Volume 14 · Issue 01 · 2022

In 2021, a series of important progress has been made in the field of diabetes prevention, diagnosis, treatment and management at home and abroad. The author summarizes the important progress, covering the diabetes map released by the International Diabetes Federation, the progress in the research and clinical treatment of type 1 diabetes and type 2 diabetes, and sorts out the important guidelines and consensus released at home and abroad in 2021.

The prevalence of type 2 diabetes mellitus (T2DM) in China is increasing, and it is always the long-term strategic goal of diabetes treatment to continuously find and update strategies for managing diabetes. The American Diabetes Society and the European Diabetes Research Association encourage patients with T2DM to carry out appropriate life management and lifestyle changes, including dietary management with rational medical nutrition treatment. Intermittent fasting is a means of dietary management that limits caloric intake over a specific period of time. Since 2018, research around intermittent fasting has blossomed everywhere, presenting a thriving scene. For this new concept, how to combine its practical role and apply it to the lifestyle management of T2DM patients can be described as opportunities and challenges coexist, and we need to look at the problem more comprehensively.

Tianjin Gestational Diabetes Prevention Project started in 1998. It monitored the prevalence of gestational diabetes mellitus (GDM) in six districts of the city, explored the risk factors of GDM, and developed a GDM prediction model. The project found that lifestyle interventions within 15 weeks of pregnancy reduced the risk of GDM by 20%; Intensive lifestyle intervention GDM can improve pregnancy outcome and reduce the incidence of macrosomia; GDM increases maternal postpartum diabetes risk, and its peak occurs 3 to 6 years postpartum and before the age of 40 years; GDM intervention during pregnancy was ineffective for postpartum diabetes in mothers, but lifestyle intervention within 3 years postpartum reduced diabetes risk factors and 43% diabetes risk; Childhood obesity increases in GDM offspring, but GDM intervention during pregnancy is ineffective for infant and childhood obesity. We call for the establishment of a continuous comprehensive prevention and control strategy for GDM throughout pregnancy, pregnancy and postpartum.

In order to standardize the comprehensive management of adult occult autoimmune diabetes (LADA), the Endocrinology and Metabolism 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 Diagnosis and Treatment of Adult Occult Autoimmune Diabetes (2021 Edition) based on the latest research evidence at home and abroad. The author interpreted the relevant updates and key points.

Short-term intensive insulin therapy is one of the important methods to strengthen blood glucose control. It is suitable for newly diagnosed type 2 diabetes patients with glycosylated hemoglobin ≥9.0% or fasting blood glucose ≥11.1 mmol/L, or with obvious symptoms of hyperglycemia, and patients with type 2 diabetes who have been treated with multiple oral hypoglycemic drugs for more than 3 months and still have significant blood glucose increases (such as glycosylated hemoglobin ≥9.0%), or who have been treated with insulin and have not reached the standard after adequate dose adjustment. Implementing short-term intensive insulin therapy can help to rapidly reduce hyperglycemic toxicity and improve patient prognosis. Endocrinologists engaged in related content research have formed the compiling committee of "Expert Consensus on Short-term Intensive Insulin Therapy for Type 2 Diabetes Mellitus". Based on the 2017 "Clinical Expert Guidance on Short-term Intensive Insulin Therapy for Type 2 Diabetes Mellitus", combined with the latest evidence-based medical evidence and new research progress, the "Expert Consensus on Short-term Intensive Insulin Therapy for Type 2 Diabetes Mellitus (2021 Edition)" was formed. It covers the definition and clinical benefits of short-term insulin intensive therapy, the applicable population of treatment, blood glucose control goals and treatment plans, the follow-up blood glucose management of short-term insulin intensive therapy, the precautions of short-term insulin therapy for special people with type 2 diabetes, the causes and countermeasures of hypoglycemia, etc., and gives the path of short-term insulin intensive therapy for patients with type 2 diabetes, in order to guide clinical treatment and benefit patients.

To analyze the effect of gestational diabetes mellitus (GDM) on maternal and neonatal outcomes in twin pregnancies.

A retrospective cohort study was conducted on 772 cases of dichorionic twin pregnancies delivered in Beijing Haidian Maternal and Child Health Hospital from January 2013 to October 2019. The general clinical characteristics and the maternal and neonatal outcomes were collected, including age, parity, gestational weeks, mode of conception, delivery mode and the maternal and neonatal complications. According to the results of 75 g oral glucose tolerance test (OGTT) on gestational age 24-28 weeks, the subjects were divided into GDM group (157 cases) and normal glucose tolerance (NGT) group (615 cases). The glycated hemoglobin A_1c (HbA_1c) was tested among 137 GDM women. The GDM women were classified into two groups: the uncontrolled GDM group with HbA_1c≥5.5% (25 cases) and well-controlled GDM group with HbA_1c<5.5% (112 cases). The t test, rank sum test, χ² test and Fisher exact probability method were used for comparison between groups.

The age of GDM group was statistically significant older than that of NGT group (P<0.001). There were more women aged over 35 years in GDM group than in NGT group [28.0% (44/157) vs. 17.1% (105/615), P=0.002]. Women with GDM were significantly more obese before pregnancy than the NGT women (P=0.002). Whereas there was no significant difference in gestational weeks, cesarean section rate, premature birth rate between the two groups. There was no difference between GDM and NGT groups in the incidence of fetal growth restriction,hypertensive disorders of pregnancy, premature rupture of membranes, placental abruption, postpartum hemorrhage, neonatal low birthweight, neonatal respiratory distress, neonatal malformation or dysplasia neonatal death or admission to neonatal ward (P>0.05). Compared with the NGT group, the well-controlled GDM group and the uncontrolled GDM group, there was no significant difference in gestational weeks, cesarean section rate, premature birth rate, and incidence of fetal growth restriction,hypertensive disorders of pregnancy, premature rupture of membranes, placental abruption, postpartum hemorrhage (P>0.05). However, the incidence of premature birth, fetal growth restriction and premature rupture of membranes increased in the uncontrolled GDM group, without statistical significance (P>0.05), and no significant difference in the neonatal outcomes among them (P>0.05).

In this study, GDM did not increase the maternal and neonatal adverse outcomes in women with twin pregnancies.

To explore the association between maternal glycated hemoglobin A_1c (HbA_1c) before delivery in gestational diabetes mellitus (GDM) pregnancies, and neonatal blood glucose and birth weight.

A total of 178 pregnant women with GDM and their newborns who were born in Affiliated Hospital of Southwest Medical University from September 2018 to December 2020 were included in this study. The maternal HbA_1c within 7 days before delivery was used to reflect the accumulated blood glucose level in the past 2-3 months. Pregnant women with GDM were divided into two groups: HbA_1c≥6% group (45 cases) and HbA_1c<6% group (133 cases). Neonatal birth weight and neonatal blood glucose were selected as the outcomes. Pearson and Spearman partial correlation analysis were used to verify the linear relationships between maternal HbA_1c before delivery and the initial neonatal blood glucose levels. A multivariable linear regression model was used to analyze the association between maternal HbA_1c before delivery and neonatal birthweight. A multivariate logistical regression model was used to analyze the risk of neonatal hypoglycemia and large for gestational age (LGA).

Compared to the newborns of the GDM pregnant women with HbA_1c≥6% before delivery, the newborns in the maternal HbA_1c<6% group had higher initial neonatal blood glucose levels [(3.5±1.4) vs. (2.8±1.3) mmol/L, t=2.85, P<0.01). The result of Pearson correlation analysis showed a negative correlation between the maternal HbA_1c before delivery and the initial neonatal blood glucose (r=-0.25, P<0.001), and the similar conclusion was observed using the Spearman partial correlation analysis to adjust for potential confounding factors (r=-0.27, P<0.001). The result of multivariable linear regression model showed that, after adjusting for potential confounding factors such as gestational age, for every 0.1% reduction in maternal HbA_1c before delivery, the birth weight of the newborn was reduced by 24 g (β=24, 95%CI 16-33, P<0.001). When HbA_1c was entered in the multivariate logistical regression model as a continuous variable, the results showed that, after adjusting for potential confounding factors, for every 0.1% reduction in maternal HbA_1c before delivery, the risks of hypoglycemia and LGA decreased by 12% (OR=0.88, 95%CI 0.82-0.95, P<0.001) and 8% (OR=0.92, 95%CI 0.87-0.97, P<0.01) in their offspring. When HbA_1c was entered in the multivariate logistical regression model as a dichotomous variable, the results showed that, after adjusting for potential confounding factors, compared with the newborns of the GDM pregnant women with HbA_1c≥6% before delivery, the risks of hypoglycemia (OR=0.23, 95%CI 0.09-0.59, P<0.01) and LGA (OR=0.30, 95%CI 0.12-0.71, P<0.01) in the maternal HbA_1c<6% group were significantly decreased.

The maternal HbA_1c in GDM pregnant women before delivery is associated with the neonatal blood glucose and neonatal birthweight. The good glycemic control before delivery in GDM pregnant women significantly reduces the incidence of neonatal hypoglycemia and LGA.

To investigate the associations of trimethylamine N-oxide (TMAO) and related metabolites with insulin resistance (IR) and β-cell function among Chinese women with gestational diabetes mellitus (GDM).

This was a cross-sectional study. A GDM survey was conducted in six urban districts of Tianjin from October 2010 to August 2012. The height and weight were recorded, and the body mass index (BMI) in the first trimester was calculated. Fasting plasma glucose (FPG), fasting insulin, the levels of TMAO and related metabolites [trimethylamine (TMA), L-carnitine, choline chloride, betaine] and other indicators were also recorded. And homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were calculated by homeostasis model assessment. The HOMA-IR and HOMA-β were used to estimate insulin resistance (IR) and islet β-cell functions. According to the BMI calculated in the first trimester, all pregnant women were divided into overweight group (BMI≥24.0 kg/m²) and non-overweight group (BMI<24.0 kg/m²). According to the tertiles of HOMA-IR, the subjects were divided into three groups: the low (HOMA-IR<2.17), middle (HOMA-IR 2.17-3.39) and upper (HOMA-IR>3.39) groups. Similarly, pregnant women with different β-cell function were also divided into the low (HOMA-β<118.70), middle (HOMA-β 118.70-184.91) and upper groups (HOMA-β>184.91), if HOMA-β was stratified into tertiles. The distribution differences of TMAO and related metabolites among the three groups were compared by analysis of variance, rank sum test or chi-square analysis, where appropriate. Spearman correlation and partial correlation were used to analyze the correlations among target metabolites, HOMA-IR and HOMA-β.

A total of 145 pregnant women with GDM were enrolled. There were 48, 49 and 48 cases in the HOMA-IR upper, medium, and low groups, respectively, and 48, 49 and 48 cases in the HOMA-β upper, medium and low groups, respectively.Among HOMA-IR groups, the difference in the level of TMA was statistically significant (P<0.05). Spearman correlation analysis showed that TMA was positively correlated with HOMA-IR (r=0.19, P<0.05). After adjusting for age and BMI, partial correlation analysis showed that TMA was still positively correlated with HOMA IR (r=0.17, P<0.05), but there was no correlation with HOMA-β (P>0.05). TMAO had no correlation with HOMA-IR or HOMA-β (P>0.05). The level of TMA in overweight group was positively correlated with the level of HOMA-IR (r=0.32, P<0.05), and the correlation was slightly increased after adjusting for age (r=0.43, P<0.05). The level of TMA in the non-overweight group had no correlation with the level of HOMA-IR (P>0.05).

There is a positive correlation between the level of TMA and HOMA-IR in the first trimester, which is independent of age and pre-pregnancy BMI.

To evaluate the effects of postpartum diet and lifestyle intervention on gestational diabetes (GDM) women with different genetic risk scores (GRS).

Based on an established randomized controlled trial (RCT) evaluating the effects of a postpartum diet and lifestyle intervention between August 2009 and September 2013, women with previous GDM and non-diabetes postpartum were recruited. Information at baseline and follow-up survey after 1-year intervention were collected, including fasting blood glucose (FPG), 2-hour blood glucose (2hPG), total cholesterol (TC), body fat, waist circumference, dietary fiber intake>20 g/d, and exercise>30 min/d and other indicators. The height and body weight were recorded, and the body mass index (BMI) was calculated. After 1-year intervention, percentage reduction in initial weight, and changes in 2hPG, TC, weight, BMI, waist circumference and body fat percentage were calculated. We detected 11 postpartum type 2 diabetes mellitus (T2DM)-related single nucleotide polymorphisms (SNP) which were previously validated, and calculated the individual′s comprehensive GRS. Patients were divided into low genetic risk group (GRS<10.00) and high genetic risk group (GRS≥10.00) according to the median of GRS. In the low and high genetic risk groups, patients were divided into lifestyle intervention group and control group respectively. The t test or χ² test were used to compare the indicators between the intervention and control group.

A total of 675 patients were enrolled in the study, including 292 patients with low genetic risk (142 in the intervention group and 150 in the control group), and 383 patients with high genetic risk (188 in the intervention group and 195 in the control group), respectively. Among patients with low genetic risk, compared with control group, patients in the intervention group had a higher rate of dietary fiber intake>20 g/d (P=0.037), a lower rate of abnormal blood glucose (P=0.012), and better changed 2hPG and TC (both P<0.05). Among patients with high genetic risk, compared with control group, patients in the intervention group had a higher rate of exercise>30 min/d (P=0.003), better changed fasting insulin (P=0.038), and the changes in weight, percentage in weight change BMI, waist circumference and body fat percentage were larger (all P<0.05).

The postpartum diet and lifestyle intervention were relatively effective for GDM patients with different genetic risks. GDM patients with low genetic risk had increased dietary fiber intake, improved blood glucose and lipid levels, and lower risk of abnormal blood glucose. GDM patients with high genetic risk had larger changes in weight, BMI, waist circumference and body fat percentage, and better insulin improvement after comprehensive intervention.

To compare and screen for new simplified insulin resistance (IR) assessment indicators with high diagnostic efficacy.

We included consecutive 136 healthy participants without type 2 diabetes or impaired glucose tolerance from October 2019 to October 2020 in Peking Union Medical College Hospital, and collected their demographic data and clinical parameters, including the height, weight, waist circumference (WC), fasting plasma glucose (FPG), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), glycated hemoglobin A_1c (HbA_1c), fasting insulin (FINS) with body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA-IR) calculated. Some new simplified IR assessment indicators were calculated, including triglyceride/HDL-C ratio, triglyceride glucose (TyG) index, TyG-BMI index, TyG-WC, visceral adiposity index (VAI), lipid accumulation product (LAP), metabolic score for IR (METS-IR), and estimate of insulin sensitivity (e-IS). The subjects were divided into normal weight group (BMI<24 kg/m²) and overweight and obesity group (24 kg/m²≤BMI<30 kg/m²). The clinical parameters and the new simplified IR assessment indicators were compared between groups with t-test. Correlation between the HOMA-IR and the new simplified IR assessment indicators was analyzed with the Pearson correlation analysis. With HOMA-IR as the reference standard, the receiver operating characteristic curve was used to analyze the diagnostic efficacy of different simplified IR assessment indicators, with the area under the curve (AUC) calculated.

Total 136 participants were included, all aged (43.80±10.52) years with 45 men and 91 women. Forty participants were classified into the normal weight group, while the other 96 participants fell into the overweight and obesity group. Compared with the normal weight group, the waist circumference, HOMA-IR, TG/HDL-C ratio, TyG index, TyG-BMI, TyG-WC, VAI, LAP, and METS-IR of subjects in the overweight and obese group were significantly increased (all P<0.05). For all subjects, FPG, TG/HDL-C ratio, TyG index, TyG-BMI, TyG-WC, VAI, LAP, and METS-IR were positively correlated with HOMA-IR (r=0.409-0.478), whereas e-IS and HOMA-IR were negatively correlated (r=-0.290). TyG index, TyG-BMI, LAP, METS-IR had high AUC (0.701-0.736).

The TyG, TyG-BMI, LAP and METS-IR have certain predictive value in evaluating insulin sensitivity in the Chinese adult population.

To investigate the effect of dapagliflozin on aldosterone to renin ratio (ARR) in patients with type 2 diabetes mellitus (T2DM) complicated with hypertension.

Patients with T2DM and hypertension who were admitted to the Department of Endocrinology, Beijing Huairou Hospital from September 2019 to December 2020 were enrolled. Body weight, fasting blood glucose (FPG), glycosylated hemoglobin (HbA_1c), uric acid, plasma renin concentration, aldosterone level and other indicators were measured and recorded before treatment, and ARR was calculated. Patients were treated with dapagliflozin for 12 weeks, and hematologic indicators were collected again while ARR was also calculated. Paired t test or Mann-Whitney U test were used to compare the ARR and related indexes before and after treatment of dapagliflozin.

A total of 20 patients were enrolled. ARR before and after treatment were 0.86 (0.73, 1.20) and 0.95 (0.72, 1.32), respectively. However, there was no significant difference between them (Z=1.12, P=0.263). After 12 weeks of dapagliflozin, FPG (Z=-3.62, P<0.001), HbA_1c (Z=-3.76, P<0.001), body weight (Z=-3.19, P=0.001) and uric acid (Z=-2.71, P=0.014) decreased significantly compared with baseline.

Dapagliflozin has no effect on ARR in patients with T2DM complicated with hypertension, but it has good effects on reducing FPG, uric acid and weight loss.

To explore whether poorly-controlled blood pressure is a risk factor of painful diabetic peripheral neuropathy (DPN).

This study was a prospective study. Diabetic patients aged ≥ 18 years with undiagnosed DPN were recruited from 5 community health centers in Shanghai since 2014. Demographic data, laboratory tests and Michigan Neuropathy Screening Instrument examination were recorded at baseline and follow-up visit. And Douleur Neuropathique en 4 Questions screening and nerve conduction studies were assessed at follow-up visit. According to the criteria of painful DPN, the patients were divided into non-DPN group, painful-DPN group and painless-DPN group. The differences of systolic and diastolic blood pressure at baseline and follow-up between painful-DPN group and painless-DPN group were analyzed. And the incidence of painful-DPN were compared between poorly-controlled blood pressure group (≥130/80 mmHg, 1 mmHg=0.133 kPa) and well-controlled blood pressure group (<130/80 mmHg) by using Chi-squared test. Multivariate logistic regression model was used to explore the relationship between poorly-controlled blood pressure and painful-DPN.

Finally, 315 patients with type 2 diabetes mellitus (T2DM) were included and followed up for (5.06±1.14) years. The patients were divided into non-DPN group (n=152), painful-DPN group (n=74) and painless-DPN group (n=89). Compared with non-DPN group, the patients in painful-DPN group and painless-DPN group had older age, higher waist circumference and fasting plasma glucose at baseline (P<0.05). In addition, systolic blood pressure, diastolic blood pressure and diabetic duration at baseline were higher in patients with painful-DPN than the patients with painless-DPN (P<0.05). And the systolic blood pressure (P=0.030) and diastolic blood pressure (P=0.007) at follow-up visit in painful-DPN group were significantly higher than those in painless-DPN group. The incidence of painful-DPN was significantly higher in patients with poorly-controlled blood pressure (≥130/80 mmHg, n=132) than that in patients with well-controlled blood pressure (<130/80 mmHg, n=30) [49.24% (65/132) vs. 26.67% (8/30), P<0.05]. Furthermore, poorly-controlled blood pressure at baseline was independently associated with painful-DPN after adjusting for body mass index, glycosylated hemoglobin, age, gender, smoking, drinking, duration of T2DM, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, angiotensin converting enzyme inhibitor, other antihypertensive drugs and metformin (OR=17.921,95%CI:1.497-214.593).

Poorly-controlled blood pressure is a risk factor for painful-DPN in patients with type 2 diabetes.

Diabetes mellitus is one of the common chronic diseases that can trigger multiple systemic complications. Epigenetic dysregulation is crucial in the development of disease, and reversible chemical modification of mRNA is an important regulatory mechanism to control gene expression. N6-methyladenine (m⁶A) Dysregulation of modification is associated with the development of diabetes mellitus and its complications. The author's opinion on m⁶Recent findings on a regulation in diabetes mellitus and related complications are reviewed.

Diabetic retinopathy (DR) is one of the common and serious microvascular complications of diabetes and the leading cause of vision loss in adults worldwide. Optical coherence tomography angiography (OCTA) is a non-invasive fundus angiography technique, which can identify the retinochoroidal blood flow motion information with high resolution, image the retinochoroidal blood vessels of living tissue, and at the same time, it can realize the stratified analysis of the retinochoroidal blood vessels in each layer and quantify the vascular parameters. OCTA has been widely used in the diagnosis, monitoring, management and follow-up of retinochoroidal vascular diseases, such as DR, choroidal neovascularization, age-related macular degeneration, etc. This article reviews the application progress of OCTA in DR.

Confounding is one of the important sources of bias in clinical research and is unavoidable in observational or interventional diabetes studies. Multivariate analysis method is a common statistical method to correct confounding factors in data analysis stage. Taking diabetes research as an example, the author will introduce several common multivariate analysis methods and the problems that need attention when using multivariate analysis method to correct confounding factors.