pathophysiology of DM1

1. Type 1 Diabetes MellitusType 1 Diabetes Mellitus
Manoj SharmaManoj Sharma

2. Diabetes Mellitus Diabetes Mellitus epidemiology
•Worldwide 30 million cases in 1985 to 285 Worldwide 30 million cases in 1985 to 285
million in 2010 .million in 2010 .
•Estimated 438 million people will have Estimated 438 million people will have
DM by 2030.DM by 2030.
• T1DM accounts for 10% of all diabetics.T1DM accounts for 10% of all diabetics.
•Incidence is increasing in most Incidence is increasing in most
populationspopulations

3. •Incidence highest in northern european
countries like Finland(35/lakh childern per
year.
•Africans and east asians relatively spared
(0.7/lakh childern in karachi)
•About 4 lakh new cases occurring
annually under 14 yr world about half are
in Asia.
•Peak age of presentation
5-7 yr age
At puberty

4. Definition Definition
A chronic disorder of carbohydrate & fat A chronic disorder of carbohydrate & fat
metabolism due to absolute/or relative metabolism due to absolute/or relative
deficiency in insulin secretion &/or deficiency in insulin secretion &/or
ineffective biological responses to ineffective biological responses to
insulin resulting in hyperglycemia insulin resulting in hyperglycemia

5. Type 1 DMType 1 DM
•Due to pancreatic islet B cell destruction
predominantly by an autoimmune process.
Immune mediated in over 90% of cases
and idiopathic in less than 10% .
•The rate of B cell destruction is quite
variable being rapid in some individuals
and slow in others

6. Insulin Promotes Anabolism
Insulin lowers plasma glucose by:
1.Increasing glucose transport into
most insulin sensitive cells
2.Enhancing cellular utilization and
storage of glucose
3.Enhancing utilization of amino
acids
4.Promoting fat synthesis

7. INSULIN

9. Glucagon Is Dominant In The Fasting State
Glucagon prevents hypoglycemia.
Glucagon is secreted when plasma glucose
levels fall below 100 mg/dL.
The liver is the primary target of glucagon.
Glucagon stimulates glycogenolysis and
gluconeogenesis to increase glucose output by
the liver.
Glucagon release is also stimulated by plasma
amino acids.

10. GLUCAGON

11. Pathogenesis of T1DMPathogenesis of T1DM
Genetic susceptibility
Environmental triggers
Abnormalities in immune regulation

12. Family History & Risk For Family History & Risk For
Developing T1DMDeveloping T1DM
0.4% occurrence rate in persons
with no family history of T1DM
6-11% in offspring of person with
T1DM
5% in siblings of person with T1DM
30-40% in identical twins

13. Pathogenesis of T1DMPathogenesis of T1DM
Genes + Environment
Type 1 Diabetes
Beta Cell
Destruction
Induction of
Autoimmunity
Immune
Regulation
Trigger
? Virus

14. Role of geneticsRole of genetics
•Clear familial clustering
•Risk is 2% with diabetic mother but 7%
when father is diabetic
•Monozygotic twins concordance rate 30-
65% and dizygoyic twins has rate 6-10%

15. MHC/HLA encoded susceptibility to T1DMMHC/HLA encoded susceptibility to T1DM
•CLASS ll genes most strongly linked

•About 95% of type 1 patients possess
either HLA-DR3 or HLA-DR4 alleles
•Much of risk of HLA DR3/4 is because of
their linkage to other alleles in DQ region.

16. Genotyping has shown haplotypes DQA1
0301 AND DQB1 0302/0201 are most
strongly associated.
In addition to MHC class ll at least 20
different loci identified
• Role of HLA class1 : most significant is
HLA-B39.

17. •Polymorphism in promotor region of
insulin gene
•CTLA4 gene
•Interleukin 2 and 1 receptors genes
•Interferon induced helicase (lFlH1) gene
•PTPN22 and PTPN2
•CYP27B1

18. Environmental Factors Environmental Factors
•Variations in urban and rural areas of
same ethnic group
•Change of incidence with migration
•50% of monozygotic twins are discordant
for T1DM.
•Increase in incidence in almost all
populations in last few decades

19. Viral infectionsViral infections
•Congenital rubella syndrome : associted
with beta cell autoimmunity in 70% and
development of T1DM in 40%
•Viruses like coxsackie isolated post
mortem from islets of some T1DM
subjects
•Mumps virus : possible etiology.
•Rotaviruses

20. •Viral infectons can release B cell antigens
•Molecular mimicry: peptide sequence of
P2-C capsid of coxsackie B cross react
with GAD65 in B cell membrane.
•Kilham rat virus targets the animal B cells

21. Viral Replication
i) Direct β Cell
Lysis & Death
iii) Induction of Autoimmune
Response & b Cell Death
IFIH1 ii) Induction of Innate
Immune Response & β
Cell Death
Type 1 IFNs
MHC Class I
CD8+ T-cell
Viral Antigen
Self Antigens: IAA, GAD
Viral Induction of Insulitis

22. Other Environmental factorsOther Environmental factors
•Early exposure to cow’s milk protien and
gluten
•Other dietary factors omega-3 fatty acids
• Vitamin D defeciency
• Zinc
•Ascorbic acid
•Vit E
•Psychological stress

23. Pathogenesis and natural Pathogenesis and natural
historyhistory
•Initiation of autoimmunity
•Preclinical autoimmunity and progressive
loss of beta cell functions
•Onset of clinical disease

24. • Triggers like prenatal influences, viral
infection, diet in infancy are linked with
onset of autoimmunity
•In majority of children diagnosed before
10 years lst sign of autoimmunity appears
before 02 years.

25. Initiation of autoimmunity
•Most patients at diagnosis have islet cell
antibodies ( ICA) are composite of several
antibodies directed at pancreatic islet
molecules like
– Insulin antibodies(IAA)
– Glutamic acid decarboxylase (GAD 65)
– Tyrosine phosphatases IA-2 and IA2-b
–B cell specific zinc transporter Zn-T8

26. •Risk of clnical disease increases with
number of autoantibodies and intensity of
response (Ab titres).
•30% risk with 1 antibody and 90% when 3
are present
•ICAs serve as marker of autoimmune
process of T1DM.
•Assays for autoAb to GAD65 are
available.

27. Autoimmunity Autoimmunity
•Strong association with endocrine and
other autoimmune diseases like Schmidts
syndrome
•APECED- autoimmune
polyendocrinopathy- candidiasis
ectodermal dystrophy by mutation in AIRE
gene
•IPEX syndrome immunodysregulation
polyendocrinopathy and enteropathy

28. Progressive loss of beta cellsProgressive loss of beta cells
•Actual damage to b cells is T cell
mediated and not by ICA.
•Pancreatic islets are infiltirated by T and B
lymphocytes, monocytes/macrophages
and NK cells (insulitis)
•Release of cytokines TNF a IFN g and IL-
1 within insulitis and progressive loss of
beta cells

29. •In patients with new onset disease
treatment with
• anti CD3 monoclonal Ab
•GAD vaccine
•Anti B lymphocytes monoclonal Ab
all have shown to decrease the C-
pepetide levels.

30. InsulinitisInsulinitis
Type 1 DM

31. ? Viral Trigger
Detection of circulating autoantibodies
(ICA, GAD65, IAA, IAA-2)
Initiation of autoimmune response
Progressive loss of beta-cell
mass induced by CD4+ & CD8+
cells
Glucose
intolerance
< 15-20 % of
b-cells are
“functional”
remain
Time
(Months)
b-Cell
mass 100%
10
“Pre”-
diabetes
Genetic
predisposition
Insulitis
b-Cell injury
Eisenbarth GS. N Engl J Med. 1986;314:1360-1368
Diabetes
Natural History of T1DMNatural History of T1DM

32. Pathogenesis of Type 1DMPathogenesis of Type 1DM
Environment ?Environment ?
Viral infe..??Viral infe..??
Genetic Genetic
HLA-DR3/DR4HLA-DR3/DR4
Severe Insulin deficiencySevere Insulin deficiency
ß cell Destructionß cell Destruction
Type 1 DMType 1 DM
Autoimmune Insulinitis Autoimmune Insulinitis

34. CONCLUSIONCONCLUSION
•Increasing incidence worldwide and Asian
countries accounting for about half of this
number.
•Clear role of genetic predisposition
•Envoinmental factors like viral infections
and dietery factors also important.
• Autoimmunity and Progressive b cell
destruction before onset of clinical disease

35. •Interplay of neural, hormonal and
substrate related mechanisms leading to
hyperglycemia, hyperlipedimia and
eventual ketoacidosis.
•About 20-40% of childern with new onset
diabetes progress to DKA before
diagnosis
•Prediabetic phase as an opportunity to
prevent subjects with active insulitis to
develop clinical disease.

36. References :
•Oxford textbook of medicine
•Nelson textbook of pediatrics 19
th
edition
•Harrison’s principles of internal medicine
18
th
edition
•Lippincot’s biochemistery 5
th
edition

37. THANK YOUTHANK YOU

40. TYPE 1 DIABETES MELLITUSTYPE 1 DIABETES MELLITUS
•More recently regulatory T cell and
cytotoxic T cell abnormality were
considered to be critical in the
development of isletitis and b cell
destruction.

41. TYPE 1 DIABETES MELLITUSTYPE 1 DIABETES MELLITUS
•The polymorphism in gene encoding
cytotoxic lymphocyte antigeng4 (CTLA-
4) was found related to development of
autoimmune diabetes as well as
autoimmune thyroiditis.
•B-cell reactive T cell avidity was
proposed at the beginning of isletitis.

42. TYPE 1 DIABETES MELLITUSTYPE 1 DIABETES MELLITUS
•Certain unrecognized patients with a
milder expression of type 1 diabetes
initially retain enough b cell function to
avoid ketosis but later in life develop
increasing dependency on insulin
therapy as b cell mass diminishes
(usually 6 years after dignosis).

43. TYPE 1 DIABETES MELLITUSTYPE 1 DIABETES MELLITUS
•Islet cell antibody survey among
northern Europeans indicate that up to
15% of “type 2”patients may actually
have this mild form of type 1 diabetes
(latent autoimmue diabetes of
adulthood, LADA)

44. TYPE 2 DIABETES MELLITUSTYPE 2 DIABETES MELLITUS
•This presents a heterogeneous group
comprising milder forms of diabetes
that occur predominantly in adults but
occasionally in juveniles.
•More than 90% of all diabetes in the
United States and China are included
under this classification .
•In most cases of this type of diabetes,
this cause is unkown.

45. TYPE 2 DIABETES MELLITUSTYPE 2 DIABETES MELLITUS
•The pathogenesis currently received is
illustrated in (Figure 6-18-1 )
•Tissue insensitivity to insulin has been
noted in most type 2 patients
irrespective of weight and has been
attributed to several interrelated factors

46. Figure 6-18-1 pathogenesis of type 2 Figure 6-18-1 pathogenesis of type 2
diabetes mellitusdiabetes mellitus

47. TYPE 2 DIABETES MELLITUSTYPE 2 DIABETES MELLITUS
•These include a putative(and as yet
undefined ) genetic factor ,which is
aggravated in time by additioal
enhancers of insulin resistance such
as aging ,a sedentary lifestyle, and
abdominal –visceral obesity .
•In addition ,there is an accompanying
deficiency in the response of
pancreatic b cells to glucose .

48. TYPE 2 DIABETES MELLITUSTYPE 2 DIABETES MELLITUS
•Both the tissue resistance to insulin
and the impaired b cell response to
glucose appear to be further
aggravated by increased
hyperglycemia (glucose toxicity), and
both defects are ameliorated by
treatment that reduces the
hyperglycemia toward normal

49. TYPE 2 DIABETES MELLITUSTYPE 2 DIABETES MELLITUS
•Most epidemiologic data indicate
strong genetic influences.
•Attempts to identify genetic markers
for type 2 have as yet been
unsuccessful.

50. Other specific types of diabetes mellitusOther specific types of diabetes mellitus
•Other specific types of diabetes mellitus
is relatively rare
•Maturity –onset diabetes of the young
(MODY) is a subgroup due to monogenic
disorder characterized by non-insulin –
dependent diabetes with autosomal
dominant inhenritantance and an age at
onset of 25 years or younger.

51. Other specific types of diabetes mellitusOther specific types of diabetes mellitus
•Diabetes due to mutant insulin is a very
rare subtype of nonobese type 2
diabetes ,with no more than ten
families having been described.

52. Other specific types of diabetes mellitusOther specific types of diabetes mellitus
•Diabetes duo to a mutation of
mitochondrial DNA that impairs the
transfer of leucine or lysine into
mitochondrial , proteins has been
described.

53. Other specific types of diabetes mellitusOther specific types of diabetes mellitus
•Since sperm do not contain
mitochondria, only the mother
transmits mitochondrial genes to her
offspring.

54. Gestational diabetes mellitus (GDM)Gestational diabetes mellitus (GDM)
•GDM is defined as any degree of
glucose intolerance with onset or first
reconition during pregnancy.
•The definition appleies regardless of
whether insulin or only diet
modification is used for treatment or
whether the condition persists after
pregnancy.

55. Gestational diabetes mellitus (GDM)Gestational diabetes mellitus (GDM)
•It does not exclude the possibility that
unrecognized glucose intolerance may
have antedated or begun concomitantly
with the pregnancies.
•The prevalence may range from 1%-
14%of pregnancies, depending on the
population studied

56. Gestational diabetes mellitus (GDM)Gestational diabetes mellitus (GDM)
•GDM represents nearly 90% of all
pregnancies complicated by diabetes.
•Insulin is recommended as the only
modality of treatment even trial of oral
agents that are undertaken showed
safe.

57. Gestational diabetes mellitus (GDM)Gestational diabetes mellitus (GDM)
•Deterioration of glucose tolerance
occurs normally during pregnancy ,
particularlyi n the 3rd trimester.

58. Clinical findingsClinical findings
•Symptoms and signs
•Laboratory findings

59. Clinical findingsClinical findings
•Symptoms and signs
•The principal clinical features of the
two major types of diabetes mellitus
are listed for comparison in (Table 6-
18-3)

60. Diabetes Mellitus: Signs & Diabetes Mellitus: Signs &
SymptomsSymptoms
Three polys:
polyphagia,
polyuria, &
polydipsia
Weight loss
Fatigue
Hyperglycemia

61. Clinical findingsClinical findings
•Symptoms and signs
•Patients with type 1 diabetes present
with a characteristic symptom
complex.
•An absolute deficiency of insulin
results in accumulation of circulating
glucose and fat acids,with conseqent
hyperosmolality and hyperketonemia.

62. Clinical findingsClinical findings
•Symptoms and signs
•Patients with type 2 diabetes may or
may not present with characteristic
features.
•The presence of obesity or a strongly
positive family history for mild diabetes
suggests a high risk for the
development of type 2 diabetes.

63. Laboratory findingsLaboratory findings
•Urinary analysis
•Blood test procedures
•B cell Reserve Evaluation
• Autoantibodies
•Lipoprotein Abormalities in Diabetes

64. Clinical findingsClinical findings
•Laboratory findings
•Urinary analysis
•Glycosuria and ketonuria can be found
in diabetic patients.

65. Clinical findingsClinical findings
•Laboratory findings
•Blood test procedures
•A. Glucose Tolerance Test
•B. Glycated Hemoglobin (Hemoglobin A1)
measurements
•C. Serum Fructosamine
•D. Self –Monitoring of Blood Glucose
•E.Continuous Glucose Monitoring Systems

66. Blood test proceduresBlood test procedures
•A. Glucose Tolerance Test
•Criteria for laboratory confirmation of
diabetes mellitus if the fasting plasma
glucose level is 7.0 mmol/L(126mg/dL)
or higher on more than one occasion ,
further evaluation of the patient with a
glucose challenge is unnecessary .

67. Blood test proceduresBlood test procedures
•A. Glucose Tolerance Test
•However ,when fasting plasma glucose
is less than 7.0 mmol/L(126mg/dL) in
suspected cases ,a standardized oral
glucose tolerance test may be ordered .

68. Blood test proceduresBlood test procedures
B. Glycated Hemoglobin(HemoglobinA1)
measurements
Glycated hemoglobin is abnormally high in
diabetics with chronic hyperglycemia and
reflects their metabolic control.
It is produced by nonenzymatic condensation
of glucose molecules with free amino groups
on the globin component of hemoglobin.

69. Blood test proceduresBlood test procedures
B. Glycated Hemoglobin(HemoglobinA1)
measurements
The higher the prevailing ambient levels of
blood glucose, the higher will be the level of
glycated hemoglobin.
The major form of glycohemoglobin is termed
hemoglobin A1c,which normally comprises
only 4%-6% of the total hemoglobin

70. Blood test proceduresBlood test procedures
B. Glycated Hemoglobin(HemoglobinA1)
measurements
•Since glycohemoglobins circulate with
in red blood cells whose life span lasts
up to 120 days, they generally reflect
the state of glycemia over the
preceding 8-12 weeks, thereby
providing an improved method of
assessing diabetic control.

71. Blood test proceduresBlood test procedures
B. Glycated Hemoglobin(HemoglobinA1)
measurements
•Measurements should be made in patients
with either type of diabetes mellitus at 3-to 4
month intervals so that adjustment in
therapy can be made if glycohemoglobin is
either subnormal or if it is more than 2%
above the upper limits of normal for a
particular laboratory.

72. Blood test proceduresBlood test procedures
•C. Serum Fructosamine
•Serum fructosamine is formed by
nonenzymatic glycosylation of serum
proteins (predominantly albumin).

73. Blood test proceduresBlood test procedures
•C. Serum Fructosamine
• Since serum albumin has a much
shorter half-life than hemoglobin,
serum fructosamine generally reflects
the state of glycemic control for only
the preceding 2 weeks.

74. Blood test proceduresBlood test procedures
•C. Serum Fructosamine
•Normal values vary in relation to the
serum albumin concentration and are
1.5-2.4mmol/L when the serum albumin
level is 5 g/dL

75. Blood test proceduresBlood test procedures
•D.Self –Monitoring of Blood Glucose
•Capillary blood glucose
measurements performed by patients
themselves, as outpatients, are
extremely useful.

76. Blood test proceduresBlood test procedures
E. Continuous Glucose Monitor
Systems
The main value of these systems
appears to be in identifying
episodes of asymptomatic
hypoglycemia, especially at night.

77. B cell Reserve EvaluationB cell Reserve Evaluation
•It is estimated more than 50% of b cell
were lost at the onset of diabetes.
•The b cell reserve is usually measured
in its secreted functional proteins-
insulin.

78. B cell Reserve EvalutionB cell Reserve Evalution
•Measurement of insulin is usually used for
functional evaluation in those not on insulin,
and C-peptide can be used as an alternative
toolin those on insulin.
•Fasting and 2-hour after stimulator insulin or
C-peptide are usually measured .
•The stimulator can be glucose , arginine,
glucagons.

79. B cell Reserve EvalutionB cell Reserve Evalution
•Glucose is often replaced by standard meal
equivalent to 75g glucose.
•Reference values should be setup in each
laboratory and should be interpreted
according to adiposity, or insulin resistance
•The evaluation is not a routine practice in
clinics, but is used in research protocol.

80. AutoantibodiesAutoantibodies
•It is gradually acccepted that determination of
islet b cell autoimmunity is usual in typing of
diabetes
•Insulin autoantibody (IAA), glutamic acid
decarboxylase (GADA), islet cell antibodies
( ICA) ,-now replaced by tyrosine phosphatase
autoantibodies (IA-2,IA2-b) are the most
commonly used tests

81. AutoantibodiesAutoantibodies
•Several other antibodies were studied
for their utility in predicting type 1
diabetes.
•One is carboxypeptidase antibody
(CPH) that is thoroughly studied a
Chinese group.
•IAA is more frequently detected in very
young child diabetes.

82. AutoantibodiesAutoantibodies
•ICA, in juvenile diabetes.
•GADA, in elder diabetes.
•The autoantibodies profile can change
during the progression of disease.
• GADA appears relatively late.
•A positive result predicts the need for
insulin in 6 years.

83. Lipoprotein Abnormalities in Lipoprotein Abnormalities in
DiabetesDiabetes
•Circulating lipoprotein are just as dependent Circulating lipoprotein are just as dependent
on insulin as the plasm glucose .on insulin as the plasm glucose .
•In type 1 diabetes , moderately deficient In type 1 diabetes , moderately deficient
control of hyperglycemia is associated with control of hyperglycemia is associated with
only a slight elevation of only a slight elevation of LDL cholesterolLDL cholesterol and and
serum serum triglyceridestriglycerides and little if any change in and little if any change in
HDL cholesterolHDL cholesterol

84. Lipoprotein Abormalities in DiabetesLipoprotein Abormalities in Diabetes
•Once the hyperglycemia is corrected, Once the hyperglycemia is corrected,
lipoprotein levels are generally normal.lipoprotein levels are generally normal.
•However ,in obese patients with type 2 However ,in obese patients with type 2
diabetes, a distict “diabetic dyslipidemia” is diabetes, a distict “diabetic dyslipidemia” is
characteristic of the insulin resistence characteristic of the insulin resistence
syndromesyndrome. .

85. Lipoprotein Abormalities in DiabetesLipoprotein Abormalities in Diabetes
•Its feathers are a high serum
triglyceride level(300-400mg/L), a low
HDl cholesterol (less than 30mg/dL),
and a qualitative change in LDL
particles, producing a smaller dense
particle whose membrane carries
supro-normal amountes of free
cholesterol.

86. Lipoprotein Abormalities in DiabetesLipoprotein Abormalities in Diabetes
• These small dense LDL particles are more
susceptible to oxidation, which renders them
more atherogenic.
•Since primary disorders of lipid metabolism
may coexist with diabetes, persistence of
lipid abnormalities after restoration of normal
weight and blood glucose should prompt a
diagnostic workup and possible
pharmacotherapy of the lipid disorder.

87. Differential DiagnosisDifferential Diagnosis
•Hyperglycemia secondary to other
sources
•Secondary hyperglycemia has been
associated with various disorders of
insulin target tissues (liver, muscle , and
adipose tissue)(Table 6-18-5).

88. Differential DiagnosisDifferential Diagnosis
•Other secondary cause of carbohydrate
intolerance include endocrine
disorders-often specific endocrine
tumors-accociated with excess
production of growth hormone,
glucocorticoids, catecholamines,
glucagon , or somatostatin.

89. Differential DiagnosisDifferential Diagnosis
•A rare syndrome of extreme insulin
resistance associated with acanthosis
nigricans afflicts either young women with
androgenic features as well as insulin
receptor mutations or older people ,
mostly women , in whom a circulating
immunoglobulin binds to insulin receptors
and reduces their affinity to insulin.

90. Differential DiagnosisDifferential Diagnosis
•Medications such as diuretics ,
phenytoin , niacin, and high-dose
glucocorticoids can produce
hyperglycemia that is reversible once
the drugs are discontinued or when
diuretic-induced hypokalemia is
corrected

91. Differential DiagnosisDifferential Diagnosis
•Chronic pancrearitis or subtotal
pancreatectomy reduces the number of
functioning b cells and can result in
metabolic derangement very similar to
that of genetic type 1 diabetes except
that a concomitant reduction in
pancreatic a cells may reduce glucagon
secretion so that relatively lower doses
of insulin replacement are needed.

92. Differential DiagnosisDifferential Diagnosis
•Insulin-dependent diabetes is
occassionally associated with
Addison’s disease and autoimmune
thyroiditis (Schimidt’s syndrome, or
polyglandular failure syndrome).

93. Differential DiagnosisDifferential Diagnosis
•This occurs more commonly in women
and represents an autoimmune
disorder in which there are circulating
antibodies to adrenocortical and
thyroid tissue, thyroglobulin,and
gastric parietal cells.

94. Nondiabetic GlycosuriaNondiabetic Glycosuria
•Nondiabetic glycosuria(renal
glycosuria) is a benign asymptomatic
condition wherein glucose appears in
urine despite a normal amount of
glucose in blood , either basally or
during a glucose tolerance test.

95. Nondiadetic GlycosuriaNondiadetic Glycosuria
• Its cause may vary from an autosomally
transmitted genetic disorder to one
associated with dysfunction of the proximal
renal tubule (Fanconi’s syndrome ,chronic
renal failure), or it may merely be a
consequence of the increasd load of glucose
presented to the tubules by the elevated
glomerular filtration rate during pregnancy.

96. Nondiabetic GlycosuriaNondiabetic Glycosuria
•As many as 50% of pregnant women
normally have demonstrable sugar in
the urine, especially during the third
and fourth months.
•This sugar is practically always
glucose except during the late weeks of
pregnancy , when lactose may be
present.

97. TreatmentTreatment
•Diabetes mellitus requires ongoing
medical care as well as patient and
family education both to prevent acute
illness and to reduce the risk of long-
term complications.

98. TreatmentTreatment
•Diet
•A well-balanced，nutritious diet remains a
fundamental element of therapy.
•However, In more than half of case ,diabetic
patients fail to follow their diet .
•In prescribing a diet, it is important to relate
dietary objectives to the type of diabetes.

99. TreatmentTreatment
•Diet
•In obese patients with mild hyperglycemia,
the major goal of diet therapy is weight
reduction by caloric restriction.
•Thus ,there is less need for exchange lists,
emphasis on timing of meals ,or periodic
snacks, all of which are so essential in the
treatment of insulin – requiring nonbese
diabetics.

100. TreatmentTreatment
•ADA Recommendations
•The American Diabetes Association release
an annual position statement on medical
nutrition therapy that replaces the calculated
ADA diet formula of the past with
suggestions for an individully tailored dietary
prescription based on metabolic , nutritional,
and life style requirements .

101. TreatmentTreatment
•ADA Recommendations
•They contend that the concept of one diet for
“diabetes” and the prescription of an “ADA
diet” no longer can apply to both major type
of diabetes.
•In their recommendations for persons with
type 2 diabetes, the 55%-60% carbohydrate
content of previous diets has been reduce
considerably because of the tendency of
high carbohydrate intake to cause
hyperglycemia, hypertriglyceridemia, and a
lowered HDL cholesterol

102. TreatmentTreatment
•ADA Recommendations
•.In obese type 2 patients, glucose and lipid
goals join weight loss as the focus of
therapy .
•These patients are advised to limit their
carbohydrate content by substituting
noncholesterologenic monounstaturated oils
such as olive oil ,rapeseed (canola) oil, or the
oil in nuts and avocados.

103. TreatmentTreatment
•ADA Recommendations
•This maneuver is also indicated in type
1 patients on intensive insulin
regimens in whom near-normoglycemic
control is less achievable on higher
carbohydrate diets.

104. TreatmentTreatment
•ADA Recommendations
•They can administer 1 unit of regular insulin
or insulin lispro for each 10 or 15 g of
carbohydrate eaten at a meal .
•In these patients , the ratio of carbohydate to
fat will vary among individuals in relation to
their glycemic responses ,insulin regiments,
and exercise pattern.

105. TreatmentTreatment
•ADA Recommendations
•The current recommendations for both
types of diabetes continue to limit
cholesterol to 300 mg dairly and advise
a daily protein intake of 10%-20% of
total calories

106. TreatmentTreatment
•ADA Recommendations
•They suggest that saturated fat be no
higher than 8%-9% of total calories with
a similar proportion of polyunsaturated
fat and that the remainder of caloric
needs be made up of an individualized
ratio of monounsaturated fat and of
carbohydrate containing 20-35 g of
dietary fiber .

107. TreatmentTreatment
•ADA Recommendations
•Poultry ,veal, and fish continue to be
recommended as a substitute for red meats
for keeping saturated fat content low.
•The present ADA position statement proffers
no evidence that reducing protein intake
below 10% of intake (about 0.8 g/kg/d) is of
any benefit in patients with nephropathy and
renal impairment ,and doing so may be
detrimental.

108. TreatmentTreatment
•Dietary Fiber
•Plant components’ such as cellulose ,gum,
and pectin are indigestible by humans and
termed dietary “fiber”.
•The ADA recommends food such as
oatmeal , cereals, and beans with relatively
high soluble fiber content as staple
components of the diet in diabetics.

109. TreatmentTreatment
•Dietary Fiber
•High soluble fiber content in the diet
may also have a favorable effect on
blood cholesterol levels.

110. TreatmentTreatment
•Artifficial SweetenersArtifficial Sweeteners
•The latest position statement of ADA The latest position statement of ADA
concludes that all concludes that all nonnutritive nonnutritive
sweetenerssweeteners that have been approved that have been approved
by the FDA (such as aspartame and by the FDA (such as aspartame and
saccharin) saccharin) are safe forare safe for consumption by consumption by
all people with diabetes.all people with diabetes.

111. TreatmentTreatment
•Artifficial SweetenersArtifficial Sweeteners
• Two other nonnutritive sweeteners Two other nonnutritive sweeteners
have been approved by the FDA as safe have been approved by the FDA as safe
for general use: sucralose(Splenda) for general use: sucralose(Splenda)
and acesulfame potassium (Sunett and acesulfame potassium (Sunett
,Sweet one, DiabetiSweet),Sweet one, DiabetiSweet)

112. TreatmentTreatment
•Artifficial SweetenersArtifficial Sweeteners
•Nutritive sweetenersNutritive sweeteners such as sorbitol such as sorbitol
and fructose have increased in and fructose have increased in
popularity .popularity .
•Except for acute diarrhea induce by Except for acute diarrhea induce by
ingestion of large amounts of sorbitol –ingestion of large amounts of sorbitol –
containing foods, their relative risk has containing foods, their relative risk has
yet to be established.yet to be established.

113. TreatmentTreatment
•Artifficial SweetenersArtifficial Sweeteners
•Fructose represents a “natural ”sugar
substance that is a highly effective
sweetener which induces only slight
increases potential adverse effects of large
amounts of fructose (up to 20% of total
calories) on raising serum cholesterol and
LDL cholesterol , the ADA feels it may have
no overall advantage as a sweetening agent
in the diabetic diet.