A-Z Diabetes Mellitus

Kurniyanto
Department of Internal Medicine
Introduction
• DM is a metabolic disorder characterized by chronic hyperglycemia
• Etiology is due to
• Insulin deficient in type 1 DM
• Insulin resistant and progressive loss of insulin secretion in type 2 DM
Classification
Pathogenesis type 1 DM
• 10% of all DM cases worldwide
• Incidence in early of life, male = female
• Contributing factors
• Genetic : HLA-DR3, HLA-DR4, CTLA4, PTPN22, CD25
• Autoimmunity : islet cell autoantibody (ICA), glutamic acid decarboxylase
autoantibody (GADA), insulin autoantibody (IAA), transmembrane tyrosine
phosphatase autoantibody (IA2A)
• Environment : rubella infection, short period of breastfeeding and
introduction of cow milk, low vitamin D serum
Pathogenesis of type 2 DM
• Insulin resistance preceded defect of insulin secretion
• Genetic factor contribution
• Patophysiology
• Insulin resistance
• Impaired insulin secretion
• Excess hepatic glucose production
• Abnormal fat metabolism
Differences of DM type 1 and 2
Factor Type 1 DM Type 2 DM
Peak age of onset 12 years 60 years
Etiology Genetic, autoimmunity, environment Combination of insulin resistance and β cell
failure
Initial presentation Polyuria, polydipsia, and weight loss Hyperglycemic symptoms but often with
with ketoacidosis complication
Treatment Diet and insulin Diet, oral lowering agent and insulin
Monogenic diabetes
• MODY (maturity onset diabetes of the young)
• Mutations in genes encoding islet-enriched transcription factors or
glucokinase
• 6 type of MODY
Others cause of DM
Latent autoimmune diabetes in
adults (LADA)
• Autoimmune DM diagnosed after 35 yo
• Late onset of DM type 1
• Others call DM type 1 ½
• Autoimmunity is a hallmark
• Anti GAD  most antibody
• ICA and IAA  less common
• Insulin secretion is lower than type 2 DM
Gestational DM
• Glucose intolerance may develop during pregnancy
• Insulin resistance is related to the metabolic changes of late
pregnancy, and the increased insulin requirements
may lead to IGT.
• Most women revert to normal glucose tolerance post-partum
but have a substantial risk (30–60%) of developing DM later in life
Hyperglycemia and complication
Role of Advanced glycated end products in
diabetes complication
Assesment (ADA 2019)
Management
• Education
• Physical activity
• Nutrition therapy
• Pharmacology intervention
Pharmacology intervention
Mechanism of action
Sulfonylureas
• Mechanism of action
• Stimulating receptor on the surface of β-cells, closing potassium channel and opening a calcium
channel  insulin release
• Side effect : hypoglycemia and weight gain
• Drugs
• Glibenclamide
• Gliclazide
• Glipizide
• Chlorpropamide
• Tolbutamide
• Glimepiride
• Efficacy : loweing A1c 1-2%, low cost
• Dosage : one to two time daily
Biguanides
• Mode of action
• Lowering HGP and increase muscle glucose uptake
• Increase insulin sensitivity
• Side effect
• GI problem
• Lactic acidosis
• Vitamin B12 deficiency
• Contraindication
• Renal impairment
• Hepatic problem
• Cardiac impairment
• Drugs
• Metformin
• Efficacy : loweing A1c 0,8-2%. Low cost
• Dosage : start once daily to three time daily, maximum 3000 mg/day
 α − 𝑔𝑙𝑢𝑐𝑜𝑠𝑖𝑑𝑎𝑠𝑒 𝑖𝑛h𝑖𝑏𝑖𝑡𝑜𝑟
•  Additional drugs for those inadequate control by diet or other agents
• Reduces postprandial glucose peaks by inhibiting
• Side effect : fullness or bloating, abd pain, flatulence and diarrhea
• Drugs : acarbose
• Dosage : start once to three time daily,
maximum 300 mg/day
 Thiazolidinediones
• Insulin sensitizing agents
• Activate peroxisome proliferator activated receptor (PPAR-γ) 
stimulate gene transcription for GLUT1 and GLUT4
• Drugs : rosiglitazone and pioglitazone
• Side effect
• Weight gain
• Osteporosis
• Fluid retention
• Hepatotoxicity
 Incretin system (GLP-1 mimetics and DPP-4 inhibitor)

• Drugs
• GLP-1 agonis
• Exenitide
• Liraglutide
• Dulaglutide
• Semaglutide
• DPP4 inhibitor
• Alogliptin
• Saxagliptin
• Linagliptin
• Sitagliptin
• Vildagliptin
• Moderate efficacy,
but high cost
 Sodium glucose transporter-2 (SGLT-2)
inhibitor
• Inhibit SGLT-2 in proximal
tubules cell
• Enhanced glucosuria
• Drugs
• Ertuglifozin
• Dapaglifozin
• Empaglifozin
• Canaglifozin
• Side effect
• UTI
• Polyuria
• Worsening renal failure
• Moderate efficacy but high
cost
Insulin
• Indicated for all type 1 DM and some of type 2
• Human vs Analog insulin
• Duration of action
• Rapid
• Short
• Intermediate
• Long
• Ultralong
• High efficacy, but high cost
• Need adherence
• Single injection vs
multiple injection
• High risk of hypoglycemia
So many of them, which
one is best?
Principle of treatment (ADA 2019)
• Patient centered approach
• Consider efficacy and key patient factors
• Key patient factors
• Comorbidities : ASCVD, CKD and HF
• Hypoglycemia risk
• Effect on body weight
• Side effect
• Costs
• Patient preferred
• Lifestyle modification should be emphasized during pharmacology intervention
• Most of them start with metformin if not contraindicated
 Glycemic target (ADA 2019)
• A1C < 7,0%
• Older adults with few comorbid, A1c < 7,5%
• Older adults with complex comorbid, A1c 8-8,5%
• Preprandial capillary plasma glucose 80-130 mg/dl
• Peak postprandial capillary plasma glucose < 180 mg/dl
Diabetes complication
• Acute
• HHS
• DKA
• Hypoglycemia
• Chronic
• Microangiopathy : retinopathy, nephropathy, neuropathy
• Macroangiopathy : CVD, CAD, PAD
Pathogenesis of DKA and HHS
Management
• Initial therapy is fluid rescucitation
• High to normal sodium : 0,45% saline
• Low sodium : 0,9% saline
• Potassium replacement
• Bicarbonat therapy for lethal academia (pH < 6,9)
• Insulin i.v bolus and continuous drip
Hypoglycemia
• Symptoms
• Shakiness
• Confusion
• Irritability
• Tachycardia
• Hunger
• Seizure, coma and death
• Risk of falls, injury, vehicle accident and dementia
• Mortality is increase in frequent hypoglycemia
• Diabetes patient  impaired counterregulatory to hypoglycemia and hypoglycemia
unawareness
• Increase risk in hepatic failure and CKD
• Treatment increase risk : insulin and sulfonylurea
• Treatment of hypoglycemia
• Glucose 15-20 gr is preferred or other carbohydrate containing glucose
• Glucagon for patient can’t take oral or for level 2 hypoglycemia
• Repeat SMBG 15 min after treatment
• Evaluate treatment
• In hospital  40% dextrose 50 ml repeat every 10-20 min until BG
arise then maintain with 10% Dextrose
• Corticosteroid may be added
Somogyi and dawn phenomenon
Management of comorbidities
• Hypertension
• High risk of 10 year ASCVD, target < 130/80
• Low risk of 10 year ASCVD, target < 140/90
• Lifestyle intervention
• Drugs of choice : ACE or ARB or Thiazide diuretics or Dyhydropiridien CCB
• For DM and hypertension with albuminuria : ACE or ARB
• Dyslipidemia
• Lifestyle intervention
• Measure 10 years ASCVD risk
• High risk  high intensity statin
• Low risk  low to moderate intensity statin
• If tryglyceride > 500 mg/dl  fibrates to avoid pancreatitis
• Antiplatelet therapy
• As secondary prevention in prior CAD/CVD event
• As primary prevention in high risk ASCVD
• Cardiovascular disease
• In stable heart failure, metformin may be use
• In atherosclerosis heart disease or HF : GLP-1 agonist or SGLT-2 inh is preferred
• Chronic kidney disease
• Evaluate urinary albumin, ACE or ARB is recommended for moderate albuminuria
(30-299 mg/dl)
• Optimize blood pressure
• GLP-1 and SGLT-2 shown benefit in progression of CKD
• Diabetic retinopathy
• Evaluate at initial diagnosis
• Treatment is mandatory in macular edema,
NPDR and PDR
• Optimize BG and BP controlled
• Diabetic peripheral neuropathy
• Assest with vibration, pinprick or temperature
sensation
• All diabetes patient should be test with
10-g monofilament test
• Optimize BG control
• Pregabalin, gabapentin and duloxetine can be use as initial treatment
Diabetic
Foot
care
• Perform a comprehensive foot evaluation
• Patient with neuropathy is at high risk
• Multidisciplinary management
• Principles
• Metabolic control
• Infection control
• Wound control
• Pressure control
• Vascular control