GLUCOSE HOMEOSTASIS/

DIABETES MELLITUS
DR FRED ALLISON
 SCOPE

• INTRODUCTION
• DEFINITIONS
• METABOLIC PATHWAYS OF GLUCOSE METABOLISM
• PLASMA GLUCOSE REGULATION
• PATHOPHYSIOLOGICAL PROCESSES
• DIABETES MELLITUS
• SYMPTOMS/DIAGNOSIS
• TREATMENT
 INTRODUCTION

• GLUCOSE IS THE MOST IMPORTANT SOURCE OF ENERGY FOR MOST TISSUES.

• MANY TISSUES CAN ALSO UTILIZE FATTY ACIDS AS FUEL BUT TISSUES LACKING MITOCHONDRIA (E.G., THE
RED BLOOD CELLS) OR THOSE THAT ARE DEFICIENT IN MITOCHONDRIA (E.G., RENAL MEDULLA, TESTES)
CANNOT UTILIZE FAT FOR ENERGY (FATTY ACID OXIDATION TAKES PLACE WITHIN THE MITOCHONDRIA).
• SUCH TISSUES ARE DEPENDENT SOLELY ON GLUCOSE AS ESSENTIAL FOR SURVIVAL.
• THE BRAIN IS UNIQUE IN THAT IT CAN UTILIZE BOTH GLUCOSE AND KETONE BODIES, BUT NOT FATTY ACIDS, AS
METABOLIC FUELS.
• HOMEOSTATIC MECHANISMS GOVERNING GLUCOSE METABOLISM SERVE TO MAINTAIN FUEL SUPPLY TO THE
CENTRAL NERVOUS SYSTEM.
• IN THE POSTPRANDIAL STATE EXCESS GLUCOSE IS CONVERTED TO BOTH GLYCOGEN
(GLYCOGENESIS) AND TRIGLYCERIDES (LIPOGENESIS), AND STORED AS SUCH.
• IN THE FASTING, OR STARVATION, STATE THE LACK OF EXOGENOUS GLUCOSE IS OVERCOME
BY PRODUCTION OF ENDOGENOUS GLUCOSE
 DEFINITIONS

• LIPOGENESIS- IS DEFINED AS THE SYNTHESIS OF FATTY ACIDS FROM NON LIPID PRECURSORS.
• LIPOLYSIS-IS THE METABOLIC PROCESS THROUGH WHICH TRIACYLGLYCEROLS (TAGS) BREAK DOWN
VIA HYDROLYSIS INTO THEIR CONSTITUENT MOLECULES: GLYCEROL AND FREE FATTY ACIDS (FFAS).
• KETOGENESIS- IS A METABOLIC PATHWAY THAT PRODUCES KETONE BODIES, WHICH PROVIDE AN
ALTERNATIVE FORM OF ENERGY FOR THE BODY.
• GLUCONEOGENESIS (FORMATION OF GLUCOSE FROM AMINO ACIDS, LACTATE AND GLYCEROL)
• GLYCOGENOLYSIS (GLYCOGEN BREAKDOWN).
• GLYCOLYSIS-A PROCESS IN WHICH GLUCOSE (SUGAR) IS PARTIALLY BROKEN DOWN BY CELLS IN
ENZYME REACTIONS THAT DO NOT NEED OXYGEN.

• GLYCOGENOSIS- A METABOLIC DISORDER CAUSED BY A DEFECTIVE GLYCOGEN METABOLISM

RESULTING IN THE EXTRA GLYCOGEN STORAGE IN CELLS
• FASTING - ABSTINENCE FROM FOOD OR DRINK OR BOTH FOR HEALTH, RITUALISTIC, RELIGIOUS,
OR ETHICAL PURPOSES. THE ABSTENTION MAY BE COMPLETE OR PARTIAL, LENGTHY, OF SHORT
DURATION, OR INTERMITTENT.
• STARVATION -THE STATE OF HAVING NO FOOD FOR A LONG PERIOD, OFTEN CAUSING DEATH
 GLYCOLYSIS

THIS IS THE METABOLIC PATHWAY BY WHICH GLUCOSE IS OXIDIZED TO PYRUVATE WITH THE
PRODUCTION OF 2 ATP MOLECULES.
THE CONTROL OF THIS PROCESS IS COMPLEX BUT THE MAIN FACTORS ARE INSULIN, WHICH
ENHANCES, AND GLUCAGON, WHICH SUPPRESSES.
THESE TWO HORMONES ACT BY INFLUENCING ENZYME COMPLEXES ALONG THE GLYCOLYTIC
PATHWAY.
FURTHER OXIDATION OF PYRUVATE IN THE TRICARBOXYLIC ACID (TCA) OR CITRIC ACID CYCLE
PRODUCES A FURTHER 36 MOLECULES OF ATP.
 GLUCONEOGENESIS

THIS PROCESS, WHICH OCCURS IN THE LIVER AND RENAL CORTEX DURING
GLUCOSE-STARVED STATES,
PRODUCES GLUCOSE FROM PYRUVATE WHICH IS IN TURN DERIVED FROM PROTEIN
(ALANINE) AND LACTATE.
IT IS AN ENERGY-REQUIRING PROCESS WHICH IS BASICALLY A REVERSAL OF GLYCOLYSIS
BUT FOR THREE STEPS – THOSE CATALYSED BY THE ENZYMES HEXOKINASE,
PHOSPHOFRUCTOSE KINASE, AND PYRUVATE KINASE.
 GLYCOGENESIS AND GLYCOGENOLYSIS

GLYCOGEN SYNTHESIS (GLYCOGENESIS) FROM GLUCOSE OCCURS DURING A PLENTIFUL

GLUCOSE SUPPLY (FED STATE).
IT IS STIMULATED BY INSULIN (BY ITS ACTION ON GLYCOGEN SYNTHETASE) AND INHIBITED BY
GLUCAGON.
THE BREAKDOWN OF GLYCOGEN TO GLUCOSE-6- PHOSPHATE (GLYCOGENOLYSIS) OCCURS
DURING GLUCOPENIC STATES AND IS STIMULATED BY GLUCAGON AND CATECHOLAMINES
AND INHIBITED BY INSULIN.
• IN THE FED STATE THE LIVER CONTAINS ABOUT 70-80 GRAMS OF GLYCOGEN; MUSCLE
TISSUES CONTAIN AN ADDITIONAL 150 GRAMS.
• THE HEPATIC GLYCOGEN STORES REPRESENTS A READILY CONVERTIBLE SOURCE OF GLUCOSE
FOR ALL TISSUES---
• GLYCOGEN IS BROKEN DOWN TO GLUCOSE-6- PHOSPHATE WHICH IS THEN CONVERTED TO
GLUCOSE BY GLUCOSE-6-PHOSPHATASE.
• BECAUSE MUSCLE TISSUES LACK THE LATTER ENZYME, GLUCOSE IS NOT PRODUCED FROM
MUSCLE GLYCOGEN.
• RATHER, GLYCOGEN IS CONVERTED TO LACTATE WHICH CAN THEN BE TRANSPORTED TO THE
LIVER TO BE CONVERTED TO GLUCOSE VIA GLUCONEOGENESIS, A PROCESS KNOWN AS THE
CORI CYCLE.
• NB THESE GLYCOGEN STORES ARE LIMITED AND ARE DEPLETED AFTER 18-24 HOURS OF
FASTING.
 FATTY ACID Β-OXIDATION

THE CONVERSION OF FATTY ACIDS TO ACETYL-COA WITH THE PRODUCTION OF ENERGY IS

REFERRED TO AS Β OXIDATION AND TAKES PLACE IN THE MITOCHONDRIA.
IT OCCURS DURING GLUCOPENIC STATES AND PLAYS AN IMPORTANT ROLE IN ENERGY
SUPPLY FOR MANY TISSUES DURING FASTING.
THE ACETYL- COA CAN EITHER ENTER THE CITRIC ACID (TCA) CYCLE AND PRODUCE MORE
ENERGY (ATP) OR MAY BE DIVERTED TO THE PRODUCTION OF KETONE BODIES WHICH ARE A
MAJOR SOURCE OF ENERGY FOR THE BRAIN DURING PROLONGED FASTING/STAVATION .
 KETOGENESIS

• THE FORMATION OF KETONE BODIES (ACETOACETATE, Β-HYDROXYBUTYRATE AND

ACETONE) FROM ACETYL-COA
• OCCUR MOSTLY DURING GLUCOPENIC STATES
• OCCURS ALMOST EXCLUSIVELY IN THE LIVER ALTHOUGH THE RENALS CORTEX IS ALSO
CAPABLE OF KETOGENESIS.
 CARBOHYDRATE DIGESTION AND ABSORPTION

• ON AVERAGE, AROUND 40-45% OF DIETARY CALORIES ARE DERIVED FROM CARBOHYDRATES.

• IN A YOUNG ADULT MALE, FOR EXAMPLE, THIS REPRESENTS ABOUT 300-350G WHICH IS
MAINLY IN THE FORM OF STARCH (PLANT SOURCES) AND GLYCOGEN (ANIMAL SOURCES);
• IN ADDITION THERE MAY BE SIGNIFICANT AMOUNTS OF THE DISACCHARIDES SUCROSE AND
LACTOSE.
SALIVARY AND PANCREATIC AMYLASES CONVERT STARCH AND GLYCOGEN TO A MIXTURE OF
D-GLUCOSE AND MALTOSE; THE LATTER IS IN TURN CLEAVED INTO TWO D-GLUCOSE
MOLECULES BY INTESTINAL MALTASE LOCATED IN THE BRUSH BORDER OF THE SMALL BOWEL
EPITHELIAL CELLS.
THE D-GLUCOSE IS ACTIVELY TRANSPORTED ACROSS THE EPITHELIAL CELLS TO THE PORTAL
VENOUS SYSTEM AND CARRIED TO THE LIVER.
IN THE LIVER IT IS PHOSPHORYLATED AND ENTERS ONE OF SEVERAL POSSIBLE METABOLIC
PATHWAYS RESPONSIBLE FOR ITS DISPOSITION.
• SUCROSE AND LACTOSE ARE ALSO ACTED UPON BY BRUSH BORDER-LOCATED
DISACCHARIDASES……..
• SUCRASE CONVERTS SUCROSE TO D-GLUCOSE AND D-FRUCTOSE AND LACTASE
TRANSFORMS LACTOSE TO D-GLUCOSE AND D-GALACTOSE.
• AS IN THE CASE OF D-GLUCOSE, D-GALACTOSE AND D-FRUCTOSE ARE ACTIVELY ABSORBED
ACROSS THE GUT EPITHELIAL CELLS, TRANSPORTED TO THE LIVER, AND THEN
PHOSPHORYLATED.
 THE LIVER AND GLUCOSE METABOLISM

D-GLUCOSE IS TRANSPORTED INTO THE HEPATOCYTE BY AN

INSULIN-INDEPENDENT PROCESS AND PHOSPHORYLATED TO
GLUCOSE-6-PHOSPHATE BY THE ENZYMES HEXOKINASE AND
GLUCOKINASE.
FURTHER METABOLIC PROCESS DEPEND ON THE PREVAILING
NUTRITIONAL STATUS AND THE ACTION OF THE
COUNTER-REGULATORY HORMONES (GLUCAGON, GROWTH
HORMONE, CORTISOL, CATECHOLAMINES).
ALTHOUGH GLUCOSE DOES NOT REQUIRE INSULIN TO ENTER THE
HEPATOCYTE THE ENSUING DISPOSITION IS MARKEDLY
INSULIN-SENSITIVE.
 IN THE FED STATE

A RESULTANT HIGH INSULIN ACTIVITY, ANABOLIC ACTIVITES

PREDOMINATE WITH GLUCOSE ENTERING SEVERAL METABOLIC VENTURES:

↑GLYCOGEN SYNTHESIS AND ↓ GLYCOGEN BREAKDOWN →

↑GLYCOGEN STORAGE

↑FATTY ACID AND TRIGLYCERIDE SYNTHESIS → FAT STORAGE

INHIBITION OF GLUCONEOGENESIS → PROTEIN CONSERVATION

THE ENERGY FOR THESE ACTIVITIES ARE, IN PART PROVIDED BY
THE OXIDATION OF GLUCOSE VIA GLYCOLYSIS AND THE CITRIC
ACID CYCLE. THE NET EFFECT IS STORAGE OF GLUCOSE AS
GLYCOGEN AND TRIGLYCERIDE, AND PROTEIN
CONSERVATION.

DURING STARVATION,
AS A RESULT OF RELATIVE INSULINOPENIA AND INCREASED
ACTIVITY OF THE COUNTER-REGULATORY HORMONES, THE
LIVER REVERTS INTO A GLUCOSE-PRODUCING ORGAN.
THE IMMEDIATE STIMULUS FOR THIS ACTIVITY IS A LOW INSULIN:
GLUCAGON RATIO AND INCREASED CORTISOL AND
CATECHOLAMINE ACTIVITY, WHICH RESULT IN:
• ↓GLYCOGEN SYNTHESIS AND ↑ GLYCOGEN BREAKDOWN → ↑GLUCOSE

• ↑GLUCOSE FORMATION FROM PROTEIN (GLUCONEOGENESIS)

• ↓FATTY ACID AND TRIGLYCERIDE SYNTHESIS FROM GLUCOSE AND ↑BREAKDOWN OF FAT
STORES (LIPOLYSIS) → ENERGY AND KETONE BODIES VIA Β-OXIDATION OF THE FATTY ACIDS.
• HENCE IN THE ABSENCE OF A SUSTAINED EXOGENOUS GLUCOSE SUPPLY,
• THERE IS HEPATIC PRODUCTION OF GLUCOSE FROM GLYCOGEN AND PROTEIN AND MOST
OF THE REQUIRED ENERGY IS DERIVED FROM FAT (Β-OXIDATION OF FATTY ACIDS AND
FORMATION OF KETONE BODIES).
EXTRAHEPATIC TISSUES AND GLUCOSE METABOLISM

ALL BODY TISSUES UTILIZE GLUCOSE FOR ENERGY PRODUCTION,

ALTHOUGH MOST CAN ALSO OXIDIZE ALTERNATIVE FUELS.
INSULIN IS NECESSARY FOR GLUCOSE UPTAKE BY THE
NON-HEPATIC TISSUES.
THIS IS EFFECTED THROUGH AN INSULIN RECEPTOR WHICH, WHEN
ACTIVATED, MOBILIZES A TRANSMEMBRANE
GLYCOPROTEIN-GLUCOSE TRANSPORTER WHICH CYCLES
BETWEEN THE PLASMA MEMBRANE AND INTRACELLULAR
COMPARTMENTS.

ONCE INSIDE THE CELL THE GLUCOSE IS PHOSPHORYLATED BY

HEXOKINASE TO GLUCOSE-6- PHOSPHATE AND THEN DIVERTED
TO THE SAME PROCESSES THAT OPERATE IN THE LIVER.
 HORMONES REGULATING CARBOHYDRATE
METABOLISM
INSULIN: SECRETED BY THE Β-CELLS OF THE PANCREAS IN
RESPONSE TO A HIGH BLOOD GLUCOSE, IS A PEPTIDE HORMONE
(MW- 6000)
CONSISTING OF TWO CHAINS (A 21 AMINO ACID Α- CHAIN AND
A 30 AMINO ACID B- CHAIN) JOINED BY TWO DISULPHIDE
BRIDGES.
IT IS PRODUCED AS PROINSULIN WHICH CONTAINS AN
ADDITIONAL 31 AMINO ACID RESIDUE CONNECTING
PEPTIDE (C-PEPTIDE) JOINING THE A AND B CHAINS.
THIS IS TRANSPORTED INTO THE GOLGI COMPLEX WHERE IT IS
PROTEOLYSED TO FORM THE BIOLOGICALLY INACTIVE
C-PEPTIDE AND ACTIVE NATIVE INSULIN, BOTH OF WHICH
ARE SECRETED IN EQUIMOLAR AMOUNTS.
CONTROL OF INSULIN SECRETION. GLUCOSE IS THE MOST
IMPORTANT STIMULUS FOR INSULIN SECRETION BUT IT CAN
ALSO BE STIMULATED BY PHYSIOLOGICAL
CONCENTRATIONS OF AMINO ACIDS, KETONE BODIES,
FATTY ACIDS, ACETYLCHOLINE, AND ADRENALINE.
BLOOD GLUCOSE CONCENTRATIONS ABOVE 5.5 MMOL/L
PRODUCE AN IMMEDIATE RESPONSE WITH SECRETION
OCCURING IN TWO PHASES:
WHICH CAN BE DIVIDED INTO A AND B

A- AN IMMEDIATE BURST WITH PEAK LEVELS OCCURRING

WITHIN ONE MINUTE, FOLLOWED BY A FALL-OFF TO LOW
SECRETION LEVELS OF VARIABLE DURATION
B- A SECOND, MORE PROLONGED PEAK OF SECRETION
WHICH LASTS 15 TO 30 MINUTES.
 INSULIN ACTION.
INSULLIN DIFFUSES FROM THE CAPILLARIES AND BINDS TO
SPECIFIC CELL SURFACE RECEPTORS
WHICH ARE ACTIVATED TO PRODUCE ITS BLOOD
GLUCOSE-LOWERING AND ANABOLIC EFFECTS BY
STIMULATING GLUCOSE TRANSPORT INTO CELLS

AND INDUCING, OR INHIBITING A NUMBER OF ENZYME

COMPLEXES.
 THE MAJOR ACTIVITIES ARE:

STIMULATION OF ANABOLIC PROCESSES;

1. PROMOTES ENTRY OF GLUCOSE AND AMINO ACIDS INTO
MUSCLE CELLS AND GLUCOSE INTO ADIPOSE TISSUE CELLS.
2. STIMULATES GLYCOLYSIS BY INDUCTION OF THE ENZYMES
HEXOKINASE, PHOSPHOFRUCTOKINASE, AND PYRUVATE
KINASE, THUS INCREASING THE BUILDING BLOCKS (ACETYL
COA, ATP, NADPH) FOR MACROMOLECULES.
3. STIMULATES GLYCOGEN AND PROTEIN SYNTHESIS IN MUSCLE
TISSUES.
 INHIBITION OF CATABOLIC PROCESSES;
1. INHIBITS GLUCONEOGENESIS.
2. INHIBITS FAT BREAKDOWN AND Β-OXIDATION OF FATTY
ACIDS AND KETOGENESIS.
3. INHIBITS GLYCOGENOLYSIS.
POTASSIUM HOMEOSTASIS;
INSULIN INCREASES THE CELLULAR UPTAKE OF
POTASSIUM IONS. THIS IS INDEPENDENT OF ITS ACTION
ON GLUCOSE.
 COUNTER-REGULATORY HORMONES.

THIS GROUP OF HORMONES ARE SO CALLED BECAUSE THEY

OPPOSE THE ACTION OF INSULIN AND EXCESS PRODUCTION OF
ANY OF THEM RESULTS IN HYPERGLYCAEMIA.

THEY ARE ‘STARVATION HORMONES’ WHICH ARE CALLED

INTO PLAY WHEN EXOGENOUS GLUCOSE INTAKE IS LOW AND
CONSEQUENTLY STIMULATE THE PRODUCTION OF
GLUCOSE FROM GLYCOGEN (GLYCOGENOLYSIS) AND
PROTEIN (GLUCONEOGENESIS), AND GENERATION OF
ENERGY FROM FATTY ACIDS VIA Β-OXIDATION.
GLUCAGON.
THIS STRAIGHT CHAIN POLYPEPTIDE OF 29 AMINO ACIDS
(MW 3500) IS SECRETED BY THE Α-CELLS OF THE
PANCREAS IN RESPONSE TO HYPOGLYCAEMIA (AND
INHIBITED BY HYPERGLYCAEMIA).
ITS MAIN ACTION IS TO INCREASE GLUCOSE RELEASE BY
THE LIVER BUT, IN ASSOCIATION WITH A LOW
INSULIN, IT ALSO STIMULATES FREE FATTY ACID RELEASE
AND INCREASES KETOGENESIS.
IN SUMMARY, GLUCAGON STIMULATES
GLYCOGENOLYSIS
GLUCONEOGENESIS,
Β-OXIDATION OF FATTY ACIDS
KETOGENESIS,
AND INHIBITS GLYCOGENESIS, FATTY ACID SYNTHESIS
(LIPOGENESIS), AND GLYCOLYSIS.
 CORTISOL.
CORTISOL, SECRETED BY THE ADRENAL CORTEX,
INCREASES GLUCOSE PRODUCTION BY:

1. DECREASING GLUCOSE AND AMINO ACID UPTAKE BY

MUSCLE
2. MOBILIZING MUSCLE PROTEIN TO INCREASE THE DELIVERY
OF AMINO ACIDS TO THE LIVER FOR GLUCONEOGENESIS.
3. INCREASING GLUCONEOGENESIS.
 CATECHOLAMINE.
ADRENALINE (AND TO A LESSER EXTENT NORADRENALINE) IS
SECRETED BY THE ADRENAL MEDULLA AND THE SYMPATHETIC
NERVE ENDINGS IN RESPONSE TO HYPOGLYCAEMIA.
IN THE CONTEXT OF GLUCOSE METABOLISM, CATECHOLAMINES:
1. INCREASE RELEASE OF FATTY ACIDS FROM ADIPOSE TISSUE.
2. STIMULATE GLYCOGEN DEGRADATION TO GLUCOSE.
3. INHIBIT CELLULAR GLUCOSE UPTAKE.
4. STIMULATE GLUCAGON SECRETION AND DEPRESSES INSULIN
SECRETION.

THE END RESULT IS INCREASED GLUCOSE PRODUCTION BY

THE LIVER.
GROWTH HORMONE.
THE RELATIONSHIP BETWEEN GROWTH HORMONE AND
GLUCOSE METABOLISM IS UNCLEAR BUT EXCESSIVE
SECRETION AS IN ACROMEGALY, IS OFTEN ASSOCIATED
WITH HYPERGLYCAEMIA.
GROWTH HORMONE SECRETION RESPONDS TO THE BLOOD
GLUCOSE LEVEL--- HYPERGLYCAEMIA SUPPRESSES, AND
HYPOGLYCAEMIA STIMULATES SECRETION.
 DIABETES MELLITUS
-IS A GROUP OF CHRONIC HETEROGENEOUS METABOLIC DISORDERS CHARACTERIZED BY
HYPERGLYCEMIA WITH DISTURBANCES OF CARBOHYDRATE, FAT AND PROTEIN
METABOLISM.
- IT RESULTS FROM DEFECTS OF INSULIN SECRETION, INSULIN ACTION OR BOTH.
-IT IS OFTEN ACCOMPANIED BY SPECIFIC MICROVASCULAR (RETINA, RENAL,
PERIPHERAL NERVES), AND NON-SPECIFIC MACROVASCULAR (CORONARY, CEREBRAL,
PERIPHERAL BLOOD VESSELS) COMPLICATIONS.
 DEFINITIONS

❑ WHO🡪 " A STATE OF CHRONIC HYPERGLYCAEMIA WHICH MAY RESULT FROM ENVIRONMENTAL
AND GENETIC FACTORS OFTEN ACTING JOINTLY "

❑ IN PRACTICAL TERMS 🡪 CELLS ARE STARVING IN A SEA OF GLUCOSE

❑ A COMMON AND COMPLEX MULTI-SYSTEM LEADING TO MANY DEGENERATIVE

COMPLICATIONS

❑ IT’S A METABOLIC DISORDER CHARACTERIZED BY PERSISTENT HYPERGLYCEMIA DUE TO

LACK OR DEFICIENCY IN INSULIN OR BOTH, GENETIC AND ENVIRONMENTAL FACTORS.
IN 2000, ACCORDING TO THE WORLD HEALTH ORGANIZATION, 2.8%
OF THE WORLD POPULATION (I.E AT LEAST 171 MILLION PEOPLE)
SUFFER FROM DIABETES
ITS INCIDENCE IS RAPIDLY INCREASING, AND IT IS ESTIMATED THAT
BY THE YEAR 2030, THIS NUMBER WILL ALMOST DOUBLE
THE GREATEST INCREASE IN PREVALENCE IS, HOWEVER, EXPECTED TO
OCCUR IN ASIA AND AFRICA, WHERE MOST PATIENTS WILL PROBABLY
BE FOUND BY 2030
THE INCREASE IN INCIDENCE IN DEVELOPING COUNTRIES IS BELIEVED
TO BE A FALL-OUT OF URBANIZATION AND LIFESTYLE CHANGES
THIS INCREASE IN INCIDENCE OF DM HAS MAJOR
FAR-REACHING ECONOMIC CONSEQUENCES
THE PREVALENCE OF DM IN NIGERIA IS PUT AT ABOUT 2.2%
DIFFERENCES IN PREVALENCE RATES EXIST IN DIFFERENT
PARTS OF THE COUNTRY;
* PORT-HARCOURT 7.9%
* LAGOS 7.2 %
* IBADAN 1.5%
* JOS 3.1 %

DATA FOR THE ABOVE TOWNS IS FROM THE NATIONAL NON-COMMUNICABLE DISEASE SURVEY(1997) WITH THE EXCEPTION
OF PORT-HARCOURT
 CLASSIFICATION OF DIABETES
MELLITUS
TYPE 1 DIABETES - Β-CELL DESTRUCTION, LEADS TO ABSOLUTE INSULIN
DEFICIENCY
TYPE 2 DIABETES -INSULIN RESISTANCE WITH RELATIVE INSULIN DEFICIENCY
GESTATIONAL DIABETES MELLITUS
OTHERS
GENETIC DEFECTS OF Β-CELL FUNCTION
GENETIC DEFECTS IN INSULIN PROCESSING OR INSULIN ACTION
EXOCRINE PANCREATIC DEFECTS
ENDOCRINOPATHIES
INFECTIONS
DRUGS
GENETIC SYNDROMES ASSOCIATED WITH DIABETES
 TYPE 1

- AUTO-IMMUNE DISEASE
- CONSTITUTES 5-10% OF DM
- MOSTLY APPEARS IN CHILDREN AND YOUNG ADULTS
- DEVELOPS AS A RESULT OF AUTO-IMMUNE DESTRUCTION OF BETA-CELLS
IN THE PANCREAS
- PRESENTS WITH POLYURIA, THIRST, WEIGHT LOSS, MARKED FATIGUE
CAN BE COMPLICATED BY COMA WITH KETOACIDOSIS
PATHOGENESIS OF TYPE 1 DIABETES
MELLITUS
AUTOIMMUNE DISEASE IN WHICH ISLET DESTRUCTION IS CAUSED PRIMARILY
BY T LYMPHOCYTES REACTING AGAINST AS YET POORLY DEFINED Β-CELL
ANTIGENS, RESULTING IN A REDUCTION IN Β-CELL MASS
GENETIC SUSCEPTIBILITY AND ENVIRONMENTAL INFLUENCES PLAY
IMPORTANT ROLES IN THE PATHOGENESIS.
MOST COMMONLY DEVELOPS IN CHILDHOOD, BECOMES MANIFEST AT
PUBERTY, AND IS PROGRESSIVE WITH AGE.
MOST INDIVIDUALS WITH TYPE 1 DIABETES DEPEND ON EXOGENOUS INSULIN
SUPPLEMENTATION FOR SURVIVAL, AND WITHOUT INSULIN, THEY DEVELOP
SERIOUS METABOLIC COMPLICATIONS SUCH AS ACUTE KETOACIDOSIS AND
COMA.
COMPLEX PATTERN OF GENETIC ASSOCIATION
THE PRINCIPAL SUSCEPTIBILITY LOCUS FOR TYPE 1 DIABETES RESIDES IN THE
REGION THAT ENCODES THE CLASS II MHC MOLECULES ON CHROMOSOME
6P21 (HLA-D).
BETWEEN 90% AND 95% - HLA-DR3, OR DR4, OR BOTH,
ALSO EVIDENCE TO SUGGEST THAT ENVIRONMENTAL FACTORS, ESPECIALLY
INFECTIONS, - VIRUSES MAY BE AN INITIATING TRIGGER, -MOLECULAR MINICRY
 TYPE 2

MOST COMMON FORM OF DIABETES

INVOLVES ABOUT 90-95% OF PEOPLE WITH DM
ASSOCIATED WITH:
◦ OLDER AGE
◦ OBESITY
◦ FAMILY HISTORY OF DM
◦ PRIOR HISTORY OF GESTATIONAL DIABETES
◦ PHYSICAL INACTIVITY
◦ ETHNICITY
PATIENT WITH TYPE II DM USUALLY MAKES ENOUGH
INSULIN BUT THE BODY CANNOT USE IT EFFECTIVELY =>
INSULIN RESISTANCE
GRADUALLY INSULIN PRODUCTION DECREASES OVER THE
FOLLOWING YEARS
SYMPTOMS ARE SIMILAR TO TYPE I BUT DEVELOP MORE
GRADUALLY
PATHOGENESIS OF TYPE 2 DIABETES
MELLITUS
PATHOGENESIS OF TYPE 2 DIABETES REMAINS ENIGMATIC. ENVIRONMENTAL
INFLUENCES, SUCH AS A SEDENTARY LIFE STYLE AND DIETARY HABITS,
CLEARLY HAVE A ROLE,

NEVERTHELESS, GENETIC FACTORS ARE EVEN MORE IMPORTANT THAN IN TYPE

1 DIABETES,

AMONG IDENTICAL TWINS, THE CONCORDANCE RATE IS 50% TO 90%, WHILE

AMONG FIRST-DEGREE RELATIVES WITH TYPE 2 DIABETES (INCLUDING
FRATERNAL TWINS) THE RISK OF DEVELOPING THE DISEASE IS 20% TO 40%
 Β-CELL DYSFUNCTION

IN TYPE 2 DIABETES, Β CELLS SEEMINGLY EXHAUST THEIR

CAPACITY TO ADAPT TO THE LONG-TERM DEMANDS OF
PERIPHERAL INSULIN RESISTANCE.
IN STATES OF INSULIN RESISTANCE LIKE OBESITY, INSULIN
SECRETION IS INITIALLY HIGHER FOR EACH LEVEL OF
GLUCOSE THAN IN CONTROLS.
THIS HYPERINSULINEMIC STATE IS A COMPENSATION FOR
PERIPHERAL RESISTANCE AND CAN OFTEN MAINTAIN
NORMAL PLASMA GLUCOSE FOR YEARS. EVENTUALLY,
HOWEVER, Β-CELL COMPENSATION BECOMES INADEQUATE,
AND THERE IS PROGRESSION TO HYPERGLYCEMIA.
THE TWO METABOLIC DEFECTS THAT CHARACTERIZE TYPE
2 DIABETES ARE:
(1) A DECREASED ABILITY OF PERIPHERAL TISSUES TO
RESPOND TO INSULIN (INSULIN RESISTANCE) AND
(2) Β-CELL DYSFUNCTION THAT IS MANIFESTED AS
INADEQUATE INSULIN SECRETION IN THE FACE OF INSULIN
RESISTANCE AND HYPERGLYCEMIA.
IN MOST CASES, INSULIN RESISTANCE IS THE PRIMARY
EVENT AND IS FOLLOWED BY INCREASING DEGREES OF
Β-CELL DYSFUNCTION.
GESTATIONAL DIABETES MELLITUS

DEFINED AS- HYPERGLYCEMIA DIAGNOSED DURING PREGNANCY

OCCURS IN 2-5% OF PREGNANCIES
OCCURS DUE TO PLACENTAL HORMONE CHANGES THAT EFFECT
INSULIN FUNCTION (GREATER RESISTANCE)
SCREENING USUALLY OCCURS DURING THE 24TH-28TH WEEK IN HIGH
RISK PATIENTS
CRITERIA FOR DIAGNOSIS IS DIFFERENT THAN FOR TYPE 1 AND TYPE 2
DIETARY CHANGES ARE INITIAL TREATMENT AND INSULIN IS THE ONLY
BG LOWERING AGENT USED
POSTPARTUM BG LEVELS USUALLY RETURN TO NORMAL
INCREASED RISK FOR TYPE 2 DIABETES (30-50%)
 OTHERS

• GENETIC DISEASES OF Β-CELL DYSFUNCTION 🡪 MATURITY-ONSET DIABETES OF THE YOUNG

(MODY)
• GENETIC DISEASES ASSOCIATED WITH DIABETES 🡪 WILSON’S DISEASE, HAEMOCHROMATOSIS
• GENETIC DISEASES OF INSULIN ACTION
• DISEASES OF EXOCRINE PANCREAS 🡪 CHRONIC OR ACUTE PANCREATITIS, SURGICAL
RESECTION
• ENDOCRINOPATHIES 🡪 CUSHING’S SYNDROME, PHAEOCHROMOCYTOMA, ACROMEGALY
• DRUGS 🡪 CORTICOSTEROIDS, THIAZIDE/FRUSEMIDE, DIAZOXIDE, ORAL CONTRACEPTIVES
GENETIC DEFECTS OF Β-CELL FUNCTION
MATURITY-ONSET DIABETES OF THE YOUNG (MODY) CAUSED BY MUTATIONS IN:
HEPATOCYTE NUCLEAR FACTOR 4Α (HNF4A), MODY1
GLUCOKINASE (GCK), MODY2
HEPATOCYTE NUCLEAR FACTOR 1Α (HNF1A), MODY3
PANCREATIC AND DUODENAL HOMEOBOX 1 (PDX1), MODY4
HEPATOCYTE NUCLEAR FACTOR 1Β (HNF1B), MODY5
NEUROGENIC DIFFERENTIATION FACTOR 1 (NEUROD1), MODY6
-NEONATAL DIABETES (ACTIVATING MUTATIONS IN KCNJ11 AND ABCC8,
ENCODING KIR6.2 AND SUR1, RESPECTIVELY) MATERNALLY INHERITED
DIABETES AND DEAFNESS (MIDD) DUE TO MITOCHONDRIAL DNA MUTATIONS
(M.3243A➙G) DEFECTS IN PROINSULIN CONVERSION INSULIN GENE
MUTATIONS
MATURITY ONSET DIABETES OF YOUNG
{MODY }
INSULIN SECRETORY DEFECT WITHOUT BETA CELL LOSS
AUTOSOMAL DOMINANT INHERITANCE WITH HIGH
PENETRANCE
EARLY ONSET BEFORE 25
IMPAIRED Β - CELL FUNCTION , NORMAL WEIGHT , LACK OF
GAD ANTIBODIES ,
LACK OF INSULIN RESISTANCE SYNDROME
 GENETIC DEFECTS IN INSULIN ACTION

• TYPE A INSULIN RESISTANCE (INSULIN RECEPTOR DEFECT),

• FOR EXAMPLE
• LEPRECHAUNISM,
• LIPOATROPHY
• RABSON-MENDENHALL SYNDROME
EXOCRINE PANCREATIC DEFECTS

CHRONIC PANCREATITIS

PANCREATECTOMY/TRAUMA

NEOPLASIA

CYSTIC FIBROSIS

HEMOCHROMATOSIS

FIBROCALCULOUS PANCREATOPATHY
 ENDOCRINOPATHIES

ACROMEGALY

CUSHING SYNDROME

HYPERTHYROIDISM

PHEOCHROMOCYTOMA

GLUCAGONOMA
 INFECTIONS

CYTOMEGALOVIRUS

COXSACKIE B VIRUS

CONGENITAL RUBELLA
 DRUGS
GLUCOCORTICOIDS

THYROID HORMONE

INTERFERON-Α

PROTEASE INHIBITORS

Β-ADRENERGIC AGONISTS

THIAZIDES

NICOTINIC ACID

PHENYTOIN (DILANTIN) VACOR

 GENETIC SYNDROMES ASSOCIATED
WITH DIABETES
DOWN’S SYNDROME
KLINEFELTER’S SYNDROME
TURNER’S SYNDROME
PRADER-WILLI SYNDROME
 BIOCHEMICAL CHANGES OF DIABETES
MELLITUS
Biochemical changes Causes

Hyperglycaemia ❑ Lack of insulin action

(Please see Figure 1) ❑ Decreased uptake of glucose by peripheral tissues
❑ Increased hepatic glycogenolysis
❑ Increased hepatic gluconeogenesis

Glycosuria ❑ Filtered glucose load exceeds the maximum reabsorption capacity

for glucose in renal tubules

Hypovolaemia and ❑ Excessive loss of body water and sodium as urine due to glucose
Hyperosmolality acting as an osmotic diuretic
❑ Hence leading to polyuria, dehydration and thirst sensation
 BIOCHEMICAL CHANGES OF DIABETES

Ketoacidosis ❑
MELLITUS
Unopposed lipolysis due to insulin deficiency
(Increased anion gap) ❑ Increased β-oxidation of adipose tissue derived fatty acids in liver
❑ Raised hepatic acetyl-CoA concentration and ketone body synthesis

Ketonuria ❑ Filtered ketone load exceeds the maximum reabsorption capacity

for ketone in renal tubules

Lactic acidosis ❑ Cells are starving 🡪 Glycolysis

(Increased anion gap) ❑ Dehydration 🡪 Anaerobic respiration 🡪 Glycolysis
❑ Pyruvate is turned into lactate to regenerate NAD+ for further
glycolysis
 BIOCHEMICAL CHANGES OF DIABETES
MELLITUS
Hypertriglyceridaemia ❑ Increased synthesis of triglyceride in liver and hence VLDL
synthesis

Hyponatraemia ❑ Loss of body sodium in excess of water as a result of

glucose-induced osmotic diuresis
❑ Raised plasma osmolality which will draw water from cells into
extracellular fluid diluting ECF sodium concentration
❑ Adjusted Na = Na + 1/3 x Glucose
❑ Pseudo-hyponatraemia due to increased plasma solutes such as
lipids (only occur in some analysers)

Hypernatraemia ❑ Water depletion in excess of sodium

 BIOCHEMICAL CHANGES OF DIABETES
MELLITUS
Renal impairment ❑ Dehydration
❑ Nephropathy

Hyperkalaemia ❑ Decreased entry into cells due to acidosis and insulin deficiency
(Decreased total body K+) ❑ Hyperphosphataemia due to decreased cellular uptake

Other analytes ❑ Falsely high values can be obtained due to haemoconcentration

 CLINICAL SYMPTOMS OF DIABETES MELLITUS
Symptoms Causes

Polyuria and nocturia ❑ Retention of glucose in renal tubule as glucose load exceeds the absorptive
capacity
❑ Glucose acts as an osmotic diuretic causing the production of large volumes of
urine

Thirst ❑ CNS driven response to dehydration

❑ May be mediated by angiotensin production in response to hypovolaemia

Polyphagia ❑ Hunger stimulated by non-utilization of dietary glucose

 CLINICAL SYMPTOMS OF DIABETES MELLITUS
Weight loss ❑ Increased catabolism of all metabolic fuel stores:
1. Muscle glycogen
2. Proteins
3. Adipose tissue triglyceride
❑ Fluid loss
Weakness ❑ Muscular weakness due to:
1. Proteolysis and mobilization of muscle protein
2. Reduced availability of metabolic substrate
Blurred vision ❑ Systemic dehydration of the aqueous and vitreous humor reducing
visual acuity
 CLINICAL SYMPTOMS OF DIABETES MELLITUS
Vomiting ❑ CNS driven response to ketones stimulating the area postrema in
the floor of the fourth ventricle

Hyperventilation ❑ Respiratory compensation to metabolic acidosis (raised lactate and

(Kussmaul breathing) ketoacids in plasma)
 LABORATORY INVESTIGATIONS OF DM

• THE LAB’S ROLE IN THE MANAGEMENT OF DM IS

• SCREENING
• DIAGNOSING
• TREATMENT
• MONITORING OF
• TREATMENT
• COMPLICATIONS
 LABORATORY INVESTIGATIONS OF DM

• FASTING PLASMA GLUCOSE

• RANDOM PLASMA GLUCOSE
• 2 HOURS POSTPRANDIAL GLUCOSE/ OGTT
• GLYCATED HAEMOGLOBIN ESTIMATION
• FRUCTOSAMINE ESTIMATION
• TYROID PROFILE
• LIPID PROFILE
• FULL BLOOD COUNT
• CARDIAC MARKERS
• ELECTROLYTE/UREA/CRETININE
• LIVER FUNTION TEST
• HOMONE PROFILE
 DIAGNOSIS AND MONITORING OF DIABETES
MELLITUS
• BACKGROUND INFORMATION

• SECONDARY CAUSES SHOULD ALWAYS BE EXCLUDED FIRST.

• FOR PATIENT WITH SYMPTOMS OF DIABETES, A RANDOM GLUCOSE LEVEL > 11.1 MMOL/L IS
DIAGNOSTIC.

• TEST SHOULD BE REPEATED OR FASTING GLUCOSE LEVEL IS PREFERABLY PERFORMED AND

FOLLOWED BY ORAL GLUCOSE TOLERANCE TEST (OGTT) WHEN RESULT IS IN DOUBT

• IF THE INITIAL GLUCOSE LEVEL IS VERY HIGH, DO NOT SEND THE PATIENT FOR OGTT AS IT
COULD INDUCE LIFE-THREATENING HYPERGLYCAEMIA.
 DIAGNOSIS AND MONITORING OF DIABETES
MELLITUS
Diagnosis Plasma venous glucose level in mmol/L
WHO
Normal ❑ Fasting glucose < 6.1mmol/l
❑ 2 hr post glucose load <
7.0mmol/l
Diabetes Mellitus (DM) ❑ Fasting glucose > 7.0 or
❑ 2 hr post glucose load ≥ 11.1 or
both
Impaired Glucose Tolerance ❑ Fasting glucose < 7.0 if
(IGT) measured
Impaired Fasting Glycaemia ❑ This category is of unknown significance and is not present in
(IFG) WHO’s criteria

Gestational Diabetes ❑ 75 gram OGTT performed at 24 to 28 weeks of gestation

Mellitus (GDM) ❑ Glucose levels of fasting (<5.3), 1 hr (<10) and 2 hr (<8.6) used
❑ 2 or more abnormal values are diagnostic
❑ OGTT should be performed again at 6 to 12 weeks post partum to
exclude any underlying diabetes
repare a patient for OGTT

OGTT PREPARATION
Diet ❑ No special dieting before testing
❑ Fast at least for 10 hours the night before testing

Physical Activity ❑ Rest for at least 30 minutes before testing

State of Health ❑ No inter-current illness or infections should be present

Drugs ❑ Steroids, oral contraceptives, diuretics, thyroid hormones,

smoking, nicotinic acid, diazoxide, etc
 OGTT

Glucose Load ❑ A standard 75gm glucose load is used

❑ For children, a 1.75gm per kg of body weight glucose load can
be used with a maximum of 75gm

Sampling Procedure ❑ Glucose levels at fasting and 2 hour post glucose load are
recommended
Blood Collection ❑ Specimens should be put into fluoride bottle immediately after
collection and labelling
❑ Indicate clearly the timing of specimens collection
GLYCOSYLATED HAEMOGLOBIN (HAEMOGLOBIN A1C)

CHRONIC HYPERGLYCAEMIA IS ASSOCIATED WITH NON-ENZYMATIC

CONDENSATION OF GLUCOSE WITH FREE AMINO GROUPS OF BASIC AMINO ACIDS
ON THE GLOBIN CHAINS OF HAEMOGLOBIN.

THE MAJOR FORM OF THIS COMPLEX IS HAEMOGLOBIN A1C WHICH COMPRISES

4-6% OF THE TOTAL HAEMOGLOBIN.

THE SYNTHESIS OF HAEMOGLOBIN A1C IS A TWO-STEP PROCESS WITH INITIAL

FORMATION OF AN ALDIMINE OR SCHIFF BASE (LABILE PRE-A1C COMPONENT)
WHICH THEN UNDERGOES MOLECULAR REARRANGEMENT TO FORM THE STABLE
KETOAMINE.
HEMOGLOBIN A1C LEVELS IN EXCESS OF 6% INDICATE CHRONIC
HYPERGLYCAEMIA AND THE HIGHER THE PREVAILING GLUCOSE LEVEL, THE
HIGHER THIS PERCENTAGE WILL BE.

HENCE IT HAS BEEN FOUND TO BE A USEFUL ANALYTE IN THE

EVALUATION OF THE EFFICACY OF DIABETIC THERAPY, E.G.,

TO JUDGE THE DEGREE OF CHRONIC GLUCOSE CONTROL IN BOTH TYPE I

AND TYPE II DIABETIC PATIENTS, ESPECIALLY THOSE WHO ARE
NON-COMPLIANT OR UNCOOPERATIVE.
TO OBTAIN INFORMATION ON CHRONIC DIABETIC CONTROL DURING
INTERCURRENT ILLNESS

TO MONITOR THE EFFICACY OF CHANGES IN THERAPY

TO DIFFERENTIATE TRANSIENT GLUCOSE INTOLERANCE ASSOCIATED WITH

STRESS (E.G., POST-SURGICAL STRESS) FROM PREVIOUSLY UNRECOGNIZED
DIABETES.

TO IDENTIFY INSULIN-TREATED SUBJECTS AT HIGHER RISK FOR

HYPOGLYCAEMIA.
SINCE THE LIFE SPAN OF RED CELLS IS AROUND 120 DAYS
THE GLYCOSYLATED HAEMOGLOBIN LEVEL REFLECTS THE
STATE OF GLYCAEMIA OVER THE PREVIOUS 8-12 WEEKS;

THUS, MEASUREMENTS SHOULD BE MADE AT 2-3 MONTH

INTERVALS TO MONITOR THE PATIENT’S PROGRESS.
WELL-CONTROLLED DIABETIC USUALLY HAVE VALUES
WHICH ARE SLIGHTLY HIGHER THAN THE UPPER LIMIT OF
THE REFERENCE RANGE; THOSE WITH VALUES FALLING
WITHIN THE REFERENCE INTERVAL MAY EXPERIENCE MORE
FREQUENT EPISODES OF HYPOGLYCAEMIA.

THOSE CONDITIONS WITH SHORTENED RED CELL SURVIVAL

TIMES SUCH AS HAEMOLYTIC ANAEMIAS, PREGNANCY,
AND REPEATED PHLEBOTOMY, MAY PRODUCE DECREASED
VALUES.
HBA1C IS THE GOLD STANDARD
SMBG( SELF MONITORING BLOOD GLUCOSE) IS AN INTEGRAL COMPONENT OF
DIABETES MANAGEMENT – EXPERT CONSENSUS
ALL TREATMENT DECISIONS FOR TYPE 2 DIABETICS SHOULD BE BASED ON A1C
LEVELS
● CHECK A1C AT LEAST TWICE EACH YEAR IN ALL PATIENTS
SMBG (SELF MONITORING OF BLOOD GLUCOSE) IS EXTREMELY VALUABLE IN
TAILORING THERAPY TO A SPECIFIC PATIENT
 GLYCEMIC CONTROL

HBA1C < 6% - NORMAL.

HBA1C < 7% - GOAL.
HBA1C 7.0 - 7.5% - GOOD CONTROL.
HBA1C > 7.5% - ADDITIONAL THERAPY

HGA1C EVERY 3 MONTHS UNTIL AT GOAL THEN EVERY 6 MONTHS.

 SERUM FRUCTOSAMINE

NON-ENZYMATIC GLYCOSYLATION OF SERUM PROTEINS

(MAINLY ALBUMIN)
CAN BE ESTIMATED AS SERUM FRUCTOSAMINE WHICH HAS A
SIMILAR APPLICATION IN DIABETES MELLITUS TO THAT OF THE
GLYCOSYLATED HAEMOGLOBIN.
HOWEVER, ALBUMIN HAS A SHORTER HALF-LIFE (ABOUT 20
DAYS) THAN RED CELLS AND FRUCTOSAMINE ONLY REFLECTS
THE GLYCAEMIC STATUS OVER THE PAST 2-3 WEEKS.
NORMAL VALUES ARE OF THE ORDER OF 1.5-2.5 MMOI/L.
THE TEST IS SENSITIVE TO VARIATIONS IN SPECIFIC
PROTEINS, E.G., IN PATIENTS RECEIVING ONLY PARENTAL
NUTRITION, THE RESULT FLUCTUATE WIDELY DESPITE
STABLE PLASMA GLUCOSE LEVELS.
THERE IS A 1.3% INCREASE IN FRUCTOSAMINE FOR EVERY 3
G/L INCREASE IN SERUM PROTEIN CONCENTRATION.
SEVERE HYPOPROTEINAEMIC STATES (SERUM ALBUMIN <30
G/L) MAY FALSELY LOWER SERUM FRUCTOSAMINE VALUES.
 URINARY MICRO ALBUMIN

MICROALBUMINURIA (SMALL AMOUNTS OF ALBUMIN, NOT

SMALL MOLECULES) IS DEFINED AS SMALL ELEVATIONS OF
URINARY ALBUMIN EXCRETION NOT DETECTED BY
CONVENTIONAL MEANS.
IN DIABETES MELLITUS AN ELEVATED ALBUMIN EXCRETION
RATE (AER) IS ASSOCIATED WITH OTHER COMPLICATIONS SUCH
AS ELEVATED ARTERIAL PRESSURE, PROLIFERATIVE
RETINOPATHY, LIPOPROTEIN ABNORMALITIES, AND IS
PREDICTIVE OF INSIDIOUS DEVELOPMENT OF DIABETIC
NEPHROPATHY, WHICH WILL ONLY BE CLINICALLY APPARENT
AT A LATER STAGE.
THE TEST CAN BE PERFORMED ON A RANDOM SPOT URINE
BUT AN OVERNIGHT TIMED COLLECTION, TO DETERMINE
THE AER, IS THE PREFERRED METHOD BECAUSE THERE IS A
DRAMATIC INCREASE IN AER IN DIABETICS ON EXERTION
OR EXERCISE.
HOWEVER, ESTIMATION OF THE ALBUMIN: CREATININE
RATIO ON THE FIRST MORNING URINE SAMPLE IS ALSO A
USEFUL PROCEDURE.
NORMAL VALUES IN ADULT URINES ARE:

ALBUMIN CONCENTRATION: <20 MG/ML

ALBUMIN: CREATININE (MG/ML:MMOI/L) RATIO: <3.5
ALBUMIN EXCRETION RATE (AER): <15 MG/MIN

AERS GREATER THAN 20 MG/MIN ARE CONSIDERED

ABNORMAL AND VALUES IN EXCESS OF 30 MG/MIN ARE
PREDICTIVE OF SUBSEQUENT RENAL FAILURE AND
CORRELATE WITH INCREASED BLOOD PRESSURE.
DIABETIC COMPLICATIONS (MMM)
DIABETIC COMPLICATIONS (HDHDL)
 DIABETIC COMPLICATIONS

❑ OTHER COMPLICATIONS

1. ADIPOSE HYPERTROPHY DUE TO REPEATED INSULIN INJECTION

2. CATARACT
 DIABETIC KETOACIDOSIS

❑ OCCUR IN POORLY CONTROLLED TYPE 1 DIABETICS

❑ USUALLY NOT SEEN IN TYPE 2 DIABETICS DUE TO INSULIN SUPPRESSION OF

LIPOLYSIS

❑ USUALLY PRECIPITATED BY MISSED INSULIN INJECTION WITH OR WITHOUT

CONCURRENT ILLNESS (CAN BE "TRIVIAL" VIRAL INFECTION)
 DIABETIC KETOACIDOSIS
❑ BIOCHEMICAL DISTURBANCES & CLINICAL FEATURES CAN BE DEDUCED FROM ABOVE
DISCUSSIONS

1. CHANGE IN MENTAL STATE TO DROWSINESS AND COMA

2. GLYCOSURIA 🡪 FLUID AND ELECTROLYTES DEPLETION DUE TO OSMOTIC DIURESIS

• 🡪 THIRST

🡪 POLYURIA

• 🡪 FEATURES OF FLUID DEPLETION

 DIABETIC KETOACIDOSIS

1. KETOACIDOSIS

🡪 HIGH ANION GAP METABOLIC ACIDOSIS

• 🡪 KUSSMAUL BREATHING

• 🡪 HYPERKALAEMIA, HYPERPHOSPHATAEMIA

• 🡪 KETONURIA
❑ INVESTIGATION

❑ 🡪🡪 PLASMA GLUCOSE, URINE KETONES, RENAL FUNCTION TEST, ARTERIAL BLOOD GASE

❑ TREATMENT

❑ 🡪🡪 INSULIN, FLUID REPLACEMENT, CORRECTION OF ELECTROLYTE DISTURBANCES, TRE

• 🡪 BICARBONATE INFUSION SHOULD BE CAUTIOUS

 HYPEROSMOLAR NON-KETOTIC COMA
❑ MORE COMMON IN ELDERLY TYPE 2 DIABETIC PATIENTS

❑ CHARACTERIZED WITH MARKED HYPERGLYCAEMIA

❑ NO KETOACIDOSIS (BICARBONATE LEVEL USUALLY NORMAL OR MILDLY DECREASED)

❑ PLASMA OSMOLALITY IS GENERALLY > 360 MOSM/KG

❑ PATHOGENESIS IS NOT YET CLEAR

 DYSLIPIDEMIA

❑ HYPERTRIGLYCERIDAEMIA IS VERY COMMON IN DIABETICS (PART OF THE METABOLIC SYNDROME)

❑ CONTROL OF DIABETES IS UNLIKELY TO BE HELPFUL IN IMPROVING DYSLIPIDAEMIA

❑ ASSOCIATED WITH LOW HIGH DENSITY LIPOPROTEIN CHOLESTEROL (HDL-C) LEVEL WHICH IS A
NEGATIVE RISK FACTOR FOR CORONARY HEART DISEASE

❑ PRESENT TREND IS TO TREAT IF THERE ARE ASSOCIATED RISK FACTORS SUCH AS HYPERTENSION,
FAMILY HISTORY OF IHD, ETC

❑ PATHOGENESIS 🡪 INCREASED SYNTHESIS OF TRIGLYCERIDE IN LIVER AND HENCE VLDL SYNTHESIS

DIABETES MELLITUS PREVENTION

PREVENTION OF EFFECTS: COMBINATION APPROACH

◦ INCREASED EXERCISE
● DECREASES NEED FOR INSULIN

◦ REDUCE CALORIE INTAKE

● IMPROVES INSULIN SENSITIVITY

◦ WEIGHT REDUCTION
● IMPROVES INSULIN ACTION
TRIAD OF TREATMENT
• THANKS FOR LISTENING