Diabetes Melitus - Discussion

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Diabetes

Melitus
Diabetes Melitus

A relaive or absolute lack of insulin, that result in


hyperglycemia. If Left untreated, reinopathy, nephropathy,
neuropathy, and cardiovascular complicaions may result.

CLINICAL PRESENTATION

Type 2 DM

The most common type of diabetes in adults (>90%)


characterized by hyperglycemia, due to progressive loss
of insulin secretion from the beta cell as a result of
insulin resistance, resulting in relative insulin deficiency.
Majority of patients are asymptomatic at presentation,
with hyperglycemia noted on routine laboratory
evaluation
The classic symptoms of hyperglycemia (polyuria,
polydipsia, nocturia, blurred vision, and weight loss)
Polyuria occurs when the serum glucose rises
significantly > 180 mg/dL (10 mmol/L).
Patients Rarely present with a hyperosmolar
hyperglycemic state, characterized by marked
hyperglycemia, severe dehydration, and obtundation

Type 1 DM

characterized by autoimmune destruction of the


pancreatic beta cells, leading to absolute insulin
deficiency.
DKA may be the initial presentation in adults with newly
diagnosed type 1 diabetes.
Diagnosis

Diagnostic criteria

Fasting plasma glucose (FPG),


glycated hemoglobin (A1C) may be used for diagnostic
testing.
two-hour plasma glucose during a 75 g oral glucose
tolerance test (OGTT) “in pregnancy”

If the diagnostic test is consistent with prediabetes, it should be


repeated annually
A1C goals

should be individualized and balanced with regard to


prevention and delay of microvascular complications
(intensive glycemic management) with the risk of
hypoglycemia.
for most patients a reasonable goal of therapy is an A1C
value of ≤7.0 % (53 mmol/mol)
In order to achieve this A1C goal, a fasting glucose of 80
to 130 mg/dL (4.4 to 7.2 mmol/L) and a postprandial
glucose (90 to 120 minutes after a meal) less than 180
mg/dL (10 mmol/L) are generally given as targets.
A1C goal should be set somewhat higher (eg, <8 % [<64
mmol/mol]) for:
Elderly
Patients with comorbidities
With history of severe hypoglycemia or other significant
adverse medication effects
Polypharmacy
Limited life expectancy and little likelihood of benefit
from intensive therapy.
A more stringent goal (A1C <6 % [<42 mmol/mol]) is
indicated during pregnancy.
Obtain an A1C at least twice yearly in patients who are
meeting treatment goals and who have stable glycemic
management
Quarterly in patients whose therapy has changed or
requires adjustment, or who are not meeting glycemic
goals.
Lifestyle intervention

Three major components of nonpharmacologic therapy of


blood glucose and overall health in type 2 diabetes

Dietary modification
Exercise
Weight reduction (Mostly with Type II)

In addition to improving glycemia, lifestyle change and


modest weight loss also reduce the development of
obstructive sleep apnea, improve mobility and quality of
life, and reduce the need for glucose-lowering and blood
pressure medications.

Pharmacological management

Type II

Metformin is suggested as initial therapy for most patients


if there are no contraindications.

Metformin is the preferred initial therapy because of


glycemic efficacy, absence of weight gain and
hypoglycemia, general tolerability, and favorable cost.
For patients who have gastrointestinal intolerance of
metformin, slower titration, ensuring that the patient is
taking the medication with food, or switching to an
extended-release formulation may improve
tolerability.

04
Contraindications to metformin include:

eGFR <30 mL/min/1.73 m2


eGFR 30 to 44 mL/min/1.73 m2 along with active kidney disease
(ie, obviously progressive)
Active or progressive liver disease (fatty liver is not a
contraindication unless there is significant steatohepatitis)
Active excessive use of alcohol
Unstable or acute heart failure at risk of hypoperfusion and
hypoxemia
Past history of lactic acidosis during metformin therapy
Decreased tissue perfusion or hemodynamic instability due to
infection or other causes

The therapeutic options for patients who fail initial therapy with
lifestyle intervention and metformin are to add a second oral or
injectable agent, including insulin

Regardless of the initial response to therapy, the natural history of


most patients with type 2 diabetes is for blood glucose
concentrations and A1C to rise over time. worsening beta cell
dysfunction with decreased insulin release was primarily
responsible for disease progression. More severe insulin
resistance or decreased compliance with the dietary regimen
also may contribute to progression.
Several alternatives to metformin are available.

For patients without clinical CVD who cannot take metformin, options
for initial therapy include:
basal insulin.
peptidase 4 (DPP-4) inhibitors.
glucagon-like peptide 1 (GLP-1) receptor agonist-based therapies.
sodium-glucose cotransporter 2 (SGLT2) inhibitors.
sulfonylureas.
thiazolidinediones.

For patients relatively far from their hemoglobin A1C goal, insulin or a
GLP-1 receptor agonist-based therapy is preferred.
Indications for insulin therapy in DM II

Severe hyperglycemia on presentation


Difficulty distinguishing type of diabetes
Pancreatic insufficiency
Persistent hyperglycemia on oral agents
Type I

Treatment of type 1 includes the coordination of meals/diet and


activity with physiologic insulin replacement, which involves the
frequent monitoring of blood glucose levels.

Insulin regimen

The basic requirements of an optimal insulin regimen include:


administration of a basal insulin plus mealtime boluses of a rapid-
acting, ultra rapid-acting, or short-acting insulin.

Basal insulin can be delivered by daily or twice-daily injections


of an intermediate-acting or long-acting insulin preparation or
continuous subcutaneous insulin infusion (CSII) via a pump,
typically using a rapid-acting insulin preparation.
Mealtime boluses plus additional insulin used to correct
hyperglycemia are provided by a rapid-acting, ultra rapid-acting, or
short-acting insulin

Choice of insulin delivery

continuous subcutaneous delivery of insulin via a pump (CSII) can be


of particular benefit in adults with variable basal requirements,
unpredictable or varying schedules requiring flexible insulin dosing,
and in those who have not been able to achieve their glycemic goals
on MDI.
Designing an MDI insulin regimen

Initial total daily dose (TDD) – Most adults who are newly
diagnosed started on a TDD of 0.2 to 0.5 units of insulin / kg / day,
although many will ultimately require 0.6 to 0.7 units/ kg /day

Adolescents, especially during puberty, as well as adults with


infections or other acute medical conditions or stressors often
need more. The starting dose can be adjusted upward (or
downward) every few days based upon symptoms and blood
glucose measurements.

Basal bolus composition and timing

In designing an MDI injection regimen, approximately


40 to 50 % of the TDD given as a basal insulin either as:
once-daily degludec
OD U-300 glargine
once- or twice-daily U-100 glargine or detemir
twice-daily intermediate-acting insulin NPH.
The long-acting insulin can be given either at bedtime or in the
morning
NPH is usually given as approximately 2/3 of the dose in the
morning and 1/3 at bedtime.

The remainder of the TDD is given as short-acting, ultra rapid-


acting, or rapid-acting insulin, divided before meals.

Regimens that use NPH in the morning may not require a pre-
lunch dose of short-acting (regular) or rapid-acting insulin because
the peak of NPH action is occurring at that time, potentially
reducing the frequency of injections.
Injection sites
The abdomen is the preferred site for pre-meal injections of
regular insulin because absorption is quicker from this site m.
the thigh or buttock is a good site for the evening intermediate-
acting insulin (NPH) dose; the slower rate of absorption from
these sites enhances the likelihood that the insulin will last through
the night.
The site of injection is less important for rapid-acting or long-acting
insulin analogs, and therefore, they may be administered in the
abdomen, thighs, buttock, or upper arms. However, insulin
absorption may be faster in an exercising limb.

Because of the difference in pharmacokinetics of regular insulin


(duration of action, 5-8 hours) versus rapid-acting insulin analogs (2-4
hours), an increase in the dose of basal insulin may be required when
a person is switched from regular insulin (longer) to an insulin analog
for the pre-meal bolus dose

Blood glucose monitoring

All patients with diabetes mellitus who use insulin or other


glucose-lowering medications that can cause hypoglycemia
should (at least periodically) self-monitor their glucose
concentrations to help maintain safe, target-driven glucose levels
Self-monitoring is unnecessary in patients who are treated with
diet alone or who take oral or injectable agents that do not cause
hypoglycemia.

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