acarbose for prevention of type 2 diabetes mellitus the stop niddm randomised trial

For personal use. Only reproduce with permission from The Lancet Publishing Group.

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2072 THE LANCET • Vol 359 • June 15, 2002 • www.thelancet.com

Summary

Background The worldwide increase in type 2 diabetesmellitus is becoming a major health concern. We aimed toassess the effect of acarbose in preventing or delayingconversion of impaired glucose tolerance to type 2 diabetes.

Methods In a multicentre, placebo-controlled randomisedtrial, we randomly allocated patients with impaired glucosetolerance to 100 mg acarbose or placebo three times daily.The primary endpoint was development of diabetes on thebasis of a yearly oral glucose tolerance test (OGTT). Analyseswere by intention to treat.

Findings We randomly allocated 714 patients with impairedglucose tolerance to acarbose and 715 to placebo. Weexcluded 61 (4%) patients because they did not haveimpaired glucose tolerance or had no postrandomisationdata. 211 (31%) of 682 patients in the acarbose group and130 (19%) of 686 on placebo discontinued treatment early.221 (32%) patients randomised to acarbose and 285 (42%)randomised to placebo developed diabetes (relative hazard0·75 [95% CI 0·63–0·90]; p=0·0015). Furthermore,acarbose significantly increased reversion of impairedglucose tolerance to normal glucose tolerance (p<0·0001).At the end of the study, treatment with placebo for 3 monthswas associated with an increase in conversion of impairedglucose tolerance to diabetes. The most frequent side-effects to acarbose treatment were flatulence and diarrhoea.

Interpretation Acarbose could be used, either as analternative or in addition to changes in lifestyle, to delaydevelopment of type 2 diabetes in patients with impairedglucose tolerance.

Lancet 2002; 359: 2072–77

IntroductionType 2 diabetes mellitus is a major health problemassociated with excess morbidity and mortality and resultsin substantial health-care costs.1 Prevalence of thisdisorder worldwide will double over the next 25 years.2

People who develop type 2 diabetes pass through a phaseof impaired glucose tolerance. Defects in the action orsecretion of insulin are the two major abnormalitiesleading to development of glucose intolerance.3 Resistanceto insulin progressively increases when passing fromnormal glucose tolerance through impaired glucosetolerance to diabetes, whereas secretion of insulingradually decreases.4 Glucose tolerance is assumed toremain normal as long as the � cells can compensate forinsulin resistance.3 Impaired glucose tolerance willdevelop only when insulin secretion fails to compensatefully for such resistance,5 resulting in postprandialhyperglycaemia. Such a mechanism could be sufficient toinduce toxic effects of glucose, which further inhibitsecretion and action of insulin6 and contribute toprogression of impaired glucose tolerance to diabetes.Thus, any intervention in the impaired glucose tolerancephase that reduces resistance to insulin, or protects the � cells, or both, should prevent or delay progression todiabetes. The �-glucosidase inhibitor acarbose improvessensitivity to insulin and decreases postprandialhyperglycaemia, thereby releasing the stress on the � cells.7 On the basis of these observations, we aimed toassess the effect of acarbose on conversion of impairedglucose tolerance to type 2 diabetes in the Study TOPrevent Non-insulin-dependent diabetes mellitus (STOP-NIDDM) trial.8

MethodsStudy designDetails of the study design of the STOP-NIDDM trialhave been described.8 The study was a double-blind,placebo-controlled randomised trial done in Canada,Germany, Austria, Norway, Denmark, Sweden, Finland,Israel, and Spain. Patients were recruited mainly throughscreening of high-risk populations, and in particular fromfirst-degree relatives of patients with type 2 diabetes. Wescreened men and women aged between 40 and 70 yearswho had a body-mass index of between 25 and 40 kg/m2.Patients were eligible for the study if they had impairedglucose tolerance—defined as 2-h plasma glucoseconcentration of 7·8 mmol/L or greater, and less than11·1 mmol/L after a 75 g glucose load.9 Patients also had to have a fasting plasma glucose concentration of5·6–7·7 mmol/L, a value that is associated with a 3·4-fold increase in risk of progression to diabetes.10

Eligible patients were randomly allocated to placebo or100 mg acarbose three times daily, taken with the first biteof a meal. We used a computer program to generate therandom allocation sequence, which was stratified bycentre. Randomisation was done in blocks of four and six.Numbered drug containers were used to implement therandom allocation process. Patients were randomisedsequentially at each centre since the random code was

Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial

Jean-Louis Chiasson, Robert G Josse, Ramon Gomis, Markolf Hanefeld, Avraham Karasik, Markku Laakso, for The STOP-NIDDM Trial Research Group*

*Members listed at end of report

Research Centre, Centre Hospitalier de l’Université de Montréal,Hôtel-Dieu, Department of Medicine, University of Montreal,Quebec, Canada (Prof J-L Chiasson MD); St Michael’s Hospital,Department of Medicine, University of Toronto, Toronto, Ontario,Canada (Prof R G Josse MBBS); Diabetes Unit, Hospital Clinic,Universitari de Barcelona, Barcelona, Spain (Prof Ramon Gomis MD);Centre for Clinical Studies GWT, Dresden Technical University,Germany (Prof M Hanefeld DSc); Institute of Endocrinology, ChaimSheba Medical Centre, Tel Hashomer, Israel (Prof A Karasik MD);University of Kuopio, Kuopio, Finland (Prof M Laakso MD)

Correspondence to: Prof Jean-Louis Chiasson, Research Centre,Centre Hospitalier de l’Université de Montréal, Hôtel-Dieu, 3850 St Urbain Street, Room 8-202, Montreal, Quebec H2W 1T7,Canada(e-mail: [email protected])


risk reduction, and a drop-out rate of 10%, we estimatedthat 600 patients would be needed in each of the twotreatment groups for a two-tailed � of 0·05 and a 1�� of90%. Analysis was by intention to treat. We assessed thedifference between the two groups with Student’s t test forindependent samples. The primary variable was time todevelopment of diabetes, for which we used survivalanalysis to compare the two treatment groups. Formalanalysis was done with Cox’s proportional-hazards model,which was stratified by geographic region with treatmentgroup as a covariate. We also used the Kaplan-Meiermethod to calculate the probability of survival outcome.We assessed change in bodyweight from baseline toendpoint with ANCOVA.

A person (WT) from the data safety and quality reviewcommittee did the interim analysis.8 The first analysis wasdone after all participants had been followed up for 1 year,and then every 6 months for a maximum of five analyses.Differences were judged significant if p was 0·00001,0·001, 0·008, 0·023, and 0·043 for the first to fifthanalyses, respectively.

Role of the funding sourceThe study sponsor (Bayer AG) provided theinfrastructure and staff for data monitoring and collection,but had no role in study design, data analysis, datainterpretation, or in the writing of the report.

ResultsThe first patient with impaired glucose tolerance wasenrolled in December, 1995, and the last in July, 1998.The study was completed in August, 2001 after a meanfollow-up of 3·3 years (SD 1·15). Figure 1 shows the trialprofile. Of the 1429 patients who were randomised (714to acarbose and 715 to placebo), 567 (40%) were fromCanada, 382 (27%) from Germany and Austria, 334(24%) from the Nordic countries, and 73 (5%) each fromSpain and Israel. We excluded 17 patients (eight on

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THE LANCET • Vol 359 • June 15, 2002 • www.thelancet.com 2073

stratified by centre. Random codes were concealed in athree-part container label that was separated from the boxand stored in the event that investigators needed to knowthe randomisation status of the patient. An independentstatistician, who was a member of the data safety andquality review committee, generated the allocationsequence; enrolment and randomisation was handled atthe sites.

To keep the known gastrointestinal side-effects ofacarbose (flatulence, diarrhoea, or abdominal cramps) to aminumum, the drug was started at 50 mg per day, andincreased gradually to a maximum of 100 mg three timesdaily or to the maximum tolerated dose. We instructedpatients on a weight-reduction or weight-maintenancediet, and encouraged them to exercise regularly. Allparticipants met with a dietician before randomisation andyearly thereafter. Patients also completed a 3-daynutritional diary at time of eating and recorded theirphysical activities during the 3 days (2 weekdays, 1 weekend day) in the last month before each yearly visit.All patients were seen every 3 months by the co-ordinatingnurse for pill count and distribution, documentation ofadverse events, and measurement of fasting plasmaglucose, and were examined by the investigator every 6months. All patients remained in the study until the lastrandomised patient had been treated for 3 years; meanfollow-up time was 3·3 years (SD 1·15). At the end oftreatment, all patients who had not developed diabeteswere followed up on placebo in a single-blind fashion for 3months, after which outcome measures were repeated.The protocol was approved by appropriate InstitutionalReview Boards and every patient signed an informedconsent form. An independent committee (the data safetyand quality review committee), who were aware of therandomisation status, oversaw the safety of the study andthe quality of data, and did the interim analysis.8

The primary endpoint was development of diabetes,defined as a plasma glucose concentration of 11·1 mmol/Lor greater 2 h after taking 75 g glucose based on one oralglucose tolerance test (OGTT). All patients had theirtolerance to 75 g oral glucose tested yearly, but, if theplasma glucose concentration was 7·0 mmol/L or greaterduring fasting at any 3-month visit, the patient wasautomatically scheduled for an OGTT. Patients whoreached the primary endpoint remained in the study,continued on the study drug in a masked fashion, and hada yearly OGTT, unless they had to be put on additionalantidiabetic drugs.

Laboratory analysesThe 2-h plasma glucose concentration was measured inlocal laboratories with the glucose oxidase or hexokinasemethod. The glycosylated haemoglobin (HbA1c), lipidprofile, and plasma insulin were measured in two centrallaboratories, one in Toronto, Canada, and one inDresden, Germany. HbA1c was measured by high-performance liquid chromatography,11 and serum insulinby a highly specific immunoradiometric assay with a two-site monoclonal antibody.12 We measured total concen-trations of cholesterol, triglycerides, and HDL-cholesterolin serum enzymatically.13 If the concentration oftriglicerides was less than 4·51 mmol/L, we calculatedLDL-cholesterol mathematically.14 We cross-checkedmeasurements of glucose, HbA1c, insulin, and lipids every4 months for all participating laboratories.8

Statistical analysisSample calculation has been described previously.8 On theassumption of a conversion rate of 7% per year, a 36%

14 742 assessed for eligibility

714 allocated to acarbose

682 analysed

715 allocated to placebo

686 analysed

32 excluded 8 did not meet criteria for IGT 24 had no postrandom- isation data

211 discontinued early

29 excluded 9 did not meet criteria for IGT 20 had no postrandom- isation data

130 discontinued early

13 313 excluded (did not meet eligibility criteria)

1429 randomised

Figure 1: Trial profileIGT=impaired glucose tolerance


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acarbose and nine on placebo) because they did not haveimpaired glucose tolerance (2-h plasma glucose atscreening was 11·1 mmol/L or greater, or less than 7·8 mmol/L). We excluded another 44 patients (24acarbose and 20 placebo) because they had no validpostrandomisation data.

Table 1 shows the baseline characteristics of theanalysed patients. Mean fasting plasma glucoseconcentration at baseline was 6·2 mmol/L (SD 0·5), witha mean 2-h post-75 g glucose of 9·3 mmol/L (1·0). 78(11%) of 686 patients on placebo and 57 (8%) of 682 onacarbose had a plasma glucose concentration of 7·0 mmol/L or greater during fasting and a concentrationof less than 11·1 mmol/L 2 h after consumption of 75 gglucose orally, and would have been classified as havingdiabetes in accordance with the new diagnostic criteria ifdiagnosis had been confirmed by a second abnormalfasting plasma glucose on a separate day.15 629 (46%)patients had hypertension and 789 (58%) haddyslipidaemia. These patients presented with all thecharacteristics of the metabolic syndrome and were thusat very high risk of developing type 2 diabetes and macro-vascular disease.16 We measured the concentration ofautoantibodies to glutamic acid decarboxylase and

tyrosine phosphatase at baseline in 728 (53%) patientsusing a new combined radiobinding assay;17 only 16 (2%)of the 728 were positive, suggesting that inclusion of type-1 diabetes that is slow to develop was not an issue in ourtrial.18

Almost a quarter of patients discontinued early (figure 1), of whom almost a half (48%) discontinuedduring the first year. The commonest single cause of earlydiscontinuation was gastrointestinal side-effects (table 2).All these patients were assessed at 3 years to measureendpoint variables, including an OGTT. 43 (3%) of the1429 patients did not have any follow-up measurement ofendpoints, but their inclusion did not affect the results(p=0·0258).

Patients assigned to acarbose received a mean dailydose of 194 mg (SD 87). These patients were 25% lesslikely to develop diabetes than those on placebo (figures 2and 3). Inclusion of the 17 patients who did not haveimpaired glucose tolerance did not affect the efficacy ofacarbose (p=0·0016). This effect was noted at 1 year andpersisted throughout the study. Mean bodyweightdecreased from 87·6 kg (SD 15·2) to 87·1 kg (15·3)during the study in patients given acarbose and increasedfrom 87·0 kg (14·1) to 87·3 kg (15·2) in those on placebo(difference 0·77 kg [95% CI 0·01–1·54], p=0·0184).Analysis with Cox’s proportional-hazards model, withweight change as a covariate, showed that weight losscontributed to the decreased risk of diabetes (p<0·0001),but that treatment with acarbose reduced risk of diabeteseven after adjustment for change in weight (p=0·0063).The beneficial effect of acarbose was consistentirrespective of age, sex, and body-mass index (figure 2).

Acarbose (n=682) Placebo (n=686)

SexMen 329 (48%) 344 (50%)Women 353 (52%) 342 (50%)

Age (years) 54·3 (7·9) 54·6 (7·9)White 664 (97%) 670 (98%)Weight (kg) 87·6 (15·3) 87·1 (14·1)Body-mass index (kg/m2) 31·0 (4·3) 30·9 (4·2)Waist circumference (cm) 102·1 (11·7) 102·2 (11·2)Plasma glucose (mmol/L)

Fasting 6·23 (0·50) 6·24 (0·53)2-h 9·26 (1·06) 9·25 (1·01)

Plasma insulin (pmol/L)Fasting 99·34 (57·64) 98·13 (56·78)2-h 606·37 (437·46) 597·99 (414·38)

Serum lipids (mmol/L)Total cholesterol 5·76 (1·04) 5·61 (0·99)HDL-cholesterol 1·19 (0·32) 1·17 (0·33)LDL-cholesterol 3·66 (0·91) 3·54 (0·90)Triglycerides 2·07 (1·10) 2·07 (1·17)

Blood pressure (mm Hg)Systolic 131·4 (16·3) 130·9 (16·2)Diastolic 82·8 (9·4) 82·0 (9·3)

Smoking 79 (12%) 99 (14%)

Data are mean (SD) or number (%).

Table 1: Baseline characteristics of intention-to-treatpopulation


All adverse events 136 (19%)* 37 (5%)Gastrointestinal adverse events 93 (13%) 18 (3%)

Flatulence 67 (9%) 5 (1%)Diarrhoea 39 (5%) 6 (1%)Abdominal pain 23 (3%) 4 (1%)Other 9 (1%) 7 (1%)

Withdrawn consent 29 (4%) 55 (8%)

Loss to follow-up 18 (3%) 17 (2%)

Non-compliance 10 (1%) 4 (1%)

Death 6 (1%) 3 (<1%)

Moved 3 (<1%) 3 (<1%)

Protocol violation 3 (<1%) 2 (<1%)

Other 6 (1%) 8 (1%)

Total 211 (30%) 130 (18%)

Values are number (%).

Table 2: Reasons for premature discontinuation

Overall

Age (years)�55>55

SexMenWomen

Body-massindex (kg/m2)�30<30

221/682 (32%)

Acarbose

128/370 (35%) 92/311 (30%)

111/329 (34%)110/353 (31%)

132/361 (37%) 89/321 (28%)

285/686 (42%)

Placebo

147/354 (42%) 137/329 (42%)

144/344 (42%)141/342 (41%)

163/368 (44%)121/318 (38%)

0·0015

p

0·05590·0084

0·03820·0089

0·02690·0115

0·75 (0·63–0·90)

Hazard ratio(95% CI)

0·79 (0·62–1·0)0·70 (0·53–0·91)

0·77 (0·60–0·99)0·71 (0·56–0·92)

0·77 (0·61–0·97)0·70 (0·53–0·92)

0·0

Favoursacarbose

Favoursplacebo

0·5 1·0 1·5 2·0

Figure 2: Effect of acarbose on development of diabetesData were calculated with Cox’s proportional-hazard model adjusted forage, sex, and body-mass index.

1·000·950·900·850·800·750·700·650·600·550·500·450·40

Cum

ulat

ive

prob

abili

ty

Days after randomisation10

0030

020

050

040

070

060

090

080

011

0010

0013

0012

00

Acarbose

p=0·0022

Placebo

Patients at riskAcarbosePlacebo

682686

655671

628655

612640

531512

523505

515497

497470

463434

447427

432414

349331

268255

212208

Figure 3: Effect of acarbose and placebo on cumulativeprobability of remaining free of diabetes over time


higher in patients on acarbose than in those on placebo(p<0·0001).

At the end of treatment, all patients were givenplacebo in a single-blind fashion for 3 months, afterwhich all outcome measures were repeated, including anOGTT. During this placebo-treatment period,incidence of diabetes in patients who had not converted(also excluding those who discontinued prematurely)was higher in the group originally assigned to acarbose(47 of 306), than in the group first randomised toplacebo (21 of 199).

The most common side-effects were gastrointestinalsymptoms, which were more frequent in those givenacarbose than in those given placebo (p<0·0001; table4), but were judged to be mild to moderate in severity.The data safety and quality review committee deemedthat no serious adverse events were related to the studydrug.

DiscussionOur results have shown that pharmacologicalintervention with acarbose in patients with impairedglucose tolerance can delay progression to type 2diabetes. The risk of progression to diabetes over 3·3years was reduced by 25%. Furthermore, acarboseincreases the probability that impaired glucose tolerancewill revert to normal glucose tolerance over time.

Although changes in lifestyle are effective inprevention of type 2 diabetes,19–21 our findings and thoseof the US Diabetes Prevention Program (DPP)21 provideevidence that pharmacological intervention can alsodelay progression of impaired glucose tolerance todiabetes.22 The magnitude of the benefit of changes inlifestyle in the Finnish Diabetes Prevention Study19 andin the DPP21 was higher than the benefit we recordedwith acarbose (58% vs 25%). However, we are probablyunderestimating the efficacy of acarbose since ourresults are diluted by the 211 (30%) patientsrandomised to acarbose who discontinued prematurelyand therefore did not take the study drug throughoutmost of the study. Furthermore, if we analyse the resultsof only patients whose diabetes was confirmed by asecond OGTT or by two measurements of fastingplasma glucose, the number of events decreases, and,although the absolute risk reduction (8·7%) does notchange, the relative risk reduction is increased to 36·1%and 32·4%, respectively. Such a risk reduction is verysimilar to the magnitude observed with metformin in theDPP (31%) and the lifestyle change in the Da Qingstudy (36%).20 In the Finnish, DPP, and Chinesestudies, interventions consisted of individualisedintensified programmes, and as such, these trials couldnot be double-blind. Such bias could have affected theoutcome of the trial since either diet or exercise reducedprogression of impaired glucose tolerance to diabetes by36%, whereas diet plus exercise had no additional effect.

Yearly incidence of diabetes in our impaired glucosetolerance population on placebo was 12·4%—a muchhigher incidence than that suggested by epidemiologicaldata (1·5–7·2%)23 and the Finnish Study (6%),19 butlower than the Da Qing study (15·7%).20 The higherincidence of diabetes in our impaired glucose tolerancepopulation than in those of epidemiological data and theFinnish study was probably due, at least in part, to therequirement of a fasting plasma glucose of 5·6 mmol/Lor greater, since this requirement has been shown toincrease conversion to diabetes by a factor of 3·4.10 Itwas probably also partly due to use of only one OGTTfor diagnosis of diabetes. In fact, incidence of diabetes

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Body-mass index (as did weight change) significantlyaffected development of diabetes (p=0·0066), whereas ageand sex did not (p=0·8634 and p=0·4385, respectively).None of the three covariates, however, modified thepositive effect of acarbose treatment (p=0·0012,p=0·0015, and p=0·0016, respectively).

2 years after the study started, the diagnostic criteriawere modified in two ways: fasting plasma glucose wasdecreased to 7·0 mmol/L, and whichever variable wasused, it had to be confirmed on a separate day.15 Thus, ifwe use fasting plasma glucose of 7·0 mmol/L or greater ontwo consecutive visits as the criterion, 117 (17%) patientsdeveloped diabetes in the acarbose group compared with178 (26%) in the placebo group (hazard ratio 0·68 [95%CI 0·54–0·85], p=0·0010), resulting in an absolutereduction of 8·7% and a relative reduction of 32·4%.Furthermore, if we use any two positive OGTTs with a 2-h plasma glucose of 11·1 mmol/L or greater, 105 (15%)patients converted to diabetes in the acarbose groupcompared with 165 (24%) in the placebo group (hazardratio 0·64 [0·4981–0·8129], p=0·0003) for an absolutereduction of 8·7% and a relative reduction of 36·4%.

Based on one abnormal plasma glucose concentration2 h after 75 g glucose load, cumulative incidence ofdiabetes was 221 (32·4%) in the acarbose-treated groupversus 285 (41·5%) in the placebo group. Incidence of thedisorder was thus 101 cases per 1000 person-years in theacarbose group and 121 cases per 1000 person-years inthe placebo group, with a risk difference of 9·1% over3·3 years.

Treatment with acarbose not only decreasedprogression to diabetes by 25%, but also improvedglucose tolerance in patients who reverted to normalglucose tolerance (table 3). The probability of reverting tonormal glucose tolerance over time was significantly

Glucose tolerance

No data NGT IGT DM

Study drugAcarbose (n=682) 26 (4%) 241 (35%) 194 (28%) 221 (32%)Placebo (n=686) 18 (3%) 212 (31%) 171 (25%) 285 (42%)

Values are number of patients (%). NGT=normal glucose tolerance.IGT=impaired glucose tolerance. DM=diabetes mellitus. *In patients who hadnot converted to diabetes.

Table 3: Effect of acarbose and placebo on deterioration orimprovement* of glucose tolerance in patients with IGT


Adverse eventsGastrointestinal 597 (83%) 426 (60%)Flatulence 486 (68%) 196 (27%)Diarrhoea 229 (32%) 123 (17%)Abdominal pain 125 (17%) 89 (12%)Dyspepsia 53 (7%) 62 (9%)Nausea 36 (5%) 39 (5%)Constipation 27 (4%) 35 (5%)Gastroenteritis 31 (4%) 36 (5%)Gastritis 18 (3%) 19 (3%)Anorexia 1 (<1%) 3 (<1%)General symptoms 415 (58%) 444 (62%)Cardiovascular 220 (31%) 287 (40%)Respiratory 229 (32%) 282 (39%)Musculoskeletal 243 (34%) 277 (39%)Metabolic and nutritional 222 (31%) 231 (32%)Nervous 195 (27%) 221 (31%)Urogenital 178 (25%) 198 (28%)Skin 148 (21%) 168 (24%)Haematological and lymphatic 32 (4%) 42 (6%)Endocrine 28 (4%) 31 (4%)Patients with adverse events 698 (98%) 675 (95%)

Values are number (%).

Table 4: Frequency of adverse events


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was reduced to 7·9% if a second OGTT was used toconfirm the diagnosis. The higher incidence of diabetesin the Da Qing study than in other studies could be dueto ethnic differences.24

Our results also suggest that acarbose effectivelyreduced risk of developing diabetes irrespective of age,sex, and body-mass index. Thus, all patients withimpaired glucose tolerance could benefit from acarbosetreatment, especially since the drug has no toxic effects.25

When we discontinued acarbose at the end of thestudy, incidence of diabetes increased in the groupinitially assigned to acarbose. Caution is needed ininterpretation of this observation, since the analysis wasdone on a subgroup of the intent-to-treat population,which excluded those who had already converted todiabetes and those who had discontinued prematurely.Therefore, the most that can be said is that acarbosetreatment should probably be continued to maintain thepreventive effect of the study drug on development ofdiabetes.

What are the possible mechanisms by which acarboseprevents diabetes? Results of many studies10,26 have shownthat the higher the 2-h plasma glucose concentration aftera 75 g glucose load in patients with impaired glucosetolerance, the higher the conversion rate to diabetes.Acarbose significantly decreases the postprandial rise inplasma glucose.7 This effect of acarbose could decreasetoxic effects of glucose and thus delay conversion ofimpaired glucose tolerance to diabetes. It could alsopossibly explain, at least in part, why acarbose treatmentwas associated with an increased reversion to normalglucose tolerance. We have previously shown thatacarbose could decrease resistance to insulin in patientswith impaired glucose tolerance.7 Since such resistance isan important factor in development of type 2 diabetes,such an effect could have a role in delaying progression ofimpaired glucose tolerance to diabetes in our study. Thesmall weight loss in the acarbose group probablycontributed to delaying onset of diabetes.19–21 However,acarbose was still effective after adjustment for weightloss (p=0·0063). The molecular mechanisms still needinvestigation.

Our results suggest that 11 patients with impairedglucose tolerance would need to be treated for 3·3 yearsto prevent one event of development of diabetes. Lifestylemodification has already been shown to prevent type 2diabetes. Our results show that intervention withacarbose is also effective. Whether these two treatmentoptions can be used together remains to be determined.Nevertheless, recommendations for screening andtreatment of impaired glucose tolerance should now bereassessed.

ContributorsAll authors particpated in development of study design, implementationof the study, and in interpretation of the results.

The STOP-NIDDM Trial Research Group:Canada—S Arndt, H Conter, G A Costain, D Finegood, H C Gerstein, J A Hunt, C J Joyce, D Lau, L A Leiter, H Lochnan, S M Ludwig, P Maheux, N W Rodger, S A Ross, E A Ryan, T M S Wolever, J-F Yale.Germany—P Algenstaedt, UR Fölsch, T Linn, H-J Lüddeke, S Matthaei, C May, R Paschke, K Rett, W Scherbaum, G Schernthaner. Austria—H Schmechel, E Standl, T Temelkova-Kurktschiev, H Weiss, J Ziegelasch. Israel—H Bar On, O Cohen, M Kidron, M Maislos, I Raz, P Segal, T Shoster. Nordic countries—D Andersson, M Carstensen, S Efendic, J Eriksson, B Forsén, T Forsen, K Furuseth, K Hermansen, A B Hertzenberg Faehn, A Latva-Nevala, A Pulkkinen, S Vaaler, M Vanhala, P Vanhala, M Viitaniemi, A Wajngot. Spain: I Conget, A Costa.

Conflict of interest statementNone declared

AcknowledgmentsThe STOP-NIDDM trial was funded by an unrestricted research grantfrom Bayer AG. We thank the coordinating nurses and dieticians in allcentres, Susanne Bordeleau-Chénier for preparing the report andillustrations, and Michael Hummel (Schwabing Hospital, Munich,Germany) for measurement of autoantibodies; Bayer AG for provisionof staff and infrastructure for site monitoring and data collection,especially M Seger, S Demas, M Bungert, D Petzinna, C Pinol, G Morera, K Mattila, P Valtonen, S Tal; and Glen Saunders, who didall the statistical analysis.

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ARTICLES


Rare site for anintramuscular lipoma

K Shiraki, M Kamo, T Sai, R Kamo

We examined an 8-year-old girl who had a right medial canthus mass present for 3 years. Computed tomography showedthe mass to be enveloped by an enlarged ring-shaped medial rectus muscle, and a biopsy specimen showed mature adiposetissue. 6 years later, because of the increased, elevated appearance of the medial canthus, surgical removal was attempted.Preoperative magnetic resonance imaging showed the mass to be enveloped by medial rectus muscle (figure, A, B), with part of the muscle entrapped inside the mass. The mass was of the same signal intensity as that of theorbital adipose tissue on T1-weighted and T2-weighted images; signal-intensity was decreased on a fat-suppressed T1-weighted image (figure, C), and gadolinium enhancement was lacking. Histopathologic examination again showed matureadipose tissue infiltrating striated muscle fibres (figure, D). We know of no other report of intramuscular lipoma in amuscle as small as the external ocular muscle.

Department of Ophthalmology, Osaka City Kita Municipal Hospital (M Kamo MD, T Sai MD); Department of Ophthalmology (K Shiraki MD),Department of Dermatology (R Kamo MD), Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585 Japan

Clinical picture

acarbose for prevention of type 2 diabetes mellitus the stop niddm randomised trial

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