Diabetes screening diagnosis Mohsen Eledrisi MD FACE FACP

Diabetes: screening & diagnosis Mohsen Eledrisi, MD, FACE, FACP Department of Medicine Hamad Medical Corporation Doha, Qatar www. eledrisi. com

Session objectives • Recognize criteria for screening for diabetes • Describe available screening tests for diabetes • Identify diagnostic criteria for diabetes & prediabetes • Discuss management of prediabetes

What’s in a name? What does “Diabetes Mellitus” mean?

The name “Diabetes” “…the disease appears to me to have got the name diabetes, which signifies a siphon, because the fluid does not remain in the body, but uses the man’s body as a ladder…” Aretaeus (130 -200 BC)

The full name “ Urine with the smell, color, and flavor of honey ” • He introduced the term “mellitus” (honey) • So named “Diabetes Mellitus” Thomas Willis (1621 -1675)

• Diabetes = to pass • Mellitus = honey “Passing honey [sweet water]”

Consultation • A 42 -year-old healthy man is getting a “check up” • He has no complaints. Not physically active • Father had diabetes “ at an old age” • Examination: unremarkable. Only BMI 29. 2 • Fasting glucose 6. 6 mmol (120 mg) • Other tests are normal • How would you approach?

Criteria for testing for diabetes in asymptomatic adults 1. Adults with BMI ≥ 25 (≥ 23 in Asian Americans) and have any of the following additional risk factors: • Physical inactivity • First-degree relative with diabetes • High-risk race/ethnicity (e. g. , African American, Latino, Native American, Asian American, Pacific Islander) • Hypertension (≥ 140/90 mm. Hg or on therapy for hypertension) • History of cardiovascular disease • HDL cholesterol level < 0. 90 mmol (35 mg) and/or a triglyceride level > 2. 82 mmol (250 mg) • Women with polycystic ovary syndrome (PCOS) • Other clinical conditions associated with insulin resistance (e. g. , severe obesity, acanthosis nigricans) American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15

Criteria for testing for diabetes in asymptomatic adults (2) 2. Patients with prior GDM 3. All persons starting at age 45 years If results are normal, testing should be repeated at least at 3 -year intervals, with consideration of more frequent testing depending on initial results (e. g. , those with prediabetes should be tested yearly), and risk status American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15

Screening for diabetes Fasting plasma glucose How to prepare? - Fasting at least 8 hours - Water is allowed

Which units do you use? 1 mmol/L glucose = 18 m/d. L mmol = mg 18 mg = mmol 18 Example: 10 mmol = 180 mg

Fasting plasma glucose • Normal: < 5. 6 mmol (100 mg) • Diabetes: 7 mmol (126 mg) • Impaired fasting glucose (IFG) [Prediabetes]: 5. 6 to 6. 9 mmol (100 -125 mg) American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15

Screening for diabetes Which test? Fasting plasma glucose Hb. A 1 c 75 -g OGTT American diabetes association: “any of these tests can be used” American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15

Precaution Capillary glucose (glucometer) should not be used for the diagnosis of diabetes

75 -gram OGTT Oral Glucose Tolerance Test

When to do 75 -g OGTT? • Pregnancy (screening for GDM) • Screening for DM after GDM • Screening for post-transplantation DM • Diagnosis of cystic fibrosis-related DM • To confirm the diagnosis of DM (an option) • Screening for DM (an option) American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15

How to do 75 -gram OGTT Fasting and 2 -hour glucose

75 -gram OGTT 2 -hour glucose Normal < 7. 8 mmol (140 mg) Impaired Glucose Tolerance (IGT) (Prediabetes) 7. 8 -11 mmol (140 -199 mg) Diabetes 11. 1 mmol (200 mg) American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15

Use of A 1 c to diagnose DM ≥ 6. 5 Diabetes 5. 7 - 6. 4 Prediabetes < 5. 7 Normal American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15

Limitations of A 1 c • Causes of inaccurate A 1 c: 1) Quality of laboratory 2) Hemoglobin variants (hemoglobinopathies) 3) RBC turnover: • Sickle cell disease, glucose-6 -phosphate dehydrogenase deficiency • Pregnancy • Hemodialysis, Erythropoietin therapy • Recent blood loss or transfusion 4) Iron deficiency anemia, post-partum, HIV treatment American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15

Alternative to A 1 c • If A 1 c is considered inaccurate: – For screening: • Use plasma glucose – For DM follow up: • Use home glucose

How to diagnose DM ? Fasting glucose 7 mmol (126 mg) OR 2 -hour glucose post 75 grams OGTT 11. 1 mmol (200 mg) OR Hb. A 1 c ≥ 6. 5 OR Symptoms of diabetes and random glucose 11. 1 mmol (200 mg) American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15

Confirming the diagnosis of DM If 1 test is abnormal Symptoms of DM & random glucose 11. 1 mmol (200 mg) - Repeat same test - Or do a different test Diagnosis is confirmed If 2 tests are discordant Example: - A 1 c 6. 3 - Fasting PG 135 mg (7. 5 mmol) Repeat the test showing DM (FPG in this example) American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15

Back to our case • Fasting glucose 6. 5 mmol (120 mg) • He has impaired fasting glucose (prediabetes ) • What are the consequences of this condition? • What is your plan of care?

Why is prediabetes important? • High risk of type 2 DM • High risk of cardiovascular disease • Associated with obesity, HTN, dyslipidemia • Number or persons with prediabetes is more than those with DM

How to manage prediabetes?

Diabetes prevention program Persons with prediabetes (mainly IGT) • Group on lifestyle changes: - Weight loss of 7 % - Structured exercise program [moderate intensity] (150 min. /week) • Group on Metformin Risk of DM by 58 % Risk of DM by 31 % Diabetes Prevention Program Research Group. N Engl J Med 2002; 346: 393.

Effect of lifestyle changes on diabetes prevention Effect Study F/U DPPOS (USA) 15 y Risk of DM by 27 % Da Qing (China) 23 y Risk of DM by 45 % DPS (Finland) 7 y Risk of DM by 43 % Nathan D, et al. Lancet Diabetes Endocrinol 2015; 3: 866 Li G, et al. Lancet Diabetes Endocrinol 2014; 2: 474; Lindstorm J, et al. Lancet 2006; 368: 1673

Management of prediabetes • Lifestyle changes: – Weight loss of 7% – Physical activity (moderate intensity at least 150 minutes/week) • Screen and treat CVD risk factors: HTN, dyslipidemia • Metformin (especially for): • BMI ≥ 35 • Prior gestational diabetes • Age < 60 years • Metformin is not recommended for age ≥ 65 years* • Self-management education & support • Testing for diabetes yearly American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 34 *Endocrine Society guidelines. J Clin Endocrinol Metab 2019; 104: 1520

Classification of diabetes 1) Type 1 diabetes 2) Type 2 diabetes 3) Gestational diabetes 4) Specific types of diabetes due to other causes: (e. g. maturity-onset diabetes of the young, cystic fibrosis), glucocorticoids, after organ transplantation American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15

Pathophysiology of type 2 DM incretin effect Insulin Glucagon gut carbohydrate delivery & absorption Hyperglycemia + hepatic glucose production Neurotransmitter dysfunction glucose uptake renal glucose reabsorption Lipolysis

Natural history of type 2 DM Prediabetes Undiagnosed diabetes Diabetes Insulin resistance Insulin secretion Postprandial glucose Fasting glucose Microvascular complications Macrovascular complications 5 -10 5 -6 Ramlo-Halsted BA, Edelman SV. Prim Care 1999; 26: 771 Year

Diabetes: why care? • Risk of cardiovascular disease (CAD, stroke, PAD) • # 1 cause of chronic kidney disease and dialysis • # 1 cause of non-traumatic limb amputations • # 1 cause of blindness in adults • Major cause of disability and work absenteeism • It confers an equivalent risk to ageing 15 years • A huge economic impact (complications, meds, labs, . ) American Diabetes Association. Diabetes Care 2021; 44 (suppl 1): S 15 Peters S, et al. Lancet 2014; 383: 197; Center for disease control www. cdc. gov

Summary: key points • Screening for diabetes: age ≥ 45, prior GDM & high risk • Screening tests for DM: FPG, A 1 c or OGTT • Confirm the diagnosis of diabetes: repeat or alternate test • Lifestyle changes first for prediabetes • Metformin for selected patients with prediabetes