HEMOGLOBIN A1C TRIALS

  • Severe low blood sugar episodes (hypoglycemia) were more common in the intensive group in all the trials
  • Average length of time subjects had been diagnosed with diabetes upon enrollment: UKPDS < 1 year; ACCORD 10 years; ADVANCE 8 years; VADT 12 years [3]
  • Kidney disease defined as incidence of proteinuria. For kidney failure, there was no significant difference between intensive and standard therapy in any of the trials. [4]
  • The following is a synopsis of 4 large trials that compared significant clinical outcomes in Type 2 diabetics

    • In each trial, patients were divided into 2 groups:
      • 1. Intensive treatment - group with a lower A1C goal, typically ≤ 7%
      • 2. Standard treatment - group with A1C goal around 7 - 8%
  • Legend:
    • Intensive A1C = average A1C achieved in intensive therapy group
    • Standard A1C = average A1C achieved in standard treatment group
    • I = Intensive therapy group was significantly better
    • S = Standard therapy group was significantly better
    • NS = No Significant difference between groups
Trial
(trial length)
Intensive
A1C
Standard
A1C
Overall
mortality
Heart
disease
Eye
disease
Kidney
disease
Neuropathy
UKPDS
(11 yrs)
7.0 7.9 NS NS I I I
ACCORD
(3.5 yrs)
6.4 7.5 S S I I I
ADVANCE
(5 yrs)
6.4 7.0 NS NS NS I NS
VADT
(5.6 yrs)
6.9 8.5 NS NS NS I NS

















  • Severe low blood sugar episodes (hypoglycemia) were more common in the intensive group in all the trials
  • Average length of time subjects had been diagnosed with diabetes upon enrollment: UKPDS < 1 year; ACCORD 10 years; ADVANCE 8 years; VADT 12 years [3]
  • Kidney disease defined as incidence of proteinuria. For kidney failure, there was no significant difference between intensive and standard therapy in any of the trials. [4]
  • The following is a synopsis of 4 large trials that compared significant clinical outcomes in Type 2 diabetics

    • In each trial, patients were divided into 2 groups:
      • 1. Intensive treatment - group with a lower A1C goal, typically ≤ 7%
      • 2. Standard treatment - group with A1C goal around 7 - 8%
  • Legend:
    • Intensive A1C = average A1C achieved in intensive therapy group
    • Standard A1C = average A1C achieved in standard treatment group
    • I = Intensive therapy group was significantly better
    • S = Standard therapy group was significantly better
    • NS = No Significant difference between groups
Trial
(trial length)
Intensive
A1C
Standard
A1C
Overall
mortality
Heart
disease
Eye
disease
Kidney
disease
Neuropathy
UKPDS
(11 yrs)
7.0 7.9 NS NS I I I
ACCORD
(3.5 yrs)
6.4 7.5 S S I I I
ADVANCE
(5 yrs)
6.4 7.0 NS NS NS I NS
VADT
(5.6 yrs)
6.9 8.5 NS NS NS I NS





Reference [36]
A1C values (%) Average blood sugar
(mg/dl)
5 97
6 126
7 154
8 183
9 212
10 240
11 269
12 298
13 326
14 355
15 384










  • Reference [43]
Small nerve fibers
Function
  • Pain sensation (nociception)
  • Hot/cold sensation
Symptoms
  • Pain, burning, electric shocks, tingling
  • Exaggerated response to painful stimuli (hyperalgesia)
  • Pain from minimal contact (e.g. socks, shoes, bed sheets) (allodynia)
  • Pain is typically worse at night
Exam findings
  • Loss of thermal discrimination (hot/cold)
  • Loss of pinprick sensation
  • Hyperalgesia

  • Reference [43]
Large nerve fibers
Function
  • Pressure
  • Balance and position sense (proprioception)
Symptoms
  • Numbness
  • Tingling
  • Poor balance
Exam findings
  • Loss of ankle reflexes
  • Loss of sense of vibration
  • Loss of proprioception
  • Loss of light touch sensation (10-g monofilament)


  • Reference [43]
System Symptoms
Cardiovascular
  • Resting tachycardia
  • Orthostatic hypotension
  • Abnormal blood pressure regulation
  • Hypoglycemia unawareness
Gastrointestinal
  • Gastroparesis
  • Esophageal dysfunction (dysphagia, GERD)
  • Diarrhea and constipation
  • Fecal incontinence
  • Hypoglycemia unawareness
Urogenital
  • Bladder dysfunction (incontinence, frequency, etc.)
  • Erectile dysfunction
  • Female sexual dysfunction
Sudomotor (sweat glands)
  • Gustatory sweating (face and neck sweating when eating)
  • Dry skin
  • Hypoglycemia unawareness











  • Lipid levels should be monitored annually or as needed
  • CVD risk factors defined as: LDL cholesterol ≥ 100 mg/dL; high blood pressure; smoking; overweight and obesity
  • Ezetimibe + moderate-intensity statin may be used in patients who cannot tolerate high-intensity statins
  • See statin intensity chart
  • Reference [26,38]
Age Risk factors Recommended
statin intensity
< 40 years None None
Any CVD risk factor Moderate or high
Documented CVD High
40 - 75 years None Moderate
Any CVD risk factor High
Documented CVD High
> 75 years None Moderate
Any CVD risk factor Moderate or High
Documented CVD High