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19.1 Diabetes Mellitus

Table of Contents

Diabetes mellitus is a clinical syndrome characterized by persistent hyperglycemia (blood glucose values higher than the normal range) due to deficiency or diminished effectiveness of insulin.

Classification

Diabetes mellitus can be classified as follows:

  • Type 1 Diabetes Mellitus (T1DM) – due to autoimmune β-cell destruction, usually leading to absolute insulin deficiency
  • Type 2 Diabetes Mellitus (T2DM) – due to a progressive loss of β-cell insulin secretion frequently with underlying insulin resistance
  • Gestational Diabetes Mellitus (GDM) – diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation
  • Specific types of diabetes – due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young (MODY), diseases of the exocrine pancreas (such as cysticfibrosis), and drug- or chemical-induced diabetes (such as with glucocorticoid use, in the treatment of HIV/AIDS, or after organ transplantation)

Note: MODY includes patients between the ages of 25–45 who present with very high blood glucose with or without ketones. They may require insulin initially followed by oral hypoglycaemic agents or may require insulin for the rest of their lives.

Diagnostic Criteria

  • Main clinical features of diabetes are thirst, polydipsia, polyuria, tiredness, loss of weight, blurring of vision.
  • Many people have no classical symptoms and may only present late with the symptoms related to complications e.g pruritus vulvae and balanitis due to infections, paraesthesia or pain in the limbs, non-healing ulcers, and recurrent bacterial infection.

WHO diagnostic Criteria 2006

  • Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL)
  • Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours after a 75 g oral glucose load as in a glucose tolerance test
  • Symptoms of hyperglycemia and casual plasma glucose ≥ 1 mmol/L (200 mg/dL)
  • Glycated hemoglobin (HbA1c) ≥ 6.5%.

Diagnosis of gestational diabetes (WHO criteria 2013)

  • Fasting plasma glucose 5.1–6.9 mmol/l
  • 2–hour plasma glucose 8.5–11.0 mmol/l following a 75g oral glucose load.

Note: Fasting plasma glucose higher than 6.9 mmol/l or 2–hour plasma glucose higher than 11.0 mmol/l are considered overt diabetes rather than GDM.

At risk screening

Early diagnosis and good control reduces the risk of costly complications and reduces the deterioration of islet function in T2DM. The following people should therefore be screened with fasting blood glucose or HbA1c at least yearly when they visit health facilities:

  • Individuals with impaired glucose tolerance or impaired fasting glucose or a history of a cardiovascular event
  • Those aged ≥40 years with body mass index (BMI) ≥30 kg/m2 or hypertension
  • Children and adolescents who are overweight or obese and who have two or more additional risk factors for diabetes.
  • Women with a history of gestational diabetes mellitus or polycystic ovary syndrome
  • People on long-term steroids or immunosuppressants.
  • All pregnant women at the first antenatal visit if overweight, have had big babies (birth weight >4 kg), gestational diabetes, previous stillbirths or neonatal deaths. Screening should be repeated in the second trimester if negative.
  • All women during the 2nd or 3rd trimester (for gestational diabetes)

Management and non-pharmacological treatment

For people with glucose intolerance the risk of T2DM and its associated mortality may be reduced by:

  • dietary modification
  • physical activity
  • weight reduction
  • medication with metformin.

Table 19.1: Goals for optimum management of diabetes

Diet Advise same as for people without diabetes
Body mass index Therapeutic goal is 5–10% weight loss for people who are overweight or obese, but aim for BMI<25 kg/m2
Waist circumference <102 cm for men, <88 cm for women
Physical activity At least 30 minutes of moderate physical activity on most days of the week (total ≥150 minutes/week)
Cigarette consumption 0 per day
Alcohol consumption Not more than 2 standard drinks (20 g) per day for men and women
Blood glucose level Non-pregnant: 4–6 mmol/L fasting; 6–8 mmol/L postprandial

Pregnant: ≤5.0 mmol/l fasting, ≤6.7 mmol/l postprandial

Self-monitoring of blood glucose is recommended to improve outcomes

HbA1c Target ≤7% (6.5–7.5%)
Lipids Total cholesterol: <5.2 mmol/L

HDL-C: ≥1.0 mmol/L

LDL-C: <2.6 mmol/L

Triglycerides: <1.7 mmol/L

Blood pressure Target ≤140/90 mmHg

For those with albuminuria/proteinuria <130/80 mmHg

Urine albumin Spot collection: <20 mg/L
Urine albumin-to-creatinine ratio (UACR): women: <3.5 mg/mmol; men: <2.5 mg/mmol

The algorithm below is a stepwise guide towards achieving the above goals. Lifestlye measures are the first step but they are lifelong.

Algorithm for the Glycaemic Management of T2DM

Refer to Downes et al. for evidence for combination therapy.

Healthy lifestyles

  • Dietary control aims to maintain the blood sugar level within an acceptable range as follows:
    • Each meal should consist of a wide variety of nutritious foods from the core food groups (vegetables, fruits, grains, meat and proteins, dairy products)
    • 45-50% of energy intake should be in the form of carbohydrates
    • Complex carbohydrates are preferable to simple sugars
    • Carbohydrates and calories should be evenly distributed throughout the day with small/light meals in between the three main meals
    • Meals must not be missed
    • Sugar and sugar-containing food/drinks should be avoided. They are only recommended when a patient feels faint, or ill and cannot eat normally.
    • Sweetners, diabetes foods and drinks are not essential.
    • It is also recommended that a light/small meal should be taken before and after playing sport.
  • Encourage weight loss if the patient is obese or has body mass index (BMI) of more than 25 kg/m2. Loss of body weight often results in improved glycaemic control, BP and lipid profiles.
  • Increase physical activity levels (e.g. brisk walking): at least 30 minutes of moderate activity at least five times a week.
    • Low-level aerobic exercise (eg brisk walking for half an hour per day) and physical resistance training improves glucose tolerance, energy expenditure, feeling of wellbeing and mood, work capacity, improved BP, lipid profiles and increased functional mobility in older people.
    • Medicine dosages and or food intake may need adjustment to avoid hypoglycaemia.
  • Encourage patients to stop taking alcohol or limit to 1 drink per day for women and 2 drinks per day for men. For women who are pregnant, planning a pregnancy or breastfeeding, not drinking alcohol is the safest option.
Note:
Consistency in carbohydrate intake, and spacing and regularity of meals may help some patients manage blood glucose and weight.
Inclusion of snacks in meal plans should be balanced against the potential risk of weight gain and/or hypoglycaemia.
A small amount of sugar as part of a mixed meal or food (eg one teaspoon of sugar/honey added to breakfast cereal) may not adversely affect the blood glucose level.
Foods naturally high in sugars such as fruit and dairy are recommended

Pharmacological Treatment

Treatment with oral hypoglycemics

  • Review the blood glucose at follow-up clinic and adjust medicines as needed until blood glucose is controlled.
  • If dietary control on its own fails or blood glucose levels are persistently high (fasting >11 mmol/l or random >15 mmol/l) initiate:
    A: Metformin 500 mg twice daily with or after meals. Increase, as required, until a maximum of 2000mg in 2–3 divided doses. If
    Metformin is contraindicated then use
    A: Glibenclamide 2.5–15mg once daily
    OR
    A: Glimepiride 1–2mg twice daily
    OR
    A: Gliclazide 40–320mg twice daily
  • If the maximum dose of metfotmin does not result in adequate glycaemic control, either one of the above sulphonylureas may be added, starting with the lower dose and increasing until control is achieved or the maximum dose is reached.
  • If a combination of both medicines is still inadequate, then insulin should be added as detailed below in the section on insulin.
Note

• Metformin is contraindicated in those with severe renal, liver and cardiac failure. The lower dosage are appropriate when initiating treatment in elderly patients with uncertain meal schedules, or in patients with mild hyperglycemia

• Activity of sulphonylurea is prolonged in both hepatic and renal failure; sulphonylureas are best taken 15 to 30 minutes before meals

• Several recent guidelines provide succinct summaries on current evidence for use of oral drugs in the management of diabetes.

Treatment with Insulin Injection

T1DM is treated with insulin injections. Oral agents are not to be used in T1DM

Insulin injections are indicated in T2DM in the following conditions:

  • Initial presentation with fasting blood glucose more than 15 mmol/l
  • Presentation in hyperglycaemic emergency
  • Peri-operative period especially major or emergency surgery
  • Other medical conditions requiring tight glycaemic control
  • Organ failure: Renal, liver, heart etc
  • Diabetes in pregnancy not well controlled with diet or oral drugs
  • Latent autoimmune diabetes of adults (LADA)
  • Contraindications to oral drugs
  • Failure to meet glycaemic targets with oral drugs.

Note: The maximum glucose lowering efficacy of oral drugs is usually evident by six months and therefore the efficacy of any added therapy must be assessed within six months and an alternative drug instituted in case of failure.

Insulin injections should be initiated by a doctor able to fully instruct the patient in its use but insulin will be available at lower health facilities for management of stable patients who require prescription refills.

Table 19.2: Types of insulin as per WHO Essential Medicine List

Type of Insulin Name Basal or short acting
Short acting A: Insulin–short acting (human) soluble Short acting
Intermediate acting A: Insulin–intermediate acting (human) Basal
Pre-mixed insulin A: Intermediate and short acting insulin (70/30) Basal + Short acting

Insulin as substitution therapy

  • Oral medicines are discontinued (unless the patient is obese where metformin will be continued)
  • A Pre-mixed insulin is introduced at a dosage of 0.2 IU/kg body weight and this is split into: ⅔ in the morning and ⅓ in the evening
  • Inject 30 minutes before the morning and the evening meals.

Insulin as supplemental therapy

  • Neutral Protamine Hagedorn (NPH) insulin administered at night before 22:00h at a total daily dose of 0.1–0.2 IU/kg body weight.
  • The oral medicines are continued (half maximum dose of sulphonylureas and metformin dose of 2 g/day)
  • Blood glucose levels are monitored.

Insulin for T1DM

  • Use insulin such as short acting, intermediate and mixed insulin.
  • Most people with T1DM should be treated using a combination of prandial (rapid or short-acting insulin) and basal (intermediate or long acting insulin) insulins subcutaneously
  • Give prandial insulin 3 or more times a day approximately 30 minutes prior to start of a meal
  • Give basal insulin before the evening meal.
  • Total daily insulin requirements are generally between 0.5 to 1 unit/kg/day
    • Give 1/3 of the total dose as basal
    • Give the remaining 2/3 of the total dose as prandial before meals.
    • The amount for each meal should depend on the carbohydrate content of the meal, pre-meal blood glucose, and anticipated activity.
  • At initiation of insulin therapy, give appropriate advice on hypoglycaemia, sick days, physical activity, SMBG and diet.

Self-monitoring in patients with T2DM

Self Monitoring Blood Glucose (SMBG) is usually recommended in the following patients:

  • patients on insulin and glucose lowering agents that can cause hypoglycaemia (sulphonylureas)
  • when monitoring hyperglycaemia arising from illness
  • with pregnancy and pre-pregnancy planning
  • when changes in treatment, lifestyle or other conditions requires data on glycaemic patterns
  • when HbA1c estimations are unreliable (eg haemoglobinopathies)

Table 19.3: Clinical monitoring of people with diabetes

Initial visit 3 Month visit Annual visit
History and diagnosis

Physical examination

• Height and weight

• Waist/Hip circumference

• Blood pressure

• Detailed foot examination

• Tooth inspection

• Eye examination

o Visual acuity+ Fundoscopy

• ECG

• Biochemistry

o Blood sugar
o Glycosylated Haemoglobin (HbA1c)
o Lipid profile (TC,HDC,LDLC,TG)
o Serum creatinine
o Urine: glucose, ketones, protein

• Education

• Nutritional advice

• Medication if needed

• Relevant history

• Weight

• Blood pressure

• Foot inspection

• Biochemistry

o Blood Glucose

• Urine protein

• Education advice

• Nutrition advice

• Review therapy

• HbA1c every six months

History and examination
– as at initial visitBiochemistry as at initial visit
TC=Total cholesterol, HDLC=high density lipoprotein, LDLC= low density lipoprotein, TG=Tryglycerides

Surgery in diabetes

General measures

Correct pre-operative management depends on type of surgery (major or minor), type of diabetes and recent diabetes control.

  • Surgery should be delayed if possible if HBA1C >9% or blood glucose fasting >10 mmol/l or random glucose > 13 mmol/l.
  • Screen for nephropathy, cardiac disease, retinopathy and neuropathy and inform surgical team.

If on diet or oral agent therapy and well controlled and surgery is minor:

Omit therapy on morning of surgery

Resume therapy when eating normally

If on insulin therapy or poor glycaemic control or major surgery:

  • Use continuous IV insulin infusion
  • Start at 8 am and stop when eating normally.
  • Monitor blood glucose before, during and after surgery
  • Aim for blood glucose levels of 6–10 mmol/l.

For major surgery (glucose-insulin potassium regimen)

  • Once snack is missed, start an IV regimen irrespective of the size of the procedure
  • Maintain insulin administration (hourly) to avoid lipolysis and ketoacidosis in patients with restricted oral intake and thus prevent DKA
  • Administer 5% dextrose in maintenance IV fluids
    AND
  • Short-acting insulin (16 Units) + KCl 10mmol/L added to 500mls of 10% dextrose.
    • Infuse at 80ml/hr IV.
    • If obese or initial blood glucose is high (>14mmo/l) consider higher dose of insulin (20 Units)
    • If very thin or usual insulin dose is very low consider lower dose (12 Units)
  • Monitor blood glucose levels hourly (aim for 6–10 mmo/l)
    • If blood glucose is low or falling reduce dose by 4 Units
    • If blood glucose is high or raising increase dose by 4 Units
  • Patients receiving Multiple Daily Insulin Therapy (MDIT) should receive preoperative basal insulin dose without interruption in the perioperative period. When oral intake is restricted, regular insulin may be given every 4–6 hrs to control hyperglycemia. When a diet is tolerated, the MDIT regimen should be resumed
  • Post operatively: give 5–10% dextrose IV 1 litre + KCl 20ml + 2/3 of total daily dose of insulin over 8hrs and repeat until able to take orally
  • Continue the infusion until 60 minutes after the first meal.
  • Resume usual therapy after first meal
  • Check electrolytes daily

Note:

  • Diabetic patients should be first on the operation list
  • Minor surgery: does not involve general anesthesia or starvation
  • Major Surgery: involves a general anesthesia and therefore a period of fasting

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