Mitochondrial diabetes mellitus

This review discusses the current insight by which mutations in mitochondrial DNA (mtDNA) contribute to the development of particular disease states with emphasis on diabetes mellitus. Mitochondria are the power factories of the cells and produce ATP by oxidizing reducing equivalents via the respiratory chain. These reducing equivalents originate mainly from the citric acid cycle that also occurs within the mitochondria. Human mitochondria contain their own genetic material in the form of circular DNA that encodes for only a fraction of the mitochondrial components. The other mitochondrial components are nuclear encoded. Pathogenic mutations in mtDNA can affect the activity of the respiratory chain, thereby leading to the reduced generation of ATP. However, mitochondria not only produce ATP but they also regulate cytosolic concentrations of signaling molecules such as calcium and iron ions. The metabolic processes within mitochondria such as the citric acid cycle determine the concentration of metabolites that can also act as signalling molecules. Furthermore, the respiratory chain and mitochondrion-associated monoamine oxidase are major producers of reactive oxygen radicals. As a result, mutations in mtDNA can deregulate multiple processes within cells and the balance of this deregulation may contribute to the clinical phenotype.     

线粒体tRNAleu(UUR)基因突变糖尿病

目的 探讨线粒体tRNA^leu(UUR)基因突变糖尿病（MDM）在沈阳地区汉族人中的检出率及其临床表现。方法 应用聚合酶链反应／ApaI酶解法检测100例母亲患有糖尿病（DM）的2型DM患者的tRNA^leu(UUR)基因。结果 100例患者中3例有此基因突变；结合家系调查除认识了本病一般临床表现外，尚发现几种少见表现类型：孪生儿MDM、未被证实为母系遗传的MDM及尚未发病的MDM致病基因携带者。结论 本病在有DM家族史、尤其母亲患有DM的2型DM患者中的检出率为3％；孪生儿MDM更体现了本病呈母系遗传的特点，另有一例未被证实为母系遗传的MDM，需对其进一步研究。     

Mannose-binding lectin gene polymorphisms are associated with gestational diabetes mellitus

Insulin resistance is a feature of gestational diabetes mellitus (GDM). Inverse correlations between indexes of insulin sensitivity and serum markers of inflammation have been observed and, particularly, TNF-alpha has been shown to be associated with the appearance of insulin resistance in pregnancy. Mannose-binding lectin (MBL) is a protein member of the collectin family. Its deficiency is genetically determined and predisposes to recurrent infections and chronic inflammatory diseases. To test the hypothesis that a genetic predisposition to a proinflammatory state could favor the appearance of GDM during pregnancy, we studied R52C and G54D polymorphisms of MBL2 gene and plasma MBL levels from 105 consecutive GDM women and 173 healthy pregnant women. An association was found between G54D and GDM [odds ratio, 2.03 (1.18-3.49); P < 0.01], and this association remained significant when the presence of both mutated alleles was considered [odds ratio, 1.76 (1.04-2.96); P < 0.05] but not for the R52C. GDM patients who carried the G54D mutation required insulin therapy more frequently (56.4 vs. 30.4%, chi(2) =5.83; P = 0.027) and had heavier infants (3326.4 +/- 546.9 vs. 3087.5 +/- 395.5 g; P < 0.05) than GDM women homozygous for the wild-type allele. An inverse correlation in GDM patients between neonatal weight and plasma MBL levels (r = -0.320; P = 0.002) was found, remaining significant after adjustment for confounding variables. In conclusion, pregnant women bearing the G54D MBL allele have a greater risk for developing GDM and having heavier infants.     

Hemostatic changes in gestational diabetes mellitus

The purpose was to characterize the hemostatic changes in women with gestational diabetes mellitus (GDM). In this case–control study, 50 women with newly diagnosed GDM at 24–28 weeks of pregnancy and 41 normal pregnant women, matched for age, body mass index, and gestational age, were enrolled. Anthropometric, metabolic patterns, coagulation parameters, and plasminogen were measured in each subject. Plasma fibrinogen levels, plasminogen, and von Willebrand factor (vWF) activities were significantly higher in patients with GDM as compared to normal pregnant women (p < 0.001, p < 0.001, and p < 0.05, respectively). Although protein S was significantly elevated in diabetic group (p < 0.05), free protein S was similar in both groups. Coagulation factors VIII and IXa were significantly higher in patients with GDM (p < 0.001 and p < 0.01, respectively). In the group with GDM, factor VIII was positively correlated with HbA1c (r = 0.192, p < 0.001). A weak but significant negative correlation was observed between protein S and fasting glucose (r =−0.006, p < 0.05). GDM potentiates the alteration in coagulation and fibrinolysis during normal pregnancy. The question of whether the hemostatic balance is unchanged or shifts toward a hypercoagulable status remains unanswered.

     

Circulating Pro-Neurotensin in gestational diabetes mellitus

Background and aims

Pro-Neurotensin (NT), a stable surrogate parameter of NT, has recently been introduced as a peptide predicting the development of obesity, diabetes mellitus, cardiovascular diseases, and cardiovascular mortality. However, regulation of Pro-NT in gestational diabetes mellitus (GDM) remains uninvestigated.

1,5 Anhydroglucitol in gestational diabetes mellitus

Objective

1,5 Anhydroglucitol (1,5 AG) is reported to be a more sensitive marker of glucose variability and short-term glycemic control (1–2?weeks) in patients with type1 and type 2 diabetes. However, the role of 1,5 AG in gestational diabetes mellitus (GDM) is not clear. We estimated the serum levels of 1,5 AG in pregnant women with and without GDM.

Autonomic modulation in gestational diabetes mellitus

AimsThe aim of this study was to evaluate the influence of gestational diabetes mellitus (GDM) and positional aortocaval compression on cardiovascular autonomic nervous system (ANS) function in late pregnancy.MethodsPregnant women with (n = 31) and without (n = 12) GDM were evaluated at 30–35 weeks gestation and 2–3 months postpartum. Measures of ANS function included power spectral analysis (performed sitting) and RR-variation during deep breathing (performed supine). Time-related changes (late pregnancy versus 2–3 months postpartum) for measurements of cardiovascular ANS function were analyzed using multivariate analysis of variance for repeated measures.ResultsBaseline characteristics were similar for both groups. Comparing ANS measures for GDM + versus GDM − women during pregnancy and postpartum revealed no significant differences. Time related changes indicated that during late pregnancy total spectral power, low frequency (LF) power, high frequency (HF) power, and RR-variation during deep breathing were significantly reduced (p < 0.001 for all). The LF/HF ratio, however, was not significantly affected during late pregnancy (p = 0.678).ConclusionsOur results suggest decreased activity in both branches of the ANS during mid-third trimester pregnancy, but no significant change in sympathovagal balance. Aortocaval compression appears to affect ANS function whether tests were performed sitting or supine for GDM + and GDM − women.     

Decreased stature in gestational diabetes mellitus

Summary Short stature has been associated with various degrees of abnormal glucose tolerance in middle-aged people, where the effects of age and metabolic control would be difficult to exclude. We chose to examine body stature in women with gestational diabetes mellitus (GDM), a prediabetic state affecting a young group of people. A sample of 2772 Greek pregnant women, referred for GDM screening was examined. After a 100-g oral glucose tolerance test, 1787 women were classified as normal (N), 300 women were found with one abnormal glucose value (OAV) and 685 women with GDM. Basal insulin resistance was calculated in 640 women by homeostasis model assessment. In addition, 51 pregnant women with pre-existing Type II (non-insulin-dependent) diabetes mellitus and 109 with pre-existing Type I (insulin-dependent) diabetes mellitus were included in the study. There was a gradual decrease in mean height (cm) as glucose intolerance became more severe: N: 161.0 ± 6.2, OAV:160.2 ± 6.1, GDM:158.7 ± 6.3, Type II diabetes 158.2 ± 7.0 (p < 0.001, analysis of variance]. Height in Type I diabetes (160.1 ± 5.9) did not differ from the normal group. The difference in height between the normal and GDM groups remained (p < 0.001) when body weight, age, birth before or after 1960 and educational status were also taken into account. An independent correlation was also found between height and insulin resistance (n = 640) adjusted for the above mentioned variables. In conclusion, short stature appears to be associated with glucose intolerance as an independent variable, even when this intolerance is both mild and temporary. The previously unrecognised independent association of stature with basal insulin resistance merits further investigation. [Diabetologia (1998) 41: 997–1001] Received: 2 February 1998 and in final revised form: 28 April 1998     

关注妊娠糖尿病

自1979年世界卫生组织首次将妊娠糖尿病作为糖尿病的一大亚型独立划分出来至今的30．年间,妊娠糖尿病患病率不断增加,其对母婴健康的影响巨大,值得密切关注。妊娠糖尿病的病理机制可能与妊娠期问胰岛素抵抗加剧,以及胰岛素信号转递过程中多个环节受损有关,尚需更多的探索。为了保证母婴健康,对妊娠糖尿病的临床与基础研究仍需进一步加强。     

妊娠糖尿病发病机制研究进展

妊娠糖尿病(GDM)主要指妊娠期首次发现的糖耐量异常.GDM与非妊娠期的糖尿病都是遗传因素与环境因素共同作用所致的多基因复杂疾病,其发病机制涉及遗传易感性、胰岛素抵抗和分泌缺陷、慢性炎性反应等.而且,GDM病史是女性产后发展为糖尿病的高危因素.因此,深入了解GDM的发病机制具有重要意义.     

妊娠糖尿病的药物治疗

妊娠糖尿病是在妊娠过程中首次发现的任何程度的糖耐最异常,其发病机制与多种因素相关.妊娠期间血糖水平对母体、妊娠结局及围产儿的预后有着重要的影响.治疗妊娠糖尿病的药物选择要求能够有效控制血糖,及对胎儿影响小,低血糖事件少,患者依从性好等.目前治疗妊娠糖尿病的药物仍以胰岛素为主,但部分口服降糖药也逐渐进入人们的视野.现就妊娠糖尿病的药物治疗进行概述.     

CDKAL1基因多态性与妊娠期糖尿病及其临床特点的相关性研究

目的 探讨我国南方人群中CDKAL1基因两个SNP位点rs7754840和rs10448033的多态性与GDM易感性的关系. 方法 采用病例对照研究,分别选取GDM患者(GDM组)153例和正常糖耐量的孕妇(GNGT组)180名.采用聚合酶链反应-限制性片断长度多态性分析法(PCR-RFLP)测定两个SNP位点多态性分布,并进行统计学分析. 结果 GDM组孕前BMI、FPG、TG均高于GNGT组,TC、HDL-C及LDL-C均低于GNGT组(P＜0.05).SNP位点rs7754840基因型(CC,GC,GG)频率和等位基因频率与GNGT组比较,差异均无统计学意义(P=0.937、0.933);而SNP位点rs10440833基因型(AA,AT,TT)与GNGT组比较,差异有统计学意义(P=0.024),且风险基因型TT的频率高于GNGT组(TTvs TC+CC,P=0.032);GDM组A等位基因频率高于GNGT组[OR(95％CI):1.519(1.114～2.071),P=0.008];AA基因型患者的FPG高于其他基因型(P=0.011),TG高于TT基因型(P=0.007),HDL C低于TT基因型(P=0.001). 结论 CDKAL1基因SNP位点rs7754840与GDM无相关性;SNP位点rs10440833与GDM的易感性相关,且该位点多态性可能与血糖、TG及LDL-C的水平有关.     

中国人家族性糖尿病人群中线粒体tRNALys基因突变筛查

线粒体赖氨酸基因的三个突变-tRNALyB8296A→G,tRNALyB8344A→G和tRNALyB8363G→A与日本人糖尿病的发病相关。本研究在糖尿病患者及对照组中均未发现这三个突变,提示这三个点突变均不是中国人线粒体糖尿病发病的原因。     

妊娠糖尿病的危险因素

妊娠糖尿病是糖尿病分型中的一种独立类型.目前,妊娠糖尿病公认的危险因素包括年龄大于25岁、孕前体重指数大于25 kg/m2、非高加索白人、糖尿病家族史等.近年研究证实,妊娠糖尿病还与其他一些因素相关,如多囊卵巢综合征、身高偏矮、携带HBsAg、高血压等.及早的发现和干预这些高危因素,对于改善孕妇及子代的预后,减少人群中糖尿病的发病率有深远影响.     

Glucokinase gene in gestational diabetes mellitus: population association study and molecular scanning

Summary Mutations of the glucokinase gene result in early-onset familial Type 2 (non-insulin-dependent) diabetes mellitus, and several members of the mutant glucokinase kindreds were originally diagnosed as having gestational diabetes. This study examined the glucokinase gene in 270 American Black women, including 94 with gestational diabetes whose diabetes resolved after pregnancy (gestational diabetes only), 77 with gestational diabetes who developed Type 2 diabetes after pregnancy (overt diabetes), and 99 normal control subjects who were recruited during the peripartum period. Two simple sequence repeat polymorphisms flanking either end of the glucokinase gene were evaluated. No association was found between glucokinase alleles and gestational diabetes only or overt diabetes, after adjustment for multiple comparisons. To detect single base changes, all 11 exons and proximal islet and liver promoter regions were examined by polymerase chain reaction plus single-stranded conformational polymorphism analysis in 45 gestational diabetes only patients who had not yet developed Type 2 diabetes. Nine coding region variants were identified: Ala¹¹ (GCC) to Thr¹¹ (ACC) in islet exon 1, and 8 variants either in untranslated regions or in the third base of a codon. Four variant sites were found in introns, but none in splicing consensus sequences. Analysis of the promoter regions revealed two common variants, GA at islet –30 (24%), and GA at liver –258 (42%). The frequencies of the promoter variants, determined by allele specific polymerase chain reaction analysis, did not differ among the three groups. Thus, no significant coding sequence glucokinase mutations were found in 90 alleles from 45 patients with gestational diabetes. Further studies will be required to rule out a minor role of the newly-described promoter region variants as susceptibility factors in this disorder.     

Prediction of postpartum diabetes in women with gestational diabetes mellitus

Aims/hypothesis  

We studied the incidence of postpartum diabetes after gestational diabetes mellitus and investigated biochemical and clinical predictors of postpartum diabetes.