Carbohydrate Metabolism Notes

Carbohydrate Metabolism

Carbohydrates are polyhydroxy aldehydes or ketones, serving as a primary energy source in the body. They consist of carbon, hydrogen, and oxygen, with a hydrogen-to-oxygen ratio of 2:1, similar to water.

Classification of Carbohydrates

1. Based on Complexity:

• Monosaccharides: Simple sugar units (e.g., glucose, fructose). General formula is $C<em>n(H</em>2O)_n$.
• Oligosaccharides: 2-10 monosaccharide molecules linked by glycosidic bonds (e.g., lactose, maltose, raffinose). General formula is $C(H<em>2O)</em>{n-2}$.
  • Disaccharides: Composed of two monosaccharides (e.g., sucrose = glucose + fructose).
  • Trisaccharides: Composed of three monosaccharides (e.g., raffinose = glucose + fructose + galactose).
  • Tetrasaccharides: Composed of four monosaccharides (e.g., stachyose = glucose + fructose + 2 galactose).
  • Pentasaccharides: Composed of five monosaccharides (e.g., verbascose = glucose + fructose + 3 galactose).
• Polysaccharides: Polymers of monosaccharides with high molecular weight, yielding more than 10 monosaccharide units upon hydrolysis (e.g., starch, cellulose). General formula is $(C<em>6H</em>{10}O<em>5)</em>n$.
  • Homopolysaccharides: Composed of the same type of monosaccharide (e.g., starch, cellulose, dextran, glycogen).
  • Heteropolysaccharides: Composed of different monosaccharides (e.g., heparin, hyaluronic acid).

2. Based on Reactivity:

• Reducing Sugars: Act as reducing agents, giving positive results in Tollens', Benedict's, and Fehling's tests (e.g., glucose, fructose, maltose, lactose).
• Non-reducing Sugars: Do not act as reducing agents, giving negative results in the aforementioned tests (e.g., sucrose).

3. Based on Functional Group:

• Aldoses: Contain an aldehyde functional group (e.g., glucose).
• Ketoses: Contain a ketone functional group (e.g., fructose).

Biological Roles of Carbohydrates

• Main source of energy (e.g., glucose).
• Energy storage (e.g., glycogen in animals, starch in plants).
• Structural components (e.g., exoskeleton of organisms).
• Involved in detoxification processes.
• Pentose sugars are crucial components of nucleic acids.
• Lactose is a disaccharide found in milk.
• Agar-agar is used as a culture medium in labs.
• Precursors for organic compounds like fats and amino acids.

Glycolysis

Glycolysis is the sequence of reactions that convert glucose (or glycogen) to pyruvate (aerobically) or lactate (anaerobically), producing ATP. It's also known as the Embden-Meyerhof pathway (E.M. pathway).

Phases of Glycolysis:

• A. Energy Investment Phase: Requires ATP.
  1. Phosphorylation of Glucose: Glucose is phosphorylated to glucose 6-phosphate via hexokinase or glucokinase. This is an irreversible reaction that is ATP and $Mg^{2+}$ dependent.
     $Glucose + ATP \rightarrow Glucose-6-phosphate + ADP$
  2. Isomerization: Glucose 6-phosphate isomerizes to fructose 6-phosphate using phosphohexose isomerase and $Mg^{2+}$.
     $Glucose-6-phosphate \leftrightarrow Fructose-6-phosphate$
  3. Phosphorylation of Fructose 6-phosphate: Fructose 6-phosphate is phosphorylated to fructose 1,6-bisphosphate by phosphofructokinase. This step is irreversible.
     $Fructose-6-phosphate + ATP \rightarrow Fructose-1,6-bisphosphate + ADP$
• B. Splitting Phase:
  4. Cleavage of Fructose 1,6-bisphosphate: Fructose 1,6-bisphosphate splits into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate via aldolase.
     $Fructose-1,6-bisphosphate \leftrightarrow Glyceraldehyde-3-phosphate + Dihydroxyacetone-phosphate$
  5. Interconversion of Triose Phosphates: Phosphotriose isomerase catalyzes the reversible conversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, yielding two molecules of glyceraldehyde 3-phosphate per glucose molecule.
     $Dihydroxyacetone-phosphate \leftrightarrow Glyceraldehyde-3-phosphate$
• C. Energy Generation Phase: Produces ATP and NADH.
  6. Oxidation of Glyceraldehyde 3-phosphate: Glyceraldehyde 3-phosphate dehydrogenase converts glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate, producing NADH + H+.
     $Glyceraldehyde-3-phosphate + NAD^+ + P_i \leftrightarrow 1,3-Bisphosphoglycerate + NADH + H^+$
  7. Substrate-Level Phosphorylation: Phosphoglycerate kinase acts on 1,3-bisphosphoglycerate, synthesizing ATP and forming 3-phosphoglycerate.
     $1,3-Bisphosphoglycerate + ADP \leftrightarrow 3-Phosphoglycerate + ATP$
  8. Isomerization of 3-Phosphoglycerate: 3-Phosphoglycerate converts to 2-phosphoglycerate by phosphoglycerate mutase.
     $3-Phosphoglycerate \leftrightarrow 2-Phosphoglycerate$
  9. Dehydration: Enolase generates phosphoenolpyruvate from 2-phosphoglycerate, requiring $Mg^{2+}$ or $Mn^{2+}$ .
     $2-Phosphoglycerate \leftrightarrow Phosphoenolpyruvate + H_2O$
  10. Substrate-Level Phosphorylation: Pyruvate kinase transfers a high-energy phosphate from phosphoenolpyruvate to ADP, forming ATP. This reaction is irreversible.
      $Phosphoenolpyruvate + ADP \rightarrow Pyruvate + ATP$

Conversion of Pyruvate to Lactate (Anaerobic Conditions):

Under anaerobic conditions (lack of $O_2$), pyruvate is reduced by NADH to lactate via lactate dehydrogenase. The NADH used here comes from the glyceraldehyde 3-phosphate dehydrogenase reaction. Lactate formation regenerates $NAD^+$, allowing glycolysis to continue in the absence of oxygen.

$Pyruvate + NADH + H^+ \leftrightarrow Lactate + NAD^+$

Energetics of Glycolysis:

Aerobic Condition:

• ATP Investment:
  • Glucose to glucose 6-phosphate (Hexokinase): -1 ATP
  • Fructose 6-phosphate to fructose 1,6-bisphosphate (Phosphofructokinase): -1 ATP
• ATP Generation:
  • Glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate (Glyceraldehyde 3-phosphate dehydrogenase): 2 NADH (2 x 3 = +6 ATP)
  • 1,3-bisphosphoglycerate to 3-phosphoglycerate (Phosphoglycerate kinase): 2 ATP
  • Phosphoenolpyruvate to pyruvate (Pyruvate kinase): 2 ATP
• Total ATP formed: 6 + 2 + 2 = 10 ATP
• Total ATP utilized: 1 + 1 = 2 ATP
• Net gain of ATP: 10 - 2 = 8 ATP

Anaerobic Condition:

• ATP Investment:
  • Glucose to glucose 6-phosphate (Hexokinase): -1 ATP
  • Fructose 6-phosphate to fructose 1,6-bisphosphate (Phosphofructokinase): -1 ATP
• ATP Generation:
  • 1,3-bisphosphoglycerate to 3-phosphoglycerate (Phosphoglycerate kinase): 2 ATP
  • Phosphoenolpyruvate to pyruvate (Pyruvate kinase): 2 ATP
• Net gain of ATP: 4 - 2 = 2 ATP

Significance of Glycolysis:

• Occurs in all cells of the body, within the cytosol.
• Can occur aerobically or anaerobically (producing lactate in the latter).
• Major ATP synthesis pathway in tissues lacking mitochondria (e.g., erythrocytes, cornea, lens).
• Brain, retina, skin, renal medulla, and GIT derive significant energy from glycolysis.
• Pyruvate is used in amino acid biosynthesis.
• Essential for skeletal muscle during exercise with limited oxygen supply.
• Generates ATP for energy.

Citric Acid Cycle (Krebs Cycle/TCA Cycle)

The citric acid cycle is the primary metabolic pathway for energy supply, involving the oxidation of acetyl CoA to $CO<em>2$ and $H</em>2O$ within the mitochondria.

Pathway:

1. Formation of Citrate: Oxaloacetate condenses with acetyl CoA via citrate synthase to form citrate.
   $Oxaloacetate + Acetyl CoA + H_2O \rightarrow Citrate + CoA-SH$
2. Isomerization of Citrate to Isocitrate: Citrate isomerizes to isocitrate through a two-step reaction (dehydration followed by hydration) using aconitase, with cis-aconitate as an intermediate.
   $Citrate \leftrightarrow cis-Aconitate + H_2O \leftrightarrow Isocitrate$
3. Formation of α-Ketoglutarate: Isocitrate dehydrogenase dehydrogenates isocitrate to oxalosuccinate, which then decarboxylates to form α-ketoglutarate. NADH and $CO<em>2$ are produced. $Isocitrate + NAD^+ \rightarrow Oxalosuccinate + NADH + H^+ \rightarrow α-Ketoglutarate + CO</em>2$
4. Conversion of α-Ketoglutarate to Succinyl CoA: α-Ketoglutarate dehydrogenase complex catalyzes oxidative decarboxylation of α-ketoglutarate to succinyl CoA.
   $α-Ketoglutarate + CoA-SH + NAD^+ \rightarrow Succinyl CoA + CO_2 + NADH + H^+$
5. Formation of Succinate: Succinyl CoA converts to succinate via succinate thiokinase, coupled with phosphorylation of GDP to GTP, which is then converted to ATP.
   $Succinyl CoA + GDP + P_i \leftrightarrow Succinate + CoA-SH + GTP \leftrightarrow Succinate + CoA-SH + ATP$
6. Conversion of Succinate to Fumarate: Succinate is oxidized to fumarate by succinate dehydrogenase, producing FADH2.
   $Succinate + FAD \rightarrow Fumarate + FADH_2$
7. Formation of Malate: Fumarase catalyzes the conversion of fumarate to malate with water addition.
   $Fumarate + H_2O \leftrightarrow Malate$
8. Conversion of Malate to Oxaloacetate: Malate is oxidized to oxaloacetate by malate dehydrogenase, generating NADH. Oxaloacetate then combines with another acetyl CoA molecule to continue the cycle.
   $Malate + NAD^+ \rightarrow Oxaloacetate + NADH + H^+$

Energetics of Citric Acid Cycle (per Acetyl CoA):

• Isocitrate to oxalosuccinate (Isocitrate dehydrogenase): 1 NADH (1 x 3 = 3 ATP)
• α-ketoglutarate to succinyl CoA (α-Ketoglutarate dehydrogenase): 1 NADH (1 x 3 = 3 ATP)
• Succinyl CoA to succinate (Succinate thiokinase): 1 ATP
• Succinate to fumarate (Succinate dehydrogenase): 1 FADH2 (1 x 2 = 2 ATP)
• Malate to oxaloacetate (Malate dehydrogenase): 1 NADH (1 x 3 = 3 ATP)
• Total ATP produced per acetyl CoA: 12 ATP
• Net gain per glucose molecule (2 acetyl CoA): 24 ATP

Significance of Citric Acid Cycle:

• Final common oxidative pathway for all major food components.
• Source of reduced coenzymes for the respiratory chain.
• Amphibolic role: Both catabolic and anabolic.
  • Succinyl CoA: Porphyrin and heme synthesis.
  • Oxaloacetate and α-ketoglutarate: Precursors for aspartate and glutamate (amino acids, purines, and pyrimidines).
• Excess carbohydrates are converted to neutral fats.
• Anaplerotic role: Replenishes cycle intermediates.
  • Pyruvate carboxylase: Pyruvate to oxaloacetate.
  • Malate dehydrogenase: Pyruvate to malate.
• Cycle components directly or indirectly control key enzymes in other pathways.

Summary of TCA Cycle:

$Acetyl CoA + 3 NAD^+ + FAD + GDP + P<em>i + 2 H</em>2O \rightarrow 2 CO<em>2 + 3 NADH + 3 H^+ + FADH</em>2 + GTP + CoA$

HMP Shunt/Pentose Phosphate Pathway/Hexose Monophosphate Shunt

This is an alternative pathway to glycolysis and the TCA cycle for glucose oxidation. Enzymes are located in the cytosol. It's highly active in tissues like the liver, adipose tissue, adrenal gland, erythrocytes, testes, and lactating mammary gland.

Pathway:

• Oxidative Phase:

  • Glucose 6-phosphate dehydrogenase converts glucose 6-phosphate to 6-phosphogluconolactone.
  • Gluconolactone hydrolase hydrolyzes 6-phosphogluconolactone to 6-phosphogluconate.
  • Phosphogluconate dehydrogenase decarboxylates 6-phosphogluconate to ribulose 5-phosphate.

• Non-Oxidative Phase:

  • Ribulose 5-phosphate epimerase produces xylulose 5-phosphate from ribulose 5-phosphate.
  • Ribose 5-phosphate ketoisomerase converts ribulose 5-phosphate to ribose 5-phosphate.
  • Transketolase transfers a two-carbon moiety from xylulose 5-phosphate to ribose 5-phosphate, yielding glyceraldehyde 3-phosphate (3-carbon) and sedoheptulose 7-phosphate (7-carbon).
  • Transaldolase transfers a three-carbon fragment from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate, yielding fructose 6-phosphate (6-carbon) and erythrose 4-phosphate (4-carbon).
  • Transketolase acts on xylulose 5-phosphate, transferring a two-carbon fragment to erythrose 4-phosphate to generate fructose 6-phosphate and glyceraldehyde 3-phosphate.

  Significance
  1. A considerable proportion of glucose metabolism appears to take place through HMP
  2. It gives rise to the formation of pentoses
  3. This pathway helps in the interconversion of pentose and hexoses
  4. It is independent of the TCA cycle components
  5. One of the most important functions of HMP is to provide NADPH

Significance of HMP Shunt:

• Significant proportion of glucose metabolism occurs through this pathway.
• Generates pentoses.
• Interconverts pentoses and hexoses.
• Independent of TCA cycle components.
• Provides NADPH.

Importance of Pentoses:

Hexoses are converted into pentoses (e.g., ribose 5-phosphate), which are used for synthesizing nucleic acids (DNA, RNA) and nucleotides (ATP, FAD, CoA).

Importance of NADPH:

1. Required for the reductive biosynthesis of fatty acids and steroids. Highly active in lipogenic tissues (e.g., liver, adipose tissue).
2. High concentration of NADPH in eye lens preserves transparency.
3. In RBCs, it maintains reduced glutathione concentration, preserving membrane integrity and keeping iron in the reduced state (preventing methemoglobin accumulation).
4. Required for phagocytosis by WBCs.
5. Cytochrome P450 system in the liver detoxifies drugs via NADPH-dependent reactions.

Glucose 6-Phosphate Dehydrogenase Deficiency (G6PD):

G6PD deficiency is an inherited sex-linked trait, more severe in RBCs. Reduced G6PD activity impairs NADPH synthesis in erythrocytes, leading to methemoglobin and peroxide accumulation, causing hemolysis.

Clinical Manifestations:

• Most patients are asymptomatic.
• Some develop:
  • Hemolytic anemia
  • Hemolytic jaundice
  • Dark urine
  • Fatigue
  • Breathlessness
  • Tachycardia

G6PD Deficiency and Malaria:

G6PD deficiency is associated with malaria resistance because the malaria parasites are dependent on the HMP shunt and reduced glutathione for optimum growth in RBCs.

Diagnosis:

Detect reduced G6PD activity in RBCs.

Management:

• Avoid oxidative stress.
• Symptomatic treatment of hemolysis.
• Oxygen therapy.
• Blood transfusion to maintain RBC levels.

Glycogen Metabolism

Glycogen is the storage form of glucose in animals, analogous to starch in plants. It's stored in the liver (6-8%) and muscle (1-2%). Liver glycogen maintains blood glucose levels, while muscle glycogen serves as a fuel reserve during muscle contraction.

Glycogenolysis (Glycogen Degradation):

Glycogenolysis is the degradation of stored glycogen in the liver and muscle. Synthesis and degradation pathways are independent, using a unique set of cytosolic enzymes.

Pathway:

1. Action of Glycogen Phosphorylase: Glycogen phosphorylase cleaves α-1,4-glycosidic bonds, yielding glucose 1-phosphate. This continues until four glucose residues remain near a branching point (α-1,6-glycosidic link), forming a limit dextrin.
   $Glycogen<em>{(n \&plus\;1)} + P</em>i \rightarrow Glycogen_n + Glucose-1-phosphate$

2. Action of Debranching Enzyme: Debranching enzyme has two activities:

   • Amylo α-1,6-glucosidase: Breaks the α-1,6 bond at the branch point, releasing free glucose.
   • Remaining glycogen is again available for glycogen phosphorylase and debranching enzyme to repeat the reactions.

3. Formation of Glucose 6-Phosphate and Glucose: Glycogen phosphorylase and debranching enzyme produce glucose 1-phosphate and free glucose in an 8:1 ratio. Phosphoglucomutase converts glucose 1-phosphate to glucose 6-phosphate. Liver, kidney, and intestine contain glucose 6-phosphatase, which cleaves glucose 6-phosphate to glucose.
   $Glucose-1-phosphate \leftrightarrow Glucose-6-phosphate$
   $Glucose-6-phosphate + H<em>2O \rightarrow Glucose + P</em>i$

Glycogenesis (Glycogen Synthesis):

Glycogenesis is the synthesis of glycogen from glucose in the cytosol, requiring ATP, UTP, and glucose.

Pathway:

1. Synthesis of UDP-glucose: Hexokinase (muscle) and glucokinase (liver) convert glucose to glucose 6-phosphate. Phosphoglucomutase converts glucose 6-phosphate to glucose 1-phosphate. UDP-glucose pyrophosphorylase synthesizes uridine diphosphate glucose (UDPG) from glucose 1-phosphate and UTP.
   $Glucose + ATP \rightarrow Glucose-6-phosphate + ADP$
   $Glucose-6-phosphate \leftrightarrow Glucose-1-phosphate$
   $Glucose-1-phosphate + UTP \leftrightarrow UDP-glucose + PP_i$

2. Requirement of Primer: Glycogenin (a protein) serves as a primer. Glycogen initiator synthase transfers the first molecule of glucose to glycogenin, which then takes up a few glucose residues to form a fragment of primer.

3. Glycogen Synthesis by Glycogen Synthase: Glycogen synthase forms α-1,4-glycosidic linkages, transferring glucose from UDP-glucose to the non-reducing end of glycogen.

4. Formation of Branches: Branching enzyme glucosyl α-4-6 transferase transfers a small fragment of five to eight glucose residues from the non-reducing end of glycogen chain to another glucose residue, forming an α-1,6 bond.

Two ATP molecules are consumed, one for glucose phosphorylation and one for UDP to UTP conversion.

Glycogen Storage Diseases (GSD):

Metabolic defects involving glycogen synthesis and degradation.

Gluconeogenesis

The synthesis of glucose from non-carbohydrate compounds (lactate, pyruvate, glucogenic amino acids, propionate, and glycerol). Occurs mainly in the cytosol, although some precursors are produced in the mitochondria. Predominantly takes place in the liver and, to some extent, in the kidney matrix.

Pathway:

Gluconeogenesis resembles the reversed pathway of glycolysis, but it's not a complete reversal. Three (out of 10) reactions of glycolysis are irreversible. The seven reversible reactions are common to both glycolysis and gluconeogenesis. The three irreversible steps of glycolysis are bypassed by alternate enzymes specific to gluconeogenesis.

1. Conversion of pyruvate to phosphoenolpyruvate: This takes place in two steps:

   • Pyruvate carboxylase converts pyruvate to oxaloacetate in presence of ATP and $CO<em>2$ within the mitochondrial matrix. $Pyruvate + ATP + CO</em>2 + H<em>2O\rightarrow Oxaloacetate + ADP + P</em>i$
   • Oxaloacetate is converted to malate, transported into the cytosol, and then regenerated. Phosphoenolpyruvate carboxykinase converts oxaloacetate to phosphoenolpyruvate in the cytosol, with GTP.
     $Oxaloacetate + GTP \rightarrow Phosphoenolpyruvate + GDP + CO_2$
     2 ATP equivalents are utilized in the conversion of pyruvate to phosphoenol pyruvate.

2. Conversion of fructose 1,6-bisphosphate to fructose 6-phosphate:

Fructose 1,6-bisphosphatase converts fructose 1,6-bisphosphate to fructose 6-phosphate, requiring $Mg^{2+}$ ions.

$Fructose-1,6-bisphosphate + H<em>2O\rightarrow Fructose-6-phosphate + P</em>i$

3. Conversion of glucose 6-phosphate to glucose:

Glucose 6-phosphatase catalyzes the conversion of glucose 6-phosphate to glucose. Primarily present in the liver and kidney, but absent in muscle, brain, and adipose tissue.

$Glucose-6-phosphate + H<em>2O\rightarrow Glucose + P</em>i$

Gluconeogenesis from Lactate (Cori Cycle):

Under anaerobic conditions, pyruvate is reduced to lactate by lactate dehydrogenase. Lactate must be reconverted to pyruvate for its further metabolism. Lactate from the muscle travels through the blood to the liver, where it is oxidized to pyruvate. Pyruvate is then converted to glucose via gluconeogenesis, which is then transported back to the skeletal muscle. This cycle is referred to as the Cori cycle.

Significance:

1. Brain, central nervous system, erythrocytes, testes, and kidney medulla depend on glucose for a continuous energy supply. The human brain requires about 120 g of glucose per day.
2. Glucose is the only energy source for skeletal muscle under anaerobic conditions.
3. During fasting, gluconeogenesis is essential to meet basal glucose requirements and maintain citric acid cycle intermediates.
4. Gluconeogenesis clears metabolites (e.g., lactate, glycerol, propionate) from the blood.

Hormonal Regulation of Blood Glucose Level

1. Insulin

   • Increases glucose utilization and energy production.
   • Secreted by β cells of the pancreas.
   • Increases glucose uptake from extracellular fluid by muscles, adipocytes, and mammary glands.
   • Enhances glycolysis by inducing synthesis of phosphofructokinase and pyruvate kinase.
   • Stimulates NADPH formation.

2. Glucagon

• Stimulated by a fall in blood sugar level and secreted by the α cells of pancreas.
• Antagonistic to insulin and increases blood sugar level by converting glycogen to glucose
• Increases glycogenolysis.
• Decreases hepatic glycogenesis.

1. Adrenaline

• Has glycogenolytic and gluconeogenetic action which increases blood sugar level by enhancing hepatic glycogenolysis
• Stimulating the synthesis of key enzymes for
  gluconeogenesis
• Reduces the blood glucose utilisation

1. Glucocorticoids

• act as insulin antagonist
• Increases gluconeogenesis in liver by acting on key gluconeogenetic enzymes
• Decreases amino acid incorporation in to protein by increasing protein catabolism in extra hepatic tissues

1. Growth hormones

• Antagonistic to insulin
• Enhances hepatic gluconeogenesis, mobilise fatty acids from adipocytes
• It increases muscle and cardiac glycogen level by reducing glycolysis
• It has diabetogenic effect

1. Prolactin

• It has diabetogenic and anti-insulin effects like growth hormones

1. Thyroid hormones
   • Raise blood sugar
   • Hyperthyroidism produces hyperglycemia
   • Enhances intestinal absorption rate of glucose
   • Increases hepatic glycogenolysis

Diabetes Mellitus (DM)

A metabolic disorder characterized by high blood sugar (glucose) level, caused by either lack of insulin secretion or decreased sensitivity of tissues to insulin.

Types:

• Type I/Insulin-dependent diabetes mellitus (IDDM)
  • Occurs in childhood (particularly between 12-15 yrs age). It accounts for about 10 to 20% of the known diabetics
  • Due to destruction of B-cells of pancreas which leads to total deficiency of insulin
• Type II/Non-Insulin-dependent diabetes mellitus (NIDDM)
  • Most common accounting for 80 to 90% of the diabetic population
  • Occurs mostly due to the absence or deficiency of insulin receptors
• Gestational diabetes: Hyperglycemia occurring in pregnancy then sensitivity of insulin receptors increases
• Others: Genetic defect of B cells, pancreatic diseases, drug induced DM (steroids, diuretics)

Clinical features

• Polyuria: Excess urine formation with increase in frequency of voiding urine
• Polydipsia: Abnormally great thirst due to excess loss of water
• Polyphagia: Intake of excess food
• Ketoacidosis: Increased mobilization of fatty acids results in overproduction of ketone bodies which often leads to ketoacidosis.
• Glucosuria: Increased blood glucose causes loss of glucose in urine
• Blurred vision
• Loss of weight
• Fatigue and headache

Diagnosis:

• Clinical examination of symptoms
• Laboratory tests (urine tests, single blood sugar estimation, oral glucose tolerance test)

Management:

• Dietary management: low calories (i.e. low carbohydrate and fat), high protein and fiber
  rich diet
• Hypoglycemic drugs: Sulfonylureas such as acetohexamide, tolbutamide and glibenclamide
• Management with insulin: short acting and long acting.