|
Current Diabetes Reviews
ISSN: 1573-3998
Current Diabetes Reviews
Volume 2, Number 2, May 2006
Contents
Pathophysiology and Treatment of Diabetic Peripheral
Neuropathy: The Case for Diabetic Neurovascular Function as
an Essential Component Pp. 131-145
Keri A. Kles and Aaron I. Vinik
[Abstract]
Preconception Care for Diabetic Women: Background,
Barriers, and Strategies for Effective Implementation Pp.
147-161
David A. Sacks
[Abstract]
Dysfunction of Cellular Transporters and Predisposition
to Diabetic Nephropathy Pp. 163-183
Gianpaolo Zerbini, Daniela Gabellini, Dora Ruggieri and
Anna Maestroni
[Abstract]
Cultured Adult Animal Neurons and Schwann Cells Give
Us New Insights into Diabetic Neuropathy Pp. 169-183
Kazunori Sango, Haruhiro Saito, Masahiko Takano, Akiko
Tokashiki, Shuji Inoue and Hidenori Horie
[Abstract]
Type 2 Diabetes and Obesity in Children and Adolescents:
Experience from Studies in Taiwanese Population Pp.
185-193
Ling-Yin Chang, Hung-Yuan Li, Jung-Nan Wei and Lee-Ming
Chuang
[Abstract]
Relationship Between Inflammation, Insulin Resistance
and Type 2 Diabetes: ‘Cause or Effect’? Pp.
195-211
Jerry R. Greenfield and Lesley V. Campbell
[Abstract]
Hormones and the Autonomic Nervous System are Involved
in Suprachiasmatic Nucleus Modulation of Glucose Homeostasis
Pp. 213-226
Marieke Ruiter, Ruud M. Buijs and Andries Kalsbeek
[Abstract]
Clinical Thiazolidinediones as PPARγ
Ligands with the Potential for the Prevention of Cardiovascular
Disease in Diabetes Pp. 227-239
Stephanie T. de Dios, Richard C. O’Brien and Peter
J. Little
[Abstract]
Reactive Species, Cellular Repair and Risk Factors
in the Onset of Type 2 Diabetes Mellitus: Review and Hypothesis
Pp. 241-259
Leonid E. Fridlyand and Louis H. Philipson
[Abstract]
Overcoming Barriers to Evidence-Based Diabetes Care
Pp. 261-269
Richard W. Grant and James B. Meigs
[Abstract]
Abstracts
[Back to top]
Pathophysiology and Treatment of Diabetic Peripheral
Neuropathy: The Case for Diabetic Neurovascular Function as
an Essential Component
Keri A. Kles and Aaron I. Vinik
Worldwide, diabetes and its complications are major causes
of morbidity, decreased quality of life, mortality and increasing
health care costs. Patients with diabetes attempt to control
blood pressure, lipids and blood glucose levels to decrease
their risk of macrovascular and microvascular complications,
such as diabetic peripheral neuropathy (DPN). Even with control
of these risk factors for vascular disease, many patients
still develop complications. Targeted therapies to the underlying
mechanisms of diabetic neuropathy are essential to slow the
progression of the disease. This review describes the signs,
symptoms and diagnosis of DPN. Additionally, new therapies
and the complex etiology that contributes to the development
of diabetic neuropathy are described (oxidative stress, hyperglycemia,
advanced glycated end products, autoimmunity, neurotrophic
factors and protein kinase C β).
[Back to top]
Preconception Care for Diabetic Women: Background,
Barriers, and Strategies for Effective Implementation
David A. Sacks
Major congenital anomalies (MCAs) are defined as those which
are lethal and/or which cause major handicaps and/or which
require surgery. While the general population risk for having
a baby with an MCA is one to three percent, that for a woman
who has pregestational diabetes mellitus is three to six times
as great. Fetal organogenesis takes place from the fifth to
the eighth post-menstrual weeks. A body of evidence suggests
that maternal hyperglycemia early in gestation is either contributory
to fetal teratogenesis or is a surrogate marker for the causative
agent of MCAs in infants of diabetic mothers. Given that organogenesis
begins at the time of a woman’s first recognition of
pregnancy, and given the one or more weeks thereafter needed
to establish prenatal care, it is essential that the woman
who has diabetes attempt to lower her glucose concentrations
and treat any intercurrent complications (e.g. hypertension,
retinopathy) prior to the initiation of efforts to conceive.
The elements of a preconception care program for pregestational
diabetic women include health care provider education, patient
recruitment and retention, education about family planning
and distribution of contraception, the diagnosis and treatment
of complications of diabetes, the establishment of control
of maternal glucose, and the transition to intensive prenatal
care. The support and encouragement of health care personnel,
family, and friends is essential for patient retention and
compliance with the often rigorous demands of good preconception
care.
[Back to top]
Dysfunction of Cellular Transporters and Predisposition
to Diabetic Nephropathy
Gianpaolo Zerbini, Daniela Gabellini, Dora Ruggieri and
Anna Maestroni
Diabetic nephropathy is presently the first reason of end
stage renal failure in Europe and the USA and its worldwide
prevalence is rapidly increasing. Several studies have demonstrated
that diabetes per se is not sufficient to induce
nephropathy and a genetic predisposition has to be present
as well.
Looking for genetic markers, investigators have been helped
by the finding that a predisposition to hypertension facilitates
the development of nephropathy in diabetic patients. Prompted
by the evidence that essential hypertension is characterized
by a number of defects at cellular level, similar dysfunctions
have been searched also in cells obtained from diabetic patients
with nephropathy.
Increased Na-Li countertransport and Na-H exchange activities,
slower Ca pump and faster cell proliferation rate have been
found in cells obtained from patients affected by diabetic
nephropathy. The definition of these intermediate phenotypes
represents a necessary step toward the identification of the
molecular dysfunction(s) underlying the development of diabetic
nephropathy.
The present review will focus on the description of the different
cell dysfunctions identified in patients affected by diabetic
nephropathy, their pathophysiologic meaning and will try to
define an unifying hypothesis that, by linking together the
different dysfunctions, will highlight a few areas “at
risk”, candidate to home the primitive genetic abnormality.
[Back to top]
Cultured Adult Animal Neurons and Schwann Cells Give
Us New Insights into Diabetic Neuropathy
Kazunori Sango, Haruhiro Saito, Masahiko Takano, Akiko
Tokashiki, Shuji Inoue and Hidenori Horie
Since we introduced cultured dorsal root ganglia (DRG) neurons
from streptozotocin (STZ)-induced diabetic mice as “an
in vitro model to study diabetic neuropathy”
(Sotelo et al., 1991), more than 30 papers have been
devoted to the study of diabetic neuropathy with culture systems
of neurons and Schwann cells derived from adult animals. So
far, methods for dissociated cell culture of peripheral neurons
(mainly DRG neurons) and Schwann cells, and for explant culture
of peripheral ganglia and retinas have been applied to diabetic
animals or patients. In addition to these diabetic cells,
adult animal neurons and Schwann cells cultured under high
glucose conditions and adult animal neurons exposed to diabetic
serum have been utilized. The findings from these culture
models clearly show that the exposure of mature neurons and
Schwann cells to hyperglycemic conditions in vivo
or in vitro can alter their biophysical and biochemical
properties (e.g., cell viability, neurite outgrowth
activity, polyol metabolism and electrophysiological features).
Therefore, the cultured neurons and Schwann cells can be useful
tools for investigating the precise mechanisms leading to
diabetic neuropathy and the efficacy of therapeutic agents
for the prevention and treatment of that condition.
[Back to top]
Type 2 Diabetes and Obesity in Children and Adolescents:
Experience from Studies in Taiwanese Population
Ling-Yin Chang, Hung-Yuan Li, Jung-Nan Wei and Lee-Ming
Chuang
Global prevalence of type 2 diabetes mellitus in children
is rising recently, likely due to an increasing rate of childhood
obesity. In Taiwan, an annual program of mass screen for diabetes
with two-staged design, i.e. diagnosis by fasting plasma glucose
when glycosuria was positive in two consecutive urine samples,
has been conducted since 1992 for all schoolchildren aged
6 to 18. A recent survey showed that the incidence of type
2 diabetes is 6-fold higher than those of type 1 diabetes.
The prevalence of diabetes is elevated during puberty and
is higher in girls than in boys. Obesity is the most important
risk factor of type 2 diabetes in childhood and adolescence.
Besides, genetics, family history, polycystic ovarian syndrome,
ethnicity, and puberty are also risk factors of pediatric
diabetes. We also briefly discuss the current state of management
of obesity and type 2 diabetes, with special emphasis on behavioral
and lifestyle modification, the need to create adequate and
safe environment, and the psychological as well as family
support in children and adolescents. Limited experience of
the pharmacological agents in terms of their long-term effect
and safety is also discussed.
[Back to top]
Relationship Between Inflammation, Insulin Resistance
and Type 2 Diabetes: ‘Cause or Effect’?
Jerry R. Greenfield and Lesley V. Campbell
Inflammation has been implicated as an important aetiological
factor in the development of both insulin resistance and type
2 diabetes mellitus. This conclusion is predominantly drawn
from studies demonstrating associations between elevated (but
‘normal range’) levels of circulating acute phase
inflammatory markers, typified by C-reactive protein (CRP),
and indices of insulin resistance and the development of type
2 diabetes. There is debate as to whether these associations
are independent of body fatness or, rather, an epiphenomenon
of obesity, particularly central obesity, a strong predictor
of insulin resistance and type 2 diabetes and an important
source of inflammatory cytokines, such as interleukin-6. Some
of this controversy and the inability to draw definitive conclusions
from these studies relate to the fact that most studies measure
body fat and its distribution indirectly using anthropometric
estimates, such as Body Mass Index and waist circumference,
rather than directly by dual-energy X-ray absorptiometry,
computed tomography or magnetic resonance imaging. Furthermore,
use of the term inflammation may be inappropriate when describing
mild elevations of CRP in the ‘normal range’ in
the absence of the other changes that characterise classical
inflammatory diseases, such as a reduction in levels (or evidence
of consumption) of complement proteins. Debate as to whether
obesity mediates the association between circulating levels
of inflammatory markers and insulin resistance can be resolved
by well-designed studies using body fat measured by gold-standard
methods. In this review, we present evidence to support the
suggestion that body fat is the primary determinant of circulating
inflammatory marker levels in the basal state and that marginally
elevated levels of circulating interleukin-6 and CRP in obesity
are a consequence rather than a cause of insulin resistance.
The importance of genetic influences in determining both body
fatness and circulating CRP levels will also be discussed.
The review will conclude with a discussion of possible mechanisms
linking body fat and insulin resistance to elevated circulating
levels of inflammatory markers, including the possible role
of the toll-like family of immune receptors.
[Back to top]
Hormones and the Autonomic Nervous System are Involved
in Suprachiasmatic Nucleus Modulation of Glucose Homeostasis
Marieke Ruiter, Ruud M. Buijs and Andries Kalsbeek
Glucose is one of the most important energy sources for
the body in general, and the brain in particular. It is essential
for survival to keep glucose levels within strict boundaries.
Acute disturbances of glucose homeostasis are rapidly corrected
by hormonal and neuronal mechanisms. Furthermore, changes
in energy expenditure associated with the light-dark cycle
induce variations in the plasma glucose concentration that
are more gradual. Organisms take advantage of adapting their
internal physiology to the predictable daily changes in energy
expenditure, because it enables them to anticipate these changes
and to prevent unnecessary disturbance of homeostasis. The
hypothalamic biological clock, located in the suprachiasmatic
nucleus (SCN), receives light information from the eyes and
transmits this information to the rest of the body to synchronize
physiology to the environment. Here we review several studies
providing evidence for biological clock control of the daily
variation in several aspects of glucose metabolism. Although
both hormones and the autonomic nervous system can stimulate
glucose uptake or production by organs in the periphery, we
have shown that the biological clock control of glucose metabolism
mostly occurs through the autonomic nervous system. The critical
involvement of the biological clock is also indicated by several
studies, indicating that disturbance of the biological clock
is often associated with metabolic diseases, such as obesity,
diabetes mellitus and hypertension.
[Back to top]
Clinical Thiazolidinediones as PPARγ
Ligands with the Potential for the Prevention of Cardiovascular
Disease in Diabetes
Stephanie T. de Dios, Richard C. O’Brien and Peter
J. Little
Thiazolidinediones (TZDs) are PPARγ
ligands and the newest class of agents in routine clinical
practice for the treatment of hyperglycemia in type 2 diabetes.
The prime reason for treating hyperglycemia and related aspects
of the metabolic syndrome is to prevent accelerated cardiovascular
disease (CVD) in diabetes. The formation and subsequent rupture
of atherosclerotic “plaques”, establishes CVD
as the major cause of premature mortality in diabetes. Metabolically,
TZDs act as insulin sensitizers resulting in improved glucose
uptake, lower blood glucose and reduced hyperinsulinemia,
however, they also appear to have beneficial direct vascular
actions. TZDs have a range of actions directly on vascular
cells and the predominance of the reported actions is potentially
beneficial. TZDs inhibit vascular smooth muscle cell proliferation,
inhibit the expression of adhesion molecules and modify the
structure of vascular proteoglycans in a manner that results
in reduced lipid binding. These actions manifest as reduced
lipid deposition in the vessels of animals with experimental
diabetes and atherosclerosis. Early clinical data indicates
that TZDs may prevent or delay CVD including atherosclerosis
and restenosis following coronary angiography. TZDs may be
the first class of oral hypoglycemic agents with significant
anti atherogenic effects to combat one of the major complications
of diabetes.
[Back to top]
Reactive Species, Cellular Repair and Risk Factors
in the Onset of Type 2 Diabetes Mellitus: Review and Hypothesis
Leonid E. Fridlyand and Louis H. Philipson
Insulin resistance (IRe) and a failure of insulin secretion
are the major features of the early pathophysiology of type-2
diabetes mellitus (T2D) but the etiology is still not well
understood. We suggest that: 1. The cellular mechanisms that
protect against oxidative stress per se are capable of creating
a reactive species-dependent IRe. 2. Reactive species-induced
mitochondrial dysfunction can lead to disruption of lipid
metabolism, increased intracellular lipid content, and can
also contribute to lipid-dependent IRe in myocytes and adipocytes.
3. Metabolic secretagogues that stimulate insulin secretion
by the activation of initial steps in the glucose-stimulated
insulin secretion pathway can also lead to increased reactive
species production and cellular destruction contributing to
β-cell
damage and apoptosis. These events that underlie the repair
mechanisms in β-cells,
muscle and adipocytes, are important factors in the early
etiology of T2D, leading to both IRe and decreased insulin
secretion. This hypothesis is supported by data from multiple
disciplines and includes aging, obesity and genetic factors
in promoting multiple failures in this system leading to the
onset of T2D. On the basis of this hypothesis therapeutic
strategies should be directed towards increasing insulin secretion
and reducing IRe without increasing reactive species production
or concentration. Pharmacological or other approaches that
result in the activation of mitochondrial biogenesis could
be beneficial for both IRe and T2D.
[Back to top]
Overcoming Barriers to Evidence-Based Diabetes Care
Richard W. Grant and James B. Meigs
Despite evidence-based guidelines that advocate aggressive
management of hyperglycemia, hypertension, and hyperlipidemia,
patients with diabetes continue to suffer from high rates
of cardiovascular and microvascular complications and can
expect a lifespan reduction of 10 to 15 years. Our current
inability to effectively and widely translate clinical evidence
into usual practice represents a major barrier to reducing
the burden of diabetes and its complications.
Diabetes care represents a complex interaction between patients
(and their families and communities), physicians (and other
providers), and the health care system. Because multi-drug
regimens are typically required to control hyperglycemia and
the diabetes-related risk factors of hypertension and hyperlipidemia,
polypharmacy is the natural consequence of providing evidence-based
medical care to patients with type 2 diabetes. Within this
context, we review the current evidence regarding the following
three potential barriers to effective care: 1) Medication
adherence in the setting of complex medical regimens, 2) Lack
of medication adjustment among patients above risk factor
goals, and 3) Limitations of currently organized care systems
to manage complex chronic diseases such as diabetes. We also
describe recent results of controlled trials of population-level,
informatics-based interventions to improve diabetes care.
|
