digoxin and Diabetes-Mellitus--Type-2

The pharmacologic, pharmacokinetic, safety, clinical efficacy, and role of sitagliptin in the management of type 2 diabetes mellitus are reviewed.. Sitagliptin is a dipeptidyl-peptidase IV (DPP4) inhibitor that increases insulin release and decreases glucagon levels by preventing the activation of incretin hormones--glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. The clinical trials reviewed provide evidence that sitagliptin, either alone or in combination with metformin or thiazolidinediones, is effective in reducing glycosylated hemoglobin (HbA(1c)), fasting plasma glucose, and two-hour postprandial glucose levels in patients with type 2 diabetes. Specifically, sitagliptin has a role in patients who have been compliant with their oral hypoglycemic agents but unable to attain target HbA(1c) values with monotherapy and lifestyle modifications. Sitagliptin is generally well tolerated, with the frequency of adverse events being similar to placebo and a low frequency of hypoglycemia. Sitagliptin does not appear to alter the pharmacokinetics of metformin, rosiglitazone, glyburide, simvastatin, warfarin, or oral contraceptives. The addition of sitagliptin to a patient's oral antidiabetic regimen would necessitate close monitoring for adverse events and possible drug interactions. The sitagliptin dosage recommended by the manufacturer is 100 mg once daily as monotherapy or in combination with metformin or a thiazolidinedione. No formal pharmacoeconomic evaluations of sitagliptin therapy have been conducted.. Sitagliptin, a DPP4 inhibitor, offers a novel treatment option for patients with type 2 diabetes mellitus.

Topics: Diabetes Mellitus, Type 2; Digoxin; Drug Interactions; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Metformin; Pyrazines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Thiazolidinediones; Triazoles

Taspoglutide, a glucagon-like peptide-1 agonist, like native glucagon-like peptide-1, delays gastric emptying time and prolongs intestinal transit time, which may alter the pharmacokinetics of concomitantly administered oral drugs. The effect of taspoglutide on the pharmacokinetics of five oral drugs commonly used in patients with type 2 diabetes mellitus was assessed in healthy subjects.. Five clinical pharmacology studies evaluated the potential drug-drug interaction between multiple subcutaneous taspoglutide doses and a single dose of lisinopril, warfarin, and simvastatin and multiple doses of digoxin and an oral contraceptive containing ethinylestradiol and levonorgestrel. The extent of interaction was quantified using geometric mean ratios and 90% confidence intervals for the maximum plasma concentration and area under the plasma concentration-time curve. In addition to pharmacokinetics, pharmacodynamic effects were assessed for warfarin and the oral contraceptive.. Among the tested drugs, the effect of taspoglutide on the pharmacokinetics of simvastatin was most pronounced, on the day of taspoglutide administration, the average exposure to simvastatin was decreased by - 26% and - 58% for the area under the plasma concentration-time curve and maximum plasma concentration, respectively, accompanied by an increase in average exposure to its active metabolite, simvastatin β-hydroxy acid (+ 74% and + 23% for area under the plasma concentration-time curve and maximum plasma concentration, respectively). Although statistically significant changes in exposure were observed for other test drugs, the 90% confidence intervals for the geometric mean ratio for maximum plasma concentration and area under the plasma concentration-time curve were within the 0.7-1.3 interval. No clinically relevant changes on coagulation (for warfarin) and ovulation-suppressing activity (for the oral contraceptive) were apparent.. Overall, multiple doses of taspoglutide did not result in changes in the pharmacokinetics of digoxin, an oral contraceptive containing ethinylestradiol and levonorgestrel, lisinopril, warfarin, and simvastatin that would be considered of clinical relevance. Therefore, no dose adjustments are warranted upon co-administration.

Topics: Administration, Oral; Adult; Angiotensin-Converting Enzyme Inhibitors; Anticholesteremic Agents; Anticoagulants; Cardiotonic Agents; Case-Control Studies; Contraceptives, Oral; Diabetes Mellitus, Type 2; Digoxin; Drug Interactions; Female; Glucagon-Like Peptide 1; Healthy Volunteers; Humans; Injections, Subcutaneous; Lisinopril; Male; Middle Aged; Peptides; Pharmaceutical Preparations; Simvastatin; Warfarin

Type 2 diabetes mellitus (T2DM) is a well-recognised risk factor for cardiovascular disease and the prevalence of atrial fibrillation (AF) is higher among patients with T2DM. Direct current cardioversion (DCCV) is an important management option in persistent AF. We sought to determine independent risk factors for immediate and short-term outcomes of DCCV for treatment of AF in patients with T2DM.. Retrospective outcome analysis of DCCV for persistent AF in 102 T2DM patients compared with 102 controls.. DCCV was successful in 68 (66.6%) people with T2DM compared to 86 (84.3%) in the control group (. T2DM, higher HbA1c, digoxin treatment, and structural and functional cardiac abnormalities are independent risk factors for immediate DCCV failure and AF relapse.

Topics: Aged; Atrial Fibrillation; Diabetes Complications; Diabetes Mellitus, Type 2; Digoxin; Electric Countershock; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Retrospective Studies; Risk Factors; Stroke Volume

Coronary heart disease, stroke, and peripheral vascular disease are the most common causes of mortality in patients with type 2 diabetes mellitus (T2DM). The aim of these studies was to assess the potential for pharmacokinetic interaction between dapagliflozin, a sodium glucose co-transporter-2 inhibitor being developed for the treatment of T2DM, and four medications commonly prescribed in patients with T2DM and cardiovascular disease: simvastatin, valsartan, warfarin, and digoxin.. Potential pharmacokinetic interactions between 20 mg dapagliflozin, 40 mg simvastatin, or 320 mg valsartan were assessed in an open-label, randomized, five-period, five-treatment, unbalanced crossover study in 24 healthy subjects. In a second study, the effects of steady-state dapagliflozin on the pharmacokinetics of 25 mg warfarin or 0.25 mg digoxin were assessed in an open-label, randomized, two-period, two-treatment crossover study in 30 healthy subjects divided into two cohorts. The potential pharmacodynamic interaction between dapagliflozin and warfarin was also evaluated.. All treatments were well tolerated. Neither simvastatin nor valsartan had any clinically meaningful effect on the pharmacokinetics of dapagliflozin. Dapagliflozin increased the area under the curve for simvastatin, simvastatin acid, and valsartan by approximately 19%, 30%, and 6%, respectively, and decreased the maximum observed plasma concentration of valsartan by approximately 6%. These effects were not considered clinically meaningful. In addition, dapagliflozin had no effect on the pharmacokinetics of either digoxin or warfarin. The pharmacodynamics of warfarin were also unaffected by dapagliflozin.. In these studies the co-administration of dapagliflozin and simvastatin, valsartan, warfarin, or digoxin was well tolerated without clinically meaningful drug-drug interaction.

Topics: Adult; Anti-Arrhythmia Agents; Anticholesteremic Agents; Anticoagulants; Antihypertensive Agents; Benzhydryl Compounds; Cross-Over Studies; Diabetes Mellitus, Type 2; Digoxin; Drug Interactions; Female; Glucosides; Humans; Hypoglycemic Agents; Male; Middle Aged; Simvastatin; Sodium-Glucose Transporter 2 Inhibitors; Tetrazoles; Valine; Valsartan; Warfarin

Gentamicin is frequently used to treat infectious diseases in patients receiving digitalis therapy. The aim of this study is to evaluate the effect of gentamicin on serum digoxin level.. Twenty-four diabetic patients and patients with congestive heart failure and twelve normal healthy volunteers were enrolled in this study. The patients received digoxin treatment 0.25 mg/day. Gentamicin in a dose of 80 mg i.m. twice a day for 7 days was prescribed for these patients to treat chest infection. Serum digoxin and creatinine levels were determined before and after gentamicin administration.. Gentamicin induced a significant increase in serum digoxin level of diabetic patients and patients with congestive heart failure. Serum creatinine level increased significantly before and after i.m. injection of gentamicin.. The present study indicated that increase serum digoxin level when combined with gentamicin should be considered a risk factor for digitalis toxicity.

Topics: Adult; Anti-Bacterial Agents; Cardiotonic Agents; Creatinine; Diabetes Mellitus, Type 2; Digoxin; Drug Interactions; Gentamicins; Heart Failure; Humans; Male; Middle Aged

To test the hypothesis that digoxin, an inhibitor of Na(+)-K(+)-ATPase activity, accelerates the progression of diabetic retinopathy.. We compared the incidence and risk of retinopathy in 120 digoxin-taking vs. 867 non-digoxin-taking diabetic participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) and in 117 digoxin-taking vs. 1,883 non-digoxin-taking diabetic subjects in the Early Treatment Diabetic Retinopathy Study (ETDRS). In both studies, retinopathy was detected by grading stereoscopic color photographs using the modified Airlie House classification scheme, and a two-step difference in baseline retinopathy grade was considered significant.. After controlling for other risk factors, we found no statistically significant association with either 4-year incidence of retinopathy (WESDR) or progression of retinopathy (WESDR and ETDRS) in patients taking digoxin at baseline compared with those not taking digoxin.. These data suggest that digoxin therapy does not adversely affect the course of diabetic retinopathy.

Topics: Adult; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Digoxin; Female; Humans; Incidence; Longitudinal Studies; Male; Risk Factors; Wisconsin

Topics: Diabetes Mellitus, Type 2; Digoxin; Glucosides; Heart Failure; Humans; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Dysfunction, Left

Activation of TGR5 stimulates intestinal glucagon-like peptide-1 (GLP-1) release, but activation of the receptors in gallbladder and heart has been shown to cause severe on-target side effects. A series of low-absorbed TGR5 agonists was prepared by modifying compound 2 with polar functional groups to limit systemic exposure and specifically activate TGR5 in the intestine. Compound 15c, with a molecular weight of 1401, a PSA value of 223 Å(2), and low permeability on Caco-2 cells, exhibited satisfactory potency both in vitro and in vivo. Low levels of 15c were detected in blood, bile, and gallbladder tissue, and gallbladder-related side effects were substantially decreased compared to the absorbed small-molecule TGR5 agonist 2.

Topics: Administration, Oral; Animals; Caco-2 Cells; Cell Line; Diabetes Mellitus, Type 2; Drug Discovery; Humans; Intestinal Mucosa; Intestines; Male; Mice; Molecular Targeted Therapy; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Small Molecule Libraries

The purpose of this study is to investigate the regulation of P-glycoprotein expression in the kidney under diabetic condition. Renal P-glycoprotein expression was examined in inbred mice with type 1 or type 2 diabetes by Western blotting. The underlying mechanisms of P-glycoprotein regulation were examined in Madin-Darby canine kidney type II (MDCK-II) cells by Western blotting or qRT-PCR. (3)H-digoxin uptake was measured for P-glycoprotein activity in cells under various treatments. The results showed that P-glycoprotein expression was lower in kidneys of diabetic mice than in controls. In MDCK-II cells, treatments with insulin or IL-6 did not cause any change in P-glycoprotein expression, whereas TNF-α tended to increase P-glycoprotein expression at a concentration of 1 ng/ml. On the other hand, P-glycoprotein expression was reduced under high glucose conditions (450 mg/dl), while superoxide production was increased, and the reduction in P-glycoprotein expression was abolished by N-acetylcysteine (an antioxidant) and staurosporine (a nonselective PKC inhibitor). Treatment with oxidizing agents (H(2)O(2), BSO) or PMA (a PKC activator) reduced P-glycoprotein expression. Antioxidant (N-acetylcysteine or glutathione) co-treatment abolished the H(2)O(2)-induced and BSO-induced reduction in P-glycoprotein expression, whereas it did not prevent the effect of PMA. The PMA-induced P-glycoprotein down-regulation was prevented by co-treatment of LY333531 (a PKC-β inhibitor). (3)H-digoxin levels were higher in MDCK-II cells with high glucose, PMA or H(2)O(2) treatments. In conclusion, P-glycoprotein expression is lower in kidneys of diabetic mice and in MDCK-II cells under high glucose conditions. Hyperglycemia induced reactive oxygen species and activated PKC in MDCK-II cells, leading to the decrease in P-glycoprotein expression.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport; Blood Glucose; Body Weight; Cell Membrane; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Digoxin; Dogs; Down-Regulation; Female; Hyperglycemia; Insulin; Interleukin-6; Kidney; Madin Darby Canine Kidney Cells; Male; Mice; Protein Kinase C; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Autoimmune Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diagnosis, Differential; Digoxin; Female; Humans; Nausea; Weight Loss

Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents.. We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI.. The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48-0.87]) or metformin with or without other agents (0.72 [0.59-0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45-0.68]) and beta-blockers (0.76 [0.61-0.95]) were associated with reduced mortality.. Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Case-Control Studies; Diabetes Mellitus, Type 2; Digoxin; Female; Heart Failure; Humans; Hypoglycemic Agents; Male; Metformin; United Kingdom

Topics: Acarbose; Aged; Aged, 80 and over; Cardiotonic Agents; Diabetes Mellitus, Type 2; Digoxin; Drug Interactions; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Heart Failure; Humans; Hypoglycemic Agents; Inositol; Male

Topics: Aged; Aged, 80 and over; Blood Glucose; Cardiotonic Agents; Diabetes Mellitus, Type 2; Digoxin; Fatal Outcome; Female; Glucose Intolerance; Glyburide; Humans; Hypoglycemic Agents; Male; Metformin

Topics: Biological Factors; Blood Pressure; Cardenolides; Diabetes Mellitus, Type 2; Digoxin; Enzyme Inhibitors; Humans; Hypertension; Saponins; Sodium-Potassium-Exchanging ATPase

The serum concentrations of digoxin-like immunoactivity (DLIA) were measured in 99 patients: 20 healthy volunteers (HV), 15 patients with insulin-dependent diabetes mellitus (IDDM), 14 patients with non-insulin-dependent diabetes mellitus without hypertension taking oral hypoglycemic (OHA) agents (NIDDM/-HT), 11 patients with NIDDM without hypertension taking insulin (NIDDM/-HT+INS), 12 NIDDM patients with hypertension taking OHA (NIDDM/+HT), nine NIDDM patients with hypertension taking insulin (NIDDM/+HT/+INS), 10 patients with essential hypertension with normal insulin levels (HT/-HI), and in eight patients with essential hypertension with hyperinsulinemia (HT/+HI). The numbers (%) of subjects with DLIA levels above the detection limit of the assay used (> 0.1 nmol/L) were, in the NIDDM/-HT group, 12/14 (85.7%) and in the NIDDM/+HT group, 9/12 (75%), significantly higher (P < .05) than in the HV (7/20; 35%), IDDM (3/15; 20%), and HT/-HI groups (2/10; 20%). The number and percentage of subjects with DLIA levels above the detection limit in the HT/+HI group was six of eight (75%), significantly (P < .05) higher than in the IDDM and HT/-HI groups, and tended to be higher than in the HV group (P < .055). Means and SD of serum DLIA levels (nmol/L) in the NIDDM/-EH (0.18/0.09) and NIDDM/+EH (0.19/0.15) groups were significantly higher (P < .05) than in the HV (0.09/0.07), IDDM (0.05/0.05), and EH/-HI (0.06/0.06) groups. DLIA levels in the HT/+HI group (0.15/0.12) were significantly higher (P < .05) than in the IDDM and HT/-HI groups. The percentage of DLIA levels above the detection limit, as well as the mean and SD of DLIA in the NIDDM group taking OHA, did not differ from those in subjects taking insulin. In all subjects studied (n = 99), DLIA correlated with C-peptide (r = 0.30; P < .01) and glomerular filtration (GF) (r = -0.21; P < .05). After exclusion of insulin-treated patients, DLIA correlated significantly with plasma glucose (PG; r = 0.25; P < .05), immunoreactive insulin (IRI; r = 0.41; P < .001), C-peptide (r = 0.27; P < .05), and GF (r = -0.26; P < .05) (n = 64). Correlation of DLIA with IRI (r = 0.33; P < .05; n = 38) also persisted after exclusion of patients taking insulin and those with DLIA levels below the detection limit. Similarly, DLIA also correlated with C-peptide (r = 0.64; P < .05) and IRI (r = 0.70; P < .05) in the subgroup of 10 patients with the highest levels of DLIA (> 0.25 nmol/L). None of the sera (n = 15) with different DLIA

Topics: Adult; Antibodies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Digoxin; Humans; Hypertension; Hypoglycemic Agents; Immunoassay; Insulin; Middle Aged

Substances with digoxin- and ouabain-like immunoactivity (DLIA) are specific inhibitors of Na(+)-K(+)-ATPase which increase the total amount of intracellular stored calcium (Ca2+i). In diabetic patients, DLIA levels have been reported to be increased. Although this increase is probably secondary to sodium retention and volume expansion (included in diabetic subjects by hyperinsulinemia and/or diabetic nephropathy), the question arises of whether it has pathophysiological consequences: namely, whether substances with DLIA, via their effect on Na(+)-K(+)-ATPase activity and Ca2+i stores, could in diabetic subjects facilitate development of hypertension and/or modulate insulin sensitivity or insulin secretion. Clinical findings of correlations of DLIA to blood pressure, insulin levels and to degree of insulin resistance, together with experimental findings of decreased Na(+)-K(+)-ATPase activity, increased Ca2+i and decreased Mg2+i in both diabetic and hypertensive subjects, support these hypotheses. However, the issue of whether or not these relations are causative and whether or not defects in intracellular milieu are primary or secondary to non-insulin-dependent diabetes mellitus has not been resolved yet. Moreover, pathogenesis of both diabetes mellitus and hypertension is multifactorial and includes many other factors. Therefore, further efforts should be made to elucidate the exact role of substances with DLIA in diabetes mellitus.

Topics: Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Digoxin; Glucose; Humans; Hyperinsulinism; Hypertension; Immunoassay; Insulin; Insulin Secretion; Models, Biological; Ouabain

Erythrocyte plasma membranes of non-insulin dependent diabetic humans (NIDDM) and healthy humans were prepared by hypotonic lysis. The specific activity of (Na(+)-K+)-ATPase of NIDDM membranes, both in the absence and presence of digoxin were lower than the specific activity of normal enzymes (83.6 percent and 74.0 percent of the normal enzyme respectively). Addition of digoxin decreased the activity of this enzyme (38.0 percent in NIDDM and 30.0 percent in normal enzyme). Although the affinity of the pump for ATP was similar in both membranes of NIDDM and normal humans (K(m) for ATP = 19.9 +/- 0.24 microM ATP and 20.0 +/- 0.21 microM ATP respectively), the Vmax of NIDDM membranes was more than 20 percent lower than that of the normal enzyme. The specific activity of Mg(2+)-dependent Ca(2+)-pumping ATPase (Ca(2+)-Mg(2+)-ATPase) of NIDDM membrane was lower than 80 percent of the specific activity of the normal enzymes. While the affinity of the pump for ATP was lower in the membranes of NIDDM (Km for ATP = 50.0 +/- 4.3 microM ATP) in comparison to normal membranes (Km for ATP = 63.1 +/- 38 microM ATP), the Vmax of NIDDM membranes was similar to the normal enzyme. Altogether, these findings suggest that both the (Na(+)-K+)-ATPase and Ca(2+)-pumping ATPase of NIDDM membranes are less functional than the enzymes in normal erythrocytes.

Topics: Ca(2+) Mg(2+)-ATPase; Diabetes Mellitus, Type 2; Digoxin; Erythrocyte Membrane; Humans; Sodium-Potassium-Exchanging ATPase

In diabetic patients, several factors contribute to volume expansion and have to be counteracted by humoral and neuronal feedback control systems. We investigated N-terminal proatrial natriuretic factor (ANF1-98) and digoxin-like immunoreactive factor (DLIF), which are two counteracting hormones, and their interrelationship, with additional consideration given to autonomic nervous function in diabetic patients. ANF1-98 and DLIF were measured in 64 diabetic patients. Autonomic nervous function was assessed using nine autonomic nervous function tests. The patients were subdivided into two groups, one with four or more (group 1) and one with less than four abnormal results in autonomic function tests (group 2). Compared with group 2, group 1 demonstrated detectable DLIF levels less often (17.2 vs. 45.7, P = 0.0195) and increased levels of ANF1-98 (mean +/- SEM: 850.0 +/- 108.8 vs. 554.8 +/- 45.9 pmol/L, P = 0.0099). However, the groups did not differ in blood pressure, daily sodium, and daily potassium excretion. The number of abnormal autonomic function tests correlated significantly with ANF1-98 (P = 0.0002). In patients with detectable DLIF, DLIF correlated with ANF1-98 (P = 0.0080). These results demonstrate close interactions between the autonomic nervous system and the two natriuretic hormones. In patients with autonomic nervous dysfunction, higher levels of ANF may possibly compensate for the lack of the natriuretic DLIF to counteract hypertension and chronic volume expansion.

Topics: Adult; Aged; Atrial Natriuretic Factor; Autonomic Nervous System; Cardenolides; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Digoxin; Female; Humans; Male; Middle Aged; Peptide Fragments; Protein Precursors; Saponins

The aim of this study was to compare the intensity of typical late complications in diabetic patients (n = 65, 28 type I, 37 type II) who were not on glycoside drugs with low vs. high serum levels of digoxin-like immunoreactive factor (DLIF: group I, n = 42, DLIF < or = the detection limit of 0.2 ng ml-1; and group II, n = 23, mean +/- SEM: 1.17 +/- 0.31 [0.25-4.96] ng ml-1). For detection of nephropathy, urinary albumin excretion (24 h) and creatinine clearance tests were used. For coronary heart disease a questionnaire and standard ECG; for peripheral occlusive vascular disease a questionnaire; for eye disease a fundoscopy; for neuropathy a neurological score system; and for autonomic neuropathy a standardized test battery was employed. Patients with high DLIF levels showed better test results in vibratory perception (95.7 +/- 1.5 vs. 82.8 +/- 3.8%, normal finding = 100%, 2p = 0.016), had better percentile localizations concerning maximal pupillary area in darkness (28.4 +/- 6.6 vs. 8.1 +/- 1.8%, 2p = 0.0004), contraction velocity at 1 s (21.5 +/- 5.8 vs. 8.0 +/- 2.2%, 2p = 0.012), and dilation velocity at 6 s (23.0 +/- 6.8 vs. 10.5 +/- 2.5%, 2p = 0.041), had less retinopathy (with retinopathy: 26.1% vs. 64.3%, 2p = 0.0028), and better percentile localizations in the respiratory sinus arrhythmia test (68.4 +/- 7.3 vs. 44.1 +/- 4.9%, 2p = 0.0064). There was no difference concerning nephropathy, blood pressure, coronary heart disease and peripheral vascular disease. Separate analysis according to the type of diabetes confirmed the results in each group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Blood Proteins; Cardenolides; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Digoxin; Female; Humans; Male; Middle Aged; Saponins; Severity of Illness Index

In order to elucidate the causal relationship between (Na(+)-K+)ATPase and diabetic nephropathy, we studied the erythrocyte (Na(+)-K+)ATPase activity in Type 2 diabetic patients, 20 with microalbuminuria and 27 without microalbuminuria and in 16 control subjects. (Na(+)-K+)ATPase activities in microalbuminuric patients (0.273 +/- 0.012 mumol Pi/mg protein/h, mean +/- SE) were significantly reduced compared with those without microalbuminuric patients (0.308 +/- 0.011 mumol Pi/mg protein/h, p < 0.05) and control subjects (0.330 +/- 0.011 mumol Pi/mg protein/h, p < 0.01). Microalbuminuric patients had higher systolic blood pressure (133 +/- 3 vs 124 +/- 3 mmHg, p < 0.05) and greater frequency of parental hypertension (50% vs 19%, p < 0.05) than those without microalbuminuria. (Na(+)-K+)ATPase activities in diabetic patients with hypertension were significantly reduced compared with those in diabetic patients without hypertension. Moreover, (Na(+)-K+)ATPase activities in diabetic patients with parental hypertension were significantly reduced compared with those in patients without parental hypertension. There was no difference in erythrocyte Na+ content between with and without microalbuminuria or hypertension or parental hypertension in diabetic patients. Erythrocyte Na+ content was significantly negatively correlated with (Na(+)-K+)ATPase activity in control subjects (r = -0.619, p < 0.05), but not in diabetic patients (r = -0.194). Plasma digitalis-like substances showed no correlation with (Na(+)-K+)ATPase activities in diabetic patients with microalbuminuria or hypertension or parental hypertension. We concluded that the reduction of erythrocyte (Na(+)-K+)ATPase activity may be related to a familial predisposition to arterial hypertension and may partly be responsible for the development of diabetic nephropathy in Type 2 diabetic patients.

Topics: Adult; Albuminuria; Blood Proteins; Cardenolides; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Digoxin; Erythrocytes; Female; Humans; Hypertension; Kinetics; Male; Middle Aged; Reference Values; Saponins; Sodium-Potassium-Exchanging ATPase

Digoxin pharmacokinetics was studied in eight patients with uncomplicated type II diabetes mellitus and seven healthy volunteers. After a single oral dose of digoxin (1 mg), the drug concentration was measured in the serum collected at different time intervals, using a radioimmunoassay method. The diabetics had a higher serum concentration of drug when compared to control. The clearance rate of digoxin was significantly reduced in diabetics when compared to healthy volunteers. The elimination half-life of about 22 hours in both groups is much less than that reported in Western data. Possible reasons for this discrepancy are discussed.

Topics: Administration, Oral; Adult; Aged; Diabetes Mellitus, Type 2; Digoxin; Humans; Male; Middle Aged