Volume 10 · Issue 04 · 2018

diabetic retinopathy (DR) is one of the common chronic complications of diabetes and one of the main causes of blindness in adults^[1,2,3]。 DR seriously threatens the quality of life of diabetic patients, and at the same time brings a serious economic burden to society.

Recently, the American Society of Physicians published in the Annals of Internal Medicine (Annals of Internal Medicine) a study on drug treatment of type 2 diabetes mellitus with glycosylated hemoglobin (HbA_1c) Guidelines for Control Target Updates^[1]。 The key points of the guidelines include: (1) Physicians should determine individualized blood sugar control goals for patients based on the pros and cons of therapeutic drugs, patient preferences, health status and life expectancy, medical burden and other specific conditions; (2) HbA in most patients with type 2 diabetes who will be treated with drugs_1cThe control target is set at 7% ~8%; (3) When patients with type 2 diabetes HbA_1c<At 6.5%, it should be considered to reduce the therapeutic intensity of hypoglycemic drugs; (4) For patients with a life expectancy of less than 10 years, long-term care, or patients with chronic diseases (such as dementia, malignant tumors, end-stage renal disease, severe chronic obstructive pulmonary disease or congestive heart failure), the purpose of hypoglycemic therapy is to relieve the clinical symptoms caused by hyperglycemia, rather than pursue HbA_1cMeet the mark.

Diabetic nephropathy (DKD) is one of the most important chronic microvascular complications of diabetes, and it is the most common cause of end stage renal disease (ESRD) worldwide. ESRD caused by diabetes is as high as nearly 45% in the United States and developed Asian countries; Although it is relatively low (15% ~20%) in China at present, it is still the second leading cause of ESRD^[1,2]Moreover, with the rapid increase of diabetes prevalence in China in the past 30 years, ESRD caused by diabetes is bound to increase significantly with time. Because ESRD patients need expensive dialysis or kidney transplantation treatment, and the risk of cardiovascular events and death is significantly increased, this puts a heavy burden on patients and society. Therefore, early diagnosis and early intervention are the core strategies to prevent the occurrence, development and harm reduction of DKD.

chronic kidney diseases (CKD) include chronic kidney structural and functional damage caused by various causes. Diabetic nephropathy (DKD) refers to CKD caused by diabetes. The early changes of DKD include glomerular hyperfiltration, renal tubular epithelial cell hypertrophy, etc. The clinical manifestations are microalbuminuria, followed by mesangial and interstitial changes, thickening of basement membrane, increased urinary albumin excretion, and finally leading to glomerular sclerosis and gradual loss of renal function^[1]。 The clinical diagnosis of DKD mainly depends on the appearance of albuminuria and/or a decrease in estimated glomerular filtration rate (eGFR). At present, 20% to 40% of diabetic patients in China are complicated with DKD, which has become the main cause of CKD and end-stage renal disease (ESRD)^[2]。 In addition, DKD increases the risk of cardiovascular events such as coronary heart disease and stroke, and is also related to the increased risk of death in diabetic patients.

With the improvement of understanding of the pathophysiological mechanisms of type 2 diabetes, new therapeutic targets and drugs are constantly emerging. At present, there are 9 types of drugs clinically used to treat diabetes, including sulfonylureas, glidenides, dipeptidyl peptidase IV (DPP-4) inhibitors, biguanides, thiazolidinediones (TZDs), α-glycosidase inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and insulin^[1]。 In view of the fact that about 30% of diabetic patients will be complicated with diabetic nephropathy (DKD), when choosing hypoglycemic drugs, in addition to considering the hypoglycemic effect, it is also necessary to choose appropriate drugs according to the situation of kidney damage. In recent years, it has been found in clinical and basic research that some hypoglycemic drugs may also have the function of protecting the kidney independently of lowering blood sugar while lowering blood sugar. This undoubtedly brings the drug treatment of diabetes into a new stage. Drugs with dual functions of lowering blood sugar and protecting kidney will inevitably have more advantages in clinical use. However, the current understanding of the nephroprotective effects of these drugs remains uncertain, and the translation of existing research evidence into clinical practice still needs to be cautious. This paper will review and prospect the existing evidence, the remaining problems and the future research direction.

To investigate the correlation between body compositions (body fat, skeletal muscle, lean tissue) and diabetic retinopathy (DR) and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).

A total of 1 017 hospitalized T2DM patients (582 males and 435 females) in our hospital from March 2013 to September 2016 were enrolled. According to their medical history and corresponding auxiliary examination, they were divided into four groups: T2DM with DKD group (n=389), T2DM without DKD group (n=628); and T2DM with DR group (n=288), T2DM without DR group (n=729). The clinical data and anthropological measurements were collected and body compositions, including total body fat (TBF), fat mass index (FMI), visceral adipose tissue (VAT), appendage lean mass/ height² (ALMH), total lean mass (TLM), et al, were measured by dual-energy X-ray absorptiometry. The correlations between body compositions and DKD or DR were analyzed. The t test, U test, Chi square test analysis were used for statistical analysis. Logistic regression was used to estimate the association of body compositions with DKD or DR.

There were statistically significant differences in T2DM duration, hypertension history, age, systolic blood pressure (SBP), low-density lipoprotein-cholesterol, triglyceride and uric acid (UA) between T2DM patients with DKD and those without DKD (all P<0.05). T2DM duration, SBP, glycated hemoglobin A_1c (HbA_1c), hypertension history, fasting plasma glucose and UA in T2DM with DR were also significantly different from those without DR (all P<0.05). In terms of body compositions, VAT [(133±46) vs (116±41) cm², t=-5.782, P<0.001], FMI [7.44 (6.28-9.11) vs 6.72 (5.76-8.26) kg/m², Z=-4.537, P<0.001], BMI [25.4 (23.4-27.7) vs 24.2 (22.3-26.2) kg/m², Z=-5.534, P<0.01], TBF [29.04% (25.72%-34.33%) vs 27.29% (24.40%-33.60%), Z=-2.838, P<0.01] in T2DM patients with DKD were significantly increased compared with those without DKD. There were no significant difference in body compositions between T2DM patients with DR and without DR (all P>0.05). Multivariate logistic regression was used to correct the confounding factors such as HbA_1c, total cholesterol, TLM, ALMH, gender, age, duration of T2DM etc. The risk of DKD in patients with T2DM was significantly increased with the increase of VAT [low rank as a reference, median rank OR=1.73, 95%CI (1.14, 2.62), high rank OR=2.47, 95%CI (1.45, 4.22)] and was not related with FMI. In the DR group, both VAT and FMI were not significantly associated with the risk of DR (P>0.05).

VAT is an independent risk factor for DKD.

To explore clinical features and potential risk factors of normoalbuminuric chronic kidney disease (CKD) in type 2 diabetic patients.

Clinical information and laboratory data of patients with type 2 diabetes mellitus (T2DM) hospitalized from January 2012 to November 2016 were collected. The t test, non-parametric test and χ ² test were used for comparison between groups.

The prevalence of CKD in hospitalized patients with T2DM was 33.84%(355/1 049). In patients with renal impairment [CKD stage≥3, estimated glomerular filtration rate <60 ml·min ^-1·(1.73 m²)^-1], 25.3%(25/99) patients had normal albuminuria, 32.3%(32/99) had microalbuminuria while 42.4% (42/99) had macroalbuminuria. Compared to CKD patients with albuminuria (ALB-CKD 3-5), CKD patients with normoalbuminuria (NA-CKD) presented younger age [(54.5±11.3) vs (74.8±4.9) years, t=12.49, P<0.05], shorter diabetes duration [10 (5, 22) vs 14(10, 20) years, Z=2.97, P<0.05], higher body mass index (BMI) [(26.6±3.6) vs (24.4±3.7) kg/m², t=2.26, P<0.05], lower total cholesterol [4.00(3.09, 4.80) vs 4.62(3.90, 5.36) mmol/L, Z=2.53, P<0.05] and lower systolic blood pressure [132(120, 144) vs 141(130, 164) mmHg, Z=2.47, P<0.05] (1 mmHg=0.133 kPa). Logistic regression showed that anemia [OR=0.084, 95%CI(0.02-0.35)] and BMI [OR=0.83, 95%CI(0.72-0.95)] were independently associated with NA-CKD.

T2DM patients with NA-CKD presented with younger age, shorter diabetes duration, higher BMI while they have better control of hypertension and hyperlipidemia. Obesity and anemia are risk factors of the occurrence of NA-CKD in T2DM.

To investigate the relationship of soluble CD₁₄₆ (sCD₁₄₆) with atherosclerosis and future cardiovascular events in patients with diabetic kidney disease (DKD).

A total of 105 DKD patients at chronic kidney disease(CKD) (68 male, 37 female) stage 1-3 were enrolled and another 94 type 2 diabetes mellitus patients without DKD (64 male, 30 female) entered the control group from January 2013 to December 2015 in our hospital. Plasma concentration of sCD₁₄₆ was measured. Doppler ultrasounds of carotid and lower extremity artery were performed. All the DKD patients were retrospectively followed up (medium follow-up 28 months).The differences of sCD₁₄₆ between DKD patients and control group was analyzed and the relationship between sCD₁₄₆ and proteinuria and renal function was evaluated in DKD patients. The association between sCD₁₄₆ and atherosclerosis was explored in DKD patients. Kaplan-Meier method was used to evaluate the predictive value of sCD₁₄₆ in future cardiovascular events.

The level of sCD₁₄₆ in diabetes mellitus patients was lower than that of DKD group[the level of sCD₁₄₆ was (435±150) and (602±274) μg/L, respectively, t=-5.246, P<0.001]. Spearman analysis showed the positive association between sCD₁₄₆ and serum creatinine (r=0.36, P<0.001), urinary albumino-to-creatinine ratio (r=0.225, P=0.001) and its negative correlation with eGFR (r=-0.376, P<0.001). The elevation of sCD₁₄₆ was further associated with the progression of CKD[the levels of sCD₁₄₆ in patients of CKD stage 1, 2 and 3 were (472±172), (590±223), (685±340) μg/L, respectively, F=164.203, P<0.001]. In DKD group, the upregulation of sCD₁₄₆ was associated with both the increase of carotid intima-media thickness (r=0.577, P<0.001) and femoral intima-media thickness (r=0.765, P<0.001). Patients with higher level of sCD₁₄₆ tended to have more carotid plaques [OR(95%CI)=17.302(2.752-108.780), P=0.002], unstable carotid plaques [OR(95%CI)=6.404(1.036-39.608), P=0.046] and unstable plaques in lower extremity arteries [OR(95%CI)=13.641(1.942-95.825), P=0.009] after the adjustment of other cardiovascular risks. Patients with higher concentration of sCD₁₄₆ tended to have poorer cardiovascular outcomes (Log rank χ ²=9.366, P=0.049).

The measurement of plasma sCD₁₄₆ is a noninvasive way which can sensitively reflect the progression of renal function and atherosclerosis, and it can also be a good marker to predict cardiovascular outcomes in DKD patients at CKD stage 1-3.

To observe the clinical features of type 2 diabetes mellitus (T2DM) complicated with skin pruritusand the related factors.

According to complication of skin pruritus whether or not, a total of 225 patients with T2DM in endocrinology department and dermatology clinic of our hospital from July 2015 to July 2016 were divided into T2DM group with skin pruritus group (n=63) and T2DM non-skin pruritus group (n=162). The clinical data and biochemical indicators were compared between these two groups. The risk factors of T2DM combined with skin pruritus were analyzed with Multifactor Logistic regression.

(1) In this study, the incidence of T2DM combined with skin pruritus was 28.00%(63/225). There were no statistically significant differences on incidenceof T2DM combined with skin pruritus with age (≤60, >60 years), fasting plasma glucose (FPG) (<6.1, 6.2~6.9, ≥7 mmol/L), 2 h plasma glucose (2hPG) (≤7.8, 7.9~11.0, ≥11.1 mmol/L), glycated hemoglobin A _1c (HbA_1c) (<6.5%, ≥6.5%) diabetic family history, and the prevalence of diabetic retinopathy and diabetic peripheral neuropathy (χ²=6.867-22.222, all P<0.05). (2) The diabetes mellitus course, FPG, 2hPG, HbA_1c, insulin usage, hyperlipidemia, as well as the prevalence of diabetic retinopathy and diabetic nephropathy, were higher in T2DM with skin pruritus group than those in T2DM non-skin pruritus group [(13.7±2.0) vs (12.0±1.9) years, (7.7±1.1) vs (6.3±2.0) mmol/L, (11.6±3.0) vs (8.4±2.7) mmol/L, 9.8%±1.7% vs 7.9%±2.5%, 57.14%(36/63) vs 23.47%(38/162), 50.79%(32/63) vs 22.22%(36/162), 50.79%(32/63) vs 24.07%(39/162), 52.38%(33/63) vs 46.30%(75/162), t=-1.535--2.917, χ ²=15.241-23.583, all P<0.01]. (3) Logistic regression analysis revealed that age>60 years, diabetes mellitus course>10 years, FPG≥7.0 mmol/L, HbA_1c≥6.5%, combine with hyperlipidemia, diabetic retinopathy and diabetic peripheral neuropathy were risk factors for T2DM complicated with skin pruritus (β=0.075-0.609, allP<0.05).

The incidenceof T2DM with skin pruritus was higher. The risk factors for T2DM complicated with skin pruritus included age>60 years, diabetes mellitus course>10 years, FPG≥7.0 mmol/L, HbA_1c≥6.5%, combine with hyperlipidemia, diabetic retinopathy and diabetic peripheral neuropathy.

To investigate the relationship among plasma slit guidance ligand 2 (slit2) and pre-diabetes and type 2 diabetes mellitus (T2DM).

A total of 143 subjects recruited in Department of Endocrinology of Xinqiao Hospital from Jun 2017 to Dec 2017, 51 patients diagnosed with newly T2DM (T2DM group, 27 male, 24 female), 39 patients diagnosed with pre-diabetes (pre-DM group, 15 male, 24 female), and 53 subjects diagnosed with normal glucose tolerance (NGT group, 18 male, 35 female). Clinical data were collected, intravenous glucose tolerance test were examined and fasting plasma slit2 was assayed by ELISA. Acute insulin response (AIR), the area under the curve of the first-phase (0-10 min) insulin secretion (AUC), glucose disposition index (GDI), homeostasis model assessment for β cell function index (HOMA-β), and insulin resistance index (HOMA-IR) were measured.

(1) The levels of slit2 in T2DM group and pre-DM group were significantly higher than those in NGT group respectively [(2.9±2.2), (3.0±2.8) vs (1.6±1.3) μg/L, t=3.45, 3.35, both P<0.01]. (2) Slit2 was positively correlated with body mass index, waist circumference, fasting plasma glucose, 2 h plasma glucose, glycated hemoglobin A_1c, fasting insulin, HOMA-IR and triglycerides (r=0.174-0.389, all P<0.05), and negatively correlated with AUC, AIR, GDI (r=-0.485--0.438, all P<0.01). (3) Multiple logistic regression analysis did not show the relationship between slit2 and T2DM after HOMA-IR, AIR, AUC and GDI were corrected respectively (OR=0.857-4.482, P>0.05) .

The concentrations of plasma slit2 are closely correlated with glycol metabolism status which increased in patients with pre-diabetes and type 2 diabetes. The association between slit2 and diabetes is affected by insulin resistance and the first-phase of glucose-stimulated pancreatic β-cell function. Slit2 may be proposed as an indicator for glucose tolerance status, and it may be involved in the mechanism of type 2 diabetes mellitus.

To explore clinical characteristics and pathogenesis of fulminant type 1 diabetes mellitus (FT1DM) and autoimmune thyroid disease (AITD) caused by drug-induced hypersensitivity syndrome (DIHS).

Data of a case of FT1DM and Hashimoto's thyroiditis induced by DIHS was collected and analyzed. A systemic search was performed in PubMed for articles published between 2000 and 2017 and identified literatures were reviewed.

The case was confirmed as DIHS with presentation of rashes, hepatic and renal damage, and followed by FT1DM and thyroids dysfunction. A total of 26 cases of DIHS induced T1DM were reported, including 23 cases of FT1DM and 3 cases of typical T1DM, which mostly occurred in 2 weeks to 2 months after DIHS. AITD induced by DIHS were found in 11 cases, with the onset in 1 to 17 months after DIHS.

Autoimmune endocrine disorders could be secondary to DIHS. Close monitoring of endocrine glands function after DIHS and tracing DIHS history before the onset of T1DM and AITD are necessary.

diabetic neuropathy (DN) is a neurological disease that gradually occurs due to long-term hyperglycemia causing metabolic disorders in the body, and microcirculation disorders causing ischemia and hypoxia. DN is one of the most common chronic complications of diabetes^[1]。 DN is considered to be a heterogeneous group of diseases because of its different symptoms and signs due to its risk factors, course of disease, neurological type, pathological changes and underlying mechanisms. The lesions can involve various parts of the nervous system, including the central nervous system and peripheral nerves, with the latter being the most common. distal symmetric polyneuropathy (DSPN) is the most common type of diabetic peripheral neuropathy (DPN), accounting for about 75% of DN^[2]。 The harm of DN includes pathological changes and functional abnormalities in the organs and tissues innervated by the involved nerves. Abnormal sensation and pain are common in clinic. In addition, motor and sensory nerve disorders of the lower limbs can cause diabetic foot disease, resulting in foot deformities or ulcers, which are the main causes of non-traumatic amputation. Therefore, it is particularly important to master the relevant theories of DN, early diagnosis and scientific treatment. In this paper, the research progress in epidemiology, etiology and risk factors, pathogenesis, diagnosis and treatment of DN is reviewed.

Diabetic nephropathy (DKD) is a common complication of diabetic patients and is the main cause of end-stage renal disease^[1]。 The pathogenesis of DKD is complex, and many factors, such as hyperglycemia, hemodynamic changes and the activation of polyol pathway, advanced glycosylation end products, protein kinase C activation, oxidative stress and genetics, are involved in the pathogenesis of DKD. More and more studies have shown that inflammation plays an important role in the development of DKD. Some scholars have proposed that DKD is a chronic inflammatory disease^[2]。 Searching for specific inflammatory markers to detect DKD early and explore new therapeutic targets has become a research hotspot in recent years. pentraxin (PTX) 3 protein is considered to be a rapid and sensitive marker reflecting inflammation in chronic kidney disease (CKD)^[3], some studies have shown that PTX3 is a better indicator of DKD inflammation than C-reactive protein (CRP)^[4]。 Therefore, the relationship between PTX3 and DKD is also increasingly concerned. In this paper, the role of PTX3 in DKD and its related mechanisms are reviewed.

Type 1 diabetes mellitus (T1DM) is an absolute insulin deficiency caused by T lymphocyte-mediated destruction of pancreatic islet beta cells^[1,2]。 T1DM is divided into autoimmune diabetes and idiopathic T1DM according to the presence or absence of islet autoantibodies. Among them, autoimmune diabetes can be divided into classical T1DM and adult occult autoimmune diabetes (LADA) according to the acute onset. The global incidence of T1DM is increasing year by year. In the 1980s and 1990s, the incidence of T1DM in China was about 0.51/100,000 people per year. The latest survey data show that the incidence of T1DM in the overall population of China is 1.01/100,000 people per year^[3]。 It can be seen that due to the huge population base and gradually increasing incidence rate, the annual incidence of T1DM in China is huge. Therefore, it is of great social significance to actively carry out research on the pathogenesis of T1DM and find potential new targets for early warning, diagnosis and treatment.