Parkinson’s disease patients have impaired insulin secretion

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

Meanwhile, PD patients had lower insulin levels from 30 minutes onwards and a lower insulin AUC, although not significantly so.

In short, “PD patients had higher blood glucose following oral glucose intake without … the expected concomitant rise in insulin levels, suggesting an under-active insulin response. PD patients with advanced disease” – all the patients had had PD for more than 5 years – “have impaired blood glucose levels in response to oral glucose intake,” said lead investigator Ana Marques, MD, of the Université Clermont Auvergne in Clermont-Ferrand, France.

“Blood glucose dysregulation should be screened in PD patients with moderate to advanced disease. Insulin releasing drugs should possibly be preferred [over] insulin sensitizer drugs in PD patients with diabetes,” she said at the annual meeting of the American Academy of Neurology.

Higher blood glucose levels were also associated with longer PD duration, lower dopaminergic therapy doses, and higher degrees of dysautonomia. Mean PD duration in the study was about 8 years, and mean levodopa-equivalent dose 884 mg/d.

The findings add weight to the proposed and still somewhat controversial link between PD and diabetes. “Dysglycemia appears to be another nonmotor consequence of PD,” Dr. Marques said. Because insulin production “is modulated by the autonomic nervous system, the severity of dysautonomia in PD could be linked with blood glucose dysregulation. Sympathetic denervation might lead to beta-cell dysfunction.”

 

Subjects were 61 years old, on average; two-thirds were men. The mean BMI was about 25 kg/m². Patients were excluded if they had a change in dopaminergic therapy in the previous month, previous deep brain stimulation, medications that would interfere with glucose metabolism, or diabetes, among other things.

PD patients had slightly higher fasting urine glucose (P = .02). They also had lower fasting plasma insulin, but the difference wasn’t statistically significant (P = .5). Dysglycemia was also associated with higher BMI. Male gender and higher levodopa-equivalent doses were protective.

“The association between dysglycemia and PD is bilateral. In many studies, PD enhances the risk, but dysglycemia and particularly diabetes have been reported to increase the risk of PD. It goes both ways. There’s a lot that remains to be understood,” Dr. Marques said.

There was no external funding, and the investigators had nothing to disclose.

aotto@mdedge.com

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

Meanwhile, PD patients had lower insulin levels from 30 minutes onwards and a lower insulin AUC, although not significantly so.

In short, “PD patients had higher blood glucose following oral glucose intake without … the expected concomitant rise in insulin levels, suggesting an under-active insulin response. PD patients with advanced disease” – all the patients had had PD for more than 5 years – “have impaired blood glucose levels in response to oral glucose intake,” said lead investigator Ana Marques, MD, of the Université Clermont Auvergne in Clermont-Ferrand, France.

“Blood glucose dysregulation should be screened in PD patients with moderate to advanced disease. Insulin releasing drugs should possibly be preferred [over] insulin sensitizer drugs in PD patients with diabetes,” she said at the annual meeting of the American Academy of Neurology.

Higher blood glucose levels were also associated with longer PD duration, lower dopaminergic therapy doses, and higher degrees of dysautonomia. Mean PD duration in the study was about 8 years, and mean levodopa-equivalent dose 884 mg/d.

The findings add weight to the proposed and still somewhat controversial link between PD and diabetes. “Dysglycemia appears to be another nonmotor consequence of PD,” Dr. Marques said. Because insulin production “is modulated by the autonomic nervous system, the severity of dysautonomia in PD could be linked with blood glucose dysregulation. Sympathetic denervation might lead to beta-cell dysfunction.”

 

Subjects were 61 years old, on average; two-thirds were men. The mean BMI was about 25 kg/m². Patients were excluded if they had a change in dopaminergic therapy in the previous month, previous deep brain stimulation, medications that would interfere with glucose metabolism, or diabetes, among other things.

PD patients had slightly higher fasting urine glucose (P = .02). They also had lower fasting plasma insulin, but the difference wasn’t statistically significant (P = .5). Dysglycemia was also associated with higher BMI. Male gender and higher levodopa-equivalent doses were protective.

“The association between dysglycemia and PD is bilateral. In many studies, PD enhances the risk, but dysglycemia and particularly diabetes have been reported to increase the risk of PD. It goes both ways. There’s a lot that remains to be understood,” Dr. Marques said.

There was no external funding, and the investigators had nothing to disclose.

aotto@mdedge.com

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

Meanwhile, PD patients had lower insulin levels from 30 minutes onwards and a lower insulin AUC, although not significantly so.

In short, “PD patients had higher blood glucose following oral glucose intake without … the expected concomitant rise in insulin levels, suggesting an under-active insulin response. PD patients with advanced disease” – all the patients had had PD for more than 5 years – “have impaired blood glucose levels in response to oral glucose intake,” said lead investigator Ana Marques, MD, of the Université Clermont Auvergne in Clermont-Ferrand, France.

“Blood glucose dysregulation should be screened in PD patients with moderate to advanced disease. Insulin releasing drugs should possibly be preferred [over] insulin sensitizer drugs in PD patients with diabetes,” she said at the annual meeting of the American Academy of Neurology.

Higher blood glucose levels were also associated with longer PD duration, lower dopaminergic therapy doses, and higher degrees of dysautonomia. Mean PD duration in the study was about 8 years, and mean levodopa-equivalent dose 884 mg/d.

The findings add weight to the proposed and still somewhat controversial link between PD and diabetes. “Dysglycemia appears to be another nonmotor consequence of PD,” Dr. Marques said. Because insulin production “is modulated by the autonomic nervous system, the severity of dysautonomia in PD could be linked with blood glucose dysregulation. Sympathetic denervation might lead to beta-cell dysfunction.”

 

Subjects were 61 years old, on average; two-thirds were men. The mean BMI was about 25 kg/m². Patients were excluded if they had a change in dopaminergic therapy in the previous month, previous deep brain stimulation, medications that would interfere with glucose metabolism, or diabetes, among other things.

PD patients had slightly higher fasting urine glucose (P = .02). They also had lower fasting plasma insulin, but the difference wasn’t statistically significant (P = .5). Dysglycemia was also associated with higher BMI. Male gender and higher levodopa-equivalent doses were protective.

“The association between dysglycemia and PD is bilateral. In many studies, PD enhances the risk, but dysglycemia and particularly diabetes have been reported to increase the risk of PD. It goes both ways. There’s a lot that remains to be understood,” Dr. Marques said.

There was no external funding, and the investigators had nothing to disclose.

aotto@mdedge.com

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008