Volume 12 · Issue 08 · 2020

As one of the important indicators of type 2 diabetes management, fasting blood glucose has an extremely important influence on overall blood glucose control, beta cell function, and the occurrence of microvascular and macrovascular complications. Basal insulin is an important means to control fasting blood glucose. Optimizing the treatment of basal insulin can effectively control fasting blood glucose to reach the standard, thus achieving long-term benefits. However, at present, the use of basal insulin in clinical practice has problems such as late starting time and untimely dose adjustment, which makes the fasting blood glucose compliance rate low. In order to achieve the best fasting blood glucose treatment, the author will elaborate on the individualized fasting blood glucose control goals and the combination of basal insulin to provide clinical guidance.

Metabolic surgery is a gradual evolution from bariatric surgery, and its surgical methods have undergone continuous changes. At present, it has become an important means for treating morbid obesity and type 2 diabetes with obesity. Its therapeutic mechanism involves reduced food intake and digestion, adjustment of gastrointestinal hormone secretion pattern, alteration of intestinal flora and other ways. However, from the macro level, it can be understood that it mainly plays a role by reconstructing energy homeostasis and the "setting point" of human body's behavioral cognition of food, while some patients' weight gain or poor surgical effect can be understood as "setting failure".

Pregnancy is a risk factor for aggravating the condition and complications of type 1 diabetes mellitus (T1DM). Standardized and strict management of T1DM patients covering the whole process before and during pregnancy is very important for the improvement of maternal and infant outcomes. The management of T1DM complicated with pregnancy requires the cooperation of endocrinology, obstetrics, pediatrics, nutrition and other multidisciplinary departments. Therefore, this consensus is formulated to provide a reference for the whole pregnancy management of patients with T1DM complicated with pregnancy.

Diabetic foot ulcer (DFU) combined with peripheral arterial disease (PAD) is an important factor in amputation in patients. By asking about medical history, symptoms and signs, and a physical examination, it can help to determine whether a patient has severe PAD. The abnormal pulsation of foot arteries and chill skin are of great value in the diagnosis of DFU patients with PAD. When the signs of skin atrophy and chill skin are combined in series (used successively), the diagnosis rate of PAD in DFU patients can be improved. However, when the hair loss and skin atrophy signs are combined (used simultaneously), it helps to rule out the diagnosis of PAD. By carefully studying clinical signs and symptoms, PAD diagnosis can be improved, and DFU patients can be avoided from missing the best opportunity for treatment.

Diabetic chronic limb threatening ischemia (CLTI) is a challenging clinical problem with high risk of diabetic foot ulcer (DFU) and limb loss. For lower limb ischemia in diabetic patients, limb rescue and treatment institutions should have professional facilities and mechanisms, carry out vascular reconstruction through the best drug treatment, rapid diagnosis, timely endovascular intervention or open surgery and other technical means, combined with professional wound management, to form a holistic treatment based on a multidisciplinary professional team, so as to achieve good treatment effect and limb saving rate. Vascular surgeons involved in the management of diabetic CLTI should be proficient in various technical means, equipment and equipment for the opening and shaping of distal inferior genicular artery lesions, especially antegrade and retrograde approaches. Multidisciplinary integrated team specialized holistic treatment can achieve excellent limb saving rate of DFU patients.

To investigate the current status of preconception care (PCC) among Chinese women with type 1 diabetes mellitus (T1DM) and assess their needs.

An online questionnaire survey was conducted from December 2016 to January 2018 in the patient community consisted of users of TangTangQuan^®, a mobile application dedicated for the management of T1DM. We recruited women with T1DM who aged 14 year and elder. Data including the basic information of women with T1DM, their perspectives on current status of PCC and their needs were collected. Spearman correlation analysis was used in correlation analysis and Wilcoxon rank sum test was used to compare the differences.

A total of 386 valid responses were received at the end of the survey, which covered 28 provinces of China. Among the participants of the survey, 72.8% (281/386) were aged 21 to 35 years and 25.4% (98/386) had glycated hemoglobin A_1c>6.5%, while 48.8% (62/127) who experienced pregnancy had been confronted with adverse pregnancy outcomes. Only 12.4% (48/386) of the participants thought they had sufficient knowledge on PCC, and their educational background correlated positively with the knowledge degree (r_s=0.162, P<0.01). 72.6% (280/386) reported less than 10 min per visit to the doctor, significantly shorter than their ideal time for full communication (Z=-14.109, P<0.01). 86.0% (332/386) expressed that T1DM impacted on their relationship, marriage and childbearing.

There is an urgent need for Chinese women with T1DM to receive PCC. It will be helpful for women with T1DM to facilitate the participation in PCC and relieve their psychological burden by enhancing professional and social support for them.

To investigate the prevalence of the autoimmune thyroid disease (AITD) and the metabolic control in adult patients with type 1 diabetes mellitus (T1DM).

A total of 1 158 adult patients (≥18 years; male/female, 524/634) registered in the Guangdong T1DM Translational Study from June 2011 to November 2018 were selected into the analysis, with 982 patients in T1DM only group and 176 patients in comorbid AITD group. According to thyroid function at enrollment, patients with comorbid AITD were further divided into hyperthyroidism group (n=42), hypothyroidism group (n=31) and normal thyroid function group (n=103). Biochemical information such as glycated hemoglobin A_1c(HbA_1c), body mass index (BMI), thyroid stimulating hormone (TSH) were collected at enrollment and one-year follow-up. Changes of indexs at one-year follow up were further analyzed between groups. Statistical analysis was performed using t test, Mann-Whitney U or chi-square test.

At onset, patients with comorbid AITD presented more serious metabolic disorder. After one-year follow-up, both groups showed significant reduction in HbA_1c ［AITD group: 8.40% (7.03%, 10.78%) vs 7.65% (6.60%, 8.93%), P<0.01; T1DM group: 8.50% (7.20%, 10.80%) vs 7.75% (6.70%, 9.10%),P<0.01］ and higher BMI, ln glucose disposal rate compared with baseline. However, between-groupdifferences were not significant (bothP>0.05). After one-year follow-up, TSH level was still lower in hyperthyroidism group compared with normal thyroid function group ［0.15 (0.01, 0.39) vs 1.92 (1.34， 3.17) nmol/L,P<0.05］. Instead of the significant improvement on HbA_1c level in hypothyroidism group and normal thyroid function group, there was no difference in hyperthyroidism group. Moreover, compared with normal thyroid function subgroup, there was significantly higher BMI ［(22.37±2.89) vs (20.71±2.77) kg/m², P<0.05］ and systolic/diastolic blood pressure in hypothyroidism subgroup ［systolic blood pressure: 120 (110, 129) vs 111 (103, 122) mmHg；diastolic blood pressure: 78 (75, 81) vs 70 (63, 77) mmHg, 1 mmHg=0.133 kPa, bothP<0.05］.

Metabolic disorder was more serious in adult T1DM patients with AITD. After one-year follow-up, there was no significant improvement on glycemic control in T1DM patients with AITD and hyperthyroidism, and those with hypothyroidism were easier to have higher BMI and blood pressure.

To evaluate the efficacy and safety of sotagliflozin, LX4211, a dual inhibitor of sodium-glucose cotransporter 1（SGLT1） and SGLT2, a dual inhibitor of SGLT1 and SGLT2, combined with insulin in the treatment of type 1 diabetes mellitus (T1DM).

The US national library database(Medline), Netherlands medical abstracts database (Embase), evidence-based medicine database (The Cochrane Library), Chinese biomedical literature database, Wanfang and China knowledge network(CNKI) were searched, and the randomized controlled trial(RCT) on the treatment of T1DM published from the establishment of the database to August 2019 was selected. Review Manager 5.3 system was used to analyze the effectiveness and safety of sotagliflozin by meta.

A total of 3 083 cases of T1DM were included in 4 articles of RCT (intervention cycle 12/52 weeks), including 1 818 in the sotagliflozin group and 1 265 in the placebo control group. Compared with placebo, sotagliflozin combined with insulin could effectively reduce glycosylated hemoglobin level WMD=-0.29% (95%CI:-0.35%--0.23%), fasting plasma glucose (FPG) level WMD=-15.91 mg/dl (95%CI:-22.13- -9.68 mg/dl), and reduce the percentage of daily insulin dose by -9.14% (95%CI:-11.16%--7.11%). The percentage of single insulin dose was reduced by -10.76% (95%CI:-14.60%--6.92%), and the percentage of basal insulin dose was reduced by -8.28% (95%CI:-10.33%--6.22%). Among them, 400 mg has more advantages than 200 mg in reducing glycosylated hemoglobin A_1c （HbA_1c）, FPG, daily insulin dose and single insulin dose. In addition to reducing blood sugar, sotagliflozin also has the effect of losing weight and improving blood pressure. However, the drug increases the risk of diabetic ketoacidosis (OR=10.28, 95%CI: 3.88-27.24) and does not reduce the incidence of hypoglycemia.

Compared with placebo, sotagliflozin combined with insulin can effectively reduce FPG, HbA_1c and insulin dosage in patients with T1DM, but it is necessary to arouse the vigilance of clinicians and avoid the occurrence of diabetic ketoacidosis, through selection of appropriate population and educational management.

To establish a new electrochemiluminescence-zinc transporter 8 autoantibody (ECL-ZnT8A), and evaluate its clinical application value.

From January 2016 to December 2019, 100 patients with type 1 diabetes mellitus (T1DM), 150 patients with type 2 diabetes mellitus (T2DM) and 360 healthy controls (158 for establishing the method, 202 for identifying the sensitivity and specificity of the method) were detected by ECL-ZnT8A. 120 patients (60 healthy controls, 50 T1DM patients and 10 with positiveserum ZnT8A) were detected by both of ECL-ZnT8A and radio-binding assay (RBA) -ZnT8A. The differences of ZnT8A index and prevalence among the groups were compared by t test, one-way ANOVA and chi square test.

(1) The optimal concentrations of ZnT8-Biotin and ZnT8-Sulfo-TAG were 400 ng/ml and 200 ng/ml respectively. (2) ECL-ZnT8A intra-batch coefficient of variation (CV) was 3.4%-8.2%, inter-batch CV was 10.5%-12.8%, and the repeatability of negative or positive results was 100%. (3) ECL-ZnT8 showed high sensitivity (97.7%) and specificity (96.1%). The consistent rate with RBA-ZnT8A was 96.70% (116/120,Kappa=0.929), and the index of ZnT8A was positively correlated (r=0.806, P=0.01). (4) The prevalence of ECL-ZnT8A in the patients with T1DM was 52.00% (52/100), significantly higher than 0.99% (2/202) in the healthy controls (χ²=118.528, P<0.01) or 1.33% (2/150) in the T2DM patients (χ²=90.955,P<0.01).

ECL-ZnT8A assay can be detected without radioactive concern, it has promising clinical application value.

To examine the associationof serum 25-hydroxyvitamin D［(25(OH)D］ with lower limb arterial plaques and ankle brachial index(ABI)<0.9 in postmenopausal women with type 2 diabetes mellitus （T2DM）.

In the observational study, the 298 postmenopausal women with T2DM were selected. The lower limb arterial plaque was assessed by color Doppler ultrasound and ABI was measared. The patients were divided into three groups including the lower limb artery without plaque group (non-plaque group, 133 cases), the lower limb arterial plaque with ABI≥0.9 group (plaque with ABI ≥0.9 group, 108 cases) and the lower limb arterial plaque with ABI<0.9 group (plaque with ABI<0.9 group, 57 cases). Serum 25(OH)D levels were detected by chemilumine scence assay and compared among the three groups. The risk factors for arterial plaques of lower limb and ABI<0.9 was analyzed by multivariate logistic regression analysis.

Compared with the non-plaque group ［(15.29±6.46) ng/ml］, the serum level of 25(OH)D was significantly decreased in the plaque with ABI≥0.9 group ［(13.40±5.04) ng/ml］ and the plaque with ABI<0.9 group ［(12.02±4.02) ng/ml］ (P<0.05). At different levels of 25(OH)D quartile, there was a difference between the lower limb artery with plaque and without (P<0.05), while no difference was found between ABI≥0.9 and ABI<0.9, and no difference was found among no plaque, plaque with ABI≥0.9 and plaque with ABI<0.9 (P>0.05）. Age, systolic blood pressure (SBP), high-density lipoprotein-cholesterol (HDL-C), glycated hemoglobin A_1c(HbA_1c), diabetic duration, hypersensitive C-reactive protein (hs-CRP), 25(OH)D and macroangiopathy were significantly associated with the risk of lower limb arterial plaques in postmenopausal women with T2DM (allP<0.05). Age, SBP, triglyceride, diabetic duration. 25(OH)D and macroangiopathy were closely related to the risk of ABI<0.9 in postmenopausal women with T2DM (allP<0.05).

In postmenopausal women with T2DM the decreased level of 25(OH)D increased the risk of arterial plaque of lower limb and ABI<0.9.

To explore the protective effect of myeloid-derived growth factor (MYDGF) on atherosclerosis in apolipoprotein E (ApoE)^-/-mice.

MYDGF^+/+ApoE^-/- mice (AKO) and MYDGF^-/-ApoE^-/-mice (DKO) were fed with western diet for 12 weeks. According to adeno-associated viral (AAV)-MYDGF intervention, AKO and DKO mice were divided into 6 groups as follows: AKO group, DKO group, AKO-green fluorescent protein (GFP) group, DKO-GFP group, AKO-MYDGF group, and DKO-MYDGF group (n=8 in each group). The t test was used for comparison between two groups.

After 12 weeks of intervention, endothelial-dependent vasodilation function of DKO mice decreased (t=12.26，P<0.05); surface area of plaque increased ［(13.56±3.10)% vs (42.01±3.29)%,t=17.80, P<0.01］; cross-sectional plaque area increased ［(7.46±1.86)% vs (21.54±2.18)%,t=13.87, P<0.01］; the area of aorta inflammatory infiltration in mice ［macrophages (CD68), T lymphocytes (CD3)］ and the serum levels of inflammatory factors (tumor necrosis factor α, interleukin-1β and interleukin 6) were significantly increased (t=7.51-51.52, all P<0.01); body weight, triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein (LDL-C) levels, and free fatty acid (FFA) levels increased (t=2.42-9.29, all P<0.05) whereas High-density lipoprotein (LDL-C) levels decreased (t=9.865, P<0.01) compared with the AKO group. On the contrary, after supplementation of MYDGF, the vasodilation function of AKO-MYDGF and DKO-MYDGF groups improved significantly (t=4.38-5.17, all P<0.05); the plaque area decreased ［surface area: AKO-GFP: AKO-MYDGF: (15.22±1.47)% vs (6.85±1.37)%, DKO-GFP: DKO-MYDGF: (43.16±2.73)% vs (17.93±2.04)%; cross-sectional area: AKO-GFP: AKO-MYDGF: (10.42±1.24)% vs (6.31±0.72)%, DKO-GFP: DKO-MYDGF: (19.33±1.04)% vs (13.24±1.14)%,t=8.10-20.97, all P<0.01］; inflammatory infiltration and levels of inflammatory factors decreased significantly (t=6.29-40.79, all P<0.01); metabolism disorders were improved compared with AKO-GFP and DKO-GPF groups (t=2.16-4.75, P<0.05).

MYDGF can improve endothelium-dependent vasodilation function of AopE^-/-mice, reduce plaque areaand levels of inflammatory factors, and improved metabolic profiles. The data suggest that MYDGF may alleviate atherosclerosis in AopE^-/- mice through lessening inflammation levels.

To investigate the changes of Heat shock protein B8 (HSPB8) and autophagy in hippocampal neurons of diabetic mice.

Ten 8-week-old male C57BL/KS db/db mice were selected as the diabetes group and 10 wild-type (db/m) mice were selected as the control group.Fasting blood glucose and body weight were measured. Western blot was used to detect the expression of HSPB8, Bcl-2-related immortalized gene 3 (BAG3), autophagy related protein beclin-1 and microtubule related protein 1-light chain 3 (LC3) in hippocampus of each group. HT-22 cells were cultured and stimulated with glucose concentrations of 18, 25 and 33 mmol/L for 48 h respectively, as high glucose models in vitro. The HSPB8, BAG3, beclin-1 and LC3 proteins in each group were detected by Western blot. The expression of BAG3, P62 and LC3 was detected by Western blot after overexpression and silencing of HSPB8 by cell transfection. Ht-22 cells were stimulated by 33 mmol/L high glucose, and the autophagy was observed by RFP-GFP-LC3. Independent sample t test and one way analysis of variance were used for statistical analysis.

Compared with db/m group, the expression of HSPB8， BAG3， Beclin-1 and LC3-Ⅱ/LC3-Ⅰin the hippocampus of db/db mice increased (1.647±0.150 vs 0.781±0.181, 1.832±0.243 vs 0.821±0.197, 0.756±0.104 vs 0.518±0.170, 1.431±0.201 vs 1.014±0.118, t=4.130-9.131，all P<0.05). Compared with the control group, the expression levels of HSPB8， BAG3， Beclin-1 and LC3-Ⅱ/LC3-Ⅰ protein in high glucose stimulated HT-22 cells increased in a concentration dependent manner (allP<0.05). Compared with the control group, the expression of BAG3, LC3-Ⅱ/LC3-Ⅰdecreased in the HSPB8 knocked group, while p62 expression decreased in the HspB8 over expression group (0.481±0.161 vs 1.804±0.147, 0.615±0.311 vs 2.091±0.210, 1.013±0.213 vs 1.615±0.194, 1.211±0.154 vs 0.978±0.187; 1.817±0.152 vs 0.891±0.151, 1.112±0.091 vs 0.743±0.162, 1.692±0.170 vs 0.587±0.132, 1.236±0.186 vs 1.751±0.131,t=5.560-20.510, all P<0.05). Compared with the control group, the red fluorescent spots in HSPB8 overexpressed HT-22 cells increased (2.059±0.310 vs 0.819±0.151，t=9.830, P<0.01).

The expression of HSPB8 in the hippocampal tissue of 8-week-old diabetic mice is up-regulated, which may enhance autophagy by promoting the fusion of autophagosome and lysosome.

The author summarized two mother-daughter patients with myotonic dystrophy type 1 (DM1) who were first diagnosed with diabetes who were admitted to the Department of Endocrinology of Zhu Xianyi Memorial Hospital of Tianjin Medical University in May 2019. Both patients were complicated with muscular atrophy and premature cataract, with similar medical history in their families and autosomal dominant inheritance. The trinucleotide CTG in the 3'UTR region of DMPK gene was repeated more than 50 times, and the diagnosis of DM1 was clear. There was no hyperinsulinemia in both patients, but the insulin dosage was large (0.98, 0.70 U/Kg) and the blood glucose control was poor (glycosylated hemoglobin 10.8%, 11.0%). The blood glucose control of patients combined with pioglitazone and metformin improved. The key words "myotonic dystrophy" and "diabetes" were used to search the full-text database of Chinese journals, Wanfang database and Pubmed, and 4 case reports of DM1 complicated with diabetes were screened out. Combined with the 2 patients reported in this article, the summary analysis was performed, which suggested that insulin sensitizers thiazolidinediones and metformin were effective in controlling blood glucose in DM1 patients. For diabetic patients with multi-system manifestations such as muscular symptoms and early cataract, attention should be paid to the screening and correct diagnosis and treatment of myotonic dystrophy, a rare disease.

Compound hypersensitivity induced by exogenous insulin is a rare adverse reaction related to insulin therapy, which is characterized by local injection reaction of rash and pruritus combined with fluctuation of blood glucose and local lipoatrophy. The diagnosis and treatment of this disease is difficult, especially in diabetic patients with endogenous insulin deficiency, and the treatment is often extremely difficult. A 52-year-old female patient showed a rapid decline in endogenous islet function after one month of intensive insulin therapy, accompanied by recurrent severe hypoglycemia, local pruritus, rash and local lipoatrophy after injection, and positive insulin autoantibodies. After subcutaneous pumping of insulin analogues with 5-10-fold dilution of normal saline for 1 year, the onset of hypoglycemia and local reaction of injection were effectively alleviated.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by progressive destruction of pancreatic islet β cells, which mostly occurs in children and adolescents. Studies suggest that early immune intervention can fundamentally delay the progression of the disease and even achieve the goal of reversal. Immune intervention drugs are important immunotherapy methods for T1DM, with good prospects. They mainly include antigen-specific and non-antigen-specific immunotherapy (including immune cell targeted therapy and cytokine therapy, etc.). This article reviews the current progress of immune intervention drug therapy, and provides more evidence for future clinical treatment.

Diabetes is a worldwide epidemic disease, its prevalence is increasing day by day, and diabetes-related complications have the characteristics of high disability and mortality. There are two main measures for blood glucose management in diabetic patients: hypoglycemic drugs and non-hypoglycemic drugs. In recent years, more and more studies have shown that intestinal flora is closely related to diabetes. Some hypoglycemic drugs such as metformin and acarbose can have certain effects on intestinal flora and its related metabolites. With the deepening of the research on intestinal flora, the interventions of non-hypoglycemic drugs in diabetes management, such as diet and exercise, can not only help patients improve blood sugar, but also have a certain impact on intestinal flora and its metabolites, thus benefiting patients.

Based on the completed basic and clinical studies related to glucagon-like peptide-1 receptor agonist (GLP-1RA), the protective mechanism of GLP-1RA was summarized from the aspects of blood glucose control, weight reduction, lipid metabolism improvement, endothelial function improvement, blood pressure reduction and cardiovascular protection, and the similarities and differences and possible mechanisms of cardiovascular protection of GLP-1RA were expounded.

Sodium-glucose cotransporter 2 inhibitor (SGLT-2i) has protective effects on metabolic stress and cardiovascular and kidney. These benefits other than hypoglycemic benefits have received increasing attention, but the mechanisms related to their metabolic regulation and cardiorenal benefits are still unclear. Based on this, the author elaborated the details of metabolic regulation of SGLT-2i on type 2 diabetes and the possible mechanisms of cardiovascular and renal benefits.