Upregulation of SCUBE2 expression in dyslipidemic type 2 diabetes mellitus is associated with endothelin-1

Type 2 diabetes mellitus (T2DM) is a major health problem for morbidity and mortality world-wide due to diabetic vascular complication. Following T2DM, dyslipidemia is known well for the main reason of vascular complication leading to atherosclerosis and impaired life expectancy in diabetes. Thus, a new prediction marker in T2DM could help prevent the progression disease despite of metabolic control. Signal peptide–CUB-EGF like containing protein 2 (SCUBE2), has been detected in vascular endothelium and was affected by cytokines. Recently, SCUBE2 was reported to increase in atherosclerotic human coronary artery, involving vascular smooth muscle cells (VSMCs) and macrophages. The aims of this study were to examine the expression level of SCUBE2 in T2DM patients with dyslipidemia and its correlation with endothelial dysfunction marker, endothelin-1 (ET-1) in this group. This study design was cross sectional control study, recruited 28 patients diagnosed as T2DM who were found with dyslipidemia and 15 healthy control subjects. Our results showed that T2DM patients showed higher LDL cholesterol, triglycerides, and ET-1 expression level compared to healthy subjects. Further, we found that SCUBE2 had strong correlation with ET-1 in these dyslipidemic T2DM patients. In conclusion, our study confirmed first that SCUBE2 was upregulated in T2DM with dyslipidemia. Moreover, Pearson correlation analysis of ET-1 and SCUBE2 in this group showed high correlation r = 0.797, P < 0.001, suggesting that SCUBE2 may plausible target in vascular function changes in dyslipidemic T2DM. Improving our exploration of these findings may lead to uncover SCUBE2 involvement in diabetic vascular complication in T2DM.     

Epidemiology of gestational diabetes mellitus and its association with Type 2 diabetes.

Gestational diabetes (GDM) is defined as carbohydrate intolerance that begins or is first recognized during pregnancy. Although it is a well-known cause of pregnancy complications, its epidemiology has not been studied systematically. Our aim was to review the recent data on the epidemiology of GDM, and to describe the close relationship of GDM to prediabetic states, in addition to the risk of future deterioration in insulin resistance and development of overt Type 2 diabetes. We found that differences in screening programmes and diagnostic criteria make it difficult to compare frequencies of GDM among various populations. Nevertheless, ethnicity has been proven to be an independent risk factor for GDM, which varies in prevalence in direct proportion to the prevalence of Type 2 diabetes in a given population or ethnic group. There are several identifiable predisposing factors for GDM, and in the absence of risk factors, the incidence of GDM is low. Therefore, some authors suggest that selective screening may be cost-effective. Importantly, women with an early diagnosis of GDM, in the first half of pregnancy, represent a high-risk subgroup, with an increased incidence of obstetric complications, recurrent GDM in subsequent pregnancies, and future development of Type 2 diabetes. Other factors that place women with GDM at increased risk of Type 2 diabetes are obesity and need for insulin for glycaemic control. Furthermore, hypertensive disorders in pregnancy and afterwards may be more prevalent in women with GDM. We conclude that the epidemiological data suggest an association between several high-risk prediabetic states, GDM, and Type 2 diabetes. Insulin resistance is suggested as a pathogenic linkage. It is possible that improving insulin sensitivity with diet, exercise and drugs such as metformin may reduce the risk of diabetes in individuals at high risk, such as women with polycystic ovary syndrome, impaired glucose tolerance, and a history of GDM. Large controlled studies are needed to clarify this issue and to develop appropriate diabetic prevention strategies that address the potentially modifiable risk factors.     

The influence of fasting insulin level in post-gestational diabetes mellitus women receiving low-glycaemic-index diets

Post-gestational diabetes mellitus (GDM) women are recommended weight loss to manage increased cardio-metabolic risks. We investigated the effects of lowering diet glycaemic index (GI) on fasting blood glucose (FBG), serum lipids, body weight and composition of post-GDM women with varying fasting insulin levels (INS). Seventy-seven Asian, non-diabetic women with previous GDM (aged 20–40 years, mean BMI: 26.4±4.6 kg m⁻²) were recruited. At baseline, 20 subjects with INS <2 μIU ml⁻¹ and 18 with INS ⩾2 μIU ml⁻¹ received conventional dietary recommendations (CHDR) only. CHDR emphasised energy and fat intake restriction and encouraged increase in dietary fibre intakes. Twenty-four subjects with INS <2 μIU ml⁻¹ and 15 with INS ⩾2 μIU ml⁻¹, in addition to CHDR, received low-GI education (LGI). Changes in FBG, serum lipids, body weight and body composition were evaluated. Subjects with INS <2 μIU ml⁻¹ had similar outcomes with both diets. After 1 year, subjects with INS ⩾2 μIU ml⁻¹ who received LGI education had reductions in FBG and triglycerides. Subjects who received CHDR observed increase in both FBG and triglycerides (P<0.05). Among all subjects, diet GI was lower and dietary fibre intakes were higher in LGI compared with CHDR subjects (all P<0.05). Thus, in Asian post-GDM women with normal/higher INS, adding low-GI education to CHDR improved management of FBG and triglycerides.     

金属硫蛋白1E基因多态性与2型糖尿病的关系

目的探讨金属硫蛋白（MT）IE基因多态性与2型糖尿病（T2DM）的关系。方法采用PCR-RFLP法检测149例T2DM患者和244例正常对照者的MTIE基因上的一个SNP-rs 8708274，应用SPSS统计学软件处理数据，进行统计学分析。结果病例组和对照组等位基因T和G比较差异有显著性（x^2=4．072，P〈0．05）；TT，TG，GG三种基因型频数分布在病例组和对照组中存在差异（x^2=8．252，P〈0．05）。结论在中国北方汉族人群中MTIE rs 708274位点基因多态性可能与T2DM相关。     

妊娠期糖尿病尾加压素Ⅱ基因多态性与胰岛素抵抗的关系

目的 探讨尾加压素Ⅱ(UTS2)基因rs228648的单核苷酸多态性与GDM及IR的关系.方法 选取GDM患者(GDM组)120例和糖耐量正常孕妇(GNGT) 100名,采用限制性片段长度多态性聚合酶链反应方法检测UTS2基因型,并分析相关临床资料. 结果 两组UTS2基因rs228648的基因型分布,差异有统计学意义(X2=9.94,P=0.007).GDM组危险等位基因G的分布频率高于GNGT组[147(61.25％)粥94(47.00％),X2=8.94,P=0.01].GDM组G/G基因型FIns、胰岛素抵抗指数(HO-MA-IR)均高于非G/G基因型(P=0.00). 结论 UTS2基因多态性与GDM发病相关,G/G基因型可能是GDM的易感基因;UTS2基因G/G基因型与GDM患者IR的发生有关.     

妊娠糖尿病孕妇骨代谢状况的研究

目的探讨妊娠糖尿病（GDM）孕妇与正常孕妇骨代谢特点的异同。方法比较67例妊娠糖尿病患者（GDM组）与13例正常糖耐量孕妇（NGT组）血钙、磷、ALP、250HD、CTx、24h尿钙、跟骨超声（SOS）等骨代谢指标的异同。然后将GDM组患者分为A、B两组,分别给予低、高两种不同剂量钙和维生素D干预至分娩前,比较两组治疗前后上述指标的差异。结果GDM组血钙、磷为（2．3±0．1）mmol／L、（1．3±0．2）mmol／L,NGT组血钙、磷分别为（2．2±0．1）mmol／L,（1．1±0．1）mmol／L（P〈0．05）;GDM组和NGT组24h尿钙均升高;GDMB组24h尿钙治疗前为（11．0±6．9）mmol／L,治疗后为（8．2±4．3）mmol／L,明显下降（P〈0．05）。结论GDM孕妇骨代谢特点和NGT孕妇基本相同,24h尿钙均显著增加。GDM可能导致血钙、磷轻度增加。补充足量的钙剂和维生素D可使尿钙丢失减少。     

Potential protective effect of lactation against incidence of type 2 diabetes mellitus in women with previous gestational diabetes mellitus: A systematic review and meta‐analysis

Lactation may protect women with previous gestational diabetes mellitus (GDM) from developing type 2 diabetes mellitus, but the results of existing studies are inconsistent, ranging from null to beneficial. We aimed to conduct a systematic review to gather available evidence. Databases MEDLINE, CINAHL, PubMed, and EMBASE were searched on December 15, 2015, without restriction of language or publication year. A manual search was also conducted. We included observational studies (cross‐sectional, case‐control, and cohort study) with information on lactation and type 2 diabetes mellitus incidence among women with previous GDM. We excluded case studies without control data. Data synthesis was conducted by random‐effect meta‐analysis. Fourteen reports of 9 studies were included. Overall risk of bias using RoBANS ranged from low to unclear. Longer lactation for more than 4 to 12 weeks postpartum had risk reduction of type 2 diabetes mellitus compared with shorter lactation (OR 0.77, 95% CI 0.01‐55.86; OR 0.56, 95% CI 0.35‐0.89; OR 0.22, 95% CI 0.13‐0.36; type 2 diabetes mellitus evaluation time < 2 y, 2‐5 y, and >5 y, respectively). Exclusive lactation for more than 6 to 9 weeks postpartum also had lower risk of type 2 diabetes mellitus compared with exclusive formula (OR 0.42, 95% CI 0.22‐0.81). The findings support the evidence that longer and exclusive lactation may be beneficial for type 2 diabetes mellitus prevention in women with previous GDM. However, the evidence relies only on observational studies. Therefore, further studies are required to address the true causal effect.     

Lack of suppression of plasma glucagon levels in late pregnancy persists postpartum only in women with previous gestational diabetes mellitus

Abstract The aim of the present study was to examine fasting (0) and postglucose glucagon levels in normal and gestational diabetes mellitus (GDM) pregnancy, as available data are somewhat conflicting. To this end we studied 18 women with GDM at 26–32 weeks of pregnancy and compared these with 26 normal pregnant women matched for age and BMI. We also examined glucagon suppressibility postpartum (2–4 months) in the same ex-GDM women, in whom normal glucose tolerance was confirmed (WHO criteria) and compared these with 17 controls matched for age and BMI. Glucose, insulin and glucagon levels were measured during a 100 or 75 g oral glucose tolerance test (OGTT) respectively. In pregnant women, baseline and 3 h after glucose ingestion, plasma glucagon levels were significantly higher (p<0.05) in women with GDM compared to normal women. Interestingly, in normal pregnancy a significant increase (p<0.01) of postglucose plasma glucagon levels at 1 and 2 h compared to baseline levels was observed, while there was no change in GDM pregnancy. In postpartum euglycaemic women, there was no difference in basal glucagon levels between the two groups. A differential glucagon response during OGTT was observed: in control women there was a significant glucagon suppression (p<0.01) at 2 h, while there was a significant glucagon increase (p<0.01) 1 h after glucose ingestion, in ex-GDM women. We conclude that (a) absence of the suppressibility of glucagon in ex-GDM women with normal OGTT may indicate insulin resistance and might be involved in the natural history towards glucose intolerance; and (b) nonsuppression of glucagon in normal late pregnancy as well as in pregnancy complicated by GDM may be due to physiological insulin resistance of the cells during this period.     

数据包络分析在老年2型糖尿病经济学评价中的应用

目的 探讨数据包络分析（DEA）在2型糖尿病不同医疗方案经济学评价中的应用。方法 采用临床随机试验的方法，将入组的2型糖尿病患者分为不同的医疗方案组进行治疗，然后进行随访观察。对各随访期内的成本和医疗后果进行测量，然后使用DEA对不同医疗方案的投入和产出进行综合评价。结果 常规治疗组和强化治疗组1年例均总费用分别为1403．78元和1460．83元，差异无统计学意义（P〉0．05）；强化治疗组的各临床疗效优于常规治疗组，且获得了比常规治疗组更多的质量调整生命年（QALYs）（P〈0．05）。与常规治疗方案相比，强化治疗方案为DEA有效，其投入和产出达到了最优。结论 DEA可作为2型糖尿病不同医疗方案经济学评价的有效手段，强化治疗方案比常规治疗方案具有更好的经济学效果。     

The older patient with diabetes: a practical approach

Type 2 diabetes mellitus is very prevalent among persons aged 60–80 years old. This population is expected to increase in number and is characterized by the presence of comorbidities, long standing diabetes, frailty, high rate of cognitive impairment and limited life expectancy. These characteristics have a significant impact on diabetes and treatment among the elderly, much as diabetes predisposes to these conditions. In this article we will describe mechanisms that may lead to insulin resistance and diabetes among the elderly and also how these conditions contribute to the development of frailty and cognitive impairment. Hypoglycemia and it's consequences are important considerations when planning the treatment of diabetes. Treatment options in light of new goals and the danger of hypoglycemia will be detailed. Copyright © 2013 John Wiley & Sons, Ltd.     

The changes of Lp-PLA2 in patients with gestational diabetes and its clinical significance

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and associated with adverse pregnancy outcomes. The aim of this study was to investigate the changes of lipoprotein-associated phospholipaseA2 (Lp-PLA2) level and its correlation with biochemical indexes in patients with GDM.This observational cross-sectional study was performed among 52 GDM and 48 healthy pregnant women. Automatic biochemical analyzer was employed to test the biochemical indexes, including fasting plasma glucose (FPG), Hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). The lipoprotein-associated phospholipaseA2 (Lp-PLA2) level was evaluated by enzyme-linked immunosorbent assay, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated.The levels of FPG, HbA1c, HOMA-IR, TG, TC and LDL-C were significantly increased while high-density lipoprotein cholesterol (HDL-C) level was significantly decreased in the GDM group when compared with those in the control group. Lp-PLA2 level in maternal blood in the GDM group was significantly higher than that in the control group (199.125 ± 23.494 vs165.825 ± 15.576 ng/mL, P < .05) and logistic regression analysis further confirmed the association of Lp-PLA2 levels with GDM. Furthermore, Lp-PLA2 positively correlated with HOMA-IR, TC, and LDL-C.Our results confirmed the association of Lp-PLA2 with GDM. This broadens our knowledge on the pathophysiology of GDM and provides insights into the development of new targets for the prevention and treatment of GDM.     

The emerging role of metformin in gestational diabetes mellitus

Metformin use during pregnancy is controversial and there is disparity in the acceptance of metformin treatment in women with gestational diabetes mellitus (GDM) in Australia. Despite short term maternal and neonatal safety measures, the placental transfer of metformin during GDM treatment and the absence of long‐term safety data in offspring has regulators and prescribers cautious about its use. To determine the current role in GDM management, this literature review describes the physiological changes that occur in GDM and other forms of diabetes in pregnancy (DIP) and international changes in guidelines for GDM diagnosis. Management options are considered, with a focus on the evolving evidence for metformin, its mechanism of action, the maternal, foetal and neonatal outcomes associated with its use and benefit vs risk when compared with the current gold standard, insulin. Investigation reveals a favourable balance of evidence to support the safety and long‐term benefits, to mother and child, of using metformin as an alternate to insulin for treatment of GDM. Recent findings of the gastrointestinal‐directed action of metformin are at least as important as the hepatic effect and the availability of a novel delayed‐release metformin dose form to exploit this new information provides a product and therapeutic strategy ideally suited to the use of metformin in GDM.     

Molecular mechanism of insulin resistance in type 2 diabetes mellitus: role of the insulin receptor variant forms

Type 2 diabetes is a heterogeneous and polygenic disorder resulting from interaction of genetic factors with environmental influences. Numerous candidate genes for insulin signaling proteins have been screened, but no single major susceptibility gene for type 2 diabetes has been identified. Due to its pivotal role in insulin action, the insulin receptor was considered a plausible candidate gene. The insulin receptor exists in two isoforms differing by the absence (Ex11^?) or presence (Ex11⁺) of a 12 amino acid sequence in the COOH‐terminus of the α‐subunit, as a consequence of alternative splicing of exon 11. The Ex11^? binds insulin with two‐fold higher affinity than the Ex11⁺. This difference is paralleled by a decreased sensitivity for metabolic actions of insulin. Some, but not all, studies have reported that expression of the low‐affinity Ex11⁺ is increased in target tissues from type 2 diabetic patients, thus suggesting that alterations in abundance of the two isoforms might contribute to insulin resistance. Insulin and type 1 IGF receptors have been shown to form hybrid receptors in tissues co‐expressing both molecules. Hybrid receptors bind IGF‐I, but not insulin, with high affinity, and behave as IGF‐I holoreceptors, rather than insulin receptors, in terms of receptor autophosphorylation, and hormone internalization. It has been shown that the abundance of hybrid receptors is increased in skeletal muscle and adipose tissue from type 2 diabetic patients, and is negatively correlated with in vivo insulin sensitivity. Mutations in the insulin receptor gene have been identified in studies which examined an appropriately sized population of patients with type 2 diabetes. The prevalence of mutations in the insulin receptor gene ranged from 0.4%–7.8%. This review will focus on the structural and functional heterogeneity of the insulin receptor, and will discuss the pathogenetic role of insulin receptor variant forms and polymorphisms in the development of the common form of type 2 diabetes. Copyright © 2001 John Wiley & Sons, Ltd.     

海水浴体疗操对老年2型糖尿病患者的心脏康复作用

目的:探讨海水浴体疗操运动对老年2型糖尿病(DM)患者的心脏康复作用。方法:应用本院设计的海水浴体疗操1套,对疗养期间62例老年2型DM患者(DM组)进行4疗程运动治疗。使用超声心动图仪观察患者体疗前、后LAD、EF、FS、E/A指标变化,并与健康老人(对照组)对照;使用常规心电图描记并观察DM组体疗前后的心电图变化。结果:DM组体疗前各指标较对照组有显著差异(P<0.01,P<0.05);体疗后与前对比:LAD缩小,E/A、FS、EF值明显增高,有非常显著统计学意义(P<0.01)。体疗后心电图窦性心律增至66.1％,Petfv1异常率减至24.2％,ST-T异常率减至17.7％,P均<0.01。结论:海水浴体疗操运动对DM患者心脏康复有较好疗效。