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outcomes. Neuropathy evaluations included
the Michigan Neuropathy Screening Instrument
(MNSI) questionnaire completed at baseline in
5145 participants (ILI n = 2570, DSE n = 2575) and
repeated annually thereafter and the MNSI phys-
ical examination and light touch sensation testing
conducted in 3775 participants (ILI n = 1905, DSE
n = 1870) 1–2.3 years after discontinuation of the
intervention.
RESULTS
At baseline, the MNSI questionnaire
scores were 1.9 ± 0.04 and 1.8 ± 0.04 in the ILI
and DSE groups, respectively (difference not
statistically significant). After 1 year, when weight
loss was maximal in the ILI group (8.6 ± 6.9%)
compared with DSE (0.7 ± 4.8%), the respec-
tive MNSI scores were 1.7 ± 0.04 and 2.0 ± 0.04
(p ≤ 0.001). Subsequently, the scores increased
gradually in both groups, but remained signifi-
cantly lower in the ILI group for the first 3 years
and at the end of follow-up. In both groups,
there was a significant association between
changes in the MNSI scores and changes in
body weight, HbA1c and serum lipids. There
were no significant between-group differences
in the proportions of participants with MNSI
physical examination scores ≥2.5, considered
to be indicative of diabetic neuropathy. The light
touch sensation measured separately in either
the right or left big toes (halluces) did not differ
between ILI and DSE, but when the data were
combined for both toes, light touch was better
preserved in the ILI group.
CONCLUSIONS/INTERPRETATION
ILI resulted in a
significant decrease in questionnaire-based
DPN, which was associated with the magnitude
of weight loss. In both the ILI and DSE groups,
changes in the MNSI score were also related
to changes in HbA1c and lipids. There were no
significant effects of ILI on physical examination
measures of DPN conducted 1–2.3 years after
termination of the active intervention, except for
light touch sensation, which was significantly
better in the ILI group when measurements were
combined for both toes. However, a potential
limiting factor to the interpretation of the physi-
cal examination data is that no baseline studies
are available for comparison.
Effects of a long-term lifestyle modification
programme on peripheral neuropathy in over-
weight or obese adults with type 2 diabetes:
the Look AHEAD Study.
Diabetologia
2017 Mar
27;[EPub Ahead of Print], The Look AHEAD
Research Group.
are considered compatible with neuropa-
thy and scores above 4 are abnormal.
At baseline, the MNSI questionnaire scores
were 1.9 ± 0.04 and 1.8 ± 0.04 in the ILI
and DSE groups, respectively (P = NS).
After 1 year, weight loss was maximal in
the ILI group (8.6% ± 6.9%) compared with
DSE (0.7% ± 4.8%); the respective MNSI
scores were 1.7 ± 0.04 and 2.0 ± 0.04 (P ≤
0.001), indicating progression in the DSE
group. Subsequently, the scores increased
gradually in both groups, but remained sig-
nificantly lower in the ILI group for the first
3 years and at the end of follow-up. In both
groups, there was a significant associa-
tion between changes in the MNSI scores
and changes in body weight, HbA1c, and
serum lipids. There were no significant
between-group differences in the propor-
tions of participants with MNSI physical
examination scores ≥2.5, considered to be
indicative of diabetic neuropathy. The light
touch sensation measured separately in
either the right or left big toes (halluces) did
not differ between ILI and DSE, but when
the data were combined for both toes, light
touch was better preserved in the ILI group.
The authors conclude that lifestyle changes
are associatedwith loss of weight, which low-
ers the risk for questionnairebut not objective
neuropathy. The pattern of response to the
intervention is very much akin to that seen in
the Diabetes Control and Complications Trial
(DCCT) and in the DPP trial wherein there is
an initial response in the active group and
this is slowly reversed, albeit at a slower rate,
than in the conventionally treated group. This
is the Nike curve of diabetes management.
It argues for a window of opportunity when
aggressive treatment will have a maximal
effect, which wanes. However, lifestyle inter-
ventions are very difficult to sustain and may
paradoxically encourage increased caloric
intake and sedentary behavior. Patients fre-
quently adapt by reducing activity levels
when not exercising and increasing caloric
intake following exercise bouts.
Thus, while this literature supports the
premise that CSPN and DPN associ-
ated with metabolic syndrome may be
amenable to therapy, development of a
well-tolerated, sustainable, pharmacologic
approach is needed.
There are five drugs available in the United
States for long-term weight loss: orlistat,
lorcaserin, phentermine-topiramate (TPM),
naltrexone-bupropion, and liraglutide. Mean
weight loss varies from 4% to 9%, with phen-
termine-TPM generally associated with the
highest loss (8.6–9.3%), with 70% of patients
experiencing >10% weight loss. It has been
shown to improve symptoms using the Nor-
folk QOL-DN (quality of life) tool, improve
physical measures of neuropathy, and
induce regeneration of IENF. It is now being
examined in the US in a multicenter study
and no doubt will surely be a wonderful
antidote to our intrinsically slothful popula-
tion! The Holy Grail for neuropathy, which
is the major contributor to foot ulcers and
amputations, is an agent that addresses
the underlying biology of the disease, and
there are many in the wings including gene
therapy. In 1982, an editorial in
The Lancet
said, “All we can do for neuropathy is make
the diagnosis and commiserate with the
patient.” Now there is a whole lot more!
Dr Vinik is Professor of
Medicine/Pathology/
Neurobiology, and Director
of Research and
Neuroendocrine Unit at
Eastern Virginia Medical
School, Strelitz Diabetes
Center, Virginia.
MICROVASCULAR COMPLICATIONS
15
VOL. 1 • NO. 1 • 2017