Volume 16 · Issue 05 · 2024

Exocrine pancreatic diabetes mellitus (DEP) is a special type of diabetes mellitus secondary to exocrine pancreatic diseases. It is often accompanied by different degrees of exocrine pancreatic insufficiency, and the main clinical feature is "fragile diabetes mellitus", which is prone to alternating hyperglycemia and hypoglycemia. At present, clinical management is difficult, and there is still a lack of unified treatment guidelines. This article reviews the research progress of DEP hypoglycemic therapy, including lifestyle management, drug therapy, pancreatic islet transplantation, pancreatic β cell regeneration, etc., in order to provide reference for clinical treatment.

Diabetic neuropathy is the most common chronic complication of diabetes and one of the important risk factors for diabetic foot ulcer. Early diagnosis and early prevention and treatment of diabetic neuropathy are particularly important for grass-roots physicians. Therefore, the Neurological Complications Group of the Diabetes Branch of the Chinese Medical Association and the Grassroots Diabetes Prevention and Treatment Management Office of the National Basic Public Health Service Project jointly formulated the National Grassroots Diabetic Neuropathy Diagnosis and Treatment Guidelines (2024 Edition), which focuses on the overview, classification and clinical manifestations, screening and diagnosis methods, prevention and treatment, patient follow-up and referral of diabetic neuropathy based on the Expert Consensus on Diagnosis and Treatment of Diabetic Neuropathy (2021 Edition) written by us, aiming to guide and help grass-roots doctors to standardize and comprehensively manage diabetic neuropathy, prevent and treat diabetic neuropathy early, and delay the progression of the disease.

To explore the application value of common indicators in the risk assessment model for diabetic foot (DF) complicated with necrotizing fasciitis (NF).

This was a cross-sectional study. A retrospective analysis was performed on 815 patients with DF, who were admitted to the First Affiliated Hospital of Chongqing Medical University from October 2018 to April 2022. Patients were divided into DF group (703 cases) and DF with NF group (DNF, 112 cases) according to whether NF was combined. Clinical data (age, body mass index, course of disease, diabetic complications, necrosis of the foot skin, body temperature, blood routine, creatinine, fibrinogen, albumin, glycated hemoglobin A_1c, hypersensitive C-reactive protein, etc.) of the two groups were analyzed, and indicators of statistical and clinical significance were converted into categorical variables. Multivariate logistic regression was used to develop a new risk assessment model for DNF (NRADNF) and to construct a nomogram. Model discriminability was assessed by area under receiver operating characteristic (ROC) curve (AUC), accuracy was evaluated by Hosmer-Lemeshow goodness-fit test, effectiveness was evaluated by decision curve analysis, and stability was evaluated by bootstrap repeated sampling.

The constructed NRANDF model includes 6 indicators: age ≥60 years old (OR=0.378, P<0.001), body temperature ≥38 ℃ (OR=3.119, P=0.001), foot skin necrosis (OR=1.974, P=0.012), neutrophil-lymphocyte ratio ≥8.5 (OR=2.500, P=0.002), hs-CRP>20 mg/L (OR=2.455, P=0.006), hemoglobin ≤100 g/L (OR=1.833, P=0.026). The AUC (95%CI) was 0.815 (0.773, 0.857), and Hosmer-Lemeshow goodness-fit test showed that the model performed well overall (χ²=8.736, P=0.272). The result of decision curve analysis suggested that the model had a net clinical benefit, and internal verification using bootstrap showed that ROC curves were essentially identical before and after repeated sampling.

The NRADNF model has good predictive efficiency, clinical utility and the included indicators are easy to obtain, it can be used in the clinic for preliminary screening of DNF.

To investigate the effects of triglyceride-glucose (TyG) index and its variability on diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).

This study was a prospective cohort study. A total of 1 986 patients with T2DM who had regular visits at 6 centers of the Lee′s United Clinics in Taiwan, China from January 1, 2002 to December 31, 2018 and no DKD at baseline were selected as the study subjects, and prospective follow-up was performed. Age, sex, serum creatinine, triglycerides (TG), fasting plasma glucose (FPG), urine microalbumin and urine creatinine were collected, and the TyG index, estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were calculated, and the mean value of TyG index and the variability of TyG index were calculated according to the TyG index once a year at baseline and follow-up years. DKD was diagnosed according to the diagnostic criteria of the Clinical guideline for the prevention and treatment of diabetic kidney disease in China (2021 Edition). According to whether the patients had DKD at the end of the follow-up, they were divided into DKD group and non-diabetic kidney disease (NDKD) group, and according to the mean value of TyG index, the patients were divided into T₁ group (mean TyG index <8.67), T₂ group (8.67≤ mean TyG index <9.09) and T₃ group (mean TyG index ≥9.09), and according to the variability of TyG index, the patients were divided into T′₁ group (TyG index variability <0.29) and T′₂ group (0.29≤ TyG index variability <0.43) and T′₃ group (TyG index variability ≥0.43). The t-test of two independent samples was used to compare the differences in the relevant indexes between the DKD group and the NDKD group, the Cox proportional hazards regression model was used to study the relationship between TyG index and DKD, and between TyG index variability and DKD, and the generalized linear mixed model was used to explore the effects of factors including TyG index on DKD.

The follow-up period was (7.27±3.48) years. At the end of follow-up, of the 1 986 patients with T2DM, 676 were in the DKD group and 1 310 were in the NDKD group. Compared with the NDKD group, the UACR, mean TyG index and TyG index variability in patients with T2DM in the DKD group were higher, while the eGFR was lower (all P<0.05). The results of Cox proportional hazards regression model showed that after adjusting for confounding variables, the risk of DKD in patients with T2DM in the T₃ group was the highest compared with that in the T₁ group, which was 68.9% higher than that in the T₁ group (HR=1.689,95%CI 1.376-2.073, P<0.001); compared with the T′₁ group, the risk of DKD was highest in the T′₃ group, which was 74.2% higher than that in the T′₁ group(HR=1.742,95%CI 1.421-2.135, P<0.001). The results of the generalized linear mixed model show that the TyG index of each year during the follow-up process has a significant effect on the occurrence of DKD (β=0.244, 95%CI 0.111-0.376, P<0.001).

Elevated TyG index and its variability both increase the risk of DKD in patients with T2DM, and the TyG index and its variability are independent risk factors for the DKD.

To observe the expression of β-amyloid (Aβ) in pancreas and brain of type 2 diabetes mellitus (T2DM) mice during the progression of T2DM.

A total of 36 control mice and 36 T2DM mice were randomly divided into 6 groups (13 weeks, 16 weeks, 19 weeks, 22 weeks, 25 weeks, 28 weeks). One group of mice was sacrificed at 3-week intervals starting at 13 weeks of age, and the total observation period was from 13 weeks to 28 weeks. Immunohistochemical analysis and enzyme-linked immunosorbent assay (ELISA) were used to observe the distribution and expression of Aβ in pancreas and brain tissue of T2DM mice. Western blotting and ELISA were used to detect the expression of amyloid precursor protein (APP) and β-site amyloid precursor protein cleavage-1 (BACE-1). The t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups. Spearman correlation analysis was used to analyze the correlation between pancreatic Aβ content and homeostasis model assessment of insulin resistance index (HOMA-IR) and insulin/proinsulin ratio.

With the progression of T2DM, the deposition of Aβ in pancreatic islets and brain hippocampus gradually worsened compared with control mice (P<0.05). The expression of Aβ in pancreas and hippocampus of T2DM mice were gradually increased with the progress of T2DM (P<0.05). The expression levels of APP and BACE-1 in the two tissues initially increased and then decreased with disease progression (P<0.05). In addition, with the progression of the disease, the level of pancreatic islet function in the T2DM group gradually decreased, which was significantly correlated with the gradual increase of pancreatic Aβ deposition. Spearman correlation analysis showed that the correlation coefficients of HOMA-IR and insulin/proinsulin with pancreatic Aβ deposition were 0.837 0 and 0.728 1, respectively (P<0.001).

The expression of Aβ in the pancreas and brain of T2DM mice changes in synchrony with disease progression.

To investigate the mechanism by which methyltransferase-like 3 (METTL3) is involved in diabetes-induced endothelial cell apoptosis by promoting the N6-methyladenine (m6A) modification of forkhead box O (FOXO) 3 and its expression.

A model of advanced glycosylation end products (AGE)-induced damage in human aortic endothelial cells (HAEC) was constructed. HAEC were divided into 6 groups: cell control group, cell AGE group, cell control+negative control small interfering RNA (siRNA) group, cell AGE+negative control siRNA group, cell AGE+FOXO3 siRNA group, and cell AGE+METTL3 siRNA group, and 3 parallel groups were set in each group. The m6A modification profiles were detected and analyzed by methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and bioinformatics techniques. The m6A modification level of FOXO3 mRNA was detected by RNA-binding protein immunoprecipitation (RIP). Apoptosis was detected by flow cytometry. Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the expression level of FOXO3 mRNA, and Western blotting was used to detect the expression level of FOXO3, METTL3. Six 6-week-old ApoE knockout male mice were divided into simple atherosclerosis group and diabetic atherosclerosis group by randomized numerical table method. The protein expression of mouse FOXO3, METTL3 was detected by Western blotting, and the expression of mouse FOXO3 and METTL3 in endothelial cells was detected by immunofluorescence co-localization. Two independent samples t-test was used for intergroup comparison.

Total m6A modification and m6A modification of FOXO3 were significantly higher in the cellular AGE group compared with the cellular control group (P<0.001), and the protein expression of FOXO3 and METTL3 was significantly higher (P<0.05). Protein expression of FOXO3 and METTL3 was significantly elevated in endothelial cells in the aortic plaque region of diabetic atherosclerotic mice compared with that of mice with simple atherosclerosis (P<0.05). Apoptosis was significantly reduced in the cell AGE+FOXO3 siRNA group compared to the cell AGE+negative control siRNA group (P<0.01). The m6A modification of FOXO3 (P<0.001) and FOXO3 protein expression were significantly decreased (P<0.05) and apoptosis was significantly reduced (P<0.001) in the cellular AGE+METTL3 siRNA group compared with the cellular AGE+negative control siRNA group.

AGE induces significant changes in m6A modification in HAEC, METTL3 is involved in diabetes-induced apoptosis in vascular endothelial cells by promoting m6A modification of FOXO3 mRNA and regulating its expression.

To investigate the clinical manifestations, biochemical characteristics, therapeutic measures and perinatal outcomes of pregnant patients with human insulin and its analogues allergy.

Four patients with human insulin/insulin analogue allergy during pregnancy who attended the Department of Endocrinology of Peking Union Medical College Hospital from January 2000 to December 2022, and 14 such patients reported publicly from the National Library of Medicine database (PubMed), the Dutch Medical Abstracts database (Embase), the Chinese Journal Full-Text Database (CNKI), and Wanfang database from the establishment of the database to June 2023 were selected as the study subjects, with a total of 18 patients. Patient race, age, type of allergic insulin, allergic symptoms, insulin autoantibody (IAA) and total immunoglobulin E (TIgE) /specific immunoglobulin E (sIgE) titer results, treatment measures for allergy, and perinatal outcome [including premature birth, diabetic ketoacidosis (DKA), fulminant type 1 diabetes mellitus (FT1DM)] were collected. Simple summary statistics were used to describe the results of the clinical data of patients.

Of the 18 patients, 4 were of unknown ethnicity, and 13 of the 14 with ethnic records were of Asian descent, aged (32 ± 4) years; Ten patients were allergic to multiple human insulin/insulin analogs, among which insulin detemir had a higher incidence of allergy, and 5 patients were allergic only to it; Thirteen patients showed only local reactions to the injection, while 5 patients showed systemic symptoms, including urticaria at the non-injection site, chest tightness and choking, and decreased blood pressure. Autoantibodies were measured in 7 patients, of which insulin autoantibodies (IAA) were detectable in 5 cases and TIgE/sIgE titers were increased in 5 cases. In terms of treatment, 7 patients only needed to change the type of insulin, 2 patients were successfully switched to metformin treatment, and 6 patients were successfully desensitized (1 case was desensitized by multiple subcutaneous insulin injections, and the remaining 5 cases were desensitized by subcutaneous insulin pump). Of the 9 patients with recorded perinatal outcomes, the mean gestational age at delivery was only (36.7 ± 3.5) weeks; Three patients developed diabetic ketoacidosis (DKA) with concomitant preterm delivery [1 with euglycemic DKA and 2 with progression to fulminant type 1 diabetes mellitus (FT1DM)].

Human insulin/insulin analogue allergy during pregnancy is rare but tends to be ethnically clustered, and allergic symptoms can affect the whole body. Treatment measures can consider switching insulin type or switching to metformin first, and desensitization treatment should be performed if necessary. If improperly handled, the risk of adverse perinatal outcome is extremely high, which needs to be paid attention to.

This paper reports the course of phosphorus supplementation therapy with severe hypophosphatemia during ketoacidosis in a type 1 diabetic patient with renal insufficiency. The patient was a 30-year-old woman who was admitted to hospital because she "found blood sugar to rise for more than 20 years and anorexia for 1 week". After admission, relevant examinations were completed, and the results showed that blood glucose was 38.9 mmol/L, blood pH was 7.04, blood bicarbonate was 2.3 mmol/L, urine ketone body 3+, glycosylated hemoglobin (HbA_1c) 15.8%, fasting insulin<0.20 mU/L, fasting C-peptide 0.33 μ g/L, serum creatinine 228.0 μ mol/L, estimated glomerular filtration rate (eGFR) 24.1 ml·min^-1· (1.73 m²）^-1Blood potassium was 5.64 mmol/L, blood sodium was 130.0 mmol/L, blood chlorine was 82.4 mmol/L, blood phosphorus was 3.15 mmol/L, and blood magnesium was 1.38 mmol/L. Clearly diagnosed as type 1 diabetic ketoacidosis, diabetic nephropathy, renal insufficiency, electrolyte disorder, and given the treatment of fluid rehydration, insulin hypoglycemic, acid suppression and symptomatic support. During the treatment, the blood phosphorus decreased rapidly, and the blood phosphorus concentration of the patient on the third day of admission<0.1 mmol/L, urine phosphorus<1.1 mmol/L. After 17 days of phosphorus supplementation and concurrent hypoglycemic and fluid rehydration, the patient's condition gradually improved and was discharged. On the 20th day, the patient's blood phosphorus had reached 0.78 mmol/L. For diabetic patients with renal insufficiency, the dose of intravenous sodium phosphate should be appropriately reduced and the infusion speed should be strictly controlled. At the same time, the electrolyte level including blood phosphorus and renal function should be closely monitored, and the blood phosphorus level should be controlled within an appropriate range. That is, phosphorus supplementation should be stopped to avoid the occurrence of hyperphosphatemia.

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes, and peroneal muscular atrophy (CMT) is one of the most common hereditary peripheral neuropathies. However, there are few reports of diabetes combined with CMT. A case of type 2 diabetes mellitus complicated with peroneal muscular atrophy misdiagnosed as DPN was reported in order to improve clinicians' understanding of this disease. The proband was a 57-year-old male who was admitted to hospital because of "blood sugar increase for more than 8 months and numbness and pain in his limbs for 3 months". Physical examination showed claudication gait, foot varus when walking, high arch, and muscle atrophy in both lower limbs. Genetic testing revealed the presence of peripheral nerve myelin protein 22 (PMP22) gene heterozygous repeat mutation, confirmed as type 2 diabetes with CMT1A type. Family verification revealed that his father was also presentPMP22The gene was repeatedly amplified, but there was no diabetes, and the clinical manifestation of its parent CMT1A was atypical. Both type 2 diabetes and CMT1A can cause peripheral neuropathy, and the clinical phenotype of some CMT patients is similar to that of DPN. Clinicians need to make careful differential diagnosis of DPN.

To report a case of adult type 3 diabetes mellitus (MODY3) with adolescent onset and the course of drug therapy in his family. The patient was a 15-year-old male who was admitted to the hospital due to "polydipsia and polyuria and weight loss for 3 months". According to clinical data and genetic testing, a family of adult type 3 diabetes mellitus (MODY3) with adolescent onset was diagnosed, and the patient and his family were treated with drugs. Through continuous glucose monitoring (CGM), it was found that the patient's blood glucose improved significantly after changing insulin to repaglinide, but it needed to be combined with drugs such as voglibose, sitagliptin, and insulin degluco, while his confirmed family members were treated with prandial insulin (insulin aspart 30), and the blood glucose control reached the standard. During the 4-year follow-up, the patient had good glycemic control, no significant progress in monitored islet function, and no diabetic complications. In this paper, the diagnosis and treatment process of this patient and family members are reported and the related therapeutic drugs of MODY3 are discussed in combination with literature review, in order to provide reference for making more reasonable and individualized treatment plans for similar patients.

Diabetes-related cognitive impairment is a cognitive decline that occurs during the course of diabetes and seriously affects the quality of life of diabetic patients. Mitochondrial dysfunction is one of the important pathogenesis mechanisms of diabetes-related cognitive impairment. Mitochondrial autophagy is an important component of mitochondrial quality control system, which plays a role in removing damaged mitochondria in cells, maintaining mitochondrial quality and protecting mitochondrial function, and is very important for maintaining the healthy form and normal function of mitochondria. This paper reviews the role and mechanism of mitophagy in diabetes-related cognitive impairment in order to provide theoretical basis for the prevention and treatment of diabetes-related cognitive impairment.

Due to the changes in diet and exercise patterns, the incidence of obesity in China is increasing year by year. Depression is a mental disorder related to environmental, genetic and psychological factors. There is a two-way link between obesity and depression. The presence of one disease often leads to the occurrence of another disease, but its mechanism is not clear. The changes of intestinal flora in obese patients have been confirmed by many parties. In recent years, more and more studies have shown that the changes of intestinal flora caused by obesity can participate in the occurrence and development of depression by promoting neuroinflammation, regulating intestinal metabolism, and changing the structure of various functional regions of the brain. This paper reviews the research progress and mechanism of obesity involved in the occurrence of depression by causing changes in intestinal flora.

Non-coding RNA (ncRNA), as a common form of diabetic epigenetics, plays an important role in the development of diabetes. N6-methyladenosine (m6A) is a methylation modification of RNA formed by the catalysis of the 6th nitrogen atom of adenine (A) by methyltransferase. m6A is the most abundant known ncRNA modification method, which can regulate most processes of target RNA metabolism, including RNA maturation, splicing, translation and RNA stability, thereby regulating downstream signaling pathways and changing cell physiological functions. Existing studies have shown that ncRNA m6A modification plays an important role in many diseases such as diabetes. This paper summarizes the role of ncRNA m6A modification in diabetes mellitus and its complications, and looks forward to the future research direction of ncRNA m6A modification in the development of diabetes mellitus, so as to provide reference for scientific research.

Tilpotide is a new single-molecule multi-target drug designed and developed based on the sequence of natural glucose-dependent insulin-promoting peptide (GIP), which can achieve the joint long-lasting agonization of GIP receptor and glucagon-like peptide-1 receptor (GLP-1R) "imbalance" and "bias" produce an effect that is not equivalent to the simple superposition of the activation of the two receptors, helping patients with type 2 diabetes (T2DM) to achieve potent hypoglycemia, superior weight loss and multi-faceted metabolic benefits. Tilpotide has been associated with the repair of various pathophysiological mechanisms of T2DM, including improvement of insulin secretion function and insulin sensitivity of pancreatic islet beta cells; Reduce the level of glucagon secreted by islet alpha cells; Promote adipose tissue energy storage and reduce circulating lipids and lipid ectopic deposition at high insulin levels, promote lipolytic energy supply and adipose tissue reduction at energy restriction; Affect the central nervous system to regulate appetite and food preference; Delays gastric emptying. Starting with the molecular structure and pharmacological characteristics of tilpotide, as well as the known mechanism of action on target organs/tissues, this paper discusses its potential impact on the management of T2DM.

With the rapid development of digital technologies such as big data, Internet, Internet of Things, and artificial intelligence, digital health has ushered in an unprecedented stage of development, constantly innovating diabetes management strategies, but it also faces some challenges while showing a good development trend. This article mainly summarizes the application of digital health in diabetes management, and provides reference for the development and promotion of digital health in the field of diabetes management.

Epidemiological data show that the prevalence of type 2 diabetes in China continues to increase and shows a younger trend. The increase of obesity rate is the main influencing factor of type 2 diabetes, but the mechanism is unknown. Exosomes have a variety of molecular biological functions, are the carriers of material transport and information transmission between cells, and can participate in the regulation of various physiological and pathological processes of the body. In recent years, it has been found that lipid-derived exosomal microRNA plays a key role in the progression of obesity to type 2 diabetes. This article reviews its research progress.

Hydrogen is an inert gas with small volume and small molecular weight. In recent years, more and more trials have proved that it has protective effects in a variety of diseases. The possible mechanisms are antioxidant stress, anti-inflammatory and anti-apoptotic. This article mainly summarizes the protective effect of hydrogen in diabetic models and patients. It is hoped that higher quality clinical trials will further verify its effect in the future, and it is also hoped that hydrogen can further enter the clinic and benefit patients.