DISORDERS OF

CARBOHYDRATE 1
(Hyperglycemia and Diabetes Mellitus)
REGULATION OF BLOOD GLUCOSE
CONCENTRATION
Blood glucose is regulated by a complex
interplay of multiple pathways, controlled
by several hormones.
Glycogenesis
Glycogenolysis
Gluconeogenesis
Glycolysis ―› Krebs cycle ―› Oxidative
Phosphorylation
Hexosemonophosphate shunt
 HORMONAL REGULATION
INSULIN
COUNTERREGULATORY HORMONES
 GLUCAGON
 EPINEPHRINE
 CORTISOL
 GROWTH HORMONE
OTHERS
Thyroxine- indirectly influence
Somatostatin (GHIH)- inhibits GH,
Insulin and glucagon secretion
 DIABETES MELLITUS
DEFINITION
Diabetes mellitus is a group of metabolic
diseases charaterised by hyperglycaemia
resulting from defects in insulin secretion,
insulin action or both.
The subsequent chronic hyperglycaemia is
associated with long term damage, dysfunction
and failure of various organs especially the
eyes, kidneys, nerves, heart and blood vessels.
 EPIDEMIOLOGY
World-wide prevalence of Type 2 300m
(2025)
¼ Caucasian have IGT/dysmetabolic
syndrome (prediabetes)
Type 2 now in children and adults
Nigerian prevalence approx. 2.2%
IDF 5th edition 2012 4.83%
 CLASSIFICATION OF DM
 Type 1 Diabetes (complete insulin deficiency due
to ß-cell destruction)
 A: Immune-mediated
 B: Idiopathic
 Type 2 Diabetes (ranging from predominantly
insulin deficient to predominantly insulin resistant;
most affected individuals have some degree of both
components; the use of insulin in a Type 2 patient does
NOT reclassify that patient as a Type 1)
 Other specific types (Secondary Diabetes)
 Genetic defects in ß-cell function
 Maturity-onset Diabetes of Youth (MODY 1-9)
 Genetic defects in insulin action
 Exocrine pancreatic diseases. Eg (pancreatitis,
pancreatectomy)
 Other endocrinopathies eg (Cushing’s, acromegaly,
pheochromocytoma, glucagonoma, thyrotoxicosis, others
 Drug/chemical-induced eg steroids, diazoxide,
thiazides, L-asparaginase,
 Infections eg. congenital rubella, CMV, others
 Uncommon forms of immune-mediated diabetes (“Stiff-man”
syndrome, anti-insulin receptor antibodies, others)
 Other genetic syndromes. Down, Klinefelter’s, Turner’s,
Prader-Willi, Laurence-Moon-Biedl, Friedreich’s ataxia,
Huntington’s chorea, myotonic dystrophy, porphyria, others

 Gestational Diabetes Mellitus (GDM)

 Impaired Glucose Tolerance (IGT)
 Impaired Fasting Glucose (IFG)
 CLASSIFICATION contd
Type 1 diabetes
Immune mediated diabetes: Cellular –mediated
autoimmune destruction of B cells of the pancreas
Markers include:
 islet cell autoantibodies (ICAs)
 Autoantibodies to insulin (IAAs)
 Autoantibodies to glutamic acid dehycarboxylase (anti-
GAD65)
Type 1 contd.

 Auto antibodies to tyrosine phosphatases

1A-1; 1A-2ß
 HLA associations with linkage to DQA, and
B genes and the DRB genes
 Very late manifestation
- absence of C-peptide
 Type 1 contd.
IDIOPATHIC TYPE 1 DIABETES

Minority of cases of Type 1

No auto immune markers.
Strongly inherited
No HLA associations
usually in children, ketoacidosis prone
increased in adolescents
TYPE 2 DIABETES

There is insulin resistance with relative

insulin, but NOT ABSOLUTE deficiency.
Often goes undiagnosed for many years
Auto-immune destruction does not occur.
Not ketosis prone
Patients at increased risk with an increase in
age, obesity and lack of physical activity.
Strong complex genetic predisposition.
GESTATIONAL DIABETES MELLITUS
Any degree of glucose intolerance with
onset or first recognition during pregnancy.
Diabetic women who became pregnant are
not included.
At risk of developing DM subsequently
Definition applies regardless of mode of
therapy or whether it persists after
pregnancy.
DIAGNOSTIC CRITERIA FOR DIABETES
MELLITUS (ADA)
1. Symptoms of diabetes plus casual plasma
glucose concentration> 200mg/dl
(11.1mmol/L)

Casual is defined as anytime of day without

regard to time since last meal.
OR
2. FPG > 126mg/dl (7.0mmol/L). Fasting is
defined as no caloric intake for at least 8hr
 OR
3. 2-h. PG > 200mg/dl (11.1mmol/L) during an
OGTT (using 75g anhydrous glucose
dissolved
300ml of water)

** In the absence of unequivocal hyperglycemia,

with acute metabolic decompensation, the
criteria should be confirmed by repeat testing
on a different day.
***What about glycosuria?
Impaired Fasting Glucose & Impaired glucose tolerance
refer to a metabolic stage intermediate between normal
glucose homeostasis and diabetes ie prediabetes
IFG = FPG >110mg/dl/(6.1)mmol/L - <126 mg/dl
(7.0mmol/L)
Upper limit of normal fasting plasma glucose
=109mg/dl(6.1mmol/L)
IGT = FPG < 126mg/dl (7.0mmol/l)
2h PG(Post load) >140(7.8mmol/L) and <200mg/dl
(11.1mmo/L)
Table 1. Values for diagnosis of diabetes mellitus and other categories of
hyperglycaemia

Glucose concentration, mmol/L (mg/dL)

Whole blood Plasma

Venous Capillary
Venous
Diabetes Mellitus:
Fasting >6.1 (>110) >6.1 (>110) >7.0 (>126)
or
2-h post glucose load >10.0 (>180) >11.1 (> 200) >11.1 (> 200)
or both
Impaired Glucose Tolerance (IGT):
Fasting (if measured) < 6.1 (< 110) < 6.1 (< 110) < 7.0 (< 126)
and
2-h post glucose load > 6.7 (>120) and >7.8 (>140) and ≥7.8 (≥ 140)
< 10.0 (< 180) < 11.1 (< 200) < 11.1 (< 200)

Impaired Fasting Glycaemia (IFG):

Fasting >5.6 (>100) and 5.6 (>100) and >6.1 (>110)and
< 6.1 (< 110) < 6.1 (< 110) < 7.0 (< 126)
and (if measured)
2-h post glucose load < 6.7 (< 120) < 7.8 (< 140) < 7.8 (< 140)
 CLINICAL FEATURES
Polyuria (excessive urine production),
Polydipsia (excessive thirst),
Polyphagia (increased food intake),
rapid weight loss, mental confusion,
and possible loss of consciousness (due
to increased glucose to brain).
 METABOLIC FEATURES
Hyperglycaemia and glycosuria
Increased urine specific gravity
Increased serum and urine osmolality
ketonemia and ketonuria
Decreased blood and urine pH
(acidosis)
Electrolyte imbalance
 COMPLICATIONS
 ACUTE
Diabetic ketoacidosis (DKA)
Hyperosmolar non ketotic coma (HONK)
Hypoglycaemia
 CHRONIC
Diabetic Neuropathy
Diabetic Nephropathy
Diabetic Retinopathy
Diabetic foot
Metabolic Syndrome
ACUTE COMPLICATIONS
HYPOGLYCAEMIA
Varies from FPG 40-70mg/dl depending
on previous long clinical symptom and
cognitive ability

Causes: Errors from care providers

Altered pharmakinetics of drugs
change in drug sensitivity
inadequate carbohydrate
 DIABETIC KETOACIDOSIS
Usually precipitated by infection or vomiting
Insulin deficiency leads to:
 Switch from hepatic glycolysis to gluconeogenesis
and glycogenolysis with consequent hyperglycaemia
Unrestrained lipolysis  NEFA to liver
Switch from NEFA re-esterification to oxidation 
Ketone bodies (3 hydoxybutyrate + acetoacetate. &
acetone
Kussmaul kien (deep)respiration
 laboratory findings
Hyperglycaemia
Metabolic acidosis with  anion gap
Ketonemia
Electrolyte changes:
 Total body deficit of water (5-8litres);,
K+(300-1000mmol), Na (400-700mmol)
 Hypomagnesaemia,
Hypophosphataemia
Hyperkalaemia 20 to acidosis
Low plasma Bicarbonate
MONITORING OF DM

BLOOD (Plasma, serum)

GLYCEMIA
Glycated proteins: HBA1c & Fructosamine
ELECTROLYTES ( Na, K, PO4,) and UREA
Creatinine
Acid Base Status: Blood pH, HCO3
Evaluation of complications (RFT, Lipids)
URINE
Glycosuria
Urinary albumin (Microalbuminuria)
Albumin:creatinine ratio (ACR)
Ketones
 HYPEROSMOLAR NON KETOTIC
COMA (HONK)

Opposite ends of a spectrum with DKA

Insulin is relative and not absolute
Hyperglycaemia is more severe than
DKA
Patient is older
Infection is major ppt. Cause
Pathophysiology:

Marked hyperglycaemia/hyperosmolality
Minor ketosis and acidosis

Why absent significant ketosis in HONK?

Dehydration and hyperosmolality inhibit

lipolysis and ketogenesis
 CHRONIC COMPLICATIONS
DIABETIC NEPHROPATHY
Macroscopic features
Enlarged kidney - tubular hypertrophy and
hyperplasia. Interstitial expansion

End stage renal disease - small kidney

Pyelonephritis - Renal scarring
Papillary necrosis – common in infection.
Clinical nephropathy
Urinary albumin concentration (UAC) >300mg/l(30mg/dl)
Urinary albumin excretion rate (UAER) >300mg/24 hr
Urinary albumin excretion >500mg/24 hr
Microalbuminuria(Paucialbuminuria)
UAC 30-300 mg/l
UAER 20-200µg/min (timed overnight collection)
30-300 mg/mmol - male
Albumin: Creatinine ratio (ACR) 2.5-25 mg/mmol - male
30-300 mg/g-male
3.5-25 mg/mmol- female
40-300mg/g - female
DIABETIC RETINOPATHY
Microaneurysm, excessive vascular
permeability, vasoobliteration,
proliferation of new vessels and fibrous
tissue.
Contraction of vitreous and fibrous
vascular proliferations
Risk Factors ↑ prolonged hyperglycaemia
PERIPHERAL NEUROPATHY
Diabetic Neuropathy: is a clinical state of
nerve damage in a patient. The patient
complains of symptoms (pains,
paraesthesia) or is shown to have
neurological deficit.

Likely to lead to problems (anaesthetic

foot)
 DIABETIC FOOT
It is infection, ulceration and/or
destruction of deep tissues associated
with neurological abnormalities and
various degrees of peripheral vascular
disease in lower limb
40 - 60% of non traumatic lower limb
diabetic amputations
85% of diabetic lower limb amputations
arise from foot ulcers
4-10% prevalence in diabetic population
 METABOLIC SYNDROME
Insulin resistance and the dysmetabolic
syndrome are closely associated
95% are insulin resistant
It is the genesis of macrovascular disease
complications
Insulin resistance,  hyperinsulinism 
hyperglycaemia of Type 2 DM deleterious
vascular changes  artherosclerosis
progression  myocardial infarction and
stroke
 ASSIGNMENT

WHAT IS OGTT?
What are the indications for it?
Describe the procedure and draw the
different possible OGTT curves