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

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

2. Historical highlights • 2nd 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.

3. 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!...

4. 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

5. 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)

6. 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 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

7. 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?

8. 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!

9. 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?

10. Who should be screened for diabetes? • Family history of type 1 or type 2diabetes (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

11. 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;

12. 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

13. 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)

14. 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

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

16. 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 HbA1C and a TSH

17. 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) • 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)

18. 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 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

19. 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)

20. 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)

21. 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)

22. 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

23. 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…

24. 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

25. 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.

26. 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

27. 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 ?

28. 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

29. 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

30. 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

31. 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)

32. Surgical vs. medical? • Intensive medical therapy vs. gastric bypass or sleeve gastrectomy • After 1 year, the primary endpoint, a HBA1C 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

33. 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

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

35. 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 T2DM • Sigal RJ et al. Diabetes Care 27:2518, 2004)

36. 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,

37. 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

38. Type 1A diabetes • Type 1A 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

39. 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 + weight loss—polyuria, polydipsia, polyphagia • Classic presentation is in a Caucasian, blue-eyed, blonde-haired kid named…

40. 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?

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

42. 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—TH1 and TH2 • Taking the TH2 pathway increases the risk of allergies and autoimmune disease?

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

44. 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

45. 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 for celiac (Diabetes Care 2006; 29:2452-2456)—share HLA-DQB1 with Type 1 DM

46. 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 (may present with peripheral neuropathy in addition to anemia) • May develop years later—always have a high index of suspicion

47. Digression on B12 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 • 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)

48. Diagnosis of diabetes • Glucose levels—fasting plasma glucose or oral glucose tolerance test • Hemoglobin A1C (glycated hemoglobin or glycosylated hemoglobin)

49. Glucose levels • FBG--Before 1997 the diagnosis of DM was defined as a fasting blood glucose level of 140 mg/dL (7.8 mmol/L) or more OR • OGTT with a 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) w/ 75 Gm of oral glucose • In 1997 the WHO and ADA lowered the dxthreshhold to 126 mg/dL (7.0 mmole/L)—the level at which retinopathy becomes detectable • The diagnosis is confirmed by repeat testing on a separate day

50. Glucose levels • In symptomatic patients, a random plasma glucose level of 200 mg/dL (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