Diuretics and diabetes mellitus

The term "diuretics" describes a concerning pharmacological action and side effects heterogeneous class of drugs. The special advantage of using diuretics includes reducing edema and expanded plasma volume often associated with hypertension and cardiovascular disease. Diuretics are one of the 5 major classes of antihypertensive agents recommended for the initial drug therapy of hypertension. However, currently treatment of hypertension with diuretics is controversial, because of potentially adverse effects on the cardiovascular risk profile, including deterioration in glucose control especially in patients with impaired glucose tolerance. Additionally there is concern about excess mortality associated with diuretic therapy and diabetes mellitus. The metabolic side effects on glucose metabolism and lipid profile are related to the type of diuretic and its dosage. The adverse effects of thiazides on insulin action, glycemia and lipid profile are dose dependent and can be minimized by using low doses. In contrast, indapamide seems not to alter glucose metabolism and lipid profile. The choice of diuretic depends on concomitant disease. In patients with nephropathy potassium sparing agents should not be used, however furosemid can be used even in high doses. Beside focus on indication of diuretics in patients with diabetes and their metabolic side effects treatment of therapy resistant hypertension in these patients are discussed in this review.     

Lipid peroxidation parameters and activities of lysosomal enzymes in patients with diabetes mellitus

The processes of lipid peroxidation and activities of lysosomal enzymes were studied in 56 patients with type I and II diabetes mellitus. The rate of lipid peroxidation of red cell membranes was assessed from the activities of enzymatic (NADPH-dependent) and nonenzymatic (ascorbate-dependent) lipid peroxidation, from accumulation of acylhydroperoxides, intermolecular joints, and from spontaneous red cell hemolysis. Activities of lysosomal enzymes (cathepsins, acid DNAse, and beta-galactosidase) were measured in leukoconcentrate. The activity of enzymatic system of lipid peroxidation and acylhydroperoxide content in red cell membranes were found increased. In parallel with this, a deficiency in leukocytic lysosomes of beta-galactosidase and DNAse was revealed. The detected metabolic disturbances may be regarded as one of the pathogenetic mechanisms of development of diabetic angiopathies. A relationship was revealed between changes in lipid peroxidation parameters and activities of lysosomal enzymes, on the one hand, and diabetes mellitus type and duration, on the other.     

Psychiatric manifestations of systemic lupus erythematosus

Low-intensive laser radiation used by topical, intravenous, and transendoscopic routes was employed in the complex antituberculosis therapy of 120 patients with pulmonary tuberculosis concurrent with chronic nonspecific respiratory diseases (n = 48), diabetes mellitus (n = 20 patients), gastrointestinal diseases (n = 45). The results of treatment were compared with the parameters of 62 patients with the similar clinical and X-ray characteristics of a tuberculosis process and concomitant diseases. It was ascertained that laser therapy might enhance the efficiency of treatment of patients with concurrent abnormality statistically significantly, by reducing the time of bacterial isolation, closure of decay cavities in the lung tissue, hospital treatment and by accelerating the onset of stable remission of concomitant diseases.     

Hyperinsulinemia and hypofibrinolysis: effects of short-term optimized glycemic control with continuous insulin infusion in type II diabetic patients

A defect in the fibrinolytic system results from an increase in type 1 plasminogen activator inhibitor (PAI-1) in diabetes. It can be considered an independent risk factor for the development of cardiovascular disease. In obese and type II diabetic patients, plasma PAI-1 level correlates with fasting insulinemia. However, during the euglycemic clamp, acute hyperinsulinemia does not increase PAI-1 production. The present study was undertaken to investigate the effect of optimized glycemic control by continuous subcutaneous insulin infusion (CSII) on the hypofibrinolytic state for 14 days in 16 type II diabetic patients with poor metabolic control despite maximal oral antidiabetic treatment. Plasma PAI-1 activity levels decreased from 13.38 +/- 2.85 IU/mL to 6.77 +/- 1.81 IU/mL (P = .002) during CSII, along with a concurrent improvement in insulin sensitivity (index obtained by basal glycemia-nadir glycemia/basal glycemia) during the insulin sensitivity test (0.121 +/- 0.03 v 0.057 +/- 0.02, P = .02). These results suggest that insulin resistance rather than hyperinsulinism may be involved in the hypofibrinolytic state in type II diabetic patients. The positive correlation between the changes in triglycerides and in PAI-1 activity (r = .589, P = .026) strongly suggests a role for triglycerides in the impairment of fibrinolysis, which could be a link between insulin resistance and hypofibrinolysis.     

Biochemical changes in tuberculosis patients with different somatic types

In 100 patients with various types of pulmonary tuberculosis who were residents in Eastern Siberia, somatic types and glucose postload sugar curves and immunological status were studied and the findings were compared with the specific features of the process and its dynamics during chemotherapy. Thoracomuscular and thoracogracial somatic types were found in two thirds of cases among patients with pulmonary tuberculosis. Persons with these somatic types developed chiefly infiltrative tuberculosis. Uncorrectable abnormalities in the sugar curves were detected in all somatic types in patients with pulmonary tuberculosis. Most substantial carbohydrate metabolic changes (curves of the rigid pattern) are associated with the asthenic constitution. Immunological changes are unassociated with the type of constitution.     

Injuries in young female players in European team handball

The basis for treatment of lipid disorders in patients with non-insulin-dependent diabetes mellitus is weight reduction by diet and exercise, and additional control of glycaemic condition with oral antidiabetics, alone or in combination with insulin. Hypercholesterolaemic, mildly hypertriglyceridaemic non-insulin-dependent diabetes mellitus patients respond to cholesterol malabsorption caused by dietary sitostanol ester margarine, while long-term statin treatment of respective coronary patients significantly lowers the recurrence of coronary events, in addition to improving the lipid disorder. However, no information is available concerning the preventive effect of long-term improvement of lipid disorders in non-insulin-dependent diabetes mellitus patients without coronary heart disease, or in patients with the 'classical' type of diabetic lipid disorder, that is, hypertriglyceridaemia with low HDL and normal-low LDL-cholesterol levels. In this group of patients, beneficial lipid effects can be obtained (although perhaps not normalization) with fibrates alone or, especially, in combination with current statins.     

Interpreting outcomes

Analysis of clinical forms of tuberculosis in patients of a pulmonological showed that 65.5% of them had infiltrative tuberculosis, 13.8% fibrocavernous tuberculosis, 10.4% disseminated tuberculosis, 6.9% focal tuberculosis, and 1.7% tuberculoma. It was ascertained that in these patients destructive tuberculous changes were common and occurred in 67.2% and tuberculosis was concurrent with other lung diseases in 70.7%. This follows that special attention should be given to the patients of pulmonological hospitals and sputum tests for mycobacteria are to be performed 3 times.     

T cell cytokine responses in persons with tuberculosis and human immunodeficiency virus infection

Tuberculosis causes more extensive and life-threatening disease in patients with HIV infection than in immunocompetent persons. To investigate the hypothesis that these severe manifestations of tuberculosis may be due to alterations in cytokine production, we evaluated cytokine patterns in HIV-infected tuberculosis patients. Upon stimulation with Mycobacterium tuberculosis in vitro, PBMC from HIV-infected tuberculosis patients had reduced proliferative and type 1 responses, compared with HIV-seronegative tuberculosis patients. The reduction in proliferative responses was independent of the CD4 cell count, but the reduced type 1 response was a direct result of CD4 cell depletion. There was no enhancement of type 2 cytokine production in HIV-infected patients, although production of IL-10 was prominent in all tuberculosis patients. In HIV-infected tuberculosis patients, M. tuberculosis-induced proliferative responses were significantly enhanced by neutralizing antibodies to IL-10 but not by antibodies to IL-4 or by recombinant IL-12. The M. tuberculosis-induced type 1 response was augmented both by antibodies to IL-10 and by recombinant IL-12. Tuberculosis in the context of HIV infection is characterized by diminished type 1 responses, probably induced by immunosuppressive cytokines produced by macrophages/monocytes, rather than by type 2 cells.     

Epidermiology and associated risk factors of hyperlipoproteinemia

With the world-wide increase of the number of ischemic heart diseases the significance of the so-called factors of risk which initiate an arteriosclerosis or can deteriorate it, respectively, has increased. In the Dresden study concerning the most important factors of risk we found the following frequencies: obesity 8.2%, hyperlipoproteinemia 7.4%, hyperuricemia 3.8%, diabetes mellitus 2.0%, hypertension 17.2% and smoking 30.3%. From the investigations results the great significance of the combination of factors of risk which has a potentiating effect. The hyperlipoproteinemias of type III-V most frequently show a disturbed carbohydrate tolerance and hypertension. In them also the most frequent severe changes of the ECG appear. Myocardial infarctions concerned above all type II-IV. Apparantly concerning the vascular system patients with the combination hyperlipoproteinemia and carbohydrate metabolism are particularly endangered. The "metabolic syndrome" (obesity, diabetes mellitus, hyperlipoproteinemia, hyperuricemia, steatosis hepatis) with the increase of the viscosity of blood and plasma as well as disturbances of coagulation together with other factors of risk further the development of arteriosclerosis or has a directing influence on it. Nevertheless, the concept of the significance of the factors of risk is not able to predict the risk in every case. With the help of the apoproteins the metabolic risk is to be more exactly estimated by the determination of the lipid values in the individual classes of lipids or by classification.     

Polylactide macroporous biodegradable implants for cell transplantation. II. Preparation of polylactide foams by liquid-liquid phase separation

Good metabolic control may improve cardiac function in diabetic patients. It is not known, however, whether this functional improvement is associated with concomitant electrocardiographic changes. The aim of the present prospective study was to evaluate the quantitative electrocardiographic and vectorcardiographic correlates of metabolic control, left ventricular function and dimensions, and autonomic nervous function in patients with newly diagnosed Type 2 diabetes. We studied 35 patients (20 men, 15 women; age 52 +/- 6 years (mean +/- SD) with normal electrocardiograms at 1.5 and 15 months after the diagnosis of Type 2 (non-insulin-dependent) diabetes. During the follow-up, body weight decreased, and significant improvement was observed in metabolic control, cardiac function and autonomic nervous function. Concomitantly, maximal spatial vector of T wave increased from 238 +/- 122 to 284 +/- 141 microV (P < 0.01), and this increase was correlated with a decrease in glycosylated haemoglobin A1C (r = -0.45, P < 0.01) and plasma insulin (r = -0.46, P < 0.01). In addition, duration of QRS complex shortened from 94 +/- 9 to 92 +/- 8 ms (P < 0.05), and this shortening was correlated with an increase in heart rate variability (r = -0.34; P < 0.05) and a decrease in peak early to late left ventricular filling flow velocity (r = 0.35, P < 0.05). These changes were most prominent in patients with co-existing hypertension and coronary artery disease. In conclusion, improving metabolic control of diabetes is associated with changes in ventricular repolarization and shortening of QRS complex duration.     

The compositional abnormalities of lipoproteins in diabetic renal failure

BACKGROUND: Diabetic nephropathy (DN) is a common cause of chronic renal failure (CRF). Patients with DN have abnormal lipoprotein metabolism that can be influenced by both the impairment of renal function and the metabolic control of diabetes. The aim of the study was to explore the specific compositional lipoprotein abnormalities in patients with insulin-dependent DN in comparison with diabetic patients without nephropathy and non-diabetic CRF patients. METHODS: The lipid and apolipoprotein (apo) composition of major lipoprotein density classes was determined in 20 patients with insulin-dependent diabetes mellitus and nephropathy and compared with that in seven diabetic patients without nephropathy, 20 patients with non-diabetic CRF, and nine healthy control subjects. Lipoproteins isolated by preparative ultracentrifugation were very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). RESULTS: Patients with DN had a plasma lipid and apolipoprotein profile characteristic of renal dyslipoproteinaemia with increased concentrations of triglycerides and cholesterol, reduced levels of apoA-I and apoA-II and increased levels of apoB, apoC-II, apoC-III and apoE. These changes were more pronounced in diabetic than in non-diabetic patients with comparable degrees of renal failure. All density classes were characterized by abnormal concentration and composition of some lipid and apolipoprotein constituents. DN patients had a more than four-fold increase of VLDL mass, a three-fold increase of IDL mass, and a significant reduction of HDL mass compared to control subjects. They also had significantly higher concentrations of apoB, apoC-peptides and apoE particularly in VLDL and IDL, and to some extent in LDL. In HDL, DN patients had lower cholesterol, apoA-I, apoA-II and apoC-II levels than controls. The major compositional change in DN patients was a significant increase in the relative content of apoC-peptides in IDL and LDL. The lipoprotein abnormalities were more pronounced in patients with high HbA1c values. In addition, lower GFR and increased proteinuria were associated with higher concentrations of triglycerides and apoC peptides in VLDL, IDL, and LDL in DN patients. CONCLUSIONS: The results indicate that patients with DN share the characteristic features of dyslipidaemia of CRF with accumulation of intact or partially delipidized apoB-containing lipoproteins enriched in apoC-peptides and apoE, which are present not only in VLDL and IDL but also in LDL density range. The alterations are more marked in DN than in nondiabetic CRF patients reflecting the additional impact of metabolic control. Increased levels of these lipoproteins may represent risk factors for the accelerated development of atherosclerotic vascular disease in these patients.     

Oxidative stress in diabetic macrovascular disease: does homocysteine play a role?

BACKGROUND: Non-insulin-dependent diabetes mellitus (NIDDM) and hyperhomocysteinemia are both associated with increased lipid peroxidation (oxidative stress). This may contribute to the accelerated vascular disease associated with these conditions. It is not known whether the coexistence of elevated homocysteine levels will stimulate oxidative stress further than that caused by diabetes alone. METHODS: Plasma concentrations of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, were measured in patients with NIDDM who had previously had a methionine load test; some of the patients had hyperhomocysteinemia. RESULTS: Plasma TBARS concentrations were elevated in diabetics with vascular disease. The additional presence of hyperhomocysteinemia was not associated with a further increase in plasma TBARS concentrations. CONCLUSIONS: Lipid peroxidation is increased in patients with diabetes mellitus and macrovascular disease and is not further elevated by the coexistence of elevated homocysteine levels. It is possible that diabetes maximally stimulates oxidative stress and any further acceleration of vascular disease in patients who have coexistent hyperhomocysteinemia is mediated through mechanisms other than lipid peroxidation.     

Human immunodeficiency virus infection alters antigen-induced cytokine responses in patients with active mycobacterial diseases

Peripheral blood cells from 29 patients with active Mycobacterium avium (MAC) or Mycobacterium tuberculosis diseases were tested for mycobacterial antigen-induced interferon (IFN)-gamma and interleukin (IL)-4 production. Among MAC patients, human immunodeficiency virus (HIV) infection was associated with an 80% decrease in those who produced IFN-gamma, resulting in a predominantly type 2 cytokine profile. HIV infection in patients with tuberculosis correlates with a 37% increase in those producing IL-4 and a type 1 to type 0 profile shift. These qualitative changes were independent of CD4+ or CD8+ cell numbers. The amounts of both IFN-gamma and IL-4 were decreased in the HIV-infected population. Quantitative reduction of IFN-gamma was the result of fewer secreting cells rather than a down-regulation at the single-cell level. Disseminated disease was restricted to 2 of 5 HIV-infected MAC patients with a type 2 cytokine profile and 4 of 5 HIV-infected tuberculosis patients with a type 0 profile. These results demonstrated a shift in mycobacterial antigen-specific cytokine profiles from type 1 to type 0 and to type 2, in parallel with AIDS progression.     

The dynamics of cardiac contraction in dogs with alloxan diabetes

Development of alloxan diabetes was accompanied in dogs by regular changes in the phasic structure of the cardiac contractions. Direction of the changes in the indices of phasic analysis in the groups of dogs with an average (up to 144.3 +/- 12.5 mg%) and marked (up to 258.0 +/- 22.8 mg%) increase in the blood sugar level was the same, but their expression increased with the elevation of hyperglycemia. In marked hyperglycemia there was established an increase (in comparison with normal values) of the index of myocardial tension, a shortening of the period of ejection, a decrease of the mechanical coefficient and of the intrasystolic index, this coinciding with the character of changes of the corresponding indices in the patients suffering from diabetes mellitus, depending on the severity of the disease. The data obtained pointed to the significant influence of metabolic changes (assessed by hyperglycemia level) on the contractile function of the heart.     

Tuberculous anal ulcer

Two patients with anorectal tuberculosis, without prior or concurrent knowledge of active pulmonary infection with mycobacteria, are described. Anal fissure in an unusual location which is slow to heal should have a biopsy performed, with appropriate stains and cultures carried out, to rule out tuberculous disease. Chemotherapy is then highly effective for ulcerative perianal tuberculosis.     

A new diarrhea pathogen: entero-adherent-invasive-toxigenic Escherichia coli

The number of Americans with diabetes mellitus has increased 50% since 1983 to 16 million. An interesting and startling factor is that only half of these diabetics are aware they have the disease. Diabetes mellitus can lead to blindness, heart disease, stroke, nerve damage, kidney failure, and periodontal disease. It is the fourth leading cause of death in the United States. A metabolic disorder affecting insulin metabolism and associated blood glucose intolerance regulation, diabetes may be classified by the following categories: type I-insulin dependent diabetes mellitus which is commonly found in children and adolescents and type II-non-insulin-dependent or adult-onset diabetes which occurs in patients over forty and is associated with obesity. The dental hygienist's role in education, prevention, and therapeutics has expanded to detection and recognition of oral manifestations of diabetes. The dental hygienist may be the first to recognize the presence of the disease. This article aims to acquaint the dental hygienist with the clinical picture of a dental patient with diabetes mellitus.     

Time for more active lipid-lowering treatment of patients with diabetes. Negative effect of hyperlipidemia on beta-cells is a neglected field

Type 2 diabetes mellitus is a common metabolic disorder whose prevalence is increasing in the western world. The ravaging complications of the disease constitute a major cause of hospitalisation and cardiovascular morbidity, and despite intensive research the pathogenic mechanism remain unknown. The article summarises some recent advances in the field of islet beta-cell dysfunction caused by hyperlipidaemia in the diabetic state, which results in perturbed insulin secretory capacity and overt glucose intolerance. In contrast to hyperglycaemia, the detrimental effects of hyperlipidaemia have been a relatively neglected area of diabetes research. However, the direct inhibitory effects of long-term hyperlipidaemia on beta-cell function, 'lipotoxicity,' should form the basis of a more active approach to lipid screening and pharmacological treatment of hyperlipidaemia in diabetes patients. Intervention in the leptin pathway may prove beneficial in future treatment strategies.     

Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study

OBJECTIVE: Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications. RESEARCH DESIGN AND METHODS: In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured. RESULTS: After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients. CONCLUSIONS: Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.     

Buttonhole ulceration and perforation of the rectum

Immune status was examined in 231 patients facing pneumoconiosis and coniotuberculosis so as to observe a dependence on pneumoconiosis type (silicosis, electric welder's pneumoconiosis), severity of the process, activity of tuberculosis. Markedly changed T and B immunity, having already appeared at initial stage of the disease, were revealed. Those changes due to the tuberculosis activity were characterized by lymphocytosis, marked functional immaturity of T lymphocytes, depressed B lymphocytes count, elevated serum Ig level.