Glucose intolerance in middle-aged subjects--a cause of hypertension?

At a health survey of 819 middle-aged, 47-54-year-old, males and females in a Swedish urban area with a participation rate of 70%, the prevalence of glucose intolerance (GI) was 6.2%, 51 subjects (7.0% of females and 5.3% of males), as the result of two subsequent 75 g oral glucose tolerance tests according to the WHO criteria. In comparison with normoglycemic subjects from the same health survey, with both fasting and 2-hour glucose values less than 5.0 mmol X l-1, the GI group was characterized by higher mean relative body mass index, higher mean blood pressure and rate of hypertension, higher rate of low-degree physical activity during leisure and had more often a family history of diabetes in first-degree relatives. Smoking was less prevalent in GI subjects. Hypertension was more frequent in obese (relative body mass index (BMI) 120-150%) GI subjects than NGT subjects. Finally, comparison of all GI subjects with all normoglycemic subjects of the survey, with use of analysis of covariance, showed that mean systolic and diastolic blood pressures were higher in GI subjects, independently of age, BMI and also smoking.     

The angiotensin-I converting enzyme I/D polymorphism is not associated with type 2 diabetes in individuals undergoing coronary angiography. (The Ludwigshafen Risk and Cardiovascular Health Study)

The deletion (D) allele of the angiotensin-I converting enzyme (ACE) is associated with higher ACE activity and has been implicated only recently in the pathogenesis of type 2 diabetes in Caucasian subjects. We have studied the ACE I/D polymorphism in 1054 patients with type 2 diabetes and in 2251 individuals without type 2 diabetes in Caucasians persons undergoing coronary angiography. Further parameters of glucose metabolism (fasting glucose, HbA1c, insulin, C-peptide, pro-insulin, and pancreatic beta-cell function) were analyzed according to the ACE I/D genotype in a subgroup of 2000 individuals in whom an oral glucose challenge was performed. The genotypes ACE II, ID, DD occurred at similar frequencies in patients with type 2 diabetes mellitus (21.0, 50.8, and 28.3%, respectively) compared to non-diabetic individuals (23.3, 49.2, and 27.5%, respectively). There was no association of the ACE D allele with all type 2 diabetes mellitus (OR 1.16, 95%CI, 0.94-1.43), nor with known (OR 1.28, 95% CI, 0.99-1.68) or newly diagnosed diabetes (OR 1.00, 95% CI, 0.75-1.32). These findings were not materially altered when we adjusted for age and gender, cardiovascular risk factors and anti-diabetic or cardiovascular medication. Further the ACE D-allele was not associated with angiographic coronary heart disease or myocardial infarction. The ACE I/D genotype is not associated with type 2 diabetes mellitus, glucose metabolism, coronary heart disease, or myocardial infarction.     

The length of the CTLA-4 microsatellite (AT)N-repeat affects the risk for type 1 diabetes. Diabetes Incidence in Sweden Study Group

CTLA-4 is important to down-regulating T cell responses and has been implicated in type 1 (insulin dependent) diabetes mellitus in both linkage and association studies. The aim of our study was to relate the polymorphic (AT)n microsatellite in the 3' untranslated sequence of the CTLA-4 gene to diabetes risk. We studied 616 consecutively diagnosed 0-34 year-old Swedish patients and 502 matched controls by PCR-based genotyping fo determine the length of the 3'-end (AT)n repeat region of the CTLA-4 gene and categorizing alleles as predominantly monomorphic short (S) or highly polymorphic (in length) long (L) alleles. The odds of type 1 diabetes of subjects with the L/L genotype was estimated to be 1.84 times that of subjects with the S/S genotype (95% CI 1.44-2.73, p=0.002). Further analysis of the long alleles, partitioned into intermediate (I) length and very long (VL) alleles, suggested that L alleles act recessively in conferring diabetes risk (p=0.0009). This study suggests that the 3'-end (AT)n repeat region of the CTLA-4 gene represents a recessive risk factor for type 1 diabetes.     

Increased incidence of autoimmune disorders as a late complication in children with early onset dermatitis and/or milk allergy

Subjects with atopic dermatitis and autoimmune disorders share some similar immune response disorders. The aim of this study was to see whether subjects with early onset atopic dermatitis run a risk of eventually developing autoimmune diseases. The results of a questionnaire of 145 adolescents (70 f, 75 m, mean age 18.2 years, range 16-23 years) was compared with those of a group of 262 controls (112 f, 150 m, mean age 17.5 years, range 16-21 years), 164 of whom reported no atopic symptoms and were treated as a separate group for statistical analysis. As compared with the non-atopic controls, the study group subjects showed a significantly increased incidence of autoimmune disorders (9% vs. 1%), the relative risk ratio of a subject with infantile onset atopic eczema getting a gastrointestinal (GI) immune-mediated disease being 2.4 (CI(95)2.1-2.8) and of getting some other autoimmune disorder 3.1 (CI(95)2.8-9.7). The positive skin prick tests showed a negative association with the manifestation of a GI or other autoimmune disorder. The subjects with infantile dermatitis also reported recurrent abdominal pains (23% vs. 15%), and milk-induced gastrointestinal symptoms (19% vs. 10%) significantly more even as young adults than the controls. Our study showed that infantile atopy increases a predisposition to autoimmune disorders, suggesting that these two entities might have a common immunological determinant. While a high incidence of chronic GI complaints among the study subjects suggests the ongoing activity of local immune responses. However, more detailed prospective studies are needed to confirm these observations.     

神经源分化因子基因多态性与2型糖尿病的关联性研究

目的　探讨神经源分化因子 (neurogenic differentiation factor 1,Neuro D)基因多态性与 2型糖尿病发生的关联性。方法　运用错配聚合酶链反应 -限制性片段长度多态性方法检测了中国湖北地区汉族 32 4例 2型糖尿病 (其中以发病年龄 40岁为界 ,分为早发及晚发两组 )及 12 4名正常对照者 ,Neuro D基因第 45位密码子碱基变异 (GCC→ ACC)。结果　 Neuro D基因在所测人群中未发现有纯合变异者。在早发 2型糖尿病组 ,其 AT基因型频率为 2 6 .8% ,与正常对照组 (10 .5 % )及晚发 2型糖尿病组 (11.6 % )比较 ,差异有显著性 (分别为χ2 =7.85 ,P=0 .0 0 5 ;χ2 =8.81,P=0 .0 0 3) ;Thr45等位基因频率在早发 2型糖尿病组及正常对照组、晚发 2型糖尿病组分别为 13.4%、5 .2 %和 5 .8% ,差异亦有显著性 (χ2 =7.15 ,P=0 .0 0 8;χ2 =8.13,P=0 .0 0 4) ;晚发 2型糖尿病组与正常对照组比较 ,Ala45 Thr基因型频率 (11.6 % vs10 .5 % ,P>0 .0 5 )及等位基因频率 (5 .8% vs 5 .2 % ,P>0 .0 5 )差异不明显 ,Thr45等位基因与早发 2型糖尿病发生相关 (OR=2 .5 2 ,95 % CI:1.42～ 4.49) ;基因型为 AT型的 2型糖尿病患者其空腹血浆 C肽水平较 AA型患者低 ,差异有显著性 (P<0 .0 5 )。结论　 Neuro D基因多态性与早发 2型糖尿     

CDKAL1基因rs7754860位点G<C多态性与2型糖尿病易感关系的Meta分析*◆

背景：遗传学研究显示2型糖尿病可能存在遗传易感性,但研究结论存在一定的差异。 目的：探讨CDKAL1(细胞周期素依赖激酶5调节亚单位相关蛋白1类似物1)基因rs7754860位点G相似文献   

The Length of the CTLA-4 Microsatellite (AT)N-Repeat Affects the Risk for Type 1 Diabetes: For the Swedish Childhood Diabetes Study Group

CTLA-4 is important to down-regulating T cell responses and has been implicated in type 1 (insulin dependent) diabetes mellitus in both linkage and association studies. The aim of our study was to relate the polymorphic (AT)_n microsatellite in the 3′ untranslated sequence of the CTLA-4 gene to diabetes risk. We studied 616 consecutively diagnosed 0-34 year-old Swedish patients and 502 matched controls by PCR-based genotyping to determine the length of the 3′-end (AT)_n repeat region of the CTLA-4 gene and categorizing alleles as predominantly monomorphic short (S) or highly polymorphic (in length) long (L) alleles. The odds of type 1 diabetes of subjects with the L/L genotype was estimated to be 1.84 times that of subjects with the S/S genotype (95% CI 1.44-2.73, p=0.002). Further analysis of the long alleles, partitioned into intermediate (I) length and very long (VL) alleles, suggested that L alleles act recessively in conferring diabetes risk (p=0.0009). This study suggests that the 3′-end (AT)_n repeat region of the CTLA-4 gene represents a recessive risk factor for type 1 diabetes     

Diseases Concomitant With Asthma in Middle-Aged and Elderly Subjects in Korea: A Population-Based Study

Purpose

Asthma is prevalent in many countries. Few studies have investigated the association between asthma and concomitant diseases. We retrospectively analyzed the fourth Korean National Health and Nutrition Survey database, performed in 2008 using nationwide stratified random sampling to obtain a representative cohort of the Korean population.

Methods

We evaluated the association between both self-reported ever-asthmatics and wheezers and concomitant diseases such as arthritis, hypertension, gastrointestinal (GI) ulcers, dyslipidemia, diabetes mellitus, rhinitis, depression, stroke, and obesity in subjects aged ≥40 years. A multivariate analysis was performed to identify concomitant diseases independently associated with asthma, after adjustment for age, gender, income, cigarette smoking, and other chronic diseases.

Results

Of the total of 4,445 subjects, 2,596 (58.4%) were female and the mean age was 58.3 years. Of the 4,445 subjects, 195 (4.4%) had been diagnosed with asthma at some point, and 444 (10%) were wheezers. Multivariate analysis showed that arthritis (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.26-2.42), rhinitis (OR 1.78, 95% CI 1.14-2.78), depression (OR 1.45, 95% CI 1.05-2.07), and obesity (OR 1.61, 95% CI 1.08-2.40) were significantly associated with self-reported ever-asthma, and arthritis (OR 1.50, 95% CI 1.19-1.909), hypertension (OR 1.34, 95% CI 1.07-1.67), GI ulcers (OR 1.48, 95% CI 1.05-2.08), rhinitis (OR 1.60, 95% CI 1.16-2.19), depression (OR 1.94, 95% CI 1.51-2.48), and obesity (OR 1.56, 95% CI 1.17-2.09) were significantly associated with wheezers.

Conclusions

These findings indicate that arthritis, rhinitis, depression, and obesity may be associated with both self-reported ever asthma and wheezers in the Korean population.     

2型糖尿病患者的肺弥散功能检测分析(英)

目的：检测2型糖尿病患者的肺通气和弥散功能，探讨肺脏是否为糖尿病慢性病变的靶器官。方法： 对107名2型糖尿病患者行肺通气及弥散功能检测，并与61名年龄、性别匹配的健康者比较。糖尿病患者需行糖化血红蛋白（HbA1c）、尿白蛋白排泄率（AER）检测、眼底检查以及神经传导速度检查，以评价血糖控制水平以及糖尿病微血管病变状况。结果： 2型糖尿病组肺通气功能与正常对照组相比，无显著差异。2型糖尿病组一氧化碳弥散量（DLCO）及单位肺泡容积的一氧化碳弥散量（DLCO/VA）较对照组明显降低（P<0.05）。DLCO、DLCO/VA与微血管病变积分呈负相关（r分别为-0.291、 -0.324，P<0.01）。此外，DLCO/VA还与年龄、病程呈负相关（r分别为-0.269、-0.236，P<0.05）。结论： 2型糖尿病患者虽然肺通气功能基本正常，但有弥散功能受损，提示肺脏可能也是糖尿病慢性病变的靶器官之一。     

Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance

BACKGROUND: Type 2 diabetes mellitus is increasingly common, primarily because of increases in the prevalence of a sedentary lifestyle and obesity. Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known. METHODS: We randomly assigned 522 middle-aged, overweight subjects (172 men and 350 women; mean age, 55 years; mean body-mass index [weight in kilograms divided by the square of the height in meters], 31) with impaired glucose tolerance to either the intervention group or the control group. Each subject in the intervention group received individualized counseling aimed at reducing weight, total intake of fat, and intake of saturated fat and increasing intake of fiber and physical activity. An oral glucose-tolerance test was performed annually; the diagnosis of diabetes was confirmed by a second test. The mean duration of follow-up was 3.2 years. RESULTS: The mean (+/-SD) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group (P<0.001 for both comparisons between the groups). The cumulative incidence of diabetes after four years was 11 percent (95 percent confidence interval, 6 to 15 percent) in the intervention group and 23 percent (95 percent confidence interval, 17 to 29 percent) in the control group. During the trial, the risk of diabetes was reduced by 58 percent (P<0.001) in the intervention group. The reduction in the incidence of diabetes was directly associated with changes in lifestyle. CONCLUSIONS: Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects.     

Effect of Combination Therapy with Coenzyme Q10 on Functional and Metabolic Parameters in Patients with Type 1 Diabetes Mellitus

Functional state of the kidneys, severity of metabolic disturbances, intensity of LPO, and activity of the antioxidant system in 30 patients (18-36 years old) with type 1 diabetes mellitus and diabetic nephropathy of different compensation were studied before and after standard therapy or combination treatment with coenzyme Q10. Similar parameters were evaluated in 20 healthy subjects of the same age group. The development of metabolic disturbances in patients with type 1 diabetes mellitus (decompensated form) was accompanied by activation of LPO and inhibition of the antioxidant system. These patients were characterized by oxidative stress, diabetic nephropathy with associated proteinuria, and impairment of water excretion, electrolyte excretion, and nitrogen excretion in the kidneys. Combination therapy with coenzyme Q10 had a positive effect on LPO and antioxidant system. This treatment was followed by the relief of hyperglycemia, decrease in the concentrations of glycosylated hemoglobin and LDL cholesterol, and improvement of nitrogen metabolism.     

Gene expression of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in skeletal muscle from type 2 diabetic subjects

The gene of the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase gives rise to several splice variants. We hypothesized that the expression of p85alpha splice variants may be altered in skeletal muscle from subjects with type 2 diabetes mellitus. Skeletal muscle biopsies were obtained from nine type 2 diabetic and eight healthy men, matched for age, body mass index (BMI) and physical fitness. PI 3-kinase activity in skeletal muscle following in vitro insulin stimulation was reduced in subjects with type 2 diabetes. p85alpha mRNA was elevated fourfold in type 2 diabetic as compared to healthy control subjects ( P<0.05). p85alpha mRNA abundance was positively correlated with plasma insulin concentration ( P<0.01) and serum glucose concentration ( P<0.01). Despite this, protein levels of p85alpha, p55alpha, and the novel human p50alpha were not altered in type 2 diabetic subjects. Thus, although gene expression of full-length p85alpha is increased in skeletal muscle from type 2 diabetics, this is not reflected by increased protein levels. Therefore, defects in PI 3-kinase activity are likely due to impaired activation of the enzyme rather than changes in protein expression of the isoforms of the regulatory subunit.     

Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients

Mutations in the small heterodimer partner gene (NR0B2; alias SHP) are associated with high birth weight and mild obesity in Japanese children. SHP mutations may also be associated with later obesity and insulin resistance syndrome that induces diabetes. To investigate this possibility, the prevalence of SHP mutations in Japanese with and without type 2 diabetes mellitus and the functional properties of the mutant proteins were evaluated. Direct sequencing of two exons and flanking sequences of SHP in 805 diabetic patients and 752 non-diabetic controls identified 15 different mutations in 44 subjects, including 6 novel mutations. Functional analyses of the mutant proteins revealed significantly reduced activity of nine of the mutations. Mutations with reduced activity were found in 19 patients (2.4%) in the diabetic group and in 6 subjects (0.8%) in the control group. The frequency difference between DM and control subjects adjusted for sex and age was statistically significant (P=0.029, odds ratio 2.67, 95% CI 1.05-6.81, 1-beta=0.91). We conclude that SHP mutations associated with mild obesity in childhood increase susceptibility to type 2 diabetes in later life in Japanese.     

D-二聚体联合纤维蛋白原对2型糖尿病患者急性肺栓塞的诊断价值

目的:探讨D-二聚体(D-dimer,D-D)联合纤维蛋白原(fibrinogen,FIB)对2型糖尿病内科住院患者急性肺栓塞的诊断价值.方法:选择2013年1月至2016年3月经CT肺动脉造影确诊急性肺栓塞的2型糖尿病内科住院患者及同期排除肺栓塞的2型糖尿病患者各80例,检测D-D及FIB水平.结果:在2型糖尿病急性肺栓塞患者中,D-D及FIB水平明显高于对照组.D-D和FIB单独检测诊断急性肺栓塞时的灵敏度、特异度、约登指数及ROC曲线下面积分别为:72.5％,42.5％;62.5％,91.25％;0.35,0.338;0.675(95％CI:0.597～0.747),0.669(95％CI:0.590～0.741);两者联合检测诊断急性肺栓塞时灵敏度为85.0％,特异度为60.0％,约登指数为0.45,工作特征曲线(receiver operatorcharacteristic,ROC)下面积为0.773(95％CI:0.700～0.835).D-D和FIB联合检测诊断急性肺栓塞时的ROC曲线下面积与单独检测D-D,FIB比较,差异有统计学意义(P＜0.01).结论:D-D联合FIB可作为2型糖尿病内科住院患者急性肺栓塞早期诊断时简单易行可靠的检测指标.     

深圳地区人群2型糖尿病相关基因多态性的研究

目的研究分析深圳地区2型糖尿病（DM）相关基因浆细胞膜糖蛋白（PC-1）基因K121Q多态性，探讨其于2型DM的关系。方法选择214例2型DM患者和295例非DM对照人群作病例对照研究。聚合酶链反应-限制性酶切片段长度多态性（PCR-RFLP）检测PC-1基因K121Q多态性。并分析其与2型DM的相关性。结果PC-1基因PCR扩增片段大小为240bp，与预期的扩增片段大小相符。扩增片段经限制性内切酶AvaⅡ酶切后，产生Q与K两个等位基因，出现2种基因型条带，分别为KK型和QK型。509例研究对象中，KK基因型者433例，所占比例最高，为85．07％；KQ基因型者次之，有76例，占14．93％；未见QQ基因型。K等位基因频率为92．53％，Q等位基因频率为7．47％。各组基因型频率及等位基因频率比较，差异均有统计学意义（P〈0．05）。以是否患2型糖尿病为因变量，PC．1基因K121Q基因型为自变量，进行Logistic回归分析。单因素分析结果表明，与KK基因型者相比，KQ基因型与2型DM存在显著相关性，其P=0．034，OR=1．84，OR95％CI为（1．05-3．24）。结论PC-1基因K121Q多态性与2型糖尿病存在相关性，KQ基因型可能是2型糖尿病的危险因素之一。     

Change in serum cholinesterase activity in Jamaican diabetics.

This study investigates the alteration of serum cholinesterase levels in diabetics and its possible relationship to blood glucose, insulin, triglyceride, and cholesterol levels. Fourteen phasic insulin-dependent diabetes mellitus patients were compared with 10 insulin-dependent diabetes mellitus, 10 noninsulin-dependent diabetes mellitus, and 10 normal controls. Each group was matched for age, sex, body mass index, and duration of diabetes. Mean age was 56.7 +/- 2.5 years; mean body mass index, 24.0 +/- 0.8 kg/m2; and mean duration of diabetes, 14.2 +/- 2.2 years. Serum acetylcholinesterase, insulin, triglyceride, and cholesterol levels as well as fasting blood sugar were all assayed using standard techniques. Results suggest an associated increase of serum acetylcholinesterase with triglyceride levels in diabetics and may point to a possible association between increased serum acetylcholinesterase and vascular complications in Jamaican diabetics.     

Celiac disease associated antibodies in persons with latent autoimmune diabetes of adult and type 2 diabetes

BACKGROUND: Celiac Disease (CD) is present in 1-16.4% of patients with type 1 diabetes mellitus. The most important serological markers of CD are anti-endomysial (EMA), anti-tissue transglutaminase (tTGA) and antigliadin antibodies (AGA). AIM/HYPOTHESIS: The objective of this work is to determine the frequency of tTGA and/or AGA in latent autoimmune diabetes of adult (LADA) and subjects with type 2 diabetes (T2DM), as well as to evaluate their relation with several clinical and biochemical characteristics. SUBJECTS AND METHODS: Forty three subjects with LADA and 99 with T2DM were studied. The presence of AGA, tTGA was determined in the sera of these patients. The variables: sex, age, duration of diabetes, treatment, body mass index (BMI) and fasting blood glucose concentration were also recorded. RESULTS: No differences were found in the frequency of celiac disease associated antibodies between LADA and T2DM subjects. The presence of celiac disease related antibodies was more frequent in patients with a normal or low BMI. CONCLUSIONS: Celiac disease does not seem to be related with pancreatic autoimmunity in type 2 diabetes. Celiac disease causes a decrease of body mass index in type 2 diabetes while pancreatic islet autoimmunity in this entity masks this effect.     

Diabetes mellitus--definition, classification and diagnosis

Diabetes mellitus comprises of a group of heterogeneous disorders which have an increase in blood glucose concentrations in common. The current classifications for diabetes mellitus type 1-4 are described and the main features of type 1 and type 2 diabetes are compared to allow for better discrimination between these diabetes types. Furthermore, the criteria for the correct biochemical diagnosis during fasting and during oral glucose tolerance tests are summarized. These data form the basis of the recommendations of the Austrian Diabetes Association for the clinical practice in diabetes.