The document discusses disorders of carbohydrate and lipid metabolism. It begins by defining diabetes mellitus as a metabolic disease characterized by hyperglycemia. It then describes the two main types: insulin-dependent diabetes mellitus (IDDM), which results from destruction of insulin-producing beta cells and requires insulin treatment; and non-insulin dependent diabetes mellitus (NIDDM), which is more common and often associated with obesity. It further discusses disorders like glycogen storage diseases, pentosuria, galactosemia, and regulation of blood glucose levels. Lipid disorders like hyperlipidemia are also briefly mentioned.

1. TEJASVI NAVADHITAMASTU
“Let our (the teacher and the taught) learning be radiant”
Let our efforts at learning be luminous and filled with joy, and endowed with the force of purpose
Paper XII: CLINICAL AND DIAGNOSTIC BIOCHEMISTRY
Dr. Prabhakar Singh. D.Phil. Biochemistry
Department of Biochemistry, VBSPU, Jaunpur
Unit I: Disorders of carbohydrate metabolism – Insulin dependent and insulin
independent, glucose and galactose tolerance tests, sugar level in blood, renal threshold
for glucose, factors influencing blood glucose level. Regulation of blood glucose
concentration, melituria, glycogen storage diseases, pentosuria, galactosemia.
Disorder of lipids: plasma lipoproteins, cholesterol, triglycerides and phospholipids
in health and disease, hyperlipidemia, hyperlipoproteinemia, Gaucher’s disease,
ketone bodies.

2. DIABETES MELLITUS
Diabetes mellitus is a metabolic disease, more appropriately a disorder of fuel metabolism. It is
mainly characterized by hyperglycemia that leads to several long term complications.
Diabetes mellitus is broadly divided into 2 groups, namely insulin-dependent diabetes mellitus
(IDDM) and non-insulin dependent diabetes mellitus (NIDDM). This classification is mainly based
on the requirement of insulin for treatment.
Diabetes mellitus is the third leading cause of death(after heart disease and cancer) in
many developed countries. It affects about 6 to 8% of the general population. The complications of
diabetes affect the eye, kidney and nervous system. Diabetes is a major cause of blindness, renal
failure, amputation, heart attacks and stroke.
The term diabetes, whenever used, refers to diabetes mellitus. It should, however, be noted that
diabetes insipidus is another disorder characterized by large volumes of urine excretion due to
antidiuretic hormone deficiency
Diabetes mellitus is a clinical condition characterized by increased blood glucose level
(hyperglycemia)due to insufficient or inefficient (incompetent) insulin. In other words, insulin is
either not produced in sufficient quantity or inefficient in its action on the target tissues. As a
consequence, the blood glucose level is elevated which spills over into urine in diabetes mellitus

3. INSULIN-DEPENDENT DIABETES MELLITUS (IDDM)
 IDDM, also known as type I diabetes or (less frequently) juvenile onset
diabetes, mainly occurs in childhood (particularly between 12-15 yrs age).
 IDDM accounts for about 10 to 20% of the known diabetics. This disease is
characterized by almost total deficiency of insulin due to destruction of E-
cells of pancreas.
 The E-cell destruction may be caused by drugs, viruses or autoimmunity.
Due to certain genetic variation, the E-cells are recognized as non-self and
they are destroyed by immune mediated injury.
 Usually, the symptoms of diabetes appear when 80-90% of the E-cells
have been destroyed. The pancreas ultimately fails to secrete insulin in
response to glucose ingestion.
 The patients of IDDM require insulin therapy

4. NON-INSULIN DEPENDENT DIABETES MELLITUS (NIDDM)
 NIDDM, also called type II diabetes or (less frequently) adult-onset diabetes, is
the most common, accounting for 80 to 90% of the diabetic population.
NIDDM occurs in adults (usually above 35 years) and is less severe than IDDM.
 The causative factors of NIDDM include genetic and environmental. NIDDM
more commonly occurs in obese individuals. Overeating coupled with
underactivity leading to obesity is associated with the development of NIDDM.
Obesity acts as a diabetogenic factor and leads to a decrease in insulin
receptors on the insulin responsive (target) cells.
 The patients of NIDDM may have either normal or even increased insulin
levels. Many a times weight reduction by diet control alone is often sufficient
to correct NIDDM.
 Recent research findings on NIDDM suggest that increased levels of tumor
necrosis factor-D (TNF-D) and resistin, and reduced seretion of adiponectin by
adipocytes of obese people cause insulin resistance (by impairing insulin
receptor function).

5. COMPARISON OF TWO TYPES OF DIABETES MELLITUS

7. INTERPRETATION OF GTT
1. The fasting plasma glucose level is 75–110
mg/dl in normal persons. On oral glucose
load, the concentration increases and the
peak value (140 mg/dl) is reached in less
than an hour which returns to normal by 2
hours. Glucose is not detected in any of the
urine samples.
2. In individuals with impaired glucose
tolerance, the fasting (110-126 mg/dl) as
well as 2 hour (140-200 mg/dl) plasma
glucose levels are elevated. These subjects
slowly develop frank diabetes at an
estimated rate of 2% per year. Dietary
restriction and exercise are advocated for
the treatment of impaired glucose
tolerance.
3. A person is said to be suffering from
diabetes mellitus if his/herfasting plasma
glucose exceeds 7.0 mmol/l (126 mg/dl)
and, at 2 hrs.11.1 mmol/l (200 mg/dl).

11. Metabolic changes in diabetes

13. INSULIN

14. 1. Alpha cells producing glucagon (15–20% of total islet cells)
2. Beta cells producing insulin and amylin (65–80%)
3. Delta cells producing somatostatin (3–10%)
4. PP cells (gamma cells) producing pancreatic polypeptide (3–5%)
5. Epsilon cells producing ghrelin (<1%)
6. Somatostatin: inhibits alpha cells and beta cells
The function of PP is to self-regulate pancreatic secretion activities (endocrine and
exocrine); it also has effects on hepatic glycogen levels and gastrointestinal secretions.
Amylin, or islet amyloid
polypeptide (IAPP), is a 37-
residue peptide hormone. It is
cosecreted with insulin from the
pancreatic β-cells in the ratio of
approximately 100:1. Amylin plays
a role in glycemic regulation by
slowing gastric emptying and
promoting satiety, thereby
preventing post-prandial spikes in
blood glucose levels.

18. Insulin receptor mediated signal
transduction (IRS—Insulin receptor substrate) Insulin mediated glucose transport

19. REGULATION OF BLOOD GLUCOSE LEVEL
(HOMEOSTASIS OF BLOOD GLUCOSE)

24. HYPOGLYCEMIA

25. DISORDERS OF GALACTOSE METABOLISM
CLASSICAL GALACTOSEMIA

26. Galactokinase Deficiency
The defect in the enzyme galactokinase, responsible for phosphorylation of galactose, will also
result in galactosemia and galactosuria. Here again galactose is shunted to the formation of
galactitol. Generally, galactokinase-deficient individuals do not develop hepatic and renal
complications. Development of cataract occurs at a very early age, sometimes within an year after
birth. The treatment is the removal of galactose and lactose from the diet.

27. GALACTOSE TOLERANCE TEST (GTT)
1. Galactose is a monosaccharide, almost exclusively metabolized
by the liver.
2. The liver function can be assessed by measuring the utilization
of galactose. This is referred to galactose tolerance test.
3. The subject is given intravenous administration of galactose
(about 300 mg/kg body weight). Blood is drawn at 10 minute
intervals for the next 2 hours and galactose estimated.
4. In the normal individuals, the half-life of galactose is about 10-
15 minutes. This is markedly elevated in hepatocellular
damage(infective hepatitis, cirrhosis).

28. Glycosuria Renal threshold substances

29. Pentosuria
Pentosuria is a condition where the sugar xylitol, a pentose, presents in the urine in
unusually high concentrations. It was characterized as an inborn error of carbohydrate
metabolism in 1908. It is associated with a deficiency of L-xylulose reductase, necessary for
xylitol metabolism. L-Xylulose is a reducing sugar, so it may give false diagnosis of diabetes,
as it is found in high concentrations in urine. However, people with pentosuria do not have
nonstandard metabolism of glucose, like diabetics.Patients of pentosuria have a low
concentration of the sugar d-xyloketose. Using, Phenyl pentosazone crystals, phloroglucin
reaction, and absorption spectrum, pentose can be traced back as the reducing substance in
urine, with those that have pentosuria. Those diagnosed with Pentosuria are predominantly
of Jewish root. However, it is a harmless defect, and no cure is needed.
Research has shown that pentosuria appears in 3 forms.
1. Essential pentosuria: The most widely studied is essential pentosuria, where a couple of
grams of L-xylusol are released into a person’s system daily. Xylulose, contained in red
blood cells, is composed of both a major and minor isozyme. For those diagnosed with
essential pentosuria, the major isozyme appears to be the same as the minor one.
2. Alimentary pentosuria: It can be acquired through fruits high in pentose.
3. Drug-induced pentosuria: It can be developed by those exposed to morphine, fevers,
allergies, and some hormones.

30. Melituria
sugar in the urine; specific types are named for the sugar in question
,such as FRUCTOSURIA, GALACTOSURIA, GLYCOSURIA, and LACTOSURIA.
Fructosuria: the presence of fructose in the urine.
Essential fructosuria a benign, autosomal recessive disorder of carbohydrat
e metabolism due to a defect infructokinase and manifested only by fructose i
n the blood and urine.
Excretion of lactose (milk sugar) in the urine; a common finding during pre
gnancy and lactation, and in new borns, especially premature babies.
Lactosuria: [lak″to-su´re-ah] elevated levels of lactose, as seen in lactose
intolerance or during lactation.

31. GLYCOGEN STORAGE DISEASES
The metabolic defects concerned with the glycogen synthesis and degradation are
collectively referred to as glycogen storage diseases.
These disorders are characterized by deposition of normal or abnormal type of glycogen in
one or more tissues. A summary of glycogen metabolism along with the defective enzymes in
the glycogen storage disorders
VON GIERKE’S DISEASE (TYPE I)

32. Summary of glycogen metabolism with glycogen storage diseases (Red blocks
indicate storage disease, I–von Gierke’s disease; II–Pompe’s disease; III–Cori’s disease;
IV–Anderson’s disease; V–Mc Ardle’s disease; VI–Her’s disease; VII–Tarui’s disease)

33. GLYCOGEN STORAGE DISEASES – BIOCHEMICAL LESIONS AND CHARACTERISTIC FEATURES