Diabetes Mellitus

Dr. Stanley Binagi

MMed Internal Medicine
 Definition of diabetes mellitus

• Is a group of metabolic diseases characterized by hyperglycemia and

glucose intolerance resulting from defects in insulin secretion,
impaired effectiveness of insulin action, or both.
OR
• Is a syndrome of impaired carbohydrate, fat and protein metabolism
caused by either lack of insulin secretion or decreased sensitivity of
the tissue to insulin.
 Prevalence of DM

• Is now one of the most common NCD globally

• worldwide ~ pts with DM - 246 million by 2000
• In Africa ~ 7 mill DM pts,
• ~ 482,000- East African countries
– ~ Tanzania 201,000
– ~ Kenya 183,000
– ~ Uganda 98,000.
• Tanzania prevalence: 10.03% (Kinimi et al, 2017)
 Classification
• Type 1 ( Insulin-dependent diabetes)
(beta-cell destruction, usually leading to absolute insulin
deficiency)
• Autoimmune ( Type 1A)
• Idiopathic ( Type 1B)

• Type 2 (Non-insulin dependent diabetes)

(may range from predominantly insulin resistance with
relative insulin deficiency to a predominantly secretory defect with
or without insulin resistance)

• Gestational diabetes
 Other specific types
• Genetic defects of beta-cell function
• MODY 1-6 (dominantly inherited, family members affected)
• Mitochondrial DNA mutation- maternally transmitted (↓insulin, ↓B cells)
• Wolfram’s syndrome (DI,DM, Optic atrophy, deafness-DIDMOAD)

• Genetic defects in insulin action

Lipoatrophic diabetes
Leprechaunism
Rabson-Mendelian syndrome

• Diseases of the exocrine pancreas

 Fibrocalculous pancreatopathy
 Cystic fibrosis
 Haemochromatosis/thalassaemia
 Cong absence of pancreas
• Endocrinopathies:
Cushing syndrome,
Hyperthyroidism
Pheochromocytoma
Somatostatinoma (tumor of D cells)
Conns syndrome
Acromegaly or gigantism
Glucagonoma (tumor of A cells)
Drug- or chemical-induced:
• asparaginase, corticosteroids, PI, diazoxide, thiazide,
alpha interferon, pentamidine   
• Infections- congenital rubella, CMV
• Uncommon forms of immune-mediated
diabetes
• Polyendocrine autoimmune deficiencies (APS I and II)

• Other genetic syndromes: Down, Klinefelter,

Turner, Prader-Willi, Lawrence Moon Biedl syndrome
T1DM
 Clinical Presentations
Non-emergency

• Polyuria, polydypsia, wt loss

• Recent onset of enuresis in a previously toilet-trained
child, which may be misdiagnosed as UTI
• Vaginal candidiasis, especially in pre-pubertal girls.
• Vomiting, which may be misdiagnosed as
gastroenteritis.
• Chronic weight loss or failure to gain weight in a
growing child.
• Irritability and decreasing school performance.
• Recurrent skin infections.
 Clinical Presentations
Emergency
• Severe dehydration, frequent vomiting.
• Continuing polyuria despite the presence of
dehydration.
• Weight loss because of fluid loss.
• Flushed cheeks because of the ketoacidosis.
• Acetone detected on the breath.
• Kussmaul respiration, disordered sensorium
• Shock
• Hypotension (a late sign and rare in children with
DKA).
 DIAGNOSIS

o Classic symptoms
• Polyuria, Polydipsia, Weight loss despite increased appetite, Lethargy
o Blood glucose
• Fasting > 7.0 mmol/L, Random > 11.1 mmol/L, 2 abnormal values
recommended in asymptomatic children, 1 abnormal value in
symptomatic children
o Urinalysis for ketones, glucose
o HbA1c
o Screen for infection
 Diagnosis of DM
NORMAL IMPAIRED DIABETES

FASTING < 100 100-125 ≥126 mg/dl

mg/dl mg/dl (7 mµ)
(5.6 mµ)
ORAL GTT <140 140-199 ≥200 mg/dl
(2 hours) mg/dl mg/dl (11.1mµ)
(7.8 mµ)
 Treatment
Aim of therapy:
• Provide normal growth, puberty, psychomotor development
and well being (for children)
• Achieve and maintain blood glucose target levels:
– Fasting or pre-prandial: 70 to 130 mg/dl (3.9-7.2 mmol/L)
– After meals: < 180 mg /dl (10 mmol/L)
– Night: not below 60 mg/dl (3.3 mmol/L)
– Standardized HbA1c < 7.5%
• Avoid severe or frequent hypoglycemias
 Treatment for T1DM

• Fluids in emergency presentation

• Insulin lifelong
• Treat infection
• Exercises
• Education
• Monitoring
 Understanding different types of insulin
Insulin type Onset Peak Duration
Soluble short-acting insulin 30 2-4 5-8 hours
(Actrapid) minutes hours
Isophane intermediate-acting 2 hours 6-10 18-28
insulin (Insulatard) hours hours

Can be mixed together in a single syringe, while essentially retaining

the properties of the two components.
 Usual daily insulin requirement 0.5-1 unit/kg

2/3
Insulatard
2/3 am
1/3 Actrapid
Total insulin
requirement 1/2
Insulatard
1/3 pm
1/2 Actrapid

Insulin is typically given 30 minutes before breakfast and dinner. Use

this just as a starting point. Titration of insulin in response to blood
sugars is critical.
 Insulin requirements
• Remission period
– < 0.5 IU/kg/24 hours
• Pre-pubertal period
– 0.6–1.0 IU/kg/24 hours
• Pubertal period
– 1.0–2.0 IU/kg/24 hours
 Insulin regimens
• Twice daily injection regimen:
– 2/3 of daily dose before breakfast,
– 1/3 before supper
– both 2/3 intermediate-acting and 1/3 short-acting insulin
• Three-times daily injection regimen:
– 40–50% before breakfast (2/3 intermediate- and 1/3 short-
acting)
– 10–15% short-acting before supper
– 40% intermediate-acting before bed.
• Multiple injection regimen:
– 30–40 % (intermediate or long acting) before bed
– the rest (short-acting or rapid analogs) before main meals
Modes of injection; syringe and pens
Modes of injection; Insulin pumps
 Diet
• Nutritional advice should take into consideration:
– individual requirements
– local customs
– family dietary habits
• General recommendations:
– eat a broad variety of food
– eat plenty of bread, cereals, vegetables and fruit
– eat only small amounts of sugar
– in young children fat intake should not be restricted
– older children and adolescents should eat a low fat diet
– choose food with small amounts of salt
– encourage breast-feeding at least until six
months of age
 Diet principles
• Number of meals:
– 3 main meals
– 2-3 snacks
– adapted to age, physical activity and insulin regimen
• Energy intake:
– 1000 calories (4180 Kj) + 100 calories/year of age or
calculating the specific total EE (is better!!!)
– 50–55% of energy from carbohydrates
– 30% of energy from fat
– 15–20% of energy from protein
Food Guide pyramid
 Effects on exercises
• Increases insulin sensitivity
• Improves the physical state
• Reduces the risk of cardiac diseases
• Reduces the risk of hypertension
• Does not improve metabolic control
• Increases the risk of hypoglycaemia
 During surgery < 3h
• Insulin:
– in the morning intermediate-acting insulin, 1/2 to 2/3 of
total daily dose
– if blood glucose is above 20 mmol/l supply with a small
dose short-acting insulin
– in the evening give intermediate-acting insulin, 1/3 of daily
dose
• Fluid:
– glucose 5% intravenously, volume according to age
• Blood glucose monitoring:
– every 1–2 hours
– values between 10–14 mmol/l
 Type 2 DM

General Characteristics include:

– Presents in older patients usually above the age of 40
years, but now also being seen more commonly in younger
people
– Type 2 diabetes in children and adults is acknowledged as
a very important and growing problem
– Patients are in most cases obese but also can be non obese
patients with diabetes.
– Insulin resistance
– absence of circulating autoantibody
– There is still function of beta cells of the pancreas to produce
insulin, hence responds well with oral hypoglycemic agents

– responds well on diet or/and oral hypoglycemic agents.

Occasionally may need insulin treatment for control. In this
situation known as 2nd failure

– Is frequently undiagnosed for many years because hyperglycemia

develops gradually

– Hyperosmolar Hyperglycemia Syndrome is common, diabetes

keto-acidosis is uncommon
Differences in clinical features between type
1 and type 2 diabetes mellitus
Type 1 Type 2
• Age-young usually<30- • Age-Elderly >40-45yrs
35yrs • Onset-Slow or insidious
• Onset-Sudden or acute • Typical symptoms-no
• Typical symptoms -yes • Plasma insulin- high
• Plasma insulin- low • Ketosis –no (not common)
• Ketosis –yes (often DKA)
• Weight –lean, rapid weight • Weight –normal to obese
loss before diagnosis
• Genetic- weak • Genetic -strong
• Metabolic syndrome -no • Metabolic syndrome-yes
• Treatment- insulin • Treatment: Diet, OHA,
Insulin
 Pre disposing factors for type 2 DM

• Mostly overweight and obese adults

• Urbanization with sedentary life
• Change in dietary habits
• Positive family background of DM
• Often dyslipidemia and hypertension
• Women with prior gestational diabetes mellitus
• Cigarette smoking
 Risk of type 2 diabetes in children
• Is not a rare disease in children and adolescence
• The age of onset for type 2 diabetes is becoming increasingly
younger: Asian, African, American, Japanese,, and populations
• It is thought that genetic and environmental factors are
involved with the increasing prevalence of obesity which is
major factor in childhood
• Features suggestive of childhood type 2 diabetes are obesity,
acanthosis nigrans, slow onset, and belonging to a high-risk
ethnic group
•
 Pathogenesis of T2DM
• Remains enigmatic
• BUT there are predisposing factors:
– Genetic defects: much greater than T1DM
– Environmental factors: sedentary, obesity, diet
• Beta-cell dysfunction
– Malfunction of insulin receptors occurs in peripheral cells
and include insensitivity of these receptors cause blood
glucose to rise and this will stimulate the pancreatic beta-
cells to secrete more insulin result into hyperinsulinemia
can maintain normal plasma glucose for years
 Cont…
• In time beta-cell compensation become inadequate to
overcome target tissue resistance –this is the prelude to
worsening hyperglycemia and the appearance of clinical
diabetes
 Symptoms
• Basic • Other
– Elevated blood glucose – Muscle cramps
– Obesity – Polyphagia
– Thirst – Blurred vision
– Polyuria – Hypertension
– Dehydration – Myocardial infarction, stroke
– Fatigie with very bad prognosis
– Fungal and bacterial – Macroangiopathic
infections complications (foot problems,
gangrene)

– COMA DIABETICUM
 Diagnostic criteria of T2DM
• Symptoms of DM and 1 abnormal blood
glucose* value
– Random Blood Glucose (RBG) > 11.1 mmol/L
(200 mg/dl)
– fasting ³ 7,0 mmol/l (126 mg/dl)
– 2h after 75 g glucose or casual ³ 11,1
• No symptoms present
– two abnormal BG values on 2 days (as above)

*Only on laboratory analyzers,

from venous whole blood;
uncertainity  0,5 mmol/l
 Management
Aimed at;
• changes in lifestyle (non pharmacological)
• pharmacological intervention to control
glycaemia to as near euglycemic levels as
possible
• delay or prevent the onset of the long-term
complications of DM.
 Non-pharmacological Management
• change in life style
– Reduction in fat and saturated fat intake
– Reduction in carbohydrate
– Reduction in alcohol intake
– Increase in fibre food intake
– Stopping smoking
 Cont…
• Increase in physical activity levels by
– Brisk walking, jogging, riding a bicycle and
Stretching exercises.
– Frequency: 4-5 days per week.
– Duration: 30 minutes preceded and followed by
stretching and flexibility exercises for 10 – 15
minutes.
 DM Education
• Early signs and symptoms of hyperglycemia
• Signs and symptoms oh hypoglycemia
• Drugs of DM
• Diabetic diet
• Physical activity part of management DM
• Self monitoring Blood glucose and urine sugar
(glucometers and Benedict’s test, clinistix
 Cont…
• About foot care to avoid diabetic foot.
• aware of the complications of DM
• the importance of regular medical
consultations.
• Parents or caretakers of children and elderly
patients with DM should also be educated on
above mentioned points.
 Pharmacological treatment
• A. Sulfonylureas
o 1st Generation
Tolbutamide (Orinase)
Chlorpropamide (diabenese)
Tolazamide
(Tolinase)
Acetohexamide (Dymetor)
o 2nd Generation 
Glipzide
Glyburide (Dionil)
Gliclazide
Glimepiride
 Pharmacological…
• B. Biguanides
Metformin
• C. Thiazolidines
Rosiglitazone
Pioglitazone
• D. Meglitinides
Nateglinide
Repaglinide
 Pharmacological…
• E. Alpha-Glucosidase inhibitors
Acarbose
Meglitol
• INSULIN THERAPY IN TYPE 2 DIABETES
MELLITUS
• Dose: Type 2 DM; 0.2 – 0.5 IU/kg Bwt.
Note: In cases of severe hyperglycaemia a dose
of 1 IU/kg Bwt may be needed for control.
Initial Rx

Life style 1-2 Broad benefit Insufficient

metformin 1-2 Wt neutral GI, Renal D

Addtn Rx
Insulin 1.5-3.5 No dose limit, rapidly Many injections,
effective, improve monitoring, wt gain,
lipid profile hypoglycemia,

sulfonylureas 1-2 Rapidly effective Hypoglycemia, wt gain

Less well validated

TZD .5-1.4 Improve lipid profile, Fluid retention, CHF,

potential decrease in expensive, increase in
MI (pioglitazone) MI (rosiglitazone)
Source: Tanzania Standard Treatment Guideline 2017.
 COMPLICATIONS

• SHORT TERM COMPLICATIONS

– Non-Ketotic hyperosmolar hyperglycaemic
syndrome
– Diabetic ketoacidosis (DKA)
– Lactic acidosis
– Hypoglycaemia
– Bacterial and Fungal infection
 Long term complications
• Macrovascular complications
• Coronary artery disease
• Peripheral arterial disease
• Cerebrovascular disease

• Microvascular complications
– Diabetic retinopathy and macular oedema
– Diabetic neuropathy
– Diabetic nephropathy

• Miscellaneous complications
• Gastointestinal (gastroparesis, diarrhea)
• Genitourinary (uropathy/ sexual dysfunction)
• Dermatologic
• Infections
• Cataracts, glaucoma
• Periodontal disease.
 DM COMPLICATIONS
- MECHANISMS
So HOW does diabetes damage blood vessels?
Best understood mechanism is by non-enzymatic
glucosylation (glycation) of proteins and other
macromolecules.

Other mechanisms postulated : include changes in NADP+

and NADH levels associated with alternative glucose
metabolic fates when usual pathways are saturated.
One of the proteins which is glycated is Hemoglobin. Because it
is found in the blood, it is convenient to measure as HgA1c.

Because RBCs (and thus Hg) survive in the blood for 90-120
days, the HgA1c provides a means to assess glycemic control
over this period.
Chronic hyperglycemia causes increased glycation of proteins,
resulting in Advanced Glycation End-products (AGEs)

These can cause damage through loss of function, turning on/off

signal pathways within cells, or alteration in gene expression.
 DM 2 PREVENTION, 21st CENTURY

 NUTRITION
 calories ß composition , micronutrients Ý
 SMOKING & ALCOHOL ß
 Walking Ý (PHYSICAL ACTIVITY)
 HEALTH AWARENESS Ý
 weight control
 blood lipids, glucose
 blood pressure
 inherited and acquired health risks
THANK YOU