Volume 12 · Issue 02 · 2020

With the rapid development of medicine, all kinds of new detection methods emerge one after another, which makes almost no one in the world in a completely healthy state, and also makes the concept of medical field gradually shift from treating diseases to preventing diseases, among which the field of diabetes is no exception. The rapid epidemic of diabetes has gradually become one of the biggest burdens in the medical field of all countries in the world. Therefore, the original intention of the concept of prediabetes was to be able to identify potentially high-risk groups as early as possible and thus explore effective interventions. However, the definition of prediabetes has been debated for nearly 20 years. The author summarizes the origin and evolution of prediabetes, and puts forward his own views on these controversies.

Type 1 diabetes mellitus (T1DM) is an absolute insulin deficiency caused by T lymphocyte-mediated islet β cell-specific immune damage, which in turn leads to an increase in blood sugar. Insulin replacement is the main clinical treatment at present. Although it can control hyperglycemia, it can't stop the progressive failure of pancreatic islet function and effectively prevent the occurrence of diabetes-related complications. Based on the pathophysiological characteristics of T1DM, cell therapy aims to protect or even reconstruct the endogenous insulin secretion system through islet β cell replacement or regenerative therapy, thereby improving the disease progression and prognosis. It is a research direction that has attracted much attention in the field of T1DM therapy. This article will focus on the research status and development direction of islet transplantation and pluripotent stem cells in the treatment of T1DM.

This management recommendation aims to strengthen the scientific management of patients with diabetes complicated with SARS-CoV-2 pneumonia and improve the prognosis. Hospitalized diabetic patients complicated with novel coronavirus pneumonia can formulate corresponding individualized blood glucose control goals and treatment strategies according to their condition. For mild and common patients, it is recommended to adopt strict or general blood sugar control goals and apply subcutaneous insulin therapy; For severe or critical patients, it is recommended to adopt a relatively loose blood glucose control target (fasting blood glucose 7.8-10.0 mmol/L, and 2 h postprandial blood glucose 7.8-13.9 mmol/L) and treat with intravenous insulin infusion. For non-hospitalized diabetic patients, it is recommended to strengthen self-management and adhere to the treatment.

To investigate the effects of nuclear factor erythroid 2-related factor 2(Nrf2) and phosphatidylinositoll 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway on proliferation of human papillary thyroid carcinoma K1 cells under high glucose environmental conditions, and explore the role of glucose metabolism-related enzymesin the proliferation of K1 cells.

According to different treatment factors, K1 cells were divided into five groups: normal glucose group (5.5 mmol/L glucose cultured for 48 h), high glucose group (5.5 mmol/L glucose cultured for 24 h, then 25 mmol/L glucose cultured for 24 h), Nrf2siRNA group (transfected cells in 5.5 mmol/L glucose for 24 h, then cultured in 25 mmol/L glucose for 24 h), NcsiRNA group (negativly transfected cells for 24 h under 5.5 mmol/L glucose conditions, then cultured in 25 mmol/L glucose for 24 h), LY294002 group (negativly transfected cells for 24 h under 5.5 mmol/L glucose conditions, plus 50 μmol/L LY294002 pre-incubation for 0.5 h and then cultured in 25 mmol/L glucose for 24 h). Cell proliferation was detected by MTT assay, distribution of Nrf2 in K1 cells was detected by immunofluorence staining, and the expression levels of PI3K, p-PI3K, Akt, p-Akt, Nrf2 (nuclear and cytoplasmic protein), G6PD (glucose-6-phosphate dehydrogenase) and PKM2 (pyruvate kinase M2) proteins were detected by Western blot. The two groups of data were compared by independent sample t test, and the multiple groups of data were compared by one-way anova.

Compared with the normal glucose group, the proliferation rate of K1 cells, protein expression of PI3K, p-akt/Akt, Nrf2, G6PD and PKM2 [(87.31±3.67)% vs (126.64±5.41)%, 0.272±0.039 vs 0.425±0.019, 0.168±0.035 vs 0.446±0.021, 0.308±0.026 vs 0.597±0.014, 0.421±0.024 vs 0.626±0.026,0.198±0.023 vs 0.314±0.023, t=6.109-16.951, all P<0.05], as well as the proportion of Nrf2 distribution in the nucleus [(21.6±4.5)% vs (91.2±3.5)%, χ ²=98.497] were significantly increased in the high glucose group (P<0.01). Compared with the high glucose group, the proliferation rate of K1 cells in Nrf2 siRNA group was significantly decreased, and the protein expression of G6PD and PKM2 was down-regulated, the difference was statistically significant (t=8.936, 7.056, 8.843, all P<0.01), and the LY294002 group also showed a similar trend (t=7.228, 6.351, 7.910, all P<0.01). Compared with the high glucose group, the protein PI3K and Akt levels of K1 cells in LY294002 group were not significantly changed, p-PI3K, p-Akt, nuclear Nrf2, cytoplasmic Nrf2 protein levels and the ratio of nuclear and cytoplasmic Nrf2 were significantly inhibited (t=5.748-23.572, all P<0.01).

High glucose can activate PI3K/Akt signaling pathway, up-regulate Nrf2 expression and nuclear translocation, and up-regulate the expression of pentose phosphate and glycolytic pathway-related enzymes PKM2 and G6PD to promote the proliferation of K1 cells.

Analyse the clinical features and gene mutations of a child with HK1-HI.

The children and their parents ethylenediamine traacetic acid anticoagulated 3 ml were taken separately for gene sequencing analysis.Genetic variation related to clinical phenotypes that are clear or likely to be relevant to the subject is verified by Sanger sequencing.

This child started from 5 months after birth. Effective for diazoxide treatment. Her pancreatic scan results showed that the histological classification of the child was diffuse. A c.886 C>A (p. L296M) heterozygous mutation was found in the 12th exon of the HK1 gene, which changed the amino acid 296 of the encoded product from leucine (Leu, L) to A. Thionine (Met, M). This mutation was paternal inheritance.

Mutations in the paternal inherited HK1 gene in Chinese children may lead to the occurrence of HK1-HI. This type of CHI has an earlier onset and shows effectiveness to diazoxide. Most of his histological types are diffuse.

To explore the value of fingertip capillary whole blood glucose (CBG) combined with Chinese Diabetes Risk Score (CDRS) in screening for type 2 diabetes mellitus (T2DM) and pre-diabetes [impaired fasting glucose (IFG) and impaired glucose tolerance (IGT)].

From July to August 2018, 3 798 community residents from Jiangsu branch center of the study on evaluation of innovated screening tools and determination of optimal diagnostic cut-off points for type 2 diabetes in Chinese multi-ethnic(SENSIBLE study) were included. The fingertip fasting CBG (FCBG) and 2-hour CBG after glucose load (2 h-CBG) were measured. Oral glucose tolerance test (OGTT) was used as the "gold standard" for the diagnosis of T2DM or pre-diabetes. Receiver operating characteristic curve (ROC) was used to evaluate the cut-off point and the screening efficacy of CBG alone and combined CDRS.

(1) According to the World Health Organization(WHO) diagnostic criteria in 1999, the optimal cut-off point for screening T2DM by FCBG was 6.7 mmol/L, and 6.2 mmol/L when combined with CDRS (≥ 25). The sensitivity (specificity) of FCBG, CDRS (≥ 25) and FCBG+CDRS (≥ 25) were 79.48% (91.20%), 91.17%(27.56%) and 78.96%(78.22%), respectively. (2) The optimal cut-off point for screening IFG by FCBG was 6.0 mmol/L, and 6.1 mmol/L when combined with CDRS (≥ 25). The sensitivity (specificity) of the three methods were 82.31%(68.94%), 89.93%(27.53%) and 75.18%(74.11%), respectively. Compared with CDRS (≥ 25), the AUC of FCBG+CDRS (≥25) in screening for T2DM and IFG were increased by 32.3% and 27.1%, respectively. (3) The optimal cut-off point for IGT screening by 2 h-CBG was 8.2 mmol/L, and 8.5 mmol/L in combination with CDRS (≥25). The sensitivity (specificity) of 2 h-CBG, CDRS (≥ 25) and 2 h-CBG+CDRS (≥25) were 88.66%(76.04%), 84.85%(28.58%) and 80.67%(77.87%), respectively. Compared with CDRS (≥25), the AUC of 2 h-CBG+CDRS (≥25) in screening IGT was increased by 43.6%.

CBG and CDRS are both effective tools for screening T2DM and pre-diabetes, and their combination can further improve the screening efficiency.

To assess the clinical inertia and associated factors in type 2 diabetic (T2DM) patients with diet/exercise intervention or oral antidiabetic drugs (OADs) therapy.

Patients with baseline glycated hemoglobin A_1c (HbA_1c)≥7.0% who participated the study of "Direct Medical Cost Investigation of Diabetes in Chinese Urban Tertiary Hospitals" from March 2015 to May 2015 were recruited and their medication data of baseline and 6-month after follow-up were compared. Clinical inertia was defined as the failure to upgrade treatment after 6 months of follow-up [uninitiated with additional another OAD, glucagon-like peptide 1 (GLP-1) receptor agonist or insulin]. Multivariate Logistic regression was used to analyze the independent predictive factors of clinical inertia.

A total of 178 patients [101 males and 77 females, (58±11) years, (7±7) years duration of diabetes] with the mean HbA_1c (8.6±1.6)% were recruited in this study. 52.2%(93/178) T2DM patients experienced clinical inertia in the 6 months following-up period. Upgraded treatment include: additional initiated with another OADs [30.9%(55/178)]or insulin [16.3%(29/178)] or GLP-1 receptor agonists [0.6% (1/178)]. The main factors associated with clinical inertia were HbA_1c 7.5%-8.9% (OR=3.437, 95%CI:1.421-8.309) and HbA_1c≥9.0% (OR=9.738, 95%CI:3.634-26.901), diabetic retinopathy (OR=2.732, 95%CI:1.004-7.431), taking ≥2 OADs (OR=2.651, 95%CI:1.248-5.635) and diabetic duration (OR=1.064, 95%CI:1.005-1.126).

Clinical inertia affects more than half of T2DM patients with substandard glycemic control. Patients with longer duration of diabetes, poor glycemic control, taking ≥2 OADs and complicated diabetic retinopathy are more likely to have clinical inertia.

To investigate the effects of glucagon-like peptide-1 analogs on sleep-disordered breathing and diabetic microangiopathy in patients with type 2 diabetes mellitus and obstructive sleep apnea-hypopnea syndrome (OSAHS).

A total of 239 patients with T2DM in the Department of Endocrinology and Sleep Center of Henan Provincial People′s Hospital were collected for polysomnography monitoring and diabetic microangiopathy screening from January 2017 to December 2018. A total of 93 patients with T2DM and OSAHS were included, who were diagnosed with diabetic microangiopathy, 50 patients treated with liraglutide as the treatment group, and 43 patients treated with conventional hypoglycemic drugs as the control group. After 6-month treatment, changes of body mass index, waist circumference, HbA_1c, blood pressure, lipid profile, uric acid, apnea hypopnea index and the improvement of diabetic microangiopathy in the two groups were compared. Student-t test, Rank-sum test or Chi-square test were used for comparison between the two groups. ANCOVA and partial correlation analysis were used to evaluate the correlation between each index and AHI variation value. Multivariate Logistic regression analysis was used to analyze the correlation between liraglutide and the improvement of diabetic microangiopathy.

After 6-month treatment, compared with control group, BMI, waist circumference, HbA_1c, systolic blood pressure, and AHI were decreased more significantly in treatment group[(-1.85±2.46) vs (0.02±0.46) kg/m², (-3.24±10.34) vs (-0.07±0.88) cm, (-0.83±0.55)% vs (-0.06±0.40)%,(-7.92±14.16) vs (-0.56±16.16) mmHg (1 mmHg=0.133 kPa) , (-3.16±3.52) vs (0.5±1.54) time/h, t=2.159-7.703, all P<0.05], diabetic microangiopathy was improved more significantly in treatment group [26.0%(13/50) vs 9.3%(4/43), χ ²=4.315, P<0.05]. The change in AHI after treatment was positively correlated with changes in BMI, waist circumference and HbA_1c (r=0.238, 0.232 and 0.317, all P<0.05), and was negatively correlated with age (r=-0.21, P<0.05). After adjusting for age, duration of diabetes, BMI, waist circumference, HbA_1c, and systolic blood pressure, liraglutide was associated with AHI variation value (F=8.155, P=0.005). After adjusting for age, duration of diabetes, BMI, waist circumference, HbA_1c, systolic blood pressure, and AHI, multivariate Logistic regression analysis showed that liraglutide could improve diabetic peripheral neuropathy (OR=3.426, 95%CI:1.024-11.460, P=0.046).

Liraglutide may improve sleep-disordered breathing and diabetic microangiopathy in patients with type 2 diabetes mellitus and obstructive sleep apnea-hypopnea syndrome, but has no effect on diabetic nephropathy and diabetic retinopathy.

To evaluate the relationship between β-cell function and sudomotor function in patients with type 2 diabetes mellitus (T2DM).

A total of 385 patients with T2DM who were hospitalized in the Department of Endocrinology, General Hospital of Eastern Theater Command from March 2016 to May 2018 were enrolled. According to the hands and feet electrochemical skin conductance (HESC, FESC) assessed with SUDOSCAN, patients were divided into normal sudomotor function group (n=262) and sudomotor dysfunction group (n=123). Basal insulin secretion was assessed with homeostasis model assessment of β-cell (HOMA-β). Early-phase insulin secretion function was assessed with the ratio of 30 min increment in C-peptide levels to 30 min increment in glucose levels (ΔC-P30/ΔG30) and the ratio of 30 min increment in insulin levels to 30 min increment in glucose levels (ΔI30/ΔG30). Total β-cell function was assessed with ratio of area under the curve (AUC) of C-peptide to the AUC of glucose in 120 min (C-P _AUC/G_AUC) and ratio of the AUC of insulin to the AUC of glucose in 120 min (I_AUC/G_AUC).

(1) Compared with those in the normal sudomotor function group, ΔC-P30/ΔG30 and ΔI30/ΔG30 in sudomotor dysfunction group were lower [0.19(0.08, 0.30) vs 0.30(0.19, 0.53) and 1.47(0.67, 3.28) vs 2.26(1.28, 4.65), respectively, Z=-5.495,-3.897, all P<0.05], and also C-P_AUC/G_AUC and I_AUC/G_AUC were much lower [0.07(0.04, 0.16) vs 0.12(0.06, 0.25) and 2.79(0.76, 6.35) vs 3.30(1.35, 8.32) respectively, Z=-3.894, -2.092, all P<0.05]. (2)Both ΔC-P30/ΔG30 and ΔI30/ΔG30 were positively correlated with HESC ( r=0.306, 0.272, respectively, all P<0.05) and FESC (r=0.304, 0.233, respectively, all P<0.05). (3) Multiple linear stepwise regression analysis showed that ΔC-P30/ΔG30, diabetes duration, age, glycated hemoglobin and plasma uric acid were independent factors that impacted on the sudomotor function.

Early-phase insulin secretion dysfunction independently related with sudomotor dysfunction in T2DM patients. Evaluation of sudomotor function maybe necessary for screening diabetic peripheral neuropathy in patients with early-phase insulin secretion dysfunction.

The purpose of this systematic review was to evaluate evidence for different guideline recommendations regarding needle reuse, rotation, injection site for a certain type of insulin and needle length, and to assess whether these recommendations are evidence-based.

A search of computer was carried out in PubMed, Medline, Embase, CNKI, Weipu data, Wanfang data from 1946 to December 2016, and diabetes education official websites in United States, Australia, Canada, Denmark, Hongkong (China), Netherlands and United Kingdom for insulin injection guidelines published before December 2016. All inclusions of guidelines for insulin injection followed the criteria of inclusion and exclusion. Two researchers independently screened and evaluated the quality of included guidelines with Appraisal of Guidelines for Research and Evaluation, and then extracted relevant data for analysis.

In the original search, 967 100 literatures were identified, and 10 guidelines were included in the final review. Guidelines were published from 2007 to 2016. We found that evidence of recommendations on using the pen needle only once, rotating the injection sites among different anatomic areas (abdomen, thigh, arm and buttocks) and determining the injection sites by insulin type are not accurate enough.

In these existing guidelines for insulin injection, some recommendations are not fully strict. Further randomised clinical trial is warranted to provide scientific basis for developing the recommendations.

The quality of sleep has a direct impact on the physical and psychological health of individuals, and there is a significant relationship between personality tendency and sleep quality. The former can have an important impact on the latter. We investigated the sleep status and the occurrence of type D personality in patients with type 2 diabetes mellitus by questionnaire, and explored the relationship between them. The questionnaire survey used D-type personality scale and Pittsburgh sleep quality index scale, and the results showed that the scores of all dimensions of sleep quality in D-type personality group were higher than those in non-D-type personality group; Except for the use of hypnotic drugs, the differences in the scores of other dimensions of sleep quality between the two groups were statistically significant, suggesting that sleep disorders in patients with type 2 diabetes may be related to type D personality, and personality characteristics should be considered when formulating intervention programs.

Drugs may induce elevated blood glucose by affecting the secretory function of islet beta cells or reducing the sensitivity of peripheral tissues to insulin. Non-endocrine hormone drugs that easily lead to hyperglycemia or diabetes mainly include antihypertensive drugs, lipid-lowering drugs, antipsychotic drugs, immunomodulatory drugs, etc. The diagnosis of drug-induced hyperglycemia is mainly based on the clinical medication history, the sequence of related drug use and the occurrence of hyperglycemia, and the change trend of blood glucose after drug withdrawal or drug reduction.

Diabetic peripheral neuropathy is the most common complication in diabetic patients, and auxiliary detection is one of the important diagnostic methods. Nerve conduction velocity is a commonly used auxiliary detection method in clinic. It mainly detects the conduction function of large myelinated nerve fibers (A α and A β), but it cannot measure small fiber lesions. However, small fiber neuropathy often occurs before large fiber neuropathy. When diabetic patients have abnormal sensation such as warm or cold or autonomic dysfunction, it is often suggested that small fiber nerve function such as A δ nerve fiber and unmyelinated C nerve fiber is impaired. The methods of detecting small fiber nerves mainly include: quantitative sensory test, skin sympathetic reflex, corneal confocal microscope, skin biopsy, etc. These methods are important for the diagnosis and intervention of small fiber neuropathy.

In recent years, with the emergence of a large amount of high-quality evidence-based medical evidence, the decision-making philosophy of various authoritative diabetes diagnosis and treatment guidelines has gradually turned to focus on hypoglycemic drugs with clear cardiovascular benefits or safety. Dipeptidyl peptidase-4 inhibitors, as the earliest new hypoglycemic drugs to carry out cardiovascular outcome studies (CVOT), have confirmed their cardiovascular safety. The newly announced cardiovascular outcome study using linagliptin versus glimepiride in the treatment of patients with type 2 diabetes mellitus (T2DM) (CAROLINA) is currently the only CVOT and linagliptin using the active drug (glimepiride) as a control. The cardiovascular and renal safety outcome trial (CARMELINA) for the treatment of adult T2DM patients at high risk of heart and/or kidney disease complements each other, confirming the long-term cardiovascular safety of linagliptin in a wider T2DM population, and providing more evidence-based evidence for choosing the optimal treatment plan for T2DM patients.