"Doctor, Is My Sugar Normal?"
http://www.100md.com
《新英格兰医药杂志》
We live in an era in which the public interest in medical matters is high. When so much information and misinformation are available on the Internet, many patients devote a fair share of time to matching their most recent laboratory results with the "normal" values cited in health-related Web sites or even in the advertisements for their medication. It seems reasonable for patients to strive to achieve the best possible results from medication or other treatments, and patients' requests for information about the desired goals of treatment are to be commended.
Frequently, as physicians, we are asked, "Are my laboratory results normal?" On the surface, this seems to be a benign, straightforward question that should lend itself to a simple answer. But, in fact, over the past several decades, the complexity of this question has been compounded by the increased number of epidemiologic studies that point out how differences in sex, ethnic background, age, and a multiplicity of other factors may determine what is "normal." In addition, outcome studies permit a retrospective analysis of the meaning of laboratory results of the past. Thus, if after 20 years of follow-up of a large cohort of subjects who had an original laboratory value of x milligrams per deciliter, lesion y is detected in a significant number of these subjects, it becomes useful to cite x milligrams per deciliter as a marker of the future appearance of that lesion. As a result of such outcome studies, there has been a redefinition of what is normal and what should be the desired level or goal of therapeutic interventions.
Moreover, advances in technology that allow for more precise measurements of common substances in tissues, blood, and other body fluids have altered our conceptions of the values that are considered normal or in the normal range. As a consequence, the accepted normal values for fasting plasma glucose and low-density lipoprotein (LDL) cholesterol levels have been lowered over the past two decades. For patients and their families, explanations of these complexities and the variables that affect normalcy are not always easy to comprehend; understanding requires time and clarity from the health care provider who explains the results.
An often-asked question is, "Doctor, how is my cholesterol count?" The textbooks of the 1940s and early 1950s, which were written before the discovery that an elevated cholesterol level was a risk factor for coronary artery disease, cited only the value of total cholesterol. However, as knowledge about lipoprotein metabolism accumulated and the important relationship of LDL cholesterol to atherosclerosis became clear, the emphasis on LDL, or "bad," cholesterol caught the public's eye. The messages of the successive reports1,2,3,4 of the National Cholesterol Education Program are noteworthy examples of the trend of translating clinical and epidemiologic studies to define normal values and, by implication, desired goals for treatment. As the number of therapeutic trials and epidemiologic studies and the understanding of the molecular biology and physical chemistry of lipoprotein metabolism progressed, the desired goal of treatment became a lowering of LDL cholesterol in both men and women, to prevent coronary heart disease and other macrovascular consequences of atherosclerosis. Similarly, over the past 12 years, the expert panel responsible for the National Cholesterol Education Program has suggested that therapeutic intervention begin at lower levels of LDL cholesterol than previously defined. This recommendation is particularly applicable to persons with risk factors other than elevated cholesterol levels, especially persons with diabetes.4
The LDL cholesterol story of the past two decades is analogous in a number of ways to the recent history of diabetes. In 1979, the National Diabetes Data Group5 recommended criteria for the diagnosis of diabetes: a fasting plasma glucose level of 140 mg per deciliter (7.77 mmol per liter) or less was considered to be within the normal range and not indicative of diabetes. Over the next several years, the World Health Organization and numerous national diabetes associations reaffirmed this criterion and also included among the categories of abnormalities impaired glucose tolerance. Once more, as the numbers of reported epidemiologic and therapeutic studies increased and it became apparent that certain end points — in this case, diabetic retinopathy — might serve as markers of diabetes and an indicator of the border between normal and abnormal fasting glucose levels, an international expert committee6 convened in 1997 and recommended that the upper limit of normal fasting plasma glucose levels be 126 mg per deciliter (7.00 mmol per liter) and that the diagnosis of diabetes be made when the fasting plasma glucose level exceeded that value. That group of experts also defined the normal fasting plasma glucose level as being no higher than 110 mg per deciliter (6.10 mmol per liter) and introduced the concept of impaired fasting glucose levels, thus identifying persons whose fasting plasma glucose levels ranged from 110 to 125 mg per deciliter as having impaired fasting glucose levels.
Neither the 1979 nor the 1997 recommendation won universal approval from the physician community. Especially questioned were the discrepancies that exist when fasting plasma glucose values are used as criteria for diagnosis, as compared with postprandial values or the levels noted after a standard glucose load (i.e., an oral glucose-tolerance test). In addition, since the publication of the recommendations of the National Diabetes Data Group, the use of glycosylated hemoglobin levels as means to assess the glycemic control of patients with diabetes has become an accepted standard. Why, some argue, should this measurement not serve as a diagnostic tool, too?
Although these debates continue to simmer, many new data related to the diagnosis of diabetes have appeared, and recently the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus issued a follow-up report.7 That group analyzed data from four diverse populations to determine what level of fasting plasma glucose predicted the future outcome of diabetes and, by applying a statistical analysis, concluded that a level of 110 mg per deciliter was "inappropriately high as a lower limit" of impaired fasting glucose and recommended changing the cutoff point for impaired fasting glucose to 100 mg per deciliter (5.60 mmol per liter). The Expert Committee accepts that the criteria for fasting plasma glucose and for 2-h post-prandial evaluate "different metabolic states" and that the impaired fasting glucose level identifies a lesser portion of the population than will the criterion for impaired glucose tolerance. Once again, the recommended upper level of the normal range for fasting plasma glucose levels has been lowered. But the pot continues to boil.
In this issue of the Journal, Tirosh and colleagues demonstrate that among a large cohort of healthy young Israeli military men who were followed for periods of up to 12 years, higher initial fasting plasma glucose levels within the normoglycemic range can foretell the onset of diabetes.8 The absolute incidence of diabetes among persons with fasting plasma glucose levels of 91 to 99 mg per deciliter (5.05 to 5.50 mmol per liter) over the follow-up period was 2.3 percent. Not unexpectedly, men with a high body-mass index or an increased fasting level of triglycerides were at greater risk for diabetes even though their fasting plasma glucose levels were within the normal range. When it is appreciated that fasting plasma glucose levels represent a continuum, as do the other circulating fuels, and that the border between "normal" and "abnormal" is a shady zone influenced by weight, age, other metabolic substrates, sex, and other factors, the complexity of the answer to the question of whether one's blood sugar is normal becomes apparent.
Although the study reported by Tirosh et al. deals only with men, there is no reason to believe that the lessons from the study are sex specific. Fasting plasma glucose levels in the high-normal range (91 to 99 mg per deciliter) in young men and women warrant counseling with regard to weight and lifestyle, as well as an assessment of the lipid profile. Markers of future disease are always very useful when prevention is possible.9 There is ample evidence that this situation is true in the case of diabetes. "Yes, your glucose level is normal, but let's do something about that weight and your sedentary lifestyle" is too frequently the most appropriate response to the question, "Doctor, is my sugar normal?"
Source Information
From the Francis Peabody Society, Harvard Medical School, Boston.
References
The Expert Panel. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Arch Intern Med 1988;148:36-69.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993;269:3015-3023.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-239.
National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979;28:1039-1057.
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183-1197.
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 2003;26:Suppl 1:S5-S20.
Tirosh A, Shai I, Tekes-Manova D, et al. Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med 2005;353:1454-1462.
Lindstrom J, Eriksson JG, Valle TT, et al. Prevention of diabetes mellitus in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study: results from a randomized clinical trial. J Am Soc Nephrol 2003;14:Suppl 2:S108-S113.(Ronald A. Arky, M.D.)
Frequently, as physicians, we are asked, "Are my laboratory results normal?" On the surface, this seems to be a benign, straightforward question that should lend itself to a simple answer. But, in fact, over the past several decades, the complexity of this question has been compounded by the increased number of epidemiologic studies that point out how differences in sex, ethnic background, age, and a multiplicity of other factors may determine what is "normal." In addition, outcome studies permit a retrospective analysis of the meaning of laboratory results of the past. Thus, if after 20 years of follow-up of a large cohort of subjects who had an original laboratory value of x milligrams per deciliter, lesion y is detected in a significant number of these subjects, it becomes useful to cite x milligrams per deciliter as a marker of the future appearance of that lesion. As a result of such outcome studies, there has been a redefinition of what is normal and what should be the desired level or goal of therapeutic interventions.
Moreover, advances in technology that allow for more precise measurements of common substances in tissues, blood, and other body fluids have altered our conceptions of the values that are considered normal or in the normal range. As a consequence, the accepted normal values for fasting plasma glucose and low-density lipoprotein (LDL) cholesterol levels have been lowered over the past two decades. For patients and their families, explanations of these complexities and the variables that affect normalcy are not always easy to comprehend; understanding requires time and clarity from the health care provider who explains the results.
An often-asked question is, "Doctor, how is my cholesterol count?" The textbooks of the 1940s and early 1950s, which were written before the discovery that an elevated cholesterol level was a risk factor for coronary artery disease, cited only the value of total cholesterol. However, as knowledge about lipoprotein metabolism accumulated and the important relationship of LDL cholesterol to atherosclerosis became clear, the emphasis on LDL, or "bad," cholesterol caught the public's eye. The messages of the successive reports1,2,3,4 of the National Cholesterol Education Program are noteworthy examples of the trend of translating clinical and epidemiologic studies to define normal values and, by implication, desired goals for treatment. As the number of therapeutic trials and epidemiologic studies and the understanding of the molecular biology and physical chemistry of lipoprotein metabolism progressed, the desired goal of treatment became a lowering of LDL cholesterol in both men and women, to prevent coronary heart disease and other macrovascular consequences of atherosclerosis. Similarly, over the past 12 years, the expert panel responsible for the National Cholesterol Education Program has suggested that therapeutic intervention begin at lower levels of LDL cholesterol than previously defined. This recommendation is particularly applicable to persons with risk factors other than elevated cholesterol levels, especially persons with diabetes.4
The LDL cholesterol story of the past two decades is analogous in a number of ways to the recent history of diabetes. In 1979, the National Diabetes Data Group5 recommended criteria for the diagnosis of diabetes: a fasting plasma glucose level of 140 mg per deciliter (7.77 mmol per liter) or less was considered to be within the normal range and not indicative of diabetes. Over the next several years, the World Health Organization and numerous national diabetes associations reaffirmed this criterion and also included among the categories of abnormalities impaired glucose tolerance. Once more, as the numbers of reported epidemiologic and therapeutic studies increased and it became apparent that certain end points — in this case, diabetic retinopathy — might serve as markers of diabetes and an indicator of the border between normal and abnormal fasting glucose levels, an international expert committee6 convened in 1997 and recommended that the upper limit of normal fasting plasma glucose levels be 126 mg per deciliter (7.00 mmol per liter) and that the diagnosis of diabetes be made when the fasting plasma glucose level exceeded that value. That group of experts also defined the normal fasting plasma glucose level as being no higher than 110 mg per deciliter (6.10 mmol per liter) and introduced the concept of impaired fasting glucose levels, thus identifying persons whose fasting plasma glucose levels ranged from 110 to 125 mg per deciliter as having impaired fasting glucose levels.
Neither the 1979 nor the 1997 recommendation won universal approval from the physician community. Especially questioned were the discrepancies that exist when fasting plasma glucose values are used as criteria for diagnosis, as compared with postprandial values or the levels noted after a standard glucose load (i.e., an oral glucose-tolerance test). In addition, since the publication of the recommendations of the National Diabetes Data Group, the use of glycosylated hemoglobin levels as means to assess the glycemic control of patients with diabetes has become an accepted standard. Why, some argue, should this measurement not serve as a diagnostic tool, too?
Although these debates continue to simmer, many new data related to the diagnosis of diabetes have appeared, and recently the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus issued a follow-up report.7 That group analyzed data from four diverse populations to determine what level of fasting plasma glucose predicted the future outcome of diabetes and, by applying a statistical analysis, concluded that a level of 110 mg per deciliter was "inappropriately high as a lower limit" of impaired fasting glucose and recommended changing the cutoff point for impaired fasting glucose to 100 mg per deciliter (5.60 mmol per liter). The Expert Committee accepts that the criteria for fasting plasma glucose and for 2-h post-prandial evaluate "different metabolic states" and that the impaired fasting glucose level identifies a lesser portion of the population than will the criterion for impaired glucose tolerance. Once again, the recommended upper level of the normal range for fasting plasma glucose levels has been lowered. But the pot continues to boil.
In this issue of the Journal, Tirosh and colleagues demonstrate that among a large cohort of healthy young Israeli military men who were followed for periods of up to 12 years, higher initial fasting plasma glucose levels within the normoglycemic range can foretell the onset of diabetes.8 The absolute incidence of diabetes among persons with fasting plasma glucose levels of 91 to 99 mg per deciliter (5.05 to 5.50 mmol per liter) over the follow-up period was 2.3 percent. Not unexpectedly, men with a high body-mass index or an increased fasting level of triglycerides were at greater risk for diabetes even though their fasting plasma glucose levels were within the normal range. When it is appreciated that fasting plasma glucose levels represent a continuum, as do the other circulating fuels, and that the border between "normal" and "abnormal" is a shady zone influenced by weight, age, other metabolic substrates, sex, and other factors, the complexity of the answer to the question of whether one's blood sugar is normal becomes apparent.
Although the study reported by Tirosh et al. deals only with men, there is no reason to believe that the lessons from the study are sex specific. Fasting plasma glucose levels in the high-normal range (91 to 99 mg per deciliter) in young men and women warrant counseling with regard to weight and lifestyle, as well as an assessment of the lipid profile. Markers of future disease are always very useful when prevention is possible.9 There is ample evidence that this situation is true in the case of diabetes. "Yes, your glucose level is normal, but let's do something about that weight and your sedentary lifestyle" is too frequently the most appropriate response to the question, "Doctor, is my sugar normal?"
Source Information
From the Francis Peabody Society, Harvard Medical School, Boston.
References
The Expert Panel. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Arch Intern Med 1988;148:36-69.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993;269:3015-3023.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-239.
National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979;28:1039-1057.
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183-1197.
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 2003;26:Suppl 1:S5-S20.
Tirosh A, Shai I, Tekes-Manova D, et al. Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med 2005;353:1454-1462.
Lindstrom J, Eriksson JG, Valle TT, et al. Prevention of diabetes mellitus in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study: results from a randomized clinical trial. J Am Soc Nephrol 2003;14:Suppl 2:S108-S113.(Ronald A. Arky, M.D.)