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Definition of diabetes
Characterized by hyperglycaemia
Defects in insulin production Autoimmune or other destruction of beta cells Insulin insensitivity
Definition of diabetes
Chronic hyperglycaemia associated with long-term damage to:
Eyes Kidneys Nerves Heart and blood vessels
3
230 million affected in 2006 350 million within 20 years Most rapid in Indian and Asian subcontinents
Classification
1. Type 1 diabetes
autoimmune
LADA idiopathic 2. Type 2 diabetes Insulin resistance Deficiency of insulin
5
Classification
3. Other specific types MODY Defects in insulin action Diseases of the pancreas Endocrine disorders Drug- or chemical-induced Infections
Classification
Uncommon forms of immunemediated diabetes Other genetic syndromes 4. Gestational diabetes
Blood glucose
Glycogen synthesis
Glycolysis
Gluconeogenesis (amino acids)
Blood glucose
Blood glucose
Blood glucose
Converted to triglycerides
Clinical diabetes
Pre-diabetes Honeymoon Chronic phase Time (months - years)
15
No autoimmune markers
Permanent insulinopenia
Ketoacidosis People of African and Asian origin
16
Lack of treatment
Autumn/winter peaks
18
Type 2 diabetes
90%-95% of people with diabetes Insulin insensitivity and relative insulin deficiency Obesity or overweight Complications often present at diagnosis
19
Age (years)
21
Insulin requirements
Insulin insensitivity
Age (years)
22
Insulin requirements
Insulin insensitivity
Age (years)
23
Hypertension Dyslipidaemia Abdominal obesity Overweight Polycystic ovary disease Acanthosis nigricans Schizophrenia
26
Diagnosing diabetes
Normal Impaired fasting glucose* Impaired glucose tolerance** <6.1mmol/L <110mg/dL 6.1 to 6.9mmol/L* 110 to 126mg/dL 7.8 to 11mmol/L** 126 to 200mg/dL Diabetes
FPG
28
Intermediate states Increased risk of developing diabetes Prevention strategies to prevent or delay progression Increased risk of cardiovascular disease
29
30
Urinary ketones
Antibodies
C-peptide
31
Summary
Type 1 diabetes Results from progressive beta-cell destruction People with type 1 diabetes need insulin therapy to live
32
Summary
Type 2 diabetes Often characterized by insulin insensitivity and relative rather than absolute insulin deficiency A progressive condition Most people with type 2 diabetes will need insulin within 5 to 10 years of diagnosis
33
minerals
1986 2004
<60 45-65*
12-20 10-20
<30 20-35
<10% saturated fat
Carbohydrates: 45-65% (mostly starch) Dietary fibre: minimum 20g/1000 kcal Fats: 20-35% Protein: 10-20% (0.8 g/kg/day) Sodium: <3000 mg/day Vitamins and minerals: supplements not necessary with balanced diet
Fluids
amounts of fluid
Energy
Produced by utilizing food in the body Measurements of energy: - usually measured in kilojoules (kJ) - calories or kilocalories (kcal) - 1 kcal = 4.2 kJ
Energy recommendations
Appropriate intake for acceptable body weight Lower-calorie diets recommended for overweight people with diabetes Increased-energy diets recommended
- during pregnancy and lactation - during recovery from severe and prolonged illness
Proteins
Provide amino acids Help to build muscle mass Animal sources Plant sources
Protein recommendations
0.8 g protein per kg bodyweight per day 10-20% of total energy per day Higher amounts not encouraged for people with diabetes
Carbohydrates
Should provide main source of energy for the body (>50%) Nutrient that most influences blood glucose levels Source of simple sugars glucose, fructose
Amount and source of carbohydrates should be considered when planning meals Carbohydrates should mainly come from
whole grains: wheat, rice, pasta, etc potatoes legumes, beans, pulses fruit and vegetables milk
Carbohydrate recommendations
Sucrose white sugar Permissible source for up to 10% of total daily energy needs Does not increase glycaemia more than starch Part of a balanced meal High sucrose contributes to obesity and dental caries
American Diabetes Association; Canadian Diabetes Association
Couscous
Lentils Banana
52
99 72
0.3 cup
0.5 cup 1 small
12.1
19.9 16.9
Benefits of fibre
High-fibre diet is healthy Mixture of soluble and insoluble fibre - slows absorption of glucose - reduces absorption of dietary fats - retains water to soften stool - may reduce the risk of colon cancer - may reduce the risk of heart disease
Fats
The most concentrated source of energy Foods may contain fat naturally or have it added during cooking 1 g fat provides 9 kcal
Fat recommendations
High in monounsaturated fats (>10%) Low in saturated fats (<10%) Low in polyunsaturated fats (up to 10%) Low in hydrogenated fat
Fats
Common sources of different fats Saturated red meats, butter, cheese, margarine, ghee (clarified butter), whole milk, cream, lard Polyunsaturated safflower oil, sunflower oil, corn oil Monounsaturated olive oil, canola oil, rape seed oil, groundnut oil, mustard oil, sesame oil
Trans fats
Formed when liquid fats, such as oils, are chemically hydrogenated Raise LDL cholesterol and lower HDL cholesterol
Fish oils
Balance of omega-3 and omega-6 fatty acids part of a healthy diet Fish oils good source of omega-3 fatty acids Two or three portions of fish are recommended per week Fish-oil supplements not recommended
Blackgram, cowpea, rajmah, soya Green leafy Fenugreek, mustard Walnut, flaxseed Mustard, soya bean oil, canola oil
Long chain n3 PUFA (omega-3) biologically active product of alpha linolenic acid Ghafoorrunissa et al, NIN 1994
Cholesterol
Intake of cholesterol should be restricted People with diabetes should consume less than 300 mg of cholesterol a day Minimizing consumption of saturated fat will help decrease cholesterol
Vitamins
Organic substances present in very small amounts in food Essential to good health A balanced meal automatically provides all necessary vitamins Either fat-soluble or watersoluble
Antioxidants help protect against heart disease and other health complications Good sources of antioxidants including fruit and vegetables should be eaten daily Recommended daily intake five portions
Minerals
Minerals present in bones, teeth, soft tissue, muscle, blood and nerve cells Help maintain physiological processes, strengthen skeletal structures, preserve heart and brain function and muscle and nerve systems Act as a catalyst to essential enzymatic reactions Low levels of minerals puts stress on essential life functions
Sodium recommendations
Most people consume too much salt Daily intake should not exceed 6000 mg Daily sodium intake should not exceed 2400 mg Salt intake should be restricted in hypertension, heart disease, kidney failure Diet should be based on fresh foods
Carbohydrates: 45-65% (mostly starch) Dietary fibre: min 20 g/1000 kcal Fats: 20-35%
- saturated <10% - polyunsaturated <10% - monounsaturated >10% - cholesterol <300 mg/day
Protein: 10-20% (0.8 g/kg/day) Sodium: <2400 mg/day Vitamins and minerals: with a balanced diet, supplements not needed
Physical activity
577 persons >25 years Random selection from clinics 6 years follow-up
68% cumulative incidence 44% (reduction of 31%) 41% (reduction of 46%) 46% (reduction of 42%) 58% decreased incidence in the diet + exercise group
522 persons, 40-64 years BMI >25 Random selection by persons 3.2 years follow-up
Diet + exercise
Modifies visceral fat and distribution of body fat Increases muscle mass
Apple shape
Pear shape
Types of exercise
Aerobic exercise uses large muscle groups and requires oxygen for sustained periods Anaerobic (resistance) exercise uses large muscles which do not require oxygen for short periods of exercise
Recommendations
People with type 2 diabetes should accumulate 150 minutes of moderateintense aerobic exercise each week, spread over 3 non-consecutive days
People with diabetes should be encouraged to perform resistance exercise 3 times a week
CDA 2003
Recommendations
The American College of Sports Medicine recommends 20 to 60 minutes of exercise most days a week Aerobic exercise, such as walking, jogging, swimming, skipping, bike riding, should be sufficient to raise the pulse or increase respiration
In resistance training, it is better to use repetitive light weights than heavy weights
Identify an activity that will be enjoyed Start slowly, perhaps 5-10 minutes at a time Increase duration and intensity slowly Consider doing exercise in a group or with a partner Prevent boredom by varying the activities
Summary
Aims of treatment
Beta-cell dysfunction
Insulin production
Henry 1998
Mechanisms of action
GLP-1 (incretins) improve response to glucose level
Alpha-glucosidase inhibitors slow absorption of sucrose and starch Thiazolidinediones and biguanides reduce insulin resistance
Two (or more) oral blood glucoselowering medicines that have different mechanisms of action Two medications rather than increase in initial medicine to maximum dosage Fewer side effects than monotherapy at higher doses
Target for people who can achieve it (without too much hypoglycemia)1
Target for most people with diabetes IDF Global guideline for Type 2 diabetes3
< 6%
4-6 mmol/L
5-8 mmol/L
<7%
<6.5%
1CDA
IDF 2005
<9%
<25
>9%
CDA 2003
Increasing or adding
If goals have not been reached within 2-3 months, medication should be increased or medication from a different class added
Target levels should be reached within 6 months Insulin should be added if necessary to reach target levels
Biguanides
Action not fully understood Decreases glucose production in liver Mild and variable effect on muscle sensitivity to insulin
Side effects Gastrointestinal (nausea, abdominal discomfort or diarrhea and occasional constipation) Lactic acidosis
Biguanides
Contraindications
Renal insufficiency Liver failure Heart failure Severe gastrointestinal disease
Advantages
Do not cause hypoglycaemia when used as monotherapy Do not cause weight gain; may contribute to weight loss
Biguanides
First-line treatment in overweight or obese people
Do not cause weight gain
Have some effect on resistance at the periphery
Biguanides
Caution
Should be discontinued 24 hours before procedures requiring intravenous contrast dye Can be restarted 48 hours after the procedure if renal function is not compromised
Sulphonylureas
Increase insulin secretion regardless of blood glucose levels Many different medicines in this class
Side effects
Hypoglycaemia Stimulate appetite and provoke weight gain Nausea, fullness, heartburn Occasional rash Swelling
Sulphonylureas
Short-acting secretagogues Meglitinides increase insulin secretion in response to increasing blood glucose levels (i.e. after eating)
Side effects Hypoglycaemia (probably less than sulphonylureas) Weight gain
Sulphonylureas
Contraindications
Type 1 diabetes Pregnancy Breastfeeding
Sulphonylureas - Use cautiously with liver or kidney disease Meglitinides - Severe impairment of liver function
Thiazolidinediones
Improve sensitivity to insulin in muscle, adipose tissue and liver Reduce glucose output from liver Changes fat distribution by decreasing visceral fat and increasing peripheral fat
Side effects Weight gain, fluid retention Upper respiratory infection and headache Decrease in haemoglobin
Slow digestion of sucrose and starch and therefore delay absorption Slow post-meal rise in blood glucose
Side effects Flatulence, abdominal discomfort , diarrhoea As mono-therapy will not cause hypoglycaemia Hypoglycaemia when used with other medicine (e.g. a sulphonylurea)
Improves beta-cell responsiveness to increasing glucose levels Decreases glucagon secretion Slows gastric emptying Results in a feeling of fullness Must be injected subcutaneously twice a day, within 3060 minutes before a meal Reduces HbA1c by ~1%
Side effects Nausea Weight loss Diarrhoea Risk of hypoglycaemia when used with a sulphonylurea
Summary
Lifestyle changes first Start medicine as soon as needed Add a different kind No delay starting insulin
Insulin
Insulin
Breakfast Lunch
Supper
Insulin action
1.
2.
3. 4. 5.
Type 1 diabetes Women with diabetes who become pregnant or are breastfeeding Transiently in type 2 diabetes in special situations In type 2 diabetes, inadequately controlled on glucose-lowering medicines (secondary failure)
Insulin therapy
Insulin therapy aims to replicate the normal physiological insulin response
age
dexterity glycaemic targets
Rapid
lispro aspart Short soluble regular Intermediate NPH lente 1-2 1-3 4-6 3-4 1-2 6-12 6-12 8-20 3-24 3-8 18-24 18-24 24 or more 24 or more 12-24 (dosedependent) -1 2-4 6-8 <
Long acting
ultralente glargine detemir
Exercise
Ambient and body temperature Insulin type Incomplete re-suspension
Insulin
20
Intermediate-acting insulin
40
Insulin
20
40
Insulin
20
Intermediateacting insulin
Basal-bolus regimen
60 40
Insulin
20
Intermediateacting insulin
60
40
Insulin
20
<6.5%
Treatment targets should be individualized, especially for very young and very old Absence of hypoglycaemia
*CDA
2003,
*1ADA
2004,
*2
IDF 2005
Adjusting insulin
Pattern management
Watch levels for 2-3 days
Adjusting insulin
Flexible dose guideline
Eating more Exercising more
Side effects
Hypoglycaemia
Weight gain Lipohypertrophy Lipoatrophy Insulin oedema
Allergic reaction
Summary
All people with type 1 diabetes must be treated with insulin The majority of people with type 2 diabetes will need insulin within 5 to 10 years of diagnosis Insulin therapy should not be used as a threat Insulin regimens should be individualized Insulin should be adjusted to achieve blood glucose as close to target range as possible
Macrovascular disease
Macrovascular disease
What is an event?
Macrovascular disease
Major cause of increased morbidity and mortality in diabetes Underlying abnormality: atherosclerosis
Williams 1999
What is atherosclerosis?
Process in which deposits of fatty substances, cholesterol, cellular waste products and calcium build up in the wall of an artery. This build up is called plaque Plaques can grow large enough to significantly reduce the blood flow through an artery. An acute event occurs when they become fragile and rupture
Diabetic neuropathy
Autonomic neuropathy
Postural hypotension
Autonomic Neuropathy
Urine retention
Gastroparesis
Erectile dysfunction
Constipation
Diarrhea
Nerve Entrapment
Cranial nerves Seventh nerve - Bells palsy: risk of corneal ulcer Third nerve closed eye Sixth nerve pupil directed nasally
Carpal tunnel
Mononeuropathy
Amyotrophy Radiculopathy
Bilateral
Equal symptoms
Age
Height Excessive alcohol
Diabetic nephropathy
Risk factors
Hyperlipidaemia
Hypertension Genetic predisposition Glomerular hyper-filtration during early period Ethnicity Long disease duration Smoking
Diabetic nephropathy
About 20% to 30% of people with diabetes In type 2 diabetes, a smaller fraction of these progress to CKD People with type 2 diabetes over half of those with diabetes starting on dialysis
Type 1 diabetes
Decreasing incidence over past 35 years Overall incidence 2.2% at 20 years duration 7.8% at 30 years duration
Finne 2005
10 to 15 years
Microalbuminuria (incipient diabetic nephropathy) Proteinuria (clinical overt diabetic nephropathy) Chronic renal failure
Protein
Microalbuminuria:
Exercise Menstruation Pregnancy Poor glycaemic control Urinary tract infection Hypertension Cardiac failure
Transient microalbuminuria
>2 consecutive measurements >20 g/min therafter 3 measurements normal Example: AER (g/min x 1,73m) 200 200
100
50 20 g/min 15 g/min
100
50 20
10 5 2
1/90 5/90 7/90 10/90 2/92 6/91 10/91 4/92
10 5 2
9/87 1/88 2/89 7/89
2/87 4/87 2/88 4/88 5/88 8/88 10/89
Permanent microalbuminuria
3 consecutive measurements >20 g/min Example: AER (g/min x 1,73m) 200 Girl 100 Age: 21 years diabetes duration: 50 10 years 20 g/min 15 g/min 10 5 2
6/94 8/87 10/88 11/88 12/88 4/89 1/90 7/90 9/90 10/90 12/90 9/91 11/92 12/93 7/95
278 253
200 100 50
20
10 5 2 1
Urinalysis for proteinuria Spot urine for microalbuminuria morning and resting or preferably with albumin/creatinine ratio (normal <2.5mg/mmol in men and <3.5mg/mmol in women) Serum creatinine; preferably with adjustment of body size Calculated glomerular filtration rate Repeat the tests at about yearly intervals if normal If GFR <60ml/min test 3-6 monthly
Microalbuminuria
Presence of microalbuminuria is an indication for screening of vascular disease and intensive intervention
Diabetes Control and Complications Trial (DCCT) occurrence of microalbuminuria by 40% occurrence of macroalbuminuria by 50% United Kingdom Prospective Diabetes Study (UKPDS) overall microvascular complication rate by 25%
Institution of tight metabolic control after onset of overt proteinuria or renal insufficiency is important for general health but not all that helpful in preventing chronic kidney disease
Diabetic nephropathy
Treatment
intensive treatment of blood pressure target <130/80mmHg reduce salt in diet reduce alcohol
Sacks, 2001
Hypoglycaemia
Definition of hypoglycaemia
When the level of glucose falls in the blood so that the cells in the periphery, and eventually the brain cells, do not get
Endogenous insulin secretion suppressed Release of glucagon, epinephrine, cortisol, growth hormone Autonomic response
Glucagon
Hypoglycaemia stimulates release
Epinephrine
Hypoglycaemia
Symptoms Low blood glucose Relief of symptoms when blood glucose raised
Symptoms of hypoglycaemia
Mild
Capable of selftreating Tremors, palpitation, sweating, hunger, fatigue Adrenergic
Moderate
May require prompting Headache, mood changes, low attentiveness Neuroglycopenic
Severe
Not capable of selftreatment Conscious or unconscious
Neuroglycopenic
Consequences of hypoglycaemia
Management
Mild or moderate Test if possible 15 g glucose; re-test Glucose tablets Fruit juice Soft drink Sugar Re-treat if level remains low
CDA 2003
Management
Severe 20 g glucose glucagon intravenous dextrose Manage seizure place person on their side if not too agitated
Diabetic retinopathy
Diabetic retinopathy Diabetic cataract: early senile true diabetic (Snowflake) Recurrent iritis
Diabetic retinopathy
A silent complication with no initial symptoms When symptoms occur, treatment is more complicated and often impossible Screening for retinopathy is of the utmost importance
Type 1 diabetes: within 5 years of diagnosis Type 2 diabetes: at time of diagnosis Thereafter, every 1 to 2 years, depending on the status of the retina
Blurred vision: common symptom of hyperglycaemia Epidemiology: any retinopathy: 21-36% vision-threatening retinopathy: 6-13%
Normal retina
Macula
Optic disc
Hard exudates
Haemorrhage
Proliferative retinopathy
New vessels
Pre-retinal haemorrhage
Scar tissue
Fluorescein leakage
Dot haemorrhage
Blot haemorrhage
Fluorescein leakage
What is DKA?
High blood glucose, ketones, acidosis and dehydration
Absolute or relative insulin deficiency Increase in counter-regulatory hormones Breakdown of fat and muscle Biochemical triad hyperglycaemia ketoacids metabolic acidosis
Incidence of DKA
Varies Death mainly from cerebral oedema Most common at onset in type 1 diabetes Recurrent episodes Can occur in type 2 diabetes
33%
20-38% <10%
Booth 2001, Joslin 2005
Diabetic ketoacidosis
Insulin deficiency Glucose uptake Glycerol Hyperglycaemia Glucosuria Osmotic diuresis Electrolyte depletion Dehydration Acidosis
Adapted from Davidson 2001
Gluconeogenesis
DKA investigations
Immediate for diagnosis Capillary blood glucose, urinary glucose and ketones
Urgent for assessment and treatment Blood glucose Blood gases Electrolytes, urea, creatinine
Ketones
Osmolality
Electrolytes
>10 mild
>12 moderate to severe pH <7.30, HCO3 <15 (mild) pH <7.00, HCO3 <10 (severe)
DKA treatment
Rehydration 1. Correct shock with bolus saline 2. Rehydration rate depends on clinical status, age and kidney function Normal saline (0.9%) for resuscitation and rehydration initially Glucose/saline solution when glucose around 14 mmol/L (252mg/dL) Rehydrate steadily over 48 hours 3. Consider NG tube Potassium Essential after resuscitation and when urine output confirmed
Kitabchi et al 1976
DKA treatment
Insulin Infusion: 0.1 units/kg/hour after resuscitation, saline established and BG falling
Rate should be increased by 1020% if glucose not fallen by 2-3 mmol/L (45-54mg/dL) over first hour Monitoring BG, BP, urine output and hourly neurological status Blood gases and electrolytes 2hourly initially
What is HHS?
0.5% of primary diabetes hospital admissions ~15% mortality rate Can occur in type 1 diabetes and younger people
Kitabchi et al 2001
Joslin 2005
Booth 2001
Precipitating factors
Electrolytes
Anion gap Blood gases
Blood: <0.6 mmol/L >320mOsm/kg - (raised Na, BG, urea) Raised Na, BG, urea creatinine <12
pH >7.30 normal or raised HCO3
Jones 2001
Treatment
Rehydration Caution!
Monitoring
HHS complications
Complication Hypoglycaemia Prevention Prevent by adding glucose infusion when glucose <14mmol/L (250 mg/dL) Early potassium replacement and monitoring
Hypokalaemia
Fluid overload