EDUCATION :: DIABETES
Using HbA1c testing for diabetes diagnosis and management
By H. Roma Levy, MS D
iabetes mellitus (diabetes) is a disease characterized by dysregulated glucose metabolism resulting in high blood sugar (hyperglycemia). Diabetes is a growing problem worldwide. In 2017, approximately 425 million adults (ages 20—79 years) had some form of diabetes. By 2045, it is esti- mated that this number will grow to 629 million—an increase of 48 percent—if preventive actions are not taken.1
Diabetes
presents a significant health and financial burden. In 2017, diabetic complications were responsible for 4 million adult deaths worldwide, and diabetes-related healthcare expenditures topped $726 billion (USD).1
Insulin receptors
Cells require glucose for energy; however glucose cannot dif- fuse through most cell membranes. Cellular glucose uptake is regulated by the interaction of the pancreatic hormone insulin with cellular insulin receptors.2
atic beta cells in response to a carbohydrate-rich meal.3
Insulin is released from pancre- Upon
binding to the insulin receptor, a long-signal cascade assembles transmembrane glucose channels to admit glucose.2
Insulin
levels decrease as glucose is sequestered. This feedback loop, along with glucose storage by the liver in the form of glycogen, helps to maintain blood glucose within a fairly narrow range.3 Diabetes occurs when either insulin production or receptor function become impaired.
Pathophysiology of diabetes There are three primary types of diabetes. Type 1 diabetes (T1D) is a chronic and incurable autoimmune disease that usually occurs in childhood or adolescence but can develop later due to injury or other pancreatic disease. In T1D, T cells gradually destroy insulin-producing beta cells, creating insulin deficiency. Insulin production eventually becomes so deficient that it cannot support appropriate glucose regulation necessary for normal cell functionality.1,4,5 Type 2 diabetes (T2D) accounts for up to 95 percent of all cases in developed countries.1,4
Rank
of poor diet and weight management, and can develop at any age.1
T2D is primarily a disease While it too
is a chronic disease, a recent large scale study demonstrated that remission can be achieved through significant calorie restriction and behavior modification.6 In T2D, cells become insensitive (resis- tant) to insulin due to insulin receptor or long signal cascade component mal- function. Reduced glucose uptake results in hyperglycemia.2
Inflammatory cyto-
As T2D progresses, increased insulin production in response to hyper- glycemia triggers beta cells to release of chemokines that result in their self- destruction by signaling IL-1ȕβrelease by infiltrating macrophages.8
46 JULY 2019
MLO-ONLINE.COM
kines released from excess lipocytes also impair the action of insulin on insulin receptors.7
1 2 3 4 5 6 7 8 9
10
China India
United States Indonesia Brazil
Pakistan Gestational diabetes (GD) is diabetes or hyperglycemia
that develops in the second or third trimester of pregnancy due to insulin resistance caused by interference of placen- tal hormones. It can also have its origins in unrecognized impaired glucose tolerance or T2D prior to conception. GD can resolve shortly after birth, although Kitzmiller et al. report that postpartum glucose abnormalities can per- sist in 26.4 to 48.9 percent of women.9
GD increases the
mother’s lifetime risk of developing T2D to about 60 percent. Gestational diabetes carries risks for both the mother and the developing fetus and requires close monitoring. Impaired glucose tolerance (prediabetes) is diagnosed when blood sugar is consistently elevated above normal but remains below the T2D diagnostic cutoff. It may be present for several years before frank T2D is diagnosed. Individuals with impaired glucose tolerance are at increased risk of progressing to T2D. Fortunately, impaired glucose tolerance is reversible through lifestyle modifications, diet, and weight loss, however lack of awareness contributes significantly to the growing diabetes epidemic. (Table 1)1
Diabetes testing Two primary tests are used to diagnose and monitor diabetes and prediabetes. Fasting or nonfasting blood glucose testing pro- vides a moment-in time snapshot of glucose levels. Since glucose levels can fluctuate considerably over the course of hours and days, glucose testing cannot provide good insight into long term glycemic control. Hemoglobin A1c (HbA1c) measures a specific form of glycated hemoglobin and does not require fasting. Com- pared with fasting plasma glucose (FPG) and glucose tolerance testing, HbA1c is less affected by day-to-day variation in blood glucose levels: it reflects the average blood glucose level over the preceding 90 to 120 days, and thus provides more accurate information on glycemic control.4
Country
Estimated undiagnosed individuals
61.3 million 42.2 million 11.5 million 7.6 million 5.7 million 4.6 million
Russian Federation 4.5 million Mexico Egypt
Bangladesh
4.5 million 4.4 million 3.9 million
).
Estimated diagnosed individuals
114.4 million 72.9 million 30.2 million 10.3 million 12.5 million 7.5 million 8.5 million 12.0 million 8.2 million 6.9 million
Proportion undiagnosed
53.6% 57.9% 38.2% 73.7% 46.0% 61.5% 53.7% 37.4% 53.1% 56.0%
Table 1. Countries with the highest levels of undiagnosed diabetes (ages 20-79 years) in 2017. These countries (with the exception of Bangladesh) also carry the highest burden of diagnosed diabetes (adapted from IDF Diabetes Atlas, Eighth edition, 20171
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