Type 2 Diabetes Glucose Management Goals

Type 2 Diabetes Glucose Management Goals

Optimal management of type 2 diabetes requires treatment of the “ABCs” of diabetes: A1C, blood pressure, and cholesterol (ie, dyslipidemia). This web page provides the rationale and targets for glucose management; AACE guidelines for blood pressure and lipid control are summarized in Management of Common Comorbidities of Diabetes.

Glucose Targets

Glucose goals should be established on an individual basis for each patient, based on consideration of both clinical characteristics and the patient's psychosocioeconomic circumstances.1 Accordingly, AACE recommends individualized glucose targets (Table 1) that take into account the following factors2:

  • Life expectancy
  • Duration of diabetes
  • Presence or absence of microvascular and macrovascular complications
  • Comorbid conditions including CVD risk factors
  • Risk for development of or consequences from severe hypoglycemia
  • Patient's social, psychological, and economic status

Table 1. AACE-Recommended Glycemic Targets for Nonpregnant Adults2


Treatment Goal

Hemoglobin A1C

Individualize on the basis of age, comorbidities, and duration of disease

  • ≤6.5 for most
  • Closer to normal for healthy
  • Less stringent for “less healthy”

Fasting plasma glucose (FPG)

<110 mg/dL

2-hour postprandial glucose (PPG)

<140 mg/dL

The American Diabetes Association (ADA) also recommends individualizing glycemic targets (Table 2) based on patient-specific characteristics3:

  • Patient attitude and expected treatment efforts
  • Risks potentially associated with hypoglycemia as well as other adverse events
  • Disease duration
  • Life expectancy
  • Important comorbidities
  • Established vascular complications
  • Resources and support system

Table 2. ADA-Recommended Glycemic Targets for Nonpregnant Adults4


Treatment Goal

Hemoglobin A1C

  • <7.0 for most
  • <6.5% for “healthy”
  • Short duration of diabetes
  • Long life expectancy
  • No significant CVD
  • No significant hypoglycemia or other adverse effects of treatment
  • <8.0% for "less healthy"
  • History of severe hypoglycemia
  • Limited life expectancy
  • Advanced complications
  • Extensive comorbid conditions
  • Long-standing, difficult-to-control diabetes

Fasting plasma glucose (FPG)

80-130 mg/dL

2-hour postprandial glucose (PPG)

<180 mg/dL

Evidence and Rationale for Recommended Glucose Targets

The AACE and ADA recommendations are based on findings from 4 major clinical trials in type 2 diabetes mellitus (T2DM) and 1 trial in type 1 diabetes mellitus (T1DM), as listed in Table 3.

Table 3. Major Diabetes Trials

T2DM Trials

T1DM Trials

  • United Kingdom Prospective Diabetes Study (UKPDS)5 and Post-trial Monitoring6
  • Action to Control Cardiovascular Risk in Diabetes (ACCORD)7-9
  • Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-release Control Evaluation (ADVANCE)10
  • Veterans Affairs Diabetes Trial (VADT)11
  • Diabetes Control and Complications Trial (DCCT)12 and DCCT Epidemiology of Diabetes Interventions and Complications (EDIC)13

The main message from these trials is that improved glycemic control is associated with significant reductions in the risk of microvascular complications in all types of patients and with reduced long-term risk of macrovascular disease in younger patients with a short duration of diabetes (either newly diagnosed T2DM or T1DM diagnosed within 5 years of study entry) whose glycemia was intensively controlled soon after diagnosis.5,6,8-10,12,13 In older patients with a longer duration of T2DM and/or multiple cardiovascular risk factors, intensive glucose control did not significantly reduce the risk of macrovascular disease or mortality.7,10,11 However, it may not be surprising that it has been difficult to demonstrate improved CVD outcomes with modest improvements in glycemia in subjects who have had intensive treatment of blood pressure and dyslipidemia.14

Glucose control aimed at normal (or near-normal) glycemia may be considered for adults with recent onset of T2DM and no clinically significant CVD, with the aim of preventing the development of microvascular and macrovascular complications over a lifetime, if it can be achieved without substantial hypoglycemia or other unacceptable adverse consequences. Although it is uncertain that the clinical course of established CVD is improved by strict glycemic control in the average patient with type 2 diabetes, the progression of microvascular complications is clearly reduced. A less stringent goal (A1C 7% to 8%) may be considered for individuals with history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions, or long-standing diabetes in which the general goal has been difficult to attain despite intensive efforts, including diabetes self-management education, intensive lifestyle recommendations, and optimal use of available antihyperglycemic medications.2

Microvascular Complications

Reducing hyperglycemia is the primary means of preventing the microvascular complications of diabetes, although treating elevated blood pressure (when present) is also vital for microvascular risk reduction.2 Hyperglycemia damages tissues via at least 4 mechanisms15:

  • Increased polyol pathway flux
  • Increased advanced glycation end-product (AGE) formation
  • Activation of protein kinase C (PKC) isoforms
  • Increased hexosamine pathway flux

Each of these pathogenic mechanisms results from overproduction of reactive oxygen species (ROS) at a cellular level. In brief, excess glucose increases the amount of electrons that pass through mitochondria in endothelial cells, which in turn increases production of superoxide (a major ROS). The resulting oxidative stress contributes to the development of both microvascular and macrovascular complications of diabetes.15

Diabetic Kidney Disease

Diabetic kidney disease (DKD; or diabetic nephropathy) is the leading cause of kidney failure in the United States and affects approximately 40% of patients with diabetes.16,17 In addition, patients with both diabetes and kidney disease have a 2- to 3-fold higher risk of cardiovascular complications and death relative to patients who have diabetes but normal kidney function.18,19

DKD results from an interplay between hyperglycemia, increased levels of angiotensin II, and increased blood pressure in genetically susceptible individuals (family history of nephropathy is critical). These factors collectively increase oxidative stress, proinflammatory cytokines, and mechanical injury from hemodynamic stress.20-22 Key features of the resulting damage include21:

  • Accumulation of matrix in the mesangial area, which reduces the capillary surface area available for filtration
  • Nephron dropout due to tubulointerstitial fibrosis
  • Dysfunction of the glomerular endothelium
  • Thickening of the glomerular basement membrane (GBM)
  • Podocyte injury

These changes occur more or less in concert with each other. Collectively, they lead to a progressive breakdown in the glomerular filtration barrier, which increases the permeability of renal tissues to proteins. Increasing proteinuria further exacerbates the damage caused by hyperglycemia, angiotensin II, and hypertension, progressively worsening renal function.21

From a clinical perspective, DKD is characterized by an initial period of hyperfiltration, which in a subgroup of genetically susceptible individuals is followed by a declining glomerular filtration rate (GFR) and proteinuria that increases to a varying degree.23,24 Starting at diagnosis of T2DM, annual assessment of serum creatinine to estimate GFR and a spot urine albumin:creatinine ratio should be performed to identify, stage, and monitor disease progression.2,24,25

Recently, the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) endorsed the effort by Kidney Disease: Improving Global Outcomes (KDIGO) to update the classification system for kidney disease severity (Table 4). While the thresholds for both estimated GFR and albuminuria remain unchanged in the new classification, 3 albuminuria stages have been added to enhance the GFR stages. Stage 3 CKD has also been subdivided at an estimated GFR of 45 mL/min per 1.73 m2, and there is a new emphasis on clinical diagnosis in addition to GFR and albuminuria stages.25 It is also important to remember that patients may have developed chronic kidney disease (CKD) prior to onset of T2DM—nearly 18% of patients with prediabetes have CKD.17

Table 4. KDIGO Chronic Kidney Disease Classification—Composite Ranking for Relative Risks25





Albuminuria stages(mg/g)












Optimal and high normal


Very high and nephrotic










GFR stages
(mL/min per 1.73 m2 body surface area)


High and optimal


Very low

Very low



Very high





Very low

Very low



Very high



Mild to moderate






Very high


Moderate to severe






Very high








Very high


Kidney failure


Very high

Very high

Very high

Very high

Very high

Neither a spot urine albumin level without simultaneous measurement of urine creatinine, nor measurement of serum creatinine alone, should be used for screening. By themselves, spot urine albumin tests are suboptimal and fraught with errors because albumin excretion can be increased by exercise, febrile illness, urinary tract infection, hematuria, severe hypertension, heart failure, and even high-grade hyperglycemia. Therefore, it is prudent to confirm albuminuria status with repeated testing before establishing a firm basis for therapeutic intervention for diabetic nephropathy. Ideally, 3 (minimum of 2) separate spot urines should be collected to evaluate the albumin to creatinine ratio over several days, with the result determined by the mean value. Serum creatinine alone is also an inaccurate measure of kidney function and should only be used with a GFR-estimating equation such as the Modification of Diet in Renal Disease (MDRD) equation. Many laboratories now routinely report the estimated GFR, and the National Institutes of Health also has GFR calculators.2

Prevention of the development or progression of diabetic nephropathy includes optimal control of plasma glucose (A1C <7%) and blood pressure (<130/80 mm Hg), inhibition of the renin-angiotensin-aldosterone system (RAAS), and modification of other risk factors such as smoking and hyperlipidemia. Antihypertensive drugs that block RAAS—namely angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs)—provide nephroprotective benefits beyond their blood pressure–lowering effects. When therapy with one of these agents is initiated, renal function and serum potassium levels must be closely monitored.2 Nondihydropyridine calcium channel blockers (CCBs; eg, diltiazem or verapamil) will help further reduce albuminuria.26 ACE inhibitors or ARBs should not be combined with aliskiren, an orally active direct renin inhibitor. Such combinations are contraindicated due to an increased risk of renal impairment, hypotension, and hyperkalemia in patients with diabetes.27

In general, patients with stage 1-2 DKD should consume no more than the recommended daily allowance of protein (0.8 g/kg per day), and further protein restriction (0.6-0.8 g/kg per day) may be beneficial in slowing GFR decline in patients with more severe DKD (stages 3-4).2,24

Prompt referral to a nephrologist is indicated when the diagnosis of diabetic nephropathy is in doubt (eg, patients with nonclassic presentation, suspected IgA nephropathy, rapidly worsening nephropathy, or active urinary sediment). Patients with advanced or severe kidney disease (estimated GFR <30 mL/min/1.73 m2) also should be cared for in consultation with a nephrologist to delay the progression of nephropathy for as long as possible, unless the T2DM caregiver is adept at delivering optimal management of risk factors for worsening nephropathy, such as hyperglycemia, hypertension, and dyslipidemia.2 Evidence suggests that referral of patients with stage 4 CKD to a nephrologist is cost-effective and delays the time to dialysis treatment.28 Patients with stage 5 CKD require renal replacement therapy. Mortality while receiving such therapy is higher in patients with diabetes than in patients without diabetes, largely because of CVD complications.29 Renal transplantation is the preferred replacement therapy for T2DM patients who have end-stage kidney disease because long-term outcomes are superior to those achieved with dialysis.2


Diabetic retinopathy is the leading cause of blindness in adults in the United States.16 About 30% of patients with newly diagnosed T2DM may have some evidence of diabetic retinopathy, and the prevalence increases with duration and severity of disease—among insulin users with T2DM, approximately two-thirds may have retinopathy.30

There are 4 main types of diabetic retinopathy lesions, which increase in severity2:

  • Background or nonproliferative retinopathy
  • Macular edema
  • Preproliferative retinopathy
  • Proliferative retinopathy

The rates of more severe retinopathy increase with the duration of T2DM. In the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) study, macular edema was found in 3% of patients within 5 years of diagnosis, but in 28% after 20 years duration.16,30,31 Therefore, the goal is to detect clinically significant retinopathy before vision is threatened, and both AACE and the ADA recommend referral to an experienced ophthalmologist for an annual dilated eye examination starting at diagnosis of T2DM.2,4 Patients with active lesions may be followed up more frequently, while those who have had repeatedly normal eye findings can be seen less frequently. The complete ophthalmologic examination can also detect other common conditions such as cataracts, glaucoma, and macular degeneration.2


Diabetic neuropathy encompasses multiple disorders involving proximal, distal, somatic, and autonomic nerves (Table 5). The majority, and possibly all, T2DM patients have at least mild nerve damage, which may present as acute and self-limiting or a chronic, indolent condition.2,16 In addition to those with T2DM, patients with metabolic syndrome and prediabetes are at risk for various neuropathies, which develop as a result of oxidative stress and inflammation.2,36 Optimal control of glucose, lipids, and blood pressure are essential to the management of all forms of diabetic neuropathy.2

Table 5. Diabetic Neuropathies: Key Characteristics and Management Recommendations2



Clinical Features




Single nerve involvement



  • Carpal tunnel syndrome
  • Proximal lumbosacral
  • Thoracic
  • Cervical radiculoplexus neuropathies involving the proximal limb girdle

Inflammatory demyelinating conditions


Distal neuropathy

Large-fiber sensorimotor polyneuropathy

Symmetric, glove and stocking distribution with

  • Loss of sensation
  • Poor coordination
  • Ataxia

Low-impact activities that improve muscular strength and coordination and challenge the vestibular system

  • Pilates
  • Yoga
  • Tai chi

Small-fiber neuropathy

Symmetric, glove and stocking distribution with

  • Loss of sensation
  • Pain
  • Autonomic features

Protect insensate feet from ulceration

  • Padded socks
  • Daily inspection by patient
  • Moisturizing lotions

Treat neuropathic pain

  • Amitriptyline
  • Gabapentin
  • Pregabalin
  • Duloxetine
  • Topical lidocaine




  • Tachycardia
  • Exercise intolerance
  • Orthostatic hypotension, weakness, fatigue, syncope

Associated with significant mortality and possibly also

  • Silent myocardial ischemia
  • Coronary artery disease
  • Stroke
  • Diabetic nephropathy progression
  • Perioperative morbidity

Intensive control of CV risk factors


For tachycardia, exercise intolerance:

  • Supervised exercise
  • ACE inhibitors
  • b-adrenergic blockers

For hypotension, weakness, etc:

  • Mechanical measures
  • Clonidine
  • Midodrine
  • Octreotide
  • Erythropoietin



Gastroparesis, erratic glucose control

Frequent small meals
Prokinetic agents

  • Metoclopramide
  • Domperidone
  • Erythromycin



Abdominal pain, early satiety, nausea, vomiting, bloating, belching

Bulking agents
Tricyclic antidepressants
Pyloric Botox
Gastric pacing




High-fiber diet
Bulking agents
Osmotic laxatives
Lubricating agents



Diarrhea (often nocturnal, alternating with constipation)

Soluble dietary fiber
Gluten and lactose restriction
Anticholinergic agents
Pancreatic enzyme supplements


Sexual dysfunction

Erectile dysfunction

Sex therapy
Psychological counseling
5′-phosphodiesterase inhibitors
Prostaglandin E1 injections



Vaginal dryness

Vaginal lubricants


Bladder dysfunction

Frequency, urgency, nocturia, urinary retention, incontinence

Intermittent catheterization


Sudomotor dysfunction

Heat intolerance
Dry skin

Emollients and skin lubricants
Botulinum toxin


Pupillomotor and visceral dysfunction

Vision blurring
Impaired light adaptation to ambient light
Argyll-Robertson pupil

Care with driving at night



Impaired visceral sensation

  • Silent myocardial infarction
  • Hypoglycemia unawareness

Control of risk factors
Control of plasma glucose levels

Each type of neuropathy is diagnosed according to specific criteria and tests too numerous to list here. More detail can be found in the 2011 AACE Medical Guidelines for Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan as well as other reviews.2,37

Macrovascular Complications

Hyperglycemia increases CVD both directly and by indirect effects on other cardiovascular risk factors.2 Diabetes is considered a cardiovascular risk equivalent, because the risk of a cardiovascular event is roughly the same for patients with diabetes but without a history of CVD as for patients without diabetes but with a prior event.38,39 Nevertheless, the beneficial effects of intensive glycemic control in reducing vascular complications may be considered to be inversely related to the extent of vascular disease at the time it is initiated.14 Evidence from the DCCT and UKPDS follow-up studies suggests that intensive glucose control in younger, healthier patients without cardiovascular disease significantly reduces the risk of developing macrovascular complications later in life; this is known as the legacy effect or metabolic memory.6,13 However, as mentioned, in older patients with T2DM and existing CVD or extensive risk factors, intensive glucose control has not provided a significant benefit, and patients with long-standing, very difficult-to-control glycemia may be at even greater risk from intensive therapy.7,10,11,40 For these reasons, glucose control goals must be set individually, as described above, and macrovascular risk reduction should focus on treatment of other cardiovascular risk factors2:


  1. 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;154:554-559.
  2. Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17 Suppl 2:1-53.
  3. 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;35:1364-1379.
  4. American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care. 2013;36(suppl 1):S11-66.
  5. 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. 1998;352:837-853.
  6. 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;359:1577-1589.
  7. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2559.
  8. Ismail-Beigi F, Craven T, Banerji MA, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376:419-430.
  9. Chew EY, Ambrosius WT, Davis MD, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010;363:233-244.
  10. 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;358:2560-2572.
  11. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129-139.
  12. The 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 Engl J Med. 1993;329:977-986.
  13. 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;353:2643-2653.
  14. Skyler JS, Bergenstal R, Bonow RO, et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Diabetes Care. 2009;32:187-192.
  15. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813-820.
  16. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2011.
  17. Plantinga LC, Crews DC, Coresh J, et al. Prevalence of chronic kidney disease in US adults with undiagnosed diabetes or prediabetes. Clin J Am Soc Nephrol. 2010;5:673-682.
  18. Foley RN, Murray AM, Li S, et al. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol. 2005;16:489-495.
  19. Collins AJ, Li S, Gilbertson DT, Liu J, Chen SC, Herzog CA. Chronic kidney disease and cardiovascular disease in the Medicare population. Kidney Int Suppl. 2003:S24-31.
  20. Lai KN, Leung JC, Tang SC. The renin-angiotensin system. Contrib Nephrol. 2011;170:135-144.
  21. Remuzzi G, Bertani T. Pathophysiology of progressive nephropathies. N Engl J Med. 1998;339:1448-1456.
  22. Wolf G, Chen S, Ziyadeh FN. From the periphery of the glomerular capillary wall toward the center of disease: podocyte injury comes of age in diabetic nephropathy. Diabetes. 2005;54:1626-1634.
  23. Radbill B, Murphy B, LeRoith D. Rationale and strategies for early detection and management of diabetic kidney disease. Mayo Clin Proc. 2008;83:1373-1381.
  24. Levin A, Rocco M. KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. American Journal of Kidney Diseases. 2007;49:S12-S154.
  25. Levey AS, de Jong PE, Coresh J, et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int. 2011;80:17-28.
  26. National Kidney Foundation. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43:S1-290.
  27. Food and Drug Administration. FDA Drug Safety Communication: new warning and contraindication for blood pressure medicines containing aliskiren (Tekturna).  Rockville, MD: US Department of Health and Human Services; 2012; Available from: http://www.fda.gov/Drugs/DrugSafety/ucm300889.htm.
  28. Levinsky NG. Specialist evaluation in chronic kidney disease: too little, too late. Ann Intern Med. 2002;137:542-543.
  29. Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341:1725-1730.
  30. Williams R, Airey M, Baxter H, Forrester J, Kennedy-Martin T, Girach A. Epidemiology of diabetic retinopathy and macular oedema: a systematic review. Eye (Lond). 2004;18:963-983.
  31. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology. 1984;91:1464-1474.
  32. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405-412.
  33. Adler AI, Stratton IM, Neil HA, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000;321:412-419.
  34. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317:703-713.
  35. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119:789-801.
  36. Figueroa-Romero C, Sadidi M, Feldman EL. Mechanisms of disease: the oxidative stress theory of diabetic neuropathy. Rev Endocr Metab Disord. 2008;9:301-314.
  37. Vinik A. Diabetic neuropathy in older adults. In: Pathy MSJ, Sinclair AJ, Morley JE, editors. Principles and Practice of Geriatric Medicine. Hoboken, NJ: Wiley; 2010.
  38. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227-239.
  39. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229-234.
  40. Riddle MC, Ambrosius WT, Brillon DJ, et al. Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes Care. 2010;33:983-990.