Case 2: A 42 year-old male with a new diagnosis of diabetes mellitus. History - 1

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1 Case 2: A 42 year-old male with a new diagnosis of diabetes mellitus Bruce Knutsen, MD Michael Slag, MD Lisa Thomas, RN, CDE Essentia Health Diabetes and Endocrinology Conference October 14, 2011 History - 1 JD is a 42 yr-old male, who was well and on no medications, until about 3 months ago when he started feeling fatigue and a slight increase in thirst. He lost about 10 lbs without particular effort. At the time of his employer s annual health screening he was found to have a random glucose of 220 mg/dl. Family history indicated that a grandparent on either side had adult-onset diabetes and his mother had hypothyroidism due to Hashimoto s Thyroiditis. 1

2 History - 2 Weight 210 pounds (95.4 Kg) Height 5 10 (178.3 cm) BMI 30 Blood pressure 138/88 No other significant exam findings A1c-8.2% Urine glucose - positive Does he need additional laboratory tests? 1) Electrolytes 2) Creatinine 3) Lipid Profile 4) Urine Microalbumin 5) TSH 6) A, B, and C 7) All of the above 2

3 Would any of these be helpful? 1) C-peptide 2) GAD-65 (glutamic acid decarboxylase) Ab 3) IA-2 (protein tyrosine kinase-like protein) Ab 4) Insulin antibodies 5) A and B 6) None of the above 7) All of the above What kind of Diabetes is this? 1) DM1 2) DM2 3) MODY 4) LADA 5) DM1.5 3

4 Criteria for the Diagnosis of Diabetes Mellitus A1C 6.5%. (performed in a laboratory using a NGSP certified method) or FPG 126 mg/dl (7.0 mmol/l). (ie, no caloric intake for at least 8 h) or 2-hr plasma glucose 200 mg/dl (11.1mmol/l) during an OGTT (WHO method, glucose load of 75 g glucose) or Random plasma glucose 200 mg/dl (11.1 mmol/l) in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis *In the absence of unequivocal hyperglycemia, result should be confirmed by repeat testing DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 Screening for and diagnosis of GDM 1 step Method 75-g OGTT with plasma glucose: fasting, 1, and 2 hrs, at weeks of gestation in women not previously diagnosed with overt diabetes. The OGTT should be performed in the morning after an overnight fast of at least 8 hrs. The diagnosis of GDM is made when any one of the following plasma glucose values are exceeded: Fasting 92 mg/dl ( 5.1 mmol/l) 1 hour 180 mg/dl (10.0 mmol/l) 2 hour 153 mg/dl ( 8.5 mmol/l) DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org 4

5 2 Step Testing for GDM 100-g 3hr OGTT* *2 or more thresholds must be met or exceeded Step 1 is a 50-g 1 hr loading test at weeks of gestation Glucose 1 hour later > 140 mg/dl identifies ~80% Diabetes Care 2000;23(suppl 1):S4-S19 > 130 mg/dl identifies ~90% Characteristics of Type 1, Type 2, and LADA (Latent Autoimmune Diabetes in Adults) Type 1 LADA Type 2 Typical age of onset Youth or adult Adult-Younger Adult-Older % of all diabetes ~10% ~15% ~75% Progression to insulin dependence Rapid (days/weeks) Latent (months/years) Slow (years) Presence of autoantibodies Yes (IAA, IA2, GAD) Yes (usually GAD) No Insulin dependence At diagnosis Within 6 years Over time, if at all Insulin resistance No Some Yes 5

6 Eponyms for Latent Autoimmune Diabetes in Adults Latent type 1 diabetes Latent autoimmune diabetes in adults (LADA) Slowly progressive IDDM (SPIDDM) Slow-onset IDDM Slowly progressive type 1 diabetes Type 1 1/2 diabetes LADY-like Autoimmune diabetes not requiring insulin at diagnosis LADA type 1 and type 2 Slowly progressive β-cell failure Slowly progressive adult-onset type 1 diabetes Antibody-positive phenotypic type 2 diabetes with obesity Latent autoimmune diabetes in children (LADC) doi: /diabetes.54.suppl_2.S68 Diabetes December 2005 vol. 54 no. suppl S68-S72 Differential Diagnosis of Diabetes Ab, antibody; HLA, human leukocyte antigen; LADA, latent autoimmune diabetes adult; MODY, maturity-onset diabetes of the young Melmed: Williams Textbook of Endocrinology, 12th ed 6

7 Autoantibodies Markers of Beta Cell Autoimmunity Islet Cell Antibodies (ICA), anti beta cell cytoplasmic proteins Glutamic Acid Decarboxylase Antibodies (GAD-65) Insulin Autoantibodies (IAA) IA-2A, anti-protein tyrosine phosphatase Autoantibodies against GAD 65 are found in 80% of type 1 diabetics at clinical presentation + ICA and IA-2A at diagnosis for type 1 diabetes range from 69-90% and 54-75%, respectively IAA prevalence correlates inversely with age at onset of diabetes: -usually the first marker in young children at risk for diabetes -present in ~70% of young children at time of diagnosis Shivam Champaneri, MD, and Christopher Saudek, MD, immunology/full_autoantibodies_in_type_1_diabetes.html?contentinstanceid=528535&siteid=522025#n100ea Proposed model of the pathogenesis and natural history of type 1 diabetes mellitus IAA, insulin autoantibodies; GADA, glutamic acid decarboxylase antibody; ICA, islet cell antibody; IVGTT, intravenous glucose tolerance test. (Adapted from Atkinson MA, Eisenbarth GS: Type 1 diabetes: new perspectives on disease pathogenesis and treatment, Lancet 358: , 2001.) Kliegman: Nelson Textbook of Pediatrics, 19th ed 7

8 Etiologic Classification of Diabetes Type 1 diabetes (cell destruction, usually leading to absolute insulin deficiency) A. Immune mediated B. Idiopathic Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance) Other specific types Genetic defects of -cell function MODY 1-6, Others Genetic defects in insulin action, various types of specific insulin resistance Diseases of the exocrine pancreas Endocrinopathies: Acromegaly, Cushing s, Pheochromocytoma, Hyperthyroidism, Drug or chemical induced: Nicotinic acid, Diazoxide, adrenergic agonists, Thiazides, Infections; Congenital rubella, Cytomegalovirus, Others Uncommon immune-mediated diabetes; Stiff-man syndrome, insulin receptor Ab Other genetic syndromes; Myotonic dystrophy, Prader-Willi syndrome, Others, Gestational diabetes mellitus Note** Patients with any form of diabetes may require insulin treatment at some stage of their disease. Such use of insulin does not, of itself, classify the patient. Modified from: DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S65 care.diabetesjournals.org What Course would you Predict? 1) Resolution of diabetes with weight loss 2) Long term control with Metformin 3) Rapid progression to insulin 4) Slow progression to insulin 5) Near term renal dialysis 8

9 What Initial Treatment should be Considered? 1) General Diabetes Education including nutrition and exercise 2) Metformin 3) Insulin 4) Incretin analog, Exenatide (Byetta) 5) Dipeptidyl Peptidase-4 (DPP4) inhibitor (Januvia) 6) 1 and 2 7) 2 and 4 Non-Insulin Medication Classes 9

10 Insulin Options Enter Title Text Here October 12, Cochrane Database of Systematic Reviews 2011 Interventions for latent autoimmune diabetes (LADA) in adults In summary, this review demonstrates that insulin treatment may be preferable compared to sulphonylurea treatment but there is little evidence regarding other forms of treatment. Future studies are needed, should have a clear definition of LADA, investigate patient-important outcomes and use a common method of measuring stimulated C-peptide (a marker of natural insulin production reflecting improved beta-cell function of the pancreas). Last assessed as up-to-date: December Brophy S, Davies H, Mannan S, Brunt H, Williams R. Interventions for latent autoimmune diabetes (LADA) in adults. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. No.: CD DOI: / CD pub3 10

11 Initial Education Team: Patient Provider Diabetes Educator Nutrition Decrease simple sugar Consistent Carbohydrate grams for women grams for men grams for snacks Carbohydrate counting 11

12 Benefits Exercise Requires decrease insulin amounts Healthy weight Other benefits Balance Carbohydrate, Insulin and Exercise Realistic Time:150 minutes per week Ability/Motivation Blood Glucose Testing 2-4 times a day Motivation to test. Insurance driven Meter Type: Insurance driven Ease of use Coding Vision impaired Meter accuracy 15% variance Lancet Device 12

13 3 years later He has been lost to follow up and now presents with diabetic ketoacidosis and pneumonia. What happened? 1) All insulin production has ceased 2) He has stress hyperglycemia 3) He has non-diabetic ketoacidosis Should this patient be started on an Insulin Pump? 1) Yes 2) No 13

14 Insulin Pump candidate Ability Problem solving capability Carbohydrate Counting Understand risks Ketoacidosis Infection Responsible Appointments Testing Blood Glucose 4 times a day Testing Ketones Motivation Insulin Pump Candidate Unpredictable Blood Glucose Readings A1C over 7% Frequent hypoglycemia Nocturnal Hypoglycemia/ Hyperglycemia Lifestyle Career 14

15 Affordability - Insurance coverage Expensive Insurance Varies coverage % May require 3 months of blood glucose records Office notes See provider every 3 months Will patient be on Medicare at some point?? Cost Comparison Type Insulin Pump Monthly Supplies Animas Medtronic Paradigm OmniPod Accu-Chek Spirit $6345 Around $6000 $900 $6195 $ $149 $450 $151 15

16 Medicare requires: Fasting glucose and C-Peptide measurements. Fasting Glucose 225 mg/dl C-Peptide can be no greater than 110% of lowest value of the reference range Positive Autoantibody tests GAD65 Insulin Autoantibody Islet Cell autoantibody - Summary - Characteristics of LADA Adult age at diagnosis (usually over 25 years of age) Initial presentation masquerades as non-obese type 2 diabetes (does not present as diabetic ketoacidosis) Initially can be controlled with meal planning with or without diabetes oral medications Insulin dependency gradually occurs, frequently within months Positive antibodies, often GAD-65 Low C-peptide levels Unlikely to have a family history of type 2 diabetes May have a family history of other autoimmune disorders 16

17 References 1) Atkinson MA, Eisenbarth GS: Type 1 diabetes: new perspectives on disease pathogenesis and treatment, Lancet 358: , ) Brophy S, Davies H, Mannan S, Brunt H, Williams R. Interventions for latent autoimmune diabetes (LADA) in adults. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. No.: CD DOI: / CD pub3 3) care.diabetesjournals.org 4) DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY ) doi: /diabetes.54.suppl_2.S68 Diabetes December 2005 vol. 54 no. suppl S68-S72 6) 7) 8) 9) immunology/full_autoantibodies_in_type_1_diabetes.html?contentinstancei d=528535&siteid=522025#n100ea 10) Kliegman: Nelson Textbook of Pediatrics, 19th ed 11) Modified from: DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S65 12) Shivam Champaneri, MD, and Christopher Saudek, MD,