Page 461 Wednesday, Apr Page il 18, 2007 11:07 AM Prediabetes: a position statement from the Australian Diabetes Society and Australian Diabetes Educators Association Stephen M Twigg, Maarten C Kamp, Timothy M Davis, Elizabeth K Neylon and Jeffrey R Flack onditions in which blood glucose levels are elevated but not in the range of diabetes mellitus occur commonly. The term Prediabetes, the presence of impaired fasting glucose/
C"prediabetes" has recently been adopted internationally to glycaemia and/or impaired glucose tolerance, affects about describe many of these conditions, but no national or international 16.4% of Australian adults.
management guidelines have been published. This position statementhas been developed as outlined in Box 1 to provide consensus-based People with prediabetes are at increased risk of developing
clinical care guidelines for patients with prediabetes.
diabetes, and cardiovascular and other macrovascular The Medical Journal of Australia ISSN: 0025- 729X 7 May 2007 186 9 461-465 Management includes reducing cardiovascular disease risk
The Medical Journal of Australia 2007 In 2002, the American Diabetes Association and the United States factors, specifically lipid and blood pressure abnormalities, Department of Health and Human Services2 defined prediabetes as and smoking-cessation counselling. To help prevent Position Statement the condition in which blood glucose levels are elevated above the progression to diabetes, people with prediabetes who are normal range but do not satisfy the criteria for the diagnosis of overweight or obese require intensive lifestyle intervention. diabetes mellitus,3 defined by the World Health Organization.4 For Medication to help prevent diabetes may also be used, but practical purposes, only a single plasma glucose measurement in the only after a minimum of 6 months of lifestyle intervention.
defined category, rather than two on separate days, is required to In people with prediabetes, there is no role for routinely
diagnose prediabetes, with testing done in the absence of severe testing: capillary blood glucose; glycated haemoglobin metabolic stress or illness.
(HbA1c) levels; serum insulin or pancreatic C-peptide levels; With current usage, prediabetes can be applied as a label for a or testing for ischaemic heart disease or the microvascular disorder or as a risk category for diabetes and cardiovascular disease.
complications of diabetes.
There is no clear evidence which of these has the greater clinical utility.
In addition, even within the established biochemical ranges for Follow-up assessment of glycaemia in prediabetes requires a formal 75 g oral glucose tolerance test, initially performed impaired fasting glucose/glycaemia (IFG) and impaired glucose toler-ance (IGT), in most populations there is no glycaemic threshold for annually, with subsequent individualised testing frequency.
the risk of prospective diabetes, cardiovascular disease, or all-cause MJA 2007; 186: 461–465 mortality.5 The single category of prediabetes thus incorporates acontinuum of "cardiometabolic risk".
shown a positive association of prediabetes with increasing age, Although the American Diabetes Association has recently defined particularly for IGT.7 On the basis of the similar cardiovascular profiles IFG as a fasting plasma glucose level of 5.6–6.9 mmol/L,5 this has not of prediabetes and diabetes,10 the clinical risk factors for prediabetes been adopted in this position statement. There is evidence that such a have been described as those for type 2 diabetes.11 low threshold glucose level may cause the IFG category to lose Prediabetes is often an incidental finding in people who are specificity and positive predictive value as a risk factor for diabetes.6 undergoing biochemical testing for diabetes. As in type 2 diabetes,12 Thus, the biochemical range used for IFG is the WHO definition of screening for prediabetes among adults who are overweight, using a ⭓6.1mmol/L and <7.0mmol/L (Box 2).4 stepped approach of a fasting plasma glucose (FPG) measurementthen, if indicated, a 75 g oral glucose tolerance test (OGTT), appearsmore cost-effective than a 75 g OGTT as a first-line investigation, Prevalence, pathogenesis and detection
especially in screening the general community.13 In the AusDiab study, a cross-sectional survey of adults aged 25 years No prospective data are available to determine whether screening and older,7 IGT affected 10.6% of subjects, being more common in for the presence of prediabetes gives long-term health benefits. Thus, women (11.9% v 9.2% in men), and IFG was present in 5.8%, being currently, because of the lack of fully defined risk factors for prediabe- more prevalent in men (8.1% v 3.4% in women). This represents an tes and the lack of longer-term intervention data, screening specifically overall prediabetes prevalence of 16.4% in Australian adults (⭓ 25 for prediabetes is not recommended. We acknowledge that it will occur, in association with biochemical screening for diabetes.12 As in type 2 diabetes, the pathogenesis of prediabetes is linked to According to current guidelines,12 if in screening for type 2 diabetes, a relative insulin deficiency and tissue insulin resistance causing abnor- formal laboratory FPG measurement is between 5.5 and 6.9 mmol/L, mal blood glucose levels despite secondary hyperinsulinaemia.8 A then a formal 75 g OGTT should be performed to exclude diabetes.
recent review suggests that IFG is associated with hepatic insulinresistance, resulting in fasting hyperglycaemia, and IGT is associated Clinical significance of prediabetes
predominantly with skeletal muscle insulin resistance.8 Although, intuitively, risk factors for prediabetes may mirror those of type 2 diabetes, no prospective studies have comprehensively Given the natural history of prediabetes, about 3%–10% of people per identified risk factors for prediabetes development. A study of pre- year with prediabetes develop diabetes. Data are particularly well menopausal women found that obesity and waist circumference were substantiated for IGT. In the Diabetes Prevention Program,14 with associated with prediabetes,9 and other cross-sectional studies have subjects who had IGT, with or without IFG, there was about a 10% MJA • Volume 186 Number 9 • 7 May 2007
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people with type 2 diabetes.7 Aim: To develop recommendations for the clinical management Some data indicate that people with IGT and normal levels of of prediabetes for physicians and allied health care professionals.
fasting plasma glucose have a greater risk of CVD than those with Source: The Prediabetes Working Party, formed in late 2004, IFG.19,21 In addition, when other known CVD risk factors, such as comprises representatives from the Australian Diabetes Society hypertension and lipid abnormalities, are adjusted for statistically, (ADS) Council and the Australian Diabetes Educators Association IGT, but possibly not IFG, remains as an independent CVD risk (ADEA) Board.
factor.20 An increasing plasma glucose level in IGT is associated with a Methods: A review of peer-reviewed journals was conducted greater risk of cardiovascular death.20 using MEDLINE (1966 – 30 September 2005). To provide a historical profile to the term "prediabetes" and a more complete approach to Associations with the metabolic syndrome therapy, specific key relevant references outside of these dates were The metabolic syndrome (MetS) refers to a clustering in an individual also included. Relevant articles were identified using the subject of CVD risk factors and diabetes susceptibility.24 People with MetS headings "glucose intolerance" and "prediabetes". To ensure all appropriate articles were identified, the text words "IGT", "IFG", have about a twofold increased risk of developing diabetes and "impaired glucose tolerance", "impaired fasting glucose", and cardiovascular disease, compared with those without the syndrome.25 "impaired fasting glycemia" were used.
Several MetS definitions exist, with two being widely used.26,27 Levels of evidence: Articles retrieved were graded according to Recently, a third definition has been adopted by the International their level of evidence (based on the National Health and Medical Diabetes Federation.28 Each definition has impairment of glucose Research Council [NHMRC] levels of evidence [I, II, III (including III-1, metabolism as an optional criterion, although some consider only III-2, III-3), and IV] designated E1, E2, E3, and E4, respectively).1 IFG. Most adults who have prediabetes will also have MetS. Whether When an NHMRC level of evidence for a clinically relevant aspect prediabetes or MetS best defines diabetes and cardiovascular risk of prediabetes management was lacking, consensus expert opinion remains to be determined.
of the Prediabetes Working Party (designated E5) was applied.
Final recommendations: Comments from members of the ADS Council and ADEA Board on the draft position statement were Management of prediabetes
received and considered. Final clinical recommendations were then The management of prediabetes is determined by the increased risk of prepared by the Prediabetes Working Party and approved by the developing both diabetes and cardiovascular disease.19 Diabetes pre- ADS Council and ADEA Board. vention studies in people with prediabetes have been conducted. Incontrast, prevention of subsequent cardiovascular complications in annual rate of progression to diabetes in the control group. Other prediabetes has not been studied specifically.
studies have shown similar or somewhat lower rates for progression Lifestyle intervention from IGT or IFG to diabetes.15,16 The combination of IFG and IGTconfers a greater risk of diabetes than either category alone. Overall, Several randomised, prospective studies of subjects with prediabetes prediabetes confers about a sixfold increased risk of diabetes com- have documented beneficial effects of lifestyle intervention in prevent- pared with normal glucose tolerance.
ing type 2 diabetes. In the Diabetes Prevention Program,14 targets in In most populations studied, the rates of conversion from IFG and the lifestyle intervention arm were weight loss of 7% and moderate IGT to diabetes are similar, with IGT having greater sensitivity17 but physical activity (such as brisk walking) for a total of 150min weekly.
less specificity18 than IFG in predicting diabetes risk. Each category Although most subjects did not achieve these goals, an average of 6% has a similar positive predictive value.5 In an 11-year follow-up study (5.6kg) of body weight was lost and 57% of subjects undertook the among adults with IGT in Mauritius, 46% developed diabetes, 28% targeted amount of physical activity. After an average follow-up of 2.8 remained unchanged in category, 4% developed IFG, and glucose years, there was a 58% relative risk reduction in progression to diabetesin the lifestyle-intervention group compared with the controls. By the levels normalised in 24%. Among adults with IFG, 38% developed end of the study, while most of the weight lost in the intervention arm diabetes, 7% remained unchanged, 17% developed IGT, and glucoselevels normalised in 38%.18 Thus, many people with prediabetes (aquarter or more) may revert long term to having normal glucose 2 Criteria for diagnosing prediabetes — impaired fasting
tolerance, and after a protracted follow-up, only about 50% of people glucose (IFG) level and impaired glucose tolerance
with IGT or IFG will develop diabetes.
Cardiovascular disease risk Plasma glucose level Prediabetes (IFG or IGT) In comparison with adults who have normal glucose tolerance, peoplewith prediabetes have an increased risk of developing cardiovascular disease (CVD) and cardiovascular and all-cause mortality.19-21 There is a two- to threefold increased prospective risk of cardiovascular and 2-hour post-glucose load* events,13 which is most marked in younger adults with prediabetes.22 These rates for cardiovascular events approach those in people who have type 2 diabetes.23 Prediabetes is associated with increased ratesof the cardiovascular risk factors found in people with type 2 diabetes.21 In Australia, increased serum triglyceride levels, decreased and 2-hour post-glucose load* ⭓ 7.8 and < 11.1 high-density lipoprotein (HDL) cholesterol levels, hypertension and * A standardised 75 g oral glucose tolerance test. central adiposity are more common in adults with prediabetes com- MJA • Volume 186 Number 9 • 7 May 2007
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Multiple medications have been shown in randomised, double- Similarly, in the Finnish Diabetes Prevention Study,15 after 3.2 years blinded, prospective studies to reduce the incidence of diabetes in of follow-up, there was a 58% relative risk reduction in the incidence people with prediabetes. In each of these studies, patients in all of diabetes in the lifestyle intervention group compared with controls.
intervention arms commonly received general healthy lifestyle advice Those who achieved the greatest number of the five pre-established in addition to active medication or placebo. In the Diabetes Prevention lifestyle goals in the study (weight reduction > 5%; fat intake < 30% of Program, subjects allocated at random to metformin therapy, 850 mg total energy intake; saturated fat intake < 10% of total energy intake; twice daily, showed a 31% risk reduction in progression to diabetes dietary fibre intake ⭓ 15 g/1000 kcal; and at least moderate intensity compared with the control group.14 Younger age (< 60 years) and exercise for > 4 hours weekly) showed the lowest rate of diabetes overweight predicted greatest benefit. Adherence to metformin was development. The Da Qing IGT and Diabetes Study16 of adults with about 70%, compared with 75% for placebo. When metformin was prediabetes compared a control group with three treatment groups: stopped, its benefit in preventing diabetes was maintained in about diet alone, exercise alone, or diet plus exercise. Over 6 years, the 83% of subjects. The combined effect of intensive lifestyle interven- relative risk reduction in progression to diabetes was 31% in the diet tion and metformin therapy was not studied in the Diabetes Preven- group, 46% in the exercise group, and 42% in the combination group.
tion Program.
Two other recent randomised clinical trials have also indicated that In the STOP-NIDDM trial, the glucosidase inhibitor acarbose lifestyle intervention is effective in reducing the incidence of diabetes (100 mg three times daily) reduced progession to diabetes by about in subjects with prediabetes from different ethnic groups. In 458 25% after 3.3 years.34 Acarbose may also reduce the occurrence of Japanese men with IGT, the cumulative 4-year incidence of diabetes cardiovascular events,34 but this finding needs to be confirmed inother studies.35 In the TRIPOD study,36 women with a history of was 9.3% in the lifestyle control group, versus 3.0% in the intensive gestational diabetes (a condition predisposing to diabetes) were less intervention group, with a relative reduction in development of likely to develop diabetes when treated with troglitazone (an agent diabetes of 67%.29 In the Indian Diabetes Prevention Programme, subsequently withdrawn because of idiosyncratic liver dysfunction).
lifestyle modification in 531 subjects with IGT at enrolment delayed This positive finding is likely to be a class effect of the thiazolidinedi- the development of type 2 diabetes in Asian Indian subjects, with a 3- one group of medications, particularly as the recent DREAM study year cumulative incidence of diabetes of 55% in the control group showed that rosiglitazone, 8 mg daily, taken for a median of 3 years, compared with 39% in the lifestyle intervention group.30 The relative reduced the risk of diabetes or death by 60% in subjects with risk reduction of 29% with lifestyle modification was similar to that in prediabetes.37 In the XENDOS study,38 the gastrointestinal lipase a parallel group treated with both metformin and lifestyle intervention.
inhibitor orlistat taken three times daily reduced diabetes risk by 37% Sustained moderate loss of body weight in people with prediabetes over 4 years in obese adults with prediabetes.
is an important predictor of a positive outcome of lifestyle interven- None of these medications is approved for use in people with tion. It is difficult to dissect out the role that macronutrients played in prediabetes on the Pharmaceutical Benefits Scheme. In addition, protecting against development of diabetes, although most of the considering the beneficial effects of diet and exercise, in general, intervention studies did focus on reducing total energy intake from fat, medication cannot be recommended in preference to lifestyle inter- including reducing saturated fat intake, and increasing dietary fibre vention in preventing diabetes. It is suggested that a minimum 6 intake. By contrast, at present there is insufficient information to months of lifestyle intervention be trialled before pharmacotherapy is determine whether reducing dietary total carbohydrate intake, or commenced, as the nadir of weight loss occurred at this time in the glycaemic index or load, will protect against the development of Diabetes Prevention Program.14 Definitions of failure would include diabetes.31 Factors other than a reduction in body weight are likely to weight gain rather than weight loss and no evidence of increased have retarded the development of diabetes, potentially through physical activity or achievement of recommended macronutrient improvements in insulin sensitivity or reduction in central body fat.30 dietary change.
Physical activity may work through mechanisms involving improvedinsulin sensitivity and weight-loss maintenance.
Managing macrovascular risk and screening for
end-organ complications

Health care delivery In prediabetes, for people without known cardiovascular disease, no In the Finnish Diabetes Prevention Study and the Diabetes Prevention targets have been established for ischaemic heart disease risk factors.
Program, multidisciplinary teams included a physician, dietitian, Because people with prediabetes have a similar overall cardiovascular nurse, psychologist and a physiotherapist. In each of the studies, there risk to those with type 2 diabetes, we recommend that macrovascular was expertise in nutrition, physical activity and behavioural change.
treatment targets for adults with prediabetes and diabetes should be Individual patient education and coaching was used to implement the same. Thus, blood pressure targets should generally be < 130/ intensive lifestyle change. The economic cost of implementing such an 80 mmHg.39 For individuals without a known history of macrovascu- approach in routine clinical care in people with prediabetes may not lar disease, lipid targets in prediabetes should be in line with National be justifiable,32 and it has been proposed that an emphasis on group Heart Foundation of Australia guidelines40 for primary prevention interventions may provide a more cost-effective approach, although (total cholesterol, < 4.0 mmol/L; HDL cholesterol, > 1.0 mmol/L; trig- this has not been formally tested.33 Cost-efficient, practical health care lycerides, < 1.7 mmol/L; and calculated low-density lipoprotein (LDL) delivery models for the lifestyle aspects of diabetes prevention require cholesterol, < 2.5 mmol/L).41 Antiplatelet therapy for cardiovascular further study. In the interim, methods that lead to sustained improve- prophylaxis in prediabetes is the same as recommended in type 2 ments in nutrition and physical activity levels should be encouraged.
diabetes. Cigarette smokers should be counselled to stop smoking.
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betes. In addition, serum insulin and pancreatic C-peptide levels have Definition and detection: "Prediabetes" is defined as the presence no established clinical role in prediabetes.
of impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). A single abnormal reading at formal testing is adequate to Screening for end-organ complications define prediabetes. People who have prediabetes are at increased People with prediabetes who are asymptomatic for ischaemic heart risk of developing diabetes, although a proportion of those with disease should be assessed individually, and a history of symptoms prediabetes can revert to normal glucose tolerance. Prediabetes and macrovascular risk factors obtained before a decision is made to may be incidentally detected when screening for diabetes. There investigate for possible myocardial ischaemia.
is no current proven clinical role for specifically screening for FPG and 2-hour levels post-glucose load are associated with prediabetes. This is consistent with current National Health and retinopathy and nephropathy, with approximate thresholds near or Medical Research Council guidelines for screening for diabetes (E5).
below the current diagnostic criteria for diabetes.43 Thus, only rarely Reducing cardiovascular risk: People with prediabetes are at do people with prediabetes develop these microvascular complica- increased risk of developing cardiovascular and other macrovascular disease (E2). Assessment and management of risk factors for tions.43 A painful form of neuropathy, which tends to be transient, cardiovascular disease, specifically lipid and blood pressure may also rarely develop in prediabetes.44 However, no evidence exists abnormalities, should be undertaken. Although there have been no to indicate that routine screening for microvascular disease in predia- intervention studies specific to prediabetes, the blood pressure and betes affects clinical outcome.
lipid targets suggested are equivalent to those for type 2 diabetes, as is the use of prophylactic antiplatelet therapy (E5).
Glycaemia reassessment at follow-up
Preventing progression to diabetes: The appropriate intervention for people with prediabetes who are overweight or obese should The appropriate interval for retesting of adults with prediabetes using be intensive lifestyle intervention (E1), aiming to achieve: a minimum a 75 g OGTT is arbitrary. Initially, 12 months may be appropriate, of 5%–7% body weight loss, with reduced total fat and saturated consistent with current WHO guidelines for diabetes screening, fat intake to < 30% and < 10% of total daily calories, respectively; especially to assess rate of change of abnormal glucose tolerance.4 If a optimal dietary fibre intake; and 150 minutes of physical activity per particular patient develops factors in the interim that increase the risk week (E2). The multidisciplinary approach is the treatment method of developing diabetes, such as significant weight gain, then earlier with strongest evidence (E2). It is recommended that a minimum 6 testing may be indicated. After the initial 12-month follow-up, with a months of lifestyle intervention be trialled before pharmacotherapy is considered (E5). Pharmacotherapy may particularly involve 75 g OGTT, if the results do not show deterioration in glycaemia, the metformin,* (850 mg twice daily), which appears to be relatively retesting interval could be increased, for example to 2 or 3 years.
more efficacious in younger (< 60 years) and more overweight Box 3 summarises the clinical recommendations for prediabetes.
people (E2). Other options include orlistat* (120 mg three times daily); acarbose* (100 mg three times daily); or a thiazolidinedione* (eg, rosiglitazone 8 mg daily or pioglitazone) (E2).
We thank the Project Officer, Dr Abdullah Omari (ADS paid consultant), and the Testing generally not required: In the absence of specific clinical ADS Council members who were not part of the Prediabetes Working Party for indications in an individual, there is no role for routinely conducting their contribution: Dr Wah Cheung, Dr Alicia Jenkins, Professor Mark Febbraio, Dr the following tests in people who have prediabetes: capillary blood Terri Allen, and Associate Professor Glenn Ward. The ADS members who com- glucose measurement, using a home blood glucose meter; glycated mented on the draft statement are also recognised, as is the contribution of the ADEA Board, especially Ms Shirley Cornelius. Assistance from ADS Secretary, Ms 1c) level; serum insulin or pancreatic C-peptide Suzie Neylon, and the Executive Officer of the Australian Diabetes Professional levels; tests for ischaemic heart disease (if there is no clinical Organisations, Mr Chris Thorpe, is acknowledged with thanks.
evidence for the condition); tests for microvascular complications of diabetes, such as retinopathy screening or neuropathy assessment; or tests for microalbuminuria or proteinuria (E5).
Follow-up: Follow-up testing of glycaemia in prediabetes requires a Stephen Twigg has received speaker fees for educational meetings in diabetes, fromAlphapharm, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi-aventis and Servier.
formal 75 g oral glucose tolerance test, initially performed annually. In subsequent years, the frequency of this test can be individualised, with retesting at intervals of 1–3 years (E5).
Author details
Stephen M Twigg, MB BS, FRACP, PhD, Associate Professor,1
* Note that none of the medications mentioned is approved for management of prediabetes on the Pharmaceutical Benefits Scheme. The medication doses Maarten C Kamp, FRACP, MHA, Senior Endocrinologist,3 Associate given are based on studies of prevention of diabetes in people with impaired glucose tolerance. Most of these studies have not been replicated to date and Timothy M Davis, FRACP, Diabetologist, General Physician,5 Professor of in at least one study the validity of the methodology remains questionable. Hence, lifestyle intervention to prevent diabetes and help reduce Elizabeth K Neylon, DAA, CDE, Dietitian, Area-Wide Diabetes Education cardiovascular risk should be preferentially emphasised (E5). Coordinator7Jeffrey R Flack, FRACP, MMed, Senior Staff Endocrinologist, Director8 Clinical Associate Professor91 Department of Medicine, University of Sydney, Sydney, NSW.
Tests for glycaemia 2 Royal Prince Alfred Hospital, Sydney, NSW.
By definition, people with prediabetes have relatively mild and less 3 Gold Coast Hospital, Gold Coast, QLD.
marked elevations in blood glucose levels compared with those with 4 Griffith University, Brisbane, QLD.
diabetes. Particularly as capillary whole-blood glucose measurements 5 Fremantle Hospital, Fremantle, WA.
using portable monitors have significant attendant error (> 10%),42 6 School of Medicine and Pharmacology, University of Western Australia, there is no role for routine home capillary blood glucose monitoring in Fremantle, WA.
people with prediabetes. No data exist to define the utility of 7 South Metropolitan Health Service Area, Department of Health, Perth, WA.
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44 Singleton JR, Smith AG, Bromberg MB. Increased prevalence of impaired 23 Wood D, De Backer G, Faergeman O, et al. Prevention of coronary heart disease glucose tolerance in patients with painful sensory neuropathy. Diabetes Care in clinical practice: recommendations of the Second Joint Task Force of Euro- 2001; 24: 1448-1453.
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(Received 13 Sep 2006, accepted 20 Feb 2007) MJA • Volume 186 Number 9 • 7 May 2007
Cyan process 75.0° 120.0 LPI Magenta process 15.0° 120.0 LPI Yellow process 0.0° 120.0 LPI Black process 45.0° 120.0 LPI


American Quarterly, Volume 64, Number 4, December 2012, pp. 845-849(Article) Published by The Johns Hopkins University PressDOI: 10.1353/aq.2012.0061 For additional information about this article Access provided by Project Muse/Jhup (9 Oct 2014 08:08 GMT) "Reinvigorating the Queer Political Imagination" 845 "Reinvigorating the Queer Political

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