1. Diabetes mellitus is a metabolic disorder characterized by high blood glucose due to insulin deficiency or resistance. It affects carbohydrate, fat, and protein metabolism and can cause serious complications if left untreated. 2. There are four main types of diabetes: type 1 caused by lack of insulin; type 2 caused by insulin resistance; gestational diabetes during pregnancy; and other rare forms. 3. Management involves lifestyle changes like diet, exercise and weight control as well as pharmacological therapy with insulin or oral drugs depending on the type of diabetes.

1. MEDICAL BIOCHEMISTRY AND
NUTRITION MBC 120
DIABETES MELLITUS
Mr. Ndonji
BSc. Chemical and Biological Sciences (Double Major)
(UNZA)

2. INTRODUCTION
• Diabetes Mellitus is a carbohydrate metabolic disorder that is characterized by
persistent hyperglycemia due to relative insulin deficiency, peripheral tissue
resistance to insulin or both.
• It affects carbohydrate, fat and protein metabolism.
• Diabetes is usually irreversible and, although patients can lead a reasonably
normal lifestyle, its late complications result in reduced life expectancy and
major health costs.
• If left untreated, it can cause many complications.

3. CLASSIFICATION
DM can be classified into 4 major classes
1. Type 1 Diabetes Mellitus
2. Type 2 Diabetes Mellitus
3. Gestational Diabetes Mellitus
4. Others

4. TYPE 1 DM
• This is due to β- cell destruction in the pancreas. Causes of this include
Idiopathic, Genetic predisposition, Viral infection and Autoimmune attacks.
• There is little to no insulin production due to the loss of these insulin
producing cells but peripheral tissues are still sensitive to insulin.
• It usually occurs in childhood or early adulthood (less than 30 years) hence
termed early onset diabetes mellitus.
• It accounts for approximately 10% of all diabetic cases.
• Treatment is with insulin injections

5. TYPE 2 DM
• It is due to peripheral tissue resistance to the action of insulin. Causes include
genetic predisposition, obesity, sedentary lifestyle, high fat diet and stress.
• Insulin concentrations in the blood may be low, normal or above normal ranges.
• It usually has a late onset (over 40 years).
• It accounts for about 90% of all diabetic cases.
• It responds well to oral hypoglycemic drugs such as Metformin and
Glibenclamide

6. TYPE 1 DM VS TYPE 2 DM
•

7. GESTATIONAL DM
• This is the kind of Diabetes that begins during pregnancy and resolves with
delivery.
• Women who experience this are at a higher risk for developing DM later on in
life.
• It resembles type 2 DM in several aspects.
• It occurs in about 2–10% of all pregnancies and may improve or disappear after
delivery

8. OTHER CAUSES OF DM
1. Chronic pancreatitis
2. Pancreatectomy
3. Oral contraceptives
4. Corticosteroids
5. Genetic defects in insulin production
6. Cushing’s syndrome

9. PATHOPHYSIOLOGY
• Insulin is a protein hormone that facilitates glucose uptake by peripheral tissues from
the blood stream.
• It is the only human hormone that is capable of reducing high blood glucose levels,
hence the deficiency of insulin or the insensitivity of its receptors plays a central role in
all forms of diabetes mellitus
• It does this by attaching to receptors located on the surfaces of peripheral cells and
increasing the number of glucose transporters such as the GLUT 4 and moving them to
the surface of the cells. Such cells include adipocytes and muscle cells.
• This in turn increases the cell membrane’s permeability to glucose.
Insulin also
• Increases the peripheral utilization of glucose.
• Increases the storage of glucose by converting it into glycogen in the liver and muscle
cells.
• Inhibiting glycogenolysis and gluconeogenesis
• Encourages lipid storage and protein synthesis and reduces lipolysis and proteolysis.

10. EFFECTS ON CARBOHYDRATE METABOLISM
• When insulin levels are low or peripheral tissues are resistant to it, certain
carbohydrate metabolic reactions are triggered in an attempt to provide
cells with adequate amounts of glucose for energy production.
• Blood glucose levels are persistently high
• Gluconeogenesis: glucose is produced from short chain carbohydrates and
other non-carbohydrate molecules (such as proteins and fatty acids).
• Glycogenolysis: the break down of glycogen to form glucose.
• Glycogenesis (the formation of glycogen) is inhibited.
• All these processes further increase the blood glucose levels.

11. EFFECTS ON PROTEIN METABOLISM
• When insulin levels are low or peripheral tissues are resistant to it, certain
protein metabolic reactions are triggered in an attempt to provide cells with
adequate amounts of glucose for energy production.
• Proteolysis (the breakdown of proteins) occurs. This in effect slows down
growth.
• Proteolysis enables cells to have raw material for gluconeogenesis.
• Proteolysis also reduces the rate of protein synthesis as less amino acids will be
available for the production of proteins.

12. EFFECTS ON FAT METABOLISM
• When insulin levels are low or peripheral tissues are resistant to it, certain
fat metabolic reactions are triggered in an attempt to provide cells with
adequate amounts of energy.
• Fat storage is inhibited
• Fats and triglycerides in adipose tissue are broken down to fatty acids. This
increases the concentration of free fatty acids (FFA) in the blood.
• The fatty acids are then utilized for energy production and in
gluconeogenesis.
• The net result is weight loss.

13. PATHOPHYSIOLOGY CONTINUED
• When blood glucose levels are too high, the glucose threshold of
reabsorption is reached in the kidneys and this results in Glycosuria.
• This increases the osmotic pressure of the urine leading to polyuria and
increased fluid loss.
• Lost blood volume will be replaced osmotically from water held in body cells
and other body compartments leading to dehydration thereby resulting into
polydipsia.
• Lack of insulin action leads to persistently high levels of blood glucose, poor
protein synthesis, and break down of fat storage

14. CLINICAL FEATURES
• Polyuria
• Polydipsia
• Polyphagia
• Glycosuria
• Weight loss
• Fatigue
• Body weakness due to muscle wasting
• Muscle cramps due to electrolyte imbalances
• Blurred vision
• Vaginal Candidiasis/Balanitis

15. DIAGNOSTIC CRITERIA
SYMPTOMS OF DIABETES PLUS
i. Random Blood sugar (RBS) concentration ≥11.1 mmol/L OR
ii. Fasting plasma sugar (FBS) of >7 mmol/L OR
iii. 2-hour Postprandial Plasma Glucose ≥ 11.1 mmol/L after a glucose load of
75g ( during oral glucose tolerance test)
N.B. These criteria should be confirmed by repeat tests on a different day
iv. Haemoglobin A1c (HbA1c): An HbA1c >6.5% (48 mmol/mol) would be
considered diagnostic of diabetes, whereas a level of 5.7–6.4% (39–46
mmol/mol) would denote increased risk of diabetes

16. OTHER INVESTIGATIONS
• Urea, electrolytes and creatinine
• Liver function tests
• Urinalysis or blood analysis for ketones
• Fundoscopy
• Infection screen: full blood count, blood and urine culture, C-reactive protein,
• Chest X-ray, ECHO and ECG
• EEG

17. MANAGEMENT
• Management comprises pharmacological and non-pharmacological management.
• PHARMACOLOGICAL MANAGEMENT
• Type 1 DM: since this type of diabetes is due to insufficient insulin secretion by
the pancreas, management is with injectable insulin.
• Type 2 DM: since this is caused by insulin resistance by peripheral tissues,
management is with oral hypoglycemic drugs. These drugs include Metformin
and Glibenclamide.

18. NON PHARMACOLOGICAL MANAGEMENT
1. EXERCISE:
Patients should be encouraged to exercise regularly as this improves glucose
utilization. Patients on Insulin therapy should limit their exercises as they are at
risk of developing hypoglycemia.
2. WEIGHT REDUCTION:
Patients should be encouraged to maintain normal weight. Obese patients
should be encouraged to lose weight as weight reduction improves peripheral
glucose sensitivity. This will then lead to reduced demand for/reduced dosages
of injectable insulin and oral hypoglycemic drugs

19. NON PHARMACOLOGICAL MANAGEMENT
3. DIET CONTROL
• The recommended dietary Energy composition of the diabetic regimen is as
follows:
1) Total fat intake <30%: low cholesterol diet is recommended.
2) Carbohydrate; 45-65% of total energy is compatible with good glycaemic
control.
3) Protein; similar to general population, 15-20% of dietary energy (1 –
1.5g/Kg/day).
4) Alcohol intake should be restricted.

20. CARBOHYDRATE REQUIREMENTS DIET CONTROL
Carbohydrate Requirements
• The amount, type and timing of carbohydrate intake is vital in diabetics.
• Carbohydrate intake needs to be balanced against hypoglycaemic action of
medication (insulin/oral hypoglycemic drugs) in order to achieve near-normal
blood glucose levels.
• Consumption of soluble fibre-containing foods hinders the absorption of
cholesterol and delays the rate of postprandial glucose absorption as foods rich in
soluble fibre have a low GI.
• Consumption of insoluble fibre-containing foods has minimal effect on glycaemia
or lipidemia but increases satiety value by lowering energy density of a diet.
Thus, counteracts obesity risk factors.
• Avoid simple sugars (e.g. sugar, soft drinks, honey, and other sweets). Fresh fruits
such as watermelon and lemon can be freely taken as opposed to oranges and
bananas that must be taken with caution.

21. DIET CONTROL
Vitamins
• Poorly controlled diabetics may lead to water soluble vitamin deficiencies
because of polyuria.
• Nutritional supplements and food items rich in water soluble vitamins
(dark green vegetables, citrus fruits, etc) should therefore, be consumed
as needed.
• Antioxidant-rich food items (fruits and vegetables) are also advised in
order to promote cardiovascular health.

22. COMPLICATIONS OF DM
Acute Complications
• Diabetic ketoacidosis (DKA)
• Hyperglycemia and hypoglycemia
• Hyperosmolar hyperglycemic state (HHS)
Chronic Complications
1. Microvascular:
• Diabetic Retinopathy
• Diabetic Nephropathy
• Diabetic Neuropathy
2. Macrovascular: Stroke, hypertension, CAD, diabetic foot, dental caries,
UTI, Vaginal candidiasis and balanitis