Diabetes Mellitus

(DM)

Prepared by: Kessy Innocent, MD.

 Blood sugar and health
Sugar (glucose) is
an important source Insulin is produced
of energy by the pancreas when
blood sugar is high

What is eaten is
absorbed into Insulin keeps blood
the blood sugar level within
the normal range
for health
What is diabetes?
• Diabetes mellitus (DM) is a group of diseases characte
rized by abnormal high levels of blood glucose resulti
ng from defects in insulin production, insulin action,
or both.
• OR
• diabetes mellitus describes a metabolic disorder of m
ultiple aetiology characterized by chronic hyperglycae
mia with disturbances of carbohydrate, fat and protei
n metabolism resulting from defects in insulin secreti
on, insulin action, or both.

• The effects of diabetes mellitus include long–term da

mage, dysfunction and failure of various organs.
Symptoms of Diabetes
People with diabetes often have typical complaints (symptom
s): NB- T2D may be asymptomatic for long time.
 Thirst and frequent drinking
 More frequent urination, particularly at night
 Unexplained weight loss
 Fatigue
 Blurred vision
 Frequent infections : skin, genital
Burden of Diabetes
• International Diabetes Federation (IDF) data indicate t
hat by the year 2025, the number of people affected
will reach 333 million –90% of these people will have
Type 2 diabetes.

• In most Western societies, the overall prevalence has r

eached 4-6%, and is as high as 10-12% among 60-70
-year-old people.

• The annual health costs caused by diabetes and its co

mplications account for around 6-12% of all health-c
are expenditure.
Reason for increasing prevalenc
e of type-2 diabetes
The disease is reaching epidemic proportions becaus
e:
 Rates of overweight/obesity have increased
 We have become a physically inactive species
 Our diets are increasingly unhealthy
Types of Diabetes
• Type 1 Diabetes Mellitus
• Type 2 Diabetes Mellitus

• Other types:
 LADA ( latent acquired DM in adults)
 MODY (maturity-onset diabetes of yout
h)
 Secondary Diabetes Mellitus
 Gestational DM
Type 1 diabetes
• Also called insulin-dependent diabetes mellitus (IDDM)
or juvenile-onset diabetes.
• Type 1 diabetes develops when the body’s immune sy
stem destroys pancreatic beta cells, the only cells in th
e body that make the hormone insulin that regulates b
lood glucose (autoimmune related DM).
• Xtics: insulin deficiency.
• This form of diabetes usually strikes children and you
ng adults <30yrs.
• Type 1 diabetes accounts for 5% to 10% of all diagnos
ed cases of diabetes.
• Risk factors for type 1 diabetes may include autoimmu
ne, genetic, and environmental factors.
Type 2 diabetes
 Also called non-insulin-dependent diabetes mellitus (NIDDM) or ad
ult-onset diabetes.
 Type 2 diabetes may account for about 90% to 95% of all diagnosed
cases of diabetes.
 Xtics: insulin resistance, a disorder in which the cells do not use ins
ulin properly.
 - however, later as the need for insulin rises, the pancreas gradually
loses its ability to produce insulin.
 Type 2 diabetes is associated with older age >40yrs, obesity, family
history of diabetes, history of gestational diabetes, impaired glucos
e metabolism, physical inactivity, and race/ethnicity.
 Differences between type-1 and type-2 Diabetes
Mellitus
• TYPE 1 DM
• Young age <30yrs
• Pathophysiology: insulin deficiency
• Normal BMI (not obese)
• No immediate family history
• Short duration of symptoms/ short course of illness over weeks.
• Complications includes diabetic coma (DKA)
• Insulin always required in management

• TYPE 2 DM
• - Older age >40yrs
• - Pathophysiology: insulin resistance
• - obese, physical inactivity + unhealthy diets are risks.
• - +ve family hx (1st degree relative have higher risks)
• - longer duration of symptoms (asymptomatic for long time)
• - complications includes HHS
• - treatment mainly requires oral hypoglycemics, however insulin may be requir
ed in some circumstances.
Other types of DM
• Other specific types of diabetes result from specific
genetic conditions (such as maturity-onset diabetes
of youth), pregnancy, surgery eg pancreatectomy, d
rugs, metabolic syndrome, infections, and other illn
esses.

• Such types of diabetes may account for 1% to 5% of

all diagnosed cases of diabetes.
Gestational diabetes
 A form of glucose intolerance that is diagnosed in some women during pre
gnancy.
 Gestational diabetes occurs more frequently among African Americans, Hi
spanic/Latino Americans, and American Indians. It is also more common a
mong obese women and women with a family history of diabetes.
 During pregnancy, gestational diabetes requires treatment to normalize m
aternal blood glucose levels to avoid complications in the infant.
 After pregnancy, 5% to 10% of women with gestational diabetes are found
to have type 2 diabetes.
 Women who have had gestational diabetes have a 20% to 50% chance of
developing diabetes in the next 5-10 years.
 LADA
• Latent Autoimmune Diabetes in Adults (LADA) is a for
m of autoimmune (type 1 diabetes) which is diagnosed
in individuals who are older than the usual age of onse
t of type 1 diabetes (>30yrs).
• Alternate terms that have been used for "LADA" includ
e Late-onset Autoimmune Diabetes of Adulthood, "Slo
w Onset Type 1" diabetes, and sometimes also "Type 1.
5
• Often, patients with LADA are mistakenly thought to h
ave type 2 diabetes, based on their age at the time of
diagnosis.
LADA (cont.)
• About 80% of adults apparently with recently diagno
sed Type 2 diabetes but with GAD auto-antibodies
(i.e. LADA) progress to insulin requirement within 6
years.

• The potential value of identifying this group at high

risk of progression to insulin dependence includes:
• the avoidance of using metformin treatment
• the early introduction of insulin therapy
MODY
• MODY – Maturity Onset Diabetes of the Young

• MODY is a monogenic form of diabetes with an autosomal

dominant mode of inheritance:
• Mutations in any one of several transcription factors or in the enzy
me glucokinase lead to insufficient insulin release from pancreatic
ß-cells, causing MODY.
• Different subtypes of MODY are identified based on the mutated g
ene.

• Originally, diagnosis of MODY was based on presence of n

on-ketotic hyperglycemia in adolescents or young adults in
conjunction with a family history of diabetes.

• However, genetic testing has shown that MODY can occur a

t any age and that a family history of diabetes is not always
obvious.
Secondary DM
Secondary causes of Diabetes mellitus include:
 Acromegaly,
 Cushing syndrome,
 Thyrotoxicosis,
 Pheochromocytoma
 Glucagonoma (3Ds- Diarrhoea, DM, DVT)
 Chronic pancreatitis,
 Cancer
 Drug induced hyperglycemia:
◦ Atypical Antipsychotics, Beta-blockers, Calcium Channel Blockers, Corticosteroids, Fluoroquinol
ones, Naicin, Phenothiazines, Protease Inhibitors, Thiazide Diuretics.
 Pre-diabetes

 Prediabetes is a term used to distinguish people who a

re at increased risk of developing diabetes. People with
prediabetes have impaired fasting glucose (IFG) or imp
aired glucose tolerance (IGTT) or both.
 Overtime, progression of prediabetic state to DM is ine
vitable unless measures taken ie weight loss, health die
ts and physical activities.
Pre-diabetes FBG: sugar level is elevated 100 to 125mg/d
L after an overnight fast but is not high enough to be cl
assified as diabetes [DM FBG >=126mg/dl or 7mmol/l].

Pre-diabetes GTT: blood sugar level is elevated 140 to 199 mg

/dL after a 2-hour oral glucose tolerance test, but is not hi
gh enough to be classified as diabetes [OGTT >=200mg/dl o
r 11.1mmol/l].

Treatment : life style modifications only.

Diagnosis of Diabetes Mellitu
s
Criteria for the Diagnosis of Diabetes

Hb A1C ≥6.5%
OR
Fasting plasma glucose (FPG)
≥126 mg/dL (7.0 mmol/L)
OR
2-h plasma glucose ≥200 mg/dL
(11.1 mmol/L) during an OGTT
OR
A random plasma glucose ≥200 mg/dL
(11.1 mmol/L)
ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S9; Table 2.1
Diabetes Mellitus- Complication
s
 DM- Complications
Acute complications
• DKA- >>Type 1
• HHS- Type 2
• Hypoglycemia (due to dr
ug effects)
 Chronic complications

• Macro-vascular complications
 IHDs/CHDs
 CVAs
 PVDs
• Micro-vascular complications
 D. retinopathy, cataracts, glaucoma
 D. Nephropathy
 D. Neuropathy (autonomic + peripheral)
• Others:
* immunopathy → Infections
* DM foot
Mechanisms
Genetic susceptibility

*Repeated acute changes

in cellular metabolism

Hyperglycemia Tissue damage

**Cumulative long term

changes in stable
macromolecules

Independent accelerating factors

Mechanisms of Hyperglycaemia Induced Damag
e (3 pathways)
• Polyol pathway – excess glucose is converted to fructose via sorbitol
as intermidiate compound, sorbitol causes tissue damage by oxidativ
e stress.
• protein kinase C pathway: glucose metabolism during glycolysis, lead
s to increase in intermidiate products ie diacylglycerol (DAG) → vascu
lar dysfunction.
• Non enzymatic glycosylation pathway: glucose interacts with reactiv
e amino groups in cellular proteins forming AGES (advanced glycosyla
ted end products) which causes oxidative stress and tissue damage
Macro-vascular Complicatio
ns
 Macro-vascular Complication
s
• Ischemic heart disease
• Cerebrovascular disease
• Peripheral vascular disease
- Diabetic patients have a 2 to 6 times higher risk for dev
elopment of these complications than the general popu
lation.
- Overall life expectancy in diabetic patients is 7 to 10 years shorter than
non-diabetic people.
Note: complications and mortality are more pronounced in pt with both
HTN and DM. DM itself is a risk to develop HTN.
Hypertension in Type 1 and 2 Diabete
s
Type 1 Type 2
• Develop after several yrs • Develop after several ye
of DM ars of DM
• Ultimately affects ~30% • Ultimately affects ~30%
of patients of patients
• HTN occurs secondary to • HTN occurs secondary to
nephropathy insulin resistance
• Activation of the RAAS • Activation of the sympat
hetic NS
Dyslipidaemia in DM
• Most common abnormality is se HDL and se Triglyserides & LDL.
• A low HDL is the most constant predictor of CV disease in DM.
• Target lipid values: LDL <2.6 mmol/l, HDL >1.15 mmol/l, TG < 2.5 mmol/l.
• Treatment involves tight glucose control + lipid lowering medications eg H
MG-CoA reductase inhibitors ie statins.

• Indications of lipid lowering meds:

- T2DM age >40yrs.
- long standing DM >10yrs.
- pre-existing CVDs.
- CKD >=stage 3.
- pt with high CVDs risks.
Micro-vascular Complications
Eye Complications related to DM
• 01. Cataracts

→ Cataract is a non enzymatic glycation of lens protein (opacifica

tion of lens - blindness).
02. Glaucoma
→ glaucoma is the abnormal increase in ocular pressures which r
esults to damage in optic nerve - blindness.
03. Diabetic retinopathy
- DR is the leading cause of blindness in diabetic population. 80-100
% of pt will develop DR after 20yrs.
- Maculopathy is most common in type 2 patients and can cause sev
ere visual loss.
- 4 stages of DR,
Pre-proliferative; micro aneurysms, venous dilatation, cotton wool spots and micro
hemorrhages.
Proliferative; new vessels formation + vitrous hemorrhages.
Advanced diabetic eye disease; retinal detachment and/or tears + neovascular
glaucoma.
Maculopathy; macula edema and ischaemia.
Diabetic Nephropathy (DN)
• Diabetes has become the most common cause of end stage re
nal failure.
• About 20 – 30% of patients with diabetes develop evidence of
nephropathy within 10yrs.
• The prevalence of DN is higher in Black Americans than in Whi
tes.
• Stages of DN-
Stage I: glomerular filtration and kidney hypertrophy.
Stage II: urine albumin excretion <30mg/24hrs.
Stage III: micro-albuminuria 30-300mg/24hrs.
Stage IV: overt nephropathy, albuminuria >300mg/24hrs.
Stage V: ESRD.
NB- albuminuria increases risk of renal damage. (should be treated with RAAS i
nhibitors).
Diabetic Neuropathy
- Sensorimotor neuropathy (acute/chronic): numbness and paraes
thesia with gloves and stockings manner. (effects includes painless u
lcers, charcots arthropathy, callosities).
- Autonomic neuropathy eg orthostatic hypotension, diabetic gastro
pathy (nocturnal diarrhoea), erectile dysfunction.
- Mononeuropathy: eg CN palsies such as IV, VI, VII.
- Proximal motor neuropathy: Amyotrophy – most common proximal ne
uropathy, affects the Quadriceps muscles with weakness and atrophy.
(synonym: Diabetic Femoral radiculo-neuropathy).
Diabetic Amyotrophy
Infections
• The association between diabetes and increased su
sceptibility to infection is due to immunopathies fro
m DM (DM → impaired macrophages function) incr
easing risk for infection and delayed healing.
• Common infections includes pneumonias &TB, fung
al infections, severe UTI, necrotizing fascitis, cholec
ystistis, otitis.
• Risks are reduced with glycemic control.
Diabetes Mellitus
Management
 Initial Evaluation

• Ensure a detailed hx and examination

• Pt diabetic hx (new/known, period of diagnosis, meds and dosage).
• Current complaints.
• Observe for presence of diabetes complications.
• Risk factors for DM and complaints/complications eg poor glycemic
controls.
• Past medical hx.

• Physical examination
- BMI, Blood pressure determination (including orthostatic), Fundoscopic examin
ation, Thyroid palpation, Skin examination (for acanthosis nigricans in T2DM a
nd insulin injection sites).
Palpate for peripheral pulses eg dorsalis pedis R/O PAD.
Determination of proprioception, vibration, and monofilament sensation.

ADA. 3. Initial Evaluation and Diabetes Management Planning. Diabetes Care 2015;38(suppl 1):S17
Components of the Comprehensive
Diabetes management
Referrals
• Eye care professional (opthalmologists) for annual dila
ted eye exam.
• Family planning for women of reproductive age or OB
GY care if pregnant (complications to fetus eg congeni
tal anomalies and neonatal complications)
• Nutritionists for diabetic diet.
• Diabetes self-management education/support
• Mental health

ADA. 3. Initial Evaluation and Diabetes Management Planning. Diabetes Care 2015;38(suppl 1):S18
 [a] Non pharmacological Rx

• Diabetic diet (less carbohydrates & fats, more

proteins, vegetables).
• Physical activities, at least 30mins of aerobic
activity/day (muscle cells takes glucose witho
ut need of insulin during exercise).
• Smoking cessation (both DM and smoking the
higher the risks of CVDs).
• Follow up for sugar monitoring and regular ch
eck up for early detection of complications.

ADA. 4. Foundations of Care. Diabetes Care 2015;38(suppl 1):S22

 [b] Pharmacological Rx

• Type 1 DM: insulin 0.5-1iu/kg/day

AM (2/3 of total daily dose) PM (1/3 of total daily dose)

2/3 long acting + 1/3 short actin 2/3 long acting + 1/3 short actin
g g

• How? SubQ
• When? Just before feeding.
• Short acting dosage can be given TDS instead
of AM-PM.

ADA. 4. Foundations of Care. Diabetes Care 2015;38(suppl 1):S22

• Type 2 DM: oral hypoglycemics
• Start with life style modii + single drug titrate to max d
osage (preferably metformin except CKD Egfr <30). wh
y metformin ? ---advantages---
• If glycemic control not archived add 2nd drug ie sulphon
ylureas and titrate.
• If glycemic control not archieved add 3rd drug and titrat
e +/- basal insulin.
• Consider insulin after max three drugs.
• INDICATIONS OF INSULIN IN T2DM
- admitted pt severly ill patients
- DKA/ HHS
- surgery
- pregnancy
- moderate – severe infections
- insulin deficiency sec pancreatic insufficiency sec long st
anding insulin resistance.
- resistant hyperglycemia to4. oral
ADA. hypoglycemics.
Foundations of Care. Diabetes Care 2015;38(suppl 1):S22
ADA. 4. Foundations of Care. Diabetes Care 2015;38(suppl 1):S22
• Benefits of new drugs SGLT2 inhibitors in DM, HTN
and HF.

ADA. 4. Foundations of Care. Diabetes Care 2015;38(suppl 1):S22

ADA. 4. Foundations of Care. Diabetes Care 2015;38(suppl 1):S22
ADA. 4. Foundations of Care. Diabetes Care 2015;38(suppl 1):S22
THANKS
(ahiJn)

ADA. 4. Foundations of Care. Diabetes Care 2015;38(suppl 1):S22