DIABETES MANAGEMENT

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

  • Reference [43]
FDA-approved therapies for DM neuropathy
Drug Dosing
(ADA recommended)
Other
Pregabalin (Lyrica®)
  • Starting: 25 - 75 mg one to three times a day
  • Effective: 300 - 600 mg a day
  • FDA-approved for diabetic peripheral neuropathy
  • Preferred first-line agent by ADA
  • See pregabalin for more
Duloxetine (Cymbalta®)
  • Starting: 20 - 30 mg once daily
  • Effective: 60 - 120 mg/day
  • May be given in one or two divided doses
  • FDA-approved for diabetic peripheral neuropathy
  • Preferred first-line agent by ADA
  • See duloxetine for more
Other therapies (non FDA-approved)
Gabapentin (Neurontin®)
  • Starting: 100 - 300 mg one to three times a day
  • Target: 900 - 3600 mg/day
  • Efficacy has been mixed in clinical trials
  • See gabapentin for more
Venlafaxine (Effexor®)
  • Starting: 37.5 mg once daily
  • Target: 75 - 225 mg/day
  • Has shown some effectiveness in clinical trials
  • See venlafaxine for more
Amitriptyline (Elavil®)
  • Starting: 10 - 25 mg once daily
  • Target: 25 - 100 mg/day
  • Has shown some effectiveness in small trials
  • See amitriptyline for more









ADA 2018 Lipid Treatment Recommendations in Diabetics
Age < 40 years
  • No ASCVD and no ASCVD risk factors: No statin recommended
  • No ASCVD with ASCVD risk factors: Moderate-intensity statin may be considered
  • ASCVD present: High-intensity statin recommended. If LDL ≥ 70 mg/dl despite maximally tolerated statin, consider adding ezetimibe or PCSK9 inhibitor
Age ≥ 40 years
  • No ASCVD and no ASCVD risk factors: Moderate-intensity statin
  • No ASCVD with ASCVD risk factors: At the least, moderate-intensity statin. High-intensity statin should be considered.
  • ASCVD present: High-intensity statin recommended. If LDL ≥ 70 mg/dl despite maximally tolerated statin, consider adding ezetimibe or PCSK9 inhibitor

  • Reference [46]
ADA ASCVD Risk Factors
  • LDL ≥ 100 mg/dl
  • Hypertension
  • Chronic kidney disease (GFR < 60 ml/min)
  • Albuminuria ≥30 mcg of albumin/mg creatinine
  • Smoking
  • History of premature ASCVD in a first-degree relative (ASCVD in males < 55 years and females < 65 years)











  • Reference [48]
ADA Classification of Hypoglycemia
Level Blood sugar (mg/dl)
I 54 - 69
II < 54
III A severe event characterized by altered mental and/or physical status requiring assistance