Diabetes Mellitus

A condition of impaired carbohydrate metabolism characterized by fasting or postprandial high levels of blood glucose that results from inadequate insulin production, insulin resistance and/or impaired glucose uptake.

Prediabetes: Refers to blood glucose values intermediate between normal and overt diabetes; however, not everyone with prediabetes will develop type 2 diabetes.

Impaired fasting glucose: Fasting blood glucose 6.1-6.9 mmol/L [CDA – Clinical Practice Guidelines (CGP) 2008] or 100-125 mg/dL [American Association of Clinical Endocrinologists (AACE) DM Guidelines 2011]

Impaired glucose tolerance: Blood glucose measurement on a glucose tolerance test of 7.8-11.0 mmol/L in the 2-hour sample (CDA-CGP 2008) or 140-199 mg/dL (AACE Diabetes Mellitus Guidelines 2007)

CLASSIFICATION:

• Type1 Diabetes (T1DM): Results from destruction of insulin producing pancreatic beta cell leads to absolute or near total deficiency of insulin
• Type 2 Diabetes (T2DM): Characterized by variable degree of insulin resistance and impaired secretion
• Gestational Diabetes (GDM): Any degree of glucose intolerance with onset or first recognition during pregnancy
• Other specific types: Uncommon conditions or diabetes associated with other diseases or drug use

Emergencies and conditions associated with diabetes mellitus

Type 1 diabetes (formerly called insulin-dependent diabetes or juvenile-onset diabetes)

Risk Factors

• Certain human leukocyte antigen (HLA) types
• Family history of 1^st degree relatives
• Identical twins ~30-70%

Type 2 diabetes (formerly called non-insulin-dependent diabetes or adult-onset diabetes)

Insulin resistance and relative deficiency of insulin secretion are central causes of Type 2 DM.

• Genetic factors: >70% concordance in monozygotic twins
• Immune-mediated: Transplant recipients
• Drug or chemical induced: Such as, corticosteroids and some anti-psychotics
• Infection: Such as HIV
• Systemic Infections: Hemochromatosis, cushing’s disease, acromegaly etc.

Risk Factors

• Age ≥40 years
• Family history of T2DM: 1^st degree relatives
• Race/ethnicity:
  • Aboriginal/Hispanic/Asian/African/Pacific Islander
• History of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)
• History of vascular disease
• History of gestational diabetes (GDM)
• History of delivery of a macrosomic infant: wt. >4 kg (>9 lbs)
• Hypertension (blood pressure >140/90 mmHg)
• Dyslipidemia
• Obesity/overweight (body mass index >25 kg/m²)
  • Particularly visceral or central obesity
• Polycystic ovary syndrome
• Acanthosis nigricans
• Schizophrenia

Gestational diabetes

Risk factors

• Advancing maternal age
• Family history of DM in first-degree relative
• Race/ethnicity:
  • Aboriginal/Hispanic/Asian/African/Pacific Islander
• History of abnormal glucose metabolism
• Low fiber and high glycemic index diet
• Overweight or obese state
• Polycystic ovarian syndrome
• Prior gestational diabetes (GDM)
  • ~80% chances in subsequent pregnancies
• Sedentary life style

Prevalence:

• International Diabetes Foundation 2010 worldwide estimates: ~285 million cases
• Canadian Diabetes Association (CDA) 2010: 7.6% of the Canadian population has diabetes that means 2.7 million Canadians are affected. It is estimated that this will rise to 4.2 million or 10.8% of the population by 2020

Factors influencing prevalence and incidence of diabetes include:

• Age: Increases with aging
• Sex: Men > Women
• Race: First Nations (data from British Columbia suggests the prevalence to be 40% higher than other residents) – (www.ndss.gc.ca)

U.S. Centers for Disease Control and Prevention (CDC) 2005 estimates: ~20.8 million persons, or 7% of the population

Race (age >20 years)

• African Americans: ~13.6%
• Latinos: ~10%
• Native Americans: ~15%

Gestational diabetes

Affects ~2-4% of pregnant Canadian women (~8-18% in some ethnic communities) and ~3-5% pregnant women in the US depending on their risk factors.

Increased risk for:

• Perinatal mortality and morbidity
• Development of diabetes later in the life

Ref: Report from the National Diabetes Surveillance System: Diabetes in Canada, 2009.

Decreased insulin secretion by the pancreatic beta cells and/or decrease in insulin action leads to reduced intracellular uptake of glucose causing increase in blood glucose levels i.e. hyperglycemia.

Type 1 DM

Autoimmune and/or idiopathic process → Effects on pancreatic beta cells → decreased or no production of insulin → increased blood glucose levels → hyperglycemia

Type 2 DM

Mainly insulin resistance and relative insulin deficiency leads to decrease glucose transport in muscles, impaired hepatic glucose production, altered fat metabolism, resulting in metabolic dysfunction; increase in blood glucose, lipid and protein levels.

Prolonged hyperglycemia leads to:

• Osmotic diuresis due to glucosuria
• Hypovolemia and hemoconcentration due to loss of water, sodium, and potassium
• Hyperosmolarity due to excessive blood sugar and increasing sodium concentration
• Tissue hypoxia due to decrease in blood flow to the organs because of increased blood viscosity
• Neurologic signs and symptoms due to intracellular fluid and electrolyte shift

Gestational diabetes

Gestational diabetes (GDM) develops when maternal insulin secretion is not sufficient to meet increased demand secondary to marked resistance.

General features in all types:

• Polyuria/polydipsia/polyphagia
• Weight loss/fatigue/weakness
• Paraesthesias
• Blurry vision (resolves as hyperglycemia is controlled)
• Frequent urinary tract and yeast infections
• Dry or pruritic skin
• Poor wound healing

Type 1 diabetes

• Usually younger age
• Nausea/vomiting/abdominal discomfort
• Muscle cramps
• Headaches

May present with Diabetic Ketoacidosis (DKA) hyperglycemic state with symptoms such as: Abdominal pain, hypotension, fruity odor to breathe, palpitations, rapid breathing, dry mouth, decreased perspiration, confusion may lead to coma.

Type 2 Diabetes
General features of T2DM and/or hyperglycemic complications include nephropathy, neuropathy, retinopathy and cardiovascular disease.

Individuals with hyperosmolar hyperglycemic state (HHS) (complication) developing over days; may present as follows:

• Weight loss/dehydration
• Hypotension/tachycardia
• Poor skin turgor and dryness
• Lethargy/somnolence/confusion

Late presentation

• Hallucinations/aphasia/seizures
• Nystagmus/hemianopsia/hemiplegia
• Altered mental status/coma

Hypoglycemia (complication):

Can occur in both type 1 and type 2 diabetes mellitus

Mild hypoglycemia:
CNS stimulates → surge of epinephrine and norepinepherine → causing

• Tremors, tachycardia, and palpitation
• Sweating, nervousness and hunger

Moderate hypoglycemia:
Deprives brain cells of required energy → CNS functional impairment → causing

• Headache, lightheadedness, inability to concentrate
• Confusion, memory lapse, irritation, emotional changes
• Slurred speech, numbness of lips and tongue, irrational behavior
• Double vision, and drowsiness

Severe hypoglycemia
Total impairment of CNS functions often requires assistance of another person

• Disoriented, seizures may occur
• Unarousable from sleep
• May lead to loss of consciousness

Metabolic syndrome (association)

• Mainly results because of central abdominal obesity and insulin resistance
• Characterized by a clustering of metabolic abnormalities, including: Obesity, abdominal obesity, elevated triglycerides, HDL cholesterol, hypertension and impaired fasting plasma glucose/DM
• The diagnostic criteria are not universal and varies among governing organizations e.g. International Diabetes Federation (IDF), World Health Organization, and National Cholesterol Education Program (NCEP)

CHRONIC COMPLICATIONS OF DIABETES MELLITUS

Microvascular Complications:

• Ocular complications (diabetic retinopathies): Blurred vision, eye floaters, visual impairment → blindness
• Diabetic nephropathies
  • Swelling of the feet and ankles
  • Weakness
  • Loss of appetite
  • Upset stomach
  • Insomnia and difficulty sleeping
  • Confusion and trouble concentrating
  • Patients are often asymptomatic at diagnosis and progress from microalbuminuria to more severe degrees of dysfunction

Neuropathies include and present as follows:

• Peripheral Neuropathy
  • May be focal (mono-neuropathy involving 1 nerve) or symmetric (poly-neuropathy), plexopathy (injury to brachial or lumbar nerve plexus)
  • Sensory – paresthesia, burning sensations, decreased sensation on light touch, decreased proprioception, carpal tunnel syndrome
  • Motor – limb weakness, dropped foot, and deformities of foot and joints
• Autonomic Neuropathies effects almost all systems of the body
  • Cardiovascular: Tachycardia, orthostatic hypotension, silent or painless MI
  • Gastrointestinal: Bloating, nausea, vomiting, delayed gastric emptying may occur
  • Renal system: Decreased sensation of bladder fullness, urinary retention, recurrent urinary infections caused by incomplete emptying of bladder
  • Adrenal medulla: Neuropathies involving the medulla diminish adrenergic symptom. (sweating, nervousness and palpitations) puts them at risk of developing hypoglycemia without any symptoms
  • Sudomotor neuropathies: Absence of sweating and dry foot causing foot ulcers
  • Sexual dysfunction

Macrovascular Complications:

A) Coronary heart disease: Cardiovascular disease (including silent MI) is higher in individuals with diabetes as compared to non-diabetics. Patients with diabetes should be routinely monitored for cardiovascular risks, edema, dyspnea or orthopnea.

B) Peripheral vascular disease: Pale cool extremities, decreased lower leg hair should be assessed periodically.

C) Cerebrovascular disease: Changes in mental state, motor weakness, slurred speech are the alarming signs to seek medical emergency

The Diabetic Foot

Usually it is the combination of several factors, including

• Diabetic neuropathy, trauma, and deformity, ischemia, callous formation, edema

Diabetic foot disorders include:

• Foot ulcers, infections, ischemic necrosis, gangrene, callous formation, charcot neuroarthropathy

In asymptomatic individuals consider screening for diabetes if any of the following risk factors are present:

• Age ≥40 years (every 3 years)
• First-degree relative with type 2 diabetes
• Members of a high risk ethnic group
• Hypertensive (≥140/90 mmHg)
• Cardiovascular disease
• Hyperlipidemia
• Sedentary life style
• Overweight (BMI ≥25.0 kg/m²)/abdominal obesity
• Delivered a baby >4.5 kg (>9 pounds)
• History of gestational diabetes mellitus
• Previously found impaired glucose tolerance or impaired fasting glucose
• Polycystic ovary syndrome
• Psychiatric illness (e.g. schizophrenia)
• Acanthosis nigricans

Systematic screening:

The basic laboratory measures for screening are:

Fasting plasma glucose (FPG)

• Usually first screening test
• Normal: <6.1 mmol/L (<110 mg/dL)
• Diabetes: ≥7.0 mmol/L (≥126 mg/dL)

2-hour plasma glucose in a 75-g oral glucose tolerance test (OGTT): indicated in

• When the FPG is 6.1 to 6.9 mmol/L (110-125 mg/dL)
• When FPG is 5.6 to 6.0 mmol/L (100-108 mg/dL) and ≥1 risk factors
• Impaired glucose tolerance is high (e.g. for individuals with risk factors)
• The test should be performed after an overnight fast of 8 to 14 hours and after at least 3 days of unrestricted diet (i.e. ≥150 g carbohydrate per day) and unlimited physical activity

Diagnostic criteria for diabetes

Guidelines for Plasma Glucose Levels for diagnosis of IFG, IGT and diabetes

Metabolic Syndrome

Metabolic Syndrome refers to a combination of metabolic derangements in which obesity and glucose impairment play a central role.

However, the diagnostic criteria are not universal and variance occurs among the governing organization e.g. International Diabetes Federation (IDF), World Health Organization (WHO), and National Cholesterol Education Program (NCEP) etc. There have also been attempts to unify the various criteria through a Harmonized definition.

Diagnostic criteria for metabolic syndrome

Screening and Diagnostic Criteria for Gestational Diabetes Mellitus (GDM):

All pregnant women for gestational diabetes mellitus:

• Low risk: Screen at 24 to 28 weeks gestation
• High risk: Screen at 20 weeks gestation

In all pregnant women: Measure FPG at the first prenatal visit (before 20 wks)

There are two approaches for GDM screening.

One-step approach:

• 75-g Oral Glucose Tolerance Test (75-g 2-h OGTT)
  • Fasting plasma glucose level: ≥5.3 mmol/L (≥95 mg/dL)
  • 1-hour plasma glucose level: ≥10.0 mmol/L (≥180 mg/dL)
  • 2-hour plasma glucose level: ≥8.6 mmol/L (≥155 mg/dL)
• Interpretation: Two or more of the plasma concentrations must be met or exceeded for a positive diagnosis on the OGTT

Two-step approach:

• Initially screen with 50-g glucose challenge test (GCT)
• If PG is <7.8 mmol/L, then reassess in subsequent trimesters
• If 1h PG is between 7.8 to 10.2 mmol/L (140 to 180 mg/dL), should undergo (75-g 2-h OGTT)
• If 1h PG is ≥10.3 mmol/L, it is diagnostic of GDM

History (known or suspected DM):

• Family history of DM and its complications
• Personal history of other autoimmune disorders
• Risk factors e.g. hypertension/CVD/hyperlipidemia etc.
• Medications/immunization
• Physical activity
• Dietary intake such as; total calories, sugar, fats, frequency of meals
• Smoking, ethanol use
• Diarrhea, constipation
• Gestational diabetes
• Polyuria, polydipsia, nocturia, polyphagia, blurred vision, fainting, numbness, recurrent infections, skin ulcer
• Symptoms and/or signs of hypoglycemia:
  • Palpitations, sweating, anxiety, hunger, tremor, confusion, seizures
• Symptoms and/or signs of acute hyperglycemia
  • Nausea/vomiting, abdominal pain, shortness of breath, altered sensorium, fruity odor on breath, respiratory difficulty

Physical examination:

Should include assessment of

• Weight or body mass index: Overweight (BMI 25-29.9) or obese (BMI ≥30)
• Central obesity: Defined as waist circumference with ethnicity specific values. If an individual is obese (BMI ≥30) waist circumference need not be measured
• Dilated retinal examination (Retinopathy)
  • Conducted at the time of diagnosis of T2DM or 5 years after T1DM is diagnosed, then annual examinations should be performed
• Blood pressure of >130/80 mmHg considered hypertension in DM
• Foot exam: Look for skin ulcers, hammer or claw toes, charcot foot, and dry skin (potential site for ulceration)
• Lower extremity examination: To seek evidence of peripheral neuropathy
• Peripheral Arteries:
  Check for diminished pulsation. Ankle brachial index test is helpful and compares blood pressure measured at both ankles (ankle pressure) with both arm (brachial pressure) to assess for a gradient that might suggest the presence of peripheral artery disease (PAD)

Note: It is calculated by dividing the higher of the two ankle pressures by the highest systolic brachial pressure.

– Interpretation of ankle brachial index

• Skin examination:
• Diabetic dermopathy: Roundish brown or purplish color, slightly-indented patches of skin
  • Diabetic dermopathy: Roundish brown or purplish color, slightly-indented patches of skin
  • Furuncles: Tender, pinkish-red, swollen nodule
  • Carbuncles: Hot red nodule with visible layers of pus under the surface of the skin
  • Candidiasis: Creamy white patches in the mouth or on the throat; skin rashes, patches, and blisters in the groin between fingers and toes and under the breasts; vaginal itching and irritation
  • Necrobiosis lipoidica diabeticorum: 1 to 3 mm well-circumscribed erythematous papules or nodules; center of the rash are usually yellow
  • Poorly healing abrasions or ulcerations
  • Nail disease: e.g. Onychomycosis, ingrown toe nails etc.
• Oral examination: For periodontal disease

Laboratories

• Complete blood count
• Serum glucose level
  • Random blood sugar ≥11.1 mmol/L
  • Fasting blood sugar ≥7.0 mmol/L
  • 2h post prandial in a 75 g OGTT ≥11.1 mmol/L
• Hemoglobin A1C ≥6.5% (except in children, adolescents, pregnancy and type 1 diabetes)
• C-peptide assay (connecting peptide assay)= absence means Type1 diabetes
• Lipid Profile
  • LDL-C: <2.6 mmol/L (primary target)
  • LDL-C: Approximately 1.7 mmol/L if high risk for CVD (primary target)
  • TC/HDL-C ratio: <4.0 (secondary target)
• Urinalysis
  • Glucosuria
  • Ketonuria
  • Albuminuria
  • Creatinine clearance
  • Random ACR (normal: men <2.0, women <2.8)
• Cultures if presenting with infection
• ECG
• Other tests according to presence of complications

Nursing and Patient Care Considerations

• Advise 8-hour fast overnight for fasting glucose, sips of water are allowed
• Refrain from smoking before the test
• Postprandial test, no food should be eaten during the 2-hour interval
• Random blood glucose, note the time and content of the last meal
• Usual daily routine must be followed 3 days prior to oral glucose tolerance test (OGTT)
• Cigarette, oral contraceptives, phenytoin, salicylate and other effect the results of the OGTT
• OGTT diagnostic for diabetes mellitus if 2-hour value is 200 mg/dL or greater
• Glycated hemoglobin (glycohemoglobin, HbA1_c) is used to monitor glycemic control over 60-120days
• HbA1_c results are only effected in red blood disorders, no preparation require
• C-peptide assay (connecting peptide assay) marker of endogenous insulin production use to differentiate between type 1 and 2
• Absence of C-peptide indicates no beta cell function → T1DM
• Require overnight fast or after stimulation with sustacal, IV glucose, or 1 mg of glucagon subcutaneously
• Fructosamine assay can be done when HbA1_c is not indicated e.g. red blood diseases
• Test may not be reliable in hypoalbuminemia

Gerontologic considerations:
High blood sugar levels are commonly seen in fifth decade of life and are usually age related. The cause is still unknown ~10% to 30% of elderly have age related hyperglycemia.

Factors playing role in age related hyperglycemia include:

• Poor diet
• Physical inactivity
• Decrease in lean body mass (where ingested carbohydrates are stored)
• Altered insulin secretion
• Increase in fat tissue → increase in insulin resistance

Nursing Alert

Capillary blood glucose values obtained by finger stick samples tend to be higher than values in venous samples.

Clinical Guidelines

Diagnostic criteria

• FPG ≥7.0 mmol/L or
• Casual PG ≥11.1 mmol/L + symptoms of diabetes or
• 2hPG in a 75 g OGTT ≥11.1 mmol/L
• Hemoglobin A1C ≥6.5% (check every 3-4 months)

There are 5 components of diabetes management:

1. Nutrition
2. Exercise
3. Monitoring
4. Pharmacologic therapy
5. Education

1) Nutrition:

• Restrict dietary carbohydrates and saturated fats to maintain ideal body weight
• Meal planning and its teaching to control blood glucose and lipid levels

Following points should be considered in meal planning

• Life style
• Usual eating times
• Ethnic and cultural background
• Readiness to change

a) Medical Nutrition therapy (MNT):
Gradual weight loss advised to obese individuals (especially T2DM) with achievable short term goals such as 5 kg in 3 months

• Recommended caloric restriction for overweight
  • Men = 1200-1800 kcal/day
  • Women = 1000-1500 kcal/day
• Caloric intake should be distributed as follows
  • Carbohydrates= 45%-65%
  • Proteins = 15%-20%
  • Total fat = <35% (<7% saturated fats) with <300 mg/day of cholesterol
• In patients with LDL = >5.5 mmol/L (100mg/dL)
  • Total fat consumed = <25% (7% saturated fat) with 11.9 mmol/L (200 mg/d)of cholesterol
• Protein intake = 0.8 gm/kg/day in progressive kidney disease
• Potassium and phosphorus intake restricted in severe chronic kidney disease
• Carbohydrate counting is useful in adjusting insulin dose
  • 1 carbohydrate “exchange” is 15gm or 60 kcal

Vitamin and Mineral supplements

Routine supplementation is not necessary, except for

• Vitamin D: 10 μg (400 IU) supplementation considered if >50 years
• Folic acid: 0.4 mg to 1.0 mg/day folic acid prior to conception and during early weeks of pregnancy is recommended
• Alcohol: Ingestion may mask the symptoms of hypoglycemia, reduce hepatic production of glucose and impair an individual’s judgment
• Alcohol Avoidance: Advised in certain medical conditions such as severe hypertriglyceridemia, pancreatitis, advanced neuropathy, liver disease, prior history of alcohol abuse, pregnancy and lactation
• Alcohol Restriction:
  • Two standard drinks per day or 14 drinks per week for men
  • One standard drink/day or 9 drinks/week for women and lighter weight men
  • One standard drink is equivalent to:
    • 5oz /142 ml of wine (12% alcohol)
    • 1.5oz /43 ml of spirits (40% alcohol)
    • 12oz /341 ml regular strength beer (5% alcohol)

b) Smoking: Cessation of smoking and smoke-free environment is important in the overall management of diabetics to reduce cardiovascular risk.

c) Vaccination:

• An annual influenza vaccine is advised to reduce the risk of complications associated with influenza epidemics
• One-time pheumococcal revaccination is recommended for individuals >64 years old if the original vaccine was given >5 years prior

Ref: Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2008; 32:S1-S201.

Following actions according to the nutritional principles should be taken:

• Carbohydrates (fruits, starches, and vegetables) should alternatively be included
• Proteins selecting lean meat will help reduce fat and cholesterol intake
• Fats should be used sparingly with <7% of total calories derived from saturated fats
• Avoid skipping or delaying meals
• Substitute foods high in fiber instead of processed foods when possible, e.g. whole-grain bread in place of white bread
• Eat fresh fruit and vegetables in place of juices
• Do not season foods with salt or salt-containing spices
• Use salt-containing condiments sparingly
• Do not fry foods, instead bake, broil, or boil foods and discard fat
• Eat raw or steamed vegetables to retain fiber
• Trim all visible fat from meat; skim off fat from stews or other prepared dishes
• Distribute small snacks in between meals, enhance glucose control in T2DM
• Unplanned activity may call for an additional snack
• Consume alcohol with food to avoid hypoglycemia
• Do not omit food from meal plan in exchange for alcohol
• Limit “diet” soda intake to 2 L/day

2) Exercise:

Improves glycemic control and strength, lipid profile, increases cardio respiratory fitness and maintains weight.

a) Aerobic exercises:
Recommended for a minimum of 2.5 hrs/week, with >10 min per session of moderate- to vigorous-intensity, with no more than 2 consecutive days without exercise.

b) Moderate exercises: Examples of recommended exercises in patients who have 50-70% of maximum heart rate.

• Biking/brisk walking
• Continuous swimming
• Dancing/raking leaves
• Water aerobics

c) Vigorous exercises:
Recommended in patients who have >70% of maximum heart rate

• Brisk walking up an incline
• Jogging/aerobics
• Hockey/basketball
• Fast pace swimming
• Fast dancing

d) Resistance exercises
Weight bearing or other forms of resistance exercises that requires muscular strength conducted 3 times per week, in addition to aerobic exercise. Suggest beginning initially with instruction by an exercise specialist. Examples:

• Exercise with weight machines
• Weight lifting: Start with 1 set of 10-15 repetitions at moderate weight. Progress to 2 sets of 10-15 repetitions, then 3 sets of 8 repetitions at a heavier weight

Precautions for exercise in diabetics:

• Pre-exercise screening for retinopathy, neuropathy and cardiovascular disease
• Use proper foot wear, and inspect feet daily
• Avoid exercise in extreme weather
• Avoid exercise during the period of poor metabolic control

Gerontologic consideration:

• Gradual and consistent exercise should be planned, due to increased in cardiovascular, and other physical impairments in elderly
• Exercise in this group decrease blood glucose and gives sense of well being

3) Monitoring: Blood glucose monitoring helps evaluate

• Effectiveness of medication
• Reflects glucose levels after meals
• Assess glucose response to exercise regimen
• Episodes of hypoglycemia and hyperglycemia to determine appropriate treatment

a) Nurse needs to evaluate patients skills including

• Visual acuity
• Fine motor coordination
• Cognitive ability
• Comfort with technology
• Willingness and cost

Patients for self monitoring blood glucose (SMBC) are selected who have:

• Unstable diabetes
• Tendency to develop severe ketosis or hypoglycemia
• Hypoglycemia without warning symptoms

Schedule for glucose monitoring is determined by the patient and health care provider.

Following consideration should be taken in account

• Medication and meal timings
• Schedule tests; considering cost effectiveness
• Intensify monitoring during stress and illnesses or when there is change in therapy

b) T2DM controlled with oral hypoglycemic or single injection (intermediate-acting insulin) require before breakfast and supper or bedtime monitoring.

c) T1DM using multiple-dose regimen may require four to six times/day monitoring

d) Alternate site for testing has been recommended only who use the fingertips for occupational activities (e.g. musicians, etc.), although it is not accurate:

• Check with the glucometer manufacturer to see if it is approved for alternate site testing
• Do not use an alternate site when accuracy is critical
• If alternate site is used, the area should be rubbed until it is warm before testing

e) Providing initial teaching about self monitoring blood glucose (SMBG) technique

Equipment for glucose monitoring includes:

• Blood glucose meter
• Test strip
• Disposable gloves
• Lancet/lancing device
• Alcohol wipe
• 2 × 2 gauze or clean tissue
• Cotton ball
• Log book to keep a record

Procedure for (SMBG):

• Hands should be washed in warm water, to increase the blood flow to the fingers and be dried
• Use alcohol wipe and thoroughly dry before finger is lanced
• Prepare the meter by validating the proper calibration with the strips to be used, after turning it on (this usually involves matching a code number on the strip bottle to the code registered on the meter)
• Meter indicates its readiness
• Prick the fingertip laterally avoiding the most sensitive area using the lancet, obtaining a large hanging drop of blood, (insufficient blood samples will give inaccurate readings)
• Apply the blood carefully to the strip test area, (few meters have wipe system in which the blood is wiped out firmly before reading is taken)
• Blood contact time with the test strip can vary with each glucose meter. Precise timing is crucial for accurate results
• The lanced finger is covered with gauze or a tissue until bleeding subsides. If necessary, an adhesive bandage is then applied

Glycosylated hemoglobin (HgbA1c): Reflects average blood glucose levels over a period of 2-3months.

• If the patient reports normal glucose levels and A1c is high then the patient technique is inaccurate or there is some calibration problems
• Glycemic Targets = A1c ≥6.5% in order to reduce the risk of microvascular and macrovascular complications

Urine testing for glucose:
Before glucometers were available, urine testing was the only way to monitor

• Advantage: It is non-invasive and a cost effective method
• Disadvantage: Results are only positive when the blood glucose level is at renal threshold of 9.9-11.1 mmol/L, cannot detect hypoglycemia

Testing for Ketones:

Urine dipsticks are most commonly used to measure ketonuria

Should be performed whenever

• In patients with T1DM have persistent glucosuria or blood glucose levels ≥14.0 mmol/L for 2 testing period in a row
• Pregnancy with pre-existing diabetes
• Gestational diabetes

Pharmacological Therapy:

If the patient’s glycemic target is not achieved after 4 weeks of medical nutrition therapy, pharmacologic therapy is indicated.

Hypoglycemic agents often used are:

• Insulin therapy
• Oral glucose-lowering agents

Type 1 Diabetes Mellitus (T1DM)

Basal-bolus insulin regimens (e.g. multiple daily injections or continuous subcutaneous insulin infusion) are the regimens of choice for all adults with T1DM.

Insulin regimens should be customized to the individual’s

• Treatment goals
• Lifestyle/general health
• Diet/age
• Motivation
• Hypoglycemia awareness status
• Ability for self management

All individuals with T1DM should be counseled about the risk, prevention and treatment of insulin induced hypoglycemia. In some cases you would see a honeymoon period.

Insulin Regimens:

Total Daily Dosing (TDD) for 70 kg person

TDD = 0.5 x 70 = 35 units approximately

Basal-bolus regimens/Multiple daily injections (MDI)

• Bolus (60% of TDD): Short or rapid-acting insulin before each meal
• Basal (40% of TDD): Intermediate or long acting insulin at bedtime or intermediate insulin split twice per day

CSII (continuous subcutaneous insulin infusion)

Fast acting insulin is used and multiple basal infusion rates can be programmed according to requirement.

• Initially calculate dose as total pre-pump dose “x” and multiply it by 80% = 0.8x
• Start the basal rate at 50% of that (0.4x) and divide it by 24 hours = (x/60) units/hr
• Divide the total carbohydrates/day into 3 equal meals and give 50% of the pre-pump dose as three equal boluses of (0.4x/3) = (x/7.5) units/meal
• If no prior insulin history is known estimate total dose by 0.44 times the weight in kilograms

Available Insulin Preparations

Type 2 Diabetes Mellitus

Once T2DM established, initiate and maintain lifestyle modification. Begin oral antihyperglycemic agents for patients with T2DM who do not achieve glucose control with diet and exercise alone as per recommendations

Hyperglycemia management in type 2 diabetes

• Available Insulin Preparations
• Commonly used oral antihyperglycemic agents

GLP-1 receptor agonist

Exenatide:
Approved recently as adjunctive therapy for use in combination with sulfonylurea, metformin, or both.

• Indicated in combination with metformin, and/or sulfonylurea to improve glycemic control in patients with T2DM, when maximally tolerated doses of these oral therapies in addition to diet and exercise do not provide adequate glycemic control

Liraglutide:

• Once daily dosing in patients with T2DM in combination with metformin therapy or combined metformin and sulfonylurea therapy when maximally tolerated doses of these oral therapies in addition to diet and exercise do not provide adequate glycemic control

Combined formulations are also available:

• Rosiglitazone + Metformin
• Rosiglitazone + Glimepiride
• Sitagliptin + Metformin

Newer therapeutic agents:

Amylin analogue

Pramlintide (available in Canada now)

• Adjunctive treatment with mealtime insulin in in T2DM; in patients who have failed to achieve desired glucose control despite optimal insulin therapy

Bromocriptine mesylate (available in the USA):

• FDA – approved novel treatment for T2DM as an adjunct to diet and exercise to improve glycemic control in adults with T2DM

Gestational diabetes mellitus(GDM):

Once diagnosed monitor four times daily.

Goals:

• Fasting: 3.8-5.2 mmol/L (68-94 mg/dL)
• 1 hour postprandial: 5.5-7.7 mmol/L (99-139 mg/dL)
• 2 hour postprandial: 5.0-6.6 mmol/L (90-119 mg/dL)

Patients with GDM are high risk patients for T2DM, should be re-evaluated 6 wks and 6 months after delivery.

Diabetes sick-day

During illness or infection blood glucose level often rises even though person is not eating.

Goals for sick-day management

• Prevention of hyperglycemia and hypoglycemia
• Maintenance of hydration

Sick-day guidelines

• Always take insulin or diabetes medication
  • Take at least the usual dosage of insulin
  • Sometimes an increase in the dosage of insulin is required
• Monitor blood glucose and urine ketones every 4 hrs
  • Drink plenty of fluids, 6-8 oz. of fluid every hour is recommended
• If unable to eat, drink fluids that contain carbohydrates (e.g. fruit juices, regular soda)
  • Try to eat usual amount of carbohydrate (CHO), may be divided into smaller meals and snack, if having difficulty eating, eat or drink 15 grams of carbohydrate every hour or 45-50 grams of carbohydrate every 3-4 hours

Metabolic syndrome

• Treat underlying causes (overweight/obesity and physical inactivity)
  • Intensify weight management
  • Increase physical activity
• Treat lipid and non-lipid risk factors
• Treat hypertension
  • ACE inhibitor or ARB (angiotensin receptor blocker) is usually prescribed for patients with diabetes
• Treat elevated triglycerides
  • Statin if predominantly high LDL
  • Fibrate if predominantly high triglycerides
• Use antiplatelet therapy (e.g. aspirin) for patients with CAD, stroke, PAD unless otherwise contraindicated

Acute complications of diabetes mellitus:

• Hypoglycemia
• Diabetic ketoacidosis (DKA)
• Hyperosmolar hyperglycemic state (HHS)

Hypoglycemia

Indications for hospitalization hypoglycemia:

• If induced by sulfonylurea
• Deliberate drug overdose
• Coma, seizure
• Persistent neurological changes

Management:

Mild to moderate hypoglycemia:

15 gm of fast acting carbohydrate can be given in any one of the following ways as follows:

• Three or four commercially prepared glucose tablets
• Regular soft drink or fruit juice (120-180 ml)
• Hard candies or 6 life savers (1 = 2.5 g of carbohydrate)
• 3 teaspoons or 3 packets of table sugar dissolved in water
• 15 mL (1 tablespoon) of honey

Retest blood glucose levels after ~15 minutes, and administer another 15 g glucose if blood glucose levels remains <4.0 mmol/L (72 mg/dL)

Note: 15 gm of carbohydrate will produce a blood glucose increment of approximately 2.1 mmol/L (38 mg/dL) in 20 minutes

Severe hypoglycemia in a conscious person:

• Oral ingestion of 20 g of carbohydrate, preferably as glucose tablets or equivalent.is administered
• Retest blood glucose after ~15 minutes, and retreat with another 15 g of glucose if the blood glucose level remains <4.0 mmol/L (72 mg/dL)

Note: 20 g oral glucose dose will produce a blood glucose increment of approximately 3.6 mmol/L (65 mg/dL) at 45 minutes

Severe hypoglycemia in an unconscious person or unable to have oral intake at home:

• Administer glucagon 1 mg, either SC or IM in the deltoid or anterior thigh
• This should produce blood glucose rise from 3.0-12 mmol/L (54-216 mg/dL) within 60 minutes
• Once patient regains consciousness, high carbohydrate source snack is provided

Severe hypoglycemia in an unconscious person with IV access (usually hospital setting):

• Administer glucose 10-25 g (20-50 ml of D50W) IV over 1 to 3 minutes
• Assure patency of IV line because hypertonic solution of 50% DW is very irritable to the veins

Diabetic ketoacidosis (DKA):

Potentially fatal complication, occur in upto 5% of type1 DM patients.

Risk Factors:

• Interruption in insulin therapy
• Sepsis, trauma and MI, etc.
• Pregnancy

Indications for hospitalization with DKA include:

• Plasma Glucose Levels= 14.0 mmol/L (>250 mg/dL)
• Arterial PH = < 7.30
• Serum Bicarbonate = <15 mEq/L
• Moderate ketonemia or ketonuria

Management:

• Oxygen and airway management as needed
• Immediate IV access
• Hydration as follows

0.9% NaCl IV usually 1-2 liters should be given rapidly (if cardiac functions are normal) followed by 0.5 to 1 liter/hr until vital signs are stabilized, and urine output has been maintained.

Hypotonic saline (0.45%) in patients with severe hypernatremia (>150 mEq/L).

Replenish total body water deficit by giving:

• High or normal sodium levels are: 0.45% saline at 150-500 ml/hr

Note: Avoid the risk of cerebral edema, do not exceed change in osmolality >3 mmol/kg/hr.

The goal is to replace approximately 50% of the total body water (TBW) deficit in the first 8 hours and the remainder in the subsequent 16 hours.

Formula: Total body water deficit (L) = 0.6 x wt (kg) x [1-140/serum sodium]

Potassium replacement

• Potassium deficit should always be assumed. Insulin therapy should be held if K⁺ is <3.3 mmol/L, and potassium should be replaced immediately at the rate of 40 mmol/hr in a solution of one liter of 0.9% normal saline
• 10-20 mEq/hr of potassium should be added to the 2^nd or 3^rd liter of fluid unless the patient has hyperkalemia (>5.5 mmol/L or ECG evidence) or renal failure or oliguria

Monitoring

• Blood glucose levels hourly and serum electrolytes every 1-2 hours
• Continuous ECG monitoring is required

Insulin therapy:

Is necessary for resolution of the ketoacidosis, can be withheld initially in patients with marked hypokalemia.

• Immediately give IV bolus of 10-15 unit of Insulin, followed by continuous infusion of regular insulin at an initial rate of 5-10 units/hr. Dilute 100 units in 100 ml of 0.9% saline, infuse at the rate of 10 ml/hr will deliver 10 units/hr
• Target: Decrease of 2.8-4.1 mmol/hr (50-75mg/dL/hr) of blood glucose levels

Do’s And Don’ts:

• If insulin resistance is suspected then hourly dose of regular insulin should be increased by 50-100%
• Avoid reduction at rate >5.5 mmol/L/hr (100 mg/dL/hr) due to osmotic encephalopathy
• Maintain insulin infusion over 1-2 units/hr, and continue till patient clinically improved. Once oral intake resumes insulin can be given SC

Dextrose:

• Administer Dextrose 5% in 0.45% saline once plasma glucose level decrease to 14.0 mmol/L (250 mg/dL). Decrease insulin rate to 0.05 units/kg/hr to avoid hypoglycemia

Bicarbonate

• Serum bicarbonate level and closure to anion gap is a reliable parameters to evaluate metabolic recovery
• Bicarbonate therapy is considered in shock or coma, severe acidosis (pH <7.0), plasma bicarbonate (<5 mEq/L), acidosis induced cardiac or respiratory dysfunction, and severe hyperkalemia
• Sodium bicarbonate, 50 mEq/L of 200 ml D5W can be given over 1 hr, can be repeated every 1-2 hrs until pH≥ 7.0

Phosphate and magnesium

• Stores are depleted, but are not replaced if the patients resume oral intake. However, magnesium is replaced if patient is at risk of ventricular arrhythmias

Antibiotics

Should be started promptly if there are documented infections.

• Empiric broad spectrum antibiotics can be considered if patient is in sepsis

Complications of DKA requiring immediate recognition and prompt treatment:

Lactic acidosis:
Despite of optimal DKA management, some patients may exhibit persistent anion gap with refractory metabolic acidosis, due to prolonged dehydration, shock, and sepsis or tissue hypoxia.

Management requires the following:

• Adequate volume replacement
• Control of sepsis
• Liberal and judicious use of bicarbonates

Arterial thrombosis results in stroke, MI or ischemic limb.

• Routine anticoagulation is not recommended
• Treatment guided by clinical scenario

Cerebral edema may occur from over rehydration, especially in children, and should be quickly recognized (headache, papilledema, altered sensorium); brain CT scan may assist diagnosis.

• Treat immediately by IV mannitol

Rebound ketoacidosis may result from premature discontinuation of IV insulin or inadequate SC doses of insulin.

Hyperosmolar hyperglycemic state (HHS):
Usually occurs in patients with type 2 diabetes mellitus and has no or little ketosis.

Indications for hospitalization HHS includes:

• Plasma Glucose Levels: 22.1 mmol/L (≥400 mg/dL)
• Serum osmolality: >320 mmol/kg
• Impaired mental status

Management:

• Oxygen and airway management as needed
• Immediate IV access
• Hydration
  • Do not exceed change in osmolality >3 mmol/kg/hr
  • The goal in fluid administration is to replace approximately 50% of the total body water (TBW) deficit in the first 8 hours and the remainder in the subsequent 16 hours

Potassium replacement

• Potassium deficit should always be assumed. Insulin therapy should be held if K⁺ is <3.3 mmol/L, and potassium should be replaced immediately at the rate of 40 mmol/hr in a solution of one liter of 0.9% normal saline
• 10-20 mEq/hr of potassium should be added to the 2^nd or 3^rd liter of fluid unless the patient has hyperkalemia (>5.5 mmol/L or ECG evidence) or renal failure or oliguria

Monitoring

• Blood glucose levels hourly and serum electrolytes every 1-2 hours
• Continuous ECG monitoring is required

Insulin therapy
Not critical for the treatment of HHS as compared to hydration which should always precede insulin administeration.

• Generally insulin use is recommended to reduce plasma glucose levels

Dextrose

• Administer Dextrose 5% in IV fliuid once plasma glucose level decrease to 14.0 mmol/L (250 mg/dL), to avoid hypoglycemia
• Decrease insulin rate to 0.05 units/kg/hr

Seizure control

• Requires normalization of osmolality and glucose; standard antiepileptic’s may be ineffective
• Avoid phenytoin, which inhibits the release of endogenous insulin and has been associated with HHS

Bicarbonate

• One ampoule (50 mmol) of sodium bicarb in 200 ml of D5W over 1 hr, repeated every 1-2 hrs, until pH ≥7.0 is considered in adults with shock or who are having pH <7.0
• Watch for delayed metabolic acidosis and hypokalemia

Phosphate and magnesium

• Stores are depleted, but are not replaced if the patients resume oral intake. However, magnesium is replaced if patient is at risk of ventricular arrhythmias

Antibiotics
Should be started promptly if there is documented infections.

• Empiric broad spectrum antibiotics can be considered if patient is in sepsis

Complications of HHS include:
Thromboembolic events, cerebral edema, adult respiratory distress syndrome and rhabdomyolysis.

Management of chronic complications of Diabetes Mellitus

(i) Microvascular: includes

• Diabetic retinopathy
• Diabetic neuropathy: Includes peripheral and autonomic neuropathy, as briefly summarized in the tables
• Diabetic nephropathy

(ii) Macrovascular

Coronary heart disease (CHD), stroke, and peripheral vascular disease (PVD) accounts for 80% of deaths in patients with diabetes.

• Cardiovascular risk should be assessed and treated aggressively
• Cigarette smoking should be discouraged
• Good glycemic control after acute MI is beneficial
• In peripheral vascular disease (PVD) similar goals are to be achieved as described above for (CHD)
• Antiplatelet agents are recommended for secondary prevention in patients with stroke or heart disease and may have modest benefit in primary prevention in high risk vascular patient(Framingham >20%-xcluding diabetes)
• Exercise and agents such as pentoxifylline 400 mg TID and cilostazol 100 mg BID (the latter not currently available in Canada) may be helpful in intermittent claudication

(iii) The Diabetic Foot:

Proper foot care is advised to avoid problems, which includes; bathing, drying and lubricating without leaving the moisture to accumulate between the toes. Wear close toe shoes which fit well, and trimming toenails straight across and file sharp corners.

Mild to moderate ulceration

• Rest, elevation and relief of pressure are essential
• Oral antibiotics should be started immediately e.g. amoxicillin/clavulenic acid 800 mg PO BID; cloxacillin 500 mg QID, first generation cephalosporin or clindamycin are recommended
• If cellulitis does not respond with oral antibiotics IV should be started

Moderate to severe ulceration

• Infections require hospitalization and IV antibiotics
• Debridement may be required; both aerobic and anaerobic cultures are sent
• Empiric antimicrobials are given intravenously and the coverage is tailored according to response and cultures, agents like clindamycin, vancomycin, and fourth generation cephalosporin’s, ampicillin/sulbactum may be considered

Moderate to severe with ischemia or significant local necrosis

• Determine presence of bone involvement and peripheral vascular disease
• IV antibiotics, surgical debridement, bed rest, cultures are the mainstay of treatment
• Presence of osteomyelitis, requires 6-12 week of IV Antibiotics
• Localized or generalized ulcers with gangrene require amputation

Additional information for individuals with diabetes; hospitalized for reasons other than diabetes

5) Education:
Physical activity, diet and emotional or physical stress all effect diabetic control directly.

Developing a diabetic teaching plan is vital to provide education. Following tips have been recommended by diabetic societies:

• Healthy eating
• Being active
• Monitoring
• Medication and compliance
• Problem solving
• Reducing risks

More generalized approach to provide education is as follows:

Basic or initial survival skills should include

• Simple definition
• Normal and desired blood sugar levels
• Effect of exercise on insulin sensitivity → decrease in blood glucose
• Diet, stress and illness cause increase in blood sugar levels
• Treatment with insulin or oral hypoglycemic there schedule and relation with the meals
• Monitoring blood glucose and ketones
• Recognizing treatment and prevention of acute complications, (hypoglycemia and hyperglycemia)
• Where to buy how to store and administer insulin, syringes and how to monitor (Glucometer and supplies)
• When and how to reach the doctor

Advance (in depth) or continuing education will include:

• Prevention of long term complication e.g. foot care management, eye care, general hygiene and risk factor management
• Foot care:
  • Properly bathing, drying and lubricating without leaving the moisture to accumulate between the toes
  • Wear close toe shoes which fit well, new shoes should be broken in slowly(i.e. worn for 1-2 hrs)
  • Trimming toenails straight across and file sharp corners, if they are thickened or visual deficit should be trimmed by podiatrist
  • Reduce risk factor (smoking and high lipids) for peripheral vascular disease
  • Should consult physician for any persistent wound
• Alternative methods for insulin delivery includes:
  • Pen
  • Jet injectors
  • Pump (continuous subcutaneous insulin infusion [CSII])
  • Implantable and inhalant insulin delivery

Assessing Readiness to Learn:

• Assess patients coping strategies, and reassure the patient and family
• Evaluate patient’s literacy levels, financial resources, lack of health insurance and family support, since all of them influence diabetes treatment and education plan
• In newly diagnosed patients misconception related to insulin or other hypoglycemic agents may cause anxiety should give them simple and direct information

Teaching experienced patients:

• Continue assessing patients skills and self care behavior
• If patients have developed long term complications they may experience grieving process again
• Discuss the fears and answer them appropriately

Determining teaching methods:

• If desired use various tools e.g. booklets, video tapes
• Handouts should match the patients learning skills
• Patients should be encouraged to attend activities sponsored by local hospitals

Teaching patients self administration of Insulin

Equipment:

• Prescribed bottle of insulin
• Disposable insulin syringe and needle or insulin pen injection device with insulin cartridge
• Cotton ball and alcohol or alcohol wipe

Technique:

i) Injecting

• Give the patient syringe or device with insulin dose
• Show and ask the patient to select and clean the area
• Ask the patients to hold the syringe as a pen
• Show how to then ask the patient to pinch and hold the subcutaneous tissue from the anterior of his/her thigh or stomach between the thumb and the forefinger
• In lean and thin patients to inject at 45 degree angle in the pinched area, and at 90 degrees in taut skin for heavier patients
• Always instruct to rotate sites, and inject with slow and consistent pressure
• Ask to release the skin and withdraw the needle

ii) Loading

• If suspension gently rotate the bottle, need to mix well
• Wiping with alcohol not require store in clean place in original packing
• Inject same volume of air into the vial, as what needs to withdrawn
• If devise is being used follow manufacturers instructions

iii) To load a mixture of long and short-acting insulin from different vials

• Inject air equal to the number of units to be injected into each vial. Use the same sequence each time, for example, always NPH insulin first
• Creates positive pressure in vial, so that insulin will be withdrawn from each vial without mixing.
• Then one by one withdraw the specific dose from each vial, it doesn’t matter which one first

iv) Teaching:

• Reuse of a syringe is not recommended, should be recapped and stored in a clean place if to be reused
• Determine and prescribe appropriate needle length ,shorter needles are more comfortable to use depending on the obesity of the patient
• Advise the patient to store in clean place and wiping the vial with alcohol swab is not necessary
• Check manufacturer recommendations for when to discard insulin vials and pens; recommendations may vary from 10 to 30 days after opening
• Teach patient how to mix insulin after checking manufacturer’s recommendations
• Avoid prefilling syringes because manufacturers have no data on the stability. If it’s the only option, store in refrigerator or suggest an insulin pen injection device
• Help the patient develop a plan for the disposal of needles
• Sharps can be placed in a hard plastic or metal container, when half full secure container with duct tape and mark do not recycle and place it in the trash

Promoting home and community-based care:

• Assess reason for glucose control do not assume ignorance, provide the complete information and evaluate understanding of the patient
• Determine physical or emotional problems impairing patients self care e.g. denial, depression or decreased visual acuity
• Help patient to establish priorities between personal, family or work and self care
• Assess for infections and emotional stress, can be the cause for higher glucose levels despite compliance

Continuing Care:

• Age, socioeconomic status, chronic complications and co morbidities all direct the frequency of follow-ups in the clinic
• In addition to follow-ups, encourage for health screening and immunization
• Encourage to join supportive groups

Insulin secretagogue

Sulfonylurea, first-generation agents

• Chlorpropamide
• Tolazamide
• Tolbutamide

Sulfonylurea, second-generation agents

• Glimepiride
• Glipizide
• Glyburide

Meglitinide drugs

• Nateglinide
• Repaglinide

Mechanism

• Blocks ATP-dependent potassium channels in the β-cell membrane → Depolarizes the β-cell → Facilitating calcium entry through calcium channels → Increased calcium influx induces insulin secretion from the pancreatic beta cells
• Decrease in serum glucagon level
• Enhances peripheral utilisation of glucose
• Decrease in hepatic insulin degradation and gluconeogenesis
• First generation sulfonylureas are differ with second-generation in their pharmacokinetics and lower dosage
• Meglitinides does not contain sulphur in their structure and have a rapid onset and short duration of action as compared to sulfonylurea

Dose:

Sulfonylurea, first-generation agents

Chlorpropamide

• 100-250 mg PO once daily; may titrate by 50-125 mg/day at 3-5-day intervals; Max. 500 mg/day

Tolazamide

• 100-250 mg PO once daily; with breakfast or the first main meal of the day; may increase dose by 100-250 mg/day every week if needed; Max. 1 g/day

Note: If >500 mg/day; divide in 2 doses over 24 hrs

Tolbutamide

• 1-2 g/day PO in 2-3 divided doses; usual 500-3000 mg/day; maintenance dose of >2g/day seldom required

Sulfonylurea, second-generation agents

Glimepiride

• 1-2 mg PO once daily; with breakfast or the first main meal; may increase dose by 1-2 mg/day every 1-2 wks; usual 1-4 mg PO once daily; Max. 8 mg/day

Dose in Renal Impairment: Cl_Cr <22 mL/minute à Start 1 mg PO once daily; may increase dose slowly

Glipizide

• 5 mg PO once daily; may titrate dose by 2.5-5 mg/day as needed at least with an intervals of several days; Max. 15 mg/dose and 40 mg/day (divide dose if >15 mg/day); for extended release tablet maximum dose is 20 mg/day

Dose in Hepatic Impairment: Start with 2.5 mg/day

Glyburide

• 2.5-5 mg PO once daily; may titrate by 2.5 mg/day every week; Max. 20 mg/day in divided doses

Meglitinide Drugs

Nateglinide

• Initial and maintanence 120 mg PO TID before meals; 60 mg PO TID in patients who are near HbA_1c goal; can be given alone or in combination with metformin or a thiazolidinedione

Repaglinide

• HbA_1c <8% or Not treated previously → Start 0.5 mg PO with each meal; usual 0.5-4 mg
• HbA_1c is ≥8% or Treated previously → Start 1-2 mg PO with each meal; usual 0.5-4 mg

Note: May titrate dose by double upto 4mg /dose; to a Maximum dose of 16 mg/day. At least lapse of one week is required to reassess the glucose levels

Dose in Renal Impairment: ClCr 20-40 mL/minute → Initial 0.5 mg before each meal, titrate carefully; ClCr <20 mL/minute → Use not established

Dose in Hepatic Impairment: conservative doses should be used

Biguanides

• Metformin

Mechanism

• Decreases hepatic glucose production, decreasing intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilization)

Dose

Metformin

Immediate-release form

• 500 mg PO BID or 850 mg PO daily; may increase by 500 mg/wk or 850 mg/every other week; Max of 2550 mg/day in 3 divided doses

Extended-release form

• 500 mg PO daily; Usual 1-2 gram PO daily; May increase dose 500 mg/day every week to max 2g/day. Always use divided doses if giving >2000 mg/day for better tolerance

Concomitant with insulin therapy

• Start Metformin 500 mg PO daily; may increase by 500 mg/day weekly until adequate control is achieved; Max 2000 mg/day

Alpha-glucosidase inhibitors

• Miglitol
• Acarbose

Mechanism

• Competitive inhibitor of pancreatic α-amylase and intestinal brush border α-glucoside hydrolase → which results in delayed digestion/absorption of carbohydrates → leading to post meal lowering of glucose, delaying glucose absorption.

Dose:

Miglitol

• 25 mg/day PO TID at the start of each meal; may increase to 50 mg PO TID at least after 4-8 weeks and to 100 mg TID after 3 months, if required; Max. 300 mg/day

Acarbose:

• Initial 25 mg PO TID at the start of each meal; usual 150-300 mg/day PO TID; may increase dose every 4-8 weeks prn; Max. in ≤60kg: 150 mg/day in 3 divided doses, >60 kg: 300 mg/day in 3 divided doses

Insulin Sensitizers (Thiazolidinediones)

• Pioglitazone
• Rosiglitazone

Mechanism

Increases the insulin sensitivity without increasing pancreatic insulin secretion

• An agonist for peroxisome proliferator-activated receptor-gamma (PPARgamma) → found in key target tissues for insulin action → activate nuclear PPARgamma receptors → this influences the production of a number of gene products involved in glucose and lipid metabolism → lowers blood glucose

Dose:

Pioglitazone

• 15-30 mg/day PO once daily; may increase upto 45 mg/day; Max. 45 mg/day

Rosiglitazone

• Initial 4 mg/day PO once daily or in 2 divided doses; if inadequate response after 8-12 weeks the dose may be increased to 8 mg in 2 divided doses; Max. 8 mg/day

Note: Adjunct with a sulfonylurea, maximum dose is 4 mg/day

Dipeptidyl peptidase IV inhibitors

• Sitagliptin
• Saxagliptin
• Linagliptin (available now in Canada)

Mechanism

Inhibits dipeptidyl peptidase IV (DPP-IV) enzyme resulting in

• Prolonged active incretin levels
• Incretin hormones regulate glucose homeostasis by
  • Increasing insulin synthesis and release from pancreatic beta cells
  • Decreasing glucagon secretion from pancreatic alpha cells

Decreased glucagon secretion results in decreased hepatic glucose production.

Dose:

Sitagliptin

• 100 mg PO once daily; Max 100 mg/day
• 75-85% renally excreted

Dose in Renal Impairment: ClCr 15 to <50 mL/min → 50 mg PO once daily; ClCr <30 mL/min → 25 mg PO once daily

Saxagliptin

• 5 mg PO once daily
• Approximately 50% renal excretion

Dose in Renal Impairment: ClCr 15-50 mL/min → 2.5 mg PO once daily; end-stage renal disease → not recommended

Linagliptin

• 5 mg PO daily with or without food
• Minimal renal excretion

Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist

• Exenatide
• Liraglutide

Mechanism

Activates glucagon-like-peptide-1 (GLP-1) receptor, this

• Increases insulin secretion and B-cell growth/replication
• Decreases inappropriate glucagon secretion
• Delay gastric emptying

Doses:

Exenatide:

• Initial 5 mcg SC BID; within 60 minutes prior to meals; may increase to 10 mcg SC BID after 1 month, if needed

Note: Give at least interval of 6 hours between dosing and do not take after meal.

Liraglutide:

• Start 0.6 mg SC daily x 1 week at least; then increase to 1.2 mg SC daily; after at least 1 week may increase to 1.8 mg SC daily as needed to achieve maximum effect

TYPES OF INSULIN:

Rapid-acting Insulin

• Insulin lispro
• Insulin aspart
• Insulin glulisine

Short-acting

• Regular insulin

Intermediate-acting

• NPH insulin (NPH = Neutral Protamine Hagedorn, also known as isophane insulin)

Long-acting, subcutaneous

• Insulin detemir
• Insulin glargine

Combinations

• 50/50 (50% NPH, 50% regular)
• 70/30 (70% NPH, 30% regular)
• 70/30 (70% protamine aspart, 30% aspart)
• 75/25 (75% protamine lispro, 25% lispro)
• 50/50-(50% protamine lispro, 50% lispro)

Mechanism

Insulin acts via specific membrane-bound receptors on target tissues.

• Enhanced peripheral glucose uptake and protein synthesis
• Inhibits hepatic glucose production, lipolysis, and proteolysis

Insulin increases the cellular permeability of several electrolytes, such as

• Potassium, magnesium, and phosphate

Insulin activates sodium-potassium ATPase; this promotes the intracellular movement of potassium.

Rate of absorption, onset, and duration of activity may be affected by:

• Site of injection, exercise, lipodystrophy, local blood supply, temperature

Dose:

Rapid-acting Insulin: Duration effect of Rapid-acting Insulin is <5 hours

Insulin Lispro; Insulin Aspart; Insulin Glulisine

• Usual total insulin requirement 0.5-1 units/kg/day SC divided in 3-4 doses
  • Give <15min before meals or within 20 min after starting a meal
• IV infusion: Diluted in NS or D₅W to concentrations of 0.025-2 units/mL. Stable for 48 hours at room temperature

Dose in Renal Impairment:

• Insulin Lispro: ClCr 10-50 → Decrease dose 25%; ClCr <10 → Decrease dose 50%; Dialysis → No supplement
• Insulin Aspart; Insulin Glulisine: Decrease the dose

Short-acting Insulin: Duration effect of Regular Insulin is ~5-8 hours

Regular Insulin:

• Usual insulin requirement 0.5-1 units/kg/day SC divided in 2-3 doses. Give <15min before meals or within 20 min after starting a meal
• IV infusion: Diluted in NS or D₅W to concentrations of 0.025-2 units/mL

Dose in Renal Impairment:

• ClCr 10-50 → decrease dose 25%; ClCr <10 → decrease dose 50%; Dialysis → no supplement

Diabetic ketoacidosis/Hyperosmolar hyperglycemic state

• IV Bolus: 0.1 units/kg bolus (optional)
• IV Infusion: 0.1-0.14 units/kg/hour.

Note: If no IV bolus was administered, patients should receive a continuous infusion of 0.14 units/kg/hour

• SC/IM: 0.4 units/kg bolus (0.2 units/kg as an IV and 0.2 units/kg as SC or IM); then 0.1 units/kg given every hour SC or IM

Hyperkalemia

• IV: 10 units IV regular insulin mixed with 50 mL D₅₀W given over 15-30 minutes OR 50 mL D₅₀W over 5 minutes followed by 10 units regular insulin IV push over seconds (in imminent cardiac arrest)

Intermediate-acting Insulin: Duration effect of NPH insulin is ~10-18 hours

NPH insulin:

• Usual total insulin requirement 0.5-1 units/kg/day SC (divided in 2-3 doses). Give <15min before meals or within 20 min after starting a meal

Dose in Renal Impairment:

• ClCr 10-50 → Decrease dose 25%; ClCr <10 → decrease dose 50%; Dialysis → no supplement

Long-acting Insulin: Duration effect of Insulin Detemir is ~16-23.2 hours; and Insulin Glargine is Upto 24 hours

Insulin Detemir

• Type 1 DM: Start 0.5-1 units/kg/day SC in divided dose; usual dose 0.5-1.2 units/kg/day SC in divided doses
• Type 2 DM: Start 0.1-0.2 units/kg SC (every evening) or 10 units SC every evening or divided in 2 doses; may increase dose by 2 units/day every third day until glycemic targets achieved

Insulin Glargine

• Type 1 DM: Start 0.5-1 units/kg/day SC in divided dose; usual dose 0.5-1.2 units/kg/day SC in divided doses
• Type 2 DM: Initial 10 units SC daily at bed time; may increase dose by 2 units/day every third day until glycemic targets achieved

Newer therapeutic options

Amylin analogue

• Pramlintide (available in USA not in Canada)

Mechanism

Decreases the rise of postprandial plasma glucose by

• Prolonging of gastric emptying time
• Suppresses postprandial glucagon secretion
• Promotes satiety leading to reduction of caloric intake and potential weight loss

Doses:

Note: When initiating pramlintide, decrease current insulin dose by 50% to avoid hypoglycemia

• Type 1 DM: Initial 15 mcg SC immediately prior to meals; may increase by 15 mcg SC every third day to target dose of 30-60 mcg, if needed and nausea is tolerable

Note: Consider Pramlintide discontinuation if 30 mcg dose is not tolerated

• Type 2 DM: Initial 60 mcg SC immediately prior to meals; may increase to 120 mcg SC after 3-7 days, if needed and nausea is tolerable

Note: If nausea occurs at 120 mcg dose, decrease dose to 60 mcg

Dopamine receptor agonist

• Bromocriptine

Mechanism

• Exact mechanism is not known
• Activates postsynaptic dopamine receptors in the striatum and substantia nigra
• Bromocriptine also suppresses growth hormone production and decreases prolactin secretion
• Results in reversal of insulin resistance and decreases in glucose production
• It decreases fasting and postprandial hyperglycemia without increasing insulin levels

Doses:

• Type 2 DM: Start 0.8 mg PO every morning; may increase by 0.8 mg every week as tolerated to maximum dose of 4.8 mg/day; usual dose 1.6-4.8 mg PO every morning

A For newly diagnosed ndividual’s and acute complications

History, physical assessment and diagnosis should include:

• Onset of signs and symptoms (to evaluate since how long the patients had symptoms before being diagnosed)
• Physical, social and emotional factors, which affect the ability to learn and cope with self care activities
• Fluid and electrolyte deficit related to polyurea and dehydration
• Imbalanced diet and physical activity, in relation to nutrition required while on hypoglycemic agents
• Timely recognition of acute complication
• Incomplete knowledge about the disease itself and self care
• Physical impairment and social factors resulting in self care deficit
• Fear and anxiety related to misinformation and complications

Acute or potential complication to be recognized and diagnosed:

• Hypoglycemia
• Hyperglycemia and ketoacidosis
• Hypokalemia
• Fluid overload, pulmonary edema, cardiac failure
• Cerebral edema

For patients with diabetes as a secondary diagnosis:

In addition to assessment of primary problem, in individual’s with diabetes diagnosis includes

• Hypo and hyperglycemia (inadequate control of blood glucose levels due to release of stress hormones)
• Skin breakdown
• Survival and self care skills (deficient in depth knowledge of diabetes)
• Long term complications
• Imbalanced nutrition
• Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar nonketotic syndrome (HHNS)

Goals:

For newly diagnosed and diabetes as a secondary diagnosis

• Maintain FBS: 6.1 mmol/L (110 mg/dL), and RBS: <7.8 mmol/L (140 mg/dL)
• Maintain fluid and electrolyte balance
• Maintain weight with adequate nutrition
• Maintain skin integrity by regular self examination and professional assessment
• Provide optimal teaching to perform diabetes survival skills and self care
• Avoid complications by close monitoring

For newly diagnosed and diabetes as a secondary diagnosis

Maintaining fluid and electrolyte imbalance

• Intake and output charting
• Administer IV fluids and electrolytes as prescribed
• Check serum electrolytes(especially sodium and potassium)
• Monitor vitals for dehydration

Improve nutrition

• An adequate caloric intake is achieved, to maintain weight
• Optimal glucose control along with diet plan
• Consider patients dietary habits and primary health problems
• Monitor for signs of DKA and HHNS

Reducing Anxiety

• By providing emotional support, setting aside time to talk

Maintaining Skin Care

• Daily assessments for dryness and breaks
• Excessive soaking and lubrication in between the toes should be avoided
• For bed ridden patients with neuropathies, the heels are elevated above the bed by placing the pillows under the legs to ovoid skin ulcer
• Dermal ulcers to treated aggressively

Improving self care

• Teaching survival skills as discussed earlier in this document
• Self monitoring, different treatment modalities (e.g. insulin, diet, exercise)
• Recognition, prevention, and treatment of acute complications

Evaluating and Improving knowledge deficit

• Assess patient level of understanding of diabetes management
• Inpatients can exhibit monitoring, administration, dietary, and exercise knowledge by doing it during admission and provides a chance of reinforcement
• Provide assistance in prevention of short and long term complication strategies

Monitoring and managing of acute complications

• Fluid overload: Monitor vitals, Intake/Output charting, heart rate, rhythm, and respiratory rate and sounds.
• Hypokalemia: Should be anticipated as a result of rehydration. In DKA, cautiously replace potassium after evaluating kidney function.
• Hyperglycemia and ketoacidosis: May lead to the diagnosis of diabetes, and carries a potential of recurrence after treatment
• Hypoglycemia: Triggered by missing meals or increased exercise without adjusting the hypoglycemic agents. Intensive insulin regimen increases the risk of hypoglycemia. Review signs and symptoms of hypoglycemia with the patient and how to avoid and treat it.
• Cerebral edema: Unknown etiology, commonly seen with rapid reduction in blood glucose levels. Hourly flow sheets are used to monitor blood sugar levels, serum electrolytes, intake/output and neurological sings.

Promoting home and community based care

• Teaching patient self care
• Providing continuing care (in cases where a patient is admitted for other health problem and the nurse observes deficiencies in self care knowledge, home care referral can be arrange)

Expected Patient Outcomes
For newly diagnosed and patients with diabetes as a secondary diagnosis:

• Recognize, prevent and treat acute complications by promptly reporting to the physician
• Have knowledge of survival skills, and prevention care
• Able to recognize the acute and late complications
• Have knowledge of treatment modalities – if on insulin can self inject with correct technique
• Understands the importance of self monitoring and is able to monitor blood glucose and ketones in urine
• Is aware of routine self-examination such as foot exam, skin etc.
• Knows the effect of diabetes on the eye, and have the understanding that retinopathy may not effect vision unless serious damage occurs – knows when to see optometrist/ophthalmologist
• Knows sick day rule and how to manage, and when to call in physicians
• Knows the macrovascular risk factors and take measures to control them to avoid cardiovascular, cerebrovascular and peripheral vascular diseases

• Ketone bodies disturbs the acid- base balance when in excess, and results in diabetic ketoacidosis (DKA), signs and symptoms as abdominal pain, nausea, vomiting, hyperventilation, and fruity breath. If left unattended may lead to coma and death. Fluid replacement and insulin treatment should be started ASAP
• In hyperglycemic emergencies, due to insulin infusion potassium levels may drop quickly, so replacement should begin as soon as the 1st bag of N/S is started, followed by close monitoring of potassium levels along with other tests
• Always read the labels before administering insulin
• Insulin molecules adhere to the inner surface of the infusion set, so first 50 mls of the solution be discarded it may contain decrease concentration
• Monitor elders carefully, hypoglycemia can occur undetected and results in fall
• Dehydration is a problem with high chronic BS levels

Core Resources:

• American Association of Clinical Endocrinologists (AACE) medical guidelines for clinical practice for developing a diabetes mellitus comprehensive care plan, Endocr Pract 2011;17 (S2):1-53
• American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011;34:S62-S69
• Compendium of Pharmaceuticals and Specialties (CPS). Canadian Pharmacist association. Toronto: Webcom Inc. 2012
• Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2008;32:S1-S201
• Day RA, Paul P, Williams B, et al (eds). Brunner & Suddarth’s Textbook of Canadian Medical-Surgical Nursing. 2^nd ed. Philadelphia: Lippincott Williams and Wilkins; 2010
• Foster C, Mistry NF, Peddi PF, Sharma S, eds. The Washington Manual of Medical Therapeutics. 33^rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010
• Goldenberg RM, Cheng AYY, Punthakee Z, Clement. Use of Glycated Hemoglobin (A1C) in the Diagnosis of Type 2 Diabetes Mellitus in Adults (Position Statement) Can J. Diabetes 2011; 235: 247-249
• Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. 6 ^th ed. Toronto: Webcom Inc. 2011
• Grundy SM, Cleeman JI, Bairey Merz CN, et al, for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004; 110:227-239
• International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32:1327-1334
• Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 11^th ed. New York: McGraw-Hill; 2009
• Leiter LA, Fitchett DH, Gilbert RE, Gupta M, et al. Cardiometabolic Risk in Canada: A Detailed Analysis and Position Paper. Canadian Journal of Cardiology 27 (2011) e1-e33
• Longo D, Fauci A, Kasper D, et al (eds). Harrison’s Principles of Internal Medicine. 18 ^th ed. New York: McGraw-Hill; 2011
• McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49^th ed. New York: McGraw-Hill; 2010
• Medical Guidelines for Clinical Practice for the Management of Diabetes Mellitus 2007; American Association of Clinical Endocrinologists
• Pagana KD, Pagana TJ eds. Mosby’s Diagnostic and Laboratory Test Reference. 9 ^th ed. St. Louis: Elsevier-Mosby; 2009
• Report from the National Diabetes Surveillance System (NDSS): Diabetes in Canada, 2009 Chronic Disease Surveillance Division. Centre for Chronic Disease Prevention and Control. Ottawa
• Rowland LP et al. (2010) Merritt’s Neurology (^th ed.) Philadelphia: Lippincoot Williams and Wilkins
• Skidmore-Roth L. ed. Mosby’s drug guide for nurses. 9^th ed. St. Louis: Elsevier-Mosby; 2011
• Skidmore-Roth L, ed. Mosby’s nursing drug reference. 24^th ed. St. Louis: Elsevier-Mosby; 2011
• http://www.diabetes.ca/files/for-professionals/CPGExecSummaryEssentials.pdf

Online Pharmacological Resources:

• e-Therapeutics
• Lexicomp
• RxList
• Epocrates

Journals/Clinical Trials:

• American Association of Clinical Endocrinologists Board of Directors, American College of Endocrinologists Board of Trustees. America Association of Clinical Endocrinologists/American College of Endocrinology statement on the use of hemoglobin A1c for the diagnosis of diabetes. Endocr Pract. 2010;16:155-156
• Cushman WC, Evans GW, Byington RP et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus.N Engl J Med 2010; 362:1575-1585
• Duckworth W, Abraira C, Moritz T, et al. Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes N Engl J Med 2008; 358:2560-2572
• Espinola-Klein C, Rupprecht HJ, Bickel C et al. Different Calculations of Ankle-Brachial Index and Their Impact on Cardiovascular Risk Prediction. Circulation. 2008;118:961-967
• 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
• Ginsberg HN, Elam MB, Lovato LC et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010 29; 362:1563-74
• Grenon SM, Gagnon J, Hsiang Y. Ankle-Brachial Index for Assessment of Peripheral Arterial Disease N Engl. J. Med. 2009, 361 e40
• Harris, MI (ed). Diabetes in America, 2^nd ed, National Institutes of Health Publication No. 95-1468, 1995
• Kahn B.B., Flier J.S. Obesity and insulin resistance J Clin Invest. 2000;106:473-481
• Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289:76
• Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2006; 29:1963
• 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 12; 358:2560-72
• Scognamiglio R, Negut C, Ramondo A, et al. Detection of coronary artery disease in asymptomatic patients with type 2 diabetes mellitus. J Am Coll Cardiol 2006; 47:65
• Trachtenbarg DE. Diabetic Ketoacidosis. Am Fam Physician. 2005 71:1705-1714
• WHO Consultation. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. WHO website. http://www.who.int/entity/diabetes/publications/report-hba1c_2011.pdf. Accessed June 14, 2011