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Approach to the Patient with Prediabetes
Med Star Clinical Research Center, Washington, D.C. 20003 Prediabetes consists of impaired fasting glucose and/or impaired glucose tolerance and is a
significant risk factor for the development of type 2 diabetes, microvascular, and macrovascular
disease. The values used to define prediabetes are arbitrary, because prediabetes represents an
intermediary category along the continuum from normal glucose levels and tolerance to overt
hyperglycemia. The progression from prediabetes to type 2 diabetes occurs over many years,
strong evidence to support intervention to delay the progression from prediabetes to diabetes.
Large, randomized prospective studies with lifestyle intervention and/or various modes of
pharmacotherapy have demonstrated successful delay of diabetes. Several issues in the man-
agement of prediabetes remain controversial, such as the role of pharmacotherapy and when
to escalate treatment. This article will review some of the issues surrounding the identification
and treatment of prediabetes, with an interpretation of the available data to help guide
management. (J Clin Endocrinol Metab
93: 3259 –3265, 2008)
A46-yr-old female is referred to you for an abnormal fasting andtotalcholesterolto175mg/dl(4.5mmol/liter).Byage54,the
glucose of 115 mg/dl (6.4 mmol/liter). She has no significant patient’s weight steadily climbs to 68.2 kg (150 lb), and she reports past medical history. She takes several vitamins but no prescribed less diligence with her lifestyle changes. An OGTT reveals FPG of medications. Her family history is remarkable for type 2 diabetes in 123 mg/dl (6.8 mmol/liter) with 2-h glucose of 252 mg/dl (14 mmol/ her father. Her physical examination is notable for a height of 152.5 liter) and HbA1c of 6.9%. The OGTT is repeated within 6 wk, cm (60 inches), weight of 64.9 kg (142.8 lb), body mass index (BMI) revealing a FPG of 148 mg/dl (8.2 mmol/liter) and 2-h glucose of of 27.9 kg/m2, and blood pressure of 121/80 mm/Hg. A 75 gram 224 mg/dl (12.4 mmol/liter), consistent with a diagnosis of type 2 oral glucose tolerance test (OGTT) is performed to evaluate her for diabetes. Her total cholesterol is 286 mg/dl (7.4 mmol/liter), LDL-c undiagnosed diabetes, revealing a fasting plasma glucose (FPG) of 206 mg/dl (5.3 mmol/liter), HDL-c 42 mg/dl (1.1 mmol/liter), and 117 mg/dl (6.5 mmol/liter) and 2-h glucose of 153 mg/dl (8.5 mmol/ triglycerides 189 mg/dl (2.1 mmol/liter). She is started on metformin liter). A hemoglobin A1c (HbA1c) is 6.4%, and lipid panel reveals 850 mg twice daily, a statin, and aspirin. Blood pressure is 138/80mm Hg, urine microalbumin level is normal, and she has no evi- a total cholesterol of 278 mg/dl (7.2 mmol/liter), low-density li- poprotein cholesterol (LDL-c) of 218 mg/dl (5.6 mmol/liter), high-density lipoprotein cholesterol (HDL-c) of 40 mg/dl (1.0 mmol/liter), and triglycerides of 99 mg/dl (1.1 mmol/liter). Intensivelifestyle recommendations, including a goal weight loss of 7% Clinical question no. 1: What is prediabetes?
through a healthy low-calorie, low-fat diet and increased physical Prediabetes broadly refers to an intermediate stage between com- activity of 150 min/wk, are recommended. The patient is seen every pletely normal glucose levels and the clinical entity of type 2 6 months with FPG performed semiannually and HbA1c and diabetes, encompassing both IFG and impaired glucose tolerance OGTT performed annually. Over the next few years, the patient complied with the lifestyle recommendations and lost 6 kg (9%) of As defined by the American Diabetes Association (ADA), pre- her body weight, with fasting glucoses ranging from 95–108 mg/dl diabetes is a FPG of at least 100 mg/dl (5.6 mmol/liter) but less (5.3– 6 mmol/liter), HbA1c in the range of 6.1– 6.3%, and annual than 126 mg/dl (7.0 mmol/liter), which is frequently termed IFG, OGTT revealing isolated impaired fasting glucose (IFG). With this or an abnormal 2-h response to a 75-g OGTT of at least 140 intervention, her LDL-c decreased to 115 mg/dl (3.0 mmol/liter) mg/dl (7.8 mmol/liter) and less than 200 mg/dl (11.1 mmol/liter), Abbreviations: ADA, American Diabetes Association; BMI, body mass index; DPP, Diabetes Prevention Program; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; HDL-c, high-density lipoprotein cholesterol; 2hPG, 2-h postchallenge plasma glucose; IFG, impaired Copyright 2008 by The Endocrine Society fasting glucose; IGT, impaired glucose tolerance; LDL-c, low-density lipoprotein choles- doi: 10.1210/jc.2008-1091 Received May 20, 2008. Accepted July 21, 2008.
terol; OGTT, oral glucose tolerance test; QALY, quality-adjusted life years.
J Clin Endocrinol Metab, September 2008, 93(9):3259 –3265 J Clin Endocrinol Metab, September 2008, 93(9):3259 –3265 which is often termed IGT. The World Health Organization de- should prompt further investigation with a FPG or OGTT (14).
fines IGT similarly as the ADA, but IFG is defined at a fasting Thus, in this patient, an initial FPG and HbA1c followed by an glucose of at least 110 mg/dl (6.1 mmol/liter) (1, 2).
OGTT if FPG was less than 126 mg/dl (7 mmol/liter) and HbA1c The definitions of diabetes and prediabetes are based on assess- was less than 7% would complete her diagnostic evaluation. All ments of disease risk as well as population distributions of plasma were performed initially, confirming the patient’s diagnosis of pre- glucose (2). Data suggesting a threshold of plasma glucose above diabetes (IFG with IGT) and excluding the possibility of undi- which the incidence of retinopathy significantly increases has been used to help define diabetes (3, 4). This has been brought into ques-tion with recent data, with the Diabetes Prevention Program (DPP)showing that 7.9% of participants with IGT had findings consistent Clinical question no. 3: What is the natural
with diabetic retinopathy, and 12.6% of patients with diabetes had course of untreated prediabetes?
evidence of diabetic retinopathy early in the conversion to diabetes The progression from prediabetes to type 2 diabetes occurs over (5). In addition, the primary cause of morbidity and mortality in many years before the development of overt hyperglycemia seen diabetes is cardiovascular disease. Multiple prospective studies have in diabetes (17). The risk of progressing to diabetes is greater in demonstrated that cardiovascular events increase linearly with 2-h individuals with both IFG and IGT compared with isolated IFG postchallenge plasma glucose (2hPG) at levels well below the levels or isolated IGT alone (10, 11). The risk of progressing to diabetes diagnostic of diabetes. The DECODE (Diabetes Epidemiology: depends on the degree of insulin resistance and deficiency of Collaborative Analysis of Diagnostic Criteria in Europe) study, for insulin secretion as well as other diabetes risk factors, such as age, example, demonstrated a graded increase between 2hPG and car- family history, overweight/obesity, or history of gestational di- diovascular disease mortality and a J-shaped relation between fast- abetes or polycystic ovary syndrome.
ing glucose and mortality (6). Such data suggest evidence of disease The average annual risk of developing diabetes for someone before the official diagnosis of diabetes. Thus, we should reconsider with normoglycemia is approximately 0.7% per year (18). In con- the approach of viewing isolated values of glucose with a threshold trast, this risk is about 5–10% per year in individuals with IFG or model, but instead view glucose as a continuous variable in risk IGT (10). In the DPP, which enrolled subjects with elevated fasting factor assessment for both cardiovascular and diabetic microvas- glucose (Ն95 mg/dl, or Ն5.3 mmol/liter) and IGT, 11% of indi- viduals in the standard arm progressed to diabetes annually (19).
Over the lifetime, a majority of patients with IFG, IGT, or both Clinical question no. 2: Does this patient have
would develop type 2 diabetes in the absence of intervention.
prediabetes at presentation?
Prediabetes is not only a significant risk factor for progression to type 2 diabetes but is also considered a risk factor for mac- This patient meets criteria for IFG, consistent with prediabetes, even rovascular disease and for retinopathy. Some of this risk may be before performing an OGTT. However, it is difficult to exclude the associated with progression to overt diabetes, but there is still possibility that this patient does not already have type 2 diabetes by increased risk in individuals who have not yet progressed to FPG alone. Fasting glucose alone is reported to miss the detection diabetes. A metaanalysis of 38 prospective studies, for example, of approximately 30% of cases of type 2 diabetes (2, 3, 7). This suggests that postchallenge blood glucose levels in the nondia- percentage may be even higher as reported in the Rancho Bernardo betic range appear to have a linear relationship with cardiovas- cohort and in the DPP. In the Rancho Bernardo cohort, 70% of cular disease risk and a possible threshold risk with fasting women and 48% of men aged 50 – 89 had new diabetes diagnosed plasma glucose of about 100 mg/dl (5.6 mmol/liter) (20).
on the basis of an elevated 2-h plasma glucose alone (8). In the DPP,87% of cases of new diabetes were detected based on initial eleva-tion of 2hPG, as opposed to only 34% that were detected based on Clinical question no. 4: What is the evidence
supporting intervention for prediabetes, and
Upon presentation, an OGTT should be considered to defini- does treatment alter the natural course of
tively diagnose whether the patient has prediabetes or has unrec- prediabetes?
ognized type 2 diabetes mellitus. Diagnosis impacts prognosis, be-cause patients diagnosed with both IFG and IGT develop diabetes There is ample evidence that intensive lifestyle intervention and approximately twice as often as individuals with either isolated IFG various modes of pharmacotherapy reduce the risk of progres- or isolated IGT (10, 11). In addition, cardiovascular risk is greater sion to diabetes, but is the progression to diabetes truly being in those with IGT or diabetes based on the 2hPG (6, 12). The prevented, or is the hyperglycemia of diabetes being treated OGTT, however, requires additional time and resources, is early? Are the treatment interventions sustainable? And finally, considered less reproducible than the FPG, and thus would is there any impact of treatment of prediabetes on long-term require an additional confirmatory test if abnormal (9, 13).
microvascular and macrovascular comorbidities? Alternatively, there is growing acceptance for the role of HbA1c in the screening, diagnosis, and prognosis of diabetes (14 –16). Ac- Lifestyle approaches or metformin therapy for diabetes
cording to a recent panel recommendation, an HbA1c of 7% or prevention?
higher would suggest the presence of diabetes, along with a confir- Lifestyle changes have consistently demonstrated benefit in pre- matory test, whereas an elevated HbA1c of at least 6.5– 6.9% venting or delaying the progression from IGT to diabetes. The Chi- J Clin Endocrinol Metab, September 2008, 93(9):3259 –3265 nese Da Qing study of more than 500 IGT subjects was one of the 25%, suggesting the possibility that metformin was not just first to show the benefit of long-term diet and exercise intervention masking a diagnosis of diabetes but also helped to delay the to prevent diabetes (21). Both the Finnish Diabetes Prevention progression of prediabetes (25). Whether metformin was really Study and the DPP demonstrated a 58% reduction in the progres- changing the natural history of the disease would have been sion from IGT to diabetes with intensive lifestyle changes compared better delineated if the washout period had been longer.
with standard lifestyle advice (19, 22). In the DPP, lifestyle inter- Does the combination of lifestyle intervention and metformin vention with a goal of at least 7% weight loss and at least 150 min confer additive benefit? The Indian Diabetes Prevention Pro- of physical activity per week appeared to have greater impact on gramme (IDPP-1), which showed a very high progression rate to older persons and those with a lower BMI (19). With a BMI goal of diabetes of 55% over 3 yr in subjects with IGT, evaluated the less than 22 kg/m2 in the intensive lifestyle group compared with less combination of metformin with intensive lifestyle changes com- than 24 kg/m2 in the standard group, a Japanese study in males with pared with either treatment alone. Although the tolerated level of IGT resulted in a 67.4% risk reduction in diabetes over 4 yr (23).
metformin was only 250 mg twice daily compared with the 850 The interventions involved are intense, and require a firm mg twice daily in the DPP, a combination of metformin with commitment from patient, provider, and society alike. Even with lifestyle change had no additional benefit compared with the the multifaceted approach of lifestyle intervention in the DPP, treatment with either metformin or lifestyle changes alone (26).
only 38% of the participants in the lifestyle intervention group Computer modeling from the DPP estimates that over a lifetime, achieved the weight loss goal of at least 7% at the end of the 83% of participants treated with standard intervention would de- study, while only 58% met the goal of at least 150 min of mod- velop diabetes, compared with 63% of those treated with lifestyle erate intensity activity (19). Yet, there was clear benefit in the intervention and 75% of those treated with metformin. Lifestyle intervention. Encouraging is the follow-up of the Finnish Dia- intervention would delay the onset of diabetes by 11.1 yr, and met- betes Prevention Study, in which participants were followed for formin would delay the onset of diabetes by 3.4 yr (Fig. 1). Lifestyle an additional median 3 yr after the 4-yr intervention period. No intervention would increase life expectancy by 0.5 yr and reduce the diet or exercise counseling was provided in the annual follow- incidence of blindness by 39%, end-stage renal disease by 38%, up visits. During the total follow-up, the intervention group amputation by 35%, stroke by 9%, and coronary heart disease by maintained a 43% reduction in relative risk of developing dia- 8% (27). Supportive of this, both traditional (hypertension and betes compared with the standard control group. The risk re- dyslipidemia) and nontraditional (C-reactive protein and fibrin- duction was greatest, however, in those who maintained the life- ogen) risk factors were significantly reduced with intensive style goals of weight loss, reduced fat intake, increased fiber lifestyle treatment in the DPP (28, 29).
intake, and increased physical activity (24).
Despite such intriguing data from computer modeling, im- On the other hand, metformin at 850 mg twice daily resulted provements in long-term health outcomes (i.e. mortality and re- in a 31% reduction in progression to diabetes in the DPP, being duction in cardiovascular events) from diabetes prevention ef- more effective in younger individuals and in participants with a forts have yet to be proven. The longest follow-up outcomes higher BMI (19). In addition, after a 1- to 2-wk washout period, study to date is the Da Qing Diabetes Prevention Outcome Study, metformin demonstrated a persistent reduction in diabetes by evaluating participants 14 yr after the initial 6-yr intervention FIG. 1. Simulated cumulative incidence of diabetes among adults with impaired glucose tolerance by the Diabetes Prevention Program treatment group. [Reproduced
with permission from W. H. Herman et al.: Ann Intern Med 142:323, 2005 (27) American College of Physicians.]
J Clin Endocrinol Metab, September 2008, 93(9):3259 –3265 period. Participants in the intensive lifestyle intervention arm Back to the patient . . . clinical question no. 5:
sustained a 43% reduction in diabetes incidence over the 20-yr Should this patient’s prediabetes be treated?
period. There was no reported difference in cardiovascular dis-ease events or mortality, although the study had limited power to The evidence is undisputable that diabetes can be delayed or prevented by either intensive lifestyle modification and/or a va-riety of pharmacotherapies. This patient should have her predi- Pharmacological intervention in diabetes prevention
abetes addressed, diabetes diagnosed or excluded, and should be Other methods of pharmacotherapy have also demonstrated treated. The risks of treatment, particularly with lifestyle inter- prospective benefit in disease prevention. Acarbose was associ- vention, are low and the benefits extend beyond the prevention ated with a 25% reduction in progression from IGT to diabetes of diabetes. In addition, lifestyle intervention is a highly cost- after 3 yr in the STOP-NIDDM (Study to Prevent Non-Insulin- effective method of treating prediabetes. Elegant cost analyses of Dependent Diabetes Mellitus) trial. This effect disappeared with the DPP showed that compared with placebo, lifestyle interven- discontinuation of the acarbose, suggesting that acarbose may tion would cost $635 more over a lifetime and produce a gain of have masked the progression to diabetes (31). This trial also 0.57 quality-adjusted life years (QALY), or a cost per QALY demonstrated a 49% relative risk reduction in cardiovascular gained of about $1100. The estimated cost per QALY gained for disease with acarbose, reduction in hypertension, and a reduc- metformin intervention extended over the lifetime compared tion in progression of carotid intima-media thickness (32, 33).
with placebo was approximately $31,300 but was substantially These data suggest that maintenance of normoglycemia may help lower at $1755 if the cost of generic metformin was substituted prevent long-term macrovascular morbidity.
in the calculation (27). Eddy and colleagues (43) have estimated The most enticing data to suggest a biological delay in the pro- higher cost-effectiveness ratios, but several other models have gression from prediabetes to diabetes with pharmacotherapy are now demonstrated the relative cost-effectiveness of lifestyle in- from Buchanan and colleagues (34, 35). In both the TRIPOD (Tro- terventions as well as metformin (44).
glitazone in Prevention of Diabetes) and PIPOD (Pioglitazone in Thus, there is no significant deterrent to treating this patient’s Prevention of Diabetes) studies in Hispanic women with a history prediabetes, and a detailed conversation between provider and of gestational diabetes, Buchanan et al. (34, 35) showed that tro- patient should ensue. Factors such as the availability of resources glitazone and pioglitazone, respectively, stabilized pancreatic ␤-cell for participation in an intensive lifestyle program and the pa- function compared with placebo. Women in the placebo arm of tient’s commitment of time toward dietary and lifestyle changes TRIPOD had a decline in ␤-cellfunction.Pioglitazonestabilizedthis should be reviewed. If pharmacotherapy is considered, a detailed decline in ␤-cell function in the PIPOD study, and this effect per- discussion of the goals, available data, and potential side effects sisted after an extended washout period of the pioglitazone (35).
The TRIPOD and PIPOD studies also demonstrated decrease incarotid intima-media thickness with troglitazone and pioglitazone,respectively, suggesting a cardioprotective effect (36, 37).
Clinical question no. 6: How should
In the DREAM study (Diabetes Reduction Assessment prediabetes be treated?
with Ramipril and Rosiglitazone Medication), rosiglitazoneincreased the regression of IFG or IGT to normoglycemia and Published guidelines on the approach to the patient with predi- reduced the incidence of the composite outcome of diabetes or abetes include a consensus statement from the ADA, the Indian death by 60% over 3 yr (38). After a washout period, the Health Services (IHS) Guidelines for care of the adults with pre- incidence of diabetes in the placebo and rosiglitazone groups diabetes and/or metabolic syndrome, and a position statement were similar (39). Of note, rosiglitazone also reduced the risk from the Australian Diabetes Society and Australian Diabetes of renal disease, suggesting that maintenance of normoglyce- Educators Association (Table 1). The recommendations on mia may impact development of microvascular disease (40).
treatment of prediabetes differ slightly. The ADA consensus Although there was no effect on cardiovascular outcomes, statement stratifies therapy based on whether the patient has there was an increase in congestive heart failure events com- isolated IFG, isolated IGT, or a combination of IFG and IGT, pared with placebo (0.5 vs. 0.1%) (38). The increased risk of allowing for consideration in differences in the underlying phys- weight gain, congestive heart failure, fractures (41), and cost iology and disease progression. Lifestyle modification with a associated with rosiglitazone must be weighed against its po- weight loss goal of 5–10% is recommended along with moderate physical activity of about 30 min daily. Recommendations for The recently reported ACT NOW (ACTos NOW for the Pre- use of metformin are tailored around individuals who may have vention of Diabetes) study demonstrated a remarkable 81% re- greater benefit from metformin as seen in the DPP and those who duction in the conversion of IGT to type 2 diabetes over a mean are at greater risk of progression to diabetes. Thus, metformin is 2.6 yr with pioglitazone compared with placebo. Improvements considered in individuals less than 60 yr of age, individuals with in insulin sensitivity and ␤-cell function were seen despite a a BMI of at least 35 kg/m2, and individuals with increased risk weight gain of 3.9 kg with pioglitazone compared with 0.8 kg such as family history of diabetes in first-degree relatives, ele- with placebo. The results from the washout period will help vated triglycerides, reduced HDL-c, hypertension, or HbA1c determine whether the improvements seen were due to biological more than 6.0% (11). The IHS guidelines similarly advocate delay of diabetes or early treatment of hyperglycemia (42).
lifestyle changes with consideration for metformin on an indi- J Clin Endocrinol Metab, September 2008, 93(9):3259 –3265 TABLE 1. Key features of selected published recommendations on prediabetes
Indian Health Services
Australian Diabetes Society
Guidelines for care of adults
and Australian Diabetes
with prediabetes and/or the
Educators Association
ADA consensus statement
metabolic syndrome in
position statement
(2007) (11)
clinical settings (2006) (45)
(2007) (46)
mmol/liter) with 2hPG Ͻ140mg/dl (7.8 mmol/liter) (7.8 mmol/liter) but Ͻ200mg/dl (11.1 mmol/liter) Individuals with risk factors for diabetes elevated triglycerides, reduced HDL-c, hypertension, HbA1c Ͼ6.0% vidualized basis (45). The Australian guidelines recommend life- Clinical question no. 7: When should one
style intervention as first-line therapy for a minimum of 6 months escalate interventions for prediabetes?
before consideration of pharmacotherapy (46).
Inthispatient’scase,intensivelifestylechangeswererecommended, The issue of when one should escalate intervention depends on and the patient’s commitment to these changes were reviewed. Met- the goals of treatment of prediabetes. Is the primary goal com- formin therapy was not considered as initial therapy but may be con- plete normalization of glucose levels or rather deterring progres- sidered in higher-risk patients as outlined by the ADA. Metformin was sive ␤-cell dysfunction? How will the primary goal reduce long- added when there was clear evidence of glycemic deterioration, or term mortality and morbidity? We look toward goals in type 2 progression of underlying disease, as evidenced by increase in FPG, diabetes to address these important questions. In their 2006 joint increase in HbA1c, and increase in 2hPG.
consensus statement, the ADA and the European Association for If pharmacotherapy for prediabetes is initiated, it is im- the Study of Diabetes (EASD) espoused an HbA1c goal as close portant for both patient and provider to realize that any ther- to the nondiabetic range as possible, or at least less than 7%. The apy will require a long-term commitment. In addition, it is consensus statement recommended a “call to action to initiate or important to review with the patient that there are limited data change therapy” for an HbA1c of at least 7% (47). This HbA1c demonstrating the long-term health benefits of pharmacolog- recommendation was based on issues of practicality and pro- ical intervention compared with lifestyle intervention. Fur- jected reduction in long-term complications. However, the re- thermore, one might debate which drug is the appropriate cent ACCORD (Action to Control Cardiovascular Risk in Dia- choice. The use of metformin is supported by its relative betes) trial also brings to light issues of safety in intensification safety, cost effectiveness, and long-term data in the DPP. The of therapy. In this trial of more than 10,000 subjects with type 2 ideal pharmacological intervention must demonstrate long- diabetes, intensive therapy with a goal HbA1c less than 6.0% term safety, health benefit (reduced incidence of diabetes, ma- compared with a standard HbA1c goal of 7.0 –7.9% resulted in crovascular and microvascular complications, and mortality), increased mortality after a mean 3.5 yr of follow-up (48). Given cost effectiveness, and the ability to halt the biological pro- these findings, reasonable goals in prediabetes include 1) pre- gression from prediabetes to diabetes. These factors will re- vention of glycemic deterioration as an indicator of preservation main the subject of current and future research endeavors in of ␤-cell function and 2) modification of nonglycemic risk factors (e.g. dyslipidemia and hypertension) to minimize long-term car- J Clin Endocrinol Metab, September 2008, 93(9):3259 –3265 diovascular risk. Should this involve pharmaceutical interven- and provider commitment to diagnosis and treatment, and level tion, safety and avoidance of hypoglycemia are imperative.
of adherence with recommended treatment. Although there may Which measures would alert the practitioner to deterioration be debate on the details of management of prediabetes, there is of glycemic control, or need for further intervention, over time? no longer any controversy that prediabetes needs to be addressed There are several options to consider, including FPG, repeat and treated. Preventing diabetes is the only way of decreasing the OGTT, HbA1c, or any combination of these tests.
immense current and future burden of diabetes and the attendant Although FPG is convenient and can be coupled with fasting lipid tests, FPG alone has limitations. As previously stated, FPGprovides an incomplete picture of chronic glycemic control andchange, providing poor sensitivity (ϳ40 – 60%) in detecting di-abetes (49). Postprandial hyperglycemia due to insulin resistance Acknowledgments
and insufficient ␤-cell compensation are often more prominent Address all correspondence and requests for reprints to: Robert in prediabetes than fasting hyperglycemia. At lower levels of Ratner, Med Star Clinical Research Center, 650 Pennsylvania Avenue HbA1c (e.g. Ͻ7.3%), postprandial glucose contributes more to the overall diurnal hyperglycemia than FPG (50).
Disclosure Statement: The authors have nothing to disclose.
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Prozess der Lernplattformauswahl in k -MedLuka Divac-Krnic, Oliver Merkel, Andreas Faatz, Stefan Hoermann, Cornelia Seeberg,Email: {luka, merkel, afaatz, hoermann, seeberg, steinmetz} Multimedia Communications (KOM) Department of Electrical Engineering & Information Technology& Department of Computer ScienceMerckstraße 25 • D-64283 Darmstadt • GermanyPro


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