12
VOLUME 10 NUMBER 1 • MARCH 2013
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Correspondence to: Dr David Webb
Gauteng medical writer
e-mail:
Prof MAK Omar
Department of Endocrinology, Nelson Mandela School of Medicine,
University of KwaZulu-Natal, Durban
Dr Adri Kok
Union Hospital, Alberton, Gauteng
Tel: +27 (0) 11 907 8827
S Afr J Diabetes Vasc Dis
2013;
10
: 12–16
Insulin-related weight gain in patients with type 2
diabetes: case examples, mechanisms and an approach
to management
DAVID WEBB, MAK OMAR, ADRI KOK
Introduction
In patients with type 2 diabetes, tight glucose control is associated
with a significant reduction in the risk of diabetes-related
complications. In the United Kingdom Prospective Diabetes study
(UKPDS), each 1% reduction in HbA
1c
level was associated with
a 21% reduction in risk for diabetes-related endpoints, 21% for
deaths related to diabetes, 14% for myocardial infarction and 37%
for microvascular complications, with no obvious threshold of HbA
1c
below which risk no longer decreased.
1
Compared to patients with
Case study 1
A 64-year-old male who has had type 2 diabetes for 19 years came for an assessment. His other problems were hypertension, dyslipidaemia
and silent cardiac ischaemia. Up to seven years ago he had been on gliclazide, but, because of poor glycaemic control (HbA
1c
= 8.1%), insulin
glargine was added as a basal insulin. His weight at the time was 92.8 kg. Since then he had steadily gained weight, having put on 5 kg. He
then went on a strict diet and exercise programme, while metformin was substituted for gliclazide and insulin glargine was continued. He lost
2 kg with these measures and the weight remained stable at 94.6 kg for three months. His HbA
1c
level was 9.2 % at this visit.
A GLP-1 analogue was then added. This resulted in steady weight loss as well as improvement in glycaemic control so that a year
later his weight was 84.4 kg and HbA
1c
level was 6%. Meanwhile, over this period, the dose of his basal insulin had to be reduced from
66 to 30 units nocte.
Case study 2
Mr B is a 60-year-old male patient, diagnosed with type 2 diabetes 10 years ago. For the last six years he has been treated with oral
hypoglycaemic drugs and high doses of insulin. On a regimen of aspart/protamine aspart 30/70, 102 units daily in split doses, his
HbA
1c
level was 8.1% and his weight had steadily increased to 158.9 kg. He was switched to basal bolus insulin plus pioglitazone and
metformin. On a total daily dose of glargine 50 units plus aspart 48 units in divided doses, his HbA
1c
level improved to 6.1%, but his
weight increased further to 165.4 kg (body mass index > 45 kg/m
2
).
Six months ago he was started on a GLP 1 analogue. On a current regimen of insulin detemir 14 units nocte, with aspart as required,
a GLP1 analogue and metformin 1 g twice daily, his weight has decreased to 141.8 kg, and waist circumference from 146 cm in 2006
to 137 cm in 2012. His HbA
1c
level is 7.4%. Subjectively, he feels better and reports improved quality of life in terms of energy and effort
tolerance, improved sleep, and less joint pain. He is motivated to continue with his weight loss and improving his diabetes control.
less stringent glycaemic goals and despite a loss of between-group
differences in glycated haemoglobin concentrations after one year,
relative risk reductions in those randomised to tight control with
a sulphonylurea or insulin persisted after 10 years, with 9% risk
reduction for any diabetes-related endpoint, 24% for microvascular
disease, 15% for myocardial infarction and 13% for death due to
any cause.
2
Consequently, current treatment guidelines recommend
ambitious targets for HbA
1c
levels. The 2012 guidelines from the
American Diabetes Association and European Association for
the Study of Diabetes (ADA/EASD) and also from the Society of
Endocrinology Metabolism and Diabetes of South Africa (SEMDSA)
recommend maintaining HbA
1c
levels below 7% for the majority of
patients.
3,4
This may be achieved by maintaining fasting or pre-meal
glucose levels between 4.0 and 7.0 mmol/l.
4
However, these goals may be difficult to achieve and even harder
to maintain. Various studies indicate that fewer than 40 to 60% of
patients achieve HbA
1c
< 7%.
5
Even in those who do, because of
progressive decline in pancreatic beta-cell function and increasing
insulin resistance in the presence of obesity, poor dietary intake
and a lack of physical activity, a fasting plasma glucose of less than
7.8 mmol/l will be maintained in less than 50% of patients on oral
hypoglycaemic monotherapy after three years, and in less than a
third of patients after six years.
6,7
