Volume 170 Issue 8

Research Consultants in cases of intended euthanasia or assisted suicide in the Netherlands Bregje D Onwuteaka-Philipsen, Gerrit van der Wal, Piet J Kostense and Paul J van der Maas MJA 1999; 170: 360-363 For editorial comment, see Hendin Abstract - Introduction - Methods - Results - Discussion - Acknowledgement - References - Authors' details - - More articles on Ethics Abstract Objective: To investigate how often physicians act as a consultant in the review of intended euthanasia and assisted suicide (EAS), by whom physicians are asked to act as a consultant, and the consultant's reasons for not agreeing with the intended performance of EAS. Design: A retrospective descriptive study. Setting: The Netherlands. Participants: A stratified random sample of 405 Dutch physicians. Main outcome measures: Number of times the physician has been a consultant; how often a physician had previously been asked to be a consultant by the same treating physician; why consultants advised against EAS. Results: 42% of interviewed physicians had acted as a consultant for EAS and 11% had been a consultant more than three times. Half the physicians who acted as a consultant more than once were invited to do so by the same attending physician, and 41% of consultants had previously consulted the attending physician. The main reasons consultants advised against EAS were because treatment options were still available, the patient's request was not well-considered or persistent, and the patient's suffering was not unbearable and hopeless. Conclusions: Many physicians have at some time been a consultant in a case of intended EAS, but only very few have been able to gain experience in consultancy. To guarantee high standards of consultation, it may be advisable to appoint and train specific consultants for EAS. Introduction In the Netherlands, physicians can be involved in euthanasia or assisted suicide (EAS) either by performing or by being consulted by another physician who intends to perform EAS. Consultation is considered to be an important aspect in the review of cases of EAS,1 and is a requirement that must be met to avoid prosecution for performing EAS. Consultation takes place in about 99% of reported cases of EAS (41% of cases are reported) and in about 37% of unreported cases. In 88% of cases of EAS in which consultation took place the consultant had seen the patient.2,3 In a consultation, a physician formally confers with an independent colleague in considering whether to grant a request for EAS. The consultant determines whether the patient's physician has acted according to the requirements for prudent practice: the patient's request is voluntary, well-considered and persistent, the patient's suffering is unbearable and hopeless, and there are no alternatives for treatment remaining. A consultant should be competent and independent of both the attending physician and the patient, and should visit the patient.1,4 Consultation for EAS is a relatively new task for physicians, and is not part of general medical training. Physicians generally are not used to pronouncing formal judgement on the decision-making process of their colleagues and are not used to seeing patients in a consultancy role. Moreover, consultants need to have knowledge relevant to EAS, such as the possibilities of palliative care.5 Gaining experience as a consultant seems to be important for a physician to become comfortable in this role. As part of a nationwide study on EAS and other practices involving the end of life in the Netherlands,3,6 we set out to determine how often physicians act as a consultant, whether physicians frequently consult the same colleague (or vice versa), whether groups of physicians are asked to be a consultant more often than other groups, the reasons why consultants do not agree with the intended performance of EAS, and the extent to which the consultant feels responsible for the attending physician's final decision to grant or refuse a request for EAS. Methods Study population For this retrospective, descriptive study, we interviewed a stratified random sample of Dutch physicians.2 Participants were stratified according to specialty. The physicians in each stratum were ordered by postal code of their work address and every nth physician was selected. The stratum size was based on the frequencies of medical decisions concerning the end of life and the homogeneity of the patient population (morbidity and age) per stratum. To interview the desired number of physicians, 559 were included in the sample; 83 did not meet the selection criteria and 21 had a chronic illness or could not be located. Of the remaining 455, 50 (11%) did not respond. The final sample of 405 physicians included 124 general practitioners, 74 nursing home physicians (nursing homes in the Netherlands are multifunctional institutions which care for predominantly elderly patients with chronic diseases and physical and/or mental disorders and handicaps) and 207 specialists in cardiology, surgery, internal medicine, respiratory medicine and neurology (oncology and palliative care are not distinct specialties in the Netherlands, but are practised by specialists in other disciplines, such as internal medicine). Physicians in the above-listed specialties attend 87% of all deaths occurring in hospitals. Together with the general practitioners and nursing home physicians, they attend about 95% of all deaths in the Netherlands. Physicians who were not practising in their registered specialty in the same institution since 1 January 1994 were excluded. Measuring instruments The interviews were conducted from November 1995 to February 1996 by 30 experienced physicians who were specially trained for the study. The questionnaire consisted mainly of open-ended questions for the respondents, with prestructured response categories for the interviewers. In the interviews, the definitions of euthanasia, assisted suicide and consultation (Box 1) were explicitly described to the respondents. The interviews took about 2-3 hours. For this study we predominantly used data on how often the respondents had been consultant ever and in 1994 and 1995, and data on the most recent case (all 108 cases occurred between 1994 and 1996) in which the respondent had been a consultant. Analysis To make the data of the stratified samples representative for all deaths in the Netherlands, we weighted the data per stratum. We calculated weights based on the proportion of the various types of physicians in the sample. In addition, the weights of the five specialties were corrected for the 13% of in-hospital deaths that were attended by other medical specialists. Proportions and 95% confidence intervals for these proportions were obtained by direct standardisation7 to adjust for marked variation among the different types of physicians. The normal approximation to the binomial distribution was used. Estimates of the number of consultations in 1995 were based on the (weighted) data on how often each physician had acted as consultant in 1994 and 1995. Multiple logistic regression analyses were used to obtain insight into determinants of whether physicians had ever been a consultant. Because of the stratification according to specialty, the variable "specialty" was included in all analyses. To deal with this categorical variable we used indicator variables, choosing the general practitioners as the reference category. Results In 1995, in the Netherlands, we estimate that almost 4000 consultations took place in cases of intended EAS. In most of these, the consultant was a general practitioner; nursing home physicians rarely acted as a consultant (Box 2). Physicians who had been a consultant Of the 405 physicians in the sample, 42% at some time had been a consultant in intended EAS (Table 1). In 1994 (the year in which the notification procedure was legally enforced) or 1995, 32% of physicians had been a consultant -- general practitioners more often than medical specialists, and specialists more often than nursing home physicians (Box 2). Eight physicians had refused to act as a consultant, for various reasons: lack of time (2), not independent of the attending physician or the patient (2), doubt whether requirements for prudent practice had been met (2), disagreement with notification procedure (1), or the attending physician did not intend to perform euthanasia (1). Eleven per cent of the physicians had been a consultant more than three times (Box 3), and in 1995, 3% had been a consultant three or more times. Previous consultations between consultant and consulting physician Half of the physicians who had been a consultant more than once had previously been consulted by the same physician who consulted them in their most recent case. In 24% of these cases, the treating physician and the consultant had previously acted as consultants for each other (Box 4). Physicians who previously consulted or had been consulted by the same physician agreed more often with the intended EAS than physicians who did not (90% v. 80%), but this difference was not significant. Reasons for advising against EAS The 28 physicians who had at some time advised against the performance of EAS were each asked to describe up to three such cases. Together, they described 48 cases in which they had given this advice. In 42 cases EAS was not carried out, in three it was, and in three instances the consultant did not know the outcome. The consultants gave the following reasons for advising against EAS: there were still alternative treatment options (20 cases), the patient's request was not well-considered or persistent (12 cases), the patient's suffering was not unbearable and hopeless (nine cases), the request was made under pressure of the family (five cases), the patient was already dying (five cases), and the attending physician felt manipulated by the patient (one case). The consultant's responsibility Sixty-five per cent of consultants considered that they had joint responsibility only in those cases in which the attending physician acted according to their judgement, and 30% did not consider that they had any joint responsibility. Medical specialists felt that they had joint responsibility more often than general practitioners (80% [95% CI, 68.6%-91.3%] v. 61% [95% CI, 47.7%-74.6%]). Determinants of having been a consultant With univariate analyses corrected for specialty, physician's age, sex, religion, region in which the physician lives, belief that every case of EAS should be reviewed and belief that consultation should take place in every case of EAS were not significantly related to whether the physician had been a consultant. The results of multiple logistic regression analysis for those determinants that were predictive in the univariate analysis are shown in Box 5. Male physicians had more often been a consultant than female physicians. The strongest association was found for the variable "ever performed EAS". Physicians who had performed EAS had been a consultant more frequently than physicians who had never performed EAS. Discussion We estimate that consultation with another physician in cases of intended EAS took place almost 4000 times in the Netherlands in 1995 (see Box 6). In about 60% of consultations, the consultant was a general practitioner. Overall, 42% of Dutch physicians had been a consultant; 11% had been a consultant more than three times. The most common reason why consultants advised against the performance of EAS was the availability of alternative treatment options. Most consultants considered that they have joint responsibility for the final decision to grant or refuse a request for EAS. Male physicians, general practitioners and physicians who had performed EAS had more frequently been a consultant. The forming of "pairs" of consultants suggests that familiarity is very important in the choice of consultant. An earlier study found that an important reason for choosing a consultant is accessibility and that physicians mainly consult physicians of their own specialty.2 A problem with these consultations may be that the independence of the consultant with regard to the attending physician might be threatened. This is suggested by the fact that "consultants of a pair" more often agree with the intended performance of EAS than other consultants, although this difference is not statistically significant. A possible way of assuring independence of the consultant while safeguarding the consultant's accessibility would be to appoint independent trained consultants who could be contacted by all physicians in a region. Such a system was implemented for general practitioners in Amsterdam in 1997.8 It might also be useful in increasing the frequency of consultation, and possibly the reporting of EAS. The reasons given by consultants for advising against EAS all related to the requirements for prudent practice; the fact that physicians very rarely carry out EAS when the consultant advises against it suggests that consultation can have an important function in assuring the quality of this kind of medical practice. However, our results do not show how often consultants agreed with EAS in cases in which not all the requirements for prudent practice were met. Nursing home physicians, neurologists, surgeons and cardiologists are less likely than general practitioners to have been a consultant. A possible explanation is that, for being asked to act as a consultant, it is not only important to have carried out EAS, but also to have done so relatively frequently: general practitioners, respiratory specialists and specialists in internal medicine carry out EAS more frequently than other physicians.6 In general, Dutch physicians do not have much experience in acting as a consultant in cases of intended EAS. Of the 42% of physicians who have been a consultant, only 27% had been a consultant more than three times, and only 3% more than 10 times. Because acting as a consultant differs greatly from a physician's normal working relationship with colleagues and patients, and because the consultation concerns a matter of life and death, it is important that consultants are experienced and specifically trained. A training program for consultants, in which the skills needed, knowledge about the requirements for prudent practice, palliative care and medicotechnical aspects of EAS are addressed, has been developed by the Royal Dutch Medical Association. In the future it might be advisable to permit only specifically trained physicians to act as a consultant. Acknowledgement This study was funded by the Dutch Ministry of Health, Welfare and Sports and the Ministry of Justice. We are indebted to Professor J Th M van Eijk for his comments on previous versions of this manuscript. References Board of the Royal Dutch Medical Association. Vision on euthanasia. In: Euthanasia in the Netherlands. 5th ed. Utrecht 1996. 24-56. Van der Wal G, van der Maas PJ. Euthanasia and other medical decisions concerning the end of life. The Hague, the Netherlands: Staatsuitgeverij, 1996 (in Dutch). Van der Wal G, van der Maas PJ, Bosma JM, et al. Evaluation of the notification procedure for physician-assisted death in the Netherlands. N Engl J Med 1996; 335: 1706-1711. Van der Wal G, Dillmann RJM. Euthanasia in the Netherlands. BMJ 1994; 308: 1346-1349. Onwuteaka-Philipsen BD. The role of the consultant. In: Legemaate J, Dillmann RJM, editors. Physician-assisted death: between norm and practice. 105-114. Bohn Stafleu Van Loghum, Houten 1998 (in Dutch). Van der Maas PJ, van der Wal G, Haverkate I, et al. Euthanasia, physician-assisted suicide, and other medical practices involving the end of life in the Netherlands, 1990-1995. N Engl J Med 1996; 335: 1699-1705. Armitage P, Berry G. Statistical methods in medical research. 3rd ed. Oxford: Blackwell, 1994; 436-440. Dillman RJM, Krug CHM, Onwuteaka-Philipsen B, et al. Support and consultation in cases of euthanasia in Amsterdam. Med Contact 1997; 52: 743-745 (in Dutch). (Received 7 Jul, accepted 21 Dec, 1998) Authors' details Institute for Research in Extramural Medicine, Vrije Universiteit, Amsterdam, The Netherlands. Bregje D Onwuteaka-Philipsen, MSc, Researcher, and Department of General Practice, Nursing Home Medicine and Social Medicine; Gerrit van der Wal, MD, PhD, Professor, and Department of General Practice, Nursing Home Medicine and Social Medicine; Piet J Kostense, PhD, Epidemiologist/Statistician, and Department of Epidemiology and Biostatistics. Department of Public Health, Erasmus University, Rotterdam, The Netherlands. Paul J van der Maas, MD, PhD, Professor. Reprints will not be available from the authors. Correspondence: B D Onwuteaka-Philipsen, Vrije Universiteit, Institute for Research in Extramural Medicine, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Email: B. Philipsen. EMGOATmed.vu.nl Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> 1: Definitions Euthanasia was defined as the administration of drugs with the explicit intention of ending the patient's life, at the patient's explicit request. Assisted suicide was defined as the prescription or supply of drugs with the explicit intention of enabling the patient to end his or her own life. Consultation was defined as consultation of a colleague, as stipulated in the notification procedure for EAS. Back to text 2: Physicians consulted in cases of intended EAS, and number of consultations in 1995 in the NetherlandsGeneral practitioners Medical specialists (n=124)* (n=207)† Proportion§ (95% CI) Proportion§ (95% CI) Physicians consultedEver consulted49% (40.2%-58.1%) 30% (23.9%-36.6%) Consulted in 1994 or 199540% (31.3%-49.1%) 22% (16.5%-28.2%) Number (95% CI) Number (95% CI) Consultations in 19952502 (2004-3086) 1424 (1217-1631) Nursing home physicians Total (n=74)‡ (n=405) Proportion§ (95% CI) Proportion§ (95% CI) Physicians consultedEver consulted19% (10.9%-30.1%) 42% (35.6%-47.7%) Consulted in 1994 or 199514% (6.77%-23.7%) 32% (25.1%-40.4%) Number (95% CI) Number (95% CI) Consultations in 199559 (33-98) 3985 (3419-4551) * 4 missing observations; †1 missing observation; ‡ 6 missing observations; § Calculated by direct standardisation.7 Back to text 3: Number of consultations (ever and in 1995) by physiciansGeneral practitioners (n=124)* Specialists (n=207)* Total (n=405)* Proportion‡ (95% CI) Proportion‡ (95% CI) Proportion‡ (95% CI) Number of consultations everno consultation51% (41.9%-59.8%) 69% (62.3%-75.5%) 58% 1 consultation15% (8.61%-21.4%) 10% (5.9%-14.7%) 13% more than one34% (25.7%-42.7%) 21% (15.1%-26.4%) 29% 2 or 323% 7% 18% 4 or 5 5% 4% 5% 6 to 10 5% 7% 5% more than 101% 2% 1% Number of consultations in 1995no consultation54% (70.0%-85.0%) 83% (77.3%-88.1%) 80% one or more46% (36.9%-54.7%) 17% (11.9%-22.7%) 20% 1 consultation32% 9% 13% 2 consultations9% 3% 4% more than 25% 5% 3% * General practitioners: 4 missing observations; medical specialists: 2 missing observations; total: 7 missing observations. †Includes 74 nursing home physicians. ‡ Calculated by direct standardisation.7 Back to text4: Previous consultations between attending physician and consultant*General practitioners (n=40) Specialists (n=39) Total (n=80) Proportion‡ (95% CI) Proportion‡ Proportion‡ Attending physician previously consulted the consultant§53% (36.1%-68.5%) 40% 50% Consultant previously consultedthe attending physician¶46% (30.1%-62.8%) 22% 41% Attending physician and consultantpreviously consulted each other§28% (14.6%-43.9%) 11% 24% CI = confidence interval. * Analysis is restricted to those physicians who had been a consultant twice or more and described their most recent consultation for EAS. †Numbers are too small for calculating confidence intervals. ‡ Calculated by direct standardisation. § Medical specialists: 4 missing observations; total: 4 missing observations. ¶General practitioners: 1 missing observation; medical specialists: 3 missing observations; total: 4 missing observations. Back to text5: Determinants of having ever been a consultant (n = 405)*Number Odds ratio (95% CI) Specialtygeneral practice119 1 nursing homemedicine72 0.42 (0.20-0.87) neurology34 0.36 (0.15-0.89) respiratorymedicine35 0.96 (0.43-2.12) surgery35 0.36 (0.15-0.90) cardiology32 0.21 (0.07-0.65) internal medicine64 0.78 (0.41-1.49) Male327 2.14 (1.08-4.85) Ever carried outEAS166 3.04 (1.91-4.85) * 14 missing observations. CI = confidence interval. EAS = euthanasia or assisted suicide. Back to text6: Confirmation of our estimate of number of consultations From our data on how often physicians had acted as a consultant in 1994 and 1995, we estimated that almost 4000 consultations took place in 1995. This estimate is reasonably consistent with the estimate we can make based on other data. There were 3600 granted requests for EAS, and 44% of 6100 refused requests. Consultation occurs in 63% of acceded requests (in 10%, the attending physician consults two, and in 2% three or more, colleagues) and in 16% of refused requests.2,3 Number of consultations = 0.63 x 3600 + 0.63 x 0.1 x 3600 + 0.63 x 0.02 x 3600 x 2 + 0.16 x 0.44 x 6100 = 3015 consultations. This estimate does not take into account the (unknown) frequency of consultation in the approximately 2625 (0.43 x 6100) requests for EAS that were not carried out because the patient died.6 Back to text

Bregje D Onwuteaka-Philipsen · Piet J Kostense

Healthcare Insulin lispro: experience in a private practice setting Alan E Stocks MJA 1999; 170: 364-367 For editorial comment, see Boyages Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - More articles on Endocrinology Abstract Objective: To assess the benefits (or otherwise) of changing patients with unstable type 1 diabetes to insulin lispro (Humalog, Aza Research). Participants and setting: 150 patients with type 1 diabetes treated in a private metropolitan physician practice. Main outcome measures: Glycohaemoglobin (%HbA1c) value; frequency of hypoglycaemia; patients' perceptions of the two regimens. Results: 125 of 150 patients completed the study; 12 (8%) withdrew because they were dissatisfied with lispro. Including these 12 patients, 80/137 patients (58%) felt better physically and 98 (72%) were more satisfied with treatment with lispro. Of the 125 patients who completed the study, 65 (52%) achieved lower HbA1c values, with 22 (18%) experiencing a fall of 1% or more; 78 patients (62%) noted less daytime hypoglycaemia and 103 (82%) experienced less nocturnal hypoglycaemia. Thirty-nine patients (31%) with less daytime hypoglycaemia and 52 (42%) with less nocturnal hypoglycaemia also experienced a fall of more than 0.2% in HbA1c value (mean, 1.0%; range, 0.3%-3.2%). There was no change in body weight or in hypoglycaemia unawareness. Conclusion: Many patients with unstable type 1 diabetes, when changed to insulin lispro, experience significant clinical and biochemical benefits. Introduction Subcutaneous injection of conventional soluble or regular insulin in people with type 1 diabetes has several disadvantages compared with circulating insulin in the non-diabetic: the onset of action of regular insulin is too slow, so that ideally it should be injected 30-60 minutes before meals (causing safety concerns if the meal is then delayed or forgotten), and this delayed peak of action makes it difficult to control the postprandial rise in blood glucose level. Attempts to reduce postprandial hyperglycaemia by increasing the insulin dose increase the risk of hypoglycaemia 4-6 hours later. Moreover, the action of regular insulin persists too long, increasing the risk of late hypoglycaemia, especially nocturnal hypoglycaemia. Finally, the absorption of regular insulin is very variable from day to day, and this contributes to unstable and unpredictable blood glucose levels. These disadvantages have led to the development of the insulin analogue insulin lispro (Box 1). With its more rapid action it should alleviate many of these concerns. Patients can eat immediately after injecting insulin lispro, which is more convenient, and postprandial hyperglycaemia is much reduced.5 Lispro is more predictably absorbed, which should give fewer day-to-day blood glucose fluctuations, and, in turn, should reduce the risk of unpredictable hypoglycaemia by day and night,6 giving greater patient confidence. Patients should be able to reduce or cease between-meal snacks without an increased risk of hypoglycaemia, and this could lead to weight loss. However, when compared with treatment with regular insulin, glycohaemoglobin values (expressed as %HbA1c) have been reported to change very little in unselected patient groups treated with lispro.5,7 In this study, the effectiveness of lispro was assessed in a group of patients selected because they were having difficulty achieving smooth, safe and satisfactory glycaemic control with conventional insulins. A change to lispro was not offered to patients whose diabetes was well controlled without significant hypoglycaemia (ie, in this group the change was not made primarily for reasons of personal convenience). The objective was to ascertain whether their glycaemic control could be improved (without increasing the risk of hypoglycaemia in these unstable patients), and whether their health and their tolerance of diabetes could be improved. Methods In one practice managing patients with diabetes, the first 150 patients who were changed to insulin lispro were studied. The reason(s) for the change are shown in Box 2 (in most patients there was more than one reason). Despite previous intensive insulin therapy, all except two patients had problems with their glycaemic control or with hypoglycaemia with conventional insulins; of the 17 patients listed as being changed for reasons of convenience, 15 had other significant problems as well (eg, unpredictable blood glucose level fluctuations). All patients injected insulin four times daily using a basal-bolus insulin regimen. Lispro was injected using a 1.5 mL injector pen (B-D Pen, Aza Research, Sydney). Most patients (81%) injected Protaphane at bedtime using a NovoPen 3 (Novo Nordisk, Sydney), the remainder using other long-acting insulins (eg, Monotard [Novo Nordisk], Ultratard [Novo Nordisk] or Humulin UL [Aza]). No patient injected a long-acting insulin before breakfast. All patients were asked to monitor their blood glucose level seven times daily initially, using their previous blood glucose monitor, before and two hours after meals and at bedtime, and were invited to telephone each morning before breakfast to report levels until their blood glucose and insulin doses were stable. Patients were instructed to use a sliding scale to adjust their lispro doses if their blood sugar levels were unexpectedly greater than 10 mmol/L or less than 5 mmol/L (Box 3). An attempt was made to encourage patients with HbA1cvalues below 7% to strive for higher blood glucose levels and to try to avoid their blood glucose level falling below 4 mmol/L, in the hope of decreasing lack of awareness of hypoglycaemia. All patients were asked to complete a questionnaire (Box 4). All responses are entirely subjective, and no statistical analysis of these was undertaken. Changes in HbA1c values and body weight were recorded, usually after 4-6 months. For purposes of classification, a variation in HbA1c between 2 0.2% and + 0.2% was regarded as no change, a rise or fall of 0.3%-0.9% as a minor increase/decrease, and a rise or fall of 1.0% or more as a major change. Similarly, a change in weight of 2 0.2 kg to + 0.2 kg was regarded as no change, a rise/fall of 0.3-1.9 kg as a minor increase/decrease, and a rise/fall of 2 kg or more as a major change. Changes in insulin doses and HbA1c are given as means and 95% confidence intervals (CIs) (Microsoft Excel). Correlations were determined by analysis of variance (ANOVA). Student's two-tailed t test was used to calculate the P values. Results The 150 patients were aged 13-86 years (mean, 46.6 years). There were 63 males and 87 females, who had been receiving treatment for diabetes for between one and 54 years (mean, 22.1 years). Eight of the 150 patients were lost to follow-up. Twelve patients had stopped injecting lispro (usually within one month) and reverted to conventional insulins: five reported that lispro made their diabetes more unstable, three that it produced more hypoglycaemia, and four that it made them feel unwell. Two patients had not started taking lispro, and three patients failed to have a repeat HbA1c measurement. Thus, there were 125 patients who completed a questionnaire and presented all the data necessary for analysis. Insulin doses: Nearly all patients needed to adjust their insulin doses, but there was wide individual variation. More patients needed to reduce than increase the daily dose of lispro (52 v. 39 patients), while more increased their bedtime insulin than reduced it (62 v. 19 patients). However, the mean dose adjustments were small: the total daily dose of insulin rose by 1.3 units (95% CI, 0.11, 2.49), the dose of lispro was reduced by 0.4 units (95% CI, 2 0.76, 1.56), and the bedtime insulin dose rose by 1.8 units (95% CI, 0.88, 2.72). Blood glucose fluctuation: Sixty-nine of 125 patients (55%) reported that their blood glucose level fluctuated less on lispro, 38 (30%) that there was no difference and 18 (14%) that their blood glucose levels fluctuated more. Fifty-one (41%) reported that their overall blood glucose levels were lower, 58 (46%) that there was no change, and 16 (13%) that their overall blood glucose levels were higher on lispro. Glycohaemoglobin (%HbA1c): In general, the changes in HbA1c values agreed with the patients' perceptions of their overall blood glucose control. Sixty-five patients (52%) had a fall in HbA1c of 0.3% or more, with 22 (18%) achieving an HbA1c value at least 1.0% lower with lispro. In 22 patients (18%) the HbA1c value rose by 0.3% or more, and in six patients (5%) it rose by 1.0% or more. From Box 5 it can be seen that the HbA1c value did not change significantly in patients whose initial level was less than 8%, but there was a highly significant reduction in those with initially higher levels, and in the group as a whole. The greatest improvement was seen in patients with initial HbA1c values of 8%-9%, of whom 51% (23/45) achieved HbA1c values less than 8% (Box 6). The group of patients whose HbA1c value fell took slightly more insulin (3.35 units/day; 95% CI, 1.81, 5.16), while those whose HbA1c value rose took slightly less (2 1.55 units/day; 95% CI, 2 4.17, 1.07). There was no correlation between individual changes in HbA1c and the total daily insulin dose (r = 0.152, P = 0.08), but an increased bedtime insulin dose was weakly correlated with a lower HbA1c value (r = 0.238, P < 0.02). Hypoglycaemia: The frequency of both daytime and nocturnal hypoglycaemia was reduced after the change to lispro, as shown in Box 7. Seventy-eight patients (62%) noted fewer daytime episodes, with 53 patients (42%) reporting that they had experienced much less hypoglycaemia or none at all. The frequency of nocturnal hypoglycaemia was even more dramatically reduced, with 103 patients (82%) noting fewer episodes. Forty-one patients (33% of the total) became completely free of nocturnal hypoglycaemia. Despite the reduction in episodes of hypoglycaemia, there was little change in hypoglycaemia awareness, 31 patients reporting that hypoglycaemia was harder to recognise, while 24 reported easier recognition. Only one patient complained of new hypoglycaemia unawareness. There was no apparent association between reduced awareness of hypoglycaemia and the HbA1c value achieved with lispro, nor with major reductions in HbA1c values. Thirty-nine patients (31%) experienced a fall in HbA1c value (mean, 1.0%; range, 0.3%-3.2%) associated with less daytime hypoglycaemia, and 52 patients (42%) achieved a lower HbA1c value (mean, 0.9%; range, 0.3%-3.2%) associated with a reduction in nocturnal hypoglycaemia. Weight: On changing to lispro, five patients were underweight, with body mass index (BMI) less than 20 kg/m2, 69 were normal (20-25 kg/m2), and 51 were by definition overweight (BMI >25 kg/m2). There was no systematic change in body weight: 55 patients lost weight, with 19 losing more than 2 kg, while 45 patients gained weight, of whom 25 gained more than 2 kg. There was no relationship between BMI at the commencement of the study and subsequent weight change, nor between weight change and changes in HbA1c values. Two-thirds of patients reduced their between-meal snacks, but only 18 (14%) were able to omit their mid-morning snack, while 33 (26%) and 26 (21%) were able to omit afternoon tea and bedtime supper altogether. Wellbeing and satisfaction: If the 12 patients who withdrew from the study are included (making a total of 137 patients), 80 patients (58%) reported feeling physically better when taking lispro, and 48 (35%) said they were much better. Ninety-eight patients (72%) reported greater satisfaction with the new insulin regimen, of whom 64 (47%) said they were much more satisfied. Of the 125 patients who completed the study, 10 (8%) reported that they were less satisfied with treatment, with three patients being much less satisfied -- and to these must be added the 12 patients who withdrew because of dissatisfaction with lispro, making a total of 16% (22/137). Discussion Many of the patients experienced significant clinical and biochemical benefits after changing to insulin lispro. This insulin analogue seems to be more physiological than regular insulin, but it is still not perfect, as indicated by the 16% of patients who were dissatisfied. Patients were selected because of difficulties with their glycaemic control or hypoglycaemia rather than for personal convenience, and this may partly explain the different results from those in earlier studies of lispro,5,7 in which no significant change in HbA1c was noted in cohorts of unselected patients. The aim was to provide an insulin regimen which would minimise the risks of both hypoglycaemia and long term complications. Results from the Diabetes Control and Complications Trial (DCCT) suggest that there is a curvilinear relationship between high HbA1c values and an increased risk of microvascular complications, and that a similar curvilinear relationship exists between lower HbA1c values and an increased risk of severe hypoglycaemia and hypoglycaemia unawareness.8 In practice, achieving HbA1c values between 7% and 8% seems to offer reasonable protection against both problems. During routine therapy with regular insulin the use of a sliding scale to correct unexpected high or low blood glucose levels is not logical, as this insulin works too slowly to achieve the desired result; however, with lispro, patients can add or subtract small doses, which helps in returning aberrant glucose levels to the desirable range more quickly. Most patients learn to use this method easily. More than half the group experienced a fall in HbA1c, which in 20% of patients was 1% or more. The greatest improvement occurred in patients whose initial HbA1c value was only moderately elevated (HbA1c, 8%-9%), and, of these subjects, more than 50% were able to achieve a value which, according to results from the DCCT,8 should offer better protection against microvascular complications. However, although patients with initially poor glycaemic control (HbA1c, >9%) often achieved HbA1c values less than 9%, only 4 of 24 (17%) achieved values below 8%; the remainder must be regarded as being still at increased risk of complications. Most patients in whom HbA1c values were initially less than 7% proved resistant to attempts to raise their blood glucose level, with only a third achieving HbA1c values of 7% or higher (Box 6). According to the DCCT, the risk of hypoglycaemia unawareness in this group is considerable,8 and it is pleasing to note that 10 of these 15 patients (Box 6) experienced less daytime hypoglycaemia and 13 had less nocturnal hypoglycaemia, with no significant change in hypoglycaemia awareness. Patients, their relatives and their physicians all welcome any reduction in risk of hypoglycaemia, and many will deliberately try to avoid hypoglycaemia by reducing insulin doses, even though this leads to poor overall glycaemic control and increases the risk of microvascular complications. It is particularly gratifying that 31% of the patients had less daytime hypoglycaemia and 42% had less nocturnal hypoglycaemia associated with a fall in HbA1c value, indicating greater safety together with better glycaemic control. A lower frequency of hypoglycaemia should be associated with improved hypoglycaemia awareness,9 but this did not eventuate. On the other hand, there was little evidence of any progression of hypoglycaemia unawareness over the short duration of the study. There was no correlation between individual changes in HbA1c and changes in either the daily dose of lispro or the total daily insulin requirement. Dose adjustments were small, but an inverse correlation was found with the bedtime insulin dose; this was sufficiently weak to indicate that other factors are likely to have contributed to this finding.10 Insulin lispro does not suit every patient with type 1 diabetes, but with careful education in its use many experience significant benefits, and achieve greater confidence and satisfaction. The advent of new long-acting and short-acting insulin analogues in the near future is awaited with interest; they will need careful clinical evaluation by both patients and their treating physicians. Conflict of interest: None. References Dimarchi RD, Chance RE, Long HB, et al. Preparation of an insulin with improved pharmacokinetics relative to human insulin through consideration of structural homology with insulin-like growth factor 1. Horm Res 1994; 41 (Suppl 2): 93-96. Ciszak E, Beals JM, Baker JC, et al. Role of C-terminal B-chain residues in insulin assembly; the structure of hexameric Lys B28 Pro B29-human insulin. Structure 1995; 3: 615-622. Howey DC, Bowsher RR, Brunelle RL, Woodworth JR. [Lys(B28), Pro(B29)]-human insulin. A rapidly absorbed analogue of human insulin. Diabetes 1994; 43: 396-402. Bhaskar R, Chou MCY, Field JB. Time action characteristics of regular and NPH insulin in insulin-treated diabetics. Clin Endocrinol Metab 1980; 50: 475-479. Anderson JH, Brunelle RL, Koivisto VA, et al, and the Multicenter Insulin Lispro Group. Reduction of postprandial hyperglycaemia and frequency of hypoglycaemia in IDDM patients on insulin-analog treatment. Diabetes 1997; 46: 265-270. Holleman F, Schmitt H, Rottiers R, et al, the Benelux-UK Insulin Lispro Study Group. Reduced frequency of severe hypoglycaemia and coma in well controlled IDDM patients treated with insulin lispro. Diabetes Care 1997; 20: 1827-1832. PfŸtzner A, KŸstner E, Forst T, et al, on behalf of the German Insulin Lispro/IDDM study group. Intensive insulin therapy with insulin lispro in patients with Type 1 diabetes reduces the frequency of hypoglycaemic episodes. Exp Clin Endocrinol 1996; 104: 25-30. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977-986. Amiel SA. Limits of normality: the mechanisms of hypoglycaemia unawareness. Diabetic Med 1994; 11: 918-924. Sokal RR, Rohlf FJ. Biometry: the principles and practice of statistics in biological research. 2nd ed. New York: WH Freeman, 1981: 562-565. (Received 17 Aug 1998, accepted 18 Feb 1999) Authors' details The Brisbane Clinic, Brisbane, QLD. Alan E Stocks, AM, FRCP(Ed), FRACP, Physician. Reprints will not be available from the author. Correspondence: Dr A E Stocks, Brisbane Clinic, 79 Wickham Terrace, Brisbane, QLD 4000. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> 1: Insulin lispro Insulin lispro (Humalog, Aza Research) is an insulin analogue in which the amino acid sequence proline-lysine at positions 28 and 29 on the B chain of human insulin has been reversed.1 This molecule exists in solution as a monomer, unlike regular human insulin, which, in solution, is mainly in the dimeric or hexameric form.2 Monomeric insulin is more rapidly absorbed into the circulation from a subcutaneous injection site, and its action is much more rapid than conventional insulins. The onset of action is almost immediate, peak action occurs 60-90 minutes after injection and the total duration of action is 5-6 hours.3 Comparative figures for regular insulin are onset 30-45 minutes, peak 3-6 hours and total duration of action 8-16 hours.4 Back to text2: Reason(s) for change to insulin lispro (number of patients)Unstable/unpredictable bloodglucose levels139 Frequent hypoglycaemia(eg, more than twice a week)81Hypoglycaemia unawareness(needing assistance)53High glycohaemoglobin value(HbA1c >9.5%)14Weight gain/obesity37Convenience17Back to text 3: Suggested sliding scaleMealtime blood glucose level (mmol/L)Lispro adjustment (units)< 2.5-32.5-3.5-23.6-4.9-15-10010.1-12.5+ 112.6-15+ 215.1-17.5+ 317.6-20+ 4>20+ 5Back to text 4: QuestionnaireBlood sugar level overall?Higher -- LowerBlood sugar fluctuations?Greater -- LessDaytime hypoglycaemia? More -- Less -- NoneNocturnal hypoglycaemia?More -- Less -- NoneEase of recognition?Easier -- HarderBetween-meal snacks?Yes -- No/Same -- LessWeight change?Gain -- LossFeel different physically?Better -- WorseSatisfaction with treatment?Happier -- Less happyBack to text 5: Analysis of changes in glycohaemoglobin (HbA1c) valueInitialPatientsMean HbA1c value (95% CI)HbA1cn (%)Before lisproAfter lisproP<7%14 (11%)6.45%6.85%0.12(6.17%, 6.73%)(6.35%, 7.35%)7.0%-8.0%42 (34%)7.59% 7.58%0.88(7.51%, 7.67%)(7.38%, 7.78%)8.1%-9.0%45 (36%)8.50%8.01%<0.001(8.42%, 8.58%)(7.86%, 8.16%)>9%24 (19%)9.75%8.92%<0.001(9.49%, 10.39%)(8.41%, 9.43%)Total125 (100%)8.22%7.92%< 0.001group(8.03%, 8.41%)(7.75%, 8.09%)Back to text 6: Change in glycohaemoglobin (HbA1c) valuesInitial HbA1cnFinal HbA1cn<7%(15)<7%107%-8%2>8%3 7.0%-8.0%(41)<7%67%-8%28>8%7 8.1%-9%(45)<7%27%-8%21>8%22 >9%(24)<8%48%-9%9>9%11Back to text 7: Frequency of hypoglycaemiaDaytimeNocturnalMuch more3 (2%)1 (1%)More20 (16%)7 (6%)Unchanged24 (19%)14 (11%)Less25 (20%)19 (15%)Much less48 (38%)43 (34%)None at all5 (4%)41 (33%)Back to text

Alan E Stocks

Position Statement New classification and criteria for diagnosis of diabetes mellitus Position Statement from the Australian Diabetes Society,* New Zealand Society for the Study of Diabetes, Royal College of Pathologists of Australasia and Australasian Association of Clinical Biochemists Peter G Colman,* David W Thomas, Paul Z Zimmet,* Timothy A Welborn, * Peter Garcia-Webb and M Peter Moore MJA 1999; 170: 375-378 Introduction - What are the new diagnostic criteria? - What about the oral glucose tolerance test? - Diabetes in pregnancy - How has the classification of diabetes changed? - Impaired glucose tolerance and impaired fasting glycaemia - References - Authors' details - - More articles on Endocrinology Introduction Recently, there has been major growth in knowledge about the aetiology and pathogenesis of different types of diabetes and about the predictive value of different blood glucose levels for development of complications. In response, both the American Diabetes Association (ADA) and the World Health Organization (WHO) have re-examined, redefined and updated the classification of and criteria for diabetes, which have been unchanged since 1985. While the two working parties had cross-representation, they met separately, and differences have emerged between their recommendations. The ADA published its final recommendations in 1997,1 while the WHO group published its provisional conclusions for consultation and comment in June 1998.2 The WHO process called for comments on the proposal by the end of September 1998, with the intention of finalising definitive classification and criteria by the end of December 1998 and of publishing these soon thereafter. However, WHO publications need to go through an internal approval process and it may be up to 12 months before the final WHO document appears. A combined working party of the Australian Diabetes Society, New Zealand Society for the Study of Diabetes, Royal College of Pathologists of Australasia and Australasian Association of Clinical Biochemists was formed to formulate an Australasian position on the two sets of recommendations and, in particular, on the differences between them. This is an interim statement pending the final WHO report, which will include recommendations on diabetes classification as well as criteria for diagnosis. We see it as very important to inform Australasian health professionals treating patients with diabetes about these changes. Position Statement key messages What are the new diagnostic criteria? The new WHO criteria for diagnosis of diabetes mellitus and hyperglycaemia are shown in Box 1. The major change from the previous WHO recommendation3 is the lowering of the diagnostic level of fasting plasma glucose to 7.0 mmol/L, from the former level of 7.8 mmol/L. For whole blood, the proposed new level is 6.1 mmol/L, from the former 6.7 mmol/L. This change is based primarily on cross-sectional studies demonstrating the presence of microvascular4 and macrovascular complications5 at these lower glucose concentrations. In addition, the 1985 WHO diagnostic criterion for diabetes based on fasting plasma glucose level ( 7.8 mmol/L) represents a greater degree of hyperglycaemia than the criterion based on plasma glucose level two hours after a 75 g glucose load ( 11.1 mmol/L).6 A fasting plasma glucose level of 7 mmol/L accords more closely with this 2 h post-glucose level. Recommendation: The ADA and the WHO committee are unanimous in adopting the changed diagnostic level, and the Australasian Working Party on Diagnostic Criteria recommends that healthcare providers in Australia and New Zealand should adopt it immediately. Clinicians should note that the diagnostic criteria differ between clinical and epidemiological settings. In clinical practice, when symptoms are typical of diabetes, a single fasting plasma glucose level of 7.0 mmol/L or 2 h post-glucose or casual postprandial plasma glucose level of 11.1 mmol/L suffices for diagnosis. If there are no symptoms, or symptoms are equivocal, at least one additional glucose measurement (preferably fasting) on a different day with a value in the diabetic range is necessary to confirm the diagnosis. Furthermore, severe hyperglycaemia detected under conditions of acute infective, traumatic, circulatory or other stress may be transitory and should not be regarded as diagnostic of diabetes. The situation should be reviewed when the primary condition has stabilised. In epidemiological settings, for study of high-prevalence populations or selective screening of high-risk individuals, a single measure -- the glucose-level 2 h post-glucose load -- will suffice to describe prevalence of impaired glucose tolerance (IGT). What about the oral glucose tolerance test? Previously, the oral glucose tolerance test (OGTT) was recommended in people with a fasting plasma glucose level of 5.5-7.7 mmol/L or random plasma glucose level of 7.8-11.0 mmol/L. After a 75 g glucose load, those with a 2 h plasma glucose level of < 7.8 mmol/L were classified as normoglycaemic, of 7.8-11.0 mmol/L as having IGT and of 11.1 mmol/L as having diabetes. The new diagnostic criteria proposed by the ADA and WHO differ in their recommendations on use of the OGTT. The ADA makes a strong recommendation that fasting plasma glucose level can be used on its own and that, in general, the OGTT need not be used.1 The WHO group2 argues strongly for the retention of the OGTT and suggests using fasting plasma glucose level alone only when circumstances prevent the performance of the OGTT. There are concerns that many people with a fasting plasma glucose level < 7.0 mmol/L will have manifestly abnormal results on the OGTT and are at risk of microvascular and macrovascular complications. This has major ramifications for the approach to diabetes screening, particularly when the Australian National Diabetes Strategy proposal,7 launched in June 1998 by Dr Michael Wooldridge, Federal Minister for Health and Aged Care, has early detection of type 2 diabetes as a key priority. Recommendation: The Australasian Working Party on Diagnostic Criteria has major concerns about discontinuing use of the OGTT and recommends that a formal recommendation on its use in diabetes screening be withheld until the final WHO recommendation is made. However, in the interim, the OGTT should continue to be used. Diabetes in pregnancy The ADA has retained its old criteria for diagnosis of gestational diabetes.1 These differ from those recommended by both WHO2 and the Australian Working Party on Diabetes in Pregnancy8 and are generally not recognised outside the United States. The new WHO statement retains the 1985 WHO recommendation that both IGT and diabetes should be classified as gestational diabetes. This is consistent with the recommendations of the Australasian Diabetes in Pregnancy Society, which recommended a diagnostic 2 h venous plasma glucose level on the OGTT of 8.0 mmol/L. In New Zealand, a cut-off level of 9.0 mmol/L has been applied.8 How has the classification of diabetes changed? The proposed new classification encompasses both clinical stages and aetiological types of hyperglycaemia and is supported by numerous epidemiological studies. The classification by aetiological type (Box 2) results from new knowledge of the causes of hyperglycaemia, including diabetes. The terms insulin-dependent and non-insulin-dependent diabetes (IDDM and NIDDM) are eliminated and the terms type 1 and type 2 diabetes retained. Other aetiological types, such as diabetes arising from genetic defects of -cell function or insulin action, are grouped as "other specific types", with gestational diabetes as a fourth category. The proposed staging (Box 3) reflects the fact that any aetiological type of diabetes can pass or progress through several clinical phases (both asymptomatic and symptomatic) during its natural history. Moreover, individuals may move in either direction between stages. Impaired glucose tolerance and impaired fasting glycaemia Impaired glucose tolerance (IGT), a discrete class in the previous classification, is now categorised as a stage in the natural history of disordered carbohydrate metabolism. Individuals with IGT are at increased risk of cardiovascular disease, and not all will be identified by fasting glucose level. In reducing the use of the OGTT, the ADA recommended a new category -- impaired fasting glycaemia (IFG) -- when fasting plasma glucose level is lower than that required to diagnose diabetes but higher than the reference range (< 7.0 mmol/L but 6.1 mmol/L). Limited data on this category show that it increases both risk of progressing to diabetes9 and cardiovascular risk.5 However, data are as yet insufficient to determine whether IFG has the same status as IGT as a risk factor for developing diabetes and cardiovascular disease and as strong an association with the metabolic syndrome (insulin resistance syndrome). IFG can be diagnosed by fasting glucose level alone, but if 2 h glucose level is also measured some individuals with IFG will have IGT and some may have diabetes. In addition, the number of people with OGTT results indicating diabetes but fasting plasma glucose level < 7.0 mmol/L is unknown, but early data suggest there may be major variation across different populations.10 A number of studies, including the DECODE initiative of the European Diabetes Epidemiology Group, have reported that individuals classified with IFG are not the same as the IGT group.11-15 The European Group believes that, on available European evidence, the ADA decision to rely solely on fasting glucose level would be unwise. Recommendation: The Australasian Working Party on Diagnostic Criteria recommends immediate adoption of the new classification. However, clinicians should be aware that some cases of diabetes will be missed unless an OGTT is performed. Thus, if there is any suspicion or other risk factor suggesting glucose intolerance, the working party continues to recommend use of an OGTT pending the final WHO recommendation. References Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20: 1183-1197. Alberti KGMM, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional Report of a WHO Consultation. Diabet Med 1998; 15: 539-553. World Health Organization. Diabetes mellitus. Report of a WHO study group. Technical report series 727. Geneva: WHO, 1985. McCance DR, Hanson RL, Charles MA, et al. Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes. BMJ 1994; 308: 1323-1328. Charles MA, Balkau B, Vauzelle-Kervoeden F, et al. Revision of diagnostic criteria for diabetes [letter]. Lancet 1996; 348: 1657-1658. Finch CF, Zimmet PZ, Alberti KGMM. Determining diabetes prevalence: a rational basis for the use of fasting plasma glucose concentrations? Diabet Med 1990; 7: 603-610. Colagiuri S, Colagiuri R, Ward J. National diabetes strategy and implementation plan. Canberra: Diabetes Australia, 1998. Hoffman L, Nolan C, Wilson D, et al. Gestational diabetes mellitus -- management guidelines. The Australasian Diabetes in Pregnancy Society. Med J Aust 1998; 169: 93-97. Charles MA, Fontbonne A, Thibult N, et al. Risk factors for NIDDM in white population. Diabetes 1991; 40: 796-799. Keen H. Impact of new criteria for diabetes on pattern of disease. Lancet 1998; 352: 1000-1001. DECODE Study Group on behalf of the European Diabetes Epidemiology Study Group. Will new diagnostic criteria for diabetes mellitus change phenotype of patients with diabetes? Reanalysis of European epidemiological data. BMJ 1998; 317: 371-375. De Vegt F, Dekker JM, Stehouwer CDA, et al. The 1997 American Diabetes Association criteria versus the 1985 World Health Organization criteria for the diagnosis of abnormal glucose tolerance. Diabetes Care 1998; 21: 1686-1690. Harris MI, Eastman RC, Cowie CC, et al. Comparison of diabetes diagnostic categories in the US population according to 1997 American Diabetes Association and 1980-1985 World Health Organization diagnostic criteria. Diabetes Care 1997; 20: 1859-1862. Unwin N, Alberti KGMM, Bhopal R, et al. Comparison of the current WHO and new ADA criteria for the diagnosis of diabetes mellitus in three ethnic groups in the UK. Diabet Med 1998; 15: 554-557. Chang C-J, Wu J-S, Lu F-H, Lee H-L, et al. Fasting plasma glucose in screening for diabetes in the Taiwanese population. Diabetes Care 1998; 21: 1856-1860. Authors' details Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, VIC. Peter G Colman, FRACP, MD, Director. Chemical Pathology Services, Women's and Children's Hospital, Adelaide, SA. David W Thomas, FRACP, FRCPA, Head. International Diabetes Institute, Melbourne, VIC. Paul Z Zimmet, FRACP, MD, Director. Diabetes Centre, Sir Charles Gairdner Hospital, Perth, WA. Timothy A Welborn, FRACP, PhD, Head. St John of God Pathology, Perth, WA. Peter Garcia-Webb, MD, FRCPA, Chemical Pathologist. Diabetes Centre, Christchurch Hospital, Christchurch, NZ. M Peter Moore, FRACP, Clinical Director. Reprints will not be available from the authors. Correspondence: Dr P G Colman, Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, VIC 3050. Email: peter.colmanATnwhcn.org.au Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> Key messages Diagnosis of diabetes is not in doubt when there are classical symptoms of thirst and polyuria and a random venous plasma glucose level 11.1 mmol/L. The Australasian Working Party on Diagnostic Criteria for Diabetes Mellitus recommends: Immediate adoption of the new criterion for diagnosis of diabetes as proposed by the American Diabetes Association (ADA) and the World Health Organization (WHO) - fasting venous plasma glucose level 7.0 mmol/L; Immediate adoption of the new classification for diabetes mellitus proposed by the ADA and WHO, which comprises four aetiological types - type 1, type 2, other specific types, and gestational diabetes - with impaired glucose tolerance and impaired fasting glycaemia as stages in the natural history of disordered carbohydrate metabolism. Awareness that some cases of diabetes will be missed unless an oral glucose tolerance test (OGTT) is performed. If there is any suspicion or other risk factor suggesting glucose intolerance, the OGTT should continue to be used pending the final WHO recommendation. Back to text 1: Values for diagnosis of diabetes mellitus and other categories of hyperglycaemia2Glucose concentration (mmol/L [mg/dL]) Whole blood Venous Capillary Diabetes mellitusFasting 6.1 ( 110) 6.1 ( 110) or 2 h post-glucose load 10.0 ( 180) 11.1 ( 200) or bothImpaired glucose tolerance (IGT)Fasting (if measured)< 6.1 (< 110) < 6.1 (< 110) and 2 h post-glucose load 6.7 ( 120) 7.8 ( 140) and < 10.0 (< 180) and < 11.1 (< 200) Impaired fasting glycaemia (IFG)Fasting 5.6 ( 100) and 5.6 ( 100) and < 6.1 (< 110) < 6.1 (< 110) 2 h post-glucose load (if measured)< 6.7 (< 120) < 7.8 (< 140) Glucose concentration (mmol/L [mg/dL]) Plasma* Venous Capillary Diabetes mellitusFasting< 7.0 ( 126) 7.0 ( 126) or 2 h post-glucose load 11.1 ( 200) 12.2 ( 220) or bothImpaired glucose tolerance (IGT)Fasting (if measured)<7.0 (<126) < 7.0 (< 126) and 2 h post-glucose load 7.8 ( 140) 8.9 ( 160) and < 11.1 (< 200) and < 12.2 (< 220) Impaired fasting glycaemia (IFG)Fasting 6.1 ( 110) and 6.1 ( 110) and < 7.0 (< 126) < 7.0 (< 126) 2 h post-glucose load (if measured)< 7.8 (< 140) < 8.9 (< 160) For epidemiological or population screening purposes, the fasting or 2 h value after 75 g oral glucose may be used alone. For clinical purposes, the diagnosis of diabetes should always be confirmed by repeating the test on another day, unless there is unequivocal hyperglycaemia with acute metabolic decompensation or obvious symptoms. Glucose concentrations should not be determined on serum unless red cells are immediately removed, otherwise glycolysis will result in an unpredictable underestimation of the true concentrations. It should be stressed that glucose preservatives do not totally prevent glycolysis. If whole blood is used, the sample should be kept at 0-4oC or centrifuged immediately, or assayed immediately. Table reproduced with permission from Alberti KGMM, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional Report of a WHO Consultation. Diabet Med 1998; 15: 539-553. Copyright John Wiley & Sons Limited. Back to text2: Aetiological classification of disorders of glycaemia* Type 1 (-cell destruction, usually leading to absolute insulin deficiency) Autoimmune Idiopathic Type 2 (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with or without insulin resistance) Other specific types Genetic defects of -cell function Genetic defects in insulin action Diseases of the exocrine pancreas Endocrinopathies Drug or chemical induced Infections Uncommon forms of immune-mediated diabetes Other genetic syndromes sometimes associated with diabetes Gestational diabetes * As additional subtypes are discovered, it is anticipated they will be reclassified within their own specific category. Includes the former categories of gestational impaired glucose tolerance and gestational diabetes. Table reproduced with permission from Alberti KGMM, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional Report of a WHO Consultation. Diabet Med 1998; 15: 539-553. Copyright John Wiley & Sons Limited. Back to textBack to text

Peter G Colman · David W Thomas · Paul Z Zimmet · Timothy A Welborn · Peter Garcia-Webb