Diabetes Mellitus
in Primary Care

Grzegorz

Grzegorz

Margas

Margas

Joanna Nowak, 41 years old housewife has been

Joanna Nowak, 41 years old housewife has been

complaining from intensive thirst and polyuria for two

complaining from intensive thirst and polyuria for two

weeks. In this time she lost approx. 2 kg. Since her older

weeks. In this time she lost approx. 2 kg. Since her older

brother is diabetic, using his tests at home she detected

brother is diabetic, using his tests at home she detected

presence of sugar in the urine. She was healthy in the

presence of sugar in the urine. She was healthy in the

past. She had never complained from fever, dysuria,

past. She had never complained from fever, dysuria,

back pain, cough or headache. She had regular menses.

back pain, cough or headache. She had regular menses.

She gave birth three healthy children, every with birth

She gave birth three healthy children, every with birth

weight above 3,5 kg, but no above 4 kg. Her family

weight above 3,5 kg, but no above 4 kg. Her family

history is positive - brother is diabetic on oral glucose-

history is positive - brother is diabetic on oral glucose-

lowering drugs, mother has impaired glucose tolerance.

lowering drugs, mother has impaired glucose tolerance.

There are no other endocrine disturbances.

There are no other endocrine disturbances.

Mrs. Nowak weights 65 kg at height 155 cm. BP 130 / 85

Mrs. Nowak weights 65 kg at height 155 cm. BP 130 / 85

mmHg, HR 75/min - regular. Apart from slight

mmHg, HR 75/min - regular. Apart from slight

overweight physical examination did not reveal any

overweight physical examination did not reveal any

other pathology.

other pathology.

1 What is your diagnostic

1 What is your diagnostic

consideration?

consideration?

2 What additional examinations

2 What additional examinations

should be performed?

should be performed?

3 What is your treatment?

3 What is your treatment?

Additional

Additional

investigations ordered

investigations ordered

by you showed:

by you showed:



Glycaemia: 15, 6 mmol/l,

Glycaemia: 15, 6 mmol/l,



C

C

holesterol 250 mg / dl, TG 300

holesterol 250 mg / dl, TG 300

mg / dl

mg / dl



G

G

lucosuria (5 %), without acetone.

lucosuria (5 %), without acetone.

Diabetes Mellitus in

Diabetes Mellitus in

Primary Care

Primary Care



Detection

Detection



Treatment

Treatment

Definition

Definition



A disorder of carbohydrate

A disorder of carbohydrate

metabolism associated with

metabolism associated with

relative or absolute deficiency

relative or absolute deficiency

of insulin

of insulin

Diabetes mellitus type

Diabetes mellitus type

1

1



Insulin dependent diabetes mellitus, IDDM

Insulin dependent diabetes mellitus, IDDM



β

β

-cell destruction usually leading to absolute

-cell destruction usually leading to absolute

insulin deficiency

insulin deficiency



more prevalent in young persons

more prevalent in young persons



little or no endogenous secretion of insulin and

little or no endogenous secretion of insulin and

therefore requiring insulin replacement

therefore requiring insulin replacement



more severe

more severe

Etiology of diabetes

Etiology of diabetes

type 1

type 1



Genetic factors:

Genetic factors:

–

increased frequency of HLA DR3 and HLA DR4

increased frequency of HLA DR3 and HLA DR4

–

Increased frequency of diabetes in siblings

Increased frequency of diabetes in siblings



Immunological

Immunological

–

Islet cell antibodies present in the early stages of

Islet cell antibodies present in the early stages of

the disease

the disease

–

Immune-suppresion with cyclosporin A soon after

Immune-suppresion with cyclosporin A soon after

the onset of the diabetes can produce lasting

the onset of the diabetes can produce lasting

remission of IDDM

remission of IDDM



Environmental

Environmental

–

Viral infection (Coxsackie B and rubella) trigger in

Viral infection (Coxsackie B and rubella) trigger in

genetically-predisposed individuals

genetically-predisposed individuals

–

Breast-feeding can offer some protection against

Breast-feeding can offer some protection against

the development of diabetes

the development of diabetes

Diabetes mellitus type

Diabetes mellitus type

2

2



Non-insulin dependent diabetes mellitus,

Non-insulin dependent diabetes mellitus,

NIIDM)

NIIDM)



From predominantly insulin resistance with

From predominantly insulin resistance with

relative insulin deficiency to predominantly

relative insulin deficiency to predominantly

an insulin secretory defect with insulin

an insulin secretory defect with insulin

resistance

resistance



mature onset

mature onset



insulin still produced

insulin still produced



associated with obesity

associated with obesity

Etiology of diabetes

Etiology of diabetes

type 2

type 2



Genetic factors: more important

Genetic factors: more important

than in IDDM

than in IDDM



Insulin resistance

Insulin resistance



Abnormal beta-cell function

Abnormal beta-cell function



Environmental factors:

Environmental factors:

–

Obesity

Obesity

–

Physical activity

Physical activity

–

Diet

Diet

Insulin

dependent

(type I)

10%

Non-insulin

dependent

(type II)

90%

Prevalence

Prevalence

Diagnosed DM

Undiagnosed DM

IFG

0

5

10

15

20

25

30

35

20-39

40-49

50-59

60-74

>75

Age

% of population

Age at first diagnosis

Age at first diagnosis

0-9

1%

10-19

3%

20-29

10%

30-39

13%

40-49

13%

50-59

13%

60-69

27%

>70

20%

Diabetics in practice of 2000

Diabetics in practice of 2000

patients

patients

120

120

60

60

Patients with DM

Patients with DM

Patients with undiagnosed

Patients with undiagnosed

DM

DM

Diabetes type 1

Diabetes type 1

presentation

presentation



Severe acute

Severe acute

diabetes

diabetes

–

Dehydratation

Dehydratation

–

Nausea and

Nausea and

vomiting

vomiting

–

Abdominal pain

Abdominal pain

–

Circulatory

Circulatory

collapse

collapse

–

Stupor

Stupor





coma

coma



Subacute

diabetes:

– Polyuria and

polydypsia

– Loss of weight
– Fatigue and

weakness

– Pruritus
– Paraesthesiae
– Visual

disturbances

Diabetes type 2

Diabetes type 2

presentation

presentation



Many are asymptomatic

Many are asymptomatic



Symptoms are often mild and gradual-

Symptoms are often mild and gradual-

thirst, polyuria and loss of weight

thirst, polyuria and loss of weight

developing over several months

developing over several months



Other symptoms:

Other symptoms:

–

Susceptibility to staphylococcal skin infections

Susceptibility to staphylococcal skin infections

–

Candida vaginitis

Candida vaginitis

–

Balanitis

Balanitis

–

Increased mortality from atherosclerotic

Increased mortality from atherosclerotic

complications

complications

 

 

A seventy-one-year-old man was found to have

A seventy-one-year-old man was found to have

diabetes when he presented with thirst,

diabetes when he presented with thirst,

polyuria, and gangrene of the right big toe,

polyuria, and gangrene of the right big toe,

which required amputation of the leg. His

which required amputation of the leg. His

record showed that five years previously he

record showed that five years previously he

had been treated for balanitis. Three years

had been treated for balanitis. Three years

previously he had pain in both legs. X-ray

previously he had pain in both legs. X-ray

showed flattening of the lumbosacral disc. He

showed flattening of the lumbosacral disc. He

was treated with a plaster cast and was off

was treated with a plaster cast and was off

work four months. The orthopedic report stated

work four months. The orthopedic report stated

that his leg reflexes were absent and that there

that his leg reflexes were absent and that there

was sensory loss on the inner side of the left

was sensory loss on the inner side of the left

foot. Later in the same year he was treated for

foot. Later in the same year he was treated for

a purulent blister on the finger. There was no

a purulent blister on the finger. There was no

record of any urine tests.

record of any urine tests.

Screening for diabetes mellitus

Screening for diabetes mellitus

patients with at least one of the following risk

patients with at least one of the following risk

factors:

factors:



Age > 45

Age > 45



obesity (BMI >27)

obesity (BMI >27)



diabetes mellitus in close family

diabetes mellitus in close family



diabetes mellitus during pregnancy or borning child > 4 kg

diabetes mellitus during pregnancy or borning child > 4 kg



Hypertension

Hypertension



HDL cholesterol < 0,9 mmol/l and/or triglycerides > 2,2

HDL cholesterol < 0,9 mmol/l and/or triglycerides > 2,2

mmol/l

mmol/l



IGT or IFG in recent test

IGT or IFG in recent test



cardiovascular event in the history

cardiovascular event in the history



symptoms of diabetes

symptoms of diabetes



If results are normal: repeat every three years

If results are normal: repeat every three years

Diagnostic criteria

Diagnostic criteria

Normal

IFG

IGT

Diabetes

mellitus

Random

< 5,5

mmol/l

 11,1

mmol/l

Fasting

< 6,1

mmol/l

6,1 – 6,9

mmol/l

 7,0

mmol/l

2 h after

intake 75

g glucose

< 7,8

mmol/l

< 7,8

mmol/l

7,8 – 11,0

mmol/l

 11,1

mmol/l

Symptomatic

Symptomatic

or

or

glycosuria

glycosuria

or

or

incidental hyperglycaemia:

incidental hyperglycaemia:

Check

Check

random venous plasma glucose

random venous plasma glucose

–

If

If

≥11.1 mmol/l = "Diabetes"

≥11.1 mmol/l = "Diabetes"

–

If

If

>5.5 mmol/l

>5.5 mmol/l

then

then

proceed to next

proceed to next

step (and review cause of symptoms)

step (and review cause of symptoms)

Diagnosis of Diabetes Mellitus

Diagnosis of Diabetes Mellitus

Diagnosis of Diabetes Mellitus

Fasting glucose:

Fasting glucose:



normal

normal

< 6,1 mmol/l

< 6,1 mmol/l



IFG

IFG

6,1-6,9 mmol/l

6,1-6,9 mmol/l



diabetes

diabetes

≥

≥

7,0 mmol/l

7,0 mmol/l

Diagnosis of Diabetes Mellitus

Diagnosis of Diabetes Mellitus

OGTT (venous plasma glucose):

OGTT (venous plasma glucose):



If

If

2-h >11.0 mmol/l = "Diabetes"

2-h >11.0 mmol/l = "Diabetes"



If

If

2-h

2-h





11.0 mmol/l and

11.0 mmol/l and





7.8

7.8

mmol/l = "IGT"

mmol/l = "IGT"



If fasting >6.0 mmol/l and 2-h

If fasting >6.0 mmol/l and 2-h

<7.8 mmol/l = "IFG"

<7.8 mmol/l = "IFG"

1. Fasting glucose estimations requires

1. Fasting glucose estimations requires

no caloric intake for at least 8 hours

no caloric intake for at least 8 hours

–

diagnosis cannot be based on a single

diagnosis cannot be based on a single

abnormal glucose estimation in the

abnormal glucose estimation in the

absence of symptoms

absence of symptoms

2. Venous plasma glucose estimation is

2. Venous plasma glucose estimation is

preferred

preferred

HbA

HbA

1c

1c

(glycated haemoglobin) can

(glycated haemoglobin) can

be useful in clinical diagnosis and

be useful in clinical diagnosis and

follow-up

follow-up

–

HbA

HbA

1c

1c

>7.5 % = fasting plasma

>7.5 % = fasting plasma

glucose

glucose





7.0 mmol/l

7.0 mmol/l

–

HbA

HbA

1c

1c

>6.5 % = fasting plasma

>6.5 % = fasting plasma

glucose >6.0 mmol/l

glucose >6.0 mmol/l

Objectives of

Objectives of

treatment

treatment



To relieve symptoms

To relieve symptoms



To prevent or delay complications

To prevent or delay complications



To prolong life

To prolong life

Management

Management



Survival in diabetes depends

Survival in diabetes depends

primarily on the presence or

primarily on the presence or

absence of vascular complications

absence of vascular complications

Treatment

Treatment



Education

Education



Diet

Diet



Drugs

Drugs

–

Biguanides

Biguanides

–

Sulphonylureas

Sulphonylureas

–

Acarbose

Acarbose



Insulin

Insulin

Diabetics are managed

Diabetics are managed

by:

by:



Diet alone

Diet alone

30%

30%



Diet and drugs

Diet and drugs

40%

40%



Insulin

Insulin

30%

30%

Diet

Diet



Non-insulin dependent type II diabetes

Non-insulin dependent type II diabetes

is highly correlated with obesity

is highly correlated with obesity



There is popular misconception that

There is popular misconception that

eating too much sugar causes diabetes

eating too much sugar causes diabetes



Excessive energy intake, usually from

Excessive energy intake, usually from

a high fat consumption, which

a high fat consumption, which

contributes to obesity and may in turn

contributes to obesity and may in turn

cause diabetes

cause diabetes

Diet in DM

Diet in DM



Moderate caloric restriction

Moderate caloric restriction



Reduction of total fat (especially

Reduction of total fat (especially

saturated)

saturated)



Limiting the total carbohydrate

Limiting the total carbohydrate

intake (not only simple sugars,

intake (not only simple sugars,

but also bread, rice, potatoes etc.)

but also bread, rice, potatoes etc.)



Meals should be spaced throughot

Meals should be spaced throughot

the day

the day

PHYSICAL EXERCISE

PHYSICAL EXERCISE



Can benefit insulin sensitivity, blood

Can benefit insulin sensitivity, blood

pressure, and blood lipid control

pressure, and blood lipid control



Should be taken at least every 2-3

Should be taken at least every 2-3

days for optimum effect

days for optimum effect



May increase the risk of acute and

May increase the risk of acute and

delayed hypoglycaemia

delayed hypoglycaemia



Examples :

Examples :

–

brisk walking, swimming, jogging

brisk walking, swimming, jogging

Oral glucose-lowering

Oral glucose-lowering

drugs

drugs

Begin

Begin

oral agent therapy when :

oral agent therapy when :



an adequate trial of life-style

an adequate trial of life-style

intervention / education has been given

intervention / education has been given



either

either

(usually): HbA

(usually): HbA

1c

1c

>6.5 %, fasting

>6.5 %, fasting

venous plasma glucose >6.0 mmol/l

venous plasma glucose >6.0 mmol/l



or

or

(occasionally) if thin and no other

(occasionally) if thin and no other

arterial risk factor: HbA

arterial risk factor: HbA

1c

1c

>7.5 %, fasting

>7.5 %, fasting

venous plasma glucose

venous plasma glucose





7.0 mmol/l

7.0 mmol/l

Oral glucose-lowering

Oral glucose-lowering

drugs

drugs



First-generation agents

First-generation agents

–

Tolbutamide, Chlopropamide

Tolbutamide, Chlopropamide



Second-generation sulfonylureas

Second-generation sulfonylureas

–

Glipizide, Glibenclamide, Gliclazide

Glipizide, Glibenclamide, Gliclazide



Third generation sulfonylureas

Third generation sulfonylureas

–

Glimepiride, Repaglinide

Glimepiride, Repaglinide



Inhibitor of hepatic gluconeogenesis

Inhibitor of hepatic gluconeogenesis

–

Metformin

Metformin



Inhibitors of rapid glucose absorption

Inhibitors of rapid glucose absorption

–

Glycosidase inhibitors e.g. Acarbose

Glycosidase inhibitors e.g. Acarbose



Insulin sensitisers

Insulin sensitisers

–

Troglitazone

Troglitazone

Metformin

Metformin



Acts by decreasing hepatic

Acts by decreasing hepatic

gluconeogenesis and increases tissue

gluconeogenesis and increases tissue

sensitivity to insulin

sensitivity to insulin



Strong evidence base in the

Strong evidence base in the

overweight: patients tend to lose

overweight: patients tend to lose

weight

weight



Hypoglycaemia is very rare

Hypoglycaemia is very rare

Sulphonylureas

Sulphonylureas



Act by increasing insuline secretion

Act by increasing insuline secretion



Good evidence base, provided patient

Good evidence base, provided patient

has useful islet

has useful islet

β

β

-cell function

-cell function



May increase patient’s weight

May increase patient’s weight



First-line treatment in non-obese patients

First-line treatment in non-obese patients

who are poorly controlled by diet and

who are poorly controlled by diet and

exercise

exercise



May lead to hypoglycaemia 4 or more

May lead to hypoglycaemia 4 or more

hours after food, especially in elderly

hours after food, especially in elderly

patients

patients

Repaglinide

Repaglinide



first beta-cell mediated prandial glucose regulator

first beta-cell mediated prandial glucose regulator



allows for the rapid release of insulin from pancreatic

allows for the rapid release of insulin from pancreatic

beta-cells followed by a rapid lowering of blood glucose

beta-cells followed by a rapid lowering of blood glucose

(fast in-fast out)

(fast in-fast out)



stimulates insulin secretion from pancreatic beta

stimulates insulin secretion from pancreatic beta

cells

cells



closes ATP-sensitive potassium channels on the

closes ATP-sensitive potassium channels on the

beta cells membrane

beta cells membrane



binds to a distinct binding site from sulphonylurea

binds to a distinct binding site from sulphonylurea

compounds

compounds



In contrast to sulphonylureas, REPAGLINIDE

In contrast to sulphonylureas, REPAGLINIDE

preserves insulin biosynthesis in the pancreatic

preserves insulin biosynthesis in the pancreatic

islet cells

islet cells

Alpha-glucosidase

Alpha-glucosidase

inhibitors

inhibitors

(acarbose)

(acarbose)



Effective control of post-prandial

Effective control of post-prandial

hyperglycaemia,

hyperglycaemia,



Poorly tolerated by many patients

Poorly tolerated by many patients

Troglitazone

Troglitazone



Lowers blood glucose by improving target cell

Lowers blood glucose by improving target cell

response to insulin.

response to insulin.



Mechanism of action dependent on the

Mechanism of action dependent on the

presence of insulin.

presence of insulin.



Troglitazone decreases hepatic glucose

Troglitazone decreases hepatic glucose

output and increases insulindependent

output and increases insulindependent

glucose disposal in skeletal muscle.

glucose disposal in skeletal muscle.



Its mechanism of action is thought to involve

Its mechanism of action is thought to involve

binding to nuclear receptors (PPAR) that

binding to nuclear receptors (PPAR) that

regulate the transcription of a number of

regulate the transcription of a number of

insulin responsive genes critical for the

insulin responsive genes critical for the

control of glucose and lipid metabolism.

control of glucose and lipid metabolism.

Insulin therapy in NIDDM

Insulin therapy in NIDDM



Many of the patients have raised

Many of the patients have raised

insulin levels in their blood, giving

insulin levels in their blood, giving

more insulin may enhance the

more insulin may enhance the

development of atherosclerosis

development of atherosclerosis

Mortality

Mortality



Diabetics have excess mortality

Diabetics have excess mortality

rates –

rates –

3-fold compared with

3-fold compared with

non-diabetics. Those on insulin

non-diabetics. Those on insulin

have 5-fold excess

have 5-fold excess



Causes of death in diabetics:

Causes of death in diabetics:

–

Ischaemic heart disease

Ischaemic heart disease

–

Renal failure

Renal failure

–

Infections

Infections

Follow-up in patients with

Follow-up in patients with

diabetes

diabetes

Routine follow-up every 3-4 months

Routine follow-up every 3-4 months



Weight and blood pressure

Weight and blood pressure



Blood sugar control

Blood sugar control



Urine examination for ketones and

Urine examination for ketones and

albumin (including microalbuminuria)

albumin (including microalbuminuria)



Symptoms and signs of any

Symptoms and signs of any

complications especially vascular

complications especially vascular

disease

disease

Annual Review

Annual Review



Symptoms:

Symptoms:

–

ischaemic heart

ischaemic heart

disease,

disease,

–

peripheral vascular

peripheral vascular

disease,

disease,

–

neuropathy,

neuropathy,

–

erectile dysfunction

erectile dysfunction



Feet:

Feet:

–

footwear,

footwear,

–

deformity / joint

deformity / joint

rigidity,

rigidity,

–

poor skin condition,

poor skin condition,

–

ischaemia,

ischaemia,

–

ulceration,

ulceration,

–

absent pulses,

absent pulses,

–

sensory impairment

sensory impairment

Annual Review

Annual Review

Annual Review



Eyes:

Eyes:

–

visual acuity

visual acuity

–

retinal review

retinal review



Kidney damage:

Kidney damage:

–

albumin excretion

albumin excretion

–

serum creatinine

serum creatinine

Annual Review

Annual Review

•

Arterial risk:

•

blood glucose,

•

blood pressure,

•

blood lipids,

•

smoking

•

Attendance: podiatry / ophthalmology

/ other

Morbidity

Morbidity

Complications of the diabetes are

Complications of the diabetes are

related to

related to



Degree of control

Degree of control



Duration of disorder

Duration of disorder



Type of diabetes

Type of diabetes



Age of diabetic

Age of diabetic