Diabetes Mellitus

Prof. Dr. Ahmet AYDIN

İÜ Cerrahpaşa Tıp Fak.

Çocuk Sağlığı ve Hastalıkları ABD

Beslenme ve Metabolizma Bilim Dalı Başkanıwww.beslenmebulteni.com e-posta: besahmet@yahoo.com

DIABETES MELLITUS

• A syndrome characterized by hyperglycemia resulting from absolute or relative impairment in insulin secretion and/ or insulin action

Characteristic Type I (Juvenile) DM Insulin Dependent DM

Type II DMNon-insulin Dependent

Age of onset

Type of onset

Associated obesity

Propensity to ketoacidosis

Insulin secretion

Most commonly <30y

Usually abrupt

No

Yes

Minimal or low

Most commonly >30y

Insidious

Yes

No

High (Insulin resistance)

Characteristic Type I (Juvenile) DM Insulin Dependent DM

Type II DMNon-insulin Dependent

Nutritional statusSpecific HLA antigensIslet cell (ICA) and anti-GAD antibodies at diagnosisIslet pathology

Response to sulfonylureas

Thin, catabolic state

Yes

Yes

Insulitis, selective loss of ß-cellsNo

Obese or normal

No

No

Normal islets

Initially yes

GESTATIONAL DIABETES

• Occurs in 2% of pregnancies. A consequence of the diabetogenicity of the gravid state in women with marginal insulogenic capacity.

• It generally reverts to normal following parturition. Gestational diabetes generally progress to type II diabetes mellitus.

MATURITY ONSET DIABETES OF THE YOUNG (MODY)

• Some cases of type II diabetes occur in young, nonobese adolescents with an autosomal dominant inheritance (a mutation in glucokinase gene).

SECONDARY DIABETES• Pancreatic disease: Cystic fibrosis, pancreatitis,

alcoholism, hemochromatosis, pancreatectomy,

• Endocrinopathies: Cushing's syndrome, pheochhromocytoma, glucagonoma, aldosteronoma, acromegaly. autoimmune diseases (Grave's Disease, Hoshimoto's disease, Addisson's disease)

• Chemical diabetes: glucocorticoids, thiazide diuretics, clonidine, lithium, oral contraceptives, phenothiazines,

• Genetic syndromes: Turner's syndrome, leprechaunism, Prader-Willi syndrome

Epidemiology

• Prevalence: (USA)• At 5 years of age: 1:4300• At 16 years of age: 1:360•

Incidence: • 30 new cases annually per 100,000

population in Finland• 15 new cases annually per 100,000

population in USA• 1 new cases annually per 100,000

population in Japan

• Seasonal incidence: greater frequency in autumn and winter months (infections)

• Age of presentation: Rare in infants

Peaks of presentation

5-7 years of age: increased exposure to infections (the beginning of school)

At the time of puberty: pubertal spurt induced by gonadal steroids and GH

Tissue antigens

• Inheritance of HLA-DR3 or HLA-DR4 antigens appears to confer 2- to 3-fold increased risk for developing diabetes mellitus.

• When both HLA-DR3 and HLA-DR4 are inherited risk for developing Type I diabetes is increased by 7- to 10- fold.

• The homozygous absence of aspartic acid at position 57 of the HLA-DQ –chain confers an approximately 100-fold increased risk for developing diabetes mellitus.

Signs and symptoms

• The classical symptoms of DM are polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).

• Symptoms may develop quite rapidly (weeks or months) in type 1 diabetes, particularly in children.

• However, in type 2 diabetes symptoms usually develop much more slowly and may be subtle or completely absent.

Signs and symptoms

• Type 1 diabetes may also cause a rapid yet significant weight loss (despite normal or even increased eating) and irreducible mental fatigue.

• All of these symptoms except weight loss can also manifest in type 2 diabetes in patients whose diabetes is poorly controlled, although unexplained weight loss may be experienced at the onset of the disease.

• When the glucose concentration in the blood is raised beyond its renal threshold (about180mg/dL, although this may be altered in certain conditions, such as pregnancy), reabsorption of glucose in the proximal renal tubuli is incomplete, and part of the glucose remains in the urine (glycosuria).

• This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss.

• Lost blood volume will be replaced osmotically from water held in body cells and other body compartments, causing dehydration and increased thirst.

Signs and symptoms/ diabetic ketoacidosis

• Patients (usually with type 1 diabetes) may also initially present with diabetic ketoacidosis (DKA), an extreme state of metabolic dysregulation characterized by;

- The smell of acetone on the patient's breath; - A rapid, deep breathing known as Kussmaul breathing; - Polyuria; nausea; vomiting and abdominal pain (mimicking

acute abdomen);

- Any of many altered states of consciousness or arousal (such as hostility and mania or, equally, confusion and lethargy).

• In severe DKA, coma may follow, progressing to death.

• Diabetic ketoacidosis is a medical emergency and requires immediate hospitalization.

DIAGNOSTIC CRITERIA FOR DIABETES MELLITUS

Type I (juvenile) diabetes mellitus

• Classical symptoms + random blood glucose >200 mg/dL or

• Fasting blood glucose >126 mg/dL on more

than two occasions or

• Sustained elevation blood glucose >140 mg/dL on oral glucose tolerance test (OGTT) on more than two occasions (If fasting blood glucose >140 mg/dL on two occasions OGTT is not needed).

Type II diabetes mellitus

• Classical symptoms + random blood glucose >200 mg/dL or

• Fasting blood glucose >126 mg/dL on two occasions or

• Two hours blood glucose >200 mg/dL on oral glucose tolerance test (OGTT) on more than two occasions

• Normal Fasting blood glucose <110 mg/dL

• Impaired fasting glucose: 110-126 mg/dL

• Impaired glucose tolerance Two hours blood glucose >140 mg/dL

on oral glucose tolerance test (OGTT) on more than two occasions

Gestational diabetes

Two or more of following abnormalities during oral glucose tolerance test (100g)

• Fasting blood glucose: >105 mg/dL

• 1-hour blood glucose: >190 mg/dL

• 2-hour blood glucose: >165 mg/dL

• 3-hour blood glucose: >145 mg/dL

1999 WHO Diabetes criteria

Condition 2 hour glucose Fasting glucose mmol/l(mg/dl)

Normal

Impaired fasting glycaemia

Impaired glucose tolerance

Diabetes mellitus

<140 mg/dL

<140 mg/dL

≥140 mg/dL

≥200 mg/dL

<110 mg/dL)

110-126mg/dl

<126 mg/dL

≥126 mg/dL

Loading dose of glucose

• 1.75 g/kg for children

• 75 g for adults

• 100 g for childbearing women

HUMAN INSULINS BY RELATIVE COMPARATIVE ACTION

Onset (hour)

Peak (hour)

Maximal duration

(hour)

Very short acting Lispro(Novorapid®,Humalog®)Short acting Kristalize (Actrapid®)Medium actingNPH (Insulotard®)LenteLong acting UltralenteGlargine (Lantus ®)

<0.25

0.5-1.0

2-43-4

3-54

0.5-1.5

2-3

6-106-12

10-16—

3-4

3-6

10-1612-18

18-2024

* Most insulin preparations are stable at room temperature for months

Daily insulin therapy• Insulin dose: 0.1-2.0 U/kg/day

• Conventional therapy: - 2/3 Before breakfast + 1/3 before dinner (generally 2/3 NPH+1/3 regular insulin mixture)

• Intensive therapy - %20-30 before breakfast (regular or lispro insulin) - %20-30 before lunch (regular or lispro insulin) - %20-30 before dinner (regular or lispro insulin) - %20-30 at bedtime (glargine, NPH insulin or

mixture)

Nutritional therapy• The caloric intake should consist of approximately 55%

carbohydrates, 30% fat, 15% protein

• The caloric intake may be divided as follows; - 20% for breakfast - 10% for midmorning - 20% for lunch - 10% for midafternoon - 30% for dinner - 10% for evening snack

• Rapidly digested and absorbed (refined) sugars (sucrose, beverages etc) should be avoided.

• Aspartame can be used as sweetener (!?).

Exersize • No form of exercise including competitive sports

should not be forbidden to the diabetic child.

• Exercise improves glucoregulation by increasing insulin receptors.

• A major complication of exercise is the presence of a hypoglycemic reaction during or after the exercise. (increased absorption rate of insulin from the injection side)

• Therefore refined sugar in the form of fruit juice or carbonated beverages or candy should be available.

Causes of hypoglycemia in type I diabetes mellitus

• Inappropriate insulin regimens• Day-to-day variability of insulin absorption

from subcutaneous tissue (up to 50-10 %).

• Renal failure: increases half life of insulin

• Delayed and/or decreased intake of foods

• Gradual impairment of counterregulatory hormones (loss of glucagon, cortisol and adrenalin response)

Causes of hyperglycemia in type I diabetes mellitus

• Inappropriate insulin regimens

• Early and/or increased intake of foods

• Dawn phenomenon: Morning hyperglycemia due to insufficient intake of insulin or increased intake of food

• Smogy phenomenon: Morning rebound hyperglycemia due to increased intake of insulin

Diabetic ketoacidosis

Causes of diabetic ketoacidosis

• Infection: diarrhea, vomiting, and/or high fever (40%),

• Missed or inadequate insulin (25%), and

• Newly diagnosed or previously unknown diabetes (15%).

• Other causes: trauma, stress, surgery (10-15%).

• No identifiable cause (5-10%).

Management of diabetic ketoacidosis (0-12 hours)

Fluid volume

Fluid type

Dextrose

Potassium

Bicarbonate

Insulin (regular)

Deficit (1/4) + maintenance (1/4) : replace evenly *

% 0.9 NaCl**

Add 5% dextrose once blood glucose <300mg/dL

30-40 mEq/L (after urination)

if pH > 7.0 noneif pH ≤ 7.0 and cardiac functions are disturbed: 1-3 mEq/kg/dose0.1 U/kg/hour IM or IV once blood glucose <300 mg/dL: 0.05 U/kg/hour IM or IV

Management of diabetic ketoacidosis (12-24 hours)

Fluid volume

Fluid type

Potassium

Bicarbonate

Insulin (regular)

Deficit (3/4) + maintenance (3/4): replace evenly.

%0.45 NaCl ( in 5% Dextrose)

30-40 mEq/L None

0.25U/kg/6 hours (SC)

Management of diabetic ketoacidosis

• In case of hypovolemic shock, give 10 mL/kg 0.9% NaCl within first 0.5-1 hour

• If corrected serum sodium level is >160 mEq/L, give 0.45 % NaCl

• Corrected serum sodium = actual serum sodium + 2.75 mEq/L for every 100 mg glucose over 100 mg

• IV fluid therapy can be stopped after 12th hour, if patient’s condition is well.

Chronic complications

Late (chronic) complications of diabetes mellitus

• Late complications occur after several years of poorly controlled hyperglycemia.

• Most vascular complications can be delayed, prevented or even reversed by tight glycemic control, reflected by near normal glycosylated hemoglobin (HbA1C) levels.

Diabetic Retinopathy

• The initial retinal changes seen in ophthalmoscopic examination (background retinopathy) do not significantly alter vision.

• But it can progress to macular edema or proliferative retinopathy with retinal detachment or hemorrhage which can cause blindness.

• Cataracts: Sorbitol accumulation

Diabetic Retinopathy

Nephropathy

• GFR may be increased initially.

• Then microalbuminuria (<300 mg/dL) develops.

• Macroalbuminuria (>300 mg/dL) signals a progressive decrease in GFR and with a high likelihood development of end-stage renal disease.

• ACE inhibitors (captopril) can prevent proteinuria in both hypertensive and non hypertensive diabetics.

Neuropathy

• Diabetic neuropathy commonly occurs as a distal symmetric predominantly sensory polyneuropathy (less often motor polyneuropathy).

• Diabetic polyneuropathy may cause numbness, tingling, paresthesias in the extremities less often deep seated pain hyperesthesias.

• Autonomic neuropathy can cause postural hypotension, disordered sweating, impotence, delayed gastric emptying , esophageal dysfunction, constipation or diarrhea.

Other complications• Foot ulcers and joint problems are important causes

of morbidity in diabetes mellitus.

• The risk of infections from fungi and bacteria is increased because of because of decreased cellular immunity caused by acute hyperglycemia, circulatory deficits caused by hyperglycemia and sensory polyneuropathy.

• Peripheral skin infections, recurrent urinary infections, otitis externa (pseudomonas) oral and vaginal thrush are most common.

• CVS complications: hypertension, atherosclerosis, strokes, coronary heart disease