Short-term Improvements In Glycaemic Control Research Articles

1088-P: Postprandial Dynamics of Glucagon Secretion in Type 2 Diabetic Patients: Changes Associated with Short-Term Improvements in Glycemic Control

Objective: Type 2 diabetic patients were examined for their postprandial dynamics of glucagon secretion as well as for changes in these dynamics associated with short-term improvements in their glycemic control. Methods: A total of 75 type 2 diabetic patients admitted for glycemic control who were not receiving incretin-related drugs (I) and SGLT2 inhibitors (S) at admission, 5 type 1 diabetic patients, 5 nondiabetic patients were subjected to meal tolerance tests (MTTs) during early morning fasting hours at admission. Blood samples were drawn from these patients preprandially, and 30, 60, and 120 minutes postprandially to measure their glucose, C-peptide and glucagon (Mercodia) values. Of the type 2 diabetic patients, those who improved glycemic control without both I and S (n = 10), were examined for changes in the postprandial dynamics of glucagon associated with improvements in glycemic control. Results: The AUC C-peptide values was shown to be the lowest in type 1 diabetic patients, followed by type 2 diabetic patients and nondiabetic patients, and with AUC-glucose values and AUC-glucagon values were shown to be the highest in type 1 diabetic patients, followed by type 2 diabetic patients and nondiabetic patients. Of the type 2 diabetic patients, those with BMI ≥ 25 kg/m2 and BMI < 25 kg/m2 were not significantly different in their AUC glucose, while those with BMI ≥ 25 kg/m2 had significantly larger AUC C-peptide and AUC glucagon values than those with BMI < 25 kg/m2. MTTs performed after improving glycemic control showed significantly smaller AUC glucose, significantly elevated AUC C-peptide, and significantly smaller AUC glucagon values in those improving glycemic control without both I and S after admission. Conclusions: Study results are in agreement with the conventional finding that decreased α-cell insulin action associated with decreased insulin secretion or insulin resistance leads to glucagon over-secretion secondarily. Disclosure R. Kanai: None. Y. Mori: None. R. Nishimura: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly Japan K.K., Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Sanofi K.K., Takeda Pharmaceutical Company Limited.

Impact of a Telephonic Intervention to Improve Diabetes Control on Health Care Utilization and Cost for Adults in South Bronx, New York.

Self-management education and support are essential for improved diabetes control. A 1-year randomized telephonic diabetes self-management intervention (Bronx A1C) among a predominantly Latino and African American population in New York City was found effective in improving blood glucose control. To further those findings, this current study assessed the intervention's impact in reducing health care utilization and costs over 4 years. We measured inpatient (n = 816) health care utilization for Bronx A1C participants using an administrative data set containing all hospital discharges for New York State from 2006 to 2014. Multilevel mixed modeling was used to assess changes in health care utilization and costs between the telephonic diabetes intervention (Tele/Pr) arm and print-only (PrO) control arm. During follow-up, excess relative reductions in all-cause hospitalizations for the Tele/Pr arm compared with PrO arm were statistically significant for odds of hospital use (odds ratio [OR] 0.89; 95% CI 0.82, 0.97; P < 0.01), number of hospital stays (rate ratio [RR] 0.90; 95% CI 0.81, 0.99; P = 0.04), and hospital costs (RR 0.90; 95% CI 0.84, 0.98; P = 0.01). Reductions in hospital use and costs were even stronger for diabetes-related hospitalizations. These outcomes were not significantly related to changes observed in hemoglobin A1c during individuals' participation in the 1-year intervention. These results indicate that the impact of the Bronx A1C intervention was not just on short-term improvements in glycemic control but also on long-term health care utilization. This finding is important because it suggests the benefits of the intervention were long-lasting with the potential to not only reduce hospitalizations but also to lower hospital-associated costs.

1214-P: Effect of Short-Term Improvements in Glycemic Control with SGLT2 Inhibitor Therapy on Insulin and Glucagon Secretion: How Does It Differ With or Without Concurrent DPP-4 Inhibitor Therapy

Objective: We investigated the effect of short-term improvements in glycemic control with SGLT2i therapy on insulin and glucagon secretion with or without concurrent DPP-4 inhibitor (DPP-4i) therapy. Patients and Methods: 78 type 2 diabetic patients admitted for glycemic control and subjected to meal tolerance tests (MTT) on the next day after admission and immediately before discharge using the same diabetes diet while off treatment were subjected to retrospective analysis. Of these, 41 patients were found to have received SGLT2i after admission, with 15 of these also found to have received concurrent DPP-4i. The patients were divided into those not receiving SGLT2i (n=37), those receiving SGLT2i without concurrent DPP-4i (n=26) and those receiving SGLT2i with DPP-4i (n=15) and were compared for changes in postprandial insulin and glucagon secretion. All patients were evaluated at admission and discharge for insulin secretion in terms of ΔCPR/ΔPG 0-30 min and AUC-CPR 0-2h, and as well as for glucagon (G) secretion in terms of ΔG/ΔPG 0-30 min and AUC-G 0-2h during the MTT. Results: There was no significant difference between the 3 groups in their HbA1c, C-peptide index, and urinary CPR excretion at admission. With improvements in glycemic control, ΔCPR/ΔPG 0-30min and AUC-CPR 0-2h were significantly increased, and AUC-PG 0-2h were significantly decreased, in all groups. Again, with improvements in glycemic control, AUC-G 0-2h was significantly decreased in those not receiving SGLT2i, increased in those receiving SGLT2i without DPP-4i, and decreased in those receiving both SGLT2i and DPP-4i. Conclusions: Postprandial insulin secretion was shown to be restored after short-term improvements in glycemic control irrespective of SGLT2i or concurrent DPP-4i, while glucagon secretion was shown to be increased with SGLT2i without DPP-4i but decreased with combined SGLT2i and DPP-4i. Disclosure M. Matsui: None. H. Takahashi: None. S. Sawano: None. Y. Mori: None. K. Utsunomiya: None.

2351-PUB: Influence of Short-Term Improvements in Glycemic Control with Intensive Insulin Therapy on Pancreatic a-Cell Function and the Relationship between Concurrent SGLT2 Inhibitor Therapy and Insulin Withdrawal

Objective: We investigated the relationship between insulin withdrawal (IW), endogenous insulin recovery, and concurrent SGLT2 inhibitor (SGLT2i) therapy. Patients and Methods: Of the 78 type 2 diabetic patients admitted for glycemic control and subjected to meal tolerance tests (MTT) on the next day after admission and immediately before discharge using the same diabetes diet while off treatment, 39 patients who had received intensive insulin therapy after admission were subjected to retrospective analysis. Of these, 26 patients in whom insulin withdrawal had been achieved during admission were divided into those who had received concurrent SGLT2i therapy (n=19) and those who had not (n=7). Insulin secretion in terms of ΔCPR/ΔPG 0-30 min and AUC-CPR 0-2 h during the MTT was compared at admission and discharge. Results: 1) While there was no significant difference between those with IW and those without IW in their age, BMI, HbA1c, C-peptide index and urinary CPR excretion at admission, significantly more patients with IW had received SGLT2i than those without IW (P &amp;lt; 0.001). Again, ΔCPR/ΔPG 0-30 min and AUC-CPR 0-2 h were significantly (p&amp;lt;0.001) increased in those with IW but not in those without IW. 2) In those with IW, while ΔCPR/ΔPG 0-30 min and AUC-CPR 0-2 h were significantly (p&amp;lt;0.05) increased in both of those with SGLT2i and those without, the time to IW was shown to be significantly shorter (p&amp;lt;0.01), the maximum daily insulin dose lower, and the duration of hospital stay shorter, in those with SGLT2i therapy than in those without. Conclusions: Study results confirmed that endogenous insulin secretion was significantly restored in those with IW and that the time to IW was significantly shorter in those with concurrent SGLT2i therapy than in those without, suggesting a role for SGLT2i in achieving IW. Disclosure M. Matsui: None. H. Takahashi: None. S. Sawano: None. Y. Mori: None. K. Utsunomiya: None.

Longitudinal association between periodontitis and development of diabetes

BackgroundClinical trials have shown very modest short-term improvements in glycemic control among participants with diabetes after periodontitis treatment. Few longitudinal studies suggest that periodontitis may be related to prediabetes/diabetes risk. MethodsWe evaluated 1206 diabetes free participants in the San Juan Overweight Adults Longitudinal Study (SOALS) and 941 with complete 3-year follow-up data were included. The National Health and Nutrition Examination Survey (NHANES) methods were used to assess periodontitis. Diabetes and prediabetes were classified using American Diabetes Association cutoffs for fasting and 2-hour post-load glucose and HbA1c. We used Poisson regression adjusting for baseline age, gender, smoking, education, family history of diabetes, physical activity, waist circumference, and alcohol intake. ResultsOver the 3-year follow-up, 69 (7.3%) of the 941 individuals developed type 2 diabetes, and 142 (34.9%) of the 407 with normal glycemia at baseline developed prediabetes. In multivariable models, greater mean pocket depth and mean attachment loss at baseline were associated with lower risk of developing prediabetes/diabetes over the follow-up (IRR = 0.81; 95% CI: 0.67–0.99, and IRR = 0.86; 95% CI: 0.74–0.99, respectively). Increase in periodontal attachment loss from baseline to follow-up was associated with higher prediabetes/diabetes risk (multivariate IRR = 1.25; 95% CI: 1.09–1.42), and increase in pocket depth was associated with >20% fasting glucose increase (multivariate IRR = 1.43; 95% CI: 1.14–1.79). The inverse associations persisted after additionally adjusting for baseline income, sugar-sweetened beverages, number of teeth, oral hygiene, glycemia, or previous periodontal therapy. ConclusionsThere is no association between periodontitis and risk of prediabetes/diabetes in this longitudinal study.

Low Carbohydrate Diets and Type 2 Diabetes: What is the Latest Evidence?

IntroductionLow carbohydrate diets are again in the spotlight and have been identified as particularly appropriate for people with type 2 diabetes. There is confusion amongst both health professionals and people with diabetes about the suitability of these diets. This review aims to provide an overview of the latest evidence and to explore the role of low carbohydrate diets for people with type 2 diabetes.MethodsAn electronic search of English language articles was performed using MEDLINE (2010–May 2015), EMBASE (2010–May 2015), and the Cochrane Central Register of Controlled Trials (2010–May 2015). Only randomized controlled trials comparing interventions evaluating reduced carbohydrate intake with higher carbohydrate intake in people with diagnosed type 2 diabetes were included. Primary outcomes included weight, glycated hemoglobin, and lipid concentrations.ResultsLow carbohydrate diets in people with type 2 diabetes were effective for short-term improvements in glycemic control, weight loss, and cardiovascular risk, but this was not sustained over the longer term. Overall, low carbohydrate diets failed to show superiority over higher carbohydrate intakes for any of the measures evaluated including weight loss, glycemic control, lipid concentrations, blood pressure, and compliance with treatment.ConclusionRecent studies suggest that low carbohydrate diets appear to be safe and effective over the short term, but show no statistical differences from control diets with higher carbohydrate content and cannot be recommended as the default treatment for people with type 2 diabetes.

Presentation and effectiveness of early treatment of type 2 diabetes in youth: lessons from the TODAY study.

The objectives were to (i) describe the characteristics of a large ethnically/racially and geographically diverse population of adolescents with recent-onset type 2 diabetes (T2D), and (ii) assess the effects of short-term diabetes education and treatment with metformin on clinical and biochemical parameters in this cohort. Descriptive characteristics were determined for subjects screened for Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) who met criteria for diagnosis of T2D (n = 1092). Changes in clinical and biochemical parameters were determined for those who completed at least 8 wk of the run-in phase of the trial, which included standardized diabetes education and treatment with metformin. Further analysis determined whether these changes differed according to the treatment at screening. Demographic, biochemical measurements, and anthropometrics at screening and changes over 8 wk of run-in were the outcome measures. Subjects screened for TODAY had a median age of 14 yr and median hemoglobin A1c (HbA1c) of 6.9% (52 mM/M), 2/3 were female, and ethnic/racial minorities were overrepresented. Dyslipidemia and hypertension were common comorbidities. During run-in, HbA1c, body mass index, low-density lipoprotein cholesterol, triglycerides, and blood pressure significantly improved. Nearly all participants on insulin therapy at screening were able to attain target HbA1c following insulin discontinuation. Treatment with metformin and diabetes education provided short-term improvements in glycemic control and cardiometabolic risk factors in a large adolescent T2D cohort. Nearly all insulin-treated youth could be successfully weaned off insulin with continued improvement in glycemic control.

Short‐term metabolic change is associated with improvement in measures of diabetic neuropathy: a 1‐year placebo cohort analysis

Randomized clinical trials have frequently shown improvement in diabetic sensorimotor polyneuropathy in placebo-treated participants, counter to the prevailing concept that it deteriorates with time. We aimed to determine the variables associated with this paradoxical nerve function improvement. Participants with diabetic sensorimotor polyneuropathy randomized to placebo in a multi-centre, double-blind study were evaluated for the primary outcome of 1-year change in the summed sensory nerve conduction velocity of the bilateral sural and non-dominant median nerves. Association with clinical and biochemical variables measured at 13 time points were examined. The 134 participants had mild to moderate diabetic sensorimotor polyneuropathy of 4.6 years' duration and mean 1-year improvement of 2.0 ± 8.0 m/s. Primary outcome measures were available for 122 participants (91%). In multivariate analyses, the change in HbA(1c) and serum triglycerides from baseline to 2 months demonstrated the strongest association, even independent of baseline and end-of-study levels. According to quintiles of change, we determined thresholds: participants with salutary improvement in HbA(1c) (exceeding a drop of -0.8%) or whose triglycerides did not increase (by 0.32 mmol/l or more) experienced significant improvement (2.9 m/s), while those with salutary levels of both these variables had an exaggerated improvement (5.1 m/s). In comparison, those with non-salutary changes in both variables experienced a loss of -4.9 m/s (ANOVA P=0.0014). In mild to moderate diabetic sensorimotor polyneuropathy, short-term improvements in glycaemic control and serum triglyceride levels have an independent, additive and durable effect on restoration of nerve function.

Using Meal-Based Self-Monitoring Blood Glucose (SMBG) Data to Guide Dietary Recommendations in Patients With Diabetes

The purpose of this article is to describe how self-monitoring of blood glucose (SMBG) data is a useful tool for identifying and managing postprandial hyperglycemia (PPHG). PPHG and postprandial glucose excursions occur frequently in patients with diabetes even when hemoglobin A1C is controlled below 7.0%, and convey increased risk of cardiovascular morbidity and mortality. Consequently, effective management of diabetes must include control of postprandial glucose levels. Postprandial plasma glucose (PPG) depends on the composition of meals, specifically the amount of carbohydrates. Reduced-carbohydrate diets offer short-term improvements in glycemic control and other metabolic parameters, but await the support of long-term efficacy and safety studies. Glucose profiling and paired-meal SMBG are useful tools for detecting PPHG and glucose excursions. They provide immediate feedback to patients on the effect of foods and meals, thereby allowing appropriate food and medication adjustments to improve postprandial glycemic control.

Therapy conversion to insulin detemir among patients with type 2 diabetes treated with oral agents: A modeling study of cost-effectiveness in the United States

The aim of this study was to gain a preliminary indication of the long-term clinical and economic implications of converting treatment for patients with type 2 diabetes to insulin detemir+/-oral hypoglycemic agents (OHAs) in a routine clinical practice setting in the United States. With the use of outcome data and patient characteristics reported from an ongoing prospective observational trial, a validated computer simulation model of diabetes was used to project the clinical and cost outcomes associated with therapy conversion to insulin detemir over a 35-y period from (1) OHA only, (2) neutral protamine Hagedorn insulin (NPH)+/-OHA, and (3) insulin glargine+/-OHA. Cost-effectiveness was assessed from a third-party healthcare payer perspective for the year 2005. Costs and clinical outcomes were discounted at a rate of 3%. Treatment with insulin detemir+/-OHA was associated with increases in quality-adjusted life expectancy of 0.309, 0.350, and 0.333 quality-adjusted life-years (QALYs) versus treatment with OHA alone, NPH+/-OHA, and insulin glargine+/-OHA, respectively. Increases in pharmacy costs were partially offset by reduced complications, rticularly renal complications and neuropathy. Projected incremental cost-effectiveness ratios were well within the range considered to represent good value in the United States, at $7412, $6269, and $3951 per QALY gained for treatment with Idet+/-OHA versus OHA alone, NPH+/-OHA, and Iglarg+/-OHA, respectively. On the basis of preliminary evidence of short-term improvements in glycemic control and reduced hypoglycemia, therapy conversion to insulin detemir+/-OHA from OHA alone, NPH+/-OHA, or insulin glargine+/-OHA was projected to increase quality-adjusted life expectancy and to represent a cost-effective treatment option in the United States.

Spotlight on Pioglitazone in Type 2 Diabetes Mellitus1

Pioglitazone (Actos(trade mark)) is an antihyperglycemic agent that, in the presence of insulin resistance, increases hepatic and peripheral insulin sensitivity, thereby inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptake. Pioglitazone is generally well tolerated, weight gain and edema are the most common emergent adverse events, and there are no known drug interactions between pioglitazone and other drugs. In clinical trials in patients with type 2 diabetes mellitus, pioglitazone as monotherapy, or in combination with metformin, repaglinide, insulin, or a sulfonylurea, induced both long- and short-term improvements in glycemic control and serum lipid profiles. Pioglitazone was also effective in reducing some measures of cardiovascular risk and arteriosclerosis. Pioglitazone thus offers an effective treatment option for the management of patients with type 2 diabetes.

Pioglitazone

Pioglitazone is an antihyperglycaemic agent that, in the presence of insulin resistance, increases hepatic and peripheral insulin sensitivity, thereby inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptake. Pioglitazone is generally well tolerated, weight gain and oedema are the most common emergent adverse events, and there are no known drug interactions between pioglitazone and other drugs. In clinical trials in patients with type 2 diabetes mellitus, pioglitazone as monotherapy, or in combination with metformin, repaglinide, insulin or a sulphonylurea, induced both long- and short-term improvements in glycaemic control and serum lipid profiles. Pioglitazone was also effective in reducing some measures of cardiovascular risk and arteriosclerosis. Pioglitazone thus offers an effective treatment option for the management of patients with type 2 diabetes.