes of Lipofectamine 2000/plasmid DNA-encoding VEGF into a collagen-chitosan scaffold/silicone membrane bilayer dermal equivalent.The DNA complexes were released in a sustained manner and showed the effective transfection capacities to up-regulate the expression of VEGF in vitro.To overcome cutaneous contraction of rodents and mimic the wound healing mechanisms of the human,a reformative rat model of full-thickness diabetic chronic wound was adopted.Under the treatment of Ga-BDEs,speeding wound healing was observed,which is accompanied by the accelerated infiltration and phenotype shift of macrophages and enhanced angiogenesis in early and late healing phases,respectively.These proved that Ga-BDEs possess the functions of immunomodulation and pro-angiogenesis simultaneously.Subsequently,the better regeneration outcomes,including deposition of oriented collagen and fast reepithelialization,were achieved.All these results indicated that,being different from traditional pro-angiogenic concept,the up-regulated expression of VEGF by Ga-BDEs in a sustained manner shows versatile potentials for promoting the healing of diabetic chronic wounds.

STATUS AND CONTROL POLICY OF MAIN CHRONIC DISEASES IN COMMUNITY HEALTH MANAGEMENT BASES IN SHANGHAI AND GUANGDONG

Objective To investigate the current conditions of the main chronic diseases and to make the control policy in community health management base in China. MethodsThe questionnaire consisting of prevalence, awareness rate, management rate, behavior correct rate, control rate, and medicine obey was used to survey the chronic disease condition in 2009. A total of 809 736 residents were randomly selected from Shanghai and Guangdong, China. ResultsThe hypertension prevalence was 17.81%. From sex analysis, the female has higher rate than male in hypertension prevalence, understand rate, management rate, behavior correct rate, control rate, and medicine obey rate. From age analysis, the prevalence, understand rate, management rate, control rate, and medicine obey were increasing along with the age, but behavior correct rate was not in this condition. The diabetes prevalence was 6.92%. To compare with Shanghai and Guangzhou in 5 aspects, the prevalence of chronic diseases was alike. Except lower behavior correct rate in Shanghai, management rate, behavior correct rate, control rate, and medicine obey rate were higher in Shanghai. ConclusionThe government must take main principle in chronic disease control. Base construction of community health management and increase management level of chronic diseases should be enhanced and practitioner's knowledge of chronic disease management should also be enhanced.

ORIGINAL ARTl CLESSilybin Decreases Erythrocytic Sorbitol Level and ImprovesPeripheral Nerve Conduction Velocity in Patients with Non-lnsulin Dependent Diabetes Mellitus

The effects of silybin on erythrocytic sorbitol level and peripheral nerve conduction veloci-ty were studied in 14 cases of noninsulin dependent diabetes mellitus (NIDDM) . Atter oral administrationof silybin 231 mglday for 4 weeks, no blood glucose change was observed in patients with NIDDM, whilethe erythrocytic sorbitol level was significantly decreased from 72. 55 21. 61 to 39. 53 14. 94 nmol/g .Hb (P<0. 01) . At the same time, peripheral nerve conduction vefocity was also improved. These resultsindicate that silybin is an effective aldose reductase inhibitor which can improve the disorder of polyolpathway in NIDDM patients and prevent chronic complications of diabetes.

Bioactive skin-mimicking hydrogel band-aids for diabetic wound healing and infectious skin incision treatment

The treatment of diabetic chronic wounds remains a global challenge due to the up-regulated inflammation response,oxidant stress,and persistent infection during healing process.Developing wound dressing materials with ideal biocompatibility,adequate mechanical strength,considerable under-water adhesion,sufficient anti-inflammation,antioxidant,and antibacterial properties is on-demand for clinical applications.In this study,we developed a bioactive skin-mimicking hydrogel band-aid through the combination of tannic acid(TA)and imidazolidinyl urea reinforced polyurethane(PMI)(TAP hydrogel)and explored its potentials in various medical applications,including hemostasis,normal skin incision,full-thickness skin wounds,and bacterial-infection skin incision on diabetic mice.TA was loaded into PMI hydrogel network to enhance the mechanical properties of TAP hydrogels through multiple non-covalent interactions(break strength:0.28-0.64 MPa;elongation at break:650-930%),which could resist the local stress and maintain the structural integrity of wound dressings during applications.Moreover,owing to the promising moisture-resistant adhesiveness and organ hemostasis,outstanding anti-inflammation,antibacterial,and antioxidant properties,TAP hydrogels could efficiently promote the recovery of skin incision and defects on diabetic mice.To further simulate the practical situation and explore the potential in clinical application,we also verified the treatment efficiency of TAP hydrogel in S.aureus-infected skin incision model on diabetic mice.

Development of a novel RNAi therapy:Engineered miR-31 exosomes promoted the healing of diabetic wounds

Rationale:Chronic wounds associated with diabetes exact a heavy burden on individuals and society and do not have a specific treatment.Exosome therapy is an extension of stem cell therapy,and RNA interference(RNAi)-based therapy is a type of advanced precision therapy.Based on the discovery of chronic wound-related genes in diabetes,we combined exosome therapy and RNAi therapy through an engineering approach for the treatment of diabetic chronic wounds.Methods:We combined exosome therapy and RNAi therapy to establish a precision therapy for diabetes-associated wounds via an engineered exosome approach.Results:First,chronic diabetic wounds express low levels of miR-31-5p compared with nondiabetic wounds,and an miR-31-5p mimic was shown to be effective in promoting the proliferation and migration of three wound-related cell types in vitro.Second,bioinformatics analysis,luciferase reporter assays and western blotting suggested that miR-31-5p promoted angiogenesis,fibrogenesis and reepithelization by inhibiting factor-inhibiting HIF-1(HIF1AN,also named FIH)and epithelial membrane protein-1(EMP-1).Third,engineered miR-31 exosomes were generated as a miR-31-5p RNAi therapeutic agent.In vivo,the engineered miR-31 exosomes promoted diabetic wound healing by enhancing angiogenesis,fibrogenesis and reepithelization.Conclusion:Engineered miR-31 exosomes are an ideal disease pathophysiology-initiated RNAi therapeutic agent for diabetic wounds.