Diabetes Mellitus Part II - Diabetes will be used interchangeably with diabetes mellitus (DM) Diabetes actually means excessive excretion of urine DM refers to the disorder of carbohydrate, fat and protein metabolism with absolute or relative insulin deficiency Complications - - - The complications of diabetes can be broken down into acute and chronic complications o Acute complications include hypoglycemia and hyperglycemic states of diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic syndrome o Chronic complications can be further broken down into the: Microvascular complications of retinopathy, neuropathy and nephropathy Macrovascular complications of cerebrovascular disease, peripheral vascular disease and coronary artery disease Other - infections Triggers or underlying etiology of acute complications often includes concurrent illness and factors related to the management of plasma glucose levels including noncompliance with diet or pharmacology therapy or side effects of pharmacological therapy Chronic hyperglycemia and the resultant metabolic events have been associated with the underlying etiology of chronic complications of diabetes o Hyperglycemia affects cells that do not effectively reduce the transport of glucose into the cell in a hyperglycemic state, resulting in intracellular hyperglycemia. 1 o Examples of cells that are vulnerable to chronic hyperglycemia include: capillary endothelial cells in the retina, mesangial cells in the renal glomerulus and neurons and Schwann cells in the peripheral nerves o There are several theories that are well documented and describe the metabolic mechanisms that are associated with the tissue-damaging effects of chronic hyperglycemia and the resultant diabetic complications Questions – Acute diabetic complications - - 1. What is the normal plasma glucose level? o This question is not as straightforward as it may first seem. Plasma glucose varies based on last meal. That being said the homeostatic mechanisms of the body generally maintain glucose at a level < 6.0 mmol/L 2. What source of energy does the brain rely on solely? o The answer is glucose. Take a minute to think about what may be some of the clinical manifestations of hypoglycemia considering that the brain relies solely on glucose as a source of energy Hypoglycemia - Hypoglycemia is defined by o The development of neurogenic/autonomic and/or neuroglycopenic symptoms. Activation of the SNS results in the neurogenic or autonomic symptoms of trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Abrupt cessation of glucose delivery to the brain results in neuroglycopenic symptoms of difficulty concentrating, confusion, weakness, drowsiness, vision changes, difficulty speaking, headache and dizziness. Symptoms are variable among individuals, especially in children and the elderly; however are usually consistent for each person o Below than normal blood glucose (BG) levels. Generally hypoglycemia occurs when BG levels are between 2.5 – 3.3 mmol/L. In diabetic patients treated with insulin or an insulin secretagogue, BG levels < 4 mmol/L are considered hypoglycemia o Symptoms respond to the administration of carbohydrate Hypoglycemia may be caused by exogenous, endogenous or functional mechanisms In diabetic patients, the exogenous mechanism of drug induced hypoglycemia is most common. The negative social and emotional impact may make patients reluctant to intensify pharmacological therapy. Furthermore, there are short and long term risks of hypoglycemia. Short-term risks are safety related. For example, it would be unsafe if an individual experienced a hypoglycemia while driving 2 - or operating machinery. Prolonged coma can be associated with transient neurological symptoms, like paresis, convulsions and encephalopathy. Long term risks of severe hypoglycemia are mild intellectual impairment and very rarely permanent neurologic sequelae like hemiparesis and pontine dysfunction Severity of hypoglycemia is divided into mild, moderate and severe o Mild: autonomic symptoms, able to self-treat o Moderate: autonomic and neuroglycopenic symptoms, and individuals are able to self- treat o Severe: individuals are unable to self-treat, they require assistance, unconsciousness may occur. BG usually < 2.8 mmol/L Hypoglycemia - Etiology, Risk, Pathophysiology - - - Etiology in diabetes o The cause of hypoglycemia in diabetes is 2-fold: o 1st, relative excess of insulin in the blood which can be the result of too much exogenous insulin or when insulin secretagogues like sulfonylureas are used. Hypoglycemia is more common in type 1 diabetes and occurs in more than 90% of type 1 diabetics and often limits the management of the disease. Hypoglycemia can also occur in type 2 diabetics, particularly in those taking insulin secretagogues or using exogenous insulin o 2nd, the cause of hypoglycemia can also be linked to deficits in glucose counterregulation. This second point is particularly important in type 1 diabetes. Specifically, glucagon and epinephrine release during hypoglycemia become defective, which blunts the otherwise autonomic symptoms associated with mild or moderate hypoglycemia and puts these patients at risk of developing severe hypoglycemia Some risk factors for hypoglycemia include; exercise, alcohol, older age, renal dysfunction, infection, error in insulin dose, medication changes, cognitive dysfunction, mental health issues o Specific risk factors for severe hypoglycermia in type 1 diabetics include prior episode of severe hypoglycemia, current low hemoglobin A1C of < 6%, hypoglycemia unawareness, long duration of diabetes, autonomic neuropathy, low economic status, adolescence, pre-school children who are unable to detect and/or treat mild hypoglycemia on their own The pathophysiology of hypoglycemia is triggered by the relative excess of insulin causing a decrease in blood sugar. A decrease in endogenous insulin secretion is the first line of defense against hypoglycemia. This is critical in patients who have residual insulin secretion. Normally, beta cells suppress insulin secretion at a plasma glucose level of about 4.6 mmol/L 3 o Hypoglycemia activates the SNS via the hypothalamus, resulting in the stimulation of the adrenal gland to release counterregulatory hormones. You should now be thinking about the stress response specifically the hypothalamicpituitary-adrenal axis. o The role of the liver in sympathoadrenal response to hypoglycemia is 2-fold. First the portal vein may play a role in sensing hypoglycemia and activating the counterregulatory response. Secondly, as you already know, glucagon stimulates glycogenolysis and gluconeogenesis in the liver. o Counterregulatory hormones including norepinephrine, epinephrine, growth hormone and cortisol, cause an increase in glucose production and decrease glucose uptake in the periphery, specifically adipose and muscle tissues. Now you should take the time to link the effects of each of these hormones to the autonomic symptoms of hypoglycemia. o Neuroglycopenic symptoms occur due to an abrupt cessation of glucose delivery to the brain Hypoglycemia - Treatment Treatment in conscious person - Treatment in conscious person with mild to moderate hypoglycemia: o 15g carbohydrate → 2.1 mmol/L increase within 20 mins Treatment in conscious person with severe hypoglycemia: o 20g carbohydrate → 3.6 mmol/L increase at 45 mins In both cases, patients should re-test BG in 15 mins and retreat with another 15 or 20 g of carbohydrate if BG < 4.0 mmol/L Treatment in unconscious person - Treatment in unconscious person with severe hypoglycemia in greater than or equal to 5 years of age: o A) 1mg glucagon SC or IM o B) IV glucose 10-25g (20-50 cc D50W) over 1-3 mins - Examples of 15 g of carbohydrates includes 15 g of glucose tablets, 3 teaspoons or 3 packets of table sugar dissolved in water, 175 ml of juice or regular soft drink, 6 Life Savers, 1 tablespoon of honey. Monosaccharides like glucose are preferred as they are absorbed directly into the bloodstream Some clinical PEARLS to remember from first diabetes module are that if a patient is taking an alpha-glucosidase inhibitor, dextrose not sucrose should be used to treat hypoglycemia - 4 - Secondly, glucagon will be ineffective in patients whose glycogen stores are depleted. Glucagon will not be as effective in individuals who have consumed more than 2 standard alcoholic drinks within the previous few hours or those who have advanced liver disease Hyperglycemic Emergencies - - Hyperglycemic emergencies are life threatening associated with significant morbidity and even mortality 2 hyperglycemic conditions associated with diabetes are: o Diabetic ketoacidosis (DKA) o Hyperglycemic hyperosmolar nonketotic syndrome (HHNKS) The features of each of these conditions can overlap, however there are some distinct differences o Both conditions arise from either a relative or absolute insulin deficiency o Some form of trigger that causes an increase in counterregulatory hormones and resultant hyperglycemia o Osmotic diuresis and extracellular fluid volume depletion or hypovolemia with HHNKS o Acid-base imbalance specifically metabolic acidosis due to ketoacidosis is less likely to occur in HHNKS but always present in DKA o Electrolyte imbalances occurs due to metabolic acidosis and osmotic diuresis. The most serious electrolyte imbalance is hypo and hyperkalemia due to the associated risk for cardiac arrhythmias o Adverse neurological sequalae including cerebral edema, coma and death are reported in both conditions DKA/HHNKS Pathophysiology - - - 1st, there is an insulin deficiency and some precipitating factor that increases counterregulatory hormones including glucagon o Glucagon directly stimulates glycogenolysis in the liver. o Counterregulatory hormones including glucagon, cause decreased glucose uptake in the peripheral tissues Protein breaks down to provide amino acids to the liver for gluconeogenesis Adipose tissue also breaks down to form glycerol for gluconeogenesis if there is a relative insulin deficiency and free fatty acids to form ketones in the liver in the case of absolute insulin deficiency. o Specific ketones formed are called beta-hydroxybutyric and acetoacetic acids which result in metabolic acidosis The result of glycogenolysis and gluconeogenesis is hyperglycemia o Hyperglycemia causes osmotic diuresis and large losses of electrolytes in the urine. The total body deficit of water in adults is usually about 5-7 L in DKA and 5 - 7-12 L in HHNKS which represents a loss between 10-15% of body weight. If left untreated, circulatory failure ensures Hyperosmolality and metabolic acidosis can both cause CNS depression and if left untreated, coma As you can visually appreciate whether the hyperglycemia condition is classified as DKA or HHKS depends upon whether or not there is a relative or absolute insulin deficiency DKA/HHNKS - DKA usually affects type 1 diabetics and HHNKS usually affects type 2 diabetics o DKA is more common and it is estimated that between 500010,000 patients are admitted to hospital in Canada every year because of DKA. HHNKS is less common and it is estimated that between 500-1000 patients are admitted to hospital in Canada every year because of HHNKS o Mortality is lower in DKA, ranging from 4-10% and even reported as less than 5% in your textbook. The 6 - mortality rate for HHNKS is higher ranging from 10-50%. The range is likely due to underlying illness o Hyperglycemia is characteristic of both conditions however the plasma glucose levels are much higher in HHNKS o Extracellular fluid volume depletion and the resultant electrolyte imbalance are common in both conditions however ECFV depletion is greater in HHNKS. This makes sense as plasma glucose levels are higher in HHNKS resulting in greater osmotic diuresis. A diagnostic marker for HHNKS is an plasma osmolarity of greater than or equal to 320 mOsm/L o In DKA, metabolic acidosis is less than or equal to 7.3 and associated decreased bicarbonate. Bicarbonate levels are usually 15 mmol/L or less. In HHNKS, pH is usually normal o Since there is ketone production in DKA, the presence of the typical acetone breath which is sometimes described as a fruity odor, is usually noticed at time of presentation. Also, Kussmaul-Kien respiration (rapid, shallow breaths) due to metabolic acidosis can also be present especially with severe metabolic acidosis. These clinical features are not usually present in HHNKS DKA and HHNKS are complex hyperglycemic disorders that have overlapping features and some distinct differences. For example, hypotension and tachycardia may be present in either DKA or HHNKS due to ECFV depletion Management of DKA/HHNKS - - - Key principles of the management of DKA and HHNKS involve the following; o Fluid rehydration to restore normal ECFV and tissue perfusion o Correction of hyperglycemia by addressing absolute or relative insulin deficiency o Resolution of ketoacidosis usually occurs with insulin therapy and fluid rehydration o For severe acidosis, sodium bicarbonate NaHCO3 may be used in the adult population. It is usually not used in pediatrics o Monitor and correct electrolytes, specifically potassium o Diagnosis and treatment of coexisting illness which may have been precipitating factors. o Monitor for and prevent complications, specifically adverse neurological sequelae like cerebral edema This is a very simplified summary of the management of DKA and HHNKS. There are specific clinical algorithms used to manage DKA in both adults and children. The next two slides shown the algorithms found in the CDA guidelines to manage DKA in adults and children Potassium is added to maintenance fluid even if potassium levels are not abnormally low because when metabolic acidosis begins to correct, potassium shifts back into the 7 - cell. Since there is already an overall depletion of potassium due potassium having moved out of the cell during metabolic acidosis and loss of potassium via osmotic diuresis, it is imperative to anticipate this to avoid life threatening arrhythmias Lastly, a sudden change in extracellular fluid osmolality can occur if hyperglycemia is corrected to quickly, which can result in cerebral edema Cerebral edema is more common in DKA and in children. It can be deadly or have devastating neurological consequences Chronic/Long-term Complications - - Chronic and more long-term complications of diabetes can cause disease in several body systems CDA states that 10% of all acute care hospital admissions are related to diabetes or its complications. It is fortunate that good diabetes care and management which includes health teaching can prevent or delay the onset of complications 2 landmark studies, one called Diabetes Control and Complications Trial which looked at type 1 diabetes and the United Kingdom Prospective Diabetes Study which looked at type 2 diabetes found that intensive diabetic treatment can reduce the incidence of complications 8 - o 80% of people with diabetes will die of a heart attack or stroke o 50% of diabetics have chronic kidney disease and chronic kidney disease with diabetes is the leading cause of kidney failure in Canada o Blindness caused by diabetes is the most common cause of blindness in people aged 65 years and younger o Neuropathy can cause minor injuries to go unnoticed which if untreated can lead to infection and gangrene. o 7/10 non traumatic limb amputations are due to diabetes. I have highlighted only some of the most common complications although others are not really all that uncommon. For example, erectile dysfunction was the first clinical sign of diabetes in up 12% of males with diabetes Chronic complications - Theories of pathogenesis - Theories of pathogenesis that will help explain why these chronic complications occur Polyol Pathway - - - The polyol pathways is an alternative metabolic pathway for tissues not requiring insulin for glucose transport o These include the kidney, red blood cells, blood vessels, eye lens and nerves Aldose reductase normally converts toxic aldehydes to inactive alcohols, however, in the presence of hyperglycemia, glucose is shunted to this pathway and aldose reductase converts glucose to sorbitol In the process, a cofactor called NADPH (Nicotinamide adenine dinucleotide phosphate) is consumed. NADPH is normally an essential cofactor for regenerating glutathione 9 - which is a critical intracellular antioxidant. This increases the susceptibility of the cell to intracellular oxidative stress Sorbitol is then slowly converted to fructose by sorbitol dehydrogenase Accumulation of sorbitol and fructose causes increases in intracellular osmotic pressure which attracts water and leads to cell injury o This is a key part of the pathophysiological process for visual changes and catrarcts in diabetic patients o Also in nerves, sorbitol interferes with ion pumps, damages Schwann cells and disrupts nerve conduction o Swollen red blood cells can become stiff and perfusion can be compromised AGE Formation - Glycoprotein also known as advanced glycation end products or AGEs are basement membrane components in the microcirculation Recurrent or persistent hyperglycemia increases the formation of AGEs to be formed through the non-reversible binding of glucose to proteins, lipids and nucleic acids Specifically hyperglycemia increases AGEs in collagen and other proteins in red blood cells, blood vessel walls & interstitial tissues AGEs + their receptor (RAGE) have properties that can cause tissue injury or pathologic conditions associated with diabetes o Some of these effects include modification of intracellular proteins, specifically those involved in gene transcription; cross-linking and trapping of proteins; thickening of the basement membrane; increased permeability in blood vessels and nerves; stimulation of cellular proliferation; inducing lipid oxidation, oxidative stress and inflammation; inactivation of NO and loss of vasodilation and diminished endothelial function; and promotion of platelet adhesion and reduced fibrinolysis Tissue Oxygenation/Oxidative Stress - - - Tissue oxygenation theories suggest that many of the chronic complications arise from a decrease in oxygen delivery in small vessels o One described pathway is a defect in red blood cells which impairs the release of oxygen from hemoglobin Chronic hyperglycemia increases production of reactive oxygen species and subsequent damaging effects of oxidative stress o Advanced glycation end products (AGEs), nitric oxide dysfunction and nicotinamide adenine dinucleotide phosphate or NADPH discussed in the context of the polyol pathways are some of the contributors to increased reactive oxygen species in the setting of chronic hyperglycemia Reactive oxygen species damage large and small vessels contributing to artherogenesis, cardiovascular disease, nephropathy and neuropathy 10 Protein Kinase C - - - Intracellular hyperglycemia increases the synthesis of diacylglycerol (DAG) which activates protein kinase C o These are critical intracellular signaling molecules that regulate many vascular functions including permeability, vasodilator release, endothelial activation and growth factor signaling The consequences of elevated DAG and PKC are; o Blood flow abnormalities due to decreased endothelial NO synthase which is a vasodilator and increased endothelin-1 which is a vasoconstrictor o Increased vascular permeability and angiogenesis due to increased vascular endothelial growth factor o Capillary & vascular endothelial growth factor o Capillary & vascular occlusion due to increased collagen and fibronectin, and decreased fibrinolysis respectively o Pro-inflammatory gene expression o Increased ROS & disordered mitochondrial function in response to chronic hyperglycemia Clinically, vascular damage and associated disease of the retina, kidney and nerves can be caused by activation of Protein kinase C in these blood vessels Hexosamine Pathway - - The increased hexosamine pathway activity is a newer piece of the diabetes pathogenesis puzzle Chronic hyperglycemia causes shunting of excess intracellular glucose into the hexosamine pathway, and O-linked glycosylation of proteins causes alteration in signal transduction pathways & oxidative stress Specifically, O-linked attachment of N-acetylglucosamine on serine and threonine residues of transcription factors often results in pathologic changes in gene expression that are associated with insulin resistance & CV complications Microvascular disease - - Microvascular diabetic complications are the leading cause of blindness, end-stage renal disease and various neuropathies It is characterized by thickening of the basement membrane, endothelial cell hyperplasia, thrombosis and pericyte degeneration These microvascular changes occur in a hyperglycemic state. Specifically accumulation of AGEs, and resultant tissue injury and pathologic conditions contributes to microvascular complications in diabetes Frequency of these complications seems to be proportionally related to duration of diabetes & blood glucose levels 11 - - The Diabetes Control and Complications trial demonstrate that diabetics with tightly controlled glucose were half as likely to have renal and eye complications as those diabetics receiving standard therapy Microvascular complications in diabetes involves mainly the retina, nerves, kidneys and GI system Neuropathy - - - - - - In the western world, diabetic neuropathy is the most common cause of neuropathy. Within 10 years of the onset of diabetes, detectable sensorimotor polyneuropathy will develop in 40-50% of people with both type 1 and type 2 diabetes There are 2 main pathologic changes seen in diabetic neuropathies o 1st, vessel ischemia due to thickening of the walls of the nutrient vessels that supply the nerve. o 2nd, the segmental demyelination process affecting the Schwann cells. Slowed nerve conduction accompanies this demyelination process The underlying pathophysiology is multi-factorial and includes microangiopathy, oxidative stress, growth factor deficiency, abnormal signaling from AGE-RAGE interaction, increased polyol pathway and inflammation Neuropathies can be subclinical, and peripheral nerve dysfunctions can only be detected with electromyographic (EMG) testing before progressing to the clinical stage, in which symptoms or clinically detectable neurologic deficits are present Somatic neuropathy may involve the spinal cord posterior root, ganglia or the peripheral nerves o Degeneration of the nerves begins in the periphery, and sensory nerve involvement usually precedes motor nerve involvement o Distal symmetric polyneuropathy is the most common form of neuropathy and involves the smaller unmyelinated peripheral C fibers and the larger myelinated A-delta fibers. Sensory dysfunction usually occurs first and is distal, bilateral and symmetric o Loss of small nerve function results in neuropathic pain and loss of sensation o Loss of large nerve function results in sensory loss of proprioception and vibration, ataxia and loss of coordination Autonomic neuropathy involves sympathetic and parasympathetic nervous system dysfunction o In the bladder, there may be loss of bladder sensation, urine retention and recurrent infections o In the GI system, there may be dysfunction of GI enteric nerves which may lead to nausea, bloating, gastroparesis, diarrhea, constipation o In men, sensory and autonomic dysfunction may lead to erectile dysfunction. 3445% of Canadian men with diabetes have erectile dysfunction 12 - - - o Autonomic neuropathy can lead to dysfunction of sweating and body temperature regulation o CV autonomic neuropathy, specifically in type 1 diabetes, is associated with heart rate variability, changes in baroreceptor reflexes, postural hypotension, arrhythmias, exercise intolerance and painless MI Rapid screening for neuropathy is described in the CDA guidelines, comprehensive neurological exam is warranted in patients with signs or symptoms of neuropathy. Asking a patient about falls and foot injuries can provide valuable information when assessing for diabetic neuropathy. o EMG which stands for electromyography testing testing, can provide information on subclinical neuropathy Management and prevention of neuropathy involves good glycemic control Neuropathic pain may be managed with tricyclic antidepressant, anticonvulsants like Gabapentin and opioid analgesia Autonomic neuropathies are managed by 1st ruling out any specific CV, GI or GU pathology through assessment by a specialist and then treated primarily by expert opinion of the specialists Of note, specific to nursing, there is a section in the CDA guidelines on foot care which may be relevant to clinical and is a key intervention for individuals with diabetic neuropathy Nephronpathy - - - - Diabetic nephropathy generally occurs due to lesions of the glomeruli on the kidney Glomerular changes include o Capillary basement membrane thickening o Diffuse glomerular sclerosis o Nodular glomerulosclerosis. Nodular glomerulosclerosis is also called Kimmeistiel-Wilson syndrome and is specific to people with diabetes Chronic kidney disease is usually a clinical diagnosis that relies on signs/symptoms and laboratory findings that assess kidney function. If there is any doubt about the diagnosis, a kidney biopsy may be performed It seems that genetics plays a role in which individuals with diabetes develop kidney disease Risk factors for development of this diabetic complication include genetic and familial predisposition, hypertension, poor glycemic control, smoking, hyperlipidemia and microalbuminuria Microalbuminuria or albumin in the urine is one of the 1st clinical manifestations of kidney dysfunction. Once microalbuminuria is detected, urine should be sent for albumin/creatinine ratio (A/Cr) 13 - o Some of the chronic kidney disease signs & symptoms include fluid and electrolyte imbalances, hypoproteinemia, edema due to decreased plasma oncotic pressure, fluid overload and hypertension Prevention and management include good glycemic control, maintaining normal blood pressure, prevention or reduction in proteinuria using pharmacologic agents like ACE inhibitors or angiotensin receptor blockers or through restricting protein in diet, treatment of hyperlipidemia and smoking cession Retinopathy - - - - Unfortunately, almost 100 % of people with type 1 diabetes and 60% of people with type 2 diabetes have some form of retinopathy within 20 years of their diabetes diagnosis Diabetes is the leading cause of acquired blindness o Abnormal retinal vascular permeability, microaneurysms, neovascularization lead to hemorrhage, scarring and retinal detachment Both prevention & management include achievement of glycemic control, preventing and treating hypertension and hyperlipidemia Regular dilated eye examinations should be part of the plan of care for all individuals with diabetes Treatment for retinopathy includes: laser, surgery specifically vitrectomy in more severe forms of retinopathy, and specific pharmacologic agents like antagonists to growth factors If you are interested, the CDA guidelines section on retinopathy reviews some of the recent research trials. Information on these specific trials is not testable material Macrovascular Disease - Stats, Risk, Pathophysiology - - The prevalence of macrovascular disease is increased 2-4 times in people with diabetes 50-75% of all people with type 2 diabetes will die from macrovascular disease Risk factors for macrovascular disease include; obesity, HTN, hyperglycemia, hyperinsulinemia, hyperlipidemia, altered platelet function, endothelial dysfunction, systemic inflammation evidenced by increased C reactive protein (CRP) and increased fibrinogen The underlying pathophysiology of macrovascular complications is atherogenesis or atherosclerosis Hyperglycemia triggers advanced glycation end products (AGE’s) and protein kinase C (PKC) activation causing endothelial dysfunction. Oxidative stress also causes endothelial dysfunction o Risk factors contribute to endothelial dysfunction, formation of foam cell and fibrous plaque, and eventual complicated atherosclerotic lesion 14 Macrovascular Disease - Forms - - - CAD o Coronary artery disease is the most common cause of death in people with type 2 diabetes and is common in type 1 diabetes as well o The risk for CAD is higher in diabetes than general public even when HTN & hyperlipidemia taken into account PVD o Peripheral vascular disease is compounded by microvascular disease of neuropathy o Often the atherosclerotic process in the peripheral vessels along with neuropathy can lead to gangrene & amputation. o 70% of non-traumatic limb amputations are due to diabetes Cerebrovascular disease o Lastly, cerebrovascular disease or stroke is twice as common in people with diabetes o Ischemic stroke is more common than hemorrhagic stroke Patient teaching - How to avoid or delay complications associated with diabetes? o Maintain normoglycemia (Hgb A1C < 7%) through a healthy lifestyle/diet and medications when needed o Decrease other risk factors for diabetic complications (i.e. obesity, hyperlipidemia, HTN) o Identify and treat complications Conclusion - To conclude o Achieving glycemic control is paramount to preventing/delaying onset of diabetic complications o Pathophysiology is multi-factorial, and hyperglycemia underlies/triggers all complications o Complications are a/w significant morbidity & mortality in both type 1 and type 2 diabetes 15 Pathophysiology of DKA and HHNKS 16 17 18
