U.S. Department of Health and Human Services

Principle 6: Control Blood Glucose to Prevent or Delay Diabetes

Poor blood glucose control (A1C > 9.0 percent) is associated with symptoms that can include frequent urination, thirst, blurred vision, fatigue, and recurring infections. Treatment of adults with type 2 diabetes with poor glucose control to lower A1C to a mean of 7.5 percent has been shown to improve quality of life and work productivity. 1 Beyond relief of immediate symptoms associated with poor control, the goal of blood glucose control is to reduce long-term complications of diabetes.

The Diabetes Control and Complications Trial (DCCT) 2 found that measures of early microvascular complications were reduced 50 to 76 percent in participants with type 1 diabetes randomized to intensive control. The intensively controlled group achieved an average A1C of about 7 percent compared with controls with an average A1C of about 9 percent. The Epidemiology of Diabetes Interventions and Complications (EDIC) 3 follow-up observational study of the DCCT showed that participants also had benefits that endured and grew over the following 2 decades despite equivalent subsequent A1C levels. During EDIC, the treatment group had major reductions in eye, nerve, kidney, and heart complications and less than half the number of cardiovascular disease (CVD) events than in the conventionally treated group.

Similarly, in people with newly diagnosed type 2 diabetes, the United Kingdom Prospective Diabetes Study 4 and its 10-year follow-up observational study 5 found that reduced complications persisted for at least a decade after a finite period of intensive glycemic control (average A1C of 7 percent compared with 7.9 percent with standard treatment). As in DCCT/EDIC, significant microvascular benefits persisted, and macrovascular benefits emerged with reduced myocardial infarction.

Three randomized trials designed to test the benefits of near-normalization of blood glucose on CVD in participants with long-standing type 2 diabetes found no benefit in the primary macrovascular outcome, 6, 7, 8 and one found increased mortality. 6 These trials did demonstrate reduction in some early microvascular disease measures, such as albuminuria, with lowering of A1C below 7 percent.

Risks of blood glucose control

Findings from the three clinical trials indicate that caution is needed in setting A1C goals lower than 7 percent in people with long-standing type 2 diabetes who have CVD or multiple CVD risk factors. 6, 7, 8 All three trials showed that near-normal glucose control increased the risk of severe hypoglycemia. Moreover, the intensive blood glucose control group (A1C goal < 6.0 percent) of the Action to Control Cardiovascular Risk in Diabetes (ACCORD)6 trial was stopped early at 3.5 years due to a 20 percent relative risk increase in mortality in the intensive control group compared to standard glucose control (A1C goal 7.0–7.9 percent). The increase in mortality overshadowed the modest reduction in myocardial infarction risk. ACCORD studied older people (mean age 62 years) with a 10-year average duration of diabetes and known CVD or multiple CVD risk factors. A randomized trial of early insulin replacement to normalize blood glucose in people with prediabetes or early type 2 diabetes found a neutral effect on CVD, increased hypoglycemia, and modest weight gain. 9

Hypoglycemia is the leading limiting factor in the glycemic management of type 1 and insulin-treated type 2 diabetes. 10 Mild hypoglycemia may be inconvenient or frightening to people with diabetes, and more severe hypoglycemia can result in falls, seizures, machinery/motor vehicle accidents, or other injury. Treatment of hypoglycemia (plasma glucose < 70 mg/dL) requires ingestion of 15 to 20 grams of glucose- or carbohydrate-containing foods. An individual with severe hypoglycemia who is unable to ingest fast-acting carbohydrates should be treated using emergency glucagon kits, which require a prescription. Those in close contact with people who have hypoglycemia-prone diabetes should be instructed in the use of such kits.

Prevention of hypoglycemia is particularly critical for people treated with insulin and/or sulfonylureas. People with diabetes should understand factors (such as physical activity or missed meals) that increase their risk of hypoglycemia and ways to prevent and treat it.

In type 1 diabetes and severely insulin-deficient type 2 diabetes, the syndrome of hypoglycemia unawareness, or hypoglycemia-associated autonomic failure, can severely compromise stringent diabetes control and quality of life. The deficient counter-regulatory hormone release and autonomic responses in this syndrome are both risk factors for and caused by hypoglycemia. Temporary relaxation of glycemic control to avoid hypoglycemia may reverse hypoglycemia unawareness. 10

A1C treatment goals

Because the benefits of intensive glucose control emerge slowly and the risks associated with hypoglycemia are more immediate, people with longer life expectancy have more to gain from intensive glucose control. Treatment targets should be individualized based on duration of diabetes, age/life expectancy, comorbid conditions, known CVD or advanced microvascular complications, hypoglycemia unawareness, and discussion with the person of benefits and risks of specific levels of glycemic control.11

  • Consider A1C targets as close to non-diabetic levels (< 6.5 percent) as possible without significant hypoglycemia in people with short duration of diabetes, little comorbidity, and long life expectancy.
  • Consider less stringent A1C targets (e.g., 8 percent) for people with a history of severe hypoglycemia, limited life expectancy, extensive comorbid conditions, advanced complications, major impairments to self-management (e.g., visual, cognitive, social), or long-standing diabetes where the A1C goal is difficult to attain despite optimal efforts.
  • Reassess A1C targets and change (lower or higher) as appropriate.

Blood glucose management

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The initiation and adjustment of therapy should target glucose values as close to an agreed-upon goal as possible without compromising the individual’s safety. Medical nutrition therapy and physical activity are essential from diagnosis onward for people with diabetes. People on insulin or oral agents that stimulate insulin secretion are at increased risk for hypoglycemia.

  • For people with type 1 diabetes, basal and meal-related insulin doses may be taken several times a day via multiple injections or an insulin pump in an attempt to normalize glucose metabolism and simulate normal insulin physiology.
  • For people with type 2 diabetes, metformin (together with lifestyle modification) is recommended as the initial therapy at time of diagnosis unless metformin is contraindicated.
  • Over time, people with type 2 diabetes may require combination therapy with other glucose-lowering medications to maintain the target A1C. Information about advantages and disadvantages of the available medication classes can help guide therapy selection.* 12, 13, 14

Use of strategies to help people with diabetes take their medicines as directed can improve adherence, clinical outcomes, productivity, and quality of life. 15

*Glucose-lowering medications differ in their mechanisms of action. Risks and side effects also vary. Comparative effectiveness studies provide insufficient evidence on long-term risks and benefits of other oral agents, glucagon-like peptide-1 receptor agonists, or insulin to guide the selection of a second agent when metformin is not sufficient to meet treatment goals.

Blood glucose assessment

  • Use A1C values to guide therapy to achieve individualized glycemic targets.** 16 Although point-of-care A1C tests give immediate results and may be useful for changing therapy, they are less accurate than clinical laboratory results, and there is no evidence that immediate results lead to better outcomes for people with diabetes than conventional laboratory testing. 17
  • Regular self-monitoring of blood glucose (SMBG) or continuous glucose monitoring may help with self-management and therapy adjustment and with assessment of hypoglycemia and hyperglycemia. SMBG is useful for individuals taking insulin, but benefit has not been consistently shown in people not on insulin. Individual characteristics should determine how often self-monitoring is done; the specific testing method; and the way results are used, recorded, and reported.
  • The following correlations between A1C values and mean plasma glucose may help health care providers set appropriate blood glucose targets for people required to self-monitor their blood glucose.
A1C percent Mean ​​plasma glucose, mg/dL
6 126
7 154
8 183
9 212
10 240
11 269
12 298

**See Principle 9 for information about variant hemoglobins that can alter some A1C test results.

Bariatric surgery

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In obese people with uncontrolled type 2 diabetes, medical therapy plus bariatric surgery has been shown to induce short-term remission of diabetes18, 19 and to improve glycemic control at 3 years.20 Further study is necessary to assess the durability of these results over longer time periods. Bariatric surgery has been shown to delay the onset of type 2 diabetes,21 but the long-term risks and benefits of the surgery are not yet known.

References

1. Testa MA, Simonson DC. Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled, double-blind trial. JAMA. 1998;280(17):1490–6.

2. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Eng J Med. 1993;329(14):977–86.

3. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643–53.

4. United Kingdom Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.

5. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577–89.

6. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–59.

7. Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–72.

8. 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(2):129–39.

9. Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367(4):319–28.

10. Cryer PE. Hypoglycaemia: the limiting factor in the glycaemic management of Type I and Type II diabetes. Diabetologia. 2002;45(7):937–48.

11. Ismail-Beigi F, Moghissi E, Tiktin M, Hirsch IB, Inzucchi SE, Genuth S. Individualizing glycemic targets in type 2 diabetes mellitus: implications of recent clinical trials. Ann Intern Med. 2011;154(8):554–9.

12. Management of Diabetes Mellitus Update Working Group. VA/DoD Clinical Practice Guideline for the Management of Diabetes Mellitus. Version 4.0. Washington, DC: Veterans Health Administration and Department of Defense; 2010.

13. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15(6):540–59.

14. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6):1364–79.

15. Viswanathan M, Golin CE, Jones CD, et al. Interventions to improve adherence to self-administered medications for chronic diseases in the United States: a systematic review. Ann Intern Med. 2012;157(11):785–95.

16. Sacks DB. Hemoglobin A1c in diabetes: panacea or pointless? Diabetes. 2013;62(1):41–3.

17. Al-Ansary L, Farmer A, Hirst J, et al. Point-of-care testing for Hb A1c in the management of diabetes: a systematic review and metaanalysis. Clin Chem. 2011;57(4):568–76.

18. Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366(17):1567–76.

19. Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient—2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Endocr Pract. 2013;19(2):337–72.

20. Schauer PR, Bhatt DL, Kirwan JP, et al . Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N Engl J Med. 2014;370(21):2002–13.

21. Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012;367(8):695–704.