Definition Diabetes Mellitus

• The general term diabetes comes from a Greek word meaning “siphon”;
Aretaeus, a Cappadocian physician , wrote: “The epithet diabetes has been
assigned to the disorder, being something like passing of water by a siphon”.
It refers to the frequent urination associated with this condition.
• The name of this disease is derived from the fact that glucose “spills over” into
the urine when the blood glucose concentration is too high (mellitus is derived
from a Latin word meaning “honeyed” or “sweet”).

Definition:
• Diabetes mellitus is a clinical syndrome characterized by the extracellular
hyperglycemia and intracellular hypoglycemia in addition to glucosuria and
ketosis produced by either deficiency or diminished effectiveness of
endogenous insulin.
OR
• The hyperglycemia of diabetes mellitus results from either the insufficient
secretion of insulin by the beta cells of the islets of Langerhans or the inability
of secreted insulin to stimulate the cellular uptake of glucose from the blood.
• Diabetes mellitus, in short, results from the inadequate secretion or action of
insulin.
 Diabetes: The Global Threat
•

1995 2000 2010

Type 1 3.5 million 4.4 million 5.5 million

Type 2 114.8 million 146.8 million 215.3 million

TOTAL 118.4 million 151.2 million 220.7million

 Prevalence( diabetes Atlas.”IDF”)
At least 171 million people worldwide have
diabetes;
likely to be more than double by 2030;
Around 3.2 million deaths every year are
attributable to complications of diabetes;
six deaths every minute (WHO, 2007).
At least 20 million diabetics in India.
 Types of diabetes?(Goodman
and Gilman’s)
 Type 1 diabetes mellitus
• Autoimmune type 1 diabetes mellitus
(type 1A)
• Non-autoimmune type 1 diabetes
mellitus (type 1B)
 Type 2 diabetes mellitus
 Each year, about 160,000 people
die from diabetes and its
complications
• Cardiovascular disease: 75% of deaths
• Stroke: risk is 2.5x higher
• Hypertension: 60-65% risk
• Kidney disease: 19-34% of diabetes
population
• Blindness: 14-40% of diabetes population
• Amputations: 50% of diabetes population
Amino Acid Sequence of Bovine Insulin
Hormones secreted by pancreas
• Each islet contains 4 types of hormone producing cells.
  or A cells – Secrete GLUCAGON
 or B cells – Secrete INSULIN
 or D cells – Secrete SOMATOSTATIN
 F cells – Remainder of the pancreatic islet cells & secrete
PANCREATIC POLYPEPTIDE
• Glucagon elevates the blood glucose levels
• Insulin lowers the blood glucose level
• Somatostatin acts in a paracrine manner to inhibit both insulin
and glucagon release from neighboring beta and alpha cells.
• Pancreatic polypeptide somatostatin secretion
Factors regulating insulin secretion
Action of Insulin
 Factors effecting Insulin secretion
•The secretion of the hormone insulin by the Beta cells of the
pancreas is stimulated by glucose and the parasympathetic nervous
system
.•In essence, insulin signals the fed state it stimulates
•The storage of fuels and the synthesis of proteins in a variety of
ways. For instance, insulin initiates protein kinase cascades
•it stimulates glycogen synthesis in both muscle and the liver and
suppresses gluconeogenesis by the liver,
•Insulin also accelerates glycolysis in the liver, which in turn
increases the synthesis of fatty acids.
Family of glucose transporters
 Glucose Transporters in human
• The insulin receptor is a disulfide-bonded dimer of alpha beta pairs even when insulin
is not bound.
• Several glucose transporters mediate the thermodynamically downhill movement of
glucose across the plasma
• membranes of animal cells. Each member of this protein family, named GLUT1 to
GLUT5, consists of a single polypeptide chain about 500 residues long
• GLUT1 and GLUT3, present in nearly all mammalian cells, are responsible for basal
glucose uptake. Their K M value for glucose is about 1 mM, significantly less than the
normal serum-glucose level, which typically ranges from 4 mM to 8 mM. Hence,
GLUT1 and GLUT3 continually transport glucose into cells at an essentially constant
rate.
• GLUT2, present in liver and pancreatic b cells, is distinctive in having a very high K M
value for glucose (15 20 mM). Hence, glucose enters these tissues at a biologically
significant rate only when there is much glucose in the blood.
• The pancreas can thereby sense the glucose level and accordingly adjust the rate of
insulin secretion. Insulin signals the need to remove glucose from the blood for storage
as glycogen or conversion into fat (Section 30.3). The high K M value of GLUT2 also
ensures that glucose rapidly enters liver cells only in times of plenty.
• GLUT4, which has a K M value of 5 mM, transports glucose into muscle and fat cells.
The presence of insulin, which signals the fed state, leads to a rapid increase in the
number of GLUT4 transporters in the plasma membrane. Hence,insulin promotes the
uptake of glucose by muscle and fat. The amount of this transporter present in muscle
membranes increases in response to endurance exercise training.
• GLUT5, present in the small intestine, functions primarily as a fructose transporter.
 Role of Insulin
 Insulin lowers the concentration of glucose in blood by
• Inhibits hepatic glucose production (liver)
• Stimulates hepatic glucose uptake (liver)
• Stimulates glucose uptake (muscle)
• Inhibits flow of gluconeogenic precursors to the liver
(e.g., alanine, lactate, and pyruvate)

 Inhibits flow of gluconeogenic precursor to liver

(glycerol) and reduces energy substrate for hepatic
gluconeogenesis (nonesterfied fatty acids) (adipose
tissue)
Sign & Symptoms of DM
Risk Factors
 HIGH BLOOD SUGAR
How it may
feel

Blurry vision.
Thirsty, dry throat.

Always very tired.

Frequent urination.
Complications
 Multiple mechanisms of vascular damage
associated with dysglycaemia
Insulin resistance
 FFA
Lipaemia Obesity
Pancreas Skeletal
muscles Adipo-
Hyper-
insulinaemia TNF- cytes

FFA
Hypertension Dyslipidaemia
VLDL ( triglycerides)
Advanced C-reactive
Genetic protein
predisposition glycation HDL
end products  Fibrinogen

PAI-1

Hyperglycaemia Liver

Glycated
protein Thrombosis

FFA: free fatty acid; HDL: high-density lipoprotein,

PAI: plasminogen activator inhibitor, TNF: tumour Libby P, et al. Circulation 2002;106:2760–63.
necrosis factor, VLDL: very low-density lipoprotein
Diabetic Secondary Complications:
Overview

Macro-
angiopathy

Micro-angiopathy

Metabolic-toxic
damage
(neuropathy)
 Macrovascular complications
Cerebrovascular Stroke (22%*)
circulation
Angina
MI (34.7%*)
Coronary
Sudden death
arteries
Renal damage
Renal
arteries

Peripheral vascular
Peripheral disease
arteries Gangrene
and amputation (2.7%*)
 Long Term Complications
– Renal disease is more prevalent among patient
with type 1 diabetes
– Cardiovascular complication is more prevalent
among older patient with type 2 diabetes
• MACROVASCULAR COMPLICATION
– Result from changes in the medium to large blood
vessels
– Blood vessel wall thicken, scleroses and become
occluded by plaque that adheres to the vessel wall
• Three main types of macrovascular
complication
a.CAD typical ischemic symptoms
b.CVA
c.Peripheral vascular disease.
• MICROVASCULAR COMPLICATIONS AND
DIABETIC RETINOPATHY
1. Diabetic microvascular diseases.
a. AKA microangiopathy
b. Characterized by capillary basement membrane thickening
c. Basement membrane surrounds the endothelial cells of the
capillary
d. Increase blood glucose level reacts through a series of
biochemical response to thicken the basement membrane
to several times it’s normal thickness
c. 2 areas are affected
– Retina
– Kidney
f. changes in microvasculature
• microaneurysm
• intraretinal hemorrhage
• hard exudates
• focal capillary closure
c. 3 main stages of retinopathy
• Non proliferative
• Preproliferative
• Proliferative
 Type 1 and type 2 diabetes- lead to visual distortion and loss of
central vision
• preproliferative retinopathy- is considered a
precursor to the more serious proliferative
retinopathy
• proliferative retinopathy widespread vascular
changes and loss of nerve fibers
• if visual changes occur during preproliferative
stage caused by macular edema
PROLIFERATIVE RETINOPATHY
1. characterized by proliferation of new blood vessel growing
from the retina into the vitreous
2. Blood vessel are prone to bleeding
3. Vitreous hemorrhage caused visual losses associated with
proliferative retinopathy.
4. NORMAL vitreous are clear allowing light to be
transmitted to the retina
5. If hemorrhage occur the vitreous becomes clouded and
cannot transmit light resulting in loss of vision
6. Another consequence is that vitreous hemorrhage
resorption of blood in the vitreous leads to the formation of
fibrous scar tissue
7. scar tissue place traction in the retina resulating in retinal
detachment and subsequent visual loss
8. SIGNS AND SYMPTOMS
• Blurry vision secondary to macular edema
• Indicative of hemorrhaging
1. floaters
2. cobwebs in visual field
3. sudden visual changes – spotty hazy
vision complete loss of vision
• Nausea during dye injection
• Yellowish fluorescent discoloration of the
skin and urine
 Other Complications from Diabetes

A. Increased susceptibility to infection

• Predisposition is combined effect of other complications
• Normal inflammatory response is diminished
• Slower than normal healing
B. Periodontal disease
C. Foot ulcers and infections: predisposition is
combined effect of other complications
D. Male erectile dysfunction
• Half of all diabetic men have erectile dysfunction
 CLINICAL FEATURES AND
BIOCHEMICAL CORRELATIONS
• Polyuria
• Polydypsia
• Polyphagia
• Weakness and fatigue
• Diabetic Ketoacidosis
• Hypercholesterolemia leading to atherosclerosis
• Weight loss
• Hemoconcentration- related to dehydration
• Hypovolemia- decreased blood volume
• Hyperviscosity – thick concentrated blood
• Hypoperfusion- decreased circulation
• Hypokalemia and Hyponatremia
• Kussmaul respirations
 CLINICAL FEATURES AND
BIOCHEMICAL CORRELATIONS
• Polyuria:
– Frequent and excessive urination
– Osmotic diuresis caused by excess glucose in urine
– Water loss can be severe along with sodium, chloride, and
potassium
• Polydipsia:
– Excessive thirst associated with dehyration
• Polyphagia:
– Cells do not receive glucose leading to starvation which triggers
excessive eating
• Weakness and fatigue
– Due to lack of glucose available for ATP formation.
• Weight loss
– Catabolism of lipids and proteins as a part of gluconeogenesis
 CLINICAL FEATURES AND
BIOCHEMICAL CORRELATIONS
• Diabetic Ketoacidosis (DKA)
– DKA results in altered lipid metabolism.
– increased concentrations of total lipids,
cholesterol, triglycerides, and free fatty acids.
– free fatty acids are shunted into ketone body
formation due to lack of insulin; the rate of
formation exceeds the capacity for their
peripheral utilization and renal excretion
leading to accumulation of ketoacids, and
therefore metabolic acidosis.
 CLINICAL FEATURES AND
BIOCHEMICAL CORRELATIONS
• Kussmaul respirations:
– Excess acids cause increased H+ and CO2 levels
– Stimulate brain to increase rate and depth of
respirations to excrete acid and carbon dioxide
– Acetone is exhaled thus breath has “fruity” odor
– Ultimately, pH will drop
• Hypokalemia and Hyponatremia
– Lack of insulin causes depletion of potassium
and sodium
• Blood vessels changes
– Macrovascular:
• Coronary heart disease, cerebrovascular
accidents; & peripheral vascular disease
• Major risk factor for CAD, MI
– Microvascular:
• Nephropathy (Kidney dysfunction)
• Neuropathy (Nerve dysfunction)
• Retinopathy (Vision problems)
 DIABETIC RETINOPATHY
• Diabetes results in changes in veins, arteries and
capillaries in the body.
• Risk of developing diabetic retinopathy: damage
occurs to the fragile blood vessels inside the retina.
• Could develop cataracts (clouding of the naturally
clear lens in the eye).
• May develop glaucoma (a disease of the optic
nerve).
• Two Forms – Non proliferative Diabetic Retinopathy
(NPDR) and
• Proliferative Diabetic Retinopathy (PDR).
 NPDR
• Early stage diabetic retinopathy
• Hard exudates on the central retina (macula).
• Microaneurysms (small bulges in blood
vessels of the retina that often leak fluid).
• Retinal hemorrhages (tiny spots of blood that
leak into the retina).
• Macular edema (swelling/thickening of
macula).
• Macular ischemia (closing of small blood
vessels/capillaries).
 PDR
• Later stage diabetic retinopathy
• Vitreous hemorrhage (new, abnormal blood
vessels bleed into vitreous gel in center of
eye, preventing light rays from reaching the
retina).
• Traction retinal detachment (new, abnormal
blood vessels begin to shrink and tug on
retina; may cause retina to detach).
• Neovascular glaucoma (neovascularization
occurs in the iris, causing pressure to build
up in the eye, damaging the optic nerve).
Insulin also accelerates the conversion of pyruvate into acetyl CoA by stimulating the
dephosphorylation of the complex. In turn glucose is funneled into pyruvate.

Synthesis of Proinsulin by Bacteria. Proinsulin, a precursor of insulin, can be

synthesized by transformed (genetically altered) clones of E. coli. The clones
contain the mammalian proinsulin gene. Bacteria produce much of the insulin
used today by millions of diabetics.
 Insulin Stimulates Glycogen Synthesis by Activating Protein
Phosphatase 1
The presence of glucagon signifies the starved state and initiates
glycogen breakdown while inhibiting glycogen synthesis. When blood-
glucose levels are high, insulin stimulates the synthesis of glycogen by
triggering a pathway that activates protein phosphatase 1.
The first step in the action of insulin is its binding to a receptor tyrosine
kinase in the plasma membrane. Multiple phosphorylations again serve
as the instigation for a regulatory wave of dephosphorylations. The
binding of insulin to its receptor leads to the activation of an insulin-
sensitive protein kinase that phosphorylates the RGl subunit of PP1 at a
site different from that modified by protein kinase A. This
phosphorylation leads to the association of the RGl subunit with PP1 and
the glycogen molecule. The consequent dephosphorylation of glycogen
synthase, phosphorylase kinase, and phosphorylase promotes glycogen
synthesis and blocks its degradation. Once again we see that glycogen
synthesis and breakdown are coordinately controlled.
Insulin Activates Protein Phosphatase 1. Insulin triggers a cascade
leading to the activation of protein phosphatase 1, which results in the
stimulation of glycogen synthesis and inhibition of its breakdown. The activated
receptor tyrosine kinase switches on a putative master kinase that
phosphorylates the insulin-sensitive protein kinase. In turn, the glycogen-
targeting subunit (RGl subunit) of the phosphatase is phosphorylated, which
activates the enzyme.
Insulin Secretion. The electron micrograph shows the release of insulin
from a pancreatic b cell. One secretory granule is on the verge of fusing with
the plasma membrane and releasing insulin into the extracellular space, and
the other has already released the hormone.
Insulin accelerates the uptake of blood glucose into the liver by GLUT2. The level of
glucose 6-phosphate in the liver rises because only then do the catalytic sites of
glucokinase become filled with glucose. Glucokinase is active only when blood-
glucose levels are high. Consequently, the liver forms glucose 6-phosphate more
rapidly as the blood glucose level rises. The increase in glucose 6-phosphate coupled
with insulin action leads to a buildup of glycogen stores. The hormonal effects on
glycogen synthesis and storage are reinforced by a direct action of glucose itself.
Phosphorylase a is a glucose sensor in addition to being the enzyme that cleaves
glycogen. When the glucose level is high, the binding of glucose to phosphorylase a
renders the enzyme susceptible to the action of a phosphatase that converts it into
phosphorylase b, which does not readily degrade glycogen. Thus, glucose allosterically
shifts the glycogen system from a degradative to a synthetic mode.
The high insulin level in the fed state also promotes the entry of glucose into muscle
and adipose tissue. Insulin stimulates the synthesis of glycogen by muscle as well as by
the liver.
The entry of glucose into adipose tissue provides glycerol 3-phosphate for the synthesis
of triacylglycerols. The action of insulin also extends to amino acid and protein
metabolism. Insulin promotes the uptake of branched-chain amino acids (valine,
leucine, and isoleucine) by muscle.
Indeed, insulin has a general stimulating effect on protein synthesis, which favors a
building up of muscle protein. In addition, it inhibits the intracellular degradation of
proteins.
The large amount of glucose formed by the hydrolysis of glucose 6-phosphate derived
from glycogen is then released from the liver into the blood. The entry of glucose into
muscle and adipose tissue decreases in response to a low insulin level. The diminished
utilization of glucose by muscle and adipose tissue also contributes to the maintenance
of the blood glucose level. The net result of these actions of glucagon is to markedly
increase the release of glucose by the liver.
Type 1 Diabetes Mellitus
 Type 1 Diabetes Mellitus
Juvenile onset Diabetes
• Type I diabetes, or insulin-dependent diabetes mellitus
(IDDM) also known as Juvenile onset Diabetes, is caused by
autoimmune destruction of the insulin secreting beta cells of
the islets of Langerhans and usually begins before age 20.
• The term insulin dependent means that the individual requires
insulin to live.
• Recent evidence in mice suggests that killer T lymphocytes
may target an enzyme known as glutamate decarboxylase in
the beta cells. This autoimmune destruction of the beta cells
may be provoked by an environmental agent, such as infection
by viruses.
In type I diabetes, insulin is absent and consequently glucagon is
present at higher-than-normal levels. In essence, the diabetic person
is in biochemical starvation mode despite a high concentration of
blood glucose. Because insulin is deficient, the entry of glucose into
cells is impaired. The liver becomes stuck in a gluconeogenic and
ketogenic state.
The excessive level of glucagon relative to insulin leads to a
decrease in the amount of F-2,6-BP in the liver. Hence, glycolysis is
inhibited and gluconeogenesis is stimulated because of the opposite
effects of F-2,6-BP on phosphofructokinase and fructose-1,6-
bisphosphatase .
The high glucagon/insulin ratio in diabetes also promotes glycogen
breakdown. Hence, an excessive amount of glucose is produced by
the liver and released into the blood.
 Ketoacidosis
• The absence of insulin has two major biochemical consequences. First,
the liver cannot absorb glucose and consequently cannot provide
oxaloacetate to process fatty acid-derived acetyl CoA.
• Because carbohydrate utilization is impaired, a lack of insulin leads to
the uncontrolled breakdown of lipids and proteins.
• Large amounts of acetyl CoA are then produced by beta-oxidation.
However, much of the acetyl CoA cannot enter the citric acid cycle,
because there is insufficient oxaloacetate for the condensation step.
Recall that mammals can synthesize oxaloacetate from pyruvate, a
product of glycolysis, but not from acetyl CoA; instead, they generate
ketone bodies.
• A striking feature of diabetes is the shift in fuel usage from
carbohydrates to fats; glucose, more abundant than ever, is spurned. In
high concentrations, ketone bodies overwhelm the kidney's capacity to
maintain acid-base balance. The untreated diabetic can go into a coma
because of a lowered blood pH level and dehydration.
Synthesis of Ketone Bodies by the Liver
 Ketogenesis
• Both Acetoacetate and beta
hydroxybutyrate are acidic and if levels of
these ketone bodies are too high, the pH
of the blood drops resulting in
ketoacidosis.
• This is very rare and generaly happens
only in untreated type I Diabetes and
Alcoholics
Type II, or non-insulin-dependent, diabetes accounts for more than 90% of
the cases and usually develops in middle aged, obese people. The exact
cause of type II diabetes remains to be elucidated, although a genetic basis
seems likely.
Insulin Recepter
 Food Intake and Starvation Induce Metabolic
Changes

Insulin signals the fed state: it stimulates the formation of glycogen and
triacylglycerols and the synthesis of proteins. In contrast, glucagon
signals a low blood-glucose level: it stimulates glycogen breakdown and
gluconeogenesis by the liver and triacylglycerol hydrolysis by adipose
tissue. After a meal, the rise in the blood-glucose level leads to increased
secretion of insulin and decreased secretion of glucagon. Consequently,
glycogen is synthesized in muscle and the liver.
When the blood-glucose level drops several hours later, glucose is then
formed by the degradation of glycogen and by the gluconeogenic
pathway, and fatty acids are released by the hydrolysis of
triacylglycerols. The liver and muscle then use fatty acids instead of
glucose to meet their own energy needs so that glucose is conserved for
use by the brain.
 Food Intake and Starvation Induce Metabolic
Changes
The metabolic adaptations in starvation serve to minimize protein
degradation. Large amounts of ketone bodies are formed by the liver
from fatty acids and released into the blood within a few days after the
onset of starvation. After
several weeks of starvation, ketone bodies become the major fuel of the
brain. The diminished need for glucose decreases the rate of muscle
breakdown, and so the likelihood of survival is enhanced.
Diabetes mellitus, the most common serious metabolic disease, is due to
metabolic derangements resulting in an insufficiency of insulin and an
excess of glucagon relative to the needs of the individual. The result is
an elevated blood glucose level, the mobilization of triacylglycerols, and
excessive ketone-body formation. Accelerated ketone-body formation
can lead to acidosis, coma, and death in untreated insulin-dependent
diabetics.
Mechanism of Insulin Secretion
Action of Insulin on Carbohydrate, Protein
and Fat Metabolism
• Carbohydrate
• Facilitates the transport of glucose into muscle
and adipose cells
• Facilitates the conversion of glucose to
glycogen for storage in the liver and muscle.
• Decreases the breakdown and release of
glucose from glycogen by the liver
Action of Insulin on Carbohydrate, Protein
and Fat Metabolism
• Protein
• Stimulates protein synthesis
• Inhibits protein breakdown; diminishes
gluconeogenesis
Action of Insulin on Carbohydrate, Protein
and Fat Metabolism
• Fat
• Stimulates lipogenesis- the transport of
triglycerides to adipose tissue
• Inhibits lipolysis – prevents excessive
production of ketones or ketoacidosis
Alternate routes for taking Insulin
 Beta-cell replacement
(Shimon Efrat)
 Beta-cell replacement is considered the optimal
treatment for type 1 diabetes, however, it is
hindered by a shortage of human organ donors.
 Given the difficulty of expanding adult beta cells
in vitro, stem/progenitor cells, which can be
expanded in tissue culture and induced to
differentiate into multiple cell types, represent an
attractive source for generation of cells with
beta-cell properties.
Stem cells for the treatment of diabetes
(Burns CJ et al)
 Bone marrow-derived stem cells could initiate pancreatic regeneration.
 Pancreatic stem/progenitor cells have been identified, and the formation
of new beta cells from duct, acinar and liver cells is an active area of
investigation.
 Some agents including glucagon-like peptide-1/exendin-4 can stimulate
the regeneration of beta cells in vivo .
 Overexpression of embryonic transcription factors in stem cells could
efficiently induce their differentiation into insulin-expressing cells.
 New technology, known as protein transduction technology, facilitates
the differentiation of stem cells into insulin-producing cells.
 Recent progress in the search for new sources of beta cells has opened
up several possibilities for the development of new treatments for
diabetes.
 Potential role of leptin in diabetes.
 Regulating appetite control and energy metabolism, plays a major role
in islet cell growth and insulin secretion.
 Diabetes—Treatment Goals
• FPG 90—130 mg/dl
• A1c <7%
• Peak PPG <180 mg/dl
• Blood pressure <130/80 mmHg
• LDL-C <100 mg/dl
• Triglycerides <150 mg/dl
• HDL-C >40 mg/dl*
*for women HDL-C goal may be increased by 10 mg/dl

American Diabetes Association Standards of medical care in diabetes. Diabetes Care 30:S4-S36, 2007
Retinopathy
Retinopathy
Diabetic Foot
Gengrene
 Sweeteners and Diabetes
• Sugar alcohols and nonnutritive
sweeteners are safe when
consumed within the daily intake
levels established by the Food and
Drug Administration (FDA) (A)

Nutrition recommendations and interventions for diabetes. Diabetes Care 31:S61-S78,

2008
 Nutritive Sweeteners: Sugar
Alcohols
• Sorbitol, mannitol, xylitol, isomalt, lactitol,
hydrogenated starch hydrolysates
• Lower glycemic response, lower calorie content
than sucrose
• Not water-soluble so often combined with fats in
foods; often deliver as many calories as
sucrose-sweetened foods
• Unlikely to have a beneficial effect on blood
sugars
• In large quantities, may cause GI distress and
diarrhea
 Non-Caloric Sweeteners
• Saccharin  (Sweet’N Low®)

• Aspartame (NutraSweet®)

• Acesulfame potassium, acesulfame-K

(Sweet One®)

• Sucralose (SPLENDA®)
 Non-nutritive Sweeteners
• All FDA-approved non-nutritive sweeteners can
be used by persons with diabetes
• Include aspartame, acesulfame K, sucralose, and
saccharin
• FDA has established an acceptable daily intake
(ADI) for food additives
• Average intake of aspartame is 2 to 4 mg/kg/day,
whereas the ADI is 50 mg/kg/day
• ADI of Acesulfame K is 15 mg/kg, which is the
equivalent of a 60 kg person eating 36 teaspoons
of sugar daily.
 Protein and Diabetes
• High-protein diets are not recommended as a
method for weight loss at this time. The long-term
effects of protein intake >20% of calories on
diabetes management and its complications are
unknown.
• Although such diets may produce short-term weight
loss and improved glycemia, it has not been
established that these benefits are maintained long
term, and long-term effects on kidney function for
persons with diabetes are unknown.

Nutrition recommendations and interventions for diabetes.

Diabetes Care 31:S61-S78, 2008
 Dietary Fat
• Saturated Fat: <7% of total calories (A)
• Cholesterol: <200 mg/day in people with
diabetes
• Minimize intake of trans-fatty acids (E)
• Two or more servings of fish per week
providing n-3 polyunsaturated fatty acids
are recommended
Nutrition recommendations and interventions for diabetes.
Diabetes Care 31:S61-S78, 2008
 Optimal Mix of Macronutrients
• The best mix of protein, Carbohydrate and
fats varies depending on individual
circumstances.
• The DRIs recommend that healthy adults
should consume 45-65% of energy from
CHO, 20-35% from fat, and 10-35% from
protein
• Total caloric intake must be appropriate for
weight management
Nutrition recommendations and interventions for diabetes.
Diabetes Care 31:S61-S78, 2008
 Lipid Goals in Diabetes
• LDL cholesterol <100 mg/dl
• HDL cholesterol
Men >40 mg/dl
Women >50 mg/dl
• Triglycerides <150 mg/dl

American Diabetes Assoc. Standards of Medical care for Adults with Diabetes.
Diabetes Care 30 (supplement 1) 2007. Accessed 2/13/07
Blood Pressure Goals in Diabetes
• Patients with diabetes should be
treated to a systolic blood
pressure <130 mmHg (C)
• Patients with diabetes should be
treated to a diastolic blood
pressure of <80 mmHg (B)
American Diabetes Assoc. Standards of Medical Care in Diabetes-2007.
Diabetes Care 30 (supplement 1) 2007. Accessed 2/14/07
 Energy Balance, Over-wieght and
Obesity
• In overweight and obese insulin-resistant individuals, modest weight
loss has been shown to improve insulin resistance. Thus, weight
loss is recommended for all such individuals who have or are at risk
for diabetes.
• For weight loss, either low-carbohydrate or low-fat calorie-restricted
diets may be effective in the short term (up to 1 year).
• For patients on low-carbohydrate diets, monitor lipid profiles, renal
function, and protein intake (in those with nephropathy), and adjust
hypoglycemic therapy as needed.
• Physical activity and behavior modification are important
components of weight loss programs and are most helpful in
maintenance of weight loss. (B)
• Weight loss medications may be considered in the treatment of
overweight and obese individuals with type 2 diabetes and can help
achieve a 5–10% weight loss when combined with lifestyle
modification. (B)

Nutrition recommendations and interventions for diabetes. Diabetes

Care 31:S61-S78, 2008
 Micronutrients
• There is no clear evidence of benefit from vitamin or mineral
supplementation in people with diabetes (compared with the general
population) who do not have underlying deficiencies.
• Routine supplementation with antioxidants such as vitamins E and
C and carotene is not advised because of lack of evidence of
efficacy and concern related to long term safety.
• Benefit from chromium supplementation in individuals with diabetes
or obesity has not been clearly demonstrated and therefore can not
be recommended.
• Those who may need supplementation include those on extreme
weight-reducing diets, strict vegetarians, the elderly, pregnant or
lactating women, clients with malabsorption disorders, congestive
heart failure (CHF) or myocardial infarction (MI)
• Chromium and magnesium are beneficial only if the client is
deficient.

Nutrition recommendations and interventions for diabetes.

Diabetes Care 31:S61-S78, 2008
 Primary sites of action of oral
Hypoglycaemic Agents
-glucosidase Biguanides
inhibitors

Sulfonylureas/
meglitinides Thiazolidinediones

 Glucose
output
 Carbohydrate  Insulin
breakdown/ resistance
absorption
 Insulin
secretion
 Insulin
resistance
 Oral Hypoglycemic Agents
Classification of Oral Hypoglycemic Agents
• Sulfonylureas :
Glipizide (Glucotrol), Chlorpropamide (Diabinese),
Tolazamide (Tolinase)
• Meglitinides :
Repaglinide (Prandin), Nateglinide (Starlix)
• Biguanides :
Metformin (Glucophage)
• Alpha-glucoside Inhibitors :
Acarbose (Precose), Miglitol (Glyset), Voglibose
• Thizaolidinediones (Glitazones) :
Rosiglitazone (Avandia), Pioglitazone (Actos)
Thank you for your
attention!

Any Questions?