HOMA insulin sensitivity index and the risk of all-cause mortality and cardiovascular disease events in the general population: the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) study.

AIMS/HYPOTHESIS: We assessed whether the relationships between insulin sensitivity and all-cause mortality as well as fatal or non-fatal cardiovascular disease (CVD) events are independent of elevated blood glucose, high blood pressure, dyslipidaemia and body composition in individuals without diagnosed diabetes. METHODS: Between 1999 and 2000, baseline fasting insulin, glucose and lipids, 2 h plasma glucose, HbA(1c), anthropometrics, blood pressure, medication use, smoking and history of CVD were collected from 8,533 adults aged >35 years from the population-based Australian Diabetes, Obesity and Lifestyle study. Insulin sensitivity was estimated by HOMA of insulin sensitivity (HOMA-%S). Deaths and fatal or non-fatal CVD events were ascertained through linkage to the National Death Index and medical records adjudication. RESULTS: After a median of 5.0 years there were 277 deaths and 225 CVD events. HOMA-%S was not associated with all-cause mortality. Compared with the most insulin-sensitive quintile, the combined fatal or non-fatal CVD HR (95% CI) for quintiles of decreasing HOMA-%S were 1.1 (0.6-1.9), 1.4 (0.9-2.3), 1.6 (1.0-2.5) and 2.0 (1.3-3.1), adjusting for age and sex. Smoking, CVD history, hypertension, lipid-lowering medication, total cholesterol and waist-to-hip ratio moderately attenuated this relationship. However, the association was rendered non-significant by adding HDL. Fasting plasma glucose, but not HOMA-%S significantly improved the prediction of CVD, beyond that seen with other risk factors. CONCLUSIONS/INTERPRETATION: In this cohort, HOMA-%S showed no association with all-cause mortality and only a modest association with CVD events, largely explained by its association with HDL. Fasting plasma glucose was a better predictor of CVD than HOMA-%S.

Validity of self-reported cardiovascular disease events in comparison to medical record adjudication and a statewide hospital morbidity database: the AusDiab study.

Epidemiological studies often rely on self-reported cardiovascular disease (CVD) information, but this may be inaccurate. We investigated the accuracy of self-reported CVD (myocardial infarction, stroke, coronary artery bypass surgery and coronary artery angioplasty) during the follow up of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Self-reported CVD events, including the date of the event and hospital admission details, were collected with an interviewer-administered questionnaire. Of the 276 self-reported CVD events, 188 (68.1%) were verified by adjudication of medical records. Furthermore, linkage to the statewide Western Australian Hospital Morbidity Database (WAHMD) showed that CVD events were unlikely to be missed, with only 0.2% of those denying any CVD event being recorded as having had an event on the WAHMD. The adjudication of medical records was as accurate as record linkage to the WAHMD for validation of self-reported CVD, but combining the results from both methods of ascertainment improved CVD event identification.

The metabolic syndrome as a tool for predicting future diabetes: the AusDiab study.

OBJECTIVE: To compare the ability of the metabolic syndrome (MetS), a diabetes prediction model (DPM), a noninvasive risk questionnaire and individual glucose measurements to predict future diabetes. DESIGN: Five-year longitudinal cohort study. Tools tested included MetS definitions [World Health Organization, International Diabetes Federation, ATPIII and European Group for the study of Insulin Resistance (EGIR)], the FINnish Diabetes RIsk SCore risk questionnaire, the DPM, fasting and 2-h post load plasma glucose. SETTING: Adult Australian population. SUBJECTS: A total of 5842 men and women without diabetes > or =25 years. Response 58%. A total of 224 incident cases of diabetes. RESULTS: In receiver operating characteristic curve analysis, the MetS was not a better predictor of incident diabetes than the DPM or measurement of glucose. The risk for diabetes among those with prediabetes but not MetS was almost triple that of those with MetS but not prediabetes (9.0% vs. 3.4%). Adjusted for component parts, the MetS was not a significant predictor of incident diabetes, except for EGIR in men [OR 2.1 (95% CI 1.2-3.7)]. CONCLUSIONS: A single fasting glucose measurement may be more effective and efficient than published definitions of the MetS or other risk constructs in predicting incident diabetes. Diagnosis of the MetS did not confer increased risk for incident diabetes independent of its individual components, with an exception for EGIR in men. Given these results, debate surrounding the public health utility of a MetS diagnosis, at least for identification of incident diabetes, is required.

Differences in height explain gender differences in the response to the oral glucose tolerance test- the AusDiab study.

AIM: To determine the extent of gender-related differences in the prevalence of glucose intolerance for the Australian population and whether body size may explain such differences. METHODS: Cross-sectional data were collected from a national cohort of 11 247 Australians aged > or = 25 years. Glucose tolerance status was assessed according to both fasting plasma glucose (FPG) and 2-h plasma glucose (2hPG) levels following a 75-g oral glucose tolerance test (OGTT). Anthropometric and glycated haemoglobin measurements were also made. RESULTS: Undiagnosed diabetes and non-diabetic glucose abnormalities were more prevalent among men than women when based only on the FPG results (diabetes: men 2.2%, women 1.6%, P = 0.02; impaired fasting glycaemia: men 12.3%, women 6.6%, P < 0.001). In contrast 16.0% of women and 13.0% of men had a 2hPG abnormality (either diabetes or impaired glucose tolerance, P = 0.14). Women had a mean FPG 0.3 mmol/l lower than men (P < 0.001), but 2hPG 0.3 mmol/l higher (P = 0.002) and FPG-2hPG increment 0.5 mmol/l greater (P < 0.001). The gender difference in mean 2hPG and FPG-2hPG increment disappeared following adjustment for height. For both genders, those in the shortest height quartile had 2hPG levels 0.5 mmol/l higher than the tallest quartile, but height showed almost no relationship with the FPG. CONCLUSIONS: Men and women had different glycaemic profiles; women had higher mean 2hPG levels, despite lower fasting levels. It appeared that the higher 2hPG levels for women related to lesser height and may be a consequence of using a fixed glucose load in the OGTT, irrespective of body size.

Preferred clinical measures of central obesity for predicting mortality.

OBJECTIVE: To define the clinical measures of obesity that best predict all cause mortality and cardiovascular disease (CVD) mortality. DESIGN AND SETTING: Eleven-year mortality follow-up of an Australian urban population sample of 9309 adults aged 20-69 years in 1989. Baseline measures of obesity included body mass index (BMI), waist circumference (WC), waist-to-stature ratio and the waist-to-hip ratio. The age-standardized hazard ratios for mortality were calculated for 1 s.d. above the mean for each measure of obesity using Cox regression analysis. We constructed receiver operator characteristic (ROC) curves to assess sensitivity and specificity of the measures and to identify approximate cut-points for the prediction of risk. RESULTS: Waist-to-hip ratio was superior by magnitude and significance in predicting all cause mortality (male hazard ratio 1.25, P=0.003, female hazard ratio 1.24, P=0.003) and CVD mortality (male hazard ratio 1.62, P<0.001, female hazard ratio 1.59, P<0.001). Waist-to-stature ratio and WC were highly significant but less powerful predictors for CVD mortality. ROC analysis showed higher 'area under the curve' values for waist-related measures in males, with similar less marked trends in females. The ROC cut-points yielded values that corresponded to current promulgated criteria. CONCLUSIONS: The waist-to-hip ratio is the preferred clinical measure of obesity for predicting all cause and CVD mortality. WC is a practical alternative. Waist-to-stature ratio is not more useful than WC alone.

Diagnostic thresholds for diabetes: the association of retinopathy and albuminuria with glycaemia.

AIM: We examined the association of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG) and HbA1c with retinopathy and microalbuminuria using both deciles of glycaemia and change point models, to validate current diagnostic criteria for diabetes and to identify therapeutic thresholds for glycaemic control. METHODS: The Australian Diabetes Obesity and Lifestyle study (AusDiab), conducted in 1999-2000, included adults aged > or =25 years from 42 randomly selected areas of Australia. Retinopathy and albuminuria were assessed in participants identified as having diabetes (based on self report and oral glucose tolerance test), impaired fasting glucose, impaired glucose tolerance and in a random sample with normal glucose tolerance. Data were available for 2,182 participants with retinal photographs and 2,389 with urinary albumin/creatinine results. RESULTS: The prevalence of retinopathy in the first 8 deciles of FPG and HbA1c and the first 9 deciles of 2hPG were 7.2, 6.6, and 6.3%, respectively and showed no variation with increasing glucose or HbA1c. Above these levels, the prevalence rose markedly to 18.6% in the top 2 deciles of FPG, 21.3% in the top 2 deciles of HbA1c and 10.9% in the top decile of 2hPG. The thresholds for increasing prevalence of retinopathy were 7.1 mmol/l for FPG, 6.1% for HbA1c and 13.1 mmol/l for 2hPG. The prevalence of microalbuminuria rose gradually across deciles of each glycaemic measure. Thresholds were less clear than for retinopathy, but were seen at a FPG of 7.2 mmol/l and HbA1c of 6.1%, with no evidence of a threshold effect for 2hPG. CONCLUSIONS: The prevalence of retinopathy rose dramatically in the highest deciles of each glycaemic measure, while for microalbuminuria the increase of prevalence was more gradual. The FPG values corresponded well with the WHO diagnostic cut-point for diabetes, however the 2hPG value did not. HbA1c thresholds were similar for both retinopathy and microalbuminuria and compared well to values shown in other studies. These results support current targets for FPG and HbA1c in preventing microvascular complications.

Prevalence of diabetic complications in relation to risk factors.

The prevalence of diabetic complications is reported from a cross-sectional study of rural diabetic subjects in Western Australia. Logistic-regression analysis has been used to discover potential risk factors associated with each complication. A distinction has been made between time-related variables (age, age at diagnosis, duration of diabetes) and other risk variables. We have attempted to identify the major time-related risk variables for each complication and then examined the effect of other risk variables after accounting for the major time-related variables. The important time-related variables were found to be duration of diabetes for retinopathy, age for macrovascular disease, duration and age at diagnosis of diabetes for sensory neuropathy, and age for renal impairment. When matched on these important time-related variables, the overall prevalences of complications for insulin-dependent (IDDM) compared with non-insulin-dependent (NIDDM) diabetic patients were essentially the same. An exception is renal impairment, for which IDDM patients had a higher prevalence than did NIDDM patients of the same age. After allowing for time-related variables, the analysis also demonstrates positive independent associations between diabetic control (glycosylated hemoglobin) and retinopathy and between diabetic control and macrovascular disease. Plasma cholesterol (positively) and high-density lipoprotein cholesterol (negatively) were related independently to both macrovascular disease and renal impairment. Very few differences in the risk-factor profiles for complications were found for IDDM compared with NIDDM patients after allowing for time-related variables.

Diabetic staff simulation of insulin-dependent diabetic life.

Diabetic staff members, including doctors, nurses, and paramedical personnel, participated in a 1-wk experiment in which the life-style of a patient with insulin-dependent diabetes was stimulated. The respondents underwent reaching in (1) urine testing and recording results, (2) twice daily "insulin" regimen, and (3) diet involving regularly spaced carbohydrate in meals and snacks. Evaluation was conducted at several levels. The nurse educator assessed the pseudo-patients' performance. Staff members evaluated the teaching. Most important, the staff came to appreciate unforseen minutiae and pitfalls in the practical aspects of daily living as ordinarily prescribed by medical attendants. The simulation experiment is recommended for all staff involved in diabetic education.

Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations.

In the 1966 study of the population of Busselton, Australia, blood sugar and serum insulin levels were measured one hour after an oral glucose load, in addition to the conventional cardiovascular risk factors. The six-year incidence of coronary heart disease (CHD) and the 12-yr mortality from CHD and from all cardiovascular diseases is described in relation to the initial baseline variables measured using the upper 20th percentile values (age-specific and sex-specific) to define the risk ratios. In younger subjects (ages less than 60 yr), elevated blood pressure levels for both sexes (risk ratios from 2.9 to 5.2) and elevated serum cholesterol concentrations for males (risk ratios from 3.0 to 3.3) were strong predictors of cardiovascular risk. In men aged 60 to 69 yr, those with upper range one-hour serum insulin concentrations showed marked associations with the six-year incidence of CHD, the 12-yr mortality from CHD, and the 12-yr mortality from all cardiovascular diseases (risk ratios were 2.0, 2.3, and 2.4, respectively). The relationship of elevated serum insulin and cardiovascular mortality persisted when males of all ages were analyzed, and it appeared to be independent of the other major risk factors. In females, no association between serum insulin and CHD or cardiovascular disease could be found. Although the age and sex specific upper 20th percentile values for one-hour blood sugar concentrations showed a low grade association in patients with subsequent cardiovascular disease end points, more noticeable risk ratios were demonstrated at the higher blood sugar level of 200 mg/100 ml or greater (in the age group 60 yr and over, risk ratios were 2.2 in males and 2.6 in females.

Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis.

OBJECTIVE: To investigate duration of the period between diabetes onset and its clinical diagnosis. RESEARCH DESIGN AND METHODS: Two population-based groups of white patients with non-insulin-dependent diabetes (NIDDM) in the United States and Australia were studied. Prevalence of retinopathy and duration of diabetes subsequent to clinical diagnosis were determined for all subjects. Weighted linear regression was used to examine the relationship between diabetes duration and prevalence of retinopathy. RESULTS: Prevalence of retinopathy at clinical diagnosis of diabetes was estimated to be 20.8% in the U.S. and 9.9% in Australia and increased linearly with longer duration of diabetes. By extrapolating this linear relationship to the time when retinopathy prevalence was estimated to be zero, onset of detectable retinopathy was calculated to have occurred approximately 4-7 yr before diagnosis of NIDDM. Because other data indicate that diabetes may be present for 5 yr before retinopathy becomes evident, onset of NIDDM may occur 9-12 yr before its clinical diagnosis. CONCLUSIONS: These findings suggest that undiagnosed NIDDM is not a benign condition. Clinically significant morbidity is present at diagnosis and for years before diagnosis. During this preclinical period, treatment is not being offered for diabetes or its specific complications, despite the fact that reduction in hyperglycemia, hypertension, and cardiovascular risk factors is believed to benefit patients. Imprecise dating of diabetes onset also obscures investigations of the etiology of NIDDM and studies of the nature and importance of risk factors for diabetes complications.

Familial correlations, cohabitation effects, and heritability for cardiovascular risk factors.

Familial correlations in cardiovascular risk factors were investigated with use of data from a community-based sample of 1319 nuclear families involving 4178 adult persons collected in the Busselton Population Health Surveys over the period 1966 to 1981. The risk factors considered were systolic blood pressure, diastolic blood pressure, body mass index, triceps fatfold, and cholesterol. All risk factors showed positive familial correlations, with correlations generally being lower for spouses than for parent-offspring pairs or for siblings. Spouse correlations showed little variation with age, suggesting that observed correlations are primarily due to assortative mating and not to cohabitation. The parent-offspring correlations tended to decline with age of (adult) offspring; this observation suggests that the effect of a shared household environment during childhood and adolescence diminishes over time when living apart during adulthood. The sibling correlations decreased with age for blood pressure and serum cholesterol and increased with age for body mass index and triceps fatfold. The estimated heritabilities were 27% for systolic and diastolic blood pressure, 37% for serum cholesterol, 52% for body mass index, and 23% for triceps fatfold. These results confirm that substantial familial aggregation of cardiovascular risk factors occurs and that much of this aggregation has a genetic basis, although assortative mating (in spouses) and environmental influences (in offspring and siblings) are also present. The nuclear family should be considered as a point of intervention in cardiovascular disease prevention programs.

Australian Diabetes Screening Study: impaired glucose tolerance and non-insulin-dependent diabetes mellitus.

In preventing non-insulin-dependent diabetes mellitus (NIDDM) and its complications, screening high-risk individuals complements public health measures. Our screening instrument for patients of general practitioners was a questionnaire for self-determined high-risk groups plus a laboratory measurement of a random venous plasma glucose level. Collaborating practitioners evaluated 100 consecutive outpatients aged 40 years or older. The questionnaire identified patients with two or more diabetic symptoms or with two or more risk factors, and they were recommended to have their blood tested. For those with a random plasma glucose greater than 5.5 mmol/L, oral glucose tolerance tests (OGTTs) were advised. Of 50,859 subjects completing the study, there were 1,013 cases (2.0%) of new diabetes, 1,704 cases (3.4%) of impaired glucose tolerance (IGT), and 5,508 cases (10.8%) of previously diagnosed diabetes. Symptoms alone were a relatively poor discriminant. Almost all newly identified NIDDM and IGT patients had two or more risk factors for NIDDM. The risk ratios for abnormal glucose tolerance were as follows: high blood pressure, 2.4; overweight, 2.0; and positive family history, 1.7. Selection of cutoff points higher than 5.5 mmol/L would have substantially reduced the rate of newly discovered NIDDM and IGT. Screening for NIDDM and IGT in general practice is feasible and can be achieved with little disruption of office procedures. In preventive programs of this nature, the low screening threshold of 5.5 mmol/L for random venous plasma glucose maximizes the case-finding rate.

Assessing the risk of diabetic retinopathy.

We used multiple logistic regression to analyze cross-sectional data on 1,006 patients with diabetes mellitus who were examined in a rural diabetic screening program. The factors found to have independent and significant associations with the presence of retinopathy were duration of diabetes, albuminuria, serum creatinine, glycosylated hemoglobin, and plasma glucose levels, blood pressure, and percentage of desirable weight. By comparing the contribution of each significant factor to the deviance from the regression models, we estimated the relative importance of each. Duration of diabetes was by far the most important predictive factor. The logistic model provided a good fit to the observed prevalence rates in various risk groups but was less satisfactory for predicting the presence or absence of retinopathy in individual patients. The discovery of presently unknown risk factors may improve this situation.

Serum insulin is a risk marker for coronary heart disease mortality in men but not in women.

Serum insulin 1 h post-glucose load is examined in this prospective study of 2971 Caucasoid subjects aged > 20 years in 1966 and followed to 1989. The serum insulin levels as a continuous variable show no significant linear association with coronary heart disease (CHD) deaths in either sex after accounting for age by Cox proportional hazards analysis. In males the quintile classes of serum insulin show a striking U-shaped pattern with both the highest and lowest quintiles having significant associations with CHD deaths. In females the insulin quintiles show no direct association. Analysis for interactions of risk variables indicate that in females the relative protection of low cholesterol levels is abolished by hyperinsulinaemia after 12 years. Thus, serum insulin is not a direct aetiological risk factor for CHD. The findings suggest that the associations are likely to be due to confounding effects of unmeasured variables including lipid subfractions.

Self-reported health and use of health services: a comparison of diabetic and nondiabetic persons from a national sample.

Population-based epidemiological and health service utilisation information on diabetes and other noncommunicable diseases is still scarce in Australia. Such information is needed by health economists, policy makers and service providers. Data from the 1989-90 National Health Survey conducted by the Australian Bureau of Statistics have been used to obtain estimates of the prevalence of cardiovascular morbidity, life-style factors, use of hospital and medical services, and self-assessed health and happiness for Australian persons with diabetes. Prevalences are compared with those for persons without diabetes. Those with diabetes had two to three times the prevalence of most cardiovascular conditions, similar levels of exercise (except for diabetic women over 40 years of age who exercised less than their nondiabetic counterparts), lower levels of alcohol consumption (except for younger men, who had a similar frequency of heavy drinking as their nondiabetic peers), similar levels of smoking, a higher prevalence of overweight, and significantly greater frequency of hospital admissions, use of outpatient services and general practitioner consultations. About half of the people with diabetes assessed their health as good or excellent but 90 per cent stated that they were happy or very happy. No differences between diabetic people living in capital cities and other areas were found. These results have implications for education and life-style behaviour modification programs for people with diabetes. Research into the prevention and more effective management of diabetes and its complications is required in order to contain the escalating health care burden associated with diabetes in Australia.

New classification and criteria for diagnosis of diabetes mellitus. The Australasian Working Party on Diagnostic Criteria for Diabetes Mellitus.

Diagnosis of diabetes is not in doubt when there are classical symptoms of thirst and polyuria and a random venous plasma glucose level > or =11.1 mmol/L. The Australasian Working Party on Diagnostic Criteria for Diabetes Mellitus recommends: Immediate adoption of the new criterion for diagnosis of diabetes as proposed by the American Diabetes Association (ADA) and the World Health Organization (WHO) - fasting venous plasma glucose level > or =7.0 mmol/L; Immediate adoption of the new classification for diabetes mellitus proposed by the ADA and WHO, which comprises four aetiological types - type 1, type 2, other specific types and gestational diabetes - with impaired glucose tolerance and impaired fasting glycaemia as stages in the natural history of disordered carbohydrate metabolism; Awareness that some cases of diabetes will be missed unless an oral glucose tolerance test (OGTT) is performed. If there is any suspicion or other risk factor suggesting glucose intolerance, the OGTT should continue to be used pending the final WHO recommendation.