SUGAR and its SWEET Demise

(Too much…too little…)

 DIABETES MELLITUS
Top 10 Mortality and Morbidity (WHO)
explosively increasing despite
being noncommunicable
 DIABETES MELLITUS:
(Global Pandemic)

1980- 30 Million
1997- 123 Million
2007- 250 Million
2013- 380Million

IDF:2 %
• Diabetes currently affects >380million people worldwide
• It is expected to affect >500 million by 2030
3 New Cases every 10 sec Mostly in low/mid income countries
10 Million/Year
78,000 children develop DM/year
183M unaware that they
have DM Greatest at 40-59 years old

2013 - 380 Million

2030 - 552 Million
 Global prevalence of
Diabetes Mellitus

A PANDEMIC
2013 TOP DISEASE
10 2030 TOP 10
India Projected estimate
China India
USA China
…. USA
….
PHILIPPINES
NOT INCLUDED [Link]
Burden of diabetes

⦿ Number of diabetics worldwide is expected

to increase alarmingly due to:
› Population ageing
› Unhealthy diet (Westernization)
› Obesity and sedentary lifestyle
› Socio-economic, urbanization, westernization
and economic development
SCANDINAV
Highest incidence of Type 1
IA (FINLAND 35/100,000)

Northern Europe &

USA rate of Type 1
Intermediate

Japan &
China
Lower rate of Type 1

PACIFIC
ISLANDS Highest incidence of Type 2

India &
US intermediate incidence of Type 2
Russi
lowest incidence of Type 2
a
 Endocrine Pancreas
Cell Type Approximate Secretory
Percent of Islet Products
Mass (%)
B Alpha (α) cell 25 Glucagon,
proglucagon

I Beta (β) cell 55 Insulin, C-peptide,

proinsulin, amylin

G δ Cell (delta) 10 Somatostatin-14

ε Cell 3 Ghrelin
A PP cell1 5 Pancreatic
polypeptide (PP)
1
Within pancreatic polypeptide-rich lobules of adult islets, located only in the posterior
portion of the head of the human pancreas, glucagon cells are scarce (< 0.5%) and F cells
make up as much as 80% of the cells.
DIABETES MELLITUS

SIPHON

HONE
Y
 D
Group of
M Metabolic Disorders with
the phenotype of
VASCULAR
and
NON- VASCULAR
complications HYPERGLYCEMI
Hyperlipidemia A
Hyperaminoacidemia
 Spectrum of Glycemia
(3 Broad Categories of GLUCOSE Tolerance)

Normal Pre DM (Impaired Glucose) DM

IFG IGT
FPG <100mg%
100 – 125mg% > 126 mg% or
<5.6 mmol
5.6 – 6.9mmol > 7 mmol /L

2Hrs < 140mg%

Post 140 – 199mg% > 200 mg%
Glucose < 7.8 mmol 7.8 –11.1mmol > 11.1 mmol /L
Load
Points to
remember…
Normal Frank Diabetes
Pre Diabetes FPG = >126mg%
FPG = <100mg%
2HPG= <140 mg% 2HPG = >200mg%

IFG IGT
100-125mg% 140-199mg%
5.6- 6.9 mmol/L 7.8-11.1mmol/L
 PRE - DIABETES

Blood sugars above normal BUT below Diabetes levels

Same MACROvascular complications as DM

Can lead to full blown “DM” anytime

Can be prevented….
Diet
Lifestyle Modification
Oral Medication

***Finnish DPS; China’s Da Qing in IGT ; DPP***

DIAGNOSIS OF DIABETES MELLITUS
✔ FPG ≥126 mg/dl (7mmol/L).
Criteria for diabetes
OR mellitus
✔ Symptoms of hyperglycemia(polydipsia,
polyuria,unexplained weight loss)

and a
casual PG ≥200 mg/dl (11.1
mmol/L)
OR
✔ 2-h plasma glucose of ≥200 mg/dl (11.1
mmol/L) during a 75 gm OGTT.

✔ Glycosylated hemoglobin (HbA1c) ≥ 6.5%

American Diabetes Association June 2009

 Measures of Glycemia
Fasting
• No caloric intake for 8-12 hours
Plasma prior to test
Glucose

Casual
• Anytime regardless of
Plasma meal
Glucose

Post Prandial
• 2 hours after a meal
Glucose
 Measures of Glycemia
• Reflects glucose average, past 6-8
Hemoglobin wks
• Dxtic Test for DM (>6.5%)
A1C • Means CONTROL or Ongoing Complx

Fructosamine • Reflect mean glucose over 1-2 wks

Glycated • Best used in GDM monitoring
Serum Protein

• Oral anhydrous glucose given as load

Oral Glucose • 75 g- non pregnant adults
• 100 g- pregnant adults
Tolerance Test • .75 g/kg BWt-children, not to exceed .75gms
Points to
remember…

FPG
HbA1C

Most reliable & OGTT

most convenient tests Still valid means for
for identifying DM in DX of DM but NOT
asymptomatic individuals used in routine
clinical use
Etiologic Classification of DIABETES MELLITUS
(based on PATHOGENIC process)

Type 1 DM: near total or absolute INSULIN DEFICIENCY

A. Immune-Mediated
B. Idiopathic

Type 2 DM: Heterogenous- “Ominous OCTET”

Insulin Resistance (liver, muscle,fat)
Insulin Deficiency
Incretin Defect – Increase GLUCAGON activity(alpha cell)
Increased Glucose reabsorption at Renal Tubules
Neurotransmitter defect (Brain)

GDM(Gestational DM) - Glucose elevations anytime during pregnancy

*NOT on : AGE of Onset (Juvenile / Adult Onset)

*NOT on THERAPY : (IDDM-Insulin Dependent / NIDDM- Non Insulin Dependent)
 Types of Diabetes
Type 1 Type 2 Gestational DM

• Absolute Insulin • Heterogenous

deficiency • Diet
• Auto-immun • Lifestyle
e (viral) • Treatment:
• Idiopathic medications:
(oral tabs &/or
• Treatment: insulin)
Insulin shots

GDM Treatment
•Diet
•Orals (Metformin)
•Insulin
Points to remember…
Near total to Absolute INSULIN DEFICIENCY
Type 1
Treatment: INSULIN

Type 2 Heterogenous group characterized by:

Impaired INSULIN Insulin ↑Glucose

Secretion/Deficiency Resistance Production
Ominous OCTET
(meaning?)
Type I/II

X
IDDM/Juvenile Onset DM
NIDDM/Adult Onset DM

Maturity Onset Diabetes of the Young (Subtype of DM )

MODY
-ADI (Autosomal Dominant Inheritance)

GDM DM in Pregnancy (30-60%-later in life)

Ominous Octet
Role of INSULIN:
 Pancreatic Acini

Duct

Islets of Langerhans

Alpha cells

Delta cells

Beta Cells
 Second
Receptor
Translocation
Insulin
messenger
Phosphorylates
bindspathways
to
of
Alter
Glucose
Insulin-receptor
tyrosine
protein
transporter
kinase
synthesis
AndSubstrate
existing
receptor
GLUTproteins
4(IRS)

P
TYROSINE
KINASE
P

P
Glucose
IRS Hexokinase
P
IRS
Glu-6-phosphate
Second
GLUT 4
Islet messenger
Transcripti pathways
Metabolism/
on storage
factors

Protein Glycogen Glucose

synthesis synthesis transport
Points to remember…

Preproinsulin 86AA→precursor of proinsulin

C Peptide
Proinsulin precursor of insulin
Insulin A & B Chain

Useful marker of Insulin Secretion

C Peptide
Discriminate endo/exogenous insulin

Glucose Key regulator of insulin secretion by B Cells

Glucokinase Glucose phosphorylation

Rate limiting steps controlling glucose
regulated insulin secretion
 FOOD
Storage In Fat Depots
Inhibition of Lipolysis
“Fat-Loving” Hormone

I
l u cose G
G I
Insulin G I
Secretion Insulin

G
G

I
G
Pancreas I G
G
I
I G
G
Restrain I
G Uptake of
of HG
I
G

glucose

Insulin Effects
 Norma
Carbohydrates
(CHO)
Proteins (CHON) Fats
l

Glucose Amino Acids Blood lipids/Cholesterol

INSULIN blood

ENERGY

cells muscles fat cells

 Carbohydrates
DM
Proteins (CHON) Fats
(CHO)

Glucose Amino Acids Blood lipids/Cholesterol

Hyperaminoaci
Hyperglycemia demia
Hyperlipidemia

ENERGY INSULIN or defective INSULIN

cells
Muscle Weight loss
Weakness/
Sleepiness

Always
tired/fatigued
 DIABETES: PATHOPHYSIOLOGY

Exagerated
lipolysis
I
l u cose G
G I
Beta Cell G I
Insulin

G
G
Dysfunction

I
G
Pancreas I G
G
I
I G
G
I
G
Decreased
Glycogenolysis
I
G

Glucose
&
Uptake
gluconeogenesis

Lack Insulin Action

 3 METABOLIC
BS ABNORMALITIESNonvascular
HYPERGLYCEMIA

BAA HYPERAMINOACIDEMIA
Problem
B Fats HYPERLIPIDEMIA Skin GUT GIT Nerves

Vascular
Problems
macrovascular microvascular

BRAIN HEART LIMBS EYES KIDNEY NERVES

Retino- Nephro Neuro

cvd cad pvd pathy -pathy -pathy

“TRIOPATHIES ”
 Blood and
Blood
Vessels

Big Small

Cerebrovascular
CVD
Brain Eyes Retinopathy

Cardiovascular
CAD
Heart Kidneys Nephropathy

Peripheral Vessel
Disease (PVD)
Limb Nerves Neuropathies
(Numbness of Extremeties
IMPOTENCE)
PATHOPHYSIOLOGY:
 Diabetes Mellitus 1
Type 1 Diabetes
- primarily B-cell destruction Type 1A (autoimmune)
- results in insulin dependence - associated with specific
- commonly detected before haplotypes or allelles
30 years at DQ-A and DQ-B loci
of HLA complex
- concommitant autoimmune d/o

Type 1B (idiopathic)
- no evidence of autoimmune d/o
- progressive dse w/ marked
hyperglycemia
- African or Asian origin
 Genetic Considerations
(T1DM)
⦿ Most individuals have:
HLA DR3 and/or DR4 haplotype.

⦿ Haplotypes most strongly associated with Type 1 DM:

DQA1*0301, DQB1*0302, and DQB1*0201

› Seen in 40% of children with type 1 DM vs. normal U.S. population

› However, most individuals with predisposing haplotypes do not
develop diabetes.
 Genetic Considerations (T1DM)

⦿ Haplotype DQA1*0102, DQB1*0602:

› extremely rare in individuals with Type 1 DM (<1%)
› provide “protection from type 1 DM”

⦿ Risk of developing Type 1 DM is increased 10x in relatives of

individuals with the disease.

The risk is relatively low:

› 3–4% (if parent has T1DM)
› 5–15% in a sibling (depending on which HLA haplotypes are
shared)
› Hence, most individuals with T1DM do not have a
first-degree relative with this disorder.
 Type 2 DM
blood glucose levels rise due to

*impaired insulin secretion (Insulin Deficiency)

*Peripheral insulin resistance (Muscle,Liver,Fat)
*Excessive hepatic glucose production
***From the Triumvirate to the OMINOUS OCTET***

> commonly detected after 40 y.o.

> Obesity (visceral or central ) is very common

> Preceeded by a period of abN glucose homeostasis(Pre-DM)

classified as:
-impaired fasting glucose (IFG)
-impaired glucose tolerance (IGT)

> eventually leads to β-cell failure (resulting in insulin dependence)

 THE OMINOUS OCTET of T2DM

Decreased
Decreased Insulin Secretion Incretin Effect
Increased
(Insulin Deficiency)
Lipolysis (FAT cells)

Increased HYPERGLYCEMIA Kidneys:

Glucagon Increased
Secretion Glucose
Reabsorption

Skeletal Muscle:
Decreased Glucose
Uptake

Increased Neurotransmitter
HGP
Dysfunction

DeFronzo RA. Diabetes. 2009; 58:773-795

 Pathophysiology of Type 2 Diabetes:

Glucose Incretin
production effect

Glucose Insulin β
uptake Poor secretion
Glucose
Homeostasis
Glucagon α
Lipolysis
secretion

Neurotransmitter Glucose
dysfunction reabsorption

▪ Multiple drugs in combination may be required to improve glucose homeostasis

▪ Treatment should target underlying pathophysiology

Dysfunctions outlined in orange are the three core pathophysiologies of type 2 diabetes, known as the triumvirate.
DeFronzo RA. Diabetes. 2009;58:773-795.
 in Type 2 DM
Neurotransmitter
pancreas Dysfunction
Insulin Resistance
Islet cell dysfunction
Skeletal
MUSCLE
B Cell A Cell FAT
Suppression of A cell LIVER
Insulin secretion
(Insulin deficiency) (↑Glucagon activity)

↓ Peripheral uptake of glucose

Dietary ↑ HEPATIC GLUCOSE
glucose PRODUCTION
absorption in ↑ Lipolysis →↑FATTY ACIDS
the gut

↓ Protein Synthesis→↑AA
↓Incretins
HyperLIPIDEMIA
HYPERGLYCEMIA
HyperAMINOACIDEMI
Dysfunctional
RAAS and ↑ Glucose
A 45
Insulin Resistance
 Other consequences of Insulin Resistance

INSULIN RESISTANCE

↑ Production of
TG in the liver
Arteries Platele
ts

Diabetic Increased stiffness, hypertension, Procoagulant

dyslipidemia endothelial dysfunction changes

Atherothrombotic
arterial disease
Adapted from Yki-Järvinen H, 2003
 Vicious Circle of Adipocyte Hypertrophy,
Macrophage Recruitment and Activation
Increased nutrient influx

Adipose hypertrophy and Macrophages

hyperplasia allow adipose
Adipocytes tissue to grow

Larger adipocytes secrete

macrophage-attracting
Preadipocytes chemokines

Chemokines
Cytokines
Free fatty acids (FFA)

Increased FFA release by insulin

resistant adipocytes activates
Activated macrophages block macrophages
preadipocyte recruitment and worsen
insulin resistance in mature adipocytes,
increasing FFA release and
macrophage activation Adapted from Virtue S & Vidal-Puig A Biochim Biophys Acta [Link]-49
Effects of elevated plasma FFA levels

⦿ Insulin resistance in muscle

⦿ Inhibition of normal function of insulin to
suppress hepatic glucose production
⦿ Impair insulin-stimulated glucose uptake
⦿ FFA are substrate for hepatic triglyceride
synthesis leading to increased plasma VLDL
and triglyceride levels
⦿ Impair endothelial function
 2Type
Predisposing
2 DIABETES
Genesfactors:
MELLITUS
VS Environmen t
Pulls the trigger

Load the canon

DM
Obesity

Inactive lifestyle
 TOO
stressful

TOO SEDENTARY
Or
Habitually INACTIVE
Walking the dog
Poor diet
 Where’s
my COKE!!!
 diuretics
mannitol

stress drugs

infection lifestyle
Diabetes is NOT a Mild Disease
Leading 2 to 4 fold
cause Stroke increase in
cardiovascular
of blindness mortality
in working and stroke
age Diabetic
adults Retinopathy

Diabetic Cardiovascular
Nephropathy Disease
Leading cause of
end-stage renal Diabetic
disease Neuropathy
Leading cause of non-traumatic
lower extremity amputations
 complications
ACUTE CHRONIC

DKA HHS VASCULAR NONVASCULAR

Diabetic Hyperglycemic
Ketoacidosis micro macro Infection
Hyperosmolar State

EYES KIDNEY NERVE BRAIN HEART LIMBS CHF

Primarily in Primarily in •Neuro cvd cad
type 1 type 2
•Nephro
pathy
pathy pvd GUT
Retino
pathy DERMA

GASTROPARESIS
DIARRHEA

Associated with
CATARACT
GLAUCOMA
•absolute or relative insulin
deficiency

•Volume depletion-dehydration
•Acid-base abnormalities

•Potentially serious complications

 Clinical Features of DKA
Symptoms:
❄ Nausea /vomiting
❄ Abdominal pain
❄ Thirst/polyuria

Physical Findings:
❄ Tachycardia
❄ Dry mucous membranes/reduced skin turgor
❄ Hypotension/dehydration
❄ Tachypnea/Kussmaul respirations
❄ Abdominal tenderness
❄ Lethargy /obtundation/ Cerebral edema/ possibly coma
Diabetic Ketoacidosis
 Laboratory Values in DKA & HHS
DKA HHS
Glucose 250-600 600-1200
Na+ (meq/L) 125-135 135-145
K+ (meq/L) Normal to 🡹 Normal
Mg+ Normal Normal
Cl- Normal Normal
PO4 🡹 Normal
Crea (mg/dl) Slightly 🡹 Moderately 🡹
Osmolality (mOsm/ml) 300-320 330-380
Plasma Ketones ++++ +/-
Serum HCO3 (meq/L) < 15 meq/L Normal to slightly 🡹
Arterial pH 6.8-7.3 > 7.3
Arterial pco2, mmHg 20-30 Normal
Anion gap [Na (Cl+Hco3)],l meq/L 🡹 Normal to slightly 🡹
 Clinical features

Prototypical patient :
₪ elderly individual with Type 2 DM
₪ several week history of polyuria, weight loss,
and diminished oral intake
₪ culminates in mental confusion, lethargy, or
coma
P.E.:
profound dehydration
hypotension
tachycardia
altered mental status

₪ Notably absent symptoms :

nausea, vomiting, and abdominal pain
Kussmaul’s respiration characteristic of DKA
 Mechanisms of Complications

Theories:
1.) increased intracellular glucose
2.) hyperglycemia increases glucose
metabolism via the sorbitol pathway
3.) hyperglycemia increases the formation of
diacylglycerol
4.) hyperglycemia increases the flux
through the hexosamine pathway
 Maybe asymptomatic and
slowly “COMPLICATES”

once with symptoms…

In REALITY nothing more but a cry

from suffering ORGANS.
 COMPLICATIO
NS

RENAL FAILURE IMPOTENCE

DIALYSIS
LIMB
BLINDNESS AMPUTATION

Top
Cause HEART
STROKE
ATTACK
Diabetic Retinopathy

Vitreous Hemorrhage

Proliferative

Normal retina Pre-proliferative

Diabetic Retinopathy
Diabetic Nephropathy
Diabetic Neuropathy

Autonomic
Neuropathy

Constipation

Peripheral
Erectile dysfunction
Neuropathy
Diabetic Neuropathy
Diabetic foot
Hypoglycemia
HYPOGLYCEMIC SHOCK
How do we screen for pre-diabetes
and diabetes among
asymptomatic patients?
 screeni
ng
• Most reliable/convenient
FPG test for DM in
asymptomatic individual

• All ind. >45 yo → screened

ADA every 3 years
• Ind. w/ BMI>25+
•Add’n RF = early age
and often FHx
•↓ PA
AA/Pacific
Islander/NA/Asian-Ame
rican
Is your Blood sugar level
…..
 Who gets DM?

young or old
rich or poor
with or without a family history
 GENETIC OBESITY
INACTIVITY

Metabolic
Dysregulation

Diabetes
Dyslipidemia
Insulin Resistance

Hyperinsulinemia
Hypertension
Atherosclerosis

Certain Pro-inflammatory/
cancers Non-alcoholic
Pro-coagulant
fatty Liver
state
Fertile ground for DM RISK
FACTORS
: Overweight/
Waist/Hip Ratio
Age=>40 Obesity
Men = >1
Women >.85

Physical DIET
Take drugs Poor Diet
Inactivity that
Low↑inBS
fiber
Loaded with
Calories,
Sugars, Sat.
Hx of
Family Hx of Fats
glucose
DM
elevation
Smoking
Abnormal PCOS
Blood High BP Hx of Vascular
Problems
Cholesterol
 Criteria for Screening among Asymptomatic Patients:

1. Testing should be considered among all adults

1. Testing should be done on all adult patients who are overweight
who
(BMI ≥25 are
kg/m 2 overweight (BMI ≥25kg/m2) with risk
) and who have risk factors:
1. factors:
Physical inactivity
2. First -degree
physical inactivity
relative
- 1st degree
3. Members relative
of high-risk withpopulation
ethnic diabetes
- high-risk
4. Diagnosed ethnic
GDM, or population
delivery of baby ≥9lbs
- women
5. Polycystic whosyndrome
ovary delivered baby >9lbs or diagnosed GDM
- hypertension
6. HPN≥140/90 (BP≥140/90) or on treatment
or on treatment
7. HDL-C - HDL-C <35
<35, of mg/dl and/or
Triglyceride >250triglyceride >250 mg/dl
- polycystic
8. Conditions of IR ovary syndrome
(obesity, (PCOS)
acanthosis nigricans)
- previously
9. History of CVD diagnosed IFG or IGT
- other conditions
2. In the absence with IR (severe obesity,
of the above,pre-testing acanthosis
for pre-diabetes and
diabetes should nigricans)
begin at 45 years old.
3. If results- are
history of CVDrepeat at 3-year intervals.
normal,
2. In the absence of above criteria, screen at age 45
*** <4years.
– low risk >5 – high risk
3. If results are normal, repeat testing every 3-years
American Diabetes Association Jan 1, 2009
 Risk Factors:
⦿ Age > 40 y/o
⦿ Race/Ethnicity ( Asian American, Pacific Islanders, Latino)
⦿ Family History
⦿ History of Previous Elevations in Sugar
GDM or had big babies> 9lbs
Drug-induced elevations in BS
⦿ Hypertension >140/90
⦿ Hyperlipidemia ( high cholesterol or high triglycerides or
high LDL, Low HDL )
⦿ Smoker
⦿ Overweight/ Obese (BMI> 25)
⦿ Sedentary Lifestyle or Habitual INACTICITY
⦿ Polycystric Ovarian Syndrome; Acanthosis Nigricans
⦿ History of Vascular Disease

⦿ *** <4 – LOW Risk >5 - HIGH Risk

 Signs and
Symptoms
Always Frequent/voluminous
↑thirst
tired/sleepy/irritable urine

Always hungry Blurred vision Sexual problem

Vaginal Numbness/tingling of
Poor wound healing
itchiness/discharges hands/feet
 GOOD GOOD
NEWS!!! NEWS!!!

D IS
PREVENTABLE

M
NEWS!!! GOOD NEWS!
GOOD
GOOD NEWS!!!GOOD NEWS
GOOD NEWS!!!GOOD NEWS!
To prevent gain Knowlege
DM not pounds or
kgs weight
NEWS!!! GOOD GOOD
 X X X
>200 mg %

GLUCOTOXIC
COMPLICATIONS

>200 mg %
LUNCH

SNACKS
DINNER
SNACKS

SNACKS
bf
 GOALS OF TREATMENT

(1) Eliminate symptoms related to

hyperglycemia
(2) Reduce or eliminate the long-term
microvascular and macrovascular
complications of DM
(3) Allow the patient to achieve as normal a
lifestyle as possible
 Who need exogenous insulin :
⦿ Type I (insulin dependent) diabetes patients whose
body produces no insulin.
⦿ Type 2 diabetes patients that do not always produce
enough insulin.

Treatment

▪ subcutaneous injection
Insulin Analogs:

⦿ Fatty Acid Acylated insulins

⦿ Insulin Lispro (Humalog®) (1996)

⦿ Insulin Aspart (NovoLog®) (2000)

⦿ Insulin Glargine (Lantus®) (2002)
⦿ Insulin Detemir (Levemir®) (Jun.,2005)

⦿ Insulin Glulisine (Apidra®) (Jan., 2006)

"Ok, doc says it'll feel like a mosquito bite"
Insulin Injection Areas
 Types of
Insulins
appearance Clear (rapid/analogues) vs Cloudy (zinc)

source Pork/beef/human/analogues

Action Short/rapid/intermediate/long

premixed Fixed combination of rapid/int.

 Proposed recommendations for use
of metformin based on eGFR
eGFR LEVEL ACTION
(mL/min per 1.73 m2)

≥60 No renal contraindication to metformin Monitor

renal function annually
≥45 - 60 Continue use
Increase monitoring of renal function (q 3–6 mos)
≥30 - <45 Prescribe metformin with caution
Use lower dose (e.g., 50%, or half-maximal dose)
(LOWER dose ) Closely monitor renal function (every 3 months)
Do not start new patients on metformin

<30 (STOP) Stop metformin

Additional caution is required in patients at risk for acute kidney injury or with anticipated significant fluctuations in renal
status, based on previous hx, other comorbidities, or potentially interacting medications.

Use of Metformin in the Setting of Mild-to-Moderate Renal Insufficiency Lipska

KJ, Bailey CJ , Inzucchi [Link] Care June 2011 vol. 34 no. 6 1431-1437
 ECCr = (Estimated Creatinine Clearance Rate)
(using Cockcroft-Gault formula)

(Ex: 68y/o;F;70kgs;crea-1.68mg) Female = (140- 68) x 70 kg x 0.85

72 X 1.6 mg/dL
= 37.1875 mL/min

(Ex: 68y/oM;70kgs;crea-1.68mgs) Male= (140- 68) x 70kg

72 X 1.6 mg/dL
= 43.75 mL/min
Constant is 1.23 for men and 1.04 for women
 Obesity

PCOS
(Polycystic Ovarian Syndrome)

NAFLD
(Non Alcoholic Fatty Liver Disease)