DM

Definition
• Diabetes mellitus is a chronic metabolic
disorder characterized by sustained elevat-
ed blood glucose (hyperglycemia) resulting
from defects in insulin secretion, action
or both
Pathogenesis
Natural history of TYPE 2 DM
S/S OF DM
 Classification of Diabetes
1. Type 1 diabetes
– β-cell destruction..always need insulin
2. Type 2 diabetes
– Progressive insulin secretory defect/ insulin
resistance
3. Gestational Diabetes Mellitus (GDM)
4. Other specific types of diabetes
• Maturity onset diabetes of the young (mody)
• Monogenic diabetes syndromes
• Diseases of the exocrine pancreas, e.g., cystic
fibrosis
• Drug- or chemical-induced diabetes
CRITERIA FOR THE DIAGNOSIS OF DIABETES
Fasting plasma glucose (FPG)
(7.0 mmol/L)
OR
2-h plasma glucose ≥200 mg/dL
(11.1 mmol/L) during an OGTT
OR
HBA1C ≥6.5%
OR
Classic diabetes symptoms + random
plasma glucose
(11.1 mmol/L)
• Fasting is defined as no caloric intake for at
least 8 hours.
• 2-hour postprandial glucose test should be
performed using a glucose load containing the
equivalent of 75-g glucose dissolved in water.
INTERMEDIATE HYPERGLYCEMIA
• Fasting 6.1 to 7.0 mmol/l
• Rbs 7.8 to 11.0 mmol/l
 Type 1 Diabetes
• Blood glucose rather than A1C should be used to dx type 1 diabetes in
symptomatic individuals.
• Usually young <30 to 35 yrs
• They often present with acute symptoms of diabetes and markedly elevated
blood glucose levels, and some cases are diagnosed with life-threatening
ketoacidosis
• Lean, often rapid weight loss be -
fore diagnosis
• Insulin secretion Insulin deficient,
• needs insulin
treatment at diagnosis
• Type 1 Diabetes may present
at a later age and this is referred to as Latent Autoimmune Diabetes in
Adults (LADA).
• Acute complication of DKA , Hypoglycemia- associated with
treatment
 TYPE 2 DM

• accounts for 90–95% of all diabetes

• insulin resistance and usually relative (rather than absolute) insulin
deficiency.
• Slow, insidious onset, progressive disease.
Patient could be undiagnosed for years
• asymptomatic glucosuria present
• Initially inadequate insulin secretion, with pro-gressive deficiency
over time due to beta cells exhaustion
• Consider testing in asymptomatic adults of any age with BMI ≥25
kg/m2
• For all patients, testing should begin at age 45 years.
• If tests are normal, repeat testing carried out at a minimum of 3-year
intervals is reasonable.
 DM IN PG/gestational dm
• Hyperglycemia at 2nd or 3rd trimester
• screening for undiagnosed type 2 diabetes at the first prenatal
visit in women with diabetes risk factors.
• In pregnant women not known to have diabetes, GDM testing
should be performed at 24 to 28 weeks of gestation.
• DX is made by 75 g OGTT , 1 hour 10.0mmol/l, 2HRS RBS OF
>8.5
• Fasting/HBA1C
• Meds insulin, AND but new study showed metformin superior
benefits
• Tight sugar control with 3 mnthly hba1c to prevent
complications
MANAGEMENT
• Early diagnosis
• Treatment to target
• Regular screening for complications and
comorbid conditions
• Education on diabetes and complications,
self-care and diet
• Community awareness on diabetes
Recommendations: Glycemic Goals in Adults

• HBA1C goal for many nonpregnant adults is <7.5%

• <6.5% for select patients if achievable without
significant hypoglycemias or other adverse effects.
• <8% for patients with a history of severe
hypoglycemia, limited life expectancy, or other
conditions that make <7% difficult to attain. E.g
heartfailure pts, elderly pts, frail patients
Mean Glucose Levels for Specified
A1C Levels
  Mean Glucose
Mean Plasma
Glucose*
A1C% mmol/L
6 7.0
<6.5  
6.5-6.99  
7 8.6
7.0-7.49  
7.5-7.99  
8 10.2
8-8.5  
9 11.8
10 13.4
11 14.9
12 16.5
 Pharmacologic
Approaches
to
Glycemic Treatment
 Types of Insulin
categories of insulin: -
Forms
1. Rapid acting/ Short acting …..regular/soluble insulin, Humalog,
– Onset 30-60 minutes DOA 5-8 hours , GIVEN 30 minutes prior to
meal
2. Intermediate-acting insulin– e.g. NPH insulin, Humulin N,
– Onset 2-4HRS minutes DOA 12-24 hours , 30 minutes prior to
meal

3. Long-acting – e.g. Levemir, Lantus

– Onset 1-2 hours DOA 20-24 hours GIVEN once or twice daily

4. Pre-mix short-acting (regular) and intermediate-acting (NPH)

insulins – usually in the combination 70/30 (Mixtard, Humulin, Humalog 75/25),
Humulin 50/50
• Onset 30 minutes DOA 8-24 hours GIVEN 30 minutes prior to
meal
The two most common regimens used

i. Basal bolus regimen (the preferred option) -

with short or rapid acting
insulin given with main meals (usually three
times per day)
ii. intermediate-acting or long-acting insulin
given once or twice daily
(evening, or morning and evening).
iii. Twice-daily insulin using pre-mixed insulin or
short acting and NPH
 Insulin requirements

• Start at 0.5 to 1 units per kg/ day or

• This can be given using either of the following regimens:
a. Basal bolus regimen e.g lantus
b. Twice-daily injections mixtard
C. Basal Bolus Regimen - also called Multiple Daily Injections (MDI). This
is the preferred option
• * 10 iu tds for regular insulin (in adults only)
• *Mixtard.. give 2/3 in the morning and 1/3 in the evening
 Then titrate depending on sugar levels

by changing by a preferably maximum 6 iu per day.

*If fasting is high increase evening dose ,
*if evening/lunch sugars before meals are high increase morning dose
 Short-acting and long-acting insulin
analogues
•
If short-acting (soluble)/rapid acting and long-acting analogue insulins
are
used, give:
• 60% of the total daily dose as short-acting (soluble) insulin (divided
up
between 3-4 pre-meal boluses)
• 40% of the total daily dose as a single evening injection of long-
acting
analogue insulin.
• E.g
• 42 kgs child.. Given 0.5 /kg = 21 iu
• Give bolus of 9 iu dinner (40%) , then 4 iu tds ( 60 %)
• Pre-pubertal children (outside the partial remission phase) usually
require 0.5-1.0 IU/kg/day.
• During puberty, requirements may rise substantially above 1 and
even up to 2 U/kg/day.
• The ‘‘correct’’ dose of insulin is that which achieves the best
attainable
glycaemic control for an individual child or adolescent, without
causing obvious Hypoglycemia, and resulting in normal growth and
development
 important to note
• Insulin requirements can decrease for a time
during the “honeymoon
period” before rising again.
• The total daily dose required will generally
increase as the child grows,
and once puberty ensues a higher dose per kg
per day is often needed.
HYPOGLYCEMIA
 Hypoglycemia

• Insulin-treated patients with hypoglycemia unawareness or

an episode of severe hypoglycemia should be advised to raise
glycemic targets to strictly avoid further hypoglycemia for at
least several weeks, to partially reverse hypoglycemia
unawareness, and to reduce risk of future episodes.
 Insulin storage
•
i. Insulin vials should be stored at 4-8 °C in a refrigerator where available or
in some other method of cooler. In hot climates where refrigeration is not
available, cooling jars, earthenware pot, and charcoal pot will help to
preserve insulin activity.
ii. If using PEN device, insulin can be kept at room temperature for 28 days
iii. Insulin must NEVER be frozen.
iv. Direct sunlight or extreme heat (in hot climates or in a vehicle) damages
insulin.
• v. Patients should not use insulins that have changed in appearance
(clumping, frosting, precipitation, or discolouration).
vi. Once opened, an insulin vial should be discarded after 4 weeks.
 Pramlintide
• FDA approved for T1DM
• Amylin analog
• Delays gastric emptying, blunts pancreatic
glucose secretion, enhances satiety
• Induces weight loss, lowers insulin dose
• Requires reduction in prandial insulin to
reduce risk of severe hypos

American Diabetes Association Standards of Medical Care in Diabetes.

Approaches to glycemic treatment. Diabetes Care 2017; 40 (Suppl. 1): S64-S74
 Management of type 2 DM

Management of Type 2 diabetes entails the following

components:
i. Treatment of hyperglycemia
ii. Treatment of hypertension and dyslipidemia
iii. Prevention and treatment of micro-vascular
complications
iv. Prevention and treatment of macro-vascular
complications
v. Prevention and treatment of non-vascular
complication
 Treatment of hyperglycemia
•
Treatment of hyperglycaemia in type 2 diabetes consist of the following;
a. Non -pharmacological
i. Education
ii. Diet
iii. Physical activity
iv. Blood glucose monitoring
b. Pharmacological
i. Oral glucose lowering agents (oral hypoglycaemic agents)
ii. Insulin
iii. Combination Therapies – e.g. Oral glucose lowering agents and insulin
iv. Non-insulin injectable glucose lowering agents (GLP-1 agonists
Antihyperglycemic Therapy in T2DM
 OGLAS
• BIGUANIDES
Metformin..
• MOA: (i)Reduce glucose production in liver (ii) cause
(mild) reduction in peripheral insulin resistance
• s/e Abdominal pain,nausea, loose bowel
motions, lactic acidosis
Vitamin B12 deficien-
cy with prolonged use. Peripheral neuropathy and
anemia
• Dose 500mg to 2000mg/ day
 Sulfonyl ureas
• MOA.. Increase insulin release from the pancrease b cells.
• First-generation drugs
tolazamide and tolbutamide.
• Second-generation
Glibenclamide ( nogluc) dosing 5mg to 10mg
Gliclazide mr (glycinorm/ diamicron), starting 30mg max 120mg per
day. LOW RISK OF HYPOGLYCEMIA, GOOD 24 HR SUGAR CONTROL
• Third generations .
Glimepiride, 1 to 4mg LESS RISK OF HYPO
C/I in pregnancy
 DPP4 INHIBITORS..

MOA. Increase incretin by inhibiting enzyme that

degrades. Incretin increases insulin release
1. sitagliptin(januvia)
• Dose..50 to 100mg per day
• Vidagliptin
• Linagliptin
• Usually comes combined with metformin as
• Triviamet, inosita, sitamet
 SGLT inhibitors..newer drugs
• Increase excretion of glucose from the
kidneys..act on proximal convoluted tubule to
inhibit glucose reabsorption
• Cardiac and renal protection
• Empagliflozin dosage 10mg to 25 od
(empiget)
• Dapagliflozin 5 to 10mg
• s/e UTI, DKA,genital candidiasis,hypotension
 Indications for insulin in T2DM
•
• Poor glycaemic control
• HbA1c still ≥8% despite
previous attempts to
improve with lifestyle
modication and
maximum oral therapy
• Patient is symptomatic
(weight loss, polyuria,
polydipsia, recurrent
infections)
• Steroid-induced diabetes
• Patient unable to tolerate
or has contraindication
to OGLAs
• Gestational diabetes or
diabetes in pregnancy
not controlled on OGLAs
• Painful neuropathy
• Foot ulceration and
infection
Recommendations: Pharmacological Therapy For T2DM

• If noninsulin monotherapy at maximal

tolerated dose does not achieve or maintain
the A1C target over 3 months, add a second
oral agent.
• Use a patient-centered approach to guide
choice of pharmacologic agents.
• Don’t delay insulin initiation in patients not
achieving glycemic goals.
 Complications

Microvascular
• Neuropathy..constipations ,,NEUROPATHIC PAINS
• vascular.. foot care risk of diabetic foot, malabsortion
• Retinopathy ..regular eye check ups
Macrovascular..
• Be aware of risk of MI
• strokes
• nephropathies..regularly do urine tests..check for
proteinuria