Normal glucose vs. diabetes

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Hi All,

It seems that having low blood glucose levels as CRers may indicate improvement,

even relative to the higher but " normal " levels generally seen in ad lib

dieters,

based on the pdf-available below paper and its review.

Other factors related to CR and various normal glucose levels were in my

interest,

as seen below.

Arky RA.

" Doctor, is my sugar normal? " .

N Engl J Med. 2005 Oct 6;353(14):1511-3. No abstract available.

PMID: 16207855

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? "

Tirosh A, Shai I, Tekes-Manova D, Israeli E, Pereg D, Shochat T, Kochba I,

Rudich A;

Israeli Diabetes Research Group.

Normal fasting plasma glucose levels and type 2 diabetes in young men.

N Engl J Med. 2005 Oct 6;353(14):1454-62.

PMID: 16207847

ABSTRACT

Background The normal fasting plasma glucose level was recently defined as less

than

100 mg per deciliter (5.55 mmol per liter). Whether higher fasting plasma

glucose

levels within this range independently predict type 2 diabetes in young adults

is

unclear.

Methods We obtained blood measurements, data from physical examinations, and

medical

and lifestyle information from men in the Israel Defense Forces who were 26 to

45

years of age.

Results A total of 208 incident cases of type 2 diabetes occurred during 74,309

person-years of follow-up (from 1992 through 2004) among 13,163 subjects who had

baseline fasting plasma glucose levels of less than 100 mg per deciliter. A

multivariate model, adjusted for age, family history of diabetes, body-mass

index,

physical-activity level, smoking status, and serum triglyceride levels, revealed

a

progressively increased risk of type 2 diabetes in men with fasting plasma

glucose

levels of 87 mg per deciliter (4.83 mmol per liter) or more, as compared with

those

whose levels were in the bottom quintile (less than 81 mg per deciliter [4.5

mmol

per liter], P for trend <0.001). In multivariate models, men with serum

triglyceride

levels of 150 mg per deciliter (1.69 mmol per liter) or more, combined with

fasting

plasma glucose levels of 91 to 99 mg per deciliter (5.05 to 5.50 mmol per

liter),

had a hazard ratio of 8.23 (95 percent confidence interval, 3.6 to 19.0) for

diabetes, as compared with men with a combined triglyceride level of less than

150

mg per deciliter and fasting glucose levels of less than 86 mg per deciliter

(4.77

mmol per liter). The joint effect of a body-mass index (the weight in kilograms

divided by the square of the height in meters) of 30 or more and a fasting

plasma

glucose level of 91 to 99 mg per deciliter resulted in a hazard ratio of 8.29

(95

percent confidence interval, 3.8 to 17.8), as compared with a body-mass index of

less than 25 and a fasting plasma glucose level of less than 86 mg per

deciliter.

Conclusions Higher fasting plasma glucose levels within the normoglycemic range

constitute an independent risk factor for type 2 diabetes among young men, and

such

levels may help, along with body-mass index and triglyceride levels, to identify

apparently healthy men at increased risk for diabetes.

.... Table 1.Age-Adjusted Baseline Characteristics of 13,163 Men According to

Quintiles of Normal Fasting Plasma Glucose Levels.*

==========================

Characteristic Quintile 1 (N=2529) Quintile 2 (N=2545) Quintile 3 (N=2598)

Quintile

4 (N=2719) Quintile 5 (N=2772) P Value for Trend

==========================

Fasting plasma glucose level (mg/dl)

Mean 76.4 ±4.5 84.2 ±1.4 88.6 ±1.1 92.5 ±1.1 96.9 ±1.4 —

Median 78 84 89 92 97 —

Range 50 –81 82 –86 87 –90 91 –94 95 –99 —

Age (yr)32.4 ±4.6 32.6 ±4.8 32.5 ±4.7 32.6 ±4.8 33.0 ±4.7 <0.001

Triglyceride level (mg/dl)

Median 96 99 103 109 116 <0.001

25th,75th percentile 66,138 69,148 72,153 76,162 78,171

HDL cholesterol level (mg/dl)46.5 ±21.6 45.5 ±20.7 45.7 ±20.9 45.5 ±20.9 44.9

±21.4

0.05

Total cholesterol:HDL cholesterol ratio 4.9 ±3.1 5.0 ±2.9 5.2 ±2.9 5.2 ±2.9 5.3

±3.0

<0.001

Blood pressure (mm Hg)

Systolic 118.3 ±13.0 119.2 ±12.9 119.3 ±13.0 119.9 ±13.0 120 ±13.0 <0.001

Diastolic 76.2 ±9.5 76.8 ±9.4 76.8 ±9.5 77.2 ±9.5 77.2 ±9.5 <0.001

Body-mass index 25.0 ±3.9 25.3 ±3.8 25.5 ±3.9 25.6 ±3.9 25.9 ±3.9 <0.001

Family history of diabetes (%)†16.8 17.7 16.5 18.6 19.6 0.03

Smoking status (%)

Current 34.9 32.4 31.3 32.6 33.1 0.25

Former 19.5 19.4 19.4 19.3 20.9 0.34

Physical activity (%)‡11.8 13.0 13.5 12.0 11.3 0.21

Activity index (min/wk)§153.0 151.0 156.0 152.0 152.0 0.96

Mean follow-up (yr)5.5 5.5 5.7 5.8 5.9 0.03

======================

*Plus –minus values are means ±SD.To convert the values for glucose to

millimoles

per liter,multiply by 0.05551.To convert the values for triglycerides to

millimoles

per liter,multiply by 0.01129.To convert the values for cholesterol to

millimoles

per liter,multiply by 0.02586.

†A family history of diabetes indicates the presence of type 2 diabetes in a

first-degree relative.

‡Physical activity denotes engagement in physical activity for a minimum of 20

minutes at least three times per week.

§The activity index is the number of reported minutes of physical activity per

week

among subjects who engaged in physical activity.

Al Pater, PhD; email: old542000@...

__________________________________

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