There really is an epidemic of type 2 diabetes.
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Adolescent↗
Biomedical subjects
S Colagiuri
Publications and source records attributed to S Colagiuri.
Derivation and validation of diabetes risk score for urban Asian Indians.
OBJECTIVE: Simple risk scores for identifying people with undiagnosed diabetes have been developed, mostly in Caucasian groups. This may not be suitable for Asian Indians, therefore this study was undertaken to develop and validate a simple diabetes risk score in an urban Asian Indian population with a high prevalence of diabetes. We also tested whether this score was applicable to South Asian migrants living in a different cultural context. RESEARCH DESIGN AND METHODS: A population based Cohort of 10,003 participants aged >or=20 years was divided into two equal halves (Cohorts 1 and 2), after excluding people with known diabetes. Cohort 1 (n=4993) was used to derive the risk score. Validation of the score was performed in the other half of the survey population (Cohort 2) (n=5010). The validation was also done in a separate survey population in Chennai, India (Cohort 3) (n=2002) (diagnosis of diabetes was based on OGTT) and in the South Asian Cohort of the 1999 Health Survey for England (n=676) (fasting glucose value>or=7 mmol/l and HbA1c>or=6.5% were used for diagnosis). A logistic regression model was used to compute the beta coefficients for risk factors. The risk score value was derived from a receiver operating characteristic curve. RESULTS: The significant risk factors included in the risk score were age, BMI, waist circumference, family history of diabetes and sedentary physical activity. A risk score value of >21 gave a sensitivity, specificity, positive predictive value and negative predictive value of 76.6%, 59.9%, 9.4% and 97.9% in Cohort 1, 72.4%, 59%, 8.3% and 97.6% in Cohort 2 and 73.7%, 61.0%, 12.2% and 96.9% in Cohort 3, respectively. The higher distribution of risk factors in the UK Cohort means that at the same cut point the score was much more sensitive but also less specific. (sensitivity 92.2%, specificity 25.7%, positive predictive value of 21.6% and negative predictive value of 93.7%). CONCLUSIONS: A diabetes risk score involving simple non-biochemical measurements was developed and validated in a native Asian Indian population. This easily applicable simple score could play an important role as the first step in the process of identifying individuals with an increased likelihood of having prevalent but undiagnosed diabetes. The different distribution of risk factors with the migrant Asian Indians living in England and the different relationship between sensitivity and specificity for the same score demonstrate that risk scores and cut-points developed and tested even within one ethnic group cannot be generalized to individuals of the same ethnic group living in a different cultural setting where the distribution of risk factors for diabetes is different.
Adult↗
Can a screening programme for diabetes be applied to another population?
AIMS: To compare the performance of a Danish diabetes screening protocol in populations from Denmark and Australia. METHODS: The populations used were the Inter99 population from Denmark and the AusDiab population from Australia. The Inter99 study included 6270 individuals aged 30-60 years, randomly selected from Copenhagen County. The AusDiab study included 7079 individuals also aged 30-60 years, randomly selected from throughout Australia. In both studies, all individuals without known diabetes underwent an oral glucose tolerance test (OGTT). Screening using a Danish risk score as an initial step was followed by measurement of fasting plasma glucose (FPG). RESULTS: The characteristics of the study populations showed some differences in risk profile, with more individuals in the AusDiab study being obese, whilst in the Danish cohort, mean blood pressure was higher, less people took anti-hypertensive medication and there was a higher prevalence of screen-detected diabetes. Comparing the Australian and Danish populations, overall performance of the screening protocol was similar-area under area receiver operator characteristic (ROC) curve 0.75 vs. 0.77, sensitivity 71 vs. 76% and positive predictive value (PPV) 6 vs. 9%. Small but statistically significant differences were observed in specificity (70 vs. 66%; P < 0.001) and percentage of the population requiring further testing (31 vs. 36%; P < 0.001). Combining the risk score with FPG > or = 6.1 mmol/l showed a similar pattern. Again, specificity was slightly but significantly higher in the Australian population (95 vs. 93%; P < 0.001) and percentage of the population requiring further testing was lower (5 vs. 8%; P < 0.001). CONCLUSIONS: The Danish risk score performed well when applied to a geographically different Caucasian population and is a suitable tool for detecting people at high risk of undiagnosed diabetes.
Adult↗
Creating a pandemic of prediabetes: the proposed new diagnostic criteria for impaired fasting glycaemia.
AIMS/HYPOTHESIS: In November 2003 the American Diabetes Association expert committee on the diagnosis and classification of diabetes mellitus suggested a revision of the diagnostic criteria for IFG, lowering the diagnostic threshold from 6.1 to 5.6 mmol/l. The aim of the present study was to evaluate the consequences of this change with respect to: (i) the prevalence of IFG in five different countries; (ii) the concordance between IFG and IGT (classification of individuals); and (iii) the cardiovascular risk profile of these groups. Finally we discuss the likelihood that intervention for cardiovascular risk and prevention strategies developed for individuals with IGT are applicable to subjects with IFG. METHODS: The first part of the study is based on the population-based Danish Inter99 study, where 6265 individuals, aged 30 to 60 years and without previously diagnosed diabetes, underwent an oral glucose tolerance test. The second part is based on the DETECT-2 project, in which studies from China, India, France and USA were used to analyse the impact of the proposed revision of the diagnostic criteria in different ethnic groups. RESULTS: The proposed change in diagnostic criteria would increase the prevalence of IFG in Denmark from 11.8 to 37.6%. The proposed IFG category would identify 60.0% of all subjects with IGT compared to 29.2% with the old criteria, but among individuals with the new IFG category only 18.5% would also have IGT. Individuals with isolated IFG had lower insulin levels and a lower cardiovascular risk profile with the proposed criteria compared with the current WHO criteria. Data from the DETECT-2 study confirmed the marked increase in the prevalence of IFG, and the estimated number of individuals in the age range 40 to 64 years with IFG in urban India, urban China and the USA would increase by 78%, 135% and 193% respectively. CONCLUSIONS/INTERPRETATION: The proposed revised diagnostic criteria will lead to a dramatic increase in the prevalence of IFG, but the concordance rate between IFG and IGT remains low. This new IFG group will have a more favourable cardiovascular risk profile than the current IFG group as defined by the WHO. This seriously questions whether the existing intervention strategies are applicable to the new category of individuals with IFG.
Adult↗
Hypoglycaemia with insulin aspart: a double-blind, randomised, crossover trial in subjects with Type 1 diabetes.
AIMS: To compare the effects of the rapid-acting insulin analogue insulin aspart and soluble human insulin on hypoglycaemia and glycaemic control in patients with Type 1 diabetes when injected immediately before meals as part of intensive insulin therapy. METHODS: In this multinational, double-blind, randomised, crossover trial, 155 patients with Type 1 diabetes (HbA(1c) < 8.0%) were symmetrically randomised to two 16-week treatment periods on either type of insulin, both injected 0-5 min before meals. NPH insulin was given as basal insulin once or twice daily as needed, and insulin dosages were regularly adjusted using pre-defined algorithms to maintain tight glycaemic control. Treatment periods were separated by a 4-week washout. RESULTS: The rate of major nocturnal (24.00-06.00 h) hypoglycaemic episodes was 72% lower with insulin aspart than with human insulin (0.067 vs. 0.225 events/month; P = 0.001). Total rate of major hypoglycaemia did not differ significantly between treatments (insulin aspart/human insulin relative risk 0.72; 95% CI 0.47-1.09, P = 0.12). The rate of minor events was significantly reduced by 7% with insulin aspart (P = 0.048). Reductions in rate of hypoglycaemia were achieved with maintained overall glycaemic control: Mean HbA(1c) remained constant, slightly below 7.7% on both treatments. CONCLUSIONS: The use of insulin aspart in an intensive insulin regimen in patients with tightly controlled Type 1 diabetes led to clinically significant reductions in major nocturnal hypoglycaemia with no deterioration in glycaemic control. Major nocturnal hypoglycaemia appears to be a strong clinical indication for the use of rapid-acting insulin analogues during intensive insulin therapy.
Adolescent↗
Detecting undiagnosed diabetes in urban Asian Indians--role of opportunistic screening.
BACKGROUND: The aim of the study was to determine the proportion of incidental to symptomatic diagnosis of diabetes and to compare the profile of symptomatic and incidentally diagnosed diabetic subjects. METHODS: One thousand newly diagnosed diabetic subjects (WHO criteria) were studied. Clinical, demographic, anthropometric details, blood pressure, glycaemic and lipid parameters were recorded. Reasons for medical check up were noted. RESULTS: Among the 1000 subjects, 29% were symptomatic for diabetes and 71% were incidentally diagnosed to have diabetes. Symptomatic subjects were younger, had higher glycaemia and prevalence of hypertension. CONCLUSION: The results show that majority of type 2 diabetic subjects remain asymptomatic and opportunistic screening for diabetes would be required for the early diagnosis of the disorder.
Adult↗
Body composition of Aboriginal Australian women: comparison with age-matched Caucasians.
Although Aboriginal Australians (AA) exhibit an android fat deposition profile and suffer from a high incidence of type 2 diabetes, a comprehensive body composition assessment of AA has not yet been reported. The body composition of 16 non-diabetic AA women and 16 healthy age- and weight-matched Caucasian women (C) showed no significant ethnic differences in height, total body bone mineral density, total and appendicular skeletal muscle mass, and % fat. The abdominal fat-to-lean soft tissue ratio correlated more highly with age in AA ( r=0.79, p<0.001) than in C ( r=0.59, p<0.05) and with % fat in AA ( r=0.67, p<0.01) than in C ( r=0.54, p<0.05). However, analysis of variance showed that the difference between the two ethnic groups was not significant. Key findings are that dual-energy X-ray absorptiometry can accurately assess adiposity, and that hip girth should emerge as a valid predictor of central adiposity, in AA women.
Absorptiometry, Photon↗
Comparability of venous and capillary glucose measurements in blood.
AIM: Diabetes and glucose intolerance are diagnosed by measurement of glucose in blood. Glucose is usually measured as venous plasma or capillary whole blood and diagnostic criteria frequently provide equivalence estimates for these two methods. This study examined the relationship between glucose measured in capillary and venous samples collected at random, fasting and 2 h after oral glucose. METHODS: Simultaneous measurements of venous plasma and capillary blood glucose were performed on random samples in 609 people, fasting samples in 685 people, and 2 h after oral glucose samples in 463 people. Separate capillary and venous samples were collected each time. A variance component model was used to construct conversion algorithms between venous and capillary results. RESULTS: The relationship between venous and capillary glucose values varied, with venous plasma being higher than capillary blood for random and fasting samples but lower for sampling 2 h after oral glucose. Discrepancies were observed between measured capillary blood values and the published WHO capillary blood equivalence values for venous plasma values for all except a fasting venous value of 7.0 mmol/l. For example, for a fasting venous plasma glucose of 6.1 mmol/l the WHO equivalent value is 5.6 mmol/l, while the measured value was 5.2 mmol/l, and for a 2-h venous plasma glucose of 11.1 mmol/l the WHO value is 11.1 mmol/l, while the measured result was 11.7 mmol/l. CONCLUSIONS: These results highlight the difficulty in equating glucose levels from one sampling and measuring procedure to another, and raise uncertainties about current published equivalence values which could lead to misclassifications in glucose tolerance status.
Analysis of Variance↗
Physiological validation of the concept of glycemic load in lean young adults.
Dietary glycemic load, the mathematical product of the glycemic index (GI) of a food and its carbohydrate content, has been proposed as an indicator of the glucose response and insulin demand induced by a serving of food. To validate this concept in vivo, we tested the hypotheses that 1). portions of different foods with the same glycemic load produce similar glycemic responses; and 2). stepwise increases in glycemic load for a range of foods produce proportional increases in glycemia and insulinemia. In the first study, 10 healthy subjects consumed 10 different foods in random order in amounts calculated to have the same glycemic load as one slice of white bread. Capillary blood samples were taken at regular intervals over the next 2 h. The glycemic response as determined by area under the curve was not different from that of white bread for nine foods. However, lentils produced lower than predicted responses (P < 0.05). In the second study, another group of subjects was tested to determine the effects of increasing glycemic load using a balanced 5 x 5 Greco-Latin square design balanced for four variables: subject, dose, food and order. Two sets of five foods were consumed at five different glycemic loads (doses) equivalent to one, two, three, four and six slices of bread. Stepwise increases in glycemic load produced significant and predictable increases in both glycemia (P < 0.001) and insulinemia (P < 0.001). These findings support the concept of dietary glycemic load as a measure of overall glycemic response and insulin demand.
Adult↗
The 'carnivore connection'--evolutionary aspects of insulin resistance.
Insulin resistance is common and is determined by physiological (aging, physical fitness), pathological (obesity) and genetic factors. The metabolic compensatory response to insulin resistance is hyperinsulinaemia, the primary purpose of which is to maintain normal glucose tolerance. The 'carnivore connection' postulates a critical role for the quantity of dietary protein and carbohydrate and the change in the glycaemic index of dietary carbohydrate in the evolution of insulin resistance and hyperinsulinaemia. Insulin resistance offered survival and reproductive advantages during the Ice Ages which dominated human evolution, during which a high-protein low-carbohydrate diet was consumed. Following the end of the last Ice Age and the advent of agriculture, dietary carbohydrate increased. Although this resulted in a sharp increase in the quantity of carbohydrate consumed, these traditional carbohydrate foods had a low glycaemic index and produced only modest increases in plasma insulin. The industrial revolution changed the quality of dietary carbohydrate. The milling of cereals made starch more digestible and postprandial glycaemic and insulin responses increased 2-3 fold compared with coarsely ground flour or whole grains. This combination of insulin resistance and hyperinsulinaemia is a common feature of many modern day diseases. Over the last 50 y the explosion of convenience and takeaway 'fast foods' has exposed most populations to caloric intakes far in excess of daily energy requirements and the resulting obesity has been a major factor in increasing the prevalence of insulin resistance.
Biological Evolution↗
Postprandial hyperglycemia and insulin sensitivity differ among lean young adults of different ethnicities.
Both postprandial hyperglycemia and insulin resistance (IR) have implications for the development of cardiovascular disease. The present study was designed to examine differences in postprandial glycemia and insulin sensitivity among young adults of different ethnic origins. Lean, healthy subjects (n = 60) from five ethnic groups [20 European Caucasians, 10 Chinese, 10 South East (SE) Asians, 10 Asian Indians and 10 Arabic Caucasians] were matched for age, body mass index, waist circumference, birth weight and current diet. A 75-g white bread carbohydrate challenge was fed to assess postprandial glycemia and insulinemia. Insulin sensitivity was assessed in three groups by the euglycemic-hyperinsulinemic clamp and in all subjects by homeostasis model assessment (HOMA) modeling. Postprandial hyperglycemia (incremental area under the curve) and insulin sensitivity (M-value) both showed a twofold variation among the groups (P < 0.001) and were significantly related to each other (R(2) = 56%, P < 0.001). Young SE Asians had the highest postprandial glycemia and lowest insulin sensitivity, whereas European and Arabic Caucasian subjects were the most insulin sensitive and carbohydrate tolerant. These findings suggest that IR is evident even in lean, young adults of some ethnic groups and is associated with significant increases in postprandial glycemia and insulinemia in response to a realistic carbohydrate load.
Adolescent↗
Association of a functional inducible nitric oxide synthase promoter variant with complications in type 2 diabetes.
Complications of diabetes have a genetic influence. Since increased inducible nitric oxide synthase (iNOS) gene ( NOS2A) expression can contribute to tissue damage, NOS2A is a worthy candidate for such a role. We therefore tested a 4-bp insertion/deletion (+/-) polymorphism 0.7 kb upstream of NOS2A for association with complications in type 2 diabetes patients, and also performed transient transfection experiments to examine the effect of this variant on promoter activity in kidney cells in culture. We investigated 379 Caucasian type 2 diabetes patients of British/European descent, 93 of whom had microalbuminuria, 26 overt nephropathy, 46 retinopathy, and 73 clinical neuropathy. Genotyping for the variant was carried out by PCR and automated Genescan analysis. Transient transfection studies involved the renal HEK 293 cell line and luciferase reporter gene constructs containing 1.1 kb of 5'-flanking DNA from '+' or '-' allele homozygotes. We found that the '+' allele frequency in patients without microalbuminuria was 12%, but was 23% in those with microalbuminuria ( P=0.0005), and was 26% in those with nephropathy ( P=0.0007), 22% in those with retinopathy ( P=0.037), and 23% in those with neuropathy ( P=0.045). The odds ratios for homozygote +/+ to have microalbuminuria or nephropathy were 2.4 (95% CI 1.4-4.2, P=0.0023) and 5.4 (95% CI 1.8-16, P=0.0009), respectively. Luciferase reporter gene constructs containing 1 kb of NOS2A promoter DNA for each allele were made and sequence analysis confirmed that the +/- variation was the only sequence difference present. Transient transfection of these into HEK 293 cells revealed 25 times higher reporter gene activity for the '+' allele compared with the '-' allele. Gel shift analysis with 30mer oligonucleotides corresponding to each allele showed specific binding to nuclear extracts, being greater for the '+' allele. Thus the '+' allele of the NOS2A promoter variant may confer higher iNOS expression, and could contribute to complications of type 2 diabetes, especially in the approximately 5% of patients homozygous for this variant.
Albuminuria↗
TNFRSF1B in genetic predisposition to clinical neuropathy and effect on HDL cholesterol and glycosylated hemoglobin in type 2 diabetes.
OBJECTIVE: Genetic variation in the tumor necrosis factor (TNF) receptor 2 gene (TNFRSF1B) has shown association with insulin resistance in type 2 diabetes, hypercholesterolemia, coronary artery disease, and essential hypertension. Here we tested the TNFRSF1B marker used in the latter studies in type 2 diabetes patients. RESEARCH DESIGN AND METHODS: A case-control study of a microsatellite marker with five alleles (CA13- CA17) in intron 4 of TNFRSF1B was performed in 357 well-characterized white patients and 183 healthy control subjects. RESULTS: The CA16 allele was associated with clinical neuropathy (frequency = 27% in 69 patients with the condition versus 16% in 230 subjects without the condition; chi2 = 9.0, P = 0.011; odds ratio = 2.1 [95% CI 1.2-3.8]). No association was seen with other complications or diabetes itself. The CA16 allele tracked with elevation plasma HDL cholesterol (1.3 +/- 0.2, 1.2 +/- 0.4, and 1.1 +/- 0.2 for CA16/CA16, CA16/-, and -/-, respectively; n = 9, 110, and 218, respectively; P = 0.009) and reduction in plasma glycosylated hemoglobin (6.6 +/- 0.3, 8.3 +/- 0.2, and 8.1 +/- 0.1 for CA16/CA16, CA16/-, and -/-, respectively; n = 9, 102, 205, respectively; P = 0.007) Significance remained after Bonferroni correction for multiple testing. CONCLUSIONS: Genetic variation in or near TNFRSF1B may predispose clinical neuropathy, reduced glycosylated hemoglobin, and increased HDL cholesterol in type 2 diabetes patients. The latter could be part of a protective response.
Aged↗
The lower limb in people with diabetes. Position statement of the Australian Diabetes Society.
Diabetic lower-limb problems result in significant social, medical and economic consequences and are the most common cause of hospitalisation for people with diabetes. In people with diabetes, amputations are 15 times more common than in people without diabetes, and 50% of all amputations occur in people with diabetes. Peripheral neuropathy, vascular disease, infection and deformity of the feet are the major predisposing factors leading to ulceration or amputation. All people with diabetes should receive basic footcare education, and regular foot examinations. The risk for the development of ulceration can be assessed by basic clinical examination of the foot. Management strategies depend on the risk category, and range from basic education and annual review to specialist care by a multidisciplinary team.
Aged↗
Insulin sensitivity predicts glycemia after a protein load.
Protein ingestion results in small but distinct changes in plasma glucose and insulin. We hypothesized that the glycemic and/or insulin response to protein might be related to the degree of insulin sensitivity. Our aim was to determine the relationships between insulin sensitivity (assessed by euglycemic-hyperinsulinemic clamp) and postprandial glucose, insulin, C-peptide, and glucagon responses to a 75-g protein meal and a 75-g glucose load. Sixteen lean healthy Caucasian subjects (mean +/- SD age, 25 +/- 6 years; body mass index [BMI], 23.1 +/- 1.7 kg/m2) participated in the study. After the protein meal, the mean plasma glucose declined gradually below fasting levels to a nadir of -0.36 +/- 0.46 mmol/L from 60 to 120 minutes, showing wide intraindividual variation. Insulin sensitivity (M value) was 1.1 to 3.9 mmol/L/m2 min in the subjects and correlated inversely with the plasma glucose response to the protein meal (r = -.58, P = .03), ie, the most insulin-sensitive subjects showed the greatest decline in plasma glucose. In contrast, there was no correlation between insulin sensitivity and the insulin or glucagon response to the protein load, or between the M value and the metabolic responses (glucose, insulin, C-peptide, and glucagon) to the glucose load. Our study suggests that the net effect of insulin and glucagon secretion on postprandial glucose levels after a protein meal might depend on the individual's degree of insulin sensitivity. Gluconeogenesis in the liver may be less susceptible to inhibition by insulin in the more highly resistant subjects, thereby counteracting a decline in plasma glucose.
Adult↗
The use and perceived value of diabetes clinical management guidelines in general practice.
OBJECTIVE: To assess attitudes to and use of NSW Health Department (NSWHD) guidelines for the clinical management of diabetes mellitus by divisions of general practice, general practitioners, patients and allied health professionals. METHOD: A mail cross sectional survey of divisions of general practice and a series of focus groups of GPs, patients and allied health professionals, on extent of use and perceived usefulness of the NSWHD guidelines. RESULTS: Forty divisions had or recently concluded a diabetes shared care project. Thirteen out of the 31 diabetes projects with guidelines reported using the NSWHD guidelines. Nineteen divisions were aware of the NSWHD guidelines. While the general response to the guidelines in both the survey and the focus groups was positive, there were suggestions for modifications. Many respondents were not aware of the guidelines. CONCLUSION: Optimal use of the guidelines in general practice requires improved dissemination and an implementation strategy based not only on GP education but also systems to reduce barriers to implementation and to support better quality of GP care.
Attitude of Health Personnel↗
Evolutionary aspects of diet and insulin resistance.
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Animals↗
Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.
OBJECTIVE: To compare the effect of repaglinide in combination with metformin with monotherapy of each drug on glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 83 patients with type 2 diabetes who had inadequate glycemic control (HbA1c > 7.1%) when receiving the antidiabetic agent metformin were enrolled in this multicenter, double-blind trial. Subjects were randomized to continue with their prestudy dose of metformin (n = 27), to continue with their prestudy dose of metformin with the addition of repaglinide (n = 27), or to receive repaglinide alone (n = 29). For patients receiving repaglinide, the optimal dose was determined during a 4- to 8-week titration and continued for a 3-month maintenance period. RESULTS: In subjects receiving combined therapy, HbA1c was reduced by 1.4 +/- 0.2%, from 8.3 to 6.9% (P = 0.0016) and fasting plasma glucose by 2.2 mmol/l (P = 0.0003). No significant changes were observed in subjects treated with either repaglinide or metformin monotherapy in HbA1c (0.4 and 0.3% decrease, respectively) or fasting plasma glucose (0.5 mmol/l increase and 0.3 mmol/l decrease respectively). Subjects receiving repaglinide either alone or in combination with metformin, had an increase in fasting levels of insulin between baseline and the end of the trial of 4.04 +/- 1.56 and 4.23 +/- 1.50 mU/l, respectively (P < 0.02). Gastrointestinal adverse events were common in the metformin group. An increase in body weight occurred in the repaglinide and combined therapy groups (2.4 +/- 0.5 and 3.0 +/- 0.5 kg, respectively; P < 0.05). CONCLUSIONS: Combined metformin and repaglinide therapy resulted in superior glycemic control compared with repaglinide or metformin monotherapy in patients with type 2 diabetes whose glycemia had not been well controlled on metformin alone. Repaglinide monotherapy was as effective as metformin monotherapy.
Australia↗