Reviews/Commentaries/ADA Statements CONSENSUS STATEMENT

Impaired Fasting and Impaired Glucose Tolerance Implications for care

1 5 DAVID M. NATHAN, MD ROBERT R. HENRY, MD had other recognized risk factors for diabe- 2 6 MAYER B. DAVIDSON, MD RICHARD PRATLEY, MD tes including obesity, a prior history of ges- 3 7 RALPH A. DEFRONZO, MD BERNARD ZINMAN, MD 4 tational , or a positive family history ROBERT J. HEINE, MD, PHD, FRCP of diabetes. All of these trials demonstrated reductions in the development of diabetes of 25–60% over the period of follow-up. ype 2 diabetes is now epidemic. In the glucose tolerance (IGT), to diabetes may The largest reductions (ϳ60%) were ac- U.S., there has been a 61% increase in take many years; however, current esti- complished with lifestyle interventions T incidence between 1990 and 2001 mates indicate that most individuals (per- aimed at weight loss and increasing physical (1). There are currently 1.5 million new haps up to 70%) with these pre-diabetic activity and with thiazolidinediones cases per year, and the prevalence in 2005 states eventually develop diabetes (4–10). (4,5,24,25,27). Lesser degrees of reduction was almost 21 million (2). The epidemic has During the pre-diabetic state, the risk of a (25–30%) have been achieved with other affected developed and developing coun- CVD event is modestly increased (11–22). drugs (5,23,24,28). tries alike, and the worldwide prevalence of With the development of diabetes, how- The availability of interventions that diabetes is projected to increase dramati- ever, there is a large increase in risk for have been shown to decrease the develop- cally by 2025 (3). The increase in type 2 CVD, as well as for long-term complications ment of diabetes has stimulated consider- diabetes is related to lifestyle changes that affecting the eyes, kidneys, and nervous sys- ation whether such interventions should be have resulted in overweight, obesity, and tem. The complications of diabetes, which recommended and implemented, in whom, decreased physical activity levels. These en- are the cause of major morbidity and mor- and under what circumstances. To address vironmental changes, superimposed on ge- tality, are related to its duration, chronic these issues, the American Diabetes Associ- netic predisposition, increase level of glycemia, and other risk factors. ation convened a consensus development resistance, which, in concert with progres- Although clinical trials have demon- conference on 16–18 October 2006 focus- sive ␤-cell failure, results in rising glycemia strated the effectiveness of intensive glyce- ing on the pre-diabetic states of IFG and in the nondiabetic range. In addition to the mic and blood pressure control to reduce IGT. Following the presentations of invited risk for diabetes, and im- the long-term complications of diabetes, the speakers and in-depth discussions, a seven- paired insulin secretion are accompanied by public health burden of the disease remains member panel of experts in diabetes, endo- a host of major cardiovascular disease enormous. The magnitude of the epidemic, crinology, and metabolism developed this (CVD) risk factors including hypertension coupled with complex treatment require- consensus position based on the questions and dyslipidemia. Further reduction in in- ments that are difficult and costly to imple- below. The expert members were also asked sulin secretion over time results in increas- ment, make the prevention of diabetes a to note where additional information or ing glycemia and the development of critical public health goal. Between 1997 studies would be necessary to answer these diabetes, which in turn is associated with and 2006, eight major clinical trials exam- questions. the development of microvascular and car- ined whether lifestyle or pharmacologic in- diovascular complications. terventions would prevent or delay the The transition from the early metabolic development of diabetes in populations at QUESTION 1: What are IFG abnormalities that precede diabetes, im- high risk by virtue of having IFG and/or IGT and IGT, and what is their paired fasting glucose (IFG) and impaired (4,5,23–28). The study populations often natural history? — How much does IFG, IGT, or the combination of both ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● conditions increase the risk for subse- From 1Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; the 2Clinical quent development of diabetes? Does IFG Center for Research Excellence, Charles R. Drew University of Medicine and Science, Los Angeles, California; and/or IGT increase the development of 3 4 the University of Texas Health Science Center, San Antonio, Texas; the Diabetes Center, VU University cardiovascular disease? If so, are the ef- Medical Center, Amsterdam, the Netherlands; the 5Department of Medicine, University of California, San Diego, California; the 6Department of Medicine, University of Vermont, Burlington, Vermont; and the fects of IFG and/or IGT independent of 7Departments of Endocrinology and Metabolism, Mount Sinai Hospital, University of Toronto, Toronto, associated known cardiovascular risk fac- Ontario, Canada. tors including the subsequent develop- Address correspondence to Richard Kahn, American Diabetes Association, 1701 North Beauregard St., ment of diabetes? Alexandria, VA 22311. E-mail: [email protected]. IFG and IGT represent intermediate Panel disclosures can be found on p. 757. Abbreviations: CVD, cardiovascular disease; DPP, Diabetes Prevention Program; DREAM, Diabetes states of abnormal glucose regulation that Reduction Assessment with Ramipril and Rosiglitazone Medication; FPG, fasting plasma glucose; IGT, exist between normal glucose homeosta- impaired glucose tolerance; IFG, impaired fasting glucose; NGT, normal glucose tolerance; OGTT, oral sis and diabetes. IFG is now defined by an . elevated fasting plasma glucose (FPG) A table elsewhere in this issue shows conventional and Syste`me International (SI) units and conversion Ն Ͻ factors for many substances. concentration ( 100 and 126 mg/dl) DOI: 10.2337/dc07-9920 (29). IGT is defined by an elevated 2-h © 2007 by the American Diabetes Association. plasma glucose concentration (Ն140 and

DIABETES CARE, VOLUME 30, NUMBER 3, MARCH 2007 753 Consensus Statement

Table 1—Classification of glucose tolerance states

2-h plasma glucose in FPG level OGTT State (mg/dl) (mg/dl)* IFG 100–125 Ͻ200 Isolated IFG 100–125 Ͻ140 IGT Ͻ126 140–199 Isolated IGT Ͻ100 140–199 Combined IFG/IGT 100–125 140–199 NGT Ͻ100 Ͻ140 *Standard 75-g OGTT.

Ͻ200 mg/dl) after a 75-g glucose load on the oral glucose tolerance test (OGTT) in the presence of an FPG concentration Ͻ126 mg/dl (29,30). With the definitions above, there is overlap between the two groups. To study the separate characteristics of IFG and Figure 1—Plasma glucose concentration during an OGTT performed in subjects with IFG, IGT, IGT, classifications of isolated IFG and NGT, or combined IFG/IGT (CGI). Adapted with permission from ref. 54. isolated IGT that are mutually exclusive have been created (isolated IFG ϭ FPG of groups (30–34). IFG and IGT also differ ing diabetes associated with IFG needs to be 100–125 mg/dl with the 2-h value Ͻ140 significantly in their age and sex distribu- reevaluated. mg/dl; isolated IGT ϭ 2-h value of 140– tion; the prevalences of both metabolic Numerous longitudinal studies indi- 199 mg/dl with the fasting level Ͻ100 disorders increase with advancing age. cate that both IFG and IGT are associated mg/dl). The combined characteristics of IGT is more frequent in women than in with a modest increase in the hazard ratio IFG and IGT have been studied by iden- men (34–36). Unfortunately, most of the (ϳ1.1–1.4) for CVD, with IGT being a tifying populations that fulfill both crite- published literature on IFG is based upon slightly stronger risk predictor (11–22). ria (FPG ϭ 100–125 mg/dl and 2-h the older cut point (110–125 mg/dl). The majority of this risk appears to be con- value ϭ 140–199 mg/dl). Conversely, The natural history of both IFG and ferred by progression to diabetes, when the normal glucose tolerance (NGT) is de- IGT is variable, with ϳ25% progressing risk of CVD increases two- to fourfold. fined as FPG Ͻ100 mg/dl and 2-h plasma to diabetes, 50% remaining in their ab- Many cardiovascular risk factors (e.g., low glucose Ͻ140 mg/dl (Table 1). normal glycemic state, and 25% reverting HDL cholesterol, hypertension, and ele- IFG was defined in 1997 by the to NGT over an observational period of vated triglycerides) are prevalent in IFG and American Diabetes Association as a means 3–5 years (9,37–38). Individuals who are IGT, but it is unclear whether they occur of classifying individuals who had fasting older, overweight, and have other diabe- more frequently in one state than the other glucose levels between normal and diabe- tes risk factors are more likely to progress. (44–49). However, after adjustment for tes (30). It was meant to be analogous to Moreover, low insulin secretion and se- known cardiovascular risk factors, both IFG IGT as an intermediate metabolic state be- vere insulin resistance identify individu- and IGT remain as independent, albeit tween normal and diabetes, but based on als more likely to progress to diabetes weak, risk factors for CVD in some studies the FPG. The original FPG range (110– (39). With longer observation, the major- but not in others (11–22). Even so, it is un- 125 mg/dl) was changed in 2003 to 100– ity of individuals with IFG or IGT appear clear whether the CVD risk associated with 125 mg/dl so that the population risk of to develop diabetes. IFG or IGT can be attributed to the devel- developing diabetes with IFG would be Both IFG and IGT have a heteroge- opment of diabetes during follow-up or similar to that with IGT (29). The change neous pathogenesis, and this may contrib- whether these states per se convey such risk in the cut point increased the overall prev- ute to different rates of progression to (37,50,51). alence of IFG approximately three- to diabetes. Also, the poor precision and accu- fourfold. It is clear, however, that IGT and racy of glucose measurements (40) and the QUESTION 2: What is IFG do not define the same individuals. poor reproducibility of the glucose toler- known about the patho- The prevalence of IFG and IGT varies ance test itself (41–43) contribute to the dif- genesis of IFG and IGT? — The widely, with recent data from the U.S. in- ficulty of defining the natural history of IFG/ epidemiologic differences between IFG dicating the prevalence of IFG to be IGT in any one individual. Individuals with and IGT suggest that different pathophys- ϳ26% and somewhat older data showing both IFG and IGT have approximately dou- iologic mechanisms contribute to these a 15% prevalence of IGT (2). Both are ble the rate of developing diabetes com- disturbances in glucose homeostasis (52– expected to increase in the foreseeable fu- pared with individuals with just one of 55). During a standard 75-g OGTT, peo- ture. The prevalences of IFG and IGT vary them. However, with recent changes in the ple with isolated IGT have, by definition, considerably among different ethnic cut point defining IFG, the risk of develop- FPG levels that are similar to those with

754 DIABETES CARE, VOLUME 30, NUMBER 3, MARCH 2007 Nathan and Associates

NGT. However, following glucose inges- tance, results in prolonged a progressive decline in ␤-cell function or tion the plasma glucose concentration after a glucose load. increased insulin resistance, an interven- rises excessively at all time points and re- tion that improved these pathophysio- mains elevated (by definition Ն140–199 QUESTION 3: How do we logic disturbances would also slow the mg/dl) after 120 min (Fig. 1). On the define the natural history rate of progression to diabetes. other hand, in isolated IFG, the FPG is of IFG/IGT, and can we A wide variety of interventions have higher (by definition 100–125 mg/dl) alter it? — At the simplest level, the been shown to alter the natural history than in NGT and isolated IGT, and the natural history of both IFG and IGT can be of IFG/IGT progression to diabetes. All plasma glucose concentrations at 30–60 defined in terms of progression to diabetes. of the controlled clinical trials to date min in the OGTT are greater than in both As discussed earlier, the majority of people have measured changes in glycemia as NGT and isolated IGT. Thereafter, the with IFG/IGT will develop progressive hy- their primary outcome. None of the plasma glucose concentration in IFG de- perglycemia and eventually meet criteria for completed studies allow us to deter- clines to near-baseline values at 120 min. diabetes. A definition of natural history mine definitively whether the interven- These two very distinct oral glucose toler- based on glucose levels has the advantage tions “reset the clock” or altered the rate ance curves reflect different pathophysio- of being relatively easy to measure and of progression. Of note, the results of logic disturbances in glucose homeostasis quantitate. published studies (25,56) support a in isolated IFG and isolated IGT. The A second definition of the natural his- beneficial effect on the underlying plasma glucose curves in people with tory could be based on the underlying pathophysiology, specifically a reduc- both IFG and IGT reflect the characteris- pathophysiological abnormalities associ- tion in insulin resistance and an im- tics of both. ated with the development of hyperglyce- provement in relative insulin secretion. Although both isolated IFG and iso- mia. A progressive decline in insulin There clearly is a need for further lated IGT are insulin-resistant states, they secretion or increase in insulin resistance studies that quantitate changes in ␤-cell differ in their site of insulin resistance could be used to define the natural his- function/mass and insulin sensitivity over (51,54). People with isolated IFG pre- tory. A natural history definition based on time in response to interventions. Such dominantly have hepatic insulin resis- pathophysiologic parameters might be studies may discover specific effects of tance and normal muscle insulin more sensitive to and discriminate better different interventions on the underlying sensitivity, whereas individuals with iso- among the various effects of particular in- pathogenesis of the disease. Since studies lated IGT have normal to slightly reduced terventions than changes in glycemia. On to demonstrate improvements in hard hepatic insulin sensitivity and moderate the other hand, a nonglycemic definition outcomes (e.g., changes in the incidence to severe muscle insulin resistance. Not of the natural history is more compli- of micro- or macrovascular disease) may surprisingly, individuals with both IFG cated, more expensive to measure, and not be feasible, future research studying and IGT manifest both muscle and he- less easily translatable to clinical practice, the effect(s) of interventions on the patho- patic insulin resistance. and its long term consequences may be physiology of IFG, IGT, and diabetes The pattern of insulin secretion also dif- more difficult to interpret. might establish important therapeutic fers between IFG and IGT. People with iso- A third possible definition of “natural targets. lated IFG have a decrease in first-phase history” could be based on the complica- (0–10 min) insulin secretory response to tions of hyperglycemia, including micro- QUESTION 4: Do intravenous glucose and a reduced early- vascular and macrovascular disease. interventions that prevent phase (first 30 min) insulin response to oral Because the relative risk of developing the progression from IFG/ glucose. However, the late-phase (60–120 these complications is low as long as in- IGT to diabetes also pre- min) plasma insulin response during the dividuals remain in the IFG/IGT glycemic vent the development/ OGTT is normal in isolated IFG. Isolated range, studies that use this definition are worsening of diabetes- IGT also has a defect in early-phase insulin likely to be impractical. related microvascular com- secretion in response to an oral glucose load Just as there are different potential plications, cardiometabolic and in addition has a severe deficit in late- definitions of the natural history of IFG risk factors (e.g., hyper- phase insulin secretion. and IGT, there are different ways in which tension and dyslipidemia), The combination of hepatic insulin the natural history can be altered. The or CVD events? — The prevention resistance and defective insulin secretion progression to diabetes is a time- or delay of diabetes should lead to a de- in isolated IFG results in excessive fasting dependent phenomenon; one possible al- crease in duration-dependent diabetes- hepatic glucose production accounting teration is simply to “reset the clock” related microvascular complications; for fasting hyperglycemia. The impair- without changing the rate of the deterio- however, direct data are not available to ment in early insulin response in combi- ration. It is possible that some interven- determine whether this occurs. Published nation with hepatic insulin resistance tions will lower glycemia initially but do trials have not been sufficiently powered results in the excessive early rise of plasma nothing to change the subsequent rate of to show a reduction in these hard out- glucose in the 1st hour of the OGTT. rise of glycemia. This mechanism will de- comes. One of the other major reasons to However, the preservation of late insulin lay crossing the glycemic threshold that recommend therapeutic interventions for secretion combined with normal muscle defines diabetes. individuals with IFG/IGT is the potential insulin sensitivity allows glucose levels to A second possible way to alter the nat- to reduce the long-term increased risk of return to the preload value in isolated ural history is based on changes in the CVD associated with diabetes. The poten- IFG. In contrast, in isolated IGT the de- underlying rate of deterioration in the tial for achieving this goal can be assessed fective late insulin secretion, combined pathophysiologic abnormalities. Thus, if by evaluating three distinct outcomes: with muscle and hepatic insulin resis- we defined the natural history in terms of cardiovascular risk factors, surrogate

DIABETES CARE, VOLUME 30, NUMBER 3, MARCH 2007 755 Consensus Statement markers of atherosclerosis, or clinically QUESTION 5: Are there cate that an intensive lifestyle intervention significant cardiovascular events. Inter- adequate data to recom- provides the greatest reduction in the oc- ventions that similarly reduce the pro- mend interventions to pre- currence of diabetes, along with a modest gression from IFG/IGT to diabetes may vent or delay diabetes in reduction in CVD risk factors, and has a have different effects on the CVD out- IFG/ IGT at this time? — The favorable safety profile. The lifestyle mod- comes above. An example of dissociation epidemic increase in diabetes and its serious ification studies were associated with vir- between diabetes delay/prevention and long-term consequences strongly support tually no serious untoward effects. In reduction in CVD risk factors is seen by efforts to prevent its occurrence, with the addition, lifestyle modification is likely to comparing the effects on blood pressure expectation that morbidity and mortality have other beneficial health-related ef- of intensive lifestyle change versus met- will be decreased. Even in the absence of fects (4,5,58). formin, both of which reduced diabetes direct data regarding the benefits of diabetes For all of these reasons, lifestyle mod- development in the Diabetes Prevention prevention on long-term complications, the ification therapy emphasizing modest Program (DPP) (58). Intensive lifestyle Panel believes in principle that early inter- weight loss (5–10% of body wt) and mod- change was associated with no increase in vention is justified based on the following: erate-intensity physical activity (ϳ30 min incident hypertension compared with a the goal of delaying the onset of diabetes daily) is the treatment of choice for indi- significant increase in the metformin and and postponing its requirement for treat- viduals with IFG/IGT. While it is likely placebo arms. On the other hand, in the ment, which is often complex; the prospect that the population enrolled in the clinical Diabetes Reduction Assessment with of preserving ␤-cell function; and the like- trials may not exactly mirror the general Ramipril and Rosiglitazone Medication lihood that microvascular, and perhaps car- population, it seems very likely that life- (DREAM) trial, rosiglitazone both de- diovascular, complications will be delayed style modification would benefit all peo- creased the development of diabetes and or prevented. ple with IFG/IGT. reduced blood pressure (27). The strong association between dia- A more difficult issue is whether drug Of the usual surrogate measures of ath- betes and obesity suggests that our first therapy is warranted to delay/prevent di- erosclerosis, only carotid intima-media priority is maintenance of healthy weight abetes in individuals with IFG/IGT. Al- thickness has been studied in diabetes pre- and obesity prevention. All individuals though several drugs successfully slowed vention trials. In both the TRIPOD (Trogli- who are overweight or obese, regardless progression to diabetes, there are many tazone in Prevention of Diabetes) study (25) of their blood glucose value, should be issues that need to be considered before and STOP-NIDDM (Study to Prevent Non– intensively counseled to lose weight and medications can be recommended. Insulin-Dependent Diabetes Mellitus) (23), to exercise. In addition, interventions at Metformin was the first drug shown to treatment with troglitazone and acarbose, the community level, such as changes in be effective (5). Although its effectiveness respectively, was associated with a reduced school-based meals and exercise pro- was about half that achieved with lifestyle rate of increase in carotid intima-media grams, community infrastructure changes modification (31 vs. 58%), substantially thickness over time compared with conducive to increasing exercise fre- greater benefit was seen in a subset of placebo. quency, and legislation that promotes a younger and obese individuals. The drug is The only study to show a significant healthy lifestyle, are required. inexpensive and has a long history of use beneficial effect of an intervention on As mentioned above, a number of showing virtually no long-term serious side CVD events was the STOP-NIDDM study well-designed and executed clinical trials effects and only a low prevalence (5–10%) (57). Acarbose treatment was associated have demonstrated the value of lifestyle of modest side effects, such as nausea and with a 49% relative risk reduction of the modification or pharmacological therapy gastrointestinal disturbances. composite CVD outcome (P ϭ 0.03), an to prevent or delay the onset of diabetes. Acarbose appears to be as effective as unexpected finding given the relatively These completed prevention trials indi- metformin, but many patients cannot tol- small number of CVD events (15 in the treated group, 32 in the placebo group). Conversely, in the DREAM study (27), a Table 2—Treatment recommendation for individuals with IFG, IGT, or both significant increase in congestive heart failure events was seen with rosiglitazone Population Treatment compared with placebo (0.5 vs. 0.1%, P ϭ 0.01), although the total number of IFG or IGT Lifestyle modification (i.e., 5–10% weight loss congestive heart failure events was small and moderate intensity physical activity ϳ30 (14 vs. 2 events). min/day) In summary, intensive lifestyle inter- ventions can have substantial effects on Individuals with IFG and IGT and any of Lifestyle modification (as above) and/or diabetes delay/prevention and modest, al- the following: metformin* beit statistically significant, effects on ● Ͻ60 years of age CVD risk factors. Whether these changes ● BMI Ն35 kg/m2 will translate into meaningful reductions ● Family in first- in CVD events remains to be demon- degree relatives strated. The impact on CVD risk factors or ● Elevated triglycerides events when pharmacologic agents are ● Reduced HDL cholesterol used to prevent/delay diabetes is even less ● Hypertension clear and may differ depending on the ● A1C Ͼ6.0% medication used. *Metformin 850 mg twice per day.

756 DIABETES CARE, VOLUME 30, NUMBER 3, MARCH 2007 Nathan and Associates erate its gastrointestinal side effects, and it IFG/IGT should be the same as cur- quired. On the other hand, the Panel rec- is relatively costly. Orlistat is similar to rently recommended for screening for ommends that metformin therapy be acarbose in effectiveness and is also diabetes. At present, FPG and 2-h considered in individuals similar to those poorly tolerated, but because it is now an OGTT are the tests of choice to identify included in the DPP with confirmed IFG over-the-counter drug, it should be less all states of hyperglycemia (59). Either and IGT who had the greatest benefit with costly. Of note, however, the study show- test is suitable, and each has advantages metformin (see QUESTION 5) Therefore, ing the effectiveness of orlistat was not and disadvantages, such as conve- both abnormalities (IFG and IGT) must designed as a prevention trial (28); there- nience, cost, and reproducibility. Iden- be documented if metformin is to be fore, the effect of the drug in diabetes pre- tification of individuals with IGT, which used. vention is not as clearly established as is recommended in order to institute The most efficient sequence of test- with the other drugs. metformin therapy, can be made only ing is an FPG first (currently recom- Most recently, the results of the with a 2-h OGTT, while identification of mended as the preferred test to detect DREAM Study (27) indicated that rosigli- FPG requires measurement of the diabetes) followed by the 2-h OGTT on a tazone was as effective in delaying/ plasma glucose concentration after an subsequent day to demonstrate the pres- preventing diabetes as lifestyle modi- overnight fast. ence of combined IFG/IGT. If individuals fication in the Finnish or DPP studies If only lifestyle modification is with IFG/IGT are treated with metformin, (4,5). However, rosiglitazone is costly and planned, a confirmatory test is not re- the Panel recommends that routine moni- was associated with a sevenfold increase in heart failure, although the number of such cases was small. Panel Disclosures Based on this synopsis of the available trial results, the Panel recommends that Mayer B. Davidson, MD only metformin be considered as drug ther- apy for individuals with IFG/IGT. In the Research Support: Eli Lilly, Merck, Pfizer Speakers Bureau: Amylin, Eli Lilly, GlaxoSmithKline, Pfizer DPP, the subsets of the study cohort that Advisory Panel: Amylin, GlaxoSmithKline, Merck, sanofi-aventis had substantially increased benefit from metformin were those participants Ͻ60 Ralph A. DeFronzo, MD years of age and those who had a BMI Ն35 Research Support: Bristol Myers Squibb Company, Takeda Pharmaceuticals North kg/m2. Therefore, the Panel also recom- America, Pfizer, Novo Nordisk, Amylin, Eli Lilly Speakers Bureau: Takeda Pharmaceuticals North America, Amylin mends that metformin be limited to such Advisory Panel: Bristol Myers Squibb Company, Takeda Pharmaceuticals North individuals. Since individuals with associ- America, Novo Nordisk, Amylin ated risk factors for diabetes, e.g., family his- Consultant: Amgen tory in first-degree relatives, elevated Robert J. Heine, MD, triglycerides, low HDL cholesterol, and hy- PhD, FRCP pertension, are more likely to progress to Research Support: Amylin, Eli Lilly, Novartis, GlaxoSmithKline, Novo Nordisk, diabetes, the presence of one or more of Pfizer, Merck, Astellas these factors may contribute to the decision Speakers Bureau: Novartis, Merck to treat with metformin. In addition, to bet- Advisory Panel: Amylin, Eli Lilly, Novartis, GlaxoSmithKline, Novo Nordisk, ter target a population likely to benefit from sanofi-aventis, Pfizer, Merck, Astellas metformin therapy, an unpublished analy- Robert R. Henry, MD sis of data from the DPP (see QUESTION 6) Research Support: Amylin, AstraZeneca, Boehringer Ingelheim, Bristol Myers- suggests that an A1C Ն6.0% approximately Squibb, GlaxoSmithKline, Novartis, Novo Nordisk, Roche, doubles the rate of progression to diabetes Sankyo, sanofi-aventis, Takeda Pharmaceuticals Advisory Panel: Amylin, AstraZeneca, Bristol Myers-Squibb Company, in an IFG/IGT population. GlaxoSmithKline, Eli Lilly, Roche, Sankyo, sanofi-aventis, A summary of these recommenda- Takeda Pharmaceuticals tions is shown in Table 2. Future recom- Speakers Bureau: GlaxoSmithKline, Eli Lilly, sanofi-aventis, Takeda mendations may include other Pharmaceuticals medications if they prove to be effective, Stock/Shareholders: GlaxoSmithKline, Merck, Pfizer, Schering-Plough Consultant: Novartis, Boehringer Ingelheim, sanofi-aventis have a good safety profile, are tolerable, and are of relatively low cost. David M. Nathan, MD Research Support: Novo Nordisk, sanofi-aventis QUESTION 6: Who should be screened and with Richard Pratley, MD Research Support: Novartis, sanofi-aventis, Pfizer, Eli Lilly, Merck, Takeda what methods and fre- Pharmaceuticals quency to prevent/delay Speakers Bureau: Merck the adverse consequences Stock/Shareholder: Novartis of IFG/IGT? — Screening for IFG/ Consultant: Takeda Pharmaceuticals IGT is fundamentally no different from Bernard Zinman, MD screening for diabetes. The same risk Research Support: Eli Lilly, GlaxoSmithKline, Novartis, Novo Nordisk, Merck factors associated with diabetes are, not Speakers Bureau: Eli Lilly, GlaxoSmithKline surprisingly, associated with IFG/IGT. Advisory Panel: Eli Lilly, GlaxoSmithKline, Novartis, Novo Nordisk, Amylin, Thus, the population to be screened for Johnson & Johnson, Merck, Pfizer, sanofi-aventis

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