diabetes case study

1. DIABETES MELLITUS

2. DEFINITION:
It is a chronic endocrine disorder characterised by
hyperglycaemia due to impaired insulin secretion with or
without insulin resistance
It is associated with abnormalities in carbohydrate, fat and
protein metabolism

3. Aetiological classification of DM :
Type-1: Insulin dependent DM (IDDM)
type-1(A) – autoimmune
type-1(B) - idiopathic
Type-2: Non-insulin Dependent DM (NIDDM)
Other specific types:
1. MODY: maturity onset diabetes of young
2. LADA: latent autoimmune diabetes in adults
3. Genetic defects of β- cell function
4. Genetic defects in insulin action
5. Gestational diabetes
6. Disease of exocrine pancreas
7. Endocrinopathies

4. AETIOLOGY
Type-1
Genetic factors:
I. Concordance in twins-50%
II. Susceptible gene on chromosome 6
Environmental factors:
I. Viral infections
II. Experimental inductions with
chemicals
III. Bovine milk proteins
Autoimmune factors:
I. Islet cell antibodies
II. CD8 T-lymphocyte mediated
destruction of β cells
Type-2
Genetic Factors:
I. Concordance in twins-80%
Constitutional factors:
I. Obesity
II. Hypertension
III. Low physical activity
Insulin resistance
Inceased hepatic glucose output
hyperglycaemia

5. EPIDEMIOLOGY
In the US, an estimated 6.3% of the population has DM
Type I DM accounts for approximately 10 % of cases and type II for 90 %
DM is listed as sixth leading cause of death in US
According to Diabetes Atlas in 2011 in India currently around 40.9 million
people are suffering from Diabetes. It is expected to rise to 69.9 million by
2025

6. PATHOPHYSIOLOGY OF TYPE-1
Immune mediated destruction of β cells of pancreas
Absolute deficiency of insulin
Hepatic glycogenolysis
Increased gluconeogenesis
Decresed glucose uptake by insulin sensitive tissues
Incresed secretion of glucagon, cortisol, catecholamines
Hyperglycaemia

7. PATHOPHYSIOLOGY OF TYPE-1
In insulin defiency
hyperglycaemia
Increased
glucose
output
Unrestrained
hepatic
glycogenolys
is
gluconeogen
esis

8. PATHOPHYSIOLOGYTYPE-2
Insulin resistance
Hyperinsulinaemia maintains glucose for sometime
Gradual deterioration of β cells
Hyperglycaemia
In insulin resistance adipose tissue secretes called adipokines associatedwith
endothelial dysfunction, inflammation, thrombosis
Adiponectin an adipokine that prevents vascular damage is low in NIDDM
Type -2 is also associated with Syndrome-X
Syndrome-X: It is group of risk factors commonly found in NIDDM including
1. Insulin resistance & glucose intolerance
2. Hypertension
3. Central obesity
4. Atherosclerosis
5. Dyslipidaemia

9. CONTRASTING FEATURES OF TYPE 1 & 2
IDDM
β cell destruction
Islet cell antibodies
Strong genetic link
Onset at below 30 yrs
Faster onset of symptoms
Insulin therapy
Patients are not obese
Extreme hyperglycaemia leads to
diabetic ketoacidosis
NIDDM
No β cell destruction
No islet cell antibodies
Very strong genetic link
Onset at 40 yrs
Slower onset of symptoms
Diet control and oral
hypoglycaemic agents
Patients are obese
Extreme hyperglycaemia leads to
HONK hyperosmolar non-ketotic
coma

10. CLINICAL PRESENTATION
The common symptoms are:
Polyuria
Polydipsia
Polyphagia accompanied by marked weight loss
&fatigue
Nocturia
Blurred vision
Type-1: Diabetic ketoacidosis
Type-2: Glycosuria
Recurrent infections
Retinopathy
Hyperosmolar non ketonic hyperglycaemia

11. DIAGNOSIS CRITERIA FOR DM
Patient status Plasma glucose
value mg/dl
Diagnosis
Fasting value <100 Normal
Fasting value 110-125 Impaired fasting
glucose
Fasting value ≥126 Diabetes
2hr after 75g of oral
glucose load
140-200 Impaired glucose
tolerance
2hr after 75g of oral
glucose load
≥200 Diabetes
Random value ≥200 Diabetes

12. GLYCAEMIC GOALS OF THERAPY
S:NO
BIOCHEMICAL
INDEX
ADA
1 HbA1c <7%
2 Pre Prandial
. Plasma glucose
90-130 mg/dl
3 Post Prandial
Plasma Glucose
<180 mg/dl

13. TREATMENT
Non
pharmacotherapy:
Type-1: insulin
administration
with balanced
diet
Type-2: caloric
restriction is
required

14. A Plate Model For Meal Planning In DM
FIBRE
Vegetables
fruits
PROTEINS
Fish
Meat
Eggs
CAROHYDRATES
Rice
Bread
potatoes

15. PHARMACOTHERAPY OF TYPE-1
Insulin is a 2 chain polypeptide having 51 aminoacids
A chain contains- 21 aminoacids
B chain contains- 30 aminoacids joined together by disulphide bonds
Insulin secreted by β cells of pancreas
Average secretion of insulin is 40 units
The half life of insulin is 4-5min
Glucose is major stimulant for insulin release
Insulin is synthesised in β cells as singlet peptide chain as PREPROINSULIN
From preproinsulin(110 aminoacids) are removed to form proinsulin

16. SYNTHESIS, STORAGE & RELEASE OF INSULIN
Insulin is synthesised in β cells as singlet peptide chain as PREPROINSULIN
From preproinsulin(110 amino acids) 24 AAs are removed to form
PROINSULIN
The ‘C’-peptide is split off by “PROTEOLYSIS” in Golgi Apparatus
Insulin and ‘c’-peptide are stored in granules within cell
The ‘c’-peptide is secreted along with insulin into blood

17. TYPES OF INSULINS AND THEIR PHARMACOKINETICS..
Type of
insulin
Onset Peak(h) Duration(h) Max
duration(h)
Appearance
Rapid acting
Aspart 15-30min 1-2 3-5 5-6 clear
Lispro 15-30min 1-2 3-5 4-6 clear
Glulisine 15-30min 1-2 3-4 5-6 clear
Short acting
Regular 0.5-1hr 2-3 3-6 6-8 clear
Intermediate
acting
NPH 2-4hr 4-6 8-12 14-18 cloudy
Lente 3-4hr 6-12 12-18 20 cloudy
Long acting
Ultralente 6-10hr 10-16 18-20 24 cloudy
Glargine 4-5hr - 22-24 24 clear

18. INSULIN REGIMENS IN DM:
Mealtime
plus basal
regimen
Twice daily
regimen

19. Mealtime plus bolus injection concept contains:
Immediate or long-acting insulin : basal component
Short or rapid acting insulin : bolus component
Bolus component insulins are given before meals
It mimics the normal physiological insulin release
Major disadvantage of this regimen is it requires multiple
injections

20. Twice daily regimen concept contains:
Split mixed injections of morning dose of short acting insulin (regular)
Long/intermediate insulin (NPH) before breakfast and again before evening
meal
Regular insulin covers breakfast and evening meal
morning NPH insulin provides basal insulin for the day and covers mid day meal
Evening NPH provides insulin for rest of day
Starting dose may be 0.6units/kg/day with 2/3rd in morning and 1/3 in evening

21. PHARMACOTHERAPY OF TYPE-2 DM
Oral hypoglycaemic agents are used in management of NIDDM
The different oral hypoglycaemic agents are:
Sulfonyl ureas
Short acting insulin secretarygogues
Biguanides
Thiazolidinediones
α-glucosidase inhibitors
Combination products

22. SULFONYL UREAS
Sulfonylureas act by stimulating the secretion of insulin from
islets of pancreas by binding to receptors on β cells
Examples: Chlorpropamide
Tolbutamide
Glipizide
Glyburide
Adverse effects: hypoglycaemia,
Dilutional hyponatremia
Cholestatic jaundice (chlorpropamide)

23. BIGUANIDES
They act by:
Supress hepatic gluconeogenesis and glucose output from liver
Enhance insulin-mediated glucose disposal in muscle and fat
Retard intestinal absorption of glucose
Promote peripheral glucose utilisation by enhancing anaerobic glycolysis
Examples: Metformin
Adverse effects: Anorexia, Metallic Taste. Diarrohea

24. INSULIN SECRETARYGOGUES / MEGLITINIDES
They act by stimulating the secretion of insulin from islets of pancreas by
binding to receptors on β cells
Examples: repaglinide
nateglinide
Advrese effects: Hypoglycemic risk appears to be less with meglitinide than
with sulfonylureas.
Note: Repaglinide must be avoided in liver disease

25. THIAZOLIDONEDIONES
These are PPAR-γ(Peroxisome proliferator-activated receptors (PPARs) agonists, a nuclear
transcription factor important in fat cell differentiation and fatty acid
metabolism.
enhance insulin sensitivity in muscle, liver, and fat tissues indirectly
Examples: pioglitazone
rosiglitazone
Adverse Effects: plasma volume expansion, weight gain
Contraindication: Contraindicated in CHF & Liver Disease, Pregnancy

26. α-Glucosidase Inhibitors
They inhibit the α glucosidases – the final enzymes essential for
digestion of carbohydrates in small intestine mucosa thereby
prolonging the absorption of carbohydrates
Regular use tend to reduce HbA1c, body weight , triglyceride levels
Examples: Acarabose
Adverse effects: flatulence, abdominal discomfort

27. S: no Drug name dose mg/day
SULFONYL UREAS
1 chlorpropamide 250
2 tolbutamide 1000-2000
3 glipizide 5
SHORT ACTING INSULIN
SECRETARYGOGUES
1 nateglinide 120 with meals
2 repaglinide 0.5-1 with meals
BIGUANIDES
1 metformin 500 twice a day
THIAZOLIDINEDIONES
1 pioglitazone 15
α- GLUCOSIDASE INHIBITORS
1 acarabose 25 mg tid

31. DIABETIC EMERGENCIES
HYPOGLYCAEMIA
DIABETIC KETOACIDOSIS
HYPEROSMOLAR NON-KETONIC HYPERGLYCAEMIA

32. Long Term Complications
Macrovascular diseases: cardiovascular diseases
Hypertension
peripheral vascular disease
Microvascular disease: Retinopathy
Nephropathy
peripheral neuropathy
Micro& macrovascular disease: Diabetic foot problems/ ulcers
Charcot arthropathy

36. REFERENCES:
Triplitt CL, Reasner CA, Isley WL, Diabetes mellitus. In Dipiro JT, Talbert RL,
Yee GC, Matzake GR, Wells BG, Posey M, editors, Pharmacotherapy: a
pathophysiologic approach, 6th edition. New York, Mcgraw-Hill Medical
Publishing Division. Page: 1333 – 1368
Hackett EA, Thomas SM, Diabetes mellitus. In Walker R, Whittlesea C, editors,
Clinical pharmacy and therapeutics, 4th edition. New York, Churchill
Livingstone. Page: 629 – 654.
Kroon LA, Assemi M, Carlisle BA, Diabetes mellitus. In Koda-Kimble MA,
Young LY, KradjanWA, Guglielmo JB, editors, Applied therapeutics: the
clinical use of drugs. 8th edition. Philadelphia, Lippincott Williams & Wilkins.
Page: 50 (1-74).
Insulin, oral hypoglycaemic drugs and glucagon. In Tripathi KD, Essentials of
medical pharmacology, 6th edition. New Delhi, Jaypee brothers medical
publishers(P) LTD. PAGE:254 - 274

37. THANKQ

38. What are the examples of saturated fats?
Saturated fats are cheifly of animal origin: beef, pork, milk products
Saturarated fats of plant origin : cocoa butter, palm oil,
coconut oil

39. What are endocrinopathies
Endocrinopathies are diseases associated with a disorder of
endocrine glands that affects mainly their hormonal secretion

40. What is normal value of adiponectin
5-10 Mcg

41. INSULIN RELEASE:
Hypoglycaemia
Glut 2
Glucose-6-phosphate
ATP( outflow of K+)
Altered ion channel activity( influx of ca+2)
Release of insulin

42. why metformin dosage adjustment is required in renal
insufficiency patients?
Metformin is excreted unchanged through the kidney so in renal
insufficiency patients, there will be accumulation of metformin
which leads to lactic acidosis.

43. Patient education for diabetes?
Insulin therapy:
• injection technique
• types of insulin
• onset and peak actions
• storage and stability.
Urine testing:
Glucose,ketones.
Cardiovascular risk factors:
- Smoking.
- Hypertension.
- Obesity.
- Hyperlipidaemia.
Footcare.
Regular medical and opthalmological examinationS.

44. In children the Type 2 Diabetes is a reason for great concern. Obesity has
been the major reason for Type 2 Diabetes in children. In children it has
caused major issues. It can also be genetically in case of children. If parents
are suffering from this disease it can be genetically transferred to children as
well.
The mutation of the Islet Amyloid Polypeptide gene has been the main reason
for causing Type 2 Diabetes in many cases the mutation of this gene can
cause even more problems to the offspring.
In December of 2000 the FDA approved Metformin for pediatric patients 10
years and older that have Type II Diabetes. Six years prior, Metformin was
approved by the Food and Drug Administration for use in adults with Type II
Diabetes and since has become one of the most widely prescribed agents for
the disease.

45. Clinical Use in Children
The benefit of metformin was first demonstrated in children identified as at risk for the
development of type 2 diabetes, those with both fasting hyperinsulinemia and a
positive family history.
In 2001, Freemark and Bursey conducted a randomized, placebo-controlled, double-
blind trial in 29 obese adolescents (ages 12-19 years) with known risk factors for
diabetes.
All subjects had a body mass index (BMI) greater than 30 kg/m2, a fasting insulin
concentration greater than 15 microunits/ml, and a first or second degree relative with
type 2 diabetes. All had fasting glucose concentrations less than 110 mg% and a
hemoglobin A1c less than 6%. Patients received either metformin 500 mg twice daily or
placebo for 6 months.
Metformin administration resulted in a 1.3% decline in BMI compared to baseline. The
average BMI value rose by 2.3% in the placebo group. Treatment resulted in a decline
in fasting blood glucose (84.9 to 75.1 mg%) and fasting insulin levels (31.3 to 19.3
microunit/ml), while blood glucose rose slightly in the placebo group and insulin
levels remained unchanged. There were no significant changes in hemoglobin A1c,
serum lipids, or lactate in either group. Based on their results, the authors concluded
that metformin may be considered as an adjunct to diet and exercise in adolescents at
risk for type 2 diabetes.