The E23K variant in the Kir6.2 subunit of the ATP-sensitive K+ channel does not augment impaired glucose tolerance in Caribbean subjects with a family history of type 2 diabetes

The E23K variant of the Kir6.2 gene has been shown to be associated with type 2 diabetes mellitus in Caucasian subjects. Because offspring of type 2 diabetic patients have a genetically increased risk of developing diabetes, we sought to identify the E23K variant of the Kir6.2 gene in offspring of Caribbean patients with type 2 diabetes and assess the contribution of this variant to impaired glucose tolerance in these subjects. Forty-six offspring of patients with type 2 diabetes and 39 apparently healthy subjects whose immediate parents were not diabetic (‘control’) were studied after an overnight fast. Anthropometric indices were measured and blood samples were collected. Fasting and 2 h plasma glucose, insulin and lipids were subsequently determined. Insulin resistance was calculated using the homeostatic model assessment technique. The offspring and control subjects had similar frequencies of the E23K polymorphism (52.6 vs 45.5 per cent, P>0.05) and the frequency of the E23K variant did not differ significantly between gender and ethnic distributions, irrespectively of a family history of diabetes (P>0.05). There were no significant differences in biochemical risk factors for developing diabetes in offspring carriers of the E23K variant compared with offspring non-carriers of the mutation. Offspring with the E23K mutation had even significantly higher 2 h insulin concentrations when compared with control subjects. It is concluded that the presence of the Kir6.2 E23K genotype in Caribbean subjects with an immediate positive family history of diabetes does not confer significantly higher levels of biochemical risk factors for the development of type 2 diabetes.

Insulin promoter factor-1 mutations and diabetes in Trinidad: Identification of a novel diabetes-associated mutation (E224K) in an Indo-Trinidadian family

This study investigated the prevalence of insulin promoter factor-1 (IPF-1) mutations in familial early-onset diabetes mellitus in Trinidad. We screened 264 unrelated subjects with type 2 diabetes diagnosed before 40yr of age and a family history of diabetes for mutations in the minimal promoter and coding region of the IPF-1 gene (IPF1). This study population included 169 patients of East Indian descent (Indo-Trinidadians) 66 of African descent (Afro-Trinidadians), and 29 of mixed ancestry. We identified five IPF1 variants, including one new missense mutation E224K, the previously described diabetes-associated duplication P242 P243dupP, two silent mutations in the codons for Leu54 (c.162G>A) and Ala256 (c.768C>A), and a substitution in the 5'-untranslated region (c.-18C>T). The E224K mutation was found in two unrelated diabetic Indo-Trinidadians and 0 of 60 controls. It was present on the same haplotype in both patients suggesting a founder effect. The E224K mutation cosegregated with early-onset diabetes or impaired glucose tolerance in a large family, suggestive of the type 4 form of maturity-onset diabetes of the young rather than type 2 diabetes. Functional studies of E224K showed reduced transactivation activity. IPF1 mutations leading to synthesis of a mutant protein may contribute to the development of familial early-oneset diabetes/maturity-onset diabetes of the young in Indo-Trinidadians (AU)

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 percent in rural Cameroon, 2.0 percent in urban Cameroon, 8.5 percent in Jamaica, and 14.6 percent in Manchester, with no difference between sexes (men: 1.1 percent, 1.0 percent, 6.5 percent, 15.3 percent, women: 0.5 percent, 2.8 percent, 10.6 percent, 14.0 percent), 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.(Au)

Prevalence of diabetes and impaired glucose tolerance in Nigerians, Jamaicans and US blacks

The prevalence of type 2 diabetes, impaired glucose tolerance and associated risk factors were compared in sample surveys in Africa and the Caribbean with the Third National Health and Nutrition Survey (NHANES-III) from the United States. A total of 856 Nigerians, 1286 Jamaicans, and 1827 US blacks were included in the study. Body mass index (BMI) increased in a stepwise fashion across the three population groups, ie, 23 kg/m2 in Nigerians, 26 kg/m2 in Jamaicans, and 28 kg/m2 in US blacks. The persons aged 25-74, were 1 percent, 12 percent, 13 percent. Jamaican women were found to have the same prevalence of type 2 diabetes as US women (14 vs 13 percent, respectively); mean BMI was likewise very similar (28 kg/m2 in Jamaican and 29 kg/m2 in US women). BMI and waist-to-hip ratio were both associated with type 2 diabetes prevalence. Findings of this study confirm the marked gradient in type 2 diabetes risk among these genetically related populations and suggest that the blacks in the island nations of the Caribbean and the United States are at particularly high risk. Nigerians exhibited remarkably well-preserved glucose tolerance. Understanding the factors that limit the risk of type 2 diabetes in West Africa, beyond relative absence of obesity, would have considerable public health significance.(Au)

Ethnic differences in glucose tolerance: the diet (fatty acid) rather than genetic variation

This study examined the possible role of plasma fatty acids (FA) and serum lipid composition in ethnic differences in glucose tolerance (GT). In carefully taken population samples (77 percent response) aged 45-74 years, 75 g GT test results were compared between 100 African-Caribbeans (AfC) [53 women (w)], 188 white Europeans (60w) and 113 Gujratis (55w), excluding known diabetics. 2 hr normoglycaemic (ng) AfC (n=70) had considerably lower age and sex adjusted fasting non-esterified (NE) FA at 0.42 (mean, 95 percent CI 0.36-0.48) mmol/l vs 0.58 (0.52-0.64) mmol/l in Europeans and 0.58 (0.51-0.65) mmol/l in Gujratis (F=8.2, p=0.0004). NEfA were significantly (26-52 percent) greater in, with no ethnic difference between, glucose intolerants (GIT). Gujratis had higher proportion of serum linoleate (18.2n-6) at 35.3 (34-36.6 percent) than AfC (27.4, 26-29 percent) or whites (24, 23-26 percent) but half or less of docosahexanoate (22:6n-3) - 1.2(0.8-15)percent vs 2.7(2.3-3) percent and 2.4(2-2.8) percent in both ng and GIT groups. With BMI and insulin, NEFA were independently associated with 2 hr glucose accounting for much of the ethnic difference.(AU)

Prevalence of glucose intolerance and dyslipidaemias in Bermuda - Poster Presentation

Diabetes and dyslipidaemias are major problems in Bermuda. To assess the magnitude of this problem, we determined the prevalence of glucose intolerance

Standardised comparison of glucose tolerance and diabetes prevalence in four African/African-Caribbean populations in Britain, Jamaica and Cameroon

To study factors promoting the emergence of diabetes in African-Caribbean (AfC) as the second largest ethnic minority in Britain and how these compare with genetically similar populations in Jamaica (origin of 80 percent AfC) and Cameroon, using the same protocol we carried out 75g glucose tolerance tests in representative community samples aged 25-74 years, by WHO criteria. As results were similar by gender, sexes are combined here. [See table] Diabetes prevalence (age-standardised) increased from Africa to the Caribbean to Europe and was highest in Manchester men. Body mass index showed a striking increase from rural to younger urban Cameroonians. Increasing NIDDM prevalence is paralleled across site by changes in nutritional and lifestyle factors, also measured using standardised methods. Even in Cameroon, prevalence approaches rates in whites in Europe.(AU)

Nutritional influences on the emergence of diabetes mellitus and high blood pressure in Afro-origin populations in Cameroon, Jamaica, and Caribbean migrants to Europe - abstract

Our four nation study is establishing the role of nutrition in evolving diabetes mellitus (DM) and high blood pressure (BP) in these Afro-origin populations. Using highly standardized methods, we are testing whether increasing energy (particularly fat) and Na+ intakes, and decreased K+, Ca+ and antioxidant intakes, are associated with decreasing glucose tolerance (GT) and increasing BP within and between centres. Random community samples, aged 25 - 74 years, are stratified by sex up to 1,500/centre to generate sufficient index cases of impaired (I) GT and `high' BP (> 140 and/or 90 mm Hg but < 160 to 95 mm Hg) for an intervention trial and incident phase. During a 2-hr 759 glucose tolerance test (GTT), a food frequency questionnaire (FQQ), built up from food dairies and 24-hr recalls, and repeat 24-hr urines are supplying mean energy, fat, carbohydrate, fibre, protein and cation intakes. To date, 894 Jamaicans have been seen at the Spanish Town site, some 780 people (360 Afro-Caribbean) in Manchester, with 180 GT tested, 416 Cameroonians (246 urban) and a pilot study completed in Paris. Rates of IGT and DM run at approximately 8 percent and 14 percent in Jamaica, 15 percent of each in Manchester, and 4-8 percent in Cameroon through Jamaica to Manchester. Those at risk of hypertension (> 140 and/or 90 mm Hg) are similarly distributed. As baseline prevalence rates are established, the nutritionally-based intervention programme will be piloted as a randomized trial. Such efforts offer the chance for primary prevention of high BP, diabetes mellitus and their complications in these populations, before or as they face an epidemic from them (AU)

Relationship of glucose intolerance to coronary risk in Afro-Caribbeans compared with Europeans

Afro-Caribbeans have low mortality rates from coronary heart disease, despite a high prevalence of diabetes mellitus. We examined 1166 Afro-Caribbean and European men and women aged 40-64 years in a community survey in London, UK. Prevalence of glucose intolerance (combining impaired glucose tolerance, new and known diabetes) was 31 percent in Afro-Caribbeans and 14 percent in Europeans (p<0.001). In men, the prevalence of probable coronary heart disease was 6 percent in Afro-Caribbeans and 13 percent in Europeans (p<0.01). Triglyceride was lower in Afro-Caribbeans than Europeans; in men, HDL cholesterol was higher. Afro-Caribbeab men were less centrally obese, while Afro-Caribbean women were more centrally obese than their European counterparts. Fasting and 2-h insulin levels were higher in Afro-Caribbeans than Europeans. Glucose intolerance was associated with high triglyceride, low HDL cholesterol and central obesity in European but not in Afro-Caribbean men. In Europeans, fasting triglyceride was 1.49 mmol/l in normoglycaemic and 1.89 mmol/l in glucose intolerant men (p<0.05), in Afro-Caribbean men triglyceride was 1.08 and 1.22 mmol/l, respectively. Waist hip ratio was 0.94 in normoglycaemic, and 0.98 in glucose intolerant European men (p<0.001). In Afro-Caribbean men, waist hip ratio was 0.93 in both groups. At each level of insulin, glucose or central obesity, triglyceride was lower in Afro-Caribbean men and women than in Europeans. We speculate that despite high insulin levels, Afro-Caribbeans have a favourable lipoprotein pattern which persists in the presence of glucose intolerance, and may be related to body fat distribution. This could begin to explain their low rates of coronary heart disease (AU)

Diabetes mellitus and risk factors in a French West Indian island - abstract

Diabetes mellitus is an important cause of morbidity and mortality in the Caribbean. In order to design and implement specific prevention programmes, it is necessary to estimate the prevalence of glycaemic disorders and study the risk factors involved. This paper presents the results of such a study from a representative sample of the adult population in Guadeloupe. The estimated total prevalence of glycaemic disorders was 13.2 per cent of the adult population over 18 years of age. Impaired glucose tolerance (IGT) appeared in 7.4 per cent of subjects. The prevalence of diabetes mellitus was 5.8 per cent (95 per cent confidence interval: 4.4-7.2). Insulin-dependent patients represent 14 per cent of all diabetics. The associated factors studied were sex, age, obesity, parental diabetes status and ethnicity. The relative risk (RR) for age in non-obese non-diabetic parent patients was 5.1. In older subjects, RR for diabetic parent without obesity was 3.2 and for obesity alone 1.8. For obesity and diabetic parent, RR was 5.0. In this case, there was additivity of these two factors. Except age, the individual predominant factor of Diabetes mellitus was the presence of a diabetic parent; this was more evident in the small and closed Indian group. In the Public Health approach, i.e. taking into account the prevalence of each risk factor in the population, obesity was the most important. It is also the one and only factor which could be reached directly by a prevention programme (AU)

Glutathione, red cell sodium and glucose intolerance in Jamaican hypertension - abstract

Hypertensive patients have been shown to have both an increased intracellular sodium and glucose intolerance. The increased intracellular sodium has been proposed as the underlying defect responsible for the hypertension while the glucose intolerance is thought to be due to insulin resistance/hyperinsulinaemia, another feature of hypertension. Both the intracellular cation content and glucose tolerance are processes regulated by cell membrane receptors. It is therefore possible that an alteration of membrane mediated processes could result in the changes noted above. Decreases in glutathione (GSH) levels have been reported to alter cell membrane function as well as render the cell more susceptible to free radical damage. This study was undertaken to determine whether Jamaican hypertensives showed glucose intolerance and intracellular cations, and whether such changes could be associated with altered GSH status. Hypertensive patients being treated in the Hypertension Clinic and normotensive volunteers were studied. Blood samples were taken after an overnight fast and red cell sodium, potassium, blood glutathione, glycosylated haemoglobin and glycosylated plasma protein, were measured. Glycosylated plasma proteins and haemoglobin were measured as an index of glucose tolerance. Red cell sodium was higher in hypertensive than in control subjects. Potassium content was not different. Glycosylated haemoglobin and plasma proteins were higher in the hypertensives and blood glutathione concentration lower than in the normotensive individuals. The occurrence of high cell socium and glycosylated haemoglobin in the hypertensive patients supports the hypothesis of defective sodium transport and insulin receptor mechanisms contributing to the genesis of hypertension. The presence in this setting of a low glutathione concentration raises the question of the role of disordered thiol status in these abnormal membrane processes (AU)