DIABETES OVERVIEW AND UPDATE Barb Bancroft RN MSN

DIABETES OVERVIEW AND UPDATE Barb Bancroft, RN, MSN, PNP Chicago IL

Historical highlights • 2 nd century A. D. Greek physician, Areteaus, noted that “Diabetes is a mysterious disease…{in which} the flesh and limbs melt into urine. ” • The term “diabetes” is from the word for ‘siphon’, and it describes the continuous flow of fluids and food in and out of the body that leaves him constantly thirsty, copiously voiding urine and severely emaciated.

Historically…the name had something to do with the kidney… Diabetes (Greek)— “to siphon” Mellitus— “sweet” or “honeyed” Insipidus—”tasteless” (1674)“Taste thy patient’s urine, for if it be sweet…” ---Dr. Thomas Willis Most diabetics lived 3 -6 years NURSE!. . . • •

Back porch diagnosis and dipsticks • Urine specimens on the back porch…flies, ants, or bees…meant sugar in the urine… • It wasn’t thaaaat long ago that we “dipstick’d” the urine for sugar

What’s in a name? The evolution… • • • “Sugar diabetes” Juvenile Onset Diabetes Mellitus (JODM) Adult Onset Diabetes Mellitus (AODM) Insulin Dependent Diabetes Mellitus (IDDM) Non-insulin Dependent Diabetes Mellitus (NIDDM) Type I (Roman numeral used) Type II (Roman numeral used) Type 1 (Arabic number) Type 2 (Arabic number)

And, it’s not thaaaaaat easy either…other types… • Type 1 A (autoimmune) • Type 1 B (idiopathic) • LADA (latent autoimmune diabetes in adults)—also referred to as Type 1. 5 Consider this diagnosis in a “skinny, type 2 diabetic that doesn’t respond well to oral drugs”—usually misdiagnosed) • MODY (maturity onset diabetes of the young) • Still making insulin? Do a C-peptide level – less than 1 ng/ml (0. 331 mmol/L) = no insulin; above 1 ng/ml = still making insulin

Definition • Chronic disorder of carbohydrate, fat and protein metabolism characterized in its fully expressed clinical form by an absolute deficiency of insulin (Type 1 diabetes) or a relative insulin deficiency (Type 2 diabetes). • Huh?

Definition • Type 1—pancreatic beta cell failure due to autoimmune disease (NO or minimal insulin) (actually type 1 A—most common) • Type 2—insulin resistance AND pancreatic beta cell dysfunction (50% normal insulin secretion with dx; after 6 years w/ disease, drops to 25%; eventually zero…) • PLUS…diabetes is a prothrombotic, proinflammatory, a proatherosclerotic and a proaccelerated proaging disease! So be PROactive in DX and RX!

RISK FACTORS for DIABETES • • • Who’s sitting in YOUR waiting room? Primary care? OB? Geriatrics? Pediatrics? Who’s laying in that bed in the coronary care unit? Stroke unit?

Who should be screened for diabetes? • Family history of type 1 or type 2 diabetes (first degree relative) THE FOLLOWING ARE RISKS FOR TYPE 2 DIABETES • Family history of early coronary heart disease • Undesirable lipid levels • Hypertension or being treated for hypertension • High risk race (black, Native American, Asian, Pacific Islander) and Ethnic group (Hispanic) • Obesity • Impaired glucose tolerance/impaired fasting glucose—metabolic syndrome, PCOS, gestational diabetes, baby weighing greater than 9 lbs. • Physical inactivity • If none of the above, start screening at 45 yr/ every 3 yr

First question--family history? • A family history of diabetes—for both type 1 and type 2 • Type 2—almost all cases have a parent or grandparent; identical twin concordance rate is 80% • Type 1— 50 -90% don’t have a family history; identical twin concordance rate is 35 -50%; 5% chance (one in twenty) if sibling has T 1 DM;

Type 1 diabetes--How many genes? • In the past five years researchers have found dozens of genes with links to diabetes • Approximately 50 genes for type 1—about half are genes that coordinate the HLA system that helps the body recognize self vs. non-self; explains why other autoimmune diseases are associated w/ T 1 DM • Celiac disease and Hashimoto’s thyroiditis

Type 1 diabetes—how many genes? • Other genes that have been found mediate the immune response to viruses (explains the viral hypothesis as a possible trigger)

Type 2 diabetes--how many genes? • Approximately 38 genes for type 2 • Genes that control the amount of insulin produced by the beta cells— and whether or not the insulin produced can overcome the insulin resistance

Family history of early coronary artery disease • What’s early? • 1 st degree relative

Undesirable lipid levels • HDL less than 35 mg/dl (0. 91 mmol/L) • Triglycerides greater than 150 mg/dl (1. 70 mmol/L) • Think diabetes or hypothyroidism with the above lipid profile • Draw a FBS or Hb. A 1 C and a TSH

Reducing triglycerides • Fish oil capsules (omega 3 s) can also reduce the TG (1 gm/day lowers TG by 5 -10%; statins (rosuvastatin/Crestor, specifically) by 30%; diet changes by 20%--increased fiber, decreased trans fats, reduce added sugars, limiting alcohol) • Higher doses for high TG (platelet problems with higher doses)— 4 gm/day • New info—doesn’t protect against CAD for primary prevention (Arch Intern Med 2012; 172: 686)

Hypertension—which comes first? • Persistent 135/80 warrants testing for DM) • 50 -60% have both DM and HTN at diagnosis— “the deadly duo” • In a diabetic patient, a systolic pressure of 130 -139 mm. Hg with a diastolic pressure of 85 -89 mm. Hg, although classified as “high normal”, warrants PROMPT treatment • However, lowering the BP to less than 120/70 doesn’t appear to improve outcomes

High risk groups for type 2 DM • • • Indian (from India)(#1) Asian (#2) Black/brown Hispanic Pacific Islanders Native American Indians Dark skinned individuals have a higher risk of Type 2 diabetes Could it have something to do with vitamin D? Beta cells also have vitamin D receptors on their surface, and people with vitamin D deficiency are at increased risk for type 2 (darker skin increased melanin—decreased vitamin D conversion)

Type 2 diabetes risk factors--weight • 85% are overweight or obese • (however, 2/3 of all overweight people and 1/3 of obese patients will never develop diabetes)

Let’s dispel a few “old” myths…#1 • Is a calorie just a calorie? • OLD ANSWER? YES, of course…cut calories? Lose weight… • NEW ANSWER? Not exactly…potatoes have been found to pack on the pounds more than the same amount of calories in walnuts… • What kind of potatoes? FRENCH FRIES…then chips, soda, red meat, mashed potatoes • (N Engl J Med June 23, 2011)

Location, location • Abdominal (visceral)--obesity and insulin resistance (fat in the liver and muscle is insulin resistant) • It’s a new organ…it’s metabolically active • It produces inflammatory mediators such as TNF-α, IL-6, C-reactive protein, and adiponectin • Waist greater than 102 cm (40 inches) in males and 88 cm (35 inches) in females • Actually your waist should be ½ your height

What is the best way to reduce belly fat? WALKING… • Ladies…the bad news… • exercise not only reduces insulin resistance it also jump starts weight loss…

Metabolic syndrome • DEFINITION: A clustering of risk factors that, in the aggregate, sharply increase the risk of cardiovascular disease and diabetes • By the time a diagnosis of diabetes is made, 7090% of patients have metabolic syndrome, irrespective of ethnicity or the definition used • Female to male ratio -- (2: 1) • Weight or body mass index is a major risk factor; 5% of normal weight; 22% overweight, and 60% of obese individuals have the metabolic syndrome

NCEP--ATP III guidelines for metabolic syndrome • Central obesity—waist size greater than 40. 2 inches in men, 34. 6 inches in women • High TG (>150 mg/d. L/1. 7 mmol/L or greater) or being treated for high triglycerides • Low HDL (less than 40 mg/d. L/1. 03 mmol/L in men, less than 50 mg/d. L / 1. 30 mmol/L in women)—or being treated for low HDL • Hypertension (≥ 130/85 mm Hg) or being treated for HTN • Fasting glucose ≥ 100 mg/d. L/ 5. 5 mmol/L or being treated for diabetes • WHO guidelines add microalbuminuria (urinary albumin to creatinine ratio 30 -300 mg/g.

Other risk factors for Type 2 diabetes —Gestational Diabetes • Gestational diabetes— 5 -9% of pregnant women in U. S. ; rates have increased 122% between 1989 and 2004 • Risk factors—obesity, advanced maternal age (over 40? 6 x greater risk) FH of DM, history of GDM or abnormal glucose metabolism, , ethnicity—Indian and Pakistani women have a 4 x greater risk; Middle Eastern and African American women have a 2 x greater risk; Lower income—higher risk

Impaired glucose tolerance • Baby weighing greater than 9 lbs. or a • Small for Gestational Age (SGA) babies • Were YOU, as a baby, exposed to intrauterine hyperglycemia ?

Polycystic Ovary Syndrome (PCOS) • First article published in 1922 by 2 French MDs entitled: “The Diabetes of Bearded Ladies…” • Metabolic syndrome is 2 -3 x higher in women with PCOS • Type 2 diabetes is 10 x higher in women with PCOS • Liver and muscle tissues are insulin resistant; ovary is NOT; hyperinsulinemia triggers androgen production with hirsutism and decreased ovulation • Metformin (Glucophage) increases insulin sensitivity, decreases hyperinsulinemia, decreases androgens, and improves ovulation

Abnormal beta cell function— increased risk of type 2 DM • “Oh, I’m so hypoglycemic…” • ONLY if it’s a documented history of hypoglycemia • Documented with an oral glucose tolerance test • Beta cells are not functioning normally after a glucose load, hence beta cell dysfunction • ~30 - 70% risk of developing type 2 DM

Duodenal exclusion surgery? • Is the cure for diabetes just a scalpel away? Not so fast…Many diabetic patients that have had gastric by -pass surgery that bypasses the duodenum and the upper small intestine have observed that their diabetes disappeared within weeks of the procedure —before any substantial weight loss. Postprandial hyperglycemia and the return of diabetes… • Gut bacteria and obesity—firmacutes vs. bacteriodetes

The surgical treatment of obesity • Roux-en-Y gastric bypass or biliopancreatic diversion surgery vs. standard medical therapy • 2 year follow-up • Complete remission with gastric bypass 75%; 95% for biliopancreatic diversion, as compared with NO remission w/ medical therapy (Mingrone)

Surgical vs. medical? • Intensive medical therapy vs. gastric bypass or sleeve gastrectomy • After 1 year, the primary endpoint, a HBA 1 C of 6% or less, only 12% of medical therapy patients achieved this goal, 42% in gastric bypass achieved the goal, and 37% in the sleeve-gastrectomy group (Schauer) • Interesting…. more to come with surgery for type 2 diabetes

Age and type 2 diabetes • The older you are, the higher the risk • Start screening at 45 and every 3 years afterwards • 50% of all type 2 diabetics are over 60; • 18% are 65 -75; • 40% of people over 80 have diabetes

Sedentary lifestyle • Lifestyle (Lack of physical activity and sedentary lifestyle) • GET OFF THE COUCH • GET OFF THE LAZY BOY • Move it, move it

What does exercise do? • Improvements in glucose tolerance due to an increase in insulin sensitivity independent of weight loss • Increase glucose uptake; decrease hepatic glucose production • Aerobic & resistance • Effect is 24 – 72 hours; no more than 2 consecutive days w/out • Prevention of T 2 DM • Sigal RJ et al. Diabetes Care 27: 2518, 2004)

Secondary diabetes • Exocrine pancreatic disease—cystic fibrosis • A 60 -year-old with newly diagnosed Type 1 DM and weight loss? Think pancreatic cancer • Cushing’s disease or syndrome • Drugs—corticosteroids, L-dopa, sympathomimetics, niacin, glucosamine, thiazide diuretics, HAART , beta blockers • Atypical anti-psychotics--Weight gain= Clozapine (Clozaril)(biggest offender) and #2 is Olanzapine (Zyprexa); 10 weeks/10 pounds • Risperidone w/ intermediate weight gain,

Do the statin drugs increase the risk of type 2 diabetes? • Latest findings…yes, BUT the statins’ proven power to prevent heart attacks and strokes outweighs ANY potential increase in type 2 diabetes risk • Study of postmenopausal women— 6. 4% not taking statins developed type 2 DM vs. 9. 9% among statin users (over an 8 year period) • Manson J. Harvard Medical School, 1/10/12

Type 1 A diabetes • Type 1 A DM—primarily diagnosed in pre-teens or teenagers; onset prior to age 40 in the majority of patients; • A Pediatrician with 2000 patients will have 3 -6 children in the practice with Type 1 diabetes • Caucasians greater than darker skinned individuals • Sardinia #1, Finland #2, Sweden #3

Type 1 A Diabetes • Associated with immune response genes and HLA-DR 3 and HLA-DR 4 (99%; 53% with both; only 3% of people without T 1 A DM have both; also DQB 1 (genetic background of Northern Europeans—Sardinia, Finland) • Autoimmune attack against beta cells of pancreas (antiglutamic acid decarboxylase antibodies—anti-GAD; ICA {islet cell antibodies}; IAA {Insulin autoantibodies})—months to years • Present with 3 p’s + weight loss—polyuria, polydipsia, polyphagia • Classic presentation is in a Caucasian, blue-eyed, blondehaired kid named…

Autoimmune disease • What triggers the autoimmune response in a genetically susceptible individual? • The most likely culprit is one of the childhood viruses…cross reaction? Molecular mimicry? • Coxsackie B? Measles? Influenza A or B? • Or?

Triggers of Type 1 diabetes… • Type 1 diabetes has increased by 5% per year since the 1980 s • In addition to viruses… • 3 other suspects. .

Too little sun—vitamin D deficiency • • Sunphobia Sunscreen maniac moms The overuse and abuse of sunscreen!! Kids playing inside (the “thumb tribe”) Pushes the immune system in the wrong direction— Abnormal regulatory T cells? 2 pathways—TH 1 and TH 2 Taking the TH 2 pathway increases the risk of allergies and autoimmune disease?

Too little dirt • The hygiene hypothesis— GUT bacteria and priming the immune system • Germphobic (mysophobic) *moms • LET THEM EAT DIRT! • (*irrational fear of DIRT)

Too much cow’s milk… • Decreased risk in babies who are breast fed • Increased risk in drinking cow’s milk early in life—is there a protein in cow’s milk that triggers diabetes in genetically susceptible individuals? • Large scale clinical trial called TRIGR, testing this hypothesis and is scheduled for completion in 2017

Other autoimmune diseases associated with Type 1 diabetes • Celiac disease—(12. 3% of T 1 DM kids in Denmark have celiac disease; 6. 4% in US have both—growth problems, iron deficiency anemia)—younger the age at DX for DM the greater the risk for celiac (Diabetes Care 2006; 29: 2452 -2456)—share HLA-DQB 1 with Type 1 DM

Autoimmune disease • Thyroid disease (Hashimoto’s thyroiditis) — 4. 8% with T 1 DM and HT); clinical presentation; check their TSH • Pernicious anemia– 2. 6%—antibodies to intrinsic factor resulting in a B 12 deficiency (may present with peripheral neuropathy in addition to anemia) • May develop years later—always have a high index of suspicion

Digression on B 12 deficiency… 3 possible causes in patients with DM 1) pernicious anemia (autoimmune) in type 1 diabetes 2) metformin in type 2 diabetes 3) use of PPIs in either type 1 or type 2 diabetes • B 12 deficiency can cause peripheral neuropathy which may be falsely attributed to the neuropathy of diabetes (check B 12 levels and check MCV as B 12 deficiency can also result in a macrocytic anemia)

Diagnosis of diabetes • Glucose levels—fasting plasma glucose or oral glucose tolerance test • Hemoglobin A 1 C (glycated hemoglobin or glycosylated hemoglobin)

Glucose levels • FBG--Before 1997 the diagnosis of DM was defined as a fasting blood glucose level of 140 mg/d. L (7. 8 mmol/L) or more OR • OGTT with a 2 -hour plasma glucose level of 200 mg/d. L (11. 1 mmol/L) w/ 75 Gm of oral glucose • In 1997 the WHO and ADA lowered the dx threshhold to 126 mg/d. L (7. 0 mmole/L)—the level at which retinopathy becomes detectable • The diagnosis is confirmed by repeat testing on a separate day

Glucose levels • In symptomatic patients, a random plasma glucose level of 200 mg/d. L (11. 1 mmole/L)or more also establishes the diagnosis • The OGTT identifies more patients w/DM but is more expensive, more complex and has lower reproducibility—used today for gestational DM

Impaired glucose tolerance/impaired fasting glucose • Impaired glucose tolerance (as defined by an oral glucose tolerance test (OGTT)— 2 -hour plasma glucose level of 140 -199 mg/d. L (7. 8 to 11. 0 mmol/L) • OR • Impaired fasting glucose—single blood draw testing sugar at a specific moment in time (ADA) — 100 to 125 mg/d. L (5. 6 mmol/L – 6. 9 mmol/L) • Impaired fasting glucose (WHO)— 110 to 125 mg/d. L (6. 1 – 6. 9 mmol/L)

Progression to diabetes • Persons categorized as “impaired” by either of these definitions have approximately a 5 -10% annualized risk of diabetes, a risk that is greater than a factor of 5 – 10 than persons with normal glucose tolerance or normal fasting glucose • If you have both the risk is approximately 10 – 15% Inzucchi SE. Diagnosis of diabetes. N Engl J Med 2012 (August 9); 367 (6): 542 -550)

Diagnosis of diabetes • Hemoglobin A 1 C—gold standard for measuring long-term glycemic control—how does it work? RBC life span • Glucose binds irreversibly with hemoglobin over the lifespan of the RBC (glycated hemoglobin) – over 2 to 3 months • Normal range is 4 -6% • Diagnosis of diabetes with level greater than 6. 5% (ADA, WHO) • Pre-diabetes—A 1 C range of 5. 7 -- 6. 4% • Identifies fewer patients w/ diabetes than FPG or OGTT • 1/3 of patients dx with FPG only; 1/3 with A 1 C only; last third w/ both tests • Certain conditions interfere with A 1 C –SCA, CKD, EPO; decreased RBC turnover

Notes on Hb. A 1 C • TIGHT control in the Type 2 diabetic does NOT always lead to the best outcomes (ADVANCE and ACCORD studies—a Hb. A 1 C of ~7 are more feasible and provide better outcomes

What about the geriatric patient? • Each patient case is individualized • Quality of life is the biggest concern • We usually think of long-term complications of treating diabetes, but in the elderly there can be some significant short-term complications

The Geriatric patient • Blood sugar -- Hb. A 1 C in the 8 -9% range is reasonable in older patients unable to live independently; less than 7% with a significant higher incidence of functional decline & deaths (regardless of Tx type) (Yau, J Am Geri Soc 2012 July; 60: 1215) • Too low? hypoglycemia can break a hip • However, hyperglycemia can lead to polyuria, incontinence, bed-wetting with skin excoriation, decubitus ulcers, dehydration, weight loss, visual changes (diplopia) • Excoriation, decubitus ulcers • Consider co-morbidities before aggressively treating— 8 years needed benefit of glycemic control in reducing microvascular complications (retinopathy, nephropathy)

Co-morbidities? • 2 -3 years for benefit from BP and lipid control for reducing macrovascular complications • However, starting a patient on a “statin” drug also has short-term benefits • Statins will decrease short term mortality and morbidity • Stabilize plaques and decrease inflammation which in turn decreases the risk of a plaque rupture, thrombosis and an MI or Stroke • Blood pressure? Hypotension can break a hip, but hypertension can increase the risk of stroke

What about kids? • More liberal numbers for kids and developing brains who are more vulnerable to the effects of hypoglycemia and who may not be able to effectively recognize or speak about the symptoms of hypoglycemia

INSULIN and GLUCAGON • Insulin is a growth hormone—stores fat and sugar and stimulates protein synthesis after the meal • Produced by the beta cells of the pancreas • Too much insulin? WEIGHT GAIN • Glucagon is a catabolic hormone produced during the fasting state; breaks down stored glycogen • Produced by the alpha cells of the pancreas • Too much? WEIGHT LOSS

Right after a meal (The postprandial state) • The pancreatic beta cells produce insulin • Insulin binds to insulin receptors and facilitates glucose entry into liver and muscle cells to be stored as glycogen (glycogenesis) • Lipogenesis—insulin binds with insulin receptors and facilitates the entry of lipids into adipocytes • Protein synthesis—insulin facilitates the transport of amino acids into muscle • GROWTH (anabolic hormone)

The fasting state • Between meals and overnight • The pancreatic alpha cells produce glucagon • Glucagon triggers glycogenolysis (breaks down stored glucose in the liver) to maintain a steady state of blood glucose (LIVER) • Lipolysis—breaks down fat tissue and forms free fatty acids • Gluconeogenesis—turns proteins into sugar

Ketoacidosis (DKA) in Type 1 diabetes • Diabetic ketoacidosis is a prolonged fasting state with an absolute deficiency of insulin; • Glucagon is working overtime—glycogenolysis; lipolysis; and gluconeogenesis • Increased counterregulatory activity—↑ cortisol, ↑ catecholamines, ↑ growth hormone=↑ BS • All contribute to hyperglycemia and osmotic diuresis • fatty acid release (ketones in the urine—osmotic diuresis)--ketoacidosis • A young girl presenting with alternating hypoglycemia and DKA – consider an eating disorder

Diabetic ketoacidosis (DKA) • One in four cases of Type 1 diabetes presents with DKA • Blood sugar > 300 mg/d. L (fruity breath odor) • Significant ketosis – urine acetoacetate (ketones), blood hydroxybutyrate) • Acidosis (p. H< 7. 3 or HC 03 < 15) (mild – 7. 2 – 7. 3; moderate 7. 1 – 7. 2; severe < 7. 1 or less than 7. 2 in a child less than 5)

DKA – presenting complaints • Gastroenteritis—abdominal pain, vomiting but NO diarrhea • Dehydration (usually 7 -10%)—but excessive urine output! (tachycardia, hypotension) • Respiratory distress—but no lung findings Kussmaul’s respirations (acidosis)(hyperventilation with slow, deep sighing breathing) • Confusion, decreased reflexes, coma

DKA--monitoring • Flow sheets for vital signs, labs, rates of insulin, fluids, dextrose • CLOSE ATTENTION to detail • Neuro status—checks every hour • ICU for severe acidosis, altered LOC, < 5 yrs, increased risk of cerebral edema

Treatmentn of DKA—it’s complicated • Dehydration is your biggest concern initially (10 -20 m. L/kg for 1 -2 hours) • GIVE FLUIDS…what kind? NS; change to ½ or ¾ depending on clinical status • CHECK ELECTROLYTES & p. H • Add K+ if less than 5. 5 and with urination; 20 m. Eq/L if 4. 5 to 5. 5; 40 m. Eq/L if less than 4. 5 • Regular insulin IV (0. 1 U kg/hr) • Then what? Check electrolytes and p. H (Blood gases every hour) • Should bicarb be given? RARELY, if EVER

Pathophysiology of Type 2 DM • Early in the disease—as the body becomes resistant to insulin, the beta cells in the pancreas must pump out more hormone to compensate; people with beta cells that can’t keep up with insulin resistance can’t move the glucose into the muscle, fat and liver cells • Insulin resistance is characterized by a rise in postprandial blood sugars • Hyperinsulinemia results. • What are the consequences of hyperinsulinemia?

Hyperinsulinemia results in… • Increased triglycerides and decreased HDLs • Triggers release of angiotensin 2 → aldosterone • Vasoconstriction and sodium and water retention— hypertension • Stimulate fat storage (CHO to fats) • Prothrombotic (increased AT 2) • Proinflammatory (increased AT 2) • Triggers endothelial cell dysfunction-fancy way of saying, deposits LDL cholesterol and triglycerides into the arterial walls • YIKES!!

Type 2 diabetes • Metabolic derangements aren’t usually as severe as Type 1 • Few symptoms initially, 2 P’s (no polyphagia), weight gain due to hyperinsulinemia • Other symptoms—fatigue, diplopia, nocturia (nocturnal diarrhea) • Skin infections, vaginal yeast infections, poor wound healing (BS >180 mg/d. L or 9 mmol/l), neuropathy • “Silent” for a full decade in some individuals

Treatment: Lifestyle changes • Must be a part of any intervention • Exercise 30 minutes daily if possible or every other day for sure… • And, nutritional counseling with reduced calorie diet (more later)

Drugs, drugs • Primary -- targets for Hb. A 1 C – 6. 5% to 7% • Secondary – fasting BG less than 120 mg/d. L • Post-prandial – less than 140 mg/d. L

Oral drugs--#1 for Type 2 diabetes

Oral Drugs—the #1 oral drug • Metformin (glucophage) does not have any direct effect on insulin release from the pancreas—doesn’t require insulin to work • Primary action: DECREASE hepatic glucose production; also, decreases glucose absorption via the GI tract, and may increase sensitivity of insulin receptors • Problem? GI blues (titrate slowly; nighttime dosing/give with food), need functioning organs-kidneys and heart especially (check serum creatinine before starting metformin) • Se Creatinine--Cut-off is 1. 4 (50 -90 mmol/L) in females and 1. 5 (70 -120 mmol/L) in males;

Metformin (Glucophage) • Other benefits: lowers BP, increases HDL, lowers LDL; • has been shown to be safe during PG (? Use for gestational diabetes? )(N Engl J Med May 8, 2008) • Improvement in menstrual irregularities and hirsutism (PCOS)--fertility • Metformin and breast cancer reduction (54%)— Diabetes Care December 2010 • Metformin and slowing the aging process • B 12 deficiency may occur • Rare, rare, for lactic acidosis

Oral drugs for type 2 DM… • 2 nd tier: The “Glitazone” sister— pioglitazone (Actos) (troglitazone/Rezulin and rosiglitazone/Avandia are history)—black box warning for bladder cancer with Actos • Alter muscle and adipocyte metabolism to improve sensitivity to insulin with secondary effects in the liver • May prolong beta cell function • Problem? Volume expansion, heart failure, dilutional anemia, weight gain (peripheral, not central; may exacerbate macular edema) • Good news? Reduce triglycerides; reduce fatty liver

OLD Drugs…effective, safe, and cheap drugs • Oral sulfonylureas—Glipizide (Glucotrol) and glyburide (Diabeta, Micronase, Glynase) (used for gestational diabetes)and glimipiride (Amaryl)… • Increase the secretion of insulin from the pancreas and increase receptor sensitivity; ? Promote beta cell failure? ? • Problem? Weight gain, hypoglycemia • glimipiride (Amaryl)—safe use in elderly--decreased incidence of hypoglycemia

Oral drugs before a meal • • • Repaglinide (Prandin)* Nateglinide (Starlix) prevent postprandial excursions Great if your meals are sporadic Prandin* (better than Starlix)

The “gliptins” • Weight neutral • Sitagliptan (Januvia) inhibits enzymes in the intestine responsible for breaking down incretins; incretins potentiate insulin release • Saxagliptin (Onglyza) • Linagliptin (Tradjenta)

Better…drug combinations • • • Actosplus Met (metformin/pioglitazone) Metaglip (glipizide and metformin) Glucovance (glyburide and metformin) Duetact (pioglitazone HCl and glimepiride) Janumet (sitagliptan and metformin) Kombiglyze (onglyza + metformin)

Incretin mimetics (April 28, 2005)— • What are incretins? Incretins are responsible for approx. 60% of the post-meal insulin secretion, but the action of the incretins is impaired in diabetics) • Exenatide (Byetta and Bydureon)—isolated from saliva of a Gila Monster • Generally added on to Type 2 diabetics who are already receiving metformin, a sulfonylurea, or both and do not have optimal control • Acts at the GLP-1 receptor, promoting insulin release • Weight loss is a + side effect (due to slowing of gastric emptying and “feeling full”) • 2 nd generation—liraglutide (Victoza)

The new face of Victoza • Liraglutide (Victoza)…qd • Bydureon (Byetta once a week) • Better than Byetta as it reduces Hg. A 1 C 1. 6% vs. 0. 9% for Byetta • Weight loss greater than Byetta but less than liraglutide • Bydureon nausea 14% vs. Byetta at 35%

“Hi YA’LL…”—my name is Paula Deen • The WEEK magazine had a contest…after she was diagnosed with type 2 diabetes they asked the readers to come up with the name of her new restaurant • What was the winning name?

The discovery of insulin (“pancreatic extract”) • Frederick Banting and his assistant, Charles Best experimented on diabetic dogs over the summer of 1921, and finally, dog number 92, a collie, hopped off the table after an injection and wagged her tail—this was the breakthrough • In the spring of 1922, Elizabeth Hughes, age 11, daughter of Justice Charles Evans Hughes, traveled to Toronto to receive insulin; she weighed 49 pounds when she arrived • Shortly after starting insulin she weighed 60 pounds • She lived another 60 years—By the time she died in 1981, at age 74, she had received 42, 000 insulin shots

Insulin • Prior to the discovery of insulin, diabetic children rarely survived more than 3 years • The first child to use insulin in the U. S. was the son of an executive for Eastman Kodak—his insulin was smuggled across the Canadian/U. S. border

Eli J. Lilly and Company (Indianapolis) • Won the right to mass produce insulin • First partnership negotiated among academia, individual physicians and the pharmaceutical industry • Chicago played a major role—slaughterhouses began sending trainloads of frozen porcine (pig) and bovine (cow) pancreas’ to Lilly’s plant in Indianapolis. • By 1932 insulin’s price had fallen by 90 percent

Insulin • Insulin is the number one choice for type 1 diabetes due to the absolute deficiency of this hormone when diagnosed • However, the pancreas will eventually give out in patients with T 2 DM and the oral agents will no longer work; over the course of 15 years, the proportion of patients using oral agents alone declines from 65% to 25%, with a corresponding increase in those using insulin • BUT new studies show that insulin should be started EARLIER in Type 2 DM…better glucose control than w/ oral meds

Insulins • Old “down –on-the-farm” insulins • Anything with the last name “ine”—bovine, porcine • Rapid-acting insulins include aspart (Novolog), glulisine (Apidra), lyspro (Humalog), • Regular insulin—Novolin R and Humulin -R • Intermediate acting insulin—neutral protamine Hagedorn (NPH)—Humulin N, Novolin N • Long-acting insulins include detemir (Levemir), glargine (Lantus)

Starting a patient on insulin • Blood sugar diary—blood sugar readings at different times of the day—fasting, before meals, two-hour postprandial, and bedtime to isolate when non-goal blood sugars are occurring • Are they having trouble with the early morning rise in glucose, the “dawn” phenomenon?

NPH continues to have some usefulness • Used to cover the DAWN phenomenon in patients – either type 1 or type 2; some type 2 patients have normal BS all day with oral agents, but their early morning rise isn’t controlled; NPH at 10 – 11 p. m. to maximize its glucose-lowering effects in the ddawn hours (~3 to 8 a. m. ) when there is a natural increase in the “counter-regulatory” hormones—cortisol, GH, glucagon) • Don’t use it too early—ie. At bedtime or early evening, as this will increase the risk for nocturnal hypoglycemia

Daily basal insulins • LANTUS (insulin glargine) or LEVEMIR (insulin detemir)—longacting basal insulins; they don’t have a peak; provide constant levels over 24 hours; • If the blood sugars are mild to moderately high “around the clock, ” the addition of a daily basal insulin is indicated • How do you switch from NPH to Lantus? Easy • Can you mix other types of insulin with Lantus? NO • Does Lantus “look” funny? YES, compared to NPH, it’s clear • Lantus and Levemir stabilize endothelial cells…HUH? Reduce atherosclerosis risk

Before we get to the complications of diabetes • First of all, not all complications are inevitable • Better control, and a better understanding of the disease process decreases “inevitable” complications • The death rate from diabetes has been DECREASING even though the numbers are increasing • SO, somebody out there is listening!!!

Complications of type 2 diabetes • Since we KNOW what the complications can be, let’s start working on prevention as soon as the disease is diagnosed • Accelerated atherosclerosis • Coronary artery disease, cerebrovascular disease, peripheral vascular disease—diffuse disease; triple vessel CAD • 10 x greater risk of CHF in females with diabetes and a 6 x greater risk of CHF in males with diabetes • Risk of stroke is 2. 5 -4 x greater in diabetics

Peripheral arterial disease • Atherosclerosis of the aorta, iliac arteries, femoral arteries • Intermittent claudication • Risk of amputation is 15 -40 x higher in the diabetic • A diabetic foot ulcer precedes amputation 85% of the time • Let’s hear it for WOCNs! • FOOT CARE!!

Wound care: What do they do with all of that circumcised foreskin? • Apligraf • Regranex (PDGF) • How about honey for wounds? ?

Are they on aspirin and/or Plavix (clopidogrel)? • Diabetes is a pro-inflammatory disease! • Diabetes is a pro-thrombotic disease • ASA is not for men under 50 and women under 60 UNLESS… other risk factors (smoking, HTN, high LDL) are present • Plavix if allergic to ASA • Plavix after a coronary event or cerebral event • Plavix with a stent • Diabetes Care , June 2010

Are they on a “Statin” to improve LDL cholesterol levels? ? And to decrease inflammation? • If not, why not? • LDL-levels should be reduced to 70 mg/d. L • Say yes to the “statin” sisters—lova (Mevacor), atorva (Lipitor), prava (Pravachol), simva (Zocor), fluva (Lescol), rosuva (Crestor), pitavastatin (Livalo) • Statins are anti-inflammatory, anti-lipid, decrease plaque formation, stabilize plaques and prevent plaque rupture • HDL greater than 40 mg/d. L in men, greater than 50 in women • Statins may also slow the progression of chronic renal disease (Fried)

Statin drugs • Should all diabetics be on statins REGARDLESS of their LDL level? • YES…YES…their anti-inflammatory effects are even more beneficial; and even if their LDL level is normal, their LDLs tend to be small and dense (Pattern B—think BBs floating around in the arteries); statins may change the size of LDLs to large and LOOSE (Pattern A)! • Small dense LDLs are even more damaging to artery walls • The reason their LDLs are small and dense is because their triglycerides are too high--PAY ATTENTION to TG!! • Fibric acid derivatives (fenofibrate) lower TG and increase particle size; extended release niacin also increases particle size

FYI • Particle size and particle number can be determined by the NMR (nuclear magnetic resonance) Lipo. Profile—cost ~ $100 to $120, slightly higher than a lipid profile • Many insurance companies cover the cost of NMR, including Medicare • Goal for particle number is less than 1000 nmil/L and goal for LDL size is 20. 6 nm or greater

What’s not to love about the statins? Yeah, yeah…side effects • Myalgias **(other causes in elderly patients…) • Myositis; rhabdomyolysis (rare)(0. 46 per 1 billion prescriptions for DEATH from rhabdomyolysis) • About 1/20 patients experiences muscle pain or weakness • Reduce the dose, don’t stop the drug • Change to Crestor? Give the statin every other day? • Check the creatine kinase if muscle aches and pains are severe

Dental care and diabetes • 1 to 2 periodontal treatments per year decreased diabetes costs by 11 -12% • Univ of Michigan School of Public Health • January 8, 2009, Science Daily • Neuropathy and dry mouth • Increased risk of yeast infections • The cardiovascular/dental health connection has been questioned

Hypertension and the diabetic • 50 -60% of all newly diagnosed diabetics have hypertension • VIGOROUSLY treat hypertension to reduce the cardiovascular risks and to reduce the risk of nephropathy • What drugs should be chosen for the treatment of hypertension? (Usually 2 are needed) First line therapy should be either the…

Prils • • • Captopril (Capoten) Enalapril (Vasotec) Lisinopril (Prinivil, Zestril) Perindopril (Aceon) Moxepril (Univasc) Benazepril (Lotensin) Quinapril (Accupril) Trandolapril (Mavik) Ramipril (Altace) • DO NOT USE DURING PREGNANCY!! or ARBs • • losartan—Cozaar valsartan—Diovan candesartan—Atacand irbesartan—Avapro telmisartan—Micardis olmesartan—Benicar Eprosartan—Tevetan Azilsartan--Edarbi

What should the 2 nd anti-hypertensive drug be? • Thiazide diuretic? (may increase BS) • Beta-blocker if they have tachycardia, angina or previous MI (may mask symptoms of hypoglycemia) • Calcium Channel blocker—verapamil or diltiazem for renoprotection • Amlodipine (Norvasc)—another calcium channel blocker

Diabetic nephropathy • Nearly 24 million people in the U. S. have diabetes; 180, 000 are living with kidney failure as a result of diabetes • Approximately 3% of newly diagnosed patients with type 2 diabetes have overt nephropathy • In patients with type 1 diabetes, the development of nephropathy usually begins after 5 years of diabetes duration, with an increasing incidence of nephropathy over the next decade of duration to a peak at about 15 to 17 years of having had diabetes

The GOOD news… • For people who live with diabetes for more than 25 years without any signs of kidney failure, the risk of ever developing it decreases ANOTHER WAY TO PUT IT… • Patients who have no proteinuria after 20 -25 years have a risk of developing overt renal disease of approximately 1% per year

The Bad News… • Kids diagnosed with TYPE 2 diabetes have a 4 fold increased risk of renal failure vs. youth with TYPE 1 diabetes • Kids with TYPE 2 diabetes have a 23 -fold increase of renal failure and a 39 -fold risk of dialysis compared to kids without DM • Dart A. Diabetes Care, June 2012; 35(6): 1265 -1271

Diabetic nephropathy…PREVENTION!! • Treat high blood pressure! • Reduce the animal protein in the diet! Especially if they have any evidence of renal involvement— the amino acids valine and lysine from animal meat increase intraglomerular hypertension and accelerate kidney damage • Reduce serum glucose! • SAY YES to the ACE inhibitors or ARBs—the PRILS or SARTANS (something to inhibit Angie and Al (Angiotensin and Aldosterone)

Treatment of Diabetic Nephropathy • Intensive target-driven treatment with targets of: < 6. 5% Hb. A 1 C, total serum cholesterol of <175 mg/d. L, and a normal blood pressure • Behavior modification program with diet and exercise, aspirin, and ACE inhibitors or ARBs • All-cause death decreased vs. placebo group (30% vs. 50%) • Decreased CV death, CV events, neuropathy, nephropathy, and retinopathy (Goede P et al. N Engl J Med 2008 Feb; 358: 580)

A quick look at the functioning unit of the kidney…Blood supply to and from the glomerulus • Afferent arteriole delivers blood to the • Glomerulus—a tuft of capillaries • Blood exits via the efferent arteriole

Barb’s artwork: the healthy kidney… • Afferent arteriole (vasodilated via (prostaglandins) • Blood entering glomerulus • Glomerulus→filter • Efferent arteriole (vasoconstricted via (angiotensin 2) • Blood exiting glomerulus PG filter AT 2 Toilet

The Diabetic Kidney…insulin resistance, hyperglycemia, hypertension, animal protein • Afferent arteriole ( vasodilation by ( prostaglandins) • Blood entering glomerulus • Glomerulus→filter • Efferent arteriole ( vasoconstriction via ( angiotensin 2) • Blood exiting glomerulus **CVD and microalbuminuria Microalbuminuria**

Microalbuminuria Indicates a stage of early nephropathy Greater than 30 mg/day or, Greater than 20 μg/min, or an albumin to creatinine ratio of 30 -300 μg/mg creatinine • Confirmed when 2 out of 3 tests are positive in a 3 month period • •

Boosting HDLs to protect the kidney • ** Higher HDLs--for every 21 -mg/d. L increase in HDLs, people are ½ as likely to develop albuminuria (Diabetes Care January 06) • Say yes to STATINS • OUCH… • Interesting side effects of statins in women • “I never had diabetes, now I have diabetes…”

Digression on the diabetic diet… • Diabetic Diet—circa 1917 • “Forty-eight hours after admission to the hospital the patient is kept on ordinary diet to determine the severity of his diabetes. Then he is starved, and no food allowed save whiskey and black coffee. Whiskey is given in the coffee: one ounce of whiskey every two hours, from 7 a. m. until 7 p. m. This furnishes roughly about 800 calories. The whiskey is not an essential part of the treatment: it merely furnishes a few calories and keeps the patient more comfortable while he is being starved. ” (Starvation Treatment for Diabetes— 1917)

Other diets • • • Exchange diet Counting carbs diet Glycemic index diet Mediterranean diet The ALL YOU CAN EAT diet

The Cardiologist’s diet? • “If it tastes good, spit it out!” • The Old Country Buffet Diet

In addition to reducing animal protein, is there such a thing as a “diabetic diet”? • Low calorie (PORTION CONTROL) • Low-fat (especially trans and saturated fats) • Low protein (especially ANIMAL protein to protect the kidneys) • High fiber (20 -35 grams per day) • Carbohydrates—what type? Count those carbs! • One visit to a nutritionist can save $13, 872 person over a 4 year period; savings in hospital charges…one visit makes a HUGE difference

What about the Atkin’s diet to lose weight? NOOOO • The Atkin’s diet is PRO-inflammatory • Saturated and trans fats • Increases intraglomerular hypertension

Know how to estimate portion size… • One teaspoon of peanut butter is the size of your thumb’s first joint • Roll the dice…cheese portion • Think baseball or tennis ball size for a portion of fruit or pasta • Think deck of cards or palm of your hand (sans fingers) for a portion of meat, fish, or chicken • Dove soap bar or mouse for the size of a baked potato

Burning calories to lose weight… • Besides the obvious activities for burning calories—walking, biking, hiking, swimming… • The “little” things mean a lot too…

When you’re just about ready to take a bite. . • It takes 2 hours and one minute for a 130 -pound person to walk off the calories in a Mc. Donald’s BIG MAC; • 3 hours and 26 minutes to walk off a Burger King Double Whopper, with cheese

Burn more calories than you take in… • Stand up when talking on the phone…burn an extra 15 calories • Chewing gum…burn an extra 11 calories • Tighten your rear-end when walking through a doorframe… 15 extra calories per squeeze • FIDGET

Burning calories • Kiss your honey every a. m. burns 6 -12 calories depending on the intensity of the kiss

Burning calories… • A wild ride in the hay burns 125 to 300 calories depending on how wild that ride happens to be! • New partner or “same old”…? ?

Helpful hints for burning calories. . • Passionate kiss three times a day… + • Mad, passionate love twice a week… = • 32, 000 calories per year, the equivalent of a 9 pound weight loss

OR. . . • Banging your head against the steps for one hour burns 150 calories…this is a suggested alternative when a wild ride in the hay isn’t an option.

Diabetic peripheral neuropathy (DPN)— FOOT CARE • Monofilament screening for sensory loss at every office visit • Longest nerves first • Small fiber loss resulting in the loss of pain, light touch, and temperature sensation • Large fiber loss later—loss of vibration and proprioception • Stocking-glove distribution

Diabetic peripheral neuropathy— “Now where did I put that sewing needle? ” Tingling or burning Walking on hot coals Walking on shards of glass—lancinating/shooting pains Treatment—analgesics, antidepressants Amitriptyline/Elavil, (duloxetine/Cymbalta), anticonvulsants (pregabalin/Lyrica) or (gabapentin/Neurontin) • Opioids as necessary • Acupuncture, TENS, magnets (but not with an insulin PUMP) • •

Autonomic neuropathy • Evaluated and followed by a cardiologist • Orthostatic hypotension (also common w/ aging) • Resting tachycardia is an important sign of the LOSS of vagal input • Silent ischemia and congestive heart failure • Need a beta-blocker (atenolol {Tenormin) • metoprolol {Lopressor, Toprol XL}), bisoprolol/Monocor/Zebeta • Metoprolol or carvedilol (Lopressor or Coreg) with CHF

Autonomic neuropathy • Gastroparesis (wide swings in blood sugar with slowed digestion interfering with the timing of insulin), early satiety, chronic N & vomiting of food digested hours before • Metoclopramide (Reglan, Maxeran), erythromycin, cisapride (special use), domperidone (Motilium)(Canada only) • Gastric pacer

Erectile dysfunction • Atherosclerosis and neuropathy are the 2 major causes • ED is an accurate indicator of CVD • The Pfizer riser (and relatives—Levitra and Cialis) are effective treatments in 50% of the cases • Injections, implants, and suction devices • VED not TED

Autonomic neuropathy • Impaired bladder emptying with hydroureter, hydronephrosis, chronic infection • Urecholine, Du. Void

Diabetic Retinopathy—number 1 cause of blindness in U. S. • SEE the EYE GUY once a year!

And lastly…TREAT the DEPRESSION! • Pick a pill any pill • Happy patients are compliant patients • SSRIs improve selfesteem • Diabetes is a 24/7 job

Thank you. • Barb Bancroft, RN, MSN, PNP • www. barbbancroft. com • BBancr 9271@aol. com

Bibliography • Bloomgarden ZT, Comi RJ, Kendall DM. New therapies to achieve glycemic control and weight loss in T 2 DM. Patient Care 2006 (February): 46 -53. • Fogel N, Zimmerman D. Management of Diabetic Ketoacidosis in the ED. Clinical Pediatric Emergency Medicine 2009; 10(4). • Fried LF, Orchard TJ, Kasiske BL. Effect of lipid reduction on the progression of renal disease: a meta-analysis. Kidney Int 2001; 59: 260 -9. • Feudtner C. Bittersweet: Diabetes, Insulin, and the Transformation of Illness. (Chapel Hill: The University of North Carolina Press, 2003) • Gebel E. The other diabetes. Diabetes Forecast 2010 May: 46 -48. • Gondeck K. LDL particle number and size. ADVANCE for NPs and PAs. January 2012 • Migrone G, et al. Bariatric surgery vs. intensive medical therapy in obese patients with diabetes. N Engl J Med 2012; 366: 1577 -85.

Bibliography • Nestler JF. Metformin for the treatment of polycystic ovary syndrome. N Engl J Med 2008 Jan 3; 358: 47 -54 • Nissen SE and Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007 Jun 14; 356: 2457 -71. • Psaty BM and Furber CD. Rosiglitazone and cardiovascular risk. N Engl J Med 2007 Jun 14; 356: 2522 -4. • Ribowsky J. Gestational Diabetes. ADVANCE for NPs & PAs; November 2010; 31 -48. • Shah AA, Durso SC. Applying clinical practice guidelines in caring for older adults with diabetes. Patient Care 2007 (February): 18 -25. • Is Avandia a flawed drug or was the big new study flawed? Prescriber’s Letter 2007 (July).

Bibliography • Insulin glulisine (Apidra): A New Rapid-Acting Insulin. The Medical Letter 2006; 48(1233). • Sitagliptin (Januvia) for Type 2 Diabetes. The Medical Letter 2007; 49(1251). • Sitagliptin/Metformin (Janumet) for Type 2 Diabetes. The Medical Letter 2007; (49)1262). • Expanding the Therapeutic Options for Type 2 Diabetes Mellitus. Clinical News 2006 (December supplement). • Gavi S, Hensley J. Diagnosis and management of type 2 diabetes in adults: A review of the ICSI guideline. Geriatrics (2009); 64(6): 12 -17. • Gebel E. Why Me? Diabetes Forecast 2010 (October); 44 -50.

Bibliography • Sernyak MJ, Leslie DL, Alarcon RD et al. Association of diabetes mellitus with the use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatr 2002; 159: 561 -6. • Szerszen A, Seminara DP, Castellanos MR. Glucose control in the hospitalized elderly—a concern not just for patients with diabetes. Geriatrics (2009); 64(6): 18 -20. • Umpierrez GE, Palacio A, Smiley D. Sliding Scale Insulin Use: Myth or Insanity? The American Journal of Medicine 2007; 120 (7). • Umpierrez GE, Isaacs SD, Bazargan N, et al. Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed hyperglycemia. J of Clin Endoc and Metabol (2002); 87(3): 978 -82. • Vasconcelos A. Could surgery spell the end of diabetes? New Scientist, Sept 2007

LADA (Latent autoimmune diabetes in adults)— 10% of all diabetics • Typical age of onset – adult • Progression to insulin dependence – months to years • Presence of autoantibodies—yes • Insulin dependence – within 6 years • Insulin resistance – some The presence of autoantibodies distinguishes this type from type 2 and no need for insulin within the first six months distinguishes it from type 1. Consider this diagnosis in a “skinny, type 2 diabetic that doesn’t respond well to oral drugs”—usually misdiagnosed

MODY— 1 to 5% of all diabetics • Maturity-onset diabetes of the young • Monogenic (single gene abnormality)—the pancreas cannot make enough insulin and/ or a defect in insulin secretion; autosomal dominant • Usually diagnosed before age 25 • 6 different subtypes—some don’t require insulin and can be treated with oral medications • doesn’t progress to ketoacidosis; persistent hyperglycemia; continued partial insulin secretion with no insulin resistance; mild to moderate hyperglycemia with a range of 130 – 250 (7 -14 mmol); absence of ++ antibodies or other autoimmune diseases

Intrauterine hyperglycemia and future risk of Type 2 DM or prediabetes 1) offspring of women with diet-treated gestational DM (21% of offspring develop T 2 DM or prediabetes ) 2) offspring of genetically predisposed women with a normal OGTT (12% develop T 2 DM or prediabetes) 3) Offspring of women with T 1 DM (11% develop T 2 DM or prediabetes) 4) Offspring of women from the normal population (4% develop T 2 DM or prediabetes) (Diabetes Care 2008 Feb 01: 31(2): 340 -6)

Estimated average glucose—a calculated conversion of A 1 c • e. AG = 28. 7 x A 1 c – 46. 7 • A 1 c (%) e. AG (mg/d. L) 5. 5 97 6 126 (7 mmol) 7 154 8 183 9 212 (11 mmol) 10 240 11 269 12 298 e. AG is a running average over the past 3 months of all glucose fluctuations; used to help patients correlate their numbers with A 1 c.

Symlin (Pramlinitide) • Amylinomimetic agent for type 1 and type 2 diabetes— synthetic analogue of the hormone amylin, which is deficient in patients with diabetes • Acts by slowing gastric emptying, curbing appetite, and suppressing postprandial plasma glucagon and hepatic glucose output • Adjunct therapy for patients with T 1 DM and T 2 DM who use mealtime insulin and have not maintained glycemic control despite optimal insulin therapy with or without oral drugs; cut mealtime doses by 50% with Symlin • Improves postprandial blood glucose and promotes weight loss