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Can we Bridge the Gap between clinical practice &Guidelines in T2DM ?


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By Dr. Ashraf Al- Abasiry , MBBCh,MSc Internist Specialist


Diabetes: Worldwide Epidemic Diabetes : i s fast becoming the epidemic of the 21st century, Diabetes : is expected to affect nearly 550 million people, about seven per cent of the world's  adult population , by 2030 , Worldwide 3.2 million diabetes-related deaths are reported annually, a number equivalent to that of HIV/AIDS-related deaths. One in every 20 deaths is attributed to diabetes equating to 8,700 deaths per day, or 6 deaths every minute.


Type 2 Diabetes : is by far the most common type of diabetes in adults (>90 percent) and is characterized by hyperglycemia and variable degrees of insulin deficiency and resistance. The majority of patients are asymptomatic and hyperglycemia is noted on routine laboratory evaluation, prompting further testing. The frequency of symptomatic diabetes has been decreasing in parallel with improved efforts to diagnose diabetes earlier through screening.


Classic symptoms of hyperglycemia include polyuria, polydipsia, nocturia, blurred vision and, infrequently, weight loss. Morbidity from diabetes is a consequence of both macrovascular disease (atherosclerosis) and microvascular disease (retinopathy, nephropathy, and neuropathy). In type 2 diabetes, disease onset is insidious, and diagnosis is often delayed. As a result, diabetic microvascular complications may be present at the time of diagnosis of diabetes [ 1 ], and their frequency increases over time Li C, Balluz LS, Okoro CA, et al. Surveillance of certain health behaviors and conditions among states and selected local areas --- Behavioral Risk Factor Surveillance System, United States, 2009. MMWR Surveill Summ 2011; 60:1. 1- Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis. Diabetes Care 1992; 15:815.


Brain Cerebrovascular disease Transient ischemic attack Cerebrovascular accident Cognitive impairment Complications of Diabetes Heart Coronary artery disease Coronary syndrome Myocardial infarction Congestive heart failure Extremities Peripheral vascular disease Ulceration Gangrene Amputation Macrovascular Microvascular Eye Retinopathy Cataracts Glaucoma Kidney Nephropathy Microalbuminuria Gross albuminuria Kidney failur e Nerves Neuropathy Peripheral Autonomic


"Never offer the devil a ride. He will always want to be in the driving seat…!" BK .


Clinical Practice Guidelines Of TYPE 2 D M Of TYPE 2 D M How can we Bridge The Gap ?


Who to Screen for Diabetes?


Screening for Diabetes Mellitus Diagnose type 2 diabetes mellitus (DM) at a stage early enough that effective treatment can minimize the risk of severe microvascular and macrovascular complications. RECOMMENDATIONS 1-Screening for pre-diabetes or diabetes should be considered for all adults age ≥45. 2. Screening for pre-diabetes or diabetes should be considered in younger adults who are overweight or obese (BMI ≥ 25 kg/m2 ) or are at high risk for DM based upon established risk factors at 1-3 year Intervals.


3. Screening for pre-diabetes or diabetes should occur at a frequency of 1-3 years. More frequent screening can be performed depending upon prior HbA1c or FPG results, and patient or clinician preferences. 4. Fasting plasma glucose (FPG) is the preferred diagnostic test for pre-diabetes and DM and is also a component of diagnostic testing. 5. HbA 1 c can be used to screen for pre-diabetes or diabetes, when obtaining a blood sample in a fasting state is undesirable, but fasting plasma glucose test is required for the purpose of diagnosis.


6- Diagnosis of DM is made if any of the following: a- Fasting plasma glucose (FPG) is ≥126 mg/dL on at least two occasions, or b. A single HbA1c reading of ≥ 6.5%, confirmed with a FPG ≥126 mg/dL. These tests can be done on the same or different days; or c. Symptoms of hyperglycemia and a casual (random) glucose ≥ 200 mg/dL on two occasions. However, casual (random) plasma glucose is not recommended as a routine screening test


Diagnosis of Diabetes: Values for Diabetes/Pre-Diabetes


DEFINITION / DESCRIPTION : This update of the Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus is designed for primary care providers. This guideline applies to adult patients with diabetes mellitus Type2 receiving treatment in the Primary Care Department.


Purpose : This guideline describes the care objectives for the prevention, diagnosis and management of diabetes mellitus (DM) in non-pregnant adults. The algorithms serve as a guide that providers can use to determine best interventions and timing of care for their patients in order to optimize quality of care and clinical outcomes. The AACE/ACE algorithm is intended to be an algorithm, flowchart, or treatment pathway that can be easily learned and followed by primary care providers and nondiabetologists .


TREATMENT GOALS 1- Degree of glycemic control   Improved glycemic control significantly reduces risk of diabetes-related complications. UKPDS results indicated that a 1% reduction in A1C would reduce the risk of microvascular complications by 37%, but have less effect (16%) on macrovascular complications . . Target A1C goals in patients with type 2 diabetes should be tailored to the individual, balancing the improvement in microvascular complications with the risk of hypoglycemia. .


2- Cardiovascular risk factor management     In addition to glycemic control, vigorous cardiac risk reduction (smoking cessation,aspirin, blood pressure control, reduction in serum lipids, diet, and exercise) should be a top priority for all patients with type 2 diabetes.


3- Effectiveness of early detection  :  Cost-effectiveness analyses have suggested that diabetes screening in older adults is cost-effective. The benefits of early detection for all screening strategies included a reduced incidence of myocardial infarction and microvascular complications and an increase in quality-adjusted life years (QALYs) over 50 years of age. The most cost-effective strategies were those that started between the ages of 30 and 45 years, with screening repeated every three to five years.


This document is organized into discrete sections that address the following topics: 1- obesity , 2- prediabetes, 3- management of hyperglycemia through lifestyle modifications, pharmacotherapy and insulin, 4- management of hypertension , 5- management of hyperlipidemia, and other risk-reduction strategies.


48-year-old woman with newly diagnosed asymptomatic type 2 diabetes. She presented with results from polyclinic that revealed:   (HbA 1c ) o f 7.4 % and a RBS: level of 172 mg/dL . Since she received the results 3 months ago, She has improved her diet and has begun walking 30 minutes twice per week. She subsequently was seen by a primary care physician who obtained additional fasting laboratory data. FBS: 136  HbA 1c   6.9% , (BUN) 22 mg/dL , creatinine 1.1 mg/dL , (TCh) : 210 mg/dL , (HDL) cholesterol 36 mg/dL , TG 240 mg/dL , (LDL) cholesterol 130 mg/dL , (AST) 42 IU/L, and (ALT) 48 IU/L . A screening test for microalbuminuria was negative . TSH : normal Case Study 1


F/H : mother with diabetes who died at age 66 following an acute myocardial infarction. Her father, a smoker, had hypertension and died of a cerebrovascular accident at age 70 years . A physical examination reveals that body mass index [BMI], 32 kg/m2 ). Her BP :is 138/82 mm Hg, HR is 76 /Mm and regular, and waist circumference is 38". The remainder of the physical exam was unremarkable. Fundoscopy was normal.


Because the patient has type 2 diabetes based on a fasting plasma glucose of 172 mg/dL and an HbA 1c of 7.4 % , what approach should be considered for initial therapy in addition to continuing attempts to help her modify her lifestyle? 1- Basal insulin therapy starting at 18 U every night, with self-titration of insulin. 2-Basal insulin 18 U daily and metformin 500 daily. 3- Metformin 500 mg twice daily. 4- Glimepiride 2 mg once daily. 5- A GLP-1 receptor agonist daily.


Follow-up Visit Patient returns 3 months after treatment on metformin 500 mg twice daily with an HbA 1c  of 6.9% and a fasting plasma glucose of 127 mg/dL . She reports occasional nausea and mild but tolerable intermittent diarrhea. The AACE/ACE algorithm strongly recommends that the physician should monitor therapy closely (every 2 to 3 months) and intensify treatment until the goal for HbA 1c  has been achieved.


How would you modify Her therapy at this point? 1- Increase metformin to 1000 mg twice daily. 2- Add an incretin-based therapy (DPP-4 inhibitor or GLP-1 receptor agonist). 3- Add glibenclamide 5 mg twice daily. 4- Add basal insulin 15 to 20 U at bedtime.


Noura is a 58-year-old mother of 3 with a 2-year history of type 2 diabetes. At the time of diagnosis, FBS was : 118 mg/dl and her HbA 1c  was 6.9% . Initial laboratory tests demonstrated diabetic dyslipidemia: Total Chol: was 202 mg/dL , T G : 227 mg/dL , HDL cholesterol 38 mg/dL , and LDL cholesterol 119 mg/dL . Other blood chemistry values were unremarkable except for mild elevations of AST and ALT. There was no microalbuminuria. Case Study 2


Her family history includes "borderline" diabetes in her father and 2 uncles with diabetes, one of whom died from acute myocardial infarction at age 64 years. Upon physical examination, (BMI, 34 kg/m2 ). Her blood pressure was 138/80 mm Hg , heart rate 82 /m. Waist circumference was 37". No retinopathy was present, but there was decreased peripheral vibratory sensation in both lower extremities


Noura was instructed to begin exercise and a caloric control program with the goal of achieving a 7% reduction in body weight over 3 months.  She embraced this idea because she was reluctant to begin medications Her HbA 1c  decreased to 6.8% over a period of 4 months. The patient continued on this program but now admits she is less successful at maintaining caloric restriction, and her busy home and work schedules are no longer permitting her to exercise with the same frequency. She has not engaged in any substantial exercise in the past 8 weeks.


Follow-up Noura returns 10 months after her previous visit. Her weight has returned to the value at the initial visit (BMI, 34 ), Her HbA 1c   is 7.8%, and her FBG is 156 mg/dL. Her dyslipidemia and blood pressure have not changed significantly.


In addition to continuing to reinforce lifestyle measures, what is the next therapeutic step for achieving glycemic control in this patient, based on the AACE/ACE algorithm? 1- Metformin 1000 mg twice daily. 2-Metformin 850 mg twice daily plus a DPP-4 inhibitor or a GLP-1 receptor agonist. 3-Metformin plus basal insulin. 4-Metformin plus a sulfonylurea. 5-Metformin plus pioglitazone.


The patient was placed on metformin 850 twice daily and a DPP4-I . Three months later, the patient's HbA 1c  was 6.6% , her fasting plasma glucose was 107 mg /dl


Mansour is a 51-year-old male construction worker with a 9-year history of type 2 diabetes. For the first 3½ years, he was treated with metformin up to 2000 mg daily. Subsequently, he was treated with metformin plus a amaryl tab for 4½ years. His HbA 1c  increased progressively over those 8 years. Pioglitazone 30 mg daily was then added to the metformin plus sulfonylurea combination. Now, 14 months later, he presents with a fasting plasma glucose of 162 mg/dL and an HbA 1c  of 9.2% . Case Study 3


He reports polyuria, nocturia (2 to 3 times nightly), and dryness of the mouth. He has lost 4 kg lbs during this period. He notes progressive fatigability for the past several months. He is physically active on his job. He is not following any particular diet but claims to be "careful" with what he eats. He has no history of cardiovascular disease


On physical examination, his blood pressure is 130/82 mm Hg, pulse is 95 beats per minute, (BMI, 29). There is diminished vibratory sense over both lower extremities. Achilles deep tendon reflexes are absent bilaterally. His HbA 1c  is 9.2% . There are no abnormalities in thyroid, liver, or renal function test results. Trace microalbuminuria is present. A lipid panel reveals the following: total cholesterol 180 mg/dL , HDL cholesterol 42 mg/dL, triglycerides 158 mg/dL, and LDL cholesterol 107 mg/dL .


What is the most likely cause of the patient's progressive severity of hyperglycemia? 1-Excessive food intake with excess carbohydrates. 2-Inadequate exercise. 3-Progressive beta-cell failure…. 4 -Increasing insulin resistance. 5-Progressive beta-cell failure and increasing insulin resistance.  


According to the AACE/ACE algorithm, what is the preferred next therapeutic step that should be taken to treat Mansour 's poorly controlled diabetes? 1- Add a GLP-1 receptor agonist or a DPP-4 inhibitor to his existing 3 medications (ie, use quadruple therapy) 2- Discontinue the sulfonylurea and add a GLP-1 receptor agonist or a DPP-4 inhibitor to metformin and the thiazolidinedione 3- Initiate basal insulin therapy, with or without continuation of metformin. 4- Initiate basal-bolus insulin therapy, with or without continuation of metformin. 5- Seek an endocrine consultation.


Follow-up Mansour was treated with basal insulin with continuation of metformin and the sulfonylurea, but the thiazolidinedione was discontinued. Despite improvements in his fasting plasma glucose and a reduction of his HbA 1c  from 9.2% to 8.4%, he remained far from his HbA 1c  goal (ideally,< 7 % ). After several months, the sulfonylurea was discontinued. and basal-bolus insulin was introduced, together with more intensive self-monitoring of blood glucose while continuing metformin. His current regimen is basal-bolus insulin combined with metformin 850 mg twice daily. His most recent HbA 1c  is 6.8% . .



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