Letters to the Editor
Glycemic Control Is an Important Consideration in Diabetes Care
Am Fam Physician. 2014 Oct 15;90(8):524-526.
Original article: “Lending a Hand” to Patients with Type 2 Diabetes: A Simple Way to Communicate Treatment Goals
Issue date: February 15, 2014
Available at: https://www.aafp.org/afp/2014/0215/p256.html
to the editor: We appreciate the recommendations in this editorial, and agree that smoking cessation, blood pressure control, the use of metformin (Glucophage) as first-line therapy for diabetes mellitus, and the addition of statins to prevent cardiovascular events are important. However, we disagree with some of the statements regarding the importance of glycemic control. We think that the statement in Figure 1 that glycemic control has no effect on mortality or clinically relevant complications is not supported by the existing evidence.
The literature supports glycemic control (A1C less than 7%) to prevent the onset and progression of microvascular complications, which we think are clinically relevant. Glycemic control is directly associated with the onset and progression of retinopathy and nephropathy.1–5 In addition, results from the 10-year follow-up of the U.K. Prospective Diabetes Study (UKPDS) found that patients with newly diagnosed diabetes who were randomized to the intensive treatment group (sulfonylurea, insulin, or metformin) had a decreased incidence of microvascular complications, myocardial infarction, and death from any cause.3 Results of the ACCORD and ADVANCE studies indicated that patients with existing cardiovascular disease may not be candidates for intensive glycemic control.4,5 However, newly diagnosed patients without significant microvascular or macrovascular complications can benefit from glycemic control in the short term (to prevent microvascular complications) and long term (to potentially prevent myocardial infarction and death from any cause).3
As recommended in the current American Diabetes Association standards of medical care in diabetes, the goals of glycemic control must be individualized.6 Not all patients are candidates for an A1C goal of less than 7%, nor are all patients candidates for an A1C goal of less than 8% or 6.5%. Clinicians should present the potential benefits and risks of various glycemic goals to patients and practice shared decision making to determine individual goals.
Author disclosure: No relevant financial affiliations.
REFERENCESshow all references
1. Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non–insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28(2):103–117....
2. 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) [published correction appears in Lancet. 1999;354(9178):602]. Lancet. 1998;352(9131):837–853.
3. 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):1577–1589.
4. Gerstein HC, Miller ME, Byington RP, et al.; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–2559.
5. Patel A, MacMahon S, Chalmers J, et al.; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–2672.
6. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(suppl 1):S14–S80.
in reply: We thank Dr. Keeble and colleagues for their attention to our editorial and for the opportunity to clarify our approach. We wholeheartedly agree that management decisions should be tailored to each individual patient. Our model is a helpful way to rank the interventions that maximize length and quality of life for most overweight patients with type 2 diabetes.
There are four key issues pertaining to the concern about glycemic control: (1) the difference between disease-oriented and patient-oriented outcomes; (2) the types of cited studies; (3) our focus on overweight patients with diabetes; and (4) the harm associated with excessive glycemic reduction.
First, the UKPDS showed that only one of its 21 composite outcomes was significantly affected by intensive glycemic control: laser photocoagulation rates. Vision loss—the outcome that matters most—was not affected.1 Photocoagulation rates are an excellent example of disease-oriented evidence, which supports interventions that affect intermediate outcomes, but not patient-oriented outcomes such as morbidity and mortality.
Second, many studies that support glycemic reduction are invalid. Although the 10-year follow-up of UKPDS showed a reduction in macrovascular events and mortality, it was an open-label follow-up and, thus, prone to bias.1 In addition, subsequent high-quality studies have not shown a reduction in all-cause mortality,2,3 but have shown an increased risk of severe complications of hypoglycemia.3,4
Third, our article specifically addressed the care of U.S. patients with type 2 diabetes who have a body mass index greater than 25 kg per m2. In the Japanese study cited by Dr. Keeble and colleagues, the average body mass index was 19 kg per m2.5 The 10-year follow-up of UKPDS showed a benefit from glycemic control partially because the study included nonobese patients who do benefit from insulin therapy.1 When only overweight patients were included, there was no benefit.
Finally, our primary concern is the significant increase in mortality associated with insulin therapy once the A1C falls below 7.5%.4 We are disappointed that national organizations still recommend pharmaceutically lowering blood glucose levels despite evidence that fails to show benefit and instead demonstrates potential harm.
The reason we based our model on a hand is that regardless of whether aggressive glycemic reduction is beneficial in overweight patients with type 2 diabetes—and the best evidence strongly suggests that it is not—clinicians must spend their time with patients focusing on the other life-prolonging “fingers” of diabetes care. Poor control of hypertension is associated with high blood glucose levels, meaning that clinicians spend too much time on the “pinky” of glycemic control and not enough time on blood pressure control.6
Let's stop reversing the hand and start saving lives.
Author disclosure: No relevant financial affiliations.
REFERENCESshow all references
1. 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):1577–1589....
2. Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ. 2011;343:d4169.
3. Hemmingsen B, Lund SS, Gluud C, et al. Intensive glycaemic control for patients with type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ. 2011; 343:d6898.
4. Currie CJ, Peters JR, Tynan A, et al. Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet. 2010;375(9713):481–489.
5. Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non–insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28(2):103–117.
6. Bolen SD, Samuels TA, Yeh HC, et al. Failure to intensify antihypertensive treatment by primary care providers: a cohort study in adults with diabetes mellitus and hypertension. J Gen Intern Med. 2008;23(5):543–550.
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