Effect of ruboxistaurin on urinary transforming growth factor-beta in patients with diabetic nephropathy and type 2 diabetes.
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Adult↗
Biomedical subjects
Janet B McGill
Publications and source records attributed to Janet B McGill.
Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus.
OBJECTIVES: The purpose of this study was to determine if myocardial fatty acid utilization (MFAU) and myocardial fatty acid oxidation (MFAO) are increased in diabetic patients. BACKGROUND: Experimental models of diabetes mellitus demonstrate that MFAU and MFAO are increased, and that this dependence on myocardial fatty acid metabolism may be detrimental to cardiac function. Whether similar metabolic changes occur in humans with diabetes mellitus is unclear. METHODS: Eleven healthy non-diabetic control patients (5 women, ages 25 +/- 5 years) and 11 otherwise healthy patients with type 1 diabetes mellitus (T1DM) (8 women, ages 36 +/- 10 years, HbA1c 8.4 +/- 1.9%) underwent positron emission tomography for the determination of myocardial blood flow (MBF); myocardial oxygen consumption (MVO2); myocardial glucose utilization (MGU); and MFAU, MFAO, and %MFAO. RESULTS: Plasma lactate, insulin, and MBF levels were similar between the two groups. However, plasma glucose (5.71 +/- 0.98 mumol/ml vs. 5.28 +/- 0.65 mumol/ml, p = 0.04), free fatty acid levels (0.60 +/- 0.24 mumol/ml vs. 0.19 +/- 0.07 mumol/ml, p < 0.0001), and MVO2 (6.64 +/- 2.21 vs. 4.51 +/- 1.39 mumol/g/min, p = 0.007) levels were higher in the T1DM subjects. Furthermore, compared with control patients, T1DM subjects exhibited higher MFAU (213 +/- 135 nmol/g/min vs. 57 +/- 28 nmol/g/min, p = 0.0004), MFAO (206 +/- 131 nmol/g/min s. 50 +/- 26 nmol/g/min, p = 0.0002), and %MFAO (94 +/- 6% vs. 81 +/- 19%, respectively, p = 0.04). In contrast, MGU was lower in T1DM subjects than in controls (207 +/- 108 nmol/g/min vs. 403 +/- 191 nmol/g/min, p = 0.0008). CONCLUSIONS: Humans with diabetes mellitus exhibit increased MFAU and MFAO and reduced MGU consistent with observations obtained in experimental models of diabetes.
Adult↗
Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial.
CONTEXT: In patients with diabetes mellitus, depression is a prevalent and recurrent problem that adversely affects the medical prognosis. OBJECTIVE: To determine whether maintenance therapy with sertraline hydrochloride prevents recurrence of major depression in patients with diabetes. DESIGN: A randomized, double-blind, placebo-controlled, maintenance treatment trial. Patients who recovered from depression during open-label sertraline treatment continued to receive sertraline (n = 79) or placebo (n = 73) and were followed up for up to 52 weeks or until depression recurred. SETTING: Outpatient clinics at Washington University, St Louis, MO, the University of Washington, Seattle, and the University of Arizona, Tucson. PATIENTS: One hundred fifty-two patients with diabetes (mean age, 52.8 years; 59.9% female; 82.9% with type 2 diabetes) who recovered from major depression (43.3% of those initially assigned) during 16 weeks of open-label treatment with sertraline (mean dose, 117.9 mg/d). INTERVENTION: Sertraline continued at recovery dose or identical-appearing placebo. MAIN OUTCOME MEASURES: The primary outcome was length of time (measured as the number of days after randomization) to recurrence of major depression as defined in DSM-IV. The secondary outcome was glycemic control, which was assessed via serial determinations of glycosylated hemoglobin levels. RESULTS: Sertraline conferred significantly greater prophylaxis against depression recurrence than did placebo (hazard ratio = 0.51; 95% confidence interval, 0.31-0.85; P = .02). Elapsed time before major depression recurred in one third of the patients increased from 57 days in patients who received placebo to 226 days in patients treated with sertraline. Glycosylated hemoglobin levels decreased during the open treatment phase (mean +/- SD glycosylated hemoglobin level reduction, -0.4% +/- 1.4%; P = .002). Glycosylated hemoglobin levels remained significantly lower than baseline during depression-free maintenance (P = .002) and did not differ between treatment groups (P = .90). CONCLUSIONS: In patients with diabetes, maintenance therapy with sertraline prolongs the depression-free interval following recovery from major depression. Depression recovery with sertraline as well as sustained remission with or without treatment are associated with improvements in glycosylated hemoglobin levels for at least 1 year.
Age of Onset↗
Alterations in left ventricular structure and function in type-1 diabetics: a focus on left atrial contribution to function.
This study was designed to determine the effects of type 1 diabetes mellitus (T1DM) on left ventricular (LV) and particularly left atrial (LA) structure and function. We evaluated 88 non-obese subjects: 44 with T1DM, 44 age- and gender-matched normal controls (age 39 +/- 11 years). LV and LA structure and function were quantified using two-dimensional echocardiography, pulse-wave Doppler, and tissue Doppler imaging, including early and late diastolic myocardial velocities (Em global and Am global, respectively). The T1DM subjects averaged higher heart rate, relative wall thickness, and ejection fraction, and lower indexed end-systolic volume than normal controls (P < .001, P < .05, P = .01, and P < .05, respectively). T1DM was related to A wave velocity, Am global, A wave integral, LA ejection fraction, and LA systolic ejection fraction (P < .01, P < .05, P < .0005, P < .001, and P < .0005, respectively). In multivariate analyses, T1DM was an independent predictor of the A wave integral, LA ejection fraction, and LA systolic ejection fraction (P < .01, P < .01, and P < .005, respectively). Thus, despite increased relative wall thickness, LV systolic function is increased and early diastolic filling is normal in T1DM subjects; however, they possess changes in LA transport function suggesting increased reliance on LA contribution to LV filling.
Adolescent↗
Epidemiology of obesity and chronic kidney disease.
The obesity epidemic has reached nephrology in the form of increasing numbers of patients with chronic kidney disease (CKD) caused by obesity-related metabolic disorders, IgA nephropathy, stone disease, and a unique glomerulopathy now known as obesity-related glomerulopathy (ORG). Obesity has been identified as an independent risk factor for CKD, and patients with central adiposity or high waist-to-hip ratios appear to have the highest risk. The metabolic syndrome is a risk factor for albuminuria and CKD, and studies now show that the risk of CKD increases with increased numbers of components of the metabolic syndrome. Obesity is not just a bystander or accelerator of other kidney diseases, but has unique histopathologic characteristics that can cause progressive kidney disease. ORG may accompany and worsen IgA nephropathy, urate nephropathy, and possibly even diabetic nephropathy. The origins of obesity-related kidney disease can be traced to insufficient glomerular complement from birth, and low birth weight may be an important precursor to obesity and its many comorbidities. Intervention strategies may need to target prenatal care through the elderly to combat this problematic epidemic.
Albuminuria↗
Clinical safety of the selective PKC-beta inhibitor, ruboxistaurin.
The aim of this manuscript is to report the safety profile of patients treated with ruboxistaurin mesylate (RBX; LY333531), a selective protein kinase C-beta (PKC-beta) inhibitor, for up to 4 years. Data from patients with diabetes (1396 RBX 32 mg/day; 1408 placebo) were combined from 11 placebo-controlled, double-masked studies. The proportion of patients who reported one or more serious adverse events was greater in the placebo group than in the RBX-treated group (23.2 versus 20.8%, respectively). There were 51 deaths (21 RBX; 30 placebo) reported in this patient cohort; none of the deaths was attributed to study drug by the investigators. Common adverse drug reactions (> or = 1/100 - < 1/10 patients) that were reported in the RBX-treated patients were dyspepsia and increased blood creatine phosphokinase. In controlled, randomised clinical trials, RBX had an adverse event profile comparable to placebo, and was well tolerated.
Humans↗
Paradoxical increase in ventricular torsion and systolic torsion rate in type I diabetic patients under tight glycemic control.
OBJECTIVES: This study sought to characterize the early features of diabetic cardiomyopathy by magnetic resonance imaging (MRI) tagging. BACKGROUND: The earliest manifestations of diabetic cardiomyopathy have not been well established, especially under tight glycemic management. We hypothesized that torsion measurements would identify subclinical contractile alterations in type I diabetics with normal left ventricular ejection fraction, mass, blood pressure, and aggressive glycemic control. We also sought to characterize the influence of elevated resting heart rates (HRs) of diabetics on torsion. METHODS: Sixteen patients with type I diabetes and 10 control patients underwent cine and tagged MRI with a 1.5-T scanner. Torsion, strain, and their rates were measured. To quantify the influence of chronotropic and inotropic stimulation on torsion, nine healthy volunteers underwent MRI tagging at rest, after atropine injection, and after exercise. RESULTS: Diabetic patients (hemoglobin A1c, 6.8 +/- 0.4%) had a higher resting HR (77.0 +/- 12.4 beats/min vs. 59.0 +/- 5.6 beats/min; p < 0.01), higher maximal torsion by 23% (3.5 +/- 0.9 degrees/cm vs. 2.7 +/- 0.4 degrees/cm; p < 0.01) and higher maximal systolic torsion rate (TR-s) by 25% (0.013 +/- 0.003 degrees/cm/s vs. 0.010 +/- 0.002 degrees/cm/s, p = 0.01). Torsion did not significantly change with chronotropic stimulation (p = 0.30). CONCLUSIONS: In diabetics under tight glycemic control, we observed a surprising increase in torsion and TR-s unrelated to chronotropic influences of HR. We propose that increased torsion and TR-s could represent early predictive markers of the propensity to cardiac dysfunction in asymptomatic type I diabetics. Furthermore, these findings seem fundamental to the diabetic state itself and unaccounted for by other comorbidities.
Adult↗
Differential effects of beta-blockers on albuminuria in patients with type 2 diabetes.
Increases in the cardiovascular risk marker microalbuminuria are attenuated by blood pressure reduction using blockers of the renin-angiotensin system. Such changes in microalbuminuria have not been observed when beta-blockers are used. A prespecified secondary end point of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial was to examine the effects of different beta-blockers on changes in albuminuria in the presence of renin-angiotensin system blockade. Participants with hypertension and type 2 diabetes were randomized to either metoprolol tartrate (n=737) or carvedilol (n=498) in blinded fashion after a washout period of all antihypertensive agents except for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Blinded medication was titrated to achieve target blood pressure, with a-5 month follow-up period. The current analysis examined microalbuminuria, using spot urine albumin:creatinine, in participants who had values at screening and trial end. A greater reduction in microalbuminuria was observed for those randomized to carvedilol (-16.2%Delta; 95% confidence interval, -25.3, -5.9; P=0.003). Of those with normoalbuminuria at baseline, fewer progressed to microalbuminuria on carvedilol versus metoprolol (20 of 302 [6.6%] versus 48 of 431 [11.1%], respectively; P=0.03). Microalbuminuria development was not related to differences in blood pressure or achievement of blood pressure goal (68% carvedilol versus 67%, metoprolol). Presence of metabolic syndrome at baseline was the only independent predictor of worsening albuminuria throughout the study (P=0.004). Beta-blockers have differential effects on microalbuminuria in the presence of renin-angiotensin system blockade. These differences cannot be explained by effects on blood pressure or alpha1-antagonism but may relate to antioxidant properties of carvedilol.
Adrenergic beta-Antagonists↗
A multilevel ecological approach to promoting walking in rural communities.
BACKGROUND: Walking is a key focus of public health interventions yet is particularly uncommon in rural residents. This study's purpose was to determine whether a multilevel community intervention affected rates of moderate physical activity, in particular walking. METHODS: A quasi-experimental design examined changes in walking in six rural intervention communities in Missouri and six comparison communities in Arkansas and Tennessee in 2003-2004. Interventions were developed with community input and included individually tailored newsletters; interpersonal activities that stressed social support and health provider counseling; and community-wide events such as fun walks. A dose variable estimated exposure to intervention activities. Primary outcomes were rates of walking and moderate physical activity in the past week. RESULTS: At follow-up (n = 1531), the percentage of respondents who met the recommendation for walking was the same across the intervention and comparison areas. Among the dependent variables, walking showed some evidence of a positive linear trend across dose categories (P = 0.090). After adjusting for covariates and baseline rates, intervention participants in the moderate and high dose categories were about three times more likely to meet recommended guidelines for walking. CONCLUSIONS: Some evidence of effectiveness was shown for a multilevel intervention approach to promote walking.
Adolescent↗
The effects of plasma insulin and glucose on myocardial blood flow in patients with type 1 diabetes mellitus.
OBJECTIVES: The objective of this study was to determine the impact of insulin and glucose on myocardial vasodilator function in patients with type 1 diabetes mellitus (T1DM). BACKGROUND: The relative importance of plasma insulin and glucose levels on the abnormal vasodilator function observed in T1DM is unknown. METHODS: Twenty T1DM patients underwent positron emission tomography studies to measure myocardial blood flow (MBF) (in ml/g/min) at rest (MBFr) and during adenosine (MBFa), both under baseline metabolic conditions and then during either hyperinsulinemic-euglycemic clamp (HE) (n = 10; 40 +/- 9 years, 8 female subjects, hemoglobin A1c [HbA1c] 7.8 +/- 1.1%) or hyperinsulinemic-hyperglycemic clamp (HH) (n = 10; 44 +/- 12 years, 8 female subjects, hemoglobin A1c 7.7 +/- 0.6%). RESULTS: Both groups showed similar MBFr and MBFa under baseline metabolic conditions (p = NS). Compared with baseline conditions, MBFr increased in the HH group (p < 0.005), whereas it did not change in the HE group. Compared with baseline conditions, MBFa decreased in the HH group (p < 0.05) but did not change in the HE group. Myocardial perfusion reserve (MPR) (MBFa/MBFr) was similar between the HE and HH groups at baseline (p = NS). During clamp, MPR tended to decrease in the HH group (p < 0.1) but did not change in the HE group (p = NS) when compared with baseline conditions. However, during the clamp MPR was significantly lower in the HH group when compared with the HE group (p < 0.0001). CONCLUSIONS: In the short term, hyperglycemia has a deleterious effect on myocardial vasodilator function, which outweighs the beneficial effect of hyperinsulinemia.
Adult↗
Rationale--Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease.
BACKGROUND: Patients with chronic kidney disease (CKD) have a high burden of mortality and cardiovascular morbidity. Additional strategies to modulate cardiovascular risk in this population are needed. Data suggest that anemia is a potent and potentially modifiable risk factor for cardiovascular disease in patients with CKD, but these data remain unsubstantiated by any randomized controlled trial (RCT). Furthermore, the clinical practice guidelines for anemia management in patients with CKD are based on limited data. The need for new RCTs to address critical knowledge deficits, particularly with regard to the impact of anemia therapy on cardiovascular disease and survival, is recognized within the guidelines and independent comprehensive reviews of the existing published trial data. STUDY DESIGN: The Trial to Reduce Cardiovascular Events with Aranesp (Amgen Inc, Thousand Oaks, Calif) (darbepoetin alfa) Therapy (TREAT) is a 4000-patient, multicenter, double-blind RCT, designed to determine the impact of anemia therapy with darbepoetin alfa on mortality and nonfatal cardiovascular events in patients with CKD and type 2 diabetes mellitus. Subjects will be randomized in a 1:1 manner to either darbepoetin alfa therapy to a target hemoglobin (Hb) of 13 g/dL or control, consisting of placebo for Hb > or =9 g/dL or darbepoetin alfa for Hb <9 g/dL until Hb is again Hb > or =9 g/dL. TREAT is event-driven and has a composite primary end point comprising time to mortality and nonfatal cardiovascular events, including myocardial infarction, myocardial ischemia, stroke, and heart failure. TREAT will provide data that are critical to evolution of the management of cardiovascular risk in this high-risk population.
Anemia↗
The effect of ruboxistaurin on nephropathy in type 2 diabetes.
OBJECTIVE: Ruboxistaurin selectively inhibits protein kinase C-beta and ameliorates kidney disease in animal models of diabetes. The purpose of this study was to evaluate the effects of ruboxistaurin on diabetic nephropathy in humans. RESEARCH DESIGN AND METHODS: A randomized, double-blind, placebo-controlled, multicenter, pilot study was performed to evaluate the effects of 32 mg/day ruboxistaurin for 1 year in persons (n = 123) with type 2 diabetes and persistent albuminuria (albumin-to-creatinine ratio [ACR] 200-2,000 mg/g), despite therapy with renin-angiotensin system inhibitors. The primary end point was a change in the ACR. Estimated glomerular filtration rate (eGFR) (four-component equation from the Modification of Diet in Renal Disease study) was also calculated. RESULTS: At baseline, urinary ACR was 764 +/- 427 mg/g (means +/- SD), and eGFR was 70 +/- 24 ml/min per 1.73 m2. Systolic and diastolic blood pressures were 135 +/- 14 and 75 +/- 9 mmHg, respectively. HbA(1c) was 8.0 +/- 1.2%. After 1 year, urinary ACR decreased significantly (-24 +/- 9%) in participants treated with ruboxistaurin (P = 0.020) and nonsignificantly (-9 +/- 11%) in the placebo group (P = 0.430). The ACR-lowering effect of ruboxistaurin appeared by 1 month. eGFR did not decline significantly in the ruboxistaurin group (-2.5 +/- 1.9 ml/min per 1.73 m2) (P = 0.185), whereas the placebo group lost significant eGFR over 1 year (-4.8 +/- 1.8 ml/min per 1.73 m2) (P = 0.009). Between-group differences for changes in ACR and eGFR were not statistically significant, but this pilot study was underpowered to determine such differences. CONCLUSIONS: In persons with type 2 diabetes and nephropathy, treatment with ruboxistaurin reduced albuminuria and maintained eGFR over 1 year. Ruboxistaurin may add benefit to established therapies for diabetic nephropathy.
Black or African American↗
Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial.
CONTEXT: Beta-blockers have been shown to decrease cardiovascular risk in patients with hypertension and type 2 diabetes mellitus (DM); however, some components of the metabolic syndrome are worsened by some beta-blockers. OBJECTIVE: To compare the effects of beta-blockers with different pharmacological profiles on glycemic and metabolic control in participants with DM and hypertension receiving renin-angiotensin system (RAS) blockade, in the context of cardiovascular risk factors. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, parallel-group trial (The Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives [GEMINI]) conducted between June 1, 2001, and April 6, 2004, at 205 US sites that compared the effects of carvedilol and metoprolol tartrate on glycemic control. The 1235 participants were aged 36 to 85 years with hypertension (>130/80 mm Hg) and type 2 DM (glycosylated hemoglobin [HbA1c], 6.5%-8.5%) and were receiving RAS blockers. Participants were followed up for 35 weeks. INTERVENTIONS: Participants were randomized to receive a 6.25- to 25-mg dose of carvedilol (n = 498) or 50- to 200-mg dose of metoprolol tartrate (n = 737), each twice daily. Open-label hydrochlorothiazide and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure target. MAIN OUTCOME MEASURES: Difference between groups in mean change from baseline HbA1c following 5 months of maintenance therapy. Additional prespecified comparisons included change from baseline HbA1c in individual treatment groups, treatment effect on insulin sensitivity, and microalbuminuria. RESULTS: The 2 groups differed in mean change in HbA1c from baseline (0.13%; 95% confidence interval [CI], -0.22% to -0.04%; P = .004; modified intention-to-treat analysis). The mean (SD) HbA1c increased with metoprolol (0.15% [0.04%]; P<.001) but not carvedilol (0.02% [0.04%]; P = .65). Insulin sensitivity improved with carvedilol (-9.1%; P = .004) but not metoprolol (-2.0%; P = .48); the between-group difference was -7.2% (95% CI, -13.8% to -0.2%; P = .004). Blood pressure was similar between groups. Progression to microalbuminuria was less frequent with carvedilol than with metoprolol (6.4% vs 10.3%; odds ratio, 0.60; 95% CI, 0.36-0.97; P = .04). CONCLUSIONS: Both beta-blockers were well tolerated; use of carvedilol in the presence of RAS blockade did not affect glycemic control and improved some components of the metabolic syndrome relative to metoprolol in participants with DM and hypertension. The effects of the 2 beta-blockers on clinical outcomes need to be compared in long-term clinical trials.
Adrenergic beta-Antagonists↗
Circulating 1,5-anhydroglucitol levels in adult patients with diabetes reflect longitudinal changes of glycemia: a U.S. trial of the GlycoMark assay.
OBJECTIVE: 1,5-Anhydroglucitol (1,5AG) is a major circulating polyol arising primarily from ingestion and excreted competitively with glucose. Japanese studies have demonstrated reduced concentrations of 1,5AG in serum in hyperglycemic patients in comparison with euglycemic subjects and a gradual normalization of 1,5AG values for patients responding to antihyperglycemic therapies. In this first U.S. study, we assessed the ability of 1,5AG measurements to monitor glycemic control in a cohort of 77 patients with diabetes (22 with type 1 diabetes, 55 with type 2 diabetes) who presented with suboptimal glycemic control at baseline (defined as HbA(1c) >or=7%). RESEARCH DESIGN AND METHODS: Each patient received therapies consisting of combinations of diabetes education, nutritional counseling, and addition or dose adjustment of various insulins or oral antihyperglycemic medications. Therapy was targeted to reduce mean HbA(1c) by >or=1.0% over the monitoring period. 1,5AG, HbA(1c), fructosamine, and random glucose measurements were performed at baseline and at 2, 4, and 8 weeks after the initiation of therapy. RESULTS: 1,5AG, fructosamine, and glucose values progressed significantly toward euglycemia by week 2 of monitoring (Wilcoxon's signed-rank test, P < 0.05), with median changes of 93, -7, and -13% for 1,5AG, fructosamine, and glucose, respectively. In contrast, HbA(1c) values did not respond significantly to therapy until week 4. On an individual patient basis, 89.6% of patients displayed longitudinal changes of 1,5AG from baseline to week 8 in concordance with HbA(1c). 1,5AG was also highly correlated with HbA(1c) and fructosamine (Spearman rho = -0.6459 and -0.6751, respectively; both P < 0.0001). CONCLUSIONS: We conclude that 1,5AG responds sensitively and rapidly to changes in glycemia and monitors glycemic control in accordance with established markers.
Adult↗
Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes.
OBJECTIVE: To investigate the effect of 3-months' daily administration of high doses of sucralose, a non-nutritive sweetener, on glycemic control in subjects with type 2 diabetes. DESIGN: A multicenter, double-blind, placebo-controlled, randomized study, consisting of a 6-week screening phase, a 13-week test phase, and a 4-week follow-up phase. SUBJECTS/SETTING: Subjects with type 2 diabetes (age range 31 to 70 years) entered the test phase of this study; 128 subjects completed the study. The subjects were recruited from 5 medical centers across the United States and were, on average, obese. INTERVENTION: Subjects were randomly assigned to receive either placebo (cellulose) capsules (n=69) or 667 mg encapsulated sucralose (n=67) daily for the 13-week test phase. All subjects blindly received placebo capsules during the last 4 weeks of the screening phase and for the entire 4-week follow-up phase. MAIN OUTCOME MEASURES: Glycated hemoglobin (HbA1c), fasting plasma glucose, and fasting serum C-peptide were measured approximately every 2 weeks to evaluate blood glucose homeostasis. Data were analyzed by analysis of variance using repeated measures. RESULTS: There were no significant differences between the sucralose and placebo groups in HbA1c, fasting plasma glucose, or fasting serum C-peptide changes from baseline. There were no clinically meaningful differences between the groups in any safety measure. CONCLUSIONS: This study demonstrated that, similar to cellulose, sucralose consumption for 3 months at doses of 7.5 mg/kg/day, which is approximately three times the estimated maximum intake, had no effect on glucose homeostasis in individuals with type 2 diabetes. Additionally, this study showed that sucralose was as well-tolerated by the study subjects as was the placebo.
Administration, Oral↗
Fat-free foods supplemented with soy stanol-lecithin powder reduce cholesterol absorption and LDL cholesterol.
OBJECTIVE: The objective of this work was to show that fat-free, lecithin-formulated soy stanols lower cholesterol absorption and serum LDL cholesterol. DESIGN: Reduction in cholesterol absorption was measured in paired single-meal tests with or without formulated soy stanols (acute test), and changes in serum lipids were investigated in a 10-week, randomized, double-blind parallel trial in which formulated stanols or lecithin vehicle were given three times daily for the last 4 weeks (chronic test). SUBJECTS/SETTING: Forty-five normal or mildly hypercholesterolemic subjects were recruited for both studies. The 21 subjects (16 female, 5 male; mean age 32.5 years) in the absorption studies had the following mean lipid values: LDL cholesterol, 2.79 mmol/L and total cholesterol, 4.73 mmol/L. For the lipid reduction, 24 subjects (16 female, 8 male; mean age 50.6 years) were enrolled with mean LDL cholesterol and total cholesterol of 3.72 mmol/L and 5.66 mmol/L, respectively. INTERVENTION: Reduction in cholesterol absorption was measured using a lemonade beverage or egg whites that contained 625 mg stanols. Throughout the chronic study, subjects followed the American Heart Association Step I diet. During the 4-week treatment phase, subjects consumed daily a lemonade-flavored beverage containing either placebo or formulated soy stanols (1.9 g). MAIN OUTCOME MEASURES: Inhibition of cholesterol absorption was determined from the difference in plasma deuterated cholesterol enrichment after a test meal containing stanol-lecithin and one with lecithin vehicle only. In the chronic study, the primary endpoints were changes in LDL and total cholesterol. STATISTICAL ANALYSES PERFORMED: Paired or unpaired t tests were used to determine statistical significance. RESULTS: Stanol-lecithin reduced cholesterol absorption by 32.1% (P=.0045, n=10) and by 38.2% (P=.0022, n=11) when delivered in a lemonade-flavored beverage and in egg whites, respectively. Reduction in cholesterol absorption was strongly related to the initial level of absorbed cholesterol tracer in serum (r(s)=-0.739). Stanol-lecithin given in a beverage reduced total serum cholesterol by 10.1% (P=.0019, n=24) and LDL cholesterol by 14.3% (P=.0016, n=24). APPLICATIONS/CONCLUSIONS: Powdered soy stanol-lecithin lowers cholesterol absorption and LDL cholesterol when consumed in fat-free foods.
Adult↗
Serum 1,5-anhydroglucitol (GlycoMark ): a short-term glycemic marker.
1,5-Anhydroglucitol (1,5-AG), the 1-deoxy form of glucose, has been measured and used clinically in Japan for over a decade to monitor short-term glycemic control. Evaluation of glucose control otherwise requires measuring plasma glucose or glycated proteins whose levels reflect average glucose concentration over the half-life of the protein analyzed. Hemoglobin A1c measurements reflect blood glucose levels over that past 2-3 months, while fructosamine can be used to evaluate glycemic control over 10-14 days. In contrast, 1,5-AG levels in blood respond within 24 h as a result of glucose's competitive inhibition of 1,5-AG reabsorption in the kidney tubule. When glucose levels rise, even transiently, urinary loss of 1,5-AG occurs, and circulating levels fall. Because of changes in renal hemodynamics in normal pregnancies, 1,5-AG appears of limited usefulness in evaluation of gestational diabetes. However, the characteristics of 1,5-AG levels in patients with moderate to near-normal glycemic control suggest that it may be a valuable complement to frequent self-monitoring or continuous monitoring of plasma glucose to confirm stable glycemic control. Measurements performed daily or weekly in a given patient would suggest that overall glycemic control has been stable or improved if 1,5-AG levels are stable or increasing. If 1,5-AG levels fall, greater attention to glucose monitoring and both lifestyle and medical management could be prescribed to correct the glycemic excursions that would underlie such changes. The behavior of this analyte is different from all others used in the management of diabetes, creating potential opportunities for its use in clinical practice.
Biomarkers↗
Continuous subcutaneous insulin infusion and multiple daily injection therapy are equally effective in type 2 diabetes: a randomized, parallel-group, 24-week study.
OBJECTIVE: Compare the efficacy, safety, and patient satisfaction of continuous subcutaneous insulin infusion (CSII) therapy with multiple daily injection (MDI) therapy for patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 132 CSII-naive type 2 diabetic patients were randomly assigned (1:1) to CSII (using insulin aspart) or MDI therapy (bolus insulin aspart and basal NPH insulin) in a multicenter, open-label, randomized, parallel-group, 24-week study. Efficacy was assessed with HbA(1c) and eight-point blood glucose (BG) profiles. Treatment satisfaction was determined with a self-administered questionnaire. Safety assessments included adverse events, hypoglycemic episodes, laboratory values, and physical examination findings. RESULTS: HbA(1c) values decreased similarly for both groups from baseline (8.2 +/- 1.37% for CSII, 8.0 +/- 1.08% for MDI) to end of study (7.6 +/- 1.22% for CSII, 7.5 +/- 1.22% for MDI). The CSII group showed a trend toward lower eight-point BG values at most time points (only significant 90 min after breakfast; 167 +/- 48 vs. 192 +/- 65 mg/dl for CSII and MDI, respectively; P = 0.019). A total of 93% of CSII-treated subjects preferred the pump to their previous injectable insulin regimen for reasons of convenience, flexibility, ease of use, and overall preference. Safety assessments were comparable for both treatment groups. CONCLUSIONS: Insulin aspart in CSII therapy provided efficacy and safety comparable to MDI therapy for type 2 diabetes. Patients with type 2 diabetes can be trained as outpatients to use CSII and prefer CSII to injections, indicating that pump therapy should be considered when initiating intensive insulin therapy for type 2 diabetes.
Blood Glucose↗