diabetes mellitus ADA 2018 Dr.shamsaee

Screening for Diabetes Testing should begin at age 45 for all people. B Consider testing for prediabetes in asymptomatic adults of any age w/ BMI ≥25 kg/m2 or ≥23 kg/m2 (in Asian Americans) who have 1 or more add’l risk factors for diabetes. B If tests are normal, repeat at a minimum of 3-year intervals. C

Screening for Type 2 Diabetes FPG, 2-h PG after 75-g OGTT, and the A1C are equally appropriate. B In patients with diabetes, identify and, if appropriate, treat other CVD risk factors. B Consider testing for T2DM in overweight/obese children and adolescents with 2 or more add’l diabetes risk factors. E

Risk factors for Prediabetes and T2D

Prediabetes FPG 100–125 mg/dL (5.6–6.9 mmol/L): IFG OR 2-h plasma glucose 140–199 mg/dL (7.8–11.0 mmol/L): IGT A1C 5.7–6.4%

Criteria for the Diagnosis of Diabetes Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) OR 2-h plasma glucose ≥200 mg/dL (11.1 mmol/L) during an OGTT A1C ≥6.5% Classic diabetes symptoms + random plasma glucose ≥200 mg/dL (11.1 mmol/L)

Detection and Diagnosis of GDM Test for undiagnosed T2DM at the 1st prenatal visit in those with risk factors. B Test for GDM at 24–28 weeks of gestation in women not previously known to have diabetes. A Screen women with GDM for persistent diabetes at 4–12 weeks postpartum, using the OGTT. E

One-Step Strategy 75-g OGTT; Measure plasma glucose at fasting and at 1 and 2 hours. GDM dx’d when plasma glucose exceeds: Fasting: 92 mg/dL (5.1 mmol/L) 1 h: 180 mg/dL (10.0 mmol/L) 2 h: 153 mg/dL (8.5 mmol/L)

Two-Step Strategy Step 1: In women not previously dx’d with overt diabetes, perform 50-g GLT (nonfasting); Measure plasma glucose at 1 hour. If 1 hour plasma glucose level is ≥140 mg/dL* (7.8 mmol/L), proceed to step 2.

Step 2: 100-g OGTT is performed while patient is fasting. The diagnosis of GDM is made if 2 or more of the following plasma glucose levels are met or exceeded.

Evaluation and Assessment of Comorbidities Autoimmune Diseases (T1D) Cancer Cognitive Impairment Dementia Fatty Liver Disease Fractures Hearing Impairment HIV Low Testosterone (Men) Obstructive Sleep Apnea Periodontal Disease Psychosocial Disorders

Lifestyle Management Weight loss if overweight DASH-style diet Moderation of alcohol intake Increased physical activity

Glycemic Targets Two primary techniques available for health providers and patients to assess effectiveness of management plan on glycemic control Patient self-monitoring of blood glucose (SMBG) A1C

Pharmacologic Approaches to Glycemic Treatment Metformin, if not contraindicated and if tolerated, is the preferred initial pharmacologic agent for T2DM. A Consider insulin therapy (with or without additional agents) in patients with newly dx’d T2DM who are markedly symptomatic and/or have elevated blood glucose levels (>300 mg/dL) or A1C (>10%). E

If noninsulin monotherapy at maximal tolerated dose does not achieve or maintain the A1C target over 3 months, add a second oral agent, a GLP-1 receptor agonist, or basal insulin. A Use a patient-centered approach to guide choice of pharmacologic agents. E Don’t delay insulin initiation in patients not achieving glycemic goals. B

Choice in ASCVD Potential benefit: Metformin and Pioglitazone Benefit: Liraglutide and Canagliflozin and Empagliflozin Others: Neutr

Choice in CHF Benefit: Canagliflozin and Empagliflozin Potential risk: Saxagliptin and Alogliptin Increase risk: TZDs Others: Neutr

Choice in CKD Benefit: Liraglutide and Canagliflozin and Empagliflozin Others: Neutr

Effects on weight Loss : SGLT2 inhibitors, GLP1R agonists, Metformine (moderate) Gain : TZD, Sulfonylureas, Insulin Neutr : DPP4 inhibitors

No dose adjustment required TZD Colesevelam Bromocriptine (quick release) Liraglutide Pramlintide

Metformine No dose adjustment if eGFR >45 do not initiate OR assess risk/benefit if currently on metformin if eGFR 30–45; discontinue if eGFR <30

Concentrated Insulin Products Several concentrated insulin preparations are currently available. U-500 regular insulin, by definition, is five times as concentrated as U-100 regular insulin and has a delayed onset and longer duration of action than U-100 regular, possessing both prandial and basal properties. U-300 glargine and U-200 degludec are three and two times as concentrated as their U-100 formulations and allow higher doses of basal insulin administration per volume used. The FDA has also approved a concentrated formulation of rapid-acting insulin lispro, U-200 (200 units/mL). These concentrated preparations may be more comfortable for the patient and may improve adherence for patients with insulin resistance who require large doses of insulin.

Combination Injectable Therapy If basal insulin has been titrated to an acceptable fasting blood glucose level (or if the dose is.0.5 units/kg/day) and A1C remains above target, consider advancing to combination injectable therapy.

In general, GLP-1 receptor agonists should not be discontinued with the initiation of basal insulin. Basal insulin plus GLP-1 receptor agonists are associated with less hypoglycemia and with weight loss instead of weight gain but may be less tolerable and have a greater cost .

Sulfonylureas, DPP-4 inhibitors, and GLP-1 receptor agonists are typically stopped once more complex insulin regimens beyond basal are used. In patients with suboptimal blood glucose control, especially those requiring large insulin doses, adjunctive use of a thiazolidinedione or SGLT2 inhibitor may help to improve control and reduce the amount of insulin needed.

When initiating combination injectable therapy, metformin therapy should be maintained while other oral agents may be discontinued.

premixed insulin NPH/Regular 70/30, 70/30 aspart mix, 75/25 or 50/50 lispro mix. Studies have demonstrated the noninferiority of basal insulin plus a single injection of rapid-acting insulin at the largest meal relative to basal insulin plus a GLP-1 receptor agonist relative to two daily injections of premixed insulins. If one regimen is not effective consider switching to another regimen to achieve A1C targets.

Type 1 Diabetes Most people with T1DM should be treated with multiple daily injections of prandial insulin and basal insulin . Consider educating individuals with T1DM on matching prandial insulin dose to carbohydrate intake, premeal blood glucose, and anticipated activity. E Most individuals with T1DM should use insulin analogs to reduce hypoglycemia risk. A

Start usually with 0.5 ( 0.4 _ 1) u/kg/d Higher doses required : During puberty Following presentation with ketoacidosis

The insulin analogsThe insulin analogs The analogs are associated with less hypoglycemia, less weight gain, and lower A1C than human insulins in people with type 1 diabetes. Longer-acting basal analogs (U-300 glargine or degludec) may additionally convey a lower hypoglycemia risk compared with U-100 glargine in patients with type 1 diabetes

The inhaled insulin Rapid-acting inhaled insulin used before meals in patients with type 1 diabetes was shown to be noninferior when compared with aspart insulin for A1C lowering, with less hypoglycemia observed with inhaled insulin therapy . Because inhaled insulin cartridges are only available in 4-, 8-, and 12-unit doses, limited dosing increments to fine-tune prandial insulin doses in type 1 diabetes are a potential limitation.

Pramlintide FDA approved for T1DM Amylin analog Delays gastric emptying, blunts pancreatic glucose secretion, enhances satiety Induces weight loss, lowers insulin dose Requires reduction in prandial insulin to reduce risk of severe hypos Pen injector 15-30-45-60-120 sc

Metformin Adding metformin to insulin therapy may reduce insulin requirements and improve metabolic control in patients with type 1 diabetes. In one study, metformin was found to reduce insulin requirements and led to small reductions in weight and total and LDL cholesterol but not to improved glycemic control.

Cardiovascular Disease and Risk Management Blood pressure should be measured at every routine visit. B People with diabetes and hypertension should be treated to blood pressure goal of <140 /90 mmHg. A Lower targets, such as BP<130/80 mmHg, may be appropriate for certain individuals at high risk of CVD, if they can be achieved without undue treatment burden. C

Treatment for hypertension should include a: ACE inhibitor Angiotensin II receptor blocker (ARB) Thiazide-like diuretic Dihydropyridine calcium channel blockers Multiple drug therapy (two or more agents at maximal doses) generally required to achieve BP targets.

An ACE inhibitor or angiotensin receptor blocker, at the maximum tolerated dose indicated for blood pressure treatment, is the recommended first-line treatment for hypertension in patients with diabetes and urinary albumin–to– creatinine ratio >300 mg/g creatinine (A) or 30–299 mg/g creatinine (B). If one class is not tolerated, the other should be substituted. B

Lipid Management Intensify lifestyle therapy & optimize glycemic control for patients with: C Triglyceride levels >150 mg/dL (1.7 mmol/L) and/or HDL cholesterol <40 mg/dL (1.0 mmol/L) in men and <50 mg/dL (1.3 mmol/L) in women For patients with fasting triglyceride levels ≥ 500 mg/dL (5.7 mmol/L), evaluate for secondary causes and consider medical therapy to reduce the risk of pancreatitis. C

Combination therapy (statin/fibrate) doesn’t improve ASCVD outcomes and is generally not recommended A. Consider therapy with statin and fenofibrate for men with both trigs ≥204 mg/dL (2.3 mmol/L) and HDL ≤34 mg/dL (0.9 mmol/L). B

Antiplatelet Agents As a primary prevention strategy in those with type 1 or type 2 diabetes at increased cardiovascular risk Includes most men or women with diabetes age ≥50 years who have at least one additional major risk factor, including: Family history of premature ASCVD Hypertension Smoking Dyslipidemia Albuminuria

Use aspirin therapy (75–162 mg/day) as secondary prevention in those with diabetes and history of ASCVD. A For patients w/ ASCVD & aspirin allergy, clopidogrel (75 mg/day) should be used. B

In asymptomatic patients, routine screening for CAD isn’t recommended & doesn’t improve outcomes provided ASCVD risk factors are treated. A Consider investigations for CAD with: Atypical cardiac symptoms (e.g. unexplained dyspnea, chest discomfort) Signs or symptoms of associated vascular disease incl. carotid bruits, transient ischemic attack, stroke, claudication or PAD EKG abnormalities (e.g. Q waves) E

Management of Diabetes in Pregnancy Provide preconception counseling that addresses the importance of glycemic control as close to normal as safely possible, ideally <6.5% to reduce the risk of congenital anomalies. B

Women w/ preexisting type 1 or type 2 diabetes who are pregnant or planning to become pregnant should be counseled on the risk of development and/or progression of diabetic retinopathy. Eye exams should occur before pregnancy or in the first trimester & then be monitored every trimester and for 1 year postpartum as indicated by degree of retinopathy. B

Lifestyle change is an essential part GDM mgmt Lifestyle change is an essential part GDM mgmt. and may suffice for many women. Add medications if needed to achieve glycemic targets. A Insulin is the preferred medication for treating hyperglycemia in GDM, as it does not cross the placenta. Metformin and glyburide may be used but both, particularly metformin, cross the placenta. All oral agents lack long-term safety data. A

Fasting and postprandial SMBG are recommended in both GDM and preexisting diabetes in pregnancy to achieve glycemic control. Some women with preexisting diabetes should also test blood glucose preprandially. B In pregnant patients with diabetes and hypertension, BP targets 120-160/80-105 are suggested. E

For women with gestational diabetes or preexisting type 1 or type 2 diabetes in pregnancy, the following targets are recommended: Fasting ≤95 mg/dL (5.3 mmol/L) and either One-hour postprandial ≤140 mg/dL (7.8 mmol/L) or Two-hour postprandial ≤120 mg/dL (6.7 mmol/L)