Volume 02 · Issue 04 · 2010

Diabetic patients are prone to periodontal disease, which is one of the complications of diabetes that has been recorded in textbooks for a long time. However, because vascular complications of diabetes are the main cause of disability and death, internal medicine or endocrinologists pay more attention to whether the blood sugar, blood pressure and blood lipids of diabetic patients are controlled, and whether antiplatelet therapy is needed, but rarely pay attention to patients' oral problems.

periodontitis (periodontitis) is a chronic non-specific inflammatory disease caused by bacterial infection, with a prevalence of more than 80% in adults in China. The Third National Oral Health Epidemiological Survey showed that the periodontal health rate was only 14.5% in the 35-44 year old group, and the prevalence and severity of periodontitis increased with age^[1]。 Long-term poor control of blood sugar in diabetic patients can lead to a variety of complications. Some scholars have proposed that periodontitis is the sixth complication of diabetes^[2]There is a close bi-directional relationship between the two^[3]。 This article mainly introduces the research progress of the interaction between periodontitis and type 2 diabetes.

Diabetes mellitus is a complex group of multi-system metabolic abnormalities, which can also have many effects on oral tissue, and sometimes even be the main factor causing oral lesions. Patients with poor blood sugar control are highly prone to severe or recurrent bacterial or fungal infections. This article introduces the occurrence of various oral mucosal diseases in diabetic patients, in order to arouse the attention of diabetic doctors.

To investigate the periodontal status of the patients with type 2 diabetes mellitus (T2DM) and to characterize the relationship between periodontitis and diabetes.

A total of 118 subjects with T2DM, 78 subjects only with hypertension (HBP) and 50 systemic healthy subjects were enrolled from January to May 2009 in Beijing. Periodontal index including plaque index (PLI), probing depth (PD), bleeding index (BI), attachment loss (AL) and the number of missing teeth were recorded. Then Logistic regression model was set to analyze the relationship between periodontitis and diabetes.

PLI(2.2±0.5), PD((3.6±0.8)mm), AL((4.9±1.9)mm), the number of missing teeth(10±8) and the prevalence of severe periodontitis(76.3%) in diabetic patients were significantly higher than those in both HP and systemic healthy subjects. Compared with non-diabetic subjects, diabetic patients had a higher risk of moderate or severe periodontitis, with OR=5.8-38.9. After adjusting age, gender, smoking and PLI, poorer controlled diabetes was still associated with higher risk of moderate or severe periodontitis with OR=31.21, while in well-controlled group with OR=6.99.

T2DM patients had poorer periodontal status than non-diabetic subjects. Diabetes, especially poor-controlled subjects, may be associated with increased risk of moderate or severe periodontitis.

To explore the association between diabetes mellitus and metabolic syndrome, smoking, and the interaction between metabolic syndrome and smoking.

Subjects were recruited from the prospective cohort study on the prevention of multiple metabolic disorders and metabolic syndrome in Jiangsu province of China. A total of 3598 subjects (1451 men and 2147 women) were enrolled and followed for at least 5 years. Logistic regression models were used to calculate the indices of interaction between metabolic syndrome and smoking.

After adjustment for age, sex, smoking, drinking, family history, subjects with metabolic syndrome had a 2.79(95%CI 2.03-3.83) adjusted relative risk(aRR) of developing diabetes mellitus when compared with those individuals without metabolic syndrome at baseline. The aRR of metabolic syndrome components were 1.78(95%CI 1.28-2.50) for elevated triglyceride and 3.72(2.70-5.13) for impaired fasting glucose respectively. Compared with non-smokers, the aRR of smokers were 3.03(1.69-5.45) and 5.45(2.12-14.03) respectively in individuals with or without metabolic syndrome. The results of interaction analysis were RERI=5.57(0.37-11.50), AP=0.44(0.16-0.72), SI=1.90(1.09-3.32).

Both metabolic syndrome and smoking are risk factors for diabetes mellitus. Combining effects of metabolic syndrome and smoking may contributed to addictive increase the risk for diabetes mellitus, the combined risk is more serious than the sum of the effects of metabolic syndrome and smoking.

To evaluate left ventricular structure and function in patients with asymptomatic type 2 diabetes mellitus (T2DM) by cardiac cine magnetic resonance imaging (MRI).

Sequential left ventricular short-axis cine MRI was acquired on 85 diabetic out-patients (T2DM group) and 43 normal health controls (control group) from November 2005 to January 2006. Parameters of resting left ventricular diastolic and systolic function and hemodynamics were analyzed and compared between the two groups, including end diastole volume index (EDVI), end systole volume index (ESVI), stroke volume index (SVI), cardiac index (CI), eject fraction (EF), wall thickness of end diastole (WTED), wall thickness of end systole (WTES), thickening (TN), wall motion (WM), body surface area (BSA), peak ejecting rate (PER), time of peak ejecting (TPE), peak filling rate (PFR) and time of peak filling (TPF). Two-tailed independent-samples t test, χ² test, and multiple logistic regression were used for data analysis.

In the T2DM group, ESVI was lower than the control group ((22±8) vs (25±5) ml/m^2,t=2.265, P<0.05); however, EF was higher than the control group (59%±9% vs 56%±6%, t=-2.457, P<0.05). Left ventricular wall thickness was increased than the control group, and PFR was decreased ((282±73) vs (321±99) ml/s, t=2.508, P<0.05). Multiple logistic regression model showed that hyperglycemia was the most important factor of left ventricle dysfunction (χ²=3.781, P=0.052).

Cardiac cine MRI is considered the gold standard for evaluating left ventricular function. Diabetic cardiomyopathy, manifested by diastolic dysfunction followed by abnormalities in systolic function, is common in type 2 diabetic patients without apparent cardiocomplications. Hyperglycemia may be the most important factor of diabetic cardiomyopathy.

To investigate the expression of tear proteins in type 2 diabetic patients by proteomics technique.

Fifteen type 2 diabetic patients without retinopathy, 15 patients with retinopathy, and 15 age and gender-matched non-diabetic controls were recruited and 5-10 μl basal tear samples were collected. The expressional difference of tear proteins among the three groups were analysed with 2-DE and Progenesis Samespots software. The statistical difference among the three groups were estimated by one-way analysis of variance followed by Bonferroni multiple comparison test. Pearson correlation analysis were performed between expressional volume of tear proteins and HbA1c, diabetic duration.

In comparison with non-diabetic controls, 11 tear protein expressions in diabetic patients with retinopathy were up-regulated (F value was 3.635, 3.479, 4.427, 5.031, 3.508, 5.253, 3.368, 4.186, 3.669, 3.778, and 3.856, respectively, all P<0.05), while 5 proteins down-regulated in diabetic patients with and without retinopathy (F value was 5.149, 8.179, 6.692, 4.733, and 3.539, respectively, all P<0.05). In addition, the expressional levels of 6 tear proteins were higher in diabetic patients with retinopathy than those without retinopathy (F value was 4.427, 5.031, 4.186, 3.669, 3.778, and 3.856, respectively, all P<0.05). A significant correlation was found between the expressional volume of spot 200 and HbA1c(r=0.370, P<0.05)in diabetic patients, but no any correlation was demonstrated between HbA1c and expressional volumes of the other 15 spots, or between diabetic duration and expressional volumes of spots(all P>0.05).

These differentially expressed tear proteins in diabetic retinopathy might be useful in understanding the pathogenesis and evaluating treatment.

To establish a screening method in vitro based on affinity and dissociation assay for candidate peptides of epitopes to mapping T cell epitopes of beta cell autoantigens.

Six islet cell autoantigens, including 65-kDa isoform of glutamic acid decarboxylase (GAD65), islet antigen (IA-2), preproinsulin (PPI), islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), islet amyloid polypeptide (IAPP) and glial fibrillary acidic protein (GFAP), were analyzed using SYFPEITHI and BIMAS algorithms. Fifteen peptides were identified as human leukocyte antigen(HLA)-A*0201 candidate epitopes for synthesis and screening. The peptide binding assay and temporal stability assay of peptide/HLA-A2 complexes were detected in HLA-A2 transgenic T₂ cell. One-way analysis of variances was used for data analysis.

In peptide binding assays for T₂ cell, 7 peptides which were IGRP_152-160, IGRP_215-223, IGRP_228-236, PPI_2-10, insulin B_10-18, IA-2_172-180 and GFAP_143-151 showed >80% affinity with HLA-A2 molecule. Dissociation assay showed that 4 hour-dissociation rates of insulin B_10-18, IGRP_228-236, GFAP_143-151 and IA-2_172-180 were <20%.

This study suggests that affinity evaluation of candidate of epitope peptide with HLA molecule in vitro should consider both binding assay and dissociation assay, which would be helpful to minimize the number of target peptides in experiments and facilitate novel T cell based-diagnosis for type 1 diabetes.

To investigate the changes of endothelin-1 (ET-1), calcitonin gene-related peptide (CGRP) and substance P (SP) in the lungs of type 2 diabetic rats.

A total of 10 male Wistar rats were fed with high lipid feed stuff and intravenously injected with streptozotocin to establish type 2 diabetic models. Another 8 rats were taken as normal controls. Twelve weeks after the model establishment, animals were sacrificed and the lung samples were obtained. After lastic fiber staining, the ratio of vascular wall thickness/vascular external diameter (WT%) and the ratio of vascular wall area/total vascular area (WA%) of the lung arteries were measured. The expression of ET-1, CGRP and SP was tested by immunohistochemistry, and the average optical density and the ratio of positive area to total area of field of view was investigated to evaluate the intensity of positive expression. t test was used for data analysis.

The ratio of total area of alveolar septa to total area of field of view, WT% and WA% in the diabetic rats were increased than those of the normal controls (0.42±0.10 vs 0.29±0.06, t=5.842, P<0.05; 26%±8% vs 19%±9%, t=3.023, P<0.05; 42%±8% vs 36%±9%; t=2.526, P<0.05). Compared with the normal controls, average optical density and the ratio of positive area to total area of field of view of ET-1 or SP in the diabetic rat lung were increased (ET-1: 86±5 vs 83±4, t=2.402, P<0.05; SP: 101±4 vs 100±3, t=2.530, P<0.05; ET-1: 0.016±0.017 vs 0.010±0.008, t=2.501, P<0.05; SP: 0.014±0.014 vs 0.009±0.009, t=2.127, P<0.05), but average optical density and the ratio of the positive area to total area of field of view of CGRP in the diabetic rats lung were not increased.

The expression of ET-1 may show an upward trend, which might be associated with the changed pathology of pulmonary hypertension in diabetes.

To investigate the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in the kidney of streptozocin (STZ)-induced diabetic rats and the effects of cyclosporine A (CsA) on their expression.

STZ-induced diabetic rats were randomly assigned to the non-treatment group (n=8), insulin intervention group (n=9), 1 μg·g^-1·d^-1 CsA before modeling group(n=9), 4 μg·g^-1·d^-1 CsA before modeling group(n=8), 8 μg·g^-1·d^-1 CsA before modeling group(n=8), 1 μg·g^-1·d^-1 CsA post modeling group (n=8), 4 μg·g^-1·d^-1 CsA post modeling group (n=7), or 8 μg·g^-1·d^-1 CsA post modeling group (n=7). Another 10 normal rats were used as controls. The renal expression of MMP-2 and MMP-9 mRNA and protein were determined by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The data were analyzed by one-factor analysis of variance and rectilinear correlation analysis.

At 8 weeks, the 24-h urine microalbuminuria in the diabetic group was significantly higher than that in the normal control group ((5.80±3.23) and (1.24±0.21) mg/24 h, respectively; F=4.229, P<0.01). The 24-h urine microalbuminuria was decreased after the treatment of CsA. The expression of MMP-2 and MMP-9 mRNA (MMP-2: 2.22±0.08; MMP-9: 2.55±1.10) and protein (MMP-2: 3.1±1.5; MMP-9: 2.8±1.0) in the mesengium and epithelium of the renal tubular of the diabetic group was significantly higher than that of the normal control group (MMP-2 mRNA: 0.70±0.26, F=6.031; MMP-9 mRNA: 0.37±0.24, F=5.193; MMP-2 protein: 1.0±0.0, F=7.532; MMP-9 protein: 1.0±0.0, F=6.100; all P<0.01). There was no preventive effect of insulin on the expression of MMP-2 and MMP-9. However, following the intervention of CsA, all of the abnormal expression could be downregulated. There was a positive relationship between the mRNA and protein expression of MMP-2 (r=0.618, P<0.01), while no relationship existed between those of MMP-9 (r=0.420, P>0.05).

The abnormal expression of MMP-2 and MMP-9 in the diabetic kidney could be downregulated by CsA. Diabetic nephropahty might be effectively prevented by immunosuppressive agents.

To investigate the influence of benidipine on the Rho kinase and epithelial-mesenchymal transdifferentiation of renal tubular epithelial cells from diabetic rats .

Fifty four Wistar rats(180~200) were randomly divided into the following four groups: normal(n=8), diabetes(n=13), benidipine-treatment(n=12) and fasudil-treatment(n=12). All rats were sacrificed after three months of feeding with or without benidipine or fasudil-treatment. Pathological changes to the glomeruli and renal interstitium were studied using HE staining. Expression of ROCK1, α-SMA and E-cadherin in rat renal cortex were revealed by immunohistochemistry. Changes in the MYPT1 phosphorylation profile, ROCK1, α-SMA and E-cadherin expression were revealed by Western blot. Changes in the levels of ROCK1 mRNA expression were analyzed by real-time PCR. One-way ANOVA and SNK or LSD test was used for data analysis.

Compared to the normal rats[0.39(0.23-0.55)], ROCK1 was 0.93(0.64-1.28) in diabetes group and 0.61(0.52-0.90) in benidipine group. Elevated phosphorylation of MYPT1 in diabetic rats while benidipine treatment of diabetic rats resulted in attenuated MYPT1 phosphorylation(F=7.37, P<0.01). Increased expression of ROCK1, α-SMA protein and ROCK1 mRNA and decreased expression of E-cadherin protein in diabetic rats while decreased ROCK1, α-SMA protein and ROCK1 mRNA expression and increased expression of E-cadherin protein in the benidipine intervention group(F=20.94, P<0.01; F=125.26, P<0.01; F=18.47, P<0.01; F=28.15, P<0.05).

Benidipine may reduce the epithelial-mesenchymal transdifferentiation and renal interstitial fibrosis in diabetic rats through a mechanism by which ROCK activity is inhibited.

To explore the role of adiponectin and receptors of adiponectin (AdipoR1, AdipoR2) in the development of diabetic kidney disease (DKD) in diabetes mellitus rats induced by streptozotocin(STZ).

A total of 64 SD rats were randomly divided into two groups. Thirty-two rats were in normal control(NC) group and the others were in diabetes mellitus(DM) group. The rats in DM group were injected STZ intraperitoneally with a dose of 60 mg/kg while the ones in NC group were only done with the same dose of citric acid buffer. At 2, 6, 10 and 12 weeks, weight, fast blood glucose and 24-hour urinary albumin excretion were recorded, serum fast blood insulin was also measured. Adiponectin levels in urine and serum were evaluated by ELISA. The pathological changes of kidney were examined by light microscope. Renal expression of AdipoR1, AdipoR2 was determined by immunohistochemistry.

(1)The levels of adiponectin in urine and blood in DM group were higher than that in NC group after 2 weeks(6 weeks, 10 weeks, 12 weeks, P<0.01) and increased gradually during the whole experiment.Correlative analyses revealed a positive correlation between serum adiponectin and the quantification of albumin in 24 h urine, urinary adiponectin (r=0.806, P<0.01; r=0.696, P<0.01)and between urinary adiponectin and the quantification of albumin in 24 h urine(r=0.728, P<0.01). Stepwise regression analyses showed that the quantification of albumin in 24 h urine was independently associated with adiponectin concentrations(β=0.806, P<0.01). (2)Compared the NC group, the expressions of AdipoR1 and AdipoR2 in kidney tissue were enhanced in DM group, and increased gradually(F value was 11.68, 23.20, respectively). There was a significant positive correlation between adiponectin and AdipoR1 and AdipoR2 in DM group(r=0.666, P<0.001; r=0.684, P<0.01).

With the progression of DM, the levers of adiponectin and its receptors increase which shows a significant protective effect in renal damage.

To observe the effect of triptolide on podocyte protein expression of Nephrin and Podocin and investigate its mechanism in kidney of type 2 diabetic rats.

50 eight-week SPF male Wistar rats weighted (200±20) g were randomly divided into two groups : normal control group (n=10) and model group (n=40). Rats were fed a high fat high sugar diet for 8 weeks and given a low dose of streptozotocin (30 mg/kg) developed type 2 diabetic model rats. Rats were fed with regular chow. The successfully induced rats (n=28) were randomly divided into two groups: type 2 diabetic mellitus without treatment group (n=14) and type 2 diabetic mellitus group treated with triptolide (n=14, 200 μg·kg^-1·d^-1). After administration of triptolide for 8 weeks, serum biochemistry, kidney weight/body weight and urinary albumin (UAL) were detected. The rats were sacrificed for the observation of renal histomorphology through optic microscope and transmission electron microscope. The mRNA and protein expressions of Nephrin, Podocin, osteopontin, transforming growth factor-β₁ (TGF-β₁) and monocyte\macrophage surface specific antigen (ED-1) in renal tissue were determined by quantitative real-time PCR, semi-quantitative immunohistochemical assays and western blot technique.

Compared with NC, UAL level was significantly increased in type 2 diabetic rats (F=181.51, P<0.01). The protein expressions of Nephrin (F=36.82, P<0.05) and Podocin (F=32.57, P<0.05) in the kidney were significantly decreased and mRNA expressions of Nephrin(F=88.45, P<0.01)and Podocin (F=55.43, P<0.01)were also significantly decreased in diabetic rats, compared with NC group. After administration of triptolide for 8 weeks, the protein expressions of Nephrin ((1.82±0.06) and (1.63±0.06), P<0.05) and Podocin ((1.80±0.06) and (1.60±0.06), P<0.05) were up-regulated, and the mRNA expressions of Nephrin ((0.73±0.12) and (0.19±0.08), P<0.01) and Podocin ((0.60±0.12) and (0.26±0.07), P<0.01) were also up-regulated in diabetic rats. The protein expressions of osteopontin (F=40.06, P<0.05), TGF-β₁ (F=28.84, P<0.05)and mRNA expressions of osteopontin (F=177.46, P<0.01), TGF-β₁ (F=161.27, P<0.01) were all significantly up-regulated than those in NC group (P<0.01). Triptolide inhibited the protein expressions of osteopontin ((1.27±0.03) and (1.39±0.05), P<0.05), TGF-β₁ ((1.23±0.03) and (1.44±0.02), P<0.05) and mRNA expressions of osteopontin ((2.05±0.16) and (3.26±0.26), P<0.01), TGF-β₁((4.0±0.70) and (6.5±0.71), P<0.01).

These results showed that triptolide ameliorated podocyte injury in type 2 diabetic rats. Renoprotection of triptolide on podocyte may be mediated through, at least partly, suppressing the renal inflammatory stress and infiltration of macrophage.

Patients with diabetes have an increased incidence of periodontitis, which in turn leads to increased frequency of tooth loss, impaired chewing function and restricted diet^[1]。 Oral implants can anchor inorganic allogeneic materials (implants) within the jaw bone to provide support and fixation for the restoration of missing teeth. However, pathological changes such as vascular degeneration, slow wound healing and easy infection caused by diabetes may affect the formation and maintenance of osseointegration interface^[2], resulting in implant failure and implant loss.

Since its launch in 1957, metformin has gone through more than 50 years in the field of diabetes treatment, and its clinical application value has been continuously explored. In recent years, it has been found that metformin exerts anti-tumor effects in addition to its good hypoglycemic effect. Therefore, it is of great significance to understand its latest clinical progress in this respect and explore specific anti-tumor mechanisms for a comprehensive understanding of metformin. Epidemiological studies have confirmed that diabetes, especially type 2 diabetes, is associated with the onset of some common malignant tumors such as colorectal cancer, liver cancer, pancreatic cancer, breast cancer and endometrial cancer. As the first-line drug for the treatment of type 2 diabetes, the hypoglycemic effect of metformin has been widely recognized. At the 2009 meeting of the European Society for Diabetes Research (EASD), the antitumor effect of metformin has become one of the hot topics discussed by scholars from various countries. This article summarizes the related contents.

Diabetes has become the third most serious chronic non-communicable disease in the world after tumors and cardiovascular and cerebrovascular diseases, and it is one of the main reasons for death, disability and the increase of medical expenses. The main goal of traditional hypoglycemic drug treatment is to control blood sugar within the normal range, but it faces challenges such as progressive decrease of islet β cell function, weight gain, hypoglycemic events and complications during the treatment process, which cannot meet the requirements of comprehensive diabetes management. glucagon-like peptide 1 (GLP-1) drugs based on incretin therapy have good hypoglycemic effect and less risk of hypoglycemia, and can reduce body weight, improve β cell function, lower blood pressure and blood lipids, showing many benefits. Therefore, it is necessary to apply composite endpoint to comprehensively evaluate these treatment indicators and the effect of disease management. The guidelines for the treatment of type 2 diabetes issued by major international organizations such as the International Diabetes Federation (IDF), the American Diabetes Association (ADA), the European Association for Diabetes Research (EASD) and the Diabetology Branch of Chinese Medical Association (CDS) have clearly defined the standards of the above indicators, providing a basis for the evaluation of composite endpoint.

A 24-year-old male was admitted for "thirst, polydipsia, polyuria for 5 days, nausea and vomiting for 3 days". Previous denial of history of diabetes and family history of diabetes, denial of history of autoimmune diseases. Admission physical examination: body temperature 36.7 ℃, pulse 106 beats/min, breathing 25 beats/min, blood pressure 106/59 mm Hg (1 mm Hg =0.133 kPa), body mass index 17.62 kg/m²； Acute disease, no rotten apple smell in exhalation, dry skin and mucous membranes, slightly poor elasticity; There were no cardiopulmonary abnormalities. Urinary glucose (+ + + +), urinary ketone body (+ + +) and urinary occult blood (±) were checked at admission; Blood gas analysis : pH 7.173, BE-21.6 mmol/L, HCO₃^-7.1 mmol/L; Blood potassium 6.23 mmol/L, blood sodium 117.05 mmol/L, blood chloride 89.1 mmol/L, CO₂-CP 3.3 mmol/L, Cr 179 μ mol/L; Random blood glucose 23.8 mmol/L; CK 492 U/L, amylase 65 U/L. The next day, HbA1c was checked at 6.8%; After correction of ketoacidosis, fasting C-peptide 50 pmol/L and postprandial 2 h C-peptide 70 pmol/L were checked; Glutamate decarboxylase antibody, islet cell antibody and anti-insulin antibody were all negative (immunoblotting, Shenzhen Burlaut Biological Products Co., Ltd.); Abdominal B-ultrasound showed large spleen and no obvious abnormality in pancreas; Hemoglobin was (110.7~126.0) g/L, hematocrit was 0.335~0.380, and mean erythrocyte volume was (63.2~63.5) ×10^-9L. Average hemoglobin of erythrocytes (20.81~21.10) ×10^-12g, average hemoglobin concentration (329.3-332.0) g/L, red blood cell distribution width 0.155-0.159; erythrocyte fragility 7% (>60%); Hemoglobin electrophoresis HbA 94.8% (≥94.5%), HbF 0.6% (<2.0%), HbA₂4.6%(1.0%～3.5%)； Thalassemia gene detection beta thalassemia genotype: detection of abnormal gene 17M/N heterozygous in 17 abnormal mutation deletions common in Chinese. Diagnosis: Fulminant type 1 diabetes mellitus with beta thalassemia. After admission, he was treated with active fluid rehydration and low-dose insulin. After 12 hours, the blood gas analysis was re-examined: pH: 7.375, BE: -5.6 mmol/L, HCO₃^-: 20.0 mmol/L, and switched to insulin pump to reduce glucose after 2 days. After 2 weeks, the fasting C-peptide was 80 pmol/L and the postprandial C-peptide was 100 pmol/L. After discharge, insulin pump treatment was given. After 3 months follow-up, HbA1c 6.9%, fasting C-peptide 60 pmol/L, and postprandial 2 h C-peptide 170 pmol/L were reviewed.

At the 70th Annual Meeting of the American Diabetes Society (ADA), expert forums such as the symposium "Selective Hepatic Insulin Resistance", the Banting Prize lecture "The Liver is a Target for Individualized Treatment of Diabetes", "New Insights on Insulin Resistance and Metabolic Syndrome" and "Molecular Mechanisms of Insulin Resistance" made the discussion on hepatic insulin resistance very lively and attracted the attention of diabetologists from around the world.

Physiological basis and prandial insulin secretion maintain blood glucose at normal levels. For non-obese and non-diabetic people, the daily insulin secretion is 20 to 50 U^[1]Of which basal insulin accounts for approximately 50%, with an average of 0.25 U/kg per day^[1]Therefore, in the insulin treatment of diabetes, the application of basal insulin is very important. The ideal basal insulin should be able to mimic physiological insulin secretion, and the flat concentration curve without peaks can effectively and durably reduce hyperglycemia, and it is convenient to use. At present, the basal insulins commonly used in clinic are neutral protamine zinc human insulin (NPH) and two long-acting insulin analogs-insulin detemir and insulin glargine. Long-acting insulin analogs have many advantages over NPH, with a flat action curve and a sustained action time of up to 24 h^[2]The glycemic control effect of once a day injection is reliable, and the risk of hypoglycemic events is lower. The hypoglycemic effect of insulin detemir has the unique advantages of low individual variability and less weight gain after treatment^[3]。 This article reviews the long-acting pharmacological basis and clinical efficacy of insulin detemir as follows.

The guidelines of the International Diabetes Federation clearly state that the main goal of diabetes treatment is to reduce HbA1c levels, and to achieve blood glucose standards requires simultaneous control of fasting and postprandial blood glucose. Regardless of the level of HbA1c, fasting and postprandial hyperglycemia should be treated simultaneously^[1]。 Chinese diabetic patients have decreased insulin secretion in the early stage of the disease, especially the absence of insulin secretion in the first phase, and the postprandial blood glucose level is significantly increased^[2]High proportion of patients whose fasting and postprandial blood glucose were not up to standard^[3]Therefore, the application of insulin for treatment needs to be flexibly applied to these characteristics.

Recent studies have shown that the use of sensitizing receptor insulin pump therapy combined with continuous blood glucose monitoring can reduce glycated hemoglobin levels without increasing the incidence of hypoglycemia. The aim of this study was to evaluate the effects of sensitized receptor insulin pump therapy and insulin injection therapy in patients with type 1 diabetes.

Previous studies have shown equivalent long-term cardiovascular risk in patients with type 2 diabetes and non-diabetic acute myocardial infarction. To observe differences in long-term cardiovascular risk between patients with type 2 diabetes and non-diabetic acute myocardial infarction in the Mediterranean region, the researchers conducted a prospective cohort study in a southern European population.

Islet β cell autoimmunity is characterized by the presence of autoantibodies, such as islet cell autoantibodies (ICAs), insulin autoantibodies (IAAs), glutamate decarboxylase autoantibodies (GADAs), and protein tyrosine phosphatase associated islet antigen 2 (IA-2As) present in the peripheral circulation. Studies have shown that these antibodies can effectively predict the occurrence of type 1 diabetes in first-degree relatives of patients. The purpose of this study was to evaluate the effectiveness and seroconversion rate of GADAs and IA-2As in predicting type 1 diabetes in the general population.

Patients with abnormal glucose tolerance have a high risk of diabetes and cardiovascular events. Early intervention can reduce the risk of diabetes, but the impact on cardiovascular events is still lacking in corresponding evaluation.

Alpha-glycosidase inhibitors improve postprandial hyperglycemia and reduce the risk of cardiovascular disease. However, the effects of alpha-glycosidase inhibitors on endothelial function and incretin secretion in diabetic patients with coronary heart disease are unclear.

The ACCORD study is a large-scale clinical trial conducted in 77 medical centers in North America. Its purpose is to explore the effect of intensive hypoglycemic therapy versus standard hypoglycemic therapy on cardiovascular events in type 2 diabetes.

There are more than 150 million overweight and obese children in the world, and more than one million of them may develop type 2 diabetes, hypertension, dyslipidemia, etc. in the future. This cross-sectional study analyzed the relationship of metabolic and cardiovascular risk factors in obese children and adolescents with normal fasting blood glucose, aiming to investigate whether there is reduced insulin sensitivity, decreased islet beta cell function, and adverse cardiovascular effects in this population, and to explore whether relatively high fasting blood glucose within the normal range can be used as a marker for early detection of insulin resistance and decreased beta cell function.

For children, the most serious consequence of obesity is the evolution of type 2 diabetes. For children at high risk of obesity and type 2 diabetes, the researchers set up a multivariate in-school intervention protocol, and hope to verify the impact of this protocol on the risk factors of diabetes in adolescents through this study.

Glucagon-like polypeptide-1 (GLP-1) receptor agonists can exogenously increase the concentration of GLP-1 in the body, and dipeptidyl peptidase-4 (DPP-4) inhibitors can increase the levels of endogenous GLP-1 and glucose-dependent insulin-secreting polypeptide (GIP) by reducing inactivation, which have become new targets for hypoglycemic drug therapy.