DIABETUS MELLITUS

DIABETES MELLITUS (DM) Is a common, chronic, metabolic syndrome

characterized by hyperglycemia as a cardinal biochemical feature.

The major forms of diabetes are classified according to those caused by deficiency of insulin secretion due to pancreatic β-cell damage (type 1 DM, or T1DM) and

those that are a consequence of insulin resistance

occurring at the level of skeletal muscle, liver, and

adipose tissue, with various degrees of β-cell impairment (type 2 DM, or T2DM).

 ETIOLOGIC CLASSIFICATIONS OF DM  Type I diabetes (β-cell destruction, usually leading to absolute insulin

deficiency) Immune mediated , Idiopathic

Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance)

Other specific types

- Genetic defects of β-cell function (MODY 1-6)

- Genetic Defects in insulin action

   -Pancreatitis, Drug-or chemical-induced, Trauma, pancreatectomy

  

  

  

 

DIABETES MELLITUS

Infections    Congenital rubella, coxackie virus    Cytomegalovirus Other genetic syndromes associated with

diabetes   Down syndrome   Klinefelter syndrome   Turner syndrome prader will syndrome

DIABETES MELLITUS Gestational diabetes mellitus Neonatal diabetes mellitus  Transient—without recurrence  Transient—recurrence 7–20 yr later  Permanent from onset

THE NATURAL HISTORY INCLUDES 4 DISTINCT STAGES:1. preclinical β-cell autoimmunity with

progressive defect of insulin secretion, 2. onset of clinical diabetes,3. transient remission “honeymoon period,”

and4.established diabetes associated with acute

and chronic complications and decreased life expectancy.

IMPAIRED GLUCOSE TOLERANCE. The term impaired glucose tolerance (IGT) refers

to a metabolic stage that is intermediate between normal glucose homeostasis and diabetes.

A fasting glucose concentration of 99 mg/dL is the upper limit of “normal.”

This choice is near the level above which acute-phase insulin secretion is lost in response to IV administration of glucose and is associated with a progressively greater risk of the development of microvascular and macrovascular complications.

PATHOGENESIS The autoimmune attack on the pancreatic islets

leads to a gradual and progressive destruction of β cells, with loss of insulin secretion.

It is estimated that, at the onset of clinical diabetes, 80–90% of the pancreatic islets are destroyed.

PATHOGENESIS

Regeneration of new islets has been detected at

onset of T1DM, and it is thought to be

responsible for the honeymoon phase (a

transient decrease in insulin requirement

associated with improved β-cell function).

PATHOPHYSIOLOGY

Insulin is our most important anabolic hormone! Saving , storing and up building of carbohydrate , protein

and fat. Carbohydrate -Insulin stimulates the insulin receptor on

the cell surface Glut 4 , a glucose transporter, is sent to the cell surface of the muscle to pick up glucose by endocytosis. The more insulin the more transporter!!

Glucose is phosphorylated and ready for either storing as glycogen or glycolysis and energy production (ATP)

PATHOPHYSIOLOGY

Fat -Insulin preservs the fat stores (It antagonizes

the adrenaline sensitive lipase in fat tissue)

Protein -Aminoacid uptake in the cells is

stimulated and breakdown of protein is reduced.

PATHOPHYSIOLOGY.

Insulin levels must be lowered to then mobilize

stored energy during the fasted state.

Thus, in normal metabolism, there are regular

swings between the postprandial, high-insulin

anabolic state and the fasted, low-insulin

catabolic state that affect liver, muscle, and

adipose tissue .

PATHOPHYSIOLOGY.

T1DM is a progressive low-insulin catabolic state in which feeding does not reverse but rather exaggerates these catabolic processes.

With moderate insulinopenia, glucose utilization by muscle and fat decreases and postprandial hyperglycemia appears

At even lower insulin levels, the liver produces excessive glucose via glycogenolysis and gluconeogenesis, and fasting hyperglycemia begins.

Postprandial hyperglycemia then fasting hyperglycemia will occur

PATHOPHYSIOLOGY. Hyperglycemia produces an osmotic diuresis

(glycosuria) when the renal threshold is exceeded (180 mg/dL; 10 mmol/L).

The resulting loss of calories and electrolytes, as well as the persistent dehydration, produce a physiologic stress with hypersecretion of stress hormones (epinephrine, cortisol, growth hormone, and glucagon).

These hormones, in turn, contribute to the metabolic decompensation by further impairing insulin secretion (epinephrine),

by antagonizing its action (epinephrine, cortisol, growth hormone), a

by promoting glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis (glucagon, epinephrine, growth hormone, and cortisol)

Impairing insulin secretion , antagonizing insulin

action , decrease glucose utilization , increase

glucosneogenesis and ketogenesis

PATHOPHYSIOLOGY

CLINICAL PRESENTATION

Childhood type 1 diabetes can present in several different ways.

Classic new onset Diabetic ketoacidosis Silent (asymptomatic) incidental discovery

Classic new onset - Hyperglycemia without acidosis is the most common presentation of childhood type 1 diabetes. Symptoms are caused by hyperglycemia and include polyuria, polydipsia, weight loss despite increased appetite initially (polyphagia), and lethargy.

DIABETIC KETOACIDOSIS As an initial presentation or in a known case of

DM when they omit their insulin or when there is infection or stress.

Can be classified as mild,moderate and severe DKA

Normal Mild Moderate Severe

CO 2 meq/l(venous)

20-28 16-20 10-15 <10

PH(venous) 7.35-7.45 7.25-7.35 7.15-7.25 <7.15

Clinical No change Alert but fatigued

Kussmal breathing ,sleepy

comatous

DIABETIC KETOACIDOSIS

When extremely low insulin levels are reached, keto acids accumulate. Keto acids produce abdominal discomfort, nausea, and emesis.

Dehydration accelerates, causing weakness and polyuria persists. As in any hyperosmotic state, the degree of dehydration may be clinically underestimated

Ketoacidosis exacerbates prior symptoms and leads to Kussmaul respirations (deep, heavy, rapid breathing), fruity breath odor (acetone), diminished neurocognitive function, and possible coma.

DIAGNOSIS Fasting plasma glucose ≥ 126 mg/dL (7 mmol/L)

on two occasions Symptoms of hyperglycemia and

a random venous plasma glucose ≥ 200 mg/dL (11.1 mmol/L)

Abnormal oral glucose tolerance test (OGTT) defined as a plasma glucose ≥ 200 mg/dL (11.1 mmol/L) measured two hours after a glucose load of 1.75 g/kg (maximum dose of 75 g)

Most children and adolescents are symptomatic and have plasma glucose concentrations well above ≥ 200 mg/dL (11.1 mmol/L); thus, OGTT is seldom necessary to diagnose type 1 diabetes.

CHALLENGES IN PEDIATRICS DM

There are unique challenges in caring for children and adolescents with diabetes that differentiate pediatric from adult care.

These include the obvious differences in the size of the patients, developmental issues such as the unpredictability of a toddler's dietary intake and activity level, and medical issues such as the increased risk of hypoglycemia and diabetic ketoacidosis.

Because of these considerations, the management of a child with type 1 diabetes must take into account the age and developmental maturity of the child.

GOALS  Successful management of children with

diabetes includes the following : Balancing strict glycemic control, which

reduces the risk of long-term sequelae, and avoidance of severe hypoglycemia, which is more likely with stricter control.

In children, targeted glycemic goals define what is thought to be the best balance between these long- and short-term complications.

GOALS  Maintaining normal growth, development, and

emotional maturation. Increasing self-independent management as the

child grows is an ongoing goal. Training the patient and family to provide

appropriate daily diabetes care in order to attain glucose control within the range of predetermined goals, and to recognize and treat hypoglycemia.

DKA MANAGEMENT1.Volume expansion 10-20 ml/kg R/L or N/S over 1 hour2.Insulin therapy and K+ replacement - 0.1u /kg/hr continuous insulin mxt -0.5 u/kg/ every 4-6 hourly intermittent insulin mxt -K + 20-40 meq/L of fluid3. Fluid mxt 85 ml/kg + maintenance fluid –bolus/23

hrs(0.45 % N/S and when glucose is < 250 mg/dl change the fluid to 5 % D/W

DKA MXT RISKS Hypoglycemia Cerebral edema Hypokalemia So we need to follow the child with V/S,

frequent glucose and electrolyte measurement to act accordingly.

Bed side mannitol 1gm/kg is important

Treatment Insulin Therapy. Children with long-standing diabetes and no

insulin reserve require about 0.7 U/kg/d if prepubertal, 1.0 U/kg/d at midpuberty, and 1.2 U/kg/d by the end of puberty

Basic education – about the insulin injection , meal planning ,exercise, about symptoms of hypo/hyperglycemia and importance of SMBG and the impact of poor control of DM.

EXERCISE No form of exercise, including competitive

sports, should be forbidden to the diabetic child. But the risk of hypoglycemia is there during or

within hours after exercise so BG measurement is important .

They have to take candy or carbonated juice to take immediately if there are symptoms of hypoglycemia

Onset of action

30-60 minutes

5-15 minutes

1-2 hours

1-3 hours

0.5-1 hours

Peak of action

2-4 hours

1-2 hours

5-7 hours

4-8 hours

dual

Duration of action

6-8 hours

4-5 hours

13-18 hours

13-20 hours

10-16 hours

Insulin

Soluble - Regular

Lispro- Aspart

NPH

Glargine-Detemir

Combinations

Insulin PreparationsKinetics following s.c. injection

T2DM MANAGEMENT

Weight loss and physical exercise are said to

be the main strategies in controlling glucose

level in T2DM patients

Oral hypoglycemic agents like metiformin

can be tried

Insulin if they have ketonuria

Long term complications of DM-Micro vascular

complications( Retinopathy, nephropathy)

-Macro vascular complication-Growth failure and delayed puberty

INJECTION MODELSRepeted injections

Future intelligent pumps with reliable sensors for glucose levels= mechanical pancreas