Diabetes mellitus and Carbohydrate disorder

Diabetes mellitus and Carbohydrate disorder

DIABETES MELLITUS DM 

– complex chronic metabolic disorder leading to multiorgan complications Main pathophysiological questions related to DM

Why and how the DM develops?

Why and how develop the complications of DM?

What are the mechanisms involved in manifestation of diabetic symptoms and signs  ?

Regulation of the blood glucose level depends on liver:

                1. extracting glucose from blood

                2. synthesizing glycogen

3. performing glycogenolysis

4.performing gluconeogenesis

•       Plasma glucose is tightly regulated by hormones:

 ↓Plasma glucose

  Insulin

 ↑Plasma glucose

 Glucagon

 Epinephrine

     CortisolGrowth hormone

               

Definition of DM

DM is a chronic complex syndrome induced by absolute or relative deficit of insuline which is characterized by metabolic disorders of carbohydrates, lipids and proteins.

The metabolic disturbances are accompanied by loss of carbohydrate tolerance, fasting hyperglycaemia, ketoacidosis, decreased lipogenesis, increased lipolysis, increased proteolysis and some other metabolic  disorders

                                 Classification of DM 

Base for the classification are etiopathogenetic mechanisms

involved in onset and development of DM

Types of DM

I. Diabetes mellitus - type 1: due to destruction of beta cells of pancreatic  islets

                Consequence: absolute deficit of insulin

                A. subtype: induced by autoimmunity processes

                B. subtype: idiopathic mechanism

 II.Diabetes mellitus -type 2: at the beginning-predomin of insulin resistance  and relative deficit of insulin(normo-hyper -insulinemia), later on - combination of impaired insulin secretion and simultaneous insulin resistance (hypoinsulinemia, insulin resistance)

III. Other specific types of DM

               

    · DM due to genetic defects of beta cells of pancreas islets

      and due to genetic defect of insulin function

               

     · DM due to diseases influencing exocrine functions of pancreas –

        - secondary is damaged endocrine function, too.

               

     · DM due to endocrinopathies, drugs, chemicals, infections,

        metabolic and genetic disturbances

IV. Gestational DM -

glucose intolerance which onsets for the first time  during pregnancy

WHO Diagnostic Criteria DM

􀂄 Fasting blood glucose > 126 mg/dl

􀂄 Random blood glucose > 200 mg/dl

􀂄 One value is diagnostic in symptomatic

individuals

􀂄 Two values are needed in    asymptomatic people

• Population Doubling Time in
  Some Mediterranean Countries
• (HYPOGLYCEMIA (INSULIN REACTIONS
  
   The blood glucose falls to less than
    50 -60 mg/dL.
   It can be caused by too much insulin or  oral hypoglycemic agents, too little    food, or excessive physical activity.
  
   It often occurs before meals,      
   especially if meals are delayed or  
   snacks are omitted.
• 
  
   The blood glucose falls to less than
    50 -60 mg/dL.
   It can be caused by too much insulin or  oral hypoglycemic agents, too little    food, or excessive physical activity.
  
   It often occurs before meals,      
   especially if meals are delayed or  
   snacks are omitted.
• 
  Clinical Manifestations
  
   The clinical manifestations of hypoglycemia  
   may be grouped into two categories:
   1-adrenergic symptoms
   2-central nervous system (CNS) symptoms.
   In mild hypoglycemia, as the blood glucose level falls, the sympathetic nervous system is stimulated, resulting in a rise of epinephrine or nor epinephrine.
   This causes symptoms such as sweating, tremor, tachycardia, palpitation, nervousness, and hunger
• 
  Clinical Manifestations
   In moderate hypoglycemia, the fall in blood glucose level
  deprives the brain cells of needed fuel for functioning.
   Signs of impaired function of the CNS may include inability to
  concentrate, headache, lightheadedness, confusion, memory
  lapses, numbness of the lips and tongue, slurred speech, impaired
  coordination, emotional changes, irrational or combative
  behavior, double vision, and drowsiness.
   In severe hypoglycemia, CNS function is so impaired. Symptoms
  may include disoriented behavior, seizures, difficulty arousing
  from sleep, or loss of consciousness
• Diabetic Ketoacidosis (DKA)
• Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. DKA occurs mostly in type 1 diabetes. It causes nausea, vomiting, and abdominal pain and can progress to cerebral edema, coma, and death. DKA is diagnosed by detection of hyperketonemia and anion gap metabolic acidosis in the presence of hyperglycemia. Treatment involves volume expansion, insulin replacement, and prevention of hypokalemia.
• Nonketotic Hyperosmolar Syndrome (NKHS)
• Nonketotic hyperosmolar syndrome (NKHS) is a metabolic complication of diabetes mellitus (DM) characterized by hyperglycemia, extreme dehydration, hyperosmolar plasma, and altered consciousness. It most often occurs in type 2 DM, often in the setting of physiologic stress. NKHS is diagnosed by severe hyperglycemia and serum hyperosmolarity and absence of significant ketosis. Treatment is IV saline solution and insulin. Complications include coma, seizures, and death
• Nutrition and diabetes
  􀂄 Nutritional management of DM should
  start with nutritional assessment.
  􀂄 Food for diabetic people should be:
  􀂄 High in starchy carbohydrates
  􀂄 High in NSP (fibre)
  􀂄 Low in salt and sugar (not sugar free)
  􀂄 Low in fat (mainly saturated fat)
• Nutrition and diabetes
  􀂄 Having diabetes doesn't mean that you
  have to start eating special foods.
  􀂄 Rather than a restrictive diet, a diabetic
  diet is a healthy-eating plan that is
  rich in nutrients and doesn’t differ
  from diet considered healthy for
  everyone.
  􀂄 Establish a routine for eating meals.
  Consistency is a key.
• Artificial sweetening
  agents
  􀂄 Sugar substitutes that contain little or
  no calories are called artificial
  sweeteners, non-nutritive sweeteners or
  non-caloric sweeteners.
  􀂄 Well-known artificial sweeteners include
  saccharin, sucralose and aspartame.
  􀂄 Nutritive sweeteners include sucrose
  and fructose.
• Artificial sweetening
  agents(cont)
  􀂄 Moderate use of nutritive (sucrose and
  fructose) and non-nutritive sweeteners
  (saccharin, aspartame and cyclamate)
  can be part of a well-balanced diet for
  diabetics.
  􀂄 However, diabetic patients, as other
  people, should accustom themselves to
  the low-sweetness taste.
• 
  

The Carbohydrates

• * Simple Carbohydrates
• * Complex Carbohydrates
• * Starches
• * Fiber

• Carbohydrate metabolism disorder
• First we will talk about the normal Carbohydrate metabolism in the body
• Carbohydrate metabolism:
• Carbohydrate metabolism begins with digestion in the small intestine where monosaccharides are absorbed into the blood stream. Blood sugar concentrations are controlled by three hormones: insulin, glucagon, and epinephrine. If the concentration of glucose in the blood is too high, insulin is secreted by the pancreas. Insulin stimulates the transfer of glucose into the cells, especially in the liver and muscles, although other organs are also able to metabolize glucose
• In the liver and muscles, most of the glucose is changed into glycogen by the process of glycogenesis (anabolism). Glycogen is stored in the liver and muscles until needed at some later time when glucose levels are low. If blood glucose levels are low, then eqinephrine and glucogon hormones are secreted to stimulate the conversion of glycogen to glucose. This process is called glycogenolysis (catabolism).
• If glucose is needed immediately upon entering the cells to supply energy, it begins the metabolic process called glycoysis (catabolism). The end products of glycolysis are pyruvic acid and ATP
• During strenuous muscular activity, pyruvic acid is converted into lactic acid rather thatn acetyl CoA. Durlng the resting period, the lactic acid is converted back to pyruvic acid. The pyruvic acid in turn is converted back to glucose by the process called gluconeogenesis (anabolism). If the glucose is not needed at that moment, it is converted into glycogen by glycogenesis
• Carbohydrate Metabolism Disorders
• The metabolism of the carbohydrates galactose, fructose, and glucose is intricately linked through interactions between different enzymatic pathways, and disorders that affect these pathways may have symptoms ranging from mild to severe or even life-threatening. Clinical features include various combinations of hypoglycemia (low blood sugar), liver enlargement, and muscle pain.
• Glycogen Storage Diseases 1-
• Glycogen storage diseases are caused by deficiencies of enzymes involved in glycogen synthesis or breakdown; the deficiencies may occur in the liver or muscles and cause hypoglycemia or deposition of abnormal amounts or types of glycogen (or its intermediate metabolites) in tissues
• Defects in glycolysis (rare) may cause syndromes similar to GSDs.
• 2-Galactosemia
• Galactosemia is caused by inherited deficiencies in enzymes that convert galactose to glucose. Symptoms and signs include hepatic and renal dysfunction, cognitive deficits, cataracts, and premature ovarian failure. Diagnosis is by enzyme analysis of RBCs. Treatment is dietary elimination of galactose.
• Galactose is found in dairy products, fruits, and vegetables .
• 3-Disorders of Fructose Metabolism
• Deficiency of enzymes that metabolize fructose may be asymptomatic or cause hypoglycemia, nausea and vomiting, abdominal pain, sweating, tremors, confusion, lethargy, seizures, and coma.
• Fructose is a monosaccharide that is present in high concentrations in fruit and honey and is a constituent of sucrose and sorbitol.
• 4-Disorders of Pyruvate Metabolism
• Inability to metabolize pyruvate causes lactic acidosis and a variety of CNS abnormalities.
• Pyruvate is an important substrate in carbohydrate metabolism
• Pyruvate dehydrogenase deficiency: Pyruvate dehydrogenase is a multi-enzyme complex responsible for the generation of acetyl CoA from pyruvate for the Krebs cycle. Deficiency results in elevation of pyruvate and thus elevation of lactic acid levels
• OTHER DISORDERS OF CARBOHYDRATE METABOLISM