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OBJECTIVE To examine the association between soluble tumor necrosis factor receptor 1 (sTNFR1) levels and kidney disease progression in Indigenous Australians at high risk of kidney disease. RESEARCH DESIGN AND METHODS This longitudinal observational study examined participants aged ≥18 years recruited from >20 sites across diabetes and/or kidney function strata. Baseline measures included sTNFR1, serum creatinine, urine albumin-to-creatinine ratio (uACR), HbA1c, C-reactive protein (CRP), waist-to-hip ratio, systolic blood pressure, and medical history. Linear regression was used to estimate annual change in estimated glomerular filtration rate (eGFR) for increasing sTNFR1, and Cox proportional hazards were used to estimate the hazard ratio (HR) and 95% CI for developing a combined renal outcome (first of a ≥30% decline in eGFR with a follow-up eGFR RESULTS Over a median of 3 years, participants with diabetes (n = 194) in the highest compared with the lowest quartile of sTNFR1 experienced significantly greater eGFR decline (−4.22 mL/min/1.73 m2/year [95% CI −7.06 to −1.38]; P = 0.004), independent of baseline age, sex, eGFR, and uACR. The adjusted HR (95% CI) for participants with diabetes per doubling of sTNFR1 for the combined renal outcome (n = 32) was 3.8 (1.1–12.8; P = 0.03). No association between sTNFR1 and either renal outcome was observed for those without diabetes (n = 259). CONCLUSIONS sTNFR1 is associated with greater kidney disease progression independent of albuminuria and eGFR in Indigenous Australians with diabetes. Further research is required to assess whether TNFR1 operates independently of other metabolic factors associated with kidney disease progression.

OBJECTIVE—Homocysteine is an emerging risk factor for cardiovascular and nondiabetic ocular vaso-occlusive diseases. However, studies of the relationship between homocysteine and diabetic retinopathy have reported inconsistent results. The purpose of this study was to evaluate the relationship between plasma total homocysteine concentration and diabetic retinopathy. RESEARCH DESIGN AND METHODS—We assessed the homocysteine-retinopathy relationship in 168 men and women with type 2 diabetes in a community-based, cross-sectional study. We photodocumented diabetic retinopathy status and measured plasma total homocysteine concentration using a commercial fluorescence polarization immunoassay enzymatic kit. Data for selected clinical/demographic variables and established risk factors for diabetic retinopathy were obtained from fasting blood samples and an interviewer-assisted lifestyle questionnaire. RESULTS—A higher mean plasma total homocysteine concentration was observed in diabetic individuals with retinopathy than in those without retinopathy (11.5 μmol/l [95% CI 10.4–12.5] vs. 9.6 μmol/l [9.1–10.2], P = 0.001). Furthermore, the relationship between homocysteine and diabetic retinopathy was not explained by renal dysfunction and was independent of the other major risk factors for diabetic retinopathy (duration of diabetes, A1C, and systolic blood pressure) and determinants of higher homocysteine concentrations (age, sex, and red cell folate) (odds ratio 1.20 [95% CI 1.023–1.41], P = 0.024). CONCLUSIONS—Plasma total homocysteine concentration may be a useful biomarker and/or a novel risk factor for increased risk of diabetic retinopathy in people with type 2 diabetes.

OBJECTIVE—The aims of the study were to determine whether Greek or Italian migrants to Australia have an elevated incidence of type 2 diabetes compared with Australian-born individuals and to what extent any differences can be explained by known risk factors. RESEARCH DESIGN AND METHODS—This was a prospective study of 34,097 men and women aged 40–69 years born in Greece, Italy, Australia, or New Zealand who were free from diabetes at baseline. For all self-reported cases of diabetes at the 4-year follow-up, a confirmation of diagnosis was sought from medical practitioners. Of these, anyone for whom there was no evidence against a diagnosis of type 2 diabetes was considered a case subject. RESULTS—Follow-up was completed by 29,331 (86%) participants, and 334 case subjects were identified. The cumulative incidence of type 2 diabetes among Greek (2.6%) and Italian (2.4%) migrants was more than three times that in Australian-born (0.7%) individuals. After adjusting for age only, the odds ratios (ORs) for being of Greek and Italian origin compared with Australian origin were 3.8 (95% CI 2.9–5.0) and 3.3 (2.6–4.3), respectively. The only known risk factor for type 2 diabetes that materially affected these ORs was BMI. After adjusting for BMI and age, the ORs for being of Greek and Italian origin, respectively, were 2.4 (1.8–3.2) and 2.0 (1.5–2.6). CONCLUSIONS—Greek and Italian migrants to Australia have a more than three times greater incidence of type 2 diabetes than Australian-born individuals, and this is only partly explained by BMI. Although weight control will remain important for these high-risk groups, identification of other risk factors is required.

OBJECTIVE: To examine trends in glucose tolerance and coronary risk among Aboriginal people from a group of homeland communities in central Australia during a 7-year follow-up period. RESEARCH DESIGN AND METHODS: Community-based screenings of adult volunteers were performed in 1988 (n = 437; 93% response rate) and in 1995 (n = 424; 85% response rate). A health promotion intervention program commenced after the 1988 survey that focused on the benefits of exercise and appropriate diet. RESULTS: Mean (95% CI) BMI increased significantly from 22.8 kg/m2 (22.3-23.2) to 24.2 kg/m2 (23.8-24.7) during the follow-up period (P < 0.001). This increase was similar for men and women and across all age-groups. The increase in BMI was greater among subjects residing adjacent to a store compared with those residing in communities located far from a store (P < 0.001). Decreases were evident in the prevalence of impaired glucose tolerance (IGT) (from 22.5 to 10.1% among women, P < 0.001; from 12.2 to 6.5% among men, P = 0.074) and hypercholesterolemia (from 36.7 to 25.8% among women, P < 0.01; from 52.4 to 44.0% among men, P = 0.147), but no change was evident in the prevalence of diabetes. Smoking remained rare among women (

Objective— To determine the age- and sex-specific prevalence of diabetes and to examine associations between related anthropometric and metabolic abnormalities in an Aboriginal community in central Australia with a long history of acculturation. Research Design and Methods— We used a cross-sectional survey of 353 adults > 15 yr of age (87% response rate) and measured the following parameters: weight, height, circumferences of waist and hips; glucose, insulin, cholesterol, triglyceride, and high-density lipoprotein cholesterol in fasting plasma; and plasma glucose and insulin 2 h after 75 g oral glucose. Results— The prevalence of diabetes was 29.6% in survey participants > 35 yr of age and 5.3% in those < 35 yr of age. Impaired glucose tolerance also occurred with higher frequency in those > 35 yr of age (14.8 vs. 4.7%). Of those > 35 yr of age, 75% of the women and 51% of the men were overweight or obese, with a body mass index ≥ 25 kg/m2. A large insulin response to oral glucose was evident, with the upper tertile of the 2-h insulin response six times higher than the lower tertile (113 ± 43 vs. 19 ± 8 mU/L). Hyperinsulinemia showed a strong, positive association with impaired glucose tolerance, body mass index, waist-to-hip ratio, cholesterol, and triglyceride levels and a negative association with high-density lipoprotein cholesterol levels. Cholesterol levels were on average 0.5 mM higher in men than in women. Deteriorations in carbohydrate and lipid metabolism occurred before 40 yr of age: diabetes, body mass index, waist-to-hip ratio, and fasting triglycerides and cholesterol concentrations peaked and high-density lipoprotein cholesterol concentrations reached their nadir at the end of the fourth decade. Conclusions— These data suggest that any intervention programs developed to prevent or reduce diabetes prevalence in this population should be targeted at adolescents and young adults.

OBJECTIVE To evaluate A1C for screening and diagnosis of undiagnosed type 2 diabetes defined by oral glucose tolerance testing in clinical and general populations. RESEARCH DESIGN AND METHODS A1C cut offs (≤5.5% to rule out diabetes; ≥7.0% to rule in diabetes) were derived from a clinical group (Melbourne Pathology [MP] group: n = 2,494; undiagnosed diabetes 34.6%) and then evaluated in a population-based sample (AusDiab group: n = 6,015; undiagnosed diabetes 4.6%). RESULTS For diabetes in the MP and AusDiab groups, A1C at 5.5% gave sensitivities of 98.7 and 83.5%, while A1C at 7.0% gave specificities of 98.2 and 100%, respectively. Many (61.9–69.3%) with impaired A1C (5.6–6.9%) in both populations had abnormal glucose status. CONCLUSIONS A1C ≤5.5% and ≥7.0% predicts absence or presence of type 2 diabetes, respectively, while at A1C 6.5–6.9% diabetes is highly probable in clinical and population settings. A high proportion of people with impaired A1C have abnormal glucose status requiring follow-up.

The aims of the study were to determine whether Greek or Italian migrants to Australia have an elevated incidence of type 2 diabetes compared with Australian-born individuals and to what extent any differences can be explained by known risk factors.This was a prospective study of 34,097 men and women aged 40-69 years born in Greece, Italy, Australia, or New Zealand who were free from diabetes at baseline. For all self-reported cases of diabetes at the 4-year follow-up, a confirmation of diagnosis was sought from medical practitioners. Of these, anyone for whom there was no evidence against a diagnosis of type 2 diabetes was considered a case subject.Follow-up was completed by 29,331 (86%) participants, and 334 case subjects were identified. The cumulative incidence of type 2 diabetes among Greek (2.6%) and Italian (2.4%) migrants was more than three times that in Australian-born (0.7%) individuals. After adjusting for age only, the odds ratios (ORs) for being of Greek and Italian origin compared with Australian origin were 3.8 (95% CI 2.9-5.0) and 3.3 (2.6-4.3), respectively. The only known risk factor for type 2 diabetes that materially affected these ORs was BMI. After adjusting for BMI and age, the ORs for being of Greek and Italian origin, respectively, were 2.4 (1.8-3.2) and 2.0 (1.5-2.6).Greek and Italian migrants to Australia have a more than three times greater incidence of type 2 diabetes than Australian-born individuals, and this is only partly explained by BMI. Although weight control will remain important for these high-risk groups, identification of other risk factors is required.

OBJECTIVE: To examine the impact of a 12-week walking program on body composition and risk factors for cardiovascular disease in women with type 2 diabetes and in normoglycemic women with first-degree diabetic relatives. RESEARCH DESIGN AND METHODS: There were 11 postmenopausal women with type 2 diabetes and 20 normoglycemic women of similar age and BMI who were asked to walk 1 h per day on 5 days each week for 12 weeks. Fitness (estimated VO2max) was assessed with a 1.6-km walking test; body composition was measured by dual-energy X-ray absorptiometry; and sex hormone, metabolic, and lipid concentrations were measured in serum. RESULTS: After 12 weeks, estimated VO2max improved in both groups (P < 0.005). In the diabetic women, BMI and fat content of the upper body and android waist region decreased (P < 0.05). Concentrations of fasting blood glucose (P < 0.05) HbAlc (P < 0.05), total cholesterol (P < 0.005), and LDL cholesterol (P < 0.05) decreased, while HDL cholesterol and sex hormones were unchanged. In contrast, normoglycemic women failed to lose body fat after 12 weeks of exercise in a walking program. However, their HbAlc, total cholesterol, LDL cholesterol, sex hormone-binding globulin, and total testosterone concentrations decreased (P < 0.05). On pooling the data and including diabetes as a categorical grouping variable, stepwise multiple regression analysis indicated that the change in centralized body fat, but not the change in VO2max, was related to change in fasting blood glucose. CONCLUSIONS: Twelve weeks of walking increased the fitness of diabetic and normoglycemic women. Improvement of fasting blood glucose was related to the loss of centralized body fat rather than to improved fitness.

OBJECTIVE To compare regional body fat distribution and sex hormone status of postmenopausal women with NIDDM with those of age- and BMI-matched normoglycemic women. RESEARCH DESIGN AND METHODS The regional body fat distribution and sex hormone status of 42 postmenopausal women with NIDDM were compared with those of 42 normoglycemic women matched for age and BMI, who served as control subjects. Body composition was measured by dual-energy X-ray absorptiometry, and sex hormone-binding globulin (SHBG) and testosterone were measured in serum. RESULTS Although the levels of total body fat were similar between the two groups, the women with NIDDM had significantly less lower-body fat (LBF) (P < 0.01) than the control subjects matched for age and BMI. This pattern of fat deposition in women with NIDDM was accompanied by an androgenic hormone profile, with decreased SHBG concentration and an increased free androgen index (P < 0.05 and P < 0.01, respectively). CONCLUSIONS A reduced capacity to deposit and/or conserve LBF may be an independent factor associated with (or may be a marker of) the metabolic manifestations of the insulin resistance syndrome in women with NIDDM. The possibility that the smaller relative accumulation of LBF is a consequence of the androgenic hormonal profile should be investigated in future studies.

OBJECTIVE To determine the age- and sex-specific prevalence of diabetes, impaired glucose tolerance (IGT), and coronary heart disease risk factors in a remote central Australian Aboriginal community maintaining some degree of traditional lifestyle, living in homeland communities on their ancestral land. RESEARCH DESIGN AND METHODS A cross-sectional survey of 437 subjects ≥ 15 years of age (189 men, 248 women), representing 80% of the adult population residing in the community at the time of the survey, was performed and the following parameters measured: BMI, glucose tolerance, circulating insulin and lipids, and blood pressure. RESULTS The mean BMI for this population was 22.9 ± 4.8 kg/m2. The prevalence of diabetes in the age group of 15–34 years (103 men and 140 women) was 2 and 6% for men and women, respectively. In the 35-years-and-older age group (86 men and 108 women), diabetes prevalence was 19 and 13% for men and women, respectively. Over half the diabetic subjects did not exhibit fasting hyperglycemia. IGT occurred in 8 and 15% of younger men and women, respectively, and in 17 and 32% of older men and women, respectively. Smoking was common among men (53% current smokers) but rare among women (2% current smokers). The prevalence of hypercholesterolemia, hypertriglyceridemia, hypertension, and overweight rose with increasing degrees of glucose intolerance. The two communities adjacent to the only store in the area had a higher prevalence of abnormal glucose tolerance than did the more remote homeland communities (odds ratio for abnormal glucose tolerance: 2.92; 95% CI 1.51−5.63). CONCLUSIONS Despite their relative leanness, this Aboriginal population exhibited relatively high prevalences of IGT and diabetes without fasting hyperglycemia. The data suggest a protective effect of a decentralized mode of living, as opposed to a more urbanized lifestyle, on the occurrence of glucose intolerance. Abnormal lipid profiles (particularly high triglycerides and low HDL cholesterol) and the high prevalence of smoking in men indicated a high-risk profile for coronary heart disease in this population.

OBJECTIVE To examine the effects of a high-carbohydrate low-fat (HCLF) and a modified-fat (MF) diet on body weight and metabolic control in subjects with non-insulin-dependent diabetes mellitus (NIDDM) living at home. RESEARCH DESIGN AND METHODS Twenty-four NIDDM patients followed HCLF and MF diets alternately and in random order for a 3-month period while at home, with a 1-month baseline and washout between diets. Before and after each diet, fasting glucose and lipids, HbAlc, blood pressure, and body weight were measured. Dietary preferences were assessed by questionnaire. RESULTS Subjects consumed 50% of energy as carbohydrate and 23% as fat on the HCLF diet and 40% of energy as carbohydrate and 36% as fat (over half of which was monounsaturated fat) on the MF diet. Subjects lost weight on both HCLF and MF diets (mean loss 0.7 and 1.3 kg, respectively). Although the MF diet resulted in a small decrease in fasting glucose levels, there was no significant change in HbA1c. Similarly, there was no significant difference between the diets in changes in blood pressure or fasting blood lipids. Most subjects (65%) preferred the MF diet. CONCLUSIONS Although the MF diet is not a low-fat diet, it did not appear to facilitate weight gain in subjects with NIDDM living at home. The MF diet provides an alternative for individuals unable to comply with HCLF diets.

OBJECTIVE Two experimental diets were evaluated to investigate the hypothesis that dietary fat has an independent influence on metabolic control in IDDM. RESEARCH DESIGN AND METHODS The diets had similar CHO contents (26 and 22% of energy intake) but differed markedly in fat (53 vs. 16% energy) and protein (20 vs. 62% energy). We had 10 subjects follow the low-CHO, high-fat diet, and 8 subjects follow the low-CHO, low-fat, high-protein diet. In each case, markers of glycemic and lipid control obtained after adherence to the experimental diet for 2 wk were compared with corresponding data from a preceding control period during which subjects had followed their usual diet (protein 18–19%, CHO 41–46%, fat 33–37%). RESULTS Despite the low CHO content of the high-fat diet, insulin requirements were unchanged relative to the control diet. Moreover, the glycemic response to a standard breakfast was elevated significantly (P < 0.001), suggesting that insulin resistance had either been induced or exacerbated. The small rise in total cholesterol concentration in response to the high-fat diet was accounted for by a rise in HDL cholesterol. Glycemic control and lipid metabolism were unchanged after the low-CHO, low-fat diet, although insulin requirements fell by an average of 6 U/day (P < 0.05) relative to those recorded during the 2-wk control period. CONCLUSIONS Diets high in fat are deleterious to glycemic control in IDDM, but general applicability is limited by the small sample size and short duration of this study.

A small rural Aboriginal community in northern Australia was surveyed for diabetes, impaired glucose tolerance (IGT), hyperinsulinemia, and lipid levels. Of the 122 adults >17 yr of age who participated (95% response rate), 11.5% had diabetes, 7.4% had IGT, and the remaining 81.1% had normal glucose tolerance. Both diabetes and IGT were strongly age related. This high frequency of diabetes occurred, despite the population being relatively lean. Although the body mass index (BMI) increased with age in both men and women, only 25% of the population overall had BMI >25 kg/m2. There were wide ranges of insulin responses to glucose, with the upper fertile of 2-h insulin levels being more than seven times higher than the lower fertile (144 ± 13 vs. 19 ± 1 mLI/L). Hyperinsulinemia was associated with IGT, elevated triglycerides, and lower high-density lipoprotein cholesterol levels. Lipid abnormalities were much more frequent among men than women. Cholesterol levels were an average of 0.55 mM higher and triglycerides an average of 1.05 mM higher in men than in women, and both increased with age. In conclusion, this small isolated Aboriginal population from northern Australia had an unexpectedly high frequency of diabetes (in view of their relative leanness) in association with a high frequency of metabolic abnormalities indicative of insulin resistance (hyperinsulinemia, IGT, hypertriglyceridemia).

We were interested in the demonstration by Paniagua et al. (1) that in obese insulin-resistant individuals, high-carbohydrate diets but not high-fat diets (either high monounsaturated [MUFA] or high saturated [SFA]) are associated with some redistribution of fat mass to abdominal rather than peripheral deposits. Their study confirms our earlier findings with high-carbohydrate and high-MUFA diets in people with type 2 diabetes …

A cross section of adult full-blooded Aborigines from three small isolated communities in the desert region of northwest Australia was surveyed for diabetes, impaired glucose tolerance (IGT), insulin levels, and lipoprotein lipids. Sixty-three men and 86 women from a total adult population of 330 were tested. Of the people tested, 67.6% had normal glucose tolerance, 25% had IGT, and 7.4% had diabetes. Both diabetes and IGT were strongly age related. Fasting insulin levels and insulin responses to oral glucose (elevation above basal) were elevated. Although fasting insulin rose with age, insulin response did not rise after adjustment for body mass index (BMI). Plasma triglyceride levels were high, particularly in men >35 yr old (3.13 ± 0.32 mM), but cholesterol levels were not elevated. Multiple regression analysis of fasting glucose, 2-h glucose, plasma triglyceride, fasting insulin, and insulin response for the nondiabetic subjects revealed 7) BMI was an independent risk factor for elevated 2-h glucose levels in women but not in men and was strongly related to fasting insulin concentrations in both genders; 2) fasting insulin concentration was an independent risk factor for increases in fasting glucose, insulin response, and triglyceride levels; 3) insulin response was related to the 2-h glucose level; 4) fasting and 2-h glucose levels and fasting insulin and triglyceride concentrations all rose with age in both genders, with the rate of increase generally greater in men. The most striking difference between these desert Aborigines and previously studied coastal Aborigines from the same geographical region was the significantly higher insulin response. It is possible that the more severe hyperinsulinemia in the desert Aborigines may indicate a greater degree of susceptibility to type II diabetes than in the coastal Aborigines as the duration of urbanization increases.

Recent epidemiologic studies have revealed a high prevalence of maturity-onset diabetes in certain populations that have undergone comparatively rapid urbanization. There is evidence suggesting that Australian Aborigines may respond to urbanization in this way. Thirteen full-blood Aborigines from the Mowanjum Community, Derby, Western Australia, cooperated in the present study. They spent 3 mo living in their traditional hunter-gatherer life-style, after which their insulin response to glucose was measured in a starch tolerance test. The findings were compared in follow-up studies conducted 3 mo after returning to their urban environment. Similar studies were conducted in Caucasians of comparable age and weight. Fasting glucose concentrations were lower in Aborigines than in Caucasians and were unaffected by life-style changes. Although basal insulin levels were similar in the three groups, there were striking intergroup differences in the insulin responses to glucose. The areas under the insulin curves in the first hour after starch ingestion were: urban Aborigines 4478 +/- 465 microU/ml-1/min, traditional Aborigines 2959 +/- 301 microU/ml-1/min, and Caucasians 2097 +/- 224 microU/ml-1/min. This appeared to reflect differences in the early rates of change of glucose concentrations. The data suggest that these Aborigines have an abnormally high insulin response to glucose, which is ameliorated, but not normalized, by reverting to their traditional life-style.