NeuroTalk Support Groups - levodopa screws up your blood sugar...

.....big time! High blood sugar is very serious business - ask a diabetic. Invest in a glucometer and track it for a few days. I started today and am already surprised. A lifetime of this rollercoaster can't be good. I'll let you know how it goes but I already found that my mid-day "off" was accompanied by a jump from 94 to 128!

1: Int J Neurosci. 1993 Mar-Apr;69(1-4):125-30.

The relationship between diabetes mellitus and Parkinson's disease.

Sandyk R.

NeuroCommunication Research Laboratories, Danbury, CT.

It has been reported that 50% to 80% of patients with Parkinson's disease have
abnormal glucose tolerance which may be further exacerbated by levodopa therapy.
Little is known about the impact of chronic hyperglycemia on the severity of the
motor manifestations and the course of the disease as well as its impact on the
efficacy of levodopa or other dopaminergic drugs. This issue, which has been
largely ignored, is of clinical relevance since animal studies indicate that
chronic hyperglycemia decreases striatal dopaminergic transmission and increases
the sensitivity of postsynaptic dopamine receptors. In addition, evidence from
experimental animal studies indicates that diabetic rats are resistant to the
locomotor and behavioral effects of the dopamine agonist amphetamine. The
resistance to the central effects of amphetamine is largely restored with
chronic insulin therapy. In the present communication, I propose that in
Parkinson's disease diabetes may exacerbate the severity of the motor disability
and attenuate the therapeutic efficacy of levodopa or other dopaminergic agents
as well as increase the risk of levodopa-induced motor dyskinesias. Thus, it is
advocated that Parkinsonian patients should be routinely screened for evidence
of glucose intolerance and that if found aggressive treatment of the
hyperglycemia may improve the response to levodopa and potentially diminish the
risk of levodopa-induced motor dyskinesias.

PMID: 8082998 [PubMed - indexed for MEDLINE]

Smith 2004: We hypothesized that levodopa with carbidopa, a common therapy for patients with Parkinson's disease, might contribute to the high prevalence of insulin resistance reported in patients with Parkinson's disease. We examined the effects of levodopa-carbidopa on glycogen concentration, glycogen synthase activity, and insulin-stimulated glucose transport in skeletal muscle, the predominant insulin-responsive tissue. In isolated muscle, levodopa-carbidopa completely prevented insulin-stimulated glycogen accumulation and glucose transport…..
....Several investigators have reported high rates of glucose intolerance among patients with PD (2, 3, 27). For example, in two separate studies of 30 and 57 patients with PD, respectively, ~50% of the patients displayed abnormal oral glucose tolerance (2, 27). Similarly, abnormal intravenous glucose tolerance was found in four of eight patients with PD (3). Notably, hyperglycemic effects of levodopa and dopamine have been documented in humans and laboratory animals (3, 17, 18, 33). The decarboxylase inhibitor carbidopa is given with ....
....Levodopa and its metabolite dopamine have been shown to cause hyperglycemia in humans in a number of studies (17, 18). In one study, a 1.0-g dose of levodopa given orally to seven patients with PD caused an increase in fasting plasma glucose level from 87 to 99 mg/dl within 30 min (3). Four and five hours after a 100-g glucose load, plasma glucose concentrations were still elevated (133 and 122 mg/dl) in subjects who had ingested levodopa before consuming glucose compared with plasma glucose concentrations (83 and 78 mg/dl) in subjects for whom the oral glucose load was administered without levodopa (3). In a separate study, 1.0 g of levodopa caused hyperglycemia in patients with PD who had been treated for 3 mo with levodopa (33). Furthermore, 12 mo of chronic levodopa treatment reduced oral glucose tolerance in these patients, such that mean peak plasma glucose concentrations during oral glucose tolerance tests increased from ~165 to ~190 mg/dl (33). The year of chronic levodopa treatment was associated with a threefold increase in mean peak circulating insulin concentration and a twofold increase in insulin area under the curve during an OGTT (33).

1: Toxicol Appl Pharmacol. 2006 Apr 15;212(2):167-78. Epub 2006 Feb 20.

Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress.

Rolo AP, Palmeira CM.

Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology,
University of Coimbra, 3004-517 Coimbra, Portugal.

Hyperglycemia resulting from uncontrolled glucose regulation is widely
recognized as the causal link between diabetes and diabetic complications. Four
major molecular mechanisms have been implicated in hyperglycemia-induced tissue
damage: activation of protein kinase C (PKC) isoforms via de novo synthesis of
the lipid second messenger diacylglycerol (DAG), increased hexosamine pathway
flux, increased advanced glycation end product (AGE) formation, and increased
polyol pathway flux. Hyperglycemia-induced overproduction of superoxide is the
causal link between high glucose and the pathways responsible for hyperglycemic
damage. In fact, diabetes is typically accompanied by increased production of
free radicals and/or impaired antioxidant defense capabilities, indicating a
central contribution for reactive oxygen species (ROS) in the onset,
progression, and pathological consequences of diabetes. Besides oxidative
stress, a growing body of evidence has demonstrated a link between various
disturbances in mitochondrial functioning and type 2 diabetes. Mutations in
mitochondrial DNA (mtDNA) and decreases in mtDNA copy number have been linked to
the pathogenesis of type 2 diabetes. The study of the relationship of mtDNA to
type 2 diabetes has revealed the influence of the mitochondria on
nuclear-encoded glucose transporters, glucose-stimulated insulin secretion, and
nuclear-encoded uncoupling proteins (UCPs) in beta-cell glucose toxicity. This
review focuses on a range of mitochondrial factors important in the pathogenesis
of diabetes. We review the published literature regarding the direct effects of
hyperglycemia on mitochondrial function and suggest the possibility of
regulation of mitochondrial function at a transcriptional level in response to
hyperglycemia. The main goal of this review is to include a fresh consideration
of pathways involved in hyperglycemia-induced diabetic complications.

PMID: 16490224 [PubMed - indexed for MEDLINE]
1: Toxicol Appl Pharmacol. 2006 Apr 15;212(2):167-78. Epub 2006 Feb 20.

Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress.

Rolo AP, Palmeira CM.

Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology,
University of Coimbra, 3004-517 Coimbra, Portugal.

Hyperglycemia resulting from uncontrolled glucose regulation is widely
recognized as the causal link between diabetes and diabetic complications. Four
major molecular mechanisms have been implicated in hyperglycemia-induced tissue
damage: activation of protein kinase C (PKC) isoforms via de novo synthesis of
the lipid second messenger diacylglycerol (DAG), increased hexosamine pathway
flux, increased advanced glycation end product (AGE) formation, and increased
polyol pathway flux. Hyperglycemia-induced overproduction of superoxide is the
causal link between high glucose and the pathways responsible for hyperglycemic
damage. In fact, diabetes is typically accompanied by increased production of
free radicals and/or impaired antioxidant defense capabilities, indicating a
central contribution for reactive oxygen species (ROS) in the onset,
progression, and pathological consequences of diabetes. Besides oxidative
stress, a growing body of evidence has demonstrated a link between various
disturbances in mitochondrial functioning and type 2 diabetes. Mutations in
mitochondrial DNA (mtDNA) and decreases in mtDNA copy number have been linked to
the pathogenesis of type 2 diabetes. The study of the relationship of mtDNA to
type 2 diabetes has revealed the influence of the mitochondria on
nuclear-encoded glucose transporters, glucose-stimulated insulin secretion, and
nuclear-encoded uncoupling proteins (UCPs) in beta-cell glucose toxicity. This
review focuses on a range of mitochondrial factors important in the pathogenesis
of diabetes. We review the published literature regarding the direct effects of
hyperglycemia on mitochondrial function and suggest the possibility of
regulation of mitochondrial function at a transcriptional level in response to
hyperglycemia. The main goal of this review is to include a fresh consideration
of pathways involved in hyperglycemia-induced diabetic complications.

PMID: 16490224 [PubMed - indexed for MEDLINE]