MedNexus
Volume 12 · Issue 01 · 2020
MedNexus
- Sections
- Standard and Criterion
- Focus Forum
- Editorial
- Original Article
- Short Paper
- Review Article
- New Perspective
The hemoglobin A1c (HbA1c) targets of diabetes should be individualized based on the patient-centered approach, according to numerous factors, such as age, duration of diabetes, comorbid conditions, patient motivation, risk of adverse effects. This consensus recommends a general HbA1c target of <7.0% for most adults with type 2 diabetes mellitus (T2DM). More stringent HbA1c goals is considered if these can be achieved in a safe and affordable manner without significant adverse effects of treatment. Less stringent HbA1c goals may be appropriate for certain individuals. This consensus recommends metformin as the preferred drug for monotherapy in patients with T2DM, and α-glucosidase inhibitors or insulin secretagogues as options for monotherapy. For combination therapy, it is recommended to stratify patients based on the presence of concomitant atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or chronic kidney disease (CKD). For patients with concomitant ASCVD, combination therapy with glucagon-like peptide 1 receptor agonist (GLP-1RA) or sodium-glucose co-transporter 2 inhibitor (SGLT2i) with evidence of cardiovascular benefit is recommended if available. For patients with concomitant CKD, SGLT2i with evidence of renal benefit is recommended as the preferred drug for use in combination therapy. GLP-1RA with evidence of renal benefit could be used in patients who cannot receive SGLT2i. For patients with concomitant HF, SGLT2i is recommended if conditions allow. For patients without concomitant ASCVD, HF, or CKD, the drugs for combination therapy should be selected based on factors such as baseline HbA1c levels, risk of hypoglycemia, body weight, financial situation, and drug availability.
Glycosylated hemoglobin A1c(HbA1c) is the "gold standard" to reflect the blood sugar control status of diabetic patients, but it also has some shortcomings, such as it can't reflect the fluctuation of blood sugar, it can't reflect the blood sugar control status in a short time, and it is also affected by factors such as red blood cell lifespan. HbA1c Control objectives should follow the principle of individualization, and implement hierarchical management according to patients' age, disease course, health status, risk of adverse drug reactions and other factors. Good early glycemic control can obtain benign metabolic memory effects. Metformin is the first choice for monotherapy in patients with type 2 diabetes. In combination therapy, it can be stratified according to whether patients have atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. If the patient is complicated with these diseases, it is advisable to timely combine drugs with evidence of benefit for these diseases when conditions permit; If the above diseases are not concomitant, the baseline HbA may be1cLevel, risk of hypoglycemia, weight, economic status and other factors to choose drugs.
Glycosylated hemoglobin1c(HbA1c) Since its discovery, it has been recognized as the core index to evaluate the efficacy of hypoglycemic treatment. Although in clinical practice, HbA1cThe weaknesses are constantly discovered, but with the advancement of technology, these problems are gradually solved. Especially, the establishment of standardized testing methods and quality control system, which provides HbA1cThe widespread application of HbA provides the guarantee that at present HbA1cIt has become a composite index with both diagnosis and monitoring functions. HbA1cStudy of variability and chronic complications of diabetes mellitus and HbA1cThe establishment of conversion relationship with other blood glucose monitoring indicators partially compensates for its inability to reflect the deficiency of blood glucose fluctuation. Therefore, HbA1cAlthough not perfect, its advantages in diabetes management are irreplaceable.
Blood glucose monitoring is an important part of diabetes management, which runs through the whole process of diabetes treatment and efficacy evaluation. Advances in blood glucose monitoring technology have provided more reliable blood glucose assessment indicators for diabetic patients. Continuous glucose monitoring can provide continuous and comprehensive blood glucose information throughout the day, and has advantages in evaluating blood glucose achievement, identifying hypoglycemia and quantifying blood glucose fluctuations, which has become an effective supplement to traditional blood glucose monitoring methods. Clinical research around new blood glucose monitoring technology has also established its position in international and domestic blood glucose monitoring guidelines and consensus.
To establish a method to detect the level of saliva 1,5-anhydroglucitol (1,5-AG).
From June 2017 to March 2018, 100 subjects (50 men and 50 women) with normal glucose tolerance (NGT group, n=69) or diabetes mellitus (DM group, n=31) were enrolled in the Sixth People′s Hospital affiliated to Shanghai Jiao Tong University. All subjects chewed swabs in Salivette saliva collection tubes to collect saliva. Enzymatic assay was used to explore the collection and storage methods for saliva 1,5-AG measurements. The mass spectrometry method was explored to analyze the saliva 1,5-AG levels. Differences were compared between NGT subjects and DM patients. Methods of t test and Mann-Whitney U test were used for comparison between groups, and the Spearman correlation was used for correlation analysis.
(1) Brushing teeth before saliva collection had no effect on saliva 1,5-AG levels. There was no significant difference in the volume of saliva between chewing 40-50 times, 50-60 times, and 60-70 times per minute (all P>0.05). The 1,5-AG levels in saliva stored at room temperature or 4 ℃ for 2 hours were not different from those detected immediately after collection (both P>0.05).(2) Compared with NGT subjects, DM patients had lower saliva 1,5-AG levels [(1.17±0.24) vs (0.94±0.19) μg/ml, t=4.084] and serum 1,5-AG levels [22.0 (17.6, 28.5) vs 4.6 (2.8, 8.2) μg/ml, Z=-5.421] (both P<0.05). The saliva 1,5-AG levels were positively correlated with serum 1,5-AG levels (r=0.528, P<0.05) and negatively correlated with 2 hour plasma glucose, glycated hemoglobin and glycated albumin (r=-0.366, -0.543, -0.444, respectively; all P<0.05).
Saliva collection is simple and the sample can be stored at room temperature or 4 ℃ for a short time. Saliva 1,5-AG levels can significantly differentiate DM patients from NGT subjects, which is expected to be a supplementary indicator for evaluating short-term glycemic control in DM patients.
To investigate the predictive effect of oral glucose tolerance test (OGTT) blood glucose on gestational diabetes mellitus (GDM) in the second trimester of pregnancy.
A total of 840 pregnant women were prospectively recruited from Jin Shan Branch of Shanghai Sixth Peoples′ Hospital (Zhujing area of Shanghai) between January 1st, 2017 and December 31st, 2018. All subjects received 75 g OGTT test in initial antenatal examination (8-16 gestational week) and received GDM screening in the second trimester. GDM were divided into F-GDM [only diagnosed by fasting plasma glucose (FPG)] and P-GDM (diagnosed by OGTT 1hPG or 2hPG). Correlative relationship was analyzed between OGTT FPG, OGTT 2hPG in initial antenatal examination and OGTT FPG, OGTT 1hPG, OGTT 2hPG for GDM screening in the second trimester. The receiver operating characteristic (ROC) curve was used to predict F-GDM with OGTT FPG and P-GDM with OGTT 2hPG in initial antenatal examination, the optimal cut-off points were found respectively. Then the cut-off points were used as the diagnostic criteria of GDM in the first trimester of pregnancy. Diagnostic characteristics of GDM in initial antenatal examination and GDM in the middle stage were analyzed by four-fold table. The t test was used for comparison between the two groups, Spearman correlation analysis was used for correlation, Fisher Z transformation method was used for correlation coefficient, and u test was used for comparison.
(1) FPG in initial antenatal examination was correlated with FPG, OGTT 1hPG or OGTT 2hPG in the second trimester (r1, r2, r3 was 0.461, 0.146, 0.087, respectively, all P<0.05). However, the correlation between FPG in the first trimester of pregnancy and FPG in the second trimester of pregnancy was better (r1 vs r2, r1 vs r3, both P<0.05; r2 vs r3, P>0.05). OGTT 2hPG in initial antenatal examination was correlative with FPG, OGTT 1hPG or OGTT 2hPG in the second trimester (r4, r5, r6 was 0.201, 0.425, 0.436, respectively, all P<0.05). However, the correlation between OGTT 2hPG in initial antenatal examination and OGTT 1hPG or OGTT 2hPG in the second trimester of pregnancy was better (r4 vs r5, r4 vs r6, both P<0.05; r5 vs r6, P>0.05). (2) The maximum area under the ROC curve of F-GDM predicted by FPG in initial antenatal examination was 0.781 (95%CI: 0.734-0.829, P<0.001), and the optimal cut-off of FPG was 4.95 mmol/L, the sensitivity was 67.3%, and the specificity was 74.4%. The maximum area under the ROC curve of P-GDM predicted by OGTT 2hPG in initial antenatal examination was 0.790 (95%CI: 0.742-0.839, P<0.001), the optimal cut-off of OGTT 2hPG was 7.595 mmol/L, the sensitivity was 67.9%, and the specificity was 80.8%. (3) Compared with GDM in the second trimester, GDM in initial antenatal examination diagnosed with these two cut-off values, the sensitivity was 78.0%, and the specificity was 60.7%, the positive predictive value was 33.2%, and the negative predictive value was 91.7%.
OGTT may be used to screen GDM in initial antenatal examination, FPG≥5.0 mmol/L and OGTT 2hPG≥7.6 mmol/L may be used as a reference value for abnormal blood glucose at the beginning of pregnancy.
To assess associations of bone turnover markers with metabolic syndrome (MS) among men in Henan Province.
From December 2015 to March 2016, a total of 697 male subjects were selected from the TIDE (Thyroid Disorders, lodine status and Diabetes: a National Epidemiological Survey-2014) research--Henan sub-center survey using multistage stratified cluster random sampling. All included subjects received standard oral glucose tolerance test, a physical examination (height, weight, waist circumference and blood pressure), a collection of blood samples to determine the level of plasma glucose, glycated hemoglobin A1c, total cholesterol, triglyceride (TG), high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, osteocalcin, pro-collagen type 1 N-terminal propeptide (PⅠNP), C-terminal-cross-linking telopeptide of type 1 collagen (β-CTX), 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH), and all of them completed the questionnaire. The associations between bone turnover markers and MS were analyzed using Spearman correlation and binary logistic regression, respectively.
A total of 697 men with an age of (46.6±15.9) years were included in the study. The average body mass index (BMI) was (25.97±3.69) kg/m2 (17.1-39.0 kg/m2). After adjusted for age, PTH, 25(OH)D, BMI and smoke, BMI was found as a risk factor for MS (OR=1.263, 95%CI 1.198-1.332). Spearman correlation analysis showed that OC and PⅠNP was negatively associated with MS (r=-0.154, -0.107, both P<0.01), but there was no significant correlation between β-CTX and MS. The results of the binary logistic regression analysis showed that OC was a protective factor for MS, abdominal obesity, hyperglycemia, hypertension and high TG; after adjusted for age, PTH, 25(OH) D and BMI, osteocalcin was also a protective factor for hyperglycemia (OR=0.971, 95%CI 0.947-0.995) and high TG (OR=0.955, 95%CI 0.931-0.980); further adjusted for smoke, the results were same as before. PⅠNP was a protective factor for MS, abdominal obesity, hyperglycemia and hypertension; after adjusted for age, PTH and 25(OH)D, PⅠNP was also a protective factor for abdominal obesity (OR=0.993, 95%CI 0.988-0.999); further adjusted for BMI and smoke, there was no significant correlation between PⅠNP and abdominal obesity.
Weight control is important to prevent adult males from MS, and higher levels of osteocalcin and PⅠNP may help prevent MS.
To understand the profile of serum lipid composition in type 2 diabetes mellitus (T2DM) patients with nonalcoholic simple fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), and to screen potential serum markers of NASH.
A total of 40 patients with T2DM and comorbid non-alcoholic fatty liver disease (NAFLD) who underwent liver biopsy were selected from September 2014 to October 2017 in the Department of Endocrinology, the Third Central Hospital of Tianjin. According to the results of liver biopsy (SAF score), they were divided into NAFL group (22 cases) and NASH group (18 cases). Medical profiles of the two groups were extracted and compared, ultra-high performance liquid chromatography-mass spectrometry was used for serum lipidomics analysis. T test was used to determine statistical significance between the groups. Logistic stepwise regression analysis and receiver operating characteristic (ROC) curve analysis were used to screen potential serum markers for NASH in T2DM.
The liver stiffness, NASH score, aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyltransferase (GGT), fasting blood glucose and serum ferritin levels were higher in NASH group than those in NAFL group (t=-2.76--2.06, all P<0.05). Phosphatidylcholine (35∶4)[PC (35∶4)], PC (36∶1) [PC (18∶1/18∶0)], PC (38∶3), PC (44∶5), phosphatidyl-ethnolamine (36∶2)[PE (36∶2)], PE (34∶1)c[PE-NMe2 (18∶1/16∶0)], PE (34∶1) [PE(20∶1/14∶0)], phosphatidyl serine (33∶0) [PS(33∶0)], triglyceride (54∶2)[TG (54∶2)], sphingomyelin (37∶1)[SM (37∶1)], SM (39∶1), SM (40∶1), glucosylceramide (40∶2)[GlcCer (40∶2)] were higher in NASH group than those in NAFL group (t=-2.930--1.380, all P<0.05). The levels of PC (38∶5),PC (38∶6),TG (52∶4),TG (54∶4),TG (54∶5),TG (57∶6), TG (58∶4), TG (60∶6) decreased in NASH group (t=1.982-2.431, all P<0.05); The levels of PC (36∶1) [PC (19∶1/17∶0)], PE (38∶1), PE (39∶1), TG (52∶1), N-palmitoyl phenylalanine were significantly higher in NASH group than those in NAFL group, with statistically significant differences (-3.789--2.837, P<0.005). Logistic stepwise regression analysis showed that increased PC (36∶1) and PE (38∶1) were risk factors for NASH progression in patients with T2DM complicated with NAFLD [P=0.026, 0.013, OR (95%CI): 1.213 (1.076-1.301), 1.119 (1.015-1.243)]. ROC curve analysis showed that the areas under curves of PC (36∶1) and PE (38∶1) were 0.803 and 0.785, respectively, with sensitivity 94.4% and specificity 72.7%, all higher than those of ALT, AST and GGT (the areas under the curve were 0.689, 0.734 and 0.741, the sensitivity was 72.2%, 77.8% and 77.8%, and the specificity was 68.2%, 63.6% and 68.2% respectively).
In patients with type 2 diabetes, glycero phospholipids, sphingolipids and TG changed significantly in NASH compared with NAFL. In patients with T2DM and fatty liver, PC (36∶1) and PE(38∶1) might be potential bio markers for NASH diagnosis.
To retrospectively study the clinical manifestations and molecular genetics of a pedigree of pancreatic duodenal homeobox 1 (PDX1) gene mutation with hyperglycemia in pregnancy.
We reported a family with hyperglycemia discovered during pregnancy. The proband showed hyperglycemia and malnutrition during pregnancy. The next generation sequencing of target genes of monogenic diabetes was performed and then Sanger sequencing to verify the suspected gene. Frequency and species conservation of the mutation site was analyzed. Mutation Taster, Polyphen-2, FATHMM and other software was performed for bioinfor matics analysis. Classification for pathogenicity was determined according to the American Society of Medical Genetics and Genomics. Treatment strategy was adjusted for the proband according to the gene result. We reviewed the literature of PDX1 gene mutation in hyperglycemia during pregnancy.
A PDX1 gene mutation (p.D64E) was detected in the proband. It is a novel mutation and highly conserved in species. The mutation was co-segregated with the clinical phenotypes of diabetes within the pedigrees. In addition to the defects of β-cell function, the proband also suffered from pancreatic exocrine dysfunction. After insulin and trypsin supplementation, her weight increased and the biochemical indicators returned to normal. It is reported in the literature that PDX1 gene mutations in the Caucasian population can lead to hyperglycemia during pregnancy and poor perinatal outcomes.
Our study firstly indicated that mutations in the PDX1 gene could result in hyperglycemia during pregnancy in Chinese population, suggesting that pancreatic exocrine function should be evaluated in these patients. Trypsin replacement should be prescribed in time to achieve precision therapy. Meanwhile, this study also suggests the importance of establishing screening methods for monogenetic diabetes in hyperglycemic patients during pregnancy.
To investigate the effects of metformin on bone metabolism markers and bone mineral density in postmenopausal women with abnormal glucose tolerance, and to analyze the relationship between glucose metabolism and bone metabolism after different doses of metformin intervention. From December 2016 to February 2018, 125 postmenopausal female patients with abnormal glucose tolerance were randomly divided into lifestyle intervention group (Group A), low-dose metformin group (Group B), medium-dose group (Group C), and high-dose group (Group D). After 24 weeks of intervention, body weight, blood biochemical indexes, parathyroid hormone (PTH), 25 hydroxyvitamin D [25 (OH) D], total type I collagen amino-terminal elongation peptide (PⅠNP), β-collagen degradation product (β-CTX), lumbar spine and hip bone mineral density, etc. were compared. The results showed that there were no significant differences in body mass index, blood lipid, liver and kidney function, calcium, phosphorus, PTH, 25 (OH) D, β-CTX and lumbar bone density among the four groups after treatment. After treatment, the glycosylated hemoglobin of subjects in group A was higher than that in groups B, C and D, and the difference between the latter three groups was not statistically significant; After treatment, the alkaline phosphatase, PⅠNP and hip bone mineral density of subjects in group A were lower than those in the other three groups, while the alkaline phosphatase and PⅠNP of subjects in group C were higher than those in groups B and D. However, there was no significant difference in hip bone mineral density between subjects in groups B, C and D. It shows that for postmenopausal women with abnormal glucose tolerance, metformin 1 500 mg/d treatment can not only effectively control blood glucose, but also promote bone formation and improve bone density.
There are abundant capillaries around the salivary glands, which can exchange molecules with blood. Saliva contains inorganic ions, glucose, 1,5-anhydroglucitol and other small organic molecules, as well as lipids, proteins and various hormones. Determination of saliva glucose and 1,5-anhydroglucitol has certain significance in the screening and monitoring of diabetes mellitus.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of hypoglycemic drugs, and their safety has always been one of the priorities of clinicians. Cardiovascular outcome trials have shown that the drug can reduce the risk of cardiovascular events in diabetic patients, but adverse reactions such as diabetic ketoacidosis, fracture, lower limb amputation, and acute kidney injury still need attention. This article will briefly introduce the current safety issues of SGLT2 inhibitors to help clinicians enhance their awareness of rational drug use, balance risks and benefits, and then choose the best treatment decision for patients.
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