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New practice in semaglutide on type-2 diabetes and obesity: clinical evidence and expectation

《医学前沿（英文）》 2022年 第16卷 第1期   页码 17-24 doi: 10.1007/s11684-021-0873-2

摘要： Obesity is an important risk factor of type 2 diabetes (T2D), which has become an important factor threatening human health. However, no perfect drug choice for obesity exists. Semaglutide is a kind of human glucagon-like peptide-1 (GLP-1) analog that promotes insulin secretion while inhibiting glucagon secretion through a glucose concentration-dependent mechanism. GLP-1 can also delay stomach emptying and suppress appetite to help lose weight. This review summarizes clinical evidence of the semaglutide effect on T2D and obesity and establishes expectations on future clinical trials for obesity treatment.

关键词： semaglutide     type 2 diabetes     obesity    

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Metabolomics in human type 2 diabetes research

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《医学前沿（英文）》 2013年 第7卷 第1期   页码 4-13 doi: 10.1007/s11684-013-0248-4

摘要：

The high prevalence of diabetes and diabetic complications has caused a huge burden on the modern society. Although scientific advances have led to effective strategies for preventing and treating diabetes over the past several decades, little progress has been made toward curing the disease or even getting it under control, from a public health and overall societal standpoint. There is still a lack of reliable biomarkers indicative of metabolic alterations associated with diabetes and different drug responses, highlighting the need for the development of early diagnostic and prognostic markers for diabetes and diabetic complications. The emergence of metabolomics has allowed researchers to systemically measure the small molecule metabolites, which are sensitive to the changes of both environmental and genetic factors and therefore, could be regarded as the link between genotypes and phenotypes. During the last decade, the progression made in metabolomics has provided insightful information on disease development and disease onset prediction. Recent studies using metabolomics approach coupled with statistical tools to predict incident diabetes revealed a number of metabolites that are significantly altered, including branched-chain and aromatic amino acids, such as isoleucine, leucine, valine, tyrosine and phenylalanine, as diagnostic or highly-significant predictors of future diabetes. This review summarizes the current findings of metabolomic studies in human investigations with the most common form of diabetes, type 2 diabetes.

关键词： metabolomics     type 2 diabetes     metabolic pathway     mass spectrometry     nuclear magnetic resonance (NMR)    

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Association of periodontal disease with glycemic control in patients with type 2 diabetes in Indian population

null

《医学前沿（英文）》 2017年 第11卷 第1期   页码 110-119 doi: 10.1007/s11684-016-0484-5

摘要：

This study aims to investigate the link between glycated hemoglobin and diabetic complications with chronic periodontitis. A total of 207 patients with type 2 diabetes and chronic periodontitis (CP) were divided according to tertiles of mean PISA (periodontal inflamed surface area) scores as low, middle and high PISA groups. Simultaneously a group of 67 periodontally healthy individuals (PH) was recruited. Periodontal examinations, including full-mouth assessment of probing depths (PPD), bleeding on probing, clinical attachment level and plaque scores were determined. Blood analyses were carried out for glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2 h post parandial glucose (PPG). Individuals in PH group had significantly better glycemic control than CP group. Upon one-way analysis of variance, subjects with increased PISA had significantly higher HbA1c levels, retinopathy and nephropathy (P<0.05). After controlling for age, gender, body mass index (BMI), socioeconomic status (SES), family history of diabetes and periodontitis, duration of diabetes, the mean PISA in mm2, PPD 4--6 mm (%) and PPD≥7 mm (%) emerged as significant predictors for elevated HbA1c in regression model (P<0.05). Logistic regression analysis revealed that PISA was associated with higher risk of having retinopathy and neuropathy (odds ratio). In our study, the association between glycemic control and diabetic complications with periodontitis was observed.

关键词： type 2 diabetes mellitus     hemoglobin A     glycated     chronic periodontitis    

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Effectiveness of quality of care for patients with type 2 diabetes in China: findings from the Shanghai

《医学前沿（英文）》 2022年 第16卷 第1期   页码 126-138 doi: 10.1007/s11684-021-0897-7

摘要： This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai, China. A total of 173 235 patients with type 2 diabetes in 2017 were included in the analysis. Profiles of risk factors and intermediate outcomes were determined. The patients had a mean age of 66.43±8.12 (standard deviation (SD)) years and a mean diabetes duration of 7.95±5.53 (SD) years. The percentage of patients who achieved the target level for HbA1c (<7.0%) was 48.6%. Patients who achieved the target levels for blood pressure (BP)<130/80 mmHg and low-density lipoprotein-cholesterol (LDL-c)<2.6 mmol/L reached 17.5% and 34.0%, respectively. A total of 3.8% achieved all three target levels, and the value increased to 6.8% with an adaptation of the BP target level (<140/90 mmHg) for those over 65 years. Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels: male, young age, short diabetes duration, low body mass index, macrovascular complications, no microvascular complications, prescribed with lipid-lowering medication, and no prescription of antihypertensive medication. In conclusion, nearly 50% and one-third of the patients with diabetes met the target levels for HbA1c and LDL-c, respectively, with a low percentage achieving the BP target level. The percentage of patients who achieved all three target levels needs significant improvement.

关键词： type 2 diabetes     quality of care     macrovascular complication     microvascular complication     treatment pattern     epidemiology    

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Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 94-100 doi: 10.1007/s11684-011-0116-z

摘要：

Mesenchymal stem cells (MSC) have been used in clinical trials for severe diabetes, a chronic disease with high morbidity and mortality. Bone marrow is the traditional source of human MSC, but human term placenta appears to be an alternative and more readily available source. Here, the therapeutic effect of human placenta-derived MSC (PD-MSC) was studied in type 2 diabetes patients with longer duration, islet cell dysfunction, high insulin doses as well as poor glycemic control in order to evaluate the safety, efficacy and feasibility of PD-MSC treatment in type 2 diabetes (T2D). Ten patients with T2D received three intravenous infusions of PDSC, with one month interval of infusion. The total number of PDSC for each patient was (1.22–1.51) × 106/kg, with an average of 1.35 × 106/kg. All of the patients were followed up after therapy for at least 3 months. A daily mean dose of insulin used in 10 patients was decreased from 63.7?±?18.7 to 34.7?±?13.4 IU (P<0.01), and the C-peptide level was increased from 4.1?±?3.7 ng/mL to 5.6?±?3.8 ng/mL (P<0.05) respectively after therapy. In 4 of 10 responders their insulin doses reduced more than 50% after infusion. The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment (P<0.05). No fever, chills, liver damage and other side effects were reported. The renal function and cardiac function were improved after infusion. The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple, safe and effective therapeutic approach for T2D patients with islet cell dysfunction. Further large-scale, randomized and well-controlled clinical studies will be required to substantiate these observations.

关键词： placenta stem cells     treatment of type 2 diabetes    

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From gut changes to type 2 diabetes remission after gastric bypass surgeries

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《医学前沿（英文）》 2013年 第7卷 第2期   页码 191-200 doi: 10.1007/s11684-013-0258-2

摘要：

Increasing evidence suggests that the gut may influence the host’s metabolism and ultimately change the outcomes of type 2 diabetes mellitus (T2DM). We review the evidence on the relationship between the gut and T2DM remission after gastric bypass surgery, and discuss the potential mechanisms underlying the above relationship: gut anatomical rearrangement, microbial composition changes, altered gut cells, and gut hormone modulation. However, the exact changes and their relative importance in the metabolic improvements after gastric bypass surgery remain to be further clarified. Elucidating the precise metabolic mechanisms of T2DM resolution after bypass surgery will help to reveal the molecular mechanisms of pathogenesis, and facilitate the development of novel diagnoses and preventative interventions for this common disease.

关键词： gastric bypass     T2DM     gut    

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Modulatory effect on dyslipidemia and anti-atherosclerotic function of in newly diagnosed type 2 diabetes

SUN Mingxiao, WANG Yao, CHI Jiamin

《医学前沿（英文）》 2008年 第2卷 第2期   页码 174-177 doi: 10.1007/s11684-008-0032-z

摘要： The modulatory effect of on dyslipidemia and the preventive effect on atherosclerosis in newly diagnosed type 2 diabetic patients were studied. A prospective clinical trial was conducted to test the effectiveness of in selected 201 newly diagnosed type 2 diabetic patients. All patients were randomly divided into two groups: 108 with therapy and 93 without therapy. The mean follow-up period was 22 months. The blood glucose and blood pressure of all patients were under control. Serum levels of total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) were significantly lowered and their decreased percentages were significantly higher in therapy group ( < 0.05). The number of patients with arteria iliaca intima thickening was significantly lower in group of therapy ( = 0.024). With stepwise multivariate logistic regression analysis, the decreased percentage of TG was significantly and independently related with the decreased number of patients with arteria iliaca intima thickening ( = 0.005). The study demonstrates that therapy is effective on modulating dyslipidemia in newly diagnosed type 2 diabetes patients, and may be related with the improvement of early atherosclerosis.
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The mechanisms linking adiposopathy to type 2 diabetes

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《医学前沿（英文）》 2013年 第7卷 第4期   页码 433-444 doi: 10.1007/s11684-013-0288-9

摘要：

Obesity is defined as excessive accumulation of body fat in proportion to body size. When obesity occurs, the functions of adipose tissue may be deregulated, which is termed as adiposopathy. Adiposopathy is an independent risk factor for many diseases, including diabetes and cardiovascular diseases. In overweight or obese subjects with adiposopathy, hyperlipidemia exerts lipotoxicity in pancreatic islet and liver and induces pancreatic β cell dysfunction and liver insulin resistance, which are the decisive factors causing type 2 diabetes. Moreover, adipokines have been shown to play important roles in the regulation of glucose homeostasis. When adiposopathy occurs, abnormal changes in the serum adipokine profile correlate with the development and progression of pancreatic β cell dysfunction and insulin resistance in peripheral tissue. The current paper briefly discusses the latest findings regarding the effects of adiposopathy-related lipotoxicity and cytokine toxicity on the development of type 2 diabetes.

关键词： obesity     adiposopathy     lipotoxicity     adipokines     diabetes    

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Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes

Huiwen Ren, Can Wu, Ying Shao, Shuang Liu, Yang Zhou, Qiuyue Wang

《医学前沿（英文）》 2020年 第14卷 第5期   页码 642-650 doi: 10.1007/s11684-019-0719-3

摘要： This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease (DKD). A total of 390 patients with T2DM were divided into three groups: normal albuminuria (UACR<30 mg/g, =136, NA), microalbuminuria (UACR at 30–300 mg/g, =132, MA), and clinical albuminuria (UACR>300 mg/g, =122, CA). Circulating miR-154-5p, inflammatory (C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); and tumor necrosis factor-α (TNF-α) and fibrotic markers (vascular endothelial growth factor (VEGF); transforming growth factor-β1 (TGF-β1); and fibronectin (FN)), and other biochemical indicators were assessed via real-time PCR, enzyme-linked immunosorbent assay, and chemiluminescence assay in patients with T2DM and 138 control subjects (NC). UACR, miR-154-5p, glycated hemoglobin (HbA1c), serum creatinine (sCr), blood urea nitrogen (BUN), ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were significantly higher and the estimated glomerular filtration rate (eGFR) was significantly lower in NA, MA, and CA groups than in NC subjects ( <0.05). Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c, sCr, BUN, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN and negatively correlated with eGFR ( <0.05). miR-154-5p, HbA1c, sCr, BUN, eGFR, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were important factors affecting UACR. These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.

关键词： type 2 diabetes mellitus     diabetic kidney disease     miR-154-5p     urinary albumin to creatinine ratio    

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Type 2 diabetes is causally associated with depression: a Mendelian randomization analysis

Liping Xuan, Zhiyun Zhao, Xu Jia, Yanan Hou, Tiange Wang, Mian Li, Jieli Lu, Yu Xu, Yuhong Chen, Lu Qi, Weiqing Wang, Yufang Bi, Min Xu

《医学前沿（英文）》 2018年 第12卷 第6期   页码 678-687 doi: 10.1007/s11684-018-0671-7

摘要：

Type 2 diabetes (T2D) has been associated with a high prevalence of depression. We aimed to determine the causal relation by performing a Mendelian randomization (MR) study using 34 T2D risk genetic variants validated in East Asians as the instrumental variable (IV). An MR analysis was performed involving 11 506 participants from a large longitudinal study. The T2D genetic risk score (GRS) was built using the 34 typical T2D common variants. We used T2D_GRS as the IV estimator and performed inverse-variance weighted (IVW) and Egger MR analysis. The T2D_GRS was found to be associated with depression with an OR of 1.21 (95% CI: 1.07–1.37) after adjustments for age, sex, body mass index, current smoking and drinking, physical activity, education, and marital status. Using T2D_GRS as the IV, we similarly found a causal relationship between genetically determined T2D and depression (OR: 1.84, 95% CI: 1.25–2.70). Though we found no association between the combined effect of the genetic IVs for T2D and depression with Egger MR (OR: 0.95, 95% CI: 0.42–2.14), we found an association for T2D and depression with IVW (OR: 1.75, 95% CI: 1.31–2.46) after excluding pleiotropic SNPs. Overall, the MR analyses provide evidence inferring a potential causal relationship between T2D and depression.

关键词： causal modeling     depression     Mendelian randomization     type 2 diabetes    

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Mechanism of insulin resistance in obesity: a role of ATP

《医学前沿（英文）》 2021年 第15卷 第3期   页码 372-382 doi: 10.1007/s11684-021-0862-5

摘要： Obesity increases the risk of type 2 diabetes through the induction of insulin resistance. The mechanism of insulin resistance has been extensively investigated for more than 60 years, but the essential pathogenic signal remains missing. Existing hypotheses include inflammation, mitochondrial dysfunction, hyperinsulinemia, hyperglucagonemia, glucotoxicity, and lipotoxicity. Drug discoveries based on these hypotheses are unsuccessful in the development of new medicines. In this review, multidisciplinary literature is integrated to evaluate ATP as a primary signal for insulin resistance. The ATP production is elevated in insulin-sensitive cells under obese conditions independent of energy demand, which we have named “mitochondrial overheating.” Overheating occurs because of substrate oversupply to mitochondria, leading to extra ATP production. The ATP overproduction contributes to the systemic insulin resistance through several mechanisms, such as inhibition of AMPK, induction of mTOR, hyperinsulinemia, hyperglucagonemia, and mitochondrial dysfunction. Insulin resistance represents a feedback regulation of energy oversupply in cells to control mitochondrial overloading by substrates. Insulin resistance cuts down the substrate uptake to attenuate mitochondrial overloading. The downregulation of the mitochondrial overloading by medicines, bypass surgeries, calorie restriction, and physical exercise leads to insulin sensitization in patients. Therefore, ATP may represent the primary signal of insulin resistance in the cellular protective response to the substrate oversupply. The prevention of ATP overproduction represents a key strategy for insulin sensitization.

关键词： type 2 diabetes     energy expenditure     mitochondria     hyperinsulinemia     hyperglucagonemia     AMPK    

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evaluation of renal function using diffusion weighted imaging and diffusion tensor imaging in type 2

null

《医学前沿（英文）》 2014年 第8卷 第4期   页码 471-476 doi: 10.1007/s11684-014-0365-8

摘要：

This work aims to estimate the value of diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) in detecting early-stage kidney injury in type 2 diabetic patients with normoalbuminuria (NAU) versus microalbuminuria (MAU) prospectively. A total of 30 T2DM patients with normal kidney function were recruited and assigned to the NAU group (n = 14) or MAU group (n= 16) according to 8 h overnight urinary albuminuria excretion rate (AER) results. A contemporary cohort of health check-up recipients were included as controls (n = 12). DWI and DTI scans were performed on bilateral kidney using SE single-shot EPI, and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the renal parenchyma was determined from ADC and FA maps of the three groups. ADC and FA values were compared among the three groups. According to DWI with a b value of 400 s/mm2, the MAU and NAU groups showed significantly lowered mean ADC values compared with the healthy controls (P<0.01). The mean ADC in the MAU group [(2.22±0.07)×10–3 mm2/s] was slightly lower than that of the NAU group [(2.31±0.22)×10–3 mm2/s], but this difference was not statistically significant (P>0.05). The FA value in the MAU group was higher than that in the control group (0.45±0.07 vs. 0.39±0.03, P = 0.004) but did not differ from that in the NAU group (0.42±0.03) (P>0.05). ADC and FA values may be more sensitive than urine AER in reflecting early-stage kidney injury and, hence, may facilitate earlier detection and quantitative evaluation of kidney injury in T2DM patients. Combined evaluation of ADC and FA values may provide a better quantitative approach for identifying diabetic nephropathy at early disease stages.

关键词： type 2 diabetes mellitus     microalbuminuria     diffusion weighted imaging     diffusion tensor imaging     early-stage kidney injury    

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Mechanisms of insulin resistance in obesity

null

《医学前沿（英文）》 2013年 第7卷 第1期   页码 14-24 doi: 10.1007/s11684-013-0262-6

摘要：

Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that, there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy.

关键词： type 2 diabetes     energy expenditure     inflammation     lipotoxicity     mitochondria     hyperinsulinemia     adenosine monophosphate-activated protein kinase (AMPK)    

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Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological

Hui Dong, Fu’er Lu, Nan Wang, Xin Zou, Jingjing Rao

《医学前沿（英文）》 2011年 第5卷 第3期   页码 288-293 doi: 10.1007/s11684-011-0127-9

摘要： Haemorheological abnormalities have been described in diabetes mellitus, as well as in non-alcoholic fatty liver disease (NAFLD). However, the relationship between the changes in liver fat content and haemorheology is unknown. The current study aims to show the correlation between haemorheological parameters and intrahepatic lipid content (IHLC) in patients with type 2 diabetes. The serum biochemical markers, such as fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), liver enzymes, lipid profiles, and haemorheological properties, were examined. IHLC was quantified using proton magnetic resonance spectroscopy ( H-MRS) scanning of the liver. A significant correlation was observed between IHLC and whole blood viscosity at high, middle, and low shear rates. IHLC also positively correlated with haematocrit, the reduced whole blood viscosity at low and middle shear rates, and the erythrocyte aggregation index. Diabetic patients with NAFLD exhibited significant haemorheological abnormalities compared with patients without NAFLD. In summary, haemorheological disorders are linked to non-alcoholic fatty liver in type 2 diabetes.

关键词： diabetes mellitus     type 2     haemorheology     non-alcoholic fatty liver disease    

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Cytokines and inflammation in adipogenesis: an updated review

Ning Jiang, Yao Li, Ting Shu, Jing Wang

《医学前沿（英文）》 2019年 第13卷 第3期   页码 314-329 doi: 10.1007/s11684-018-0625-0

摘要： The biological relevance of cytokines is known for more than 20 years. Evidence suggests that adipogenesis is one of the biological events involved in the regulation of cytokines, and pro-inflammatory cytokines (e.g., TNF and IL-1 ) inhibit adipogenesis through various pathways. This inhibitory effect can constrain the hyperplastic expandability of adipose tissues. Meanwhile, chronic low-grade inflammation is commonly observed in obese populations. In some individuals, the impaired ability of adipose tissues to recruit new adipocytes to adipose depots during overnutrition results in adipocyte hypertrophy, ectopic lipid accumulation, and insulin resistance. Intervention studies showed that pro-inflammatory cytokine antagonists improve metabolism in patients with metabolic syndrome. This review focuses on the cytokines currently known to regulate adipogenesis under physiological and pathophysiological circumstances. Recent studies on how inhibited adipogenesis leads to metabolic disorders were summarized. Although the interplay of cytokines and lipid metabolism is yet incompletely understood, cytokines represent a class of potential therapeutic targets in the treatment of metabolic disorders.

关键词： cytokines     inflammation     adipogenesis     type 2 diabetes mellitus     metabolic disorder    

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标题 作者 时间 类型 操作

New practice in semaglutide on type-2 diabetes and obesity: clinical evidence and expectation

期刊论文

Metabolomics in human type 2 diabetes research

null

期刊论文

Association of periodontal disease with glycemic control in patients with type 2 diabetes in Indian population

null

期刊论文

Effectiveness of quality of care for patients with type 2 diabetes in China: findings from the Shanghai

期刊论文

Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study

null

期刊论文

From gut changes to type 2 diabetes remission after gastric bypass surgeries

null

期刊论文

Modulatory effect on dyslipidemia and anti-atherosclerotic function of in newly diagnosed type 2 diabetes

SUN Mingxiao, WANG Yao, CHI Jiamin

期刊论文

The mechanisms linking adiposopathy to type 2 diabetes

null

期刊论文

Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes

Huiwen Ren, Can Wu, Ying Shao, Shuang Liu, Yang Zhou, Qiuyue Wang

期刊论文

Type 2 diabetes is causally associated with depression: a Mendelian randomization analysis

Liping Xuan, Zhiyun Zhao, Xu Jia, Yanan Hou, Tiange Wang, Mian Li, Jieli Lu, Yu Xu, Yuhong Chen, Lu Qi, Weiqing Wang, Yufang Bi, Min Xu

期刊论文

Mechanism of insulin resistance in obesity: a role of ATP

期刊论文

evaluation of renal function using diffusion weighted imaging and diffusion tensor imaging in type 2

null

期刊论文

Mechanisms of insulin resistance in obesity

null

期刊论文

Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological

Hui Dong, Fu’er Lu, Nan Wang, Xin Zou, Jingjing Rao

期刊论文

Cytokines and inflammation in adipogenesis: an updated review

Ning Jiang, Yao Li, Ting Shu, Jing Wang

期刊论文