Impact of family history of diabetes and ethnicity on -cell function in obese, glucose-tolerant individuals.

CONTEXT: The increased insulin secretion in response to reduced insulin sensitivity (SI) is heritable, but whether the genetic predisposition is restricted to members of high-risk Caucasian families is unknown. Furthermore, the relative importance of insulin resistance and defective beta-cell compensation in the increased prevalence of type 2 diabetes (T2DM) in African-American compared with Caucasian individuals is uncertain. OBJECTIVES: We tested whether obese individuals with a family history of T2DM have decreased beta-cell compensation compared with obese controls without a family history of T2DM. In addition, we compared S(I) and insulin secretion measures in African-American and Caucasian individuals. DESIGN: SI, acute insulin response to iv glucose (AIRg), maximally potentiated insulin response to arginine (AIRmax), and disposition indexes (DIs) (DI = SI * AIRg; DImax = SI * AIRmax) were compared among nondiabetic Caucasian and African-American individuals with and without a family history of diabetes. SETTING: This study was performed in an Ambulatory General Clinical Research Center. SUBJECTS: SUBJECTS were healthy, nondiabetic individuals with or without a family history of T2DM. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Comparison of SI, AIRg, AIRmax, DI, and DImax between Caucasians and African-Americans with or without a strong family history of T2DM were made. RESULTS: Obese subjects did not differ in SI, AIRg, or DI by family history of diabetes. African-Americans had 8% lower SI (P < 0.001), but 68% higher AIRg (P < 0.001) and 46% higher DI (P = 0.001) than age, gender, body mass index-matched Caucasian individuals. However, African-Americans had lower DImax compared with Caucasians. CONCLUSIONS: We found no reduction in insulin secretion in obese subjects with a family history of T2DM compared with controls, but in general, African-Americans were more insulin resistant and had lower maximal beta-cell response (DImax). The paradoxical increased DI could be explained by the reduced hepatic insulin extraction.

Retinol binding protein 4 expression in humans: relationship to insulin resistance, inflammation, and response to pioglitazone.

CONTEXT: Retinol binding protein 4 (RBP4) was recently found to be expressed and secreted by adipose tissue, and was strongly associated with insulin resistance. OBJECTIVE: The aim was to determine the relationship between RBP4 and obesity, insulin resistance, and other markers of insulin resistance in humans. DESIGN AND PATIENTS: RBP4 mRNA levels in adipose tissue and muscle of nondiabetic human subjects with either normal or impaired glucose tolerance (IGT) were studied, along with plasma RBP4. RBP4 gene expression was also measured in adipose tissue fractions, and from visceral and sc adipose tissue (SAT) from surgical patients. SETTING: The study was conducted at University Hospital and General Clinical Research Center. INTERVENTION: Insulin sensitivity (S(I)) was measured, and fat and muscle biopsies were performed. In IGT subjects, these procedures were performed before and after treatment with metformin or pioglitazone. MAIN OUTCOME MEASURES: The relationship between RBP4 expression and obesity, S(I), adipose tissue inflammation, and intramyocellular lipid level, and response to insulin sensitizers was measured. RESULTS: RBP4 was expressed predominantly from the adipocyte fraction of SAT. Although SAT RBP4 expression and the plasma RBP4 level demonstrated no significant relationship with body mass index or S(I), there was a strong positive correlation between RBP4 mRNA and adipose inflammation (monocyte chemoattractant protein-1 and CD68), and glucose transporter 4 mRNA. Treatment of IGT subjects with pioglitazone resulted in an increase in S(I) and an increase in RBP4 gene expression in both adipose tissue and muscle, but not in plasma RBP4 level, and the in vitro treatment of cultured adipocytes with pioglitazone yielded a similar increase in RBP4 mRNA. CONCLUSIONS: RBP4 gene expression in humans is associated with inflammatory markers, but not with insulin resistance. The increase in RBP4 mRNA after pioglitazone treatment is unusual, suggesting a complex regulation of this novel adipokine.

Do visual analogue scale (VAS) derived standard gamble (SG) utilities agree with Health Utilities Index utilities? A comparison of patient and community preferences for health status in rheumatoid arthritis patients.

BACKGROUND: Assessment of Health Related Quality of Life (HRQL) has become increasingly important and various direct and indirect methods and instruments have been devised to measure it. In direct methods such as Visual Analog Scale (VAS) and Standard Gamble (SG), respondent both assesses and values health states therefore the final score reflects patient's preferences. In indirect methods such as multi-attribute health status classification systems, the patient provides the assessment of a health state and then a multi-attribute utility function is used for evaluation of the health state. Because these functions have been estimated using valuations of general population, the final score reflects community's preferences. The objective of this study is to assess the agreement between community preferences derived from the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3) systems, and patient preferences. METHODS: Visual analog scale (VAS) and HUI scores were obtained from a sample of 320 rheumatoid arthritis patients. VAS scores were adjusted for end-aversion bias and transformed to standard gamble (SG) utility scores using 8 different power conversion formulas reported in other studies. Individual level agreement between SG utilities and HUI2 and HUI3 utilities was assessed using the intraclass correlation coefficient (ICC). Group level agreement was assessed by comparing group means using the paired t-test. RESULTS: After examining all 8 different SG estimates, the ICC (95% confidence interval) between SG and HUI2 utilities ranged from 0.45 (0.36 to 0.54) to 0.55 (0.47 to 0.62). The ICC between SG and HUI3 utilities ranged from 0.45 (0.35 to 0.53) to 0.57 (0.49 to 0.64). The mean differences between SG and HUI2 utilities ranged from 0.10 (0.08 to 0.12) to 0.22 (0.20 to 0.24). The mean differences between SG and HUI3 utilities ranged from 0.18 (0.16 to 0.2) to 0.28 (0.26 to 0.3). CONCLUSION: At the individual level, patient and community preferences show moderate to strong agreement, but at the group level they have clinically important and statistically significant differences. Using different sources of preference might alter clinical and policy decisions that are based on methods that incorporate HRQL assessment. VAS-derived utility scores are not good substitutes for HUI scores.