Diabetes Mellitus

Chap 10. Unit VII

Diabetes Mellitus Definition
• Metabolic disorders of fat, carbohydrate, and proteins
Diabetes MellitusResults from
• Defects in insulin secretion, insulin action (sensitivity),
or both.

• It is a chronic condition, characterized by

hyperglycemia and due to impaired insulin secretion
with or without insulin resistance.
• Commonly referred as DM
FBS
RBS
Criteria for Diabetes mellitus
Prevalence of DM in Pakistan
• 11.7 % in Pakistan

• High in Males

• High in urban areas

• KPK

• 9.2 % males
• 11.6 % Females
Classification of DM

1. Type I

2. Type II

3. Gestational
Pathophysiology the Action of Insulin
Pathophysiology Type I DM
Pathophysiology Type II DM Mechanism of insulin release
Insulin releaser after meal
Pathophysiology Type II DM
Sign and symptoms of DM

Poly urea

Polydepsia

Poly Phagia
Characteristics of DM I
< 30 years of onset
Characteristics of DM II
Complications of DM

Macrovascular

Microvascular

Diabetic Ketoacidosis

Hyperosmolar Hyperglycemic State

Diabetic Cardiomyopathy (Macrovascular Compli-)
• Most common cause of death in DM.
• Hardening of blood vessels atherosclerosis
• Insulin resistance
• Hypertension
• Silent MI due to autonomic neuropathy
• Coagulation abnormality
• Metabolic syndrome
Hypertension
• Hyperinsulinemia
• Sympathetic activation
• Hypertrophy of blood vessels
• Stiffening of blood vessels Nephropathy
• Elevated BP
• Risk of heart and brain attack.
Stroke
• Segmental arteries
• Demand vs Supply
• Increased demand but supply cant be increased
• Coagulability
Retinopathy (Microvascular)
Most common in type I DM
Loss of capillary pericytes
Most common form is background retinopathy
Retinopathy Stages

1.Background 2. pre-
• retinopathy proliferative
retinopathy
3:
4.
proliferative
Maculopathy
retinopathy
Nephropathy (Microvascular)
• 35-45 % pt of Type I DM
• loss of podocytes and development of peritubular fibrosis
• Microalbuminuria is excretion of 30 to 300 mg of albumin a day
• Clinical proteinuria is excretion of more than 0.5 g of total protein

• The incidence of nephropathy peaks at approximately 15

to 17 years and declines somewhat thereafter

• HTN helps in progression to ESRD

Neuropathy (Microvascular)
• Peripheral symmetrical sensorimotor neuropathy
• Numbness or tingling in the toes and feet
• Progressively worsen
• Ultimately, insensate feet become very vulnerable to trauma,
and neuropathic foot ulcers are frequent causes of hospitalization
and even amputation.
• Pain
• Cranial neuropathies causing diplopia (Infraction and Thrombosis)
• Amyotrophy occurs most commonly in elderly men with diabetes.
• Severe, unremitting pain and weakness in the thigh muscles.
• Depression, cachexia, and weight loss
DKA
Pure insulin deficiency
2% to 5% of patients with type 1 diabetes mellitus a year.
Dehydration
Osmotic diuresis
Vomiting
Diarrhea
DKA
Diabetic Foot Ulcers
Hyperosmolar Hyperglycemic State
Somogyi Phenomenon
Somogyi Phenomenon
1930s, Dr. Michael Somogyi
Hypoglycemia during the late evening induced by insulin
Counterregulatory hormone response
Hyperglycemia in the early morning.
Common in Type I DM
Somogyi Phenomenon Pathophysiology
Glucagon

Epinephrine

Cortisol

Growth hormone
Somogyi Phenomenon Patient History
• Morning hyperglycemia 4-8 AM
• Nocturnal hypoglycemia is missed
• Post hypoglycemic hyperglycemia
• Hypoinsulinemia
Somogyi Phenomenon Lab Findings
• Fasting blood glucose
• Nocturnal blood glucose
• Hemoglobin A1C (Hgb A1C)
• and
• Frequent glucose sampling.
Dawn Phenomenon
Dawn Phenomenon
• Also called dawn effect.
• Abnormal early-morning increase in blood sugar
2 a.m. and 8 a.m
• “Dawn phenomenon,” the night to morning elevation
of blood glucose (BG) before and, to a larger extent,
after breakfast” TI and TII DM
• Physiological

• Pathological
Dawn Phenomenon
• Nocturnal spikes of growth hormone secretion are
the most likely mechanism of the dawn phenomenon in T1D

• In T2D fasting hyperglycemia has been attributed to a transient

increase in hepatic glucose production (both glycogenolysis and
gluconeogenesis) at dawn in the absence of compensatory insulin
secretion
Dawn Phenomenon Diagnosis
• BG at 3-5 am
• And Nocturnal BG for differential diagnosis
• Continuous Glucose Monitoring System (CGMS)
TREATMENT OF DIABETES
Insulin Therapy
HBA1C to Plasma Blood glucose
GOALS of TREATMENT

• Reduce the risk for microvascular.

• Macrovascular disease complications

• Ameliorate symptoms

• Reduce mortality

• Improve quality of life.

General approach to Treatment

• Goal setting for glycemia, blood pressure.

• Lipid levels

• Dietary and exercise modifications

• Medications, appropriate self-monitoring of blood glucose (SMBG)

• Laboratory assessment of the aforementioned parameters.

• Target HbA1C should be < 7 %

Insulin Preparations
Insulin Dose
1. Fixed-Dose Insulin

2. Carbohydrate to Insulin Ratio

3. Sliding-Scale Insulin Therapy (SSI)

4. Insulin dose calculation and division based on weight age glycemia

Insulin Dose
• 0.5-1 Unit/kg
• 50 % basal and 50 % meal time
• 1-2 extra units for each 50 gm of glucose.
• Conventional Therapy
• 2/3 or 3/4 dose in breakfast and remining in dinner
• Ratio of I:R will be 2:1 or 4:2 before breakfast
• And 1: 1 before supper
• Insulin dose is usually divided so that one half is administered before
breakfast, one fourth before dinner, and one fourth at bedtime.
Conventional Insulin Therapy
Intensive Insulin Therapy
Intensive Insulin Therapy
Sliding Scale for Insulin
TREATMENT OF DIABETES
Oral Hypoglycemic Therapy
Non Pharmacological Management
Non Pharmacological Management
Pharmacotherapy
• 7-8 % HbA1c
Start with monotherapy more then 8 two drugs
• Obese pt needs Bignuides as 1st line while normal or lean require SU
• Biguinides and SU are 1st choice combination if HbA1C > 9
• Big+SU most cost effective combination.
Pharmacotherapy Biguanides
Metformin
Should be considered as a 1st choice in T2DM
Reduces HbA1C by 1.5-2 %
Reduces LDL
Reduces Weight
Improves Macrovascular complication (UKPDS)
Should be considered in lean diabetic pt
OHGs with their site of action
Sulfonylureas
• Reduces HbA1C by 1-2 %
• Initially low dose gradually titrated to max dose
• Better to divide the dose into BD or SR formulation should be used.
• Effective in New diabetics up to 5 years
• Effectively in normal or modestly obese patients
• Risky patients for hypoglycemia should be prescribed with short acting
SU
• Microvascular and macrovascular complications reduces with SU
Short-acting insulin secretagogues Meglitinides
• Short half life
• Low risk of hypoglycemia
• Reduce HbA1C by 0.5-1 %
• Rapid in action
• Reduce Post prandial Plasma glucose effectively
• Reduces glucose toxicity
• Effective as monotherapy
α-Glucosidase inhibitors
Effective only in postprandial hyperglycemia
Reduces HbA1C by 0.8 %
Taken before meal
Low risk of hypoglycemia
Thiazolidinediones
• Reduces HbA1C by 1.5 %
• Reduces Insulin resistance at Muscle fats and liver
• TZD drugs tend to decrease serum triglyceride levels and
• Increase serum HDL also increase serum LDL levels.
• Showed cardio protection
• Beta cell protection
Glucagon like Peptide-1 Agonists
Semaglutide
Glucose dependent insulin release
Lower risk of Hypoglycemia
HbA1C 1-1.6 %
Dipeptyl Peptidase-IV Inhibitors
Sitagliptin
Incretins
Low risk of hypoglycemia
DPP-4 degrades numerous biologically active peptides, including the
endogenous incretins, GLP-1
T2 DM Algorithm
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