Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study.

BACKGROUND: Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome analysis and an additional follow-up analysis. PATIENTS AND METHODS: This global, phase III, open-label trial randomized (1 : 1) 5637 patients to adjuvant ET for ≥5 years ± abemaciclib for 2 years. Cohort 1 enrolled patients with ≥4 positive axillary lymph nodes (ALNs), or 1-3 positive ALNs and either grade 3 disease or tumor ≥5 cm. Cohort 2 enrolled patients with 1-3 positive ALNs and centrally determined high Ki-67 index (≥20%). The primary endpoint was IDFS in the intent-to-treat population (cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety. RESULTS: At the primary outcome analysis, with 19 months median follow-up time, abemaciclib + ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P = 0.0009]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (HR = 0.70, 95% CI 0.59-0.82; nominal P < 0.0001) and DRFS (HR = 0.69, 95% CI 0.57-0.83; nominal P < 0.0001) benefit was maintained. The absolute improvements in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. Whereas Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data were consistent with the known abemaciclib risk profile. CONCLUSION: Abemaciclib + ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.

The impact of tabalumab on the kidney in systemic lupus erythematosus: results from two phase 3 randomized, clinical trials.

INTRODUCTION: Tabalumab is a monoclonal antibody that neutralizes membrane and soluble B-cell activating factor. Two 52-week, randomized, double-blind, placebo controlled phase 3 trials evaluated the safety and efficacy of tabalumab in systemic lupus erythematosus. METHODS: Patients with moderate to severe active systemic lupus erythematosus (without severe active lupus nephritis) were randomly assigned 1:1:1 to receive tabalumab (120 mg subcutaneously every 2 or 4 weeks) or placebo for 52 weeks. Serum creatinine concentration, estimated glomerular filtration rate, urine protein/creatinine ratio, renal flares and renal adverse events were determined monthly. Data were analyzed for the intent-to-treat population and for intent-to-treat patients with baseline urine protein/creatinine ratio >20 mg/mmol (intent-to-treat plus urine protein/creatinine ratio). RESULTS: The trials enrolled 2262 patients. At baseline, demographics, systemic lupus erythematosus disease activity, serum creatinine concentration, estimated glomerular filtration rate and urine protein/creatinine ratio were similar among the treatment arms (with the exception of disease duration). In the intent-to-treat and intent-to-treat plus urine protein/creatinine ratio populations, there were no differences between the arms in the baseline-to-endpoint change in serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates. Tabalumab resulted in a significant B-cell reduction and decreased immunoglobulin G levels at both doses. CONCLUSIONS: Compared to placebo, tabalumab did not significantly affect the serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates over 1 year in intent-to-treat or intent-to-treat plus urine protein/creatinine ratio patients. There were no significant renal safety signals.ClinicalTrials.gov identifiers: NCT01205438 and NCT01196091 Lupus (2016) 25, 1597-1601.

Increasing Clozapine Dispensing Trends in Queensland, Australia 2004-2013.

INTRODUCTION: Clozapine is the most effective treatment for treatment-resistant schizophrenia but its use is suboptimal. METHODS: Clozapine dispensing data from Queensland, Australia were extracted (2004-2013). The number of people dispensed clozapine each year and mean maintenance doses were calculated. The 18-week and 5-year cessation and treatment interruption rates were calculated using Kaplan-Meier analysis. RESULTS: Clozapine dispensings increased 36.4% (p<0.001) from 44 to 60 people per 100,000. This was estimated as 8.3% of people with schizophrenia and 33.3% of people with treatment resistant schizophrenia dispensed clozapine in 2013. Mean maintenance dose did not significantly change (364-399 mg) over 5 years of treatment. One in 7 (14.2%) people ceased within the first 3 weeks. 3-quarters (72.7%) reached maintenance therapy. The 5-year actuarial estimate of the proportion of people a) dispensed clozapine was 0.610 (S.E. 0.011) and b) with an interruption to treatment was 0.422 (S.E. 0.013). DISCUSSION: The number of patients being dispensed clozapine increased between 2004 and 2013 but clozapine is still underused. Increased use combined with continued monitoring for adverse effects will improve quality use of clozapine.

Impact of olanzapine or risperidone treatment on insulin sensitivity in schizophrenia or schizoaffective disorder.

AIM: To assess changes in insulin sensitivity in non-diabetic adults with schizophrenia or schizoaffective disorder treated with olanzapine or risperidone. METHODS: One hundred and thirty patients were randomly assigned to 12 weeks double-blind treatment with olanzapine or risperidone. Insulin sensitivity was measured using a two-step euglycaemic, hyperinsulinaemic clamp procedure. Whole-body adiposity was measured using dual-energy X-ray absorptiometry. The primary endpoint was the within-group change from baseline in insulin sensitivity normalized to fat-free mass (M(ffm) /I) during the clamp procedure's low-insulin phase, using an analysis of covariance model including the covariate weight change. RESULTS: Forty-one olanzapine-treated and 33 risperidone-treated patients completed baseline and endpoint clamp measurements. Mean M(ffm) /I during the low-insulin phase declined 9.0% (p = 0.226) in olanzapine-treated patients and 13.2% (p = 0.047) in risperidone-treated patients (between-group difference p = 0.354). During the high-insulin phase, M(ffm) /I declined 10.4% (p = 0.036) in olanzapine-treated patients and 2.1% (p = 0.698) in risperidone-treated patients (between-group difference p = 0.664). Changes in M(ffm) /I correlated inversely with changes in body weight and adiposity, which were generally higher in olanzapine-treated patients. Significant within-group increases in fasting glucose, but not haemoglobin A1c (HbA1c), were observed during olanzapine treatment. The fasting glucose change was not correlated with M(ffm) /I changes. CONCLUSIONS: Small, but statistically significant, decrements in insulin sensitivity were observed in olanzapine- and risperidone-treated patients at 1 of 2 insulin doses tested. Significant increases in fasting glucose and insulin and total fat mass were observed only in olanzapine-treated patients. Changes in insulin sensitivity correlated significantly with changes in weight or adiposity, but not with changes in glucose.

A preliminary examination of the effects of genetic variants of redox enzymes on susceptibility to oedematous malnutrition and on percentage cytotoxicity in response to oxidative stress in vitro.

BACKGROUND: The causes of oedematous vs non-oedematous childhood malnutrition (OM vs NOM) remain elusive. It is possible that inherited differences in handling oxidant stressors are a contributing factor. AIMS: To test for associations between polymorphisms in five genes and (i) risk of OM, a case-control study, and (ii) percentage cytotoxicity in peripheral blood mononuclear cells (PBMCs) exposed to hydrogen peroxide (H(2)O(2)), an in vitro cell challenge study. METHODS: Participants had been admitted previously for treatment of OM (cases, n = 74) or NOM (controls, n = 50), or were an independent set of healthy pregnant women (n = 47) who donated peripheral blood mononuclear cells. We tested for associations between genetic variation and outcome using single markers or a bivariate score constructed by counting numbers of deleterious alleles for each of 15 possible pairs of markers. RESULTS: In the case-control study there were no significant single-marker associations with OM. We did find that higher bivariate scores were associated with OM for the pair of NAD(P)H:quinone oxidoreductase 1 and catalase (odds ratio 2·00, 95% CI 1·05-3·82). In the cell challenge experiments, there were no significant associations with percentage cytotoxicity. CONCLUSIONS: Variation in this small set of genes seems unlikely to have a large impact on either risk of OM or cytotoxicity after H(2)O(2) exposure. The use of larger sample sizes to test the effects of a much larger set of genetic variants will be required in order to determine whether genetic variation contributes to the risk of OM. Such studies have potential for improving our understanding of causal pathways in OM.

Association of common DNA sequence variants at 33 genetic loci with blood lipids in individuals of African ancestry from Jamaica.

The relevance of loci associated with blood lipids recently identified in European populations in individuals of African ancestry is unknown. We tested association between lipid traits and 36 previously described single-nucleotide polymorphisms (SNPs) in 1,466 individuals of African ancestry from Spanish Town, Jamaica. For the same allele and effect direction as observed in individuals of European ancestry, SNPs at three loci (1p13, 2p21, and 19p13) showed statistically significant association (p < 0.05) with LDL, two loci (11q12 and 20q13) showed association with HDL cholesterol, and two loci (11q12 and 2p24) showed association with triglycerides. The most significant association was between a SNP at 1p13 and LDL cholesterol (p = 4.6 × 10(-8)). This SNP is in a linkage disequilibrium region containing four genes (CELSR2, PSRC1, MYBPHL, and SORT1) and was recently shown to relate to risk for myocardial infarction. Overall, the results of this study suggest that much of the genetic variation which influences blood lipids is shared across ethnic groups.

Progression from prehypertension to hypertension in a Jamaican cohort: incident hypertension and its predictors.

OBJECTIVES: To estimate the incidence of hypertension in people with and without prehypertension and determine the factors that predict progression to hypertension. METHODS: Data from a cohort of 25-74-year-old residents of Spanish Town, Jamaica, were analysed. All participants completed a structured questionnaire and had blood pressure (BP), anthropometric measurements and venous blood sampling performed by trained personnel. Blood Pressure was classified using the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-7) criteria. RESULTS: 708 persons who had the required data and were not hypertensive at baseline were included in this analysis. Mean follow-up time was 4.1 years; 28.7% of prehypertensive participants developed hypertension compared to 6.2% of normotensive participants. The unadjusted incidence rate ratio (IRR [95% CI]) for progression among prehypertensive compared to normotensive participants was 4.62 [2.96, 7.43]. Among males, the rate of progression to hypertension was significantly higher for those 45-64 years old and those who were current smokers. Among females, progression was higher for age groups 25-44 years, 45-64 years, those who were overweight (BMI > or =25), obese (BMI > or =30) and current smokers. In multivariate models, prehypertension, female gender overweight status and older age remained significantly associated with progression to hypertension among the combined prehypertensive and normotensive groups. IRR [95% CI] were: prehypertension, 3.45 [2.18-5.45]; female gender 1.81 [1.12, 2.94]; overweight, 1.87 [1.15, 2.94]; age 45-64 years, 1.73 [1.08, 2.76]; age > 65 years 2.39 [1.31, 4.34]. CONCLUSIONS: Prehypertension is associated with a three-fold increase in the incidence of hypertension. Higher BMI, age and female gender also independently predict the development of hypertension.

Prevalence of the metabolic syndrome in Jamaican adults and its relationship to income and education levels.

OBJECTIVE: To estimate the prevalence of the metabolic syndrome in Jamaican adults and to evaluate its association with socio-economic status (SES). METHODS: A cross-sectional analysis was performed using data from a cohort study of persons, 25-74 years old, living in St Catherine, Jamaica, and who were evaluated between 1993 and 2001. Participants completed an interviewer administered questionnaire and had blood pressure and anthropometric measurements performed by trained observers. Venous blood was collected for measurement of fasting glucose and lipids. The metabolic syndrome was defined using the International Diabetes Federation (IDF) and American Heart Association/National Heart Lung and Blood Institute (AHA/NHLBI) criteria. Income and education were used as markers of SES. RESULTS: Data from 1870 participants (717 males 1153 females) were analysed. Prevalence of the metabolic syndrome was 21.1% (95% CI 19.2, 22.9%) using IDF criteria and 18.4% (95% CI 16.6, 20.2%) using the AHA/NHLBI criteria. Prevalence was higher among females (27.6% [IDF], 23.0% [AHA]) compared to males (10.6% [IDF], 11.0% [AHA]). The prevalence of the metabolic syndrome increased with age. Compared to males with primary/lower education, those with secondary and tertiary education had higher odds of having the metabolic syndrome after adjusting for age; odds ratio 3.12 (1.54, 6.34) and 2.61 (1.33, 5.11) respectively. High income was also associated with increased odds of having the metabolic syndrome among males, OR = 6.0 (2.22, 16.19) adjusting for age-group. There were no significant associations among women. CONCLUSION: The metabolic syndrome is common in Jamaica. Clinicians should look for this syndrome in their patients and take steps to treat the abnormalities identified.

A comparative study of the quality and availability of health information used to facilitate cost burden analysis of diabetes and hypertension in the Caribbean.

OBJECTIVE: Non-communicable Diseases (NCDs) are leading threats to health and well-being in the Caribbean. A study was undertaken in the latter part of 2005 to compute the economic burden of diabetes mellitus and hypertension within the Caribbean Community and Common Market (CARICOM). This report critiques the quality and availability of health information which can be used to facilitate cost burden analysis of diabetes mellitus and hypertension. METHODS: A form was developed and disseminated to obtain epidemiological and health service utilization data. Subsequent visits were made to seven CARICOM member countries to collect the data. RESULTS: The results revealed (i) a number of deficiencies in the reliability and validity of the data received, in particular, those needed to facilitate the analysis of cost-specific complications such as ischaemic heart disease, cerebrovascular disease, chronic renal failure, hypertensive and diabetic retinopathy and peripheral circulatory complications; (ii) data management systems in hospitals were not linked to facilitate generation of cost-effectiveness estimates and other information required to compare options for health investment; (iii) despite repeated attempts by regional governments to develop/strengthen Health Information Systems within the Caribbean, sustainability has been significantly hampered by human, material and financial resource constraints and ongoing monitoring and evaluation is generally poor. CONCLUSION: There are deficiencies in the quality and availability of health information to facilitate cost burden analysis of hypertension and diabetes mellitus in the Caribbean Strong commitment from CARICOM governments will be necessary to address these concerns if economic evaluations are to be undertaken more frequently as part of the effort to reduce the morbidity and mortality from these diseases.

Activity, adiposity and weight change in Jamaican adults.

OBJECTIVE: Populations in developing countries are particularly vulnerable to the development of obesity in the period of rapid transition to a more modernized lifestyle. We sought to determine the relationship between activity energy expenditure (AEE), adiposity and weight change in an adult population undergoing rapid socio-economic transition. METHODS: Total daily energy expenditure (TDEE) was measured using the doubly labelled water method, resting energy expenditure (REE) using indirect calorimetry and AEE calculated as the difference between TDEE and REE, in adults from a working class community in Spanish Town, Jamaica. During six years of follow-up, weight was measured between one and four times. Mixed effects regression modelling was used to test for association between components of the energy budget and weight change. RESULTS: Men (n = 17) weighed more but women (n = 18), had significantly more body fat, 38.5% vs 24.5%, respectively (p < 0.01). Men had higher levels of EE, particularly AEE after adjustment for body weight, 66.3 versus 46.4 kJ/kg.d for men and women, respectively (p < 0.001). At baseline, adjusted AEE was inversely associated with body fat in men and women, r = -0.46 and r = -0.48, respectively (p < 0.05). Mean rate of weight change was + 1.1 and + 1.2 kg/year for men and women, respectively. No component of EE, ie TDEE, REE or AEE, significantly predicted weight change in this small sample. CONCLUSIONS: These results suggest an important role for AEE in maintaining low levels of adiposity. The lack of association between EE and weight change, however, suggests populations in transition are at risk of obesity from environmental factors (eg dietary) other than simply declining physical activity levels.

Relationship between birth weight and urea kinetics in children.

OBJECTIVE: To explore the effect of birth weight on urea kinetics in young healthy children. DESIGN: Observational study. SETTING: Tertiary center for treatment of malnutrition. SUBJECTS: A total of 17 male children, 6-24 months old, who had recovered from malnutrition. INTERVENTIONS: Urea kinetics were measured using stable isotope methodology with [(15)N(15)N]-urea over 36 h. RESULTS: Birth weight was negatively related to urea hydrolysis after controlling for the intake of protein (adjusted R (2 ) = 0.91, P = 0.001) and separately for energy intake (adjusted R (2) = 0.95, P = 0.001), age (adjusted R (2) = 0.90, P = 0.001) and rate of weight gain (adjusted R (2) = 0.91, P = 0.001). There was a tendency for higher urea production in the children with lower birth weight after controlling for nitrogen intake (adjusted R (2) = 0.93, P = 0.099), and separately for age (adjusted R (2) = 0.94, P = 0.06) and rate of weight gain (adjusted (R (2) = 0.92, P = 0.096). Urea excretion was not significantly related to birth weight. CONCLUSIONS: The salvaging of urea nitrogen following urea hydrolysis contributed significantly more to the nitrogen economy in children with lower birth weight compared to those with higher birth weight. This may be as a result of reductive adaptation in the children with lower birth weight as a consequence of inappropriate prenatal nutrition and growth.

Skin test reactivity to aeroallergens in Jamaicans: relationship to asthma.

BACKGROUND: Asthma causes significant morbidity and mortality in the developing world. It is thus important to identify modifiable risk factors. OBJECTIVES: To undertake a cross-sectional study to determine the prevalence of skin test reactivity to aeroallergens in Jamaican children and adults and the relationship of the diagnosis of asthma to the pattern of skin test positivity. METHODS: One hundred and sixty subjects without the sickle cell gene (genotype AA), eighty adults and eighty children, were recruited. Skin testing to seven aeroallergens was undertaken (atopy being diagnosed if there were at least one positive reaction). Asthma status was determined by a questionnaire and/or medical records. RESULTS: Twenty-seven (34%) of the children and forty-one (51%) of the adults were skin test positive to at least one aeroallergen. The most common positive responses in both age groups were to Dermatophagoides farinae, Dermatophagoides pteronyssinus and cockroach mix-(German and American). All adult asthmatics with current symptoms reacted to cockroach allergen. CONCLUSIONS: Appropriate steps to reduce cockroaches and cockroach sensitization might positively impact on asthma morbidity in Jamaica.

Relationship between blood pressure and physical activity assessed with stable isotopes.

Intrapopulation and interpopulation variation in blood pressure (BP) often reflects the joint effect of a complex set of risk factors, including lifestyle factors such as physical activity, diet, smoking and alcohol use. In this study, we set out to quantify the impact of habitual levels of physical activity on BP within and between three populations at contrasting levels of population risk of hypertension. Individuals were randomly sampled from communities in Nigeria (n=57), Jamaica (from Kingston, n=35) and the United States (from the Chicago area, n=32). Activity energy expenditure (AEE) (estimated from resting energy expenditure measured by indirect calorimetry and total expenditure measured with doubly labelled water) was used as an objective estimate of physical activity. In each of the three samples, there was a consistent negative correlation between BP and AEE. This negative association persisted after adjustment for age, sex and body fat (body mass index or percent fat mass). In multivariate models, adiposity was no longer a significant predictor of BP after accounting for low AEE. In conclusion these data suggest that habitual levels of physical activity may have a generalizable relationship with BP in populations with widely different social and environmental characteristics.

A randomized trial on sodium reduction in two developing countries.

Hypertension remains the most common cardiovascular risk factor in developing countries, yet the majority of patients have no access to pharmacological therapy. Population-wide preventive strategies, such as salt restriction, are an attractive alternative, but experience in resource-poor settings is limited. To address this question, we conducted a randomized crossover study of salt restriction in adults living in Nigeria and Jamaica in order to estimate the mean blood pressure (BP) response. After a 4-week run-in period to determine willingness to adhere to a low-salt diet, 56 Jamaicans and 58 Nigerians completed an 8-week crossover study of low-salt and high-salt intake. Baseline BPs were in the normotensive range (systolic=125 mmHg in Jamaica, 114 mmHg in Nigeria). Baseline urinary sodium excretion was 86.8 and 125.6 mEq/day in Nigeria and Jamaica, respectively. The mean difference between urinary sodium excretion at baseline and at the end of the 3-week low-sodium phase was 33.6 mEq/day in Nigeria and 57.5 mEq/day in Jamaica. During the high-sodium phase, mean change in urinary sodium excretion from baseline to week 3 was 35.0 and 5.5 mEq/day in Nigeria and Jamaica, respectively. The mean change in systolic BP ('high' vs 'low' sodium phase) was approximately 5 mmHg in both groups. This study suggests that the efficacy of sodium reduction in developing countries equals those noted in more affluent cultures. If promoted on a wide scale, sodium reduction could be used to treat persons with established hypertension, and more importantly, to prevent age-related increases in BP in poor communities.

Cold-induced elevation of forearm vascular resistance is inversely related to birth weight.

Fetal growth retardation has been linked to elevated blood pressure in adult life. This association between birth weight and blood pressure is present in childhood and is amplified with age. However, the mechanisms that underlie this association are largely unknown. We examined the relationship between birth weight and forearm vascular resistance and forearm blood flow in children aged 9-12.7 years. A total of 58 children were randomly selected from a cohort of 1610 born at the University Hospital of the West Indies in Jamaica where adequate antenatal and delivery records were available. Blood pressure, heart rate and forearm blood flow (by venous occlusion plethysmography) were measured at rest and after cold pressor and mental arithmetic tests. There was a significant inverse correlation between birth weight and the change in the vascular resistance for the cold pressor test (r=-0.47; P<0.001) and the mental arithmetic stress test (r=-0.26; P=0.05). The log ratio of vascular resistance under stress to resting decreased by 0.289 units per kg of birth weight (95% CI: 0.145-0.434; P=0.0002). Lower birth weight is associated with increased vascular responsiveness. Increased vascular resistance might be one mechanism linking fetal growth to subsequent elevated blood pressure.

Iron deficiency anaemia in Jamaican children, aged 1-5 years, with sickle cell disease.

OBJECTIVE: The aim of this study was to determine, using a combination of measures, the prevalence of iron deficiency anaemia (IDA) in children under five years-of-age who have sickle cell disease (SCD) and attend the Sickle Cell Clinic (SCU) of the Tropical Medicine Research Institute. MATERIALS AND METHODS: Children with homozygous sickle cell anaemia (Hb SS) or doubly heterozygous for Hb S and Hb C (Hb SC) disease who had not received a blood transfusion within three months prior to the iron measurements, were enrolled. The diagnosis of IDA was made if transferrin saturation was less than 16% with serum iron less than 10.7 micromol/l and a low mean corpuscular volume (MCV) for age. RESULTS: Twelve children (8.5%), seven with Hb SS and five with Hb SC had IDA. Adjusting for genotype, children with IDA had significantly higher red blood cell (RBC) counts (4.3 x10(9)/l vs 3.0 x 10(9)/l, p < 0.001) and total iron binding capacity (TIBC) (65.6 micromol/l vs 55.2 micromol/l, p < 0.004) but significantly lower reticulocyte (retic) counts (7.8 % vs 12.2%, p = 0.001) than children without IDA. CONCLUSION: Iron deficiency anaemia is a clinical problem which affects children with SCD in Jamaica. The higher RBC counts in the IDA group may be due to decreased haemolysis and increased red cell survival whilst the lower reticulocyte counts may be due to impaired erythropoiesis. These observations need to be extended by clinical studies to establish improved diagnostic measures for IDA in SCD. Additionally, clinical trials are needed to determine whether treatment of IDA in children with SCD reduces morbidity and is associated with clinical benefits such as improvements in neurocognitive function.

Association of waist circumference with risk of hypertension and type 2 diabetes in Nigerians, Jamaicans, and African-Americans.

OBJECTIVE: Prior studies have supported that waist circumference correlates better with visceral adipose tissue and is a better predictor of cardiovascular disease than are BMI and waist-to-hip ratio. In this study, we reexamine the role of waist size on the risk of hypertension and type 2 diabetes in African-origin populations from three contrasting environments. RESEARCH DESIGN AND METHODS: A cross-sectional survey was conducted of 5,042 men and women 25-74 years of age from Nigeria, Jamaica, and the U.S. The relationship between waist, blood pressure, and fasting blood glucose was assessed using multiple linear regression analyses. Logistic regression analyses using sex-specific empirical waist cut-points were used to determine the risks of hypertension and type 2 diabetes. RESULTS: Waist circumference was positively correlated with blood pressure and fasting blood glucose (P < 0.05). Increasing waist quartiles were significantly associated with higher risks of hypertension in the three populations, as estimated from age-adjusted odds ratios obtained from sex-specific logistic regression models. A highly elevated risk of type 2 diabetes-10-fold for Jamaican men and 23-fold for African-American women-was observed in the comparison of lowest to highest quartiles of waist circumference. CONCLUSIONS: Substantial reduction in hypertension and diabetes in men and women is achievable if the waist size is decreased in these populations. Intervention programs designed to reduce waist circumference through lifestyle modification, including exercise and diet, may have significant public health significance in reducing the incidence of hypertension and adult-onset diabetes in these populations.

Prevalence of NIDDM among populations of the African diaspora.

OBJECTIVE: Rates of non-insulin-dependent diabetes mellitus have risen sharply in recent years among blacks in the U.S. and the U.K. Increases in risk have likewise been observed in the island nations of the Caribbean and in urban West Africa. To date, however, no systematic comparison of the geographic variation of NIDDM among black populations has been undertaken. RESEARCH DESIGN AND METHODS: In the course of an international collaborative study on cardiovascular disease, we used a standardized protocol to determine the rates of NIDDM and associated risk factors in populations of the African diaspora. Representative samples were drawn from sites in Nigeria, St. Lucia, Barbados, Jamaica, the United States, and the United Kingdom. A total of 4,823 individuals aged 25-74 years were recruited, all sites combined. RESULTS: In sharp contrast to a prevalence of 2% in Nigeria, age-adjusted prevalences of self-reported NIDDM were 9% in the Caribbean and 11% in the U.S. and the U.K. Mean BMI ranged from 22 kg/m2 among men in West Africa to 31 kg/m2 in women in the U.S. Disease prevalence across sites was essentially collinear with obesity, pointing to site differences in the balance between energy intake and expenditure as the primary determinant of differential NIDDM risk among these populations. CONCLUSIONS: In ethnic groups sharing a common genetic ancestry, these comparative data demonstrate the determining influence of changes in living conditions on the population risk of NIDDM.

Standardized comparison of glucose intolerance in west African-origin populations of rural and urban Cameroon, Jamaica, and Caribbean migrants to Britain.

OBJECTIVE: To compare the prevalence of glucose intolerance in genetically similar African-origin populations within Cameroon and from Jamaica and Britain. RESEARCH DESIGN AND METHODS: Subjects studied were from rural and urban Cameroon or from Jamaica, or were Caribbean migrants, mainly Jamaican, living in Manchester, England. Sampling bases included a local census of adults aged 25-74 years in Cameroon, districts statistically representative in Jamaica, and population registers in Manchester. African-Caribbean ethnicity required three grandparents of this ethnicity. Diabetes was defined by the World Health Organization (WHO) 1985 criteria using a 75-g oral glucose tolerance test (2-h > or = 11.1 mmol/l or hypoglycemic treatment) and by the new American Diabetes Association criteria (fasting glucose > or = 7.0 mmol/l or hypoglycemic treatment). RESULTS: For men, mean BMIs were greatest in urban Cameroon and Manchester (25-27 kg/m2); in women, these were similarly high in urban Cameroon and Jamaica and highest in Manchester (27-28 kg/m2). The age-standardized diabetes prevalence using WHO criteria was 0.8% in rural Cameroon, 2.0% in urban Cameroon, 8.5% in Jamaica, and 14.6% in Manchester, with no difference between sexes (men: 1.1%, 1.0%, 6.5%, 15.3%, women: 0.5%, 2.8%, 10.6%, 14.0%), all tests for trend P < 0.001. Impaired glucose tolerance was more frequent in Jamaica. CONCLUSIONS: The transition in glucose intolerance from Cameroon to Jamaica and Britain suggests that environment determines diabetes prevalence in these populations of similar genetic origin.