DIABETES MANAGEMENT









  • Reference [48]
ADA recommendations for medical evaluation in diabetics
All diabetics
  • Comprehensive physical exam and medical history - initial and annually
  • Labs - initial and annually
    • Hemoglobin A1C, if results not available in past 3 months
    • Lipid Profile
    • Liver function tests
    • Spot urine albumin-to-creatinine ratio
    • Serum creatinine with calculated GFR
    • Vitamin B12 - when indicated if taking metformin
    • Serum potassium - if taking ACE, ARB, or diuretic
  • Referrals
    • Dilated eye exam - see eye exam recommendations below
    • Family planning for women of reproductive age
    • Registered dietician for dietary counseling
    • Diabetes self-management education
    • Dental exam
    • Mental health professional, if needed [48]
Type 1 diabetics
  • Adults
    • Thyroid Stimulating Hormone (TSH)
    • Celiac disease screening
  • Children
    • Check a TSH at diagnosis and every 1 - 2 years thereafter. Consider testing for antithyroid peroxidase and antithyroglobulin antibodies soon after diagnosis.
    • Screen children with type 1 diabetes for celiac disease by measuring IgA tissue transglutaminase (tTG) antibodies, with documentation of normal total serum IgA levels, soon after the diagnosis of diabetes, or IgG to tTG and deamidated gliadin antibodies if IgA deficient. Repeat screening within 2 years of diabetes diagnosis and then again after 5 years and as indicated (see celiac disease for more).[48]











  • Reference [48]
ADA Blood Sugar Goals for Adults
Blood sugar goals
  • Preprandial (before meal): 80 - 130 mg/dl
  • Peak post-meal blood sugar (within 1 - 2 hours after the start of a meal): < 180 mg/dl
  • Fasting blood sugar (after 8 hours of no calorie consumption): 70 - 100 mg/dl
  • The ADA does not give specific goals for fasting blood sugars, but 70 - 100 mg/dl is typically considered a normal range
A1C goals
  • Most diabetics: < 7%
  • More stringent: < 6.5%
    • If this can be achieved without significant hypoglycemia or other adverse effects of treatment (i.e., polypharmacy). Appropriate patients might include those with short duration of diabetes, type 2 diabetes treated with lifestyle or metformin only, long life expectancy, or no significant cardiovascular disease.
  • Less stringent: < 8.0%
    • Appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions, or long-standing diabetes in whom the goal is difficult to achieve despite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents including insulin.

  • Reference [48]
ADA Blood Sugar Goals for Youth with Type 1 DM
Blood sugar goals
  • Preprandial (before meal): 90 - 130 mg/dl
  • Bedtime: 90 - 150 mg/dl
A1C goals
  • Most youth: < 7.5%
  • More stringent: < 7.0%
    • A lower goal is reasonable if it can be achieved without excessive hypoglycemia

  • Reference [48]
ADA Blood Sugar Goals for Youth with Type 2 DM
Blood sugar goals
  • Preprandial (before meal): 80 - 130 mg/dl
  • Peak post-meal blood sugar (within 1 - 2 hours after the start of a meal): < 180 mg/dl
  • Fasting blood sugar (after 8 hours of no calorie consumption): 70 - 100 mg/dl
  • The ADA does not give specific blood sugar goals for youth patients with T2DM, but they can be assumed to be similar to that of most adults
A1C goals
  • Most youth: < 7%
  • More stringent: < 6.5%
    • May be appropriate for selected individual patients if this can be achieved without significant hypoglycemia or other adverse effects of treatment. Appropriate patients might include those with short duration of diabetes and lesser degrees of b-cell dysfunction and patients treated with lifestyle or metformin only who achieve significant weight improvement.

  • ADL - Activities of daily living | LTC - Long-term care
  • Reference [48]
ADA Blood Sugar Goals for Elderly
Healthy (few coexisting chronic illnesses, intact cognitive and functional status)
  • A1C goal: < 7.5%
  • Preprandial (before meal): 90 - 130 mg/dl
  • Fasting blood sugar (after 8 hours of no calorie consumption): 90 - 130 mg/dl
  • Bedtime: 90 - 150 mg/dl
Complex / intermediate (multiple coexisting chronic illnesses or 21 instrumental ADL impairments or mild-to-moderate cognitive impairment)
  • A1C goal: < 8.0%
  • Preprandial (before meal): 90 - 150 mg/dl
  • Fasting blood sugar (after 8 hours of no calorie consumption): 90 - 150 mg/dl
  • Bedtime: 100 - 180 mg/dl
Very complex / poor health (LTC or end-stage chronic illnesses or moderate-to-severe cognitive impairment or 21 ADL dependencies)
  • A1C goal: < 8.5%
  • Preprandial (before meal): 100 - 180 mg/dl
  • Fasting blood sugar (after 8 hours of no calorie consumption): 100 - 180 mg/dl
  • Bedtime: 110 - 200 mg/dl


  • I = Intensive therapy group was significantly better | S = Standard therapy group was significantly better | NS = No significant difference between groups
  • Values represent average A1C acheived in each group during the trial
  • 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]
Effect of Intensive vs Standard Therapy on Outcomes in T2DM
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 conversion table
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



Race
Overview
  • Studies have found that the A1C values differ among ethnicities independent of other glucose measures (e.g. fasting blood sugar, 2hr glucose test, continuous blood sugar monitoring) [33,34,45]
  • For patients with identical average blood sugar values, A1C values tend to run higher in non-whites compared to whites
  • Results from studies have yielded the following results
  • When compared to whites with similar fasting and post-meal blood sugar levels:
    • African-Americans have A1C values 0.4% higher
    • Hispanics have A1C values 0.15% higher
    • American Indians have A1C values 0.34% higher
    • Asians have A1C values 0.22% higher [34,45]
  • These findings suggest that race-specific A1C values may be useful in that non-whites may have higher A1C values than whites despite similar blood sugar control
  • An observational study called the ARIC study [PubMed abstract] looked at the risk of of stroke, coronary heart disease, and all-cause mortality based on baseline hemoglobin A1C values in blacks and whites
  • ARIC study findings:
    • Nondiabetic blacks had an average A1C value that was 0.4% higher than nondiabetic whites
    • Higher A1C levels were associated with a greater risk for heart disease, stroke, and death
    • Race did not modify the association of the A1C test with a person's risk for heart disease, stroke, or death
    • Since higher A1C values were still associated with higher risk of heart disease, stroke, and death after adjusting for race, the authors concluded that race-adjusted A1C values were of no clinical benefit [33]
ADA recommendations
  • The ADA does not recommend race-adjusted values for A1C
Summary
  • For patients with identical average blood sugars, A1C values run higher in non-whites compared to whites
  • In the ARIC study, race did not modify the association of the A1C value with significant clinical outcomes
  • Based on the available evidence, it would not improve care to use race-adjusted A1C values

Age

Abnormal hemoglobin
Overview
  • Patients with abnormal hemoglobin may have inaccurate A1C tests
  • Some common hemoglobin variants include Hemoglobin S, C, D, or E (Hemoglobin A is normal)
  • Abnormal hemoglobin is more common among Africans (Hemoglobin S, D and C) and people of Indian and Southeast Asian heritage (Hemoglobin E)
  • In one study, patients with sickle cell trait had hemoglobin A1C values that were 0.30% lower on average when compared to patients without sickle cell trait who had comparable 2-hour glucose tolerance tests. [PubMed abstract]
  • Some A1C testing methods are not affected by abnormal hemoglobin
  • The National Glycohemoglobin Standardization Program (NGSP) has a website that lists different lab tests and whether they are affected by hemoglobin abnormalities
Summary
  • Not all hemoglobin abnormalities cause symptoms (ex. anemia), so some affected individuals may not be aware they have an abnormality
  • If A1C tests do not agree with blood sugar measurements, and a person is from a susceptible population, then hemoglobin studies may be appropriate
  • If a hemoglobin abnormality is present, the NGSP website offers information on which tests will not be affected by the abnormality [27]

Abnormal red blood cell lifespan
Shortened life span (falsely lowered A1C)
  • The average life of a red blood cell (RBC) is 120 days
  • Conditions that are associated with increased RBC turnover include blood loss, hemolytic anemia, erythropoietin therapy, splenomegaly, spherocytosis, sickle cell disease, pregnancy (second and third trimesters), glucose-6-phosphate dehydrogenase (G6PD) deficiency, and hemodialysis. These conditions may falsely lower A1C values because the circulating red blood cells' exposure to glycosylation has been reduced.
  • In these patients, blood sugar values and/or other glycosylated proteins should be used to evaluate diabetes control [1,32,37,48]
Prolonged life span (falsely elevated A1C)
  • The average life of a red blood cell (RBC) is 120 days
  • Conditions that prolong the average RBC life span (e.g. splenectomy) may falsely elevate A1C values because the circulating red blood cells' exposure to glycosylation has been increased
  • Conditions that decrease erythropoiesis (e.g. iron deficiency, vitamin B12 deficiency, kidney failure) may also prolong the RBC life span leading to falsely elevated A1C values
  • In these patients, blood sugar values and/or other glycosylated proteins should be used to evaluate diabetes control [1,28,29,30,32,37]

Vitamin C, vitamin E, and aspirin


















  • Reference [43]
Features of distal symmetric polyneuropathy (DSPN)
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
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


  • Dosing recommendations are from the ADA
  • Reference [43,48]
FDA-approved therapies for DM neuropathy
Drug Dosing 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
  • Preferred first-line agent by ADA
  • See gabapentin for more
Venlafaxine (Effexor XR®)
  • 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






Overview
  • The ideal blood pressure (BP) range in diabetics has not been completely determined
  • The ACCORD study compared outcomes between diabetics who were treated to a target SBP of < 120 to those who were treated to a target of < 140
ACCORD Study - Intensive vs Standard Blood Pressure Control in T2DM, NEJM (2010) [PubMed abstract]
  • The ACCORD study enrolled 4733 type 2 diabetics with an average SBP of 139 mmHg
Main inclusion criteria
  • SBP 130 - 180
  • Type 2 diabetes
  • HgA1C 7.5% - 11%
  • Documented CVD or risk factors for CVD
Main exclusion criteria
  • BMI ≥ 45
  • Serum creatinine > 1.5 mg/dl
  • Significant liver disease
  • Cardiovascular event within last 3 months
Baseline characteristics:
  • Average age 62 years
  • Previous cardiovascular event - 34%
  • Average BMI - 32
  • Average BP - 139/76
  • Median duration of diabetes - 10 years
  • Average HgA1C - 8.3%
  • Average LDL - 110 mg/dl
  • Average GFR - 92 ml/min
Randomized treatment groups
  • Group 1 (2362 patients) - Target SBP < 120 mmHg (intensive therapy)
  • Group 2 (2371 patients) - Target SBP < 140 mmHg (standard therapy)
  • Blood pressure medications used were ACE/ARBs, thiazide diuretics, beta blockers, calcium channel blockers, reserpine, and/or alpha blockers
  • No specific treatment regimen or drug was required
Primary outcome: Composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes
Results

Duration: Average of 4.7 years
Outcome Intensive Standard Comparisons
Average BP at 1 year (mmHg) 119/64 133/71 p<0.05
Primary outcome (%/year) 1.87% 2.09% HR 0.88, 95%CI [0.73 - 1.06], p=0.20
Overall mortality (%/year) 1.28% 1.19% HR 1.07, 95%CI [0.85 - 1.35], p=0.55
Stroke (%/year) 0.32% 0.53% HR 0.59, 95%CI [0.39 - 0.89], p=0.01
Nonfatal myocardial infarction (%/year) 1.13% 1.28% HR 0.87, 95%CI [0.68 - 1.10], p=0.25
Hypokalemia (< 3.2 mEq/L) 2.1% 1.1% p=0.01
Estimated GFR < 30 ml/min 4.2% 2.2% p<0.001
Macroalbuminuria 6.6% 8.7% p=0.009
Average # of BP meds after first year 3.4 2.1 N/A

Findings: In patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events
Summary
  • The ACCORD trial found that intensive blood pressure therapy did not improve CVD outcomes in type two diabetics when compared to standard therapy
  • Intensive therapy increased the risk of hypokalemia and GFR < 30 ml/min while decreasing the risk of macroalbuminuria
  • For years, it had been recommended that all diabetics be treated to a blood pressure goal of < 130/80. After the ACCORD trial, the recommendation was changed so that it incorporated individual CVD risk.
ADA BP Recommendations for Adults with Diabetes
  • Blood pressure goals
    • Diabetics at lower risk of CVD: < 140/90 mmHg
      • Lower risk defined as 10-year atherosclerotic CVD risk < 15%
    • Diabetics at higher risk of CVD: < 130/80 mmHg
      • Higher risk defined as existing CVD or 10-year atherosclerotic CVD risk > 15%
  • Blood pressure medications
    • If BP is ≥ 160/100 mmHg, a two-drug regimen may be initiated
    • Drugs of choice include ACE inhibitors, ARBs, thiazide-like diuretics, or dihydropyridine calcium channel blockers
    • Do not combine ACE inhibitors, ARBs, and/or direct renin inhibitors
    • ACE or ARB is indicated in patients with urinary albumin-to-creatinine ratio ≥ 30 mg/g
    • Patients with resistant hypertension should be be considered for mineralocorticoid receptor antagonist therapy [48]
Other guidelines
ADA BP Recommendations for Youth with Diabetes
  • Blood pressure goals
    • SBP and DBP < 90th percentile for age, sex, and height
    • Elevated BP should be confirmed on 3 separate days
  • Blood pressure treatment
    • BP > 90th percentile but < 95th percentile: Initial treatment should be diet and exercise for 3 - 6 months. If goal BP is not achieved, medications should be considered.
    • BP ≥ 95th percentile: Diet, weight loss, and medication. ACE inhibitors and ARBs are preferred, but their potential for teratogenic effects should be considered with females. [48]



  • Reference [48]
ADA Lipid Treatment Recommendations for Adults with Diabetes
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
  • Lipid levels should be monitored annually or as needed [46]
  • See statin intensity chart
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
  • Lipid levels should be monitored annually or as needed [46]
  • See statin intensity chart

  • Reference [48]
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) [46]

  • Reference [48]
ADA Lipid Treatment Recommendations for Youth with Type 1 DM
Screening
  • Obtain a fasting lipid profile in children ≥ 10 years of age soon after the diagnosis of diabetes (after glucose control has been established)
  • If LDL cholesterol values are within the accepted risk level (< 100 mg/dL), a lipid profile repeated every 3 – 5 years is reasonable
Treatment
  • If lipids are abnormal, initial therapy should consist of optimizing glucose control and medical nutrition therapy using a Step 2 American Heart Association diet to decrease the amount of saturated fat to 7% of total calories and dietary cholesterol to 200 mg/day, which is safe and does not interfere with normal growth and development.
  • After the age of 10 years, addition of a statin is suggested in patients who, despite medical nutrition therapy and lifestyle changes, continue to have LDL cholesterol > 160 mg/dL or LDL cholesterol > 130 mg/dL and one or more cardiovascular disease risk factor, following reproductive counseling because of the potential teratogenic effects of statins
  • The goal of therapy is an LDL cholesterol value < 100 mg/dL [48]

  • Reference [48]
ADA Lipid Treatment Recommendations for Youth with Type 2 DM
Screening
  • Lipid testing should be performed when initial glycemic control has been achieved and annually thereafter
Treatment
  • Optimal goals are LDL cholesterol < 100mg/dL, HDL cholesterol > 35 mg/dL, and triglycerides < 150 mg/dL
  • If LDL cholesterol is > 130 mg/dL, blood glucose control should be maximized and dietary counseling should be provided using the American Heart Association Step 2 diet
  • If LDL cholesterol remains above goal after 6 months of dietary intervention, initiate therapy with statin, with goal of LDL < 100 mg/dL [48]

  • Reference [48]
ADA Recommendations for HDL and Triglyceride Levels in Adults
  • Triglycerides ≥ 150 mg/dl and/or HDL cholesterol < 40 mg/dL for men, < 50 mg/dL for women - intensify lifestyle therapy and optimize glycemic control
  • Fasting triglycerides ≥ 500 mg/dl - evaluate for secondary causes of hypertriglyceridemia and consider medical therapy to reduce risk of pancreatitis
  • In patients with ASCVD or other cardiac risk factors on a statin with controlled LDL, but elevated triglycerides (135 - 499 mg/dl), the addition of icosapent ethyl should be considered to reduce cardiovascular risk.

  • Reference [48]
ADA Recommendations for Triglyceride Levels in Youth with Type 2 DM
  • If triglycerides are > 400 mg/dL fasting or > 1,000 mg/dL nonfasting, optimize glycemia and begin fibrate, with a goal of < 400 mg/dL fasting (to reduce risk for pancreatitis)
















  • 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




  • Intranasal dose was 3 mg. Intramuscular dose was 1 mg in deltoid muscle.
  • Average blood sugar when glucagon was administered was 55 mg/dl
  • Reference [49]
Average rise in plasma glucose (mg/dl) in type 1 diabetic adults after glucagon administration
Drug 15 minutes 30 minutes 45 minutes 60 minutes
Glucagon intranasal 20 58 79 100
Glucagon intramuscular 29 71 92 113





  • Reference [48]
ADA recommendations for daily aspirin in diabetes
Primary prevention
  • Aspirin therapy (75 – 162 mg/day) may be considered as a primary prevention strategy in those with diabetes who are at increased cardiovascular risk, after a discussion with the patient on the benefits versus increased risk of bleeding
Secondary prevention
  • Use aspirin therapy (75 – 162 mg/day) as a secondary prevention strategy in those with diabetes and a history of atherosclerotic cardiovascular disease.
  • For patients with atherosclerotic cardiovascular disease and documented aspirin allergy, clopidogrel (75 mg/day) should be used
  • Dual antiplatelet therapy (with low-dose aspirin and a P2Y12 inhibitor) is reasonable for a year after an acute coronary syndrome and may have benefits beyond this period