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

DIABETES OVERVIEW AND UPDATEBarb Bancroft, RN, MSN, PNPChicago IL

Definitions—new names, new drugs, new lab tests, new numbers, and a never-ending supply of new patients • (1659) Diabetes—”to siphon” • Mellitus—”sweet” • Insipidus—”tasteless” • Nurse… • “Taste thy patient’s urine, for if it be sweet…” ---Dr. Thomas Willis

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 1A (autoimmune) • Type 1B (idiopathic) • LADA (latent autoimmune diabetes in adults)—also referred to as Type 1.5 • MODY (maturity onset diabetes of the young)

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 1A—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 proacceleratedproaging disease! So be PRO-active 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?

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 T1DM;

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/ T1DM • 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 • Believed that the known genetic links to type 2 diabetes probably account for only 6 percent of the genetic predisposition • What does that mean? Either some of the genes discovered have a bigger effect than is currently believed or that 94% of the genes are still missing • Genes discovered affect the secretion of insulin from the beta cells

Other risk factors for type 2 diabetes mellitus? • Family history of early coronary heart disease • Undesirable lipid levels • Ethnic groups • Hypertension • Weight gain • Impaired glucose tolerance—metabolic syndrome, PCOS, gestational diabetes

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

Undesirable lipid levels • HDL less than 40 mg/dl (1.04 mmol/L) in men; less than 50 mg/dl (1.3 mmol) in women • Triglycerides greater than 150 mg/dl (1.70 mmol/L)(New AHA guidelines say 100 mg/dL) • Think diabetes or hypothyroidism with the above lipid profile • Draw a FBS or HbA1C and a TSH

Reducing triglycerides • Fish oil capsules (omega 3s) 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) • EPA (ecosapentanoic acid) • DHA—docosahexanoic acid) • 1000 mg/1 gram per day for established CAD • Higher doses for high TG (platelet problems with higher doses) • READ THE LABEL • Lovaza (prescription fish oil)

Hypertension—which comes first? • Greater than 140/90 (persistent 135/80 warrants testing for DM) increases the risk of diabetes • 50-60% have both DM and HTN at diagnosis— “the deadly duo” • In a diabetic patient, a systolic pressure of 130-139 mmHg with a diastolic pressure of 85-89 mmHg, 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 ethnic groups • Indian (from India)(#1) • Asian (#2) • 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

Age and type 2 diabetes • 50% of all type 2 diabetics are over 60; • 18% are 65-75; • 40% of people over 80 have diabetes

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

What did you weigh as a kid? The odds that a person who is a normal weight at age 18 will develop diabetes later in life are 1-in-5 or 1-in-6. However, if you’re very obese at age 18, you have a 3-in-4 chance of developing diabetes. 50% of all newly diagnosed children with diabetes are type 2 WHY?

Let’s dispel a few “old” myths…#1 • Is a calorie just 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, 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

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, 70-90% 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/dL/1.7 mmol/L or greater) or being treated for high triglycerides • Low HDL (less than 40 mg/dL/1.03 mmol/L in men, less than 50 mg/dL / 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/dL/ 5.5 mmol/L or being treated for diabetes • WHO guidelines add microalbuminuria (urinary albumin to creatinine ratio 30-300 mg/g.

Where do you measure waist size? • Official guidelines—locate the top of the right iliac crest; Got it? Intersect that point with a line dropped vertically from the middle of the right armpit is where you place the paper tape measure (cloth tape measures are too easy to stretch, )

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? 6x greater risk) FH of DM, history of GDM or abnormal glucose metabolism,, ethnicity—Indian and Pakistani women have a 4x greater risk; Middle Eastern and African American women have a 2x 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 10x 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

What does exercise do? • Exercise has a role in fat placement • Exercise reduces insulin resistance; one way it may do this is to burn fat out of the muscle • Because of this, getting enough exercise may stave off type 2 diabetes in some cases

Back to type 2 diabetes--the perfect storm…Type 2 • Family history– genes that control the amount of insulin produced by the beta cells—whether or not the insulin produced can overcome the insulin resistance • Abdominal obesity • Lifestyle (Lack of physical activity and sedentary lifestyle)

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…

Secondary diabetes • Exocrine pancreatic disease—cystic fibrosis • Cushing’s disease or syndrome • Drugs—corticosteroids, L-dopa, sympathomimetics, niacin, glucosamine, thiazide diuretics • Atypical anti-psychotics--Weight gain= Clozapine (Clozaril)(biggest offender) and #2 is Olanzapine (Zyprexa); 10 weeks/10 pounds • Risperidone w/ intermediate weight gain, ziprasidone (Geodon) and aripiprazole (Abilify) with least 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 1A diabetes • Type 1A DM—primarily diagnosed in pre-teens or teenagers; onset prior to age 40 in the majority of patients; • Caucasians greater than darker skinned individuals • Finland #1 country in world with Type 1 DM

Type 1A Diabetes • Associated with immune response genes and HLA-DR3 and HLA-DR4 (99%; 53% with both; only 3% of people without T1A DM have both; also DQB1 (genetic background of Northern Europeans—Sardinia, Finland) • Autoimmune attack against beta cells of pancreas (anti-glutamic acid decarboxylase antibodies—anti-GAD; ICA {islet cell antibodies}; IAA {Insulin autoantibodies})—months to years • Present with 3 p’s—polyuria, polydipsia, polyphagia, and weight loss • Classic presentation is in a Caucasian, blue-eyed, blonde-haired 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 1980s • In addition to viruses… • 3 other suspects..

Too little sun • Sunphobia • Sunscreen maniac moms • SLAP A DERMATOLOGIEST TODAY!! • Kids playing inside (the “thumb tribe”) • Pushes the immune system in the wrong direction— • Abnormal regulatory T cells? • 2 pathways—TH1 and TH2 • Taking the TH2 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—is there a protein that aggravates the immune system and 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 T1DM 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 (Diabetes Care 2006; 29:2452-2456)—share HLA-DQB1 with Type 1 DM

Autoimmune disease • Thyroid disease (Hashimoto’s thyroiditis)—4.8% with T1DM and HT); clinical presentation; check their TSH • Pernicious anemia– 2.6%—antibodies to intrinsic factor resulting in a B12 deficiency

Digression on B12 deficiency… • B12 deficiency can cause peripheral neuropathy which may be falsely attributed to the neuropathy of diabetes (check B12 levels and check MCV as B12 deficiency can also result in a macrocytic anemia) • Metformin can contribute to B12 deficiency • PPIs can cause a B12 deficiency

Laboratory diagnosis • Hemoglobin A1C—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 • 50% of glycosylated hemoglobin is from previous month; 25% from the month before; 25% 3-4 months ago • Normal range is 4-6% • *TIGHT control in the Type 2 diabetic does NOT always lead to the best outcomes (ADVANCE and ACCORD studies—HbA1c’s of 7 are more feasible and provide better outcomes

Pre-diabetes • ...one step away. HUH? • Asymptomatic fasting blood sugars between (5.5/100mg/dl)/6.1 (110) to 7.0 mmol • Used to be called impaired glucose tolerance • May have metabolic syndrome

The Geriatric Patient and blood glucose control • Blood sugars? (may want to keep the HbA1C in the 7-8 range)—hypoglycemia can break a hip • Blood pressure? Hypotension can break a hip • Consider co-morbidities before aggressively treating • Polypharmacy • Life expectancy?

Life expectancy? • Consider co-morbidities before aggressively treating—8 years needed benefit of glycemic control in reducing microvascular complications • 2-3 years for benefit from BP and lipid control for reducing macrovascular complications

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

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