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dr. Yunus Tanggo Sp.PD, Ph.D
Bagian Ilmu Penyakit Dalam FK UKI
Definition of diabetes
Characterized by hyperglycaemia
• Defects in insulin production • Autoimmune or other destruction of beta cells • Insulin insensitivity
• Impaired action of insulin on target tissues
Definition of diabetes
Chronic hyperglycaemia associated with long-term damage to:
• • • • Eyes Kidneys Nerves Heart and blood vessels
The diabetes epidemic 230 million affected in 2006 350 million within 20 years Most rapid in Indian and Asian subcontinents 4 .
Type 1 diabetes – autoimmune – LADA – idiopathic 2.Classification 1. Type 2 diabetes • Insulin resistance • Deficiency of insulin 5 .
Other specific types MODY Defects in insulin action Diseases of the pancreas Endocrine disorders Drug.or chemical-induced Infections 6 .Classification 3.
• Uncommon forms of immunemediated diabetes • Other genetic syndromes 4. Gestational diabetes
Insulin and glucose disposal
Gluconeogenesis Glycogenolysis Glycogen synthesis Insulin
Glucose uptake Free fatty acid release
Insulin deficiency in type 1 diabetes
Glucose uptake Glycogenolysis Gluconeogenesis (amino acids) Ketone production (fatty acids) Blood glucose
Glucose uptake Protein degradation amino acids
Triglyceride degradation fatty acids
Insulin insensitivity in type 2 diabetes Glucose uptake Glycolysis Gluconeogenesis (amino acids) Blood glucose Glucose uptake Protein degradation amino acids 10 .
Insensitivity to insulin in type 2 diabetes Glucose uptake Glycolysis Gluconeogenesis (amino acids) Blood glucose Glucose uptake Protein degradation amino acids Glucose uptake 11 .
Effect of insulin resistance in type 2 diabetes Glucose uptake Glycolysis Gluconeogenesis (amino acids) Blood glucose Converted to triglycerides Glucose uptake Protein degradation amino acids Glucose uptake 12 .
Pathogenesis of type 1 diabetes • Immunological activation • Progressive beta-cell destruction • Insufficient beta-cell function • Dependent on exogenous insulin • Risk of ketoacidosis 13 .
Pathogenesis of type 1 diabetes • Genetic susceptibility • Immune factors – other autoimmune disease – antigen-specific antibodies • Environmental trigger – viruses – bovine serum albumin – nitrosamines: cured meats – chemicals: vacor (rat poison). streptozotin 14 .
years) 15 .Pathogenesis of type 1 diabetes Trigger Immunological abnormalities Genetic Beta-cell mass Clinical diabetes Pre-diabetes „Honeymoon‟ Chronic phase Time (months .
Idiopathic type 1 diabetes Non-autoimmune type 1 diabetes No autoimmune markers Permanent insulinopenia Ketoacidosis People of African and Asian origin 16 .
Epidemiology of type 1 diabetes • Increasing in recent years • Geographic variation • Relative affluence • Lack of treatment 17 IDF Diabetes Atlas .
Epidemiology of type 1 diabetes Age of onset peaks • preschool • puberty 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 .
Pathogenesis of type 2 diabetes • Multiple genes involved • Hyperinsulinaemia • Poor fetal nutrition beta-cell formation • Low birth weight/weight change • “Thrifty gene” • 7% beta-cell loss 20 .
The natural history of type 2 diabetes Beta-cell loss Insulin requirements Primary failure Insulin requirements with age Endogenous insulin Age (years) 21 .
The natural history of type 2 diabetes Beta-cell loss Hyperinsulinaemia Insulin requirements with age Endogenous insulin Insulin requirements Insulin insensitivity Age (years) 22 .
The natural history of type 2 diabetes Beta-cell loss Hyperinsulinaemia Secondary failure Effect of oral drugs Insulin requirements with age Endogenous insulin Insulin requirements Insulin insensitivity Age (years) 23 .
Epidemiology of type 2 diabetes • Dramatic increase • Aging population • Disturbing trends parallel obesity epidemic • Especially in adolescents and minority groups • Increasing in young people 24 .
Risk factors for type 2 diabetes • Age > 40 years • First-degree relative with diabetes • Member of high risk population • History of impaired glucose tolerance. impaired fasting glucose • Vascular disease • History of gestational diabetes • History of delivery of macrosomic baby CDA 2003 25 .
Risk factors for type 2 diabetes Hypertension Dyslipidaemia Abdominal obesity Overweight Polycystic ovary disease Acanthosis nigricans Schizophrenia 26 .
Signs and symptoms • Polydipsia • Polyuria • Nocturia • Visual disturbance • Fatigue • Weight loss • Infections 27 .
ADA 2004.9mmol/L* 110 to 126mg/dL 7.1 to 6.1mmol/L ≥200mg/dL 2hr PG <7.0mmol/L ≥126mg/dL ≥11.8 to 11mmol/L** 126 to 200mg/dL Diabetes FPG ≥7.Diagnosing diabetes Normal Impaired fasting glucose* Impaired glucose tolerance** <6.8mmol/L <126mg/dL CDA 2003.1mmol/L <110mg/dL 6. WHO 2002 28 .
Impaired glucose tolerance Impaired fasting glucose Intermediate states Increased risk of developing diabetes Prevention strategies to prevent or delay progression Increased risk of cardiovascular disease 29 .
Uncertain diagnosis: Oral glucose tolerance test 75 g glucose load after 8 hours fasting Readings taken in fasting state and at 1 and 2 hours Possible problems 30 .
Tests for differential diagnosis 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 .
Aims and principles .Nutrition .
Composition of food and drinks Macro-nutrients • protein • carbohydrates • fats Micro-nutrients • vitamins • minerals .
a historical perspective Distribution of calories (%) Year Before 1921 1921 1950 1971 20 40 45 Carbohydrate Protein Fat Starvation diets 10 20 20 70 40 35 1986 2004 <60 45-65* 12-20 10-20 † <30 20-35† <10% saturated fat * Based on individual assessment and treatment goals American Diabetes Association .Nutrition recommendations for people with diabetes .
Dietary recommendations for adults with diabetes 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 Essential for all body functions 40-60% of body weight is water Important to drink adequate amounts of fluid .
usually measured in kilojoules (kJ) .Energy Produced by utilizing food in the body Measurements of energy: .calories or kilocalories (kcal) .1 kcal = 4.2 kJ .
during recovery from severe and prolonged illness .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 .
Proteins Provide amino acids Help to build muscle mass Animal sources Plant sources 1 g of protein gives 4 kcal energy .
Protein recommendations 0. especially saturated Vegetable protein sources should be encouraged – lower in fat .8 g protein per kg bodyweight per day 10-20% of total energy per day Higher amounts not encouraged for people with diabetes Animal protein often high in fat.
fructose 1 g of carbohydrate provides 4 kcal .Carbohydrates Should provide main source of energy for the body (>50%) Nutrient that most influences blood glucose levels Source of simple sugars – glucose.
rice. beans. etc potatoes legumes.Carbohydrates and meal planning • • Amount and source of carbohydrates should be considered when planning meals Carbohydrates should mainly come from whole grains: wheat. pasta. 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 .
9 16.7 12.9 .1 19.3 cup 0.5 cup 1 small 12.6 17.0 20.Carbohydrate content of common foods Food Bread Rice (cooked) Pasta Chappati Corn meal Potato Amount (g) 25 52 43 35 26 85 Serving 1 slice 0.4 14.3 cup 0.3 cup 1 small 3 tablespoons 1 small Carbohydrate (g) 12.2 17.0 Couscous Lentils Banana 52 99 72 0.
slows absorption of glucose .Benefits of fibre High-fibre diet is healthy Mixture of soluble and insoluble fibre .retains water to soften stool .may reduce the risk of colon cancer .reduces absorption of dietary fats .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 .
rape seed oil. sunflower oil. mustard oil. corn oil • Monounsaturated – olive oil. cream. margarine. groundnut oil. cheese. canola oil. sesame oil .Fats Common sources of different fats • Saturated – red meats. butter. ghee (clarified butter). lard • Polyunsaturated – safflower oil. whole milk.
Trans fats Formed when liquid fats. are chemically hydrogenated Raise LDL cholesterol and lower HDL cholesterol . such as oils.
5 <0.0 Ghafoorrunissa et al.5 10 10 1 1 1 5 <0.Fats and oils Fat distribution in commonly used oils Fatty acid (grams/100grams) Saturated fatty acids Olive oil Peanut oil Canola oil Rapeseed oil Sesame oil Corn oil Cottonseed oil Soya bean oil Sunflower oil Safflower oil Coconut Hydrogenated oil Ghee/butter oil 13 18 6 8 15 12 22 15 13 13 90 24 65 MUFA 76 48 58 70 42 32 25 27 27 17 7 19 32 PUFA (ω-6) 10 34 26 12 42 55 52 53 60 70 2 3 2 PUFA (ω-3) 1 <0.5 <1.5 <0.5 <0. NIN 1994 .
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 .
soya Green leafy Fenugreek. mustard Walnut. rajmah. cowpea. flaxseed Mustard. NIN 1994 . soya bean oil.Foods rich in omega-3/ alpha linolenic acid Food group Food source Cereals and millets Wheat. bajra Pulses and legumes Vegetables Spices Nuts and seeds Oils a Blackgram. canola oil Long chain n3 PUFA (omega-3) – biologically active product of alpha linolenic acid Ghafoorrunissa et al.
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 and flavonoids 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 .
Vitamins and antioxidants recommendations A properly balanced diet will supply all the vitamins and antioxidants necessary. supplements are not necessary Multivitamin supplements are needed for people in certain circumstances .
calcium and vitamin supplementation may be desirable for elderly people . enzymes. teeth and tissue fluids Supplements not required for most.regulate vital body processes In blood. hormones.Minerals and trace elements A balanced diet supplies minerals and trace elements Inorganic . skeleton. bones.
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 .Minerals Minerals present in bones. teeth. blood and nerve cells Help maintain physiological processes. soft tissue. muscle.
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 .
saturated <10% .Summary of dietary recommendations Carbohydrates: 45-65% (mostly starch) Dietary fibre: min 20 g/1000 kcal Fats: 20-35% .cholesterol <300 mg/day Protein: 10-20% (0.monounsaturated >10% .8 g/kg/day) Sodium: <2400 mg/day Vitamins and minerals: with a balanced diet.polyunsaturated <10% . supplements not needed .
Physical activity .
Health benefits of physical activity /1 • Reduces total cholesterol levels • Increases HDL levels • Reduces blood pressure levels • Reduces joint pain and stiffness in osteoarthritis • Reduces the risk of coagulation abnormalities .
Health benefits of physical activity /2 • Reduces obesity • Reduces risk of colon and other cancers • Improves intermittent claudication • Improves cardiovascular health • Reduces coronary artery disease .
Health benefits of physical activity /3 Improves work. improves mood and self-esteem Improves quality of sleep . recreational and sports performance Decreases number of „sick‟ days Decreases fatigue in daily activities.
Health benefits of physical activity in type 2 diabetes • Improved insulin sensitivity and therefore better blood glucose control • Increased glucose utilization • Decreased glucose production from the liver • Decrease in circulating insulin levels during exercise .
40-64 years BMI >25 Random selection by persons 3.Physical activity in the prevention of type 2 diabetes Study Characteristics & duration Interventi Results on Da Qing Study (China) 1997 577 persons >25 years Random selection from clinics 6 years follow-up Diet Exercise Diet + exercise 68% cumulative incidence 44% (reduction of 31%) 41% (reduction of 46%) 46% (reduction of 42%) 58% decreased incidence in the „diet + exercise‟ group Finnish Diabetes Preventio n Study (Finland) 2001 522 persons.2 years follow-up Diet + exercise .
Physical activity and food Exercise combined with caloric restriction 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 .
such as walking. skipping.Recommendations The American College of Sports Medicine recommends 20 to 60 minutes of exercise most days a week Aerobic exercise. swimming. should be sufficient to raise the pulse or increase respiration In resistance training. jogging. it is better to use repetitive light weights than heavy weights . bike riding.
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 .Tips to help start physical activity Identify an activity that will be enjoyed Start slowly.
Physical activity should be encouraged in all people with diabetes
People need to be educated about prevention and treatment of hypoglycaemia
People should be taught to plan for periods of physical activity
Pharmacological management Blood glucose-lowering medicines
Aims of treatment
Reduce the symptoms of hyperglycaemia
Limit adverse effects of treatment
Maintain quality of life and psychological wellbeing Prevent or delay vascular complications of diabetes
Natural history of type 2 diabetes Insulin resistance Glucose level Beta-cell dysfunction Insulin production Time Normal Impaired glucose tolerance Type 2 diabetes Henry 1998 .
Mechanisms of action GLP-1 (incretins) improve response to glucose level Biguanides and thiazolidinediones reduce glucose production Insulin secretagogues: sulphonylureas and meglitinides increase insulin production Alpha-glucosidase inhibitors slow absorption of sucrose and starch Thiazolidinediones and biguanides reduce insulin resistance .
The principles of combination therapy 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 .
5% 1.0-1.8% 1.5% Canadian Diabetes Association 2003 Alpha-glucosidase inhibitor Biguanide Insulin sensitisers Most insulin secretagogues Nateglinide .5% 0.5-0.0-1.0-1.5% 1.Expected effect of blood glucoselowering medicines Class of medicine Expected decrease in HbA1C in monotherapy 0.
Targets for blood glucose HbA1C Pre-meal 2 hours postmeal 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% 4-7mmol/L1 90-130mg/dl*2 <6.0mmol/L <145mg/dl <6. 2ADA 2004.5% 1CDA 2003. 3 IDF 2005 .0mmol/L <110mg/dl 5-10mmol/L1 <180mg/dl2 <8.
Suggested starting medicine HbA1c BMI >25 Suggested medicine Biguanide – alone or in combination 1 or 2 agents from different classes <9% <25 >9% 2 medicines from different classes or insulin CDA 2003 .
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 .Increasing or adding If goals have not been reached within 2-3 months.
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 .
may contribute to weight loss .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.
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. heartburn Occasional rash Swelling . fullness.
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 .
Use cautiously with liver or kidney disease Meglitinides .Severe impairment of liver function .Sulphonylureas Contraindications • Type 1 diabetes • Pregnancy • Breastfeeding Sulphonylureas .
fluid retention Upper respiratory infection and headache Decrease in haemoglobin . adipose tissue and liver Reduce glucose output from liver Changes fat distribution by decreasing visceral fat and increasing peripheral fat Side effects Weight gain.Thiazolidinediones Improve sensitivity to insulin in muscle.
diarrhoea As mono-therapy will not cause hypoglycaemia Hypoglycaemia when used with other medicine (e. abdominal discomfort .g. a sulphonylurea) .Alpha glucosidase inhibitors Slow digestion of sucrose and starch and therefore delay absorption Slow post-meal rise in blood glucose Side effects Flatulence.
Alpha glucosidase inhibitors Contraindications • Intestinal diseases. such as Crohn‟s • Autonomic neuropathy affecting the gastro-intestinal tract Must be taken just before a meal .
within 3060 minutes before a meal Reduces HbA1c by ~1% Side effects Nausea Weight loss Diarrhoea Risk of hypoglycaemia when used with a sulphonylurea .GLP-1 (incretin mimetic agent) 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.
GLP-1 (incretin mimetic agent) Contraindications • End-stage kidney disease or renal impairment • Pregnancy • Severe gastrointestinal disease .
Summary Lifestyle changes first Start medicine as soon as needed Add a different kind No delay starting insulin .
Pharmacological management Insulin .
with surges of insulin triggered by a rise in blood glucose 60 40 20 0 Insulin Breakfast Lunch Supper .Insulin A hormone secreted by the beta cells Secreted in response to glucose or other stimuli. such as amino acids Normal response characterized by low basal levels of insulin.
Increases glucose uptake. 3. liver and adipose tissue 2.Insulin action 1. particularly in muscle. 4. 5. Suppresses glucose output from the liver Increases formation of fat Inhibits breakdown of fats Promotes amino-acid uptake and prevents protein breakdown .
Indications for insulin therapy 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 Insulin regimens should be individualized – type of diabetes – willingness to inject – lifestyle – blood glucose monitoring – age – dexterity – glycaemic targets .
Insulin types and action Onset (hrs) Peak (hrs) ¾-2½ Duration (hrs) 3½-4½ 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) ½-1 2-4 6-8 <¼ Long acting ultralente glargine detemir .
Factors affecting absorption Lipohypertrophy Dose of injection Site and depth of injection Exercise Ambient and body temperature Insulin type Incomplete re-suspension .
Insulin regimens: once a day insulin 60 40 Endogenous insulin Soluble insulin Insulin 20 Intermediate-acting insulin 0 Breakfast Lunch Supper .
Twice a day insulin 60 40 Endogenous insulin Soluble insulin Intermediateacting insulin Insulin 20 0 Breakfast Lunch Supper .
Three times a day insulin 60 40 Endogenous insulin Soluble insulin Insulin 20 Intermediateacting insulin 0 Breakfast Lunch Supper .
Basal-bolus regimen 60 40 Endogenous insulin Rapid-acting insulin analogue Insulin 20 Intermediateacting insulin 0 Breakfast Lunch Supper .
60 Long-acting insulin analogues Endogenous insulin Rapid-acting insulin analogue Long-acting insulin analogue 40 Insulin 20 0 Breakfast Lunch Supper .
especially for very young and very old • Absence of hypoglycaemia *CDA 2003.5% • Treatment targets should be individualized.Adjusting insulin – what are the targets? HbA1C Target for most people with diabetes IDF Global guideline for Type 2 diabetes*2 <7% Pre-meal 4-7mmol/L* 90-130mg/dl*1 <6. *2 IDF 2005 .0mmol/L <110mg/dl 2 hours postmeal 5-10mmol/L* <180mg/dl *1 <8.0mmol/L <145mg/dl <6. *1ADA 2004.
Starting insulin in type 2 diabetes FINFAT: start small dose intermediateacting insulin at night • Aim for target fasting levels first • Adjust by 2-4 units or 10% • Second injection only added once fasting targets reached .
Adjusting insulin Pattern management • Watch levels for 2-3 days • Address hypoglycaemia first • Aim for target fasting levels next • Adjust by 2-4 units or 10% • Wait 2-3 days .
Adjusting insulin • Flexible dose guideline • Eating more • Exercising more • Insulin to carbohydrate ratio • Evaluate with next blood glucose • Tailored to individual needs .
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 Coronary heart disease Cerebrovascular disease Peripheral vascular disease What is an “event”? .
Macrovascular disease Major cause of increased morbidity and mortality in diabetes Underlying abnormality: atherosclerosis Williams 1999 .
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.What is atherosclerosis? Process in which deposits of fatty substances. An acute event occurs when they become fragile and rupture . cholesterol.
Diabetic neuropathy .
Autonomic neuropathy Postural hypotension Arrhythmia Silent ischaemia .
Autonomic Neuropathy Urine retention Gastroparesis Erectile dysfunction Constipation Diarrhea .
Nerve Entrapment Cranial nerves Seventh nerve .Bell’s palsy: risk of corneal ulcer Third nerve – closed eye Sixth nerve – pupil directed nasally Carpal tunnel .
Mononeuropathy Amyotrophy Radiculopathy .
Peripheral Neuropathy – Sensory Motor Most common form of neuropathy Affects approximately 50% after 15 years Affects long nerves (feet and legs) first • glove and stocking distribution Bilateral Equal symptoms .
Diabetic foot disease – the high-risk foot Peripheral neuropathy Peripheral vascular disease Peripheral neuropathy and peripheral vascular disease .
Diabetic peripheral neuropathy – risk factors Poor glycaemic control Long duration Age Height Excessive alcohol .
Nerve damage – neuropathy Symptoms: • burning • pins and needles • pain No symptoms .
Painless nature of diabetic foot disease
Sensory nerve damage
Diabetic nephropathy .
Risk factors Poor glycaemic control 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 .
2% at 20 years duration • 7.8% at 30 years duration Finne 2005 .Type 1 diabetes Decreasing incidence over past 35 years Overall incidence • 2.
Natural history of diabetic nephropathy Acute renal hypertrophy-hyperfunction Normoalbuminuria 10 to 15 years Microalbuminuria (incipient diabetic nephropathy) Proteinuria (clinical overt diabetic nephropathy) Chronic renal failure .
5-35mg/mmol (women) Macroalbuminuria: >300 mg/24 hr or .Protein. microalbuminuria and Macroalbuminuria Protein Albumin Albumin Excretion Rate Microalbuminuria: 30-300 mg/24 hr 20-200 µg/min 2.5-25mg/mmol (men) 3.
Factors affecting albumin excretion Transient increases in albumin excretion • • • • • • • Exercise Menstruation Pregnancy Poor glycaemic control Urinary tract infection Hypertension Cardiac failure .
73m²) 200 200 100 50 20 µg/min 15 µg/min Girl Age: 15 years diabetes duration: 5 years 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 1 1 .Transient microalbuminuria >2 consecutive measurements >20 µg/min therafter 3 measurements normal Example: AER (µg/min x 1.
73m²) 200 Girl 100 Age: 21 years diabetes duration: 50 10 years 20 µg/min 15 µg/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 1 .Permanent microalbuminuria 3 consecutive measurements >20 µg/min Example: AER (µg/min x 1.
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 .Diabetic renal assessment 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.
Microalbuminuria Type 1 diabetes • indicates incipient nephropathy Type 2 diabetes • marker of increased cardiovascular morbidity and mortality Presence of microalbuminuria is an indication for screening of vascular disease and intensive intervention .
Interventions: glycaemic control 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 .
2001 .Diabetic nephropathy Treatment • intensive treatment of blood pressure target <130/80mmHg • reduce salt in diet • reduce alcohol Sacks.
and eventually the brain cells.Definition of hypoglycaemia When the level of glucose falls in the blood so that the cells in the periphery. do not get adequate glucose to function .
The body’s response ● Endogenous insulin secretion suppressed Release of glucagon. cortisol. epinephrine. growth hormone Autonomic response .
The body’s response • Brain lacks glucose • Temporary cognitive impairment • Wide variation in symptoms .
Glucagon Hypoglycaemia stimulates release It acts in the liver to increase glucose production – releasing stored glycogen – activating production of new glucose – stimulating production of ketones .
Epinephrine Releases stored glycogen Activates production of glucose from protein Reduces uptake of glucose Reduces production of insulin .
Cortisol and growth hormone • Reduce cellular uptake of glucose • Stimulate breakdown of proteins to make glucose • Stimulate breakdown of body fats .
Hypoglycaemia Symptoms Low blood glucose Relief of symptoms when blood glucose raised .
palpitation. hunger. low attentiveness Neuroglycopenic Severe Not capable of selftreatment Conscious or unconscious Neuroglycopenic . fatigue Adrenergic Moderate May require prompting Headache.Symptoms of hypoglycaemia Mild Capable of selftreating Tremors. sweating. mood changes.
Consequences of hypoglycaemia Mild-moderate • fear • anxiety • affects selfcare • social stigma • prejudice Severe • injury • seizures • transient paralysis • cognitive impairment • death .
People at risk of hypoglycaemia Only those taking glucose-lowering medicines or insulin Increased risk: • too little or wrong type of carbohydrate • late or missed meal • fasting or malnourishment • too much insulin or insulin secretagogues • prolonged or unplanned activity .
People at risk of hypoglycaemia Increased risk: • Recent severe hypoglycaemia • Gastroparesis • Liver disease or kidney failure • Pregnancy • Injection-related • Over-correction of high BGL .
How would you advise people to treat the following? • Mild hypoglycaemia • Moderate hypoglycaemia • Severe 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 eye disease Diabetic retinopathy Diabetic cataract: • early senile • true diabetic (Snowflake) Recurrent iritis .
treatment is more complicated and often impossible Screening for retinopathy is of the utmost importance .Diabetic retinopathy A silent complication with no initial symptoms When symptoms occur.
depending on the status of the retina . every 1 to 2 years.When to screen for retinopathy Type 1 diabetes: within 5 years of diagnosis Type 2 diabetes: at time of diagnosis Thereafter.
Diabetic eye disease Blurred vision: common symptom of hyperglycaemia Epidemiology: • any retinopathy: 21-36% • vision-threatening retinopathy: 6-13% .
Normal retina Macula Optic disc .
Non-proliferative diabetic retinopathy Hard exudates .
Severe non-proliferative retinopathy Haemorrhage Cotton wool spot .
Proliferative retinopathy New vessels Pre-retinal haemorrhage .
Advanced proliferative retinopathy Scar tissue .
Early macular oedema .
Fluorescein leakage Dot haemorrhage Blot haemorrhage .
Fluorescein leakage .
Pan-retinal laser bombing .
Diabetic ketoacidosis and hyperosmolar hyperglycaemic state .
ketones.What is DKA? High blood glucose. acidosis and dehydration Absolute or relative insulin deficiency Increase in counter-regulatory hormones Breakdown of fat and muscle Biochemical triad • hyperglycaemia • ketoacids • metabolic acidosis .
Joslin 2005 .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 Kitabchi et al 2001.
pancreatitis 33% 20-38% <10% Booth 2001. stroke. Joslin 2005 .DKA – cause or trigger Incidence New-onset diabetes Acute illness 5-40% 10-20% Insulin omission/nonadherence Infection Heart attack.
Diabetic ketoacidosis Insulin deficiency Glucose uptake Glycerol Hyperglycaemia Glucosuria Osmotic diuresis Electrolyte depletion Dehydration Acidosis Adapted from Davidson 2001 Lipolysis Free fatty acids Ketogenesis Ketonemia Ketonuria Gluconeogenesis Urinary water losses .
DKA – investigations Immediate for diagnosis Capillary blood glucose. urinary glucose and ketones Urgent for assessment and treatment Blood glucose Blood gases Electrolytes. urea. creatinine .
dehydration Low/normal Na+ and ClLow/normal/high K+ (often misleading) Low HCO3 (normal 23-31) Electrolytes Anion gap Blood gases >10 mild >12 moderate to severe pH <7.00. HCO3 <15 (mild) pH <7.30. HCO3 <10 (severe) .DKA – laboratory findings Blood glucose >14mmol/L (252mg/dL) Ketones Osmolality Urine: moderate to large Blood: >3mmol/L Increased – high blood glucose and urea/creatinine.
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?
Ketosis may be present
Coma not always present
Primarily in older people with/without history of type 2 diabetes Always associated with severe dehydration and hyperosmolar state
Kitabchi et al 2001
HHS – incidence and features 0.5% of primary diabetes hospital admissions ~15% mortality rate Can occur in type 1 diabetes and younger people Kitabchi et al 2001 .
HHS – key features Marked hyperglycaemia Hyperosmolarity Absence of severe ketosis Altered mental awareness Joslin 2005 .
steroids Insulin omission 40-60% 33% 10-15% <10% 5-15% Booth 2001 .HHS – causes or triggers Incidence Infection New-onset diabetes Acute illness Medicines.
Signs and symptoms of HHS Initially polyuria and polydipsia Altered mental status Profound dehydration Precipitating factors .
urea creatinine <12 pH >7. BG. BG.HHS – biochemical findings Blood glucose Ketones Osmolality >33mmol/L (600mg/dl) Urine: negative – small Electrolytes Anion gap Blood gases Blood: <0.(raised Na.30 normal or raised HCO3 Jones 2001 . urea) Raised Na.6 mmol/L >320mOsm/kg .
neurological function hourly until stable Electrolytes 2-hourly Cardiac or CVP monitoring Monitoring .1 unit/kg/hour to be increased with care if BG is slow to fall BG. BP.Treatment Rehydration Caution! Normal saline 1 l per hour initially Consider ½ strength normal saline Potassium Insulin Only if hypokalaemic and renal function adequate – give before insulin May be needed as slow infusion 0.
aggressive Mannitol treatment if any early signs of cerebral oedema Meltzer 2004 Vomiting/aspiration NG tube and may be nursed on side Cerebral oedema .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 Careful clinical monitoring and central line as needed Avoid fast blood glucose falls (should be <4mmol/L (72mg/dL) per hour.
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