Volume 14 · Issue 02 · 2022

Diabetes is a dynamic process shared with chronic elevated glucose level but heterogeneous pathophysiological mechanisms and distinguished other characteristics. To be prevented from its perilous outcomes, the precise disease trajectory should be ideally predicted before and after the development of diabetes and onset of complications at specific individualized level, and then high-risk subject need be identified and intervened. The exploration and explanation of diabetes experienced from ignorance to qualitative description and then accurate quantitative assessment. Paradigm shift from specific biomarker to clustering of biomarkers enable to detect and predict disease progression and treatment response. Here, we reviewed the evolution of disease definition, diagnosis and classification in diabetes and illustrated the knowledge gaps to be filled.

The discovery of insulin is a major event in the history of biomedicine and has far-reaching significance. 2021 marks the 100th anniversary of the discovery of insulin and the 50th anniversary of the discovery of insulin receptors. The author introduces the history of insulin discovery, and briefly reviews the research course of insulin chemical nature, structure analysis, chemical synthesis, determination, formulation evolution, biosynthesis and processing, and mechanism of action in the past 100 years.

The proportion of hospitalized hyperglycemia patients in China is increasing year by year, and the current situation of in-hospital blood glucose management is not optimistic. Poor glycemic control in hospitalized patients can directly lead to many adverse clinical outcomes and even death. Many hospitals have gradually adopted information-based blood glucose monitoring system combined with team guidance to implement in-hospital blood glucose management, and have achieved good results, but they also face many difficulties. To further improve the effect of blood glucose management in hospital, it is necessary to establish and improve the relevant rules and regulations of blood glucose management in hospital, build an accurate blood glucose monitoring platform in hospital, strengthen the access and management of blood glucose monitoring system, the training and authorization of operators, the establishment of quality assurance system, set up a blood glucose management project team, standardize the implementation of efficient blood glucose management process, and use electronic blood glucose management system and intelligent auxiliary management tools to realize active monitoring and timely intervention of blood glucose in hospital, reduce the damage of hyperglycemia and hypoglycemia in hospital, and ensure clinical safety.

In order to establish a standardized diabetes classification and diagnosis process, identify diabetic patients with clear etiology early, and guide the practice of precise clinical diagnosis and treatment, the Endocrinology and Metabolism Physician Branch of Chinese Medical Doctors Association and the National Clinical Medical Research Center of Metabolic Diseases (Changsha) specially organized experts to formulate the "Chinese Expert Consensus on Diabetes Classification and Diagnosis". The author interprets the background and key points of the consensus, aiming at providing reference for peer application.

Diabetes is highly heterogeneous and requires fine diagnostic typing to achieve precise treatment. How to establish a standardized etiological diagnosis process of diabetes mellitus, and comprehensively synthesize clinical manifestations, laboratory examinations and genetic tests in an orderly manner, so as to correct diagnosis of diabetes mellitus is an urgent problem to be solved in clinical practice. Based on China's clinical practice, combined with expert opinions and the latest guidelines at home and abroad, the consensus aims to standardize the process of diabetes classification and diagnosis, identify diabetic patients with clear etiology early, and guide clinical diagnosis and treatment practice. The content of this consensus mainly includes the recommendation of diabetes classification, the basis and main points of diabetes classification diagnosis, the clinical characteristics of different types of diabetes and the process of diabetes classification diagnosis, etc.

To explore the risk factors of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM) and analyze the correlation between obesity and the incidence of CKD.

Patients aged 18 to 75 years old who were diagnosed with T2DM and treated in Nanjing Drum Tower Hospital from January 2009 to June 2019 were included. General data such as gender, age, body mass index (BMI), systolic blood pressure, diastolic blood pressure, and course of diabetes, laboratory indicators such as hemoglobin (Hb), albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), uric acid, fasting blood glucose (FPG), glycated hemoglobin A_1c (HbA_1c), triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), urine albumin/creatinine ratio and estimated glomerular filtration rate were collected. Obesity and overweight were defined as BMI≥28 kg/m² and 24 kg/m²≤BMI<28 kg/m², respectively. The patients were divided into a combined CKD group and a non-combined CKD group according to whether the CKD was combined. Among the T2DM patients in the non-combined CKD group, those followed up at least once for more than 12 months and with complete follow-up data were selected and divided into a non-CKD subgroup and a CKD subgroup according to whether CKD occurred. For the comparison of indicators between the two groups, the t test, non-parametric test and χ² test were used. Single-factor and multiple single logistic regression analyses were applied to analyze the risk factors of CKD in the patients with T2DM, and the Cox proportional hazards model was used to analyze the risk factors of CKD in the T2DM patients who were followed up. Restricted cubic spline (RCS) was employed to fit the Cox regression model to evaluate the correlation between different BMI cut-off points and CKD.

A total of 3 194 patients with T2DM were enrolled, including 620 cases in the combined CKD group and 2 574 cases in the non-combined CKD group. Compared with the non-combined CKD group, the BMI of the combined CKD group was significantly higher (P=0.005). The results of the single factor logistic regression analysis showed that gender, obesity, systolic blood pressure, diastolic blood pressure, Hb, albumin, TG, TC, FPG and HbA_1c were factors influencing the incidence of CKD in the patients with T2DM (all P<0.05). The above indicators were used as independent variables to carry out the multiple factor logistic regression analysis, of which the results revealed that obesity (OR=1.058, 95%CI 1.079—2.018), increased systolic blood pressure (OR=1.042, 95%CI 1.018—1.035), increased TG (OR=1.087, 95%CI 1.008—1.171) and increased FPG (OR=1.042, 95%CI 1.003—1.083) were factors influencing the incidence of CKD in the patients with T2DM (all P<0.05). In the non-combined CKD group, a total of 753 patients with T2DM were followed up, including 571 patients in the non-CKD subgroup and 182 patients in the CKD subgroup. The results of Cox proportional hazards model analysis showed that overweight was a risk factor for the incidence of CKD upon the correction of age, course of diabetes, systolic blood pressure, AST, TG and FPG (OR=1.95, 95%CI 1.05—3.61). The results of the restricted cubic spline fitting Cox regression model suggested a non-linear correlation between the BMI and the incidence of CKD in the patients with T2DM, which was reflected in the increased risk of CKD in the T2DM patients with a BMI between 28 and 31 kg/m² (all P<0.05).

Obesity in T2DM patients is closely correlated with CKD. The T2DM patients with obesity, especially those with a BMI between 28 and 31 kg/m², are prone to develop CKD.

To investigate the association of skeletal muscle index (SMI) and serum uric acid (UA) in patients with type 2 diabetes mellitus (T2DM) without hyperuricemia in a cross-sectional study.

Body composition was assessed by dual-energy X-ray-absorptiometry among 1 104 patients with T2DM hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from June 2013 to December 2015. Clinical data were collected for statistical analysis. Muscle mass reducing was defined as SMI less than 7.0 kg/m² in men or 5.4 kg/m² in women. The subjects were divided into the non-decreased muscle mass group and the decreased muscle mass group according to their muscle mass, and the subgroups of different genders were analyzed. The association of SMI and UA was investigated by simple regression and multiple linear regression.

In total 1 104 patients, 900 were included in the non-decreased muscle mass group, and 204 were included in the decreased muscle mass group. The level of UA was statistically different between patients without and with muscle mass reducing [(318.5±90.7) vs. (282.1±92.1) μmol/L, P<0.01]. Grouped by gender, the statistically significant difference remained [men: (336.3±88.6) vs. (299.0±93.7) μmol/L, P<0.01; women: (294.9±88.1) vs. (259.9±85.6) μmol/L, P<0.01]. UA was positively and statistically significantly associated with SMI in patients with T2DM in simple linear regression (β=0.294, P<0.01). Grouped by gender, the relationship remained in simple linear regression (men: β=0.209, P<0.01; women: β=0.208, P<0.01). After adjusting for age, body mass index, diabetic foot, creatinine, high-density lipoprotein-cholesterol, hemoglobin, neutrophil percentage, hypersensitive C-reactive protein, smoking history, metformin history, UA was positively and statistically significantly associated with SMI in patients with T2DM (β=0.052, P=0.022). UA was positively and statistically significantly associated with SMI in women (β=0.087, P=0.012), and it was negatively but not statistically significantly associated with SMI in men (β=-0.005, P=0.857).

UA is positively associated with SMI in patients with T2DM without hyperuricemia, suggesting that there may be a relationship between UA and the occurrence of muscle mass reducing in T2DM.

To investigate the predictive value of glycated hemoglobin A_1c (HbA_1c) combined with atherogenic index of plasma (AIP) for the risk of type 2 diabetes mellitus (T2DM) in middle-aged and older people.

In this retrospective cohort study deriving from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal Study (REACTION study), epidemiologic data of residents≥40 years old in Dalian communities from 2011 to 2014 were analyzed. A total of 4 628 non-diabetic participants in baseline were followed up in 2014, and the final analysis consisted of 4 033 participants. All participants accomplished a standard questionnaire, a physical examination and blood tests including lipid profile, HbA_1c, fasting plasma glucose (FPG), two-hour postprandial plasma glucose (2hPG), etc. Binary logistic regression models were adopted to analyze the relationship between HbA_1c, AIP and incident T2DM, and the combined predictor was built. Receiver operating characteristic (ROC) curves were built to estimate the predictive value of the combined predictor for T2DM.

In the 3-year follow-up, drinking rate, prevalence of hypertension, levels of 2hPG and AIP increased significantly compared with baseline, while levels of FPG and HbA_lc declined, there were statistical differences (all P<0.05). Two hundred and sixty-eitht (6.65%) participants were diagnosed with T2DM in follow-up. Binary logistic regression analysis showed that, after adjusting for age, gender, smoking history, family history of diabetes, body mass index, waist circumference, hypertension, total cholesterol, low-density lipoprotein-cholesterol, increased HbA_1c and AIP were both independent risk factors of T2DM (OR=6.490, 95%CI 4.406—9.560, P<0.01; OR=2.237, 95%CI 1.352—3.700, P<0.01). ROC curve analysis showed that area under curve (AUC) of the combined predictor was 0.712 (P<0.05), which was larger than AUCs of HbA_1c and AIP (Z=3.100, P<0.05; Z=5.190, P<0.05), and the optimal cut-off point was 0.068 8.

Increased HbA_1c and AIP in baseline are independent risk factors for the incidence of T2DM in 3 years. The combined predictor of HbA_1c and AIP shows good performance for the risk of T2DM.

We conducted a network meta-analysis to compare the efficacy of acetyl-levo-carnitine (ALC) with other commonly used oral medications in patients with diabetic peripheral neuropathy (DPN).

We searched the Chinese and English electronic databases up to February 2020 to identify randomized controlled trial (RCT) that evaluated one or more of the following oral monotherapy interventions in the treatment of DPN in adults: ALC, α-lipoic acid (ALA), epalrestat, methylcobalamin (MC), and pancreatic kininogenase. The primary outcome was nerve conduction velocity (NCV). The secondary outcomes were amplitude, neurological symptoms, neurological signs, and pain. A random-effect network meta-analysis within a Bayesian framework was performed. We estimated the ranking probabilities for each intervention by use of surface under the cumulative ranking curve (SUCRA).

Fifty-five RCT with 6 473 participants were included in this network meta-analysis. All trials were two-arm studies, involving four treatments (ALC, ALA, eparlrestat, MC). Three trials related to ALC (two studies compared ALC versus placebo, and the other one versus MC) were included. Compared with MC, ALC had more improvement in NCV of median sensory nerve (MD=4.0 m/s, 95%CI 0.1—7.9 m/s). According to the ranking results, ALC might be better in improving median sensation nerve (SUCRA, 91.6%), ulnar motor nerve (SUCRA, 69.3%) and ulnar sensation nerve (SUCRA, 77.8%) compared with other commonly used oral drugs. However, the results of relative-effect network meta-analysis showed no significant difference between ALC and other drugs in NCV improvement of other nerves.

The findings of this network meta-analysis showed ALC might have beneficial effects on improving the sensory nerve function and pain intensity, and have similar performance with other commonly used oral medications on other outcomes.

To explore the characteristics of gut microbiota in patients with diabetic microvascular complications (DMC).

From September 2019 to November 2020, patients with type 2 diabetes mellitus (T2DM) who were hospitalized in Department of Endocrinology, Affiliated Hospital of Chengde Medical College were enrolled. Age, gender, smoking history, systolic blood pressure, diastolic blood pressure, body mass index (BMI), glycated hemoglobin A_1c (HbA_1c), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), γ-glutamyltransferase (GGT), creatinine (CRE), use of insulin, and gut microbiota contents such as Bacteroides, Prevosiella and Bifidobacterium were collected. According to whether there were microvascular complications, patients were divided into diabetic microvascular complications (DMC) group and diabetes mellitus (DM) group. The t-test, Mann-Whitney U test, or χ²-test were used for comparison of each index and gut microbiota content between the two groups. Spearman correlation was used to analyze the correlation between gut microbiota and each index. Multivariate logistic regression analysis was used to analyze the risk factors for DMC disease.

A total of 79 patients were enrolled. Of these, 47 were in the DMC group and 32 in the DM group. Compared with the DM group, the content of Bacteroides significantly increased in the DMC group, the contents of Prevotella and Bifidobacterium significantly decreased in the DMC group (P<0.05). Multivariate logistic regression analysis showed that the incidence of DMC increased with the increase of Bacteroides (OR=1.053, 95%CI 1.016—1.091, P=0.005). After adjusting for age, sex, history of smoking, systolic pressure, diastolic pressure, BMI, HbA_1c, blood lipids, liver enzyme, CRE, and use of insulin confounding factors, Bacteroides was a risk factor for DMC (OR=1.085, 95%CI 1.023—1.151, P=0.007). The incidence of DMC decreased with the increase of Prevobella (OR=0.843,95%CI 0.737—0.965, P=0.013). After adjusting for confounding factors, Prevobella was a protective factor for DMC (OR=0.822, 95%CI 0.681—0.993, P=0.042).

Intestinal flora disorder was found in DMC patients. The prevalence of DMC increased and decreased with the increase of Bacteroides and Prevobella, respectively. Bacteroides was a risk factor for DMC, and Prevobella was a protective factor for DMC.

To investigate the awareness rate of hypoglycemic drugs in the diabetic patients at convenient outpatient services which dispense drugs, and to explore the factors affecting the awareness rate of hypoglycemic drugs.

Diabetic patients who visited the community health service centers of Affiliated Suzhou Hospital of Nanjing Medical University convenient outpatient service and its medical alliances from December 2018 to June 2020 were selected. Baseline data such as age, gender, education level, family history of diabetes, whether the patient lives alone, number of types of hypoglycemic drugs, total number of types of drugs taken, and glycated hemoglobin A_1c (HbA_1c) were recorded. The patients were divided into complete awareness group, partial awareness group and completely unknown group according to drug awareness. Full-time clinical pharmacists provided medications education for patients in each group. The participants were given with specialist medical education, and questionnaires were given again at 12 and 24 weeks to acquire the drug awareness, moreover the patients were rechecked HbA_1c level. The comparison of clinical parameters in two or three groups was performed using t-test, analysis of variance, Kruskal-Wallis rank sum test or χ² test, and multivariate logistics regression analysis was used to analyze the possible factors affecting the awareness of hypoglycemic drugs.

A total of 1 811 diabetic patients were enrolled, of whom 29.26% (530/1 811) were fully aware, 63.56%(1 151/1 811) were partially aware, and 7.18% (130/1 811) were completely unaware. After medications education 12 weeks, the proportion of patients in the fully aware group increased to 52.90% (958/1 811), the proportion of patients in the partially aware group decreased to 42.08%(762/1 811), and the proportion of patients in the fully unaware group decreased to 5.02% (91/1 811). After education intervention 24 weeks, the proportion of the patients with complete awareness was 46.05% (834/1 811), the proportion of the partially aware group was 50.80% (920/1 811), and the proportion of the completely unaware group was reduced to 3.15% (57/1 811). There were significant differences in HbA_1c among the three groups before and 12 weeks and 24 weeks after medications education (F values were 48.21, 16.22 and 8.03, respectively, all P<0.01). The multivariate logistic regression analysis showed that after adjusting for confounding factors, age (OR=0.98, 95%CI 0.97—0.99,P<0.001), gender (OR=0.70, 95%CI 0.57—0.86,P=0.001), education level (OR=1.94, 95%CI 1.57—2.39,P<0.001), living alone (OR=0.48, 95%CI 0.35—0.65,P<0.001), family history of diabetes (OR=1.28, 95%CI 1.04—1.57,P=0.020), hypoglycemic drugs taken (OR=0.56, 95%CI 0.49—0.65,P<0.001), and total number of medications taken (OR=0.19, 95%CI 0.16—0.22,P<0.001) were the main influencing factors of hypoglycemic drug acquaintance.

The complete awareness rate of diabetic patients for hypoglycemic drugs is low, and the awareness rate is sighificantly improved after drug education. There are many factors that affect the awareness rate of hypoglycemic drugs used by diabetic patients. Among them, eldly, low educational level, the number of hypoglycemic drugs taken and the total number of drugs taken are unfavorable factors, while non-solitary, male, high education and family history of diabetes are conducive to hypoglycemic drug acquaintance.

To study the effect of high insulin on the energy utilization of β-hydroxybutyric acid (BHB) in proximal renal tubular epithelial cells (HK2) under low glucose condition and its related mechanism.

HK2 cells were treated with different BHB concentrations (0, 0.5, 1.0, 2.0, 4.0, 8.0 mmol/L) for 24 h in glucose-free and low glucose environments, to study the effect of BHB on the proliferation of HK2 cells. The effect of 2.0 mmol/L BHB on ATP production of HK2 cells was studied at different time points (0, 6, 12, 24, 48 h). HK2 cells were divided into normal control (NC) group, low glucose (LG) group, BHB intervention (LG+BHB) group and high insulin (LG+BHB+HI) group. These various groups were used to study the expression of pro-apoptotic gene Bax mRNA in HK2 cells, anti-apoptotic gene Bcl2 mRNA, apoptosis number, albumin absorption, ATP production, mitochondrial number, peroxisome proliferator activated receptor co-activator-1α (PGC1α), mitochondrial mitofusin 1 (Mfn1), mitochondrial dynamin related protein 1 (DRP1) protein and mRNA levels. HK2 cells were treated with different insulin (5 ng/ml, 50 ng/ml) to study the effects of high insulin on the expression of sodium-coupled monocarboxylate transporter 1(SMCT1) protein and mRNA. The t test was used for comparison between two groups, one-way analysis of variance (ANOVA) was used for comparison between multiple groups.

In glucose-free environment, compared with 0 mmol/L BHB group, the proliferation of HK2 cells in 2.0 mmol/L BHB group increased (P<0.05). Compared with 0 mmol/L BHB group, there was no significant difference in cell proliferation in 2.0 mmol/L BHB group under low glucose environment (P>0.05). Compared with 2.0 mmol/L BHB intervention group for 0 h, ATP production of HK2 cells in 2.0 mmol/L BHB intervention group for 24 h was significantly increased (P<0.05). Compared with NC group, Bax mRNA, apoptosis number and DRP1 mRNA of HK2 cells in LG group were increased (all P<0.05), Bcl2 mRNA expression, albumin absorption, ATP production, PGC1α and Mfn1 protein expression were decreased (all P<0.05). Compared with LG group, Bax mRNA, apoptosis number and DRP1 mRNA of HK2 cells in LG+BHB group were decreased (all P<0.05), Bcl2 mRNA expression, albumin absorption, ATP production, PGC1α, Mfn1 mRNA and protein expression were increased (all P<0.05). Compared with LG+BHB group, Bax mRNA, apoptosis number and DRP1 mRNA of HK2 cells in LG+BHB+HI group were increased (all P<0.05), Bcl2 mRNA expression, albumin absorption, ATP production, PGC1α, Mfn1 mRNA and protein were decreased (all P<0.05). Compared with the 5 ng/ml insulin intervention group, the expression of SMCT1 protein and mRNA in 50 ng/ml insulin group was decreased (P<0.05).

Hyperinsulinism could inhibit the utilization of ketone body by proximal renal tubular epithelial cells, and the mechanism might be related to the inhibition of the expression of ketone body resorption protein SMCT1.

This paper reports the clinical and genetic characteristics of two early onset diabetic families with abnormal liver function caused by mutation of hepatocyte nuclear factor 1 β (HNF1 β) gene, and reviews the literature on the characteristics of abnormal liver function in adult-onset diabetes mellitus (MODY) in HNF1 β-adolescents. Proband 1, a female, noted elevated blood glucose during pregnancy at 30 years of age. Proband 2 was male, and hyperglycemia was found during physical examination at the age of 18. All of them were highlighted by elevated liver enzymes, normal bilirubin, and no renal cyst or abnormal renal function. Whole exon capture and DNA copy number variation detection were applied to 2 probands successively, and the family members were verified according to the mutation type. The results showed that the heterozygous mutation of exon 4 of HNF1 β gene in proband 1 and his father was c.1006C>G (p.H336D), and the 17q12 microdeletion in proband 2 and his mother was 1.49 Mb. A total of 26 cases of HNF1 β mutation combined with abnormal liver function were searched through PubMed, CNKI and Wanfang databases. Literature review found that the disease spectrum caused by HNF1 β mutation/deletion was highly heterogeneous. The abnormal liver function caused by HNF1 β gene mutation was prominently manifested by elevated liver enzymes, bilirubin and liver synthesis were mostly normal, and the imaging findings were hidden. There was one case of liver transplantation, and no liver-related death was reported. It is suggested that early onset diabetic patients with unexplained abnormal liver function should be alert to the possibility of HNF1 β mutation even if it is not accompanied by renal disease. Such patients should be alert to the aggravation of abnormal liver function under stress and try to avoid the use of drugs metabolized by the liver.

Patients who need total or partial pancreatectomy due to recurrent acute or chronic pancreatitis, pancreatic trauma, benign pancreatic diseases, etc. often develop diabetes or abnormal glucose tolerance after surgery. Autologous islet transplantation can preserve the function of islet β cells, which is an effective method to solve the above problems. In recent years, with the progress of islet separation technology, transplantation protocol and perioperative management, the efficacy of autologous islet transplantation has also improved, and it has become a necessary treatment after pancreatectomy. This article expounds the contents of autologous islet transplantation in islet separation and transplantation techniques and indications, emphasizes on the curative effect of autologous islet transplantation and the potential improvement schemes to improve its curative effect, and briefly introduces the application status of autologous islet transplantation in China.

The prevalence of obesity has continued to grow globally at the rate of a pandemic for nearly five decades. Studies have shown that persistent organic pollutants are closely related to the occurrence and development of obesity. This paper reviews the effects of persistent organic pollutants on obesity in order to promote the new cognition of obesity and provide new targets for obesity prevention and treatment.

Gene therapy has gradually become an important means for treating genetic diseases, autoimmune diseases and tumors. In recent years, efforts have been made to develop efficient gene delivery vectors to overcome various physiological and systemic obstacles. Chitosan has natural bacteriostatic, hemostatic and wound healing ability, as well as good biocompatibility and biodegradability, and has been used as a candidate material for drug delivery systems and the manufacture of gene delivery systems related to wound healing. It has also been used as various gene vectors to propose new directions for the treatment of various refractory diseases, such as as as small interfering RNA vectors for combination treatment of cancer, and as microRNA vectors to promote skin wound healing in diabetic rats. The research progress of chitosan carrier gene therapy in clinical application was reviewed.

With the rapid development of Internet technology and Internet devices, the "Internet plus" management method for diabetes community management in China has been continuously applied to actual management. The author summarizes the advantages of various management schemes in the existing "Internet plus" diabetes management methods in domestic communities, in order to provide reference for the development and promotion of "Internet plus" diabetes management methods.

As the main presentation form of clinical research results, clinical research papers have great scientific value. The use of clinical research report specifications can improve the integrity, scientificity, and normative nature of papers, and is the key to producing high-quality research evidence. Combined with the classic cases of diabetes, the author will introduce the commonly used report norms and key points of paper writing in clinical research, in order to provide help and reference for writing clinical research papers on diabetes.