Pharmacological treatment

TYPE 1 DIABETES MELLITUS

TYPE 2 DIABETES MELLITUS
 TYPE 1 diabetes mellitus

The goal is to design and implement insulin

regimens that mimic physiologic insulin secretion
ADA recommendations for fasting and bedtime
glycemic goals and A1C targets
 TYPE 1 diabetes mellitus

Insulin Preparations
Current insulin preparations are generated by
recombinant DNA technology and consist of the
amino acid sequence of human insulin
Human insulin has been formulated with distinctive
pharmacokinetics to mimic physiologic insulin
secretion
TYPE 1 diabetes mellitus
 TYPE 1 diabetes mellitus

These insulin analogues have full biologic activity

but less tendency toward subcutaneous aggregation,
resulting in more rapid absorption and onset of
action and a shorter duration of action
These characteristics are particularly advantageous
for allowing entrainment of insulin injection and
action to rising plasma glucose levels following meals
 TYPE 1 diabetes mellitus

Basal insulin requirements are provided by

intermediate (NPH insulin or lente insulin) or long-
acting (ultralente insulin or insulin glargine) insulin
formulations
These are usually combined with shortacting insulin
in an attempt to mimic physiologic insulin release
with meals
 TYPE 1 diabetes mellitus

In all regimens, intermediate- or long-acting insulins

(NPH, lente, ultralente, or glargine insulin) supply
basal insulin
regular, insulin aspart, or lispro insulin provides
prandial insulin
Lispro and insulin aspart should be injected just
before or just after a meal;regular insulin is given 30
to 45 min prior to a meal
 TYPE 1 diabetes mellitus

The most common adverse reaction to insulin is

hypoglycemia
This may result from an inappropriately large dose,
from a mismatch between the time peak delivery of
insulin and food intake
The more vigorous the attempt to achieve
euglycemia, the more frequent are the episodes of
hypoglycemia
 Glycemic control tends to dominate the management
of type 1 DM, the care of individuals with type 2 DM
must also include attention to the treatment of
conditions associated with type 2 DM and
detection/management of DM-related
complications.
 TYPE 2 diabetes mellitus

Insulin secretagogues stimulate insulin secretion by

interacting with the ATP-sensitive potassium
channel on the beta cell
Non sulfonylureas also interact with the ATP-
sensitive potassium channel, stimulates insulin by
closing ATP potassium channels
TYPE 2 diabetes mellitus
TYPE 2 diabetes mellitus
TYPE 2 diabetes mellitus
 TYPE 2 diabetes mellitus

Sulfonylureas reduce both fasting and postprandial

glucose and should be initiated at low doses and
increased at 1- to 2- week intervals based on SMBG
should be taken shortly before a meal
Contraindications to the use of this drugs include type 1 DM,
pregnancy, lactation and significant hepatic and renal
sufficinecy
Non sulforylureas they have a short half-life, these
agents are given with each meal or immediately
before to reduce meal-related glucose excursions
 TYPE 2 diabetes mellitus

Insulin secretagogues are generally well tolerated

All of these agents, however, have the potential to
cause profound and persistent hypoglycemia,
especially in elderly individuals
 TYPE 2 diabetes mellitus

Biguanides Metformin is representative of this class of

agents and it is and antihyperglycemic, not
hypoglycemic
Metformin reduces glucose levels primarily by
decreasing hepatic glucose production and by
increasing insulin action in muscles and fat;
mediated by cellular kinase AMP-activated protein
kinase
TYPE 2 diabetes mellitus
 TYPE 2 diabetes mellitus

The initial starting dose of 500 mg once or twice a

day can be increased to 1000 mg bid
The major toxicity of metformin, lactic acidosis, can
be prevented by careful patient selection
 TYPE 2 diabetes mellitus

a-Glucosidase inhibitors (acarbose and miglitol)

reduce postprandial hyperglycemia by delaying
glucose absorption; they do not affect glucose
utilization or insulin secretion
They reduces intestinal absorption of starch, dextrin,
and disaccharides by inhibiting the action of alpha-
glucosidase in the intestinal border brush
 TYPE 2 diabetes mellitus

Postprandial hyperglycemia, secondary to impaired

hepatic and peripheral glucose disposal, contributes
significantly to the hyperglycemic state in type 2 DM
Therapy should be initiated at a low dose (25 mg of
acarbose or miglitol) with the evening meal and may be
increased to a maximal dose over weeks to months (50 to
100 mg for acarbose or 50 mg for miglitol with each
meal)
The major side effects (diarrhea, flatulence, abdominal
distention) are related to increased delivery of
oligosaccharides to the large bowel and can be reduced
somewhat by gradual upward dose titration
 TYPE 2 diabetes mellitus

They reduce postprandial plasma glucose level in

type 1 and 2 DM subjects
 TYPE 2 diabetes mellitus

Thiazolidinediones reduce insulin resistance, these

drugs bind to the PPAR- (peroxisome proliferator-
activated receptor- y) nuclear receptor
Thiazolidindiones are selectively agonist for nuclear
(PPARy) which activates the insulin-responsiveness
genes that regulate carbohydrate and lipid
metabolism
Agonists of this receptor promote adipocyte
differentiation and may reduce insulin resistance
indirectly because of enhanced fatty acid uptake and
storage
z
 TYPE 2 diabetes mellitus

They are contraindicated in patients with liver

disease or congestive heart failure
 TYPE 2 diabetes mellitus

Insulin should be considered as the initial therapy in

type 2 DM, particularly in lean individuals or those
with severe weight loss, underlying renal or hepatic
disease that precludes oral glucose-lowering agents,
who are hospitalized or acutely ill
Insulin therapy is ultimately required by a
substantial number of individuals with type 2 DM
because of the progressive nature of the disorder and
the relative insulin deficiency that develops in
patients with long-standing diabetes