Volume 13 · Issue 01 · 2021

Excessive intake of exogenous glucocorticoids (GC) and excessive secretion of endogenous GC may cause different degrees of blood glucose increase through various mechanisms. Both the blood glucose monitoring regimen after using exogenous GC and the hypoglycemic regimen of steroid diabetes should consider the characteristics of mainly elevated blood glucose in the afternoon. It is necessary to fully understand the characteristics and clinical screening evaluation strategies of abnormal glucose metabolism caused by GC, and adopt appropriate methods to deal with it, so as to achieve better therapeutic effect.

Diabetes has become the leading cause of end-stage kidney disease (ESRD). Patients with diabetes complicated with ESRD have large blood glucose variability and are prone to hyperglycemia and hypoglycemia events, which is closely related to the disorder of glucose metabolism in patients with ESRD. The risk of blood glucose fluctuations in ESRD patients is increased by factors such as reduced renal gluconeogenesis, impaired renal insulin clearance, defective insulin degradation due to uremia, increased glucose uptake by red blood cells during hemodialysis, impaired response to antagonistic insulin hormones (cortisol, growth hormone), nutritional deficiencies, etc. Understanding the changes of glucose metabolism disorders in ESRD patients can help clinicians better manage blood glucose and improve the quality of life of diabetic patients with ESRD.

Common clinical liver diseases are closely related to abnormal glucose metabolism, and their pathological mechanisms involve insulin resistance and islet function impairment. Viral hepatitis, metabolism-related fatty liver disease, liver transplantation and other abnormal glucose metabolism have their specific clinical characteristics, and patients with advanced and end-stage liver disease are more likely to develop hypoglycemia. The type of liver disease and liver function need to be considered when choosing hypoglycemic drugs. In addition to the hypoglycemic effect, some of the commonly used hypoglycemic drugs also have potential benefits in improving liver lesions.

With the ageing in China, the prevalence of diabetes in the elderly has increased significantly, and it is urgent to standardize the management of elderly diabetic patients. The National Geriatric Center, the Geriatric Branch of Chinese Medical Association and the Diabetes Professional Committee of China Geriatric Health Care Association organized experts to write the Guidelines for Diagnosis and Treatment of Diabetes in the Elderly in China (2021 Edition). This guide consists of 19 chapters, including epidemiology and clinical characteristics of diabetes mellitus and its complications in the elderly, comprehensive health assessment of elderly diabetic patients, blood glucose management, management of risk factors of atherosclerotic cardiovascular disease, management of acute and chronic complications, management of comorbidities and special circumstances of diabetes mellitus in the elderly, etc. This guideline emphasizes the presence of high heterogeneity in older patients with diabetes and the need for comprehensive assessment with stratified and individualized management strategies. The blood glucose management pathway, simple treatment concept and "de-intensive treatment strategy" suitable for elderly diabetic patients were proposed. The promulgation of this guideline will help to guide and help clinicians to carry out all-round and full-cycle standardized comprehensive management of elderly diabetic patients, and improve the clinical outcomes of elderly diabetic patients in China.

The author introduced and interpreted the article "Bone marrow as target organ and accomplice of diabetic vascular complications", aiming to raise awareness. This paper mainly introduces the changes of bone marrow in diabetes mellitus and the effects and mechanisms of bone marrow changes on diabetes mellitus with peripheral arterial lesions, especially ischemia that seriously threatens the limbs, and puts forward that preventing the deterioration of bone marrow can be helpful for the treatment and nursing of diabetic foot, and provides new ideas and methods for clinical treatment of diabetes mellitus with ischemia that seriously threatens the limbs from the perspective of bone marrow.

Surgical revascularization and repair of diabetic foot ulcer released by the International Diabetic Foot Working Group systematically summarizes the surgical methods and latest progress of foot preservation in patients with diabetic peripheral artery disease (PAD). The author elaborated on inflow tract lesions to the common femoral artery, distal bypass surgery, bypass surgery of the calf artery, bypass surgery of an isolated popliteal artery segment, bypass surgery of the foot artery, arteriovenous fistula, venous arterialization and free tissue grafting.

To investigate the effects of long-acting somatostatin analogues (SSA) on glucose metabolism in acromegalic patients without diabetes and the influence factors.

Clinical information of patients with growth hormone (GH) secreting adenomas were collected at pretreatment and 3 months after initiation of treatment with long-acting SSA in Huashan Hospital from January 2015 to June 2020. The patients were divided into normal glucose tolerance (NGT) group and prediabetes (preDM) group according to glucose metabolism. Insulin resistance and β cell function were compared among different glucose tolerance groups; changes in the characteristics of glucose metabolism after SSA treatment were analyzed. Subgroup analysis was performed according to changes of glucose metabolism after SSA treatment and analysis the factors affecting the changes of glucose metabolism. The patients were divided into three subgroups: blood glucose deteriorated group, blood glucose stable group and blood glucose improved group. Pearson analysis was used to evaluate the related factors affecting glucose metabolism. Paired t test or Wilcoxon rank sum test was conducted to compare the indexes before and after SSA treatment.

A total of 71 patients were enrolled in this study. There were 36 patients in NGT group, and 35 in preDM group. The fasting blood glucose increased after SSA treatment [(5.8±0.7)vs. (5.2±0.5) mmol/LP<0.05]. Homeostasis model assessment of insulin resistance declined [4.2(2.1, 6.3)vs. 2.3(1.3, 4.8), P<0.05] after SSA treatment. The glucose tolerance status deteriorated in 24 (33.8%) patients, including 16 patients in the NGT group and 8 patients in the preDM group. Deteriorated glucose tolerance status groups were younger than the stable glucose tolerance status groups [(37.4±11.8) and (45.7±12.5) years old, respectively]. The decrease of GH of deteriorated glucose tolerance status groups was significantly lower than the stable glucose tolerance status groups [-30.3% (-70.5%, 11.3%)vs. -70.3% (-91.4%, -40.4%), P<0.05]. The changes of fasting blood glucose and growth hormone before and after SSA treatment were positively correlated with the change rate of insulin resistance index evaluated by homeostasis model (r=0.318 and 0.251, P=0.013 and 0.030).

SSA can increase blood glucose in some patients with GH secreting adenomas. The outcome of glucose metabolism depends on the drug sensitivity. Moreover, young patients with poor drug efficacy are more likely to suffer from the deterioration of glucose metabolism after SSA treatment.

To investigate the efficacy and safety of liraglutide plus insulin glargine and basal-bolus insulin intensive therapy in newly diagnosed type 2 diabetes mellitus (T2DM), respectively.

In this 4-week randomized prospective pilot study, 150 newly diagnosed T2DM patients were recruited from January 2019 to June 2020 in the Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University. According to the random number table method, these patients were randomly assigned to liraglutide plus insulin glargine therapy group (experimental group, 75 cases), and basal-bolus insulin intensive therapy group (control group, 75 cases. Asparagine insulin was injected before three meals and glargine insulin was injected before going to bed) by 1∶1 matching. The primary endpoint was the time of glycaemic control. The secondary endpoint was changes in body weight from baseline, homeostasis model assessment of insulin resistance (HOMA-IR), and hypoglycemia at the 4th week. Statistical analysis was performed using independent-samples t test, paired-samples t test, covariance analysis, and Chi-square test.

Ultimately, there were 72 cases in the experimental group and 73 cases in the control group. Three patients (4.0%) in the experimental group had hypoglycemia for 4 times, while 10 patients (13.3%) in the control group had hypoglycemia for 14 times (χ²=4.227, P=0.040). The time of glycaemic control in the experimental group was (6.0±1.8) days and (5.6±1.7) days in the control group, but this statistical difference was not significant (t=1.396, P=0.165). After 4-week treatment, the weight significantly decreased by (1.61±0.73) kg from baseline in the experimental group, there was no significant statistical difference (t=2.224, P=0.029), while in the control group, the weight increased by (1.15±0.81) kg (t=1.413, P=0.162). HOMA-IR significantly decreased by 6.24±0.34 from baseline (t=18.642, P<0.01) in the experimental group, and HOMA-IR decreased by 5.80±0.29 from baseline (t=19.853, P<0.01) in the control group. Compared with the control group, HOMA-IR was improved in the experiment group could further improve (F=2.620, P=0.027) by the use of covariance analysis.

Liraglutide plus insulin glargine therapy is not inferior to basal-bolus insulin intensive therapy for newly diagnosed T2DM. Moreover, liraglutide plus insulin glargine therapy has the advantage of weight loss, reducing hypoglycemia risk, and improving insulin resistance in newly diagnosed T2DM.

To explore the association between neutrophil-to-lymphocyte (NLR) or platelet-to-lymphocyte (PLR) and renal tubular injury in type 2 diabetes mellitus (T2DM) patients.

A total of 268 patients with T2DM who were hospitalized in the Third Xiangya Hospital of Central South University from September 2018 to September 2019 were assigned to three groups according to their urine albumin/urine creatinine ratio (UACR): normal-albuminuria group (Normal group, UACR<30 mg/g), micro-albuminuria group (Micro group, 30≤UACR<300 mg/g), and macro-albuminuria group (Macro group, UACR≥300 mg/g). Basic information and clinical data of the research objects were collected. Fasting extraction of elbow venous blood to test blood routine, and biochemical indicators such as glycated hemoglobin A_1c and hypersensitive C-reactive protein (hs-CRP). NLR, PLR and estimated glomerular filtration rate (eGFR) was calculated. After detecting the levels of α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), retinol-binding protein (RBP) and urinary creatinine (Ucr), we regarded α1-MG/Ucr, β2-MG/Ucr and RBP/Ucr as indicators for responding renal tubular injury. Group differences were tested with Chi-square test, analysis of variance and nonparametric tests. Associations between inflammatory index and renal injury markers were performed by Spearman correlation coefficients. Receiver operator characteristic (ROC) analyses determined the prediction efficiency of model.

NLR and PLR levels were increased in the Macral group (94 cases) than both the Micro group(80 cases) and the Normal group(94 cases), and the difference was statistically significant (P<0.01). Compared with the Micro group, NLR levels in the Macro group were increased in Macro group (P<0.05). With the increase in NLR and PLR quartiles, there were gradual increase in UACR, urine RBP/Ucr, urine α1-MG and urine β2-MG, and the differences were statistically significant (P<0.05). Spearman correlation analysis showed that NLR and PLR had positive correletions with UACR, RBP/Ucr, α1-MG/Ucr and β2-MG/Ucr (r=0.254-0.385, all P<0.01), and a negative correlation with eGFR (r=-0.328, -0.151, both P<0.01). In addition, ROC curve analyses showed that the AUC and sensitivities of NLR in predicting UACR>30 mg/g, eGFR<60 ml·min^－1·(1.73 m²)^－1, RBP/Ucr>0.10, α1-MG/Ucr>2.08, or β2-MG/Ucr>0.07 (AUC were 0.700, 0.679, 0.717, 0.702, 0.737, respectively; sensitivities were 75.29%, 85.87%, 80.88%, 83.74%, 85.59%, respectively) were all higher than those of PLR (AUC were 0.639, 0.639, 0.659, 0.644, 0.676, respectively; sensitivities were 58.05%, 75.00%, 63.24%, 65.04%, 58.56%, respectively) and hs-CRP (AUC were 0.597, 0.559, 0.618, 0.644, 0.653, respectively; sensitivities were 62.50%, 30.12%, 63.93%, 68.42%, 70.87%, respectively).

Both NLR and PLR are closely related to renal tubular injury in patients with T2DM, and NLR is superior to PLR or hs-CRP not only in reflecting glomerular damage but also in tubular injury.

To investigate the effects of dapagliflozin on urinary exosomal microRNA (miRNA) in early-stage type 2 diabetes mellitus (T2DM) diabetic kidney disease (DKD).

A total of 60 patients with T2DM DKD were enrolled from September 2018 to September 2019 in the Department of Endocrinology and Metabolism, Huai′an Hospital Affiliated to Xuzhou Medical College. They were assigned to the following groups according to urine albumin-to-creatinine ratio (UACR): patients with 30 mg/g<UACR<300 mg/g were included in the DKD group (20 cases), and the 40 patients with T2DM with UACR<30 mg/g were divided into the traditional hypoglycemic drug treatment group (20 cases) and the dapagliflozin (DAP) group (20 cases) using the random number table method. The DKD group and DAP group were both treated with 10 mg/d dapagliflozin for 3 months. In addition, 20 healthy physical examination people were selected as control at the same period. Clinical indicators such as fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2 hPPG), glycated hemoglobin A_1c (HbA_1c) and blood lipid were detected. Body mass index (BMI) was calculated. Real-time polymerase chain reaction (PCR) and microarray were used to determine miRNA levels in urinary exosomes. Student′s t test, one-way analysis of variance (ANOVA), Chi-Square test and Wilcoxon rank sum test or the Mann-Whitney U test were used to compare the differences between groups.

In DAP group, compared with before treatment, weight, BMI, FPG and 2 hPPG were all reduced after treatment, and the differences were statistically significant (P<0.05). In DKD group, the levels of weight, BMI, HbA_1c, FPG, 2 hPPG and UACR decreased after treatment compared with those before treatment, and the differences were statistically significant (P<0.05). Compared with the control group, the expression of 5 miRNA (miR-let-7b-5p, miR-21-5p, miR-182-5p, miR-200c-3p, and miR-423-5p) in the traditional drug treatment group was up-regulated, and the differences were statistically significant (P<0.05). The expression of the 5 miRNA was also up-regulated in DKD group compared with the traditional hypoglycemic drug treatment group, and the differences were statistically significant (P<0.05). In DKD group, compared with before treatment, the expression of the 5 miRNA decreased significantly after dapagliflozin treatment (P<0.05).

Multiple dysregulations in urinary exosomal miRNA are present in the patients with early-stage T2DM DKD, and dapagliflozin could down-regulate the expression of exosomal miRNA.

To investigate the effects of exenatide on podocyte injury induced by high glucose (HG) in mice and its possible mechanisms.

According to different glucose concentrations and interventions, podocytes MPC5 cells were assigned to the following 5 groups: normal glucose (NG) group (5.5 mmol/L glucose, n=3), mannitol (MA) group (5.5 mmol/L glucose+19.5 mmol/L mannitol, n=3), HG group (25.0 mmol/L glucose, n=3), HG+exenatide group (25.0 mmol/L glucose+100 nmol/L exenatide, n=3), and HG+exenatide+LY294002 group (25.0 mmol/L glucose+100 nmol/L exenatide+50 μmol/L phosphatidylinositol-3-kinase inhibitor LY294002, n=3). Apoptosis of podocytes were stained with DeadEnd^TM fluorometric terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling system, Annexin Ⅴ-flourescein isothiocyanate and propidium iodide (PI), and assessed by flow cytometry. The expression levels of slit diaphragm protein (nephrin), phosphorylated protein kinase B (p-AKT) and phosphorylated Bcl-xL/Bcl-2 related death promoter (p-BAD) were measured by western blotting. Data among multiple groups were compared by using one-way analysis of variance (ANOVA) and the least significant difference t test.

Compared with the NG group and MA group, the percentage of apoptotic podocytes significantly increased [(28.60±2.65) % vs. (4.50±0.75)%, (4.55±0.65)%, t=-19.19, -19.15, both P<0.01], the protein levels of nephrin decreased (0.22±0.03 vs. 0.72±0.06, 0.73±0.08, t=11.43, 11.52, both P<0.01), the protein expressions of p-AKT and p-BAD were down-regulated (0.14±0.03 vs. 0.83±0.06, 0.86±0.04; 0.16±0.03 vs. 0.66±0.06, 0.68±0.04, all P<0.01) in the group cultured with HG. Compared with the HG group, the percentage of apoptotic podocytes significantly decreased and the protein levels of nephrin increased, and the protein expressions of p-AKT and p-BAD were also up-regulated in the HG+exenatide group (all P<0.01). However, compared with the HG+exenatide group, the percentage of apoptotic podocytes increased and the protein levels of nephrin decreased, and the protein expressions of p-AKT and p-BAD were also down-regulated in the HG+exenatide+LY294002 group (all P<0.05).

Exenatide prevents high glucose-induced podocyte injury by preserving slit diaphragm protein expression and preventing podocyte apoptosis. The possible mechanisms may involve the AKT/BAD signaling pathway.

Recently, the use of programmed death receptor 1 (PD-1) inhibitors in the treatment of tumors is increasingly common, and its adverse reactions are gradually recognized. Two cases of hyperglycemia caused by PD-1 inhibitor were reported. Case 1, 87-year-old female, developed dry mouth, polydipsia and polyuria after 3 cycles of sintilimab treatment for "oral squamous cell carcinoma", and finally progressed to type 1 diabetes complicated with ketosis. After insulin treatment, her blood glucose was stable, and finally died due to the progression of the primary disease. Case 2, male, 49 years old, experienced abnormal blood glucose increase after 18 cycles of nivolumab treatment due to "kidney cancer". After adjusting the hypoglycemic regimen, the blood glucose gradually stabilized. For patients treated with PD-1 inhibitors, clinicians need to strengthen the follow-up of endocrine gland function and formulate individualized treatment plans in time.

Adult-onset diabetes mellitus (MODY) type 5 in adolescents is relatively rare in the Chinese population, and its clinical manifestations are atypical. Clinicians don't know enough about it, and it is easy to misdiagnose and miss diagnosis. This study reported a case of MODY type 5 patient with rare multiple organ phenotypic abnormalities, including dorsal pancreatic agenesis, renal atrophy, renal cyst, abnormal liver function, hypomagnesemia, etc. After genetic testing, it was clear that it was caused by heterozygous deletion of exons 2~5 of hepatocyte nuclear factor 1 β gene. It is a special spontaneous gene variation, which has not been reported at home and abroad. This study supplemented the case data of this type of patients in China, and suggested that patients with no family history but early-onset diabetes and kidney disease should be screened for MODY 5 to clarify molecular diagnosis and achieve precision medicine.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of hypoglycemic drugs that have been widely used in clinical practice in recent years. In addition, current research shows that in addition to safe and effective hypoglycemic effects, SGLT2 inhibitors have clear benefits in improving cardiovascular outcomes. However, the mechanism is still unclear. Current research shows that SGLT2 inhibitors may play a protective role in protecting cardiac structure and function, delaying the process of atherosclerosis, and improving cardiovascular high-risk factors.

Primary aldosteronism (PA) accounts for 5% to 15% of hypertensive people, and is a common disease that is easily overlooked. PA patients are prone to glucose metabolism disorders, and about 23.0% ~35.3% of PA patients will be accompanied by diabetes or abnormal glucose tolerance. The mechanism may be that high aldosterone affects the function of islet β cells and the sensitivity of target tissues to insulin. The evidence of PA and lipid metabolism abnormalities is not sufficient. The characteristics and mechanisms of glucose and lipid metabolism in patients with PA are reviewed.

Diabetic macrovascular disease is an important cause of disability and death caused by diabetes, which seriously threatens the prognosis and survival rate of diabetic patients. Diabetic macrovascular disease is mainly manifested as diabetes-related macrovascular atherosclerosis, and oxidative stress, as an important pathophysiological mechanism of atherosclerosis, also plays an important role in diabetic macrovascular disease. Therefore, reducing oxidative damage or increasing antioxidant capacity of the body is also considered to be the focus of prevention and treatment of diabetic macrovascular disease. In recent years, novel hypoglycemic drugs sodium-glucose cotransporter 2 (SGLT2) inhibitors have not only shown significant cardiovascular benefits but also antioxidant effects. This article will review the antioxidant mechanisms associated with SGLT2 inhibitors in order to provide new therapeutic targets and new ideas for diabetic macrovascular disease.

Metabolic syndrome (MS) is a clinical syndrome characterized by a cluster of multiple metabolic disorders that can significantly increase the risk of cardiovascular disease and type 2 diabetes, however there is a lack of effective therapeutic agents at present. Sodium-glucose cotransporter 2 inhibitor is a novel hypoglycemic drug that promotes urinary glucose excretion and has been shown to slightly reduce body weight, improve hypertension and dyslipidemia, and its potential cardiovascular protective effects and multi-target effects are being paid more and more attention.

With the planning of transforming large medical institutions into research hospitals and the continuous promotion of evidence-based medicine, clinicians are enthusiastic about participating in clinical research while completing the basic work of clinical medical care. However, how to improve the quality of clinical research and produce high-level and standardized clinical research results is a great challenge at present. Condensed clinical research problems are the prerequisite for carrying out high-quality clinical research. The author will discuss how to put forward good clinical research questions in clinical work by expounding the attributes and sources of clinical research questions.

Pancreatic diabetes is diabetes caused by exocrine diseases of the pancreas, mainly caused by chronic pancreatitis and pancreatic cancer. At present, there is no positive diagnostic criteria, which is easy to be ignored and missed. Patients with pancreatogenic diabetes have large blood sugar fluctuations and small insulin requirements, so they are not prone to diabetic ketoacidosis. The main therapeutic drug is insulin, and some early patients can use metformin.