2. Objectives of the Lecture
īŽ Be able to define diabetes mellitus
īŽ Be able to classify diabetes mellitus
īŽ Be able to list predisposing factors
īŽ Be able to list clinical features of diabetes mellitus
īŽ Be able to list drugs used in treatment of diabetes
mellitus
Diabetes Mellitus: An Overview 229/03/2014
3. Outline
īŽ DM definition
īŽ DM epidemiology
īŽ Types of DM
īŽ Clinical features
īŽ Investigations
īŽ Treatment
īŽ Complications
29/03/2014 3Diabetes Mellitus: An Overview
4. What is Type 2 Diabetes Mellitus (T2DM)?
â Current ADA definition1
âĸ T2DM is a metabolic disease characterized by
hyperglycemia, resulting from a combination of
resistance to insulin action and an inadequate insulin
secretory response
â T2DM involves 2 primary pathogenic processes:
âĸ progressive decline in pancreatic islet function
(â insulin secretion and inadequately suppressed
glucagon secretion)2,3
âĸ diminished tissue responses to insulin (insulin
resistance)2,4
Diabetes Mellitus: An Overview 429/03/2014
ADA=American Diabetes Association
1American Diabetes Association. Diabetes Care. 2006; 29 (Suppl 1): S43âS48; 2Weyer C, et al. J Clin Invest. 1999; 104: 787â794;
3MÃŧller WA, et al. N Engl J Med. 1970; 283: 109â115; 4AhrÊn B, Pacini G. Diabetes Obes Metab. 2005; 7: 2â8.
5. Epidemiology
īŽ More than 285 million (2010) people affected
worldwide
īŽ By 2030, some 566 million people are projected to
have diabetes.
īŽ 3.2% (12.1million) from Africa in 2010
īŽ By 2030, 3.7% (23.9 million) from Africa 2010
Diabetes Mellitus: An Overview 529/03/2014
7. Classification of Diabetes
īŽ Type 1 diabetes
ī¨ β-cell destruction
īŽ Type 2 diabetes
ī¨ Progressive insulin secretory defect
īŽ Other specific types of diabetes
ī¨ Genetic defects in β-cell function, insulin action
ī¨ Diseases of the exocrine pancreas
ī¨ Drug- or chemical-induced
īŽ Gestational diabetes mellitus
Diabetes Mellitus: An Overview 729/03/2014
8. TYPE 1 DM
īŽ Due to B-cell destruction.
īŽ Require insulin for survival.
īŽ Presence of certain autoantibodies.
īŽ Type 1A â presence of autoantibodies (anti-GAD, IA2, ICAA,
and anti-insulin antibodies).
īŽ Type 1B â absence of autoantibodies (idiopathic)
Diabetes Mellitus: An Overview 829/03/2014
9. Type 2 DM
īŽ Most common form of DM
īŽ Characterized by disorder in insulin action and insulin secretion or
both.
īŽ Specific etiology unknown
īŽ Insulin resistance
īŽ Progressive B-cell failure.
īŽ They are obese.
Diabetes Mellitus: An Overview 929/03/2014
10. Predisposing Factors
īŽ Obesity
īŽ Hypertension
īŽ Strong family history
īŽ Sedentary lifestyle
īŽ Lack of exercise
īŽ Alcoholism
īŽ Smoking
īŽ Western diet
īŽ Advancing age
īŽ Diabetogenic drugs
īŽ Low birth weight
īŽ Artificial or cow milk
formulae in neonates
īŽ Viruses
īŽ Migration
Diabetes Mellitus: An Overview 1029/03/2014
12. Gestational diabetes
īŽ Carbohydrate intolerance associated with
hyperglycemia of variable severity with the onset
or first recognition during pregnancy.
īŽ In early pregnancy, fasting and post prandial
glucose concentration are normally lower than in
non pregnant women
Diabetes Mellitus: An Overview 1229/03/2014
13. Risk of developing GDM
īŽ Old women
īŽ Previous history of glucose intolerance
īŽ History of babies large for gestational age
Diabetes Mellitus: An Overview 1329/03/2014
14. Underlying causes of Type 2 Diabetes
Diabetes Mellitus: An Overview 1429/03/2014
Obesity
Insulin
resistance
-cell
defect
Impaired
glucose
tolerance
Early
diabetes
Late
diabetes
Hyperinsulinaemia
Decreased insulin
secretion
-cell failure
Saltiel AR. J Clin Invest 2000;106:163â164.
ACE/CDR/05/20746/1
17. Testing for Diabetes in
Asymptomatic Patients
īŽ Consider testing overweight/obese adults (BMI âĨ25 kg/m2)
with one or more additional risk factors
ī¨ In those without risk factors, begin testing at age 45 years
īŽ If tests are normal
ī¨ Repeat testing at least at 3-year intervals
īŽ Use A1C, FPG, or 2-h 75-g OGTT
īŽ In those with increased risk for future diabetes
ī¨ Identify and, if appropriate, treat other CVD risk factors
Diabetes Mellitus: An Overview 1729/03/2014
18. Diagnostic Criteria
Fasting Glucose
mg/dL
2-h OGTT
mg/dL
Random Glucose
mg/dL
A1c
Normal <100 <140 <200 <5.7%
Prediabetes 100-125
(IFG)
140-199
(IGT)
5.7-6.4%
Diabetes âĨ 126 âĨ 200 âĨ 200 âĨ 6.5%
Diabetes Mellitus: An Overview 1829/03/2014
Note: In the absence of unequivocal hyperglycemia, result(s) should be
confirmed by repeat testing.
19. DIAGNOSTIC CRITERIA FOR GDM
ADA ADA WHO
75g oral
glucose
(Mg/dL)
100g oral
glucose
(Mg/dL)
75g oral
glucose
(Mg/dL)
Fasting 95 95 >/= 126
1 hour 180 180
2 hour 155 155
3 hour NA 140 >/= 140
Diabetes Mellitus: An Overview 1929/03/2014
22. Eyes
(retinopathy, glaucoma,
cataracts)
Brain and Cerebral
Circulation
(stroke, TIA)
Heart and Coronary
Circulation
(angina, MI, CHF)Kidneys
(nephropathy, ESRD)
Peripheral Nervous
System
(peripheral neuropathy) Peripheral Vascular Tree
(peripheral vascular disease,
gangrene, amputation)
Tissue Damage in Many Organ Systems Leads to
Serious Long-term Complications in T2DM
Diabetes Mellitus: An Overview 2229/03/2014
CHF=congestive heart failure; ESRD=end-stage renal disease; MI=myocardial infarction; TIA=transient ischemic attack; T2DM=type 2 diabetes mellitus
Adapted from International Diabetes Federation. Complications. Available at: www.eatlas.idf.org/complications Accessed February 17, 2009.
23. Chronic Complications
īŽ Affects many organ systems.
īŽ Vascular :
ī¨ Microvascular
ī¨ Macrovascular
īŽ Non vascular:
ī¨ Gastroparesis
ī¨ Sexual dysfunction
ī¨ Skin changes
Diabetes Mellitus: An Overview 2329/03/2014
24. Mechanism of Complications
īŽ There are 3 major theories (not mutually
exclusive);
īŽ Formation of Advanced Glycosylation End Products (AGEs)
via the nonenzymatic glycosylation of cellular protein.
īŽ Increase glucose metabolism via the sorbitol pathway by
enzyme aldose reductase.
īŽ Increase formation of diacyglycerol leading to activation of
certain isoforms of protein kinase C (PKC).
Diabetes Mellitus: An Overview 2429/03/2014
27. Outline
īŽ Purpose of laboratory testing
īŽ Confirmation of diagnosis of DM
īŽ Assessment of severity and level of DM control
īŽ Identification of co-morbidities and complications
īŽ Effect of treatment
īŽ Self urine and blood glucose monitoring
īŽ Laboratory monitoring
29/03/2014 27Diabetes Mellitus: An Overview
28. Confirmation of diagnosis
īŽ FPG and 2hrPP
īŽ Urinalysis
īŽ HBA1c
īŽ Serum lipids
īŽ Serum electrolytes
īŽ Imaging studies
29/03/2014 28Diabetes Mellitus: An Overview
30. Aims of treatment
īŽ Reduce the symptoms of hyperglycaemia
īŽ Limit adverse effects of treatment
īŽ Maintain quality of life and psychological well-
being
īŽ Prevent or delay vascular complications of
diabetes
Diabetes Mellitus: An Overview 3029/03/2014
31. Basis of Treatment
īŽ Reducing insulin resistance
īŽ Replacing or augmenting insulin secretion
īŽ Reducing gluconeogenesis
īŽ Treating effects of lipolysis and reducing lipolysis
Diabetes Mellitus: An Overview 3129/03/2014
33. Glycemic Recommendations
Diabetes Mellitus: An Overview 3329/03/2014
*Individualize goals based on these values.
â Postprandial glucose measurements should be made 1â2 h after the
beginning of the meal, generally peak levels in patients with diabetes
Target Treatment
Goal
AACE/ACE 2011 ADA 2012
A1c â¤6.5% <7%
Fasting Glucose FPG <110 mg/dl Preprandial PG 70-
130mg/dl
Postprandial
Glucose
2-hr postprandial
<140mg/dl
Peak <180mg/dl
34. Blood Pressure and Lipid Goals
Blood pressure <130/80 mmHgâ
Lipids
LDL cholesterol <100 mg/dL (<2.6
mmol/L)âĄ
Diabetes Mellitus: An Overview 3429/03/2014
â Based on patient characteristics and response to therapy, higher or lower
systolic blood pressure targets may be appropriate.
âĄIn individuals with overt CVD, a lower LDL cholesterol goal of <70 mg/dL
(1.8 mmol/L), using a high dose of statin, is an option.
35. Approach to Patient with DM
īŽHistory
īŽPhysical examination
īŽLaboratory assessment.
Diabetes Mellitus: An Overview 3529/03/2014
36. Management contd
īŽ Requires a multidisciplinary team:
ī¨ Primary care provider
ī¨ Endocrinologist/Diabetologist
ī¨ Certified diabetic educator
ī¨ Nutritionist
Diabetes Mellitus: An Overview 3629/03/2014
37. Management contd
īŽ When complication arises, the team will
include;
ī¨Neurologist
ī¨Nephrologists
ī¨Cardiologist
ī¨Vascular surgeon
ī¨Ophthalmologist
ī¨podiatrist
Diabetes Mellitus: An Overview 3729/03/2014
39. Non pharmacologic treatment
īŽ Education of patients:
ī¨ Individualized or
group based
ī¨ Done by various
health professionals
ī¨ Repetitive,
interactive
ī¨ Address causes,
course, treatment
ī¨ Define target for DM
control
29/03/2014 Diabetes Mellitus: An Overview 39
41. Dietary Management of DM
īŽ Individualized, simple instructions
īŽ Aim to achieve ideal body weight and encourage
healthy eating habits and lifestyle modification
īŽ Calculate activity level and caloric requirements to
achieve above
īŽ Diet should be able to reduce hyperglycaemia,
glucotoxicity and lipotoxicity
Diabetes Mellitus: An Overview 4129/03/2014
42. The Ideal or Paleolithic Diet
īŽ 50 -65% carbohydrate, complex carbohydrates
derived mainly from whole grains and legumes, low
glycaemic index
īŽ 0.6g/kg body weight proteins (15-20%) derived from
game animals or fish, insects
īŽ 15 -25% fat derived from vegetable and nut oils.
īŽ High fiber 25 â 30g daily
Diabetes Mellitus: An Overview 4229/03/2014
43. EXERCISE IN DIABETES
īŽ Dynamic or isotonic
īŽ Graduated & individualised
īŽ Regular with adequate warm up
īŽ Appropriate footcare
īŽ Precautions in OHA or insulin dose
īŽ Contraindicated in some conditions
29/03/2014 43Diabetes Mellitus: An Overview
44. Exercise Therapy
īŽ Benefits
ī¨ Increase insulin sensitivity
ī¨ Improved long term glycaemic control â lower HbA1c
ī¨ Improved circulating lipid profile
ī¨ Improved BP control
ī¨ May promote redistribution of body fat ( reduce CVD
risk)
īŽ Health benefits â 3 days wkly
29/03/2014 44Diabetes Mellitus: An Overview
45. īŽ Individualized regimen
ī¨ State of control
ī¨ Stretching & warm-up
ī¨ Aerobic level sustainable for 30mins
ī¨ Cool down
īŽ Full evaluation before prescribing exercise
īŽ Complications/risks
īŽ Precautions for patient
29/03/2014 45Diabetes Mellitus: An Overview
48. Indications for Use of Insulin
īŽ All type 1DM patients
īŽ High risk type 2 DM patients
īŽ All pregnant diabetics not controlled with diet
īŽ All acutely or chronically ill persons with DM
īŽ All patients preparing for or just having surgery
īŽ All diabetics who have trauma, leg ulcers,
gangrene, moderately severe nephropathy,
myocardial infarction.
īŽ Any person who desires strict control
Diabetes Mellitus: An Overview 4829/03/2014
49. INSULIN DOSAGE
īŽ 0.6-1.0 units/kg body weight (ideal body weight)
īŽ Divide this dose into tds if soluble insulin OR into bd if
70/30 insulin (humulin) used
īŽ Additional 0.3 units/kg body weight added if infection,
sepsis or DKA present
īŽ Insulin to be given 30 minutes premeals if 30:70 or
soluble insulin and 30-45 min premeal if Isophane or
Lente (Humulin N) insulin
īŽ Do not add insulin to N/Saline infusion
īŽ Do not give Humulin 30:70 or Isophane (Humulin
N)insulin I.V
īŽ Adjust insulin dose with blood sugar
Diabetes Mellitus: An Overview 4929/03/2014
50. Targets for Control
īŽ Absence of symptoms, well being
īŽ Ideal body weight, BMI 20-23, maximum waist 88cm
in females and 94 in males
īŽ Blood pressure 130/80mmHg
īŽ FBS 70 -90mg/dL
īŽ 2hpp 70 â 140mg/dL
īŽ HbA1c 6 â 7%
īŽ Total cholesterol <5mmol(200mg)
īŽ No proteinuria
Diabetes Mellitus: An Overview 5029/03/2014
52. Pharmacology - Biguanides
Class Biguanides
Compound Metformin
Mechanism Activates AMP-kinase
Action(s) âĸ Hepatic glucose production
âĸ Intestinal glucose absorption
âĸ Insulin action
Glucose
Lowering Effect
âĸ Fasting
âĸ Post Prandial
Advantages âĸ No weight gain
âĸ No hypoglycemia
âĸ Reduction in cardiovascular events and mortality (UKPDS
f/u)
Disadvantages âĸ Gastrointestinal side effects (diarrhea, abdominal
cramping)
âĸ Lactic acidosis (rare)
âĸ Vitamin B12 deficiency
âĸ Contraindications: reduced kidney function
Cost Low
Diabetes Mellitus: An Overview29/03/201452
53. Pharmacology - SulfonylureasClass Sulfonylureas (2nd generation)
Compound âĸ Glibenclamide/Glyburide
âĸ Glipizide
âĸ Gliclazide
âĸ Glimepiride (3rd generation)
Mechanism Closes KATP channels on β-cell plasma membranes
Action(s) Insulin secretion
Advantages âĸ Generally well tolerated
âĸ Reduction in cardiovascular events and mortality (UKPDS f/u)
Disadvantages âĸ Relatively glucose-independent stimulation of insulin
secretion: Hypoglycemia, including episodes necessitating
hospital admission and causing death
âĸ Weight gain
âĸ Primary and secondary failure
Cost Low
Diabetes Mellitus: An Overview29/03/201453
54. Pharmacology â Meglitinides
Class Meglitinides
Compound âĸ Repaglinide (PrandinÂŽ)
âĸ Nateglinide (StarlixÂŽ)
Mechanism Closes KATP channels on β-cell plasma membranes
Action(s) Insulin secretion
Advantages Accentuated effects around meal ingestion
Disadvantages âĸ Hypoglycemia, weight gain
âĸ Dosing frequency
Cost Medium
Diabetes Mellitus: An Overview29/03/201454
55. Pharmacology â Thiazolidinediones
(TZD)
Class Thiazolidinediones (Glitazones)
Compound Pioglitazone (ActosÂŽ)
Mechanism Activates the nuclear transcription factor PPAR-
Action(s) Peripheral insulin sensitivity
Advantages âĸ No hypoglycemia
âĸ HDL cholesterol
âĸ Triglycerides
Disadvantages âĸ Weight gain
âĸ Edema
âĸ Heart failure (CI with stage III and IV)
âĸ Bone fractures
Cost High
Diabetes Mellitus: An Overview29/03/201455
56. Pharmacology â Thiazolidinediones
(TZD)
Class Thiazolidinediones (Glitazones)
Compound Rosiglitazone (AvandiaÂŽ)
Mechanism Activates the nuclear transcription factor PPAR-
Action(s) Peripheral insulin sensitivity
Advantages No hypoglycemia
Disadvantages âĸ LDL cholesterol
âĸ Weight gain
âĸ Edema
âĸ Heart failure (CI with stages III and IV)
âĸ Bone fractures
âĸ Increased cardiovascular events (mixed evidence)
âĸ FDA warnings on cardiovascular safety
Cost High
Diabetes Mellitus: An Overview29/03/201456
57. TZDs and the FDA
īŽ Rosiglitazone
ī¨ Restricted by FDA â can only be used by patients currently
benefiting from therapy or do not get adequate DM
treatment from other agents and not willing to use
pioglitazone
ī¨ 1-800-AVANDIA
īŽ Pioglitazone
ī¨ FDA alert â ongoing analysis of risk of bladder cancer
(with prolonged use >12 months)
Diabetes Mellitus: An Overview29/03/201457
58. Pharmacology â Alpha-Glucosidase
Inhibitors
Class Îą-Glucosidase inhibitors
Compound âĸ Acarbose
âĸ Miglitol
Mechanism Inhibits intestinal Îą-glucosidase
Action(s) Intestinal carbohydrate digestion and absorption
slowed
Advantages âĸ Nonsystemic medication
âĸ Postprandial glucose
Disadvantages âĸ Gastrointestinal side effects (gas, flatulence,
diarrhea)
âĸ Dosing frequency
Cost Medium
Diabetes Mellitus: An Overview29/03/201458
59. Pharmacology â Incretin Enhancers
Class DPP-4 inhibitors (incretin enhancers)
Compound âĸ Sitagliptin (JanuviaÂŽ)
âĸ Vildagliptin (GalvusÂŽ)
âĸ Saxagliptin (OnglzaÂŽ)
âĸ Linagliptin (TradjentaÂŽ)
Mechanism Inhibits DPP-4 activity, prolongs survival of endogenously released
incretin hormones
Action(s) âĸ Active GLP-1 concentration
âĸ Insulin secretion
âĸ Glucagon secretion
Advantages âĸ No hypoglycemia
âĸ Weight âneutralityâ
Disadvantages âĸ Occasional reports of urticaria/angioedema
âĸ Cases of pancreatitis observed
âĸ Long-term safety unknown (cancer ?)
Cost High
Diabetes Mellitus: An Overview29/03/201459
60. SGLT-2 Inhibitors
īŽ Sodium glucose cotransport 2 inhibitors
īŽ These are drugs which inhibit the reabsorption of
glucose in the distal tubules of the kidney
īŽ Idea for using these drugs emanated from people with
the rare familial glycosuria patients
īŽ Dapagliforzin, Canagliforzin are the first 2 in this group
īŽ Cause weight loss and reduce weight by glycosuria
īŽ Dapagliforzin failed FDA approval early last year
īŽ Canagliflorzin (Invokana) was approved by FDA in
March 2013
īŽ Side effects are nasal stuffiness and mild increase in UTI
29/03/2014
Diabetes Mellitus: An
Overview60
62. Pharmacology â Amylin Analog
Class Antihyperglycemic Synthetic Analog
Compound âĸ Pramlintide (SymilinÂŽ)
Mechanism âĸ Amylinomimetic
Action(s) âĸ Glucagon secretion (glucose-dependent)
âĸ Slows gastric emptying
âĸ Satiety
Advantages âĸ Potential weight loss
Disadvantages âĸ Meal time injections
âĸ Nausea
âĸ Hypoglycemia in combination with insulin
Cost High
Diabetes Mellitus: An Overview
Lexi-Drugs Online [Internet]. Hudson (OH) : Lexi-Comp, Inc. 1978-2012[cited 2012
August 1].
29/03/201463
63. Pharmacology â Bile Acid
Sequestrants
Class Bile acid sequestrants
Compound Colesevelam (WelcholÂŽ)
Mechanism Binds bile acids/cholesterol
Action(s) Bile acids stimulate receptor on liver to produce
glucose
Results âĸ Lowers fasting and post prandial glucose
Advantages âĸ No hypoglycemia
âĸ LDL cholesterol
Disadvantages âĸ Constipation
âĸ Triglycerides
âĸ May interfere with absorption of other medications
Cost High
Diabetes Mellitus: An Overview29/03/201464
67. Definition
īŽ An acute metabolic complication of DM
īŽ Hyperglycaemia (>300mg/dL)
īŽ Acidosis , blood pH <7.3
īŽ Increased total blood ketones, > 5 mmol/L
īŽ In clinical practice it is suspected when there is
ketonuria++ in the face of hyperglycaemia
Diabetes Mellitus: An Overview 6829/03/2014
68. Epidemiology of DKA
īŽ Few published Nigerian data
īŽ Europeans and Americans quote 10 â 30 cases
per 100, 000 population.
īŽ Commoner in females
īŽ Commoner in non-whites
īŽ Mortality higher in the elderly
Diabetes Mellitus: An Overview 6929/03/2014
69. Aetiopathogenesis/Pathophysiology
īŽ Insulin deficiency and glucagon excess leads to
excess acetyl-CoA
īŽ Acetyl CoA is converted to acetoacetate
īŽ Some acetoacetate is converted to other
ketones
īŽ These ketones require to be buffered and thus
bicarbonate is used up as pH drops
īŽ The respiratory centre is stimulated and
Kussmaulâs breathing occurs
Diabetes Mellitus: An Overview 7029/03/2014
70. Aetiopathogenesis/Pathophysiology
īŽ Urine becomes acidic, osmotic diuresis occurs
īŽ H and Na and K are lost in the urine together
with ketones
īŽ FFAs are increased due to lipolysis from
stimulation of lipoprotein lipase
īŽ A major role for initiating all the events is
elevation of counter-regulatory hormones
Diabetes Mellitus: An Overview 7129/03/2014
72. Clinical Features
īŽ Risk factors of
infection, trauma,
omission of
medication
īŽ Malaise
īŽ Weight loss
īŽ Polyuria, polydipsia,
īŽ Nausea, vomiting,
abdominal distension
īŽ Confusion, lethargy
īŽ Hypotension,
arhythmias
īŽ Severe dehydration
īŽ Acetone breath
īŽ Glycosuria and
ketonuria
Diabetes Mellitus: An Overview 7329/03/2014
73. Clinical Features contd
īŽ Deep coma and or seizures may occur
īŽ Acute abdomen may be present and confused
with surgical abdomen
īŽ Fluid loss is in range of 6 â 8 litres in adults
Diabetes Mellitus: An Overview 7429/03/2014
75. Investigations
īŽ Urinalysis
īŽ Ketostix
īŽ Electrolytes and urea
īŽ Haemogram incl WBC
īŽ Blood pH and ketones
īŽ ECG,
īŽ Urine and blood culture
īŽ Blood sugars
Diabetes Mellitus: An Overview 7629/03/2014
76. Treatment
īŽ Admit to emergency or ICU, NPO, resuscitate
īŽ Intravenous saline 6 â 8 litres in 24 hours in adults
īŽ Saline given 1 litre fast, then 1 litre in an hour, then
1 litre in 2hrs, then 1 litre 4 hourly
īŽ Soluble insulin 10 units IM or IV stat, then give 6
units hourly till RBS <250mg/dL
īŽ Sugars should drop at 50-70mg/dL per hour
īŽ If not dropping double the dose of insulin
Diabetes Mellitus: An Overview 7729/03/2014
77. Treatment (contd)
īŽ When RBS <250mg/dL change the IV fluids to
5% dextrose to run 1 pint 4 hourly and add KCl
20 â 40mmol per pint with soluble insulin 4-6
units per pint
īŽ When patient fully conscious and rehydrated
then change insulin to s/c t.d.s pre-meals at
dose of 0.2 â 0.3 units/kg body weight and allow
patient eat
Diabetes Mellitus: An Overview 7829/03/2014
78. Treatment 4
īŽ Antibiotics may be indicated if sepsis present but
it should be remembered that leucocytosis is a
regular feature of DKA
īŽ NG tube may be required if there is gastric
dilatation
īŽ Dysequillibrium syndrome is a complication of
excessive rapid lowering of blood sugar
Diabetes Mellitus: An Overview 7929/03/2014
79. Prognosis
īŽ This is good if treatment commenced early and
adequate monitoring of sugars, electrolytes and
fluid balance is done.
Diabetes Mellitus: An Overview 8029/03/2014
80. HYPEROSMOLAR
HYPERGLYCAEMIC STATE (HHS)
īŽ Definition
īŽ Epidemiology
īŽ Aetiopathogenesis/Pathophysiology
īŽ Clinical Features
īŽ Investigations
īŽ Treatment
īŽ Prognosis
Diabetes Mellitus: An Overview 8129/03/2014
81. Definition of HHS
īŽ Similar to DKA but:
īŽ Blood sugars in range of 600 â 2000mg/dL
īŽ No ketonuria or trace ketones
īŽ No anion gap or mild anion gap <10
īŽ Often have azotaemia, increased Na, K
īŽ Normal blood pH
Diabetes Mellitus: An Overview 8229/03/2014
82. Epidemiology
īŽ HHS is not as common as DKA
īŽ Commoner in elderly patients who are often
institutionalised or with cognitive impairment
īŽ Males slightly more commonly affected
īŽ Seen in type 2 DM
īŽ Rare in type 1 DM
Diabetes Mellitus: An Overview 8329/03/2014
83. Aetiopathogenesis
īŽ Patient is fairly insulin sensitive
īŽ There is still some circulating insulin sufficient to
suppress ketosis but insufficient to suppress
gluconeogenesis
īŽ Renal impairment couple with dehydration from
reduced fluid intake over a period
īŽ Often patient on diuretic
īŽ Hyperosmolarity ensues with thrombogenicity
Diabetes Mellitus: An Overview 8429/03/2014
84. Clinical features
īŽ Polyuria, polydipsia and then oliguria
īŽ Confusion or coma
īŽ Severe dehydration
īŽ No Kussmaulâs respiration
īŽ DVT or PE is common
Diabetes Mellitus: An Overview 8529/03/2014
85. Clinical Features
īŽ Severe dehydration, fluid deficit 8 â 10 litres
īŽ Altered sensorium, seizures, etc
īŽ Thromboembolic events eg DVT, PE, CVA, , MI,
etc
īŽ Vomiting and gastroparesis
īŽ Gastric erosions and haematemesis common
Diabetes Mellitus: An Overview 8629/03/2014
87. Treatment
īŽ Very similar to DKA treatment
īŽ Admit, NPO
īŽ Rehydrate with 6 â 10 litres of fluid preferably
half normal saline
īŽ Hourly soluble insulin 4-6 units after a stat
10units IV
īŽ Use heparin or enoxaparin to anticoagulate
īŽ Watch out for fluid overload if CKD present
Diabetes Mellitus: An Overview 8829/03/2014
88. Prognosis
īŽ Poorer than DKA, mortality being 50 â 90% in
most centres
īŽ Mortality may follow cerebral oedema, embolic
events or uraemia
Diabetes Mellitus: An Overview 8929/03/2014
89. Hypoglycaemia
īŽ Defined as low blood sugar
īŽ Blood sugars below 2.2mmol/L taken as
hypoglycaemia in general population
īŽ In DM patients the threshold for hypoglycaemia
is lower so coma may occur in blood sugars 50 â
80mg/dL and in those with rapid decline in blood
sugars
Diabetes Mellitus: An Overview 9029/03/2014
90. Definition
īŽ Thus Whippleâs triad often used to identify and
confirm hypoglycaemia in DM patient
īŽ Triad is made up of
īŽ - hypoglycaemic symptoms
īŽ - biochemically proven low blood sugar
īŽ - relief of symptoms after administration of sugar
or carbohydrate containing drink/meal
Diabetes Mellitus: An Overview 9129/03/2014
91. Aetiopathogenesis of Hypoglycaemia
īŽ Excess insulin whether from injections or
secretagogue
īŽ Inadequate calorie intake
īŽ Inadequate counter-regulatory response
īŽ Continued insulin secretion or insulin action
Diabetes Mellitus: An Overview 9229/03/2014
92. Risk factors for Hypoglycaemia
īŽ Skipping or postponing meals
īŽ Overdose of hypoglycaemic agents
īŽ Poor monitoring of blood sugars
īŽ Age â extremes of age, the very young and the
elderly
īŽ Alcohol and other substances that potentiate
hypoglycaemic drugs
Diabetes Mellitus: An Overview 9329/03/2014
94. Investigations
īŽ Blood sugars
īŽ Insulin assays
īŽ C-peptide
īŽ Liver, renal function tests
Diabetes Mellitus: An Overview 9529/03/2014
95. Treatment
īŽ Resuscitate with glucose containing soft drink, sugar
or glucose at home if conscious
īŽ Admit to hospital if unconscious or if first aid with
sugar at home not working
īŽ Resuscitate and give IV 10% glucose or diluted 50%
glucose via wide bore access
īŽ Give IM glucagon 1mg if available
īŽ Continue to monitor blood sugars, omit insulin or
OHAs patient was taking
Diabetes Mellitus: An Overview 9629/03/2014
96. Treatment contd
īŽ When conscious and alert encourage to eat
īŽ If delay in regaining consciousness KIV stroke,
MI, uraemia or other co-morbidities
īŽ Thus CT scan, ECG, E/U/C may be required
īŽ Prevent recurrence by drug dose adjustment
and patient education
Diabetes Mellitus: An Overview 9729/03/2014
97. Conclusion
īŽ Early detection and recognition of metabolic
complications is vital for full recovery
īŽ Self glucose monitoring will prevent these
conditions
Diabetes Mellitus: An Overview 9829/03/2014
The classification of diabetes includes four clinical classesType 1 diabetes (results from β-cell destruction, usually leading to absolute insulin deficiency)Type 2 diabetes (results from a progressive insulin secretory defect on the background of insulin resistance)Other specific types of diabetes due to other causes; e.g., genetic defects in β-cell function, genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induced diabetes (such as in the treatment of HIV/AIDS or after organ transplantation)Gestational diabetes mellitus (GDM; diabetes diagnosed during pregnancy that is not clearly overt diabetes)Some patients cannot be clearly classified as having type 1 or type 2 diabetesClinical presentation and disease progression vary considerably in both types of diabetesOccasionally, patients who otherwise have type 2 diabetes may present with ketoacidosisSimilarly, patients with type 1 diabetes may have a late onset and slow (but relentless) progression despite having features of autoimmune diseaseSuch difficulties in diagnosis may occur in children, adolescents, and adultsThe true diagnosis may become more obvious over time
Recommendations for testing for diabetes in asymptomatic patients are summarized on this slide; testing should be considered in adults of any age with BMI âĨ25 kg/m2 and one or more of the known risk factors for diabetesFor many illnesses, there is major distinction between screening and diagnostic testing; however, for diabetes, the same tests would be used for âscreeningâ as for diagnosisA1C, fasting plasma glucose (FPG), or 2-hour oral glucose tolerance test (2-h OGTT) are appropriate to test for diabetesThe same assays used for testing for diabetes will also detect individuals with prediabetesIn adults, prediabetes and diabetes meet established criteria for conditions in which early detection is appropriate; both conditions are common, increasing in prevalence, and impose significant health burdensThere is a long presymptomatic phase before the diagnosis of type 2 diabetes is usually made; relatively simple tests are available to detect preclinical diseaseAdditionally, the duration of glycemic burden is a strong predictor of adverse outcomes, and effective interventions exist to prevent progression of prediabetes to diabetes (see Section IV. Prevention/Delay of Type 2 Diabetes) and to reduce risk of complications of diabetes (see Section VI. Prevention and Management of Diabetes Complications)
In 1997 and 2003, The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus1,2 recognized an intermediate group of individuals whose glucose levels, although not meeting criteria for diabetes, are nevertheless too high to be considered normalThis group was defined as having impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)IFG: fasting plasma glucose (FPG) of 100â125 mg/dL (5.6â5.9 mmol/L)*IGT: 2-hour plasma glucose (2-h PG) on the 75-g oral glucose tolerance test (OGTT) of 140â199 mg/dL (7.8â11.0 mmol/L)Individuals with IFG and/or IGT have been referred to as having prediabetes, indicating a relatively high risk for future development of diabetesIFG and IGT should not be viewed as clinical entities in their own right but rather risk factors for diabetes as well as cardiovascular disease (CVD)IFG and IGT are associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertensionIndividuals with an A1C of 5.7â6.4% should be informed of their increased risk for diabetes as well as CVD and counseled about effective strategies to lower their risks (see Section IV. Prevention/Delay of Type 2 Diabetes)*The World Health Organization (WHO) and a number of other diabetes organizations define the cutoff for IFG at 110 mg/dL (6.1 mmol/L)A1CIn 2009, an International Expert Committee that included representatives of the American Diabetes Association (ADA), the International Diabetes Federation (IDF), and the European Association for the Study of Diabetes (EASD) recommended the use of the A1C test to diagnose diabetes, with a threshold of âĨ6.5%1, and ADA adopted this criterion in 20102The diagnostic test should be performed using a method certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized or traceable to the Diabetes Control and Complications Trial (DCCT) reference assay3Point-of-care A1C assays, for which proficiency testing is not mandated, are not sufficiently accurate at this time to use for diagnostic purposes3The A1C has several advantages to the FPG and OGTT, including greater convenience (since fasting is not required), evidence to suggest greater preanalytical stability, and less day-to-day perturbations during periods of stress and illnessThese advantages must be balanced by greater cost, the limited availability of A1C testing in certain regions of the developing world, and the incomplete correlation between A1C and average glucose in certain individualsIn addition, HbA1C levels may vary with patientsâ race/ethnicity4,5
Recommended glycemic goals for nonpregnant adults These recommendations are based on those for A1C values, with listed blood glucose levels that appear to correlate with achievement of an A1C of <7%The issue of preprandial versus postprandial self-monitoring of blood glucose (SMBG) is complex;2 in some epidemiological studies, elevated postchallenge two-hour oral glucose tolerance test (2-h OGTT) glucose values have been associated with increased cardiovascular risk independent of fasting plasma glucose (FPG)In diabetic subjects, some surrogate measures of vascular pathology, such as endothelial dysfunction, are negatively affected by postprandial hyperglycemia3Individualize based on duration of diabetes, age/life expectancy, comorbid conditions, known CVD or advanced macrovascular complications, hypoglycemia unawareness, individual patient concernsNOTE: A1c âĨ6.5% are associated with an increased risk of blood vessel damage
2nd generation is more potent than 1st generation1st generation (tolbutamide, chlorpropamide, tolazamide)Glimepiride is most potent,
Insulin secretion is glucose dependentUse with sulfonylureas is duplicate therapy
Due to risks of MI restrict use of rosiglitazone to those currently using or those whose blood sugar is not controlled with any other meds and prefer not to use actosAvandia is available only through a restricted distribution program â prescriber would call 1800avandia
DPP4 enzyme is known to suppress some cancer growth