Diabetes Therapy最新文献

Introduction: Orally administered semaglutide is the first glucagon-like peptide 1 receptor agonist (GLP-1 RA) for oral administration. As head-to-head trials assessing orally administered semaglutide as an add-on to 1-2 oral antidiabetic drugs (OADs) vs other GLP-1 RAs are limited, a network meta-analysis (NMA) was performed to assess the relative efficacy and safety of orally administered semaglutide 14 mg once-daily (QD) vs injectable GLP-1 RAs in patients with type 2 diabetes inadequately controlled on 1-2 OADs.

Methods: A systematic literature review was conducted to identify randomised controlled trials of GLP-1 RAs in patients inadequately controlled on 1-2 OADs. Data at 26 ± 4 weeks were extracted for efficacy and safety outcomes feasible for the NMA: change from baseline in glycated haemoglobin (HbA_1c), weight, HbA_1c target levels (< 7.0% and ≤ 6.5%), blood pressure, and any gastrointestinal adverse events specified in system organ class. Data were synthesised using NMA and a Bayesian framework.

Results: In total, 27 studies were included in the analyses. Orally administered semaglutide 14 mg QD was associated with significantly greater reductions in HbA_1c vs most comparators, and numerically greater reductions vs semaglutide 0.5 mg once-weekly (QW), dulaglutide 1.5 mg QW and liraglutide 1.8 mg QD. HbA_1c reductions with semaglutide 1 mg QW were numerically greater than those with orally administered semaglutide 14 mg QD. Reductions in body weight for orally administered semaglutide 14 mg QD were significantly greater than all comparators except semaglutide QW (both doses). Orally administered semaglutide QD 14 mg was associated with statistically similar odds of experiencing gastrointestinal adverse events vs injectable GLP-1 RAs.

Conclusion: Orally administered semaglutide 14 mg QD as an add-on to 1-2 OADs is one of the most efficacious GLP-1 RAs for reducing HbA_1c and body weight at 26 ± 4 weeks. Orally administered semaglutide 14 mg QD is well tolerated, with a safety profile in line with the GLP-1 RA class.

Funding: Novo Nordisk.

Introduction: The prevalence of diabetes in Kazakhstan has reached epidemic proportions, and this disease is becoming a major financial burden. In this research, regression analysis methods were employed to build models for predicting the number of diabetic patients in Kazakhstan in 2019, as this should aid the costing and policy-making performed by medical institutions and governmental offices regarding diabetes prevention and treatment strategies.

Methods: A brief review of mathematical models that are potentially useful for the task of interest was performed, and the most suitable methods for building predictive models were selected. The chosen models were applied to explore the correlation between population growth and the number of patients with diabetes as well as the correlation between the increase in gross regional product and the growth in the number of patients with diabetes. Moreover, the relationship of population growth and gross domestic product with the growth in the number of patients with diabetes in Kazakhstan was determined. Our research made use of the scikit-learn library for the Python programming language and functions for regression analysis built into the Microsoft Excel software.

Results: The predictive models indicated that the prevalence of diabetes in Kazakhstan will increase in 2019.

Conclusion: Mathematical models were used to find patterns in a comprehensive statistical dataset on registered diabetes patients in Kazakhstan over the last 15 years, and these patterns were then used to build models that can accurately predict the prevalence of diabetes in Kazakhstan.

Cardiac autonomic neuropathy (CAN) is a major complication of type 1 and type 2 diabetes mellitus (T1DM and T2DM). The increased morbidity, cardiovascular and all-cause mortality associated with CAN is established from numerous epidemiological studies. However, CAN is increasingly recognised in people with prediabetes (pre-DM) and the metabolic syndrome (MetS) with a reported prevalence up to 11% and 24% respectively. CAN is associated with components of MetS including hypertension and obesity, predating hyperglycaemia. The aetiology of CAN is multifactorial and there is a reciprocal relationship with insulin resistance and MetS. Obstructive sleep apnoea (OSA) is also associated with CAN possibly through MetS and an independent mechanism. An estimated global prevalence of the impaired glucose tolerance (IGT) form of pre-DM of 587 million people by 2045 means CAN will become a major clinical problem. CAN is independently associated with silent myocardial ischaemia, major cardiovascular events, myocardial dysfunction and cardiovascular mortality. Screening for CAN in pre-DM using risk scores with analysis of heart rate variability (HRV) or Sudoscan is important to allow earlier treatment at a reversible stage. The link between obesity and CAN highlights the therapeutic potential of lifestyle interventions including diet and physical activity to reverse MetS and prevent CAN. Weight loss achieved using these dietary and exercise lifestyle interventions improves the sympathetic and parasympathetic HRV indices of cardiac autonomic function. Further research is needed to identify high-risk populations of people with pre-DM or obesity that might benefit from targeted pharmacotherapy including metformin, sodium/glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) analogues. Bariatric surgery also improves HRV through weight loss which might also prevent CAN in severe obesity. This article reviews the literature on CAN in obesity, pre-DM and MetS, to help determine a rationale for screening, early intervention treatment and formulate future research questions in this highly prevalent condition.

Introduction: Understanding socioeconomic differences for prediabetes and type 2 diabetes (T2DM) can offer guidance for the most effective development of both prevention and intervention programmes in different settings. This study aims to determine the prevalence and risk factors for prediabetes and T2DM and to explore the effect of high body mass index (BMI) on the probability of T2DM being present among adults in China and Sweden.

Methods: This study enrolled 25,356 adults (35-64 years old) from the Shanghai Survey in China and 25,511 adults (aged 40, 50, 60) from the Västerbotten Intervention Programme in Sweden. Data on haemoglobin A1c, capillary fasting plasma glucose, 2-h plasma glucose and self-reported diagnoses of T2DM were used in the analysis. Multinomial logistic regression was used to examine the determinants of prediabetes and T2DM. The average predicted probabilities of T2DM developing or presenting were determined for the different ages and levels of BMI in each population.

Results: Chinese participants had a higher adjusted prevalence of T2DM (men 12.8% vs. 4.6%; women 10.6% vs. 3.1%) and prediabetes (men 12.4% vs. 12.2%; women 14.4% vs. 12.2%) than Swedish participants. Age, overweightedness/obesity, hypertension and a family history of diabetes were significant risk factors for prediabetes and T2DM. In both populations, the predicted probability of T2DM increased as the BMI increased in all age groups. At the same BMI level, Chinese participants were more likely to have T2DM compared to their Swedish counterparts. The average predicted probability of T2DM was less than 20% in nearly all age groups among Swedish women.

Conclusions: Chinese adults had the higher prevalence of prediabetes and T2DM and a higher probability of T2DM at the same BMI level compared with Swedish adults. These results indicate the importance of addressing the ongoing obesity epidemic as a matter of urgency in order to curb what has become an apparent diabetes epidemic in both countries.

During menopausal transition, various phenotypical and metabolic changes occur, affecting body weight, adipose tissue distribution and energy expenditure as well as insulin secretion and sensitivity. Taken together, these can predispose women to the development of type 2 diabetes mellitus (T2DM). Many women in midlife experience climacteric symptoms, including hot flashes and night sweats. Menopausal hormone therapy (MHT) is then indicated. MHT has a favourable effect on glucose homeostasis in both women without and with T2DM. T2DM was considered in the past as a cardiovascular disease (CVD) equivalent, which would suggest that women with T2DM should not receive MHT. This notion may still deter many clinicians from prescribing MHT to these patients. However, nowadays there is strong evidence to support an individualised approach after careful evaluation of CVD risk. In older women with T2DM (> 60 years old or > 10 years in menopause), MHT should not be initiated, because it may destabilise mature atherosclerotic plaques, resulting in thrombotic episodes. In obese women with T2DM or in women with moderate CVD risk, transdermal 17β-oestradiol could be used. This route of delivery presents beneficial effects regarding triglyceride concentrations and coagulation factors. In peri- or recently post-menopausal diabetic women with low risk for CVD, oral oestrogens can be used, since they exhibit stronger beneficial effects on glucose and lipid profiles. In any case, a progestogen with neutral effects on glucose metabolism should be used, such as natural progesterone, dydrogesterone or transdermal norethisterone. The goal is to maximise benefits and minimise adverse effects.

Diabetes mellitus (DM) and thyroid dysfunction (TD) often tend to coexist in patients. Both hypothyroidism and hyperthyroidism are more common in type 2 diabetes mellitus (T2DM) patients than in their nondiabetic counterparts. Current guidelines are neither clear nor specific about the frequency of thyroid function monitoring in T2DM patients. Circulating thyroid hormones affect several different organs and cells, have a major impact on glucose, lipid, and protein metabolism, and can worsen glycaemic control in T2DM. Hyperthyroidism and thyrotoxicosis can worsen subclinical DM and cause hyperglycaemia in T2DM patients, increasing the risk of diabetic complications. T2DM reduces thyroid-stimulating hormone levels and impairs the conversion of thyroxine (T4) to triiodothyronine (T3) in the peripheral tissues. Poorly managed T2DM can lead to insulin resistance and hyperinsulinaemia, which causes thyroid tissue proliferation and increases nodule formation and goitre size. In addition, while metformin can be beneficial in both T2DM and TD patients, other antidiabetics such as sulfonylureas, pioglitazone, and thiazolidinediones can negatively impact TD. Antithyroid drugs such as methimazole can impair glycaemic control in T2DM patients. Thyrovigilance in T2DM patients and diabetovigilance in TD patients may therefore be necessary to facilitate individualized care and management.Funding: Abbott India Ltd.

Introduction: Gestational diabetes mellitus (GDM) is a gestational complication that affects maternal and child health. The placenta provides the fetus with the necessary nutrition and oxygen and takes away the metabolic waste. Patients with GDM are diagnosed and treated merely on the basis of the blood glucose level; this approach does nothing to help evaluate the status of the placenta, which is worth noting in GDM. The purpose of this research was to clarify the relation between thioredoxin-interacting protein (TXNIP) and reactive oxygen species (ROS) in the placenta of patients with GDM, which has thus far remained unclear.

Methods: The expression of TXNIP in the placentas of 10 patients with GDM and 10 healthy puerperae (control group) was investigated via immunofluorescence. The relation among TXNIP, ROS, and the function of mitochondria was explored in HTR-8/SVneo cells stimulated by high glucose (HG).

Results: The results showed the expression of TXNIP in the placentas of patients with GDM was higher than that in the control group, and the expression of TXNIP in HTR-8/SVneo cells treated with HG was higher than that in the control group, causing the accumulation of ROS and changes of mitochondria, promoting apoptosis and inhibition of migration.

Conclusions: High expression of TXNIP caused by HG mediates the increasing ROS and the mitochondria dysfunction in GDM; this impairs the function of the placenta and is the basis for the prediction of perinatal outcome.