Hypertension in type II diabetes mellitus

Treatment of hypertension in patients with NIDDM should be administered with special attention not to increase insulin resistance nor to impair insulin secretion capacity. The coexisting risk for coronary artery disease and myocardial infarction should not be increased by undesired drug effects on the plasma lipoprotein profile. Late lesions of diabetes mellitus (nephropathy, neuropathy) have also to be taken into account. Consequently angiotensin converting enzyme inhibitors, if necessary combined with calcium channel blockers, should be administered first. If blood pressure is thus not sufficiently controlled, alpha-adrenergic blockers, vasodilating agents or sympatholytics may be added. Once insulin treatment is installed, or if required for other reasons (nephropathy, congestive heart failure, cardiac arrhythmia), also diuretics and beta-adrenergic blockers are indicated in antihypertensive treatment of diabetic patients.     

Endothelium-dependent vasodilation in type II diabetes mellitus

Endothelial dysfunction is a major feature of atherosclerosis and it can also serve as an early atherosclerotic marker. Evaluation and assessment of the endothelial function is important to prevent serious atherosclerotic disease especially myocardial infarction, cerebrovascular disease and renal failure. To evaluate endothelial function we measured endothelium-dependent vasodilation (flow-mediated dilatation: %FMD) of the brachial artery with ultrasound. This method is non-invasive and can be repeatable in order to follow patients individually. Progressive atherosclerosis is often observed in diabetic patients who are not hypertensive. To evaluate the impairment of the endothelial function in type 2 diabetic patients, we examined %FMD in them and compared with hypertensive patients without diabetes and control subjects. We found that type 2 diabetic patients had the same endothelial dysfunction as hypertensive patients without diabetes. %FMD in both diabetic patients and hypertensive patients was lower than in control subjects. Moreover, %FMD of type 2 diabetic patients with hypertension was lower than %FMD of type 2 diabetic patients without hypertension. These finding suggests that endothelial dysfunction develops under the conditions of hypertension and hyperglycemia. Evaluating endothelial function with ultrasound is useful for assessment of atherosclerosis in diabetes.     

Symptoms of depression in patients with type II diabetes mellitus

Patients with type II diabetes mellitus were assessed for symptoms of depression using the Zung Self-Rated Depression Scale (Zung SDS) and the Beck Depression Inventory (BDI). The patients were classified according to the presence or absence of diabetic complications, and they were compared with a group of demographically matched, nonmedically ill control subjects. The patients with diabetic complications scored significantly higher on the depression inventories than did the patients without complications and the control subjects. Factor analysis of BDI responses revealed that cognitive symptoms of depression were prominent in the diabetic patients with complications. In this group, 74% of patients scored within the range of clinical depression on the BDI; 35% scored within the range of severe depression. Symptoms of sexual dysfunction were significantly correlated with symptoms of depression in diabetic women but not in diabetic men. The findings are discussed within the context of other research in the behavioral aspects of diabetes mellitus.     

Lipoid pneumonia with chronic myelomonocytic leukemia

A case of lipoid pneumonia with chronic myelomonocytic leukemia is reported. A 61-year-old man was autopsied after suffering from myelodysplastic syndrome (chronic myelomonocytic leukemia) for 13 years. Interstitial lesions of the lungs were suspected as infiltration of leukemia cells before the autopsy. However, blastic leukemia cells were not observed in the lung, although they were seen in the bone marrow and spleen at autopsy. Instead, an unusual amount of cholesterol deposits was observed with mucormycosis and aspergillosis in the lungs. Cholesterol deposition was observed not only in perihilar but also in subpleural regions without apparent bronchial obstruction in both lungs. It is thought that malfunction of monocytes/macrophages resulted in repeated fungal infection and storage of cholesterol caused by tissue destruction and impaired tissue repairing.     

2型糖尿病患者线粒体基因8个突变位点的研究

目的：探讨线粒体DNA tRNA Leu (UUR)基因及其相邻的ND1基因8个位点的突变与2型糖尿病的关系。 方法： 采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）的分析方法，对174例2型糖尿病患者和207名健康对照的mtDNA的3 243、3 256、3 290、3 316、3 394、3 421、3 426、3 460和3 593共9个已报道的突变位点同时进行筛选，并采用测序、反向斑点杂交和基因芯片进行方法学比较和确证，对检出的突变位点采用DNASTAR和Antherprot软件进行分析。 结果： 糖尿病组检出3 316(G→A) 突变5例(2.9%)，其中2例为多个位点突变：1例伴随3 256(C→T)和3 688(G→C)，另1例伴随3 606(A→G)；3 394(T→C)突变4例(2.3%)，3 593(T→C)、3 290(T→C)和3 618(T→C)突变各1例(0.6%)； 其中3 606(A→G)、3 618(T→C)和3 688(G→C) 为新突变位点，GenBank登录号为DQ092356；对照组只检出3 316(G→A)突变1例(0.5%)。两组间仅3 394(T→C) 突变率差异显著(P<0.05)。以上8个突变位点的测序、反向斑点杂交和基因芯片检测结果完全一致。3 606(A→G)为Leu的无意义突变，3 618(T→C)为Phe的无意义突变，3 688(G→C)为有意义突变，Ala→Pro,导致ND1蛋白的二级结构发生改变。 结论： 线粒体DNA ND1基因3 316(G→A)突变伴随3 688(G→C)突变，3 394(T→C) 突变可能与2型糖尿病发病有关。     

HLA haplotypes associated with type 1 diabetes mellitus in North Indian children

Human leukocyte antigen (HLA) encoded susceptibility to develop type 1 diabetes mellitus (T1DM) has been investigated in children from North India. The results revealed significantly increased prevalence of HLA-A26, -B8, and -B50 among patients and strong positive association of the disease with DRB1*0301 (82.1% vs 13.9%, chi2=71.3, odds ratio [OR]=28.3) and a negative association with DRB1*02 (chi2=12.2, PF=38.5). HLA-DQB1*0201 occurred in 96.4% of the patients, whereas the heterodimer DQA1*0501-DQB1*0201 was present in 82.1% of patients (60.7% in single dose and 21.4% in double dose) and revealed significant deviation from the healthy controls (chi2=74.1, pc=6.0E-10). In addition to DRB1*03, positive association was also observed with DRB1*09 (14.3% vs 1.3%, chi2=13.4) and DRB1*04 (39.3% vs 15.6%, chi2=8.39). No HLA association was observed in relation to residual pancreatic beta-cell function or associated thyroid autoimmunity. Family analysis revealed involvement of multiple DR3+ve haplotypes with T1DM in North Indian children with A26-B8-DRB1*03 (25% vs 3.5%, chi2=16.9, p=3.96E-05) and Ax-B50-DRB1*03 (25% vs 0.7%, chi2=44.7, p=9.88E-11) being the most frequent haplotypes encountered among patients. The classical Caucasian haplotype A1-B8-DRB1*03 was infrequent (7.2%) among the diabetic children. The study highlights the race specificity of HLA association and disease associated HLA haplotypes in T1DM among North Indian children.     

Thromboxane biosynthesis and platelet function in type II diabetes mellitus

It has been suggested that platelet hyperreactivity in patients with diabetes mellitus is associated with increased platelet production of thromboxane. We therefore compared the excretion of a thromboxane metabolite and platelet function in 50 patients with Type II diabetes mellitus who had normal renal function and clinical evidence of macrovascular disease and in 32 healthy controls. The mean (+/- SD) excretion rate of urinary 11-dehydro-thromboxane B2 was significantly higher in the patients than in the controls (5.94 +/- 3.68 vs. 1.50 +/- 0.79 nmol per day; P less than 0.001), irrespective of the type of macrovascular complication. Tight metabolic control achieved with insulin therapy reduced the levels of 11-dehydro-thromboxane B2 by approximately 50 percent. The fractional conversion of exogenous thromboxane B2 (infused at a rate of 4.5, 45.3, or 226.4 fmol per kilogram of body weight per second) to urinary 11-dehydro-thromboxane B2 was assessed in four patients, in whom it averaged 5.4 +/- 0.1 percent; this value did not differ from that measured in healthy subjects. Aspirin in low doses (50 mg per day for seven days) reduced urinary excretion of the metabolite by approximately 80 percent in four patients. The fact that thromboxane biosynthesis recovered over the following 10 days was consistent with a platelet origin of the urinary metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)     

Magnesium, potassium and zinc deficiency in subjects with type II diabetes mellitus

The concentrations of magnesium, potassium and zinc were determined in plasma, erythrocytes, muscle biopsies, and in urine collected during 24 hours, in 18 subjects with type II diabetes mellitus (DM). Magnesium was also determined in mononuclear cells. The results were compared with those in 35 (magnesium and potassium analyses) or 26 (zinc analyses) healthy controls. Subjects with type II DM had lower concentrations of magnesium (3.79 +/- 0.32 vs. 4.29 +/- 0.22 mmol/100 g FFDS), potassium (40.5 +/- 5.17 vs. 46.1 +/- 3.81 mmol/100 g FFDS) and zinc (231 +/- 29 vs. 247 +/- 23 ng/mg FFDS) in skeletal muscle. Furthermore, the urinary excretions of magnesium and zinc were higher, as compared with those in healthy controls (5.00 +/- 2.68 vs. 3.62 +/- 1.47 mmol/24 hours, and 683 +/- 285 vs. 326 +/- 205 micrograms/24 hours, respectively). The contents of magnesium, potassium and zinc plasma did not correlate with the corresponding concentrations in skeletal muscle or circulating blood cells, as investigated in healthy controls, diabetics and in all subjects together, implying that the plasma concentrations are not useful in the assessment of electrolyte status. Hence, deficiency of electrolytes frequently occurs, and should be looked for, in subjects with type II DM.     

Determinants of post-ischaemic reactive hyperaemia in patients with diabetes mellitus type II.

Dysfunction of resistance arteries is thought to be an early reversible stage in the development of atherosclerosis. Dynamics of post-ischaemic reactive hyperaemia are believed to constitute a useful tool for monitoring resistance vessel function. Patient characteristics influencing reactive hyperaemia, however, need to be defined more precisely. Since reactive hyperaemia is a dynamic process, yielding submaximal peak values after 5 min of ischaemia, this period was chosen to investigate the determinants of reactive hyperaemia in 100 type II diabetic patients as well as in 61 control subjects. Reactive hyperaemia was measured by venous-occlusion plethysmography; clinical and laboratory data were acquired by routine methods. Statistical comparison was performed with SYSTAT 5.0 for Apple Macintosh. Overall, no significant differences between diabetic patients and controls were observed by group comparison. In control subjects, only gender showed an influence on peak reactive hyperaemia (females 40.5 +/- 15.3; males 51.8 +/- 17.7 ml min-1 100 ml-1, P < 0.01). In diabetic patients, in addition to gender, actual blood glucose (r = 0.377, P < 0.05) and meal intake (non-fasting 42.8 +/- 19.2; fasting 51.2 +/- 19.5 ml min-1 100 ml-1, P < 0.05) were found to influence reactive hyperaemia. Further investigation revealed a loss of the correlation between peak reactive hyperaemia and actual blood glucose observed in the fasting state (P < 0.001) in non-fasting diabetic patients, indicating an influence of meal intake on resistance vessel reactivity. Our results suggest that, in diabetic subjects, in addition to gender actual blood glucose and the postprandial situation impacts on peak reactive hyperaemia.     

Emphysematous cystitis in a patient with type 2 diabetes mellitus

A 62-year-old woman with a history of poorly controlled type 2 diabetes mellitus was admitted to our hospital with a 3-week history of mild fever, vomiting, and anorexia. Abdominal computed tomography (CT) showed bilateral hydronephrosis and gas accumulation in the urinary bladder wall and left ureter. Laboratory tests showed leukocytosis and elevated C-reactive protein level. Urine culture showed heavy growth of Escherichia coli. The final diagnosis was emphysematous cystitis. The patient was treated with systemic antibiotics and drainage using a urethral catheter. The clinical and radiographic findings resolved rapidly, and she was discharged from the hospital on day 28. Emphysematous cystitis is a relatively rare urinary tract infection associated with gas formation, and has the potential for a serious outcome if untreated. Early detection by imaging studies such as CT is important in providing prompt treatment and favorable clinical outcome.     

Low plasma levels of FGF-2 and PDGF-BB are associated with cardiovascular events in type II diabetes mellitus (diabetes heart study)

Objective: We tested associations of the growth factors VEGF, FGF-2, HGF and PDGF-BB with coronary artery calcium scores and cardiovascular events (CVD) in type 2 diabetes mellitus (T2DM). Methods: A cross-sectional study selected 40 frequency matched (by age, gender and race) subjects with T2DM from the first (0–111) and the third (> 1400) coronary artery calcium (CAC) score tertiles in the Diabetes Heart Study (DHS), in which 36 were with and 41 were without history of CVD events. Plasma levels of VEGF, FGF-2, HGF and PDGF-BB were measured in all subjects. Results: None of the growth factors was significantly different between the first and third CAC score tertiles. Mean plasma FGF-2 and PDGF-BB levels were significantly higher in the group without prior CVD events compared with the group with prior CVD events [mean(95%CI): 219.20 (194.42–247.15) vs. 152.93 (135.64–172.43) pg/ml, p = 0.03] and [mean(95%CI): 106.70 (89.12–127.74) vs. 61.56 (50.91–74.44) pg/ml, p = 0.03], respectively. Subgroup analysis in the first CAC tertile showed a significantly higher PDGF-BB levels in those without compared with those with CVD events [mean (95%CI): 208.36 (190.57–228.15) vs. 102.93 (80.64–125.21) pg/ml, p = 0.004]. Conclusion: Plasma growth factor levels were not significantly different between the extremes of CAC scores in T2DM. However, low plasma levels of PDGF-BB and FGF-2 are associated with prior cardiovascular events in T2DM. Studies are needed to confirm our results and also to establish temporality of this association.     

Neurodegenerative disorders associated with diabetes mellitus

More than 20 syndromes among the significant and increasing number of degenerative diseases of neuronal tissues are known to be associated with diabetes mellitus, increased insulin resistance and obesity, disturbed insulin sensitivity, and excessive or impaired insulin secretion. This review briefly presents such syndromes, including Alzheimer disease, ataxia-telangiectasia, Down syndrome/trisomy 21, Friedreich ataxia, Huntington disease, several disorders of mitochondria, myotonic dystrophy, Parkinson disease, Prader-Willi syndrome, Werner syndrome, Wolfram syndrome, mitochondrial disorders affecting oxidative phosphorylation, and vitamin B₁ deficiency/inherited thiamine-responsive megaloblastic anemia syndrome as well as their respective relationship to malignancies, cancer, and aging and the nature of their inheritance (including triplet repeat expansions), genetic loci, and corresponding functional biochemistry. Discussed in further detail are disturbances of glucose metabolism including impaired glucose tolerance and both insulin-dependent and non-insulin-dependent diabetes caused by neurodegeneration in humans and mice, sometimes accompanied by degeneration of pancreatic beta-cells. Concordant mouse models obtained by targeted disruption (knock-out), knock-in, or transgenic overexpression of the respective transgene are also described. Preliminary conclusions suggest that many of the diabetogenic neurodegenerative disorders are related to alterations in oxidative phosphorylation (OXPHOS) and mitochondrial nutrient metabolism, which coincide with aberrant protein precipitation in the majority of affected individuals.     

Good glycaemic control is associated with a better prognosis in breast cancer patients with type 2 diabetes mellitus

Although diabetes mellitus (DM) is one of the risk factors associated with increased breast cancer (BC) mortality, the effects of glycaemic control on the prognosis of BC have not been thoroughly evaluated. This retrospective study aimed to evaluate the relationship between glycaemic control and BC prognosis and to determine an optimal target of glycaemic control for BC patients with diabetes. We included 2812 stage 0–3 BC women, of whom 145 were diabetic and were 2667 non-diabetic. In those with diabetes, a mean haemoglobin A1C (HbA1C) <?7% (n?=?77) was defined as well-controlled diabetes, while a mean HbA1C >?9% (n?=?16) was defined as poorly controlled diabetes. All of the BC populations were followed from the date on which BC was diagnosed until 31 December 2015. Cox regression analysis was performed to estimate the adjusted hazards for all-cause mortality and BC-specific mortality. After controlling for the baseline and BC-related confounders, the adjusted hazard ratio (HR) for all-cause mortality and the HR for BC-specific mortality were 3.65 (95% confidence interval [95% CI] 1.13–11.82) and 8.37 (95% CI 1.90–36.91), respectively, for poorly controlled diabetic women and non-DM women. However, for the diabetic women with good glycaemic control, the HRs of all-cause mortality and BC-specific mortality were not significantly different (HR 0.91, 95% CI 0.42–1.01; HR 0.77, 95% CI 0.18–3.32, respectively) from those for both mortalities in non-DM patients. For moderate controlled diabetic women, the HRs for all-cause mortality and BC-specific mortality were 1.95 (95% CI 0.89–4.27) and 3.55 (95% CI 1.369–9.30), respectively. This pilot and retrospective cohort study reveals a relationship between glycaemic control and BC prognosis in diabetic women. In addition, well-controlled HbA1C, with maintained mean HbA1C values under 7%, may be associated with a better progression outcome of BC.     

Role of amylin in the pathogenesis of type II diabetes mellitus

Amylin, a peptide, which was isolated from the islet amyloid of type II diabetics, might play a potential role in the pathogenesis of type II diabetes mellitus. In in vitro and in vivo studies it has been shown that amylin has an effect on insulin secretion as well as on insulin sensitivity. From measurements of plasma amylin levels it is known that amylin is cosecreted with insulin and patients with hyperinsulinemia have also elevated amylin levels. In patients with impaired glucose tolerance and type II diabetes amylin levels are decreased compared to insulin. A secretory defect of amylin and its local accumulation in the islets of type II diabetics might be a cause for the insulin secretory defect in type II diabetes. Additionally, amylin can induce peripheral insulin resistance, which might also be a cause for type II diabetes mellitus. Amylin is a new pancreatic peptide, which might play an important role in the pathogenesis of diabetes mellitus.     

Immunogenetics of HLA class II in Israeli patients with adult-onset type 1 diabetes mellitus

The distribution of HLA class II alleles and genotypes in Israelis of different ethnic origin with adult-onset type 1 diabetes (T1D) was examined. The results were compared with published findings in healthy Israelis and childhood-onset T1D Israelis. An additional comparison was made between subgroups of patients with rapidly and slowly progressive adult-onset T1D (LADA). A DNA-based low-resolution analysis was performed for DRB1* and DQB1* alleles and a high-resolution analysis for DRB1*04 and DQB1*1 alleles. In all, 87% of the study group was positive for DRB1*03 or DRB1*04 compared with 36% of the healthy controls. The main alleles accounting for susceptibility to T1D were DRB1*0402, found in 77.9% of carriers of DRB1*04 and DQB1*0302, found in 74.6% of carriers of DQB1*03. The DQB1*0602 was not detected in any patient. The distribution was similar to that reported in Israeli children with T1D and significantly different from healthy Israelis. There was no significant difference in the distribution of HLA class II alleles between patients with rapidly progressive T1D or LADA. It may be concluded that the different ages of onset of T1D and its different forms of development in Israeli patients are apparently not caused by a different prevalence of HLA class II alleles.     

Mycoplasmal pneumonia associated with mesangiocapillary glomerulonephritis type II (dense deposit disease)

A 20-year-old man developed pneumonia and glomerulonephritis concomitantly with significantly rising Mycoplasma pneumoniae complement-fixing antibody titres. Renal biopsy showed mesangiocapillary glomerulonephritis type II (dense deposit disease). Attempts to demonstrate mycoplasmal antigen in the glomeruli failed. This is the third of five previously reported cases of glomerulonephritis associated with Mycoplasma pneumoniae and exhibiting dense deposit disease.     

A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians

Linkage analysis has identified a susceptibility locus for type 2 diabetes mellitus (T2DM) on chromosome 1q21-q23 in several populations. Results from recent prospective studies indicate that increased levels of C-reactive protein (CRP), a marker of immune system activation, are predictive of diabetes, independent of adiposity. Because CRP is located on 1q21, we considered it a potential positional candidate gene for T2DM. We therefore evaluated CRP and the nearby serum amyloid P-component, APCS, which is structurally similar to CRP, as candidate diabetes susceptibility genes. Approximately 10.9kb of the CRP-APCS locus was screened for polymorphisms using denaturing high performance liquid chromatography and direct sequencing. We identified 27 informative polymorphisms, including 26 single nucleotide polymorphisms (SNPs) and 1 insertion/deletion, which were divided into 7 linkage disequilibrium clusters. We genotyped representative SNPs in approximately 1300 Pima samples and found a single variant in the CRP promoter (SNP 133552) that was associated with T2DM (P=0.014), as well as a common haplotype (CGCG) that was associated with both T2DM (P=0.029) and corrected insulin response, a surrogate measure of insulin secretion in non-diabetic subjects (P=0.050). Linkage analyses that adjusted for the effect of these polymorphisms indicated that they do not in themselves account for the observed linkage with T2DM on chromosome 1q. However, these findings suggest that variation within the CRP locus may play a role in diabetes susceptibility in Pima Indians.     

Intracellular starvation in the insulin resistance syndrome and type II diabetes mellitus

Statistical associations of insulin resistance, type II diabetes, hypertension and hyperlipidemia have been well documented, but the pathophysiology of the ‘insulin resistance syndrome’ is unknown. This article explores the hypothesis that intracellular starvation plays a central role in the development of type II diabetes, hypertension and hyperlipidemia. According to this hypothesis, insulin resistance leads to inadequate intracellular glucose, which in turn leads to insufficient amounts of adenosine triphosphate needed for ion transfer, and to drive energy-requiring reactions. Indirect evidence supporting this hypothesis is presented. Intracellular starvation is also discussed as an alternative to the ‘glucose hypothesis’ to explain certain complications of diabetes.     

DC-SIGN polymorphisms are associated to type 1 diabetes mellitus

Type I diabetes mellitus (T1DM) is an autoimmune disorder featured by raised glucoses levels. It has been hypothesised that raised glucose levels in T1DM might be recognised as PAMPs, leading to immune response by overloading the cell receptors for pathogens recognition. DC-SIGN is a transmembrane protein, present in dendritic cells (DC) and macrophages: it has an important role in inflammatory response and T cells activation. Notably, DC-SIGN activation and triggering of the immune response depend on the type of ligand, which may lead to a pro or anti-inflammatory pathway. In our association study, we analysed the SNPs rs4804803 (−336 A>G) and rs735239 (−871 A>G), both at DC-SIGN promoter region, in 210 T1DM patients and 157 healthy controls, also looking for a correlation with the age of onset of the disease. We found that the allele G and genotypes G/G and A/G of SNP-871 (rs735239), as well as the alleles G-G (rs735239-rs4804803) and genotypes combined AA-GG (rs735239-rs4804803) were associated with protection of T1DM development. We did not find association between these variations with the age of onset of the disease and the presence of other autoimmune disorders. Our results suggest that SNPs in DC-SIGN promoter region can be associated to protection for T1DM in the Northeast Brazilian population.