Diabetes mellitus is
a disease of metabolic dysregulation, most notably abnormal glucose metabolism,
accompanied by characteristic long-term complications. The complications that
are specific to diabetes include retinopathy, nephropathy, and neuropathy.
Patients with all forms of diabetes of sufficient duration, including type 1
diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), are vulnerable to
these complications, which cause serious morbidity. These are microvascular
complications. High plasma glucose is the driving force in microvascular
complications of diabetes.
To
achieve glycemic goals in patients with type 2 diabetes, multiple pharmacologic agents, including sulfonylureas,
meglitinides, metformin, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl
peptidase IV (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor
agonistĀ and insulin are available. These
agents can be used singly or in combination to achieve target glycaemic
control. Unlike patients with type 1 diabetes
who have no significant insulin secretion and hence require insulin
therapy from the onset of their disease, in patients with type 2 diabetes insulin resistance with
hyperinsulinaemia is a prominent feature in the early stages of the disease.People
with type 2 diabetes mellitus thus benefit from measures to improve insulin
sensitivity such as dietary caloric restriction, exercise, and weight
management early in their disease in combination with with oral agents such as
insulin sensitizers and insulin secretagogues to achieve glycaemic target. With
progression of type 2 diabetes,
there is ultimately progressive loss of pancreatic beta-cell function and reduction
in endogenous insulin secretion. At this stage, most patients will require
exogenous insulin therapy to achieve optimal glucose control.
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Landmark
clinical trials have been able to establish the fact that optimal glycaemic
control can prevent/delay the progression of complications in people with
diabetes mellitus1. The conclusions from these trials positioned insulin
strategically as a very important agent in achieving reduced micro vascular
complications1,2.
Data
from the UnitedKingdom Prospective Diabetes Study (UKPDS) suggest that early
insulin treatment lowers macrovascular risk in type 2 diabetes mellitus3.
These trials strive to achieve glycaemic control below which no complication
would occur. However, better glycaemic control was associated with reduced
risks of complications over the whole glycaemic range (“the lower the better”)
in the UKPDS4.
In
the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, higher
mortality was recorded in the intensive glycaemia treatment arm while targeting
HbA1C of <6.0% compared with the standard therapy group targeting HbA1C from
7.0 to 7.9% 5. The intensive arm recorded more episodes of
hypoglycaemia hence the increase in mortality recorded5. No
additional benefit was recorded by lowering HbA1C <6.5% in the KUMAMOTO
study 2.
Choosing from the
wide variety of glucose-lowering interventions currently available could be a
challenge for the healthcare provider and the patients in terms of
effectiveness, tolerability, and cost of the various diabetes treatments.
However, these should not be the case as risk reductions in long-term
complications were related to the levels of glycaemic control achieved, rather
than to a specific glucose-lowering agent 1. In the Steno-2 study,
very few patients achieved the HbA1C target of 6.5% compared with the large
number of patients who reached the intensive blood pressure and serum lipid
goals6. The challenges of initiating and intensifying insulin
therapy are quite enormous and could be daunting to health care givers. This
review contains an overview of the currently available insulin preparations and
an outline of the merits and demerits of the various regimens commonly used for
the initiation and intensification of insulin therapy in patients with type 2
diabetes. Our aim is to assist clinicians in designing individualized
management plans for insulin therapy in type 2 diabetic patients.