Home Fayyaa Diabetes: Unit – 6: Management of Type 2 Diabetes: Life Style Interventions and Oral Agents

Diabetes: Unit – 6: Management of Type 2 Diabetes: Life Style Interventions and Oral Agents

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UNIT – 6
MANAGEMENT OF TYPE 2 DIABETES: LIFE STYLE INTERVENTIONS AND ORAL AGENTS

Objectives
• By the end of this session, you will be able to
1. Describe the complex nature of type 2 diabetes & match patho physiology to treatment options
2. Describe life style interventions in the management of type 2 diabetes mellitus
3. List the various classes of oral agents for the treatment of type 2 DM with emphasis on locally available ones
4. Describe mechanisms of action, side effects, efficacy & contraindications of oral antidiabetic medications
5. Identify the importance of holistic & individualized approach in the management of type 2 DM

Introduction
• Type 2 diabetes is associated with increased
morbidity and mortality. This is mainly due to
cardiovascular complications.
• Intervention that are proven to decrease these
burden are comprehensive diabetes care with
management of glycemia and other risks
• The two important components of type 2 DM
management are Life Style Modifications and
medications.

Type 2 Diabetes features
• Key Mechanisms of hyperglycemia
– Insulin resistance
– β-cell failure due to glucotoxicity & lipotoxicity
–Increased endogenous glucose production
• Liver
• Kidney
• Hyperglycemia has twin components
– Fasting hyperglycaemia
– Postprandial Hyperglycaemia

Complexity of Type 2 Diabetes
• Patients often fail to reach treatment goals
• Associated disturbances
– Over 45% are obese (BMI ≥30 kg/m2)
– As many as 75–80% have hypertension
– Over half of patients have hypercholesterolemia
– Atherothrombotic changes
• Effective management of Type 2 diabetes is
beyond glycemic control
• Need to address BP, Lipids, Obesity and others

Important issues in Management of type 2 diabetes
• Patient education on the character of the disease
– Complex disease
– Progressive disease
– Lifetime treatment and follow up
• Motivating patients to make lifestyle adjustments
–Physical activity
–Healthy food intake
• Motivation of all HCP to persist with advice and
motivation of patients

Important Issues in Management of type 2 diabetes (Cont’d)
• Early and intensive intervention
-↓Risk of microvascular and
macrovascular complications
-↓ Disease progression
– Comprehensive care improves outcome

Benefits of Glucose Lowering:
DCCT & UKPDS & follow up studies
• Lowering HbA1c leads to less micro- & macrovascular complications in type 1 & 2 DM
• Presence of ‘Glycaemic metabolic memory’
• level of glucose control in the early years of disease impacts on the development of later complications
• Patients with tighter glycaemic control during the study developed less micro- and macrovascular
complications more than 10 years after discontinuation of the study
• These observations emphasize the need to control glycaemia as tight as possible and as early in the disease process as possible.

BP and Lipid Lowering goals
• Blood pressure <140/90mmHg
✓ ACEIs or ARBs
✓ 2 or more drugs at maximal doses are needed
✓ Administer one of the drugs at bed time
• ASA for Primary prevention
o Males > 50 yrs, Females > 60 yrs + 1 CV risk
factor
• DM patients age 20 – 39 years with ASCVD risk
factors may be treated with statins and Life style
modification- Consult internist/or
Endocrrinologist/or cardiologist
• DM Patient age 40 – 75 without ASCVD risk factor
– maybe started with moderate intensity statins
• DM patients with age 50 – 70 years with high
ASCVD risk should receive High intensity statin
therapy
• High Intensity Statin Therapy – Lowers LDL by ≥ 50 %
• Atorvastatin –40 -80 mg/d
• Rosuvostatin – 20 – 40 mg/d
• Moderate Intensity statin Therapy – Lowers LDL by 30 – 40%
• Atorvastatin – 10 – 20 mg/d
• Rosuvostatin – 5 – 10 mg/d
• Simvastatin 20 – 40 mg/d
• Lovastatin – 40 mg/d

Glycemic Targets (HbA1C)
(Patient-centered)
• General Target < 7%
• More Stringent 6.0 % – 6.5 %
–Younger patients
–Newly diagnosed
–Long-standing disease, no significant complications
• Less Stringent 7.5% – 8.0%
–Older patients
–Long-standing disease & significant complications
–CV risk factors
–History of CVD

Principles of Comprehensive Management of Type 2 Diabetes
1. Lifestyle modifications
2. Individualized approach
3. Address both FPG & PPG
4. Minimize risk of hypo & weight gain
5. Major cost comes from complications and not
from medications
6. Combination therapy usually required
7. Comprehensive BP and Lipid Management
8. Initial regimen should be simple

COMPREHENSIVE DIABETES CARE
Refer to Algorithm 2
Optimal diabetic therapy involves beyond glycemic control
• Diagnosis & Management of DM specific
complications
• Modify risk factors
• Social, family, financial, employment & cultural issues
• Diabetes education
• Medical nutritional therapy
• Exercise

RECOMMENDED SCHEDULES FOR ONGOING MEDICAL CARE
• SMBG (≥3/day, individualize)
• HBA1C (2-4x/yr)
• DM Mx patient education (annual)
• MNT (annual)
• Eye exam (at Diagnosis for type 2 DM, annual or Q2-3yrs)
• Foot exam (by patients daily, by doctor 1-2x/yr)
• Microalbuminuria (annual)
• BP measurement (Quarterly)
• Lipid profile (annual)
• Others: immunization, antiplatelets

Case Study 1
• Mr. F.A is a 42 years old male patient presented for routine check up. His physical exam is non-remarkable except for BMI of 24 kg/m2. You found out that his FBS is 129 mg/dl and 132 mg/dl on two different occasions and HbA1C-7.8%
What is the best initial treatment for this patient? Why?
A. Metformin 500 mg/BID
B. Glibenclamide 2.5 mg/d
C. Start NPH insulin
D. Advice on life style interventions

1. Management -Diabetes Education
• Self-management education (SME)
– Incorporates knowledge and skills development, as well as cognitive behavioral interventions
–should be implemented for all individuals with
diabetes.
• The content of SME programs
–Must be individualized according to the individual’s type of diabetes, current state of metabolic stability, treatment recommendations, readiness for change, learning style, ability, resources and motivation.

Self Management Education
• SME is
– Fundamental component of diabetes care
– Most effective when ongoing diabetes
education and comprehensive healthcare occur
together
– Usually multidisciplinary i.e. educator, dietitian
& doctor work together
– Often group based

EDUCATION —- A CORNER STONE for diabetes care
• Diabetes Self Management Education (DSME)
• optimizes metabolic control
• Prevents and manage complications
• Maximizes quality of life, in cost effective
manner
• Should address psychosocial issues, since
emotional well-being is strongly associated
with positive diabetes outcomes

Diabetes self management education…..Cont’d
• Leads to
• Improved diabetes knowledge
• Improved self-care behavior
• Improved clinical outcomes (lower A1C, higher self reported weight loss, and improved quality of life)
• Should be continuous
• Includes follow-up support
• Should be tailored to individual patients needs
and preferences

DSME SHOULD INCLUDE
• optimal and appropriate use of therapy to address:
• basic knowledge of diabetes
• Nutrition and physical activity
• SMBG and A1C and the targets of control
• Acute complications of therapy
• Intercurrent illness
• Knowledge of late complications
• Psychological aspects of living with diabetes
• Dealing with lifestyle and life event
• Foot & skin care
• Diabetes management before, during, and after
exercise
• Risk factor–modifying activities.

Exercise Recommendations for Type 2 DM
• Exercise daily for 30 minutes (min 5 days/wk)
• Intensity should be individualized
• In type 2 DM, exercise-related hypoglycemia is
less common but can occur in individuals taking
either insulin or insulin secretagogues.

3. Psychosocial Assessment and Care
• Ongoing part of medical management of
diabetes
• Psychosocial screening/follow-up: attitudes,
medical management/outcomes
expectations, affect/mood, quality of life,
resources, psychiatric history
• Routinely screen for psychosocial problems:
depression, diabetes-related distress, anxiety,
eating disorders, cognitive impairment

4. MEDICAL NUTRITION THERAPY (MNT)
• Used by the ADA to describe the
optimal coordination of caloric intake
with other aspects of diabetes therapy
(OHA, insulin, exercise, weight loss).

Steps towards the first action
Determine :
• Past dietary history
• physical activity
• socioeconomic status
• cultural & religious practice.

Weight Assessment
• Broca’s Index:
Height in cm – 100 =
desirable weight in kg
• Body Mass Index:
Weight (kg) / Height (m2)

Waist circumference
High Waist Circumference is Risk
for CVD
Men > 94 cm
Women > 80 cm

Assessment of caloric requirement
✓ Daily caloric requirement depend the patient’s
weight, age and activity status
Total energy requirement (TER) = Basal Metabolic
rate (BMR) + Activity factor
• BMR for males = 24 kcal / kg / day
• BMR for females = 22 kcal/kg/day
Assess Activity Factor:
• Sedentary level: 25-30% BMR
• Moderate activity: 35-50% BMR
• Strenuous activity: 50-100% BMR

Dietary advice and caloric distribution
• Food must be spread evenly thought the waking
hours, and taken at regular times in relation to the
insulin dose.
• The diet must be balanced in relation to CHO, FATS, and PROTIENS
• Avoid rapidly absorbed CHO, must be nutritious & adequate amount.
• Approximately the same amount of food should be eaten every day
• Diet should be based on the ordinary foods used by the family

Nutritional Recommendations for Adults with Diabetes
• Carbohydrate
– 45–55% of total caloric intake (low-carbohydrate diets are
not recommended)
– Amount and type of carbohydrate important
– Sucrose-containing foods may be consumed with
adjustments in insulin dose
• Protein
– 10–35% of total caloric intake (high-protein diets are not recommended)

Nutritional Recommendations for Adults with Diabetes
• Fat
– 35% of total caloric intake
– Saturated fat < 7% of total calories
– <200 mg/day of dietary cholesterol
– Two or more servings of fish per week provide 3
polyunsaturated fatty acids
– Minimal trans fat consumption
• Other components
– Fiber-containing foods may reduce postprandial
glucose excursions
– Non-nutrient sweeteners

Case 1…. Ctd
The same patient came back to you on follow up after a month and his FBS is in the range of 170-200 mg/dl. You make a diagnosis of poor glycemic control.
The best next step in this patient’s glycemic
management is:
a) Optimize Metformin 850 mg/BID
b) Glibenclamide 5 mg/d
c) Vildagliptin 50 mg BID
d) Start insulin

5. Principles of Use of Oral Glucose Lowering Medications
• Used to Meet Glycemic Targets
• Should not be delayed
• Monotherapy or Combination Therapy
• Address Both Fasting & Postprandial Hyperglycemias
• Stepped-Care Approach is Recommended
• Initial Therapy is with Metformin
• When Combination Therapy Fails use Insulin as
soon as feasible.
• Watch for Side Effects

Traditional Oral Agents
1. Sulfonylureas – stimulate insulin secretion
• Glibenclamide
• Glipizide
• Glimepiride
• Gliclazide
2. Meglitinides – stimulate insulin secretion
• Repaglinide
• Nateglinide
3. Alpha Glucosidase inhibitors – delay CHO absorption
• Acarbose
• Miglitol
4. Biguanides – reduce hepatic glucose production
• Metformin
5. Thiazolodinediones- improve insulin sensitivity
• Rosiglitazone
• Pioglitazone

Newer Glucose Lowering Agents
• GLP 1 Receptor Agonists-increase insulin secretion through incretin effect of food
• Exenatide (injectable)
• Semaglutide
• DPP4 inhibitors –inhibit clearance of GLP1 by the enzyme DPP4: gliptins
• Alogliptin
• Saxagliptin
• Sitagliptin
• Vildagliptin
• SGLT2 Inhibitors – promote urinary excretion of glucose
• Canagliflozin
• Dapagliflozin
• Empagliflozin

Choice of initial glucose-lowering agent
• Patients with FPG < 180mg/dl—Life style changes -with Metformin
• Patients with FPG 180-250 mg/dL soon after initiation in
2-3 months – Optimization of single OHA, Metformin
• Patients with FPG > 250 mg/dL – combination OHAs (Metformin with lowest dose of sulphonylurea)
• Insulin can be used as initial therapy in individuals with severe hyperglycemia FPG > 250–300 mg/dL or in those who are symptomatic from the hyperglycemia.
– To reduce “glucose toxicity” to the islet cells

Metformin: Mechanism of Action
• Decrease hepatic glucose production
(gluconeogenesis, glycogenolysis) *
• Increase insulin-mediated muscle glucose
uptake
• Decrease gastrointestinal glucose absorption
• Inhibition of adipose tissue lipolysis (FFA)

Metformin: Efficacy
• Glucose effects:
– Decreases A1c by 1.5-2%
– Decreases fasting glucose by 50-70 mg/dl
• Effects on Complications and disease
progression:
– Often promotes slight weight loss
– Proven to decrease microvascular
complications of diabetes (UKPDS Trial)
– Shown to decrease progression from “prediabetes” to overt diabetes (DPP Trial)

Metformin: Side Effects
• GI Intolerance (dose-dependent)
– Nausea, Diarrhea
• Lactic Acidosis
– 1 in 40,000 patients
– Risk Factor: Renal Insufficiency (decreased clearance of lactate)
• No risk of Hypoglycemia when used as monotherapy
– No effect on pancreatic insulin secretion
• Vitamin B12 deficiency

Metformin: Contraindications
• Severe Renal Insufficiency (ESRD)
• Severe CHF-may result in Renal hypoperfusion
• Chronic Liver Disease including alcoholic lever
disease
• Chronic lung disease
• IV Contrast Studies
–Renal Effect
–Restart in 48 hours
• Major Surgery
• Severe Acute Illness

Sulphonylureas
• Stimulate Insulin Secretion
• Their Action Requires Functioning Beta Cells
• Side Effects
– Hypoglycemia
– Weight Gain
– GI Upset, Allergy
• Contraindications
– Allergy to the drug
– Type 1 DM
– Early Pregnancy
– Severe Infections
– Hepatic/Renal Failure
– Surgery

Glucagon-Like Peptide –1(GLP-1)
• Release is Rapid in Response to Meals
• Potent Insulinotropic Hormone
• Decreases Glucagon Release
• Slows Gastric Emptying
• Reduces Food Intake
• Rejuvenate β Cells (in animals)
• There is lower Plasma GLP-1 in IGT & Type 2 DM

Incretin Based Therapy
DPP4 Inhibitors:
• Inhibit GLP-1 Breakdown
• Sitagliptin
• Saxagliptin
• Vildagliptin
• Linagliptin
• Alogliptin
• Are available in Combinations with Metformin
• THESE DRUGS SHOULD BE PRESCRIBED BY
PHYSICIANS/INTERNISTS/ ENDOCRINOLOGISTS

Why are we not meeting targets?
• Reluctance by Patients and
Professionals
• Not treating to targets
• Not addressing Postprandial
Hyperglycemia
• Fear of Hypo
• Late Introduction of Insulin
• Current Drugs – not effective

Diabetes is a Polypharmacy Condition
• Glucose Control = 2-3 Drugs
• Cholesterol Control = 1-2 Drugs
• Blood Pressure Control = at least 2 Drugs
• Neuropathy Drugs
• Aspirin
• Nondiabetes Medication

Summary
• Diabetes care should be comprehensive, not
only glucocenteric
• Treating hyperglycemia early & effectively limits glucotoxicity on Beta cells & is key to future outcomes & has long term benefits
• Lifestyle interventions: DSME, diet, and exercise with other risk reductions are equally important in optimizing diabetes care

Summary….cont’d
• Different classes of oral antidiabetic medications are available
• Metformin is the first line therapy unless there is contraindication
• Patient’s glycemic level guides in initiation of single or dual therapy
• Individualization is crucial in heading
towards the therapeutic goals, one size does not fit all

END OF UNIT – 6

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