Diabetes Mellitus: Case Studies and Management

• The learning outcomes of this presentation focuses on:
  • Landmark studies in the understanding of T2DM
  • Goals of treatment for Diabetes Mellitus
  • Cardiorenal benefits of SGLT-2 inhibitors and GLP-1 agonists
  • Hypertension treatment goals in patients with diabetes
  • Recommendations for lipid lowering therapy in patients with diabetes

Fatima's Clinical Case Scenario

• Fatima is a 40-year-old female with type 2 diabetes diagnosed 2 years ago
• She also has hypertension, a family history of hyperlipidemia, and a previous history of gestational DM
• Fatima's BP is 154/78 mm Hg, HbA1C is 8.2%, and BMI is 31.7 kg/m²
• Her cholesterol is 6.2 mmol/L (240 mg/dL); HDL is 1.03 mmol/L (40 mg/dL); LDL is 5.4 mmol/L (210 mg/dL)
• Creatinine is 64 umol/L (0.74 mg/dL), with an eGFR of 95 ml/min/1.73 m²
• Fatima is currently taking Metformin 1000 mg daily, Perindopril 5 mg daily, and Aspirin 75 mg daily

What is Diabetes?

• Diabetes mellitus (DM) is a group of diseases characterized by hyperglycemia
• T2DM is a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, and protein metabolism, resulting from defects in insulin secretion, insulin action, and multiple other pathophysiologic defects
• The effects of DM include long-term damage, dysfunction, and failure of various organs

Diagnosis of Diabetes

• Diagnosed by:
  • Fasting plasma glucose ≥7.0 mmol/L (126 mg/dL)
  • HbA1c ≥48 mmol/mol (equivalent to 6.5%)
  • Two-hour plasma glucose after a 75g oral glucose load ≥11.1 mmol/L (200 mg/dL)
  • Random plasma glucose ≥11.1 mmol/L (200 mg/dL) in the presence of symptoms of hyperglycemia

Treatment Goals in Diabetes Mellitus

• Exercise
• Diet
• Cholesterol
• Blood pressure
• A1c/Anti-platelets

Type 2 Diabetes Prevention Trials

• Da Qing Study: Lifestyle intervention with IGT participants showed a risk reduction of 51% after 6 years and 43% after 20 years
• Finnish DPS: Lifestyle intervention with IGT participants showed a risk reduction of 58% after 3+ years and 7 years
• Diabetes Prevention Program: Lifestyle intervention with IGT participants showed a risk reduction of 58% after 3 years and 34% after 10 years

Diabetes Prevention Program (DPP) Results

• A 7 kg weight loss reduced risk of type 2 diabetes
• Study included 3234 patients with a BMI of 34.0 kg/m² and glucose levels of 95 – 125 mg/dl

Lifestyle Modification

• Lifestyle modification encompasses diet, physical activity, and behavioral change
• Calorie deficit of ≥ 500-750 kcal/d is recommended
• Physical activity of ≥ 150 min/week, typically aerobic, is advised
• Behavior therapy includes structured behavior change program with monitoring and personalized feedback
• Can induce weight loss of 7-10% when administered weekly in groups for 16 to 26 weeks

Cardiovascular Disease & DM

• Patients with T2D are 2-4x more likely to develop CVD and CAD than people without diabetes
• Over 50% of deaths among patients with T2D are attributable to CVD
• Patients with T2D are 2.5x more likely to develop CHF than people without diabetes

Prevalence of ASCVD (PACT-MEA Study)

• Reports prevalence estimates of ASCVD in various countries
• Prevalence estimate in Bahrain is 36.6%
• Prevalence estimate in Egypt is 19.6%
• The overall total prevalence estimate is 20.9%

Risk Factors Associated with T2DM

• Elevated glycated hemoglobin level
• Elevated blood pressure
• Albuminuria (presence of microalbuminuria or macroalbuminuria)
• Elevated LDL-C level
• Smoking

Diabetes Control and Complications Trial (DCCT)

• Study included 1441 teenagers and young adults with Type 1 diabetes, randomly assigned to two groups
• Conventional care: one or two insulin injections daily and "routine" three-month follow-up visits
• Intensive treatment: initial hospitalization for education and stabilization, four or more blood sugar tests daily, use of either insulin pump, or multiple daily insulin injections, monthly office visits, and frequent (at least weekly) telephone calls
• Intensive therapy significantly reduced retinopathy by 76%, nephropathy by 50%, and neuropathy by 60%

Comorbidities of T2DM

• 75% of people with type 2 diabetes have hypertension
• 90% are overweight/obese
• 30-60% have dyslipidemia
• In people with hypertension, 29% have type 2 diabetes
• 60-70% are overweight/obese
• and 49% have dyslipidemia

Cardiovascular Disease & Risk Management

• Multifactorial approach to reducing risk of diabetes complications involves:
  • Glycemic Management
  • Blood Pressure Management
  • Lipid Management
  • Selecting agents with cardiovascular and kidney benefits
  • Lifestyle Modification and Diabetes Education

Using Glucose-Lowering Medications to Manage Type 2 Diabetes

• Combines healthy lifestyle behaviors, diabetes self-management education and support (DSMES), and addressing social determinants of health (SDOH)
• Focuses on cardiorenal risk reduction in high-risk patients and achieving glycemic plus weight management goals
• Lists agents including combination therapy, that provide adequate efficacy to achieve and maintain treatment goals
• High efficacy for glucose lowering: Dulaglutide (high dose), Semaglutide, Tirzepatide, Insulin, Combination Oral or Injectable
• Key components of weight management include setting individualized goals, general lifestyle advice (medical nutrition therapy/eating patterns/physical activity), and potential use of medications/metabolic surgery
• Very High efficacy for weight loss includes Semaglutide, Tirzepatide
• High efficacy for weight loss includes Dulaglutide, Liraglutide

Macrovascular and Microvascular Complications of DM

• Macrovascular complications: CAD-ACS, MI requiring bypass, Stroke and, Peripheral arterial disease s/p ischemic toes amputation
• Microvascular complications: CKD, Neuropathy, and Retinopathy

Blood Pressure Targets in T2DM

• Hypertension should be confirmed via multiple measurement readings on 2 different occasions
• Hypertension is diagnosed if confirmed as systolic >130 mmHg or diastolic >80 mmHg
• If the blood pressure is >120/80, consider weight management, decreased sodium intake, decreased alcohol intake, and increased physical activity

Lipid Targets in T2DM

• Primary prevention for T2DM adults aged 40-75 without CVD: use moderate intensity statin
• Primary prevention for T2DM adults aged 40-75 with CVD risk factors: use high intensity statin
• Secondary prevention for T2DM adults of any age with atherosclerotic disease use high intensity statin
• If triglycerides are 1.5 – 5.6 despite statins consider icosapent ethyl (not approved inIreland yet) over fibrates

Anti-Platelets and T2DM

• Aspirin 75mg (or clopidogrel if aspirin allergy) is used for secondary prevention
• A possible indication exists for long-term dual anti-platlet therapy in high-risk patients
• A possible indication exists for low-dose rivaroxaban and aspirin in patients with stable coronary artery or peripheral artery disease
• In primary prevention controversial!

Weight Management in T2DM

• Obesity is a chronic and complex disease
• Weight loss of >5% provides metabolic and cardiovascular benefits
• Weight loss of 10% allows the possible remission of T2DM
• Refer to "Overview of Obesity Lecture"

Medical Nutrition Therapy (MNT)

• A treatment that should be personalized and meet individual values, preferences and treatment goals to promote long term adherence
• Administered by a registered dietitian to improve weight-related and health outcomes
• Also recommend 30-60 mins of aerobic activity on most days of the week

Three Pillars of Obesity Management that Support Nutrition and Activity

• Psychological intervention includes implementing multicomponent behavior modification
• Pharmacological includes agents semaglutide, liraglutide, naltrexone/bupropion, orlistat
• Bariatric sugery includes sleeve gastrectomy and Roux-en-Y gastric bypass

Weight Management Targets in T2DM

• Includes metabolic, ventilatory, reproductive, CV risk, ADL/QoL, anxiety/depression, body image dysphoria and economic cost

Patient-Centered Collaborative Care

• Eye care professional for annual dilated eye exam
• Registered dietician nutritionist for medical nutrition therapy
• Diabetes self-management education and support
• Dentist for comprehensive dental and periodontal examination
• Mental health professional, if indicated
• Social worker/community resources if indicated
• Podiatrist for foot care

These questions address complex aspects of diabetes mellitus management, including uncontrolled hyperglycemia, long-term complications, cardiovascular risk, and therapeutic interventions. They assesses the multifaceted approach required for comprehensive patient care.