Diabetes Mellitus
• a group of common metabolic disorders that
share the phenotype of hyperglycemia
• persistently high blood glucose levels
• DM is a major cause of
=cardiovascular disease
=chronic kidney disease
=visual loss
=amputations.
Type 1 DM, pathogenesis
• interactions of genetic, env’tal, and
immunologic factors that ultimately
lead to the
-destruction of β cells and insulin
deficiency.
The classification of diabetes includes four
clinical classes
1. Type 1 diabetes- results from B-cell
destruction (immune mediated or idiopathic)
=leading to absolute insulin deficiency
2. Type 2 diabetes-results from a progressive
insulin secretory defect on the
background of insulin resistance
• 3. Other specific types of diabetes e.g. genetic
defects in B-cell function, genetic
defects in insulin action, diseases of the exocrine
pancreas, and medicine induced diabetes
• 4. Gestational diabetes mellitus (GDM)-
diabetes diagnosed during pregnancy in
previously non-diabetic woman.
T1DM
• After all β cells are destroyed, the
inflammatory process abates, the islets
become atrophic, and most immunologic
markers disappear
• Environmental triggers include viruses
(coxsackie, rubella, enteroviruses most
prominently).
Type 2 DM, pathogenesis
• Insulin resistance and abnormal insulin
secretion
• concordance in identical twins is between 70
and 90%
• if both parents have type 2 DM, the risk
approaches 40% in offspring
T2DM
• characterized by:
= impaired insulin secretion
=insulin resistance
=excessive hepatic glucose production
=abnormal fat metabolism.
Obesity (80% or more are obese).
Prevention of Type 2 DM
• Type 2 DM is preceded by a period of IGT or
IFG,
• intensive changes in lifestyle (diet and ex. for
30’/d - 5x/wk) in individuals with IGT
prevented or delayed the development of
type 2 DM by 58% compared to.
• metformin prevented or delayed diabetes by
31% compared to.
• The ADA suggests that metformin be considered in
individuals with both IFG and IGT who are at very high
risk for progression to diabetes (
=age <60 yrs
=BMI 35 kg/m2
=family hx of DM in 10 relative
=elevated TGs
=reduced HDL
=HTN, or
=A1C >6.0%).
• Individuals with prediabetes should be
monitored annually to determine if diagnostic
criteria for diabetes are present.
Clinical features
- No recognizable symptoms in many
individuals particularly in type 2 diabetes
- Large amounts of urine (polyuria)
- - Thirst and excessive drinking of water
C/F
- Unexplained weight loss
- Blurred vision
- Recurrent skin infections
- Recurrent itching of the vulva
- Symptoms related to chronic complications
C/F
- Abnormal sensory/motor neurologic findings
on extremities
- Foot abnormalities (various deformities,
ulcers, ischemia)
- Visual impairment
Current diagnostic criteria for the diagnosis
of diabetes mellitus:
1. Fasting plasma glucose (FPG)>126 mg/dl
2. Haemoglobin A1C>6.5%
3. A random plasma glucose>200mg/dl, in patients with
classic symptoms of
hyperglycemia or hyperglycemic crisis
4. Two-hour plasma glucose>200mg/dl during an oral glucose
oral tolerance test
Investigations
Newly diagnosed patient:
- Fasting or random blood glucose
- haemoglobin (HbA1c)
- Urine ketones
- Urine protein
- Blood urea, electrolytes and creatinine
- Fasting lipid profile
- ECG (adults)
Treatment
• Objectives
- Relieve symptoms
- Prevent acute hyperglycemic complications
- Prevent chronic complications of diabetes
- Prevent treatment-related hypoglycemia
- Achieve and maintain appropriate glycemic
targets
- Ensure weight reduction in overweight and
obese individuals
Targets Gaol for Non-Pregnant Adults with Diabetes
Fasting plasma glucose (capillary) 70-130 mg/dl
Postprandial (1–2 hrs after the beginning of the
meal) plasma glucose< 180 mg/dl
Haemoglobin A1C < 7%
Treatment of Type-2 Diabetes Mellitus
Non pharmacologic
1. Medical Nutrition Therapy (MNT)
- Avoid refined sugars as in soft drinks, or adding to their
teas/other drinks.
- Be encouraged to have complex carbohydrates
- Low in animal fat
- Increase in the amount of fibre e.g. vegetables, fruits
and cereals
2. Exercise
- Regular moderate-intensity aerobic physical
activity for at least 30 minutes
at least 5 days a week or at least 150
min/week.
- Encourage resistance training three times per
week
3. Self-blood glucose monitoring (SBGM)
4. Screening and treatment of micro and macro
vascular complications
Pharmacologic
1. Oral blood glucose lowering medicines
Metformin
- the first line medicine for initiation of
therapy
- if intolerant to metformin or have a
contraindication to it, sulfonylureas can be
the initial treatment medicine.
• Metformin, 500mg, P.O.daily with meals.
-Titrate dose slowly depending on blood
=glucose levels
=HbA1C to a maximum dose 2000-2500mg.
ADRs:
• abdominal discomfort and diarrhoea, lactic acidosis
• C/Is:
Serum creatinine >1.5 mg/dL (men) >1.4 mg/dL
(women),
CHF, radiographic contrast studies, seriously ill
patients,
acidosis, hepatic failure
Sulfonylureas
Glibenclamide, 2.5mg-5mg, P.O.daily 30 minutes before
breakfast.
- Titrate dose slowly depending on HbA1c and/or fasting
blood glucose levels to
15mg daily.
- When 7.5mg per day is needed, divide the total daily
dose into 2, with the
larger dose in the morning.
- Avoid in the elderly and patients with renal
impairment.
• ADRs:
anorexia, nausea, vomiting, abdominal
discomfort and diarrhoea;
C/Is:
renal diseases, hepatic disease, alcoholism
Sulfonylureas
• Glimepiride, 1-2mg P.O. QD, administered
with breakfast or the first main meal- Titrate
dose slowly depending on HbA1c and/or
fasting blood glucose levels.- Allow several
days between dose titrations- usual
maintenance dose: 1-4mg once daily;
maximum dose of 8mg once daily
• ADRs: dizziness, headache, hypoglycemia, weakness,
heartburn, vomiting
• C/Is:
hypersensitivity to sulfonyl ureas or sulfonamides,
breast
feeding, DKA
Insulin therapy in type 2 diabetes mellitus
Indications for insulin therapy:
- Failure to control blood glucose with oral
medicines
- Temporary use for major stress, e.g. surgery,
medical illness
- Severe kidney or liver failure
- Pregnancy
- Initial therapy for a patients presenting with
HbA1C >10%, fasting blood
glucose >250 mg/dl, random glucose
consistently >300 mg/dl, or ketonuria
- In patients in whom it is difficult to distinguish
type 1 from type 2 diabetes
Treatment of Type 1 Diabetes Mellitus
Non pharmacologic
See type 2 Diabetes
Pharmacologic
Insulin
Initiation, 0.2 to 0.4 units/kg/day
Maintenance – highly variable roughly 0.6 to 0.7 units/kg/day
• Twice daily injection:
=2/3rd morning (2/3rd NPH, 1/3rd RI) and
=1/3rd evening (1/2NPH, 1/2RI)
