Diabetes Research and Clinical Practice - Volume 120 - Supplement 1 - October 2016

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Approximately 30% of diabetic subjects have chronic kidney
disease (CKD). The choice of anti-diabetic agents in patients
with CKD faces special challenges because CKD alters insulin
sensitivity and clearance, glucose transport, and metabolism
of anti-diabetic agents. CKD is also associated with increased
CV and other complications. Inappropriate selection and
dosage often aggravate renal dysfunction, cause hypogly-
cemia, morbidity and mortality, particularly CV diseases. The
glycemic goal in CKD still is not defined. The KDOQI 2012
guidelines suggest a goal HbA1C of 7% to delay the progression
of CKD. The Dialysis Outcomes and Practice Patterns Study
(DOPPS) indicated that mortality increased when HbA1C
moved from 7 –7.9%. Apparently, the glycemic goal in diabetes
with CKD is in this range. To reach this target, it is crucial to
evaluate potential side effects of all anti-diabetic agents
according to their safety, efficacy, renal metabolism and
pharmacokinetics. Based on numerous trials, the dose of
these anti-diabetic agents needs to be adjusted in patients
with varying stages of CKD. Suggested dose adjustments are:
1. Metformin: Discontinued if eGFR < 30 mL/min, <1,000 mg/
day if eGFR 30– 45 mL/min/1.73 m2.
2. Glimepiride, Glyburide (Glibenclamide): avoid use if eGFR
<60 mL/min/1.73 m2.
Gliclazide: Reduce dose if eGFR <30 mL/min, avoid use if
eGFR <15 mL/min/1.73 m2.
Glipizide: No dose adjustment required.
3. Repaglinide: Reduce dose if eGFR <30 mL/min;
Nateglinide: Caution if eGFR <30 mL/min.
4. Acarbose: Avoid use if eGFR <30 mL/min; Miglitol: Avoid
use if eGFR <30 mL/min.
5. Pioglitazone: No dose adjustment required, but caution if
CKD, CHF and hypervolemia.
6. Exenatide: Avoid use if eGFR <30 mL/min, reduce dose if
eGFR 30–50 mL/min/1.73 m2.
Liraglutide: No dose adjustment required if eGFR >30 mL/
min/1.73 m2.
Lixisenatide: Caution if eGFR <50 mL/min/1.73 m2.
7. Sitagliptin: 100 mg/day if eGFR >50 mL/min, 50 mg if eGFR
30–50, 25 mg if eGFR <30.
Saxagliptin: 2.5–5 mg/day if eGFR >50 mL/min, 2.5 mg/day
if eGFR <50 mL/min/1.73 m2.
Aloglitiptin: 25 mg/day if eGFR >50 mL/min, 12.5 mg if
eGFR 30–50 mL/min, and 6.25 mg if eGFR <30 mL/min or
ESRD. Linagliptin: No dose adjustment required.
8. Canagliflozin: Reduce dose if eGFR 45 –59/min; Empagli-
flozin: Caution if eGFR <45 mL/min;
Dapagliflozin: Avoid use if eGFR <60 mL/min/1.73 m2.
9. Insulin: No dose adjustment if eGFR >50 mL/min, 25% or
50% reduction of total daily dose if eGFR 10 –50 mL/min or
<10 mL/min/1.73 m2.
Diabetic Neuropathy: Clinical Update
S21-1
How to approach the patient with diabetic neuropathy –
Screening and diagnosis
Sung-Tsang HSIEH1,2. 1Department of Neurology, National Taiwan
University Hospital, 10002, 2Department of Anatomy and Cell
Biology, National Taiwan University, Taipei, 10051, Taiwan
Diabetic neuropathy is one of the most frequent neuropathy
in clinical practice. The manifestations of diabetic neur-
opathy are very diverse ranging from focal involvement of
carpal tunnel syndrome to systemic sensorimotor polyneur-
opathy and autonomic neuropathy. Major symptoms of
diabetic neuropathy include reduced sensation which may
lead to painless injury of the body, neuropathic pain of
different characters such as burning or tingling, and
veracious autonomic symptoms of gastroparesis, orthostatic
hypotension, chronic diarrhea, and sexual dysfunctions etc.
Efficient screening and accurate diagnosis of diabetic neur-
opathy are challenging tasks for clinical practice. Screening
instruments include questionnaires and thermal thresholds
on quantitative sensory testing which provide the first-line
assessments of potential neuropathy. Further confirmation
of neuropathy, in particular, degeneration of nerve fibers can
be diagnosed with conventional nerve conduction studies for
large-diameter nerves. Over the past decade, our group has
developed a technique of skin biopsy to examine small-
diameter sensory nerves which are responsible for thermal
and nociceptive sensations. With a 3 mm punch and special
staining on skin biopsy sections, nociceptive nerve fibers
could be demonstrated and quantified, i.e. intraepidermal
nerve fiber density (Eur J Neurol 17:903–912, 2010). This
approach has become the standard for diagnosing small fiber
neuropathy. Patients with diabetic neuropathy frequently
had different types of neuropathic pain for example burning
over the limbs or even the trunk. We tackled this issue by
establishing contact heat evoked potential (Diabetes Care
33:2654–2659, 2010) and heat-activated functional magnetic
resonance imaging (fMRI) (Hum Brain Mapp 34:2733–2746,
2013). These examinations demonstrated enhanced brain
activations due to peripheral nerve degeneration. These
assessments provide foundations for prescribing central-
acting drugs for neuropathic pain, such as antidepressants
and anticonvulsants as documented in various guidelines
for neuropathic pain. This talk will focus on the recent
advancements in screening and diagnosis of diabetic
neuropathy.
S21-2
Current and future strategies for treatment of diabetic
neuropathy
Jiro NAKAMURA1. 1Division of Diabetes, Department of Internal
Medicine, Aichi Medical University School of Medicine, Nagakute,
Japan
Diabetic neuropathy is the most common complication in
diabetic patients. The symptom of diabetic neuropathy may
cause various problems in daily life and affect the prognosis
of diabetic patients. Therefore, it is important to prevent the
development and progression of diabetic neuropathy at an
early stage.
It is obvious that the primary cause of diabetic neuropathy
is hyperglycemia itself, and previous clinical trials such as
DCCT, Kumamoto Study and EDIC Study demonstrated that
strict glycemic control could prevent the development and
progression of diabetic neuropathy. However, it is difficult to
keep normal glucose levels for 24 hours in diabetic patients,
especially in type 1 diabetic patients. Short-term hypergly-
cemia can switch on the pathogenic mechanisms. In addition,
therefore, interventions to the pathogenic mechanisms
beyond glucose are required.
Various factors such as the metabolic factors, vascular factors,
and neurotrophic factors have been proposed to explain the
pathogenesis of diabetic neuropathy. Among these factors, the
role of metabolic factors has been most extensively investi-
gated. Metabolic factors include polyol pathway hyperac-
tivity, altered protein kinase C activity, increased oxidative
stress, and enhanced non-enzymatic glycation. Each meta-
bolic deficit was originally derived from an independent
background. However, recent studies have reported close
relationships between these abnormalities, and it is now
clear that polyol pathway hyperactivity leads to other three
metabolic deficits. Based on previous studies, furthermore,
polyol pathway hyperactivity plays the major role in the
development of diabetic neuropathy. Therefore, from the
viewpoint of preventing diabetic neuropathy or treatment of
mild diabetic neuropathy, aldose reductase inhibition would
be the best therapeutic strategy. However, advanced
Speech Abstracts / Diabetes Research and Clinical Practice 120S1 (2016) S1–S39 S13