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Diabetes: get a clearer picture. (Cover Story).

Snapshots can reveal only a small, often indistinct, portion of a landscape. Any brief consideration of a topic as far-reaching and complex as diabetes is bound to suffer from the same limitations. While a snapshot can convey helpful information, it can often draw attention to particularly meaningful elements in a larger setting. The points addressed in this article -- mere snapshots -- will help laboratorians acquire a clearer picture of current diabetes knowledge, so that they can be effective patient educators and advocates, as well as technically competent health professionals.

Diabetes mellitus (DM), a complex family of diseases, is the fifth leading cause of death in this country, and complications traceable to diabetes can have a profound effect on individual lifestyle. Approximately 800,000 people in the United States are diagnosed with diabetes annually. Laboratorians are obligated to

* stay up to date on the clinical diagnostic criteria for the various disorders of glycemic control,

* be cognizant of the benefits and limitations of various screening and monitoring protocols, and

* be knowledgeable of the accuracy and reliability of clinical laboratory and patient self-monitoring testing procedures.

Snapshot 1: Deadly, disabling, escalating diabetes

The Centers for Disease Control and Prevention has characterized diabetes as deadly, disabling and on the rise. While diabetes is common and chronic, it is also controllable. Glucotoxicity, chronic exposure to hyperglycemia, leads ultimately to irreversible cell dysfunction and induces the microvascular complications (retinopathy, neuropathy and nephropathy) that are hallmarks of diabetes. (1) The laboratonan must recognize the test results that literally define diabetes, as well as the various cut points on the continuum of hyperglycemia that are indicative of other metabolic abnormalities of glucose processing, such as "pre-diabetes."

In 1997, the American Diabetes Association (ADA) announced new criteria for the classification and diagnosis of diabetes. 36 Outcomes of the report of the Expert Committee included the classification of diabetes into four categories:

* type 1 (previously known as insulindependent diabetes mellitus, or juvenile-onset diabetes),

* type 2 (noninsulin dependent diabetes [NIDDM], adult-or maturityonset diabetes),

* other "specific types of diabetes" (encompassing eight subclassifications, such as drug-or chemical-induced DM or DM caused by endocrinopathies), and

* gestational diabetes (GDM), defined as glucose intolerance first detected during pregnancy.

Use of insulin therapy to control hyperglycemia is not what distinguishes type 1 from type 2 diabetes. Many patients with type 2 diabetes eventually require insulin therapy. Accordingly, classification of diabetes by reference to the drug treatment necessary to manage the disease (e.g., insulin dependent, noninsulin dependent) has been eliminated. The importance of early diagnosis of deterioration of glucose control was incorporated into the new diagnostic criteria. To better reflect research evidence regarding the development of complications of diabetes, adjustments of thresholds for identifying various degrees or types of disordered glucose regulation were made.

For example, the 126 mg/dL (7.0 mmol/L) cut point corresponds reasonably well to the two-hour cutoff value of 200 mg/dL (11.1 mmol/L) in the oral glucose tolerance test (OGTT) and to the likelihood of future complications. To diagnose diabetes using ADA criteria, the patient must meet at least one of any of the three following criteria on two separate days:

* Display symptoms of diabetes (polyuria, polydipsia and unexplained weight loss), plus casual (random) plasma glucose concentration 200 mg/dL (11.1 mmol/L). or

* Fasting plasma glucose (FPG) 126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least eight hours, or

* Two-hour plasma glucose [greater than or equal to]200 mg/ dL (11.1 mmol/L) during an OGTT, as described by the World Health Organization (WHO), using 75 grams of anhydrous glucose dissolved in water.

In addition, the ADA lowered the upper limit of normal for FPG. Patients with an FPG [greater than or equal to]110 mg/dL (6.1 mmol/ L) but <126 mg/dL (7 mmol/L) were designated as having impaired fasting glucose (IFG). Patients with an FPG <126 mg/dL (7.0 mmol/L) and who have a two-hour plasma glucose level of [greater than or equal to]140 mg/dL (7.8 mmolIl) but <200 mg/dL (11.1 mmol/L) following a glucose tolerance test are characterized as having impaired glucose tolerance (IGT). For the diagnosis of GDM, both the ADA and the WHO recommend the two-hour glucose tolerance test, although details of the procedure and interpretation of test results remain controversial.

IGT and IFG are less clinical entities in their own right as much as they are risk categories for cardiovascular disease and/or future diabetes, respectively. Some investigators suggest that the two-hour OGTT is a more sensitive predictor for type 2 diabetes.37 The ADA reports, however, virtually no difference in the rate of progression to diabetes if a person is found to have IGT or IFG. (38) Individuals who have either IGT or IFG are viewed as "prediabetic" and should receive counseling on weight loss, physical activity and diet modification. The drug metformin, among others, is also effective in preventing the progression of IGT to type 2 diabetes, but less so than lifestyle modification.39

Evidence is accumulating that FPG levels >110 mg/dL are associated with substantial cardiovascular risk and increased risk of retinopathy is linked to FPG levels between 110 mg/dL and 119 mg/dL. (40) In the United States, approximately 17 million individuals, ages 40 to 74 years, have "pre-diabertes," (41) a stage at which awareness is generally low among primary care physicians.

Here, the laboratorian can offer clarification to the general practitioner as to the relevance of the laboratory results and the need for intervention. (42) Helping the clinician identify individuals with pre-diabetes by communicating the latest guidelines on the condition and the benefits of additional testing and lifestyle modification is part of the laboratorian's natural role as diabetes educator. For example, even a reminder that plasma glucose values are 10% to 15% higher than whole blood glucose values as obtained by a fingerstick can be helpful.

The ADA also recommends screening all individuals age 45 years and older for type 2 diabetes every three years. Individuals at increased risk (i.e., obese, hypertensive, family history of DM) should be tested at a younger age and more often. The recommended screening procedure is an FPG, rather than an OGTF, for convenience and economy. Annual testing is advised for individuals with IGT or IFG, a history of gestational diabetes, the presence of hypertension, cardiovascular problems or other conditions that may arise as complications of DM.

The WHO believes that performance of an OGTI' is a better predictor of individuals who have an inability to process glucose normally. The Expert Committee has noted, however, that an individual with an FPG [greater than or equal to]126 mg/dL may have a two-hour plasma glucose during an OGTT that does not reach the cutoff of 200 mg/dL. Significant microvascular and macrovascular complications may still occur in that person before an abnormal two-hour OGTT glucose is attained. Impaired glucose tolerance is common. As many as one-half of patients being diagnosed as having IGT reportedly progress to type 2 diabetes within a decade. In addition, IGT may as much as double the risk of developing cardiovascular disease.(43) Discussions continue on the relative clinical merits for assessing impaired glycemic control -- IGT and IFG -- and the importance and/or practicality of adopting a more proactive medical and/or educational approach in dealing with these patients.

Snapshot 2: Syndrome X

Major progress is being made in understanding the link between insulin resistance and abnormalities beyond that of impaired glucose homeostasis. Cellular resistance to insulin action appears to be at the center of a constellation of abnormalities, all of which increase the risk of atherogenesis. In insulin-resistance syndrome (IRS), or Syndrome X, the occurrence of central obesity (increased waist-to-hip ratio) and insulin resistance give rise to a host of risk factors for type 2 diabetes and cardiovascular disease.

IRS is characterized by glucose intolerance, dyslipidemia, hypertension, abnormalities in fibrinolysis and coagulation. Each of these conditions in its own right is a major risk factor for cardiovascular disease. Recent data from the third National Health and Nutrition Survey indicates that nearly one in four persons in the United States has the metabolic syndrome (age-adjusted estimate), which translates to about 47 million U.S. residents." Disturbingly, IRS has recently been documented in youth. (12,13) (Note: The creation of a diagnosis code [277.7] for metabolic syndrome in the 9th edition of the International Glassification of Diseases [ICD9 9-CM] makes reimbursement possible.)

Insulin is a powerful dilator of blood vessels; but in insulin resistance, there is an impairment in insulin-mediated vasodilation.(13) The dyslipidemic profile associated with insulin resistance and type 2 diabetes is marked by elevated triglycerides, elevation of very lowdensity lipoproteins, increased frequency of a small dense subspecies of low-density lipoproteins that is especially atherogenic and decreased high-density lipoprotein (HDL).

In 2001, the National Institutes of Health released the third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Cholesterol in Adults (ATPIII). According to ATPIII, the metabolic syndrome is present if a patient has three or more of the following risk factors: 14 waist

* waist size >40 inches (102 cm) for men or >35 inches (89 cm) for women,

* triglyceride level [greater than or equal to]150 mg/dL (1.69 mmol.L,

* blood pressure [greater than or equal to]130/85 mm Hg,

* fasting glucose value [greater than or equal to]110 mg/dL (6.11 mmol/L), or

* HDL-C level <40 mg/dL (1.03 mmol/L) for men or <50 mg/dL (1.29 mmol/L for women.

Elevated levels of free fatty acids (FFAs) have been suggested as a key component in the pathogenesis of insulin resistance, perhaps by the FFAs acting as signaling entities in various cellular processes.(15) Patients with type 1 diabetes usually have lipid profiles similar to age-matched nondiabetics. The pathogenic effect of high levels of glucose, possibly in conjunction with increased circulating FFAs or increased intracellular fat, may be mediated through increased oxidative stress from overproduction of reactive oxygen species and reactive nitrogen species. Preliminary findings suggest that oxidative stress-inflicted damage, both direct and indirect, plays a key role in the development of diabetic complications, as well as insulin resistance and cell dysfunction. Consideration is being given to the use of antioxidants as adjunct therapy in some patients. (16, 17)

Snapshot 3: Obesity and insulin resistance

Tissue resistance to insulin and relative insulin deficiency are the best predictors of type 2 diabetes. Leptin plays a role in regulating body weight and metabolism and influences insulin action in peripheral tissues. Most of the insulin resistance in patients with type 2 diabetes is linked to obesity (associated with defective leptin action), reduced physical activity, glucose toxicity and high-fat diets. Since 80% to 90% of patients with type 2 diabetes are overweight, it seems clear that there is a link between obesity, insulin resistance and type 2 diabetes. (4) About 123,000 children and teenagers have diabetes. (26) Diabetes onset due to an autoimmune-mediated destruction of pancreatic cells in patients less than 20 years of age is no longer suspected. Young people are now presenting with what was once considered a disease of middle-age or older adults. Type 2 diabetes now accounts for almost one-half of newly diagnosed diabetic youngsters, especially in obese African-American and Hispanic children. (3 4) Genetic interaction, along with decreased physical activity, obesity and changes in food consumption patterns, may explain why there are now more children under age 15 with type 2 diabetes than with type 1. (35)

While about one-third of U.S. adults are insulin resistant, most are able to produce sufficient insulin to maintain nondiabetic glucose levels. Over time, many of these individuals will experience deterioration of glycemic control and progress to type 2 diabetes. By the time type 2 patients are diagnosed, they may have lost almost one-third of cell secretory activity and further decline in cell function may be as much as 4% annually. (10) Data from a recent study supports the hypothesis that age-associated decline in mitochondrial oxidative and phosphorylation energy production, essential for glucose-induced insulin secretion, contributes to insulin resistance in the elderly, which may explain the high prevalence of diabetes in that population. (47)

Snapshot 4: Critical communication

For laboratory personnel, direct communication with patients concerning the need for diligence in using and maintaining a glucometer and vigilance in accurately documenting test results is central to the self-management of diabetes. Whether in hospitals, clinics or physicians office laboratories, lab professionals are perfectly positioned to assist patients in understanding the importance of when and how to perform self-monitoring, to explain the significance of blood glucose changes, and to reinforce the importance of attaining and maintaining personal targets for glycemic control. They can also underscore the need for immediate notification of a health professional if certain test values are determined through self-monitoring. In this way, they indisputably function as diabetes educators. (2) A laboratory's efforts to teach patients might be incorporated into a clear lab policy and coordinated with the institution's certified diabetes educator, if one exists.

Many laboratorians desire to better inform their patients about the importance of managing their disease, but language barriers often frustrate their attempts. With some segments of the multiethnic/multiracial population - African-Americans, Hispanics, Native Americans, Asian Americans and Pacific Islanders (30) and now Arab Americans (31) -- at significantly increased risk for DM, materials are available from the National Diabetes Education Program in virtually every language. (21) The International Diabetes Foundation can be accessed online for multilingual diabetes education resources. (22)

Snapshot 5: The molecular basis of diabetes

Identifying the molecular basis for insulin action on target tissues is critical -- and proving challenging. Ongoing research studies promise a better understanding of the effects and mechanisms by which hyperglycemia-induced glycation influences the structure and function of macromolecules. This includes not only glycated hemoglobin (A1C) and serum proteins (fructosamine), but also molecules whose altered function and/or structure may be the basis for diabetic complications. The measurement of advanced glycated end products for routine management of DM is also under review.

Pancreatic transplantation, or replacement of nonfunctioning insulin-producing cells (including stem cells as the islet source and xenotransplantation), offers a cure for diabetes and is among the most exciting areas of research. Genetic analysis, using state-of-the-art gene sequencing technology, is being used to determine the basis for predisposition to or protection from both types 1 and 2 diabetes. An allelic variation in the vitamin D receptor gene may influence susceptibility to type 1 diabetes. (8) The high-throughput technology and data processing used in the Human Genome project makes feasible DNA sequencing on a massive scale. Pancreatic islet cell autoantibody assessment for the prediction of individuals at high risk for type 1 diabetes can be accomplished and may, in the future, be clinically practical. The discovery of these autoantibodies in a high-risk patient, long before cell reserve is lost, makes early therapeutic intervention possible. (9) Unresolved issues, however, include identification of the triggers -- genetic and environmental -- of the autoimmune response. The role of altered T-cell activity in the pathogenesis of type 1 diabetes is under study.

Snapshot 6: DM's acute complications

In addition to the long-term complications of diabetes, a number of acute metabolic complications seen in diabetics require hospitalization or ER treatment for management. Use of intensive insulin therapy can increase the risk of hypoglycemia (blood glucose <70 mg/dL, or 3.0 mmol/L). Severe hypoglycemia may require intravenous glucose or glucagons (the hormone produced by the cells in the pancreatic islets) dosage. Poor glycemic control may lead to hyperglycemia. Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are two of the most common complications of poorly controlled diabetes.

Ketone bodies ([beta]-hydroxybutyric acid, acetoacetic acid and acetone) are products of free fatty acid metabolism, and increased ketogenesis can be detected by the measurement of acetoacetate and acetone in the urine via the nicroprusside reaction. A home ketone-testing device that permits measurement of [beta]-hydroxybutyric acid from fingerstick blood is now available.

Excessive ketone-body production, such as occurs when there is essentially no insulin production and excess glucagon, generates glucose by promoting gluconeogenesis and glycogenolysis, leading to osmotic diuresis, cellular dehydration, electrolyte imbalances, metabolic acidosis and death, if untreated. DKA is most common in type 1 patients, but it is also seen in type 2 patients, especially in African-American and Hispanic adolescents and adults.

Unlike DKA, HHS, also known as nonketotic hyperglycemia (NKG), is not associated with an accumulation of ketones or acidosis. Especially among elderly type 2 patients, coma, seizures and death can arise from development of massive hyperglycemia (>600 mg/ dL) with accompanying dehydration that further raises blood glucose levels. Extreme elevations in serum osmolality (>320 mOsmkg) occur.

Despite advances in understanding the origin of these conditions, DKA and HHS are life-threatening -- even under the best of care. Mortality rate averages of 5% for DKA and 15% for HHS are reported, but if proper treatment is delayed mortality rates increase to 15% to 28% in DKA and 17% to 50% in HHS. (29)

Snapshot 7: [HbA.sub.1c] method standardization

Developing and standardizing assessment of long-term glycemic control markers to improve patient care worldwide is moving forward. The International Federation of Clinical Chemistry and Laboratory Medicine Working Group (IFCC-WG) on [HbA.sub.1c] Standardization has developed and validated reference material and two reference methods (mass spectrometry and capillary electrophoresis) to serve as the analytical base for global harmonization. An international network of reference laboratories that incorporated these two reference methods was created by the IFCC-WG. Problems currently exist in that IFCC results are numerically different from the clinically validated Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (LIKPDS) results.

The National Glycohemoglobin Standardization Program (NGSP) began in 1996 with the goal of establishing proper calibration and comparability of assay results to the DCCT database. Glycohemoglobin assay methods used in the UKDPS were certified by the NGSP. As a result, glycohemoglobin values in the DCCT and the TJKPDS can be used to estimate risk of complications developing in patients with either type 1 or type 2 diabetes. (5, 18) The relationship of AiC results from IFCC network laboratories and from the NGSP (available at www. missouri. edu.~diabetes/ngsp.html) reference network is under evaluation. When evaluating results, it must be remembered that if IFCC reference methods are used, AiC values will be lower by 1.5% to 2.0% than if the specimen had been assayed by NGSP reference methods.(19)

In December 2002, the NCCLS (formerly the National Committee for Clinical Laboratory Standards) published document C44-A, "Harmonization of Glycohemoglobin Measurements; Approved Guideline." Harmonization refers to the process by which glycohemoglobin test results among laboratories are made comparable to a common reference. A new rapid, highly precise enzymatic assay for glycohemoglobin has been described for use in the central laboratory.(20)

Snapshot 8: GDM screening

National groups differ in assessment of data relating to the improvement of clinical outcomes to be derived from a universal screen for various disorders of glucose metabolism. Should all women be screened for GDM, or should screening be selective, based on risk? A woman is considered to be at low risk for GDM if she meets all of the following: is <25 years old, has a normal body weight before pregnancy, does not belong to a high-risk racial or ethnic group, has no history of previous adverse obstetrical outcomes, and has no personal or family history of abnormal glucose metabolism.

The U.S. Preventive Services Task Force (USPSTF), an independent panel of experts sponsored by the Agency for Healthcare Research and Quality (AHRQ), recently issued recommendations and supporting scientific evidence for screening for type 2 DM in adults and for screening for GDM. The USPSTF believes that current evidence does not support a health benefit for either mother or baby derived by routine screening of all pregnancies for GDM. Presumably, clinicians would order the screening of mothers at high risk early in prenatal care. The Task Force also was not convinced of the long-term value of routinely screening asymptomatic adults for type 2 diabetes or pre-diabetes (IGT or IFG). A recommendation was given, however, for screening type 2 diabetes in adults with hypertension, or hyperlipidemia. Complete recommendations are available on the AHRQ website at http://abrq.gov/clinic/ uspstfix.btm.(45) Other expert groups, such as the ADA and WHO, have published their own criteria and diagnostic strategies for det ection of abnormal glycemic control in symptomatic and asymptomatic men and in pregnant and nonpregnant women.

Snapshot 9: ADA evidence-based rating system

The ADA continues to be actively involved in the development, refinement and dissemination of diabetes care standards, including clinical practice recommendations. Since publication of the 2002 Clinical Practice Recommendations, the ADA has added or revised information in several areas. An evidence-based rating system (A, B, C or E) is employed by the ADA to support a given recommendation. An "A" rating indicates the recommendation is based on clear evidence from large, well-designed clinical trials or well-done meta-analyses. A recommendation whose supportive evidence comes from well-conducted cohort studies or meta-analyses is assigned a "B." This does not mean the recommendation is less important, rather that it is less well supported by currently available evidence. "C" may be assigned when supportive evidence is conflicting or from poorly controlled studies although the weight of the evidence supports the recommendation. "E" designates expert opinion for which there is currently no supporting evidence fr om clinical trials. For example, "Perform an annual test for the presence of microalbuminuria in type 1 diabetic patients with diabetes duration of [greater than or equal to]5 years and in all type 2 diabetic patients starting at diagnosis" is coded as "B." The most recent clinical practice recommendations include position statements on a breadth of topics, which are continually reviewed and revised. The full text of the Association's 2003 Guidelines is also available free on the ADA website at www.diabetes.org/ diabetescare. (44)

Snapshot 10: ACE guidelines

The American College of Endocrinology (ACE) guidelines for clinical practice recommend that in high-risk individuals, screening for diabetes should begin at 30 years of age.(40) Post-prandial glucose is recognized as a key contributor, along with pre-prandial glucose, to the level of a patient's glycated hemoglobin (AiC). ACE guidelines call for both pre- and post-prandial assessment of glucose on a regular basis, with a target pre-prandial value of 110 mg/ dL and a post-prandial level 440 mg/ dL. There is agreement that evidence supports the benefits of " tight glycemic control" in reducing the long-term complications of diabetes.(5'6) The position of the ACE is that the target for assessing and monitoring glycemic control -- determination of the patient's glycated hemoglobin level -- should be lowered to 6.5%. ADA recommendations identify an AiC target of 7%, since risk-benefit analysis has shown the potential of severe hypoglycemia rising sharply as the AlC drops below 7%. Determining AiC by methods certif ied by the NGSP and participation in a proficiency-testing program are essential.(19)

Snapshot 11: What every lab needs

The National Academy of Clinical Biochemistry (NACB) has developed and published guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes. These provide recommendations based upon the best available scientific evidence or expert consensus on glucose (including self-monitoring and noninvasive measurement, ketones, glycated hemoglobin, genetic markers, micro-albuminuria and other analytes). NACB guidelines have been reviewed by the Professional Practice Committee of the ADA and are consistent in those areas in which the ADA has also published. This type of information enables the laboratorian to offer informed suggestions on the numerous assessments essential for the diagnosis and management of diabetes, backed by confidence that the laboratory procedures under consideration have been evaluated, or "graded," based on the best available published data and consensus of experts. The quality of the scientific evidence from published data or expert consensus supporting the u se of the assays is coded using the previously cited ADA descriptors. (46) It is obligatory that laboratorians read the complete Guidelines and Recommendations to understand the rationale and fine points of each. (Note: The glossary on page 16 offers an extremely small, highly abridged sample of the complete text.)

Undiagnosed diabetes is not a benign condition; virtually every organ in the body is adversely affected. The symptoms of diabetes can be very subtle, and the laboratorian may well be the first health professional to see evidence of a problem, and needs to keep pace with the many advances in knowledge of the complex family of diseases known as diabetes mellitus. (4)

References

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(6.) The UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 1998;352:837-853.

(7.) Cryer PE, Childs BP. Negotiating the barrier of hypoglycemia in diabetes. Diabetes Spectrum 2002;1 5:20-27.

(8.) Norris JM. Can the sunshine vitamin shed lighten type 1 diabetes? Lancet 200l;358:1476-1478.

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(14.) Pearlman BL. The new cholesterol guidelines. Postgrad Med 2002:112(2):13-26.

(15.) Shulman GI. Cellular mechanisms of insulin resistance. J Clin lnvest 2000;106:171-176.

(16.) Evans JL. Goldfine ID, Maddux BA, Grodsky, GM. Are oxidative stress-activated signaling pathways mediators of insulin resistance and cell dysfunction? Diabetes 2003;52:1-8.

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RELATED ARTICLE: Glossary

GLUCOSE

* Glucose should be measured in plasma in an accredited laboratory to establish a diagnosis; for routine monitoring or therapy evaluation, other means are appropriate.

* Blood should be drawn after overnight fasting of at least eight hours; and unless glycolytic inhibitor is added to the tube, measurement should be within 60 minutes.

* On the basis. of biologic variation, glucose analysis should have analytical imprecision [less than or equal to]3.3%, bias [less than or equal to]2.5%, and total error [less than or equal to]7.9%.

* Portable glucose meters should not be used for diagnosis, and probably not screening, but they are recommended for self-monitoring of blood glucose (SMBG) for all insulin-treated patients; measurements should be at least three times daily in type 1 diabetes; frequency of analysis in GDM and type diabetes has not yet been established.

* Though controversial, the OGTT is not recommended for routine diagnosis of type 1 or 2 diabetes, primarily because of its poor reproducibility.

* Noninvasive glucose analyses are not recommended as replacements for SMBG or measurements by an accredited laboratory.

KETONES

* Ketones should be measured in urine or blood by diabetic patients at hone or in a clinical setting, especially during stress, acute illness, pregnancy with pre-existing diabetes, sustained hyperglycemia (>300 mg/dL) or when symptoms of DKA (nausea, vomiting, abdominal pain) occur.

* Methods based on the nitroprusside reaction should not be used alone to diagnose DKA, nor to monitor DKA treatment.

GLYCATED HEMOGLOBIN

* Use only A1C methods certified by the NGSP as traceable to the DCCT reference and participate in proficiency testing (PT) program.

* Use assay methods with an interassay CV<5% (ideally <3%).

* Consider pro-analytical variables that shorten RBC survival (e.g., hemoglobinopathies) or decreases average RBC age (e.g., hemolytic anemia).

* Glycated hemoglobin should be measured at least twice a year.

* Be aware that some hemoglobinopathies (e.g., Hb S, Hb C) interfere with certain assay methods and select the procedure accordingly.

GENETIC MARKERS

* Measurement of genetic markers currently is not valuable for diagnosis or management of type 1 diabetes, but may be in future.

* Genetic markers have no role for genetic testing in patients with type 2 diabetes, a heterogeneous polygenic disease.

AUTOIMMUNE MARKERS

* Autoimmune markers should only be measured in an accredited laboratory with an established QC program and participating in a PT program.

* Autoantibodies are not recommended for routine diagnosis or screening of type 1 diabetes.

MICROALBUMINURIA

* Microalbuminuria has prognostic significance for diabetic nephropathy.

* Microalbuminuria is a marker of increased risk of cardiovascular problems and death in both type 1 and type 2 diabetes.

* In the absence of clinical proteinuria, test type 1 diabetics annually beginning five years after diagnosis, beginning with the diagnosis of type 2 diabetes

* Microalbuminuria, expressed in terms of Mcg/mg Cr (creatinine clearance used as index of glomerular filtration rate): normal albumin excretion is <30; microalbuminuria is 30-300; clinical albuminuria is >300.

* Analytical CV of methods to measure microalbuminuria should be <15% (less precision is required because within-person variation of albumin excretion is large).

Bringing HOPE for diabetes treatment to China

Barry Ginsberg, MD, PhD

Diabetes is increasing significantly throughout the world, but nowhere is the problem more acute than in China. The worlds most populous country will soon become the nation with the largest number of individuals afflicted with diabetes. Today, over 16 million people in China are living with this disease. Due to patient education and training issues, however, many of these people are unaware of healthcare measures that can alleviate and postpone associated complications.

A greater prevalence of diabetes has emerged, as the Chinese have become more affluent, more sedentary, and more frequent consumers of meat. Indeed, highly affluent countries with large Chinese populations, such as Singapore and Taiwan, have the highest rates of diabetes in the world. In Asia, diabetes is increasing by 50% about every 10 years. By the year 2010, it is expected that about half of the world's population with diabetes will be in Asia.

Combating diabetes in China requires comprehensive efforts aimed at education. prevention and treatment. In 1997, Project HOPE launched The China Diabetes Program with a multimillion-dollar grant from their diabetes partners, BD, Eli-Lilly and Roche Diagnostics, to link the resources of the Chinese Ministry of Health, major medical centers and universities and Project HOPE to fight diabetes in China.

The program began with a needs assessment by a group of experts from China, the United States and Europe, who visited many of the major urban and rural medical centers of China. They formed an education, prevention and public awareness plan, called the China Diabetes Education Program (CHINDEP). Over the ensuing five years, CHINOEP has been successfully implemented across the country -- increasing both public and professional awareness of diabetes and improving the quality and availability of diabetes care.

The central theme of CHINIJEP is diabetes education with a top-down pyramid approach: educate trainers first and then educate healthcare professionals so that they can, in turn, educate people with diabetes and the general public. Initially, the program was largely dependent on consultants from the West, but now it is run entirely by Chinese professionals who disseminate knowledge from the major diabetes centers to the community.

Through the combined efforts of Western diabetes experts provided by the diabetes partners, Western-trained Chinese diabetologists, and the most influential Chinese diabetes specialists, this group, moving from city to city, first trained a large number of physicians and diabetes nurses on the best methods for preventing and treating diabetes. More important, they provided instruction on how to disseminate this knowledge throughout the region -- to other healthcare workers, to people with diabetes and to the community at large. With time, the program has been transitioned entirely over to local groups; the Western experts advise only at an annual meeting of senior technical advisors.

This program has now trained over 160,000 individuals, including healthcare professionals, local governmental officials and people with diabetes in 23 provinces in China. Frequent sessions are still held to instruct more trainers, healthcare professionals and patients. The focus on treatment continues. but with a recent new concentration on public awareness, With the help of the Chinese government, Project HOPE is now bringing diabetes to the forefront, and helping to institute diabetes prevention programs across the country. A large outcome measurement study is underway to determine their effectiveness.

The diagnostic laboratory plays a major role in helping to prevent and treat diabetes throughout the world, and China is no different. The measurement of Hemoglobin Aic (HbA1c) is becoming more common and other measures of long-term diabetes control are being introduced. Self-monitoring of blood glucose is still uncommon in China, so laboratory glucose remains an important measure. The laboratory will always have a major role in preventing (e.g., microalbumin) and treating (e.g.. renal function tests) the complications of diabetes.

Diabetes is an insidious disease -- a leading cause of blindness, kidney failure, amputation and cardiovascular disease. At a cost of about $12,000 (U.S.) per patient per year for therapy of diabetes and its complications, diabetes is now among the most costly diseases in Western societies and soon will be among the most expensive in Eastern societies, as well. Education and treatment are the keys to controlling diabetes and helping to prevent its complications. Project HOPE, along with its diabetes partners, 80. Eli-Lilly and Roche, are playing a major role in helping to address the high rate of diabetes in China.

Barry Ginsberg, MD, PhD, is vice president of medical affairs et BD, where he is involved in developing the medical strategy for new diabetes products end for ensuring the safety end efficacy of all of the products for BD Consumer Healthcare. He is also en adjunct professor of medicine at Robert Wood Johnson College of Medicine.

Sharon M. Miller is Professor Emeritus at Northern Illinois University, DeKalb. IL.
COPYRIGHT 2003 Nelson Publishing
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2003 Gale, Cengage Learning. All rights reserved.

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Author:Miller, Sharon M.
Publication:Medical Laboratory Observer
Article Type:Cover Story
Date:Jul 1, 2003
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