Diabetes Mellitus

This lecture explains the basics of diabetes mellitus, types, causes, mechanisms, symptoms, diagnosis, laboratory investigations and treatment, along with other related aspects.

Outline of Lecture

Diabetes Mellitus

Diabetes

Greek verb “diabainein” which means to stand with legs apart, as in urination

“sugar” diabetes

honey-sweet urine

“water” diabetes

bland or insipid urine

What is Diabetes Mellitus

Diabetes mellitus is a group of metabolic disorders of carbohydrate metabolism characterized by high blood glucose levels – Hyperglycemia

Hyperglycemia lead to spillage of glucose             into the urine, hence the term Diabetes – sweet urine

Glucose homeostasis

normally, blood glucose levels are tightly

controlled by insulin, a hormone produced by the

β cells in the pancreas

whenever there is an elevation of blood glucose

insulin is released from the pancreas to normalize the glucose level

in patients with diabetes mellitus, the absence or

insufficient production of insulin causes

hyperglycemia

Glucose homeostasis

What are the types

type 1 diabetes mellitus

IDDM, Juvenile onset DM

type 2 diabetes mellitus

NIDDM

gestational diabetes mellitus

secondary diabetes mellitus

Type 1 Diabetes Mellitus

the pancreas undergoes a cellular-mediated autoimmune destruction in genetically susceptible individuals, and is rendered incapable of making insulin

patients must rely on exogenously administered insulin for survival

Type 1 Diabetes Mellitus

Insulin secreting cells of the pancreatic β-cells are destroyed

results in insulin dependence

signs and symptoms occur when 90% of beta cells are destroyed resulting in severe or complete insulinopenia

commonly detected before 30

constitutes 5-10%  of DM diagnosis

Type 1 Diabetes Mellitus

suspected causes

genetic predisposition

immunologic

environmental

treatment

Insulin

Type 2 Diabetes Mellitus

patients can still produce insulin, but it is insufficient either absolutely or relative to the body’s needs

lack of sensitivity to insulin by the cells of the body (particularly fat and muscle cells)-Insulin resistance

the release of insulin by the pancreas may also be defective, and occur late in response to increased glucose levels

finally, the liver in these patients continues to produce glucose despite elevated glucose levels

Type 2 Diabetes Mellitus

the three basic patho physiological

abnormalities are:

impaired insulin secretion

excessive hepatic glucose production

insulin resistance in:

skeletal muscle

liver

adipose tissue

Type 2 Diabetes Mellitus

blood glucose levels rise due to

defects in insulin function

Insulin resistance/not islet cell antibodies

Decreased insulin secretion (rarely DKA)

Hepatic glucose overproduction

eventually leads to β-cell failure

(resulting in insulin dependence)

commonly detected after 40

signs and symptoms usually mild or absent at time of diagnosis

constitutes 90-95% of DM diagnosis

Type 2 Diabetes Mellitus

suspected causes

Genetic predisposition-90% with family hx

Strongly associated with obesity (80-90%)

Strongly associated with sedentary lifestyle

IRS/Syndrome X association

treatments

Diet (80% of patients will need wt loss)

Exercise

Medications

The Insulin Resistance Syndrome

metabolic syndrome, consists of:

insulin resistance

hyperinsulinemia

obesity

dyslipidemia

hypertension

diagnosed by three or more of the following criteria:

abdominal obesity

men > 40 inch

women > 35 inch

triglycerides >3.8mmol/L

HDL chol < 1.3mmol/L

BP: >130/85 mmHg

FPG > 6.1mmol/L

 

Gestational Diabetes Mellitus  

carbohydrate intolerance of variable severity with onset or first recognition during pregnancy

occurs in 3-5% of pregnancies

risk factors

obesity, family history of diabetes in first degree relatives, advanced maternal age, glycosuria

screening

usually done during the 24^th-28^th week in high risk patients

glucose challenge test

diagnosis

extended oral glucose tolerance test

Gestational Diabetes Mellitus

suspected causes

occurs due to placental hormone changes that effect insulin function (greater resistance)

treatments

dietary changes are initial treatment and insulin is the only plasma glucose lowering agent used

concern is both for maternal and fetal well-being

postpartum blood glucose levels usually return to normal

increased risk for Type 2 diabetes (30-50%)

Secondary Diabetes Mellitus

develops when the pancreatic tissue responsible for the production of insulin      is absent because it is destroyed by disease, such as:

chronic pancreatitis

trauma

surgical removal of the pancreas

can also result from other hormonal disturbances:

acromegaly

cushing’s syndrome

certain medications may worsen diabetes control, or

“unmask” latent diabetes:

steroids

estrogen

Hyperglycemia

Drowsy

Flushed

Thirsty

Common Symptoms

polyuria

polydipsia

polyphagia

unexplained weight loss

increased fatigue

irritability

blurred vision

slow-healing sores

frequent infections

dry, itchy skin

numbness or tingling in hands or feet

red, swollen or tender gums

Diagnosis

depends solely on demonstration of “hyperglycemia“

any one of the following is diagnostic:

classic symptoms of diabetes &

RPG > 11.1 mmol/L

FPG > 7.0 mmol/L

two hour plasma sample during OGTT > 11.1 mmol/L

Laboratory investigations

Urinalysis

glycosuria

rapid and cheap method detects as little as 0.1% of glucose (glucose sensitive dipstick)

positive tests indicate significant glycosuria

hyperglycemia (>10 mmol/L)

renal glycosuria

monitoring of treatment

screening in GDM

Laboratory investigations

proteinuria

rapid and cheap method (albumin sensitive dipstick)

24 hour urine protein (<30mg/day)

creatinine clearance (GFR)

ketonuria

type 1 diabetes (DKA)

microalbuminuria

urinary albumin in microgram concentration

more sensitive than dipstick method

detects early nephropathy

Laboratory investigations..

Fasting Plasma Glucose (FPG)

cheap and sensitive test for diagnosis

ref range: 3.3-5.6 mmol/L

overnight fast ( 8-12 hours )

FPG >7.0 mmol/L on more than one occasion confirms “diabetes mellitus”

FPG between 6.1-6.9 mmol/L denotes “impaired fasting glucose”

Laboratory investigations..

Random Plasma Glucose (RPG)

cheap but less sensitive for diagnosis

indicated only in emergency situations

ref range : 3.3-11.1 mmol/L

RPG > 11.1 mmol/L on more then one occasion and classic symptoms confirms “diabetes mellitus”

Laboratory investigations..

Oral glucose tolerance test

indications

rarely indicated

impaired glucose tolerance

impaired fasting glucose

women with bad obstetric history

patient preparation

three days of normal carbohydrate diet

overnight fast, performed in morning

no smoking, exercise or stress

Laboratory investigations..

glucose load

adults 75g glucose in 300 ml of water

pregnant women 100g glucose in 300 ml of water

samples

FPG obtained, then oral glucose is given

blood samples for plasma glucose obtained at one hour and two hour intervals after ingestion of glucose

Laboratory investigations..

interpretation

“normal” (ADA criteria)

FPG < 5.6 mmol/L

two hour plasma glucose < 7.8 mmol/l

*impaired glucose tolerance (IGT)

FPG < 7.0 mmol/L

two hour plasma sample 7.8-11.1 mmol/L

*impaired fasting glucose (IFG)

FPG 6.1-6.9 mmol/l

and two hour plasma glucose (if measured) < 7.8mmol/l

*diabetes mellitus

FPG > 7.0 mmol/L

two hour plasma sample >11.1 mmol/L

*2006 WHO recommendations (WHO does not define normal response)

Laboratory investigations..

Glycated Hemoglobin estimation

hemoglobin that has a sugar residue attached,   Hb A_1c is the major fraction (~80%)

non enzymatic attachment of glucose to Hb formed slowly & continuously through out 120 day lifespan of red cell

provides an index of average plasma glucose concentration over preceding 2-3 months

ref range: 4-7%

Laboratory investigations..

Lipoproteins estimation

generally normal in type 1 diabetes

“diabetic dyslipidemia” in type 2 diabetes

high serum triglyceride

low HDL cholesterol (good cholesterol)

high LDL cholesterol (bad cholesterol)

Laboratory investigations..

Miscellaneous tests

plasma analytes

Na⁺,K⁺,HCO₃^–,pH,urea,creatinine,osmolality & lactate levels

hyperglycemic diabetic coma

plasma insulin

no role in diagnosis of diabetes mellitus

low in type 1 diabetes

variable to high in type 2 obese diabetics

useful in diagnosis of insulinoma

Impact of Diabetes

a chronic medical condition, meaning it can last a lifetime & has social, psychological and financial impacts

Long standing untreated diabetes mellitus can lead to blindness, kidney failure, and nerve damage

Impact of Diabetes

Diabetes mellitus is also an important factor in accelerating the progress of atherosclerosis, leading to strokes, coronary heart diseases, and other blood vessel diseases

Diabetes mellitus is predicted to become the

leading cause of morbidity and death in the

coming decade

Physiological Impact

6^th leading cause of death by disease

decreases life expectancy of middle-aged people by 5-10 years

2-4 times greater risk of death due to heart disease

compounding factors include: duration of disease, glycemic control, HTN, smoking, dyslipidemia, decreased activity, and obesity

leading cause of blindness in 25-74 year olds

leading cause of non-traumatic amputations

responsible for 25-30% of all new dialysis patients

Financial Impact

estimated to cost 132 billion US $ in 2002 (ADA data)

adult Diabetes Mellitus patients have a three times more hospitalization rate than the general population

children with Diabetes Mellitus have a six times more hospitalization rate than the general population of children

Blood glucose control reduces complications of Diabetes!

Prevention of effects: combination approach

increased exercise

decreases need for insulin

reduce calorie intake

improves insulin sensitivity

weight reduction

improves insulin action

Triad of Treatment

Diet

Medication

Oral hypoglycemics

Insulins

Exercise

Diabetes treatment

Exercise

under physician supervision

check glucose prior

Diet

lower calorie

fewer foods of “high glycemic index”

spread meals evenly

Anti-Diabetic medications

Oral hypoglycemic agents

sulfonylureas

thiazolidinediones

biguanides

alpha-glucosidase inhibitors

D-phenylalinine derivatives

combinations

Insulins