Introductions and complications of Diabetes Mellitus

1. Introductions and complications of Diabetes Mellitus Dr. Nakwagala Fred Senior Consultant Physician Mulago National referral hospital 17 Oct 2018

2. What is diabetes? • Diabetes mellitus (DM) is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. • The term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. • The effects of diabetes mellitus include long–term damage, dysfunction and failure of various organs.

3. What is diabetes? • Diabetes mellitus (DM) is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. • The term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. • The effects of diabetes mellitus include long–term damage, dysfunction and failure of various organs.

4. DM and Survival

5. Types of Diabetes • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus • Gestational Diabetes • Other types: • LADA (Latent Autoimmune Diabetes of Adults} • MODY (maturity-onset diabetes of youth) • Secondary Diabetes Mellitus

6. Q1. How is diabetes screened and diagnosed? Criteria for Screening for T2D and Prediabetes in Asymptomatic Adults *At-risk BMI may be lower in some ethnic groups; consider using waist circumference. †Obstructive sleep apnea, chronic sleep deprivation, and night shift occupations. BMI = body mass index; BP = blood pressure; CVD=cardiovascular disease; HDL-C = high density lipoprotein cholesterol; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; NAFLD = nonalcoholic fatty liver disease; PCOS = polycystic ovary syndrome; T2D, type 2 diabetes.

7. Q1. How is diabetes screened and diagnosed? Diagnostic Criteria for Prediabetes and Diabetes in Nonpregnant Adults FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; PG, plasma glucose.

8. Acute and chronic complications Acute Chronic Microvascular Opthalmopathy Nephropathy Neuropathy Macrovascular diseases Cardiovascular Peripheral vascular disease Cerebral Vascular Disease • - diabetic ketoacidosis (DKA) • - hyperglycemic Hyperosmolar Syndrome (HHS) • - hypoglycemia • - Metformin associated lactic acidosis, MALT

9. Effect of Hyperglycemia • Acute, reversible intracellular metabolic changes • Cumulative, irreversible effects on stable macromolecules

10. Good glycemic control decreasesthe diabetic complications • In the DCCT trial by reducing HBA1c from 9 % to 7% the following reductions occurred. • Retinopathy 76% • Nephropathy 54 % • Neuropathy 60 % • Macro vascular 41 %

11. Acute, reversible intracellularmetabolic changes • Increased activity of polyol pathway • Modified protein kinase C activity • Early glycation products • Increased production of free radicals

12. Consequences of increasedprotein kinase C (PKC) activity

13. Biochemistry pathways

14. Effects of advanced glycationend products (AGE) • Crosslinking of extracellular proteins • Interactions with specific AGE receptors • Crosslinking with intracellular DNA

15. Hemodynamic disturbancesin diabetes • Increased blood flow • Increased permeability • Hemorrheological and coagulation abnormalities - increased plasma viscosity - decreased red-cell deformability - increased platelet aggregability

16. Structural abnormalitiesin diabetes • Leakage of glycated plasma proteins • Extracellular matrix is increased - BM is thickened - mesangial matrix is expanded - collagen is increased • Hypertrophy and hyperplasia of endothelial, mesangial and arterial smooth muscle cells

17. Diabetes and infections • Infections are more frequent: pneumonia, urinary tract, skin and mucosal infections 1.5-2 x ↑ • Infections are more severe, mortality rate is increased 2-3x ↑. • Provokes hyperglycemic crisis. • Rare, life threatening infections. • Immunization: annually influenza vaccine, pneumococcal polysaccharid vaccine > 2 years (repeat > 64 years of age, renal disease, transplantation)

18. Rare, life threatening infections.in diabetes • Rhinocerebral Mucormycosis • Malign otitis externa (Ps. aeruginosa) • Psoas abscessus (St. aureus) • Emphysematosus cholecystitis (E. coli, Cl. Perfringens) • Emphysematosus urocystitis, pyelonephritis (E. coli, K. pneumoniae) • Necrotising Fasciitis (polymicrobe)

19. DM Autonomic Neuropathy

20. Classification of diabetic neuropathy • Diffuse neuropathy -somatic np.: sensorimotor - autonomic np.: cardiovascular, gastrointestinal, genitourinary, pupil • Focal syndromes - focal np.: mononeuritis, entrapmentsyndr. - multifocal np.: proximal neuropathies • Subclinical neuropathy - abnormal electrodiagnostic tests - abnormal quantitative sensory tests - abnormal autonomic function tests

21. Cardiovascular risk in diabetes • Peripheral arterial disease 2-4x ↑ (risk of amputation 16x ↑) • CHD: risk of AMI 2-3x ↑, heart failure 5x ↑ • Stroke 2-4 x ↑ • Protection of female gender is disappeared • The macrovascular risk is 10 x ↑ in the presence of microvascular complication

22. Q12. How is CVD managed in patients with diabetes? Comprehensive Management of CV Risk • Manage CV risk factors • Weight loss • Smoking cessation • Optimal glucose, blood pressure, and lipid control • Use low-dose aspirin for secondary prevention of CV events in patients with existing CVD • May consider low-dose aspirin for primary prevention of CV events in patients with 10-year CV risk >10% • Measure coronary artery calcification or use coronary imaging to determine whether glucose, lipid, or blood pressure control efforts should be intensified CV = cardiovascular; CVD = cardiovascular disease.

23. Q12. How is CVD managed in patients with diabetes? Statin Use • Majority of patients with T2D have a high cardiovascular risk • People with T1D are at elevated cardiovascular risk • LDL-C target: <70 mg/dL—for the majority of patients with diabetes who are determined to have a high risk • Use a statin regardless of LDL-C level in patients with diabetes who meet the following criteria: • >40 years of age • ≥1 major ASCVD risk factor • Hypertension • Family history of CVD • Low HDL-C • Smoking ASCVD = atherosclerotic cardiovascular disease; CVD = cardiovascular disease; HDL-C = high density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol.

24. DM Nephropathy

25. Q9. How is nephropathy managed in patients with diabetes? Assessment of Diabetic Nephropathy • Annual assessments • Serum creatinine to determine eGFR • Urine AER • Begin annual screening • 5 years after diagnosis of T1D if diagnosed before age 30 years • At diagnosis of T2D or T1D in patients diagnosed after age 30 years AER = albumin excretion rate; eGFR = estimated glomerular filtration rate; T1D = type 1 diabetes; T2D = type 2 diabetes.

26. Diagnosis and treatment ofMicroalbuminuria • Screening once a year in T1DM (at least), at diagnosis in T2DM • Urinary albumin excretion 30-300 (299) mg / 24 h • 2 positive out of 3 samples (collected urine) (fever, urinary tract infection, heart failure etc.) • ACE-inhibitors (ARB), good metabolic control • DM + albuminuria increases the CVD mortality with 20 x

27. Q9. How is nephropathy managed in patients with diabetes? Staging of Chronic Kidney Disease CKD = chronic kidney disease; GFR = glomerular filtration rate; NKF = National Kidney Foundation. Levey AS, et al. Kidney Int. 2011;80:17-28.

28. Q10. How is retinopathy managed in patients with diabetes? Assessment of Diabetic Retinopathy • Annual dilated eye examination by experienced ophthalmologist or optometrist • Begin assessment • 5 years after diagnosis of T1D • At diagnosis of T2D • More frequent examinations for: • Pregnant women with DM during pregnancy and 1 year postpartum • Patients with diagnosed retinopathy • Patients with macular edema receiving active therapy DM = diabetes mellitus; T1D = type 1 diabetes; T2D = type 2 diabetes.

29. Q10. How is retinopathy managed in patients with diabetes? Management of Diabetic Retinopathy • Slow retinopathy progression by maintaining optimal control of • Blood glucose • Blood pressure • Lipids • For active retinopathy, refer to ophthalmologist as needed • For laser therapy • For vascular endothelial growth factor therapy DM = diabetes mellitus; T1D = type 1 diabetes; T2D = type 2 diabetes.

30. Q10. How is retinopathy managed in patients with diabetes? Management of Diabetic Retinopathy • Slow retinopathy progression by maintaining optimal control of • Blood glucose • Blood pressure • Lipids • For active retinopathy, refer to ophthalmologist as needed • For laser therapy • For vascular endothelial growth factor therapy DM = diabetes mellitus; T1D = type 1 diabetes; T2D = type 2 diabetes.