-
1.
Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?
Asakura, M, Kim, J, Asanuma, H, Hamasaki, T, Tsukahara, K, Higashino, Y, Ishikawa, T, Nakama, Y, Koba, S, Maruyama, Y, et al
Cardiovascular drugs and therapy. 2017;(4):401-411
Abstract
PURPOSE We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). METHODS This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. RESULTS The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints. CONCLUSION Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. TRIAL REGISTRATION Clinicaltrials.gov number: NCT00212017.
-
2.
Rationale and design of Diabetes Prevention with active Vitamin D (DPVD): a randomised, double-blind, placebo-controlled study.
Kawahara, T, Suzuki, G, Inazu, T, Mizuno, S, Kasagi, F, Okada, Y, Tanaka, Y
BMJ open. 2016;(7):e011183
Abstract
INTRODUCTION Recent research suggests that vitamin D deficiency may cause both bone diseases and a range of non-skeletal diseases. However, most of these data come from observational studies, and clinical trial data on the effects of vitamin D supplementation on individuals with pre-diabetes are scarce and inconsistent. The aim of the Diabetes Prevention with active Vitamin D (DPVD) study is to assess the effect of eldecalcitol, active vitamin D analogue, on the incidence of type 2 diabetes among individuals with pre-diabetes. METHODS AND ANALYSIS DPVD is an ongoing, prospective, multicentre, randomised, double-blind and placebo-controlled outcome study in individuals with impaired glucose tolerance. Participants, men and women aged ≥30 years, will be randomised to receive eldecalcitol or placebo. They will also be given a brief (5-10 min long) talk about appropriate calorie intake from diet and exercise at each 12-week visit. The primary end point is the cumulative incidence of type 2 diabetes. Secondary endpoint is the number of participants who achieve normoglycaemia at 48, 96 and 144 weeks. Follow-up is estimated to span 144 weeks. ETHICS AND DISSEMINATION All protocols and an informed consent form comply with the Ethics Guideline for Clinical Research (Japan Ministry of Health, Labour and Welfare). The study protocol has been approved by the Institutional Review Board at Kokura Medical Association and University of Occupational and Environmental Health. The study will be implemented in line with the CONSORT statement. TRIAL REGISTRATION NUMBER UMIN000010758; Pre-results.
-
3.
Sitagliptin improves glycaemic excursion after a meal or after an oral glucose load in Japanese subjects with impaired glucose tolerance.
Kaku, K, Kadowaki, T, Terauchi, Y, Okamoto, T, Sato, A, Okuyama, K, Arjona Ferreira, JC, Goldstein, BJ
Diabetes, obesity & metabolism. 2015;(11):1033-41
-
-
Free full text
-
Abstract
AIMS: To evaluate the efficacy and tolerability of sitagliptin in subjects with impaired glucose tolerance (IGT). METHODS In a double-blind, parallel-group study, 242 Japanese subjects with IGT, determined by a 75-g oral glucose tolerance test (OGTT) at week -1, were randomized (1 : 1 : 1) to placebo (n = 83), sitagliptin 25 mg (n = 82) or 50 mg (n = 77) once daily for 8 weeks. Glycaemic variables were assessed using another OGTT at week 7 and meal tolerance tests (MTTs) at weeks 0 and 8. Primary and secondary endpoints were percent change from baseline in glucose total area under the curve 0-2 h (AUC(0 -2 h)) during the MTT and OGTT, respectively. RESULTS Least squares mean percent change from baseline in glucose AUC(0 -2 h) during the MTT were -2.4, -9.5 and -11.5%, and during the OGTT were -3.7, -21.4 and -20.1% with placebo, sitagliptin 25 mg once daily, and 50 mg once daily, respectively (p < 0.001 for either sitagliptin dose vs placebo in both tests). Sitagliptin treatment enhanced early insulin response during the OGTT and decreased total insulin response, assessed as the total AUC(0 -2 h) during the MTT. Sitagliptin treatment also suppressed glucagon response during the MTT. The incidence of adverse events, including hypoglycaemia, was low and generally similar in all treatment groups. CONCLUSIONS Treatment with sitagliptin significantly reduced glucose excursions during both an MTT and an OGTT; this effect was associated with an increase in early insulin secretion after oral glucose loading as well as a blunted glucagon response during an MTT. Sitagliptin was generally well tolerated in subjects with IGT.
-
4.
Longitudinal decline of β-cell function: comparison of a direct method vs a fasting surrogate measure: the Insulin Resistance Atherosclerosis Study.
Festa, A, Haffner, SM, Wagenknecht, LE, Lorenzo, C, Hanley, AJ
The Journal of clinical endocrinology and metabolism. 2013;(10):4152-9
-
-
Free full text
-
Abstract
CONTEXT β-Cell function (BCF) declines over the course of type 2 diabetes, but little is known about BCF changes across glucose tolerance status (GTS) categories, and comparisons of direct vs surrogate measures. OBJECTIVE To assess longitudinal changes in BCF across GTS. DESIGN The Insulin Resistance Atherosclerosis Study is a multicenter, observational, epidemiologic study. SETTING Four clinical centers in the US that could identify subjects likely to have impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). PATIENTS We compared longitudinal changes in BCF in 1052 subjects over 5 years. Subjects were categorized according to baseline GTS: normal glucose tolerance (NGT: n = 547), impaired fasting glucose or impaired glucose tolerance (IFG/IGT: n = 341), and newly diagnosed type 2 diabetes (n = 164). INTERVENTIONS None. MAIN OUTCOME MEASURES BCF was assessed from a frequently sampled iv glucose tolerance test (AIR, acute insulin response), and the homeostasis model assessment of BCF (HOMA B). RESULTS NGT and IFG/IGT subjects increased their insulin secretion over time, whereas those with type 2 diabetes experienced either decline or little change in BCF. After adjustment for demographic variables and change in insulin resistance, change in HOMA B underestimated the magnitude of changes in BCF, as assessed by change in AIR. Relative to NGT, the 5-year change in insulin secretion in IFG/IGT and type 2 diabetes was 31% and 70% lower (by HOMA B) and 50% and 80% lower (by AIR). CONCLUSIONS The decline in BCF over time in IFG/IGT and type 2 diabetes may be more pronounced than previously estimated; HOMA B may underestimate this decline significantly.
-
5.
Slow-release insulin in cystic fibrosis patients with glucose intolerance: a randomized clinical trial.
Minicucci, L, Haupt, M, Casciaro, R, De Alessandri, A, Bagnasco, F, Lucidi, V, Notarnicola, S, Lorini, R, Bertasi, S, Raia, V, et al
Pediatric diabetes. 2012;(2):197-202
Abstract
BACKGROUND Early stages of glucose metabolism impairment are a period at risk in the long-term prognosis of cystic fibrosis (CF). Slow-release synthetic insulin glargine can be a therapeutic tool in this metabolic condition. METHODS In this phase 3 multicenter, controlled, two-arm, randomized clinical study, glargine was administered up to a dosage of 0.15 U/kg/die for a period of 18 months. Primary endpoint was the improvement of nutritional status [body mass index (BMI) Z score], while glucose tolerance [hemoglobin A1c (HbA1C) and respiratory function (FEV1 predicted] improvement were the secondary endpoints. RESULTS Thirty-four subjects (18 in the glargine arm and 16 in the control arm) were evaluated. Adherence to insulin treatment was excellent. No significant adverse events were reported. There were no significant differences in BMI, HbA1C and FEV1 values between the two groups nor within groups, except for HbA1C improvement in the glargine arm at month +18 (p = 0.04). CONCLUSIONS Glargine treatment was well accepted and tolerated. No real efficacy in improving clinical and glycometabolic conditions was demonstrated. Further studies are necessary to test glargine at higher dosage and for a longer follow-up period.
-
6.
Lifestyle modification and prevention of type 2 diabetes in overweight Japanese with impaired fasting glucose levels: a randomized controlled trial.
Saito, T, Watanabe, M, Nishida, J, Izumi, T, Omura, M, Takagi, T, Fukunaga, R, Bandai, Y, Tajima, N, Nakamura, Y, et al
Archives of internal medicine. 2011;(15):1352-60
Abstract
BACKGROUND Previous studies demonstrated that intensive lifestyle modification can prevent type 2 diabetes mellitus among those with impaired glucose tolerance, but similar beneficial results have not been proved among those with impaired fasting glucose levels. We investigated the efficacy of lifestyle modification on type 2 diabetes incidence among those with impaired fasting glucose levels. METHODS The present study was an unmasked, multicenter, randomized, controlled trial. A total of 641 overweight Japanese (aged 30-60 years) with impaired fasting glucose levels were recruited nationwide in Japan and randomly assigned to a frequent intervention group (n = 311) or a control group (n = 330). For 36 months after randomization, the frequent intervention group received individual instructions and follow-up support for lifestyle modification from the medical staff 9 times. The control group received similar individual instructions 4 times at 12-month intervals during the same period. The primary outcome was type 2 diabetes incidence in annual 75-g oral glucose tolerance tests, diagnosed according to World Health Organization criteria. RESULTS There were no significant differences between the allocation groups in baseline characteristics and dropout rates. Estimated cumulative incidences of type 2 diabetes were 12.2% in the frequent intervention group and 16.6% in the control group. Overall, the adjusted hazard ratio in the frequent intervention group was 0.56 (95% confidence interval, 0.36-0.87). In the post hoc subgroup analyses, the hazard ratio reduced to 0.41 (95% confidence interval, 0.24-0.69) among participants with impaired glucose tolerance at baseline, and to 0.24 (0.12-0.48) among those with baseline hemoglobin A(1c) levels of 5.6% or more (the Japan Diabetes Society method). Such risk reduction was not observed among those with isolated impaired fasting glucose findings or baseline hemoglobin A(1c) levels of less than 5.6%. CONCLUSIONS Lifestyle modifications can prevent type 2 diabetes among overweight Japanese with impaired fasting glucose levels. In addition, identifying individuals with more deteriorated glycemic status by using 75-g oral glucose tolerance test findings or, especially, measurement of hemoglobin A(1c) levels, could enhance the efficacy of lifestyle modifications. TRIAL REGISTRATION umin.ac.jp/ctr Identifier: UMIN000001959.
-
7.
[Evidence demonstrating the effect of voglibose for the prevention of type 2 diabetes mellitus: a randomised double-blind trial in Japanese subjects with inpaired glucose tolerance].
Kawamori, R
Nihon rinsho. Japanese journal of clinical medicine. 2011;:663-70
-
8.
Impact of lowering the criterion for impaired fasting glucose on identification of individuals with insulin resistance. The GISIR database.
Sesti, G, Andreozzi, F, Bonadonna, RC, De Mattia, G, Leonetti, F, Luzi, L, Marini, MA, Natali, A, Vettor, R, Bonora, E, et al
Diabetes/metabolism research and reviews. 2008;(2):130-6
Abstract
OBJECTIVE We assessed the accuracy of the American Diabetes Association (ADA)2003 definition of impaired fasting glucose (IFG) in identifying subjects with low insulin sensitivity, and determined cardiovascular risk factors in ADA2003 IFG subjects. RESEARCH DESIGN AND METHODS This study included 930 non-diabetic Italian Caucasians from the GISIR database in which subjects underwent a hyperinsulinaemic-euglycaemic clamp performed with a standard technique. Low insulin sensitivity was defined as being in the lower quartile of glucose metabolized during the last hour of the clamp (M). Subjects were stratified in the following groups: normal fasting glucose (NFG) (<100 mg/dL), IFG100 (100-109 mg/dL), ADA1997 IFG110 (110-125 mg/dL), and ADA2003 IFG (100-125 mg/dL). RESULTS The sensitivity of identifying subjects with low insulin sensitivity increased adopting the ADA2003 criterion. After Bonferroni correction for multiple comparisons, both IFG100 and ADA1997 IFG110 showed significantly higher body mass index (BMI), waist, systolic blood pressure (SBP) and diastolic blood pressure (DBP), triglyceride, fasting plasma insulin (FPI) and fasting plasma glucose (FPG), and lower insulin sensitivity as compared with NFG. As compared with IFG100, ADA1997 IFG110 showed significantly higher BMI, waist, SBP, FPI, FPG, and lower insulin sensitivity. ADA2003 IFG group showed significantly higher BMI, waist, SBP and DBP, triglyceride, cholesterol, FPI, and FPG, but lower HDL levels and insulin sensitivity compared with NFG subjects. CONCLUSIONS Although neither the ADA2003 nor the ADA1997 definition of IFG appears to be particularly efficacious for the identification of subjects' low insulin sensitivity, lowering the criterion to the ADA2003 glucose threshold increased the sensitivity without affecting the specificity. ADA2003 IFG showed a worse cardiovascular risk profile compared with NFG.
-
9.
Type 2 diabetes-associated missense polymorphisms KCNJ11 E23K and ABCC8 A1369S influence progression to diabetes and response to interventions in the Diabetes Prevention Program.
Florez, JC, Jablonski, KA, Kahn, SE, Franks, PW, Dabelea, D, Hamman, RF, Knowler, WC, Nathan, DM, Altshuler, D
Diabetes. 2007;(2):531-6
-
-
Free full text
-
Abstract
The common polymorphisms KCNJ11 E23K and ABCC8 A1369S have been consistently associated with type 2 diabetes. We examined whether these variants are also associated with progression from impaired glucose tolerance (IGT) to diabetes and responses to preventive interventions in the Diabetes Prevention Program. We genotyped both variants in 3,534 participants and performed Cox regression analysis using genotype, intervention, and their interactions as predictors of diabetes incidence over approximately 3 years. We also assessed the effect of genotype on insulin secretion and insulin sensitivity at 1 year. As previously shown in other studies, lysine carriers at KCNJ11 E23K had reduced insulin secretion at baseline; however, they were less likely to develop diabetes than E/E homozygotes. Lysine carriers were less protected by 1-year metformin treatment than E/E homozygotes (P < 0.02). Results for ABCC8 A1369S were essentially identical to those for KCNJ11 E23K. We conclude that the lysine variant in KCNJ11 E23K leads to diminished insulin secretion in individuals with IGT. Given our contrasting results compared with case-control analyses, we hypothesize that its effect on diabetes risk may occur before the IGT-to-diabetes transition. We further hypothesize that the diabetes-preventive effect of metformin may interact with the impact of these variants on insulin regulation.
-
10.
Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study.
Salopuro, T, Pulkkinen, L, Lindström, J, Eriksson, JG, Valle, TT, Hämäläinen, H, Ilanne-Parikka, P, Keinänen-Kiukaanniemi, S, Tuomilehto, J, Laakso, M, et al
International journal of obesity (2005). 2005;(10):1245-51
Abstract
OBJECTIVE Genetic variation in leptin receptor (LEPR) gene has been reported to associate with insulin and glucose metabolism and adiposity in different study settings and various populations. We wanted to evaluate the association between LEPR polymorphisms, diabetes risk and body weight in Finnish subjects with impaired glucose tolerance (IGT). METHODS We investigated the associations of the three LEPR polymorphisms (Lys109Arg, Gln223Arg, 3'UTR Del/Ins) with the conversion to type 2 diabetes and the changes in body weight in 507 individuals with IGT participating in the Finnish Diabetes Prevention Study. Participants were randomized to either an intensive diet and exercise intervention group or a control group. RESULTS After 3 years, the odds ratio for the development of type 2 diabetes in individuals in the control group with the Lys109Lys genotype was 2.38-fold higher than in individuals with other genotype combinations (P=0.016). Irrespective of group individuals with the Gln223Gln genotype had higher conversion to type 2 diabetes (OR 2.01 (95% CI 1.03-3.93)) than the Arg223 allele carriers (P=0.042). The risk was more pronounced in the control group than in the intervention group. Individuals having the 3'UTR Del/Del genotype had a slightly higher body weight throughout the study than those with the insertion allele (P=0.020), although no difference in weight change was observed. CONCLUSION Two polymorphisms (Lys109Arg, Gln223Arg) in the extracellular domain of the leptin receptor predicted the conversion to type 2 diabetes in high-risk individuals with IGT. The Del/Ins polymorphism in the 3'UTR of LEPR was associated with body weight.