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 psycho-socioeconomic circumstances.1-3 Accordingly, AACE recommends individualized glucose targets (Table 1) that take into account the following factors1,2:

  • 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 Adults1,2


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 Adults3


Treatment Goal

Hemoglobin A1C

  • <6.5% for patients who meet the following criteria:
    • Short duration of diabetes
    • Long life expectancy
    • No concurrent illness
    • Goal can be achieved without significant hypoglycemia or other adverse effects of treatment
  • <7.0%, a reasonable goal for many patients
  • <8.0% for patients who meet the following criteria:
    • History of severe hypoglycemia
    • Limited life expectancy
    • Advanced microvascular or macrovascular complications
    • Extensive comorbid conditions
    • Long-standing T2D in which A1C goal has been difficult to obtain despite intensive efforts

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 (T2D) and 1 trial in type 1 diabetes (T1D), as listed in Table 3.

Table 3. Major Diabetes Trials

T2D Trials

T1D Trials

  • United Kingdom Prospective Diabetes Study (UKPDS)4 and Post-trial Monitoring5
  • Action to Control Cardiovascular Risk in Diabetes (ACCORD)6-8
  • Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-release Control Evaluation (ADVANCE)9
  • Veterans Affairs Diabetes Trial (VADT)10,11
  • Diabetes Control and Complications Trial (DCCT)12 and DCCT Epidemiology of Diabetes Interventions and Complications (EDIC)13

The main message from this accumulated evidence is that improved glycemic control is associated with significant reductions in the risk of microvascular complications in the short-term and with reduced long-term risk of macrovascular disease, particularly if A1C can be reduced without incurring significant hypoglycemia. More recent evidence from randomized, placebo-controlled, cardiovascular outcomes studies of the sodium glucose cotransporter 2 (SGLT2) inhibitors canagliflozin and empagliflozin and the glucagon-like peptide 1 (GLP1) receptor agonist liraglutide have shown that treatment with these agents can reduce mortality in patients with type 2 diabetes (see Clinical Outcomes with Newer Antihyperglycemic Agents: FDA-Mandated CV Safety Trials).14-16

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.1,2 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.17

Diabetic Kidney Disease

Diabetic kidney disease (DKD; or diabetic nephropathy) is the leading cause of kidney failure in the United States and affects approximately 37% of patients with diabetes.18 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.19,20

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.21-23 Key features of the resulting damage include22:

  • 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.22

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.24,25 Starting at diagnosis of T2D, 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.2,25-27

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.27 It is also important to remember that patients may have developed chronic kidney disease (CKD) prior to onset of T2D—nearly 18% of patients with prediabetes have CKD.28

Table 4. KDIGO Chronic Kidney Disease Classification—Composite Ranking for Relative Risks27





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

Serum creatinine alone is 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 2

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 2) also should be cared for in consultation with a nephrologist to delay the progression of nephropathy for as long as possible, unless the T2D caregiver is adept at delivering optimal management of risk factors for worsening nephropathy, such as hyperglycemia, hypertension, and dyslipidemia.2 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 T2D 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.30 About 30% of patients with newly diagnosed T2D may have some evidence of diabetic retinopathy, and the prevalence increases with duration and severity of disease—among insulin users with T2D, approximately two-thirds may have retinopathy.31

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 T2D. 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.32 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 T2D.2,33 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.2,33


Diabetic neuropathy encompasses multiple disorders involving proximal, distal, somatic, and autonomic nerves (Table 5). The majority, and possibly all, T2D patients have at least mild nerve damage, which may present as acute and self-limiting or a chronic, indolent condition.2,33 In addition to those with T2D, patients with metabolic syndrome and prediabetes are at risk for various neuropathies, which develop as a result of oxidative stress and inflammation.2,34 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





Resting tachycardia, exercise intolerance

HRV, MUGA thallium scan, MIBG scan

Graded supervised exercise, ACE inhibitors, β-adrenergic blockers

Exercise bradycardia, exercise intolerance

HRV, MUGA thallium scan, MIBG scan, Dopamine levels and scans

Graded supervised exercise, dopaminergic agonists

Postural hypotension, dizziness, weakness, fatigue, syncope

HRV, supine and standing blood pressure, catecholamines

Mechanical measures, clonidine, midodrine, octreotide, erythropoietin


Gastroparesis, erratic glucose control

Gastric emptying study, barium study

Frequent small meals, prokinetic agents (metoclopramide, domperidone; erythromycin; lubiprostone; linaclotide; oral gastric analgesics; the combination of atropine, hyoscyamine, phenobarbital, and scopolamine; Maalox; and viscous xylocaine)

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

Endoscopy, manometry, electrogastrogram

Antibiotics, antiemetics, bulking agents, tricyclic antidepressants, pyloric botulinum toxin, 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, cholestyramine, antibiotics, somatostatin, pancreatic enzyme supplements

Sexual Dysfunction

Erectile dysfunction

H&P, HRV, penile-brachial pressure index, nocturnal penile tumes

Sex therapy, psychological counseling, 5'-phosphodiesterase inhibitors, prostaglandin E1 injections, devices, or prostheses

Vaginal dryness


Vaginal lubricants

Bladder Dysfunction

Frequency, urgency, nocturia, urinary retention, incontinence

Cystometrogram, postvoiding sonography

Bethanechol, intermittent catheterization

Sudomotor Dysfunction

Anhidrosis, heat intolerance, dry skin, hyperhidrosis

Quantitative sudomotor axon reflex, sweat test, sudorimetry, skin blood flow

Emollients and skin lubricants, scopolamine, glycopyrrolate, botulinum toxin, vasodilators, arginine supplementation

Pupillomotor and Visceral Dysfunction

Vision blurring, impaired light adaptation to ambient light, Argyll-Robertson pupil

Pupillometry, HRV

Care with driving at night

Impaired visceral sensation: silent myocardial infarction, hypoglycemia unawareness

Physical assessment, medical history

Recognition of unusual presentation of myocardial infarction, control of risk factors, control of plasma glucose levels

Abbreviations: ACE = angiotensin-converting enzyme; HRV = heart rate variability; MIBG = metaiodobenzylguanidine; MUGA = multiunit gated blood pool.

Each type of neuropathy is diagnosed according to specific criteria and tests too numerous to list here. More detail can be found in the American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for Developing a Diabetes Mellitus Comprehensive Care Plan—2015.2

Macrovascular Complications

CVD and CVD mortality is increased two- to threefold in patients with diabetes,35-38 and studies have demonstrated equivalent rates of myocardial infarction in persons with diabetes but without CVD as in people without diabetes who have had a prior cardiovascular event.39-41

It is difficult to quantitatively define the factors responsible for DM being a CVD risk factor because insulin resistance, hypertension, lipid abnormalities, endothelial dysfunction, inflammation, and procoagulant factors are all present in patients with T1D and T2D, as well as in those with less severe forms of hyperglycemia.2 As mentioned above, intensive glucose control, as well as some specific antihyperglycemic therapies, have been shown to reduce the risk of macrovascular disease, especially over the long term.5-16

The treatment of other cardiovascular risk factors is also crucial for macrovascular risk reduction, especially in the near-term1,2,42:


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