Changes in Antidiabetic Drug Prescription and Glycemic Control Trends in Elderly Patients with Type 2 Diabetes Mellitus from 2005-2013: An Analysis of the National Center Diabetes Database (NCDD-03).

Objective To analyze the changes in the pharmacotherapy and glycemic control trends in elderly patients with type 2 diabetes mellitus (T2DM) in Japan. Methods We extracted the data of 7,590 patients (5,396 men and 2,194 women; median year of birth: 1945) with T2DM registered in the National Center Diabetes Database for the years 2005 to 2013, and conducted age-stratified (<65, 65-74, and ≥75 years of age) analyses. Results The hemoglobin A1c (HbA1c) levels declined from 2005 to 2013, and for those who received antihyperglycemic drug prescription, the HbA1c levels were lower in the older age group than in the younger age group. In the ≥75 age group, dipeptidyl peptidase-4 inhibitors (DPP4i) became the most frequently prescribed drug (49.1%) in 2013, and sulfonylureas remained the second-most frequently prescribed drug (37.8%) with decreased prescribed doses. The prescription ratio of oral drugs associated with a risk of hypoglycemia was higher in patients ≥75 years of age than in those <75 years of age (40.5% and 26.4%, respectively in 2013), although it showed a downward trend. The prescription rates of insulin for patients ≥75 years of age increased during the study period. Conclusion The pharmacotherapy trends for elderly patients with T2DM changed dramatically in Japan with the launch of DPP4i in 2009. Glycemic control in a considerable portion of the ≥75 age group in Japan was maintained at the expense of potential hypoglycemia by the frequent, although cautious, use of sulfonylureas, glinides and insulin.

A positive family history of hypertension might be associated with an accelerated onset of type 2 diabetes: Results from the National Center Diabetes Database (NCDD-02).

Type 2 diabetes, which is characterized by a combination of decreased insulin secretion and decreased insulin sensitivity, can be delayed or prevented by healthy lifestyle behaviors. Therefore, it is important that the population in general understands their personal risk at an early age to reduce their chances of ever developing the disease. A family history of hypertension is known to be associated with insulin resistance, but the effect of a family history of hypertension on the onset of type 2 diabetes has not well been examined. We performed a retrospective study examining patient age at the time of the diagnosis of type 2 diabetes by analyzing a dataset of 1,299 patients (1,021 men and 278 women) who had been diagnosed as having type 2 diabetes during a health checkup. The mean ± standard deviation of the patient age at the time of the diagnosis of diabetes was 49.1 ± 10.4 years for patients with a family history of hypertension and 51.8 ± 11.4 years for patients without a family history of hypertension (p < 0.001). A multivariate linear regression analysis showed a significant association between a family history of hypertension and a younger age at the time of the diagnosis of type 2 diabetes, independent of a family history of diabetes mellitus and a male sex, suggesting that a positive family history of hypertension might be associated with the accelerated onset of type 2 diabetes.

Development of diabetes mellitus associated with quetiapine: A case series.

We aimed to describe the characteristics and clinical course of patients who developed diabetes associated with the use of quetiapine.This study included patients who received quetiapine for over a month between April 2008 and November 2013, and were diagnosed as having new-onset diabetes after initiation of quetiapine. We excluded patients who developed diabetes more than 1 year after discontinuation of quetiapine. We identified new-onset diabetes by hemoglobin A1c or prescriptions of antidiabetic drugs.Among 1688 patients who received quetiapine, hemoglobin A1c had been measured in 595 (35.2%) patients at least once during the observation period, and 33 (2.0%) patients had received hypoglycemic drugs. Eighteen (1.1%) patients were considered to have developed new-onset diabetes associated with quetiapine after a median of 1.6 years following initiation of quetiapine. Median (interquartile range) age was 54.5 (29.8) years, 8 patients were male, and median (interquartile range) duration of mental illness was 15.3 (13.8) years. Median hemoglobin A1c and body mass index (BMI) were 7.1 (1.4) % and 28.4 (7.0) kg/m, respectively. Seventeen patients had dyslipidemia when diabetes was discovered. All of these discontinued quetiapine within 3 months after the diagnosis of diabetes, and the diabetes in 4 patients had ameliorated without hypoglycemic drugs. Of 13 patients who had received either oral hypoglycemic drugs or insulin, 2 patients achieved well-controlled hemoglobin A1c without hypoglycemic drugs, and 10 patients had hemoglobin A1c 5.0% to 7.7% with the continued use of hypoglycemic drugs.We demonstrated that almost all patients who developed quetiapine-associated diabetes had dyslipidemia and increased BMI. There was no life-threatening hyperglycemia and diabetes was ameliorated just by discontinuation of quetiapine in several patients. The monitoring of metabolic parameters during antipsychotic treatment is important to diagnose and treat diabetes earlier.

The Influences of Withdrawal and Daily Dose Reduction of Pioglitazone on Metabolic Parameters in Patients With Type 2 Diabetes: A Retrospective Longitudinal Observational Study.

BACKGROUND: The aim of the study was to understand the influences of withdrawal or dose reduction of pioglitazone in patients with type 2 diabetes. METHODS: We retrospectively picked up patients who had undergone withdrawal or daily dose reduction of pioglitazone after a continuous prescription for 3 months or longer between January 2010 and March 2014. We compared the data before the withdrawal or dose reduction of pioglitazone with the data at 3 or 6 months after those by a chart-based analysis. RESULTS: Among 713 patients taking pioglitazone at least once during the studied period, 20 patients had undergone withdrawal of pioglitazone (group A) and 51 patients had undergone daily dose reduction (group B). The mean pioglitazone dose at baseline was 23 mg in subjects of group A, and 30 mg in group B. The number of subjects who had taken high-dose metformin (≥ 1,000 mg) and dipeptidyl peptidase-4 (DPP-4) inhibitors increased after the withdrawal or dose reduction of pioglitazone in both groups. Although no significant change was observed in plasma glucose and HbA1c levels, body weight significantly decreased at 3 and 6 months after the dose reduction in group B. The same tendency was observed in group A. Serum high-density lipoprotein-cholesterol (HDL-C) levels significantly decreased at 3 and 6 months after the withdrawal in group A. The serum alanine aminotransferase levels significantly increased 3 months after the withdrawal in group A. CONCLUSIONS: Present study demonstrated that the withdrawal of pioglitazone exacerbated serum HDL-C and liver function in patients with type 2 diabetes, although glycemic control could be maintained by using high-dose metformin or DPP-4 inhibitors.

Body mass index and the risk of cancer incidence in patients with type 2 diabetes in Japan: Results from the National Center Diabetes Database.

AIMS/INTRODUCTION: Both type 2 diabetes and obesity increase the risk of some types of cancers, and underlying mechanisms are thought to be, at least in part, common. In the present study, we carried out a retrospective cohort study of the relationship between body mass index (BMI) categories and cancer development in Japanese type 2 diabetic patients. MATERIALS AND METHODS: A total of 113 incident cancers including 35 cancers whose incidence was reported to be increased by obesity (27 colorectal cancers, two breast cancers in postmenopausal women, one endometrial cancer, four renal cancers and one gallbladder cancer) were identified in 2,334 type 2 diabetic patients (1,616 men and 718 women) over an average observation period of 5.1 years. RESULTS: In men, there was no significant association between the BMI categories at the start of the observation period and the development of any cancer. In contrast, the incidence of all of the cancers in the women was significantly higher in the group with a BMI of less than 22.0 kg/m2 (hazard ratio 3.07, 95% CI 1.01-9.36). In either sex, there was no significant relationship between the BMI categories and the development of cancers whose risk is known to be increased by obesity. CONCLUSIONS: The findings of the present study were limited by the relatively small number of patients in the cohort, which posed a danger of not finding significance. However, the results suggested that obesity did not become an additional risk factor for cancer in Japanese type 2 diabetic patients.

Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Metabolic Parameters in Patients With Type 2 Diabetes: A Chart-Based Analysis.

BACKGROUND: Effects of the new class of anti-diabetic drugs, sodium-glucose cotransporter 2 (SGLT2) inhibitors, on metabolic parameters in patients with type 2 diabetes remain largely unknown. METHODS: We retrospectively picked up patients who had been continuously prescribed SGLT2 inhibitors for 1 month or more between April 2014 and November 2015 by a chart-based analysis, and compared the data before the SGLT2 inhibitor treatment with the data at 1, 2, 3 and 6 months after the SGLLT2 inhibitor treatment started. RESULTS: Fifty patients were eligible for the analyses in our study. The HbA1c levels as well as body weight significantly decreased at 1, 2, 3 and 6 months after the start of SGLT2 inhibitors. Systolic blood pressure tended to decrease only at 1 and 2 months, but there was no change at 3 and 6 months. No significant change was observed in serum high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and non-HDL-C levels. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels significantly decreased at 3 and 6 months after the prescription. The hematocrit levels significantly increased at 1, 2, 3 and 6 months, and the estimated glomerular filtration rate (eGFR) levels significantly decreased at 1 month after the start of SGLT2 inhibitors. A significant correlation between reductions in HbA1c levels and HbA1c levels at baseline was observed at 1, 3 and 6 months. The decreases in serum ALT levels were also significantly correlated with the baseline ALT levels at 3 and 6 months. CONCLUSION: Present study demonstrated that SGLT2 inhibitors significantly reduced HbA1c and body weight and improved liver functions, whereas no significant change was observed in serum lipid profiles.

Daily Physical Activity Assessed by a Triaxial Accelerometer Is Beneficially Associated with Waist Circumference, Serum Triglycerides, and Insulin Resistance in Japanese Patients with Prediabetes or Untreated Early Type 2 Diabetes.

AIM: To investigate the association between daily physical activity and metabolic risk factors in Japanese adults with prediabetes or untreated early type 2 diabetes (T2D). METHODS: Daily physical activity level was measured using a triaxial accelerometer. We assessed correlations between physical activity level and waist circumference, blood pressure, fasting levels of plasma glucose, serum triglycerides, and insulin and homeostasis model assessment-insulin resistance (HOMA-IR). RESULTS: A total of 80 patients were studied. After adjustment for age and body mass index, in all subjects, physical activity level was negatively associated with waist circumference (ß = -0.124, P = 0.018) and fasting serum triglycerides (ß = -0.239, P = 0.035), insulin (ß = -0.224, P = 0.022). In men, physical activity level was negatively associated with systolic blood pressure (ß = -0.351, P = 0.044), fasting plasma glucose (ß = -0.369, P = 0.025) and insulin (ß = -0.362, P = 0.012), and HOMA-IR (ß = -0.371, P = 0.011). No significant associations were found between physical activity level and metabolic risk factors in women. CONCLUSION: Objectively measured daily physical activity is beneficially associated with waist circumference, serum triglycerides, and insulin resistance in individuals with prediabetes or untreated early T2D. (This trial is registered with UMIN000015774.).

Correlations of non-exercise activity thermogenesis to metabolic parameters in Japanese patients with type 2 diabetes.

BACKGROUND: Non-exercise activity thermogenesis (NEAT) is the energy expenditure due to physical activities besides active sports-like exercise and resistance training in daily life. METHODS: We studied 45 subjects (22 women and 23 men) with type 2 diabetes who did not take any hypoglycemic, anti-hypertensive, or cholesterol-lowering agents and asked them about physical activity concerned with NEAT using an original questionnaire modified from a compendium of physical activities. We studied the association of the NEAT score to body weight, waist circumference, blood pressure, glucose and lipid metabolism, and arterial stiffness. RESULTS: The NEAT score was negatively correlated with serum insulin levels (r = -0.42, P < 0.05) in all subjects. The NEAT score was also negatively correlated with waist circumference (r = -0.509, P < 0.05) and positively correlated with high-density lipoprotein-cholesterol levels (r = 0.494, P < 0.05) in women, and negatively associated with serum insulin levels (r = -0.732, p < 0.005), systolic (r = -0.482, P < 0.05) and diastolic blood pressure (r = -0.538, P < 0.05) in patients with abdominal obesity. Furthermore, the NEAT score was negatively associated with pulse wave velocity (r = -0.719, P < 0.005) in smokers. CONCLUSION: The study demonstrated that NEAT is associated with amelioration in insulin sensitivity, waist circumference, high-density lipoprotein-cholesterol, blood pressure and the marker for atherosclerosis in patients with type 2 diabetes.

Effects of 6-month sitagliptin treatment on glucose and lipid metabolism, blood pressure, body weight and renal function in type 2 diabetic patients: a chart-based analysis.

BACKGROUND: Sitagliptin is one of the dipeptidyl peptidase-4 (DPP-4) inhibitors which prevent the inactivation of incretins, increasing the endogenous active incretin levels. Incretins stimulate insulin secretion from pancreatic ß-cells and inhibit glucagon secretion from pancreatic α-cells, which is favorable for the treatment of diabetes. Sitagliptin is released on December, 2009, in Japan. We retrospectively studied effects of 6-month-treatment with sitagliptin on glucose and lipid metabolism, blood pressure, body weight and renal function in patients with type 2 diabetes by a chart-based analysis. METHODS: We retrospectively studied 220 type 2 diabetic patients who have taken sitagliptin for 6 months by a chart-based analysis. Subjects studied include patients treated with sitagliptin monotherapy, sitagliptin add-on therapy, and switching from glinide to sitagliptin. We selected patients who have both data before and after 6-month sitagliptin treatment and compared the data before the sitagliptin treatment with the data at 6 month after the sitagliptin treatment started. Body weight, blood pressure, plasma glucose, hemoglobin A1c (HbA1c), serum lipids, and estimated glomerular filtration rate in type 2 diabetic patients were measured almost at the same time points before and after 6-month-treatment with sitagliptin. RESULTS: Body weight was significantly reduced after 6-month sitagliptin treatment by 0.8 kg. HbA1c levels were also significantly decreased after the sitagliptin treatment by 0.6%. We found a significant and negative correlation between change in body weight and body mass index at baseline. We also observed a significant and negative correlation between change in HbA1c and HbA1c levels at baseline. The number of patients who showed the absence of urinary glucose was significantly increased after the sitagliptin treatment.

Hyperinsulinemia and insulin resistance in a patient with type 2 diabetes complicated with myelofibrosis.

Inflammation induces insulin resistance and hyperinsulinemia due to elevation of serum cytokines such as tumor necrosis factor-α and interleukins. Chronic myeloproliferative diseases including myelofibrosis show higher serum interleukin levels than healthy subjects, which has been suggested to be the useful markers for disease activity. However, an association between myelofibrosis and insulin resistance has not ever been discussed anywhere. Here we report a case of type 2 diabetes showing remarkable hyperinsulinemia and insulin resistance possibly due to myelofibrosis.