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。     

Enhanced production of interleukin-29 and related genes are associated with T helper 1 cell parameters in patients with type 2 diabetes mellitus

ObjectiveThe production of interleukin (IL)-29 and the genes related to IL-29 signaling pathway (STAT1, NF-κB, and NFATc1), and T helper (Th) 1 cells (T-bet, IFN-γ, TNF-α, and IL-2) were evaluated in type 2 diabetes mellitus (T2DM). Correlations between IL-29 and diabetes parameters, and between gene expression in IL-29 pathway and Th1 cells were also examined.Materials and Methods41 newly diagnosed patients with T2DM and 41 healthy controls were recruited. CD4⁺ T cells were purifed and the production of IL-29 in the supernatant of anti- CD3 and anti- CD28 activated Th cells was detected using ELISA. The expression of IL-29- and Th1- related genes was determined with real-time PCR.ResultsThe secretion of IL-29 and the expression levels of NF-κB, NFATc1, IFN-γ, and TNF-α in Th cells were seen to be increased in diabetes persons compared to controls. Positive connections between IL-29 with hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) were found in diabetes persons. IL-29 was positively correlated with NFATc1 and TNF-α. NFATc1 was positively related to TNF-α.ConclusionAbnormal expression levels of IL-29- and Th1- related genes are linked with T2DM pathogenesis. IL-29 may amplify the expression of Th1-specific genes especially TNF-α by upregulating NFATc1 expression.     

2型糖尿病的胃运动功能

采用核素标记^113mIn液体试餐、^99mTc固体试餐SPECT显像技术胃半排空时间（GET1／2）和胃电图（ECG）对74例2型糖尿病（DM）进行胃运动功能研究,同时检测空腹血糖。结果（1）DM中,36例（48．6％）GET1／2延迟。60例（81．1％）EGG异常;（2）22例血糖≤7.8mmol/L,无1例固相或液相GET1／2延迟;血糖77．8mmol/L的52例中,36例（69．2％）固相GET1／2延迟,其中14例（26．9％）伴液相GET1／2延迟（P＜0．01）;（3）对照组和DM组的空腹和餐后FP、AP、FZ值均无显著差异,二组餐后AP均显著高于空腹（P＜0．05）。DM组的AR、DR和RT均较对照组显著增高或排空延迟相关。胃排空延迟与EGG异常相关。结论：血糖水平与胃排空延迟相关。血糖控制不良,胃排空与EGG异常相关。     

Psychological stress and metabolic control in patients with type I diabetes mellitus

Acute psychological stress is believed to cause disturbances of metabolic control in patients with Type I diabetes. To examine the validity of this assumption, we subjected nine healthy persons (mean [+/- SEM] blood glucose level, 74 +/- 2 mg per deciliter), nine patients with Type I diabetes who had normoglycemia (130 +/- 10 mg per deciliter), and nine diabetic patients with hyperglycemia (444 +/- 17 mg per deciliter) to two acute psychological stresses: mental arithmetic and public speaking. Subjects in the three groups were matched for age, weight, sex, and socioeconomic status. For all subjects, the mean increase in heart rate was 20 beats per minute while they were doing mental arithmetic and 25 beats per minute while they were speaking publicly (P less than 0.001). In all three groups, systolic and diastolic pressure rose markedly, the plasma epinephrine level increased by 50 to 150 pg per milliliter, and the norepinephrine level by 100 to 200 pg per milliliter under both stress conditions (P less than 0.001). The plasma cortisol level rose significantly after public speaking in all groups. Neither stress induced changes in circulating levels of glucose, ketones, free fatty acids, glucagon, or growth hormone. Thus, sudden, short-lived psychological stimuli causing marked cardiovascular responses and moderate elevations in plasma concentrations of catecholamines and cortisol are unlikely to disturb metabolic control in patients with Type I diabetes.     

HLA in Czech adult patients with autoimmune diabetes mellitus: comparison with Czech children with type 1 diabetes and patients with type 2 diabetes

Type 1 diabetes results from an autoimmune insulitis, associated with HLA class II alleles. The evidence about HLA allele association is not clear in patients diagnosed after 35 years of age. In this study we have analyzed HLA alleles of DQB1 and DRB1 genes by sequence specific primer (SSP)‐PCR technique in adult patients with disease onset after 35 years of age. Two hundred and eighty‐one patients were divided into three groups according to the insulin therapy, the level of C peptide (CP), and GAD antibodies (anti‐GAD). Group 1 (type 1 diabetes in adults) was characterized by CP less than 200 pmol/L and anti‐GAD more or less than 50 ng/mL (n = 80). All of them had insulin therapy within 6 months after diagnosis. Group 2 latent autoimmune diabetes mellitus in adults (LADA) was defined by a minimum 6‐month‐long phase after diagnosis without insulin therapy, and was characterized by CP more than 200 pmol/L and anti‐GAD more than 50 ng/mL (n = 70). Group 3 (type 2 diabetes) was characterized by CP more than 200 pmol/L and anti‐GAD less than 50 ng/mL (n = 131). None ever had insulin therapy. In group 1, there was increased frequency of DRB1*04 (45.0% vs. controls 14.1%, OR = 5.0, P < 0.0005) and DQB1*0302 alleles (43.3% vs. controls 11.1%, OR = 6.1, P < 0.00005). There was increased frequency of DRB1*03 and DQB1*0201, and decreased frequency of DQB1*0602 (3.3% vs. controls 20.2%), but it was not significant. In group 2, there was a significantly increased frequency of DRB1*03 only (50.0% vs. controls 21.2%, OR = 3.7, P < 0.05). Compared with children with type 1 diabetes and adults with type 2 diabetes (group 3), we conclude that the presence of predisposing DQB1 alleles in adults with type 1 diabetes decreases with the age, probably due to environmental factors. Only the DRB1*03, but not the DQB1 gene, becomes the main predisposing allele in LADA patients. These findings suggest that the presence of HLA‐DQB1*0302 identifies patients at high risk of requiring insulin treatment. Type 1 diabetes mellitus (DM) in children or adults may have partly different immunogenetic etiopathogenesis than LADA.     

Heart rate turbulence in patients with poorly controlled diabetes mellitus type 2

Introduction

Cardiac autonomic neuropathy (CAN) causes substantial morbidity and increased mortality in patients with diabetes mellitus (DM). Besides heart rate variability (HRV), heart rate turbulence (HRT) is an important method of assessment of cardiac autonomic regulation. The aim of the study was to assess the correlation between HRT and diabetic control.

Material and methods

Fifty-nine patients met the inclusion criteria – 38 males and 21 females, age 64.4 ±7.6. The patients included had inadequately controlled DM type 2 defined as glycated haemoglobin (HbA_1c) > 9% (mean 11.8 ±2.7%). In all patients, intensive insulin treatment had been applied for 6 months. After 6 months, HbA_1c was measured. ECG Holter monitoring was performed before and after insulin treatment to evaluate the time domain HRV and HRT parameters (turbulence onset (TO) and turbulence slope (TS)).

Results

After 6 months of intensive insulin treatment, HbA_1c concentrations ranged from 6.3% (45 mmol/mol) to 11.2% (99 mmol/mol) – mean 8.5 ±3.8% (69 ±18 mmol/mol). Significant improvement of TO, TS and SDNN was observed. The TO and TS significantly correlated with HbA_1c (r = 0.35, p = 0.006 and r = –0.31, p = 0.02 respectively). Among analyzed HRV time domain parameters such as SDNN, rMSSD and pNN50, only SDNN correlated with HbA_1c (r = –0.41, p = 0.001). It was further concluded that intensive insulin therapy led to better glycemic control, resulting in improvement of HRT.

Conclusions

Heart rate turbulence may be useful in monitoring changes of the autonomic nervous system functions in patients with DM, similarly to HRV parameters.     

Crystallization of oral fluid components in patients with type 2 diabetes mellitus

Crystal aggregations of oral fluid from normal subjects and patients with type 2 diabetes mellitus were examined. Morphological signs characterizing crystal aggregations of salivary pools from patients with type 2 diabetes mellitus are described and classified.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 9, pp. 345–347, September, 2004     

Acquired perforating dermatosis in patients with chronic renal failure and diabetes mellitus

Acquired perforating dermatosis (APD) is a skin disorder occurring in the patients with chronic renal failure (CRF), diabetes mellitus (DM) or both. The purpose of this study was to clarify the clinical and histopathological features of APD, and evaluate role of scratching in the pathogenesis of APD. Twelve patients with APD associated with CRF and DM were enrolled in the study. In six patients who required hemodialysis, the lesions appeared 2-5 yr (mean 3 yr) after the initiation of dialysis, 18-22 yr (mean 19.3 yr) after the occurrence of DM. The other patients who did not receive hemodialysis noted the lesions 4-17 yr (mean 9.5 yr) after the onset of DM. All patients had an eruption of generally pruritic keratotic papules and nodules, primarily on the extensor surface of the extremities and the trunk. The histologic features of our cases showed a crateriform invagination of the epidermis filled by a parakeratotic plug and basophilic cellular debris. The period of treatment for patients who suffered from severe (7 cases) or very severe (3 cases) on the pruritus intensity was longer than that of patients who had mild pruritus (2 cases). These data showed that scratching appear to play a critical part in the pathogenesis of APD.     

Crystallization of oral fluid components in patients with type 2 diabetes mellitus

Crystal aggregations of oral fluid from normal subjects and patients with type 2 diabetes mellitus were examined. Morphological signs characterizing crystal aggregations of salivary pools from patients with type 2 diabetes mellitus are described and classified. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 9, pp. 345–347, September, 2004     

HLA in Czech adult patients with autoimmune diabetes mellitus: comparison with Czech children with type 1 diabetes and patients with type 2 diabetes.

Type 1 diabetes results from an autoimmune insulitis, associated with HLA class II alleles. The evidence about HLA allele association is not clear in patients diagnosed after 35 years of age. In this study we have analyzed HLA alleles of DQB1 and DRB1 genes by sequence specific primer (SSP)-PCR technique in adult patients with disease onset after 35 years of age. Two hundred and eighty-one patients were divided into three groups according to the insulin therapy, the level of C peptide (CP), and GAD antibodies (anti-GAD). Group 1 (type 1 diabetes in adults) was characterized by CP less than 200 pmol/L and anti-GAD more or less than 50 ng/mL (n = 80). All of them had insulin therapy within 6 months after diagnosis. Group 2 latent autoimmune diabetes mellitus in adults (LADA) was defined by a minimum 6-month-long phase after diagnosis without insulin therapy, and was characterized by CP more than 200 pmol/L and anti-GAD more than 50 ng/mL (n = 70). Group 3 (type 2 diabetes) was characterized by CP more than 200 pmol/L and anti-GAD less than 50 ng/mL (n = 131). None ever had insulin therapy. In group 1, there was increased frequency of DRB1*04 (45.0% vs. controls 14.1%, OR = 5.0, P < 0.0005) and DQB1*0302 alleles (43.3% vs. controls 11.1%, OR = 6.1, P < 0.00005). There was increased frequency of DRB1*03 and DQB1*0201, and decreased frequency of DQB1*0602 (3.3% vs. controls 20.2%), but it was not significant. In group 2, there was a significantly increased frequency of DRB1*03 only (50.0% vs. controls 21.2%, OR = 3.7, P < 0.05). Compared with children with type 1 diabetes and adults with type 2 diabetes (group 3), we conclude that the presence of predisposing DQB1 alleles in adults with type 1 diabetes decreases with the age, probably due to environmental factors. Only the DRB1*03, but not the DQB1 gene, becomes the main predisposing allele in LADA patients. These findings suggest that the presence of HLA-DQB1*0302 identifies patients at high risk of requiring insulin treatment. Type 1 diabetes mellitus (DM) in children or adults may have partly different immunogenetic etiopathogenesis than LADA.     

TNF-alpha polymorphisms and type 2 diabetes mellitus in Taiwanese patients

Type 2 diabetic mellitus (type 2 DM) comprises more than 95% of all Taiwanese patients with DM. Tumor necrosis factor-alpha (TNF-alpha) expression is linked with insulin resistance, and is under strong genetic control. The correlation between TNF promoter genotypes and type 2 DM is still controversial, because discrepancies among different studies exist. Ethnic differences play certain roles in these conflicting results, because the distribution of TNF promoter polymorphisms is different among study subjects with different racial origins. Therefore, we examined the relationship between the incidence of type 2 diabetes in Taiwanese and two polymorphisms of the TNF-alpha promoter region (positions -238 and -308) as well as the correlation between these polymorphisms and the patients' biochemical manifestations. Genomic DNA was extracted from peripheral blood cells of 261 Taiwanese patients with type 2 DM and 189 non-diabetic control study subjects, and their TNF promoter G-238A and G-308A polymorphisms were analyzed by PCR-RFLP analysis. No significant association between TNF-alpha G-238A and G-308A polymorphisms with type 2 diabetic incidence was observed. However, associations between TNF-alpha G-238A and low-density lipoprotein-cholesterol and between G-308A promoter polymorphism and high-fasting plasma glucose levels, using multiple linear regression analysis with adjustment for the subjects' age, sex, body mass index and diabetic status, were found. Our results suggested that though TNF-alpha G-238A and G-308A polymorphisms were not involved in the pathogenesis of type 2 DM, type 2 diabetic patients carrying TNFA-A or TNF-308*2 genotype might be more susceptible to diabetic complications such as atherosclerosis.     

Association between homocysteinemia and renal function in patients with type 2 diabetes mellitus

Homocysteinemia is an independent risk factor for cardiovascular disease, but information on its association with type 2 diabetes and mild renal dysfunction is limited. Plasma total homocysteine (tHcy) concentration is partly determined by renal plasma clearance. Serum cystatin C (Cys C) concentration has been introduced as a marker of renal function, specifically as an indicator of glomerular filtration rate (GFR). The aim of this study was to explore the relationships among tHcy, creatinine clearance (Ccr), serum Cys C, and microalbuminuria in a population with type 2 diabetes. Fasting plasma tHcy, serum homocysteine-related vitamins (folate and vitamin B12), serum Cys C, serum creatinine, urine microalbumin, and creatinine clearance were determined in 75 type 2 diabetic patients and 40 healthy control subjects. The patients were assigned to two groups based on urinary albumin excretion (UAE): normoalbuminuric (NAU, UAE < 30 mg/24 hr, n = 35) and microalbuminuric (MAU, UAE 30-300 mg/24 hr, n = 40). Ccr was calculated using the Cockroft-Gault formula. Plasma Hcy levels were determined by HPLC with fluorescence detection and serum Cys C by automated particle enhanced immunoturbidimetry. Plasma tHcy levels were significantly higher in normoalbuminuric and microalbuminuric patients than in controls (10.64 +/- 0.53, 13.29 +/- 0.78, 6.91 +/- 0.37 mmol/L, respectively). Serum Cys C levels in microalbuminuric diabetics were higher than in normoalbuminurics and controls (1.36 +/- 0.06, 1.12 +/- 0.04, 1.10 +/- 0.06 mg/ L, respectively). Positive correlations were noted between tHcy and Cys C levels in normoalbuminuric and microalbuminuric diabetics (r = 0.72, r = 0.64, respectively). Homocysteine and creatinine concentrations were correlated in both diabetic groups (r = 0.89, r = 0.93, NAU and MAU, respectively). Elevated plasma total homocysteine concentrations in type 2 diabetics suggest an association between homocysteinemia and deterioration of renal function, evidenced by increased serum creatinine and Cys C, Ccr, and microalbuminuria. These findings implicate homocysteinemia in the relationship between diabetic nephropathy and cardiovascular complications of diabetes.