DM

Day 1
Diabetes Mellitus
Definition
Diabetes Mellitus is a syndrome with

disordered metabolism and inappropriate
hyperglycemia due to either a deficiency of
insuline secretion or to a combination of
insuline resistance and inadequate insuline
secretion to compensate for the resistance
CMDT 2017,page#1210
Criteria for Diagnosis of Diabetes
Normal Impaired Diabets
Glucose glucose Mellitus
tolerance tolerance
Fasting plasma glucose mg/dl <100 100-125 >126
2 hours after glucose load mg/dl <140 >140-199 >200
HBa1C <5.7 5.7-6.4 >6.5
CMDT 2017,, PAGE#1215

Pathophysiology of Type 1
Diabetes Mellitus
Autoimmunity
Environment
Genetics
Bovine Serum Albumin

DEVIDSON’S 22ND EDITION PAGE#803
Pathophysiology of type 2 diabetes mellitus
Environment
Insulin Resistance
Genetics
WHO Classification of Diabetes
Mellitus
1.Type 1 Diabetes(5-10% of cases): beta cell dysfunction

Includes autoimmune and idiopathic forms.
2. Type 2 Diabetes(90% of cases):defective insuline

secretion,usually with defective insuline action.
Oxford handbook of
ENDOCRINOLOGY AND DIABETES
3RD EDITION PAGE#685
3. Other specific types:
• Genetic defect of beta cell dysfunction
 MODY
 Mitochondrial DNA Mutation
 Neonatal Diabetes
• Diseases of Exocrine pancreas
 Pancreatitis, trauma, pancreatectomy, neoplasia
• Genetic defect of insuline action
 Lipodystrophies
 Insuline recepter mutations Monogenic obesity/hyperphagia
• Endocrinopathies
 Cushings syndrome, Acromegaly, Phaeochromocytoma,
Glucagonoma,
OXFORD HANDBOOK OF ENDOCRINOLOGY
AND DIABETES 3RD EDITION PAGE#685
• Drugs or Chemical induced
 Glucocorticoids, Thyroid Hormone, Diazoxide, beta
agonists, gama interferons
• Infections
 Congenital Rubella, CMV,
• Uncommon form of immune medited Diabetes
 Anti iinsuline recepter antibodies
• Other genetic syndromes associated with diabetes
 Downs syndrome, Klinefilters Syndrome, Turners
syndrome, Wolframs syndrome, Friedrichs Syndrome
4. Gestational Diabetes Mellitus

OXFORD HANDBOOK OF ENDOCRINOLOGY
AND DIABETES 3RD EDITION PAGE#685
β-Cell mass in Type 2 diabetes
-50%
-50%
-63%
-63%
ND=non-diabetic; IFG=impaired fasting glucose; T2DM=Type 2 diabetes mellitus
Butler et al. Diabetes. 2003

Features of Type 1 and Type 2 Diabetes
DEVIDSONS 22ND EDITION PAGE#809

HARRISON’S 19TH EDITION PAGE#2401
What is Honeymoon Diabetes?
The honeymoon phase is a phase that some people
with Diabetes experience shortly after being
diagnosed.Some people experience normal or near
normal blood glucose without taking insuline.This
happens because your pancreas is still able to produce
enough insuline to help controle your blood suger.And
having one doesn’t mean your diabetes is cured.It is
only temporary.
Latent autoimmune Diabetes of the
Young(LADA)
Type 1 diabetes can occur at any age,and it

may occur in middle age or old age due to
destruction of pancreatic beta cells by
autoantibodies.The presence of pancreatic
autoantibodies confirms the diagnosis of slow
onset type 1 diabetes,termed Latent
Autoimmune Diabetes of Adults,
Pathophysioloy of beta cell destruction by
autoantibodies
Pathologically, the pancreatic islets have a modest infiltration of

lymphocytes (a process termed insulitis). After beta cells are
destroyed, it is thought that the inflammatory process abates
and the islets become atrophic. the following abnormalities in the
humoral and cellular arms of the immune system:
(1) islet cell autoantibodies;
(2) activated lymphocytes in the islets, peripancreatic lymph
nodes, and systemic circulation;
(3) T lym -phocytes that proliferate when stimulated with islet
proteins; and
(4) release of cytokines within the insulitis

Beta cells seem to be particularly susceptible to the
toxic effect of some cytokines (tumor necrosis factor α
[TNF-α], interferon γ, and interleukin 1 [IL-1]). The
precise mechanisms of beta cell death are not known
but may involve formation of nitric oxide metabolites,
apoptosis, and direct CD8+ T cell cytotoxicity.
Islet cell autoantibodies (ICAs) are a composite of

several different antibodies directed at pancreatic islet
molecules such as GAD, insulin, IA-2/ICA-512, and
ZnT-8, and serve as a marker of the autoimmune
process of type 1 DM. Assays for autoantibodies to
GAD-65 are commercially available. HARRISON’S 19TH
EDITION PAGE#2404
Maturity Onset diabetes of the Young
Commonest cause of monogenic beta cell dysfunction.

MODY is characterised by the development of Type2
DM in patients < 25 years of age.It is typically inherited
as an autosomal dominant condition.Over 6 different
types of Genetic mutations have so far been identified
as leading to MODY.
It is thought that around 1-2% of patients with diabetes
have MODY.And around 90% are misclassified as
having either Type1 o Type2 DM
PassMedicine 2017,volume3
Page#247
MODY 3
60% of cases
Due to defect in HNF-1 alpha gene
MODY 2
• 20% of cases
• Due to defect in glucokinase gene
Featues of MODY
• Typically develops in patients <25 years of age
• Family history of early onset diabetes is present
• Ketosis is not a feature
• Patients are mostly sensitive to sulfonyleureas,, insuline is
not usually necessary.
Pass medicine
2017,volume3,page#247
Dawn phenomenon and Somogyi effect
Dawn Phenomenon sometimes called Dawns
effect , is an early morning (usualy between 2a.m. and
8a.m.) incease in blood suger (glucose) relevant to
people with diabetes.Fasting hyperglycaemia (‘the
dawn phenomenon’), which arises through a
combination of the normal circadian rhythm and
release of counter-regulatory hormones (growth
hormone and cortisol) during the later part of the
night, as well as diminishing levels of overnight
isophane insulin.
Devidson’s 22ND EDITION page#825
Somogyi effect (post hypoglycemic
hyperglycemia) which is due to midnight
hypoglycemia followed by release of
glucagon and epinephrine which causes
reflex hyperglycemia increasing fasting
blood glucose level.
Day 2
History

History
Onset / Mode of onset
Duration
Treatment history
Check up (ask about glucose level monitoring, HBa1C
levels)
Hypoglycemic sign/ symptoms
Nocturnal hypoglycemia
Polyuria / Nocturnal enuresis
Hyperlgycemic sign/ symptoms
Exercise
Diet
Smoking
Bloodpressure/ HTN
Ask about Complications of DM
Microvasculer signs/ symptoms
Retinopathy
Neuropathy
Nephropathy
Macrovasculer complications
CVS signs/ symptoms
Cerebrovasculer signs/ symptoms
Peripheral arterial disease signs/ symptoms’
Others
Infections
Gastroparesis
Erectile dysfunction
Dermopathy
Diabetic foot
Postural hypotension
Pregnancy
Past History
HTN, IHD, TB, asthma, Malignancy,any surgery
Family history
DM, HTN, TB, Asthma, IHD, Malignancy,
DIET
How to review a
patient in DM clinic

HARRISON’
19TH
EDITION,
PAGE#2407
Investigations
Blood tests
Oral glucose tolerance test
Fasting blood glucose levels
Laboratory blood glucose levels/ glucose level monitoring
using portable glucometer
HBa1C level
Ketonemia
 Fasting lipid profile
Blood urea/ creatinine
LFTs
Urine tests
 Urine C/E , Urine for Microalbuminuria
 Urine for ketone bodies DEVIDSON’S 22ND EDITION PAGE#807
ECG
Xray chest
Symptoms of hyperglycemia
Thirst, dry mouth

• Polyuria
• Nocturia
• Tiredness, fatigue, lethargy
• Change in weight (usually weight loss)
• Blurring of vision
• Pruritus vulvae, balanitis (genital candidiasis)
• Nausea
• Headache
• Hyperphagia; predilection for sweet foods
• Mood change, irritability, diffiulty in concentrating, apathy
Long-term supervision of diabetes
Lifestyle issues
• General health
• Work or school
• Smoking
• Alcohol intake
• Stress or depression
• Sexual health
• Exercise
Day 3
UKPDS Trial and DCCT Trial
The evidence that improved glycemic controle

decreases the risk of microvasculer
complications of DM was established by
Diabetes controle and complications trial
(DCCT) in Type 1 Diabetes and UK
Prospective Diabetes Study (UKPDS) in Type
2 Diabetes,
Devidson s 22ND EDITION

PAGE#827
DCCT Trial
The DCCT was a large study that lasted 9
years.There was 60% overall reduction in risk of
developing diabetic complications in patients in
Type 1 Diabetes on intensive therapy with strict
glycemic controle, compared with those on
conventional therapy.No single factor other than
glycemic controle had a significant effect on
outcome.However the group who were
intensively treated to lower blood glucose had
three times the rate of severe hypoglycemia
DEVISDON’S 22ND EDITION PAGE#827
UKPDS Trial
The UKPDS showed that in Type 2 diabetes,the
frequency of diabetic complications is lower and
progression is slower with good glycemic controle and
effective treatment of hypertension , irrespective of the
type of therapy used.Extrapolation from UKPDS
suggests that ,for every 11 mmol/mol (1%) reduction in
HBa1C, there is 21% reduction in death related to
diabetes, a14% reduction in MI and 30-40% reduction
in risk of microvasculer complications.

Gestational diabetes
Gestational diabetes is defied as diabetes

with first onset or recognition during
pregnancy.
DEVIDSON’ 22ND EDITION PAGE#817

Cause of Gestational Diabetes
Inability to increase insulin secretion adequately to
compensate for pregnancy-induced insulin
resistance-------remits after delivery
New onset type 1 diabetes mellitus------does remit
after delivery
Unknown pre-existing type 2 diabetes mellitus------
does remit after delivery

Women at high risk of gestational diabetes
• BMI > 30 kg/m2

• A previous macrosomic baby weighing ≥ 4.5 kg at
birth
• Previous gestational diabetes
• A fist-degree relative with diabetes
• A high-risk ethnicity – South Asian, black Caribbean
or Middle Eastern
In Pakistani Population, All women with gestational

amenorrhea should be offered OGTT.
Diagnosis of Gestational
Amenorrhea
• Gestational diabetes is diagnosed when:
Fasting plasma glucose ≥ (92 mg/dL)

or
1-hr plasma glucose (after glucose load) ≥(180 mg/dL)
or
2-hr plasma glucose (after glucose load) ≥(144 mg/dL)
• Consider testing high-risk women at fist booking visit with an

HbA1c or fasting blood glucose
Choice of Treatment
Insulin
Oral treatment options:

Metformin
Glibenclamide
Targets for self monitoring of pregnant women
Time Target
Fasting 5.3 mmol/l (<95mg/dl)
1 Hour after meal 7.8 mmol/l (<140 mg/dl)
2 Hour after meal 6.4 mmol/l (<120 mg/dl)
Pass Medicine 2017 VOLUME3 PAGE#267

Treatment of Diabetes
Diet Exercise
Diabetes
Mellitus
Education of
Drugs Patient and
Family
Management Goals
The goals of therapy for type 1 or type 2

diabetes mellitus (DM) are to
(1) eliminate symptoms related to hyperglycemia,
(2) reduce or elimi -nate the long-term microvascular and
macrovascular complications of DM
(3) allow the patient to achieve as normal as possible

Dietary Management
Aims of dietary management

• Achieve good glycaemic control
• Reduce hyperglycaemia and avoid
hypoglycaemia
• Assist with weight management:
Weight maintenance for type 1 diabetes and
non-obese type 2 diabetes
Weight loss for overweight and obese type 2
diabetes
• Reduce the risk of micro- and
macrovascular complications
• Ensure adequate nutritional intake
• Avoid ‘Atherogenic’ Diets or those that
aggravate complications, e.g. high protein
intake in nephropathy

Current Medications for Treatment of
Diabetes
Metformin GLP-1 Analogues
Sulfonylureas α-Glucosidase
Thiazolidinediones inhibitors
DPPIV Inhibitors SGLT-2 Inhibitors
Insulins

Metformin
Decreases hepatic glucose production
Improves insulin sensitivity in periphery
Decreases intestinal absorption of glucose
Metformin
Advantages Disadvantages
Considerable HbA1c Gastrointestinal
reduction adverse effects
No Hypoglycemia Avoid in heart failure,
Inexpensive renal and hepatic
Weight neutral insufficiency
Safe in pregnancy Risk for lactic acidosis
Vit B12 malabsorption
CMDT 2017 PAGE#1224

Sulfonylureas
 Secretagogues
 Stimulates insulin release from pancreatic beta
cells
 1) First-generation sulfonylureas (tolbutamide,
tolazamide, acetohexamide, chlorpropamide)
 2) Second-generation sulfonylureas (glyburide,
glipizide, gliclazide, glimepiride)
CMDT2017 , PAGE#1221, 1222

Sulfonylureas
Advantages: Disadvantages:
Rapid, pronounced
decrease in glucose
Hypoglycemia
Once or twice daily dosing Weight gain
Inexpensive Drug Interactions
Available in combination Concern for
with other oral agents effectiveness after
several years of
treatment
Meglitinides
Sulphonylrea like drugs
Mitiglinide is a benzylsuccinic acid
derivative that binds to the sulfonylurea
receptor and is similar to repaglinide in its
clinical effects.
CMDT 2017 PAGE#1223

Thiazolidinediones (TZDs)
Two medications of this class,rosiglitazone and
pioglitazone, are available for clinical use.
These medications sensitize peripheral tissues to
insulin.
They bind a nuclear receptor called peroxisome
proliferator-activated receptor gamma (PPAR-gamma)
and affect the expression of a number of genes.
Like the biguanides, this class of medications does
not cause hypoglycemia.
CMDT 2017 PAGE#1224
Thiazolidinediones (TZDs)
Use as monotherapy or in Several weeks of therapy
combination with other before optimal glucose
reduction
medications
Peripheral edema
No hypoglycemia
Weight gain
(monotherapy or with
Monitoring of liver function
metformin)
OSTEOPOROSIS
Once or twice daily dosing
ANEMIA
Expensive
CMDT 2017 PAGE#1225,
Alpha-Glucosidase Inhibitors
Alphaglucosidase inhibitors competitively inhibit the alphaglucosidase
enzymes in the gut that digest dietary starch and sucrose. Two of these
medications-acarbose and miglitol-are available for clinical use in
the United States.Voglibose, another alpha-glucosidase inhibitor is available
in Japan, Korea, and India. Acarbose and miglitol are potent inhibitors of
glucoamylase, alpha-amylase,ansucrase but have less effect on isomaltase
and hardly any on trehalase and lactase. Acarbose binds 1000 times more
avidly to the intestinal disaccharidases than do products of carbohydrate
digestion or sucrose. A fundamental difference between acarbose and
miglitol is in their absorption.Acarbose has the molecular mass and structural
features of a tetrasaccharide, and very little (about 2%) crosses the
microvillar membrane. Miglitol, however, has a structural similarity with
glucose and is absorbable. Both medications delay the absorption of
carbohydrate and lower postprandial glycemic excursion.
CMDT 2017, PAGE#1225

Alpha-Glucosidase Inhibitors
Reduces postprandial Gastrointestinal
glucose adverse effects
Dosed with first bite of
each meal
Slight risee in hepatic
aminotransferase
Expensive
Unsafe in pregnancy
CMDT 2017 PAGE#1225
Insulin
Insulin is indicated for type 1 diabetes as
well as for type 2 diabetic patients with
insulinopenia whose hyperglycemia does
not respond to diet therapy either alone or
combined with other hypoglycemic
medications.
CMDT2017 PAGE#1228
Insulin
Rapid acting
Lispro, Aspart, Glulisine, Inhaled*
Short acting
Regular
Intermediate acting
NPH
Long acting
Glargine
Detemir
CMDT 2017 PAGE#1229
Insulin
Mimics normal pancreatic Hypoglycemia
response to glucose Weight gain
Newer delivery options Patient resistance to
injections
Frequent blood glucose
monitoring
Expensive cost of inhaled
insulin
Local allergy
Lipodystrophy
DEVIDSON’S 22ND EDITION PAGE#825 Insuline antibodies (with
IMPORTANT FACTS
Routes:  volume of injection
 Subcutaneous  skin temperature
 Intravenous (warming)
 local massage
Time:
 exercise.
 Half hour before meal
The rate of absorption Pharmacokinetics
of insulin may be  Metabolized by Liver
influenced by: and Kidney
 Insulin formulation
 the site
 Depth
Alternative insulin therapies
‘Open-loop’ systems are battery-powered portable
pumps providing continuous subcutaneous (CSII),
intraperitoneal or intravenous infusion of insulin without
reference to the blood glucose concentration.
The rate of insulin infusion is variable; it can be

programmed to match the patient’s diurnal variation in
requirements and then manually boosted at mealtimes.

Incretin Based Therapies
Incretin therapies
Oral glucose provokes a threefold to fourfold higher insulin
response than an equivalent dose of glucose given intravenously.
This is because the oral glucose causes a release of gut
hormones, principally glucagon-like peptide 1 (GLP-1) and
glucose-dependent insulinotropic polypeptide (GIP1), that amplify
the glucose-induced insulin release. This "incretin effect" of GLP-1
secretion (but not GIP1 secretion) is reduced in patients with type
2 diabetes and when GLP-1 is infused in patients with type 2
diabetes,it stimulates insulin secretion and lowers glucose
levels.GLP-1, unlike the sulfonylureas, has only a modest insulin
stimulatory effect at normoglycemic concentrations. This means
that GLP-1 has a lower risk for hypoglycemia than the
sulfonylureas.
CMDT 2017 PAGE#1226
TWO TYPES OF INCRETIN
BASED THERAPIES
GLP-1 recepter agonist
Exenatide
Liraglutide
Albiglutide
Dulaglutide
DPP4 Inhibitors
o Sitagliptin
o Saxagliptin
o Alogliptin
o Linagliptin
o Vildagliptin
CMDT 2017 PAGE #1227
Incretin effect on insulin secretion
Control subjects (n=8) People with Type 2 diabetes (n=14)
80 80
60 60
Insulin (mU/l)
Insulin (mU/l)
Incretin
40 effect 40
20 20
0 0
0 60 120 180 0 60 120 180
Time (min) Time (min)
Oral glucose load

Intravenous glucose infusion
Nauck et al. Diabetologia. 1986

GLP-1: effects in humans
• Stimulates glucose-
After food ingestion… dependent insulin secretion
• Suppresses glucagon
secretion
• Slows gastric emptying
• Leads to a reduction of
GLP-1 is secreted from
food intake
L-cells of the jejunum
• Improves insulin sensitivity
and ileum
Long-term effects
That in turn… in animal models:
• Increase of β-cell mass
Drucker. Curr Pharm Des. 2001 and improved β-cell function
Drucker. Mol Endocrinol. 2003
GLP-1 enhancement
GLP-1 secretion is impaired in Type 2

diabetes
Natural GLP-1 has extremely short
half-life
Add GLP-1 Block DPP-4, the

analogues with longer enzyme that degrades
half-life: GLP-1:
• exenatide • sitagliptin
• liraglutide • vildagliptin
Injectables Oral agents

Exenatide (Byetta)
Indicated for use with Twice daily injection
sulfonylureas, given within 60
metformin, minutes of food
thiazolidinediones Short half-life
Prefilled, disposable Gastrointestinal
pen (5 mcg, 10 mcg) adverse effects
Additional A1c Expensive
reduction: 0.5-1% Not for use in Type 1
Weight loss patients
Dipeptidyl Peptidase-IV Antagonists
The concept is to allow the endogenous

GLP-1 to remain in circulation for a longer
period.
DPP-IV inhibitors are oral, rather than
injectable.
Weight neutral.
associated with a low incidence of
hypoglycemia or gastrointestinal side
effects.
SGLT2 Inhibitors
Glucose is freely filtered by the renal glomeruli and is
reabsorbed in the proximal tubules by the action of
sodium-glucose cotransporters (SGLT). Sodium-
glucose co-transporter 2 (SGLT2) accounts for about
90% of glucose reabsorption and its inhibition causes
glycosuria in people with diabetes,lowering plasma
glucose levels. The SGLT2 inhibitors canagliflozin,
dapagliflozin, and empagliflozin are approved for
clinical use in the United States
CMDT 2017 PAGE#1227
Complication of Diabetes
Although chronic hyperglycemia is an important
etiologic factor leading to complications of DM, the
mechanism(s) by which it leads to such diverse
cellular and organ dysfunction is unknown. An
emerging hypothesis is that hyperglycemia leads
to epigenetic changes that influence gene
expression in affected cells.
Four theories, which are not mutually exclusive, on
how hyperglycemia might lead to the chronic
complications of DM include the following
pathways:

(1) Increased intracellular glucose leads to the
formation of advanced glycosylation end products,
which bind to a cell surface receptor, via the
nonenzymatic glycosylation of intra- and
extracellular proteins, leading to cross-linking of
proteins, accelerated atherosclerosis, glomerular
dysfunction, endothelial dysfunction, and altered
extracellular matrix composition.

(2) Hyperglycemia increases glucose
metabolism via the sorbitol pathway related
to the enzyme aldose reductase. However,
testing of this theory in humans, using
aldose reductase inhibitors, has not
demonstrated beneficial effects

(3) Hyperglycemia increases the formation of
diacylglycerol, leading to activation of
protein kinase C, which alters the
transcription of genes for fibronectin, type IV
collagen, contractile proteins, and
extracellular matrix proteins in endothelial
cells and neurons.

(4) Hyperglycemia increases the flux through the
hexosamine pathway, which generates fructose-6-
phosphate, a substrate for O-linked glycosylation
and proteoglycan production, leading to altered
function by glycosylation of proteins such as
endothelial nitric oxide synthase or by changes in
gene expression of transforming growth factor β
(TGF-β) or plasminogen activator inhibitor-1

Diabetes and Hypertension
Hypertension is twice as common in the diabetic population as in
non-diabetic population and it worsens the severity and
increases the risk of both macrovasculer and microvasculer
diseases.
NICE Guidelines recommend all patients with diabetes should
have a blood pressure <140/80mmHg or 130/80mmHg in the
presence of complications.
In UKPDS hypertension study, a 10/5mmHg difference in BP
was associated with a 34% risk reduction in macrovasculer
endpoints, a 37% reduction in microvasculer endpoints, and a
44% reduction in stroke
OXFORD HANDBOOK OF
ENDOCRINOLOGY AND DIABETES
3RD EDITION PAGE #818, 820,
Treatment
General
Modify risk factors such as glycemic controle, smoking, and
dyslipidemias.Reduce salt intake, wt reduction, reduce
alcohol intake, and exercise daily.
Pharmacological
 In the presence of microalbuminuria or frank protienurea
ACEI or angiotensin 2 recepter antagonist.
 In afro-caribbean, ACEI an beta blockers are less
effective than Calcium Channel Blockers.and adiuretic
maybe needed.
Several agents such as high dose thiazides and
beta blockers , can worsen diabetic controle and
exacerbate dyslipidemia., so tailor the drugs.
In those with angina, a beta blocker has added
benefits.
In those with PVD, consider vasodilators,,
e.g.calcium channel blockers.
OXFORD HANDBOOK OF
ENDOCRINOLOGY AND DIABETES 3RD
EDITION PAGE #818, 820
Diabetic Nephropathy
Diabetic nephropathy Pathogenesis
Patho-logically, the first changes coincide with

the onset of microalbuminuria and include
thickening of the glomerular basement membrane
and accumulation of matrix material in the
mesangium. Subsequently, nodular deposits are
characteristic, and glomerulosclerosis worsens
as heavy proteinuria develops, until glomeruli
are progressively lost and renal function
deteriorates.

The nephropathy that develops in type 2 DM differs from that of
type 1 DM in the following respects: (1) microalbuminuria or
macroal -buminuria may be present when type 2 DM is
diagnosed, reflecting its long asymptomatic period; (2)
hypertension more commonly accom -panies microalbuminuria
or macroalbuminuria in type 2 DM; and (3)microalbuminuria may
be less predictive of diabetic nephropathy and likelihood of
progression to macroalbuminuria in type 2 DM, in large part due
to increased CV mortality in this population. Finally, it should be
noted that albuminuria in type 2 DM may be secondary to factors
unrelated to DM, such as hypertension, congestive heart failure
(CHF), prostate disease, or infection.

DEVIDSON’S
22ND EDITION
PAGE#831
Management of DM Nephropathy
Good glycemic controle
Blood pressure controle
CVS risk factor modification
Diet control
Current CKD Guidance from NICE suggests referral of
all patients with CKD stage5 or worse to nephrology for
RRT (renal transplant/ Dialysis)

TREATMENT
The presence of established microalbuminuria
or overt nephropathy should prompt vigorous
efforts to reduce the risk of progression of
nephropathy and of cardiovascular disease by:
Aggressive reduction of blood pressure
Aggressive cardiovascular risk factor reduction
DEVIDSON’S 22ND EDITION PAGE# 831

ACE Inhibitors and ARBs decrease
albuminuria
Non dihydropyridine calcium channel
blockers
Halving the amount of albuminuria with an
ACE or ARB results in a nearly 50%
reduction in long-term risk of progression to
end-stage renal disease.

Renal replacement
therapy
Dialysis
Renal transplantation
Diabetic neuropathy
Diabetic neuropathy
Diabetic neuropathy occurs in ~50% of individuals with
longstanding type 1 and type 2 DM.It may manifest as
polyneuropathy, mononeuropathy, and/or autonomic
neuropathy.As with other complications of DM, the development
of neuropathy correlates with the duration of diabetes and
glycemic control.Additional risk factors are body mass index
(BMI) (the greater the BMI, the greater the risk of neuropathy)
and smoking.The presence of CVD, elevated triglycerides, and
hypertension is also associated with diabetic peripheral
neuropathy.
Both myelinated and unmyelinated nerve fibers are lost.
Because the clinical features of diabetic neuropathy are similar
to those of other neuropathies, the diagnosis of diabetic
neuropathy should be made only after other possible etiologies
are excluded HARRISON’S 19TH EDITION PAGE#2426
Distal Symmetrical Sensory
Polyneuropathy
Most common neuropathy in diabetes
Glove and stocking distribution of sensory neuropathy
Symptoms include:
Paraesthesiae in the feet
Pain in the lower limbs (dull, aching and/or lancinating,
worse at night, and mainly felt on the anterior aspect of the
legs)
Burning sensations in the soles of the feet
Cutaneous hyperaesthesia and an abnormal gait
(commonly wide-based)
DEVIDSON;S 22 ND
EDITION PAGE#832
 Weakness and atrophy, in particular of the
interosseous muscles
 loss of lateral and transverse arches, clawing of
the toes and exposure of the metatarsal heads.
 Foot ulcers, Calluses and charcoat joints
DEVIDSON;S 22ND EDITION PAGE#832

Asymmetrical Motor Diabetic Neuropathy
 This presents as severe and progressive weakness
and wasting of the proximal muscles of the lower
(and occasionally the upper) limbs.
 Severe pain, mainly felt on the anterior aspect of the
leg, and
hyperaesthesia and paraesthesiae.
 (‘neuropathic cachexia’)
 Tendon reflxes may be absent on the affected side
 Glycemic control
 Supportive management
 Excellent prognosis DEVIDSON;S 22ND EDITION PAGE#832
Mononeuropathy
 Severe and rapid onset
 Single nerve involvement
 Commonly affected are the 3rd and 6th cranial nerves
(resulting in diplopia), and the femoral and sciatic
nerves.
 Carpal tunnel syndrome
 Ulnar nerve compression
 Lateral popliteal nerve
 Mononeuritis Multiplex
Autonomic neuropathy
Cardiovascular
• Postural hypotension
• Resting tachycardia
• Fixed heart rate
Gastrointestinal
• Dysphagia
• ‘Gastroparesis’
• Nocturnal diarrhea
• Faecal incontinence
• Constipation, due to colonic atony
Genitourinary
• Diffiulty in micturition, urinary incontinence, recurrent infection
• Erectile dysfunction and retrograde ejaculation
Sudomotor
• Nocturnal sweats without hypoglycaemia
• Gustatory sweating
• Anhidrosis; fisures in the feet
Vasomotor
• loss of skin vasomotor responses
• Dependent oedema
• Bullous formation
Pupillary
• Decreased pupil size
• Resistance to mydriatics
• Delayed or absent reflexes to light
TREATMENT
Pain and paraesthesia from peripheralsomatic
neuropathy
Intensive insulin therapy (strict glycaemic control)
Anticonvulsants (gabapentin, pregabalin,
carbamazepine phenytoin)
Tricyclic antidepressants (amitriptyline, imipramine)
Other antidepressants (duloxetine)
• Substance P depleter (capsaicin – topical)
• Opiates (tramadol, oxycodone)
• Membrane stabilisers (mexiletine, IV lidocaine)
• Antioxidant (α-lipoic acid)

Postural hypotension
• Support stockings
• Fludrocortisone
• NSAIDs
• α-adrenoceptor agonist (midodrine)
Gastroparesis
• Dopamine antagonists (metoclopramide,
domperidone)
• Erythromycin
• Gastric pacemaker; percutaneous enteral (jejunal)
feeding
Atonic bladder
• Intermittent self-catheterisation
Excessive sweating
• Anticholinergic drugs (propantheline, poldine, oxybutinin)
• Clonidine
• Topical antimuscarinic agent (glycopyrrolate cream)
Diarrhoea
• Loperamide
• Broad-spectrum antibiotics
• Clonidine
• Octreotide
Constipation
• Stimulant laxatives (senna)
Erectile dysfunction
• Phosphodiesterase type 5 inhibitors
• Dopamine agonist (apomorphine) – sublingual
• Prostaglandin E1 (alprostadil)
• Vacuum tumescence devices
• Implanted penile prosthesis
• Psychological counselling; psychosexual
therapy

The diabetic foot
Foot ulcers and infections are also a major source of morbidity in
individuals with DM. The reasons for the increased incidence of these
disorders in DM involve the interaction of several pathogenic factors:
neuropathy, abnormal foot biomechanics, PAD, and poor wound
healing. The peripheral sensory neuropathy interferes with normal
protective mechanisms and allows the patient to sustain major or
repeated minor trauma to the foot, often without knowledge of the
injury. Disordered proprioception causes abnormal weight bearing
while walking and subsequent formation of callus or ulceration. Motor
and sensory neuropathy lead to abnormal foot muscle mechanics and
to structural changes in the foot (hammer toe, claw toe deformity,
prominent metatarsal heads, Charcot joint). Autonomic neuropathy
results in anhidrosis and altered superficial blood flow in the foot,
which promote drying of the skin and fissure formation. PAD and poor
wound healing impede resolution of minor breaks in the skin, allowing
them to enlarge and to become infected
Many individuals with type 2 DM develop a foot ulcer (great
toe or metatarsophalangeal areas are most common), and a
significant subset who develop an ulceration will ultimately
undergo amputation (14–24% risk with that ulcer or
subsequent ulceration). Risk factors for foot ulcers or
amputation include male sex, diabetes for >10 years,
peripheral neuropathy, abnormal structure of foot (bony
abnormali -ties, callus, thickened nails), PAD, smoking,
history of previous ulcer or amputation, visual impairment,
and poor glycemic control. Large calluses are often
precursors to or overlie ulcerations.

Care of diabetic foot
Preventive advice to all diabetic patients includes:

 Inspect feet every day
 Wash feet every day
 Moisturise skin if dry
 Cut or file toenails regularly
 Change socks or stockings every day
 Avoid walking barefoot
 Check footwear for foreign bodies

Wear suitable, well-fitting shoes
Cover minor cuts with sterile dressings
Do not burst blisters
Avoid over-the-counter corn/callus remedies
Do not attempt corn removal
Avoid high and low temperatures
Podiatrist
Specially manufactured and fited orthotic
footwear DEVIDSON’S 22 EDITION PAGE#835
ND
Retinopathy due to DM
Diabetic retinopathy
Diabetic retinopathy is classified into two stages: nonproliferative
and proliferative. Nonproliferative diabetic retinopathy usually
appears late in the first decade or early in the second decade of
the disease and is marked by retinal vascular microaneurysms,
blot hemorrhages, and cotton-wool spots.Mild nonproliferative
retinopathy may progress to more extensive disease,
characterized by changes in venous vessel caliber, intraretinal
microvascular abnormalities, and more numerous
microaneurysms and hemorrhages. The pathophysiologic
mechanisms invoked in nonproliferative retinopathy include loss
of retinal pericytes, increased retinal vascular permeability,
alterations in retinal blood flow, and abnormal retinal
microvasculature, all of which can lead to retinal ischemia.
Risk factors for diabetic retinopathy
• Long duration of diabetes

• Poor glycaemic control
• Hypertension
• Hyperlipidaemia
• Pregnancy
• Nephropathy/renal disease
• Others: obesity, smoking
Stages of Retinopathy
Background
 Dot and Blot
Haemorrhages Proliferative
Non-proliferative  Neovascularization at
 Hard Exudates retina
 Cotton wool spots  Rubeosis Iridis
 Venous beading  Secondary glaucoma
 Intra-retinal microvascular
abnormalities

Microaneurysm Haemorrhages
s.
Hard exudates Cotton wool spots.
Venous beading. Neovascularisation.
Neovascularisation.Vitreous haemorrhage.
Screening
Annual screening for retinopathy is essential in all diabetic
patients.
Fluorescein angiography and optical coherence tomography are
useful to detect macular edema, which is associated with a 25%
chance of moderate visual loss over the next 3 years. Duration
of DM and degree of glycemic control are the best predictors of
the development of retinopathy; hypertension and nephropathy
are also risk factors. Nonproliferative retinopathy is found in
many individuals who have had DM for >20 years. Although
there is genetic susceptibility for retinopathy, it confers less
influence than either the duration of DM or the degree of
glycemic control.
Management
Good glycaemic ------ (HbA1c 7%)
Appropriate blood pressure ( < 130/80 mmHg)
Ranibizumab------VEGF-Antagonist----Antiangiogenic
Diabetic Macular Oedema.
Retinal photocoagulation ( Argon laser treatment)
Vitrectomy ---- Tractional Retinal Detachment

Other causes of visual loss in
people with diabetes
Cataract
Age-related Macular Degeneration
Retinal Vein Occlusion
Retinal Arterial Occlusion
Non-arteritic Ischaemic Optic Neuropathy
Glaucoma.
DIABETIC KETOACIDOSIS
Medical emergency
Type 1 diabetes
Occasionaly in type 2 diabetes
mellitus
Pathophysiology
DKA results from relative or absolute insulin deficiency
combined with counterregulatory hormone excess
(glucagon,catecholamines, cortisol, and growth
hormone). Both insulin deficiency and glucagon
excess, in particular, are necessary for DKA to
develop. The decreased ratio of insulin to glucagon
promotes gluconeogenesis, glycogenolysis, and
ketone body formation in the liver, as well as increases
in substrate delivery from fat and muscle (free fatty
acids, amino acids) to the liver. Markers of
inflammation (cytokines, C-reactive protein) are
elevated in both DKA and HHS
HARRISON’S 19TH
EDITION PAGE#2418
Precipitating factors
Infction eg UTI
Surgery
MI
Pancreatitis
Chemotherapy
Antipsychotics
Wrong insuline dose / non-compliance
OXFORD HANDBOOK OF CLINICAL MEDICINE 9TH EDITION PAGE#842

Diagnosis
The cardinal biochemical features are:

Hyperketonaemia ( ≥ 3 mmol/L) and ketonuria
(more than 2 + on standard urine sticks)
Hyperglycaemia (blood glucose ≥ 200 mg/dL)
Metabolic acidosis
(venous bicarbonate < 15 mmol/L and/or
venous pH < 7.3).
Pathophysiologic events
Hyperglycemia--------Osmotic diuresis---------
Profound dehydration
Insulin deficiency------unrestrained lipolysis and
fatty acid metabolism--------Ketogenesis-------
Metabolic acidosis
Osmotic diuresis-------Na and K loss in urine

Signs and symptoms
Symptoms
• Polyuria, thirst Signs
• Weight loss • Dehydration
• Weakness • Hypotension (postural or
• Nausea, vomiting supine)
• Leg cramps • Cold extremities
• Blurred vision • Tachycardia
• Abdominal pain • Air hunger (Kussmaul
breathing)
• Smell of acetone
• Hypothermia
DEVIDSON’S 22ND EDITION PAGE#812 • Confusion, drowsiness
Investigations
 • Venous blood: for urea and electrolytes, glucose
and bicarbonate (severe acidosis is indicated by a
venous plasma bicarbonate < 12 mmol/L).
 Urine or blood analysis for ketones
 ECG
 Infection screen: full blood count, blood and urine
culture, C-reactive protein, chest X-ray
 ABGs
Management
Three drugs:
1. Insulin
2. Fluids
3. Potassium
Fluids
Start immediately
1. Commence 0.9% sodium chloride
If systolic BP > 90 mmHg, give 1 L over 60 mins
If systolic BP < 90 mmHg, give 500 mL over 10–
15 mins then re-assess.
If BP remains < 90 mmHg, seek senior review

• IV infusion of 0.9% sodium chloride with potassium
chloride
added as indicated below
1 L over 2 hrs
1 L over 2 hrs
1 L over 4 hrs
1 L over 4 hrs
1 L over 6 hrs
• Add 10% glucose 125 mL/hr IV when glucose < 14
mmol/L

Potassium

Insulin
Commence insulin treatment
50 U human soluble insulin in 50 mL 0.9%
sodium chloride infused intravenously at
0.1 U/kg body weight/hr
Continue with SC basal insulin analogue if
usually taken by patient

Monitoring
 Establish monitoring schedule
 Hourly capillary blood glucose and ketone testing
 Venous bicarbonate and potassium after 1 and 2 hrs,
then every 2 hrs
 Plasma electrolytes every 4 hrs
 Clinical monitoring of O2 saturation, pulse, BP,
respiratory rate and urine output every hour
 Treat any precipitating cause
 Ketonaemia and acidosis should have resolved (blood
ketones < 0.3 mmol/L, venous bicarbonate > 18 mmol/L).
 Request senior review if not improving
 If patient is not eating and drinking Continue IV insulin
infusion at lower rate of
2–3 U/kg/hr
 Continue IV flid replacement and biochemical monitoring
 If ketoacidosis has resolved and patient is able to eat and
drink
Re-initiate SC insulin with advice from diabetes team.
 Do not discontinue IV insulin until 30 mins after SC short-
acting insulin injection
o Catheterisation if no urine passed after 3 hrs
o Central venous line if cardiovascular system
compromised, to allow fluid replacement to be
adjusted accurately – also consider in elderly,
pregnant, renal or cardiac failure, other serious
comorbidities, severe DKA.
o Measure arterial blood gases and repeat chest X-ray
if O2 saturation < 92%
o ECG monitoring in severe cases
o Thromboprophylaxis with low molecular weight
heparin
Bicarbonate
Until ph < 7.1

Hyperglycaemic hyperosmolar state
Hyperglycaemic hyperosmolar state (HHS)

is characterised by severe hyperglycaemia
( > 30 mmol/L (600 mg/dL)),
hyperosmolality (serum osmolality > 320
mOsm/kg), and dehydration in the
absence of signifiant hyperketonaemia (<
3 mmol/L) or acidosis (pH > 7.3,
bicarbonate > 15 mmol/L).
Precipitating factors
Common precipitating factors include:
Infection,
Myocardial infarction,
Cerebrovascular event
Drug therapy (e.g. corticosteroids).

Management
• Measure or calculate serum osmolality
frequently
• Give fluid replacement with 0.9% sodium
chloride (IV). Use 0.45% sodium chloride only if
osmolality is increasing despite positive fluid
balance. Target fall in plasma sodium is
≤ 10 mmol/L at 24 hrs
• Aim for positive fluid balance of 3–6 L by 12
hrs, and replacement of remaining estimated
loss over next 12 hrs
• Initiate insulin IV infusion (0.05 U/kg body
weight/hr) only when blood glucose is not falling
with 0.9% sodium chloride alone OR if there is
significant ketonaemia (3β-hydroxybutyrate > 1
mmol/L or urine ketones > 2+).
• Treat coexisting conditions
• Give prophylactic anticoagulation
• Assume high risk of foot ulceration

Reduce blood glucose by no more
than 5 mmol/L/hr
Complications
Pontine Myelinolysis
Cerebral Oedema

Calculations
Plasma osmolarity = 2 X Na +
glucose + urea

Diet and Diabetes
Diet and Diabetes

Dietary constituents and
recommended % of energy intake
 Carbohydrate: 45–60%
 Fat (total): < 35%
n-6 Polyunsaturated: < 10%
n-3 Polyunsaturated: eat 1 portion (140 g) oily fish once or
twice weekly
Monounsaturated: 10–20%
Saturated: < 10%
 Protein: 10–15% (do not exceed 1 g/kg body
weight/day)
 Fruit/vegetables: 5 portions daily
 Salt Intake <6g/day
BACK DEVIDSON’S 22ND EDITION PAGE#820-821

What type of fat should
be used in your
household and in what
quantity?
Exercise
Aerobic exercise 30 minute 5
times per week
Counselling
Education topics important for optimal diabetes care
include self-monitoring of blood glucose; urine ketone
monitoring (type 1 DM); insulin administration; guidelines
for diabetes management during illnesses; prevention and
management of hypoglycemia; foot and skin care; diabetes
management before, during, and after exercise; and risk
factor–modifying activities.

Psychosocial Aspects Because the individual with DM
can face challenges that affect many aspects of daily life,
psychosocial assessment and treatment are a critical part of
providing comprehensive diabetes care. The individual with DM
must accept that he or she may develop complications related to
DM. Even with considerable effort, normoglycemia can be an
elusive goal, and solutions to worsening glycemic control may
not be easily identifiable. Emotional stress may provoke a
change in behavior so that individuals no longer adhere to a
dietary, exercise, or therapeutic regimen. This can lead to the
appearance of either hyper- or hypoglycemia. Eating disorders,
including binge eating disorders, bulimia, and anorexia nervosa,
appear to occur more frequently in individuals with type 1 or type
2 DM.
Nutrition
Medical nutrition therapy (MNT) is a term used by the

ADA to describe the optimal coordination of caloric intake with
other aspects of diabetes therapy (insulin, exercise, weight loss).
Primary prevention measures of MNT are directed at preventing
or delaying the onset of type 2 DM in high-risk individuals (obese
or with prediabetes) by promoting weight reduction Secondary
prevention measures of MNT are directed at preventing or
delaying diabetes-related complications in diabetic individuals by
improving glycemic control. Tertiary prevention measures of
MNT are directed at managing diabetes-related complications
(cardiovascular disease, nephropathy) in diabetic individuals.

Glycemic Index
The glycemic index is an estimate of the

postprandial rise in the blood glucose when a
certain amount of that food is consumed.
Consumption of foods with a low glycemic index
appears to reduce postprandial glucose excursions
and improve glycemic control. Reduced-calorie and
nonnutritive sweeteners are useful

HARRISON’S 19TH
EDITION PAGE#2409
Exercise has multiple positive benefits including
cardiovascular risk reduction, reduced blood pressure,
maintenance of muscle mass, reduction in body fat,
and weight loss. For individuals with type 1 or type 2
DM, exercise is also useful for lowering plasma
glucose (during and following exercise) and increasing
insulin sensitivity. In patients with diabetes, the ADA
recommends 150 min/week (distributed over at least 3
days) of moderate aerobic physical activity with no
gaps longer than 2 days. The exercise regimen should
also include resistance training

Monitoring the level of glucose
Optimal monitoring of glycemic control involves plasma

glucose measurements by the patient and an
assessment of long-term control by the physician
(measurement of hemoglobin A1c[HbA1c] and review
of the patient’s self-measurements of plasma glucose).
These measurements are complementary: the patient’s
measurements provide a picture of short-term glycemic
control, whereas the HbA1c reflects average glycemic
control over the previous 2–3 months.

Self-Monitoring of Blood Glucose
Self-monitoring of blood glucose (SMBG) is the

standard of care in diabetes management and
allows the patient to monitor his or her blood
glucose at any time. In SMBG, a small drop of
blood and an easily detectable enzymatic
reaction allow measurement of the capillary
plasma glucose.

Assessment of Long-Term Glycemic Control
Measurement of glycated hemoglobin (HbA1c) is the

standard method for assessing long-term glycemic
control. When plasma glucose is consistently elevated,
there is an increase in nonenzymatic glycation of
hemoglobin; this alteration reflects the glycemic history
over the previous 2–3 months, because erythrocytes
have an average life span of 120 days (glycemic level
in the preceding month contributes about 50% to the
HbA1c value).

In standardized assays, the HbA1c approximates the
following mean plasma glucose values:
HbA1c of 6% = 7.0 mmol/L (126 mg/dL),

7% = 8.6 mmol/L (154 mg/dL),
8% = 10.2 mmol/L (183 mg/dL),
9% = 11.8 mmol/L (212 mg/dL),
10% = 13.4 mmol/L (240 mg/dL),
11% = 14.9 mmol/L (269 mg/dL),
12% = 16.5 mmol/L (298 mg/dL).
In patients achieving their glycemic goal, the ADA
recommends measurement of the HbA1c at least twice per
year
Skills
Insuline injection technique
In most patients, insulin is injected subcutaneously
several times a day into the anterior abdominal
wall, upper arms, outer thighs and buttocks. Accidental
intramuscular injection often occurs in children and
thin adults. The rate of absorption of insulin may be
influenced by many factors other than the insulin
formulation, including the site, depth and volume of
injection, skin temperature (warming), local
massage and exercise. Absorption is delayed from
areas of lipohypertrophy at injection sites, which results
from the local trophic action of insulin, so repeated
injection at the same site should be avoided. Other
routes of administration (intravenous and
intraperitoneal) are reserved for specific circumstances
Dose of Insulin
There is no maximum dose of insulin.
1 unit of insulin can decrease blood glucose by
5-50mg/dl
Insulin is usually started at 0.5 to 1 Unit/kg body
weight and titrated upwards accordingly.
How to check blood suger
How to perform an oral glucose tolerance test (OGTT)
Which patients to test

• Fasting plasma glucose 110–126 mg/dL
• Uncertainty about the diagnosis of diabetes
Preparation before the test
• Unrestricted carbohydrate diet for 3 days
• Fasted overnight for at least 8 hrs
• Rest for 30 mins
• Remain seated for the duration of the test, with no smoking
Sampling
• Measure plasma glucose before and 2 hrs after a 75 g oral
glucose drink

Interpretation of OGTT
Fasting 2 hrs after
mg/dl glucose load,
mg/dl
Impaired fasting 110-125 <140
glucose
Impaired glucose <126 140-199
tolerance
Diabetes Mellitus >126 >200
How to take sample for fasting
lipid profile
LIPID TARGETS
CMDT 2017 PAGE#2408

HDL Cholesterol
the HDL-C measurement integrates a number of cardiovascular
risk factors, potentially explaining its strong inverse association
with ASCVD.
Low levels of HDL-C are very commonly encountered in clinical
practice. Low HDL-C is an important independent predictor of
increased cardiovascular risk and has been used regularly in
standardized risk calculators, including the most recent one from
the American Heart Association (AHA)/American College of
Cardiology (ACC). However, it remains very uncertain whether
low HDL-C is directly causal for the development of ASCVD.
HARRISON’S 19TH EDITON,PAGE#2445

HDL metabolism is strongly influenced by TRLs,
insulin resistance, and inflammation, among
other environmental and medical factors
HARRISON’S 19TH EDITON,PAGE#2445

WAIST CIRCUMFERENCE
Excess abdominal fat, assessed by
measurement of waist circumference or
waist-to-hip ratio, is independently
associated with a higher risk for diabetes
mellitus and cardiovascular disease.
Measurement of the waist circumference
is a surrogate for visceral adipose tissue
and should be performed in the horizontal
plane above the iliac crest

A. B.
What is the right method to measure waist
circumference?
Waist Circumference Measurement
Last rib margin
Mid distance
Iliac crest
Courtesy J.P. Després 2006

Eye examination
• Visual acuities (near and distance)
• Ophthalmoscopy (with pupils dilated) or
digital photography
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Day 1

Diabetes Mellitus is a syndrome with

Fasting plasma glucose mg/dl <100 100-125 >126

2 hours after glucose load mg/dl <140 >140-199 >200

HBa1C <5.7 5.7-6.4 >6.5

CMDT 2017,, PAGE#1215

Bovine Serum Albumin

1.Type 1 Diabetes(5-10% of cases): beta cell dysfunction

2. Type 2 Diabetes(90% of cases):defective insuline

4. Gestational Diabetes Mellitus

ND=non-diabetic; IFG=impaired fasting glucose; T2DM=Type 2 diabetes mellitus

Butler et al. Diabetes. 2003

DEVIDSONS 22ND EDITION PAGE#809

Type 1 diabetes can occur at any age,and it

Pathologically, the pancreatic islets have a modest infiltration of

HARRISON’S 19TH EDITION PAGE#2404

Islet cell autoantibodies (ICAs) are a composite of

Commonest cause of monogenic beta cell dysfunction.

HARRISON’S 19TH EDITION PAGE#2406

DEVIDSONS 22ND EDITION PAGE#811

Thirst, dry mouth

The evidence that improved glycemic controle

Devidson s 22ND EDITION

DEVIDSON’S 22ND EDITION PAGE#827

Gestational diabetes is defied as diabetes

DEVIDSON’ 22ND EDITION PAGE#817

DEVIDSON’S 22ND EDITION PAGE#817

• BMI > 30 kg/m2

In Pakistani Population, All women with gestational

Fasting plasma glucose ≥ (92 mg/dL)

• Consider testing high-risk women at fist booking visit with an

Oral treatment options:

Fasting 5.3 mmol/l (<95mg/dl)

1 Hour after meal 7.8 mmol/l (<140 mg/dl)

2 Hour after meal 6.4 mmol/l (<120 mg/dl)

Pass Medicine 2017 VOLUME3 PAGE#267

The goals of therapy for type 1 or type 2

HARRISON’S 19TH EDITION PAGE#2407

Aims of dietary management

DEVIDSON’S 22ND EDITION PAGE#820

DEVIDSON’S 22ND EDITION PAGE#821

CMDT 2017 PAGE#1224

CMDT2017 , PAGE#1221, 1222

CMDT 2017 PAGE#1223

CMDT 2017, PAGE#1225

The rate of insulin infusion is variable; it can be

DEVIDSON’S 22ND EDITION PAGE#826

Oral glucose load

Nauck et al. Diabetologia. 1986

GLP-1 secretion is impaired in Type 2

Add GLP-1 Block DPP-4, the

Injectables Oral agents

The concept is to allow the endogenous

HARRISON’S 19TH EDITION PAGE#2424

HARRISON’S 19TH EDITION PAGE#2424

HARRISON’S 19TH EDITION PAGE#2424

HARRISON’S 19TH EDITION PAGE#2424

HARRISON’S 19TH EDITION PAGE#2424

Patho-logically, the first changes coincide with

DEVIDSON’S 22ND EDITION PAGE#831

HARRISON’S 19TH EDITION PAGE#2425

DEVIDSON’S 22ND EDITION PAGE#831

DEVIDSON’S 22ND EDITION PAGE# 831