Volume 13 · Issue 11 · 2021

The 2021 Nobel Prize in Physiology or Medicine was awarded to American scientist David Julius, the discoverer of the transient receptor potential vanillic acid subfamily member 1 (TRPV1) of the capsaicin receptor. The discovery of TRPV1 reveals the mechanism of temperature perception and enriches people's understanding of temperature perception and adaptation to the surrounding environment. TRPV1 is also abundantly expressed in metabolic organs such as fat, liver and muscle, but its biological significance is not clear. Therefore, domestic and foreign scholars have actively explored the role of TRPV1 in regulating glucose and lipid metabolism and the therapeutic benefits of spicy meals on metabolic diseases, opening up a new field for TRPV1 to prevent and treat metabolic diseases.

The number of patients with type 2 diabetes in China ranks first in the world, which is closely related to gonadal diseases. The number of patients with type 2 diabetes complicated with gonadal diseases is also increasing year by year, especially in men, which is mainly manifested as male hypogonadism. The two affect each other, aggravate the occurrence of metabolic disorders and reduce the quality of life. This article expounds the relationship between type 2 diabetes and male gonadal diseases from three aspects: etiology, disease characteristics and treatment, and provides ideas for clinical diagnosis and treatment.

Diabetic peripheral neuropathy and (DPN) neuralgia are common chronic complications of diabetes, with increasing incidence and difficult treatment. The author expounds the multidisciplinary comprehensive diagnosis and treatment of DPN from the aspects of the multidisciplinary comprehensive treatment cooperative group in the diagnosis, differential diagnosis, treatment and postoperative follow-up, and introduces the centralized construction of diabetic neuropathy in our hospital.

Diabetes-related ophthalmopathy seriously affects the quality of life of diabetic patients in China, and its standardized management requires close cooperation between endocrinologists and ophthalmologists. It is of great significance to strengthen its comprehensive understanding and comprehensive management. Diabetes Branch of Chinese Medical Association organized experts from diabetic retinopathy group and invited domestic ophthalmologists to review relevant materials and research progress at home and abroad. Referring to relevant guidelines and expert consensus at home and abroad, combined with the specific situation of China, it deepened multidisciplinary diagnosis and treatment cooperation, and supplemented and updated the 2018 edition of "Expert Consensus on Prevention and Treatment of Diabetic Retinopathy". This consensus consists of four chapters, which systematically introduce diabetic retinopathy, diabetic cataract, diabetic keratopathy and diabetic optic neuropathy. The release of the consensus will surely help to further improve the standardized comprehensive management of patients with diabetic retinopathy and other ocular complications, and provide guidance and reference for clinicians.

To explore the correlation between pregnancy hyperglycemia and pregnancy outcome in pregnant women with type 1 diabetes mellitus (T1DM) and the possible influencing factors.

A total of 37 patients with T1DM combined with pregnancy hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2020 were selected as T1DM group. According to the 1∶2 matching principle of the same age, 74 healthy pregnant women in the same period were selected as the control group. Baseline data [methods of pregnancy termination, pregnancy complications, neonatal outcomes, history of diabetic ketoacidosis (DKA) during pregnancy etc.] were recorded and biochemical indicators such as glycated hemoglobin A_1c (HbA_1c) were detected. Conditional logistic regression model was used to analyze the difference in pregnancy outcome between the two groups, and binary logistic regression model was used to further investigate the effects of HbA_1c level during pregnancy and DKA on maternal and infant outcomes of pregnant women with T1DM.

Compared with the control group, there were higher proportion of adverse maternal outcomes (induced labor, premature delivery, hypertensive disorder in pregnancy, preeclampsia) and adverse neonatal outcomes (neonatal admission to intensive care unit, Apgar score<10 points in 5 min, perinatal death) in T1DM group, and the differences were statistically significant (P<0.05). The logistic regression analysis showed that compared with the control group, after adjusting for age and parity, the risk of induced labor [odd ration (OR)=5.561, 95% confidence interval (CI) 1.455-21.258] increased significantly in pregnant women with T1DM, furthermore, there was also a higher risk of premature birth (OR=10.219, 95%CI 2.245-46.515) and hypertensive diseases during pregnancy (OR=11.195, 95%CI 1.194-104.962), but there was no statistically significant difference in the outcome of preeclampsia between the two groups (P>0.05). The risk of neonatal respiratory distress (OR=10.082, 95%CI 1.173-86.628), perinatal death (OR=14.773, 95%CI 1.822-119.781) and neonatal admission to intensive care unit (OR=6.907, 95%CI 2.284-20.892) increased in neonates of pregnant women with T1DM. Binary logistic regression analysis showed that after adjusting for age, HbA_1c level in T1DM group was associated with an increased risk of neonatal pathological jaundice (OR=1.630, 95%CI 1.013-2.741). There were four parturients with DKA during pregnancy in the T1DM group. After adjusting for age, parity and gestational weeks, the women with DKA during pregnancy were more likely to have newborns with perinatal death (OR=27.620, 95%CI 1.007-757.507).

Pregnant women with T1DM are more likely to have adverse maternal and infant outcomes than healthy pregnant women, and poor glycemic control may be associated with perinatal death and pathological jaundice.

To evaluate the relationship of serum fetuin A levels with sex hormones and bone metabolism markers in elderly patients with type 2 diabetes mellitus (T2DM).

A cross-sectional study was conducted in the elderly T2DM patients admitted to the Department of Endocrinology, Fujian Provincial Hospital from January to October 2014. The level of total cholesterol, high-density lipoprotein-cholesterol (HDL-C), alkaline phosphatase, serum fetuin A, bone mineral density (BMD) of lumbar spine and femoral neck and serum bone metabolism markers [β-collagen specific sequence (β-CTX), osteocalcin and N-terminal lengthening peptide of type Ⅰ collagen (PINP)], sex hormones (estradiol, testosterone and free testosterone index) were measured. The t test, rank sum test and χ² test were used for comparison between groups. Pearson correlation analysis and multiple linear regression analysis were used to analyze the correlation between Lg fetuin A and clinical variables.

A total of 103 elderly T2DM patients were enrolled, including 48 females and 55 males. There was no statistically significant difference in serum fetuin A level between genders (P>0.05). The BMD value of women was lower than that of men [lumbar BMD was (0.739±0.117) and (0.930±0.161) g/cm², respectively, femoral neck BMD was (0.650±0.095) and (0.824±0.116) g/cm², respectively, P<0.01], β-CTX, osteocalcin and PINP were higher in women than those in men (allP<0.01). Serum fetuin A was negatively correlated with β-CTX in men (r=-0.307, P=0.024), but not with BMD and T value. Serum fetuin A was negatively correlated with bone mineral density of femoral neck (r=-0.336, P=0.020), but had no correlation with lumbar BMD and T value of femoral neck. There was no correlation between serum fetuin A and estradiol, testosterone and free testosterone index in elderly T2DM patients of different genders (P>0.05).Multiple linear regression analysis showed that HDL-C (β=0.349,P<0.01), alkaline phosphatase (β=-0.295,P=0.024) and β-CTX (β=-0.039, P=0.026) were independent related factor of serum fetuin A level in males. Total cholesterol (β=0.280, P=0.026) and femoral neck BMD (β=-0.083, P=0.05) were independent correlated factors for serum fetuin A levels in women.

There is no correlation between serum fetuin A level and sex hormones in elderly T2DM patients. Fetuin A is a protective factor for bone mineral density in male elderly patients with T2DM.

To explore the prevalence and clinical characteristics of non-alcoholic fatty liver disease (NAFLD), compensated advanced chronic liver disease and portal hypertension in the community patients with type 2 diabetes mellitus (T2DM).

This study was a cross-sectional study. From the registered patients with T2DM in 11 townships, towns, and sub-district offices in Huozhou, the registrants were notified by telephone to participate in this community screening project. All subjects underwent on-site physical examination (including height, weight, neck circumference, waist circumference, abdominal circumference, and blood pressure). Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were measured by transient elastography. According to the CAP value, NAFLD was categorized as: mild group (238 dB/m≤ CAP≤258 dB/m), moderate group (259 dB/m≤CAP≤291 dB/m), and severe group (CAP≥292 dB/m). According to LSM≥10 kPa and LSM≥15 kPa, it was suggested that the patients developed into the stages of compensated advanced chronic liver disease and portal hypertension, respectively. According to the body mass index (BMI), patients were divided into normal weight and underweight (BMI<24 kg/m²) group, overweight (24 kg/m²≤BMI<28 kg/m²) and obese (BMI≥28 kg/m²) group. Analysis of variance or χ² test was used for comparison between groups.

A total of 1 191 cases of T2DM in Huozhou were screened in this study. The weighted prevalence of NAFLD, compensated advanced chronic liver disease and portal hypertension were 61.5%, 6.5%, and 1.7%, respectively. Among the T2DM patients in the community, the non-NAFLD group, mild NAFLD group, moderate NAFLD group and severe NAFLD group were 460, 182, 271 and 278 cases, respectively. The comparison with the non-NAFLD group showed that BMI, neck circumference, waist circumference, hip circumference and the prevalence of hypertension increased (P<0.05). There were 731 patients with T2DM and NAFLD, including 179 patients (24.5%) in the normal weight and underweight group, 382 patients (52.3%) in the overweight group, and 170 patients (23.2%) in the obesity group, the weighted proportion of normal weight and underweight, overweight, and obese groups were 23.7%, 51.2%, and 25.1%, respectively.

The prevalence of NAFLD, compensated advanced chronic liver disease and portal hypertension is high in community patients with T2DM.

To investigate the association between time in range (TIR) and diabetic retinopathy (DR) among patients with type 2 diabetes mellitus (T2DM).

This study was designed as a prospective cohort study. A total of 1 057 patients with T2DM were prospectively recruited from April 2005 to May 2019 from Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People′s Hospital. TIR was measured with continuous glucose monitoring (CGM) at baseline. Cox proportion hazard regression analysis was used to determine the association between TIR and the risk of DR.

During a median follow-up of 7.7 years, 266 patients developed DR. The incidence rates of DR were 26.0 (63/2 419.7), 28.0 (57/2 032.9), 40.5 (79/1 950.8) and 42.0 (67/1 594.1) per 1 000 person-years in TIR>85%, 71%-85%, 51%-70%, and ≤50%, respectively (log-rankP=0.013). Cox proportion hazard regression analysis showed that after adjusting for sex, age, diabetes duration, smoking, body mass index, blood pressure, blood lipids, and estimated glomerular filtration rate, hazard ratios (HR) for DR across different levels of TIR (>85%, 71%-85%, 51%-70%, and ≤50%) were 1.00, 1.02 [95% confidence interval (CI) 0.71-1.46], 1.42 (95%CI 1.01-1.99) and 1.46 (95%CI 1.02-2.07), which had statistically significant differences (P for trend=0.01), respectively. When TIR was considered as a continuous variable, the multivariable-adjusted HR for DR associated with each 10% decrease in TIR was 1.07 (95%CI 1.02-1.13).

The current prospective cohort study indicated an association of lower TIR with an increased risk of DR among patients with T2DM, supporting the validity of TIR as an optimal marker of glucose control.

To investigate the distribution of single nucleotide polymorphisms of interleukin-2 receptor α (IL2RA) gene in Chinese Han population and its correlation with classical type 1 diabetes (T1DM).

A case-control study was conducted in T1DM patients from the First Affiliated Hospital of Nanjing Medical University and Children′s Hospital of Nanjing Medical University and healthy controls in this region from January 2008 to December 2014. The results of medical visits, such as serum C-peptide, zinc transporter 8 antibody (ZnT8A), glutamic acid decarboxylase antibody (GADA), protein tyrosine phosphatase antibody (IA-2A), and the genotyping of rs3118470 and rs2104286 in IL2RA gene were recorded. The t test, χ² test and Kruskal-Wallis H test were used to compare the general information between T1DM patients and healthy controls and the clinical characteristics of different genotypes in T1DM patients. Logistic regression was performed to compare the frequency distributions of the alleles and genotypes between T1DM patients and controls, and the potential confounders (e.g., age, sex) were adjusted. Univariate logistic regression was used to analyze the association between the polymorphism of IL2RA gene and T1DM susceptibility under different genetic models (dominant, recessive, super dominant and additive models).

The minor allele C of rs3118470 in IL2RA gene was the risk allele of T1DM (P=0.026). The polymorphisms of rs3118470 in IL2RA gene were associated with T1DM susceptibility under dominant and additive genetic models [OR(95%CI)were 0.807 (0.666-0.978) and 0.880 (0.783-0.989), respectively, bothP<0.05], but the clinical characteristics of T1DM patients were not statistically significantly different between different genotype groups (allP>0.05). There was a statistically significant difference in the positive rate of ZnT8A in T1DM patients among different genotypes of rs2104286 in IL2RA gene (P=0.035).

The polymorphisms of rs3118470 in IL2RA gene were significantly associated with the susceptibility of T1DM in Chinese Han population, and the minor allele C was the risk allele of T1DM. The polymorphisms of rs2104286 in IL2RA gene were correlated with the positive rate of ZnT8A.

To explore whether thyroid stimulating hormone (TSH) treat-to-target during early pregnancy had an impact on the incidence of gestational diabetes mellitus (GDM) in women with hypothyroidism.

A retrospective analysis was performed on naturally conceived singleton pregnant women who had accepted routinely prenatal services at the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to December 2018. The gestational weeks of the first obstetric examination were before 13 weeks and 6 days of gestation. Data of 6 978 subjects were analyzed, including 186 cases in the hypothyroidism group and 6 792 cases in the normal group. In the hypothyroidism group, according to whether TSH levels were<2.5 mU/L in the first prenatal examination, 124 cases were in the under control group and 62 cases in the non-control group. Basic information was collected at first visit, and laboratory tests were performed with fasting samples, including thyroid function [TSH, free thyroxine (FT4), thyroid peroxidase antibody (TPOAb)] and fasting plasma glucose (FPG). The 75-gram oral glucose tolerance test (OGTT) was performed at 24 to 28 weeks. The incidence of GDM and the impact of TSH levels on it between the hypothyroidism group and the normal group were explored by usingχ² test. The risk factors of GDM were analyzed by logistic regression.

The incidence of GDM in the hypothyroidism group was higher than that in the under-control group [21.5% (40/186) vs. 13.7% (929/6 792), P=0.002]. The incidences of GDM in the under-control group [20.2% (25/124)] and the non-control group [24.2% (15/62)] were higher than that of the control group (allP<0.05). Multivariate logistic regression analysis for risk factors of incidence of GDM was performed, and finally age, pregestational body mass index, history of hypothyroidism, FPG, positive TPOAb, and triglyceride were considered to be independent risk factors for incidence of GDM (P<0.05). Whether TSH met the standard was ruled out from the equation.

Compared with women with normal thyroid function, women with hypothyroidism still are at higher risk of developing GDM, whether TSH levels are under control or not.

Prader-Willi syndrome (PWS) is a group of diseases with highly heterogeneous clinical manifestations, which are prone to clinical misdiagnosis and neglect. This article collected and analyzed the clinical data of 9 patients with PWS admitted to the Department of Endocrinology of the First Affiliated Hospital of Zhengzhou University from January 2017 to April 2021, and summarized the clinical characteristics. The results showed that among the 9 patients, 4 were males and 5 were females. The detection of methylation-specific multiple ligation-dependent probe amplification technique showed that 2 cases were caused by maternal single parent diploid, and the other 7 cases were caused by paternal 15q11~13 deletion; 8 cases were complicated with diabetes, 1 case was hyperinsulinemia, and 7 cases had insulin resistance; The secondary sexual characteristics were diverse, 2 males had cryptorchidism, 5 females had no spontaneous menstrual cramps, the hypothalamus-gonad axis showed hypothalamus-pituitary function, and the growth hormone-insulin-like growth factor-1 axis showed lack of growth hormone secretion. It suggests that the clinical manifestations of PWS are highly heterogeneous, and can involve glucose metabolism, gonad and growth hormone axes simultaneously.

To investigate the relationship between adult-onset diabetes mellitus type 5 (MODY5) and 17q12 microdeletion syndrome in adolescents, as well as the common genotypes and clinical phenotypes of 17q12 microdeletion syndrome with diabetes as the first manifestation.

Genetic analysis was performed on 2 patients with diabetes mellitus of juvenile onset, combined with pancreatic and kidney dysplasia and hypomagnesemia. First, MODY-related gene mutations were detected by second-generation sequencing, and then low-depth whole genome sequencing (CNV-seq) was used to detect pathogenic copy number variation (CNV) related to the clinical phenotype of the subject, and the mental status of the patients was evaluated. A literature search was performed using the terms 17q12 microdeletion syndrome, MODY5, hepatocyte nuclear factor 1B (HNF1B), hypomagnesemia to analyze the relationship between MODY5 and 17q12 microdeletion syndrome.

The routine analysis of second-generation sequencing in 2 patients failed to find MODY-related gene mutations. Further CNV analysis revealed that both patients had 17q12 microdeletion syndrome caused by 1.40 Mb large fragment deletion at 17q12 site, including the deletion of the whole HNF1B gene causing MODY5. Both patients had a family history of diabetes, but genetic testing confirmed that both patients had no 17q12 microdeletion in their parents, and both were new variants. One patient presented with mild autistic symptoms.

Whole HNF1B gene deletion based on 17q12 microdeletion is a common gene variant type of MODY5. When conducting genetic testing on clinically suspected MODY5 patients, on the basis of second-generation sequencing, CNV and other analysis should be routinely performed to confirm whether the patient has HNF1B gene deletion or 17q12 microdeletion.

Pancreatic islets are important structures that regulate blood sugar homeostasis in the body. They are composed of various endocrine cells and originate from the foregut structure of the endoderm. During the development of pancreatic islet embryo, endocrine progenitor cells complete the differentiation and maturation of endocrine cells by regulating many gene transcription. The emergence of single cell sequencing provides a good research platform for exploring the transcriptome changes during islet development. The application of dimensionality reduction and feature selection methods makes single cell sequencing technology have significant advantages in establishing islet development map, finding islet stem cells and exploring their in vitro induction and differentiation regulation. This paper discusses the application of single cell sequencing technology in the research of islet embryo development, in order to better apply single cell sequencing technology in the research of islet development and diabetes treatment.

With the improvement of people's living standards, the incidence of non-alcoholic fatty liver disease (NAFLD) is increasing year by year, so it is particularly important to find effective drugs to intervene with NAFLD. Naringenin is an important class of natural flavonoids widely found in citrus fruits and Solanaceae. Naringin has been shown to have significant pharmacological effects in the treatment of obesity and NAFLD, including weight loss, improvement of oxidative stress and insulin resistance, reduction of inflammatory response, regulation of lipid metabolism, fatty acid oxidation, and reduction of apoptosis, among others. The author emphatically reviewed the efficacy and molecular mechanism of naringenin in the treatment of NAFLD, in order to provide a good prospect for the clinical application of naringenin in the treatment of NAFLD.

Type 2 diabetes mellitus (T2DM) is a common metabolic disease, which can not only lead to atherosclerotic cardiovascular disease, but also is closely related to sarcopenia, weakness, limited activity and even loss of independence in life in the elderly. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are two types of hypoglycemic drugs that have proven cardiovascular benefits at present, so they are widely used in clinical practice. The hypoglycemic mechanisms of both are related to changes in body composition. This article searched the literature on the effects of GLP-1RA and SGLT2i on body composition, and the results showed that the decrease in body mass was mainly manifested by a decrease in fat mass and muscle mass. This article will focus on the study of the effects of the above two drugs on the body composition of patients with T2DM and explore their association with sarcopenia.

The author verified the applicability of the model in the paper "Construction and Validation of Postprandial Glucose Estimation Model in Patients with Type 2 Diabetes" in the Chinese Journal of Diabetes, Volume 13, Issue 7, 2021, in non-diabetic populations. It is considered that the linear regression estimation model is more accurate for the assessment of overall postprandial blood glucose when applied to non-diabetic population, but has limited effect for the assessment of individual postprandial blood glucose.