Glycemic goals

Recommendations

* Lowering A1C has been associated with a reduction of microvascular and neuropathic complications of diabetes. (A)
* The A1C goal for patients in general is an A1C goal of <7%. (B)
* The A1C goal for the individual patient is an A1C as close to normal (<6%) as possible without significant hypoglycemia. (E)
* Less stringent treatment goals may be appropriate for patients with a history of severe hypoglycemia, patients with limited life expectancies, very young children or older adults, and individuals with comorbid conditions. (E)
* Aggressive glycemic management with insulin may reduce morbidity in patients with severe acute illness, perioperatively, following myocardial infarction, and in pregnancy. (B)

Glycemic control is fundamental to the management of diabetes. The goal of therapy is to acheive an A1C as close to normal as possible (representing normal fasting and postprandial glucose concentrations) in the absence of hypoglycemia. However, this goal is difficult to achieve with present therapies. Prospective randomized clinical trials such as the DCCT and the U.K. Prospective Diabetes Study (UKPDS) have shown that improved glycemic control is associated with sustained decreased rates of retinopathy, nephropathy, and neuropathy. In these trials, treatment regimens that reduced average A1C to 7% (1% above the upper limits of normal) were associated with fewer long-term microvascular complications; however, intensive control was found to increase the risk of severe hypoglycemia and weight gain. The potential of intensive glycemic control to reduce CVD is supported by epidemiological studies and a recent meta-analysis, but this potential benefit on CVD events has not yet been demonstrated in a randomized clinical trial. 

Text continued below

Recommended glycemic goals for nonpregnant individuals are shown in Table 6. A major limitation to the available data is that they do not identify the optimum level of control for particular patients, as there are individual differences in the risks of hypoglycemia, weight gain, and other adverse effects. Furthermore, with multifactorial interventions, it is unclear how different components (e.g., educational interventions, glycemic targets, lifestyle changes, pharmacological agents) contribute to the reduction of complications. There are no clinical trial data available for the effects of glycemic control in patients with advanced complications, the elderly ( 65 years of age), or young children (<13 years of age). Less stringent treatment goals may be appropriate for patients with limited life expectancies, in the very young or older adults, and in individuals with comorbid conditions. Severe or frequent hypoglycemia is an indication for the modification of treatment regimens, including setting higher glycemic goals.

More stringent goals (i.e., a normal A1C, <6%) should be considered in individual patients based on epidemiological analyses suggesting that there is no lower limit of A1C at which further lowering does not reduce the risk of complications, at the risk of increased hypoglycemia (particularly in those with type 1 diabetes). However, the absolute risks and benefits of lower targets are unknown. The risks and benefits of an A1C goal of <6% are currently being tested in an ongoing study (ACCORD [Action to Control Cardiovascular Risk in Diabetes]) in type 2 diabetes.

Elevated postchallenge (2-h OGTT) glucose values have been associated with increased cardiovascular risk independent of FPG in some epidemiological studies. Postprandial plasma glucose (PPG) levels >140 mg/dl are unusual in nondiabetic individuals, although large evening meals can be followed by plasma glucose values up to 180 mg/dl. There are now pharmacological agents that primarily modify PPG and thereby reduce A1C in parallel. Thus, in individuals who have premeal glucose values within target but who are not meeting A1C targets, consideration of monitoring PPG 1??2 h after the start of the meal and treatment aimed at reducing PPG values <180 mg/dl may lower A1C. However, it should be noted that the effect of these approaches on micro- or macrovascular complications has not been studied.

As regards goals for glycemic control for women with GDM, recommendations from the Fourth International Workshop-Conference on Gestational Diabetes suggest lowering maternal capillary blood glucose concentrations to 95 mg/dl (5.3 mmol/l) fasting, 140 mg/dl (7.8 mmol/l) at 1 h, and/or 120 mg/dl (6.7 mmol/l) at 2 h after the meal. For further information on GDM, refer to the ADA position statement.

---
AMERICAN DIABETES ASSOCIATION
DIABETES CARE, VOLUME 27, SUPPLEMENT 1, JANUARY 2004

References
1.  Bode BW (Ed.): Medical Management of Type 1 Diabetes. 4th ed. Alexandria, VA, American Diabetes Association, 2004
2.  Zimmerman BR (Ed.): Medical Management of Type 2 Diabetes. 4th ed. Alexandria, VA, American Diabetes Association, 1998
3.  Kilingensmith G (Ed.): Intensive Diabetes Management.  3rd ed.  Alexandria, VA, American Diabetes Association, 2003
4.  The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20:1183-1197, 1997
4a.World Health Organization:  Diabetes Mellitus: Report of a WHO Study Group. Geneva, World Health Org., 1985 (Tech. Rep. Ser., no. 727)
5.  The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160 - 3167, 2003
6.  Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaaniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M: Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343-1350, 2001
7.  Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV: Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: the DaQing IGT and Diabetes Study. Diabetes Care 20:537- 544, 1997
8.  The Diabetes Prevention Program Research Group:  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393- 403, 2002
9.  Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M: Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomized trial. Lancet 359:2072-2077, 2002
10.  Sjostrom L, et al: XENDOS ( Xenical in the prevention of diabetes in obese subjects):  a landmark study.  Poster presented at the International Congress on Obesity (ICO), San Paulo, Brazil, 2002
11.  Buchanan TA, Xiang AH, Peters RK, Kjos SL, Marroquin A, Goico J, Ochoa C, Tan S, Berkowitz, Hodis HN, Azen SP: Preservation of pancreatic β-cell function and prevention of type 2 diabetes by pharmacological trewatment of insulin resistance in high-risk hispanic women. Diabetes 51:2796 -2803, 2002
12.  Engelgau ME, Narayan KMV, Herman WH:  Screening for type 2 diabetes (Technical Review).  Diabetes Care 23:1563-1580, 2000 [erratum appears in Diabetes Care 23:1868 -1869, 2000]
13.  American Diabetes Association: Type 2 diabetes in children and adolescents (Consensus Statement).  Diabetes Care 23:381-389, 2000
14.  American Diabetes Association: Gestational diabetes mellitus (Position Statement). Diabetes Care 27 (Suppl. 1):S88 - S90, 2004
15.  The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of longterm complications in insulin-dependent diabetes mellitus. N Engl J Med 329: 977-986, 1993
16.  The UK 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 352: 837- 853, 1998
17.  The UK Prospective Diabetes Study Group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854 -865, 1998

May 27, 10 • Diabetes mellitus