Patient With Hyperglycemia

MS3: This patient is a 50-year-old Caucasian man with a benign medical history, to this point, who had his fingerstick blood sugar checked at a community health fair, and it was 210. He reports no symptoms at all.

Dr R: What symptoms did you ask about?

MS3: Polyuria, polydipsia, and polyphagia, or unexplained weight loss.

Dr R: Those are the classic symptoms traditionally taught for diabetes, but only a very small percentage of people who turn out to have diabetes will present with these classic symptoms.

MS3: What symptoms do they usually present with?

Dr R: Probably the two symptoms I see most commonly on initial presentation are just “fatigue” or erectile dysfunction.

MS3: Erectile dysfunction?

Dr R: Yes. Whenever a male asks me about the “little blue pill,” the first thing I check for is diabetes.

MS3: Wouldn’t they have symptoms long before ED?

Dr R: No. Diabetes is most often found as a high blood glucose reading on a routine screen or blood drawn for an entirely different reason.

MS3: How can they have this disease, but have no symptoms?

Dr R: What is the difference between disease and illness? Think back to your first year when you didn’t think the clinical courses were as important as the basic science courses.

MS3: I don’t remember.

Dr R: This difference is critical in clinical medicine. Disease is the pathophysiologic process. Illness is how it makes the patient feel. Patients present with “illness.” We usually try to diagnose “disease.”

MS3: So, if he doesn’t feel bad at all, he has a disease but no illness?

Dr R: Exactly. You were taught diseases in medical school, but patients present with illnesses. It’s an adjustment you’ll need to try to learn. Can you think of any other diseases that have no illness?

MS3: High cholesterol.

Dr R: Great. High blood pressure is another one.

MS3: Wow, those are three of the most common diseases in medicine.

Dr R: Yes, and it makes treatment more difficult since it’s hard to make an asymptomatic patient “feel” better.

MS3: But it’s easy to make them feel worse, especially with medication side effects.

Dr R: You are wise beyond your years, my young Jedi. What happens when you make an asymptomatic patient feel worse with medication?

MS3: They quit taking it.

Dr R: Therefore, patient education is critical. The patient without “illness” may not believe he has any problems. Or, even if the doctor says there’s a problem, the patient doesn’t believe it’s causing any damage. He may believe that ignorance is bliss and that it would be best never to check for problems.

MS3: This is going to be another one of those cases that’s not as simple as I thought, isn’t it?

Dr R: You betcha. Tell me more about our patient.

MS3: He has no family history of diabetes, even in uncles or aunts. He went out and bought a glucose meter and checked his blood sugars at home several times—130 and 140 before breakfast (different days) and 210 and 220 after meals. He had blood work done prior to this appointment. His physical exam is normal. His height is 5’9”, his weight 155 pounds, his blood pressure 110/70 mm Hg. His HEENT, lung, cardiac, abdominal, and extremity exams are all normal. I pulled up his labs. His A1C was 7.9. His complete metabolic profile was normal except the glucose, which was 130. His total cholesterol was 155, HDL 50, triglycerides 50, and LDL 95. His urine dipstick and urine micro-albumin were negative. He is on no medications.

Dr R: What’s your diagnosis?

MS3: Diabetes mellitus type 2.

Dr R: Does he meet the criteria for a diagnosis of diabetes?

MS3: Yes. He more than meets the ADA criteria for diagnosing diabetes. He has had at least two fasting glucoses greater than 126. And, his A1C is greater than 6.5. He also had at least two random glucoses over 200 but, without classic signs or symptoms of hyperglycemia, those random measures don’t meet the criteria. He only needed two measures, and he has had three measures above the cutoffs.2

Dr R: What makes you think he has type 2?

MS3: He’s 50 years old.

Dr R: Is there anything that seems different about him from a usual patient with type 2?

MS3: His lack of a FHx of DM.

Dr R: That’s one, what else?

MS3: I don’t know what you mean. His blood sugars are high.

Dr R: Those are just numbers. Let’s look at the patient. What is the cause of DM type 2?

MS3: Insulin resistance.

Dr R: Correct. From what cause?

MS3: Obesity.

Dr R: Absolutely. Is this patient obese?

MS3: No. His BMI is in the normal range. Uh-oh, red flag! I don’t understand. I feel a mini-lecture coming on.

Dr R: Quite so, Skywalker. A person with type 2 diabetes inherited the genes for this process from his or her parents. However, the disease doesn’t manifest itself unless the person becomes overweight. What then occurs is insulin resistance. The beta cells of the pancreas have to overproduce insulin (hyperinsulinemia) to overcome the insulin resistance at the cellular level. There is debate as to what truly causes the other diseases in this “syndrome,” this hyperinsulinemia, the genetic abnormality, or the obesity itself, but the person’s blood pressure rises, there are usually classic cholesterol changes of high triglycerides and low HDL, the patient usually develops “fatty liver,” urate levels can rise (without overt gout), women usually have varying degrees of PCOS (polycystic ovarian syndrome), and the patient usually has sleep apnea. DM2 is part of this syndrome and rarely (if ever) presents as a solo disease. DM2 is usually one of the last manifestations of this syndrome. Hypertension is usually present for years or decades before the diabetes develops to a point where we can diagnosis it with our current lab values. All of these disease processes together (or really just one disease process, Insulin Resistance Syndrome) produces total body atherosclerosis and neuropathy, which is why DM2 (really IRS) is the primary cause of heart attacks, new blindness, limb amputation, and renal failure. Always think of all the other parts of this syndrome whenever you see any one part of the syndrome.

MS3: But this patient isn’t overweight, doesn’t have hypertension, doesn’t have abnormal HDL or triglycerides, and doesn’t have abnormal ALT, AST, or urate.

Dr R: Hence my question about what makes you think he has type 2?

MS3: Isn’t he too old for type 1?

Dr R: He’s too old for the fast onset type 1 you learned about in year 2, but have you ever heard about LADA (Latent Autoimmune Diabetes of Adults)?

MS3: No.

Dr R: A lot of people aren’t fully aware of this process. Let me try to explain. Type 1 DM is caused by a lack of insulin produced by the pancreas. This lack is classically caused by a cross-reaction of antibodies designed to fight a viral infection attacking the cells of the pancreas. In children and adolescents, each patient may produce multiple classes of Islet Cell Antibodies, and these antibodies rapidly destroy the insulin-producing cells, leading to Type 1 diabetes. In adults, there is an autoimmune process that produces only one Islet Cell Antibody (ICA) in each patient and, therefore, destruction of the beta cells occurs more slowly, over a few years. A “slow” onset type 1 or LADA. These patients will need insulin within a short period of time and will not respond to drugs that reduce insulin resistance such as the glitazones since insulin resistance is not the problem.

MS3: How would you diagnose this?

Dr R: You could order Islet Cell Antibodies, but that’s expensive since any one of the six or more ICAs can be the culprit, and you’d have to order all of them. You could draw an insulin or C-peptide level (showing the patient is producing their own insulin) and then draw it again in 6 months or a year. If the patient’s level is decreasing, that is evidence of decreasing functioning beta cells and may indicate a need to get the patient on insulin. You could also keep a high index of suspicion and just see how well the medications work. If the patient doesn’t respond to glitazones or only partially responds to metformin, your suspicion goes up.

MS3: Why would they respond at all to metformin; doesn’t it work by reducing insulin resistance?

Dr R: That is one of its mechanisms. Remember that metformin has two mechanisms; it also reduces hepatic gluconeogenesis.

MS3: I thought diabetes was easy to differentiate by age alone.

Dr R: No, it is differentiated by pathophysiology and pathophysiology guides treatment. Just to throw in another wrinkle, this “non-obese” patient with diabetes could also have MODY (Maturity Onset Diabetes of the Young).

MS3: Ack! That’s first-year biochemistry.

Dr R: Actually, everything we’ve discussed so far, including the mechanisms of the medications is first-year biochemistry. MODY is a one amino acid mutation inherited disorder. There are at least six different mutations known (MODYs 1–6). The most common is a mutated glucokinase, the trigger for insulin release. The “set point” of the glucose “thermostat” is higher in these patients such that insulin is not released until the blood glucose is higher than in normal patients.

MS3: But he had no family history of diabetes.

Dr R: Great point. However, he could be the point person who developed the mutation. What have we learned today?

MS3: (1) Type 2 Diabetes Mellitus is part of a syndrome, not a solo disease, (2) If one part of the Insulin Resistance Syndrome is present, look for all the other parts, (3) A non-obese patient with diabetes might not be a type 2 and may need totally different treatment, (4) Differentiate by pathophysiology, not by age, (5) Erectile dysfunction may be a presenting symptom for diabetes, (6) Illness is different than disease, and a patient without illness can resist the idea of having a disease, (7) The underlying process can be affecting the patient for years before we can make the diagnosis, (8) Patient education is more important than anything else, and (9) Biochemistry was actually important.

Dr R: Wow, an almost honors list. You forgot to add that Dr R is the greatest teacher that ever existed.

Rick Ricer, MD, University of Cincinnati, Author
Alec Chessman, MD, Medical University of South Carolina, Editor

References

  1. Sun P, Cameron A, Seftel A, Shabsigh R, Niederberger C, Guay A. Erectile dysfunction—an observable marker of diabetes mellitus? A large national epidemiological study. J Urol 2006;176:1081-5.
  2. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33(s1):562-9.
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