clinical presentation and management of dm.pptx

lecture notes on clinical presentation and management of dm

1. Diabetes Mellitus

2. Introduction Diabetes mellitus is a chronic disorder characterized by the impaired metabolism of glucose & other energy-yielding fuels as well as by the late development of vascular and neuropathic complications Diabetes comprises a group of disorders involving distinct pathogenic mechanisms, for which hyperglycemia is the common denominator Regardless of its cause, the disease is associated with insulin deficiency , which may be absolute or relative in the context of coexisting insulin resistance

3.   CLASSIFICATION OF DIABETES MELLITUS Classified on the basis of the pathogenic process that leads to hyperglycemia Type 1 diabetes Autoimmune pancreatic β-cell destruction & characterized by absolute insulin deficiency Type 2 diabetes C haracterized by variable degrees of insulin resistance, impaired insulin secretion, & increased glucose production

4.  CLASSIFICATION (Cont’d) Other specific types Genetic defects of β-cell function Genetic defects in insulin action Disease of the exocrine pancreas e.g ., pancreatitis, trauma, pancreatectomy , neoplasia , cystic fibrosis, hemochromatosis Endocrinopathies e.g ., acromegaly , Cushing's syndrome, hyperthyroidism, pheochromocytoma , glucagonoma , somatostatinoma , Drug or chemical induced e.g ., pentamidine , nicotinic acid, glucocorticoids , thyroid hormone, diazoxide , β- adrenergic agonists, thiazides , phenytoin , interferon alfa Gestational diabetes mellitus

5. Epidemiology Type 2 DM far more prevalent than Type 1 DM The worldwide prevalence of DM has risen dramatically over the past two decades, from an estimated 30 million cases in 1985 to 415 million in 2017 Prevalence of type 2 DM is rising much more rapidly because of increasing obesity and reduced activity levels Prevalence & incidence of DM in Ethiopia clearly on the rise in the past few decades Between 1975 & 1979 prevalence was reported to be 1.2% (1.4% in males & 0.3% in females ) A study showed incidence of 8.9% of DM & another 8.9% of IGT among recently migrated Ethiopian Jews

6. In absence of unequivocal hyperglycemia and acute metabolic decompensation , these criteria should be confirmed by repeat testing on a different day. BUT WHY ARE THESE MAGIC NUMBERS SELECTED?

7. Pathobiology Insulin Secretion and Action Insulin is synthesized in pancreatic β cells Glucose concentration is the key regulator of insulin secretion Insulin acts on its target tissues (liver, muscle, and fat, primarily) through a specific insulin receptor Facilitates glucose uptake into cells Promotes the storage of carbohydrate and fat and protein synthesis Counter-regulatory hormones oppose the metabolic actions of insulin Include glucagon , growth hormone, cortisol , and catecholamines Tend to increase glucose concentration in the blood

8. INSULIN SECRETION 50% basal (18-32U), 50% in response to meals (no significant meal-meal diff. in amplitude) Secretion is pulsatile & repeated peaks both meal related & nonrelated(~5x after meal, 12xper day) Phases in response to stimulus(glucose): Rapid early peak, then more slowly rising peak (3 rd peak in vitro) Oscillations: Rapid: q8-15min, very small amplitude Slow: (ultradian) q80-150min, large amplitude Circadian: ↓resp. of β -cells in afternoon & evening

9. Metabolic Effects of Insulin Glucose homeostasis reflects a balance between hepatic glucose production and peripheral glucose uptake and utilization In the fasted state , low basal insulin levels result in diminished glucose uptake in peripheral insulin-sensitive tissues (e.g ., muscle and fat) Maintenance of stable blood glucose levels is achieved through the release of glucose by the liver (to a small extent kidney) by glycogenolysis and gluconeogenesis stimulated by Glucagon Fed State – Insulin released Stimulation of hepatic glucose uptake Acceleration of glucose uptake by peripheral tissues promotes the storage of carbohydrate and fat and protein synthesis Prevents large excursion of blood glucose level

10. Metabolic Defects in Diabetes Fasting Hyperglycemia R esults from an inappropriate increase in hepatic glucose production due to accelerated gluconeogenesis Insulin deficiency and unopposed effect of counter-regulatory hormones Fasting free fatty acid levels are also elevated in diabetes because of accelerated mobilization of fat store s Postprandial Hyperglycemia Impaired suppression of hepatic glucose production and the liver's ability to store glucose as glycogen Reduces the capacity of myocytes to extract and store ingested carbohydrate c and the excess glucose released from the liver.

11. Effects of severe insulin deficiency on body fuel metabolism Lack of insulin leads to Mobilization of substrates for gluconeogenesis and ketogenesis from muscle and adipose tissue, Accelerated production of glucose and ketones by the liver, and Impaired removal of endogenous and exogenous fuels by insulin-responsive tissues. The net results are severe hyperglycemia and hyperketonemia that overwhelm renal removal mechanisms

12. Pathogenesis Type 1 Diabetes Absolute deficiency of insulin results from an interplay of genetic, environmental, & autoimmune factors that selectively destroy insulin-producing β cells Genetic Factors Identical twins show concordance rates of 30 to 40 % Many of the genes linked to type 1 diabetes have not been identified HLA genes clearly play a dominant role 90 to 95% of type 1 patients express DR3 or DR4 class II HLA molecules

13. Pathogenesis - T1DM(Cont’d) Environmental Factors Diet and toxins have been proposed as triggers of diabetes Epidemics of mumps, congenital rubella, and coxsackie virus infection have been associated with an increased frequency of type 1 diabetes Autoimmune Factors About 80% of patients with new-onset type 1 diabetes have islet cell antibodies Antibodies to a variety of β-cell constituents have been identified β-Cell destruction is mediated by a variety of cytokines or by direct T-lymphocyte activity targeting specific β- cell antigens D iabetes does not become evident until a majority of beta cells are destroyed (~80%)

14. Temporal model for development of type 1 diabetes

15. Pathogenesis Type 2 DM Insulin resistance and abnormal insulin secretion( with resultant relative insulin deficiency) are central to the development of type 2 DM. H as a strong genetic component. Concordance in identical twins is between 70 and 90% Individuals with a parent with type 2 DM have an increased risk of diabetes; Both parents with type 2 DM, the risk approaches 40 % Environmental factors (such as obesity, nutrition, and physical activity) modulate genetic predisposition Obesity, particularly central , is very common in type 2 DM

16. Pathogenesis T2DM(Cont’d) Insulin Secretion Insulin levels generally appear normal or elevated, but relatively low to the degree of hyperglycemia due to β-Cell secretory defect As the disease progresses basal insulin levels eventually decline Insulin Resistance Decreased ability of insulin to act effectively on target tissues (especially muscle, liver, and fat), is a prominent feature of type 2 DM and results from a combination of genetic susceptibility and obesity Insulin resistance impairs glucose utilization by insulin-sensitive tissues and increases hepatic glucose output

17. Clinical Features Type 1 DM Classically , symptoms appear abruptly (i.e., during days or weeks) in previously healthy, non-obese children or young adults ( Onset usually below 30 yrs of age) Polyuria & polydypsia Consequence of osmotic diuresis secondary to sustained hyperglycemia. Results in a loss of glucose as well as free water and electrolytes in the urine Weight loss, despite normal or increased appetite, Blurred vision, which often develops as the lenses and retinas are exposed to hyperosmolar fluids. May also present with ketoacidosis An acute illness (infection ,physical stress etc) may speed the transition from the preclinical phase to clinical disease . “ HONEYMOON PERIOD”

18. Clinical Features (Cont’d) Type 2 Diabetes Insidious onset of hyperglycemia and thus relatively asymptomatic initially Presence of obesity or a strongly positive family history of diabetes suggests type 2 diabetes Diabetes may be detected only after glycosuria or hyperglycemia is noted during routine laboratory studies Chronic skin infections & generalized pruritus and symptoms of vaginitis are frequent initial complaints of women with type 2 diabetes Due to long standing(usually decades) asymptomatic hyperglycemia most patients present with features of chronic complications

19. Diagnosis Classic symptoms of polyuria , polydipsia , and unexplained weight loss and, a random (or “casual”) plasma glucose measurement of 200 mg/ dL or more An 8-hour (overnight) fasting plasma glucose measurement is most convenient; Diabetes is established if fasting glucose levels are 126 mg/ dL or higher on two separate occasions Alternatively, a 75-g oral glucose tolerance test (OGTT) may be employed Performed after an overnight fast, With use of a glucose load containing 75 g of anhydrous glucose dissolved in water; 2-hour post load glucose levels of 200 mg/ dL or higher confirm the presence of diabetes

20. Diagnosis(Cont’d) Diagnosis of Prediabetes . Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) refer to intermediate states between normal glucose tolerance and DM type 2. IFG and IGT (designated as Prediabetes ) are risk factors for development of type 2 diabetes and micro- and macrovascular complications . IGT - defined by a 2-hour OGTT, plasma glucose from 140 to 199 mg/ dL . IFG - defined by fasting plasma glucose of 100 to 125 mg/ dL .

21. Diagnosis(Cont’d) Screening Widespread use of the FPG or HbA 1c as a screening test for type 2 DM is recommended because: L arge number of individuals who meet the current criteria for DM are asymptomatic and unaware that they have the disorder, T ype 2 DM may be present for up to a decade before diagnosis, A s many as 50% of individuals with type 2 DM have one or more diabetes-specific complications at the time of their diagnosis, and Treatment of type 2 DM may favorably alter the natural history of DM ADA recommends screening all individuals >45 years every 3 years and screening individuals at an earlier age if they have risk factors.

22. ACUTE COMPLICATIONS OF DM ( DDx of coma in diabetic patients) Hyperglycemic States Diabetic Ketoacidosis (DKA) Hyperosmolar Hyperglycemic State (HHS) Hypoglycemia

23. ACUTE COMPLICATIONS OF DM Hyperglycemic States Generally classified into two broad clinical syndromes, D iabetic K etoacidosis (DKA ) & H yperosmolar H yperglycemic S yndrome ( HHS) DKA is generally seen in type 1 patients, whereas the HHS affects patients with type 2 diabetes lines of distinction are commonly blurred. HHS can present with variable degrees of ketosis and acidosis, and DKA is being seen with increasing frequency in obese type 2 patients Despite aggressive treatment, mortality rates remain high for both conditions, approaching 5% for DKA and 15% for the HHS.

24. Diabetic Ketoacidosis Three cardinal biochemical features of DKA— hyperglycemia , ketosis , and acidosis — Result from the combined effects of absolute deficiency of insulin and the excessive secretion of counter-regulatory hormones Hormonal imbalances ( decreased ratio of insulin to glucagon ) mobilize the delivery of substrates from muscle (amino acids, lactate, pyruvate ) and adipose tissue (free fatty acids, glycerol) to the liver, Where they are actively converted to glucose or to ketone bodies ( β- hydroxybutyrate , acetoacetate , acetone ) DKA may herald the onset of type 1 diabetes but most often occurs in established diabetic patients as a result of intercurrent illness

25. PRECIPITANTS OF DKA & HHS

26. DKA :Clinical Manifestations Typically involves deterioration during several days, with advancing polyuria , polydipsia , and other symptoms of hyperglycemia Other common features are weakness, lethargy, nausea and anorexia Abdominal pain in the setting of DKA is classically periumbilical and can mimic an acute abdomen Physical findings in DKA are mainly secondary to dehydration and acidosis; Dry skin and mucous membranes, reduced jugular venous pressure, tachycardia, orthostatic hypotension, depressed mental function, and Kussmaul (deep, rapid) respirations Ketosis may be recognizable by a sweet, sickly smell on the patient's breath .

27. Manifestations of DKA

28. DKA: Diagnosis Timely diagnosis of DKA is crucial and allows for prompt initiation of therapy Initial laboratory tests to be performed include routine serum chemistries (RFT , Elecrolytes ), CBC with differential, and urinalysis Diagnosis is based on the demonstration of moderate or severe hyperglycemia , ketonemia , and wide anion gap metabolic acidosis . Urine ketone reaction correlates poorly with ketonemia but is usually positive in DKA Focused search for a precipitating infection is always prudent Hyponatremia , hyperkalemia (despite a total-body potassium deficit), azotemia , and hyperosmolality are other findings

29. DKA: Management Preferably be conducted in an ICU IV access & supportive measures should be instituted without delay Fluid deficits of several liters are common and the average degree of dehydration is approximately 7-9% of body weight Initial restoration of circulating volume using isotonic (0.9%) saline 1 st liter should be infused rapidly and should be followed by additional fluids at a rate of 1 L/hr until the volume deficit is corrected Next goal is to replenish total body water deficits; Accomplished using a 0.45% saline infusion at 150- 300 mL /hr if the corrected serum sodium is normal or elevated; 0.9% NaCl at a similar rate is appropriate if corrected serum sodium is low

30. DKA: Management( Con’d ) Insulin Therapy : Sufficient insulin must be administered to turn off ketogenesis and correct hyperglycemia. IV bolus of regular insulin , 10 - 15 units (0.15 unit/kg) administered ,followed by a continuous infusion of regular insulin at rate of 5 - 10 units/hr A decrease in blood glucose of 50 - 75 mg/ dL /hr is an appropriate response Once oral intake resumes, insulin can be administered SC prudent to give the first SC injection of insulin approximately 30 minutes before stopping the IV route Dextrose (5%) should be infused once plasma glucose decreases to 250 mg/ dL and the insulin infusion rate should be decreased to 0.05 units/kg/hr to prevent dangerous hypoglycemia

31. DKA: Management( Con’d ) Potassium deficit should always be assumed or anticipated, regardless of plasma levels on admission. Insulin therapy results in a rapid shift of potassium into the intracellular compartment Potassium should be added routinely to the IV fluids at a rate of 10 -20 mEq /hr except in pts with hyperkalemia , renal failure, or oliguria Patients with hypokalemia should receive higher doses of potassium, 40 mEq /hr or greater Monitoring of therapy Measure capillary glucose every 1–2 h; measure electrolytes (especially K + , bicarbonate, phosphate) and anion gap every 4 h for first 24 h. Monitor blood pressure, pulse, respirations, mental status, fluid intake and output every 1–4 h.

32. DKA: Management(Cont’d) Bicarbonate therapy is not routinely necessary and may be deleterious in certain situations Should only be considered in pts with shock or coma, severe acidosis (pH 6.9 -7.1), plasma bicarbonate <5 mEq /L ,severe hyperkalemia IV antimicrobial therapy should be started promptly for documented bacterial, fungal, and other treatable infections. Complications of DKA include -Lactic acidosis, Arterial thrombosis , Cerebral edema , Rebound ketoacidosis

33. Hyperglycemic Hyperosmolar State(HHS) Occurs primarily in patients with type 2 DM Significantly less common than DKA but with a graver prognosis Pathophysiology Hallmarks of the HHS are severe hyperosmolarity (>320 mOsm /L) and hyperglycemia (>600 mg/ dL ) Hyperglycemia induces an osmotic diuresis that leads to intravascular volume depletion, which is exacerbated by inadequate fluid replacement. Insulin levels remain sufficient to suppress lipolysis and to avoid significant keto acid production Severely depressed endogenous insulin secretion may be unable to suppress ketone production fully

34. HHS:Clinical Features Elderly individual with type 2 DM, with a several week history of polyuria , weight loss, and diminished oral intake that culminates in mental confusion, lethargy, or coma Profound dehydration and hyperosmolality and reveals hypotension, tachycardia, and altered mental status Nausea, vomiting, and abdominal pain and Kussmaul respiration characteristic of DKA are notably absent Often precipitated by a serious, concurrent illness such as myocardial infarction or stroke, sepsis, pneumonia, and other serious infections

35. HHS(Cont’d) Laboratory Findings include hyperglycemia, often >600 mg/ dL ; plasma osmolality >320 mOsm /L; absence of ketonemia ; and pH >7.3 and serum bicarbonate >20 mEq /L. Prerenal azotemia and lactic acidosis can develo p Management The goals of therapy are: Restoration of hemodynamic stability and intravascular volume by fluid replacement Correction of electrolyte abnormalities Gradual correction of hyperglycemia and hyperosmolarity with fluid replacement and insulin therapy Detection and treatment of underlying disease states and precipitating causes.

36. HHS(Cont’d) Treatment Restoring hemodynamic stability is the first aim. Restoration of intravascular volume should be followed by correction of total body water deficit Patients with HHS may require as much as 10 -12 L positive fluid balance over 24 - 36 hours to restore total deficits Despite initial normal or high serum potassium ,rehydration and insulin therapy usually result in hypokalemia , and should be corrected. Insulin therapy plays a secondary role in the initial management of HHS Administered in similar fashion as in mgt of DKA

37. Hypoglycemia Hypoglycemia is the most frequent complication resulting from insulin therapy May also occur in patients who take oral sulfonylureas , esp. older patients or those with impaired liver or kidney function May result from delay in taking a meal or from unusual physical exertion without supplemental calories or a decrease in insulin dose. Clinical Features Symptoms of hypoglycemia can be divided into A utonomic ( adrenergic : palpitations, tremor , and anxiety; cholinergic : sweating, hunger, and paresthesia ) and N euroglycopenic ( behavioral changes, confusion, fatigue, seizure, loss of consciousness,and , if hypoglycemia is severe and prolonged, death).

38. Hypoglycemia (Cont’d) Recurrent episodes of hypoglycemia impair recognition of hypoglycemic symptoms, ( hypoglycemia un-awareness ) Increasing the risk for severe hypoglycemia . Hypoglycemia unawareness results from defective glucose counterregulation with blunting of autonomic symptoms and counterregulatory hormone secretion during hypoglycemia

39. Hypoglycemia (Cont’d) Diagnosis of Hypoglycemia is most convincingly documented by Whipple's triad: Symptoms consistent with hypoglycemia , A low plasma glucose concentration and Relief of those symptoms after the plasma glucose level is raised. The lower limit of the fasting plasma glucose concentration is normally approximately 70 mg/ dL Should be considered in any patient with episodes of confusion, an altered level of consciousness, or a seizure.

40. Hypoglycemia (Cont’d) Treatment Easily correctable if treated promply but fatal if prolonged Any comatose diabetic pt should first be considered to be hypoglycemic unless proven otherwise Readily absorbable carbohydrates (e.g., glucose and sugar-containing beverages) can be administered orally to conscious patients for rapid effect IV dextrose is indicated for severe hypoglycemia , in patients with altered consciousness, and during restriction of oral intake initial bolus, 20 - 50 mL of 50% dextrose, should be given immediately, followed by infusion of D 5 W (or D 10 W) to maintain blood glucose above 100 mg/d Glucagon, 1 mg IM (or SC), is an effective initial therapy for severe hypoglycemia

41. CHRONIC DIABETIC COMPLICATIONS Chronic complications of DM affect many organ systems and are responsible for the majority of morbidity and mortality associated with the disease Commonly seen after decades of hyperglycemia Pathogenesis of chronic complications of diabetes is complex and poorly understood Microvascular complications of diabetes may affect patients with type 1 or type 2 diabetes Macrovascular complications, which are particularly common in type 2 diabetes Progressively occur over years and decades after onset of hyperglycemia Treatment of chronic complication is usually unsatisfactory thus the best strategy is prevention through strict control of glycemia ( esp for microvascular complications)

42. Chronic Complications of DM

43. Diabetic Retinopathy Refers to progressive pathologic alterations in the retinal microvasculature , leading to areas of retinal nonperfusion , increased vascular permeability, and the pathologic proliferation of retinal vessels One of the leading causes of blindness in adults Types N on-proliferative (background) Generally no symptoms but may affect macula and impair vision Microaneurysms , hard exudates, dot and blot hemorrhages P re-proliferative 10-40% progress to proliferative within one year Macular edema , venous shunts and beading, nerve fibre layer microinfarcts (cotton wool spots) Proliferative Great risk for loss of vision Neovascularization , fibrous scarring, vitreal detachment, retinal detachment

44. microaneurysms hard exudates blot hemorrhages Neovascularization Cotton wool spots

45. Diabetic Retinopathy(Cont’d) Prevention and management Tight glycemic control Photocoagulation (eliminates neovascularization ) Vitrectomy Frequent follow-up visits with an ophthalmologist (immediate referral after diagnosis of type 2 DM; after 5 years of type 1DM)

46. Diabetic Nephropathy One of the leading cause of end-stage renal disease (ESRD). 25-45% of pts with type 1 DM develop clinically evident diabetic nephropathy during their lifetime less frequent in type 2 diabetics Natural history of diabetic nephropathy in type 1 diabetes is well described ,less clear inT2DM

47. Diabetic Nephropathy(Cont’d) Diagnosis Screening for microalbuminuria is mandatory patients with nephropathy are often asymptomatic number of effective intervention strategies can slow disease progression. Measurement of the albumin-to- creatinine ratio (normal, <30 mg albumin/g cr ) in a random urine sample is recommended for screening At least 2 – 3 measurements within a 6-month period should be performed to establish the diagnosis

48. Diabetic Nephropathy(Cont’d) Prevention and Treatment Intensive control of diabetes and hypertension is an effective intervention for incipient or established diabetic nephropathy Type 1 and type 2 patients with or without hypertension and micro- albuminuria , ACE inhibitors delay the progression of nephropathy Type 2 patients with hypertension, creatinine >1.5 mg/ dL , and macroalbuminuria , angiotensin II receptor blockers (ARBs ) delay progression of nephropathy

49. Diabetic neuropathy Sensorimotor diabetic peripheral polyneuropathy is a major risk factor for foot trauma, ulceration, and Charcot arthropathy , Responsible for 50 - 75% of nontraumatic amputations . Types

50. Diabetic neuropathy(Cont’d) Presentation Paresthesias or neuropathic pain Motor or sensory deficits (including cranial nerves) Orthostatic hypotension Impotence Voiding difficulties Foot ulcers Prevention and management Tight glucose control anti-depressants (e.g. amitriptyline ), capsaicin, and anti-epileptics (e.g . Tegretol , Neurontin ) for painful neuropathic syndromes Erythromycin and metcloromide for gastroparesis Foot care education

51. Diabetic Foot Ulcers S lowly healing plantar ulcers that result from apparently insignificant trauma Left untreated, superficial ulcers may penetrate to underlying tissues, leading to complications including cellulitis , abscess formation, joint sepsis, and osteomyelitis Gangrene may occur, and amputation may be required in severe cases . Risk factors include long-standing diabetes, poor glycemic control, and concurrent diabetic complications. To varying degrees, the diabetic foot is characterized by the combination of chronic sensorimotor neuropathy, vascular disease, autonomic neuropathy, and impaired immune function Once an ulcer has formed, it should be treated aggressively with antibiotics, appropriate local wound care, and debridement of necrotic tissue

52. Pathway to Ulceration Results from an interaction of a number of component causes Diabetic Neuropathy(80% of pts) 7% annual risk of ulceration Sensory, motor, and autonomic Decrease pain sensation and perception of pressure, Ms imbalance leading to deformities Hammer toes ,Claw toes Prominent metatarsal heads ; Reduced sweating, dry skin, and development of cracks and fissures Peripheral Vascular Disease Increased incidence by 2-4fold Promotes development of critical limb ischemia, poor wound healing and tissue loss

53. Site of foot ulcers: Toes: 51% Plantar metatarsal head: 28% Dorsum of foot: 14% Multiple ulcers: 7%

54. FOOT CARE PRESCRIPTION FOR DIABETIC PATIENTS WITH LOWER EXTREMITY SENSORY NEUROPATHY

55. Management Of Diabetic Foot Ulcers Diabetic foot ulcer heals if Arterial inflow is adequate. Infection is treated appropriately Pressure is removed from the wound and the immediate surrounding area Six interventions with demonstrated efficacy in diabetic foot wounds: Off-loading, Debridement, Wound dressings, Appropriate use of antibiotics, Revascularization, and Limited amputation

56. Principles of Management of DM Therapeutic goals are alleviation of symptoms, achievement of metabolic control , and prevention of acute and long-term complications of diabetes Patient education is integral to successful management of diabetes Dietary modification Total caloric intake can be distributed as follows: 45 - 65% of as carbohydrates, 10 - 30% as protein, and <30% as total fat (<7% saturated fat) with <300 mg/d of cholesterol Exercise improves insulin sensitivity, reduces fasting and postprandial blood glucose, and offers numerous metabolic, cardiovascular, and psychological benefits in diabetic patients.

57. Management of DM:T1DM Treatment of type 1 DM requires lifelong insulin replacement . Initial insulin dosage for optimal glycemic control is approximately 0.5 - 1.0 units/ kg/d

58. Management of DM:T1DM(Cont’d) Regimen of multiple daily insulin injections is preferred to obtain optimal control . Provides approximately 40 - 50% of the total daily dose of insulin as basal insulin supply , using one or two injections of long-acting or intermediate-acting insulin Remainder is given as three doses of rapid-acting insulin divided across the main meals Typically 1 unit of insulin per 10 - 15 g of carbohydrate consumed is typical The conventional insulin regimen uses a mixture of short- and intermediate-acting insulins administered before breakfast and before the evening meal two-thirds of the total daily dose is injected in the morning and one-third in the evening. Approximately two-thirds of each injection comprises intermediate-acting insulin and one-third is rapid-acting insulin Insulin administration by insulin infusion pump with the basal insulin and a bolus injection at each meal.

59. Management of DM:T2DM Oral therapy should be initiated early in patients with T2DM that failed glycemic control after a short-term trial of diet and exercise Monotherapy with maximum doses of insulin secretagogues , metformin , or thiazol-idinediones yields comparable glucose-lowering effects Second or third agent including insulin should be added if no response is achieved with monotherapy Insulin therapy in type 2 DM is indicated in: Patients in whom oral agents failed to sustain glycemic control DKA Nonketotic hyperosmolar crisis Newly diagnosed patients with severe hyperglycemia Pregnancy and other situations in which oral agents are contraindicated

60. Management of DM:T2DM(Cont’d)