Blood levels of alloxan in children with insulin-dependent diabetes mellitus

Alloxan is a well-known and universally used agent for evoking experimental diabetes through its toxic effect on the B cells of the Langerhans islets. In our study, blood levels of alloxan in children with insulin-dependent diabetes mellitus were investigated. The observations were made in 68 children aged 6–15 years and in a control group of 44 healthy children in the same age range. Alloxan levels were estimated spectrophotometrically. The mean level of alloxan in blood from children with insulin-dependent diabetes mellitus was 8.76±9.64 g/ml and in blood from healthy children was 1.53±1.10 g/ml. The difference was statistically significant (P<0.05). The metabolism of alloxan leads to the production of free superoxide radicals which, as is well known, injure cells and cause conditions conducive to the occurrence of diseases from autoimmunity. The results obtained suggest therefore that higher levels of alloxan in diabetic children are of significance in the onset of insulin-dependent diabetes mellitus.     

他汀类药物与新发糖尿病

大量临床试验表明他汀类药物使心血管疾病患者临床明显获益。近期临床研究提示他汀增加新发糖尿病风险,他汀与新发糖尿病的关系引起广泛关注。现有临床证据显示,尽管他汀增加新发糖尿病的风险,但他汀治疗明显降低心血管事件,新增糖尿病的风险远低于其心血管获益。由于老年人使用他汀类药物新发糖尿病的风险高于年轻人群,特别是使用大剂量他汀类药物时,需监测血糖。目前,尚无证据表明他汀相关的新发糖尿病会增加心血管风险。     

他汀类药物治疗与新发糖尿病

他汀类药物是一类可有效降低包括心肌梗死和卒中在内的心血管事件风险的降胆固醇药.临床试验和汇总分析均表明,他汀类药物治疗可增高新发糖尿病风险.文章对他汀类药物诱发糖尿病的证据、可能机制和临床意义进行了综述.     

Antihypertensive treatment and new-onset diabetes mellitus

The various antihypertensive regimens have varying effects on glucose metabolism and the development of diabetes mellitus. Recent large hypertension trials have shown great differences in the development of new-onset diabetes among antihypertensive drug therapies. The incidence of diabetes is unchanged or increased by thiazide diuretics and β-adrenergic blockers, and unchanged or decreased by angiotensin-converting enzyme inhibitors, calcium channel blockers, and angiotensin-receptor blockers. The differences in new-onset diabetes mellitus have not influenced the outcome of cardiovascular mortality and morbidity in all of the large clinical trials, but drug-induced diabetes among hypertensive patients is known to carry the same cardiovascular risk as that seen in patients with previously known diabetes; however, it might take years for the increased risk to become apparent.     

Immunoglobulin levels,immunodeficiency and HLA in Type 1 (insulin-dependent) diabetes mellitus

Summary In 129 patients with Type 1 (insulin-dependent) diabetes mellitus, 100 healthy control subjects and 91 non-diabetic first degree relatives of Type 1 patients, we investigated variation in serum IgA, IgG and IgM concentrations with sex and HLA-B phenotype. Two patients with onset before the age of 15 years were completely IgA-deficient. One additional patient was completely IgG-deficient. Excluding these three cases, diabetic patients had serum IgA and IgM concentrations comparable to control subjects. IgG levels of patients were, however, significantly lower than those of control subjects (11.66 versus 12.69 g/l p = 0.003). Non-diabetic first degree relatives of patients had IgG levels intermediate between those of diabetic patients and control subjects. There was some indication that IgA concentrations were lower in the 53 patients with HLA-B8 (1.91 versus 2.21 g/l, p = 0.038). No association was found between IgM or IgG levels and HLA phenotypes.     

Magnesium and insulin-dependent diabetes mellitus

There is accumulating evidence that the changes which occur in the metabolism of some micronutrients in diabetes mellitus might have a specific role in the pathogenesis and complications of this disease. Magnesium deficiency is the most evident disturbance of metal metabolism in insulin-dependent diabetes mellitus. Hypomagnesemia has been linked both to the acute metabolic and late chronic complication of diabetes. Of particular concern, is the association between hypomagnesemia and ischemic heart disease and severe retinopathy in humans with diabetes mellitus. Appropriate magnesium supplementation might prove beneficial in normalizing the low plasma and tissue magnesium levels and prevent or retard the development of vascular complications in diabetic patients. However, well designed and documented experiments need to be performed before the rationales for such therapy are well established.     

Elevated plasma endothelin-1 levels in diabetes mellitus

BACKGROUND: This study compares plasma endothelin-1 (ET-1) levels in patients with diabetes mellitus or hypertension with healthy controls, and investigates whether ET-1 levels are correlated with glycemic control, metabolic parameters, and vascular complications. METHODS: The study population consisted of 103 patients with type 1 diabetes, 124 patients with type 2 diabetes, 35 hypertensive patients without diabetes mellitus, and 99 controls. RESULTS: Plasma ET-1 concentrations were significantly higher in patients with type 1 diabetes (0.28 +/- 0.34 fmol/mL, P =.001), type 2 diabetes (0.31 +/- 0.32 fmol/mL, P <.0001), and hypertension (0.35 +/- 0.26 fmol/mL, P <.0001) compared to controls (0.08 +/- 0.13 fmol/mL). Diabetic patients taking angiotensin converting enzyme (ACE) inhibitors had significantly lower plasma ET-1 levels than patients without (0.22 +/- 0.20 fmol/mL v 0.38 +/- 0.39 fmol/mL, P =.029). There were significant associations between ET-1 levels and age (r = 0.38, P <.05) and systolic blood pressure (BP) (r = 0.27, P <.05) in healthy controls. In diabetes we found only nonsignificant associations between ET-1 levels and age or vascular complications and a weak association between plasma ET-1 levels and glycemic control. CONCLUSIONS: Patients with diabetes or hypertension have elevated ET-1 levels, but do not exhibit positive correlations between ET-1 levels and BP, which was observed in healthy controls. Increased ET-1 levels do not induce hypertension in diabetes, but were lower in diabetic patients taking ACE inhibitors compared to those without ACE inhibitors. There is no significant association between ET-1 levels and vascular complications. These findings suggest that the plasma ET-1 level is not a marker of endothelial dysfunction but changes in plasma ET-1 levels may precede vascular complications associated with hypertension and diabetes.     

Pathogenesis of insulin-dependent diabetes mellitus

Insulin-dependent and independent types of diabetes mellitus differ not only in clinical traits but also in some other peculiarities: a different degree of disorder of insulin secretion, relationship with the HLA system, the presence of antibodies to pancreatic islets. The latter antibodies are typical of insulin-dependent diabetes mellitus whereas in insulin-independent diabetes mellitus they are absent. Autoimmune mechanisms of the pathogenesis of diabetes mellitus are confirmed by the presence of different antibodies to pancreatic islets, including cytoplasmic, cell-bound, cytotoxic and immunoprecipitating antibodies. The above autoantibodies were characterized, and a hypothetical mechanism of the development of insulin-dependent diabetes mellitus was proposed.     

Secretin: high plasma levels in diabetes mellitus

Plasma immunoreactive secretin levels were measured in 22 newly diagnosed non-ketotic, maturity-onset diabetics and 10 healthy control subjects during 50 gram oral glucose tolerance test (OGTT). The test was repeated in the diabetic group after 6 months' dietary treatment. At diagnosis the fasting secretin levels in the diabetics were higher than in control subjects but fell within the normal range following dietary treatment. In the diabetics there was a significant positive correlation between the fasting glucose and fasting secretin levels at the time of diagnosis. Suppression of secretin levels occurred during the OGTT, both in diabetic and control subjects.     

Factor VIII inhibitor in insulin-dependent diabetes mellitus

Acquired factor VIII inhibitor was found in a 69-year-old white male with insulin-dependent diabetes mellitus. He presented with left lower abdominal pain and hematoma after a fall. Preoperative hemostasis studies were normal except for prolonged aPTT. Prolonged aPTT was not corrected by 1:1 mixture with normal fresh plasma and incubation showed further prolongation with time. Factor VIII:c was 3.5%. The inhibitor titer was 7.5 Bethesda units. The possible mechanism causing antibody to factor VIII was postulated to be an autoimmune process and/or increased immunogenicity owing to glycosylation of factor VIII coagulant protein.     

Plasma big-endothelin levels, cardiac autonomic neuropathy, and cardiac functions in patients with insulin-dependent diabetes mellitus

BACKGROUND: The alteration of endothelin (ET) levels in diabetic patients with cardiac autonomic neuropathy (CAN) has not been studied extensively and its correlation with cardiac function parameters has not been discussed. HYPOTHESIS: The aim of the present study was to discuss the correlation between the degree of cardiac autonomic neuropathy, plasma big-ET levels, and cardiac functions in diabetic patients who were clinically free of cardiovascular disease. METHODS: Twenty subjects (32.1 +/- 7.8 years, 11 men, 9 women) with insulin-dependent diabetes mellitus (IDDM) were studied to evaluate the relationship between circulating big-endothelin (big-ET1) levels, CAN, and cardiac functions. The severity of CAN was scored according to Ewing's criteria. Cardiac functions were assessed using Doppler echocardiography. RESULTS: Left ventricular systolic function in the patient group was within normal limits and comparable with the values of the control group (n = 10). The mean E/A values of diabetics with CAN (1.15 +/- 0.33, p = 0.004) and without CAN (1.34 +/- 0.17) were significantly lower than those of controls (1.57 +/- 0.27). Diabetics with CAN had significantly higher big-ET1 values (81.1 +/- 94 pg/ml) compared with others (12.4 +/- 5.9 and 21.1 +/- 17.7 pg/ml, p = 0.04). Circulating big-ET1 levels showed a significant correlation with E/A values in the control group (p = 0.01, r = -0.7) and with peak A values (p = 0.003, r = 0.64) in diabetics. The CAN score correlated negatively with E/A values (p = 0.01, r = 0.54). CONCLUSIONS: High big-ET levels might have an important role in the pathogenesis or consequences of diastolic dysfunction in diabetics with CAN. Their role in cardiac autonomic neuropathy and diastolic dysfunction should be investigated further.     

Long-term bone loss in insulin-dependent diabetes mellitus

The bone mineral content (BMC) in patients with insulin-dependent diabetes is reduced by 10% early in the disease, but due to a lack of long-term longitudinal studies it is unknown whether this diabetic osteopenia develops further through life. Over a time period of 11 years we examined the BMC in a group of seven adult insulin-dependent diabetics, in whom physiological and pathological factors affecting bone metabolism had been excluded; the patients were well regulated without diabetic complications. The BMC was not significantly decreased at the initial examination. The longitudinal study revealed a small but statistically significant fall in BMC, mainly in trabecular bone. The narrow (95%) confidence interval of median end value (93.3-99.0% of initial BMC) indicates that the annual decrease in BMC in such patients is of the order of 0.5%, a reduction that is probably clinically insignificant.     

Plasma acidic glycohydrolases in insulin-dependent diabetes mellitus

Summary We assayed plasma activities of -galactosidase, -hexosaminidase, -mannosidase, -fucosidase and -galactosidase involved in degradation of the glycoprotein molecule in 110 insulin-dependent diabetics aged 3-1/2 to 19 years and compared them to a group of normal youngsters. We correlated the plasma enzyme activities with the duration, control and sequelae of insulin-dependent diabetes. Insulin-dependent diabetics had a significantly higher plasma activity of -hexosaminidase and -mannosidase (p<0.01) and a significantly lower plasma activity of -fucosidase and -galactosidase (p<0.01). Of the 5 enzymes studied, only plasma -hexosaminidase correlated with fasting and postprandial blood sugar (p<0.01), cholesterol and triglycerides (p<0.05). Additionally, poor control of diabetes was also associated with a significantly higher plasma -hexosaminidase activity (p<0.01). Proteinuria or an abnormal Addis count suggestive of renal involvement was associated with various changes in plasma acidic hydrolases. These changes may be related to insulin deficiency rather than hyperglycemia and may be genetically determined.Deceased on August 2, 1981.     

Antibody-dependent killer-cell function in insulin-dependent diabetes mellitus

Antibody-dependent killer-cell activity (ADCC) was determined in 36 insulin-dependent diabetics (IDD) and 32 controls. The medians of cytotoxic indices obtained by using either antibody coated chicken red blood or HeLa cells as targets were statistically significantly reduced in the diabetics (P less than 0.05 for both systems). However, due to the wide range and considerable overlap of the cytotoxic indices observed in patients and controls, the biological significance of these mathematical differences remains to be determined. The duration of the disease did not have any influence on killer (K) cell function and only a slight tendency for decreased ADCC during episodes of poor metabolic control was noted. Further analysis of the influence of diabetes-associated factors did not reveal any definite correlation between the functional K cell deficit, the insulin dosage administered, the insulin antibody titers, the blood glucose at the time of sampling, the 24 hour glucosuria and IDD-associated immunogenetic factors.     

High plasma prorenin in non diabetic siblings of non insulin-dependent diabetes mellitus patients

In a large cohort (no. = 361) of NIDDM probands and their concordant/discordant siblings from no. = 132 families we studied: 1. the levels of plasma prorenin in non affected siblings of NIDDM probands as opposed to normal subjects without family history of diabetes, and 2. whether plasma prorenin raises in parallel to urinary protein loss in NIDDM patients. Prorenin (solid-phase trypsin) and micro-macroalbuminuria (radioimmunoassay) were evaluated. Plasma prorenin was higher in NIDDM probands and siblings than in non NIDDM siblings (37+/-31 vs. 25+/-15 ng/ml/h, p<0.0005) who, in turn, showed higher plasma prorenin than non diabetic controls without family history of diabetes (25+/-15 vs. 17+/-8 ng/ml/h, p<0.005). Plasma prorenin was higher in NIDDM siblings of micro-macroalbuminuric probands than in NIDDM siblings of non micro-macroalbuminuric probands (40+/-26 vs. 29+/-20 ng/ml/h, mean +/- SD, p = 0.0058) whereas no difference was found among non diabetic siblings (24+/-14 vs. 22+/-11 ng/ml/h, NS). Our data confirm that plasma prorenin is elevated in NIDDM patients, and show: 1. that the raise of plasma prorenin in non-NIDDM siblings of a diabetic patient does not depend entirely from the presence of diabetes, and 2. that plasma prorenin in NIDDM probands and their concordant siblings goes along with micro-macroalbuminuria.