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Biomedical subjects

Ronald B Goldberg

Publications and source records attributed to Ronald B Goldberg.

17 recordsLinked to original sources
PubMed2024

Increased Genetic Risk for β-Cell Failure Is Associated With β-Cell Function Decline in People With Prediabetes.

Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the association of T2D pPS with diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (β-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin, or placebo arms. Associations were tested with general linear models and Cox regression with adjustment for age, sex, and principal components. Sensitivity analyses included adjustment for BMI. Higher β-cell pPS was associated with lower insulinogenic index and corrected insulin response at 1-year follow-up with adjustment for baseline measures (effect per pPS SD -0.04, P = 9.6 × 10-7, and -8.45 μU/mg, P = 5.6 × 10-6, respectively) and with increased diabetes incidence with adjustment for BMI at nominal significance (hazard ratio 1.10 per SD, P = 0.035). The liver/lipid pPS was associated with reduced 1-year baseline-adjusted triglyceride levels (effect per SD -4.37, P = 0.001). There was no significant interaction between T2D pPS and randomized groups. The remaining pPS were associated with baseline measures only. We conclude that despite interventions for diabetes prevention, participants with a high genetic burden of the β-cell cluster pPS had worsening in measures of β-cell function.

Humans↗
PubMed2006

Impact of thiazolidenediones on serum lipoprotein levels.

The thiazolidinediones, acting through peroxisome proliferator-activated receptor chi (PPARchi), affect multiple areas of metabolism. Of increasing importance is the recognition that these agents affect lipoprotein metabolism and cause changes in serum lipid and lipoprotein levels. All three thiazolidinediones, including troglitazone (which was withdrawn in the year 2000), rosiglitazone, and pioglitazone, tend to increase high-density lipoprotein (HDL) cholesterol, increase the size/decrease the density of low-density lipoprotein (LDL) particles, and raise the level of lipoprotein(a). In addition, troglitazone and pioglitazone, but not rosiglitazone, lower triglyceride levels modestly, thereby further contributing to increases in LDL and HDL size. The mechanism for these effects is still being clarified, but may involve enhancement of triglyceride clearance (in the case of pioglitazone), alteration of apolipoprotein C-III levels, reduction of hepatic lipase, and increase in ATP binding cassette A1 (ABCA1) activity. The clinical implications of these effects need further exploration.

Clinical Trials as Topic↗
PubMed2006

Lifestyle intervention to prevent diabetes: intensive and cost effective.

PURPOSE OF REVIEW: Type 2 diabetes is a major cause of morbidity and mortality, and despite treatment advances appears to be increasing in incidence. Since individuals at risk for the disease are usually identifiable in the prediabetic phase of impaired glucose tolerance, early intervention might prevent diabetes and hence its complications from developing. Obesity and sedentary living are powerful determinants of diabetes, and thus lifestyle change is a logical approach to prevention of this disease. Recent clinical trials have now tested the effectiveness of this intervention and form the basis for this review. RECENT FINDINGS: Three clinical trials have demonstrated that, compared with usual care, lifestyle intervention significantly reduced progression rates to diabetes in prediabetic individuals. Each trial incorporated individualization and repeated long-term contacts with facilitators, in which dietary and physical activity goal setting and behavior modification were central themes. Progression to diabetes was reduced in the Da Qing study by approximately 40%, in the Finnish Diabetes Prevention Study by 58% and in the Diabetes Prevention Program by 58%. The Diabetes Prevention Program included a cost-benefit unit that estimated the per capita costs of the lifestyle intervention to exceed that of the usual care group by Dollars 3540, which translated to a cost of Dollars 15,700 per case of diabetes prevented. Lifetime cost-utility analysis demonstrated an overall cost of Dollars 1100 per quality-adjusted life year. SUMMARY: These findings make the case for translation of research findings to healthcare systems. Although there is more to be learned about effective strategies in clinical practice, it seems clear that the intervention needs to incorporate individualization and long-term interaction with trained facilitators.

Adult↗
PubMed2006

Thiazolidinediones : beyond glycemic control.

Our knowledge and understanding of the role played by peroxisome proliferator-activated gamma receptors in physiology and pathophysiology has expanded dramatically over the past 5 years. Originally described as having important functions in adipogenesis and glucose homeostasis, their pharmacologic agonists, the thiazolidinediones, were introduced as antihyperglycemic, insulin-sensitizing agents for the management of type 2 diabetes mellitus. However, it was to some degree inevitable that the thiazolidinediones would be rapidly recognized as having vasculoprotective properties beyond glycemic control that might also be beneficial. First, diabetic complications are vascular in nature, the earliest feature of these is endothelial dysfunction. Second, it is being increasingly appreciated that these complications develop through inflammatory and procoagulant pathways in which increased oxidative stress is considered a major etiologic mechanism, and which are closely linked to the presence of insulin resistance, visceral obesity, and hyperglycemia. Early appreciation that the thiazolidinediones have antioxidant, anti-inflammatory, anti-procoagulant, and antiproliferative properties in addition to their insulin-sensitizing, anti-lipotoxic properties created a marriage of investigative pathways that has not only led to a very large body of literature on the pleiotropic effects of thiazolidinediones, but also to the development of new understandings of the connections between insulin resistance, obesity, and hyperglycemia and the onset of vascular disease. Understandably, most of the focus has been directed at the macrovascular complications of diabetes, since these are the major causes of morbidity and mortality in this population. However, there is evidence that these agents may have benefits for the microvascular complications as well, and their potential role for cardiovascular disease prevention in non-diabetic patients with the metabolic syndrome is a logical extension of the work performed in diabetes. The recently reported results of the effects of pioglitazone versus placebo on cardiovascular events in patients with type 2 diabetes support the contention that these agents have vasculoprotective effects.

Blood Glucose↗
PubMed2006

Ezetimibe/simvastatin vs atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia: the VYTAL study.

OBJECTIVE: To compare the efficacy and safety of the recommended usual starting and next highest doses of ezetimibe/ simvastatin and atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia. PATIENTS AND METHODS: This double-blind, multicenter study (June 22 to December 7, 2005) consisted of adult patients randomized to the recommended usual starting (ezetimibe/simvastatin, 10/20 mg/d, vs atorvastatin, 10 or 20 mg/d) or next highest (ezetimibe/simvastatin, 10/40 mg/d, vs atorvastatin, 40 mg/d) doses. Efficacy end points included percent changes from baseline in low-density lipoprotein cholesterol (LDL-C) levels (primary) and proportion of patients attaining LDL-C levels less than 70 mg/dL (secondary). RESULTS: A total of 1229 patients participated in the study. Significantly greater mean reductions were found in LDL-C levels with ezetimibe/simvastatin, 10/20 mg/d (-53.6%; 95% confidence interval [CI], -55.4% to -51.8%), than with atorvastatin, 10 mg/d (-38.3%; 95% CI, -40.1% to -36.5%; P < .001) or 20 mg/d (-44.6%; 95% CI, -46.4% to -42.8%; P < .001), and with ezetimibe/simvastatin, 10/40 mg/d (-57.6%; 95% CI, -59.4% to -55.8%), vs atorvastatin, 40 mg/d (-50.9%; 95% CI, -52.7% to -49.1%; P < .001). Ezetimibe/simvastatin was also superior to atorvastatin in attainment of LDL-C levels less than 70 mg/dL (P < .001 for all dose comparisons). Significantly better improvements with ezetimibe/simvastatin than with atorvastatin (P < or = .001) were observed for total cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol. Ezetimibe/ simvastatin, 10/20 mg/d, reduced high-sensitivity C-reactive protein and triglyceride levels significantly more than atorvastatin, 10 mg/d (P = .02), with comparable reductions at other doses. Incidences of clinical adverse events, including serious drug-related and prespecified gastrointestinal-, gallbladder-, and hepatitis-related allergic reactions or rash events, and laboratory adverse events, including repeated elevation of hepatic transaminases or creatine kinase levels, were similar for both treatments. CONCLUSION: Ezetimibe/simvastatin provided additional lipid-modifying benefits over atorvastatin monotherapy at the recommended usual starting and next highest doses in patients with type 2 diabetes. Both treatments were generally well tolerated.

Adolescent↗
PubMed2005

Is the factor structure of the metabolic syndrome comparable between men and women and across three ethnic groups: the Miami Community Health Study.

PURPOSE: The metabolic syndrome (MS) is conceived as a cluster of disorders that increase risk for coronary heart disease and type 2 diabetes. Studies examining its structure primarily have used an exploratory factor analytic technique, but yielded discrepant results. There also is a lack of research that investigates whether the clustering pattern is similar across sex and ethnic groups. This study uses confirmatory factor analysis to evaluate the factor structure of the MS and examines its similarity between men and women and across three ethnic groups (Caucasian, African, and Cuban Americans). METHOD: A hierarchical four-factor model with an overarching MS factor uniting insulin resistance, obesity, lipid, and blood pressure factors was tested with 517 individuals from the Miami Community Health Study. RESULTS: Findings show that the proposed structure was well supported (comparative fit index=0.97) and similar between men and women and across ethnic groups. The MS was represented strongly by insulin resistance, followed by obesity, lipid factors, and, to a lesser extent, a blood pressure factor. CONCLUSIONS: This study provides empirical support for identifying and diagnosing the MS by its component factors in a diverse population.

Adult↗
PubMed2005

Ability of serum to decrease cellular acylCoA:cholesterol acyl transferase activity predicts cardiovascular outcomes.

BACKGROUND: We evaluated whether cholesterol efflux activity of serum is associated with the presence of angiographic coronary artery disease (CAD) and the risk of major adverse cardiovascular events (MACE) and death. METHODS AND RESULTS: We studied 168 men undergoing coronary angiography. Cholesterol efflux activity was measured in vitro by incubation of patient serum with human skin fibroblasts and defined as the ability of serum to decrease the pool of cholesterol available for esterification by the acylCoA:cholesterol acyl transferase (ACAT) reaction. We evaluated whether this activity was associated with the presence of CAD and the risk of MACE and death during a 4.5-year follow-up. Serum-induced changes in ACAT activity did not correlate with HDL levels or the presence of CAD. Patients in the highest tertile of change in ACAT activity had a significantly higher risk for MACE (HR, 2.15; 95% CI, 1.36 to 3.39; P=0.001) and death (HR, 2.23; 95% CI, 1.17 to 4.26; P=0.01). These correlations were independent of other risk markers including LDL, HDL, and C-reactive protein levels. CONCLUSIONS: Serum-induced depletion of cellular cholesterol available for esterification by ACAT was a strong, independent predictor of MACE and death. We speculate that the ability of serum to decrease ACAT activity depends on ATP binding cassette transporter A1 (ABCA1)-mediated efflux. Furthermore, serum samples that induce larger changes in ACAT activity contain increased levels of HDL particles that preferentially interact with ABCA1 and that these particles accumulate in the serum of patients because of low activity of ABCA1 in vivo preventing or limiting the extent of apoA-I lipidation.

Aged↗
PubMed2005

Management of diabetic dyslipidemia.

Identification and management of dyslipidemia is an important element in the multi-factorial approach to prevent coronary heart disease. Diabetic dyslipidemia typically consists of elevated triglyceride, low high-density lipoprotein cholesterol, predominance of small, dense low-density lipoprotein (LDL) particles, and average LDL cholesterol (LDL-C). Lipid-lowering therapy has a beneficial effect on cardiovascular outcomes. Statin treatment is beneficial in patients who are older than 40 years of age, irrespective of the LDL-C value. To achieve lipid targets, attention should be directed first toward nonpharmacologic therapeutic interventions, such as diet, exercise, smoking cessation, weight loss, and improving glycemic control. Although statin therapy is recommended for most subjects, judicious use of combination therapy should be considered in the highest risk subjects.

Adult↗
PubMed2005

A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia.

OBJECTIVE: Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone. RESEARCH DESIGN AND METHODS: We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals. RESULTS: Triglyceride levels were reduced by 51.9 +/- 7.8 mg/dl with pioglitazone, but were increased by 13.1 +/- 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 +/- 0.5 vs. 2.4 +/- 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 +/- 1.6 vs. 21.3 +/- 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005). CONCLUSIONS: Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.

Aged↗
PubMed2004

Sensory function and albumin excretion according to diagnostic criteria for diabetes.

OBJECTIVE: The purpose of this study was to examine sensory function and albumin excretion according to categories of glucose tolerance in individuals undergoing screening for diabetes. RESEARCH DESIGN AND METHODS: Sensory function and albumin excretion measurements were obtained in 636 individuals at the time of screening for diabetes according to American Diabetes Association glucose tolerance criteria. Sensory thresholds were measured by forced-choice techniques. Albumin-to-creatinine ratios were calculated from spot urine samples. RESULTS: Of 90 individuals whose glucose levels were in the range for diabetes, 65 had fasting glucose values >or=126 mg/dl, whereas 25 had 2-h glucose values >or=200 mg/dl, with fasting glucose values <126 mg/dl. In covariance analyses, those with fasting glucose levels >or=126 mg/dl had higher vibration (P < 0.01) and thermal (P < 0.05 for cool and warm) thresholds than those with normal glucose tolerance. This pattern was also evident for albumin-to-creatinine ratios (P < 0.001). In contrast, those with 2-h glucose values >or=200 mg/dl and fasting glucose values <126 mg/dl had sensory threshold and albumin-to-creatinine ratio values similar to those of the normal group. Individuals with fasting glucose levels >or=126 mg/dl had higher vibration threshold and albumin-to-creatinine ratio values (<0.05 and <0.01, respectively) than those with levels <126 mg/dl. CONCLUSIONS: Sensory threshold and albumin excretion values already tend to be greater than normal at screening in individuals with fasting glucose levels >or=126 mg/dl, but not in those with levels <126 mg/dl. A reliance on fasting glucose levels >or=126 mg/dl for screening might not be sufficient for early intervention and the optimal prevention of diabetes complications.

Adult↗
PubMed2003

Cardiovascular disease in patients who have diabetes.

Although cardiovascular disease continues to be the major cause of morbidity and mortality in diabetes, the understanding that multiple risk factor intervention is the cornerstone of diabetes management is leading to significant benefits for patients. Aggressive goal setting for modifiable cardiovascular risk factors that cluster in patients with diabetes, such as dyslipidemia, hypertension, and a procoagulant state, and judicious selection of efficacious therapies have been shown to produce significant reductions in cardiovascular events, and in some cases mortality, in controlled clinical trials. Although effective control of hyperglycemia per se has at most modest impact, the choice and application of antihyperglycemic therapies add to the benefit. In addition, newer agents and early intervention in prediabetic and diabetic individuals hold promise for even greater success in the prevention of this important complication of diabetes.

Cardiovascular Agents↗
PubMedDate not supplied

Type 2 diabetes mellitus among Florida children and adolescents, 1994 through 1998.

OBJECTIVES: This study was undertaken to examine the trends in the diagnosis of Type 2 diabetes mellitus among children and adolescents with new-onset diabetes seen from 1994 through 1998 at the three university-based diabetes centers in Florida. METHODS: Data were abstracted from medical records and patients were categorized as having Type 1 or Type 2 diabetes. RESULTS: There were 569 patients classified with Type 1 diabetes and 92 with Type 2 diabetes. The proportion of patients diagnosed with Type 2 diabetes increased over the five years from 9.4% in 1994 to 20.0% in 1998 (chi-square test for trend = 8.2; p=0.004). There was not an associated net increase in the total number of new diabetes patients referred over time (chi-square test for trend = 0.6, p=0.4). Those with Type 2 diabetes were more likely to have a body mass index in the 85th-94th percentile [odds ratio (OR) = 8.5; 95% confidence interval (CI) 2.5, 28.8], have a body mass index >or=95th percentile (OR = 6.8; 95% CI 2.6, 17.7), Hispanic ethnicity (OR = 6.2; 95% CI 2.2, 17.9), black race (OR = 2.8; 95% CI 1.3, 6.2), female gender (OR = 2.2; 95% CI 1.2, 4.3), and older age (OR = 1.4 for each one-year increment in age; 95% CI 1.3, 1.6), compared with those having Type 1 diabetes. CONCLUSIONS: From 1994 through 1998, there was a significant overall increase in the percentage of children referred with new-onset diabetes who were considered to have Type 2 diabetes. Factors associated with the diagnosis of Type 2 diabetes relative to Type 1 diabetes include body mass index >/=85th percentile, Hispanic ethnicity, black race, female gender, and older age.

Adolescent↗
PubMedDate not supplied

Management of dyslipidemia in diabetes.

Diabetes is associated with a high risk of cardiovascular disease. The management of dyslipidemia, a well-recognized and modifiable risk factor among patients with type 2 diabetes, is an important element in the multifactorial approach to prevent coronary heart disease. Diabetic dyslipidemia typically consists of elevated triglyceride, low high-density lipoprotein cholesterol (HDL-C), and the predominance of small dense low-density lipoprotein (LDL) particles. LDL cholesterol (LDL-C) levels in patients with diabetes are similar to those found in the rest of the population. During the past few years, clinical trials have provided evidence that lipid-lowering therapy has a similar beneficial effect on cardiovascular outcomes in diabetic and nondiabetic individuals. According to current guidelines, the primary lipid target is an LDL-C <100 mg/dL (<70 mg/dL in very high-risk patients) and, to this end, statins are the agents of choice. The appropriate management of dyslipidemia in patients with diabetes, particularly in individuals with low LDL-C, remains controversial. To achieve lipid targets, attention should be directed first toward nonpharmacologic therapeutic interventions to control dyslipidemia, such as diet, exercise, smoking cessation, weight loss, and glycemic control. Statin therapy is recommended for most subjects but, frequently, a combination of lipid-lowering agents is required. A number of combinations are possible, and several factors should be considered to improve the safety of this strategy.

Cardiovascular Diseases↗
PubMedDate not supplied

Effect of behavioral interventions on insulin sensitivity and atherosclerosis in the Watanabe heritable hyperlipidemic rabbit.

OBJECTIVE: A previous study suggested that insulin metabolic variables play a role in the progression of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. The present study sought to determine: 1) if young, individually caged WHHLs are insulin-resistant relative to New Zealand white (NZW) rabbits and 2) whether dietary or exercise interventions can improve insulin sensitivity and slow the development of atherosclerosis in these animals. METHODS: Forty-two WHHLs were assigned to a dietary, exercise, or control condition, and 12 NZWs were used as a comparison control group. The intervention ran from 3 to 7 months of age, and all animals received an intravenous glucose tolerance test at the beginning and end of the intervention. RESULTS: WHHLs were insulin-resistant relative to NZWs at 3 months of age. Whereas the dietary intervention was effective in controlling insulin resistance, WHHLs in the exercise group without dietary restriction and the control group exhibited significant increases in insulin resistance. No intervention significantly influenced the progression of atherosclerosis. CONCLUSIONS: Young WHHLs are insulin-resistant during an early period when atherosclerosis is developing rapidly. Dietary restriction, but not exercise without weight control, is effective in controlling insulin metabolic variables in the WHHL model. Although dietary intervention can reduce cardiovascular risk factors such as insulin resistance, it is not effective in slowing the development of atherosclerosis in these genetically dyslipidemic animals. Similarly, exercise training, without dietary control, does not influence the progression of disease in WHHLs.

Age Factors↗