Volume 07 · Issue 08 · 2015

The effects on health and longevity caused by diabetic complications are the main hazards of diabetes. The risk of cardiovascular complications in diabetic patients is 2-4 times higher than that in normal people^[1]Diabetes is also the leading cause of non-traumatic amputation, blindness, and end-stage renal disease^[2,3]。 Clinical studies have shown that controlling blood sugar and blood pressure, lowering low-density lipoprotein cholesterol (LDL-C), regular examination of the fundus and feet, and aspirin treatment can greatly reduce the occurrence of diabetic complications^[4,5,6]。 Due to the promotion of standardized treatment of diabetes, the proportion of major complications (including myocardial infarction, stroke, amputation, and end-stage renal disease dialysis) among diabetic patients in the United States has dropped by 1/2 to 2/3 compared with 20 years ago^[7]。 This fully shows that diabetes is a manageable disease. However, our country has a vast territory and a large population, and the development of economy has spurred the acceleration of urbanization. Therefore, we should attach importance to the treatment and prevention of diabetes complications, and find suitable methods for diabetes prevention and treatment in China.

With the rapid development of industrialization, modernization and urbanization, the popularization of high-calorie diet and less-active lifestyle, and the acceleration of the aging trend of population structure, the prevalence of diabetes in China has increased rapidly by nearly 10 times in the past 30 years^[1,2,3]。 At present, the number of diabetic patients in China exceeds 100 million, making it the country with the largest number of diabetic patients in the world. Diabetes mellitus and its various related chronic complications, including visual impairment, kidney disease, neuropathy, peripheral vascular disease, heart disease, stroke, etc., are the most important causes of disability and death in diabetic patients, and become a public health problem that cannot be ignored. Therefore, understanding and summarizing the prevalence and risk factors of chronic complications of diabetes in China will help to carry out targeted clinical and basic research in related fields, thus promoting the formulation of relevant prevention and treatment strategies.

On the morning of June 7, 2015, at the Boston International Convention and Exhibition Center in the historic city of the United States, Professor Phillip E. Scherer, director of the Touchstone Diabetes Institute of the University of Texas Southwestern Medical Center, won the Banting Medical Achievement Award, the highest award of the 75th American Diabetes Society (ADA) Annual Scientific Meeting. Professor Scherer is well known in the academic community for his discovery of adiponectin and elucidation of its physiological effects. He used methods such as cell biology, biochemistry and genetics to prove that adipose tissue is also a huge endocrine organ, playing an important role in metabolism and inflammation; He devoted himself to exploring the special contributions of special cells in metabolic regulation, and became the most famous and creative outstanding scientist in this field. He delivered an award-winning speech entitled "The Multifaceted Nature of Adipose Tissue: Therapeutic Targets for Diabetes and Other Diseases". More than 10,000 diabetes scholars from all over the world followed him in the research space of adipocyte function, adipocytokines, related metabolic "varistors" and "intermediaries". The main contents of the speech are briefly introduced below.

To explore the status of risk factors for cardiovascular diseases in patients with type 2 diabetes in Beijing communities.

We conducted a cross - sectional survey in 27 Beijing communities of adults aged 20 years or older. According to operation specification, all of the patients were collected medical history and taken both physical and correlated laboratory examinations. Glycated haemoglobin A1c(HbA_1c), lipid profile, blood pressure and body mass index(BMI) were assessed according to the Chinese guidelines for type 2 diabetes prevention and treatment(2013). Chi square test was used in comparison between groups.

A total of 2 213 T2DM patients were enrolled, which included 895 male ((59±10) yrs) and 1 318 female participants ((61±8) yrs) with type 2 diabetes. No statistic significance was found in the difference on HbA_1c(A) between the two groups (47.6% for male vs 49.5% for female, χ ²= 0.747, P=0.387). The blood pressure(B) (28.9% vs 35.2%) and body mass index (26.3% vs 31.6%, χ ²= 9.515, 7.429, bothP<0.05) were significantly lower whereas the serum low density lipid chor (LDL-C) level (C) (46.9% vs 39.8%, χ ²=10.964,P<0.05) was higher in male patients compare to female patients. Only 7.5% of the patients achieved all 3(ABC) target goals. The HbA_1c was significantly lower in group with longer diabetes duration. Compared to younger diabetes patients, the older patients had significantly higher rates in HbA_1c(40.5%, 49.9%, 54.5%), blood pressure(27.1%, 31.9%, 38.8%) and body mass index(25.8%, 29.4%, 32.9%, χ ²=26.297, 20.446, 7.866, allP<0.05).

The control rates of diabetes, hypertension, dyslipidemia and obesity in type 2 diabetes patients in Beijing communities are lower than those in the top three hospitals, especially in male and younger patients. The propaganda and intervention should be strengthen for type 2 diabetes complications in community.

To investigate the relationship between screening rates of microvascular complications and the level of diabetic knowledge in type 2 diabetic patients from Beijing community clinics.

From May of 2013 to December of 2014 we performed screenings of microvascular complications in type 2 diabetic patients from community clinics with residency over half a year in Beijing. Data were collected from questionnaires about previous screening of diabetic retinopathy, microalbuminuria and diabetic foot and diabetic knowledge scores. Logistic regressions were used to estimate the association of different levels of diabetic knowledge scores with screen rates of microvascular complications.

Data were collected from in 1 185 type 2 diabetic patients with male of 476(41.6%), female of 709(58.4%), mean age of (59±9) years, mean diabetes duration of (7±6) years. The screening rates of diabetic retinopathy, microalbuminuria and diabetic foot were 49.5%(586 /1 185), 75.3%(892 /1 185)and 41.1%(487/1 185)in type 2 diabetic patients from community clinics, respectively. The screening rates were higher in those patient with high level of diabetic knowledge than those of low level (diabetic retinopathy 70.9%(334/471)vs 35.3% (252/714); microalbuminuria 88.5% (417/471)vs 66.5% (475/714); diabetic foot 66.2% (312/471)vs 24.5% (175/714) , P<0.001). After adjusting age, gender, diabetic duration, insurance and educational level, in corresponding to the low level of diabetic knowledge, the odds ratios (95%CI) of screening diabetic retinopathy, microalbuminiuia and diabetic foot were 2.65 (2.00- 3.51), 2.46(1.73- 3.49), 3.74(2.82- 4.95) in high level patients, respectively.

The screening rates of microvascular complications were associated with the level of diabetic knowledge, independent from general educational level in type 2 diabetic patients from Beijing community clinics. Our study suggested that increasing the screening rates of microvascular complications could be benefit from emphasizing diabetic knowledge education.

To provide evidence on the primary prevention of diabetes mellitus by exploring the relationship between insomnia and diabetes.

This cross-sectional study was conducted in Jidong community, Caofeidian district, Tangshan city, Hebei Province from July to November 2013. A questionnaire was used by uniform trained community physicians to collect information on demography characteristics, behavior styles and other risk factors. Participants aged above 18 years old habitants were enrolled. The diagnostic criteria of diabetes mellitus used the American Diabetes Association diagnostic criteria in 2013. Athens Insomnia Scale (AIS) was used to evaluate the sleep quality. Logistic regression models were used to test the relationship between insomnia and diabetes.

The median age of 6 635 subjects (3 419 males, 51.5%) was 40.6 years. The prevalence of diabetes was 7.9% and insomnia was 14.3% in the total subjects, 11.9% and 7.2% in those with and without insomnia respectively (P<0.01). After stratified by age, insomnia increased the risk of diabetes in subjects aged 40- 59 years old (OR=1.46, 95%CI=1.05- 2.03). Among the eight items of AIS, function decreasing during the day was significant associated with diabetes (1.54, 1.02- 2.31).

Insomnia is a relevant factor of diabetes mellitus in people aged 40- 59 years. Function decreasing during the day, one of symptoms of insomnia, was associated with diabetes mellitus.

To analysis the characteristics and distribution of impaired glucose regulation (IGR) in Gansu province.

We selected 28 087 participants who were 20-74 years old in diabetes epidemiology survey between 2013 and 2014 in Gansu province which enrolled 31 417 participants and then divided them into 4 groups by blood glucose level after the 75 g oral glucose tolerance test (OGTT) according to the 1999 WHO diabetes diagnostic criteria: normal glucose tolerance (NGT), isolated impaired fasting glucose (I-IFG) and isolated impaired glucose tolerance (I-IGT) groups, combined IFG and IGT (IFG/IGT) groups. Then we analyzed the distribution of IGR between city and countryside, different gender and age groups and risk factors of IFG and IGT. Comparison between two groups was done within independent samplet test and chi- square test.

The prevalence of I- IFG and I- IGT in countryside was higher than in the city, the difference was statistically significant (4.4% (641/14 480) vs 2.7% (464/16 937) and 10.0% (1443/14 480) vs 9.3%(1571/16 937), χ ²=65.5 and 4.3, respectively,P<0.05). In rural area, the prevalence of I- IFG was higher in men than in women, the difference was statistically significant (4.8% (310/6 417) vs 4.1% (331/8 063), χ ²=4.4,P<0.05). In urban area, the prevalence of I-IGT was higher in men than in women, the difference was statistically significant (10.0% (765/7 666) vs 8.7% (806/9 271), χ ²=8.2,P<0.05). The prevalence of I-IGT and IFG/IGT increased with age. The prevalence of I-IGT among different age groups was 5.99%, 8.33%, 9.80%, 10.22% and 12.28%, the differences between 20 and 30,30 and 40, 50 and 60 group were statistically significant(χ²=20.95, 8.0 and 14.0,P<0. 05 all above). The prevalence of IFG/IGT among different age groups was 0.67%,1.02%,1.98%,2.51% and 3.44%.The differences between adjacent groups above 30 years old were statistically significant (χ²=18.2, 4.5 and 9.8, P<0. 05 all above). The risk factors for IFG were male, the old age, family history of diabetes, overweight and rural residents (OR=1.13, 1.16, 1.30, 1.15, 1.52,P <0.05 all above); the risk factors for IGT were the old age, drinking, overweight, general obesity and central obesity( OR=1.18, 1.17, 1.27, 1.44, 1.08,P <0.05 all above).

The characteristics and distribution of IGR between different gender, different age groups and different areas (city or countryside) were significantly different. It is helpful to pay attention to IGR and control risk factors to reduce the incidence of diabetes.

To investigate sleep quality of hospitalized type 2 diabetes mellitus(T2DM) patients, and evaluate relationship of sleep quality and metabolic indexes, resting energy expenditure and body composition.

Three hundred hospitalized T2DM patients were included and Pittsburgh Sleep Quality Index(PSQI) questionnaire was used to evaluate their subjective sleep characteristics. Their general clinical data and biochemical indexes (including blood lipid, glucose, glycosylated hemoglobin (HbA_1c) etc.) were collected and steamed bun test was carried out to get the secretion information of insulin and C-peptide in patients at 0 and 120 minutes, and then resting energy expenditure and body composition were measured. Patients with PSQI total scores ≥8 were classified as the sleep-disordered group, others were classified as normal sleep group. Independent samplet test and Independent- samples Mann- Whitney test were used to analyze normal and abnormal distribution measurement data respectively. Chi-squared test was used to analyze enumeration data. The influence factors of sleep disorder were analyzed by multivariate logistic regression analysis.

39.7% (119/300) hospitalized T2DM patients had sleeping disorder. Patients in T2DM sleep- disordered group had a female predominance (χ²=10.10,P<0.05) , higher level of HbA_1c (8.85% (7.50,10.50)% vs 8.00% (7.10,10.00)% ,Z=- 2.301,P<0.05) and lower resting energy expenditure (Z=- 3.722,P<0.05). Body fat composition analysis showed that patients in sleep- disordered group had lower muscle mass((45±8) vs (49±9) kg,t=-4.066,P<0.05) and lower skeletal muscle mass(t=- 4.083, P<0.05). Besides, in sleep-disordered group, patients had higher proportions of stroke(χ²=4.538, P< 0.05), and usage of statin drugs(73.1% vs 60%, χ ²=4.948, P<0.05). Logistic regression analysis showed that HbA_1c(OR 1.13, 95%CI 0.999- 1.279,P=0.053), usage of statin drugs (OR 1.75, 95%CI 0.957- 3.203,P= 0.069) and muscle mass (OR 0.956, 95%CI 0.927- 0.986,P=0.005) were related with sleep disorder.

Female T2DM Patients with stroke or with using of statin drugs are more likely to have sleep disorder. For T2DM patients with above risk factors, more interventions of sleep may make better sleep quality and taking more exercises may bring better glycemic control.

To investigate the effectiveness of screening non- alcoholic fatty liver steatosis with diabetes risk score in community population.

Total of 2 397 people(1 365 males and 1 032 females) was selected for the study from September 2011 to November 2012 in Xuzhou area. Serum triglyceride, total cholesterol, high density lipoprotein, low density lipoprotein and glucose were measured. Hepatic steatosis was diagnosed by abdominal ultrasound while the questionnaire on diabetes risk score to assess hepatic steatosis was conducted by specialized nutritionists. These people was divided into 5 groups according to the diabetes risk score: Q1: 0-3, Q2: 4-6, Q3: 7-10, Q4: 11-14, Q5: 15-20. The effectiveness of diabetes risk score in screening hepatic steatosis was assessed by the area under curve of receiver operating characteristics curve(ROC). Non- conditional binary logistic regression was applied to analyze related risks.

The area under the ROC for steatosis with diabetes risk score was 0.77 (95% confidence interval (CI) :0.74- 0.78); 0.75 in men(0.70- 0.79) and 0.80(0.79- 0.84) in women. The morbidity rate of steatosis raised with the increasing levels of the diabetes risk score(χ²=31.6, P<0.01). The risk of hepatic steatosis increased with the increasing levels of diabetes risk score and the odds ratio was 1.46 (95%CI:1.14- 1.87), 1.58(1.18- 2.05), 1.95 (1.30- 2.92) and 2.21 (1.20- 4.06), respectively.

The diabetes risk score might be a useful primary screening tool for hepatic steatosis.

To observe the expression and activity of adenosine monophosphateactivated protein kinase α(AMPK-α) in skeletal muscle in type 2 diabetes mellitus(T2DM), and investigate its role in lipid accumulation in skeletal muscle and insulin resistance.

A total of 20 cases with or without T2DM who received selective surgery in the Second Hospital of Shijiazhuang City between June 2013 and June 2014 were enrolled from department of orthopedics. These patients were divided into two groups: diabetic group(DM group,n=10) and non-diabetic group(NC group,n=10), 6 and 7 males and 4 and 3 females respectively, the mean age was (62±10) years and (63±9) years. Blood pressure was calculated and blood samples were drawn from an antecubial vein for measurement of plasma glucose, insulin, lipid and free fat acid(FFA). Insulin sensitivity index (ISI) was calculated. Skeletal muscle tissue was collected and analyzed en bloc for triglyceride, long-chain acyl-CoA esters(LCACoAs), AMPK-α1 and AMPK-α2 mRNA expression, as well as protein expression of AMPK-α1, AMPK-α2 and phosphorylated AMPK-α (p-AMPK- α). The data of the two groups were compared witht-test.

The levels of blood glycated hemoglobin A_1c, fasting plasma glucose(FPG), fasting insulin(FINS), triglyceride(TG), FFA were all significantly higher in DM group than those in NC group (t=4.96, 4.50, 2.28, 2.12, 2.15, allP<0.05). However, the ISI was lower in DM group than that in NC group (-4.9±0.6 vs -3.7±0.5,t=-6.71,P<0.05). The triglyceride and LCACoAs in skeletal muscle were both higher in DM group than those in NC group((6.0±1.6) μmol/g vs (4.5±1.6) μmol/g, (3.1±1.1) μmol/g vs (2.1±1.0) μmol/g, t=2.13, 2.11, bothP<0.05). Compared with those in NC group, the expression of AMPK- α2 mRNA and protein levels of AMPK- α2 and P- AMPK- α in skeletal muscle decreased in DM group((0.89±0.21)×10 ⁵ vs (1.23±0.19)×10⁵, 0.69±0.09 vs 0.77±0.08, 0.48±0.09 vs 0.57± 0.10,t=- 3.87, - 2.29, - 2.15, allP<0.05).

Abnormal fatty acid metabolism, muscle lipid accumulation and insulin resistance exist in T2DM patients. Alterations of AMPK-α2 expression and AMPK- α activity may contribute to fat accumulation in skeletal muscle and insulin resistance.

To explore the effect of insulin on the expression of adiponectin, adiponectin receptors, and adiponectin receptor-mediated signaling pathways in the testes of type 1 diabetic rats.

Thirty male 6- week Sprague - Dawley(SD) rats(body weight: 180- 200 g) were randomly divided into normal control group (group A,n=8) and streptozotocin injection group(n=22) by using random number table. Type 1 diabetic model was established by intraperitoneal injection of streptozotocin. Sixteen successfully- induced diabetic rats were randomly divided into diabetic group(group B,n=8) and diabetic treated with insulin(group C,n=8). Rats in group B were given subcutaneous protamine-zinc insulin in does of 3-5 U daily to control blood glucose at 10 mmol/L. The other two groups were given equal volume of normal saline daily. At the end of the eight-week of experiment, rats were sacrificed after blood samples were collected, and then the bilateral testes were collected quickly. Blood samples were used to detect the levels of biochemical index, insulin, adiponectin and sex hormone. Sperm number and motility were counted. The expression of testicular adiponectin, adiponectin receptors, adenosine 5'- monophosphate (AMP)- activated protein kinase(AMPK), protein kinase B(AKT), endothelial nitric oxide synthase(e- NOS), nitric oxide(NO), interleukin-6(IL-6), and tumor necrosis factor alpha(TNF-α) were assayed. Statistical analysis was performed by using LSD-t test and one way ANOVA.

There were significant pathological changes in the testes of group B than those in group A. Compared with group A, the level of testes weight, sperm number and motility were decreased in group B(t=3.899, 21.139, 26.770, allP<0.05), the testicular adiponectin and its receptor 1, the ratio of p-AMPK to AMPK were significantly decreased in group B ((0.66±0.09) vs (1.00± 0.00), (0.68±0.05) vs (1.00±0.00), (0.34±0.11) vs (1.00±0.00),t=8.658, 14.297, 5.551, respectively, allP< 0.05); however, the level of the ratio of p-AKT to AKT, e-NOS in the testes were significantly increased in group B (1.54±0.27 vs 1.00±0.00, 1.56±0.26 vs 1.00±0.00,t=5.083, 4.997, respectively, bothP<0.05). These changes could be significantly reversed by insulin treatment. Compared with group B, the level of testes weight, sperm number and motility were increased in group C (t=3.444, 18.453, 23.103, allP<0.05); the level of adiponectin and its receptor 1, the ratio of p- AMPK to AMPK were significantly increased in group C (0.85±0.11 vs 0.66±0.09, 0.82±0.06 vs 0.68±0.05, 0.87±0.40 vs 0.34±0.11,t=4.969, 6.151, 4.454, respectively, allP<0.05); surely, the level of the ratio of p-AKT to AKT, e-NOS were significantly decreased in group B than those in group A (1.31±0.25 vs 1.54±0.27, 1.24±0.29 vs 1.56±0.26,t=2.169, 2.830, respectively, bothP<0.05).

Adiponectin and its receptors and adiponectin receptor-mediated signaling pathway may play an important role in testicular tissue injury in diabetic rats. Insulin may reduce the the degree of testicular tissue damage and produce the protective effect on testicular tissues in diabetic rats by regulating the expression of adiponectin, adiponectin receptors and adiponectin receptor- mediated signaling pathways.

To investigate the effects of docosahexaenoic acid (DHA) on large conductance Ca²⁺- activated K⁺ channel (BK channel) open probabilities (NP₀) in coronary smooth muscle cells of diabetic rats.

Streptozotocin-induced diabetic rat animal model was established by injection intraperitoneally. Male SD rats (n=20) with weight of (200±20) g and age of 6-8 weeks were divided into diabetic group (n=10) and normal control group (n=10) by random number table method. Diabetic group was injected intraperitoneally with streptozotocin. Blood glucose was tested after 2 weeks. If it was less than 300 mg/dl, same dose streptozotocin was injected intraperitoneally again. Diabetes was diagnosed until blood glucose was more than 300 mg/dl for 8 weeks. The control group was injected by normal saline. Coronary smooth muscle cells in control and diabetic rats were isolated immediately by enzyme digestion method. The BK currents in coronary smooth muscle cells of control and diabetic group were recorded by single channel patch-clamp technique. Effects of DHA on NP₀ of BK channels in coronary smooth muscle cells of control and diabetic rats were compared. Studentt test or Wilcoxon rank test were used to compare the NP₀ between control and diabetic groups. One-way ANOVA or M test were applied to compare the NP₀ in different DHA concentrations groups.

When test potentials were at 0, 20, 40, 60, 80, 100, 120 mV, NP₀ of BK channels increased with test potentials in both control and diabetic group (F=15.28, 9.72, allP<0.05). After test potentials above 60 mV, the NP₀ of BK channels in diabetic group were significantly decreased (t=3.62-8.14, allP<0.05). At 0, 0.01, 0.10 , 0.30, 1.00 μmol/L DHA, DHA failed to activate BK channels in both control and diabetic group under 60 mV voltage and 1 μmol/L Ca ⁺ (F=3.02,2.61, allP>0.05). At 3, 5 and 10 μmol/L, DHA activated BK channels in a dose- dependent manner in both control group and diabetic group ( F=10.21 ,7.32, allP<0.05). The NP₀ were lower in diabetic group than in control group at the same DHA concentrations (t=2.71 - 8.54, allP<0.05).

BK tunnel capacity of the coronary smooth muscle cells in diabetic rats was impared. The protective effects of DHA on diabetic heart may be performed by activating BK channels, increasing NP₀ and dilating coronary arteries.

Perivascular fat (PVAT), that is, adipose tissue close to the adventitial layer of blood vessels, is mainly composed of adipocytes, fibroblasts, stem cells, mast cells and nerve cells. In addition to cerebral blood vessels, fat cells exist around blood vessels throughout the body (as large as the aorta and as small as the microvessels of the dermis)^[1]。 As early as 2005, an article published in the Lancet suggested that PVAT is an important hub linking visceral fat, insulin resistance and vascular diseases, and plays an important role in obesity-related diseases^[2]。 Because of the special location of PVAT, it has the function of visceral fat, can secrete a large number of adipokines and cytokines, and it can regulate the function of blood vessels through various ways. This paper will give a brief introduction to the functional research progress of PVAT.

Autoimmune diabetes accounts for about 10% ~15% of the total number of diabetic patients. Under the action of various factors, it induces autoimmune reaction of β-cells of pancreatic islets with isletitis as pathological characteristic, which makes β-cells lose the function of synthesizing and secreting insulin, and causes disorder of glucose metabolism^[1]。 According to the urgency of onset, it is divided into two types: classical type 1 diabetes mellitus (T1DM) with sudden onset and adult occult autoimmune diabetes mellitus (LADA) with slow onset. T1DM is more common than adolescents, with extremely poor islet β cell function, difficult blood sugar control, and critical complications such as ketoacidosis, which seriously affects the growth and development of children. The early clinical manifestations of LADA are similar to type 2 diabetes mellitus (T2DM), but islet β cells suffer slow immune destruction and ultimately rely on insulin therapy. Due to the limitation of laboratory diagnosis, the disease is easily misdiagnosed as T2DM and delayed treatment, which seriously affects the physical and mental health of patients, and causes huge social and economic burden, which has attracted the attention of diabetology circles in various countries^[2]。 According to the recommendations of the Diabetology Branch of Chinese Medical Association "Guidelines for the Diagnosis and Treatment of Type 1 Diabetes in China" and "Consensus on the Diagnosis and Treatment of Adult Occult Autoimmune Diabetes (LADA)", islet autoantibodies are not only an important basis for typing diagnosis, but also an important immunological index for identifying LADA from T2DM^[3,4]。 Therefore, this paper intends to review the detection methods, standardization research progress and future directions of islet autoantibodies as follows.

Diabetic neuropathic pain (DNP) is one of the most common chronic complications of diabetes, and about 30% of patients develop chronic pain during the course of the disease^[1]。 DNP is characterized by spontaneous pain, hyperalgesia, induced pain and paresthesia, which seriously affects the physical and psychological health of patients. At present, it is impossible to accurately diagnose this type of pain in clinic, and the effect of drug treatment targeting neurons is not good^[2]。 The occurrence and development of DNP involves a variety of biochemical factors and anatomical changes in the peripheral and central nervous systems. Persistent hyperglycemia acts as an initiating factor by altering neuronal axonal cell membrane voltage-gated Na⁺Ca²⁺Expression and function of isochannels^[3]Affect the production of nerve growth factor and substance P^[4]Eventually, it can cause increased excitability of peripheral receptor nerve fibers and spinal dorsal horn neurons, and abnormally increased excitability leads to spontaneous discharge of neurons and sensitization to peripheral stimuli, which may be the basis of neuropathic pain. In addition, the inflammatory microenvironment and the release of inflammatory mediators [such as tumor necrosis factor alpha (TNF-α)^[5]] is also one of the important mechanisms of DNP occurrence. In recent years, more and more studies have shown that microglia activation plays a very important role in the development of DNP^[6]。

The results of previous large international studies confirm that^[1]Intensive therapy can significantly reduce the risk of diabetic vascular complications and related death compared with conventional therapy. So, what is intensive insulin therapy? This concept originally originated from the Diabetes Control and Complications Study (DCCT). In order to control blood sugar within the normal range as much as possible, daily subcutaneous multiple needle injections (more than 3 times) or insulin pump treatment are used to achieve the purpose of simulating physiological insulin secretion. Initially, intensive insulin therapy is an alternative treatment for patients with advanced type 1 diabetes (T1DM) or type 2 diabetes (T2DM) with islet β cell failure. In recent years, its indications have gradually expanded. For newly diagnosed T2DM with obvious hyperglycemia Patients, intensive treatment can be used as a short-term treatment to quickly relieve glycotoxicity and protect and reverse the function of residual islet β cells^[2]。