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MSc Clinical Biochemistry. Carbohydrate Metabolism.

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Presentation on theme: "MSc Clinical Biochemistry. Carbohydrate Metabolism."— Presentation transcript:

1 MSc Clinical Biochemistry. Carbohydrate Metabolism.

2 Plan For The Evening. History of Diabetes and some things you did n’t know.. Carbohydrate Physiology. Diabetes Mechanisms. Treatment.Complications. Some Worked Examples.

3 It’s all Greek to Me!!! Diabetes Mellitus Diathrough Betesto go. Mellitushoney “Anyone got a sweet tooth?”

4 Not a New Disease….

5 Famous Folks. Below are just a handful of the celebrities, sportsmen, politicians and socialites who have diabetes yet have not let the condition hold them back from attaining their goals and dreams. Showbusiness Andrew Lloyd WebberAndrew Lloyd Webber,Elizabeth Taylor,Halle Berry,Sharon Stone,Victor Garber, Vanessa Williams. Elizabeth TaylorHalle BerrySharon StoneVictor Garber Andrew Lloyd WebberElizabeth TaylorHalle BerrySharon StoneVictor GarberAthletes Ayden ByleAyden Byle, Chris Southwell, Steve Redgrave, Gary Mabbutt. Chris SouthwellSteve RedgraveGary Mabbutt. Ayden ByleChris SouthwellSteve RedgraveGary Mabbutt. Musicians Damon Dash Damon Dash, Aretha Franklin,Randy Jackson, Nick Jonas. Damon Dash, Aretha Franklin,Randy Jackson, Nick Jonas.Aretha FranklinRandy Jackson Damon DashAretha FranklinRandy Jackson Artists, Authors & Comedians Artists, Authors & Comedians Jimmy Tarbuck [Comedian]HG Wells [Author] Jimmy Tarbuck [Comedian]HG Wells [Author]

6 There are currently over 2.6 million people with diabetes in the UK and there are up to half a million people with diabetes who have the condition and don't know it. Including both adults and children, we estimate that: 15 per cent of people with diabetes have Type 1 diabetes. 85 per cent of people with diabetes have Type 2 diabetes. From

7 Physiology. Glucose is the principle energy source for our body. Most organs have alternatives. Glucose and to lesser extent ketones are the only options for brain function because. Can’t store significant glucose. Can’t synthesise glucose. Can’t metabolise other substrates.

8 Insulin. Peptide Hormone Produced by  cells in the Islets of Langerhans in the pancreas Starts as pro- insulin and is cleaved to produce C-Peptide and Insulin.

9 Glucagon. Peptide Hormone Produced by the  cells in the Islets of Langerhans in the pancreas. Generally opposes action of insulin.



12 Normal Glucose Metabolism. The gut as a result of hydrolysis or hepatic conversion of a variety of ingested carbohydrates. Hepatic and some other glycogen stores (glycogenolysis) New synthesis from precursors. Gluconeogenesis occurs in the liver 70-90%ish and kidneys 10-25% from glucogenic amino acids and from glycerol, lactate and pyruvate.

13 Mechanisms Preventing /Reversing Hypoglycaemia. Adrenergic/ Sympathetic Response. Promotes glycogenolysis, gluconeogenesis and increased glucose output by the liver, reduces gluocse clearance by adipose and skeletal muscle. Promotes lipolysis to provide alternative fuel sources. Inhibits insulin secretion. Counter-regulatory Hormones. Glucagon promotes glycogenolysis, glucosneogenis and thus increased glucose output from the liver. May increase hepatic ketone production. Cortisol promotes glycogenolysis, glucosneogenis and thus increased glucose output from the liver. reduces gluocse clearance by adipose and skeletal muscle Growth Hormone promotes hepatic glycogenolysis and increased hepatic glucose output, promotes lipolysis. Other mechanisms. Insulin secretion inhibited Feelings of hunger promote eating. Hypoglycaemia per se stimulates hepatic glucose output

14 Energy Use. Glucose provides 40-60% of bodies fuel expenditure on standard Western Diet. During high intensity exercise and 4-6 hours post prandial glucose is the most prominent energy source. Glucose is also the most efficient source of energy 6 moles ATP per mole of Oxygen consumed.

15 Glucose Transport.

16 Glucose Cellular Uptake. Glucose is hydrophilic and requires a transporter to help it through the cell membrane. GLUTS potentially bidirectional. Glucose trapped in cells by phosphorylation mediated by hexokinase/glucokinase. Glucose then used for Aerobic use, anaerobic use, synthesis of other molecules i.e. ( glycerol and carbon skeletons of non- essential amino acids), or stored as glycogen.

17 The input of Insulin.  Insulin interacts with insulin receptors. The signal cascade that results from this leads to GLUT molecules migrating to the cell membrane.  The insulin and their receptor molecules are subsequently internalised. Receptors are later recycled to the surface.  It is thought that internalisation of insulin is important to convey growth and protein synthesis signals to the cell nucleus.  Also important to remove insulin from the circuation.

18 Insulin and Growth Factors. Insulin also has a measure of growth promoting activity. Insulin-like Growth Factors IGF-1 and IGF-2 are closely homologous to insulin and are weak agonists to insulin receptors. Their impact on glucose metabolism is possibly less significant. The role is more relevent as a cellular growth factorr. Tumour related hypoglycaemia can be a result of IGF excess.

19 Diabetes Diagnosis.


21 Type 1 5-10% of Diabetics. Severe insulin deficiency resulting from autoimmune  cell destruction. Absolute requirement for exogenous insulin to avoid rapid decline into cachexia, dehydration, ketoacidosis and death. Pre Banting and Best very poor almost universially fatal prognosis.


23 Type 2 Probably heterogeneous diagnosis of exclusion. Usually a measure of insulin resistance with often an ultimate insulin deficiency. Some patients initially misdiagnosed may have LADA. Usually present with obesity and increased BMI. Some argue that insulin is often required to support oral and dietary control at a median 7 years post diagnosis.

24 Type 2 continued… Leaner Type 2’s tend to be more insulin deficient, plumper Type 2’s tend to be more insulin resistant. Controversial as to which mechanism predominates in Europe. Secondary idiopathic causes may also “muddy the waters” Inheritability a strong factor.

25 Progress From Resistance to Deficiency

26 Secondary Causes to Consider. Alcohol related Haemochromatosis Coeliac Disease EndocrinePCOSSteroidAcromegaly Insulin Antibodies (Historical.)

27 Diabetic Complications. Microvascular. ? Principally due to hyper glycaemia per se Increased activation of the polyol pathway ultimately rendering cells vulnerable to oxidative stress. Sorbitol found in cateracts, peripheral nerve damage and renal glomeruli. Advanced glycation end products have also been implicated in structural changes leading to microvascular permeability.

28 Retinopathy.

29 Macrovascular. Hypertension Lipid abnormalities. More often a combination of low HDL, small dense LDL and hypertriglyceridaemia.

30 Treatment. DietExercise Smoking Cessation Aspirin Lipid lowering agents ACE inhibitors et al.

31 DCCT and UKPDS Microvascular and to some extent maybe macrovascular complications can be delayed or even prevented by tight glycaemic control. Oral Hypoglycaemic “of choice” metformin reduces hepatic glucose output Other options include sulphoylureas.

32 Diabetic Emergencies.

33 “Routine Diabetic Testing” Glucose to diagnose and monitor Microalbumin to assess early stage Diabetic Nephropathy. Renal Function Lipids.HbA1c

34 HbA1 c

35 Important Considerations Glycation Rates. Assay variability Standardisation Assay Frequency Anaemia.

36 HbA1 c Many people are advocating using HbA1 c for diagnosis! Discuss.

37 A Little Bit on Hypoglycaemia….. AcuteSubacuteChronic SweatingReduction of spont ActPersonality Changes AnxietyBehavioural ChangeDefective memory HungerTiredness/ Somnelencedepression NAUSEADizzinessPsychosis TREMULOUSNESSPoor concentrationdementia WEAKNESSSeizures PALPITATIONSComa RESTLESSNESS

38 Investigation.

39 Hypos

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