Racial differences in attitudes toward personalized medicine.

BACKGROUND/AIMS: Patient concerns regarding personalized medicine may limit its use. This study assesses racial differences in attitudes toward personalized medicine, evaluating variables that may influence these attitudes. METHODS: A convenience sample of 190 adults (≥18 years) from an academic primary care practice was surveyed regarding awareness and acceptance of personalized medicine, plus concerns and benefits regarding its use. Logistic regressions predicting awareness, acceptance and concerns were performed, controlling for race, gender, marital status, education, children, internet use, and self-reported discrimination. RESULTS: The sample was 35% non-Hispanic white (NHW) and 34.7% male. More NHW participants expressed acceptance of personalized medicine than non-Hispanic black (NHB) participants (94.4 vs. 81.9%, p = 0.0190). More NHBs were concerned about the use of genes without consent (57.3 vs. 20.6%, p < 0.0001), sharing genetic information without consent (65.0 vs. 35.6%, p < 0.0001), discrimination based on genes (62.4 vs. 34.3%, p = 0.0002), and lack of access due to cost (75.0 vs. 48.0%, p = 0.0002). In logistic regressions, NHBs (OR = 7.46, 95% CI = 3.04-18.32) and those self-reporting discrimination (OR = 2.87, 95% CI = 1.22-6.78) had more concerns about the misuse of genes and costs associated with personalized medicine. CONCLUSION: Racial differences exist in attitudes toward personalized medicine and may be influenced by self-reported discrimination. Further study to understand factors influencing the acceptance of personalized medicine could help encourage its use.

Association between vitamin D and diabetic neuropathy in a nationally representative sample: results from 2001-2004 NHANES.

AIMS: To evaluate the association between vitamin D insufficiency and peripheral neuropathy in a nationally representative sample of adults with diagnosed diabetes. METHODS: Vitamin D concentrations, medical examination variables and questionnaire results from the 2001-2004 National Health and Nutrition Examination Survey were analysed for adults ≥ 40 years old with diagnosed diabetes (unweighted n = 591, weighted n = 8.82 million). Neuropathy was defined as self report of peripheral neuropathy symptoms of painful sensation, tingling, numbness or loss of feeling in hands or feet. Additionally, Semmes-Weinstein monofilament test results were used as an indicator of neuropathy. Insufficient vitamin D was characterized as < 30 ng/ml. RESULTS: In the weighted population, 81% of adults with diabetes had vitamin D insufficiency. Vitamin D insufficiency was more common among Hispanics (92%) and non-Hispanic black people (98%) than among non-Hispanic white people (76%). Within the 3 months preceding the questionnaire, 50% reported experiencing pain or numbness (paresthesia) in their hands or feet; 37% reported pain or tingling in hands or feet; and 38% reported numbness or loss of feeling in hands or feet. Eight per cent had 4-6 insensate areas on their feet as determined by the Semmes-Weinstein monofilament test. Logistic regressions demonstrate vitamin D insufficiency is associated with the adjusted composite paresthesia measure (odds ratio 2.12; 95% CI 1.17-3.85) and the adjusted numbness measure (odds ratio 2.04; 95% CI 1.18-3.52). CONCLUSIONS: Vitamin D insufficiency is associated with self-reported peripheral neuropathy symptoms even after adjusting for demographic factors, obesity, co-morbidities, use of medications for neuropathy and diabetes duration and control.

Ethnic differences in the relationship of prediabetes with the presence of target-organ disease.

BACKGROUND: Cardiovascular risk is associated with prediabetes states. Ethnic differences in risks related to prediabetes have not been well studied. The purpose of this study was to examine the relationship between prediabetes and the presence of target-organ disease in terms of ethnic differences. METHODS: Cross-sectional analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) involved a prospective cohort of 6814 participants aged 45-84 years in the US, including Black, white and hispanic subjects from an initial examination in 2000 with no known history of heart attack, stroke or diabetes. Main outcomes were comparisons of markers for coronary artery calcification (CAC), carotid stenosis more than 25%, Ankle-Brachial Index (ABI) less than 1.0 and presence of protein in urine (>30 mg/g) between participants with normal fasting glucose (NFG) and impaired fasting glucose (IFG), and between ethnic groups with prediabetes/IFG. RESULTS: There were 2457 white, 1548 black and 1229 Hispanic participants. After adjustments, there were no differences for each outcome between normal and prediabetes black and Hispanic subjects, whereas white participants with prediabetes had significantly higher odds of carotid stenosis (OR: 1.50), low ABI (OR: 1.77) and albuminuria (OR: 1.66) compared with whites with NFG. When comparing those with IFG/prediabetes by ethnicity, blacks and Hispanics had less CAC and carotid stenosis. In addition, Hispanics had lower reduced ABIs (OR: 0.35, 95% CI 0.19-0.65) compared with whites with IFG. CONCLUSION: Prediabetes is related to the presence of several indicators of end-organ damage in white subjects, but not in blacks or Hispanics. Further longitudinal investigations into disease risks related to prediabetes in different ethnic groups are also needed.

Telomere length and adiposity in a racially diverse sample.

OBJECTIVE: To evaluate the cross-sectional relationship of anthropometric measures (body mass index (BMI) and visceral fat and the adipokines leptin and adiponectin) with telomere length in a racially diverse sample. DESIGN: Cross-sectional study of participants recruited from a health science university. SUBJECTS: Participants include 317 men and women aged 40-64 years without diagnosed diabetes, cardiovascular disease (defined as coronary heart disease or stroke/transient ischemic attack) or cancer. RESULTS: Study participants were 54.9% female, 58% non-Hispanic white (NHW) and 42% non-Hispanic Black (NHB). Of the sample, 76% were either overweight or obese. Linear regressions showed no association between the anthropometric measures (BMI (kg m(-2)), visceral fat (cm(2)), adiponectin (microg ml(-1)), leptin (ng ml(-1)) or adiponectin to leptin ratio (microg ng(-1))) assessed in a continuous manner and telomere length assay ratio, either for the whole sample or when stratified by race or by gender. CONCLUSION: This study finds no linear associations between telomere length and several measures of obesity in a sample of NHB and NHW men and women. Further studies are needed to identify factors that influence telomere length in diverse populations.

How does ethnicity affect the association between obesity and diabetes?

AIMS: To examine the utility of body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHR) in assessing diabetes risk across different ethnic groups. METHODS: Cross-sectional analysis of data for eight ethnic groups from the 2003-2004 National Health and Nutrition Examination Survey and 2003-2004 Health Survey for England was performed. In 11 624 adults > or = 20 years old, self-reported as US White, US Black, Mexican American, English White, English Black, Bangladeshi, Pakistani, Indian or Chinese the presence of diabetes, defined as self-report of doctor diagnosis or glycated haemoglobin (HbA1c) > 6.1%, was ascertained. Comparisons of proportions were made using chi2-tests. Receiver operating characteristic (ROC) curves were calculated for BMI, WC and WHR predicting diabetes. RESULTS: Other ethnic groups had a higher prevalence of diagnosed diabetes than English Whites. The crude prevalence of diabetes in English Whites of normal weight (BMI < 25 kg/m2) was 3.4%. Higher prevalences were seen in other ethnic groups (5.0-10.9%). Based on ROC curves, both WC and WHR had better discriminating ability for diabetes than BMI for both genders and some ethnic groups. CONCLUSIONS: Ethnic differences exist in the crude prevalence of diabetes, even in those characterized as normal weight by BMI. Thus, clinicians need to exercise caution in interpreting diabetes risk associated with a normal BMI. The use of other anthropometric measures, such as WC or WHR, may improve risk determination across different ethnic groups. More research is needed to determine the thresholds for different anthropometric measures that improve diabetes risk determination.

Impact of the population at risk of diabetes on projections of diabetes burden in the United States: an epidemic on the way.

AIMS/HYPOTHESIS: The aim of this study was to make projections of the future diabetes burden for the adult US population based in part on the prevalence of individuals at high risk of developing diabetes. MATERIALS AND METHODS: Models were created from data in the nationally representative National Health and Nutrition Examination Survey (NHANES) II mortality survey (1976-1992), the NHANES III (1988-1994) and the NHANES 1999-2002. Population models for adults (>20 years of age) from NHANES III data were fitted to known diabetes prevalence in the NHANES 1999-2002 before making future projections. We used a multivariable diabetes risk score to estimate the likelihood of diabetes incidence in 10 years. Estimates of future diabetes (diagnosed and undiagnosed) prevalence in 2011, 2021, and 2031 were made under several assumptions. RESULTS: Based on the multivariable diabetes risk score, the number of adults at high risk of diabetes was 38.4 million in 1991 and 49.9 million in 2001. The total diabetes burden is anticipated to be 11.5% (25.4 million) in 2011, 13.5% (32.6 million) in 2021, and 14.5% (37.7 million) in 2031. Among individuals aged 30 to 39 years old who are not currently targeted for screening according to age, the prevalence of diabetes is expected to rise from 3.7% in 2001 to 5.2% in 2031. By 2031, 20.2% of adult Hispanic individuals are expected to have diabetes. CONCLUSIONS/INTERPRETATION: The prevalence of diabetes is projected to rise to substantially greater levels than previously estimated. Diabetes prevalence within the Hispanic community is projected to be potentially overwhelming.

Cultural conflicts in the weight loss experience of overweight Latinos.

OBJECTIVE: In spite of the high prevalence of obesity in the Latino population, there is limited recent information that can be used by health-care providers to develop culturally appropriate weight loss strategies for this population. Therefore, we describe weight loss experiences, attitudes and barriers in overweight Latino adults. DESIGN: Qualitative study using focus group methodology. SUBJECTS: Twenty-one overweight adults (body mass index >/=25, age >/=20 years) self-identified as Latinos. METHODS: Subjects participated in one of three focus groups. Reccurring themes within group discussions were identified by three independent investigators, one who was ethnicity concordant. RESULTS: Themes included the presence of mixed messages when determining one's appropriate weight, with participants' desire to lose weight to be healthy (based on professional advice and personal experience) conflicting with the cultural idea that being overweight is healthy. Participants described discordance when adapting to the mainstream, leading to the loss of healthy traditional habits. Participants expressed interest in weight loss and familiarity with dieting and weight loss interventions. They desired culturally appropriate nutrition education and reassurance regarding healthy dieting from health-care providers. The importance of interactions with peers during education was another relevant theme, and participants were overwhelmingly positive about group education. CONCLUSIONS: To improve health promotion for Latinos, cultural factors distinctive to this underserved population, and barriers they articulate, should be considered when developing weight loss interventions.

Are ethnic differences in insulin sensitivity explained by variation in carbohydrate intake?

AIMS/HYPOTHESIS: Minority populations are disproportionately affected by diabetes. This health disparity may be due to less healthy diets and/or heritable factors in minority populations. These factors must be assessed concurrently to better appreciate their contribution to insulin sensitivity. METHODS: We analysed overweight, healthy adults using the National Health and Nutrition Examination Survey 1999-2000. Means for dietary intake variables and insulin sensitivity were calculated by ethnicity. Linear regressions were performed to evaluate the association between ethnicity, dietary variables, dietary glycaemic index and insulin sensitivity. Fasting insulin was used to characterise insulin sensitivity. RESULTS: Non-Hispanic whites have higher energy and fat intake, while Hispanics have higher carbohydrate intake and African-Americans have lower fibre intake. In unadjusted analyses both Hispanics and African-Americans have lower insulin sensitivity, but only Hispanics are more likely to have lower insulin sensitivity after controlling for dietary variables and BMI. CONCLUSIONS/INTERPRETATION: Ethnic differences in insulin sensitivity remain after controlling for dietary differences and other factors, suggesting that inherent metabolic differences exist. Further studies are needed to define inherent metabolic factors, as well as other non-dietary factors that affect insulin sensitivity.

Having a regular physician and attempted weight loss after screening for hypertension or hypercholesterolemia.

OBJECTIVE: To examine the relationship between having a regular physician, results of screening tests for cardiovascular risk (hypertension, hypercholesterolemia) and efforts to lose weight among obese adults. DESIGN: Analysis of a population-based telephone survey (2002 Behavioral Risk Factor Surveillance System). SETTING: Four states (Iowa, South Carolina, South Dakota, Virginia) in the US. PARTICIPANTS: Adults (> or =18 y old) who were obese (body mass index > or =30 kg/m(2)) (unweighted n=1735). MAIN OUTCOME MEASURES: Currently attempting to lose weight; changes in diet or exercise as strategies to lose weight. RESULTS: Obese individuals with a personal physician were more likely to report attempts to lose weight in the face of screening normal for hypertension or hypercholesterolemia than those without a personal physician (75.6 vs 60.5% for hypercholesterolemia, P=0.03; 74.6 vs 57.7% for hypertension, P=0.01). In adjusted models, obese individuals screening normal for hypertension but having a personal physician were significantly more likely to attempt to lose weight than individuals without a personal physician (OR 1.71, 95% CI 1.12-2.60). CONCLUSIONS: Having a regular physician is associated with a higher likelihood of attempted weight loss among obese individuals who believe that they do not have hypertension or hypercholesterolemia, than their counterparts with no regular physician. This suggests a previously unrecognized benefit of having a personal physician.

Oral health care issues in HIV disease: developing a core curriculum for primary care physicians.

BACKGROUND: Given the high occurrence of oral manifestations in patients infected with human immunodeficiency virus (HIV), the relative ease in recognizing these manifestations on physical examination, and their potential impact on the health care and quality of life in these patients, it is critical to provide adequate training for primary care physicians in this area. METHODS: Based on a review of the published literature and the consensus of a national panel of primary care physicians and dentists with clinical and research expertise in this area, a core curriculum was developed for primary care physicians regarding oral health care issues in HIV disease. RESULTS AND CONCLUSIONS: We describe the process of developing the core curriculum of knowledge, skills, and attitudes regarding oral health care issues in HIV disease. The final curriculum is in a format that allows for easy accessibility and is organized in a manner that is clinically relevant for primary care physicians.

Issues to consider in internalization of a service.

In a staff-model HMO, the demand for services may be greater in one area than in another. Services with little demand and/or high cost are usually contracted to an external provider or institution. Equipment purchases or renovation of a facility to accommodate a new service sometimes go hand in hand with internalizing a service, and capital budgeting is an integral part of the process. The decision on when it is feasible to internalize services has to be considered on two levels: service and finance. This article will look at what issues affect the organization on these two levels and will consider the cost-benefit and legal issues that need to be considered when making such a decision. A work sheet that may be used as is or modified is included.

Influence of cAMP and calcium on [3H]inositol efflux, inositol phosphate accumulation, and insulin release from isolated rat islets.

The influence of cyclic AMP (cAMP) and extracellular calcium on phosphoinositide (PI) hydrolysis in isolated islets was assessed and related to insulin output. Three stimulants were chosen to activate the beta-cell: sulfated cholecystokinin (CCK-8S, 200 nM), high-level glucose (20 mM), and the sulfonylurea tolbutamide (200 microM). The insulin secretory response to all three agonists was amplified by forskolin (which increases cAMP levels) and reduced by nitrendipine (which decreases calcium influx). All three stimulants increased the hydrolysis of inositol-containing phospholipids, an event monitored by an increase in [3H]inositol efflux from [3H]inositol-prelabeled islets and by the accumulation of labeled inositol phosphates. Forskolin, despite its positive impact on insulin secretion, reduced [3H]inositol efflux and inositol phosphate accumulation in response to all agonists. A similar inhibitory effect on these parameters was noted with nitrendipine; however, nitrendipine abolished secretion in response to all agonists. These findings support the following conclusions: 1) an increase in cellular cAMP levels reduces the quantitative impact of various agonists on these indices of PI hydrolysis; 2) despite this inhibitory effect, cAMP amplifies the insulin secretory response to these agonists; and 3) extracellular calcium is a crucial determinant of both PI hydrolysis and the ensuing insulin secretory response.

Stimulatory effects of cholecystokinin on isolated perifused islets inhibited by potent and specific antagonist L 364718 [corrected].

The influence of L 364718 on islet responsiveness to sulfated cholecystokinin (CCK-8S) was investigated. In islets whose inositol-containing phospholipids were prelabeled during a 2-h incubation period, subsequent exposure to L 364718 (1 nM) significantly impaired the secretion of insulin usually noted in response to 200 nM CCK-8S in the simultaneous presence of 7 mM glucose. A higher level of the antagonist (10 nM) completely abolished insulin secretion. L 364718 (1-10 nM) reduced the efflux of 3H from myo-[2-3H]-inositol prelabeled islets in parallel with the reduction in secretion. L 364718 (10 nM) significantly reduced the accumulation of 3H-containing inositol phosphates usually noted with CCK-8S addition. L 364718, at levels 10- to 100-fold greater than those necessary to attenuate CCK-8S-induced insulin secretion, had no adverse effect on the insulin secretory response of freshly isolated islets to 10 mM glucose alone, 5 mM D-glyceraldehyde, 15 mM alpha-ketoisocaproate, or 50 ng/ml gastric inhibitory polypeptide. L 364718 (1000 nM) had no adverse influence on carbamylcholine (1 mM)-induced phosphoinositide hydrolysis. These results establish L 364718 as a potent and highly selective antagonist of cholecystokinin's stimulatory actions on beta-cells. Because of its potency, selectivity, and oral effectiveness, in vivo studies with L 364718, aimed at unraveling the pleiotropic effects of CCK-8S on glucose and insulin homeostasis, seem feasible.

Role of phosphoinositide metabolism in induction of memory in isolated perifused rat islets.

Prior exposure of isolated perifused rat islets to 20 mM glucose or 10 mM glyceraldehyde amplifies their subsequent insulin secretory response to 10 mM glucose. The involvement of phosphoinositide turnover in the induction of this "time-dependent potentiation" (TDP) was investigated. In islets in which inositol-containing phospholipids were prelabeled with myo-[2-3H]inositol, the addition of 20 mM glucose augments the efflux of 3H. This effect persists for approximately 50 min after the cessation of stimulation. Direct measurements of labeled inositol phosphate accumulation confirmed that this increase in 3H efflux is primarily the result of a persistent increase in phosphoinositide (PI) hydrolysis and not due to the slow efflux and/or degradation of performed [3H]inositol phosphates. The duration of the increase in 3H efflux parallels the duration of TDP. Mannoheptulose abolishes both the increase in 3H efflux evoked by 20 mM glucose and TDP. The omission of extracellular calcium plus 0.5 mM ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid also abolishes both of these effects of high glucose. D-Glyceraldehyde (10 mM) addition to 3H-inositol-prelabeled islets results in an acute efflux of 3H, a persistent efflux after removal of the D-glyceraldehyde from the perifusion medium, and the induction of TDP. Similar to the results obtained with high glucose, the return of 3H efflux rates to prestimulatory values is accompanied by the abolition of TDP. These results suggest that events associated with persistent stimulant-induced increases in phosphoinositide hydrolysis may participate in the induction and maintenance of TDP.

Cholecystokinin-induced alterations in beta-cell sensitivity. Duration, specificity, and involvement of phosphoinositide metabolism.

Prior exposure of isolated perifused rat islets to the sulfated gut hormone cholecystokinin-8 (CCK-8S) dramatically increased their insulin secretory response to 7.5 mM glucose, 10 mM arginine, and 10 mM alpha-ketoisocaproate. In the case of glucose, the heightened secretory response was still apparent 60-80 min after CCK-8S removal from the perifusion medium. Prior exposure of perifused islets to arginine (10 mM), tolbutamide (25 microM), or forskolin (1.0 microM) did not sensitize them to 7.5 mM glucose. CCK-8S exposure increased 3H efflux from islets prelabeled with [3H]inositol, and the increase in 3H efflux was sustained after CCK-8S removal from the perifusion medium. The duration of this increase in 3H efflux paralleled the temporal characteristics of this sensitization process and was significantly attenuated by 25 microM asperlicin, a competitive antagonist of CCK binding to its membrane receptor. Arginine, tolbutamide, or forskolin treatment of islets did not increase 3H efflux from [3H]inositol-prelabeled islets. The results suggest that the turnover of membrane phosphoinositides induced by CCK-8S is largely responsible for this heightened state of secretory responsiveness to various stimulants. Second-messenger molecules generated during phosphoinositide turnover may be responsible for the phenomenon of sensitization displayed by islet tissue to CCK-8S addition.

Interactions of cholecystokinin and glucose in rat pancreatic islets.

The effects of sulfated cholecystokinin (CCK-8S) and glucose on insulin secretion and polyphosphoinositide (PPI) metabolism were studied in isolated rat islets. Both agonists stimulate PPI hydrolysis, inositol phosphate accumulation, 3H efflux from [3H]inositol-prelabeled tissue, and 45Ca efflux from prelabeled cells. However, the effects of CCK-8S on PPI metabolism are considerably greater than those of glucose. Furthermore, the effects of CCK-8S on PPI and Ca2+ metabolism are observed whether islets are incubated in either 2.75 or 7 mM glucose, but CCK-8S only stimulates insulin secretion (a biphasic response) when the higher glucose concentration is present. Addition of 1 microM forskolin to islets incubated in media containing 2.75 mM glucose does not influence basal insulin secretion but sensitizes the islets to the action of CCK-8S. In the presence of forskolin, CCK-8S induces a very marked first phase but no second phase of insulin secretion. We postulate that CCK-8S acts in this tissue via receptor-linked PPI hydrolysis, leading to an inositol trisphosphate-induced Ca2+ efflux. These receptor-mediated effects of CCK-8S are not altered either by the ambient glucose concentration or the cAMP content of the islets, but these two factors determine the responsiveness of the islets (in terms of insulin secretion) to a given CCK-8S signal.

Asperlicin antagonizes stimulatory effects of cholecystokinin on isolated islets.

Asperlicin, a product derived from the fungus Aspergillus alliaceus, antagonized the multiple stimulatory effects of cholecystokinin (CCK-8S) on isolated islets. At a level of 10 microM, asperlicin completely inhibited insulin release in response to 25 nM CCK-8S. Increasing the level of CCK-8S to 100 nM partially restored a secretory response, while an even greater insulin stimulatory effect was noted with 500 nM CCK-8S. The inhibitory effect of asperlicin on CCK-8S-induced release was reversible. Asperlicin exposure had no effect on glucose or glyceraldehyde-induced secretion. Asperlicin reduced, in parallel with secretion, the increase in 3H efflux from [3H]inositol prelabeled islets usually noted with CCK-8S addition. Asperlicin did not influence the small glucose-stimulated increase in 3H efflux. The results support the notion that asperlicin is a specific and potent antagonist of the multiple stimulatory effects of CCK-8S on islet tissue.

Prior cholecystokinin exposure sensitizes islets of Langerhans to glucose stimulation.

Prior, short-term exposure of isolated perifused islets to cholecystokinin (CCK8S) sensitizes them to subsequent glucose stimulation. This sensitization effect develops quickly and persists long after the removal of CCK8S from the perifusion medium. Continued binding of CCK8S to its receptor on the beta-cell and the increase in glucose metabolism noted with glucose stimulation are essential for the full expression of this response. This sensitization process may play an integral role in the postulated incretin effect of the peptide.

Interleukin 1 inhibits insulin secretion from isolated perifused rat islets.

Preincubation of collagenase-isolated rat islets for 150 min with 100 U/ml purified human interleukin 1 (IL-1) altered their ability to secrete insulin. Whereas basal release rates with 4 mM glucose were comparable in control and IL-1-treated islets, both the first and second phases of release in response to 20 mM glucose were significantly reduced from IL-1-treated tissue. IL-1 pretreatment also impaired the secretory response to the combination of 100 nM cholecystokinin plus 7 mM glucose. However, the secretory response to 10 mM alpha-ketoisocaproate was comparable in control and IL-1-pretreated islets. Reducing the IL-1 exposure time to 60 min was accompanied by an augmented first phase of release to 20 mM glucose. Second phase secretion was diminished. The use of glucose measured after the perifusion was similar in control and IL-1-treated islets. Similar to other compounds that adversely impact on beta-cell viability, the inhibitory effect of IL-1 on release may presage a cytotoxic action of monokine.