Diabetes
Diabetes mellitus:
Diabetes mellitus is a group of metabolic disorders of carbohydrate metabolism where glucose is underutilized causing hyperglycemia. There are three types of diabetes, type 1, type 2, and gestational.
Type 1:
Type 1 diabetes represents about 10% of the diabetic population and onset is usually acute and occurs mostly at a young age. In type 1 diabetes there is no insulin production due to the lack or disruption of pancreatic beta cells. Beta cells of the pancreas secrete insulin, and insulin facilitates entry for glucose into cells. Type 1 diabetics are dependent on insulin injections.
Type 2:
Type 2 diabetes represents about 90% of the diabetic population and onset can be more gradual. In type 2 diabetes, cells become insulin resistant mainly due to overstimulation. There is no problem creating insulin but rather the cells don’t respond as well to it. Type 2 diabetes can be reversible and can improve with diet and exercise.
Key players in diabetes mellitus:
Pancreatic islets (aka islets of Langerhans):
Islets of Langerhans sounds like a place in Lord or the Rings to me but it’s actually the regions of the pancreas that contain hormone producing cells. Of most importance to diabetes mellitus are alpha and beta cells of the islets of Langerhans which produce glucagon and insulin respectively.
Nerdy Note
Paul Langerhans (1847-1888), was the first to take a deeper dive into the anatomy of the pancreas. In Germany at age 21, he presented a thesis titled Contributions to the microscopic anatomy of the pancreas which described “islands of cells” that looked different than surrounding tissue. He incorrectly hypothesized these were lymph nodes, and their function as hormone producing cells was discovered years later. Still, the cells carry his name and description he used at the time. The name “islands of Paul Langerhans” didn’t have the same ring as islets of Langerhans I guess.
Vocabulary Note
There are a few terms that are very similar looking but mean totally different things. Make sure you know these!
Glycogenesis: glucose converts to glycogen
Glycogenolysis: glycogen converts to glucose
Gluconeogenesis: amino acids/fats convert to glucose
Alpha cells of pancreatic islets:
Alpha cells of pancreatic islets create the peptide hormone glucagon. Glucagon is a key player in increasing glucose levels. Glucagon stimulates the conversion of stored liver glycogen, amino acids, and fats to glucose.
Beta cells of pancreatic islets:
Beta cells of pancreatic islets create the peptide hormone insulin. Insulin decreases blood glucose levels by promoting absorption into cells. Type 1 diabetics make an autoantibody to beta islets and attack them.
Nerdy Note
Type 1 diabetes is a combination of genetic and environmental biology. When one identical twin has type 1 diabetes, there’s only about a 50% chance the other twin will have it. Genetically, the HLA genes which code for the major histocompatibility complex proteins (MHC) play a factor. MHC is a cell marker the immune system uses to identify your own cells from foreign cells like viruses and bacteria. As you can imagine, if these markers aren’t functioning properly, your own cells can be attacked.
Glucose testing:
There are a lot of different glucose tests! Let’s break them down.
Random glucose:
This test is a glucose test on a non-fasting patient. >200 mg/dL is indicative of diabetes.
Fasting glucose:
This test is a glucose test after fasting overnight. >126 mg/dL is indicative of diabetes, 100-125 prediabetes, and <100 is normal.
Oral glucose tolerance test (OGTT):
This is a glucose test that requires an overnight fasting followed by glucose ingestion. Glucose levels are then tested at 2 hours to see how well the patient’s body handled the glucose. >200 at 2 hours is indicative of diabetes, 140-199 prediabetes, and <140 is normal.
Hemoglobin A1c:
The hemoglobin A1c test is a more accurate way of testing a patient’s blood glucose. Blood glucose fluctuates during the day and after say eating a pack of skittles, so it can be difficult to get an accurate measurement. Hemoglobin A1c measures the amount of glycated hemoglobin (hemoglobin with sugar attached), and since RBCs have an average lifespan of about 120 days, the A1c measurement will give a good indication of the blood glucose from the past few months. A1c >6.5% is indicative of diabetes, 5.6-6.4% prediabetes, and <5.6% is normal.
Nerdy Note
Hemoglobin A1 is a fraction of hemoglobin that is glycated (has sugar on it). The glycated hemoglobin aren’t genetically different but rather a product of glucose running into hemoglobin. Hemoglobin A1 consists of four subgroups Hgb A1a1, Hgb A1a2, Hgb A1b, and Hgb A1c. Each different subgroup represents a slightly different sugar molecule or attachment to the hemoglobin molecule. The important one for clinical science is Hgb A1c because in the late 70’s, researchers determined A1c matched closely to actual blood glucose. Don’t get Hgb A1 (sugar) mixed up with Hgb A or Hgb A2 (structure), they’re totally different. There’s also A, A1, and A2 antigens from blood bank. Don’t get mixed up! Keep it together!
Study Tip
Remember the values that give you diabetes! Remembering the prediabetes and normal ranges can be important as well but knowing the values that are indicative of diabetes are most important. I say indicative because other than A1c, the other tests usually need two results to diagnose diabetes mellitus.
| Test | Diabetes level |
| Random | >200 mg/dL |
| Fasting | >126 mg/dL |
| Oral glucose tolerance test (OGTT) | >200 mg/dL at 2 hours |
| Hemoglobin A1c | >6.5% A1c |