Diabetes Mellitus

Introduction

Diabetes mellitus is a common metabolic
disorder characterised by persistent
hyperglycaemia, a consequence of defects in the action or secretion of insulin resulting in disturbances of metabolism of carbohydrates,
fat and protein.
It is associated with acute as well as long-term complications affecting the eyes, kidneys, feet, nerves, brain, heart and
blood vessels .

Classification

Its classification has been revised by the WHO and is based on aetiology:

Type 1:

Type 1 diabetes mellitus results from destruction (usually autoimmune) of the pancreatic P cells.

Type 2:

This is characterized by insulin resistance and/or abnormal insulin secretion (either may predominate); both are usually present.
It is the most common type of diabetes.
Gestational diabetes: appears for the first time in pregnancy

Clinical features

Type 1 diabetes:

  • Patients present at a young age (usually teens or twenties); earlier presentation may also occur.
  • Rapid onset of severe symptoms: weight loss, thirst and polyuria
  • Blood glucose levels are high and ketones are often present in the urine
  • If treatment is delayed, ketoacidosis (DKA) and death may follow
  • The response to insulin therapy is dramatic and gratifying
  • Misclassification of patients as “Type 1” is relatively common
  • Insulin-treatment is not the same as
    insulin-dependence

Type 2 diabetes:

  • Most patients present with the classical symptoms including polyuria, polydipsia and polyphagia
  • Some patients present with sepsis, diabetic coma (hyperosmolar non-ketotic states)
  • A minority is asymptomatic and therefore identified at screening
  • The patients usually do not seek medical attention early because of the insidious nature of the disease
  • Many present at diagnosis with features of diabetic complications
    • Visual difficulties from retinopathy
    • Pain and/or tingling in the feet from neuropathy
    • Foot ulcerations
    • Stroke

Gestational diabetes (GDM):

  • This is diabetes which arises in pregnancy
  • Must be distinguished from existing diabetes in women who become pregnant
  • Of particular importance because it is associated with poor pregnancy outcomes, especially if not recognised and not treated

Particular problems associated with GDM:

  • Foetal macrosomia Eclampsia
  • Intra-uterine growth retardation
  • Birth difficulties
  • Neonatal hypoglycaemia
  • Neonatal respiratory distress

Diagnosis

  • Straightforward in the majority of cases
  • May pose a problem for those with a minor degree of hyperglycaemia, and in asymptomatic subjects
    • In these circumstances, two abnormal blood glucose results on separate occasions are needed to make the diagnosis
    • If the results of point blood glucose testing are equivocal, an oral glucose tolerance test should be performed.
    • If diagnosis remains in doubt, maintainsurveillance with periodic re-testing until the diagnostic situation becomes clear
  • Take into consideration additional risk factors for diabetes before deciding on a diagnostic or therapeutic course of action.

The diagnosis of diabetes must be confirmed biochemically prior to initiation of any therapy

  • Symptoms of hyperglycaemia

Plus:

  • Random venous plasma glucose 11.1 mmol/L

Or

  • Fasting venous plasma glucose 27.0 mmol/L

Or

  • HbA1c 27%

Confirms the diagnosis of diabetes

  • In asymptomatic subjects, a single abnormal blood glucose result is inadequate to make a diagnosis of diabetes
  • Abnormal values must be confirmed at the earliest possible date using any of the following:
  1. Two separate fasting  or random blood samples or
  2. A 75 g oral glucose tolerance test

Glucose Tolerance State.Venous Plasma (mmol/L)Venous plasma (mg/dL)
Diabetes mellitus



Fasting
≥ 7≥ 126
2 hour post-75 g glucose load≥ 11.1 ≥ 200
Impaired glucose tolerance
Fasting< 7 - 7.8< 110 - 140
2 hour post-75 g glucose load< 11.1< 200
Impaired fasting glycaemia
Fasting6.1 - < 75.6 - < 6.1

Unless there is unequivocal hyperglycaemia with acute metabolic decompensation or obvious symptoms, the diagnosis of diabetes should always be confirmed by repeating the test on another day

Management

Goals:

  • Early diagnosis
  • Prevent and/or reduce short and long term morbidities
  • Prevent premature mortality
  • Improve quality of life and productivity of affected persons
  • Promote self care practices and empowerment of people with diabetes
  • Reduce the personal, family and societal burden of diabetes
  • Achievement of these goals is dependent on:
    • Successful establishment of diabetes health care team, and infrastructure to support it, including provision of education for health care professionals and for people living with diabetes.

Core components of diabetes care

  • Treatment of hyperglycaemia
  • Treatment of co-morbidities
  • Prevention and treatment of macrovascular and microvascular complications

Non-drug treatment

Education

  • The provision of knowledge and skills to people with diabetes mellitus
  • To empower them to render self-care in their management
  • Principles of Diabetes Education should be locally applicable, simple and effective
  • All members of the diabetes care team should be trained to provide the education
  • It must empower people with diabetes as well as their families
  • Provide them with adequate knowledge of diabetes and its sequelae
  • Create the right attitudes and provide resources to provide appropriate self care

The effectiveness of the programme must be evaluated and modified as necessary

What people with diabetes need to know

  • Diabetes is serious but can be controlled
  • Complications can be prevented
  • That the cornerstones of therapy are education, diet and exercise
  • Their metabolic and blood pressure targets
  • How to look after their feet and thus prevent ulcers and amputations
  • How to avoid other long term complications
  • That regular medical check ups are essential
  • When to seek medical help

Diet

  • One of the cornerstones of diabetes management is diet.
  • Based on the principle of healthy eating in the context of social, cultural and psychological influences on food choices
  • Dietary modification (and increasing level of physical activity) should be the first step in the management of newly
    diagnosed persons with Type 2 diabetes
  • It should be maintained throughout the course of diabetes management

Goals of dietary management of Type 2 diabetes mellitus

To achieve an ideal body weight:

  • An appropriate diet should be prescribed along with an exercise regimen
  • Caloric restrictions should be moderate and yet provide a balanced nutrition
  • Eat at least three meals a day. Binge eating should be avoided
  • A snack between meals can be healthy for certain groups of people
  • The diet should be individualized, based on traditional eating patterns, be palatable and affordable
  • Animal fat, salt, and so-called diabetic foods should be avoided
  • Pure (simple sugars) in foods and drinks should be avoided.
  • Eating plans should be high in carbohydrates and fibre, vegetables and fruits should be encouraged
  • Dietary instructions should be written out, even if the person is illiterate: someone at home should be available to interpret
    to him/her
  • Food quantities should be measured in volumes using available household items
    (e.g. cups), or be countable (e.g. number of fruits or slices of yam or bread)
  • Weighing scales are generally
    unaffordable and/or difficult to
    understand
  • Appetite suppressants generally yield poor and/or unsustainable weight reductions and are expensive

Physical activity

Physical activity is one of the essentials in the prevention and management of Type 2 diabetes mellitus.
Regular physical activity:

  • Improves metabolic control
  • Increases insulin sensitivity
  • Improves cardiovascular health
  • Helps weight loss
  • Gives a sense of well-being

Two main types of physical activity:

  1. Aerobic or endurance exercise e.g. walking, running
  2. Anaerobic or resistance exercise (e.g. lifting weights)

Both types of activity may be prescribed to persons with type 2 diabetes mellitus; the aerobic form is usually preferred

General principles and recommendations

Detailed evaluation

  • Cardiovascular, renal, neurological and foot assessments
  • Evaluation should be done before a formal exercise programme is commenced
  • The presence of chronic complications excludes certain forms of exercises
  • Prescribed physical activity programmes should be appropriate for:
    • The age
    • Socio-economic status
    • State of physical fitness
    • Lifestyle
    • Level of control
  • Exercise generally improves metabolic control, but can precipitate acute complications like hypoglycaemia and hyperglycaemia

Physical activity should:

  • Be regular (about 3 days/week)
  • Last at least 20-30 minutes per session
  • Be at least of moderate activity
  • Activities like walking, climbing steps (instead of taking lifts) should be encouraged
  • For sedentary persons with diabetes, a gradual introduction using a low intensity activity like walking is mandatory

Avoid exercising if:

  • Ambient glycaemia is > 250 mg/dL blood glucose
  • Patient has ketonuria
  • Blood glucose is less than 80 mg/dL

To avoid exercise-induced hypoglycaemia in patients on insulin

  • Increase peri-exercise carbohydrate intake
  • Reduce insulin dose
    • Adjust injection site (avoid exercising muscles site) For persons with type 2 diabetes mellitus on long acting insulin secretagogues
  • Extra carbohydrate should be taken before and after the exercise
  • In those on short acting secretagogues (e.g. glipizide, repaglinide) the post exercise dose should be omitted
  • Glycaemia should be monitored (using strips and meters) before and after planned physical activity
  • Delayed hypoglycaemia may occur
  • Proper footwear must always be worn during exercise
  • For a prescribed formal activity, the exercise session should consist of:
    • A warm-up period of 5-10minutes
    • The activity proper: 20-60 minutes
    • A cool-down period of 5-10minutes
  • In most parts of Africa, prescribing formal exercise in gyms or requiring special equipment is a recipe for non-adherence to
    the exercise regimen
  • Patients should be encouraged to integrate increased physical activity into their daily routine
  • The programme should impose minimum (if any) extra financial outlay in new equipment and materials

Drug treatment

Oral antidiabetic agents:

For Type 2 diabetes mellitus; indicated:

  • When individualized targets are not met by the combination of dietary modifications and physical activity/exercise
  • (In some cases) at the first presentation of diabetes (i.e. fasting blood glucose more than 11 mmol/L or random blood glucose more than 15 mmol/L)
  • May be used as monotherapy or in combination therapy, targeting different aspects in the pathogenesis of hyperglycaemia in Type 2 diabetes mellitus i.e. increasing insulin production and releasing, decreasing insulin resistance and/or decreasing hepatic glucose production
CategoryExampleMechanism of actionDaily doseSide effects
BiguanidesMetforminImproves insulin. sensitivity in the liver, muscle and adipocytes500-2500mgNausea, vomiting, abdominal pains
SulphonuylureasGlibenclamide, GlimepirideStimulates insulin release from the beta cells25-15mg ,1-6mgHypoglycaemia Weight gain
DPP IV inhibitorsVildagliptinStimulate insulin release in a glucose dependent manner50-100mgGastrointestinal upset, Abnormal liver function tests
InsulinsVarious formulationsIncrease glucose absorptionAppropriate dosesLipodystrophy, Hypoglycaemia

Sulphonylureas

  • Initial monotherapy in non-obese patients
  • Add-on as combination therapy
  • Indicated for Type 2 diabetes, maturity onset diabetes of the young, under specialist care

Contraindications

  • Allergy to sulpha drugs
  • Liver impairment
  • Severe renal failure
  • Pregnancy
  • Age > 80 years

Biguanides

Indicated in:

  • Monotherapy in obese Type 2 diabetes mellitus
  • Combination therapy
  • Metabolic syndrome
  • Allergy to sulphonylureas
    • Under specialist supervision ONLY
    • Not licensed for use in children less than 10 years old

Important notes on Oral Glucose Lowering Agents (OGLAS)

  1. Sulphonylureas and biguanides are the agents most widely available
  2. Stocking these agents would meet the diabetes care needs of most diabetes facilities
  3. The choice of OGLAS should be informed by:
    1. Lifestyle
    2. Degree of control
    3. Access to medicines
    4. Economic status
    5. Mutual agreement between the doctor and the person with diabetes
  4. Monotherapy with any of the drugs should be the initial choice
    • Use of stepped-care approach is recommended
  5. If overweight (BMI > 25 kg/m²) or if insulin resistance is the major abnormality
    • Metformin should be the first choice
    • If metformin is contraindicated, thiazolidinediones may be used
  6. Avoid metformin and long acting sulphonylureas in elderly patients.
    • Instead, use short acting sulphonylureas
  7. Combination therapy using OGLAs with different mechanisms of action is indicated if monotherapy with one of the agents has failed
  8. When oral combination therapy fails, insulin should be added to the treatment regimen or should replace the OGLAS
  9. Secondary failure of OGLAS is said to be common (5-10% of patients annually) although no reports from Africa are available

Insulin Therapy in Type 2 Diabetes

Insulin is increasingly being used

  • In combination with OGLAS or as
    monotherapy in the management of Type 2 diabetes to achieve optimum targets
  • Hyperglycaemic emergencies
  • Peri-operatively, especially major or emergency surgeries
  • Organ failure: renal, liver, heart etc
  • Latent Autoimmune Diabetes of Adults (LADA)
  • Pregnancy
  • Sensitivity to OGLAS

Regimen and dose of insulin therapy will
vary from patient to patient
Two forms of insulin therapy are often used in combination with OGLA therapy

  • Intermediate/long acting insulin plus OGLA or pre-mixed insulin

Referral to an endocrinologist should be
considered if more than 30 units of insulin are required per day 
Time Course of Action of Insulin Preparations

Insulin PreparationOnset of ActionPeak ActionDuration of ActionInjections per day
Very rapid acting (insulin analogues)10 min1h3hImmediately before meals
Short-acting30 min2-5h5-8h30 min before meals
Intermediate-acting (NPH or lente)1-3h6-12h16-24 hOnce or twice daily
Biphasic mixtures (30/70; premixed)30 min2-12h16-24 hOnce or twice daily

Monitoring glycaemic control

  • Clinical and laboratory methods are employed
  • HbAlc tests are desirable standard tests
  • Fasting plasma glucose performed in the laboratory in place of HbAlc is the best alternative when HbAlc tests is unavailable
    • Its average for repeated measurements gives a reliable indication of the control
  • Glycosuria is a poor means of assessment of control
  • Self Blood Glucose Monitoring (SBGM) should be encouraged
  • Results of self urine testing or blood glucose tests should be recorded in a logbook
  • Clinic protocols should set out in some detail, the parameters to be monitored at the initial visits, at regular follow-up visits, and at
    annual reviews
  • At the initiation of insulin therapy, appropriate advice on SBGM and diet should be given