This document discusses pharmacotherapy for diabetes mellitus. It begins by defining diabetes and describing the long-term damage it can cause. It then provides statistics on diabetes prevalence in India. The main types of diabetes - type 1, type 2, and gestational - are classified and their characteristics summarized. The mechanisms and treatments of type 1 and type 2 diabetes are explained at a high level. The document also briefly outlines diabetes investigation methods, treatment guidelines, insulin discovery and mechanisms of action, and types of insulin preparations.

1. Pharmacotherapy of Diabetes
Mellitus
Ravinder Yadav
MD Pharmacology

2. Introduction
• Diabetes is a group of metabolic disorders
characterized by chronic hyperglycemia
associated with disturbances of carbohydrate,
fat and protein metabolism due to absolute or
relative deficiency in insulin secretion and/or
action
• Diabetes causes long term damage,
dysfunction & failure of various organs

3. Diabetes Mellitus
• "Diabetes" comes from the Greek word for
"siphon", and implies that a lot of urine is
made.
• The second term,"mellitus" comes from the
Latin word, "mel" which means "honey", and
was used because the urine was sweet.

4. Diabetes In India
• According to the Indian Council of Medical
Research-Indian Diabetes study (ICMR-
INDIAB), a national diabetes study, India
currently has 63 million people with diabetes.
• India represents the world’s second largest
diabetes population after China.
• This is set to increase to over 100 million by
2030.
• The majority of people with diabetes (>90%)
have Type 2 diabetes (T2DM).

5. Classification of Diabetes
Proposed by ADA - 1997.
• Type I:
– Absolute Insulin Deficiency due to islet cell
destruction
• Either immune mediated or idiopathic
• Type II:
– Relative insulin deficiency due to impaired -cell
function
– Marked ↑ peripheral insulin resistance
• Type III: Other Specific types
• Type IV: Gestational Diabetes

6. Type 1 DM
• Type 1 diabetes is characterized by destruction of the
pancreatic beta cells, most likely due to combined
genetic, immunologic and possibly environmental
(e.g. viral) factors which contribute to cell
destruction.
• This is abnormal response of the body in which the
antibodies are direct against the normal tissues and
eventually there is damage to Islet of Langerhans ,
specific area of the pancreas that produce insulin,
reducing the production of insulin or totally no
production of insulin.

7. Type 2 DM
• Type 2 Diabetes Mellitus is a adult onset, and
non-insulin dependent. There are 2 main
problems related to insulin in type 2 diabetes,
first one is “insulin resistance “ (insulin do not
bind with the special receptor on cell surface)
and impaired insulin secretion (insulin
secreting glands release irregular amount of
insulin).

9. Differences between type-1 and type-2
Diabetes Mellitus
• Type 1
• Young age
• Normal BMI, not obese
• No immediate family history
• Short duration of symptoms
(weeks)
• Can present with diabetic
coma (diabetic ketoacidosis)
• Insulin required
• Type 2
• Middle aged, elderly
• Usually overweight/obese
• Family history usual
• Symptoms may be present
for months/years
• Do not present with
diabetic coma
• Insulin not necessarily
required
e

10. Other specific types
A) Genetic defects of Beta cell function
B) Genetic defects in Insulin action
C) Diseases of the Exocrine Pancreas
D) Secondary to Endocrinopathies
E) Drugs / Chemical induced
F) Infections
G) Uncommon form of Immune Mediated Diabetes.
H) Other Genetic Syndromes associated with Diabetes
MODY Syndromes
Lipo atrophic Diabetes
FCPD
Pancreatitis
Trauma
Neoplasia
Cystic Fibrosis
Hemochromatosis
Acromegaly
Cushings Syndrome
Pheochromocytoma
Hyperthyroidism
Steroids
Thiazides
Diazoxide
Beta Blockers
Thyroid Hormones
Congenital Rubella
CMV
Anti insulin Receptor Antibodies
Down’s Syndrome
Turners
Klinefelters

11. Gestational Diabetes
•Gestational diabetes is caused when the insulin
receptors do not function properly and glucose
intolerance increases
•This is likely due to pregnancy related factors
such as the presence of human placental lactogen
that interferes with susceptible insulin receptors.
•Increased health risk to mother and baby
•Big baby,jaundice,still birth can occur for
untreated cases
•Goes away after birth, but increased risk of
developing Type 2 DM for mother and child

12. RISK FACTORS &SYMPTOMS

13. RISK FACTORS

14. Symptoms of Diabetes

15. • Polyuria - weakness
• Polydipsia - fatigue
• Polyphagia -  blood sugar / glucose level
• weight loss - (+) glucose in urine (glycosuria)
nausea / vomiting
• changes in LOC
• Recurrent infection, prolonged wound healing
• Altered immune and inflammatory response, prone to
• infection (glucose inhibits the phagocytic action of WBC 
• resistance)
- Genital pruritus – (hyperglycemia and glycosuria favor fungal
growth : candidal infection – resulting in pruritus, common
• presenting symptom in women)

16. INVESTIGATION
– Fasting blood sugar
– Post prandial blood sugar
– HbA1C
– Lipid Profile – To diagnose dyslipidaemia
• RBS can be done only if the patient follows up
for the diagnostic tests after a meal

17. • Person to be tested should be on a normal diet for at least 3 days prior
to testing.
•The test should be done after an overnight fast of 8 – 10 hours (no
beverages including tea or coffee should be consumed),
•Draw a sample of blood after confirming fasting state of the patient.
Fasting Serum Glucose
(mg/dl)
Diagnosis
Below 110 Normal
Between 110 and 126 Pre-diabetes
Above 126 Diabetes (Must be confirmed with a
second fasting test)
Fasting Blood Sugar

18. Post Prandial Blood Sugar
• Following the collection of the fasting blood
sample for analysis of fasting serum glucose
(FSG). Patient is advised to have a normal
meal and return to the clinic after 2 hours
following the meal.
Post prandial blood sugar Diagnosis
< 140mg/dl Normal
140-200mg/dl Pre -diabetic
>200mg/dl Diabetic

19. HbA1C
• Person to be tested should be on a normal
diet for at least 3 days prior to testing.
• The test should be done after an overnight
fast of 8 – 10 hours
HbA1C Levels Diagnosis
4 – 6 Normal for those without
diabetes
6.1-7 Target range for diabetics
>7 Poor control

20. Lipid profile
Results of lipid profile Classification
LDL
< 100 optimal
100-129 Near optimal
130-159 Borderline high
160-190 High
>190 Very high
Serum triglycerides
< 150 Optimal
150-199 Borderline high
200-499 High
>500 Very high
HDL cholesterol
< 40 Low
> 60 High

21. TREATMENT GUIDELINES
Major Risk Factors (Exclusive of LDL Cholesterol)
• Cigarette smoking
• Hypertension (BP >140/90 mmHg or on antihypertensive
medication)
• Low HDL cholesterol (<40 mg/dL)
• Family history of premature CHD
• Age (men >45 years; women >55 years)

22. LDL VALUES Risk factor Treatment goal
>130 CHD Pharmacological
theraphy
>160 +2 risk factors Pharmacological
theraphy
>160-190 + 1 risk factor Life style
modification
>190 +1 risk factor Pharmocological
theraphy
TREATMENT GUIDELINES

23. Insulin

24. Discovery of insulin

25. Patient leonard thomson.,, February 15, 1923
December 15 1922
The Miracle of Insulin

26. Structure of insulin
21 amino acids
30 AA

27. Difference between human, pork, beef
insulin
Species A-chain B-chain
8th AA 10th AA 30th AA
Human THR ILEU- THR
Pork THR ILEU ALA
Beef ALA VAL ALA

28. Bioassay of insulin
• 1 IU reduces the BSL to 45 mg/dl in fasting
rabbits
• 1 mg insulin = 28 IU
• Can also be measured by radioimmunoassay
or enzyme immunoassay

29. Actions of insulin
Rapid actions Intermediary actions Long term
Sec / min Few hours > 24 hrs
E.g
Metabolic
actions
•↑ multiplication
•↑ differentiation
of cells
• Imp role in
intrauterine &
extrauterine
growth
Through DNA
e.g
• ↑ GLUT synthesis
• Synthesis of
enzymes for AA
metabolism

30. Actions of insulin
• Metabolic:
– carbohydrate, lipid , protein, electrolyte
• Vascular
• Anti-inflammatory
• Fibrinolytic
• Growth
• Steroidogenesis

31. Carbohydrate metabolism
• Over all action of insulin is to ↓ glucose level
in blood
– ↑ Transport of glucose inside the cell
– ↑ Peripheral utilization of glucose
– ↑ Glycogen synthesis
– ↓ Glycogenolysis
– ↓ Gluconeogenesis

32. Lipid metabolism
• ↓ Lipolysis
• ↑ Lipogenesis
• ↑ Glycerogenesis
• ↓ Ketogenesis
• ↑ Clearance of VLDL & chylomicrons from
blood through enzyme Vascular Endothelial
Lipoprotein Lipase

33. Protein metabolism
• Facilitates AA entry and their synthesis into
proteins and inhibit breakdown in muscles
and other cellsls
Electrolyte metabolism
• ↑ transport of K+, Ca++, inorganic phosphates

34. Other actions
• Vascular actions:
– Vasodilation by Activation of endothelial NO
production
• Anti-inflammatory action
– Especially in vasculature
• Decreased fibrinolysis
• Growth
• Steroidogenesis

35. Mechanism of action of insulin

36. Insulin Mediated Glucose Transport
G
INS
aa

Insulin
Receptor
Complex
INS
aa 
a subunit
 subunit
Insulin molecule
Storage vesicle
containing
GLUT 4
Glucose
Tyrosine Kinase Activation
Metabolised Stored as Glycogen

37. Fate of insulin
• Distributed only extracellularly
• Must be given parenterally
• Addition of zinc or protein decreases its
absorption & prolongs the DOA
• Insulin released from pancreas is in
monomeric form
• Half life of insulin = 5 -9 minutes

38. Different types of insulin preparations
• Conventional preparations of insulin
– Produced from beef or pork pancreas
– 1 % of other proteins
– Potentially antigenic
• Highly purified insulin preparations
– Gel filtration reduces or ion exchange
• Human insulins
• Newer insulin analogs

39. Conventional insulin preparations
Type Onset
(Hr)
Peak
(Hr)
DOA
(Hr)
Short acting
Regular insulin
Semilente
0.5 -1
1
2-4
3-6
6-8
12-16
Intermediate
acting
Lente
Isophane(NPH)
1-2 8-10 20-24
Long acting Ultra lente
Protamine Zinc
Insulin (PZI)
4-6 14-18 24-36

40. Highly purified insulin preparations
• Single peak insulins
– Purified by gel filtration contain 50 to 200 PPM
proinsulin
– Actrapid: purified pork regular insulin
– Monotard: purified pork lente
– Mixtard: purified pork regular(30%) +
isophane(70%)
• Mono component insulins
– After gel filtration purified by ion exchange
chromatography contain 20 PPM proinsulin
– Actrapid MC, Monotard MC

41. Human insulins
• Human (Actrapid, monotard, insulatard, mixtard)
• Obtained by recombinant DNA technology
• Advantages
– More water soluble as well as hydrophobic
– More rapid SC absorption , earlier & more defined
peak
– Less allergy
• Disadvantages
– Costly
– Slightly shorter DOA

42. Indications of human insulins
• Insulin resistance
• Allergy to conventional preparations
• Injection site lipodystrophy
• During pregnancy
• Short term use of insulin

43. Newer Insulin analogs
Type Onset Peak
(Hr)
DOA
(Hr)
Rapid
acting
Lispro
Aspart
Glulisine
5-15 min
10-15 min
5-15 min
1
1
1
3-5
3-5
5-6
Long acting Glargine
Detemir
Degludec
1-2 hrs
2-3 hrs
1-2 hrs
No peak
6-8 hr
No peak
24 hr
24 hr
42 hr

44. Insulin Lispro
• Produced by Inversing proline at B28 with
lysine at B29.
• Forms weak hexamers , dissociate rapidly
• Needs to be injected immediately before or
after meals
• Better control of meal time glycemia & lower
incidence of PP hypoglycemia

45. • Insulin aspart:
– Proline at B28 replaced by aspartic acid
– Change reduces tendency for self aggregation
• Insulin glulisine
– lysine replaces aspargine at B3 & glutamic acid
replaces lysine at position B29

46. Insulin glargine
• Prepared by adding 1 glycine at A21 together with 2
arginine residues at end of B chain
• Improved Stability
• Much better bioavailabilty
• Smooth peakless effect is obtained
• Fasting & interdigestive BGL effectively lowered
irrespective of time of day
• Lower hypoglycemic episodes
• Cannot be mixed with other insulins
• Suitable for once daily injection

47. Insulin detemir
• Soluble long acting basal insulin analog with
• Flat action profile and prolonged duration
• Threonine in B30 ommited & C14 fatty acid
chain attached to amino acid B29
• Prolonged action
– Strong self association
– Albumin binding
– Fatty acid side chain

48. Insulin analogs score over
conventional insulins
• Less nocturnal hypoglycemia
• Less weight gain
• Better efficacy
• More physiological action profiles
• Less premeal lag time (0-15 mts)
• Lispro & Glulisine even after meals
• Better PP glucose control
• Improved predictability, tolerability, and flexibility

49. Adverse effects of insulin
• Hypoglycemia
• Local reactions
– Lipodystrophy
– Lipoatrophy
• Allergy
• Obesity
• Insulin induced edema

50. Uses of insulin
• Diabetes mellitus
– Must for type I diabetics
– Can be used in type II diabetics
• Diabetic ketoacidosis
• Hyperosmolar non ketotic hyperglycemic
coma

51. Indications of insulin in type II DM
• Primary or secondary failure of oral hypoglycemics
• Pregnancy
• Perioperative period
• CKD
• Steroid therapy
• LADA
• Fasting > 300 mgms HbA1c > 10
• Unintentional wt loss with or with out ketosis
• Type 2 with DKA ( severe beta cell dysfunction )

52. Recommended sites for S/C Insulin injections

53. Insulin resistance
• State in which normal amount of insulin
produces subnormal amount of insulin
response
– ↓ insulin receptors
– ↓ affinity for receptors
• May be acute or chronic
• Requirement of > 200 Units of insulin per day
in absence of stress
• Common in type II diabetics & obese

54. Newer insulin delivery devices
• Prefilled insulin syringes
• Pen devices
• Jet injectors
• Inhaled insulin
• Insulin pumps
• External artificial pancreas
• Insulin complexed with liposomes:
intraperitoneal, rectal, oral

55. 40 units/ml
100 units/ml

57. PEN INJECTORS
• Easy to carry
• Easier to accurately measure dose
• more expensive than vials
JET INJECTORS
Needleless system.
Uses high pressure air to force a tiny
stream of insulin through the skin

58. Insulin Pump
Pro
• Simplified insulin
dosing
• Precise delivery
• Greater impact in those
with highest starting
A1c
• Slightly less insulin use
per day
Con

59. Inhaled Insulin (Exubera)
Advantages
 Improved pt convenience
 Faster onset of action compared to Regular SC insulin
 No needles risk of infection
 Potential earlier onset of insulin therapy in Type 2 DM

60. Oral antidiabetic drugs
• Sulfonylureas
• Meglitinides
• Biguanides
• Thiazolidinediones
• a-glucosidase inhibitors

61. Sulfonylureas
I Generation
– Tolbutamide
– Chlorpropamide
II Generation
– Glipizide
– Gliclazide
– Glibenclamide (Glyburide)
– Glimepiride

62. Mechanism of action
• Release of insulin by acting on SUR1 receptors
• Primarily augment phase 2 of insulin secretion
• Presence of at least 30% functional -cells
essential for their action.
• Minor action: ↓ glucagon secretion
• Extra pancreatic action: ↑sensitivity of
peripheral tissue to insulin by ↑insulin receptors

64. Pharmacokinetics
• Well absorbed orally
• Highly bound to plasma proteins > 90%
• Have low volume of distribution
• Cross placenta C/I in pregnancy
• Metabolized in liver
• Excreted in urine

65. Daily dose & Duration of action
Sulfonylureas Doses No of
doses/day
DOA
(hrs )
1 Tolbutamide 0.5 – 2 g 2-3 6-8
2 Chlorpropramide 0.1 to 0.5 g 1 36 -48
3 Glibenclamide 5 to 15 mg 1-2 18-24
4 Gliclazide 40- 240 mg 1-2 12-24
5 Glipizide 5 to 40 mg 1-2 12-18
6 Glimepiride 1 to 6 mg 1 Upto 24

66. Individual Sulfonylurea
Sulfonylureas Special points
1 Tolbutamide Short acting, low potency , hypoglycemia
least likely
2 Chlorpropramide ↑Hypoglycemia, ↑ADH , Disulfiram Like
Reaction
3 Glibenclamide Potent but slow acting, may work when
others fail
4 Gliclazide Antiplatelet, antioxidant action, may delay
Retinopathy, less weight gain
5 Glipizide Fast acting, hypoglycemia & weight gain less
likely, prefered in elderly
6 Glimepiride More extrapancreaatic action, less
hyperinsulinemia, less hypoglycemia

67. GLIMEPIRIDE
1) Lesser risk of hypoglycemia
2) Relatively safe in elderly and mild renal failure
3) Antiplatelet and antifibrinolytic activity
4) Little or no weight gain
5) FDA approved combination therapy with insulin
6) Safe and effective for use in the pediatric
population
7) ↑ Levels of plasma adiponectin & ↓ TNF α
8) Stimulates GLUT4 expression

68. Why Glibenclamide is more potent and
longer acting than other SU
1. May accumulate within  cells and directly stimulate
exocytosis of insulin granules
2. Greater/longer binding to SUR-1 receptors
3. Slower absorption and distribution
4. Inhibition of hepatic insulinase
5. Suppression of several counter-regulatory hormones
6. More suppression of Hepatic Glucose Output
7. May stimulate insulin synthesis

69. Adverse effects
• Hypoglycemia:
• GI disturbances: Nausea, vomiting, metallic
taste, diarrhoea & flatulence
• Weight gain
• Hypersensitivity
• Not safe in pregnancy
• Chlorpropamide:
– cholestatic jaundice, dilutional hyponatremia,
antabuse reaction

70. Contraindications
1. Allergy to SU
2. Renal failure
3. Significant hepatic dysfunction
4. Severe infections, stress, trauma, major surgery,
CVA
5. Pregnancy (except Glibenclamide)

71. Selection of SU
Clinical conditions Agents
Fasting & postprandial
hyperglycemia
Long acting/Intermediate acting Su.
Only postprandial hyperglycemia Glipizide
Renal impairment Glipizide
GDM Glibenclamide
Elderly (> 65) Avoid Glibenclamide, chlorpropamide
Alcoholics Avoid chlorpropamide
DM & IHD Avoid Glibenclamide.
DM, HT & Edema legs Avoid chlorpropamide

72. Meglitinide analogs
• Quick & short acting insulin releasers
• MOA: same as Sulfonylureas but act through
different receptor SUR2
• Mainly used to control Post prandial
hyperglycemia
• Less hypoglycemia

73. Repaglinide
• Well tolerated in elderly patients and in renal
impairment
• Adverse effects:
– Mild headache, dyspepsia, arthralgia, headache
• Indicated in type II DM
• Dose : start 0.5mg with meals can ↑ 16mg/day

74. Nateglinide
• Stimulates first phase of insulin secretion
• More rapid acting & shorter duration than
repaglinide
• Mainly used in post prandial hyperglycemia
without producing late phase hypoglycemia
• Little effect on fasting BSL
• Adverse effects: dizziness, nausea, flu like
symptoms
• Dose: 60 to 180 mg TDS with meals

75. Biguanides
• Metformin & phenformin
• Little or no hypoglycemia
• Also improves the lipid profile in type II
diabetic patients
• Metformin dose = 0.5 to 2.5 g/day in 2-3
divided doses

76. Mechanism of action
• Suppress hepatic & renal gluconeogenesis
• ↑ uptake & utilization of glucose by skeletal
muscles which reduces insulin resistance
• Inhibit alimentary absorption of glucose
• Interfere with mitochondrial respiratory chain
& promote peripheral glucose utilization by
enhancing anaerobic glycolysis

77. METFORMIN - INDICATIONS
• Obese Type 2 Diabetes.
• Secondary Sulfonylurea Failure state.
• To reduce Insulin requirements.
• Can be combined with Sulfonylureas,
Glitazones, Insulin.

78. Adverse effects
• Anorexia, nausea, vomiting, diarrhoea
• Metallic taste
• Loss of weight
• Skin rashes
• Lactic acidosis: rare
• Vitamin B12 deficiency: due to malabsorption
Usually does not cause hypoglycemia even in
large doses

79. Contraindications of metformin
• Renal failure –
( Sr. Crt > 1.5 / Crt. Clearance < 40 )
• Advanced Liver Disease.
• Alcohol abusers.
• Cardiac Disease.
• Pregnancy.

80. Thiazolidinediones (Glitazones)
Rosiglitazone & pioglitazone Selective agonists of PPAR
Bind to nuclear PPAR
Activate insulin responsive genes - regulate
carbohydrate & lipid metabolism
Sensitize the peripheral tissues to insulin
↓blood glucose by
↑ Glucose transport into
muscle & adipose tissue
Inhibit hepatic
gluconeogenesis
Promote
lipogenesis

81. Thiazolidinediones
• Hyperglycemia, hyperinsulinemia, and
elevated HbA1c levels are improved.
• Pioglitazone has no effect on LDL levels, ↓
triglyceride & ↑ HDL
• Rosiglitazone has inconsistent effect on lipid
profile it ↑ HDL & LDL levels
• The TZDs lead to a favorable redistribution of
fat from visceral to subcutaneous tissues.

82. • Pioglitazone:
– 15 to 45 mg once daily orally
• Rosiglitazone:
– 4 to 8 mg once daily orally
• Pt who benefit most are type II DM with
substantial amount of insulin resistance
• Also used in PCOD
• Monotherapy – Hypoglycemia rare
• Add-on Therapy – readjust dosage.
• Takes one month to act

83. Adverse effects
• Weight gain: due to fluid retention & edema
• ↑ Extracellular fluid volume
• Worsening of CHF
• ↑ Deposition of subcutaneous fat
• Mild anemia: due to hemodilution
• Hepatotoxicity : rare
• Rosiglitazone: ↑risk of fractures especially in
elderly women

84. Contraindications
• Liver disease
• Congestive heart failure
• Pregnancy
• Lactating mother
• Children

85. Alpha glucosidase inhibitors
• Acarbose
• Miglitol
• Voglibose

86. Acarbose
• Complex oligosaccharide
• Inhibits a-glucosidase as well as a-amylase
• Reduces postprandial hyperglycemia without
increasing insulin levels
• Regular use reduces weight
• In prediabetics reduces occurrence of type II
DM, hypertension & cardiac disease
• Dose: 50 to 100 mg TDS
• Given just before food or along with food

87. Adverse effects
• Flatulence, diarrhoea, abdominal pain
• Do not cause hypoglycemia by themselves but
may cause if used with Sulfonylureas
• If hypoglycemia occurs should not be treated
with routine sugar (sucrose),
• Glucose should be used
Contraindicated in inflammatory bowel disease
& intestinal obstruction

88. 88
Voglibose
• Advantages over Acarbose and Miglitol
– 20-30 times more potent then acarbose
– Does not affect digoxin bioavailability unlike
acarbose
– No dosage adjustment required in renal
impairment patients unlike miglitol
– Superior tolerability
– Dose: 0.2 to 5 mg

89. Newer drugs for Type II DM
• GLP-1 Analogues
– Exenatide
– Liraglutide
• DPP-IV Inhibitors
– Sitagliptin
– Vildagliptin
– Alogliptin
• Amylin analog:
Pramlintide

90. Exenatide
• Synthetic GLP I analogue resistant to DDP IV
• ↑ Post prandial insulin release
• Supresses glucagon release
• Supresses appetite and slows gastric emptying
• injected SC twice daily 1 hour before meals
acts for 6 to 10 hours
• Nausea is important side effect

91. Sitagliptin
• Orally active inhibitor of DPP-4
• Prevents degradation of endogenous GLP-I
• Dose: 100mg a day
• Mainly used in post prandial hyperglycemia
• No action on weight and lipids
• Costly

92. Pramlintide
• Synthetic amylin analog
• Improves overall glycaemic control,↓ PPG
• Reduces BW : anorectic action
• Well tolerated
• Given SC before meals
• SE: GI disturbances/Less hypoglycemia when
used alone
• Can be used in type I DM

93. COMPLICATIONS

95. Chronic Complications
Systems Effected Disease Health Concern
Eyes • Retinopathy
• Glaucoma
• Cataracts
• Blindness
Blood Vessels • Coronary artery disease
• Cerebral vascular disease
• Peripheral vascular disease
• Hypertension
• Heart attack
• Stroke
• Poor circulation in feet
and legs
• Heart attack, stroke,
kidney damage
Kidneys • Renal insufficiency
• Kidney failure
• Insufficient blood filtering
• Loss of ability to filter blood
Nerves • Neuropathies
• Autonomic neuropathy
• Chronic pain
• Poor nerve signaling to
organ systems
Skin, Muscle, Bone • Advanced infections
• Cellulitis
• Gangrene
• Amputation

96. Acute Complications
• Diabetic keto-acidosis (DKA)
• Insulin shock
• Hyperglycemic, hyperosmolar,
non-ketotic (HHONK) coma
• Dawn phenomenon
• Somogyi effect

97. D.K.A.
PATHOPHYSIOLOGY
NO INSULIN
MARKED HYPERGLYCEMIA
GLUCOSURIA
WEIGHT
LOSS
OSMOTIC
DIURESIS
POLYURIA
CELLULAR
HUNGER
POLYPHAGIA
POLYDIPSIA
LIPOLYSIS
OSMOTIC
DEHYDRATION

98. D.K.A.
Sign and Symptoms;
• S/sx of dm +
• Ketonuria
• Metabolic acidosis
• Kussmaul’s respiration
• Acetone breath
• Flushed face
• Tachycardia
• Circulatory collapse , coma and death

99. INSULIN SHOCK
Low blood sugar
Cause:
• Overdose of exogenous insulin
• Eating less
• Overexertion without additional calorie intake

100. INSULIN SHOCK
• S/SX:
• PARASYMPATHETIC
– HUNGER
– NAUSEA
– HYPOTENSION
– BRADYCARDIA
• CEREBRAL
– LETHARGY,
– YAWNING
– SENSORIUM CHANGES
• SYMPATHETIC
– IRRITABILITY
– SWEATING
– TREMBLING
– TACHYCARDIA
– PALLOR
• CLINICAL FINDING :
• BLOOD GLUCOSE
BELOW 55-60 mg%

101. Hyperglycemic Hyperosmolar Non-
Ketotic Coma (HHNC)
• can occur when the action of insulin is severely
inhibited
• seen in pts. w/t T2DM
Precipitating factors:
infection, renal failure, MI, CVA, GI hemorrhage,
pancreatitis, CHF, TPN, surgery, dialysis, steroids
S/Sx:
 polyuria  oliguria (renal insufficiency)
 lethargy
 temp, PR, BP, signs of severe fluid deficit
 Confusion, seizure, coma
 Blood glucose level > 600 mg/100 ml.

102. Interventions for DKA and
Hyperosmolar Coma
• Regular insulin IV push or IV drip
• 0.9% NaCl IV – 1 L during the 1st hr, 2-8 L over 24
hrs.
• administer sodium bicarbonate IV to correct acidosis
• Monitor electrolyte levels, esp. serum K+ levels
• administer K+, monitor UO hourly (30ml/hr)

103. SOMOGYI EFFECT
TOO MUCH INSULIN
HYPOGLYCEMIA
GLUCAGON IS RELEASED
LIPOLYSIS
GLUCONEOGENESIS
GLYCOGENOLYSIS
REBOUND
HYPERGLYCEMIA
+
KETOSIS

104. DAWN PHENOMENON
• The "dawn effect," also called the "dawn
phenomenon," is the term used to describe an
abnormal early-morning increase in blood
sugar (glucose) — usually between 2 a.m. and
8 a.m. in people with diabetes.

105. CHRONIC COMPLICATIONS OF
DIABETES MILLETUS
• Degenerative changes in the vascular system
– Atherosclerosis
• Neuropathy from
– Vascular insufficiency
– Hyperglycemia
• Eye complications from anoxia
– Cataract
– Diabetic retinopathy
– Retinal detachment

108. Interventions and foot care practices
–Cleanse and inspect the feet daily.
–Wear properly fitting shoes.
–Avoid walking barefoot.
–Trim toenails properly.
–Report nonhealing breaks in the skin.

109. Wound Care
• Wound environment
• Debridement
• Elimination of pressure on infected area
• Growth factors applied to wounds

110. SUMMARY
• Treatable, but not curable.
• Preventable in obesity, adult client.
• Controllable- DIET and EXERCISE
• Diagnostic Tests
• Signs and symptoms of hypoglycemia and
hyperglycemia.
• Treatment of hypoglycemia and hyperglycemia
– diet and oral hypoglycemics.
Monitoring, teaching and assessing for
complications.

111. “Of course too
much is bad for
you”
THANK
YOU