Hemostasis and fibrinolysis factors in first-degree relatives of patients with Type 2 diabetes without hypertension

First-degree relatives of type 2 diabetic patients with or without a family history of hypertension are at increased risk for cardiovascular diseases. The aim of this study was to verify some possible hemostatic alterations in first-degree relatives of type 2 diabetic, normotensive and hypertensive patients. In 78 non-diabetic, normotensive first-degree relatives of type 2 diabetic patients (47 without a family history of hypertension and 31 with a family history of hypertension) and in 36 normoglycemic, normotensive subjects with no family history of hypertension, we evaluated plasma levels of fasting glucose and insulin, tissue-type plasminogen activator (t-PA), plasminogen activator-inhibitor (PAI-1), D-dimer (DD) and prothrombin fragment 1 + 2 (F1+2). Insulin resistance, calculated by the HOMA model, and plasma levels of t-PA and PAI-1 were significantly higher in relatives of diabetics compared to controls. As far as the thrombin activation indexes are concerned, we detected a significant increase in DD and F1+2 in relatives of diabetics with hypertension compared to other study subjects. In conclusion, our data indicate that familial predisposition may influence the hemostatic system in first-degree relatives of diabetic and/or hypertensive patients.     

Type 2 diabetes mellitus in a Nigerian child: a case report

Background

Type 2 diabetes mellitus initially said to be an adult disease is now reported in children and adolescents in the developed countries because of increased incidence of obesity and sedentary habits associated with westernization and lifestyle changes. There is a paucity of reports from Africa

Method

A 9year old overweight female with a BMI of 28kg/m² and a strong family history of DM in at least two generations presented with polyuria and weight loss. The mother had gestational diabetes and is on oral hypoglycaemics. Fasting blood sugar was 11.9mmol/l. Urinalysis had +1 of glucose, no ketones. She was managed with diet control and exercise.

Result

The patient has remained euglycaemic in the past two months without drugs and is losing weight.

Conclusion

Type 2 diabetes mellitus is being reported in an obese Nigerian child with a family history of DM and high socio-economic class. Routine screening of overweight children with a family history of DM is recommended.     

Experience-based group education in Type 2 diabetes: a randomised controlled trial

Few studies have demonstrated an effect of educational interventions on glycaemic control in persons with Type 2 diabetes longer than 3-6 months after baseline. We aimed to investigate the effectiveness of an experience-based group educational programme 24 months after baseline and to pinpoint mediators that might play a role in achieving desired metabolic outcomes. We conducted a randomised controlled trial inviting self-referred persons with Type 2 diabetes (N=77 randomised). The pharmacist-led, year-long intervention was based on participants' experiences of glucose regulation during the monthly group discussions. We measured HbA1c at 0, 6, 12, and 24 months and a questionnaire was administered at baseline and final follow-up. Our findings indicated that participating in the intervention programme significantly decreased HbA1c by 0.4% at 24 months after baseline. Initial HbA1c, satisfaction with own diabetes-related knowledge, and treatment were found directly related to glycaemic outcomes. The intervention group exercised more in order to lower blood-glucose levels and was also more able to predict current blood-glucose levels before measuring it. Experience-based group education was effective in decreasing participants' HbA1c 1-year after completed intervention. Early effect of the intervention was followed by relapse after 12 months and a new, significant decrease at 24 months; this dual course implies that follow-up of educational interventions should involve several consecutive measurements to capture possible late effects. Both biomedical and subjective factors played a role in accounting for the variance of HbA1c at 2-year follow-up after baseline.     

The high-affinity Fc gamma RI on PMN: regulation of expression and signal transduction.

In this paper we report that interferon-gamma (IFN-gamma) maintains and enhances functional properties of terminally differentiated polymorphonuclear cells (PMN). Such effects are obvious when compared with untreated PMN declining in their functional response. Culture for 18 hr with 100 IU/ml of recombinant IFN-gamma resulted in the expression of about 15,000 Fc gamma RI per PMN. IFN-gamma maintained viability of PMN and prevented reduction of Fc gamma RIIIb caused by apoptosis. No alterations were found in the level of Fc gamma RIIa. Next, functional properties of Fc gamma RI were evaluated. Calcium mobilization was detected in fura-2/acetoxymethylester (AM)-loaded PMN using a spectrophotometer and the respiratory burst was measured as luminol-dependent chemiluminescence. Cross-linking of an F(ab')2 fragment of monoclonal antibody (mAb) 22.2 to Fc gamma RI gave similar results to those obtained with intact monomeric human immunoglobulin G (mhIgG) when subsequently cross-linked. Moreover, after blocking Fc gamma RIIa and Fc gamma RIIIb with respective mAb fragments, mhIgG was still effective in triggering a calcium flux demonstrating that second messenger generation was caused by Fc gamma RI engagement. Even though Fc gamma RI expression was lower than that of Fc gamma RIIa, Fc gamma RI induced a higher increase of the respiratory burst. In addition, the protein tyrosine phosphatase CD45 was able to inhibit both responses when it was co-cross-linked with CD64, suggesting involvement of tyrosine phosphorylation in early signalling steps.     

HLA-DQB1 alleles may influence the surface expression of DQ molecules in lymphomononuclear cells of type 1 diabetes mellitus patients

To evaluate the expression of human leucocyte antigen (HLA) class II (DR and DQ) molecules on lymphomononuclear cells involved in the pathogenesis of type 1 diabetes, we studied 20 patients and 20 controls matched to patients for age, sex and HLA class II profile. The coexpression of HLA and CD3, CD4, CD8, CD19 and CD14 molecules was evaluated by flow cytometry. HLA-DRB1, -DQA1 and -DQB1 alleles were assigned using amplified DNA hybridized with sequence-specific primers. The fluorescence intensity of HLA-DR and -DQ molecules observed on the surface of the lymphomononuclear cells of patients did not differ significantly from controls. Patients presented decreased percentage of double-positive CD4(+)/DQ(+) cells and increased percentage of CD19(+)/DR(+) cells, irrespective of the HLA class II profile; however, the more dramatic alteration of the lymphomononuclear phenotype profile was observed for patients possessing the HLA-DQB1*0201 allele. These patients exhibited decreased percentage of CD3(+), CD4(+), CD8(+), CD19(+) and CD14(+) cells bearing HLA-DQ molecules and decreased fluorescence intensity for HLA-DQ molecules on CD19(+) cells compared to patients without the DQB1*0201 allele. Although type 1 diabetes patients shared CD4/DQ or CD19/DR phenotype abnormalities, patients typed as DQB1*0201 presented additional abnormalities in terms of DQ expression and cell phenotypes bearing DQ molecules.     

Comparative analysis of lipid profiles among patients with type 2 diabetes mellitus,hypertension and concurrent type 2 diabetes,and hypertension: a view of metabolic syndrome

Type 2 diabetes mellitus and hypertension are independent risk factors for atherosclerotic lesions that are partly linked with dyslipidaemia. This risk is additive when diabetes and hypertension occur concurrently. In order to determine if concurrent type 2 diabetes and hypertension results in putative increases in dyslipidaemia in a Nigerian population, we compared the plasma lipid levels, atherogenic index and prevalence of dyslipidaemia among age and sex-matched indigenous Nigerians with type 2 diabetes, hypertension and concurrent diabetes and hypertension. Age and sex-matched healthy Nigerians that are free of diabetes and hypertension served as controls. The patients as a whole were more likely to have dyslipidaemia than controls (p < 0.05). High-density lipoprotein cholesterol was similar among patients and controls. Mean total cholesterol, high-density lipoprotein cholesterol; low-density lipoprotein cholesterol and triglyceride levels, atherogenic index and prevalence of dyslipidaemia did not differ significantly among patients with hypertension, diabetes, and concurrent hypertension and diabetes (p = 0.99 for each parameter). It is concluded that concurrent hypertension and type 2 diabetes does not result in a more severe dyslipidaemia than when either of the two conditions occurs in isolation. We attribute this to the common pathogenic link between hypertension, diabetes and dyslipidaemia in metabolic syndrome. Evidence, albeit indirect, of this syndrome among native Africans is, therefore, provided.     

Low IgG2 and polysaccharide response in a T cell receptor expression defect

B lymphocytes require appropriate T lymphocyte cooperation to synthesize immunoglobulins (Ig). Such interaction presumably takes place after engagement of the T cell receptor (TcR) by antigen. The present work addresses B lymphocyte function (and phenotype) in a novel type of immunodeficiency which is characterized by a TcR expression defect. In contrast to expectations, the two affected siblings that were studied displayed normal in vivo antibody responses to both endogenous and exogenous protein antigens. However, they showed impaired responses to certain polysaccharide antigens together with a selective IgG2 deficiency. These results suggest that some polysaccharide responses may be more T cell dependent than previously suspected, and support the notion that T cell dysfunctions (of this or other kind), rather than Ig gene deletions, may be the molecular basis of certain IgG2 deficiencies. To rule out a concomitant gross B cell dysfunction in these individuals, B lymphocyte phenotype and function were assayed in vitro, and found to be normal. A T cell line derived from one of the siblings displayed an abnormal TcR on the cell surface, but it showed several normal TcR-mediated functions. This suggests that the low number of peripheral T lymphocytes that have been found to express low TcR levels in these immunodeficiencies may be operational, and supplying sufficient "help" for the observed normal antibody responses to all tested protein, but not polysaccharide, antigens.     

UV-inactivation of Epstein-Barr virus: differences in early antigen expression in two different non-productive cell lines and influence of caffeine.

Two non-productive Epstein-Barr (EB) virus genome-carrying lymphoblastoid cell lines, namely Raji and NC37, were used for studying the effect of UV irradiation on the ability of P3HR-1 EB virus to induce early antigen (EA) formation. In NC37 cells infected with UV-irradiated virus the formation of EA was delayed; thus the slope of inactivation curve based on the early (24 hr) reading was steeper than that based on the late (72 hr) reading. This was not observed in Raji cells. Caffeine did not influence the percentage of EA positive cells in cultures infected with untreated virus; however, the drug exhibited a marked inhibitory effect on EA production after infection with UV-irradiated virus. The sensitivity to caffeine effect decreased more rapidly with time after infection of Raji than of NC37 cells, suggesting a higher degree of readiness of the host cell repair system in the former than in the latter cells. The caffeine effect was merely directed against the synthesis of R (restricted) component of EA; its influence on the D (diffuse) component formation was negligible.     

Dysregulation of X-linked gene expression in Klinefelter's syndrome and association with verbal cognition.

Klinefelter's Syndrome (KS) is a chromosomal karyotype with one or more extra X chromosomes. KS individuals often show language impairment and the phenotype might be due to overexpression of genes on the extra X chromosome(s). We profiled mRNA derived from lymphoblastoid cell lines from males with documented KS and control males using the Affymetrix U133P microarray platform. There were 129 differentially expressed genes (DEGs) in KS group compared with controls after Benjamini-Hochberg false discovery adjustment. The DEGs included 14 X chromosome genes which were significantly over-represented. The Y chromosome had zero DEGs. In exploratory analysis of gene expression-cognition relationships, 12 DEGs showed significant correlation of expression with measures of verbal cognition in KS. Overexpression of one pseudoautosomal gene, GTPBP6 (GTP binding protein 6, putative) was inversely correlated with verbal IQ (r = -0.86, P < 0.001) and four other measures of verbal ability. Overexpression of XIST was found in KS compared to XY controls suggesting that silencing of many genes on the X chromosome might occur in KS similar to XX females. The microarray findings for eight DEGs were validated by quantitative PCR. The 14 X chromosome DEGs were not differentially expressed in prior studies comparing female and male brains suggesting a dysregulation profile unique to KS. Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function. A screen of candidate genes may serve as biomarkers of KS for early diagnosis.     

槟榔碱对2型糖尿病大鼠胰腺β细胞PDX-1 mRNA表达的影响

目的：探讨槟榔碱对2型糖尿病大鼠β细胞分泌功能及胰腺十二指肠同源盒因子 1（pancreas duodenum homeobox 1,PDX 1）mRNA表达的影响。方法：采用高果糖饲料饲养Wistar大鼠12周制备2型糖尿病大鼠模型,40只实验动物随机分为5组：对照组、模型组、模型+1 mg/kg槟榔碱组、模型+5 mg/kg槟榔碱组、模型+10 mg/kg槟榔碱组。药物注射4周后股动脉取血检测空腹血糖、三酰甘油、总胆固醇、高密度脂蛋白、低密度脂蛋白、血清胰岛素,处死大鼠取胰腺组织,石蜡切片HE染色观察组织形态学变化,RT PCR检测β细胞内PDX 1及胰岛素mRNA的表达水平。 结果：（1）高糖作用引起Wistar大鼠胰腺β细胞PDX 1 及胰岛素mRNA 的表达水平显著下降（P＜0.01）;（2）1 mg/kg和5 mg/kg槟榔碱处理能显著上调高糖喂养Wistar大鼠胰腺β细胞PDX 1与胰岛素mRNA表达水平（P＜0.05,P＜0.01）。结论：槟榔碱可以通过上调PDX 1和胰岛素基因表达,改善高糖环境下的β细胞胰岛素合成和分泌功能的损伤。     

Big renin and biosynthetic defect of aldosterone in diabetes mellitus.

To determine the cause of selective aldosterone deficiency in two patients with diabetes mellitus, studies of renin and of aldosterone-precursor metabolites were performed under conditions of sodium depletion and ACTH stimulation. Plasma renin concentration was elevated in both patients, and stimulated plasma renin activity was low in one and normal in the other. Fractionation of plasma extracts demonstrated the presence of "big renin," a relatively inactive precursor of renin. Metabolites of aldosterone precursors were increased, suggesting deficient 18-hydroxylase in one patient and dehydrogenase in the other. The results suggest that hypoaldosteronism in diabetic patients may result from combined defects in both renin and aldosterone biosynthesis.     

Insulin prophylaxis down-regulates islet antigen expression and islet autoimmunity in the low-dose Stz mouse model of diabetes.

The aims of this study were to evaluate in an autoimmune diabetes animal model [low-dose streptozotocin (LD-STZ) mouse] (a) the efficacy of a prophylactic insulin treatment as a diabetes prevention tool, and (b) its possible mechanisms through both the insulitis evaluation and islets antigen expression. Diabetes was induced in male C57Bl6/J mice with STZ (50 mg/kg b/w for five consecutive days); insulin (1 U/day) was injected subcutaneously for ten consecutive days before the induction of diabetes and for a further ten days. Seventy-one male C57Bl6/J mice were grouped as follows: Group 1 (n = 25) made diabetic with i.p. STZ, Group 2 (n = 21) made diabetic with i.p. STZ and injected subcutaneously with insulin, Group 3 (n = 15) injected with insulin, while Group 4 (n = 10) comprised normal animals as controls. The animals of each group were killed at two intervals: half of them at day 12 and the remainder at day 24 from the beginning of the STZ treatment. A significant reduction of glycemia levels and insulitis severity was observed between mice of Group 1 vs. Group 2 at day 12 and day 24. Down-regulation of islet antigen expression (insulin, A2B5, GM2-1, ICA Ag) was achieved even without a complete metabolic suppression of beta-cell activity. In conclusion, prophylactic insulin treatment is effective to reduce glycemia levels and insulitis severity and down-regulates islet antigen expression in the LD-STZ model.     

Time perspective and weight management behaviors in newly diagnosed Type 2 diabetes: a mediational analysis

The primary objective of the current study was to examine the extent to which domain-specific time perspective predicts weight management behaviors (dietary behavior and physical activity) among those newly diagnosed with Type 2 diabetes. A secondary objective was to test potential mediators of the hypothesized effect (behavioral intention, self-efficacy and control beliefs). A total of 204 adults newly diagnosed (≤6?months) with Type 2 diabetes participated in the study, which included a baseline assessment of domain-general and domain-specific time perspective, as well as strength of intention to perform two weight-management behaviors (dietary choice and physical activity); both weight-management behaviors were assessed again at 6?month follow-up. Hierarchical multiple regression analyses revealed a prospective association between domain-specific time perspective and uptake of weight management behaviors. Individuals with newly diagnosed T2DM possessing a future-oriented time perspective reported making less frequent fatty food choices and greater increases in physical activity over the 6-month follow-up interval. These effects were selectively mediated by intention strength, and not competing social cognitive variables. For both behaviors, the total effects and meditational models were robust to adjustments for demographics, body composition and disease variables. A future-oriented time perspective is prospectively associated with superior uptake of weight management behaviors among those with newly diagnosed Type 2 diabetes. The facilitating effect of future-oriented thinking appears to occur via enhanced strength of intentions to perform weight management behaviors.     

Abnormal erythrocyte and lymphocyte chemiluminescence in chronic granulomatous disease: evidence for a generalized membrane defect

Concanavalin A (soluble)- and/or opsonized zymosan (particulate)-stimulated luminol-dependent chemiluminescence was demonstrated in normal human lymphocytes, erythrocytes, and in the membrane (ghost) fractions of polymorphonuclear neutrophils and erythrocytes. By contrast, seven patients with chronic granulomatous disease (five boys with the X-linked type and two female variants) had diminished luminescent responses to con A and/or opsonized zymosan in their lymphocytes, erythrocytes, erythrocyte membranes, as well as neutrophil membranes, suggesting generalization of the deficiency in the neutrophil oxidase system to other cells.