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Diabetes Mellitus

• Most common of the endocrine disorders
• Chronic condition
• characterized by hyperglycemia
• impaired insulin secretion with or without insulin resistance
Aetiological classification of Diabetes Mellitus
• Type 1 (beta cell desruction, usually leading to absolute insulin deficiency)
– Autoimmune
– Idiopathic
• Type 2 (may range from predominantly insulin with relative insulin deficiency to a predominantly
secretory defect with or without insulin resistance)
• Other specific types
– Genetic defects of beta cell function
– Genetic defects in insulin action
– Disease of the exocrine pancreas
– Endocrinopathies
– Drug or chemical induced, for example, nicotinic acid, glucocorticoids, high-dose thiazides,
pentamidine, interferon alpha infections
– Uncommon forms of immune-mediated diabetes
– Other genetic syndromes sometimes associated with diabetes
– Gestational diabetes

of Diabetes
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Gestational Diabetes
Other types:
 LADA (latent autoimmune diabetes of adult)
 MODY (maturity-onset diabetes of youth)
 Secondary Diabetes Mellitus


1 diabetes
Was previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes.
Disease characterized by the destruction of the insulin-producing pancreatic beta cells
Usually develops in the young (below the age of 30)
Faster onset of symptoms leading to dependency on extrinsic insulin for survival


2 diabetes
Was previously called non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes.
More common above the age of 40
Relative insulin deficiency and insulin resistance
Symptoms are generally slower in onset and less marked than those of type 1

genetic testing has shown that MODY can occur at any age and that a family history of diabetes is not always obvious. 5% to 10% of women with gestational diabetes are found to have type 2 diabetes. surgery. • After pregnancy. the different subtypes can essentially be divided into 2 distinct groups: glucokinase MODY and transcription factor MODY. LADA) progress to insulin requirement within 6 years.2 mutation) requires high-dose sulfonylurea therapy. and sometimes also "Type 1. gestational diabetes requires treatment to normalize maternal blood glucose levels to avoid complications in the infant. • However.Gestational diabetes • A form of glucose intolerance that is diagnosed in some women during pregnancy. o Originally. "Slow Onset Type 1" diabetes.e. • Such types of diabetes may account for 1% to 5% of all diagnosed cases of diabetes. • Alternate terms that have been used for "LADA" include Late-onset Autoimmune Diabetes of Adulthood. Hepatocyte nuclear factor -1alpha) requires low-dose sulfonylurea therapy and PNDM (caused by Kir6. distinguished by characteristic phenotypic features and pattern on oral glucose tolerance testing. • About 80% of adults apparently with recently diagnosed Type 2 diabetes but with GAD autoantibodies (i. Pathophysiology • Islet of Langerhans – form the endocrine component of the pancreas. and other illnesses. LADA • Latent Autoimmune Diabetes in Adults (LADA) is a form of autoimmune (type 1 diabetes) which is diagnosed in individuals who are older than the usual age of onset of type 1 diabetes. o Different subtypes of MODY are identified based on the mutated gene. • Glucokinase MODY requires no treatment. • During pregnancy. causing MODY. patients with LADA are mistakenly thought to have type 2 diabetes. Other types of DM • Other specific types of diabetes result from specific genetic conditions (such as maturity-onset diabetes of youth). infections. since insulin production decreases over a sustained period of time . • The potential value of identifying this group at high risk of progression to insulin dependence includes: • the avoidance of using metformin treatment • the early introduction of insulin therapy MODY • MODY – Maturity Onset Diabetes of the Young • MODY is a monogenic form of diabetes with an autosomal dominant mode of inheritance: o Mutations in any one of several transcription factors or in the enzyme glucokinase lead to insufficient insulin release from pancreatic ß-cells. based on their age at the time of diagnosis. • Within MODY. malnutrition. while transcription factor MODY (i. constituting 1% of the total pancreas mass • Insulin – Is synthesised in the pancreatic beta cells.e. drugs. diagnosis of MODY was based on presence of non-ketotic hyperglycemia in adolescents or young adults in conjunction with a family history of diabetes. proinsulin – 3-5 min half life – Primarily metabolised by the liver and kidney • Glucose – Is the major stimulant to insulin release • Type 1 – There is an acute deficiency of insulin that leads to unrestrained hepatic glycogenolysis and glyconeogenesis with a consequent increase in hepatic glucose output • Type 2 – The process is usually less acute. initially as a polypeptide precursor. • Women who have had gestational diabetes have a 20% to 50% chance of developing diabetes in the next 5-10 years.5 • Often.

type 2 diabetes develops Pathophysiology of insulin resistance • Abdominal fat – Found in abundance in the majority of those with type 2 diabetes – Metabolically different from subcutaneous fat and can cause lipotoxicity – Resistant to the antilipolytic effects of insulin • Excessive amounts of free fatty acids – Lead to insulin resistance in the liver and muscle Nocturnal hypoglycaemia • Hypoglycaemia occurs throughout the night • Symptoms – Restlessness – Unrested – Unwell or with headache Treatment of hypoglycaemia • Glucose oral – If the patient is able to swallow safely without the risk of aspiration • Glucose IV or IM – Unable to swallow or decrease level of consciousness Symptoms of Hypoglycaemia • Autonomic – Sweating – Trembling – Tachycardia – Palpitations – Pallor • Neuroglycopaenic – Faintness – Loss of concentration – Drowsiness – Visual disturbances – Abnormal behavior (agitation. but evenually beta cell function deteriorates and hyperglycaemia ensues If this cycle is not interrupted. aggressiveness) – Confusion – Coma • Other – Hunger – Headache – Perioral tingling/ numbness .– – Hyperinsulinaemia is able to maintain glucose levels for a period of time.

urea.Diabetic emergencies • Hypoglycaemia • Diabetic ketoacidosis • Hyperosmolar hyperglycaemic state Diabetic ketoacidosis • Occurs because the absence of insulin cause extreme hyperglycaemia • Normal restraining effect of insulin on lipolysis is removed • Non esterified fatty acids are released into the circulation and taken up by the liver. caused by hyperglycaemia. there is no significant ketone production and therefore no severe acidosis • Hyperglycaemia occurs gradually over a sustained time. caused by urinary excretion and vomiting due to stimulation of the vomiting of centre by ketones and catabolism of muscle protein • When insulin deficiency is severe and of acute onset. leading to dehydration due to osmotic diuresis • Hyperosmolarity may increase blood viscosity and risk of thromboembolism Factors precipitating HHS • Infection • Myocardial infarction (heart attack) • Poor adherence with medication regimens . acetoacetate and hydroxybutyrate are formed in increased amounts and released into the circulatation • Osmotic diuresis. causing dizziness and weakness due to postural hypotension • Weakness is increased by potassium loss. all of these symptoms are accelerated Diagnosis of Diabetic ketoacidosis • Urinalysis – Show marked glycosuria and ketonuria • Blood glucose test strip – Shows blood glucose level of more than 22 mmol/L • Formal lab measurement of glucose. which produces acetyl coenzyme A • Capacity of tricarboxylic acid cycle to metabolise acetyl coA is rapidly exceeded • Ketone bodies. electrolytes and venous bicarbonates Treatment of Diabetic ketoacidosis • Fluid volume expansion ( initially with 0. creatinine. lowers serum volume.9% sodium chloride) • Correction of hyperglycaemia and presence of ketones (by infusion of insulin) • Prevention of hypokalaemia • Identification and treatment of any associated infection Hyperosmolar hyperglycaemic state • HHS usually occurs in middle aged or elderly people • Unlike diabetic ketoacidosis.

• • Medicines which cause diuretics Impaired glucose intolerance – Ex. altered foot shape and gross deformity . – Hyperglycaemia – Dehydration – Hyperosmolarity – Mild metabolic acidosis (without marked ketone production) – Conscious levels (slight confusion to coma) – Seizures (in some case) – Sodium and potassium (normal). Glucocorticoids Diagnosis of HHS • Diagnostic features of HHS are. tight glycaemic control during pregnnancy reduces long term reinopathy – Nephrapathy • Kidneys become enlarge and glomerular filtration increases • Indicate by the detection of microalbuminuria – Peripheral neuropathy • Progressive loss of peripheral nerve fiber resulting loss in nerve dysfunction • Macro and Microvascular disease combined • 3 main types of foot ulcer – Neuropathic ulcers occurs when peripheral neuropathy loss of pain sensation – Ischaemic ulcers result from PVD and poor blood supply causing reduction in available nutrients and oxygen required for healing. Painful and usually occur on the distal ends of the toes – Neuroishaemic ulcers • Charcot arthropathy – Uncommon foot complication caused by severe neuropathy – Chronic progressive destruction of joints with marked inflammation – Reduce bone density leads to bone fractures.45% (If serum level is >150mmol/L) • Potassium (if required) • Insulin IV • Prophylaxis or treatment for thromboembolism (if required) Long term diabetic complications • Macrovascular disease – Cardiovascular disease • Most common death in people with type 2 diabetes • Hypertension – Twice as common amongst diabetic population – Affect 80% with type 2 diabetes – Peripheral vascular disease • Affects the blood vessels outside the heart • Also responsible for much of the morbidity associated with diabetic foot problems • Microvascular disease – Retinopathy • Leading cause of blindness in people under the age of 60 • Pregnancy may worsen moderate to severe reinopathy. particularly if there is a poor or sudden improvement in glycaemic control • However.9 or 0. creatinine (high) – 10 L average fluid deficit Treatment of HHS • Fluid replacement to stabilise blood pressure and improve circulation of urine output • Sodium chloride 0.

low-sugar or diet squashes and fizzy drinks. and it delays the digestion and absorption of complex carbohydrates. .  Dietary treatment should aim at: ◦ ensuring weight control ◦ providing nutritional requirements ◦ allowing good glycaemic control with blood glucose levels as close to normal as possible ◦ correcting any associated blood lipid abnormalities Exercise  Physical activity promotes weight reduction and improves insulin sensitivity. thus lowering blood glucose levels. Monounsaturated fats such as olive oil are preferred. consider use of metformin. Grill. be educated about the potential risk of hypoglycaemia and how to avoid it.  Together with dietary treatment. • Cut down on sugar and sugary foods. potatoes. margarine. acarbose or TZD. α-glucosidase inhibitors V. cheese. Insulin Secretagogues – Non-sulphonylureas IV. Two units/day for a woman and three for a man. rice and cereals. Choose low-fat yoghurt. • Dietary fibre has useful properties in that it is physically bulky. however. This provides vitamins and fibre as well as helping to balance the overall diet. thereby minimising hyperglycaemia Diet  Diet is a basic part of management in every case. Such a programme must be tailored to the individual’s health status and fitness. as sugary drinks cause blood glucose levels to rise quickly. a programme of regular physical activity and exercise should be considered for each person. Biguanides II. Food can be flavoured with herbs and spices instead of salt. and eat fewer fatty meals. steam or oven bake instead of frying or cooking with oil or other fats. Thiazolidinediones (TZDs) Oral Agent Monotherapy As first line therapy:  Obese type 2 patients. pasta.  People should. consider the use of metformin or insulin secretagogues  Metformin is the drug of choice in overweight/obese patients. Use sugar-free. • Try to eat at least five portions of fruit and vegetables every day. Insulin Secretagogues – Sulphonylureas III. TZDs and acarbose are acceptable alternatives in those who are intolerant to metformin.Treatment of DM Management of DM The major components of the treatment of diabetes are: • Diet and Exercise • Oral hypoglycaemic therapy • Insulin Therapy General dietary advice for people with diabetes • Eat regular meals based or starchy foods such as bread. Oral Anti-Diabetic Agents • There are currently four classes of oral anti-diabetic agents: I. Whenever possible. Never drink on an empty stomach as alcohol can exacerbate hypoglycaemia. for example. Sugar can still be used as an ingredient in foods and baking as part of a healthy diet. Use less butter.  Non-obese type 2 patients. wholemeal bread and wholemeal cereals which have a lower glycaemic index • Try to cut down on fat. choose high-fibre varieties of these foods. • Drink alcohol in moderation. A small glass of wine or half pint of normal strength beer is one unit. Treatment cannot be effective unless adequate attention is given to ensuring appropriate nutrition. • Use less salt as high intake can raise blood pressure. particularly saturated (animal) fats.

acarbose and metformin is recommended. . consider adding intermediate-acting/long-acting insulin (BIDS). If monotherapy fails.  Combination of insulin+ oral anti-diabetic agents (BIDS) has been shown to improve glycaemic control in those not achieving target despite maximal combination oral anti-diabetic agents.  Combining insulin and the following oral anti-diabetic agents has been shown to be effective in people with type 2 diabetes: ◦ Biguanide (metformin) ◦ Insulin secretagogues (sulphonylureas) ◦ Insulin sensitizers (TZDs)(the combination of a TZD plus insulin is not an approved indication) ◦ α-glucosidase inhibitor (acarbose) ◦ Insulin dose can be increased until target FPG is achieved. If targets are still not achieved. insulin secretagogues may be added Combination Oral Agents and Insulin  If targets have not been reached after optimal dose of combination therapy for 3 months. a combination of TZDs.

with an appropriate dose of an intermediate-acting insulin given at bedtime.  Twice-daily mixtures of short. Insulin regimens  The majority of patients will require more than one daily injection if good glycaemic control is to be achieved. When initiating this.  A regimen of multiple injections of short-acting insulin before the main meals. a once-daily injection of an intermediate acting preparation may be effectively used in some patients. consider change to multi-dose insulin therapy. hyperosmolar nonketotic coma. Further doses of short-acting insulin are given before lunch and the evening meal and an evening dose of intermediate-acting insulin is given at bedtime.  In some cases.g. severe hypertriglyceridaemia) Long-term use:  If targets have not been reached after optimal dose of combination therapy or BIDS.C. a mixture of short. Self-care should include: ◦ Blood glucose monitoring ◦ Body weight monitoring ◦ Foot-care ◦ Personal hygiene ◦ Healthy lifestyle/diet or physical activity ◦ Identify targets for control ◦ Stopping smoking Case study . surgery. insulin secretagogues should be stopped and insulin sensitisers e. This allows the patient to assume responsibility and control of his / her own diabetes management. may be used. lactic acidosis. Insulin Therapy Short-term use:  Acute illness. Metformin or TZDs. stress and emergencies  Pregnancy  Breast-feeding  Insulin may be used as initial therapy in type 2 diabetes  in marked hyperglycaemia  Severe metabolic decompensation (diabetic ketoacidosis.  Other regimens based on the same principles may be used. can be continued.and intermediate-acting insulin may be given in the morning. However. Self-Care  Patients should be educated to practice self-care. particularly when strict glycaemic control is mandatory.and intermediate-acting insulin is a commonly used regimen.

he noticed that there was a weeping sore. • Should he be more concerned? – Mr. – He is at risk of developing an infected ulcer and needs prompt treatment to prevent the problem from becoming severe. His whole left foot now looks red and swollen and when Mr. PT has sensory neuropathy since he is unable to feel the pain of the weeping sore. Questions and Answer • What is the most likely reason that Mr.PT may also have motor neuropathy. PT has probably developed sensory neuropathy in his feet. he may even risk losing his foot through amputation. PT should be concerned because his lack of sensation does not indicate that the foot injury is not serious.• Mr. – This may be due to the development of neuropathy which can weaken muscles causing alterations to the shape of the arch of the foot and toes. PT inspected it closely. PT’s shoe suddenly have started to rub his foot? – The shape of the feet of people with diabetes has been observed to change over time. – In this case. so he does not feel too concerned. – If he does not seek treatment. which he finds confusing since he has been wearing these shoes for 6 months with no problems. PT did not feel any pain associated with the sore? – Mr. • Why might Mr. 4:13 ] . his foot is not painful.” – Phil. “I can do all things through Christ who gives me strength. However. – This usually begins with the loss of the sensation of vibration and then may progressively lead onto the loss of sensation altogether. we know that Mr. – It is likely that Mr. PT is a 69 year old man with longstanding type 2 diabetes. He has recently noticed that his right shoe has been rubbing his foot.