Chemistry: analytical and immunological testing – Tracers or tags
Reexamination Certificate
2002-08-27
2003-08-05
Wallenhorst, Maureen M. (Department: 1743)
Chemistry: analytical and immunological testing
Tracers or tags
C436S014000, C436S173000, C436S181000, C422S067000, C435S014000
Reexamination Certificate
active
06602715
ABSTRACT:
BACKGROUND OF THE INVENTION
Glucose tolerance is defined as the ability to properly utilize glucose. Diabetes is not a single disease, but an array of diseases that exhibit the common symptom of glucose intolerance, an impairment in glucose utilization.
The prevalence of diabetes in the general population is approximately 6-7%. Only about half of diabetics are actually diagnosed. Studies have shown that rates for persons with glucose intolerance are equal by sex and greater for blacks than for whites.
In general, the following types of diabetes have been recognized: type I diabetes mellitus, type II diabetes mellitus, secondary diabetes mellitus, impaired glucose tolerance and gestational diabetes mellitus. The general characteristics of the symptoms of diabetes include the following:
Polyuria (excretion of large quantities of urine)
Hyperglycemia (high blood glucose levels)
Glucosuria ( abnormal presence of glucose in urine)
Polydipsia (excessive thirst)
Polyphagia (excessive hunger)
Sudden weight loss.
It has been observed that complications resulting from diabetes mellitus are the third leading cause of death in most developed countries. Diabetes is a risk factor for a variety of conditions including coronary heart disease, cerebrovascular stroke, neuropathy (nerve damage), nephropathy (kidney damage), retinopathy (eye damage), hyperlipidemia (excessive blood lipids), angiopathy (damage to blood vessels) and infection.
A number of different methods exist for determining a condition of intolerance for glucose. These include postprandial blood glucose, oral glucose tolerance test (OGTT), O'Sullivan glucose tolerance test (gestational test), hemoglobin Alc (Hb A
1
, Hb A
1c
), islet cell antibodies, GAD antibodies (glutamic acid decarboxylase) and insulin antibodies. Diabetes, however, is most readily detected when the carbohydrate metabolic capacity is tested. This is done by stressing the system with a defined glucose load as in the oral glucose tolerance test (OGTT).
The OGTT has been criticized, however, because many of the variables affecting test results are difficult to control, for instance: Patients must be on a standardized carbohydrate diet at least three days before the test. The test requires an 8 to 16 hour fast. The test should only be performed on ambulatory patients. Stress should be avoided. Exercise should be avoided. Various hormone imbalances can affect validity such as with: thyroxine, growth hormone, cortisol and catecholamines. Various drugs and medications can affect validity such as: oral contraceptives, salicylates, nicotinic acid, diuretics and hypoglycemics. Evaluation should normally be corrected for age. The greatest disadvantage of the OGTT is that it is poorly reproducible and this limits its diagnostic usefulness.
The current methods of diagnosing diabetes involve either invasive testing (ie. repeated blood collections), or use blood-borne markers (ie. glycosylated proteins, or antibodies) which offer an indirect assessment of glucose regulation. Accordingly, it is an object of the present invention to avoid the need for invasive testing or the use of blood-borne markers in determinations of glucose regulation.
SUMMARY OF THE INVENTION
The above and other objects of the invention are attained by a
13
C breath test and a kit for determining glucose regulation in a patient in need thereof.
An analytical assay is described that is based on the use of non-radioactive
13
C. Labeled expired
13
CO
2
is measured in the present assay. Isotope ratio mass spectroscopy (IRMS) is used as a detection method for
13
C, a non-radioactive isotope that occurs naturally in food and animal tissues. Non-dispersive infrared spectroscopy (NDIRS) analysis and analysis methods known in the art may be employed. The test protocol is as follows: after an overnight fast, the oral dose of
13
C uniformly labeled glucose (containing about 25 mg of
13
C glucose in combination with about 15 g of unlabeled glucose in 100 mL of tap water) is administered. Breath samples will be collected before the dose and then 1½ hours after
13
C glucose ingestion. Levels of
13
CO
2
in expired air will be measured by an IRMS method.
Advantages of this test are the following:
it is practical, sensitive and specific;
the validity of the test is not influenced by stress, exercise, hormone imbalances, or some drugs and medications
it is a non-invasive method;
it is simple to perform and can be readily used in physicians' offices or medical laboratories;
it is safe since
13
C is a naturally occurring isotope found in all carbon-containing substances;
it involves no radioactivity, and may be used in children and women.
The
13
C glucose test is safe, reliable, and specific in diagnosis of diabetes and measurement of the severity of insulin resistance in patients. The invention is also preferred to diagnose gestational diabetes and to monitor glycemic control in diabetes patients. A preferred embodiment of the invention is a kit containing the necessary material for performing the described method. This kit may contain but is not limited to a source of
13
C enriched glucose (preferably uniformly labeled D-glucose); a source of unenriched glucose; and a breath collection device. The kit may also contain a set of patient instructions for its use. In another embodiment, the kit may additionally contain a blood collection device such as a lancet or hypodermic needle and vacutainer for the additional determination of blood glucose levels.
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Ko et al.
Aspeslet Launa J.
Foster Robert T.
Lewanczuk Richard
Yatscoff Randall W.
Burns Doane , Swecker, Mathis LLP
Isotechnika Inc.
Wallenhorst Maureen M.
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