Individualizing Glycemic Targets in Type 2 Diabetes Mellitus: Implications of Recent Clinical Trials

Case Western Reserve University, Cleveland, OH, USA.
Annals of internal medicine (Impact Factor: 17.81). 04/2011; 154(8):554-9. DOI: 10.1059/0003-4819-154-8-201104190-00007
Source: PubMed


One of the first steps in the management of patients with type 2 diabetes mellitus is setting glycemic goals. Professional organizations advise setting specific hemoglobin A(1c) (HbA(1c)) targets for patients, and individualization of these goals has more recently been emphasized. However, the operational meaning of glycemic goals, and specific methods for individualizing them, have not been well-described. Choosing a specific HbA(1c) target range for a given patient requires taking several factors into consideration, including an assessment of the patient's risk for hyperglycemia-related complications versus the risks of therapy, all in the context of the overall clinical setting. Comorbid conditions, psychological status, capacity for self-care, economic considerations, and family and social support systems also play a key role in the intensity of therapy. The individualization of HbA(1c) targets has gained more traction after recent clinical trials in older patients with established type 2 diabetes mellitus failed to show a benefit from intensive glucose-lowering therapy on cardiovascular disease (CVD) outcomes. The limited available evidence suggests that near-normal glycemic targets should be the standard for younger patients with relatively recent onset of type 2 diabetes mellitus and little or no micro- or macrovascular complications, with the aim of preventing complications over the many years of life. However, somewhat higher targets should be considered for older patients with long-standing type 2 diabetes mellitus and evidence of CVD (or multiple CVD risk factors). This review explores these issues further and proposes a framework for considering an appropriate and safe HbA(1c) target range for each patient.

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    • "Glycemic goals should be determined by individual patients' duration of disease, comorbidities, and other risk factors (Inzucchi, Bergenstal, Buse, et al., 2012; Ismail-Beigi et al., 2011). Aggressive A1C lowering in individuals with advanced type 2 diabetes only modestly reduces macrovascular complications and poses added risk for these patients (Inzucchi et al., 2012; Skyler, Bergenstal, Bonow, et al., 2009). "
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    ABSTRACT: Worldwide, both underdiagnosis and undertreatment leave many patients exposed to long periods of hyperglycemia and contribute to irreversible diabetes complications. Early glucose control reduces the risk of both macrovascular and microvascular complications, while tight control late in diabetes has little or no macrovascular benefit. Insulin therapy offers the most potent antihyperglycemic effect of all diabetes agents, and has a unique ability to induce diabetes remission when used to normalize glycemia in newly diagnosed patients. When used as a second-line therapy, basal insulin is more likely to safely and durably maintain A1C levels ≤7% than when insulin treatment is delayed. The use of basal insulin analogs is associated with a reduced risk of hypoglycemia and weight gain compared to NPH insulin and pre-mixed insulin. Patient self-titration algorithms can improve glucose control while decreasing the burden on office staff. Finally, recent data suggest that addition of incretin agents to basal insulin may improve glycemic control with very little, if any increased risk of hypoglycemia or weight gain. Copyright © 2014 Elsevier Inc. All rights reserved.
    Journal of Diabetes and its Complications 12/2014; 29(2). DOI:10.1016/j.jdiacomp.2014.11.018 · 3.01 Impact Factor
    • "For patients with limited life expectancy, advanced microor macrovascular complications or extensive comorbidity, an HbA 1c goal < 8% (64 mmol/mol) may be more appropriate [1]. Other emerging clinical policies also suggest that target HbA 1c < 8% may be appropriate for older adults with long duration of diabetes and multiple or severe comorbid conditions [26] [27]. Few long-term studies have examined the contribution of HbA 1c to mortality in a population of older patients with advanced comorbidity. "
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    ABSTRACT: Aims To examine whether hemoglobin A1c levels and comorbid conditions are related to all-cause mortality in a cohort of patients with type 1 or 2 diabetes receiving continuous care for 9 years. In patients with comorbid congestive heart failure (CHF), we test for ‘reverse epidemiology,’ or whether greater HbA1c values are associated with lower risk of mortality. Methods The population for this longitudinal cohort study was 8,820 Group Health enrollees in the Seattle area with type 1 or 2 diabetes in 1997 and enrolled continuously from 1997-2006. Comorbid conditions were hypertension, coronary artery disease, congestive heart failure, depression, and chronic pulmonary disease. Mistimed HbA1c scores were addressed by multiple imputation, and Cox proportional hazards models estimated associations controlling for other risk factors. Results About 30% of the enrollees died in 1998-2006. CHF had the strongest association with all-cause mortality. Compared to enrollees with HbA1c ≥ 7.1% (54 mmol/mol) and < 7.5% (58 mmol/mol; 5th decile), enrollees with HbA1c < 6.4% (46 mmol/mol) had a significantly greater risk of death (HR range: 1.28-2.26). HbA1c > 7.5% had HR < 1.0 but were not significant. For enrollees with diabetes and CHF at baseline, HbA1c scores ≥ 8.7% (72 mmol/mol) had a significantly lower risk of death (HR range: 0.64–0.69). Conclusions In our patient population, HbA1c scores < 6.4% have significantly higher all-cause mortality. CHF is a major determinant of all-cause mortality. Adults with comorbid CHF and high HbA1c scores have lower all-cause mortality.
    Diabetes Research and Clinical Practice 07/2014; 106(2). DOI:10.1016/j.diabres.2014.07.017 · 2.54 Impact Factor
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    • "The California Healthcare Foundation/American Geriatrics Society in collaboration with other medical organizations suggested that a reasonable HbA1c goal for “relatively” healthy elderly with good functional status should be ≤53 mmol/mol (<7%). On the contrary, for frail adults or with life expectancy <5 years, and when the risks of intensive glycemic control appear to overcome the benefits, a target HbA1c of 64 mmol/mol (8%) is suggested [54,126,127]. The U.S. Department of Veterans Affairs and the U.S. Department of Defense (VA/DOD) diabetes guidelines were updated few years ago. "
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    ABSTRACT: Type 2 diabetes mellitus (T2DM) is one of the most common chronic disorders in older adults and the number of elderly diabetic subjects is growing worldwide. Nonetheless, the diagnosis of T2DM in elderly population is often missed or delayed until an acute metabolic emergency occurs. Accumulating evidence suggests that both aging and environmental factors contribute to the high prevalence of diabetes in the elderly. Clinical management of T2DM in elderly subjects presents unique challenges because of the multifaceted geriatric scenario. Diabetes significantly lowers the chances of "successful" aging, notably it increases functional limitations and impairs quality of life. In this regard, older diabetic patients have a high burden of comorbidities, diabetes-related complications, physical disability, cognitive impairment and malnutrition, and they are more susceptible to the complications of dysglycemia and polypharmacy. Several national and international organizations have delivered guidelines to implement optimal therapy in older diabetic patients based on individualized treatment goals. This means appreciation of the heterogeneity of the disease as generated by life expectancy, functional reserve, social support, as well as personal preference. This paper will review current treatments for achieving glycemic targets in elderly diabetic patients, and discuss the potential role of emerging treatments in this patient population.
    Aging 03/2014; 6(3):187-206. · 6.43 Impact Factor
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