Diabetes 3 PDF

DEFINITION  Metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects of insulin secretion, insulin action or both. OLD CLASSIFICATION (1985) ⚫ Type 1, Insulin-...

DEFINITION  Metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects of insulin secretion, insulin action or both. OLD CLASSIFICATION (1985) ⚫ Type 1, Insulin-dependent (IDDM) ⚫ Type 2, Non Insulin-dependent (NIDDM) ◦ obese ◦ non-obese ◦ MODY (between 18 to 25 years) ⚫ IGT ⚫ Gestational Diabetes Mellitus New Classification (WHO) ⚫ Is based on etiology not on type of treatment or age of the patient. ⚫ Type I(Beta cell destruction-absolute insulin deficiency) Immune mediated Idiopathic ⚫ Type II predominant insulin resistant with relative insulin deficiency predominant secretory defect with insulin resistance Other specific Types ⚫ Genetic defect of beta cell function MODY (maturity onset diabetes of the young) syndromes mitochondrial mutions ⚫ Infections Congenital rubella CMV ⚫ Disease of pancreas Pancreatitis Trauma/pancreatectomy Neoplasia Cystic fibrosis Other specific Types ⚫ Endocrinopathies Acromegaly Cushing’s Syndrome Pheochromocytoma ⚫ Drug or chemical induced Nicotinic acid Glucocorticoids Thiazides ⚫ Genetic disorder with diabetes Down syndrome Turner syndrome Klinefelter syndrome Prader willi syndrome ⚫ Gestational Diabetes Mellitus ⚫ Neonatal Diabetes Mellitus Type 1 Diabetes Mellitus Formerly called insulin-dependent diabetes mellitus (IDDM) or juvenile diabetes T1DM is characterized by low or absent levels of endogenously produced insulin EPIDEMIOLOGY Most common endocrine disorder of childhood and adolescence. The onset occurs predominantly in childhood, with 2 peak one 5-7 yr, and another at puberty but it may present at any age. In india an average prevalence of Type I diabetes is 10 per 100000 population. Risk of development of Type 1 DM ⚫ If mother has Type1DM risk in child is 2%. ⚫ If father is affected risk is 7%. ⚫ In a sibling of the index case is estimated as 6%. ⚫ Risk is 6-10% in diazygotic twins & 30-65% in monozygotic twins  Pathogenesis & Natural history The natural history includes distinct stages 1) Initiation of autoimmunity 2) Preclinical autoimmunity with progressive loss of β-cell function 3) Onset of clinical disease 4) Transient remission( “Honeymoon period”) 5) Established disease 6) Development of complications The Pancreas Beta Cells: secrete insulin. Alpha Cells: secrete glucagon Autoimmunity occurs in islet of Langerhans against the beta cells... CLINICAL PRESENTATIONS ⚫DKA ( most common presentation in pediatrics) ⚫Classical symptom triad: polyuria, polydipsia and weight loss ⚫Accidental diagnosis DIAGNOSTIC CRITERIA ⚫ Insymptomatic (polydipsia , polyurea, weight loss) children a random plasma glucose >11.1 mmol (200 mg) is diagnostic. ⚫ Hemoglobin A1C >= 6.5 % Remember: acute infections in young non-diabetic children can cause hyperglycemia without ketoacidosis. DIAGNOSTIC CRITERIA modified OGTT (oral glucose 1.75gm/kg max 75 gm) may be needed in  Asymptomatic children with hyperglycemia (RBS >140)  Symptomatic with hyperglycemia (RBS between ⚫ Fasting140 blood to glucose 200) level ⚫ 2 hours after oral glucose IGT (Impaired glucose IGT (Impaired glucose tolerance) tolerance) 6.0-6.9 mmol (100-126 7.8-11.0 mmol (140-200 mg/dl) mg/dl) Diabetic Diabetic >=7.0 mmol (126mg/dl) >=11.1 mmol (200 mg/dl) TREATMENT ELEMENTS ⚫ Education ⚫ Insulintherapy ⚫ Glycemic control Monitoring ⚫ Diet and meal planning ⚫ Prevention and early dectection of complication EDUCATION ⚫ Educate child & care givers about:  Diabetes type 1  life long Insulin therapy  self monitoring and maintaining records  Recognition of Hypoglycemia & DKA  Meal plan  Sick-day management  Possible long term complication INSULIN Therapy Insulin ⚫A polypeptide made of 2 -chains. ⚫ Discovered by Bants & Best in 1921. ⚫ Animal types (porcine & bovine) were used before the introduction of human-like insulin (DNA-recombinant types). ⚫ Recentlymore potent insulin analogs are produced by changing aminoacid sequence. Rapid-acting Insulin Examples: insulin lispro or insulin aspart Onset: Begins to work at about 5 minutes Peaktime: Peak is about 1 hour Duration: Continues to work for about 2-4 hours Regular or Short-acting Insulin Examples: insulin regular Onset: Reaches the bloodstream within 30 minutes after injection. Peaktime: Peaks anywhere from 2-3 hours after injection. Duration: Effective for approximately 3- 6 hours. Intermediate-acting Insulin Examples:NPH, Lente Onset: Reaches the blood stream about 2 to 4 hours after injection. Peaktime: Peaks 4-12 hours later. Duration: Effective for about 12 to 18 hours Long-acting Insulin Examples: insulin glargine Onset: Reaches the bloodstream 6- 10 hours after injection Duration: Usually effective for 20-24 hours Overview of Insulin and Action INSULIN CONCENTRATIONS ⚫ Insulin is available in different concentrations 40, 80 & 100 Unit/ml. ⚫ WHO now recommends U 100/ml to be the only used insulin to prevent confusion. ⚫ Special preparation for infusion pumps is soluble insulin 500 U/ml. Suggested target blood glucose range Time of checking Target plasma glucose(mg/dl) 1 Fasting or preprandial 90-145 2 Postprandial 90-180 3 Bedtime 120-180 4 Nocturnal 80-162 For children250 mg/dl Illness with fever and or vomiting abdominal pain , polyurea, drowsiness, rapid breathing ⚫ Glycosylated Hemoglobin (HbA1C) - every 3-4 monthly ADVERSE EFFECTS OF INSULIN ⚫ Hypoglycemia ⚫ Lipoatrophy ⚫ Lipohypertrophy ⚫ Obesity ⚫ Insulin allergy ⚫ Insulin antibodies PRACTICAL PROBLEMS ⚫ Non-availability of insulin in poor countries ⚫ injection sites & technique ⚫ Insulin storage & transfer ⚫ Mixing insulin preparations ⚫ Insulin & school hours ⚫ Adjusting insulin dose at home ⚫ Sick-day management ⚫ Recognition & Rx of hypoglycemia at home Management on Sick days ⚫ Insulin requirement may increase or decrease during illness. ⚫ Fever, dehydration, and the stress of illness can cause hyperglycemia due to increase production of counterregulatory hormones , whereas vomiting and loss of appetite can lead to hypoglycemia. ⚫ The risk of Ketosis is increased due to starvation and dehydration. Management on Sick days ⚫ Take plenty of fluids. ⚫ Blood glucose and urine ketones monitered frequently. ⚫ “moderate” or “large” ketones in the urine in the presence of hyperglycemia indicate insulin deficiency and risk of DKA. ⚫ Child should be given rapid acting analog or regular insulin and oral fluids and ketones should be rechecked in the next urine. ⚫ If there is vomiting with hyperglycemia and large ketones , or persistent hypoglycemia, child should be taken to emergency department. Management on Sick days URINE KETONE INSULI CORRECTION DOSE COMMENT STATUS N Negative or small q2hr q2hr for glucose Check ketones >250mg/dl every other void Moderate to large q1hr q1hr for glucose >250 Check ketones mg/dl each void go to hospital if emesis occurs. RBS 2hrly INSULIN short acting (0.1u/kg) or if RBS >250 DIET REGULATION ⚫ Regular meal plans with calorie exchange options are encouraged. ⚫ 50-60% of required energy to be obtained from complex carbohydrates. ⚫ Distribute carbohydrate load evenly during the day preferably 3 meals & 2 snacks with avoidance of simple sugars. ⚫ Encouraged low salt, low saturated fats and high fiber diet. DIET REGULATION ⚫ Avoid simple sugar ⚫ In patient with split mix regime- 6 meals-3 major(70% of total calories) -3midmeal(30% of total calories) ⚫ In children with MDI(multiple dose regime) mid meal is not essential majority of the calories should be consumed as a part of the meals, mid meal should have less than 10-15 gm of carbohydrate. DIET REGULATION Glycemic Index : ⚫ ranking of carbohydrates on a scale from 0 to 100 according to the extent to which they raise blood sugar levels after eating. ⚫ Foods with a high GI are those which are rapidly digested and absorbed and result in marked fluctuations in blood sugar levels. Like corn flakes, potato, watermelon, biscuits, chocolates ⚫ Low-GI foods, by virtue of their slow digestion and absorption, produce gradual rises in blood sugar and insulin levels, and have proven benefits diabetics. Like Most fruits and vegetables (except potato & water melon), pasta, pulses, milk, curd, EXERCISE ⚫ Decreases insulin requirement in diabetic subjects by increasing both sensitivity of muscle cells to insulin & glucose utilization. ⚫ It can precipitate hypoglycemia in the unprepared diabetic patient. PITFALLS OF MANAGEMENT ⚫ Delayed diagnosis of IDDM ⚫ The honey-moon period ⚫ Problems with diagnosis & treatment of DKA & hypoglycemia ⚫ Somogyi’s effect & dawn phenomenon may go unrecognized. Dawn Phenomenon ⚫ Blood glucose levels increase in early morning hours before breakfast due to decline in insulin levels. Which results in elevated morning glucose. ⚫ This phenomenon mainly caused by overnight growth hormone secretion and increased insulin clearance. ⚫ It’s a normal physiologic process seen in most adolescents without diabetes, who compensate with more insulin output. Child with TIDM cannot compensate. Somogyi Phenomenon ⚫ It’s a theoretical rebound from late- night or early morning hypoglycemia, thought to be from an exaggerated counter-regulatory response. ⚫ Continuous glucose monitoring systems or night time blood glucose may help clarify ambiguously elevated morning glucose levels. COMPLICATIONS OF DIABETES ⚫ Acute: DKA Hypoglycemia Hyperosmolar Coma ⚫ Late-onset:  Retinopathy  Neuropathy  Nephropathy  Ischemic heart disease & stroke Guidelines regarding monitoring for complications Parameter Recommendation HbA1c 3-4 times per year Height and Weight 3-4 times per year Nutritional At diagnosis, 4-6 weeks later counseling ,then annually. Lipid profile Prepubertal child :every 5 yr Pubertal child: within 6-12 months after diagnosis, then every 2 yrs. Blood pressure Annually after age 10 yrs. Prevention and Early detection of complication RETINOPATHY : ⚫ Screening - after 5 yr duration in prepubertal children - after 2 yr in pubertal children ⚫ Frequency- 1-2 yearly ⚫ Method preferred- fundal photography NEPHROPATHY: ⚫ Screening - after 5 yr duration in prepubertal children - after 2 yr in pubertal children ⚫ Frequency- annually ⚫ Preferred method- spot urine sample for albumin:creatinine ratio Prevention and Early detection of complication NEUROPATHY: ⚫ Screening-unclear in children ; adults at diagnosis in type 2 DM and 5yr after diagnosis in type 1DM ⚫ Frequency- unclear ⚫ Method preferred-physical examination MACROVASCULAR DISEASE: ⚫ Screening- after age 2 yrs ⚫ Frequency- every 5 yrs ⚫ Method preferred- lipid profile test Prevention and Early detection of complication THYROID DISEASE ⚫ Screening- at diagnosis ⚫ Frequency- every 2-3 yr or more frequently based on symptoms or the presence of antithyroid antibodies. ⚫ Method preferred- TSH CELIAC DISEASE: ⚫ Screening- at diagnosis ⚫ Frequency- every 2-3 yr ⚫ Method preferred- tissue transglutaminase endomysial antibody.. MANAGEMENT OF ACUTE COMPLICATIONS Diabetic Ketoacidosis ⚫ DKA,a life threatning complication of diabetes mellitus,occurs more commonly in children with type 1 DM than type 2 DM. ⚫ DKA in children is defined as hypgerglycemia(serum glucose conc. >200-300mg/dl) in the presence of metabolic acidosis (blood pH370 million people with T2DM ▶ Need to address the pathogenesis and treatment of this syndrome ▶ else, macrovascular and microvascular damages of T2DM will remain a major burden for decades to come Pathogenesis of T2DM ▶ Multifactorial etiology & complex pathophysiology Genetic predisposition Environmental factors Lifestyle choices Epigenetics Gene expression induced by lifestyle choices Natural history of T2DM Glucose (mg/dL) 350 Postmeal Glucose Prediabetes Diabetes 300 (Obesity, IFG, IGT) diagnosis 250 200 Fasting glucose 150 100 50 -15 -10 -5 0 5 10 15 20 25 30 250 Years Relative Amount 200 β-cell failure Insulin resistance 150 100 50 Insulin level 0 -15 -10 -5 0 5 10 15 20 25 30 Onset Years diabetes Macrovascular changes Microvascular changes Kendall DM, et al. Am J Med 2009;122:S37-S50. Kendall DM, et al. Am J Manag Care 2001;7(suppl):S327-S343. Classic view Incretin defect Insulin resistance β-cell failure T2DM  incretin pancreatic Gut effect carbohydrate insulin delivery & secretion peripheral absorption glucose uptake pancreatic glucagon secretion Hyperglycemia (T2DM) hepatic renal glucose glucose production excretion Defronzo RA. Diabetes. 2009 Apr;58(4):773-95 Inzucchi SE, Sherwin RS in: Cecil Medicine 2011 Which came first? Hyperinsulinemia ? Insulin resistance Pories WJ et al. Diabetes Care. 2012 Dec;35(12):2438-42 Hyperinsulinemia ? Insulin resistance Pories WJ et al. Diabetes Care. 2012 Dec;35(12):2438-42 Corkey BE. Diabetes Care. 2012 Dec;35(12):2432-37 Feedback loop between β-cells and insulin- sensitive tissues Steven E. Kahn, et al; Lancet. 2014 March 22; 383: 1068–1083 Roles of β-cell loss and α-cell dysfunction ▶ Reduction of β-cell numbers in T2DM ▶ Human pancreas is incapable of renewing ↓ function β-cells after 30yr of age ▶ Glucolipotoxicity and amyloid deposition result in β-cell apoptosis through oxidative Hyper- and endoplasmic-reticulum stress stimulation ▶ Abnormal glucagon release by α-cells ▶ elevated fasting glucagon ▶ non-suppression after meal ingestion cell loss Perl S et al. J Clin Endocrinol Metab 2010; 95: E234–39 Role of Intestines Numerous functions of GLP-1 Promotes satiety and reduces appetite Incretins GLP-1: Secreted upon the ingestion of food Bile acids Alpha cells:  Glucose-dependent postprandial glucagon secretion Liver:  Glucagon reduces Beta cells: hepatic glucose output Enhances glucose-dependent insulin secretion Stomach: Helps regulate gastric emptying Flint A, et al. J Clin Invest 1998;101:515-520. Larsson H, et al. Acta Physiol Scand 1997;160:413-422. Nauck MA, et al. Diabetologia 1996;39:1546-1553. Drucker DJ. Diabetes 1998;47:159-169. Intestinal microbiome in diabetes ▶ Gut microbiome has >100 times genetic information than human genome ▶ Gut genome + Human genome = Human metagenome Sanz Y et al. Pediatric Research (2015) 77, 236–244 Role of Brain  Sympathetic and parasympathetic NUTRIENTS LEPTIN nervous systems control glucose metabolism directly through neuronal input indirectly through circulation to affect release of insulin and glucagon and production of hepatic glucose. Vagus Hypothalamus Steven E. Kahn, et al; Lancet. 2014 March 22; 383: 1068–1083 Alzheimer’s disease (AD) ▶ Now proposed as type 3 diabetes (T3DM) ▶ Insulin resistance in brain ▶ Brain has insulin and IGF receptors ▶ There is evidence that neurons have insulin and IGF resistance in patients with AD Suzanne M. de la Monte. Eur Neuropsychopharmacol. 2014 Dec;24(12):1954-60 Role of sleep/ deprivation in diabetes Changes in diurnal patterns and quality of sleep can have important effects on metabolic processes Bass J et al. Science. 2010 Dec 3; 330(6009): 1349–1354. Role of inflammation Role of inflammation ▶ Obesity is characterised by ▶ Hypothalamic inflammation might also systemic inflammation contribute to central leptin resistance and weight gain ▶ Preclinical evidence links systemic inflammation to β-cell dysfunction ▶ CRP and its upstream regulator IL-6, are associated with insulin sensitivity and β-cell function ▶ Circulating concentrationsof IL- 1β and IL-1 receptor antagonists too are increased in T2DM Luotola K et al. J Intern Med 2011; 269: 322–32. Thaler JP et al. Endocrinology 2010;151: 4109–15. Role of environmental factors Role of environmental factors ↓ energy expenditure Obesity ↑ caloric intake β-cell Body adiposity Nutrient composition Environment dysfunction genes genes ? environmental chemicals ? microbiome T2DM Steven E. Kahn, et al; Lancet. 2014 March 22; 383: 1068–1083 Association between maternal smoking during pregnancy and overweight/obesity in offspring Thayer KA et al. Environ Health Perspect. 2012 Jun;120(6):779-89  Association between arsenic and diabetes in areas of high exposures Thayer KA et al. Environ Health Perspect. 2012 Jun;120(6):779-89 Summary Classic Insulin Relative Insulin Resistance Deficiency Hyperglycemia T2DM  incretin pancreatic Gut effect carbohydrate insulin delivery & secretion peripheral absorption glucose uptake pancreatic glucagon secretion Hyperglycemia (T2DM) hepatic renal Sleep glucose glucose Inflammation production excretion Microbiome Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011 Pathogenesis Treatment  Pathophysiology of T2DM is not like a simple bicycle with pedal-handle-wheels (IR - βCF - Glucose) It is much more complex: Thank you Thank you Questions Question 1 ▶ Which factors determine development of insulin resistance and β-cell dysfunction? A. Genes, environment and lifestyle together are important determinants B. Genetic factors alone C. Obesity alone, by triggering hyperstimulation of β-cells causing their failure D. None of the above Question 2 ▶ Example of environmentalfactors that influence development of T2DM include A. Saturated fats in diet B. Arsenic exposure C. Gut microbiome D. All of the above  Dr. Mehmet Köroğlu igugelisim gelisimedu DIABETES TYPE MELLITUS 2  INTRODUCTI ON  Type 2 diabetes is sometimes called a “life style” disease as it more common in people who don’t do enough exercise, have an unhealthy diet and obese.  Type 2 Diabetes was previously seen mainly in older adults, however it is becoming more common in young children due to obesity and overweight children. EPIDEMIOLOGY Globally 382 million people had diabetes in 2013 By 2035, this number will rise to 592 million In India 65.1 million people had diabetes in 2013 By 2035, this number will increase by 70.6% Courtesy: 2015 International Diabetes Federation Epidemiology  TYPE 2 DM  Most common type  Comprises 90 to 95% of DM cases  Most type 2 DM patients are overweight, and most are diagnosed as adults.  Approximately half of the patients are unaware of their disease  TYPE 2 DM The underlying pathophysiologic defect in type 2 DM is characterized by the following three disorders: Insulin secretary defect of the beta Increased cells production of Peripheral glucose by the resistance to liver insulin, especially in muscle cells Obesity contributes greatly to insulinresistance Insulin resistance generally decreases with weight loss  COMPONENTS OF DM-II Insulin Type 2 -cell resistance diabete dysfunction s  RISK FACTORS  NON-MODIFIABLE:  Age: 45 or more  Race : African American, Asian American, Hispanic or Latino.  Familial history : a parent, or siblings with diabetes.  RISK FACTORS  MODIFIABLE: Pre diabetes Heart and blood disease Hypertension Low HDL cholesterol and high triglycerides. Obesity Polycystic ovary syndrome Physical inactivity  CLINICAL PRESENTATION  Patients can be asymptomatic  Polyuria  Polydipsia  Polyphagia  Fatigue  Weight loss  Most patients are discovered while performing urine glucose screening PATHOPHYSIOLOGY - GENERAL Insulin is the principal hormone that regulates the uptake of glucose from the blood into cells of the body, especially liver, adipose tissue and muscle, except smooth muscle, in which insulin acts via the IGF-1 (Insulin-like growth factor - 1). Therefore, deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus.  PATHOPHYSIOLOGY  Thebody obtains glucose from three main places:  The intestinal absorption of food The breakdown of glycogen, the storage form of glucose found in the liver  Gluconeogenesis, the generation of glucose from non- carbohydrate substrates in the body. PATHOPHYSIOLOGY  Insulin plays a critical role in balancing glucose levels in the body:  It can inhibit the breakdown of glycogen or the process of gluconeogenesis.  It can stimulate the transport of glucose into fat and muscle cells.  It can stimulate the storage of glucose in the form of glycogen.  PATHOPHYSIOLOGY Insulinis released into the blood by beta cells (β-cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating.  Lower glucose levels result in decreased insulin release from the beta cells and results in the breakdown of glycogen to glucose.  This process is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin. PATHOPHYSIOLOGY  If the amount of insulin available is insufficient  If cells respond poorly to the effects of insulin  If the insulin itself is defective  Then glucose will not be absorbed properly by the body cells  The net effect is persistently high levels of blood glucose, poor protein synthesis, and break down of fat storage  Acidosis. PATHOPHYSIOLOGY  When the glucose concentration in the blood remains high over time, the kidneys will reach a threshold of reabsorption Glycosuria.  This increases the osmotic pressure of the urine polyuria increased fluid loss  Lost blood volume will be replaced osmotically from water held in body cells and other body compartments dehydration polydipsia PATHOPHYSIOLOGY - TYPE 1 Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas, leading to insulin deficiency.  This type can be further classified as immune-mediated or idiopathic.  The majority of type 1 diabetes is of the immune- mediated nature, in which a T-cell- mediated autoimmune attack leads to the loss of beta cells and thus insulin. PATHOPHYSIOLOGY - TYPE 1  Most affected people are otherwise healthy and of a healthy weight when onset occurs.  Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. oType 1 diabetes can affect children or adults, but was traditionally termed "juvenile diabetes" because a majority of these diabetes cases were in children. PATHOPHYSIOLOGY - TYPE 1 Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes.  In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors, such as a viral infection or diet. Among dietary factors, gluten may lead to type 1 diabetes, but the mechanism is not fully understood PATHOPHYSIOLOGY - TYPE 2  Type 2 DM is characterized by insulin resistance.  The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor.  In the early stage of type 2, the predominant abnormality is reduced insulin sensitivity.  Type 2 DM is due primarily to lifestyle factors and genetics. PATHOPHYSIOLOGY - TYPE 2  A number of lifestyle factors are known to be important to the development of type 2 DM, including  Obesity  lack of physical activity  poor diet  Stress  Dietary factors also influence the risk of developing type 2 DM such as  sugar-sweetened drinks  Type of fats in diet  saturated fats and trans fatty acids increasing the risk  polyunsaturated and monounsaturated fat decreasing the risk  Eating lots of white rice also may increase the risk of diabetes.  A lack of exercise is believed to cause 7% of cases  DIAGNOSIS  Fasting Plasma Glucose  Oral Glucose Tolerance Test (OGTT)  Glycoselated Hemoglobin (HbA1c)  Urinalysis Glycosuria Ketone bodies  HBA1C Measures the amount of glycated haemoglobin in blood. HbA1c is not sensitive enough to detect DM but is the gold standard for the long term monitoring.  ADDITIONAL INVESTIGATIONS;  Lipid profile  Fundoscopic examination  LFT ,  Urine analysis  ECG  Test to assess other complications  DIAGNOSTIC CRITERIA Classic signs of HYPERGLYSEMIA with CPG ≥200mg/ OGTT ≥200mg/dL Any one test should be confirmed with a second test, most often FPG ≥126mg/dL fasting plasma glucose (FPG). A1C ≥ 6.5%  “WHO” DIAGNOSTIC CRITERIA CONDITION 2 HRS GLUCOSE FASTING HbA1C GLUCOSE UNIT Mg/dl Mg/dl % Normal 250mg/dl and who have urine ketones should not begin exercise until urine tests are NEGATIVE.  Use of proper footwear.  Avoid exercise in extreme heat or cold  Have snacks after the exercise , to avoid post exercise hypoglycemia.  B. ORAL ANTI-DIABETIC AGENTS i. Biguanides ii. Insulin Secretagogues – Sulphonylureas iii. Insulin Secretagogues – Non-sulphonylureas iv.α-glucosidase inhibitors v.Thiazolidinediones (TZDs) vi. DPP4i  MAJOR CLASSES Thiazolidinediones Body to insulin +/- control hepatic Biguanides glucose production Stimulate the Sulfonylureas pancreas to make Meglitinides more insulin Slow the absorption Alpha-glucosidase of starches inhibitors Oral Anti-diabetic Agents  BIGUANIDES  Metformin : is the only drug of this class presently available in market  It does not cause hypoglycaemia  MOA : They increase glucose uptake and utilisation in skeletal muscle (thereby reducing insulin resistance) and reduce hepatic glucose production (gluconeogenesis).  Pharmacokinetic : Metformin has a half-life of about 3 hours and is excreted unchanged in the  METFORMIN  Side effects : -Dose-related gastrointestinal disturbances -lactic acidosis is a rare but potentially fatal toxic effect -Long-term use may interfere with absorption of vitamin B12  Contra indications:  Heart failure  Liver&renal problems  INSULIN SECRETAGOGUES SULFONYLUREAS : Inhibit KATP Channel of ß-cells First-generation Second- agents generation Tolbutamide Glipizide Glyburid Acetohexamid e e Glimepirid Tolazamide e  INSULIN THERAPY Short-term use: Acute illness, surgery, stress and emergencies Pregnancy Breast-feeding Insulin may be used as initial therapy in type 2 diabetes Severe metabolic decompensation (diabetic ketoacidosis, hyperosmolar nonketotic coma, lactic acidosis, severe hypertriglyceridaemia).  INSULIN THERAPY Long-term use: If targets have not been reached after optimal dose of combination therapy, consider change to multi-dose insulin therapy. INSULIN INJECTION SITES  ROUTES OF ADMINISTRATION  Subcutaneous for long term regular use  Intravenous infusion in acute conditions- diabetes Ketoacidosis, Perioperative period, Hyperosmolar Nonketotic stateONLY NEUTRAL/ CLEAR INSULIN CAN BE USED  Intraperitoneal – Peritoneal dialysis patients  Inhaled insulin- experimental  COMPLICATIONS OF INSULIN THERAPY  Hypoglycemia  Lipodystrophy  Systemic allergic reactions  Insulin resistence  Dawn phenomenon  Somagyi's phenomenon  PATIENT EDUCATION  Taking care of diabetes will help to reduce blood glucose, blood pressure, and cholesterol levels in target ranges.  Caring for your diabetes can also help prevent other health problems over the years. Follow your healthy eating plan every day. Be physically active every day. Take your medicines every day. Check your blood glucose levels every day. COMPLICATIONS OF DIABETES  COMPLICATIONS OF DIABETES MELLITUS I. Acute complications:  diabetic ketoacidosis  hypoglycemia  diabetic nonketotic hyperosmolar coma II. Chronic complications: a. b. Macrovascular Microvascular  Cerbro-vascular.  retinopathy  Cardio-vascular.  nephropat  peripheral hy vascular  neuropathy disease.  diabetic  COMPLICATIONS  All forms of diabetes increase the risk of long-term complications. These typically develop after many years (10–20)  The major long-term complications relate to damage to blood vessels.  Diabetes doubles the risk of cardiovascular disease  About 75% of deaths in diabetics are due to coronary artery disease.  Other "macrovascular" diseases (stroke)  peripheral vascular disease.  COMPLICATIONS The primary complications of diabetes due to damage in small blood vessels include damage to the eyes, kidneys, and nerves.  Damage to the eyes, known as diabetic retinopathy, is caused by damage to the blood vessels in the retina of the eye, and can result in gradual vision loss and blindness.  Damage to the kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis or kidney transplant. Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of diabetes.  HYPOGLYCEMIA  Hypoglycemia is the most frequent acute complication in diabetes.  Signs and symptoms are most common when blood glucose levels fall 300 mg/day), decrease glomerular filtration rate and rising blood pressure. About 20 – 30% of patients with diabetes develop diabetic nephropathy - Manifested as: - Microalbuminuria - Progressive diabetic nephropathy leading to end-stage renal disease  TREATMENT TO PREVENT PROGRESSION TO DN  All diabetic patients should be screened annually for microalbuminurea.  Tight glycemic control and management of the blood pressure  ACE-inhibitors are recommended to decrease the progression of nephropathy  Smoking cessation.  Proteins restriction.  Lipid reduction.  DIABETIC NEUROPATHY  Damage to the Nerves due to hyperglycemia  Types of Neuropathies… Sensory-Motor Polyneuropathy Numbness, paresthesias. Feet are mostly affected, hands are seldom affected. Complicated by ulceration (painless), charcot arthropathy Decreased deep tendon reflexes  DIABETIC NEUROPATHY Autonomic neuropathy  Can affect almost any system - Manifested by orthostatic hypotension, diabetic diarrhea, erectile dysfunction, and difficulty in urination.  RESEARCH INPUT  Effect of mechanical vibration on transcutaneous oxygen levels in the feet of type 2 diabetes mellitus patients.  Núñez Carrera L, Alessi Montero A ,et al  Journal of clinical medicine: 2016 Nov 18.  objective : To determine whether whole body vibration favors some parameters of interest related to complications associated with the diabetic foot syndrome.(Transcutaneous oxygen levels (TcPO2)>40mmHg in cases of diabetic foot syndrome are associated with a good prognosis in the resolution of ulcers.)  METHOD:54 patients with DM were included in a 12-week exercise program based on whole body vibration. Glycemic control was determined on the basis of the patients' levels of (HbA1c); sensitivity and TcPO2 levels of each foot were also recorded.  RESULTS: A significant 7mmHg increase was observed in the concentration of TcPO2.  CONCLUSION: Whole body vibration may increase TcPO2 levels with useful implications for the prevention or management of complications associated with restricted blood perfusion in the diabetic foot syndrome.  NURSING MANAGEMENT  NURSING ASSESSMENT Obtain history : it includes,  Current problems and General health history  Family history Has the patient experienced polyuria,polydipsia, polyphagia, and any other symptoms? Number of years since diagnosis of DM? Symptoms of complications?  NURSING ASSESSMENT  PHYSICAL EXAMINATION:  General: Recent wt. loss or gain, fatigue, anxiety  Skin: lesion, infections, dehydration,  Eyes: changes in vision, “floaters, halos,cataracts…  Cardiovascular: orthostatic hypotension, claudication  GI: diarrhea, increased hunger and thirst  GU: polyurea, nocturia  1. Imbalanced nutrition : more than body requirement related to intake of excess of activity expenditures. Assess the current timings and content of meals Advise patient on the importance of an individualized meal plan in meeting weight loss goals. Explain the importance of exercise in maintain / reducing body weight. Assist the patient to establish goals for weekly weight loss and incentives to assist in achieving them. Risk for injury ( hypoglycemia) related to effects of insulin, inability to eat. Closely monitor blood glucose levels to detect hypoglycemia. Instruct the patient in the importance of accuracy in insulin preparation and meal timings to avoid hypoglycemia. Treat hypoglycemia promptly with 15 to 20 gm of fast acting carbohydrates. Encourage patients to carry sugar candy all times. Encourage patient to wear identification bracelet  Deficit knowledge related to use of oral hypoglycemic agents Assess level of knowledge of disease and ability to care self. Assess adherence to diet therapy, monitoring procedures, medication, treatment, and exercise regimen. Assess for signs for hyperglycemia or hypoglycemia. Perform skin and extremity assessment for peripheral neuropathy or any injury in feet and lower extremities.  Risk for impaired skin integrity related to decreased sensation and circulation to lower extremities.  Assess feet and legs for skin temperature sensation, soft tissue injures, corn, dryness, hammer toe,  Maintain skin integrity by protecting feet from break down.  Use heel protectors, special mattresses, foot cradles for patient on bed rest.  Avoid Appling drying agent to skin. (alcohol)  Apply moisturizers to maintain suppleness and prevent cracking and fissures.  Instruct patient in foot care guidelines FOOT CARE Patient should check feet daily Wash feet daily Keep toe nails short Protect feet Always wear shoes Look inside shoes before putting them on Always wear socks Break in new shoes gradually  Ineffective coping related to chronic disease and complex self care regimen.  Discuss with the patient the perceived effect of diabetes on lifestyle, finances, family life, occupation.  Explore previous coping strategies and skills that have had positive effects.  Encourage patient and family participation in DM self care regimen  Assist family in providing emotional support.  SPECIAL PATIENT POPULATION  1. Adolescent Type 2 DM - Type 2 DM is increasing in adolescent - Lifestyle modification is essential in these patients - If lifestyle modification alone is not effective, metformin the only labeled oral agent for use in children (10-16 years) https://www.youtube.com/watch?v=OImJMiFJ 8Qo https://www.youtube.com/watch?v=OImJMiFJ 8Qo https://www.youtube.com/watch?v=jxbbBmbv u7I https://www.youtube.com/watch?v=OOhseL9j GDo https://www.youtube.com/watch?v=HJGjNTJgf 48  CONCLUSION  Type 2 diabetes is a “life style” disease, characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Caring for diabetes can also help prevent other health problems over the years.