There are extensive data from long-term, prospective, randomized clinical trials showing that improved glycemic control in type 2 diabetes reduces the incidence and progression of diabetic complications. The largest and most recent trial to address this is the United Kingdom Prospective Diabetes Study (UKPDS), which reported its findings in 1998. In this trial, approximately 4,000 newly diagnosed diabetic patients were followed for an average of 10 years, and improvements in microvascular outcomes were demonstrated with intensive diabetes control (HbA1c ~7.0%) compared with conventional control (HbA1c ~7.9%).
Treatment arms in the study included insulin, sulfonylurea, or metformin monotherapy, or combination therapy with metformin and sulfonylurea. Improved cardiovascular outcomes reached statistical significance only in the metformin monotherapy subgroup, implying that an agent that has some effects on insulin sensitivity may offer unique benefit in improving cardiovascular outcomes. The thiazolidinediones, which affect insulin sensitivity to an even greater extent than metformin, were not available at the inception of the UKPDS, and were thus not treatment options in the study.
Another important outcome of the UKPDS was the observation that all treatment groups, independent of treatment option, showed gradual and similar deterioration of glycemic control over time. This decrease in glycemic control was interpreted to result from progression of diabetes; when analyzed with the Homeostasis Model Assessment (HOMA), a computer-generated model of insulin-glucose interactions, it was found to specifically result from a decline in beta-cell insulin secretion. This is particularly relevant with regard to the thiazolidinediones, since they are the only diabetes agents that have been shown to preserve beta cell function. Thus, they may have unique potential to delay the progression of type 2 diabetes.
Based on the above and additional data, the American Diabetes Association (ADA) annually reviews its recommendations regarding standards of care for glycemic and lipid goals in patients with diabetes. In brief, the recommendations are to aim for glycemic control as near to the normal range as possible, without producing unacceptably frequent hypoglycemia, and to achieve intensive lipid control with the same targets as for patients with established coronary heart disease.The most recent recommendations are summarized in Tables 1 and 2.
| Table 1. ADA Recommended Standards of Glycemic Control* | |||
| Normal | Goal | Additional Action Suggested** | |
| Whole Blood Values | |||
| Average preprandial glucose (mg/dL)† | <100 | 80-120 | <80 / >140 |
| Average bedtime glucose (mg/dL)† | <110 | 100-140 | <100 / >160 |
| Plasma Values | |||
| Average preprandial glucose (mg/dL)‡ | <110 | 90-130 | <90 / >150 |
| Average bedtime glucose (mg/dL)‡ | <120 | 110-150 | <100 / >180 |
| HbA1c(%) | <6 | <7 | >8 |
*Adapted from the Position Statement on Standards of Medical Care for Patients with Diabetes Mellitus
**The values shown in this table are generalized to the entire population of individuals with diabetes. Patients with comorbid diseases, the very young and older adults, and others with unusual conditions or circumstances may warrant different treatment goals. These values are for nonpregnant adults. “Additional action suggested” depends on individual patient circumstances and may include enhanced diabetes self-management education, comanagement with a diabetes team, referral to an endocrinologist, change in pharmacological therapy, initiation of or increase in self-monitoring of blood glucose, or more frequent contact with the patient. HbA1c is referenced to a nondiabetic range of 4.0-6.0% (mean 5.0%, SD 0.5%).
†Measurement of capillary blood glucose; ‡Values calibrated to plasma glucose.
| Table 2. ADA Recommended Standards of Lipid Control* | ||||
| Risk | LDL Cholesterol | HDL Cholesterol | Triglycerides | |
| (men) | (women) | |||
| High | >130 | <35 | <45 | >400 |
| Borderline | 100-129 | 35-45 | 45-55 | 200-399 |
| Low | <100 | >45 | >55 | <200 |
Data are given in milligrams per deciliter.
*Adapted from the Position Statement on Standards of Medical Care for Patients with Diabetes Mellitus