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Upper Small Intestinal Protein Sensing Improves Glucose Tolerance Through Suppression of Hepatic Glucose Production
542
047-2015.
Abstracts / Can J Diabetes 39 (2015) 529e547
GLUCOSE AND METABOLISM
Upper Small Intestinal Protein Sensing Improves Glucose Tolerance Through Suppression of Hepatic Glucose Production SOPHIE HAMR*, BRITTANY A. RASMUSSEN, PAIGE V. BAUER, FRANK A. DUCA, TONY K.T. LAM Toronto, ON Intestinal lipid-sensing initiates a neuronal gut-brain-liver negative feedback pathway to lower glucose production (GP) and maintain glucose homeostasis in vivo. However, whether intestinal protein-sensing regulates GP and consequently glucose tolerance via a neuronal network remains unknown, despite the ability of high-protein feeding to improve hyperglycemia and glucose tolerance in healthy and diabetic rodents and humans. Thus, we investigated the effects of upper small intestinal protein-sensing on glucose homeostasis by first infusing intraduodenal 10% w/v casein hydrolysate (CH) during an intravenous glucose tolerance test (IVGTT) in healthy rats. Intestinal infusion of CH for 50 min improved glucose tolerance as compared to saline (AUC saline: 1186.4106.8 vs. CH: 340.29128.96, n¼8, p<0.05), independent of a rise in plasma amino acids. Thus, this protein-induced glucose-lowering effect was preabsorptive. To assess whether intestinal protein-sensing improves glucose tolerance by directly lowering GP or increasing glucose uptake (GU) independent of changes in circulating glucoregulatory hormones, we infused intestinal CH during a pancreatic (basalinsulin) euglycemic clamp and evaluated changes in glucose kinetics using tracer-dilution methodology. Intestinal CH lowered GP (% suppression from basal; saline: -18.24.9% vs. CH: 463.2%, n¼8, p<0.05) compared to saline-treated rats, while GU remained unchanged (basal GU: 13.20.7 mgkg-1min-1 vs. CH GU: 12.60.7 mgkg-1min-1, n¼8, p>0.05). These findings collectively suggest that upper small intestinal protein-sensing improves glucose tolerance by lowering GP in healthy rodents. Future studies will address the underlying preabsorptive signaling mechanisms, the potential involvement of a neuronal gut-brain-liver axis, and the capacity of intestinal proteinsensing in models of obesity and diabetes.
048-2015.
CLINICAL CARE
Health Literacy Among Patients with Type 2 Diabetes Attending an Ambulatory Diabetes Services in Ireland YVONNE FINN*, SITI S. MOHD FARUDZ, MUHAMMAD A. MAD DAN Galway, Ireland Background: The institute of Medicine (2004) defines health literacy as “The degree to which individuals have the capacity to obtain, process and understand basic health information and service needed to make appropriate health decisions”. Sub-optimal health literacy has been described as a risk factor for chronic diseases such as type 2 diabetes. It is also linked with poorer glycemic control and higher complication rates. There is no data on health literacy in patients with type 2 diabetes in Ireland. This study measures health literacy in patients with type 2 diabetes attending the ambulatory diabetes services at Galway University hospital in Ireland. Methods: Patients with type 2 diabetes attending the out-patient diabetes clinic over a 4 week period in June/July 2015 were invited to participate. Functional health literacy was measured by administering the Newest Vital Sign (NVS), a validated tool to measure health literacy. Ethics approval was obtained from Galway University Hospitals’ Ethics committee. Results: Sixty seven participants, ranging from 39 to 84 years, completed the study. Twenty seven (40%) had a high likelihood of limited functional health literacy, 16 (24%) a possible likelihood of limited health literacy and 24 (36%) had adequate health literacy.
Only 2 participants (3%) perceived their level of health literacy level as low. Conclusions: Just over one third of participants in this study had adequate health literacy. Most of the participants with a high likelihood of limited health literacy did not perceive their health literacy skills as being inadequate.
049-2015. CLINICAL CARE Validation of Cooling Detection Threshold as a Marker of Sensorimotor Polyneuropathy in Type 2 Diabetes MOHAMMED A. FAROOQI, LEIF ERIK LOVBLOM, ZOE LYSY, ELISE M. HALPERN, MYLAN NGO, EDUARDO NG, ANDREJ ORSZAG, ARI BREINERy, VERA BRILy, BRUCE A. PERKINS*y Toronto, ON Aim: The measurement of cooling detection thresholds (CDT) has been established in previous cross-sectional studies as a valid test for diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes. We aimed to validate its diagnostic performance in type 2 diabetes (T2D). Methods: 220 T2D subjects from a larger cohort underwent clinical and electrophysiological examinations including 3 small-fiber function tests: CDT, heart rate variability (HRV) and laser Doppler imaging of axon-mediated neurogenic flare responses to cutaneous heating (LDIFLARE), along with the Toronto Clinical Neuropathy Score (TCNS). Clinical DSP was defined by consensus criteria whereas preclinical DSP was defined by at least one electrophysiological abnormality. Area under the curve (AUC) and optimal thresholds were determined by receiver operating characteristic (ROC) curves. Results: Subjects were aged 6311 years with mean HbA1c of 7.51.6%. The 139(63%) clinical DSP cases had mean CDT value 18.38.9 C; the 52(24%) preclinical DSP had 25.33.5 C; and the 29(13%) controls had 27.13.8 C; (p-value<0.02 for all three comparisons). For identification of clinical DSP AUCCDT was 0.79, which exceeded AUCHRV (0.60, p¼<0.0001), AUCLDI FLARE (0.69, p¼0.0003) and AUCTCNS (0.73, p¼0.03). Optimal threshold for clinical DSP identification was <22.8 C (64% sensitivity and 83% specificity). For Preclinical DSP, AUCCDT was 0.80, and the optimal threshold was 27.5 C (83% sensitivity and 72% specificity). Conclusions: Akin to studies of T1D, CDT has acceptable diagnostic performance for the identification of both clinical and preclinical neuropathy in patients with T2D. Application of CDT as a noninvasive tool for systematic screening of early neuropathy in diabetes clinics should be considered.
050-2015. LIPIDS Cardiovascular Disease Guideline Adherence and Statin Use: Results from the Canadian Study of Longevity in Diabetes JOHNNY-WEI BAI, GENEVIÈVE BOULET, ELISE M. HALPERN, LEIF ERIK LOVBLOM, ALANNA WEISMAN, DEVRIM ELDELEKLI, HILLARY KEENAN, MICHAEL BRENT, NARINDER PAUL, VERA BRILy, DAVID CHERNEYy, BRUCE A. PERKINS*y Toronto, ON; Boston, US Background: Older patients with longstanding type 1 diabetes (T1DM) have high cardiovascular disease (CVD) risk such that statin therapy is recommended independent of prior CVD events. We aimed to determine adherence to CVD prevention guidelines in patients with 50 or more years of diabetes. Research design and methods: 309 Canadians with over 50 years of T1DM completed a medical questionnaire for presence of lifestyle and CVD pharmacological interventions and they were
047-2015.
Abstracts / Can J Diabetes 39 (2015) 529e547
GLUCOSE AND METABOLISM
Upper Small Intestinal Protein Sensing Improves Glucose Tolerance Through Suppression of Hepatic Glucose Production SOPHIE HAMR*, BRITTANY A. RASMUSSEN, PAIGE V. BAUER, FRANK A. DUCA, TONY K.T. LAM Toronto, ON Intestinal lipid-sensing initiates a neuronal gut-brain-liver negative feedback pathway to lower glucose production (GP) and maintain glucose homeostasis in vivo. However, whether intestinal protein-sensing regulates GP and consequently glucose tolerance via a neuronal network remains unknown, despite the ability of high-protein feeding to improve hyperglycemia and glucose tolerance in healthy and diabetic rodents and humans. Thus, we investigated the effects of upper small intestinal protein-sensing on glucose homeostasis by first infusing intraduodenal 10% w/v casein hydrolysate (CH) during an intravenous glucose tolerance test (IVGTT) in healthy rats. Intestinal infusion of CH for 50 min improved glucose tolerance as compared to saline (AUC saline: 1186.4106.8 vs. CH: 340.29128.96, n¼8, p<0.05), independent of a rise in plasma amino acids. Thus, this protein-induced glucose-lowering effect was preabsorptive. To assess whether intestinal protein-sensing improves glucose tolerance by directly lowering GP or increasing glucose uptake (GU) independent of changes in circulating glucoregulatory hormones, we infused intestinal CH during a pancreatic (basalinsulin) euglycemic clamp and evaluated changes in glucose kinetics using tracer-dilution methodology. Intestinal CH lowered GP (% suppression from basal; saline: -18.24.9% vs. CH: 463.2%, n¼8, p<0.05) compared to saline-treated rats, while GU remained unchanged (basal GU: 13.20.7 mgkg-1min-1 vs. CH GU: 12.60.7 mgkg-1min-1, n¼8, p>0.05). These findings collectively suggest that upper small intestinal protein-sensing improves glucose tolerance by lowering GP in healthy rodents. Future studies will address the underlying preabsorptive signaling mechanisms, the potential involvement of a neuronal gut-brain-liver axis, and the capacity of intestinal proteinsensing in models of obesity and diabetes.
048-2015.
CLINICAL CARE
Health Literacy Among Patients with Type 2 Diabetes Attending an Ambulatory Diabetes Services in Ireland YVONNE FINN*, SITI S. MOHD FARUDZ, MUHAMMAD A. MAD DAN Galway, Ireland Background: The institute of Medicine (2004) defines health literacy as “The degree to which individuals have the capacity to obtain, process and understand basic health information and service needed to make appropriate health decisions”. Sub-optimal health literacy has been described as a risk factor for chronic diseases such as type 2 diabetes. It is also linked with poorer glycemic control and higher complication rates. There is no data on health literacy in patients with type 2 diabetes in Ireland. This study measures health literacy in patients with type 2 diabetes attending the ambulatory diabetes services at Galway University hospital in Ireland. Methods: Patients with type 2 diabetes attending the out-patient diabetes clinic over a 4 week period in June/July 2015 were invited to participate. Functional health literacy was measured by administering the Newest Vital Sign (NVS), a validated tool to measure health literacy. Ethics approval was obtained from Galway University Hospitals’ Ethics committee. Results: Sixty seven participants, ranging from 39 to 84 years, completed the study. Twenty seven (40%) had a high likelihood of limited functional health literacy, 16 (24%) a possible likelihood of limited health literacy and 24 (36%) had adequate health literacy.
Only 2 participants (3%) perceived their level of health literacy level as low. Conclusions: Just over one third of participants in this study had adequate health literacy. Most of the participants with a high likelihood of limited health literacy did not perceive their health literacy skills as being inadequate.
049-2015. CLINICAL CARE Validation of Cooling Detection Threshold as a Marker of Sensorimotor Polyneuropathy in Type 2 Diabetes MOHAMMED A. FAROOQI, LEIF ERIK LOVBLOM, ZOE LYSY, ELISE M. HALPERN, MYLAN NGO, EDUARDO NG, ANDREJ ORSZAG, ARI BREINERy, VERA BRILy, BRUCE A. PERKINS*y Toronto, ON Aim: The measurement of cooling detection thresholds (CDT) has been established in previous cross-sectional studies as a valid test for diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes. We aimed to validate its diagnostic performance in type 2 diabetes (T2D). Methods: 220 T2D subjects from a larger cohort underwent clinical and electrophysiological examinations including 3 small-fiber function tests: CDT, heart rate variability (HRV) and laser Doppler imaging of axon-mediated neurogenic flare responses to cutaneous heating (LDIFLARE), along with the Toronto Clinical Neuropathy Score (TCNS). Clinical DSP was defined by consensus criteria whereas preclinical DSP was defined by at least one electrophysiological abnormality. Area under the curve (AUC) and optimal thresholds were determined by receiver operating characteristic (ROC) curves. Results: Subjects were aged 6311 years with mean HbA1c of 7.51.6%. The 139(63%) clinical DSP cases had mean CDT value 18.38.9 C; the 52(24%) preclinical DSP had 25.33.5 C; and the 29(13%) controls had 27.13.8 C; (p-value<0.02 for all three comparisons). For identification of clinical DSP AUCCDT was 0.79, which exceeded AUCHRV (0.60, p¼<0.0001), AUCLDI FLARE (0.69, p¼0.0003) and AUCTCNS (0.73, p¼0.03). Optimal threshold for clinical DSP identification was <22.8 C (64% sensitivity and 83% specificity). For Preclinical DSP, AUCCDT was 0.80, and the optimal threshold was 27.5 C (83% sensitivity and 72% specificity). Conclusions: Akin to studies of T1D, CDT has acceptable diagnostic performance for the identification of both clinical and preclinical neuropathy in patients with T2D. Application of CDT as a noninvasive tool for systematic screening of early neuropathy in diabetes clinics should be considered.
050-2015. LIPIDS Cardiovascular Disease Guideline Adherence and Statin Use: Results from the Canadian Study of Longevity in Diabetes JOHNNY-WEI BAI, GENEVIÈVE BOULET, ELISE M. HALPERN, LEIF ERIK LOVBLOM, ALANNA WEISMAN, DEVRIM ELDELEKLI, HILLARY KEENAN, MICHAEL BRENT, NARINDER PAUL, VERA BRILy, DAVID CHERNEYy, BRUCE A. PERKINS*y Toronto, ON; Boston, US Background: Older patients with longstanding type 1 diabetes (T1DM) have high cardiovascular disease (CVD) risk such that statin therapy is recommended independent of prior CVD events. We aimed to determine adherence to CVD prevention guidelines in patients with 50 or more years of diabetes. Research design and methods: 309 Canadians with over 50 years of T1DM completed a medical questionnaire for presence of lifestyle and CVD pharmacological interventions and they were