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DIABETES MELLITUS BY TIKAL KANSARA BARODA MEDICAL COLLEGE (BMC)
DIABETES MELLITUS Diabetes Mellitus (DM) refers to a group of common metabolic disorders that share the common phenotye of hyperglycemia Depending on etiology, factors contributing to hyperglycemia includes: Reduced insulin secretion Decreased glucose utilization Increased glucose production
CLASSIFICATION Type I DM  Type II DM Other specific types: Genetic deficiency of B- cell functions Hepatocyte nuclear transcriptioon factor 4 alfa (MODY 1) Glucokinase (MODY 2) HNF – 1alfa (MODY 3) Insulin promoter factor 1 (MODY 4) HNF 1beta (MODY 5) neuroD1 (MODY 6)
Genetic defects in insulin action Type A insulin resistance Leprechaunism Lipodystrophy syndromes Dieases of exocrine pancreas: pancreatitis, pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis Endocrinopathies: Acromegaly, Cushing Syndrome, pheochromocytoma, hyperthyroidism Drug or chemical induced: pentamitice, nicotinic acid, glucocorticoids, thyroid hormones, phenytion, protease inhibitors, clozapine Infections: congenital rubella, CMV, Coxsachie Uncommon forms: anti-insulin receptor antibodies Other genetic conditions associated with Diabetes: Down Syndrome, Klinefelter Syndrome, Turner’s Syndrome, Friedrich’s Ataxia, Huntington’s Chorea, Porphyria Gestational Diabetes Mellitus
SPECTRUM OF GLUCOSE HOMEOSTASIS & DM
NORMAL PHYSIOLOGY OF INSULIN ACTION http://1.bp.blogspot.com/_N-RTY7s9S4A/SJwltA7yq7I/AAAAAAAAAUg/-rtv3wsulaE/s400/Insulin.jpg
RISK FACTORS FOR DIABETES MELLITUS Family history of diabetes (parent or sibling) Obesity (BMI > 25) Habitual physical inactivity Race/ethinicity Previously identified IFG or IGT History of GDM or delivery of baby > 4 kg Hypertension ( BP > 140/90 mmHg ) HDL cholestrol level < 35 mg/dl &/or a TG level > 250 mg/dl PCOD or Acanthosisnigricans History of vascular disease
PATHOGENESIS OF DM 1 http://www.discoverymedicine.com/Didier-Hober/files/2010/08/discovery_medicine_hober_no51_figure_5.jpg
http://ocw.tufts.edu/Content/14/lecturenotes/265878/133132_medium.jpg
http://ocw.tufts.edu/data/51/673764/674515_xlarge.jpg
http://img.medscape.com/slide/migrated/editorial/cmecircle/2001/145/prato/slide02.gif
METABOLIC ABNORMALITIES OF DM TYPE DEUX
http://4.bp.blogspot.com/_l2LRboVHKr4/TMZ9sVGyxZI/AAAAAAAAAH4/-B6JocyPDOQ/s320/xxx.....111diabetes-symptoms.jpg
MAIN INSULIN RESISTANCE SYNDROMES The main insulin resistance syndromes include The Metabolic Syndrome (Syndrome X) Polycystic Ovary Syndrome (PCOS)
METABOLIC SYNDROME http://professional.diabetes.org/content/multimedia/images/lge/lge_qhscw16-metabolic%20syndrome-4%20copia.gif
http://kardiol.com/wp-content/uploads/2011/01/metabolic-syndrome-2.jpg
DIABETIC KETOACIDOSIS SYMPTOMS ,[object Object]
Thirst/Polyuria
Abdominal Pain
Shortness Of BreathPHYSICAL SIGNS ,[object Object]
Dehydration/Hypotension
Tachpnea/Kussmaul Respiration/Respiratory Distress
Abdominal Tenderness
Lethargy/Obtundation/Cerebral Oedema/Possibly Coma,[object Object]
PATHOPHYSIOLOGY OF DK
COMPARATIVE LABORATORY IN DK & HHS
http://pmj.bmj.com/content/80/943/253/F1.large.jpg
TREATMENT OF DK INITIAL EVALUATION ,[object Object]
Laboratory Tests: ABG, CBC, Urinalysis, RBS, BUN, creatinine.
ECG & CXR
Start IV fluids … 1 L of 0.9% NaCl /hr initially (15 – 20 ml/kg/hr)DIAGNOSTIC CRITERIA ,[object Object]
pH < 7.3
S. bicarbonate < 15 mEq/L
Moderate ketonuria & ketonemia,[object Object]
SHORT ACTING INSULIN IV (0.1 U/kg) or IM (0.3 U/kg) stat Then, 0.1 U/kg/hr continuous infusion; increase to 2 to 3 times, if no response by 2 – 4 hrs If initial potassium < 3.3 mEq/L, do not administer insulin till potassium corrected to > 3.3 mEq/L
ELECTROLYTE CORECTIONS POTASSIUM ,[object Object]
40 – 80 mEq/L, when initial K+ < 3.5 mEq/L or bicarbonate givenBICARBONATE ,[object Object]
If pH < 6.9, 100 mEq/L HCO3 with 20 mEq/L KCl over 2 hrs in 400 ml sterile water,[object Object]
CHRONIC COMPLICATIONS OF DM MICROVASCULAR Eye disease Retinopathy Macular oedema Neuropathy Sensory Motor Autonomic Nephropath
MACROVASCULAR Coronary artery disease Peripheral artery disease Cerebrovascular disease OTHERS Gastrointestinal Genitourinary Dermatologic Infections Cataracts Glaucoma Periodontal disease
MECHANISM OF COMPLICATIONS http://img.medscape.com/fullsize/migrated/editorial/clinupdates/2001/612/delprato_02.gif
Advanced glycosylated end-products Increased metabolism by sorbitol pathway ,[object Object]
Increases cellular osmolality
Generated reactive oxygen free radicalsDiacylglycerol activating protein kinase C Increases flux through hexoseamine pathway. PROPOSED THEORIES
OPHTHALMIC COMPLICATIONS http://images.emedicinehealth.com/images/healthwise/medical/hw/h9991431_001.jpg
TREATMENT OF OPHTHALMIC COMPLICATIONS Prevention Prophylactic photocoagulation Laser photocoagulation Panretinal focal
RENAL COMPLICATIONS OF DM Causes ESRD http://3.bp.blogspot.com/-fMj_wJT6nfo/TaiM81DjrJI/AAAAAAAAAlI/xvtxy9ZHtRI/s1600/clip_image006.jpg
Necrotisingpapillitis http://missinglink.ucsf.edu/lm/IDS_106_DM_Complications/ASSETS/DMrenalNPgross.jpg
TREATMENT OF RENAL COMPLICATIONS Maintain blood glucose level Maintain BP to < 130/80 mmHg Use ACE-I & ARBs CCBs, B-blockers, Diuretics Protein restriction 0.8 g/kg/day in microalbunemia & <0.8 g/kg/day in macroalbunemia Renal transplantation
NEUROPATHY http://pmj.bmj.com/content/82/964/95/F1.large.jpg
TREATMENT OF NEUROPATHY Improve glycemic control Reduce chances of hypertension & hypertriglyceridemia Avoid smoking, alcohol Supplement vitamins Daily care of foot wear For chronic painful neuropathy – use antidepressants, anticonvulsant
GI/GU COMPLICATIONS Delayed gastric emptying Altered small & large bowel motility Nocturnal diarrhoea Oesophageal dysfunction Erectile dysfunction Reduced sexual desire Dysparenuria Reduced vaginal lubrications Diabetic cystopathy
TREATMENT OF GI/GU COMPLICATIONS Small frequent meals Metoclopromide Domperidone Erythromycin Interacts eithmotilin receptors Loperamide Octreotide Diabetic cystopathy – self cathaterisation Sildenafil (Viagra) for erectile dysfunction
CARDIOVASCULAR COMPLICATIONS Absence of chest pain (“Silent ischemia”) is common One of the risk factors for atherosclerosis 	TREATMENT ,[object Object],[object Object]
LOWER EXTREMITY COMPLICATIONS http://missinglink.ucsf.edu/lm/IDS_106_DM_Complications/ASSETS/Ischemicfoot.jpg
http://www.podiatrytoday.com/files/imagecache/normal/PT07Diabetes1.png
http://www.onkocet.onkocet.eu/userfiles/image/plason_sds.jpg
DERMATOLOGIC COMPLICATIONS 	NECROTISING LIPOIDICA DIABETICORUM NECROBIOSIS DIABETICORUM: Atrophy of skin http://accessmedicine.net/loadBinary.aspx?name=hurs13&filename=hurs13_c014f035t.jpg http://accessmedicine.net/loadBinary.aspx?name=harr&filename=harr_c929f007t.jpg
DIAGNOSIS
SCREENING TESTS Widespread use of FPG for screening is recommended because: Large number of people who meet the criteria are unaware of their problem & are asymptomatic Epidemiological studies show that type 2 DM may be present for a decade before the diagnosis As many as 50 % of individuals with DM have one or more of the complications Treatment of DM has favorably altered the natural history of the disease
Individuals >45 years of age are to be screened every 3 years Individuals who are overweight (BMI > 25) and have an additional risk factor for the disease should also be screened
LONG TERM TREATMENT
BEFORE GIVING MEDICATIONS Diabetic education Nutrition (Medical Nutrition Therapy, MNT) Exercise
PATIENT EDUCATION Self-monitoring of blood glucose Urine ketone monitoring Self insulin administration Foot & skin care Management of hypoglycemia
MEDICAL NUTRITION THERAPY FATS 20 – 35% of total calories Saturated fats < 7% of total calories < 200 mg/day of dietary cholesterol Two or more servings of fish/week Minimal trans fats consumption CARBOHYDRATES 45 - 65% of total calorie intake Type & amount of carbohydrate is important Sucrose containing food must be consumed with adjustments in insulin PROTEINS 10 – 35% of total calorie intake OTHER COMPONENTS Fibre containing food may reduce postprandial glucose excrusions Nonnutrient sweeteners
EXERCISE Around 150 mins/week
ASSESSMENT OF LONG TERM GLYCEMIC CONTROL GLYCATED HAEMOGLOBIN (HbA1C) Non-enzymatic glycation of hemoglobin Keep less than 7% That is around < 170 mg/dl Status of around last 3 months FRUCTOSEAMINE ASSAY For prior 2 weeks Other method is : 1,5 anhydroglucitol assay
TREATMENT OF DM Type I DM Give insulin primarily Type II DM Give oral hypoglycemic drugs, primarily

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