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Biomedical subjects

Gabriel I Uwaifo

Publications and source records attributed to Gabriel I Uwaifo.

15 recordsLinked to original sources
PubMed2006

Venous thrombosis and conjugated equine estrogen in women without a uterus.

BACKGROUND: Postmenopausal hormone therapy has been associated with a 2- to 3-fold increased risk of venous thromboembolism (VT) (including deep vein thrombosis and pulmonary embolism) in observational studies and secondary prevention clinical trials. Clinical trial data on the effects of estrogen alone on VT are limited. METHODS: The Women's Health Initiative estrogen trial enrolled 10 739 women aged 50 to 79 years without a uterus. Participants were randomly assigned to receive conjugated equine estrogen (0.625 mg/d) or placebo. RESULTS: During a mean of 7.1 years, VT occurred in 111 women randomly assigned to receive estrogen (3.0 per 1000 person-years) and 86 randomly assigned to receive placebo (2.2 per 1000 person-years; hazard ratio, 1.32; 95% confidence interval, 0.99-1.75). Deep venous thrombosis was reported in 85 women randomly assigned to receive estrogen (2.3 per 1000 person-years) and 59 randomly assigned to receive placebo (1.5 per 1000 person-years; hazard ratio, 1.47; 95% confidence interval, 1.06-2.06). The VT risk was highest in the first 2 years. There were no significant interactions between estrogen use and age, body mass index, or most other VT risk factors. Comparison of Women's Health Initiative VT findings for estrogen and previous Women's Health Initiative findings for estrogen plus progestin showed that the hazard ratios for estrogen plus progestin were significantly higher than those for estrogen alone (P = .03), even after adjusting for VT risk factors. CONCLUSION: An early increased VT risk is associated with use of estrogen, especially within the first 2 years, but this risk increase is less than that for estrogen plus progestin.

Aged↗
PubMed2005

Novel pharmacologic agents for type 2 diabetes.

After many decades of relative therapeutic stagnation since the initial discovery of insulin, followed by some modifications on its structure and only having sulfonylureas and biguanides for many years, the last decade has seen a surge in new therapeutic options for the management of diabetes. The results of the United Kingdom Prospective Diabetes Study and Kumamoto study indicate the need for aggressive glycemic control and the slow inexorable clinical deterioration associated with type 2 diabetes overtime. The propensity for weight gain and hypoglycemia are the two major limitations that subcutaneous insulin and sulfonylureas have been particularly prone to. The newer antidiabetic medications and those on the horizon attempt to address these limitations. GLP-1 agonists and the DPP-IV inhibitors exploit the innate incretin system to improve glycemia while promoting satiety and weight management. Like GLP-1 related compounds, pramlintide offers the potential to address postprandial hyperglucagonemia associated with type 2 diabetes only limited by the multiple injections and gastrointestinal side effects. The glitazars offer the hope ofa new approach to diabetes care addressing not just glycemia, but dyslipidemia and other components of the metabolic syndrome, though the side effect profile remains a major unknown. The INGAP peptide represents the holy grail of diabetes care as it offers the potential of a new paradigm: that of islet regeneration and potential for a cure. But at this stage, with no human data available, it remains highly speculative. Beyond these and other novel agents being developed to meet the challenge of the worldwide epidemic of diabetes, the central place of insulin in diabetes care cannot be forgotten. In view of this the continued efforts of improvement in insulin delivery, kinetics and action have spurred such innovations as the various inhaled insulins and new insulin analogues. There is cause for guarded optimism and excitement about the years ahead. There is reason to expect that despite the growing burden of diabetes worldwide, we will be better equipped to manage it and its comorbidities and prevent its onset and possibly even cure it.

Amyloid↗
PubMed2004

A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease for which there is no known effective therapy. A proportion of patients with NASH progress to advanced fibrosis and cirrhosis. NASH is considered one of the clinical features of the metabolic syndrome in which insulin resistance plays a central role. This prospective study evaluates the role of insulin-sensitizing agent in treatment of NASH. Eighteen nondiabetic patients with biopsy-proven NASH were treated with pioglitazone (30 mg daily) for 48 weeks. Tests of insulin sensitivity and body composition as well as liver biopsies were performed before and at the end of treatment. By 48 weeks, serum alanine aminotransferase values fell to normal in 72% of patients. Hepatic fat content and size as determined by magnetic resonance imaging decreased, and glucose and free fatty acid sensitivity to insulin were uniformly improved. Histological features of steatosis, cellular injury, parenchymal inflammation, Mallory bodies, and fibrosis were significantly improved from baseline (all P < 0.05). Using strict criteria, histological improvement occurred in two-thirds of patients. Pioglitazone was well tolerated; the main side effects were weight gain (averaging 4%) and an increase in total body adiposity. In conclusion, these results indicate that treatment with an insulin-sensitizing agent can lead to improvement in biochemical and histological features of NASH and support the role of insulin resistance in the pathogenesis of this disease. The long-term safety and benefits of pioglitazone require further study.

Adult↗
PubMed2004

The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults.

Several previous reports of small cohorts have found significantly higher serum 1,25-dihydroxy vitamin D (1,25-vit D) in obese compared with nonobese whites. Based on these reports and on recent in vitro studies of adipocytes which suggest that administration of 1,25-vit D can stimulate lipogenesis and inhibit lipolysis, some investigators have proposed that high 1,25-vit D may play a role in promoting or maintaining adipocyte triglyceride stores in obese adults. To test the hypothesis that obesity is commonly associated with increased 1,25-vit D, we examined the relationships between calciotropic hormones and body adiposity in a large cohort of healthy adults. Serum intact PTH, 25-hydroxy vitamin D, and 1,25-vit D were measured in the postabsorptive state in 302 healthy adults who were Caucasian (n = 190; 71% female), African-American (n = 84; 89% female), and of other race/ethnicity (n = 28; 61% female). Results from the 154 obese subjects [body mass index (BMI) 37.3 +/- 5.8 kg/m(2); range, 30.1-58.2 kg/m(2)] were compared with those from 148 nonobese (BMI 25.6 +/- 2.9 kg/m(2); range, 18.0-29.9 kg/m(2)) age-, race-, and sex-matched participants. Body composition was measured by dual energy x-ray absorptiometry. Serum intact PTH was positively correlated with both BMI (r = 0.42; P < 0.0001) and body fat mass (r = 0.37; P < 0.0001). Serum 25-hydroxy vitamin D was negatively correlated with BMI (r = -0.4; P < 0.0001) and body fat mass (r = -0.41; P < 0.0001). Serum 1,25-vit D was also negatively correlated with BMI (r = -0.26; P < 0.0001) and body fat mass (r = -0.25; P = 0.0001). Serum 1,25-vit D was significantly lower in obese than nonobese subjects (105.7 +/- 41.1 vs. 124.8 +/- 36.7 pmol/liter; P < 0.0001) in both Caucasian and African-American adults. We conclude that, because 1,25-vit D concentrations fall with increasing adiposity, it appears unlikely that elevation in 1,25-vit D is an important hormonal mechanism causing or maintaining obesity in adults.

Adolescent↗
PubMed2004

Efficacy of orlistat as an adjunct to behavioral treatment in overweight African American and Caucasian adolescents with obesity-related co-morbid conditions.

This pilot study compared the efficacy of orlistat as an adjunctive treatment for obesity between African American and Caucasian adolescents. Twenty obese adolescents with obesity-related co-morbid conditions underwent measurements of body composition, glucose homeostasis by frequently sampled intravenous glucose tolerance test (FSIGT), and fasting lipids before and after 6 months treatment with orlistat 120 mg tid in conjunction with a comprehensive behavioral program. Weight (p < 0.05), BMI (p < 0.001), total cholesterol (p < 0.001), LDL cholesterol (p < 0.001), fasting insulin (p < 0.02) and fasting glucose (p < 0.003) were lower after treatment. Insulin sensitivity, measured during the FSIGT, improved significantly (p < 0.02), as did fasting indices such as the homeostasis model assessment for insulin resistance (p < 0.01). African American subjects exhibited significantly less improvement in weight (p < 0.05), BMI (p < 0.01), waist circumference (p = 0.03), and insulin sensitivity (p = 0.05). Improvements in cholesterol were not significantly different between African Americans and Caucasians. We conclude that Caucasians lost more weight and had greater improvements in insulin sensitivity than African Americans, but both exhibited improvements in plasma lipids. The true benefit of orlistat treatment over a comprehensive behavioral program remains to be determined in placebo-controlled trials.

Administration, Oral↗
PubMed2003

The roles of insulin resistance, hyperinsulinemia, and thiazolidinediones in cardiovascular disease.

Although it is difficult to distinguish between the relative effects of insulin resistance and hyperinsulinemia, insulin resistance is clearly associated with significantly increased cardiovascular and cerebrovascular risk. This effect is consistent across the spectrum of worsening glycemic control, from the onset of impaired glucose tolerance to the development of clinical diabetes. It is more difficult to discriminate between the roles of elevated circulating insulin and proinsulin levels; the association between insulin levels and cardiovascular risk is weak. The thiazolidinediones (TZDs) significantly improve insulin sensitivity and exert numerous effects on the vascular bed, including improved endothelial function, decreased vascular inflammation, decreased plasma free fatty acid levels, improved dyslipidemic profiles, and inhibition of vascular smooth muscle proliferation. These findings provide increasing evidence to suggest that the TZDs may have a beneficial effect on atherosclerosis and may reduce the incidence and severity of adverse cardiovascular outcomes. These effects remain to be substantiated by the results of large outcomes studies to evaluate the impact of glycemic control and reversal of insulin resistance on cardiovascular events.

Cardiovascular Diseases↗
PubMed2003

Improvement in hypertrophic cardiomyopathy after significant weight loss: case report.

A 17-year-old obese boy found to have familial apical hypertrophic cardiomyopathy on routine screening was enrolled in a weight loss program on the basis of the hypothesis that significant weight loss would improve his cardiac status. He was followed with serial dual-energy x-ray absorptiometry, electrocardiography, echocardiography, and blood pressure and pulse rate measurements. Within 1 year, he lost 49 kg, with a body mass index reduction from 43.6 to 28.1 kg/m2 and associated reductions in systolic blood pressure, diastolic blood pressure, pulse pressure, mean heart rate, rate pressure product, and echocardiographic indices of left ventricular mass that resulted in a change from the initial geometric finding of eccentric left ventricular hypertrophy to a "normal" left ventricular mass with minimal asymmetric apical left ventricular thickening. Significant weight loss in an obese adolescent with presumed familial apical hypertrophic cardiomyopathy was associated with striking improvement in cardiac functional indices, which could have profound implications for long-term cardiovascular risk.

Adolescent↗
PubMed2002

Three-month tolerability of orlistat in adolescents with obesity-related comorbid conditions.

OBJECTIVE: To study the safety, tolerability, and potential efficacy of orlistat in adolescents with obesity and its comorbid conditions. RESEARCH METHODS AND PROCEDURES: We studied 20 adolescents (age, 14.6 +/- 2.0 years; body mass index, 44.1 +/- 12.6 kg/m(2)). Subjects were evaluated before and after taking orlistat (120 mg three times daily) and a multivitamin for 3 months. Subjects were simultaneously enrolled in a 12-week program emphasizing diet, exercise, and strategies for behavior change. RESULTS: Participants who completed treatment (85%) reported taking 80% of prescribed medication. Adverse effects were generally mild, limited to gastrointestinal effects observed in adults, and decreased with time. Three subjects required additional vitamin D supplementation despite the prescription of a daily multivitamin containing vitamin D. Weight decreased significantly (-4.4 +/- 4.6 kg, p < 0.001; -3.8 +/- 4.1% of initial weight), as did body mass index (-1.9 +/- 2.5 kg/m(2); p < 0.0002). Total cholesterol (-21.3 +/- 24.7 mg/dL; p < 0.001), low-density lipoprotein-cholesterol (-17.3 +/- 15.8 mg/dL; p < 0.0001), fasting insulin (-13.7 +/- 19.0 microU/mL; p < 0.02), and fasting glucose (-15.4 +/- 7.4 mg/dL; p < 0.003) were also significantly lower after orlistat. Insulin sensitivity, assessed by a frequently sampled intravenous glucose-tolerance test, improved significantly (p < 0.02). DISCUSSION: We conclude that, in adolescents, short-term treatment with orlistat, in the context of a behavioral program, is well-tolerated and has a side-effect profile similar to that observed in adults, but its true benefit versus conventional therapy remains to be determined in placebo-controlled trials.

Adolescent↗
PubMed2002

Differences in insulin secretion and sensitivity of Caucasian and African American prepubertal children.

OBJECTIVE: To investigate whether differences in body composition of African American children (AA) and Caucasian children (C) explain differences in insulin sensitivity and secretion. STUDY DESIGN: Prepubertal nondiabetic children (31 AA and 54 C) were studied; 84% were overweight. Participants underwent a 2-hour hyperglycemic clamp, to estimate insulin sensitivity (SI(clamp)) and secretion, and dual energy x-ray absorptiometry, to assess body composition. RESULTS: AA had greater total body fat mass (P =.01), fasting, 1st phase, 2nd phase, and steady state insulin levels (P <.05). AA and C had similar glucose disposal rates, but AA had lower SI(clamp) (P <.05). Fasting, 1st phase, and steady state C-peptide were less in C (P <.05), whereas corresponding C-peptide/insulin ratios were higher (all P <.005). Insulin levels and SI(clamp) remained different in AA and C after adjustment for body fat or lean mass differences. Analyses restricted to only overweight AA and C showed similar trends. CONCLUSION: Prepubertal African American children have higher baseline and glucose-stimulated insulin and C-peptide levels, as well as reduced insulin sensitivity that is not entirely explained by differences in adiposity. The lower C-peptide/insulin molar ratio in AA suggests that they probably have lower hepatic insulin clearance than Caucasian children.

Absorptiometry, Photon↗
PubMed2002

Comparison of insulin sensitivity, clearance, and secretion estimates using euglycemic and hyperglycemic clamps in children.

The euglycemic clamp is the gold standard for estimating insulin sensitivity. The hyperglycemic clamp is easier to perform and is the gold standard for estimating beta-cell secretion. Reports in adults suggest that hyperglycemic clamps can estimate insulin sensitivity with results equivalent to euglycemic clamps. We investigated whether insulin sensitivity measures from both clamps are equivalent in children. Thirty-one lean and obese children (mean body mass index, 25.1 +/- 4.9 kg/m(2); mean age, 8.7 +/- 1.4 yr; 15 girls and 16 boys; 12 black and 19 white) were studied. All subjects underwent hyperglycemic clamps, then euglycemic clamps 2-6 wk later. Body composition was estimated by dual energy x-ray absorptiometry. Visceral and sc abdominal fat was estimated by abdominal magnetic resonance imaging. Whole-body glucose disposal and insulin sensitivity (SI clamp) derived from both clamps and normalized for total or visceral fat and lean mass were significantly correlated (r, 0.45-0.65; P < 0.05). However, absolute SI clamp values were not equivalent. Bland-Altman comparisons found that SI clamp estimates from hyperglycemic clamps became less precise as SI clamp increased. There were significant correlations between indices of beta-cell secretion from the hyperglycemic clamp and mean C-peptide values from the euglycemic clamp (P < 0.05). However, no correlation was found between measures of total insulin clearance (derived from the euglycemic clamp) and surrogates of hepatic insulin clearance (derived from the hyperglycemic clamp). In this cohort of diverse children, SI clamp values from euglycemic and hyperglycemic clamps were significantly correlated but were not equivalent, whereas the insulin clearance measures were not correlated. It cannot be assumed that the hyperglycemic clamp obviates the need for euglycemic clamp studies to accurately estimate insulin sensitivity in children.

Black People↗
PubMed2002

Effects of orlistat on fat-soluble vitamins in obese adolescents.

STUDY OBJECTIVES: To determine whether orlistat causes fat-soluble vitamin deficiencies in African-American and Caucasian adolescents. DESIGN: Prospective, open-label pilot study. SETTING: Warren Grant Magnuson Clinical Center of the National Institutes of Health. PATIENTS: Seventeen adolescents with body mass indexes above the 95th percentile for age, race, and gender who also had at least one obesity-related comorbid condition. INTERVENTION: Subjects received orlistat 120 mg 3 times/day and a daily multivitamin supplement containing vitamin A 5000 IU, vitamin D 400 IU, vitamin E 300 IU, and vitamin K 25 microg. MEASUREMENTS AND MAIN RESULTS: During 3-6 months of orlistat treatment, acute absorption of retinol (vitamin A) was not significantly altered, but absorption of alpha-tocopherol (vitamin E) was significantly reduced compared with baseline levels (p<0.001). Serum levels of vitamins A and E did not change significantly; however, there was a nonsignificant decrease in vitamin K. Mean vitamin D levels were significantly reduced compared with baseline (p<0.02) after 1 month of orlistat, despite multivitamin supplementation. CONCLUSION: It may be prudent to monitor vitamin D concentrations in adolescents who take orlistat, even when a multivitamin is prescribed.

Adolescent↗
PubMed2002

Indices of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children.

OBJECTIVE: To validate fasting indices of insulin sensitivity and secretion in a diverse pediatric population against gold standard estimates from euglycemic and hyperglycemic clamps. RESEARCH DESIGN AND METHODS: A total of 31 children (mean BMI 25.1 +/- 4.9 kg/m(2), mean age 8.7 +/- 1.4 years, 15 girls and 16 boys, 12 black and 19 white) underwent euglycemic and hyperglycemic clamps 2-6 weeks apart to derive insulin sensitivity indices (SI (Eug clamp) and SI (Hyper clamp)). Fasting samples were used to derive the homeostasis model assessment of insulin resistance index (HOMA-IR), HOMA of percent beta-cell function (HOMA-B%), quantitative insulin sensitivity check index (QUICKI), insulinogenic index, antilipolytic insulin sensitivity index (ISI-FFA), and C-peptide-to-insulin ratio. RESULTS: The QUICKI correlated best with SI (Eug clamp) (r = 0.69, P < 0.05) and had greater correlations to SI (Eug clamp) than did either SI (Hyper clamp) (r = 0.45, P < 0.05) or the HOMA-IR (r = -0.51, P < 0.05). Both fasting insulin and the insulinogenic index correlated well with first- and steady-phase insulin secretion (r's from 0.79 to 0.86, P < 0.05). HOMA-B% was not as highly correlated (r = 0.69-0.72, P < 0.05). Fasting C-peptide-to-insulin ratio was not significantly correlated with clamp-derived metabolic clearance rate of insulin. ISI-FFA was not correlated with the degree of free fatty acid suppression obtained from the clamps. CONCLUSIONS: The QUICKI, fasting insulin, and the insulinogenic index all closely correlate with corresponding clamp-derived indices of insulin sensitivity and secretion in this diverse pediatric cohort. These results, if replicated in similarly diverse populations, suggest that estimates based on fasting samples can be used to rank order insulin secretion and sensitivity in pediatric cohorts.

Black or African American↗
PubMedDate not supplied

Acanthosis nigricans in patients with nonalcoholic steatohepatitis: an uncommon finding.

OBJECTIVE: To determine the prevalence and the metabolic characteristics of acanthosis nigricans (AN) in a group of 28 study subjects with biopsy-proven nonalcoholic steatohepatitis (NASH). METHODS: The study participants (15 female and 13 male patients, 20 of whom were white subjects; mean body mass index, 32.7 +/- 5.7 kg/m2; mean age, 45.7 +/- 11.3 years) underwent an oral glucose tolerance test (OGTT), frequently sampled intravenous glucose tolerance test (FSIGT), and fasting metabolic panels. AN status was clinically determined, and fat mass was measured by dual-energy x-ray absorptiometry. RESULTS: All study subjects had insulin resistance (IR), and 15 (54%) had the metabolic syndrome (by Adult Treatment Panel III criteria). Of the 28 patients, 4 (14%) had AN (AN+) and 24 did not (AN-). AN+ subjects had a higher body mass index (37.7 +/- 5.6 versus 31.5 +/- 4.3 kg/m2), fat mass (38.9 +/- 4.0 versus 29.2 +/- 2.3 kg), and leptin levels (17.2 +/- 3.9 versus 9.3 +/- 1.6 ng/mL) (P<0.05). They also had significantly higher indices of insulin secretion: fasting and stimulated insulin and C-peptide levels from OGTT and FSIGT. Metabolic syndrome prevalence was 40% in AN- versus 75% in AN+ subjects (not significantly different). Although the AN+ group had significantly lower fasting and OGTT-derived indices of insulin sensitivity in comparison with the AN- group, their FSIGT indices were similar. Waist circumference (a surrogate of visceral adiposity) and cytokine profiles were similar in the AN+ and AN- groups. CONCLUSION: AN was not highly prevalent in our study cohort with NASH, despite the high prevalence of IR. Hyperinsulinemia and total adiposity, rather than visceral adiposity and IR, were the indices most predictive of AN. The use of AN as an index of IR in patients with NASH appears to have limited diagnostic value.

Acanthosis Nigricans↗