Skip to main content

Genetics in Type 2 Diabetes May Influence Beta Cell Mass


May 29, 2012 (Florence, Italy) — In patients with newly diagnosed type 2 diabetes, genetic differences might influence beta cell functional mass, new research suggests.
Sara Bonetti, MD, from the University of Verona and the Azienda Ospedaliera Universitaria Integrata, in Italy, and colleagues presented the findings here at the Joint 15th International Congress of Endocrinology and 14th European Congress of Endocrinology.
"This cohort of newly diagnosed type 2 diabetic patients was useful for our purposes because of the absence of the potentially confounding effects of long-lasting antidiabetic treatments and because of the limited impact of duration and severity of hyperglycemia on metabolic phenotypes," Dr. Bonetti told Medscape Medical News.
According to Dr. Bonetti and colleagues, common genetic variability is already known to influence beta cell functional mass in type 2 diabetes, but the way in which this occurs is not clear.
To investigate the role of genetics in beta cell mass, the researchers studied 590 drug-naïve, glutamic-acid-decarboxylase-negative patients newly diagnosed with type 2 diabetes. Median age was 60 years and average body mass index was 29.3 kg/m².
Dr. Bonetti and colleagues assessed beta cell functional mass using mathematical modeling of glucose/C-peptide curves during multiple oral glucose tolerance tests. Insulin sensitivity was measured using the insulin clamp technique.
Forty-five single-nucleotide polymorphisms (SNPs) were selected to represent over 90% of the common genetic variability observed in diabetes. The SNPs came from 8 genes involved in maturity onset diabetes of the young (MODY) and 2 genes associated with neonatal diabetes mellitus (NDM).
The researchers measured both derivative and proportional control of beta cell function. Derivative control measures the capability of beta cells to respond to the rate of increase in glucose concentration (i.e., it takes into account the actual and the baseline glucose concentration). Proportional control measures the capability of beta cells to respond to glucose concentration at a given moment in time.
They found that allelic variants of 4 SNPs — rs1303722 and rs882019 of glucokinase, rs7310409 of HNF1A, and rs5219 of KCNJ11 (a known type 2 diabetes risk variant) — were significantly associated with changes in derivative control of beta cell function (P = .007 to .030).
Allelic variants of 5 other SNPs — rs2869084 and rs6031544 of HNF4A, rs10774580 of HNF1A, rs1801262 of NEUROD1, and rs7129639 of ABCC8 — were found to influence proportional control of beta cell function (P = .001 to .040).
Of the 45 SNPs, 1 was found to be associated with insulin sensitivity (P = .047).
"Common variability of MODY and NDM genes is significantly associated to beta cell functional mass in patients with type 2 diabetes, potentially playing a role in the pathophysiology of the disease and in its metabolic prognosis," Dr. Bonetti and colleagues conclude.
According to Dr. Bonetti, it is possible that genetics will be used in the future to infer metabolic phenotypes that cannot be measured with standard clinical tools, and to personalize diagnosis and treatment.
However, she pointed out that many questions remain unanswered, because "type 2 diabetes is a complex disease and all genetic factors identified so far explain only a small part of the disease."
Vincenzo Trischitta, MD, associate professor of endocrinology at University La Sapienza in Rome, Italy, noted that it is well known that the genes studied modulate insulin secretion, so the findings are not surprising.
"Some data have been previously reported on the role of common variants of monogenic diabetes genes on abnormal glucose homeostasis," Dr. Trischitta told Medscape Medical News. "It makes a lot of sense that some of these variants may, in fact, affect insulin secretion, the most potent determinant of glucose homeostasis."
According to Dr. Trischitta, these data are very important becaause they help to address the pathophysiology of insulin secretion. However, he explained, clinicians "have to be aware that...genetic data on common variants have clinical relevance neither for predicting disease onset nor for treatment choices." Currently, clinicians "should be encouraged to use traditional clinical markers, which perform quite well and are not costly."
This study was supported in part by a European Foundation for the Study of Diabetes/Novartis grant. Dr. Bonetti and Dr. Trischitta have disclosed no relevant financial relationships.

Comments

Post a Comment

Popular posts from this blog

Contact Precautions May Have Unintended Consequences

Contact precautions, including gloves, gowns, and isolated rooms, have helped stem the transmission of hospital pathogens but have also had some negative consequences, according to findings from a new study. Healthcare worker (HCWs) visited patients on contact precautions less frequently than other patients and spent less time with those patients when they did visit, report Daniel J. Morgan, MD, from the University of Maryland School of Medicine and the Veterans Affairs (VA) Maryland Health Care System, Baltimore, and colleagues. Moreover, patients on contact precautions also received fewer outside visitors. "Less contact with HCWs suggests that other unintended consequences of contact precautions still exist," Dr. Morgan and coauthors write. "The resulting decrease in HCW contact may lead to increased adverse events and a lower quality of patient care due to less consistent patient monitoring and poorer adherence to standard adverse event prevention methods (such...
Post a Comment
Read more

CareFusion Issues Update on Infant Breathing Product Recall

July 5, 2012 — Medical device maker CareFusion has issued an update reminding healthcare providers of its voluntary recall of its Air Life ™ Infant Breathing Circuit, initiated back in May. The US Food and Drug Administration (FDA) has classified this action as a class 1 recall, meaning there is a reasonable probability of serious adverse health consequences or death associated with use of the defective units. The update was posted July 2 on the FDA  Website. On May 29, 2012, CareFusion sent an  Urgent Recall Notice  to customers and distributors stating that the company had identified potential risks associated with the Air Life  Infant Breathing Circuit. The action was initiated after the company received complaints of the Y adapter within the breathing circuit developing cracks during patient use. "If a crack develops in the Y adapter, this could potentially result in a leak in the closed ventilation system, leading to a loss in the intended tidal volum...
Post a Comment
Read more

FDA Approves Tapentadol ER for Diabetic Neuropathy

August 29, 2012 — The US Food and Drug Administration (FDA) has approved tapentadol extended-release (ER) ( Nucynta , Janssen Pharmaceuticals, Inc) for the management of neuropathic pain associated with diabetic peripheral neuropathy (DPN) in adults for whom a continuous opioid analgesic is required over an extended time. It is the first opioid to receive this indication, the company notes in a statement today. DPN, the most common type of neuropathy, affects an estimated 16% of the more than 25 million Americans who have diabetes. The condition is often unreported and untreated, with an estimated 2 out of 5 cases not receiving care. Tapentadol ER is already approved for the treatment of moderate to severe chronic pain in adults requiring a continuous opioid analgesic for an extended period. It is a centrally acting synthetic analgesic, although the exact mechanism of action is unknown, the release states. "Although the clinical relevance is unclear," the company n...
4 comments
Read more