Type 2 Diabetes Diagnosis and Management Case File
Eugene C. Toy, MD, Gabriel M. Aisenberg, MD
Case 51
A 52-year-old woman who presents for her yearly physical examination. She has been doing well and has no complaints today. Her medical history is notable only for borderline hypertension and moderate obesity. Last year, her fasting lipid profile was acceptable for someone without known risk factors for coronary artery disease. Her mother and older brother have diabetes and hypertension. At prior visits, you see that your preceptor has counseled her on a low-calorie, low-fat diet and recommended that she start an exercise program. However, the patient says she has not made any of these recommended changes. With her full-time job and three children, she finds it difficult to exercise, and she admits that her family eats out frequently. Today, her blood pressure is 140/92 mm Hg. Her body mass index (BMI) is 29 kg/m2. Her examination is notable for acanthosis nigricans at the neck but otherwise is normal. A Papanicolaou (Pap) smear is performed, and a mammogram is offered. The patient has not eaten yet today, so on your preceptor’s recommendation, a fasting plasma glucose test is performed, and the result is 140 mg/dL.
▶ What is the most likely diagnosis?
▶ What is your next step?
ANSWERS TO CASE 51:
Type 2 Diabetes Diagnosis and Management
Summary: A 52-year-old woman presents for her yearly physical examination with
- Medical history notable only for borderline hypertension and moderate obesity
- Family history of diabetes and hypertension
- Poor adherence to the recommended lifestyle changes
- Blood pressure of 140/92 mm Hg and BMI of 29 kg/m2
- Acanthosis nigricans at the neck, suggesting insulin resistance
- Fasting plasma glucose level of 140 mg/dL, consistent with diabetes mellitus
Most likely diagnosis: Given her obesity, family history, and the finding of acanthosis nigricans, this patient most likely has type 2 diabetes. Diagnostic criteria for diabetes as defined by the American Diabetes Association (ADA) include (1) hemoglobin A1C greater than 6.5%, (2) fasting plasma glucose of 126 mg/dL or greater, (3) 2-hour plasma glucose of 200 mg/dL or greater during oral glucose tolerance test, or (4) a random plasma glucose of 200 mg/dL in the setting of hyperglycemic symptoms.
Next step: Dietary counseling, assess for end-organ disease, and check hemoglobin A1C (Hb A1C).
ANALYSIS
Objectives
- Recognize the diagnostic criteria for type 2 diabetes. (EPA 3)
- Describe the initial medical management of diabetes. (EPA 4)
- Understand cardiovascular risk modification in diabetic patients. (EPA 4, 12)
- Understand the prevention of microvascular complications of diabetes. (EPA 12)
Considerations
This patient has a diagnosis of diabetes mellitus unless there was a laboratory error (patient not truly fasting). If this patient’s diagnosis of diabetes is confirmed, she will require patient education, lifestyle modification, and medical therapy to prevent acute and chronic complications of diabetes. Strict glycemic control can reduce the incidence of microvascular complications such as retinopathy and nephropathy. In addition, patients with diabetes are among the highest at risk for cardiovascular disease, so risk factor modifications, such as smoking cessation and lowering of cholesterol, are essential. Diabetes confers the same level of risk for coronary events, such as heart attack, as in patients with established coronary artery disease and no prior diabetes. In patients with diabetes, the target blood pressure is generally less than 130/80 mm Hg, and the percentage of low-density lipoprotein (LDL) cholesterol lowering should be based on the calculated atherosclerotic cardiovascular disease risk.
APPROACH TO:
Diabetes Mellitus
DEFINITIONS
TYPE 1 DIABETES: Autoimmune destruction of the pancreatic beta cells and complete loss of endogenous insulin production. The presentation of this type of diabetes usually is acute, with hyperglycemia and metabolic acidosis. These patients are dependent on exogenous insulin delivery.
TYPE 2 DIABETES: Heterogeneous syndrome consisting of insulin resistance, progressively decreased insulin secretion, increased hepatic gluconeogenesis, and multiple other defects; it is exacerbated by genetic factors, obesity, and/or lack of physical activity. Oral medications and injectable incretin mimetic drugs that address specific defects of type 2 diabetes are useful. Exogenous insulin may be used when oral drugs and incretin mimetic medications are no longer sufficient for adequate glycemic control.
CLINICAL APPROACH
Epidemiology
As the prevalence of obesity increases in the American population, so does the prevalence of type 2 diabetes. Ninety percent of all new cases of diabetes diagnosed in the United States are type 2, and it is estimated that this disease affects approximately 30.3 million people in the United States. Diabetes is the leading cause of blindness, renal failure, and nontraumatic amputations of the lower extremities. It is a major risk factor in patients with coronary artery disease, peripheral vascular disease, and stroke.
In contrast to type 1 diabetics, patients with type 2 diabetes usually have a prolonged asymptomatic phase. During these years of asymptomatic hyperglycemia, however, organ damage begins to occur.
Screening. The ADA recommends screening overweight and obese adults with one of the following risk factors: hypertension, HDL level below 35 mg/dL, hypertriglyceridemia above 250 mg/dL, first-degree relative with diabetes, being a member of a high-risk ethnic/race group (ie, African Americans, Hispanics, American Indians, Asian Americans, or Pacific Islanders), prediabetes, physical inactivity, history of gestational diabetes, history of cardiovascular disease, history of polycystic ovarian syndrome, or other insulin-resistant condition (eg, acanthosis nigricans, severe obesity).
Repeat screening should be done at least yearly for prediabetes and at least every 3 years for a history of gestational diabetes. For all other adult patients, the ADA recommends screening start at age 45 with a minimum of 3-year intervals between tests.
Older children and adolescents who are overweight/obese and exhibit an aforementioned risk factor should also be screened.
Pathophysiology
Most patients with type 2 diabetes mellitus are insulin resistant and hyperinsulinemic for years before developing overt diabetes. They are able to maintain normoglycemia for a long time, then develop postprandial hyperglycemia and later both postprandial and fasting hyperglycemia (eg, hyperglycemia all the time). Thus, a glucose tolerance test to detect postprandial hyperglycemia would be the most sensitive test for diabetes mellitus, but it is time consuming and difficult to perform in a clinical practice. The fasting plasma glucose is a more specific test. Hemoglobin A1C > 6.5% has now also been recognized as an acceptable diagnostic criterion (Table 51–1). In the setting of hyperglycemia symptoms, a random plasma glucose above 200 mg/dL is enough for diagnosis. If there are no clear symptoms of hyperglycemia, the diagnosis of diabetes should be confirmed on a subsequent day by repeat measurement, repeating the same test for confirmation. However, if two different tests (eg, fasting glucose and A1C) are available and are concordant for the diagnosis of diabetes, additional testing is not needed.
By using these tests, patients can be classified into one of three categories: (1) normal, (2) impaired glucose tolerance/impaired fasting glucose (eg, “prediabetic”), or (3) diabetic. Increased risk for microvascular complications of hyperglycemia is seen at a fasting glucose more than 126 mg/dL or Hb A1C > 6.5%. Once diabetes is diagnosed, therapy is instituted with three major goals, which are listed below.
- Prevention of acute complications of hyperglycemia (eg, diabetic ketoacidosis [DKA] or nonketotic hyperosmolar hyperglycemia) or hypoglycemia
- Prevention of long-term complications of hyperglycemia, for example, microvascular disease such as retinopathy or nephropathy
- Prevention of long-term complications of macrovascular disease, for example, cardiovascular or cerebrovascular disease
Treatment
The foundation of diabetes therapy is dietary and lifestyle modifications. Exercise and even small amounts of weight loss can lower blood pressure and improve glucose control. Patients should be given instruction in nutrition and encouraged to change sedentary lifestyles.
However, most people with diabetes will eventually require medical therapy, and many patients will eventually require a combination of at least two medications. Because of the difficulty in achieving and sustaining glycemic targets and achieving significant weight loss, the ADA recommends that metformin should be initiated concurrently with lifestyle intervention at the time of diagnosis.
The glycemic goal is individualized based on multiple factors (eg, hypoglycemia risk, life expectancy, other disease comorbidities) but is generally a hemoglobin A1C < 7%. If patients fail to achieve the glycemic goal with initial therapy, including lifestyle modification and metformin, therapeutic options include adding a second oral or injectable agent, including insulin, or switching to insulin monotherapy. A list of therapeutic agents for diabetes is included in Table 51–2.
When diabetes is diagnosed, other cardiovascular risk factors should be assessed. Blood pressure and lipid levels should be measured. The cardiovascular risk in those with diabetes is equivalent to those with known coronary artery disease. Statins are the preferred LDL reduction medication, with goal reduction depending on the intensity of the regimen. Moderate-dose statins should aim to reduce LDL by 30% to 50%, while high-intensity statins should aim for 50% reduction or more.
The desired blood pressure goal in an individual with diabetes and hypertension is < 140/90 mm Hg if the 10-year atherosclerotic cardiovascular risk is less than 15%; otherwise, one should pursue a lower target of < 130/80 mm Hg if it can be safely attained. Several randomized trials have demonstrated a benefit for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers in preventing the progression of proteinuria and kidney disease.
Other routine care in diabetic patients includes frequent primary care provider visits, at least every 3 to 6 months depending on the patient’s glucose control, at least yearly ophthalmologic examinations to screen for retinopathy, yearly urine screens to detect microalbuminuria, and yearly foot examinations to detect peripheral neuropathy (if patient has no prior neuropathy). Hemoglobin A1C should be checked at least every 3 to 6 months, depending on the patient’s glucose control. This test allows the clinician to know the general glucose control over the preceding 2 to 3 months.
Patients with established neuropathy should be examined at every visit and be instructed on daily self-examination and prevention of injury. In fact, neuropathy is the main risk factor for the development of a foot ulcer and subsequent development of a wound; this can progress into a nonhealing ulcer that sometimes requires surgical amputation. Thus, careful foot care and daily examination are the most important preventive steps.
CASE CORRELATION
- See also Case 48 (Oligomenorrhea Caused by Hypothyroidism and Hyperprolactinemia), Case 52 (Diabetic Ketoacidosis, Type 1 Diabetes), and Case 53 (Thyrotoxicosis/Graves Disease).
COMPREHENSION QUESTIONS
51.1 A 45-year-old man comes in for counseling about his fasting plasma glucose test after a routine health maintenance examination. On two separate occasions, the result has been 115 mg/dL and 120 mg/dL. Which of the following is the most appropriate next step at this time?
A. Reassurance that these are normal blood sugars.
B. Recommend weight loss, an ADA diet, and exercise.
C. Diagnose diabetes mellitus and start on a sulfonylurea.
D. Recommend cardiac stress testing.
E. Obtain stat arterial blood gas and serum ketone levels.
51.2 A 45-year-old obese woman presents for follow-up for her diabetes. She currently takes metformin 1000 mg twice per day, and her fasting morning glucose runs approximately 170 to 200 mg/dL. Her last serum Hb A1C level was 7.9%. She states that she conscientiously follows her diet and walks 30 minutes to 1 hour daily. Which of the following is the best next step in her care?
A. Refer to an endocrinologist for an insulin pump.
B. Stop metformin and start on glimepiride.
C. Add a second agent for the treatment of her diabetes.
D. Hospitalize her urgently.
51.3 A 75-year-old woman with type 2 diabetes for approximately 20 years, diabetic retinopathy, and diabetic nephropathy is brought into the clinic by her daughter for follow-up. The patient’s last serum creatinine level was 2.2 mg/dL. The patient currently takes a glyburide for her diabetes and lisinopril for her proteinuria. Her daughter reports that on three occasions in the past 2 weeks, her mother became sweaty, shaky, and confused, which resolved when she was given some orange juice. Which of the following conditions is most likely to be contributing to these episodes?
A. Excess caloric oral intake
B. Interaction between the ACE inhibitor and the sulfonylurea agents
C. Worsening renal function
D. Hyperglycemic amnesia
51.4 A 42-year-old woman with a past medical history of gestational diabetes during her last pregnancy 6 years previously usually has screening for type 2 diabetes every year. Which of the following screening methods has the highest sensitivity for diagnosing type 2 diabetes?
A. Fasting serum glucose
B. 2-hour glucose tolerance test
C. Hemoglobin A1C
D. Random glucose
51.5 A 36-year-old man has been recently diagnosed with type 2 diabetes. If not vaccinated previously, which of the following immunizations is most important to administer?
A. Toxoplasmosis
B. Human papilloma virus (HPV)
C. Hepatitis B
D. Rubella
ANSWERS
51.1 B. By diagnostic criteria, this patient falls into the definition of impaired fasting glucose, which is between 100 and 125 mg/dL. A normal fasting glucose level is < 100 mg/dL; diabetes can be diagnosed by a fasting glucose level of 126 mg/dL or higher. Although she does not yet meet the criteria for diabetes (answer C), she is at greater risk for developing diabetes in the future and for macrovascular disease. Intensive lifestyle changes (diet and exercise for 30 minutes per day, 5 days per week) can prevent or delay the development of diabetes. Patients should be monitored annually to screen for progression to diabetes. Cardiac stress testing (answer D) is indicated if there is chest pain or other suspicion of coronary heart disease. This patient does not have normal blood sugars (answer A) or DKA (answer E).
51.2 C. When patients fail to achieve glycemic goal (Hb A1C < 7%) using metformin and lifestyle modifications, the next step is to add a second agent (not discontinue metformin, as in answer B). Among the choices are glucagon-like peptide 1 (GLP-1) receptor agonists (eg, liraglutide), dipeptidyl peptidase 4 (DPP-4) inhibitors (eg, sitagliptin), sodium-glucose co-transporter-2 (SGLT-2) inhibitors (eg, empagliflozin), thiazolidinediones (eg, pioglitazone), sulfonylureas (eg, glipizide), and once-daily basal insulin injection (a long-acting insulin such as NPH, glargine, or detemir). If a patient has known atherosclerotic cardiovascular disease, a GLP-1 receptor agonist or SGLT-2 is preferred. If patient has heart failure or chronic kidney disease, consider an SGLT-2 inhibitor (answer B). An endocrine consultation and an insulin pump (answer A) in a type 2 diabetic are mainly needed because of failure to achieve glycemic control with multiple injections of insulin. Hospitalization for an urgent condition (answer D) is indicated if there is suspicion of a serious complication, such as HHNS.
51.3 C. Sulfonylureas have long half-lives and can cause prolonged hypoglycemia in elderly patients as well in those with renal insufficiency; glyburide is notorious for this complication. For these reasons, many practitioners will avoid sulfonylurea agents (even newer ones) in elderly patients. Another hypoglycemic agent, such as insulin, may be more appropriate in this patient, as well as less-intensive control, aiming for an Hb A1C of 8% instead of 7%. If a sulfonylurea agent must be used for some reason, then glipizide and glimepiride are the agents of choice with chronic kidney disease. Excess caloric intake (answer A) would not lead to hypoglycemia, but rather hyperglycemia. ACE inhibitors and sulfonylurea agents (answer B) may lead to a temporary sensitization of the sulfonylurea agent, but this usually resolves after a short time. Hyperglycemic amnesia (answer D) presents a cognitive decline due to hyperglycemia; this patient’s symptoms are much more consistent with hypoglycemia.
51.4 B. The 2-hour oral glucose tolerance test is used as the reference standard and has the highest sensitivity for the diagnosis of type 2 diabetes. Even with this “gold standard,” there are undiagnosed diabetics. Fasting glucose (answer A) is a fairly good test with a sensitivity of about 82% and has the advantage of reproducibility. Hemoglobin A1C (answer C) is also an acceptable test; however, the sensitivity is around 60% in patients with a hemoglobin A1C above 6.5%. The hemoglobin A1C is additionally advantageous because serum levels correlate with long-term outcomes. A random glucose (answer D) is only about 50% sensitive and is seldom used as a screening test.
51.5 C. A patient who is diagnosed with diabetes should receive the hepatitis B vaccine as soon as feasible if not vaccinated previously. The Centers for Disease Control and Prevention recommends hepatitis B vaccination for diabetics aged 18 to 59, and consideration for those > 60 years due to the increased risk of hepatitis B case fatality rate in diabetics. Diabetes confers a 60% higher infection rate versus nondiabetics. Diabetics should receive an annual influenza vaccination as well as the pneumococcal vaccine after the age of 65 if the first dose was administered prior to the age of 65. HPV vaccine (answer B) is recommended for patients between the ages of 11 and 26 years. Rubella vaccine (answer D) is routinely recommended in men; however, women in the childbearing age who are nonimmune should also be vaccinated. Toxoplasmosis vaccine (answer A) does not exist. In summary, diabetics should receive five vaccines: annual influenza vaccine, Tdap (tetanus, diphtheria, acellular pertussis) vaccine, zoster vaccine, pneumococcal vaccine, and the hepatitis B vaccine.
CLINICAL PEARLS
▶ Type 2 diabetes has a prolonged asymptomatic stage during which microvascular disease (retinopathy, nephropathy, or neuropathy) can occur. Clinicians should have a high index of suspicion and screen patients with risk factors.
▶ Lifestyle modification and metformin are the initial therapy for most patients when they are diagnosed with type 2 diabetes.
▶ The major cause of morbidity and mortality in patients with type 2 diabetes mellitus is macrovascular disease, such as coronary artery disease, stroke, and peripheral vascular disease, so aggressive cardio-vascular risk factor reduction is essential.
▶ Glycemic goals are individualized for each patient but generally include Hb A1C < 7%.
▶ Blood pressure target should be < 140/90 or < 130/80 mm Hg (depending on cardiovascular risk), and LDL cholesterol should be lowered (usually by 30% to 50%) with a statin, based on the patient’s atherosclerotic cardiovascular disease risk.
REFERENCES
American Diabetes Association. Standards of medical care in diabetes 2019. Diabetes Care. 2019;38(suppl 1):S13-S123.
Centers for Disease Control and Prevention. (2017). National Diabetes Statistics Report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services.
De Fronzo RA. From the triumvirate to the “ominous octet”: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;18:773-795.
Powers AC, Niswender KD, Evans-Molina C. Diabetes mellitus: diagnosis, classification, and pathophysiology. In: Jameson J, Fauci AD, Kasper DL, Hauser SL, Longo DL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 20th ed. New York, NY: McGraw Hill; 2019:2399-2430
Simon, K. Tests for diagnosing diabetes mellitus. Glucose tolerance test is most sensitive. BMJ. 1994;309(6953):537-538.
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