1. Management of Type 2 Diabetes Mellitus AFTER METFORMIN AND DIET DR AMAL HARFOUSH

2.  The long–term effects of diabetes mellitus include progressive development of the specific complications of retinopathy with potential blindness, nephropathy that may lead to renal failure, and/or neuropathy with risk of foot ulcers, amputation, Charcot joints, and features of autonomic dysfunction, including sexual dysfunction.  People with diabetes are at increased risk of cardiovascular, peripheral vascular and cerebrovascular disease.

3. To reduce morbidity and mortality by improving adherence to important recommendations for preventing, detecting, and managing diabetic complications.

4. Testing should be considered in all adults who are overweight (BMI >23 kg/m 2 ) and have additional risk factors: Physical inactivity A first-degree relative with diabetes High-risk ethnic population (e.g., African American, Hispanic American, Native American, Asian American, Pacific Islander) Delivered a baby weighing more than 9 lb or diagnosed with gestational diabetes mellitus Systemic hypertension (blood pressure >140/90 mm Hg or on antihypertensive therapy) High-density lipoprotein cholesterol level 250 mg/dl Polycystic ovary syndrome

5. Hemoglobin A 1c ≥5.7%, impaired glucose tolerance or impaired fasting glucose on prior testing Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans) History of cardiovascular disease

6. In those who are without these risk factors, testing should begin at age 45 yr. If screen is normal, repeat testing should be carried out at least at 3-yr intervals.

7. Dilated retinal examination by eye care specialist: if good blood sugar and blood pressure control and previous eye exam was normal, every 2 years; if diabetic changes, annually or more frequently per eye care provider Treat retinopathy. Screen for microalbuminuria if not already on an ACE inhibitor or ARB. Prescribe an ACE inhibitor (or ARB, if ACE contraindicated) for microalbuminuria or proteinuria. Serum creatinine and estimated glomerular filtration rate (eGFR Monofilament testing of feet

8. A fasting serum lielectrolytes should be obtained yearly on all adul patients with diabetes Self-monitoring of blood gluctose (SMBG) is crucial for assessing the effectiveness of the management plan. The frequency and timing of SMBG varies with the needs and goals of each patient. In most patients with type 1 DM and pregnant women taking insulin, SMBG is recommended at least 3 times/day. In patients with type 2 DM not on insulin, recommendations are unclear for pid panel, serum creatinine, and SMBG, but testing once or twice/day is acceptable in most patients Screening for thyroid dysfunction TSH level

9. Each regular diabetes visit Annually(every 3-6 monthes): Blood pressure measured and controlled Check HbA1c every 3 months if on insulin; every 6 months if on oral agents or diet only and well-controlled Optimize glycemic control Review and reinforce diet and physical activity Check weight, calculate BMI it if neuropathy present. Otherwise visual foot exam and neuropathy evaluation annually Smoking cessation counseling provided for patients with tobacco dependence

10. . Treatment of comorbidities and complications -Management of risk factors and complications. Diet, exercise, and -- pharmacologic interventions should be initiated for: -Hypertension -Cardiovascular risk -reduction Hyperlipidemia -Diabetes complications

11. Low-dose aspirin (ASA; 81 mg/day) has been proven to lower the risk of subsequent myocardial infarction, stroke, or vascular death in secondary prevention studies. The ADA recommends low-dose aspirin for primary prevention in diabetic patients with one additional cardiovascular risk factor, including age older than 40 yr, cigarette smoking, hypertension, obesity, albuminuria, hyperlipidemia, and family history of coronary artery disease. lipiMeasure fasting lipid profile at least annually in adults with low-risk d values (low-density lipoprotein [LDL] cholesterol 50 mg/dl, and triglycerides <150 mg/dl).

12. 1.All patients with diabetes older than 40 yr with one or more additional risk factors for cardiovascular disease should be on statin therapy together with lifestyle modification regardless of baseline lipid levels. 2.The primary goal is an LDL cholesterol level <100 mg/dl without overt coronaryartery disease (CAD), and in patients with overt CAD, a goal of <70 mg/dl. 3.In patients for whom target goals cannot be easily reached on maximal tolerated therapy, an alternative therapeutic goal should be the reduction in LDL of ∼ 30% to 40% from baseline.

13. Aggressive antihypertensive therapy is recommended to keep systolic blood pressure (BP) <140 and diastolic BP <90 mm Hg. Use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to decrease albuminuria and for prevention of progression of kidney disease should be considered regardless of presence of hypertension Bariatric surgery should be considered in adults with BMI >35 kg/m 2 and type 2 diabetes, especially if the diabetes is difficult to control with lifestyle and pharmacologic therapy.

14. Management of Diabetes Mellitus

15.  The major components of the treatment of diabetes are: Diet and Exercise A Oral hypoglycaemic therapy B Insulin Therapy C

16.  Diet is a basic part of management in every case. Treatment cannot be effective unless adequate attention is given to ensuring appropriate nutrition.  Dietary treatment should aim at: ◦ ensuring weight control ◦ providing nutritional requirements ◦ allowing good glycaemic control with blood glucose levels as close to normal as possible ◦ correcting any associated blood lipid abnormalities

17. The following principles are recommended as dietary guidelines for people with diabetes:  Dietary fat should provide 25-35% of total intake of calories but saturated fat intake should not exceed 10% of total energy. Cholesterol consumption should be restricted and limited to 200 mg or less daily.  Protein intake can range between 10-15% total energy (0.8-1 g/kg of desirable body weight). Requirements increase for children and during pregnancy. Protein should be derived from both animal and vegetable sources.  Carbohydrates provide 50-60% of total caloric content of the diet. Carbohydrates should be complex and high in fibre.  Excessive salt intake is to be avoided. It should be particularly restricted in people with hypertension and those with nephropathy.

18.  Physical activity promotes weight reduction and improves insulin sensitivity, thus lowering blood glucose levels.  Together with dietary treatment, a programme of regular physical activity and exercise should be considered for each person. Such a programme must be tailored to the individual’s health status and fitness.  People should, however, be educated about the potential risk of hypoglycaemia and how to avoid it.

19. Comparisons of Agents for Glycemic Control in Patients with Type 2 Diabetes Biguanide (Metformin) Contraindicated for Scr>1.4 in ♀ ; Scr>1.5 in ♂ Sulfonyl ureas(2nd gene) Thiazolidnedione Non-sulfonylurea insulin secretogogues DPP4 Inhibitor Sodium-glucose cotransporter 2 (SGLT2) Inhibitor(ganagliflozine dapagliflozine)

20. Incretin mimetic Exenatide – liraglutide `Rapid-acting insulin Lispro (Humalog) Aspart (NovoLog) Glulisiline(apidra) short acting (regular) Intermediate regular(NPH) Long acting(glargine)

21. As first line therapy:  Obese type 2 patients, consider use of metformin, acarbose or TZD.  Non-obese type 2 patients, consider the use of metformin or insulin secretagogues  Metformin is the drug of choice in overweight/obese patients. TZDs and acarbose are acceptable alternatives in those who are intolerant to metformin.  If monotherapy fails, a combination of TZDs, acarbose and metformin is recommended. If targets are still not achieved, insulin secretagogues may be added

22.  If glycaemic control is not achieved (HbA1c > 6.5% and/or; FPG > 7.0 mmol/L or; RPG >11.0mmol/L) with lifestyle modification within 1 –3 months, ORAL ANTI-DIABETIC AGENT should be initiated.  In the presence of marked hyperglycaemia in newly diagnosed symptomatic type 2 diabetes (HbA1c > 8%, FPG > 11.1 mmol/L, or RPG > 14 mmol/L), oral anti-diabetic agents can be considered at the outset together with lifestyle modification.

23. Combination oral agents is indicated in:  Newly diagnosed symptomatic patients with HbA1c >9  Patients who are not reaching targets after 3 months on monotherapy

24.  If targets have not been reached after optimal dose of combination therapy for 3 months, consider adding intermediate-acting/long-acting insulin (BIDS).  Combination of insulin+ oral anti-diabetic agents (BIDS) has been shown to improve glycaemic control in those not achieving target despite maximal combination oral anti-diabetic agents.  Combining insulin and the following oral anti-diabetic agents has been shown to be effective in people with type 2 diabetes: ◦ Biguanide (metformin) ◦ Insulin secretagogues (sulphonylureas) ◦ Insulin sensitizers (TZDs)(the combination of a TZD plus insulin is not an approved indication) ◦ α-glucosidase inhibitor (acarbose)  Insulin dose can be increased until target FPG is achieved.

25.  In elderly non-obese patients, short acting insulin secretagogues can be started but long acting Sulphonylureas are to be avoided. Renal function should be monitored.  Oral anti-diabetic agent s are not recommended for diabetes in pregnancy  Oral anti-diabetic agents are usually not the first line therapy in diabetes diagnosed during stress, such as infections. Insulin therapy is recommended for both the above  Targets for control are applicable for all age groups. However, in patients with co-morbidities, targets are individualized  When indicated, start with a minimal dose of oral anti-diabetic agent, while reemphasizing diet and physical activity. An appropriate duration of time (2-16 weeks depending on agents used) between increments should be given to allow achievement of steady state blood glucose control

26. Short-term use:  Acute illness, surgery, stress and emergencies  Pregnancy  Breast-feeding  Insulin may be used as initial therapy in type 2 diabetes  in marked hyperglycaemia  Severe metabolic decompensation (diabetic ketoacidosis, hyperosmolar nonketotic coma, lactic acidosis, severe hypertriglyceridaemia) Long-term use:  If targets have not been reached after optimal dose of combination therapy or BIDS, consider change to multi-dose insulin therapy. When initiating this,insulin secretagogues should be stopped and insulin sensitisers e.g. Metformin or TZDs, can be continued.

27.  The majority of patients will require more than one daily injection if good glycaemic control is to be achieved. However, a once-daily injection of an intermediate acting preparation may be effectively used in some patients.  Twice-daily mixtures of short- and intermediate-acting insulin is a commonly used regimen.  In some cases, a mixture of short- and intermediate-acting insulin may be given in the morning. Further doses of short- acting insulin are given before lunch and the evening meal and an evening dose of intermediate-acting insulin is given at bedtime.  Other regimens based on the same principles may be used.  A regimen of multiple injections of short-acting insulin before the main meals, with an appropriate dose of an intermediate- acting insulin given at bedtime, may be used, particularly when strict glycaemic control is mandatory.

28. Steps in Glycemic Control with Oral Agents in Patients with Type 2 Diabetes Step 1 Essential treatment for all patients with type 2 diabetes Comprehensive diabetes education Healthy eating Physical activity Metformin at maximum dose tolerated, not to exceed 2000 mg/daily*, unless not tolerated or otherwise contraindicated Re-measure A1c in 6-12 weeks after initiation or dose change of medication

29. Step 2: If A1c: < 7% or below individualized target no additional agents. ≥ 9%, consider insulin ≥ 7% but < 9%, add a second agent or insulin customized to patient. Re-measure A1c in 6-12 weeks after initiation or dose change of medication

30. Step 3. With addition of second agent, if A1c: < 7% or below individualized target no additional agents. ≥ 9%, consider insulin ≥ 7% but < 9%, consider adding a third agent or insulin customized to patient. If suboptimal control persists, despite maximal oral therapy, insulin therapy should be initiated.

31. Distress, stress and coping. Do you often feel overwhelmed by all you have to do to manage your diabetes? Are you feeling more stressed than usual? How do you cope with this stress? Psychological status. How is diabetes affecting you emotionally? Are your emotions interfering with your ability to manage your diabetes? How do you handle these feelings

32. Family planning/birth control :. Are you considering pregnancy? If so, are you at your glucose control goal? If not, are you using birth control? At least annually ask about: Identification. Do you wear or carry diabetes identification?

33. Complications screening. Do you know (1) your results on screening tests? (2) when you should be tested next? Foot care. (1) What do you do to take care of your feet? (2) Do you check your feet each day? Injection sites for insulin. Do you rotate your injection sites around your abdomen and inspect