This document provides information on diabetes, including the two main types (type 1 and type 2), pathophysiology, principles of management, diet, and various drugs used to treat diabetes such as insulins, metformin, sulphonylureas, thiazolidinediones, and acarbose. Type 1 diabetes is characterized by an absolute deficiency of insulin, while type 2 involves relative insulin deficiency coupled with insulin resistance. Management aims to minimize metabolic derangements and complications through diet, exercise, education, and medications to control blood glucose levels.

1. DIABETES

2. Introduction
• Type 1 diabetes – where insulin deficiency can lead to ketoacidosis
• Type 2 diabetes – where insulin resistance and a relative lack of
insulin lead to hyperglycaemia –
• Glucose intolerance and diabetes mellitus are increasingly prevalent
in affluent and developing countries.
• Addressing risk factors distinct from blood glucose, especially
hypertension.
• In this topic focus mainly on the types of insulin and oral
hypoglycaemic agents.

3. PATHOPHYSIOLOGY
• Insulin is secreted by β-cells of the islets of Langerhans.
• It lowers blood glucose, but also modulates the metabolic disposition
of fats and amino acids, as well as carbohydrate.
• It is secreted together with inactive C-peptide.
• its plasma concentration is low or absent in patients with type 1
diabetes.
• Diabetes mellitus fasting blood glucose concentration of
7mmol/L is caused by an absolute or relative lack of insulin.
• In type 1 diabetes there is an absolute deficiency of insulin

4. • Type 1 - patients are usually young and non-obese at presentation.
• There is an inherited predisposition.
• In type 2 diabetes there is a relative lack of insulin secretion, coupled with
marked resistance to its action.
• Type 2 diabetes is rarely associated with diabetic ketoacidosis.
• high of blood glucose levels gives rise to these effects:
• 1. diuresis (polyuria) with consequent decreased volume reduction
• 2. blurred vision.
• 3. Glycosuria predisposes to Candida infection, especially in women.
• 4. Weight loss.
• 5. retinopathy

5. PRINCIPLES OF MANAGEMENT
• In young type 1 patients there is good evidence that improved
diabetic control reduces complications.
• To minimize the metabolic derangement associated with diabetes
mellitus in order to reduce the development of such complications.
• Education and support are essential to motivate the patient to learn
how to adjust their insulin dose to optimize glycaemic control.
• In older type 2 patients, hypoglycaemic treatment aims to minimize
symptoms of polyuria, polydipsia or recurrent Candida infection.

6. DIET IN DIABETES MELLITUS
• It is important to achieve and maintain ideal body weight on a non-atherogenic
diet.
• Caloric intake must be matched with insulin injections.
• Simple sugars should be restricted because they are rapidly absorbed.
• should be replaced by foods that give rise to delayed and reduced glucose
absorption.
• Artificial sweeteners are useful for those with a ‘sweet tooth’.)
• A fibre-rich diet reduces peak glucose levels after meals and reduces the insulin
requirement.
• Saturated fat and cholesterol intake should be minimized.
• There is no place for commercially promoted ‘special diabetic foods’, which are
expensive.

7. DRUGS USED TO TREAT DIABETES MELLITUS
• INSULINS
• Insulin is a polypeptide.
• Insulin is available in several formulations
• e.g. with protamine and or with zinc) which differ in pharmacokinetic
properties, especially their rates of absorption and durations of action.
• ‘designer’ insulins are synthetic polypeptides closely related to insulin
• but with Small changes in amino acid composition which change their
properties.
• For example, a lysine and a proline residue are switched in insulin lispro,
which consequently has a very rapid absorption and onset.
• whereas insulin glargine is very slow acting and is used to provide a low
level of insulin activity during the 24-hour period.

8. Use
• Insulin is indicated in type 1 diabetes mellitus and in about one-third
of patients with type 2 disease.
• Insulin is administered by subcutaneous injection.
• The effective dose of human insulin less than that of animal insulins.
• Soluble insulin is the only preparation suitable for intravenous use.
• It is administered intravenously in diabetic emergencies
• Subcutaneously before meals in chronic management.
• Formulations of human insulins are available in various ratios of
short-acting and longer-lasting forms e.g. 30:70 commonly used twice
daily.

9. Mechanism of action
• Insulin acts by binding to transmembrane glycoprotein receptors.
Receptor occupancy results in:
• 1. activation of insulin-dependent glucose transport processes.
• 2. inhibition of adenylyl cyclase-dependent metabolism (lipolysis,
proteolysis, glycogenolysis).
• 3. intracellular accumulation of potassium and phosphate which is
linked to glucose transport in some tissues.

10. Adverse reactions
• 1. Hypoglycaemia
• 2. Insulin-induced post-hypoglycaemic hyperglycaemia (Somogyi
effect)
• 3. Local or systemic allergic reactions to insulin, with itching, redness
and swelling at the injection site.
• 4. Lipodystrophy: the disappearance of subcutaneous fat at or near
• 5. Insulin resistance, defined arbitrarily as a daily requirement of
more than 200 units.

11. ORAL HYPOGLYCAEMIC DRUGS AND TYPE 2
DIABETES
• Oral hypoglycaemic drugs are useful in type 2 diabetes as adjuncts to
dietary restraint.
• They fall into four groups:
• 1. biguanides (metformin);
• 2. sulphonylureas and related drugs
• 3. thiazolidinediones (glitazones);
• 4. α-glucosidase inhibitors (acarbose).
• type 2 diabetic patients initially achieve satisfactory control with diet
either alone or combined with one of these agents.

12. BIGUANIDES: METFORMIN
• Metformin is the only biguanide available.
• It is used in type 2 diabetic patients inadequately controlled by diet.
• Its aids weight reduction so it is a first choice drug for obese type 2
patient
• It must not be used in patients at risk of lactic acidosis
• Contraindicated in: renal failure ,alcoholics,cirrhosis, chronic lung
disease ,cardiac failure , congenital mitochondria, acute myocardial
infarction.

13. Mechanism of action
• This remains uncertain.
• Biguanides do not produce hypoglycaemia and
• They are effective in animals with removed pancreas. animal
• Effects of metformin include:
• reduced glucose absorption from the gut.
• inhibition of gluconeogenesis in the liver.

14. Adverse effects
• nausea
• metallic taste,
• anorexia, vomiting and diarrhoea.
• The symptoms are worst when treatment is initiated and a few
patients cannot tolerate even small doses.
• Lactic acidosis.
• Absorption of vitamin B12 is reduced by metformin.

15. SULPHONYLUREAS AND RELATED DRUGS
• Tolbutamide, glibenclamide, gliclazide
• Used for type 2 diabetics who have not responded adequately to diet
alone or diet and metformin with which they are additive.
• They improve symptoms of polyuria and polydipsia,
• In contrast to metformin stimulate appetite.
• Chlorpropamide, the longest-acting agent in this group has a higher
incidence of adverse effects especially hypoglycaemia.
• Tolbutamide and gliclazide are shorter acting than glibenclamide.

16. RELATED DRUGS
• Repaglinide, Nateglinide are chemically distinct, but act at the same
receptor.
• They are shorter acting even than Tolbutamide.
• but more expensive.
• They are given before meals.

17. Mechanism of action
• The hypoglycaemic effect of these drugs depends on the presence of
functioning B cells.
• Sulphonylureas like glucose, depolarize B cells and release insulin.

18. Adverse effects
• hypoglycaemia.
• Allergic reactions such rashes, drug fever,
• gastrointestinal upsets.
• transient jaundice (usually cholestatic) and
• haematopoietic changes, including thrombocytopenia, neutropenia
and pancytopenia.

19. THIAZOLIDINEDIONES (GLITAZONES
• Piolitazone, Rosiglitazone were developed from the chance finding
that a fibrate drug increased insulin sensitivity.
• Glitazones lower blood glucose and haemoglobin A1c (HbA1c) in type
2 diabetes mellitus.
• Their effect on mortality or diabetic complications not fully
established.
• but they have rapidly become very widely used.

20. Mechanism of action
• Glitazones bind to the peroxisome-proliferating activator receptor γ
(PPARγ),
• A nuclear receptor found mainly in adipocytes and also in
hepatocytes and myocytes.
• They works slowly increasing the sensitivity to insulin.

21. Adverse effects
• The first glitazones caused severe hepatotoxicity and are not used.
• Hepatotoxicity has not proved problematic with rosiglitazone or
pioglitazone,
• The most common adverse effects are weight gain
• They can also exacerbate cardiac dysfunction and are therefore
contraindicated in heart failure.
• Increased bone fractures and osteoporosis has been noted.
• They are contraindicated during pregnancy.

22. ACARBOSE
• Acarbose is used in type 2 diabetes mellitus in patients who are
inadequately controlled on diet alone or diet and other oral hypoglycaemic
agents.
• Acarbose is a reversible competitive inhibitor of intestinal α-glucoside
hydrolases and
• It delays the absorption of starch and sucrose, but has no affect the
absorption of ingested glucose.
• The postprandial glycaemic rise after a meal containing complex
carbohydrates is reduced and its peak is delayed.
• It causes increased gas formation which results in flatulence, abdominal
distension and occasionally diarrhoea.