Diabetes Mellitus

General Principles

  • Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. In 2015, diabetes was present in 12.2% of persons age >18 years in the United States and 25.2% of those over the age of 65 years. A substantial percentage of affected persons are not diagnosed. Type 2 diabetes mellitus (T2DM) represents 90%–95% of all cases of diabetes, with type 1 diabetes mellitus (T1DM) and other causes representing the remaining 5%–10%.1,2
  • Persons with diabetes are at risk for microvascular complications, including retinopathy, nephropathy, and neuropathy, and are at increased risk for macrovascular disease.
  • T2DM is accompanied by hypertension (approximately 75%) and hyperlipidemia (>50%) in adult patients and is considered a “cardiac risk equivalent” because of the excess risk for macrovascular disease, cardiovascular disease (CVD) events, and mortality.3

Classification

Diabetes mellitus is classified into four clinical classes2

  • T1DM accounts for <10% of all cases of diabetes and results from a cellular-mediated autoimmune destruction of the beta (β) cells of the pancreas.
  • T2DM accounts for >90% of all cases of diabetes. T2DM is characterized by insulin resistance followed by reduced insulin secretion from β cells that are unable to compensate for the increased insulin requirements.
  • Other specific types of diabetes include those that result from genetic defects in insulin secretion or action (known as monogenic diabetes), pancreatic surgery or disease of the exocrine pancreas (cystic fibrosis), endocrinopathies (e.g., Cushing syndrome, acromegaly), or drugs (corticosteroids, antiretroviral, atypical antipsychotics), and diabetes associated with other syndromes.
  • Gestational diabetes (GDM) is glucose intolerance with onset or diagnosis during pregnancy. The prevalence of GDM depends on the criteria used for diagnosis and varies by age and ethnic group (generally from 5%–6% of pregnancies to 15%–20% of pregnancies). Diagnostic criteria for GDM vary based on practice location with a two-step method (50-g, 1-hour screen followed by 100-g, 3-h oral glucose tolerance test [OGTT]) used in the United States and a one-step method (75-g, 2-hour OGTT) more common internationally.4 About 60% of women with GDM will develop T2DM in the ensuing 5–10 years, and all remain at an increased risk for the development of T2DM later in life.
    • All patients with GDM should undergo diagnostic testing 4–12 weeks postpartum with a 2-h OGTT or fasting plasma glucose and every 1–3 years thereafter with either test or an A1C to determine whether abnormal carbohydrate metabolism has persisted or is recurrent.4
    • Weight loss and exercise are encouraged to decrease the risk of persistent prediabetes or T2DM after delivery.

Diagnosis

  • Progression from impaired fasting glucose or impaired glucose tolerance to T2DM occurs at the rate of 2%–22% (average, about 12%) per year depending on the population studied.
  • Lifestyle modification, including a balanced hypocaloric diet to achieve 7% weight loss in overweight patients and regular exercise of ≥150 minutes per week, is recommended for persons with prediabetes to prevent progression to T2DM.5
  • Metformin may be considered in patients with prior GDM, those with body mass index (BMI) ≥35, age <60 years, or those with progressive hyperglycemia.5
  • Diagnostic criteria for prediabetes and diabetes are listed in Table 23-1.
    Table 23-1: Diagnosis of Diabetes
    Prediabetes Diagnosis (Increased 
Risk for Developing Diabetes)Diabetes Diagnosis
    A1C 5.7%–6.4% (39–46 mmol/mol)A1C ≥6.5% (48 mmol/mol)a
    Fasting plasma glucose (FPG) 
100–125 mg/dL (5.6–6.9 mmol/L) (impaired fasting glucose)FPG ≥126 mg/dL (7.0 mmol/L)a
    Oral glucose tolerance test (OGTT): Glucose 140–199 mg/dL (7.8–11.0 mmol/L) 2 h after 75-g glucose load (impaired glucose tolerance)OGTT: Glucose ≥200 mg/dL (11.1 mmol/L) 2 h after 75-g glucose loada

    Symptoms of diabetes (polyuria, polydipsia, fatigue, weight loss) and random plasma glucose level ≥200 mg/dL (11.1 mmol/L)

    aShould be repeated unless unequivocal hyperglycemia is present.

Treatment

  • Goals of therapy are alleviation of symptoms; achievement of glycemic, blood pressure, and lipid targets; and prevention of acute and chronic complications of diabetes.
  • Glycemic control recommendations are the same for T1DM and T2DM: Fasting and preprandial capillary blood glucose (BG) 80–130 mg/dL (3.9–7.2 mmol/L), postprandial capillary BG <180 mg/dL (<10 mmol/L), and A1C <7% (<53 mmol/mol) or as close to normal as possible while avoiding significant hypoglycemia.6 The American Association of Clinical Endocrinologists (AACE) recommends an A1C target of <6.5% (<48 mmol/mol) for most adults.7 This degree of glycemic control has been associated with the lowest risk for microvascular complications in patients with T1DM and T2DM.8,9
  • Intensive diabetes therapy leading to very tight glycemic control in patients with risk factors for CVD has been associated with increased mortality in two studies,10,11 but not in others.12 Hypoglycemia was implicated as the cause of higher mortality in one of the studies.11 Less tight glycemic goals may be appropriate for patients with a history of cardiovascular disease (CVD) or those at high risk for CV events.6
  • The blood pressure target for patients with diabetes is <140/90 mm Hg, but a lower goal of <130/80 mm Hg may be considered for younger patients or those at high risk of CVD.7,13 The use of either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) is recommended as first-line therapy. For patients not at goal, a thiazide diuretic should be added if the glomerular filtration rate (GFR) is >30 mL/min/1.73 m and a loop diuretic added if the GFR is <30 mL/min/1.73 m.7,13
  • High-intensity statin therapy (atorvastatin 40–80 mg daily or rosuvastatin 20–40 mg daily) is recommended in all patients with diabetes and CVD as well as in patients age 40–75 with CVD risk factors.7,13 Moderate-intensity statin therapy can be considered in patients age 40–75 with no other CVD risk factors and in patients with age <40 or >75 with CVD risk factors.
  • The low-density lipoprotein (LDL) goal for patients with diabetes and CVD is <70 mg/dL (3.9 mmol/L). If that goal is not achieved with statin therapy, the addition of either ezetimibe or a PCSK9 inhibitor is advised.7,13
  • Aspirin therapy should be advised in patients with diabetes who are older than 50 years or who have other risk factors. Low doses (75–162 mg) are appropriate for primary prevention.13
  • Assessment of glycemic control consists of the following:
    • Self-monitoring of blood glucose (SMBG) is recommended for all patients who take insulin and provides useful information for those on noninsulin therapies. Patients using multiple daily injections or insulin pumps should test their blood glucose three or more times daily. Less frequent testing may be appropriate for those on noninsulin therapies. Although most SMBG is done before meals and at bedtime, periodic testing 1–2 hours after eating may be necessary to achieve postprandial glucose targets.6
    • Continuous glucose monitoring (CGM) has been shown to reduce A1C in adults older than 25 years and reduce hypoglycemia in patients of all ages on intensive insulin therapy. CGM measures interstitial glucose, which provides a close approximation of BG values. Hypoglycemia and hyperglycemia alarms may help patients with widely fluctuating BG levels or hypoglycemia unawareness. Some of the CGM devices are approved for insulin dosing and may supplant the need for SMBG.
    • A1C provides an integrated measure of BG values over the preceding 2–3 months. A1C should be obtained every 3 months in patients not at goal or when either diabetes therapy or clinical condition changes and twice yearly in well-controlled patients. A1C should confirm results of SMBG or CGM, and discordant values should be investigated. An A1C level that is higher than expected should be evaluated by a diabetes educator to ensure meter accuracy, appropriate technique, and frequency of testing. When the A1C is lower than expected, blood loss, transfusion, hemolysis, and hemoglobin variants should be considered. The correlation between A1C and mean plasma glucose is sufficiently strong that laboratory reports may include both the A1C result and the estimated average glucose.6
    • Ketones can be detected in a fingerstick blood sample by measuring β-hydroxybutyrate with a handheld meter. Urine ketones can be qualitatively identified, using Ketostix or Acetest tablets. Patients with T1DM should test for ketones during febrile illness, for persistent elevation of glucose (>300 mg/dL [16.7 mmol/L]), or if signs of impending diabetic ketoacidosis (e.g., nausea, vomiting, abdominal pain) develop. Testing for β-hydroxybutyrate is useful in emergency departments to determine whether a patient with hyperglycemia has ketonemia.14

Management

Comprehensive diabetes management includes coordinated diet, exercise, and medication plans. Patient education in medical nutrition therapy, exercise, SMBG, medication use, and insulin dosing and administration is integral to the successful management of diabetes.

Medical Nutrition Therapy

  • Medical nutrition therapy includes dietary recommendations for a healthy, balanced diet to achieve adequate nutrition and maintain an ideal body weight.15
  • Caloric restriction is recommended for overweight individuals, with individualized targets that may be as low as 1000–1500 kcal/d for women and 1200–1800 kcal/d for men depending on activity level and starting body weight.
  • Caloric intake is usually distributed as follows: 45%–65% of total calories as carbohydrates, 10%–30% as protein, and <30% as total fat (<7% saturated fat) with <300 mg/d of cholesterol.
  • In patients with LDL cholesterol >100 mg/dL (2.6 mmol/L), total fat should be restricted to <25% of total calories, saturated fat to <7% of calories, and cholesterol to <200 mg/d.
  • Patients with progressive kidney disease may benefit from restriction of protein intake to 0.8 g/kg/d. Patients with severe chronic kidney disease (CKD) will need additional restrictions of potassium- and phosphorus-containing foods.
  • “Carbohydrate counting” is a useful skill for patients on intensified insulin therapy who adjust insulin doses based on the carbohydrate content of meals and snacks.

Exercise

Exercise improves insulin sensitivity, reduces fasting and postprandial BG levels, and offers numerous metabolic, CV, and psychological benefits in patients with diabetes.

  • In general, 150 minutes per week is recommended as part of a healthy lifestyle and has been shown to assist with the prevention and management of T2DM in adults.15
  • Patients may need individualized guidance regarding exercise, and they are more likely to exercise when counseled by their physician to do so.

References

  1. Center for Disease Control and Prevention. National Diabetes Statistics Report 2017: Estimates of Diabetes and Its Burden in the United States. Atlanta, GA: Department of Health and Human Services, Centers for Disease Control and Prevention; 2017. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statis....
  2. American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes – 2018. Diabetes Care. 2018;41(suppl 1):S13-S27.
  3. American Diabetes Association. Comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes – 2018. Diabetes Care. 2018;41(suppl 1):S28-S37.
  4. American Diabetes Association. Management of diabetes in pregnancy: standards of medical care in diabetes – 2018. Diabetes Care. 2018;41(suppl 1):S137-S143.
  5. American Diabetes Association. Prevention or delay of type 2 diabetes: standards of medical care in diabetes – 2018. Diabetes Care. 2018;41(suppl 1):S51-S54.
  6. American Diabetes Association. Glycemic targets: standards of medical care in diabetes – 2018. Diabetes Care. 2018;41(suppl 1):S55-S64.
  7. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2018 executive summary. Endocr Pract. 2018;24(1):91-120.  [PMID:29368965]
  8. The Diabetes Control and Complications Trial Research Group. The effect of intensive therapy of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986.
  9. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577-1589.  [PMID:18784090]
  10. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:3545-2559.
  11. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129-139.  [PMID:19092145]
  12. The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560-2572.
  13. American Diabetes Association. Cardiovascular disease and risk management: standards of medical care in diabetes – 2018. Diabetes Care. 2018;41(suppl 1):S86-S104.
  14. Naunheim R, Jang TJ, Banet G, et al. Point-of-care test identifies diabetic ketoacidosis at triage. Acad Emerg Med. 2006;13(6):683-685.  [PMID:16690813]
  15. American Diabetes Association. Lifestyle management: standards of medical care in diabetes – 2018. Diabetes Care. 2018;41(suppl 1):S38-S50.

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