This document provides an overview of diabetes mellitus, including the different types, causes, diagnostic criteria, complications, and treatments. It describes type 1 diabetes as an autoimmune destruction of beta cells, while type 2 diabetes has genetic and environmental risk factors such as obesity and physical inactivity. The long-term complications of diabetes include macrovascular and microvascular damage resulting from chronic hyperglycemia. Tight glycemic control can help delay the onset of these complications.
This document provides an overview of diabetes mellitus, including the different types, causes, diagnostic criteria, complications, and treatments. It describes type 1 diabetes as an autoimmune destruction of beta cells, while type 2 diabetes has genetic and environmental risk factors such as obesity and physical inactivity. The long-term complications of diabetes include macrovascular and microvascular damage resulting from chronic hyperglycemia. Tight glycemic control can help delay the onset of these complications.
This document provides an overview of diabetes mellitus, including the different types, causes, diagnostic criteria, complications, and treatments. It describes type 1 diabetes as an autoimmune destruction of beta cells, while type 2 diabetes has genetic and environmental risk factors such as obesity and physical inactivity. The long-term complications of diabetes include macrovascular and microvascular damage resulting from chronic hyperglycemia. Tight glycemic control can help delay the onset of these complications.
This document provides an overview of diabetes mellitus, including the different types, causes, diagnostic criteria, complications, and treatments. It describes type 1 diabetes as an autoimmune destruction of beta cells, while type 2 diabetes has genetic and environmental risk factors such as obesity and physical inactivity. The long-term complications of diabetes include macrovascular and microvascular damage resulting from chronic hyperglycemia. Tight glycemic control can help delay the onset of these complications.
• Describe the classical clinical features of and list the
diagnostic criteria for diabetes mellitus • Classify the different types of diabetes • Define insulin resistance and the metabolic syndrome • Identify and classify diabetes ketoacidosis, hyperosmmolar hyperglycaemic syndrome and hypoglycaemia • List long term complications of diabetes • Laboratory diagnosis • Treatment and prevention TYPES OF DIABETES Diabetes
Insipidus (DI) Mellitus (DM)
(Rare) (Common)
Cranial Nephrogenic Type 1 Type 2 Gestational
Lack of Reduced Insulin Non-Insulin Found ADH response Dependant Dependant during to ADH IDDM NIDDM pregnancy DIABETES MELLITUS - INTRODUCTION
• absolute or functional deficiency of circulating
insulin • glucose not transferred from blood to cell • hyperglycaemia overwhelms kidneys ability to reabsorb glucose • excessive polyuria and polydypsia • weight loss • long term medical problems DIAGNOSIS, CLASSIFICATION AND AETIOLOGY
Type I diabetes (T1D)
• autoimmune destruction of type b cells • linked to environmental factors – virus (coxsackie B) • 10% of all diabetes • peak incidence 10-13 years • major histocompatibility complex (MHC) – notably HLA – HLA DR3 and DR4 DIAGNOSIS, CLASSIFICATION AND AETIOLOGY
Type II diabetes (T2D)
• genetic predisposition • environmental ! - Pima indians – Arizona - two populations – lifestyle – same genetics
Agricultural Group Urban Dwellers
10% T2D 50% T2D PREVALENCE OF TYPE II DIABETES TYPE II DIABETES
• explosion in diabetes (type II) in
developing world • huge financial cost to NHS • top three killer diseases (CVS, stroke) Increased Energy Density of Food Standard food portions have increased over the last 20 years 20 years ago Today
210 calories 610 calories
500 calories 850 calories
333 calories 590 calories
Aetiology of obesity GENETIC
PSYCHOLOGICAL MEDICAL
OBESITY
LIFESTYLE Abdominal obesity increases the risk of developing type 2 24 diabetes 20 Relative risk
Carey VJ et al, 1997 Overall, 75% of patients with type 2 diabetes die from cardiovascular disease ~90% of people with type 2 diabetes are overweight or obese Insulin resistance – reduced response to circulating insulin Insulin resistance IR
WHO DEFINITIONS OF DIABETES Diabetes Fasting plasma glucose ≥7.0mmol/l (126mg/dl) or 2–h plasma glucose* ≥11.1mmol/l (200mg/dl)
Impaired Glucose Tolerance (IGT)
Fasting plasma glucose <7.0mmol/l (126mg/dl) and 2–h plasma glucose* ≥7.8 and <11.1mmol/l (140mg/dl and 200mg/dl)
Impaired Fasting Glucose (IFG)
Fasting plasma glucose 6.1 to 6.9mmol/l (110mg/dl to 125mg/dl) and (if measured) 2–h plasma glucose* <7.8mmol/l (140mg/dl)
* Venous plasma glucose 2–h after ingestion of 75g oral glucose load * If 2–h plasma glucose is not measured, status is uncertain as diabetes or IGT cannot be excluded ACUTE COMPLICATIONS OF DIABETES
1. Diabetic ketoacidosis (DKA)
• high level of ketones • acidosis (arterial blood pH < 7.3) • severe complication (~5% mortality) • T1D >> T2D
Symptoms • deep breathing, tachycardia, low bp, coma DEVELOPMENT OF KETOACIDOSIS TREATMENT OF KETOACIDOSIS
• dehydration • sodium loss } isotonic fluids
• hyperkalaemia - acidosis - K+ efflux from cells } insulin ACUTE COMPLICATIONS OF DIABETES
2. Hyperosmolar hyperglycaemic syndrome
(HHS) • marked hyperglycaemia (>50mmo/L) • no or few ketones • raised osmolality (320-340 mOsm/Kg) • formerly known as (hyperosmolar non-ketotic state) HONK • T2D >> T1D ACUTE COMPLICATIONS OF DIABETES
2. Hyperosmolar hyperglycaemic syndrome
(HHS) • high sugar intake • severe dehydration • cerebral oedema • low blood pressure • mortality ~ 30% COMPARISON OF DKA AND HHS
Sign Diabetic Hyperosmolar
Ketoacidosis hyperglycaemic syndrome Timescale short term long term onset Osmolarity rarely > 320mOsm/kg frequently < 320mOsm/kg
Ketones/acidosis Significant hyper - None or low
Hyperglycaemia Modest Severe T1D v T2D T1D T2D Mortality 5% 30% HYPOGLYCEAMIA
Causes • diet • too much insulin (treatment or misuse) • insulin secreting tumour (insulinoma)
How diagnose tumour v misuse ?
• tumour - insulin + C peptide, ratio 1:1 • misuse – no or little C peptide; ratio not 1:1 BIOSYNTHESIS OF INSULIN DIABETES IN PREGNANCY
Gestational diabetes mellitus
• 4-5 % of pregnancies • later on in pregnancy • body unable to produce enough insulin to meet demands • resolves itself after birth • indicator of future T2D 1. LONG TERM COMPLICATIONS OF DIABETES
Hyperglycaemia • excessive non-enzymatic glycation of proteins • haemoglobin – HbA1c • lipoproteins - inflammatory molecules - bind to receptors - pro-atherogenic 2. LONG TERM COMPLICATIONS OF DIABETES
Hyperglycaemia • damage to membranes • macrovascular – larger blood vessels – blockage in veins – claudication – arteries – CVD, stroke 3. LONG TERM COMPLICATIONS OF DIABETES
Hyperglycaemia • damage to membranes • microvascular – smaller blood vessels – nephropathy • bp increases • leaky membranes • albumin in urine (microalbuminaria) – retinopathy 3. LONG TERM COMPLICATIONS OF DIABETES Hyperglycaemia • microvascular – neuropathy – bladder problems – impotence – foot ulcers
Kobayashi M. Diabetes Obes Metab 1999; 1 (Suppl. 1):S32–S40.
Nattrass M & Bailey CJ. Baillieres Best Pract Res Clin Endocrinol Metab 1999; 13:309–329. DIABETES DIAGNOSIS & MONITORING 1. Blood glucose - random or fasting - oral glucose tolerance test (OGTT) Urine glucose - Multi-stix testing (Glu + Ketones)
2. Long-term indices of diabetic control
- Blood HbA1c - microalbuminuria What is the HbA1c?
• Definition: percentage of glycated
hemoglobin • Glycated hemoglobin forms over the lifespan of RBCs in proportion to degree of glycemia • Provides an estimate of the level of glycemia over lifetime of an RBC, or approximately 90 days Correlating HbA1c with glycemia Current Definitions • Non-diabetic – HbA1c < 6.0 – Fasting plasma glucose < 100 • Prediabetes – HbA1c 6.0-6.4 – Fasting plasma glucose 100-125 • Diabetes – HbA1c ≥ 6.5 – Fasting plasma glucose ≥ 126 Advantages
• relatively inexpensive • doesn’t require fasting • widely available • can do POC testing • not affected by short term lifestyle changes • less intra-individual variability Drawbacks • erythrocyte age decreased erythrocyte age lower HbA1c increased erythrocyte age raised HbA1c • genetic variants hemoglobinopathies and thalassemias • ethnicity; higher in African-Americans • elevated bilirubin higher HbA1c MONITORING AND MANAGEMENT OF GLUCOSE
1. Blood glucose - Point of Care Testing - blood glucose monitor - affected by blood pH - not accurate at high and low blood [glucose] - plasma [glucose] - measured enzymatically BEDSIDE GLUCOSE ANALYSIS • Method: - Blood reacts with chemicals on the test strip = electrical current. - high glucose levels = higher electrical current.
• Time to perform test:
- 20 seconds
• Results: - normal fasting value: 4.1 – 5.9 mmol/L - 1-2hr post food: < 8.9 mmol/L LABORATORY - RANDOM BLOOD GLUCOSE • Laboratory specimen: - Na fluoride / fluoride oxalate tube (stop glycolysis) - Min whole blood volume: 1.0 ml - Plasma / serum volume: 2.0 µl LABORATORY GLUCOSE ANALYSIS Method: - spectrophotometry - wavelength - 340nm - reactions
1. glucose + hexokinase + ATP + Mg
glucose-6-phosphate(G-6-P) + ADP
2. G-6-P + G-6-P dehydrogenase + NAD
6-phosphogluconate + NADH
• 1 molecule glucose = 1 molecule NADH
• time to perform test: ~ 10 minutes GLUCOSE LONG-TERM INDICES • HBA1c (glycated haemoglobin) - Specimen type: EDTA whole blood - Glycation at N-terminal of beta-chain in HbA0 = HbA1c - Amount of HbA1c is proportional to average daily glucose over 2-3 months.
• Microalbuminaemia - Specimen type: Urine (first thing in the morning) - Albumin Excretion Rate (AER) = detects earliest stage of diabetic nephropathy. - Definitive concentration: 30-300mg/L - Albumin/Creatinine ratio = need for timed specimens LABORATORY ANALYSIS OF HBA1c - High Performance Liquid Chromatography (HPLC)
- cation exchange chromatography
- report back % glycation
- < 6.5% represents good glucose
control Glycosylation of Hair • glycosylation of hair is in diabetes mellitus • glycosylation of hair is proportionate to HbA1c • long hair sample provides a long term record. • may have forensic application & in population studies. MENARINI 8160 MENARINI 8160 RESULTS Microalbumin Urine Analysis SUMMARY • T2D - insulin resistance - related to central obesity - long term complications • acute complications (T1D & T2D) – DKA and HHS • monitoring – glucose, Hb, microalbumin
