Diabetes Mellitus

Dr Shahjada SelimEndocrinologist

Shaheed Suhrawardy Medical College Hospital, Dhaka

Email: selimshahjada@gmail.com

Diabetes Mellitus

Diabetes is a chronic state of hyperglycemia due to deficiency of insulin secretion, its action or both.

Diabetes is a huge and growing problem, and the costs to society are high and escalating

382 million people have diabetes

By 2035, this number will rise to 592 million

Diabetes is a huge and growing problem, and the costs to society are high and escalating

Globally

382 million people have diabetes

By 2035, this number will rise to 592 million

In Bangladesh8.4 million people had diabetes in 2013

8.4 million people are likely to have diabetes in 2035

Almost half of all people with diabetes live in just three countries

• China• India• USA

Increasing development

and wealth is

correlated with

decreasing early

mortality due to

diabetes

What goes wrong in diabetes?

Multitude of mechanismsInsulin

Regulation Secretion Uptake or breakdown

Beta cells Damage

Action of Insulin on Carbohydrate, Protein and Fat Metabolism

Carbohydrate Facilitates the transport of glucose into

muscle and adipose cells Facilitates the conversion of glucose to

glycogen for storage in the liver and muscle.

Decreases the breakdown and release of glucose from glycogen by the liver

Action of Insulin on Carbohydrate, Protein and Fat Metabolism

Protein Stimulates protein synthesis Inhibits protein breakdown; diminishes

gluconeogenesis

Action of Insulin on Carbohydrate, Protein and Fat Metabolism

Fat Stimulates lipogenesis- the transport of

triglycerides to adipose tissue Inhibits lipolysis – prevents excessive

production of ketones or ketoacidosis

19

Classification of DM

1. Type 1 DM

It is due to insulin deficiency and is formerly known as. Type I Insulin Dependent DM (IDDM) Juvenile onset DM

2. Type 2 DM

It is a combined insulin resistance and relative deficiency in insulin secretion and is frequently known as.

Type II Noninsulin Dependent DM (NIDDM) Adult onset DM

20

3. Gestational Diabetes Mellitus (GDM):

Gestational Diabetes Mellitus (GDM) developing during some cases of pregnancy but usually disappears after pregnancy.

4. Other types:

Secondary DM

21

Etiology

1. Etiology of Type 1 Diabetes

22

23

2. Etiology of Type 2 Diabetes

24

a

25

Risk Factors

Type 1 DM

Genetic predispositionIn an individual with a genetic

predisposition, an event such as virus or toxin triggers autoimmune destruction of β-cells probably over a period of several years.

26

Risk Factors

Type 2 DM

Family History Obesity Habitual physical inactivity Previously identified impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) Hypertension Hyperlipidemia

27

Diagnostic Criteria

• Any one test should be confirmed with a second test, most often fasting plasma glucose (FPG).

• This criteria for diagnosis should be confirmed by repeating the test on a different day.

28

29

30

Clinical Presentation

Type 1 DM

- Polyuria- Polydipsia- Polyphagia- Weight loss- Weakness- Dry skin- Ketoacidosis

• Type 2 DM

- Patients can be asymptomatic- Polyuria- Polydipsia- Polyphagia- Fatigue

- Weight loss- Most patients are discovered

while performing urine glucose screening

Management of Diabetes Mellitus

The major components of the treatment of diabetes are:

Management of DM

Diet is a basic part of management in every case. Treatment cannot be effective unless adequate attention is given to ensuring appropriate nutrition.

A. Diet

Dietary treatment should aim at:◦ ensuring weight control◦ providing nutritional requirements◦ allowing good glycaemic control with

blood glucose levels as close to normal as possible

◦ correcting any associated blood lipid abnormalities

A. Diet

The following principles are recommended as dietary guidelines for people with diabetes:

Dietary fat should provide 25-35% of total intake of calories but saturated fat intake should not exceed 10% of total energy. Cholesterol consumption should be restricted and limited to 300 mg or less daily.

A. Diet (cont.)

Protein intake can range between 10-15% total energy (0.8-1 g/kg of desirable body weight). Requirements increase for children and during pregnancy. Protein should be derived from both animal and vegetable sources.

A. Diet (cont.)

The following principles are recommended as dietary guidelines for people with diabetes:

Carbohydrates provide 50-60% of total caloric content of the diet. Carbohydrates should be complex and high in fibre.

Excessive salt intake is to be avoided. It should be particularly restricted in people with hypertension and those with nephropathy.

A. Diet (cont.)

Physical activity promotes weight reduction and improves insulin sensitivity, thus lowering blood glucose levels.

Exercise

Together with dietary treatment, a programme of regular physical activity and exercise should be considered for each person. Such a programme must be tailored to the individual’s health status and fitness.

People should, however, be educated about the potential risk of hypoglycaemia and how to avoid it.

Exercise

There are currently four classes of oral anti-diabetic agents:

i. Biguanidesii. Insulin Secretagogues – Sulphonylureasiii. Insulin Secretagogues – Non-sulphonylureasiv. α-glucosidase inhibitorsv. Thiazolidinediones (TZDs)vi. DPP4i

B. Oral Anti-Diabetic Agents

If glycaemic control is not achieved (HbA1c > 6.5% and/or; FPG > 7.0 mmol/L or; RPG >11.0mmol/L) with lifestyle modification within 1 –3 months, ORAL ANTI-DIABETIC AGENT should be initiated.

In the presence of marked hyperglycaemia in newly diagnosed symptomatic type 2 diabetes (HbA1c > 8%, FPG > 11.1 mmol/L, or RPG > 14 mmol/L), oral anti-diabetic agents can be considered at the outset together with lifestyle modification.

B.1 Oral Agent Monotherapy

As first line therapy: Obese type 2 patients, consider use of metformin, acarbose

or TZD. Non-obese type 2 patients, consider the use of metformin

or insulin secretagogues Metformin is the drug of choice in overweight/obese

patients. TZDs and acarbose are acceptable alternatives in those who are intolerant to metformin.

If monotherapy fails, a combination of TZDs, acarbose and metformin is recommended. If targets are still not achieved, insulin secretagogues may be added

B.1 Oral Agent Monotherapy (cont.)

Combination oral agents is indicated in:

Newly diagnosed symptomatic patients with HbA1c >10

Patients who are not reaching targets after 3 months on monotherapy

B.2 Combination Oral Agents

If targets have not been reached after optimal dose of combination therapy for 3 months, consider adding intermediate-acting/long-acting insulin (BIDS).

Combination of insulin+ oral anti-diabetic agents (BIDS) has been shown to improve glycaemic control in those not achieving target despite maximal combination oral anti-diabetic agents.

B.3 Combination Oral Agents and Insulin

Combining insulin and the following oral anti-diabetic agents has been shown to be effective in people with type 2 diabetes:◦ Biguanide (metformin)◦ Insulin secretagogues (sulphonylureas)◦ Insulin sensitizers (TZDs)(the combination of a TZD plus

insulin is not an approved indication)◦ α-glucosidase inhibitor (acarbose)

Insulin dose can be increased until target FPG is achieved.

B.3 Combination Oral Agents and Insulin

Diabetes Management

Algorithm

In elderly non-obese patients, short acting insulin secretagogues can be started but long acting Sulphonylureas are to be avoided. Renal function should be monitored.

Oral anti-diabetic agent s are not recommended for diabetes in pregnancy

Oral anti-diabetic agents are usually not the first line therapy in diabetes diagnosed during stress, such as infections. Insulin therapy is recommended for both the above

General Guidelines for Use of Oral Anti-Diabetic Agent in Diabetes

Targets for control are applicable for all age groups. However, in patients with co-morbidities, targets are individualized

When indicated, start with a minimal dose of oral anti-diabetic agent, while reemphasizing diet and physical activity. An appropriate duration of time (2-16 weeks depending on agents used) between increments should be given to allow achievement of steady state blood glucose control

General Guidelines for Use of Oral Anti-Diabetic Agent inDiabetes

Short-term use: Acute illness, surgery, stress and emergencies Pregnancy Breast-feeding Insulin may be used as initial therapy in type 2

diabetes in marked hyperglycaemia Severe metabolic decompensation (diabetic

ketoacidosis, hyperosmolar nonketotic coma, lactic acidosis, severe hypertriglyceridaemia).

C. Insulin Therapy

Long-term use: If targets have not been reached after optimal

dose of combination therapy or BIDS, consider change to multi-dose insulin therapy. When initiating this,insulin secretagogues should be stopped and insulin sensitisers e.g. Metformin or TZDs, can be continued.

C. Insulin Therapy

The majority of patients will require more than one daily injection if good glycaemic control is to be achieved. However, a once-daily injection of an intermediate acting preparation may be effectively used in some patients.

Twice-daily mixtures of short- and intermediate-acting insulin is a commonly used regimen.

In some cases, a mixture of short- and intermediate-acting insulin may be given in the morning. Further doses of short-acting insulin are given before lunch and the evening meal and an evening dose of intermediate-acting insulin is given at bedtime.

Insulin regimens

Other regimens based on the same principles may be used.

A regimen of multiple injections of short-acting insulin before the main meals, with an appropriate dose of an intermediate-acting insulin given at bedtime, may be used, particularly when strict glycaemic control is mandatory.

Insulin regimens

Patients should be educated to practice self-care. This allows the patient to assume responsibility and control of his / her own diabetes management. Self-care should include:◦ Blood glucose monitoring◦ Body weight monitoring◦ Foot-care◦ Personal hygiene◦ Healthy lifestyle/diet or physical activity◦ Identify targets for control◦ Stopping smoking

Self-Care of Diabetics

55

Pharmacotherapy :Type 1 DM

Monitoring

- Most Type 1 patients require

0.5-1.0 U/kg/d- The initial regimen should be modified based

on:- Symptoms

- SMBG

- HbA1C

56

Pharmacotherapy :Type 1 DM

Monitoring

57

Diabetes Mellitus Complications

1. Hypoglycemia

- Cause: Missing meals or excessive exercise or too much insulin

- Symptoms: Tachycardia, palpitation, sweating, nausea, and vomiting. Progress to mental confusion, bizarre behavior and coma

- Treatment: Candy or sugar

IV glucose

Glucagon 1 gm IM

- Identification: MedicAler bracelet

58

Diabetes Mellitus Complications

2. Diabetes retinopathy

- Microaneurysm- Hemorrhage- Exudates

- Retinal edema- other

59

Diabetes Mellitus Complications

3. Diabetes nephropathy

- 30-40 % of all type 1 DM patients develop nephropathy in 20 years

- 15-20 % of type 2 DM patients develop nephropathy

- Manifested as:- Microalbuminuria- Progressive diabetic nephropathy leading to end-

stage renal disease

60

Diabetes Mellitus Complications

Diabetes nephropathy (Cont’d)

- All diabetic patients should be screened annually for microalbuminurea to detect patients at high risk of developing progressive diabetic nephropathy

- Tight glycemic control and management of the blood pressure can significantly decrease the risk of developing diabetic nephropathy.

- ACE-inhibitors are recommended to decrease the progression of nephropathy

61

Diabetes Mellitus Complications

4. Diabetes neuropathy

Autonomic neuropathy: - Manifested by orthostatic hypotension, diabetic diarrhea,

erectile dysfunction, and difficulty in urination.

62

Diabetes Mellitus Complications

5. Peripheral vascular disease and foot ulcer

Incidence of gangrene

of the feet in DM is 20

fold higher than control

group due to:

- Ischemia

- Peripheral neuropathy

- Secondary infection

63

Special Patient Population

1. Adolescent Type 2 DM

- Type 2 DM is increasing in adolescent - Lifestyle modification is essential in these patients

- If lifestyle modification alone is not effective, metformin the only labeled oral agent for use in children (10-16 years)

64

Special Patient Population

2. Gestational DM

- Dietary control- If blood glucose is not controlled by dietary control, insulin

therapy is initiated

- One dose of NPH or NPH + regular insulin (2:1) given before breakfast. Adjust regimen according to SMBG.

- Sulfonylureas: Effective, but require further studies to demonstrate safety.

65

Special Situations3. Diabetic ketoacidosis

- It is a true emergency

- Usually results from omitting insulin in type 1 DM or increase insulin requirements in other illness (e.g. infection, trauma) in type 1 DM and type 2 DM

- Signs and symptoms:- Fatigue, nausea, vomiting, evidence of dehydration,

rapid deep breathing, fruity breath odor, hypotension and tachycardia

66

Special SituationsDiabetic ketoacidosis (Cont’d)

- Diagnosis- Hyperglycemia, acidosis, low serum

bicarbonate, and positive serum ketones

- Abnormalities: - Dehydration, acidosis, sodium and

potassium deficit

- Patient education is important

67

Special SituationsDiabetic ketoacidosis (Cont’d)

Management:- Fluid administration: Rapid fluid administration to restore

the vascular volume, - IV infusion of insulin to restore the metabolic

abnormalities. Titrate the dose according to the blood glucose level.

- Potassium and phosphate can be added to the fluid if needed.

Follow up:- Metabolic improvement is manifested by an

increase in serum bicarbonate or pH.

-

Researches have found that lifestyle changes can prevent or delay the onset of type 2 diabetes among high-risk adults.

These studies included people with IGT and other high-risk characteristics for developing diabetes.

Prevention or delay of diabetes: Life style modification

Lifestyle interventions included diet and moderate-intensity physical activity (such as walking for 150 mins each week).

In the Diabetes Prevention Program, a large prevention study of people at high risk for diabetes, the development of diabetes was reduced 58% over 3 years.

Prevention or delay of diabetes: Life style modification

Studies have shown that medications have been successful in preventing diabetes in some population groups.

In the Diabetes Prevention Program, people treated with the drug metformin reduced their risk of developing diabetes by 31% over 3 years.

Prevention or delay of diabetes: Medications

Treatment with metformin was most effective among younger, heavier people (those 25-40 years of age who were 50 to 80 pounds overweight) and less effective among older people and people who were not as overweight. se tolerance.

Prevention or delay of diabetes: Medications

Similarly, in the STOP-NIDDM Trial, treatment of people with IGT with the drug acarbose reduced the risk of developing diabetes by 25% over 3 years.

Prevention or delay of diabetes: Medications

Other medication studies are ongoing. In addition to preventing progression from IGT to diabetes, both lifestyle changes and medication have also been shown to increase the probability of reverting from IGT to normal glucose tolerance.

Prevention or delay of diabetes: Medications

DIABETES: PROTECT OUR FUTURE

Thanks to All