DIFFERENT HYPERGLYCEMIC

STATE
Ryan I. Daet
TYPE 1 TYPE 2
Sudden, Gradual
Young Onset Adult

Insulin deficiency Cause Insulin resistance

5 Percent Prevalence 95 percent

Normal Obese
Body habitus Overweight
Thin

5-to 15 Percent Family Hx More than 50 percent

 Genetic Defects of Beta cell function

HNF 4 (MODY 1)
Gukokinase (MODY 2)
They are included in the
HNF- 1 (MODY 3)
Transcription factor hepatocyte NF6 by Jacquemin,
development E & et. Al.,
& Metabolic
Insulin promoter factor- 1 (MODY 4) 2000
homeostasis
HNF 1 (MODY Diabetes
5) & mitochondrial function by Bolo, A.P & Palmeira,
NeuroD1 (MODY 6) They
C.M, 2006influence the expression of
Mitochondrial DNA the insulin gene as well as genes
Subunits of ATP- sensitive K channel
involved in glucose transport and
metabolism
Proinsulin
 Genetic Defects in insulin action

Type A insulin Resistance

Leprechaunism
Type A insulin resistance -- Rabson-
A rare Mendenhall
disorder in syndrome
which the
A autosomal
Lipodystrophy recessive
syndrome genetic
Leprechaunism A autosomal
- bodys tissues recessive
and organs genetic
don not
disorder
disorder
Rabson- Mendenhall syndrome - Related properly
respond to the hormone
to hyperlipidemia
Lipodystrophy syndrome --- insulin
Mutation
Insulin within
resistance the coding
Mutation
- Can lead to D.M within the coding
sequence
sequenceof ofthe
theINSR gene
insulin
(insulin receptor)
receptor
F.A, Acyl-CoA, Impair insulin signaling by
CHON kinase C, increasing the inhibitory
ceramides and
Jun kinase phosphorylation of insulin
DAG
receptor substrates
 Disease of exocrine pancreas
Pancreatitis
Pancreatectomy
Decreased in the functional
Neoplasia
capability of the pancreas
Cystic fibrosis
Hemochromatosis Caused by disease process
Fibrocalculous pancreatopathy (Obstruction, inflammation &
mutations)
Mutations in carboxyl ester lipase
 Endocrinopathies
Acromegaly
Cushings syndrome
Glucagonoma Tumor
Acromegalyin intra/ extraadrenal
Tumor
Inc.
-Inc. of thegrowth
tumor
Increase
medulla ACTH delta
glycogenolysis
rare of the cells
alpha cell
hormone
Pheochromocytoma Inhibiting
Inc. aldosterone
the insulin
Inc.

Epi- gluconeogenesis
Overproduction
-gluconeogenesis
inc. insulin
inhibits of glucagon
secretion,
insulin glucose
secretion by

metabolic
Mild DM dysfuntion (insulin
Hyperthyroidism 1000
production
Dec. pg/mL (50-of
utilization
stimulating alpha 200)
glucose
2 adr. Receptor
resistance)
Somatostatinoma & -induce
dec. glucose
glucagonuptake
secretion via
Aldosteronoma Beta adr. Receptor
Increase glucagon
 Drug or Chemical induced
Glucocorticoids
Vacor
pentamide Predispose/ Precipitate D.M
nicotinic acid Inc. Glucose metabolism
diazoxide Insulin resistance
B- adrenergic agonist
thiazides
Antipsychotics
 Infections

Involved in accelerating pancreas Congenital rubella

failure
Damage the beta cell Cytomegalovirus
- 2 mechanisms
(autoimmunity)
> Influence the pancreatic cell Coxsackievirus
directly
> Indirectly by influencing
immune system which in turn
affects the pancreas
- Virus- induced type 1 & 2 DM
- Insulin Resistance
Other genetic syndromes

Wolframs syndrome
Downs syndrome
Turners syndrome
Huntingtons chorea
Gestational Diabetes
Glucose intolerance developing during pregnancy
Insulin resistance
Most women revert to normal glucose tolerance in postpartum period
THANK YOU