1. Investigations of D.M :
American Diabetes Association Plasma Glucose Diagnostic
Criteria for Diabetes Mellitus:
Test Condition
------Plasma Glucose, mg/dL - -----
Diagnosis Fasting >_8 hr 2 hr after 75 g.
oral glucose
 Normal <110 <140
 Impaired glucose tolerance (lGT) <126 >_140 - <200
 Impaired fasting glucose (lFG) >_110 - <126 <200
 Diabetes mellitus >_ 126 ---
 Diabetes mellitus <126 >_200
 Diabetes mellitus (classic symptoms
+ casual plasma glucose,>200 mg/dL) ---- ----

3. 
1. Testing for diabetes should be considered in all persons at age 45
years and older; if results are normal, testing should be repeated at 3·yr
intervals.
2. Testing should be considered at younger ages or performed more
frequently in:
• are obese ( >_20% desirable body weight or a BMI >_25 kg/m2)
• have a first-degree relative with diabetes
• are members of a high-risk ethnic population (eg, African American.
Hispanic American, Native American, Asian American, Pacific Islander)
• have delivered a baby weighing >9 Ib or have a diagnosis of
gestational D.M
• are hypertensive (>_140/90 mm Hg)
• have an HDL cholesterol level <_35 mg/dL and/or a triglyceride level
>_250 mg/ dL
• were shown to have impaired glucose tolerance or impaired fasting
glucose
• have polycystic ovary syndrome
• have history of vascular disease
• are habitually physically inactive

4. Management
the strategies of RX. Include:
 Glycemic control
 diet & exercise
 insulin therapy
 oral agents
 other therapies
 treatment of associated conditions.
 dyslipidemia
 HT
 obesity
 CHD
 treatment of complications

5. The goals of therapy :
(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. To reach these goals, the physician should
identify a target level of glycemic control for each
patient.
Index Goal
Glycemic control <11.1 mmol/L (200 mg/dL)
Hb A1C <7.0
Blood pressure <130/80
Lipids LDL <2.6 mmol/L (<100mg/dL)
HDL >1.1 mmol/L (>40 mg/dL)
TG <1.7 mmol/L (<150 mg/dL)

6.  The care of an individual with either type 1 or type 2
DM requires a multidisciplinary team.
 Central to the success of this team are the patient's
participation, which is essential for optimal diabetes
management.
 Members of the health care team include the
primary care provider and/or the endocrinologist or
diabetologist, a certified diabetes educator, and a
nutritionist.
 In addition, when the complications of DM arise,
subspecialists (including neurologists,nephrologists,
vascular surgeons, cardiologists, ophthalmologists,
and pediatrics) with experience in DM-related
complications are essential.

7. Diet & exercise :
 Adherence to nutrition and meal-planning principles is a challenging but
essential component of successful diabetes management. Diet planning
should include lifestyle and nutrition goals as well as specific biochemical and
other physiologic parameters for the individual. Insulin requirements are then
matched to the patient's diet, not vice versa.
 If type 2 diabetes is diagnosed and the patient is overweight. a diet that is
prudently low fat and low cholesterol should be started and an exercise
routine initiated but even a modest weight loss of 10- 20 pounds may
ameliorate the diabetes or cause its remission.
 Before an exercise program is prescribed for anyone older than age 35. a
determination must be made that the heart is normal and that there are no
contraindications.
 Bariatric surgery-surgery that promotes weight loss-is a popular option for
very obese individuals who are unresponsive to other forms of therapy. There
are 3 general techniques for bariatric surgery: restrictive surgery. which
restricts stomach volume; malabsorptive surgery. which minimizes the ability
of the gastrointestinal tract to absorb nutrients; and a combination of
restrictive and malabsorptive approaches.

8. Insulin therapy :
 This therapy usually involves use of a longer-acting
insulin to maintain a baseline level and then use of a
rapid-acting insulin to cover meals.
 Current insulin preparations are generated by
recombinant DNA technology and consist of the amino
acid sequence of human insulin. Animal insulin (beef or
pork) is no longer used. In the United States, most
insulin is formulated as U-100 (100 units/mL)
 Regular insulin is the traditional rapid-acting agent used
for short-term coverage; however, the development of
very rapid-acting insulins allows diabetic patients the
convenience of timing injections just a few minutes
before meals.

9.  Very rapid-acting insulins include
insulin lispro (Humalog),
insulin aspart (NovoLog),
and insulin glulisine (Apidra).
Isophane insulin suspension (NPH insulin) is an intermediate-acting insulin.
 The newer long-acting insulins with very stable absorption
characteristics that result in a constant level of basal insulin include
Glargine (Lantus)
and detemir (Levemir)
 Insulin zinc suspension (Lente insulin) and extended insulin zinc
(Ultralente insulin) are no longer available.
 Premixed combinations of various insulins are also available for
patients less able to work with all these variables.
 One commonly used regimen consists of twice-daily injections of a
long-acting insulin like NPH (detemir could be used instead) mixed
with a short-acting insulin before the morning and evening meal.
Such regimens usually prescribe two-thirds of the total daily insulin
dose in the morning (with about two-thirds given as long-acting
insulin and one-third as short-acting) and one-third before the
evening meal (with approximately one-half given as long-acting
insulin and one-half as short-acting).

10. Pharmacokinetics of Insulin Preparations
Time of Action
Preparation Onset, h Peak, h Effective Duration, h
Short-acting
Lispro <0.25 0.5–1.5 3–4
Aspart <0.25 0.5–1.5 3–4
Glulisine <0.25 0.5–1.5 3–4
Regular 0.5–1.0 2–3 4–6
Long-acting
NPH 1–4 6–10 10–16
Detemir 1–4 — 12–20
Glargine 1–4 — 24
Insulin Combinations
75/25– 75% protamine lispro, 25% lispro Up to 10–16
70/30– 70% protamine aspart, 30% aspart Up to 10–16
50/50– 50% protamine lispro, 50% lispro Up to 10–16
70/30– 70% NPH, 30% regular insulin 10–16
50/50– 50% NPH, 50% regular insulin 10–16

11.  Continuous subcutaneous insulin infusion (CSII)
pumps allow even more physiologic levels of insulin
than do traditional injections. The pump tends to be
used when multiple-injection therapy fails.
Disadvantages include a higher cost, infection at
the infusion site, and infusion failure.
Complications of insulin therapy
• Hypoglycemia
• Lipodystrophy
• Local insulin allergy
• Generalized anaphylaxis, hives, and angioedema
may also develop.
• Immunologic insulin resistance may occur because
of production of insulin-neutralizing antibodies

12. Oral agents:
* Sulfonylureas:
 The sulfonylureas have been widely used in the United States
and Canada since 1967 for treatment of type 2 diabetes. Their
major mechanism of action is stimulation of pancreatic insulin
secretion, although some studies have suggested a peripheral
augmentation of insulin action.
 The most significant adverse effect of this drug is hypoglycemia,
which, though infrequent, may be severe and prolonged,
depending on the half-life of the specific drug.
 Second-generation sulfonylurea are approximately 50-100 times
more potent than first-generation agents, and these drugs
generally need to be given only once daily.

13. *Biguanides
 A major advance occurred with the development of metformin
(Glucophage. Glucophage XR). currently the only available
biguanide. Metformin improves insulin sensitivity. it may also
lead to modest weight loss or at least stabilization (in contrast to
the weight gain that may occur with use of insulin or
sulfonylureas).
 In addition it is less likely to cause hypoglycemia and can be used
in nonobese patients.
 Metformin is generally the first agent used in patients whose
hyperglycemia cannot be controlled with lifestyle changes alone.
 Although metformin is generally very safe, patients may
complain of gastrointestinal tract symptoms, including a metallic
taste, nausea, and diarrhea. A more severe potential problem is
lactic acidosis. Although rare, this problem is more likely to occur
in patients with renal insufficiency.

14. * a-Glucosidase inhibitors
 Acarbose (Precose) and miglitol (Glyset) are administered with meals to delay
digestion and absorption of carbohydrates by inhibiting the enzymes that
convert complex carbohydrates into monosaccharides.
 Although relatively safe, these agents often cause flatulence, which limits
patient compliance, and they are to be avoided in patients with intestinal
disorders.
* Thiazolidinediones
 This new class of orally active drugs, represented by rosiglitazone (Avandia)
and pioglitazone (Actos), is thought to increase insulin sensitivity in muscle and
adipose tissue and to inhibit hepatic gluconeogenesis, thereby increasing
glycemic control while reducing circulating insulin levels. These drugs also act
to increase insulin secretion.
 The first available agent of this class, troglitazone (Rezulin), was withdrawn
from the market in 2000, when the FDA noted that this drug had a higher rate
of liver toxicity than did the other drugs. In 2010, the FDA significantly
restricted the use of rosiglitazone because of an increased risk of
cardiovascular complications in patients using this drug.
 Both rosiglitazone and pioglitazone can cause weight gain, in part owing to
the proliferation of new adipocytes. Another problem is fluid retention, which
has been associated with cases of macular edema.

15. *Meglitinides
Repaglinide (Prandin) and nateglinide (Starlix) are meglitinides, whose
mechanism of action and side effect profile are similar to those of the
sulfonylureas. However, they are more expensive and generally no
more efficacious than the sulfonylureas.
Because of their rapid onset of action and short duration, these agents are
taken daily with meals. They can be used as Single agents or in
combination therapy with other oral hypoglycemic agents.
* Other therapies
 Incretins are gut-derived factors that are released when nutrients
enter the stomach; they help to stimulate postprandial insulin
release. Incretin mimetics improve glycemic control by enhancing
pancreatic secretion of insulin in response to nutrient intake,
Inhibiting glucagon secretion and promoting early satiety. Two
recently approved injectable incretin mimetics are exenatide
(Byetta). used as adjunctive therapy for patients with type 2
diabetes who are inadequately controlled by oral agents. and
pramlintide (Symlin). a synthetic analogue of amylin. used in
patients treated with mealtime insulin.

16.  Dipeptidyl peptidase IV (DPP-IV) is an enzyme that
deactivates bioactive peptides including incretins;
therefore inhibiting this enzyme can enhance glucose
regulation. Sitagliptin (Januvia) is an oral DPP-IV
inhibitor that requires only once a day dosing. But it is
expensive. only modestly effective. and not commonly
used.
 Glucose transport inhibitors are a new class of drugs.
Glucose is filtered in the renal glomerulus and
reabsorbed in the proximal tubule. Beyond a certain
threshold (usually 160- 180 mgldL). it is excreted in the
urine. Glucose transport inhibitors prevent the
reabsorption and thereby increase the loss of glucose in
the urine. The lost calories then cause weight loss and
improved blood glucose values.

17. Pharmacokinetics of Oral Hypoglycemic Drugs
Drug Usual Daily Dose, mg Dosing per Day
First-generation sulfonylureas
Acetohexamide 500-750 Once or divided
Chlorpropamide (Dabinese) 250-500 Once
Tolbutamide (Orinase) 1000-2000 Once or divided
Second-generation sulfonylureas
Glipizide (Glucotrol) 2.5-10 Once or divided
(Glueotrol XL) 5-10 Once
Glyburide (DiaBeta, Micronase, 2.5-10 Once or divided
Glynase)
Glimepiride (Amaryl) 2-4 Once
Biguanides
Metformin (Glucophage, 1500-2550 Twice to 3 times
Glueophage XR)
a-Glucosidase inhibitors
Acarbose (Precose) 150-300 3 times
Miglitol (Glyset) 150-300 3 times
Thiazolidinediones
Rosiglitazone (Avandia) 4-8 Once or divided
Pioglitazone (Actos) 15-45 Once
Meglitinides
Repaglinide (Prandin) 2-16 3 times w/meals
Nateglinide (Starlix) 360 3 times w/meals
Other
Sitagliptin (Januvia) 100 Once

18. Is a pancreas
transplantation is
possible ???

19. Pancreatic transplantation
For type I diabetic patients, pancreas transplantation
can be performed in conjunction with renal
transplantation.
With modern techniques and immunosuppression,
there is a high transplant survival rate, and the
majority of patients become euglycemic without the
need for insulin.
Islet cells can be injected directly into the liver
without the need for formal transplantation. This
procedure has been attempted in humans, but
rejection leads to a high failure rate. Studies are under
way to identify effective immunosuppressive regimens
as well as other sites for cell placement. Islet cell-
producing stem cell research is still at a basic stage.

20. The Importance of Glucose Control
³ The Diabetes Control and Complications Trial showed that
intensive therapy aimed at maintaining near-normal glucose
levels had a large and beneficial effect on delaying the
development and retarding the progression of long-term
complications for type 1 diabetic patients. Intensive therapy
decreased the risk of the development and progression of
retinopathy, nephropathy, and neuropathy by 40%-76%..
³ A related study, the United Kingdom Prospective Diabetes Study
(UKPDS), was designed to assess the effect of intensive control
on patients with type 2 diabetes. The UKPDS showed a reduction
in complications. the risk of retinopathy progression rises almost
exponentially as the HbA1c increases. However, patients who
decrease their HbAjc by 1 percentage point (eg, from 8% to 7%)
decrease the risk of retinopathy approximately 30%, and this
benefit holds for other diabetic complications, such as
nephropathy and neuropathy.

21. ³ For patients with type 1 diabetes, intensive control also
provides protection against macrovascular
complications, such as cardiovascular disease. For
patients with type 2 diabetes, A recent study,
suggested that intensive glycemic control in patients
with type 2 diabetes might actually increase the risk of
cardiovascular mortality.
³ Studies have shown that poor control can increase the
rate of retinopathy progression after cataract surgery
and blunt the treatment response to laser for diabetic
macular edema.

22. Guidelines for Ongoing Medical Care for Patients with
Diabetes:
† Self-monitoring of blood glucose (individualized frequency)
† HbA1C testing (2–4 times/year)
† Patient education in diabetes management (annual)
† Medical nutrition therapy and education (annual)
† Eye examination (annual)
† Foot examination (1–2 times/year by physician; daily by
patient)
† Screening for diabetic nephropathy (annual)
† Blood pressure measurement (quarterly)
† Lipid profile and serum creatinine (estimate GFR) (annual)
† Influenza/pneumococcal immunizations
† Consider antiplatelet therapy

23. THANK
YOU
&
HAVE A
NICE DAY