Click here to load reader

  • date post

  • Category


  • view

  • download


Embed Size (px)




OBJECTIVESIntroductionTypes of DiabetesClinical featuresDiagnosistreatment

global pandemic principally involves type 2 diabetesa clinical syndrome characterized by an increase in plasma blood glucose (hyperglycaemia)Type 1 diabetes is caused by autoimmune destruction of insulin-producing cells ( cells) in the pancreastype 2 diabetes is characterised by resistance to the action of insulinThe diagnostic criteria for diabetes (a fasting plasma glucose 7.0 mmol/L (126 mg/dL) or glucose 2 hours after an oral glucose challenge 11.1 mmol/L (200 mg/dL)

Less severe hyperglycaemia is called impaired glucose tolerance. This is not associated with a substantial risk of microvascular disease, but is connected with an increased risk of large vessel disease3

associated with genetic as well as environmental factors such as greater longevity, obesity, unsatisfactory diet, sedentary lifestyle, increasing urbanisation

Major metabolic pathways of fuel metabolism and the actions of insulin

Aetiology and pathogenesis Type 1 diabetestype 1 diabetes is a t cell-mediated autoimmune diseasedestruction of the insulin-secreting cells in the pancreatic islets.,

marked hyperglycaemia, accompanied by the classical symptoms of diabetes, occurs only when 8090% of the functional capacity of cells has been lost6

Pathogenesis of type 1 diabetes

Risk of type 1 diabetes among first-degree relativesRelative with type 1 diabetes% overall riskIdentical twin35Non-identical twin20HLA-identical sibling16Both parentsUp to 30

Genetic predispositionthe inheritance is polygenicGenes on the short arm of chromosome 6; this locus is designated IDDM 1The HLA haplotypes DR3 and/or DR4 are associated with increased susceptibility to type 1 diabetes

Environmental predispositiondirect toxicity to cells or by stimulating an autoimmune reaction directed against cells. Viruses: mumps, Coxsackie B4, retroviruses,rubella (in utero), cytomegalovirus and EpsteinBarrvirus. dietary nitrosamines, coffee, Bovine serum albumin(BSA),

Type 2 diabetesinitially, insulin resistance leads to elevated insulin secretionthe pancreatic cells are unable to sustain the increased demand for insulin and a slowly progressive insulin deficiency develops.insulin resistance syndrome or metabolic syndrome,:adipokines:Pancreatic -cell failureGenetic predisposition

Environmental andother risk factorsDiet and obesityOvereating, underactivityAGEmore common in the middle-aged and elderly

The risk of developing type 2 diabetes increases tenfold in people with a body mass index (BMI) of more than 30 kg/m213

At diagnosis, patients are often asymptomatic or give a long history of fatigue, with or without osmotic symptoms (thirst and polyuria)

Other forms of diabetesmaturity-onset diabetes of the young (MODY) latent autoimmune diabetes of adults (LADA).

Type 1Type 2Typical age at onset< 40 yrs> 50 yrsBody weightNormal or lowObeseKetonuriaYesNoAutoantibodiesPositive in8090%NegativeFamily history ofdiabetesUncommonCommon

Other autoimmunediseaseCommonUncommon

Symptoms of hyperglycaemiaThirst, dry mouthPolyuriaNocturiaTiredness, fatigue, lethargyChange in weight (usually weight loss)Blurring of visionPruritus vulvae, balanitis (genital candidiasis) Hyperphagia; predilection for sweet foodsMood change, irritability, difficulty in concentrating, apathy

INVESTIGATIONSBlood Glucose:to make the diagnosis of diabetes, the blood glucose concentration should be estimated usingan accurate laboratory method rather than a glucometerWhole blood glucose concentrations are lower than plasma concentrations because red blood cells contain relatively little glucoseVenous plasma values are usually the most reliable BLOOD KETONE:detects -OHB the major ketone in blood during DKA

Urine testingFor Glucose with dipsticksdisadvantage of urinary glucose measurement is the individual variation in renal threshold for glucose.; albumin (both macro- and micro-albuminuria)KETONES

some drugs (such as -lactam antibiotics, levodopa and salicylates) may interfere with urine glucose tests.19

Glycated haemoglobinGlycated haemoglobin provides an accurate and objective measure of glycaemic control integrated over a period of weeks to months.HbA1c estimates may be erroneously diminished in anaemia or during pregnancy, and may be difficult to interpret with some assay methods in patients who have uraemia or a haemoglobinopathy.

increases the amount in the HbA1 (HbA1c) fraction relative to nonglycated adult haemoglobin (HbA0). IFCC-standardised HbA1c values are reportedin mmol/mol., IFCC HbA1c (mmol/mol) = [DCCT HbA1c(%)2.15] 10.92920

DiabetesFasting 7.0 mmol/L (126 mg/dL) ora random glucose 11.1 mmol/L (200 mg/dL) (IFCC HbA1c of more than 48 moll/molPre-diabetes:IFG or IGT,based upon the fasting plasma glucose 6.0 (108 mg/dL) and < 7.0 mmol/L (126 mg/dL) and 2-hour oral glucose tolerance test results (OGTT) after 75 g oral glucose drink 7.811.1 mmol/L (140200 mg/dL)stress hyperglycaemia: during severe stress, or during treatment with diabetogenic drugs

diabetes in pregnancyHigh-risk women should have a 75 g oral glucose tolerance test before 28 weeks gestationGestational diabetes is diagnosed when:Fasting plasma glucose 5.1 mmol/L (92 mg/dL) or1-hr plasma glucose (after glucose load) 10 mmol/L(180 mg/dL) or2-hr plasma glucose (after glucose load) 8 mmol/L(144 mg/dL)Consider testing high-risk women at first booking visit with an HbA1c

ManagementDietarylifestyle modification oral anti-diabetic drugs and injected therapiesInsulinsBlood glucose targets:pre-meal values between 4 and 7 mmol/L (72 and 126 mg/dL) and 2-hour post-meal values between 4 and 8 mmol/L represent optimal controlThe target HbA1c: 6.5% -7.5%

DrugsBiguanidesMetformin first-line therapy for type 2 diabetesThe main side-effects are diarrhoea, abdominal cramps, bloating and nausea.aninsulin sensitiser , its main effects are on fasting glucosedoes not cause hypoglycaemiahas established benefits in microvascular diseaseintroduced at low dose (500 mg twice daily)The usual maintenance dose is 1 g twice dailycan increase susceptibility to lactic acidosis

Sulphonylureas:gliclazide, glibenclamide, glimepiride, glipizideinsulin secretagogues, long-term benefits in lowering microvascular complicationsact by closing the pancreatic -cell ATP-sensitive potaglimepiridessium (KATP) channel, decreasing K+ efflux, which ultimately triggers insulin secretion. used as an add-on to metforminThe main adverse effects of sulphonylureas are weight gain and hypoglycaemia

Hypoglycaemia occurs because the closure of KATP channels brings about unregulated insulin secretionThe doseresponse of all sulphonylureas issteepest at low doses; little additional benefit is obtained when the dose is increased to maximal levels.25

Alpha-glucosidase inhibitors:acarbose, miglitoldelay carbohydrate absorption in the gut by inhibiting disaccharidaseslower post-prandial blood glucoseThe main side-effects are flatulence, abdominal bloating and diarrheaTHIAZOLIDINEDIONES:pioglitazoneTZDs enhance the actions of endogenous insulin, in part directly (in the adipose cells) and in part indirectly (by altering release of adipokines,such as adiponectin, which alter insulin sensitivity in the liver) hypoglycaemia does not occur

Pioglitazone has a beneficial effect in reducing fatty liver and NASH 26

DPP-4 inhibitors and GLP-1 analoguesincretin effect:The gliptins, or DPP-4 inhibitors:sitagliptin, vildagliptin, saxagliptin and linagliptin prevent breakdown and therefore enhance concentrations of endogenous GLP-1 and GIPweight-neutralinjectable GLP-1 analoguesexenatide (twice daily), exenatide MR (once weekly) and liraglutide (once daily). lower blood glucose and result in weight loss, these agents do not cause hypoglycaemia

SGLT2 inhibitorsDapagliflozinsglt2 is involved in reabsorption of glucose. inhibition results in approximately 25% of the filtered glucose not being reabsorbed, with consequent glycosuria.

Insulin therapyShort-acting insulin'srapid-acting insulins :insulin lispro,insulin aspart and insulin glulisineIntermediate acting insulinslonger-acting insulins:glargine, detemirInhaled insulin

Thank You