Diabetes Mellitus PDF

Definition Of The Disease Diabetes mellitus (DM) is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia, polyphagia, and polyuria. Later complications include vascular disease,...

Definition Of The Disease Diabetes mellitus (DM) is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia, polyphagia, and polyuria. Later complications include vascular disease, peripheral neuropathy, and predisposition to infection. Diagnosis is by measuring plasma glucose. Treatment is diet, exercise, and drugs that reduce glucose levels, including insulin and oral antihyperglycemic drugs. Prognosis varies with degree of glucose control. 1 www.tulln.lknoe.at  Insulin – The Key To Diabetes Insulin is synthesized in the pancreas within the β-cells of the islets of Langerhans. One to three million pancreatic islets form the endocrine part of the pancreasThe endocrine portion of the organ accounts for only 2% of the total mass of the pancreas. The B-cells in the islets of release insulin in two phases: The first release is rapidly triggered in response to increased blood glucose levels. The second phase is a sustained, slow release independently of sugar. When the glucose level comes down to the usual physiologic value, insulin release from the β-cells slows or stops. stimulation of glucose uptake is concerned: muscle cells and fat cells. The former are important because of their central role in movement, breathing, circulation, etc., and the latter because they accumulate excess food energy against future needs. Together, they account for about two-thirds of all cells in a typical human body. 2 www.tulln.lknoe.at  Insulin- It´s Mode Of Action Insulin binds to its receptor (1), which starts many protein activation cascades (2). These include translocation and influx of glucose through the plasma membrane (3), glycogen ( storage form of glucose )synthesis (4), glycolysis (5) and fatty acid synthesis (6), i.e. increased lipid synthesis. 3 www.tulln.lknoe.at The Circadian Rhythm Of Insulin 4 www.tulln.lknoe.at  The “Diabetic Diseases“ In Type 1 DM (previously called juvenile-onset or insulin-dependent),insulin production is absentbecause of autoimmune pancreatic β-cell destruction possibly triggered by an environmental exposure in genetically susceptible people. Destruction progresses subclinically over months or years until β-cell mass decreases to the point that insulin concentrations are no longer adequate to control plasma glucose levels. Type 1 DM generally develops in childhood or adolescence and until recently was the most common form diagnosed before age 30; however, it can also develop in adults. In Type 2 DM (previously called adult-onset or non–insulin-dependent), insulin secretion is inadequate. Often insulin levels are very high, especially early in the disease, but peripheral insulin resistance and increased hepatic production of glucose make insulin levels inadequate to normalize plasma glucose levels. Insulin production then falls, further exacerbating hyperglycemia. The disease generally develops in adults and becomes more common with age. Over 90% of adults with DM have type 2 disease. Type 2 DM is becoming increasingly common among children as childhood obesity has become epidemic: 40 to 50% of new-onset DM in children is now type 2. Obesity and weight gain are important determinants of insulin resistance in type 2 DM. 5 www.tulln.lknoe.at  General Characteristics of Types 1 and 2 DM Onset most commonly < 30 Most commonly onset > 30 yr yr Obesitiy very common No obesity Plasma insulin level may be low, normal or elevated, Extremely low or depending on insulin resistance undetectable plasma insulin vs. decreased secretion Island cell antibodies No antibodies against islet cells detectable Islets smaller, but appearing Loss of most beta-cells normal Complications of DM very Complications of DM very likely likely Response to oral drugs, at least No reponse to oral in the beginning. antidiabetic medication 6 www.tulln.lknoe.at  Diagnostic Criteria for Diabetes Mellitus and Impaired Glucose Regulation Test Normal Impaired Glucose Diabetes Regulation FPG < 100 (< 100– 125 (5.6 – 6.9) ≥ 126 (≥ 5.6) 7.0) OGTT < 140 (< 140– 199 (7.7 – 11.0) ≥ 200 (≥ 7.7) 11.1) FPG = fasting plasma glucose; OGTT = oral glucose tolerance test, 2-h glucose level. Note: All values refer to glucose levels in mg/dL (mmol/L) 7 www.tulln.lknoe.at  Treatment Options Treatment Goals Diet and exercise Blood glucose between 80 and 120 mg/dL (4.4 For type 1 DM, insulin and 6.7 mmol/L) during For type 2 DM, oral the day antihyperglycemics, Blood glucose between insulin 100 and 140 mg/dL (5.6 or both and 7.8 mmol/L) at Often ACE inhibitors, bedtime statins, and aspirin HbA1c levels < 7% *) to prevent complications *) Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non- enzymatic glycation pathway by hemoglobin's exposure to plasma glucose. 8 www.tulln.lknoe.at Oral anti-diabetic drugs Insulin Treatment enhance pancreatic All patients with type 1 DM require insulin. insulin secretion Insulin is indicated as initial therapy for women with type 2 sensitize peripheral patients who present with tissues to insulin acute metabolic impair GI absorption of Patients with type 2 DM should glucose be prescribed oral lifestyle changes are insufficient, additional oral therapy), and insulin,when ≥ 2 drugs are ineffective for 9 www.tulln.lknoe.at  Oral Anti-Diabetics and their Mechanisms of Action Sulfonylureas (SUs) are insulin secretagogues. They lower plasma glucose by stimulating pancreatic β-cell insulin secretion and may secondarily improve peripheral and hepatic insulin sensitivity by reducing glucose toxicity. Biguanides lower plasma glucose by decreasing hepatic glucose production (gluconeogenesis and glycogenolysis). They are considered Biguanides also lower lipid levels ,decrease GI nutrient absorption, and increase β-cell sensitivity to circulating glucose. Thiazolidinediones (TZDs) decrease peripheral insulin resistance (insulin sensitizers), but their specific mechanisms of action are not well have anti-inflammatory and anti-atherosclerotic effects. TZDs are effective in reducing HbA1c. α-Glucosidase inhibitors (AGIs) competitively inhibit intestinal enzymes that hydrolyze dietary carbohydrates; carbohydrates are digested and Dipeptidyl peptidase-4 inhibitors block glucagon, the most efficient antagonist to insulin. 10 www.tulln.lknoe.at Microvascular disease underlies the 3 Macrovascular disease: Large-vessel most common and devastating atherosclerosis is a result of the manifestations of DM: hyperinsulinemia, dyslipidemias, and hyperglycemia characteristic of DM. Manifestations are Retinopathy Angina pectoris and MI Nephropathy Transient ischemic attacks and strokes Neuropathy Peripheral arterial disease Diabetic neuropathy is the result of nerve ischemia due to microvascular disease, direct effects of hyperglycemia on neurons, and intracellular metabolic changes that impair nerve function. 11 www.tulln.lknoe.at In the early stage of diabetic retinopathy called Non Proliferative Diabetic Retinopathy (NPDR), Diabetes causes the blood vessels in the retina to leak and form deposits called exudates. These leaky blood vessels create a complication called Macular Edema or retinal swelling, and are the most common cause of vision loss in diabetics. In Proliferative Diabetic Retinopathy (PDR), the abnormal vessels of neovascularization are quite fragile and if not treated aggressively will often lead to a severe loss of vision due to vitreous hemorrhaging, scar tissue formation, and finally retinal 12 detachment.. www.tulln.lknoe.at  13 www.tulln.lknoe.at If actual leaking Photocoagulation is used to seal the retina and vessels are identified, stop the abnormal vessels from growing and these leaking vessels leaking. Hundreds of tiny spots are placed in the can be treated by retina to reduce the risk of vitreous hemorrhage sealing them with and retinal detachment. The eye laser treatment Laser Photocoagulati is used to destroy all of the dead areas of the on Treatment to retina where blood vessels have been closed. further resolve the When these areas go through eye laser swelling and prevent treatment, the retina stops making new blood further vision loss. vessels. 14 www.tulln.lknoe.at  Diabetic Neuropathy I Diabetic neuropathy is characterized by progressive loss of nerve fibers. The exact pathophysiologic mechanism is incompletely understood, but is most likely the combined result of oxidative stress, excessive neuronal intracellular glucose, and a disturbed cellular metabolism leading tomicrovascular injury. Diabetic neuropathy affects the peripheral nerves (left image), in a stocking- and-glove distribution, and the autonomic neurons (right image), within the gastrointestinal tract, bladder, and blood vessels. Patients with autonomic neuropathy may suffer from hypotension, gastroparesis, diarrhea, urinary incontinence, or urinary retention. 15 www.tulln.lknoe.at  Diabetic Neuropathy II Diabetic peripheral neuropathy causes sensorial A monofilament and motor symptoms. Sensorial symptoms esthesiometer is touched include loss of vibration sense, temperature to specific sites on each sense, proprioception, and reflexes as well as foot and is pushed until it numbness and painful paresthesias. Because bends. This test provides patients cannot feel their extremities, they are at a constant, reproducible risk of developing unrecognized injuries, light-touch stimulus, which fractures, and infections that can lead to severe can be used to monitor ulcers or gangrene. Loss of motor function causes change in sensation over weakness and contractures. The long nerves are time. Both feet are tested, affected first because of the disproportionate and presence (+) or delay in nerve conduction. absence (−) of sensation at each site is recorded 16 www.tulln.lknoe.at  Diabetic Neuropathy And Osteoarthropathy Neuropathic osteoarthropathy, also known as a Charcot joint, is a late complication of diabetic neuropathy. As patients lose sensation, progressive degeneration of weight-bearing joints occurs, leading to bony destruction, bone resorption, and deformity. The process is believed to be the result of the loss of proprioception and deep sensation causing recurrent trauma. Disease progression may be insidious and patients present with unsalvageable destruction. 17 www.tulln.lknoe.at  18 www.tulln.lknoe.at Nephropathy Is Glomerulopathy 19 www.tulln.lknoe.at Nephropathy Is Glomerulopathy 20 www.tulln.lknoe.at  21 www.tulln.lknoe.at Blood Purification Techniques 22 www.tulln.lknoe.at Hemodialysis 23 www.tulln.lknoe.at  Pathways Of Hemodialysis Dialysis Catheters: Pros: immediately usable, no need to puncture the skin to start the dialysis Cons: difficult to maintain without infection, when infected requires complete removal and prolonged antibiotics, frequent malfunctioning requiring further procedures, cannot shower/swim with the catheter, the catheter may cause damage to the veins over the long-term. AV Grafts: Pros: shorter time required for “maturation”, usually requires only one operation Cons: does not last as long, more prone to infections, when infected requires complete removal and prolonged antibiotics, may require declottings and other secondary procedures over the course of its usable life. AV Fistulas: Pros: best long term patency, lowest rate of infection, no foreign material used Cons: requires a longer “maturation” time (6 weeks or more), may require more than one operations to create a functional dialysis fistula 24 www.tulln.lknoe.at Pathways Of Hemodialysis 25 www.tulln.lknoe.at Peritoneal Dialysis 26 www.tulln.lknoe.at Diabetics Account For One Out Of Five Kidney Transplantations 27 www.tulln.lknoe.at Kidney Transplantation For Diabetic Nephropathy 28 www.tulln.lknoe.at Pancreas Transplantation For Diabetes 29 www.tulln.lknoe.at SKPT – Simultaneous Kidney & Pancreas Transplantation 30 www.tulln.lknoe.at Duration of Graft Survival After Kidney Transplantation LD……..Living Donors CD……..Cadaver Donors SKPT….Simultaneous Kidney Pancreas Transplantation 31 www.tulln.lknoe.at  What´s Obesity? To be considered for weight-loss surgery, you must meet the following qualifications: A body mass index (BMI) of 40 or higher (20 to 25 is considered normal). BMI is a calculated by dividing your weight in kilograms by height in meters squared. A body mass index (BMI) between 35 and 40 and have an obesity-related condition such as cardiovascular disease, diabetes mellitus, hypertension or severe sleep apnea. 32 www.tulln.lknoe.at Surgical Procedures for Morbid Obesity 33 Gastric Banding Gastric Bypass www.tulln.lknoe.at Laparoscopic Surgery For Morbid Obesity 34 www.tulln.lknoe.at Obesity Surgery- Rationale & Results 35 www.tulln.lknoe.at  36 www.tulln.lknoe.at