This document provides an update on diabetes mellitus, including its classification into four main subtypes, diagnostic criteria, screening recommendations, treatment goals, and management strategies. Type I diabetes is characterized by absolute insulin deficiency due to autoimmune destruction of beta cells. Type II diabetes accounts for 90-95% of cases and involves relative insulin deficiency and insulin resistance. Diagnosis is based on fasting plasma glucose, oral glucose tolerance testing, or HbA1c levels. The main goals of management are lifestyle modification, glycemic control, risk factor reduction, and prevention of complications through medical nutrition therapy, physical activity, pharmacotherapy including metformin and additional agents as needed.

1. AN UPDATE
ON
DIABETES MELLITUS
Dr. Malith Niluka
Registrar – Medicine
NHSL

2. CLASSIFICATION
• 4 main Sub-types
1. Type I DM
 Absolute Insulin deficiency
 Cell mediated autoimmune destruction of Beta cells
 Antibodies to  Islet cells, GAD65, Insulin
 Small %  Aetiology unknown
2. Type II DM
 90-95%
 Relative Insulin deficiency + Insulin resistance
 Strong Genetic predisposition

3. • Gestational Diabetes Mellitus (GDM)
• Specific types of DM
• Monogenic Diabetes syndromes
• MODY
• Neonatal DM
• Exocrine failure
• Cystic fibrosis
• Chronic Pancreatitis
• Drug-induced
• Steroids
• Anti-retrovirals

4. DIAGNOSIS
• Fasting plasma glucose (FPG)
• No caloric intake for at least 8 hours and for maximum of 12 hours.
• Two hour plasma glucose in 75g oral glucose tolerance test (OGTT)
• a glucose load containing the equivalent of 75g anhydrous glucose dissolved in water.
• HbA1c
• does not require fasting
• Costly
• limited availability in resource poor settings.
• HbA1C must be measured using a validated assay standardized to the National
Glycohemoglobin Standardization Program-Diabetes Control and Complications Trial
reference
• HbA1C levels can vary with age, ethnicity, anaemia, haemoglobinopathies, haemolysis,
blood loss and severe hepatic and renal disease.
• Random blood sugar (RBS)
• can be used for diagnosis of diabetes in the presence of symptomatic hyperglycaemia.

5. Diagnostic Criteria
Diagnostic test Pre-diabetes Diabetes
Fasting plasma glucose 100mg/dL (5.6 mmol/L) to 125mg/dL (6.9
mmol/L) IFG
>= 126mg/dL (7.0 mmol/L)
2hr OGTT 140mg/dL (7.8 mmol/L) to 199mg/dL (11.0
mmol/L) IGT
>= 200mg/dL (11.1 mmol/L)
HbA1c 5.7 – 6.4% (39 – 47 mmol/mol) >= 6.5% (48 mmol/mol)
Random plasma glucose >= 200mg/dL (11.1 mmol/L)

6. How to confirm the Diagnosis ?
 Classic symptoms of Hyperglycaemia or Hyperglycaemic crisis
 Any single diagnostic test confirms the diagnosis
 Additionally, RBS >= 200mg/dL (11.1 mmol/l) confirms the diagnosis
 Asymptomatic individual
 Requires TWO abnormal test results from the same sample OR in 2 separate test
samples
 If using 2 separate samples, the second test may either be a repeat of the initial test
OR a different test
 Repeat the test that has a result above the diagnostic cut-off point if a patient has
discordant results from 2 different tests

7. SCREENING FOR Type II DM
• Any adult >= 35Y of age
• Any adult < 35Y of age WITH any Risk factor
• Any adolescent with BMI > 85th centile ( >+ SD)
• Female of an eligible couple / female expecting a pregnancy

8. Risk Factors

9. MANAGEMENT
• Main goals of management include,
1) Life style modification and patient education
2) Maintenance of good glycaemic control
3) Multiple risk factor management
4) Prevention of complications

10. Medical Nutrition Therapy
• Should be individualized.
• Weight loss is recommended (at least 5-10%) for all overweight or
obese individuals with a calorie restricted diet. All patients should
attempt to have near normal body weight
(BMI – 18.5 - 23kg/m2)
• Saturated fat and trans fat intake should be reduced.
• Salt intake should be limited to less than 2.4 g sodium (ex:- 1 tea spoon of salt)

11. Physical Activity
• Moderate intensity aerobic physical activity (e.g. walking, cycling, swimming) is
recommended.
• At least 150 min/week (e.g. brisk walk 30 minutes a day 5 days a week).
• For obese patients at least 60 minutes of exercise per a day.
• Resistance training (e.g. pushups, dumbbells) is recommended at least twice a
week.
• Encourage muscle-strengthening activities that involve all major muscle groups (2
or more days per week)
• Smoking and Alcohol
• All patients should be encouraged to quit smoking.
• Alcohol is best avoided. If taken it should be less than two units per day for men
and less than one unit per day for women.

12. Glycaemic Targets

13. Initiation of Pharmacotherapy
At initial diagnosis, monotherapy with Metformin (unless contraindicated) along with lifestyle interventions is
the preferred choice as most patients cannot achieve recommended targets on lifestyle interventions alone.
In the presence of moderate to severe hyperglycaemia at diagnosis, dual/ triple therapy or insulin may be
considered.
Insulin therapy may be required if there are severe symptoms or complications at presentation. Once the
hyperglycaemia is controlled, changing over to non-insulin therapies may be possible.
Consider timely initiation of combination therapy if monotherapy appears inadequate.
The combined regimen should aim for good glycaemic efficacy, low potential for hypoglycaemia as well as
weight neutrality or ideally weight loss in the obese and cost effectiveness.
Sulphonylurea is used as the second line treatment option or as the first choice in metformin intolerant/
contraindicated patients in local setting due to absence of robust data on superiority of other agents, low cost
and availability.
Nevertheless, any combination of anti hyperglycaemic agents such as sulfonylurea, thiazolidinedione, DPP-4
inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, or insulin can be considered for the combination therapy.

14. Life style modification
+
Metformin
Glycaemic target not achieved
in 3 months
Add a Second agent
Sulfonylurea (preferred)
DPP4i
GLP1
SGLT-2i
TZD
Basal Insulin
Glycaemic target not achieved
in 3 months
Add a Third agent
Sulfonylurea
DPP4i
GLP1
SGLT-2i
TZD
Basal Insulin
Glycaemic target not achieved
in 3 - 6 months

15. Non-Insulin therapies for Type II DM
CLASS ADVANTAGES DISADVANTAGES
REDUCTION OF
HbA1c
METFORMIN Extensive experience
No weight gain
No hypoglycaemia
Likely ↓ CVD events
GI side effects
(diarrhoea, abdominal cramps)
Lactic acidosis risk (extremely rare)
Vitamin B12 deficiency(rare)
Multiple contraindications:
CKD, acidosis, hypoxia, dehydration
1 – 2%
TOLBUTAMIDE
GLICLAZIDE
GLIPIZIDE
GLIBENCLAMIDE
GLIMIPERIDE
Extensive experience
↓ Microvascular risk
Hypoglycaemia
Weight gain
1 – 2%
ACARBOSE No hypoglycaemia
↓Postprandial glucose
excursions
Gastrointestinal side effects
(flatulence, diarrhoea)
Frequent dosing schedule
0.5 – 1%
SITAGLIPTIN
VILDAGLIPTIN
LINAGLIPTIN
No hypoglycaemia
Well tolerated
Weight neutral
CVD risk neutral
Generally modest HbA1c reduction
and efficacy
Urticaria/angioedema
1%

16. CLASS ADVANTAGES DISADVANTAGES
REDUCTION OF
HbA1c
GLP-1 Agonists
• EXENETIDE
• LIRAGLUTIDE
• SEMAGLUTIDE
No hypoglycaemia
Weight reduction
Cardiovascular benefits
Gastrointestinal side effects
(nausea/vomiting)
Injectables - Training requirements
1 – 1.5%
PIOGLITAZONE No hypoglycaemia
Durability
↑ HDL
↓ Triglycerides
↓CVD events
Weight gain
Oedema/heart failure
Fractures
? ↑ Bladder cancer risk
0.5 - 1%
SGLT2 Inhibitors
• DAPAGLIFLOZIN
• CANAGLIFLOZIN
• EMPAGLIFLOZIN
No hypoglycaemia
↓ Weight
↓ Blood pressure
↑HDL/↓ TG
Effective at all stages of
T2DM
Better cardiovascular
outcome
(Empagliflozin, Dapagliflozin)
Increased Genitourinary infections
Polyuria
Euglycaemic ketoacidosis
Volume depletion
Hypotension / Dizziness
0.5 – 1%