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Diabetes and Glucose Metabolism
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  • Why would a patient secrete less insulin?? Type 1 autoimmune disease where the islet cells in the pancreas have been destroyed by antibodies and no longer produce insulin. Type II the body has been exposed to high levels of blood glucose for so long that it is desensitized to elevated sugar and produces less insulin. Also, for the same reason, the pancreas wears out from producing increased insulin for an extended period of time and therefore no longer can produce insulin in sufficient levels.

Diabetes and Glucose Metabolism Diabetes and Glucose Metabolism Presentation Transcript

  • Diabetes Mellitus andGlucose Metabolism
    Elizabeth Bunting, MS, PA-C
    Clinical Medicine I
    March 28, 2010
  • Objectives
    Describe normal glucose metabolism
    Describe the pathophysiology of Type I and Type II DM
    Describe the two major types of diabetes with reference to genetics, the age incidence, and diagnosis
    Describe the following therapies for control of blood glucose.
    Diet
    Insulin
    Name and describe the major types of insulin available
    Describe situations in which the use of insulin in Type II Diabetes is clinically correct.
    Describe how to start a patient on insulin and how to counsel a patient
  • Objectives
    Distinguish the features of DM Type II from Type I
    List the classes of antidiabetic agents and discuss their mode of action
    Describe the pathophysiology, signs, symptoms, dignostic features and treatment of
    Diabetic Ketoacidosis and coma
    Hypoglycemia and insulin shock
    Lactic acidosis
    Hyperosmolar coma
    Discuss the dawn phenomenonandSymogyi effect, including their pathophysiology and management.
  • Objectives
    List and describe the following chronic complications of diabetes
    Retinal disease leading to blindness
    Renal disease
    Vascular disease
    Cardiac disease
    Dermatologic disorders
    Gastrointestinal disease
    Discuss the epidemiology of diabetes in the U.S. and explain its socio-economic impact.
  • Objectives
    Discuss the impact of diabetes on pregnancy and include the unique risks and management
    Explain short and ling term monitoring of diabetes.
    Describe patient education principles that may help diabetic patients adhere to their prescribed treatment plan
  • Pancreatic Anatomy
  • Pancreatic Physiology
    Endocrine Gland Secretes:
    Insulin
    Glucagon
    Somatostatin (SS)
    Pancreatic Polypeptide (PP)
    Exocrine Gland Secretes
  • Ketones
    Triglycerides
    Fatty Liver
  • Pancreatic Physiology
    Endocrine and Exocrine activity
    Exocrine:
    Pancreatic Acini cells produce digestive juices
    Duct cells produce NaHCO3
    Endocrinetissue contained inIslets of Langerhans
    Endocrine:
    ALPHA CELLS secrete Glucagon (25%)
    BETA CELLS produce Insulin (60%)
    DELTA CELLS produce Somatostatin (15%)
  • Primary Pancreatic Hormone Activity
    GLUCAGON
    Stimulates breakdown of glycogen in the liver
    Activates hepatic gluconeogenesis (makes sugar)
    INSULIN
    Anabolic hormone
    Facilitates entry of glucose into cells
    Stimulates the liver to store glucose in the form of glycogen
    Promotes the storage of carbohydrate and fat and protein synthesis
  • Insulin
    Biosynthesis, secretion and action
    Mature insulin molecule and C peptide are stored together and cosecreted from secretory granules in the beta cells
    Because the C peptide is cleared more slowly than insulin, it’s a useful marker of insulin secretion
    Glucose is the key regulator of insulin secretion
    Glucose levels >70 mg/dL stimulate insulin synthesis
  • Insulin
    Biosynthesis, secretion and action
    Insulin is secreted in a pulsatile pattern
    Small secretory bursts occur about every 10 minutes
    Superimposed upon greater amplitude oscillations of about 80-150 minutes
    Incretins also play a role in insulin secretion
    Released from GI tract neuroendocrine cells following food ingestion and amplify glucose-stimulated insulin secretion and suppress glucoagon secretion
  • Insulin
    Biosynthesis, secretion and action
    50% is degraded in the liver after entering the portal venous system
    Unextracted insulin enters the systemic circulation where it binds to receptors in target sites
  • Somogyi Effect and Dawn Phenonemon
    Somogyi Effect: nocturnal hypoglycemia (from fasting) leads to a surge of counterregulatory hormones (glucagon and epinephrine) that produce hyperglycemia at around 7 AM
    Dawn Phenomenon: reduced tissue sensitivity to insulin between 5 and 8 AM
  • Diabetes Mellitus
    Syndrome with disordered metabolism and inappropriate hyperglycemia due to a deficiency of insulin secretion or to a combination of insulin resistance and inadequate insulin secretion to compensate.
    Several types exist and are caused by a complex interaction of genetics and environmental factors
    Factors that contribute to hyperglycemia include
    Reduced insulin secretion
    Decreased glucose utilization
    Increased glucose production
  • Diabetes Mellitus
    Metabolic dysregulation associated with DM causes secondary pathophysiologic changes in multiple organ systems that impose a tremendous burden on the individual and the health care system
    DM is the leading cause of ESRD, nontraumatic lower extremity amputations, and adult blindness
  • Diabetes Mellitus
    Classification
    Based on the pathogenic process that leads to hyperglycemia
    Two broad categories
    Type 1 – results from complete or near-total insulin deficiency
    Type 2 – heterogeneous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion and increased glucose production
  • Types of Diabetes
    Type 1 Diabetes - previously known as
    Insulin Dependent Diabetes Mellitus (IDDM)
    Juvenile Diabetes
    Type 2 Diabetes – previously known as
    • Non-Insulin Dependent Diabetes Mellitus (NIDDM)
    • Insulin Resistant Diabetes
    • Adult Onset Diabetes
  • Diabetes Mellitus
    Epidemiology
    Prevalence of type 2 diabetes is rising more rapidly than type 1 due to increasing obesity and reduced activity levels
    In 2007 it was estimated that 23.6 million people in the US
    ~1 million have type 1 diabetes
    Incidence increases with age
  • Diabetes
    Epidemiology
    7th leading cause of death in 2007
    Prevalence of 20.9% in individuals >60 years
    Prevalence is similar in men and women
  • Diagnosis of Diabetes
    1Give 75 g of glucose dissolved in 300 mL of water after an overnight fast in persons who have been receiving at least 150–200 g of carbohydrate daily for 3 days before the test.
    2A fasting plasma glucose  126 mg/dL is diagnostic of diabetes if confirmed on a subsequent day.
  • Diagnosis of Diabetes
    Person may have IFG and IGT
    They are at substantial risk of developing diabetes and have an increased risk of cardiovascular disease
    25-40% risk of overt diabetes over next 5 years
    Fasting glucose – the most reliable and convenient test for identifying DM in asymptomatic individuals
  • Type 1 Diabetes
  • Type 1 Diabetes
    General Considerations
    Caused by pancreatic islet B-cell destruction that leads to insulin deficiency
    Destruction is immune-mediated in > 90% of cases and idiopathic in the remainder
    Individuals with genetic susceptibility have normal beta cell mass at birth but begin to lose beta cells secondary to autoimmune destruction that occurs over months to years
    Autoimmune process is thought to be triggered by an infectious or environmental stimulus
  • Type 1 Diabetes
    Susceptibility involves multiple genes
    Major gene is located in the HLA region on chromosome 6
    The rate of pancreatic B-cell destruction ranges from rapid to slow and varies among individuals
    Features of diabetes do not become evident until ~80% of beta cells are destroyed
    Prone to ketoacidosis
    Serum C-peptide negative 1–5 years after diagnosis; plasma glucagon is elevated
  • Type 1 Diabetes
    Immunologic markers
    Islet cell autoantibodies (ICAs) – present in >75% of those diagnosed with new-onset type 1 DM
    Testing for these can be useful in classifying type of DM and identifying nondiabetic individuals at risk of developing type 1 DM
    Environmental factors
    None have been conclusively linked to diabetes
  • Type 1 Diabetes
    Prevention
    No interventions have been proven successful in preventing type 1 DM in humans
    Demographics
    Typically onset of disease is prior to age 30 (10-14 most commonly)
    Suspect especially when hyperglycemia first appears in the nonobese or elderly
  • Type 1 Diabetes
    Incidence
    Highest in Scandinavia
    Lowest in China and parts of South America
    In the United States, average is 15 per 100,000
    Incidences are higher in states densely populated with persons of Scandinavian descent such as Minnesota
    The global incidence is increasing, with an annual increase of ~3%
  • Type 1 Diabetes
    Symptoms and Signs
    Lean body habitus
    Increased thirst (polydipsia)
    Increased urination (polyuria)
    Increased appetite (polyphagia) with weight loss
    Ketoacidosis
    Paresthesias
    Recurrent blurred vision
    Vulvovaginitis or pruritus
    Nocturnal enuresis
    Postural hypotension from lowered plasma volume
  • Type I Diabetes
    Laboratory Tests
    Fasting plasma glucose ≥ 126 mg/dL or > 200 mg/dL 2 h after glucose load
    Ketonemia, ketonuria, or both
    Glucosuria
    Assess degree of glycemic control with glycosylated hemoglobin (hemoglobin A1c)
    reflects glycemic control over preceding 8–12 weeks
    Serum fructosamine
    Reflects glycemic control over preceding 2 weeks
    Helpful in presence of abnormal hemoglobins or in ascertaining glycemic control at time of conception among diabetic women
  • Type 1 Diabetes
    Laboratory tests
    Serum insulin or C-peptide
    Forms when proinsulin is broken down to form insulin and C-peptide
    C-peptide has a longer half life than insulin
    Islet cell antibodies
    Insulin autoantibody
    Screen for DM-associated conditions
    Microalbuminuria
    Dyslipidemia
    Thyroid function
  • Type 1 Diabetes
    Pharmaceutical treatment
    Insulin
    Goal is to design insulin regimens that mimic physiologic insulin secretion
    Insulin regimens usually include multiple-component insulin regimens, multiple daily injections or insulin infusion devices
    Most patients will require 0.5-1 U/kg/day of insulin divided into multiple doses, with ~50% of the insulin given as basal insulin
  • Insulin Preparations
  • A multiple-component insulin regimen consisting of long-acting insulin,one shot of glargine to provide basal insulin coverage and three shots of lispro, or insulin aspart to provide glycemic coverage for each meal.
    The injection of two shots of long-acting insulin, NPH or detemir and short-acting insulin, lispro, insulin aspart (solid red line), or regular (green dashed line)
    B= breakfast
    L= lunch
    S= supper
    HS= bedtime
    = time of insulin injection
    Infusion pump which uses lispro or aspart
  • Diet/Nutrition
    Carbohydrate counting or exchange systems to estimate the nutrient content of a meal or snack
    Estimate of the carb content of a meal determines the bolus insulin dose for a meal or snack
    Want to coordinate and match caloric intake with the appropriate amount of insulin
    A common ratio is 1-1.5 units/10g of carb, but this must be individualized
  • Type 1 Diabetes
    Other agents that improve glucose control
    Amylin (pramlintide)
    Usually cosecreted from pancreatic beta cells with insulin
    Pts who are insulin deficient are also amylin deficient
    SC injection before each meal - reduces postprandial glycemic excursion in type 1 and 2 diabetic pts
    Slows gastric emptying and suppresses glucagon
    Will decrease amount of short-acting insulin needed before the meal
  • Type 1 Diabetes
    Surgery
    Patients receiving simultaneous pancreas and kidney transplants have 85% chance of pancreatic graft survival and 92% chance of renal graft survival after 1 year
    Islet transplantation is minimally invasive
    Plagued by limitations and remains an area of investigation
  • Type 2 Diabetes
  • Type 2 Diabetes
    General considerations
    Typically > 40 years of age
    Fasting plasma glucose ≥ 126 mg/dL more than once
    OGTT > 200 mg/dL 2 h after the oral glucose
    Often associated with hypertension, dyslipidemia, and atherosclerosis
  • Type 2 Diabetes
    Pathophysiology
    Characterized by impaired insulin secretion, insulin resistance, excessive hepatic glucose production and abnormal fat metabolism
    Obesity, especially central (hip-waist ratio) is very common (present in 80%)
    Early stages – glucose tolerance remains near normal, despite insulin resistance, because the beta cells increase their insulin output
  • Type 2 Diabetes
    Pathophysiology (cont’d)
    As the disease progresses, islets are unable to sustain the hyperinsulinemic state
    IGT develops, characterized by elevations in postprandial glucose
    Further decline in insulin secretion and increase in hepatic glucose production lead to overt diabetes with fasting hyperglycemia
    Ultimately, beta cell failure may ensue
  • Type 2 Diabetes
    Genetic considerations
    Strong genetic component
    Concordance in identical twins is between 70-90%
    If both parents have type 2, the risk approaches 40% for the offspring
    General considerations
    Prevalence of obesity in type 2 diabetes mellitus
    30% in Chinese and Japanese
    60–70% in North Americans, Europeans, and Africans
    Nearly 100% in Pima Indians and Pacific Islanders from Nauru or Samoa
  • Type 2 Diabetes
    General Considerations
    Enhancers of insulin resistance are aging, sedentary lifestyle, and abdominal-visceral obesity
    Both the tissue resistance to insulin and the impaired B-cell response to glucose are further aggravated by increased hyperglycemia, and both defects improve with decreased hyperglycemia
  • Type 2 Diabetes
    Demographics
    > 90% of all diabetics in the United States have type 2 diabetes (>18 million)
    Traditionally develops after age 40, but now more frequently at younger ages due to increased rates of obesity
    No gender predominance
  • Type 2 Diabetes
    Screening
    ADA recommends screening all individuals >45 years q3 years and earlier if they are overweight and have one additional risk factor for diabetes
    Many are asymptomatic and unaware they have the disease
    Type 2 DM may be present for up to a decade before diagnosis
    Treatment of type 2 DM may favorably alter the natural history of DM
  • Risk Factors for Type 2 Diabetes
    FH of diabetes (parent or sibling with type 2)
    Obesity (BMI >25)
    Habitual physical inactivity
    Race/ethnicity – AA, Latino, Native Amer, Asian or Pacific Islander
    Previously identified with IFG or IGT
    History of GDM or delivery of baby >9 lbs
    HTN (BP >140/90)
    PCOS or acanthosisnigricans
  • Type 2 Diabetes
    History
    Be sure to ask about DM relevant aspects such a weight, FH of DM, risk factors for CV disease, exercise, smoking and ethanol use
    If previously diagnosed with DM ask about type of therapy, prior HgbA1C levels, self-monitoring BG results, frequency of hypoglycemia, assessment of pt’s knowledge about diabetes, exercise and nutrition
  • Type 2 Diabetes
    Symptoms and Signs
    Often asymptomatic
    Obesity
    Polyuria
    Polydipsia
    Weakness or fatigue
    Recurrent blurred vision
    Vulvovaginitis or pruritus
    Slow wound healing
    Peripheral neuropathy
    Acanthosisnigricans
  • Acanthosisnigricans (AN) is a brown to black, poorly defined, velvety hyperpigmentation of the skin, usually present in the posterior and lateral folds of the neck, the axilla, groin, umbilicus, and other areas
  • Type 2 Diabetes
    PE
    Special attention should be given to DM-relevant aspects such as
    Weight or BMI
    Retinal examination
    Yearly evaluation by ophthalmologist
    BP
    >130/80 mmHg is considered HTN
  • Type 2 Diabetes
    PE
    Foot examination
    Peripheral neuropathy – vibratory sensation and light touch sensation with monofilament
    Calluses
    Foot deformities
    Peripheral pulses
    Insulin injection sites
  • Type 2 Diabetes
    Associated conditions
    Insulin resistance
    CV disease
    HTN
    Dyslipidemia
    PCOS
  • Type 2 Diabetes
    Laboratory Tests
    Fasting plasma glucose  ≥126 mg/dL or >200 mg/dL 2 h after glucose load
    Glucosuria
    Ketonuria on occasion without ketonemia
    Assess the degree of glycemic control with glycosylated hemoglobin (HbA1c)
    reflects glycemic control over preceding 8–12 weeks
  • Type 2 Diabetes
    Laboratory testing
    Screen for DM-associated conditions
    Microalbuminuria
    Dyslipidemia
    Lipoprotein abnormalities in obese persons with type 2 diabetes include
    High serum triglyceride (300–400 mg/dL)
    Low high-density lipoprotein (HDL) cholesterol (< 30 mg/dL)
    A qualitative change in low-density lipoprotein (LDL) particles
    Thyroid function
  • Type 2 Diabetes Management
  • Long Term Treatment
    Goals
    Eliminate symptoms related to hyperglycemia
    Symptoms usually resolve when BG <200 mg/dL
    Reduce or eliminate the long-term microvascular and macrovascular complications
    Allow the pt to achieve as normal a lifestyle as possible
  • Long Term Treatment
    How to achieve these goals
    Pt education about DM, nutrition and exercise
    Provider education at every office visit + the use of a diabetes educator and dietician
    Nutritional recommendations
    Diet that includes fruits, vegetables, fiber-containing foods and low-fat milk
    Glycemic index – estimate of the postprandial rise in the BG when amount of that food is consumed
  • Glycemic Index
    Low glycemic index appears to reduce postprandial glucose excursions and improve glycemic control
    Short grain White Rice 72
    White Bread 70
    Graham Crackers 74
    Broccoli 10
    Corn 55
    Potato (baked) 93
    Sweet Potato 54
    Apple 38
    Watermelon 103
    Honey 58
    Fructose 23
    Walnuts 15
    Corn Chips 72
    Milk (whole) 22
    Yogurt (low-fat) 33
  • Diabetes
    Dietary Recommendations
    Cholesterol to 200 mg QD
    Protein intake to 10–35% of total calories
    Saturated fats to <7% of total calories
    Remainder of diet to consist of monounsaturated fats and carbohydrates with 20–35 g of dietary fiber
  • Long Term Treatment
    Exercise
    ADA recommends 150min/week (distributed over at least 3 days) of aerobic activity
    Reduces CV risk
    Reduces BP
    Maintains muscle mass
    Reduction in body fat and weight loss
    Lowers plasma glucose – during and following exercise
    Increases insulin sensitivity
    Formal exercise tolerance testing (stress test) is warranted in individuals prior to the start of an exercise program with any of the following: age>35 years, diabetes duration >10 years, microvascular complications, neuropathy, PAD
  • Long Term Treatment
    Monitoring of BG
    Patient’s measurements provide you with a picture of short-term glycemic control
    HbA1C reflects average glycemic control over the previous 3 months
    Self-monitoring of BG
    Frequency must be individualized
    Type 1 or type 2 on insulin - ≥3 times a day
    Type 2 on oral meds – 1-2 times a day with decreasing frequency as DM becomes controlled
    Monitor prior to a meal and supplemented with postprandial measurements
  • Type 2 Diabetes
    Pharmaceutical treatment
    Any therapy that improves glycemic control reduces “glucose toxicity” to the islet cells and improves endogenous insulin secretion
    However, type 2 DM is a progressive disorder and ultimately requires multiple therapeutic agents and often insulin
  • Classifications of glucose lowering agents
    Insulin secretagogues
    Drugs that stimulate insulin secretion
    Most effective in pt with relatively recent onset of DM (<5 years)
    Sulfonylureas (glyburide, glipizide, glimepiride)
    Meglitinide analogs (Prandin/repaglinide)
    D-phenylalanine derivative (Starlix/nateglinide)
    Side effects
    Can cause hypoglycemia, especially in the elderly
    Weight gain
  • Classifications of glucose lowering agents
    Biguanides
    Reduces hepatic glucose production and improves peripheral glucose utilization slightly
    Metformin (glucophage)
    Promotes modest weight loss
    Side Effects
    GI disturbances – nausea, bloating, diarrhea
    Lactic acidosis – can be prevented by avoiding use in renal insufficiency (creatinine >1.5 mg/dL)
    Must discontinue prior to radiographic contrast material
  • Classifications of glucose lowering agents
    αglucosidase inhibitors
    Reduce glucose absorption from the GI tract
    Reduce postprandial hyperglycemia
    acarbose, miglitol
    Not as potent as other oral agents at lowering the A1C
    Side effects
    Diarrhea, flatulence, abdominal distention (due to increased carbs/sugars in the large bowel)
  • Classifications of glucose lowering agents
    Thiazolidinediones (TZDs)
    Reduce insulin resistance
    Promote redistribution of fat from central to peripheral locations
    Circulating insulin levels decrease
    Pioglitazone (Avandia), rosiglitazone (Actos)
    Must measure LFTs prior to initiating therapy and q2 months for the 1st year of therapy
    Side effects
    Weight gain
    Peripheral edema and CHF – don’t use in CHF class III or IV
  • Classifications of glucose lowering agents
    GLP-1 receptor signaling
    “Incretins”
    Amplify glucose-stimulated insulin secretion
    Exenatide (Byetta)
    Suppresses glucagon and slows gastric emptying
    Most experience modest weight loss
    Suppresses appetite
    SC injection before morning and evening meal
    Only approved for adjunct or combo therapy with metformin, TZD or sulfonylurea
    Sitagliptin (Januvia)
    DPP-IV inhibitor, enhance incretin effect
    Promote insulin secretion and have a preferential effect on postprandial BG
    Oral medication and can be used in combination with metformin or a TZD
  • Classifications of glucose lowering agents
    Insulin therapy
    Can consider as initial therapy especially in lean individuals or those with severe weight loss, in those with underlying renal or hepatic disease, or those hospitalized or acutely ill
    Insulin is usually initiated as a single dose of long-acting insulin (determir (Levemir), glargine (Lantus)) and is most often started at bedtime
    Can use in combination with oral glucose-lowering agents (biguanides, αglucosidaseinhib, TZDs)
    As the disease progress the pt will often need prandial insulin coverage also
  • Classifications of glucose lowering agents
    Choice of initial glucose-lowering agent
    Level of hyperglycemia
    If FPG <200-250 mg/dL pts often respond to a single oral agent
    If FPG >250mg/dL pts often need >1 agent to reach goal
    Consider insulin if FPG >250-300mg/dL or in those who are symptomatic from hyperglycemia
    All oral agents except the αglucosidase inhibitors improve glycemic control to a similar degree (1-2% reduction in A1C)
  • Glycemic management
  • Classifications of glucose lowering agents
    Combination therapy with oral agents
    Mechanisms of action are different so the effect on glycemic control is additive
    several drug combinations of TZD + metformin or sulfonylurea; metformin + sulfonylurea; DPP-IV with metformin are available
  • Diabetes
    Guidelines for ongoing medical care
    Self-monitoring of blood sugar
    HbA1c (2-4 times/year)
    Screen for microalbuminuria annually
    Serum lipids annually
    Feet examination by provider 1-2 times a year, daily by pt
    Diabetic eye examination annually
  • Treatment Goals
  • Diabetes
    Hemoglobin A1C
    There is an equation
    A 1% increase in A1C translates into a 35mg/dL increase in the mean glucose
  • Diabetes
    Complications
    May be present in up to 20-50% of newly diagnosed individuals with type 2
    Retinopathy
    CV disease
    Nephropathy
    Neuropathy
    Diabetic ketoacidosis
    Hypoglycemia and altered awareness of hypoglycemia
  • Diabetes
    Prevention
    Goal of therapy is to prevent acute illness and reduce risk of long-term complications
    Type 2 DM is preceded by a period of IGT and a number of lifestyle modifications and pharmacologic agents prevent or delay the onset of DM
    Maintain a normal BMI
    Diet and exercise for 30 min/day five times/week
    ADA recommends consideration of Metformin (glucophage) in individuals with both IFG and IGT who are at high risk of progression to diabetes
    <60 years, BMI >35, +FH 1st degree relative, elevated TGs, reduced HDL, HTN or A1C >6%
  • Comparison of Diabetes S&S
  • Complications
    Acute
    Diabetic ketoacidosis
    Hyperglycemic Hyperosmolar State
    Chronic
    Duration and degree of glycemic control are the best predictors of complications
    Vascular
    Microvascular
    Retinopathy, neuropathy, nephropathy
    Macrovascular
    CAD, PAD, CV disease
    Nonvascular
    Gastroparesis, infections, skin changes, sexual dysfunction, cataracts, glaucoma, periodontal disease
  • Ocular Complications
    Diabetic retinopathy
    DM is the leading cause of blindness b/t the ages of 20-74 in the US
    Retinal vascular microaneurysms, blot hemorrhages, cotton wool spots eventually progress in most patients with continued hyperglycemia and lead to retinal ischemia
    Can be treated early with laser photocoagulation
  • Retinal Changes
  • Cardiovascular Complications
    DM major risk factor for cardiovascular disease in the US
    Annual incidence of cardiovascular death rate is increased by 3 times in diabetic men and by 4 times in diabetic women
    Risk factors for cardiovascular disease
    Insulin resistance
    Elevated urinary protein excretion
    Poor glycemic control
    Overweight or obesity
    Dyslipidemia
    HTN
    Sedentary lifestyle
    Smoking
    Monitoring of lipid levels and management of hyperlipidemia is essential in the prevention of macrovascular complications
  • Diabetic Nephropathy
    DM is the #1 cause of ESRD in the U.S.
    Leading cause of DM-related morbidity and mortality
    Begins with microalbuminuria defined as 30-300 mg/d
    After 10 years macroalbuminuria develops in 50%
    Overall risk of developing diabetic nephropathy is 20-40%
  • Diabetic Nephropathy
    Treatment
    Glycemic control slows progression
    Strict BP control
    Start ACE or ARB
    Restrict protein intake to 0.8g/kg/day
    Nephrology consultation when GFR is <60 mL/min
    More likely to develop in:
    Males
    Relatives have had kidney disease or HTN
    Poor glycemic control
    Patient has HTN
  • Diabetic Neuropathy
    Most common complication of DM Type 2
    Develops in ~50% of individuals with DM
    Peripheral neuropathy
    Most common is distal symmetric polyneuropathy
    Most frequently presents with distal sensory loss but may also have hyperesthesia, paresthesia and dysesthesia
    Begins in feet and spreads proximally, usually present at rest and worsens at night
  • Diabetic Neuropathy
    Autonomic neuropathy
    Involves the cholinergic, noradrenergic, and peptidergic
    Can involve multiple systems
    CV, GI, GU
    Postural hypotension and decreased CV response
    Gastroparesis
    Urine retention
    ED
    Treatment
    Check feet daily and take precautions (footwear)
    TCAs, anticonvulsants, duloxetine (Cymbalta) and pregabalin (Lyrica), gabapentin (Neurontin)
  • PV Disease of the Feet
    Screening and referral to footcare clinic for people with diabetes who are at high risk of developing foot ulcers reduces the risk of foot ulcers and major amputation
  • Foot structure
    Foot appearance
    Vascular status
    Neurosensory
    128 Hz tuning fork base at great toe nail
    Monofilaments
    Deep tendon reflexes
  • Skin & Mucous Membrane Complications
    Protracted wound healing and skin ulcerations
    Shin spots – pigmented pretibial papules
    Granulomaannulare – erythematous plaques on the extremities or trunk
    Repetitive candidainfection
  • Infections
    Many common infections are more frequent and severe in the diabetic population
    “malignant” or invasive otitisexterna
    Pneumonia
    UTI
    Skin and soft tissue infections
  • Hypoglycemia
    Glucose level <55 mg/dL with symptoms that are relieved promptly after the glucose level is raised
    Most convincingly documented by Whipple’s triad
    Symptoms consistent with hypoglycemia
    Low plasma glucose concentration measured with a precise method (not a glucose monitor)
    Relief of symptoms after the plasma glucose is raised
  • Physiology of glucose counterregulation
  • Hypoglycemia
    Etiology and pathophysiology
    Most commonly a result of the treatment of diabetes
    Hypoglycemia in diabetes
    Impact and frequency
    More common in type 1 DM
    Pts suffer an average of twice a week with symptomatic hypoglycemia and once a year with a severe episode
    2-4% die as a result of hypoglycemia
    Occurs in type 2 DM with sulfonylureas or insulin
  • Hypoglycemia
    Hypoglycemia in diabetes
    Conventional risk factors
    Relative or absolute insulin excess
    Insulin dose is excessive, ill-timed or the wrong type
    Influx of exogenous glucose is reduced (missed meal)
    Glucose utilization is increased (during exercise)
    Sensitivity to insulin is increased (improved glycemic control, increased fitness or weight loss)
    Endogenous glucose production is reduced (alcohol ingestion)
    Insulin clearance is reduced (renal failure)
  • Hypoglycemia
    Hypoglycemia in diabetes
    Hypoglycemic-associated autonomic failure
    Defective glucose counterregulation
    Hypoglycemia unawareness
    Fasting (postabsorptive) hypoglycemia
    Causes
    Drugs – insulin, sulfonylureas, ethanol
    Critical illness – hepatic, renal or cardiac failure, sepsis
    Endogenous hyperinsulinism – insulinoma, autoimmune, ectopic insulin secretion
  • Hypoglycemia
    Postprandial (reactive) hypoglycemia
    Occurs exclusively after meals
    Diagnosis requires documentation of Whipple’s triad after a mixed meal
    Early - rapid discharge of ingested carbohydrate into the small bowel followed by rapid glucose absorption and hyperinsulinism
    Particularly associated with dumping syndrome after gastrectomy
  • Hypoglycemia
    Symptoms
    Neuroglycopenic – CNS glucose deprivation
    Behavioral changes, confusion, fatigue, seizures, LOC
    Neurogenic
    Adrenergic – norepi release
    Palpitations, tremor and anxiety
    Cholinergic – acetylcholine release
    Sweating, hunger, paresthias
  • Hypoglycemia
    Signs
    Diaphoresis
    Pallor
    Tachycardia
    Increased systolic BP
    Transient focal neuro deficits
  • Hypoglycemia
    Laboratory Tests
    If history suggests prior hypoglycemia and a potential mechanism isn’t apparent
    Obtain plasma glucose, insulin, C-peptide under conditions when hypoglycemia would be expected, typically during fasting
    Treatment
    3 glucose tablets (20g), 4 oz of juice, 6 oz of soda, or 7 lifesavers – if pt is able and willing
    25g IV glucose or 1mg SC or IM glucagon - if pt is unable or unwilling to take orally
  • Hypoglycemia
    Treatment
    Fasting (postabsorptive) hypoglycemia
    Change dose of medication, no alcohol
    Endocrine tumor – surgical removal
    Reactive (postprandial) Hypoglycemia
    Dietary manipulation is an adjunct: reduce proportion of carbohydrates in the diet, increase the frequency and reduce the size of the meals
  • Hyperglycemia
    Will be covered in your Emergency Medicine class in the Fall
  • Any Questions ???