What characteristics at baseline are associated with the glucose-lowering effect of colestimide in patients with type 2 diabetes and hypercholesterolemia according to response to treatment?

Colestimide, an anion exchange resin, reportedly improves glycemic control in patients with type 2 diabetes. However, no studies of the glucose-lowering effect of colestimide have identified responders and nonresponders. In the present study, we compared glycemic control, lipids, and body-mass index (BMI) among patients with type 2 diabetes receiving colestimide (n=59) until 24 weeks after the start of treatment. Subjects were classified as responders to treatment (n=40), who showed a 15% or greater decrease in glycated hemoglobin (HbA1c) or a 20% or greater decrease in plasma glucose level or both after 24 weeks of colestimide treatment as compared with baseline; nonresponders showed HbA1c>11.5% or fasting plasma glucose (FPG)>250 mg/dL during the course of the study and <15% decrease in HbA1c levels or <20% decrease in FPG levels or both after 24 weeks of colestimide treatment as compared with baseline. In responders, FPG decreased significantly from 196 ± 91 mg/dL to 125 ± 47 mg/dL after 24 weeks (P<0.001), and HbA1c decreased from 9.1% ± 2.0% to 7.0% ± 0.9% (P<0.001). In nonresponders, HbA1c decreased significantly from 7.7% ± 2.9% to 7.6% ± 1.2% (P<0.05). Multiple logistic regression analysis revealed that baseline HbA1c and the presence of cholelithiasis were significant determinants of the response to colestimide treatment when corrected for sex, age, triglyceride levels, and BMI at baseline and the presence of fatty liver. In conclusion, baseline HbA1c and the presence of cholelithiasis have strong and independent influences on the glucose-lowering effect of colestimide.

Low-molecular-weight lipoprotein (a) and low relative lymphocyte concentration are significant and independent risk factors for coronary heart disease in patients with type 2 diabetes mellitus: Lp(a) phenotype, lymphocyte, and coronary heart disease.

BACKGROUND: The aim of the present prospective study was to examine whether lipoprotein (a) [Lp(a)] phenotypes and/or low relative lymphocyte concentration (LRLC) are independently associated with coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). METHODS: Serum Lp(a) concentration, Lp(a) phenotypes, and RLC were analyzed in 214 subjects. Lp(a) phenotypes were classified into 7 subtypes according to sodium dodecyl sulfate-agarose gel electrophoresis by Western blotting. Subjects were assigned to the low-molecular-weight (LMW (number of KIV repeats: 11-22) ) and high-molecular-weight (HMW( number of KIV repeats: >22 )) Lp(a) groups according to Lp(a) phenotype and to the LRLC (RLC: <20.3%) and normal RLC (NRLC; RLC: ≥20.3%) groups according to RLC. A CHD event was defined as the occurrence of angina pectoris or myocardial infarction during the follow-up period. RESULTS: During the follow-up period, 30 cases of CHD events were verified. Neutrophil count showed no correlation with CHD, while relative neutrophil concentration and RLC showed positive and negative correlations, respectively, with CHD. The Cox proportional hazard model analysis revealed the following hazard ratios adjusted for LMW Lp(a), LRLC, and LMW Lp(a) + LRLC: (4.31; 95% confidence interval [CI], 1.99-9.32; P < 0.01, 3.621; 95% CI, 1.50-8.75; P < 0.05, and 7.15; 95% CI, 2.17-23.56; P < 0.01, respectively). CONCLUSIONS: Our results suggest that both LMW Lp(a) and LRLC are significant and independent risk factors for CHD and that the combination thereof more strongly predicts CHD in patients with T2DM.

[Overview of drug therapy in elderly diabetic patients].

General treatment principles for elderly diabetic patient with type 2 diabetes are the same as those of adult care. However, hypoglycemia and other adverse effects of glucose-lowering treatment are more common in older patients. Understanding the advantages and disadvantages of each antihyperglycemic drug class helps clinicians individualize therapy for elderly patients. Especially, given the heterogeneity of the older adult population, the risk of hypoglycemia must be carefully considered before using sulfonylureas and insulin regimen. Less stringent goals for glycemic control are recommended for frail elderly diabetic patients with limited life expectancy, advanced diabetes complications, or extensive comorbid conditions. The aggressive management of cardiovascular risk factors, such as hypertension, dyslipidemia, obesity, inactivity or smoking, is likely to have even greater benefits.

Effects of bile-acid-binding resin (colestimide) on blood glucose and visceral fat in Japanese patients with type 2 diabetes mellitus and hypercholesterolemia: an open-label, randomized, case-control, crossover study.

OBJECTIVE: The objective was to examine the effects of colestimide on blood glucose, visceral fat, adipocytokines, and bile acid conjugate fractions in Japanese patients. METHODS: This study was an open-label, randomized, case-control, crossover study of colestimide 3 g/day in 40 Japanese patients with type 2 diabetes mellitus (T2D) and hypercholesterolemia. Patients were assigned to the colestimide group in which pravastatin and colestimide were administered orally and to the statin group in which pravastatin alone was administered orally. The principal outcome measures were serum lipid levels, fasting plasma glucose level in the early morning, hemoglobin A1c (HbA(1c)), visceral fat area (VFA), and serum 1,5-anhydroglucitol (1,5-AG) level. RESULTS: Serum low-density lipoprotein cholesterol levels significantly decreased from 113±38 mg/dl at baseline to 90±20 mg/dl (P=.009) at week 12 of colestimide administration. HbA(1c) significantly decreased from 7.4%±0.9% at baseline to 6.9%±0.9% (P=.001) at week 12 of colestimide administration. Serum 1,5-AG levels increased from 9.4±10.1 µg/ml to 12.4±9.5 µg/ml (P=.05) at week 12 of colestimide administration. The statin group showed no significant changes in lipids and 1,5-AG. However, ΔVFA was inversely correlated with Δcholic acid, and multivariate analysis revealed that ΔVFA was a significant explanatory variable. CONCLUSIONS: Colestimide holds promise not only for the treatment of hypercholesterolemia but also for the possible improvement of T2D and visceral fat obesity.

[An elderly patient with senile dementia showing acquired hemophilia A].

We report a case of an 82-year-old woman with senile dementia who was hospitalized at a specialist dementia hospital for 10 months. She had swelling of the left shoulder joint, subcutaneous hematoma in the left upper arm, and anemia was noted on blood examination. Her serum hemoglobin level was lower than normal at 4.6 g/dL, but there was no sign of gastrointestinal disease or gastrointestinal bleeding, and her stool specimens were negative for occult blood. Hematoma subsequently appeared on her chest and back. She had a low activation level of factor VIII (<1%), a high concentration of acquired inhibitors of factor VIII (18.5 BU/mL), and prolonged activated partial thromboplastin time (83.1 seconds). The possibility of drug-induced anemia or hematoma were ruled out. We diagnosed acquired hemophilia A (AHA), and suspected that this was the cause of her hematomas. We began treatment of her AHA with oral prednisolone and intravenous infusion of factor VIII. The bleeding improved, but she later died due to bacterial pneumonia. AHA is very rare, with a reported annual incidence of 0.1/100,000 in Japan. However, it is necessary to consider such a rare disease when we encounter bleeding in elderly patients.

Daily blood glucose profiles of glibenclamide and gliclazide taken once or twice daily in elderly type 2 diabetic patients.

AIM: The aim of this study was to evaluate the difference in daily blood glucose profiles between once- and twice-daily regimens of a moderate daily dose of glibenclamide or gliclazide in elderly patients with type 2 diabetes. METHODS: Daily blood glucose profile data were evaluated in 18 elderly type 2 diabetic patients treated with 80 mg/day gliclazide or 5 mg/day glibenclamide as monotherapy. The first daily blood glucose profile of the twice-daily regimen was performed approximately 1 week before hospital discharge, and the second was performed after taking a once-daily regimen for 4-7 days. Plasma glucose and plasma immunoreactive insulin (IRI) concentrations were measured daily at 12 time points: 08.00 (before breakfast); 10.00; 12.00 (before lunch); 14.00; 18.00 (before dinner); 20.00; 0.00; 02.00; 03.00; 04.00; 06.00; and 08.00 hours the next morning. RESULTS: Daily blood glucose profiles and plasma IRI profiles did not differ between the once- and twice-daily regimen groups in either the gliclazide group or the glibenclamide group. Plasma glucose values between midnight and early morning tended to be lower than the 08.00 hours plasma glucose value in the glibenclamide group, but not in the gliclazide group. CONCLUSION: These results suggest that the blood glucose-lowering effects of a once- and twice-daily moderate daily dose of glibenclamide or gliclazide do not differ in elderly type 2 diabetic patients. However, glibenclamide, regardless of the dosage schedule, tends to lower the plasma glucose values between midnight and early morning.

Lack of relationship between blood glucose-lowering activity of colestimide and serum cholecystokinin (CCK) concentrations in patients with type 2 diabetes.

Colestimide has been reported to lower blood glucose levels in patients with type 2 diabetes and hypercholesterolemia. We investigated the mechanism of the hypoglycemic activity of colestimide by examining changes in serum cholecystokinin (CCK) and insulin concentrations before and after its 2-week oral administration. A total of seven type 2 diabetes inpatients with hypercholesterolemia received colestimide after their blood glucose levels had stabilized. We daily measured plasma glucose levels and serum lipid concentrations, calculated Body Mass Index (BMI), and determined whole-day changes in serum immunoreactive insulin (IRI) and CCK concentrations in all study subjects. We daily measured plasma glucose levels, as well as serum IRI and CCK concentrations at 10 time points for measurement. Plasma glucose levels, as well as serum IRI and CCK concentrations before and after the 2-week oral administration of colestimide were compared. The means of total cholesterol levels and BMI decreased significantly after administration. At time points for measurement (10 : 00 and 12 : 00), plasma glucose levels decreased significantly after administration (P=0.026 and P=0.009, respectively). Diurnal changes in serum IRI and CCK concentrations were not observed after administration, except for the IRI concentration at 20: 00. The effect of colestimide on CCK may not explain the mechanism of its blood glucose-lowering activity in patients with type 2 diabetes and hypercholesterolemia.

Colestimide lowers plasma glucose levels and increases plasma glucagon-like PEPTIDE-1 (7-36) levels in patients with type 2 diabetes mellitus complicated by hypercholesterolemia.

BACKGROUND: Colestimide has been reported to lower blood glucose levels in patients with type 2 diabetes complicated by hypercholesterolemia. AIM: To examine the mechanism by which colestimide decreases plasma glucose levels in the above patients. METHODS: A total of 16 inpatients with type 2 diabetes complicated by hypercholesterolemia received colestimide for 1 week after their plasma glucose levels stabilized. We measured plasma glucose, serum immunoreactive insulin (IRI), serum lipid, plasma glucagon, and plasma glucagon-like peptide-1 (GLP-1) levels. These variables at baseline and 1 week of colestimide administration were compared. RESULTS: Preprandial plasma glucose levels (baseline: 132 +/- 33 mg/dL vs. completion: 118 +/- 43 mg/dL, P=0.073) tended to decrease after colestimide administration, while 1-hr postprandial plasma glucose levels (baseline: 208 +/- 49 mg/dL vs. completion: 166 +/- 30 mg/dL, P<0.001) and 2-hr postprandial plasma glucose levels (baseline: 209 +/- 56 mg/dL vs. completion: 178 +/- 39 mg/dL, P=0.015) decreased significantly at 1 week of colestimide administration. The 2-hr postprandial plasma GLP-1 level was significantly (P=0.015) higher at 1 week of colestimide administration as compared with the baseline level, while there were no significant changes in preprandial and 1-hr postprandial plasma GLP-1 levels. CONCLUSIONS: The GLP-1-increasing activity of colestimide may explain, at least in part, the mechanism of its blood glucose-lowering activity in patients with type 2 diabetes complicated by hypercholesterolemia.

Blood glucose-lowering activity of colestimide in patients with type 2 diabetes and hypercholesterolemia: a case-control study comparing colestimide with acarbose.

BACKGROUND: An anion exchange resin has been reported to lower blood glucose levels in patients with type 2 diabetes. AIM: To examine, in comparison with an alpha-glucosidase inhibitor, the usefulness of colestimide in lowering blood glucose levels in patients with type 2 diabetes and hypercholesterolemia. METHODS: Thirty-three patients with type 2 diabetes and hypercholesterolemia were more or less randomly assigned to receive either colestimide (17 patients) or acarbose (16 patients). At 10 time points before and after administration, plasma glucose levels and serum lipid concentrations were measured in all subjects, and the J-index and M-value were calculated. RESULTS: Patients receiving colestimide showed significant decreases in glucose levels 2 hours after breakfast (from 216.9 +/- 37.2 mg/dl before treatment to 191.1 +/- 40.9 mg/dl after treatment; p=0.008), in the J-index (from 42.6 +/- 14.5 to 32.6 +/- 9.8; p<0.001), and in the M-value (from 23.1 +/- 12.1 to 14.6 +/- 7.1; p<0.001). CONCLUSION: In patients with type 2 diabetes and hyperlipidemia, colestimide was suggested to have blood glucose-lowering activity as does acarbose.

Relation of apolipoprotein (a) phenotypes to diabetic retinopathy in elderly type 2 diabetes.

The aim of this study was to clarify the relationship between apolipoprotein (a) (apo (a) ) phenotypes and diabetic retinopathy in elderly type 2 diabetes. Serum Lp (a) concentrations and apo (a) phenotypes were analyzed in 250 diabetic patients aged 60 to 88 years old. Apo (a) phenotypes were classified into 7 subtypes (F, B, S1, S2, S3, S4, O (Null) ) by the method SDS electrophoresis with Western blotting. Patients were divided into two groups according to their apo (a) phenotypes:a low molecular weight (LMW) Lp (a) group, and a high molecular weight (HML) Lp (a) group. Patients were classified as having one of 4 types of diabetic retinopathy: no retinopathy (R0), simple retinopathy (R1), pre-proliferative retinopathy (R2), and proliferative retinopathy (R3). There was a significant association between serum Lp (a) levels and severity of diabetic retinopathy (p<0.001). A gradual trend toward increasing serum Lp (a) levels was observed across the groups (from R0 to R3). A significantly greater percentage of LMW Lp (a) was observed in the R1, R2, and R3 groups than in the R0 group (42.9% (p<0.001), 27.0% (p<0.01), and 27.3% (p<0.05) vs. 10.4%). Multiple logistic regression analysis revealed that duration of diabetes and LMW Lp (a) are independent risk factors for diabetic retinopathy. These results provide significant evidence that LMW Lp (a) contributes to an increased risk of diabetic retinopathy in elderly type 2 diabetes.