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Chronic inflammation has a pathological role in many common diseases and is influenced by both genetic and environmental factors. Here we assess the role of genetic variation in selenoprotein S (SEPS1, also called SELS or SELENOS), a gene involved in stress response in the endoplasmic reticulum and inflammation control. After resequencing SEPS1, we genotyped 13 SNPs in 522 individuals from 92 families. As inflammation biomarkers, we measured plasma levels of IL-6, IL-1beta and TNF-alpha. Bayesian quantitative trait nucleotide analysis identified associations between SEPS1 polymorphisms and all three proinflammatory cytokines. One promoter variant, -105G --A, showed strong evidence for an association with each cytokine (multivariate P = 0.0000002). Functional analysis of this polymorphism showed that the A variant significantly impaired SEPS1 expression after exposure to endoplasmic reticulum stress agents (P = 0.00006). Furthermore, suppression of SEPS1 by short interfering RNA in macrophage cells increased the release of IL-6 and TNF-alpha. To investigate further the significance of the observed associations, we genotyped -105G --A in 419 Mexican American individuals from 23 families for replication. This analysis confirmed a significant association with both TNF-alpha (P = 0.0049) and IL-1beta (P = 0.0101). These results provide a direct mechanistic link between SEPS1 and the production of inflammatory cytokines and suggest that SEPS1 has a role in mediating inflammation.

This study aimed to identify genes that are expressed in skeletal muscle, encode proteins with functional significance in mitochondria, and are associated with type 2 diabetes.We screened for differentially expressed genes in skeletal muscle of Psammomys obesus (Israeli sand rats), and prioritised these on the basis of genomic localisation and bioinformatics analysis for proteins with likely mitochondrial functions.We identified a mitochondrial intramembrane protease, known as presenilins-associated rhomboid-like protein (PSARL) that is associated with insulin resistance and type 2 diabetes. Expression of PSARL was reduced in skeletal muscle of diabetic Psammomys obesus, and restored after exercise training to successfully treat the diabetes. PSARL gene expression in human skeletal muscle was correlated with insulin sensitivity as assessed by glucose disposal during a hyperinsulinaemic-euglycaemic clamp. In 1,031 human subjects, an amino acid substitution (Leu262Val) in PSARL was associated with increased plasma insulin concentration, a key risk factor for diabetes. Furthermore, this variant interacted strongly with age to affect insulin levels, accounting for 5% of the variation in plasma insulin in elderly subjects.Variation in PSARL sequence and/or expression may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome.

Cardiovascular disease (CVD) is the most common complication of non-insulin-dependent diabetes mellitus (NIDDM) in Europeans,“z and accounts for at least 66% of deaths in NIDDM patients.3 People with diabetes have a risk of CVD two to five times that of nondiabetic individuals.‘,‘,’ Macrovascular disease, in both diabetic and nondiabetic people, was thought to be rare in developing countries that are undergoing large cultural transitions, but there is now evidence that this theory may need revision.ls5 The main implication of macrovascular diabetic disease, from the public-health perspective, is the human distress and disability associated with it, and the socioeconomic costs from premature morbidity and mortality.” Although CVD risk is consistently increased in people with diabetes, it reflects the prevalence of CVD in the non-diabetic members of that population.‘Thus, even in a low-prevalence nation, such as Japan, a person with diabetes has a CVD risk twice that of the non-diabetic person. This risk, however, is still only a fraction of the risk of a non-diabetic person from a western culture.’ But exposure to ‘westernised’ environments rapidly raises the atherosclerotic risk in people from lowprevalence nations.’ Most of the increase in atherosclerotic risk has occurred in newly industrialised nati0ns.Q’ These findings call for a reassessment of the impact of macrovascular complications, since they were rare in these populations when they lived a ‘traditional’ way of life.5,8

To evaluate how to most efficiently screen populations to detect people at high risk of incident Type 2 diabetes and those with prevalent, but undiagnosed, Type 2 diabetes. Data from 5814 adults in the Australian Diabetes, Obesity and Lifestyle study were used to examine four different types of screening strategies. The strategies incorporated various combinations of cut-points of fasting plasma glucose, the non-invasive Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK1) and a modified version of the tool incorporating fasting plasma glucose (AUSDRISK2). Sensitivity, specificity, positive predictive value, screening costs per case of incident or prevalent undiagnosed diabetes identified and intervention costs per case of diabetes prevented or reverted were compared. Of the four strategies that maximized sensitivity and specificity, use of the non-invasive AUSDRISK1, followed by AUSDRISK2 in those found to be at increased risk on AUSDRISK1, had the highest sensitivity (80.3%; 95% confidence interval 76.6-84.1%), specificity (78.1%; 95% confidence interval 76.9-79.2%) and positive predictive value (22.3%; 95% confidence interval 20.2-24.4%) for identifying people with either prevalent undiagnosed diabetes or future incident diabetes. It required the fewest people (24.1%; 95% confidence interval 23.0-25.2%) to enter lifestyle modification programmes, and also had the lowest intervention costs and combined costs of running screening and intervention programmes per case of diabetes prevented or reverted. Using a self-assessed diabetes risk score as an initial screening step, followed by a second risk score incorporating fasting plasma glucose, would maximize efficiency of identifying people with undiagnosed Type 2 diabetes and those at high risk of future diabetes.

OBJECTIVE: To compare the performance of body mass index (BMI) against waist circumference, waist: hip ratio (WHR) and waist: height ratio in the discrimination of hypertension in ethnically diverse populations. METHODS: Meta-analysis of 19 cross-sectional studies. MAIN OUTCOME MEASURES: Discrimination of hypertension (SBP/DBP ≥ 140/90 mmHg) was adjudicated from Receiver Operating Characteristic curves; optimum thresholds were defined as those that maximized sensitivity plus specificity. RESULTS: Irrespective of which measure of overweight was used, the strength of the association with blood pressure was consistently greater among Asians compared with Caucasians or Pacific Islanders; however, in all regions, and for all anthropometric measures, the increment in blood pressure, and the additional risk of hypertension, were broadly similar for the same relative increment in each of the four measures. Optimum thresholds varied by region; WHR was the most consistent between the regions, with thresholds of 0.92-0.94 for men and 0.80-0.88 for women. No anthropometric variable was systematically better than others at the discrimination of hypertension. CONCLUSIONS: Blood pressure is similarly associated with each of the four measures of overweight chosen, but the associations were stronger among Asians. WHR has advantages in terms of consistency of thresholds for hypertension across ethnic groups in the Asia-Pacific.

Objective: We examined the effect of a 14-month progressive resistance training (PRT) program on endothelial function in both a supervised training (Center) group and non-supervised training (Home) group of patients with type 2 diabetes. We studied 28 men and women with type 2 diabetes who participated in a 14-month PRT involving an initial 2-month supervised program and a 12-month maintenance program. Methods: Endothelial function testing was performed through laser doppler flow responses in the skin microcirculation to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (NaNP) and doses of 4, 8 and 16 mC were used. Measurements of vascular response (VR), HbA1c, weight and blood pressure were performed at 0, 2 and 14 months. Results: VR to ACh and NaNP was significantly increased at 14 months compared with baseline in both the Center and Home groups. However, no between-group differences were observed. A significant correlation was observed between HbA1c and VR to ACh at baseline and 8 weeks using 8 mC dose of ACh. There was a strong correlation between HbA1c at baseline and VR at 14 months using all three doses of ACh (4 mC:r = -0.546, p = 0.003, 8 mC:r = -0.470, p = 0.002, 16 mC:r = -0.547, p = 0.006). Conclusions/interpretation: Endothelial function is improved following 14 months of PRT in type 2 diabetes both in a supervised and non-supervised program. Strong correlations with HbA1c including initial HbA1c levels suggest that glycemic control may be an important factor in long-term regulation of endothelial function.

We sought to determine the risk of diabetes and IGT/IFG with grand multiparity.Women, agedor =25 years, from the Australian Diabetes, Obesity and Lifestyle Study and the Crossroads Undiagnosed Disease Study (a rural study in Victoria, Australia), participated in a household census (response 67 and 70%, respectively), subsequently attending a biomedical examination that included an oral glucose tolerance test (58% [6198] and 69% [819]).After adjusting for age, obesity and socio-economic status, diabetes, but not IGT/IFG, was less common among women with a parity of 1 to 2 (odds ratio [OR]=0.64 [0.48-0.84]) and 3 to 4 (OR=0.72 [0.53-0.96]) than in grand multiparous women. This relationship was unrelated to past hysterectomy, use of the oral contraceptive pill or menopausal status.Grand multiparity is associated with an increased risk of diabetes but not of IGT/IFG. We postulate that parity accelerates transition from IGT/IFG to diabetes, more than it does transition from normal glucose tolerance to IGT/IFG.

OBJECTIVE: To investigate whether skeletal muscle gene expression of calpain 3 is related to obesity and insulin resistance. DESIGN: Cross-sectional studies in 27 non-diabetic human subjects and in Psammomys obesus, a polygenic animal model of obesity and type 2 diabetes. MEASUREMENTS: Expression of CAPN3 in skeletal muscle was measured using Taqman fluorogenic PCR. In the human subjects, body composition was assessed by DEXA and insulin sensitivity was measured by euglycemic–hyperinsulinemic clamp. In Psammomys obesus, body composition was determined by carcass analysis, and substrate oxidation rates, physical activity and energy expenditure were measured by whole-body indirect calorimetry. RESULTS: In human subjects, calpain 3 gene expression was negatively correlated with total (P=0.022) and central abdominal fat mass (P=0.034), and with blood glucose concentration in non-obese subjects (P=0.017). In Psammomys obesus, calpain 3 gene expression was negatively correlated with circulating glucose (P=0.013) and insulin (P=0.034), and with body fat mass (P=0.049). Indirect calorimetry revealed associations between calpain 3 gene expression and carbohydrate oxidation (P=0.009) and energy expenditure (P=0.013). CONCLUSION/INTERPRETATION: Lower levels of expression of calpain 3 in skeletal muscle were associated with reduced carbohydrate oxidation and elevated circulating glucose and insulin concentrations, and also with increased body fat and in particular abdominal fat. Therefore, reduced expression of calpain 3 in both humans and Psammomys obesus was associated with phenotypes related to obesity and insulin resistance.

A study of the Hong Kong Chinese showed that the majority of subjects with young-onset diabetes (age of diagnosis35 years) present with a phenotype suggestive of Type 2 diabetes mellitus, although up to 50% subsequently need insulin treatment. The aim of this study was to use a combination of clinical, genetic and immunological markers to characterize the disease phenotype further in such individuals and to determine whether the requirement for insulin is the result of autoimmune disease.One hundred and thirty-seven Hong Kong Chinese with young-onset diabetes were studied, irrespective of their mode of presentation. The subjects were typed for alleles of the HLA-DR and -DQ genes and investigated for the presence of autoantibodies to glutamic acid decarboxylase (GAD). Plasma C-peptide concentration and requirement for insulin were also determined.One hundred and three subjects presented with a syndrome resembling Type 2 diabetes, while 34 presented with Type 1 diabetes. Of the former group, 35 patients (34.0%) were insulin-deficient, 16 (15.5%) were insulin-treated and seven (6.9%) were positive for GAD autoantibodies. Among the GAD-positive subjects presenting with Type 2 diabetes, the HLA-DRB1*03 allele may be a marker of early progression to insulin therapy.Seven subjects with Type 2 diabetes at presentation had autoantibodies to GAD. Causes other than GAD autoimmunity, however, must be sought to explain the high prevalence of insulin deficiency observed in the Chinese patients. This study highlights the heterogeneity of the pathogenic processes leading to the diabetic phenotype.

To investigate whether relative baseline leptin levels predict long-term changes in adiposity and/or its distribution.In a longitudinal study of 2888 nondiabetic Mauritians aged 25 years to 74 years who participated in population-based surveys in 1987 and 1992, changes in body mass index (BMI), waist/hip ratio (WHR), and waist circumference were compared between "hyperleptinemic," "normoleptinemic," and "hypoleptinemic" groups. "Relative leptin levels" were calculated as standardized residuals from the regression of log10 leptin on baseline BMI to provide a leptin measure independent of BMI. Analyses were performed within each sex. A linear regression model was used to assess the effect of standardized residuals on changes in BMI, WHR, and waist circumference, independent of baseline BMI, age, fasting insulin, and ethnicity.After adjusting for age and baseline BMI by analysis of covariance, there was no difference in changes in BMI, WHR, or waist circumference between men with low, normal, or high relative leptin levels. Among women, there was a significant difference in deltaWHR across leptin groups, such that the largest increase occurred in the "normal" leptin group. For both men and women, the linear regression models explained approximately 10% of variation in dependent variables, and the only significant independent variables were age, BMI, and being of Chinese origin, compared with Indian origin.These findings do not support a role for leptin concentration in predicting weight gain or changes in fat distribution in adults over a 5-year period.

The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered toor =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasmaor =6.1 to7.0 mmol l(-1); whole bloodor =5.6 to6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.

Fibrocalculous pancreatic diabetes (FCPD) is a type of diabetes secondary to tropical chronic non-alcoholic pancreatitis. Little is known about the aetiopathogenesis of FCPD. We studied glutamic acid decarboxylase antibodies (GAD-Ab) and islet cell antibodies (ICA) in patients with FCPD and compared the results with Type 1 (insulin dependent) diabetes mellitus, Type 2 (non-insulin-dependent) diabetes mellitus and non-diabetic subjects in Southern India. The prevalence of GAD-Ab was 7.0% (95% Confidence Interval (CI) 1.9-17.2) in FCPD, 47.5% (CI 31.4-64.0) in Type 1 (p0.001 compared to FCPD), 5.6% (CI 1.5-13.9) in Type 2 (non-significant (NS) compared to FCPD) and 0% in controls. The prevalence of ICA was 6.3% (CI 1.2-17.4) in FCPD, 53.8% (CI 37.1-70.0) in Type 1 (p0.001 compared to FCPD), 9.9% (CI 4.0-19.4) in Type 2 (NS compared to FCPD) and 4.7% (CI 0.4-16.1) in controls. The data suggest that in FCPD, the frequency of auto-antibodies is low and its aetiology is probably not linked to autoimmunity in the majority of the patients.

It has been shown previously in smaller studies that fasting serum leptin and insulin concentrations are highly correlated, and insulin sensitive men have lower leptin levels than insulin resistant men matched for fat mass. We have examined the association between insulin resistance (assessed by fasting insulin) and leptin after controlling for overall and central adiposity in a population-based cohort.Leptin levels were compared across insulin resistance quartiles within three categories of obesity (tertiles of body mass index (BMI)). Partial correlation coefficents and multiple linear regression models were used to assess the relationship between leptin and fasting insulin after adjusting for BMI and waist to hip ratio (WHR) or waist circumference.Subjects were normoglycemic participants of a 1987 non-communicable diseases survey conducted in the multiethnic population of Mauritius. 1227 men and 1310 women of Asian Indian, Creole and Chinese ethnicity had normal glucose tolerance and fasting serum leptin measurements.Mean serum leptin concentration increased across quartiles of fasting insulin in each BMI group and gender, after controlling for BMI, WHR and age. Furthermore, fasting insulin was a significant determinant of serum leptin concentration, independent of BMI and WHR, in both men and women. Similar results were found if waist circumference replaced BMI and WHR in the model.These results suggest that insulin resistance/concentration may contribute to the relatively wide variation in leptin levels seen at similar levels of body mass or alternatively, leptin may play a role in the etiology of insulin resistance. Further studies will be important to determine whether the hyperleptinemia/insulin resistance relationship has a role in the natural history of obesity, Type 2 diabetes mellitus and the other metabolic abnormalities associated with insulin resistance.

Presymptomatic autoantibody markers of insulin-dependent (Type 1) diabetes mellitus (IDDM) are less well characterized in adults than in children. We quantitated anti-GAD, anti-ICA512 and ICA by titration to endpoint and compared frequencies and levels in 139 Finnish women from whom 390 serum samples had been archived during antecedent pregnancies for 10 years before and up to 1 year after diagnosis of diabetes. Also, we compared the autoantibody status in adults with IDDM with that of children with newly diagnosed IDDM. Of the 35 women seropositive for 1 or more autoantibodies, 77% developed IDDM, 11% non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), 9% gestational diabetes mellitus requiring insulin (GDM-ins) and 3% GDM controlled by diet. The frequency of antibodies during the 10-year presymptomatic period was 83% for anti-glutamic acid decarboxylase (GAD), 52% for anti-ICA512 and 41% for islet cell antibodies (ICA) for those who developed IDDM, 25%, 17%, and 0% for NIDDM, 12%, 4%, and 8% for GDM-ins and 1%, 0%, and 1% for GDM-diet. Anti-GAD was found most consistently in early samples; 13 of 15 with a single autoantibody at their first test had anti-GAD. Among those who developed IDDM, the frequency of anti-GAD was constant, anti-ICA512 increased threefold, and ICA increased slightly before diagnosis. Levels of the autoantibodies varied between subjects, but were relatively stable in individual subjects. Comparison of tests on the women, and children after diagnosis of IDDM, showed the frequencies and levels to be the same for anti-GAD but lower for anti-ICA512 and ICA in adults. Our observations show in women the long latency of seropositivity before overt IDDM, the predominance of anti-GAD among these three serological markers, and the presence of these markers in NIDDM presumably representing a NIDDM phase of autoimmune insulitis.

There is evidence from animal models that postprandial insulin hypersecretion may precede the development of obesity and insulin resistance, but it is not clear if this is the case in humans. Recently, two longitudinal studies have suggested that insulin resistance acts to limit further weight gain rather than to promote it. The relationship of markers of insulin sensitivity and secretion to changes in weight and the waist to hip ratio (WHR) was therefore examined in nondiabetic Asian Indian (n = 2,169), Creole (n = 798), and Chinese (n = 189) Mauritians over a 5-year follow-up period. Younger age and lower initial body mass index (BMI) were consistent independent predictors of increase in weight in all sex-ethnic subgroups, and older age, higher BMI, and lower WHR were associated with change in WHR. Insulin sensitivity was assessed by homeostatic model assessment (HOMAS), as well as by fasting insulin and the ratio of fasting insulin to glucose. Insulin resistance predicted weight gain in Chinese men independently of baseline age and BMI. In Asian Indian and Creole men and women, these correlations were in the opposite direction (ie, insulin sensitivity predicted weight gain) but became nonsignificant when age and BMI were controlled. There was little relationship of insulin resistance/sensitivity to the change in WHR once baseline BMI was controlled. These data provide suggestive but not convincing evidence that insulin resistance may limit weight gain, and contradictory evidence in one ethnic group that insulin resistance promotes weight gain.

A total of 359 Wanigelas from Papua New Guinea and 1041 Nauruans had urinary albumin concentrations (UAC), serum insulin, and a number of cardiovascular disease (CVD) risk factors measured during population-based surveys of non-insulin-dependent diabetes mellitus. These data were used to explore the hypothesis that microalbuminuria is closely associated with insulin resistance and the metabolic syndrome. In both Nauruans and Wanigelas, worsening glucose tolerance was associated with increasing prevalence of micro- and macroalbuminuria. Within each category of glucose tolerance, microalbuminuria was associated with general worsening of cardiovascular risk factors including lipid concentrations, blood pressure and obesity, although few of the associations were statistically significant. Correlations between UAC and markers of insulin resistance (fasting insulin, fasting insulin/glucose ratio and HOMAS%, a computer-modelled estimate of insulin sensitivity) were weak and inconsistent irrespective of glucose tolerance status. Relationships between insulin sensitivity and urinary albumin in normoglycaemic Wanigelas and Nauruans, and in diabetic Nauruans, were no longer significant after adjusting for fasting glucose and body mass index. While microalbuminuria in Nauruans and Wanigelas was associated with cardiovascular risk factors irrespective of glucose tolerance, it seems unlikely on the basis of these results that the relationship is mediated through a common association with insulin resistance.

This study reports 11-year all-cause and cause-specific mortality rates according to baseline glucose tolerance for a population-based sample of adult Melanesian and Indian Fijians (n = 2638), first surveyed in 1980. Risk factors for all-cause and cardiovascular disease (CVD) mortality in subjects with non-insulin-dependent diabetes (NIDDM) are also described. The baseline survey included 75 g oral glucose tolerance tests, measurements of blood pressure, body mass index, and triceps skinfold, assays of plasma cholesterol and triglycerides, electrocardiograms, and details of smoking habits and physical activity. Mortality status was ascertained for 2546 subjects through surveillance of death certificates, medical records and interview of subjects (or relatives). Mortality rates were increased in diabetic men and women of both ethnic groups: relative risks compared to subjects without diabetes at baseline were 1.7 (CI:0.9-3.1) and 2.0 (1.1-3.7) in Melanesian and 4.2 (2.7-6.5), 3.2 (1.9-5.7) in Indian men and women, respectively. A large proportion of mortality among diabetic subjects was attributed to CVD (62%, 66% in Melanesian and 54%, 58% in Indian men and women, respectively). Mortality rates tended to be higher in Melanesians than Indians, except for diabetic men where Indians had higher total and cardiovascular disease rates. In contrast to non-diabetic Fijians, diabetic women of both ethnic groups lost their relative protection from coronary heart disease (CHD). Cox regressions for diabetic subjects showed age and fasting plasma glucose to be independent predictors of all-cause mortality in men, and age, body mass index (inversely) and systolic blood pressure in women, but lipid concentrations, and cigarette smoking were not related. After accounting for conventional CVD risk factors, diabetes conferred significantly increased risk of total, CVD, and CHD mortality. The mortality experience of Melanesian and Indian Fijians with NIDDM is similar to that documented in developed populations, with excess mortality due to cardiovascular causes.

The island nation of Mauritius, located in the southwest Indian Ocean, has a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM) among all of its ethnic groups (Hindu and Muslim Indians, African-origin Creoles, and Chinese). These high rates of NIDDM among groups of varying genetic background provide strong support for the importance of environmental components in the etiology of the disease. Research in Mauritius using a simple activity scale has suggested that physical inactivity may be one of these components. The current investigation further examined the association between glucose tolerance and physical activity in middle-aged nondiabetic residents of Mauritius using a more extensive physical activity questionnaire (the Modifiable Activity Questionnaire). Excluding individuals with NIDDM, a statistically significant (P0.05) inverse relationship between physical activity and 2-h post-load glucose concentration was found for both males (rho = -0.14) and females (rho = -0.11). Stratifying by ethnic group, similar inverse correlations were observed in Hindu, Creole, and Chinese males, and in Hindu females (P0.05), as well as weaker relationships in Muslim males and Creole females (P0.10). Total physical activity remained an independent predictor of 2-h post-load glucose concentration after controlling for body mass index, waist-hip ratio, age, and family history of NIDDM. These data are supportive of a potentially important role of physical activity in the prevention of NIDDM in middle-aged inhabitants of Mauritius.

Vibration perception threshold (VPT) was measured in 1185 Indian, Creole, and Chinese men and women in Mauritius, where the current prevalence of diabetes mellitus in adults aged 25-74 years is estimated to be 13%. Vibration perception threshold was measured using a biothesiometer, at seven sites in the hand, wrist, foot, and ankle, during a population survey in 76% of 574 known diabetic patients (KDM), 79% of 525 newly diagnosed diabetic patients (NDM), 18% of 1121 subjects with impaired glucose tolerance (IGT), and in 127 normal subjects. The association of VPT with glucose tolerance and other risk factors was assessed in order to identify individuals most at risk of foot ulceration and to determine whether risk factors and normal levels for VPT in these ethnic groups were consistent with those reported for Caucasians. After adjusting for age and height, geometric mean VPT at six of seven sites increased significantly with worsening glucose tolerance and increasing duration of diabetes in both men and women, VPT also increased significantly with level of fasting plasma glucose in men, but not women. Smoking and alcohol consumption had no effect on VPT, and body-mass index (BMI) was positively associated only at some sites. Chinese subjects had lower VPTs than Indians or Creoles. In multiple linear regression models, age, male gender, duration of diabetes, ethnic group, and height (lower extremity sites) were significantly associated with VPT among diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Obesity and pattern of fat distribution are both important factors related to poor health outcomes. Many measures of obesity and fat distribution pattern have been employed by different authors and to facilitate interpopulation comparisons and interpretation of secular trends it is necessary that standardized methods for measurement and classification are set in place. The use of BMI as a measure of fatness for epidemiological studies is widely accepted, easily measured and BMI predicts morbidity and mortality in many populations. The most appropriate level at which to define obesity is a matter of debate but systems which use BMIor = 25 andor = 30 kg/m2 as overweight, and BMI30 kg/m2 as obese for all adults are simple, easily remembered, already widely used and BMIs above 30 kg/m2 are clearly associated with increased risk of morbidity and mortality. In some populations there may be a case for using a lower cut-off but not unless there is specific evidence to support this. For the present WHR is probably the best method for assessing fat distribution, although waist circumference on its own may be more useful in determining risk levels. Standard sites for measurement of both waist and hip girths have been described. There is a large variation in the prevalence of obesity across the populations for which data is available, with high prevalences of obesity and dramatic secular trends especially apparent in modernizing Pacific Island populations. The 'thrifty genotype' hypothesis has been invoked to try and explain this situation. The clustering of obesity, NIDDM and CVD risk factors has been recognized and various 'syndromes' have been described which group different factors together, with hyperinsulinaemia and insulin resistance proposed as the underlying problem.

The aim of the study was to investigate whether the constellation of cardiovascular disease risk factors, described as Insulin Resistance Syndrome, exists in the multi-ethnic population of Mauritius, and to assess whether hyperinsulinaemia is the key feature of this syndrome. A sample of 5080 Mauritian subjects (aged 25-74 years) was examined in a noncommunicable diseases survey in 1987. Survey procedure included an oral glucose tolerance test, and anthropometric, blood pressure, plasma lipids and serum insulin measurements. Abnormal glucose tolerance (diabetes and impaired glucose tolerance), general obesity, upper-body obesity, hypertension, low HDL-cholesterol, and hypertriglyceridaemia were defined as risk factor conditions. Mean values for a series of risk factor variables were compared between reference subjects (no risk factors) and those with a risk factor condition (either one condition only, or in combination with one or more others). Prevalence estimates for each risk factor condition in combination with three or more other conditions were three to four times greater than expected by chance, and levels of risk factors for subjects with more than one risk factor condition were further away from the reference levels than for those with just one condition. Fasting and 2-h serum insulin levels were elevated for each condition when in combination with others, or to a lesser extent when isolated. However, this was not the case for isolated hypertension where insulin levels were not elevated. When adjusted for age, sex, and body mass index, insulin levels were only significantly elevated in subjects with upper-body obesity if in association with general obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship of 2-hour (post-75 g oral glucose) serum insulin levels with plasma glucose levels was studied in a population-based random sample comprising 2,627 Hindu Indians, 685 Muslim Indians, 1,351 Creoles (African, European, and Indian admixture), and 415 Chinese from the Indian Ocean island of Mauritius. Known diabetic subjects taking oral hypoglycemic drugs or insulin were excluded from these analyses; 64% of all diabetic subjects had usable glucose and insulin data. Both fasting and 2-hour postload insulin levels were significantly higher in women than in men, and levels in both sexes were significantly greater in Hindu and Muslim Indian subjects than in Creoles or Chinese even after controlling for differences in age, body mass index (BMI), waist to hip ratio (WHR), and plasma glucose level. Levels in Muslims were higher than those in Hindus; it was unclear whether these ethnic differences represented hereditary or unmeasured environmental factors closely associated with ethnicity. All four ethnic groups demonstrated similar inverted U- or V-shaped curves when 2-hour insulin was plotted against either basal or 2-hour glucose. Both quadratic (U) and two-piece (V) regression models improved over linear models for 2-hour insulin versus either fasting or 2-hour glucose in all ethnic groups, although in statistical terms they were good models only for the 2-hour glucose comparison. The two-piece models were associated with modest increases in R2 compared with the quadratic models, but it was not possible to precisely determine optimal turning points with either model. However, in all ethnic groups, 2-hour insulin levels decreased above glucose levels of 7.1 to 7.8 (fasting) and 11.3 to 13.5 mmol/L (2-hour) in quadratic models, and 7.5 to 9.5 (fasting) and 8.5 to 10.5 mmol/L (2-hour) in two-piece models. The shape and point of inflection of the quadratic and two-piece curves were influenced little by gender, obesity, fat distribution, and physical activity. These results are in accord with those observed in cross-sectional and longitudinal studies in other ethnic groups, and support the generality of the plasma glucose levels currently used to define diabetes mellitus, which physiologically correspond with a decrease in beta-cell responsiveness to glucose. Asian Indians appear to have an ethnic propensity to hyperinsulinemia that is not explained by obesity or adverse fat distribution.

There is conflicting evidence of a link between circulating insulin concentrations and blood pressure. The aim of this study, therefore, was to investigate this relationship in a representative population sample of different ethnic groups.A cross-sectional study was performed, using a random cluster sample of 5080 adults aged 25-74 years from the Indian Ocean island of Mauritius.Glucose tolerance was assessed with a 75-g oral glucose tolerance test. Hypertension and glucose tolerance were classified using World Health Organization criteria. Subjects known to have diabetes before the survey were excluded from these analyses, leaving 3104 Asian Indian, 1256 African-origin Creole and 384 Chinese subjects eligible for this study.There were statistically significant linear correlations between fasting and 2-h insulin and mean blood pressure in all sex-ethnic subgroups, except for Chinese men. However, after controlling for age and the body mass index, partial correlations were much reduced and remained significant only for fasting insulin in Indian men (r = 0.07, P0.01) and women (r = 0.09, P0.001) and 2-h insulin in Chinese women (r = 0.15, P0.05). After controlling for age and body mass index, mean fasting and 2-h insulin concentrations were not significantly different between hypertensive and normotensive subjects in any of 36 possible subgroups defined by ethnic group, gender or glucose tolerance (normal, impaired glucose tolerance or newly diagnosed diabetes). In both men and women with normal glucose tolerance (ethnic groups combined) there was no evidence of increasing systolic or diastolic blood pressure across quartiles of either fasting or 2-h serum insulin within any quartile of the body mass index. By contrast, at any given level of serum insulin there was a clear association between an increasing body mass index and increasing blood pressure, suggesting strongly that insulin is not the final pathway by which obesity influences blood pressure.This study of three ethnic groups does not support the hypothesis that the circulating insulin concentration is an independent determinant of blood pressure in populations.

Associations with insulin resistance and islet beta-cell function have been studied cross-sectionally in a population-based sample of 4278 Mauritians comprising Asian Indian, Creole and Chinese subjects. Insulin resistance and beta-cell function were estimated by a computer solved model based on fasting plasma glucose and insulin concentrations. Insulin resistance increased with declining glucose tolerance, whereas beta-cell function was highest in subjects with impaired glucose tolerance (IGT) and lowest in those with non-insulin-dependent diabetes mellitus (NIDDM). Indian subjects had the highest beta-cell function, while ethnic differences in insulin sensitivity were less marked. This may indicate that deranged beta-cell function rather than insulin resistance is the primary determinant of hyperinsulinaemia and glucose intolerance in Asian Indians. beta-Cell function declined with age more sharply than did insulin sensitivity, suggesting that the age-related decline in glucose tolerance is primarily related to loss of beta-cell function. Body mass index, waist/hip ratio, physical inactivity and female sex were independently associated with insulin resistance and beta-cell function. Subjects with a family history of diabetes had increased insulin resistance, irrespective of glucose tolerance. This or similar models may have application in longitudinal population-based studies which seek to determine the relative contributions of insulin resistance and beta-cell function to the aetio-pathogenesis of NIDDM.

Mauritius, a multiethnic island nation in the southwestern Indian Ocean, has one of the world's highest diabetes mortality rates. The prevalence of both impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) was investigated in 5080 Muslim and Hindu Indian, Creole (mixed African, European, and Indian origin), and Chinese Mauritian adults aged 25-74 yr who were selected by random cluster sampling. Based on a 75-g oral glucose tolerance test and World Health Organization criteria, the age-standardized prevalence of IGT was significantly greater in women (19.7%, 95% confidence interval [CI] 18.1-21.2) than in men (11.7%, CI 10.5-12.8). By contrast, the prevalence of NIDDM was similar in men (12.1%, CI 10.9-13.4) and women (11.7%, CI 10.5-12.8) for all ethnic groups combined. The sex difference in IGT prevalence was seen in all ethnic groups, but for NIDDM, the sex difference was not consistent across ethnic groups. However, age- and sex-standardized prevalence of IGT and NIDDM was remarkably similar across ethnic groups (16.2 and 12.4% in Hindu Indians, 15.3 and 13.3% in Muslim Indians, 17.5 and 10.4% in Creoles, and 16.6 and 11.9% in Chinese, respectively). Three new cases of diabetes were diagnosed for every two known cases. The high prevalence of abnormal glucose tolerance in Indian subjects is consistent with studies of other migrant Indian communities, but the findings in Creole and, in particular, Chinese subjects are unexpected. Potent environmental factors shared between ethnic groups in Mauritius may be responsible for the epidemic of glucose intolerance.

The production of organic acids in severe diabetic acidosis was studied to determine the contribution of various acids and to reassess alkali requirements. In 11 patients the mean total concentration of determined organic acids was 16 mEq/l., while the mean estimated base deficit was 24 mEq/l. Acetoacetic and beta-hydroxybutyric acids accounted for 75% of measured organic acid. In 10 patients the mean amount of sodium bicarbonate administered for correction of the acidosis was 185 mEq, while the mean requirement was 394 mEq.These findings imply that the methods commonly used to determine the base deficit and the alkali requirements in patients with diabetic acidosis may be invalid. The prompt administration of alkali should be limited, and we suggest that the blood pH should be restored only to 7.25.

A study of the effect of obesity on glucose tolerance in a Polynesian population (Western Samoa) has not shown a consistent relationship between the two. Although there was a trend for increasing age-standardized prevalence of impaired glucose tolerance and diabetes mellitus with increasing body mass index in males, no such trend was observed in females. The impressive differences in prevalence of abnormal glucose tolerance between rural and urban groups was altered little by adjusting for differences in distribution of body mass index. Environmental factors, such as diet, physical activity, and stress, acting independently of adiposity must have contributed significantly to the observed rural/urban differences in prevalence of abnormal glucose tolerance in Western Samoans.

The results in 116 diabetics who were performing long-term home blood-glucose monitoring (HBGM) are presented. By means of Dextrostix and portable glucose meters at home and at work, patients recorded blood glucose (BG) profiles during original treatment and subsequent adjustment, and were followed up for four to 18 months. Initially marked fluctuations in BG levels occurred, with 67% of patients demonstrating hypoglycaemia (clinically silent in 53%) followed by rebound hyperglycaemia (the Somogyi effect). Adjustment of the insulin regimen resulted in reduction in standard deviation of BG concentration from a mean of 4.4 mmol/L to 2.7 mmol/L (P less than 0.001), thus avoiding both hypoglycaemia and extreme hyperglycaemia. Daily insulin dose decreased from a mean of 44 (+/- 21 SD) units to 30 (+/- 12 SD) units per day (P less than 0.001), and the insulin regimens used are described. The results of urine tests correlated poorly with those of HBGM in 67% of patients. Patient acceptance of HBGM was excellent, and it has permanently replaced urine testing in 96% of the subjects. Management based on HBGM resulted in improved diabetic control and life-style, and reduced the frequency of hospital admissions. The need for adequate education in technique and supervision is stressed. HBGM is superior to, and more acceptable than, urine testing as a method of monitoring diabetic control.