Diseases Related to Carbohydrate Metabolism
In the metabolism of carbohydrates (such as galactose, fructose, and glucose) different enzymatic pathways are involved. Disorders affecting these pathways produce mild, severe, or even life-threatening symptoms. The resulting clinical features are hypoglycaemia, liver enlargement, and muscle pain. With the help of dietary interventions, most of these disorders can be controlled and even treated.
Diabetes Mellitus (DM)
According to the WHO, diabetes mellitus is defined as "a metabolic disorder of multiple etiology characterised by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism, resulting from defects in insulin secretion, insulin action, or both".
On the basis of clinical stages and the etiological types, DM can be classified as follows:
1) According to the Clinical Stages: Based on the clinical stages, DM can be classified as:
i) Insulin Requiring for Survival: This corresponds to the former clinical class of insulin-dependent DM.
ii) Insulin Requiring for Control: This class is characterised by the requirement of insulin for metabolic control rather than for survival.
iii) Non-Insulin Requiring: This includes those individuals in whom diabetes can be controlled satisfactorily using non-pharmacological methods or drugs, without the use of insulin. The latter two types correspond to the former class of non-insulin dependent DM.
2) According to Etiology:
Based on the etiology, DM can be classified as:
i) Type 1 DM:
This type is characterised by destruction of B-cells (insulin- producing cells) and thus insulin is required for survival. This type was previously referred to as insulin-dependent diabetes (though the term is obsolete now) and can be further classified as:
a) Type 1 Immune-Mediated DM:
In this type, autoimmune destruction of B-cells occurs. Other terms for this type of DM are insulin dependent diabetes or juvenile-onset diabetes (since it may begin during childhood).
b) Type 1 Idiopathic DM:
This form is not related to autoimmunit and the B-cell destruction is due to unknown causes.
ii) Type 2 DM:
This type is characterised by disorders of insulin action and insulin secretion. Patients have relative insulin deficiency (in contrast to absolute insulin deficiency in type I diabetes). If is also known as adult onset diabetes and was earlier referred to as non-insulin dependent diabetes (though the term is obsolete now).
iii) Other Types:
This includes those in which the underlying defect or disease process can be identified in a relatively specific manner, e.g. fibrocalculous pancreatopathy.
Causes Etiological factors for DM include:
1) Genetic Factors:
DM may be caused by abnormalities in genes present on different chromosomes and include:
i) Genetic defects of B-cell function,
ii) Mutation in mitochondrial DNA, and
iii) Genetic defects in insulin action.
2) Environmental Factors: These include:
i) Obesity associated with modern living standards,
ii) Steady urban migration, and
iii) Lifestyle changes (including consumption of alcohol).
3) Factors within the Individual: These include:
i) Production of auto-antibodies that destruct B-cells,
ii) Deficiency in insulin synthesis and secretion,
iii) Insulin resistance (because the cells do not respond to the insulin produced).
iv) Presence of diseases that may extensively damage the pancreas causing pancrcatitis, pancreatectomy, thus, resulting in DM,
v) Excessive secretion of hormones (e.g., growth hormone, cortisol, glucagon, epinephrine) that antagonise insulin action,
vi) Impairment of insulin secretion resulting from the excessive consumption of drugs,
vii) Infections caused by viruses that cause B-cell destruction. trauma, infection, pancreatic carcinoma, and Symptoms The signs and symptoras of diabetes vary widely depending upon the increase in blood sugar level. The characteristic clinical manifestations of DM include:
1) Onset of Disease:
Type1 DM usually begins during childhood and progresses rapidly. This is termed juvenile diabetes. If it begins in adults, it progresses relatively slowly and is termed as Late Autoimmune Diabetes in Adults (LADA).
2) Appearance of symptoms
In patients with type 1 DM, symptoms appear in the initial stages and are more severe than type 2 DM. Patients with type 2 DM may experience the symptoms at a later stage and may not show any symptoms during the initial stages.
3) Signs and Symptoms:
These include:
i) Ketoacidosis and presence of ketones in urine (ketones are a by-product of the breakdown of muscle and fat occurring when there is not enough available insulin),
ii) Presence of glucose in urine,
iii) Polydypsia (increased thirst),
iv) Polyuria (increase in the frequency of urination),
v) Polyphagia (extreme hunger).
vi) Unexplained loss of weight,
vii) Fatigue and headache,
viii) Irritability,
ix) Blurred vision, and
x) Frequent infections, with the retarded healing of cuts and wounds.
Diagnosis
Diagnosis of DM can be made, based on the following tests:
1) Clinical Examination:
The classical symptoms of diabetes, including polydipsia, polyphagia, and polyuria help to diagnose diabetes.
2) Laboratory Tests: These tests include:
i) Urine Tests: Urine is tested to detect the presence of glucose (glycosuria) and ketones (ketonuria).
ii) single blood sugar estimation: Fasting plasma glucose value (126 mg/dl) indicates the presence of diabetes.
iii) Oral Glucose Tolerance Test (Oral GTT): The values considered abnormal, detecting diabetes has been described in table 2.4: Table 2.4: Criteria for Diagnosis of Diabetes by Oral GTT as per WHO
Diagnosis Normal fasting value
Patient Status Plasma Glucose Value Diagnosis
1) Fasting value Below 110mg/dl (<6.Immol/L) Normal fasting value
2) Fasting value Impaired Glucose (IFG) " 110-126mg/dl (6.1- 7.0mmol/L) Fasting
3) Fasting value 126mg/dl (7.0mmol/L) or more Diabetes mellitus
4) Two-hour after 75gm 140-200mg/di oral glucose load
5) Two-hour after 75gn 2000mg/dl (11.Immol/L) oral glucose load
6) Random value (7.8- Impaired Glucose 11.Immol/L) Tolerance (IGT) " or Diabetes mellitus more 200mg/dl (11, Immol/L) more in a symptomatic patient or Diabetes mellitus
Note: Plasma glucose values are 15% higher than whole blood glucose value. " Person with IFG and IGT is at increased risk for development of Type 2 DM later.
3) Other Tests: These include:
i) Glycosylated Haemoglobin (HBAIC): This test detects the three-month average plasma glucose concentration. An increase in the fraction of glycated haemoglobin indicates an increase in the average amount of plasma glucose over the past 3 months.
ii) Extended GTT:
Oral GTT is extended for 3-4 hours for detection of symptoms of hyperglycaemia.
iii) Intravenous GTT:
It is used in place of oral GTT in patients with intestinal malabsorption.
iv) Cortisone-Primed GTT:
It is a useful aid for individuals who have a probability of diabetes.
v) Insulin Assay:
It measures insulin level in plasma by radioimmunoassay and ELISA techniques.
vi) C-Peptide Assay: C-peptide is à marker of insulin production.
Treatment
1) Non-Pharmacological Approach:
This includes dietary treatment, along with proper physical exercise:
i) Diet: Dietary treatment should be aimed at:
a) Controlling weight,
b) Restriction of cholesterol consumption, c) Avoiding excessive salt intake,
d) Use of artificial sweeteners in moderation and restricting nutritive sweeteners (sorbitol and fructose), and
e) Planning of meals such that they are evenly distributed throughout the day, maintaining the consistency of food timing and energy intake, especially in patients taking insulin.
ii) Physical Activity: Regular physical activity and exercise are recommended as it promotes weight reduction and improves insulin sensitivity, thus, lowering blood glucose levels.
2) Pharmacological Approach: This includes:
i) Insulin: Drugs used for insulin therapy can be categorised as:
a) Drugs Improving the Availability of Insulin:
The drugs included in this group are:
• Exogenous Insulin:
Insulin is administered exogenously in the form of insulin-zinc suspension (Lente insulin). isophane, protamine zinc insulin, and insulin analogues, delivered through insulin syringes, pen devices, inhalations or pumps (that can either be inhaled or implanted).
• Sulphonylureas: These include tolbutamide, chlorpropamide, glimepiride, etc.
• Meglitinide/Phenylalanine repaglinide and nateglinide. Analogues: These include repaglinide and nateglinide
b) Drugs Overcoming Insulin Resistance: The drugs included in this group are:
• Biguanides: These include administration of metformin.
• Thiazolidinediones: These include rosiglitazone and pioglitazone.
• α-Glucosidase Inhibitors: These include acarbose and miglitol.
ii) Hypoglycaemic Therapy: Hypoglycaemic drugs are administered orally and include:
a) Sulfonylureas: These include tolbutamide, chlorpropamide, glimepiride, etc.
b) Biguanides: These include administration of metformin,
c) Meglitinide/Phenylalanine Analogues: These include repaglinide and nateglinide,
d) Thiazolidinediones: These include rosiglitazone and pioglitazone.
e) α-Glucosidase Inhibitors: These include acarbose and miglitol.
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