Satoru Tsujii

Effects of exercise on C-reactive protein, inflammatory cytokine and adipokine in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

OBJECTIVE C-reactive protein (CRP), inflammatory cytokines, and adipokines contribute to atherosclerosis, insulin resistance, and development of late-onset complication in patients with type 2 diabetes. We performed a systematic review to assess effects of exercise interventions on inflammatory markers/cytokines and adipokines. MATERIALS/METHODS We searched electronic databases (MEDLINE, EMBASE, and Cochrane Controlled Trials Registry) and reference lists in relevant papers for articles published in 1966-2013. We selected studies that evaluated the effects of exercise intervention on inflammatory markers/cytokines and adipokines in adult patients with type 2 diabetes. Weighted mean differences of exercise on outcomes were derived using fixed or random effect models; factors influencing heterogeneity were identified using meta-regression analysis. RESULTS Fourteen randomized controlled trials (824 patients) were included in our meta-analysis. Exercise was associated with a significant in CRP=-0.66mg/l (95% CI, -1.09 to -0.23mg/l; -14% from baseline) and interleukin-6 (IL-6)=-0.88pg/ml (95% CI, -1.44 to -0.32pg/ml; -18% from baseline) but did not alter adiponectin or resistin levels; aerobic exercise program was associated with a significant change in leptin=-3.72ng/ml (95% CI, -6.26 to -1.18ng/ml; -24% from baseline). For IL-6, exercise was more effective in those with a longer duration in the program and larger number of sessions during study (p=0.001). CONCLUSIONS Exercise decreases inflammatory cytokine (CRP and IL-6) in patients with type 2 diabetes. Exercise could be a therapeutic option for improving abnormalities in inflammation levels in patients with diabetes.

Diabetes distress, but not depressive symptoms, is associated with glycaemic control among Japanese patients with Type 2 diabetes: Diabetes Distress and Care Registry at Tenri (DDCRT 1)

Aims  To investigate the association between glycaemic control, diabetes distress and depressive symptoms among Japanese patients with Type 2 diabetes.

Correlations between serum bilirubin levels and diabetic nephropathy progression among Japanese type 2 diabetic patients: a prospective cohort study (Diabetes Distress and Care Registry at Tenri [DDCRT 5]).

OBJECTIVE To assess the correlations between serum bilirubin levels and diabetic nephropathy development and progression in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Longitudinal data were obtained from 2,511 type 2 diabetic patients registered in a Japanese diabetes registry. To assess the independent correlations between serum bilirubin levels and either the development or progression of diabetic nephropathy, we used logistic regression analysis adjusted for potential confounders. RESULTS The median follow-up period was 503.4 days (range 238–777). The mean patient age, BMI, and HbA1c level was 65.2 years, 24.7 kg/m2, and 7.5% (58.5 mmol/mol), respectively. Baseline serum bilirubin levels were significantly associated with the urinary albumin-creatinine ratio at baseline (P < 0.001) and 1 year after registration (P < 0.001). Multivariable adjusted odds ratios for progression from microalbuminuria to macroalbuminuria for the second, third, and fourth quartile of serum bilirubin levels were 0.89 (95% CI 0.49–1.58), 0.93 (0.47–1.83), and 0.33 (0.13–0.84), respectively, showing a statistically significant linear trend across categories (P = 0.032). However, this trend disappeared after adjustment for hemoglobin levels. CONCLUSIONS Serum bilirubin levels were associated with diabetic nephropathy progression in type 2 diabetic patients independent of possible confounders. Serum bilirubin levels might be the link in the correlation between hemoglobin levels and nephropathy progression.

Elevated Levels of hs-CRP Are Associated With High Prevalence of Depression in Japanese Patients With Type 2 Diabetes: The Diabetes Distress and Care Registry at Tenri (DDCRT 6)

OBJECTIVE Because of the absence of data on the direct association between inflammation and depression in patients with diabetes, we examined the association between hs-CRP levels and the high prevalence of depression in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Cross-sectional data were obtained from 3,573 patients with type 2 diabetes recruited from a Japanese diabetes registry. A multiple logistic regression analysis adjusted for potential confounders was used to assess independent associations between hs-CRP levels and major depression, as defined by the Patient Health Questionnaire-9. RESULTS Mean age, BMI, and HbA1c levels were 66.0 years, 24.6 kg/m2, and 7.4% (57.8 mmol/mol), respectively, and 122 patients (3.4%) suffered from major depression. In the age- and sex-adjusted model, the odds ratio (OR) for major depression was 1.86 (95% CI 1.01–3.42; P = 0.045) in the highest CRP quintile compared with that in the 3rd CRP quintile; however, this association disappeared after adjustment for other possible confounders (OR 1.58 [95% CI 0.85–2.94]; P = 0.148). Among patients with a BMI of ≥25 kg/m2, a significant association was observed between the highest hs-CRP quintile and major depression (multivariable-adjusted OR 2.69 [95% CI 1.09–7.08]; P = 0.032). CONCLUSIONS We observed a significant positive association between high hs-CRP levels and depression in patients with diabetes who had a high BMI.

Patient-reported adherence to insulin regimen is associated with glycemic control among Japanese patients with type 2 diabetes: Diabetes Distress and Care Registry at Tenri (DDCRT 3)

AIMS We investigated the association between self-reported adherence to an insulin regimen and glycemic control in Japanese patients with type 2 diabetes. METHODS Data from 1441 patients with type 2 diabetes who were treated with insulin were obtained from a diabetes registry in Japan. We obtained information on self-reported adherence to an insulin regimen. Relative risk regression analysis was employed to assess the independent association of various demographic factors with good glycemic control (HbA1c<7.0% [53 mmol/mol]) while adjusting for possible confounders. RESULTS The mean age, body mass index, and number of daily insulin injections of participants were 65.4 years, 24.7 kg/m(2), and 2.3, respectively. Of all patients, 70.6% reported high adherence to their insulin regimen. Compared with participants with higher adherence, the crude relative risk of good glycemic control was 0.82 (95% CI, 0.67-1.00) for those with middle adherence and 0.64 (95% CI, 0.31-1.31) for those with lower adherence (P=0.029 for trend). Subgroup analysis confirmed this association in patients below 65 years old, but not in those 65 years old and over. CONCLUSIONS A higher adherence to a daily insulin regimen was associated with a greater likelihood of good glycemic control in Japanese type 2 diabetes patients. This association was not seen in patients of 65 years old or over. Self-reported adherence to an insulin regimen may prove useful in titrating insulin dose in patients in the younger age group, but requires further investigation.

Localized Amyloidosis at the Site of Repeated Insulin Injection in a Patient With Type 2 Diabetes

We present the case of a 69-year-old woman with type 2 diabetes mellitus who developed severe insulin resistance associated with insulin injections into a subcutaneous mass formed by repeated injections into the same site over many years. The patient (height, 150 cm; weight, 79 kg; BMI, 35.1 kg/m2) was admitted to Tenri Hospital with severe insulin resistance. She was undergoing insulin therapy since 56 years of age. Her glycemic control was fair until 63 years of age, after which it worsened and necessitated an increase in her insulin dose. This led to a 15-kg increase in body weight. On admission, her insulin regimen comprised a single injection of 33 units of neutral protamine Hagedorn insulin at bedtime and three daily injections of 33 units of premixed human insulin (70/30) before each meal. …

Effect of baseline HbA1c level on the development of diabetes by lifestyle intervention in primary healthcare settings: insights from subanalysis of the Japan Diabetes Prevention Program

Objectives To determine the effects of a lifestyle intervention on the development of type 2 diabetes mellitus (T2DM) among participants with impaired glucose tolerance (IGT), in particular in the subgroup with baseline glycated hemoglobin (HbA1c) levels ≥5.7%, in primary healthcare settings. Design Randomized controlled trial. Setting 32 healthcare centers in Japan. Participants Participants with IGT, aged 30–60 years, were randomly assigned to either an intensive lifestyle intervention group (ILG) or a usual care group (UCG). Interventions During the initial 6 months, participants in the ILG received four group sessions on healthy lifestyles by public health providers. An individual session was further conducted biannually during the 3 years. Participants in the UCG received usual care such as one group session on healthy lifestyles. Outcome measures The primary endpoint was the development of T2DM based on an oral glucose tolerance test. Results The mean follow-up period was 2.3 years. The annual incidence of T2DM were 2.7 and 5.1/100 person-years of follow-up in the ILG (n=145) and UCG (n=149), respectively. The cumulative incidence of T2DM was significantly lower in the ILG than in the UCG among participants with HbA1c levels ≥5.7% (log-rank=3.52, p=0.06; Breslow=4.05, p=0.04; Tarone-Ware=3.79, p=0.05), while this was not found among participants with HbA1c levels <5.7%. Conclusions Intensive lifestyle intervention in primary healthcare setting is effective in preventing the development of T2DM in IGT participants with HbA1c levels ≥5.7%, relative to those with HbA1c levels <5.7%. Trial registration number UMIN000003136.

Serum High-Sensitivity C-Reactive Protein Levels Are Associated With High Risk of Development, Not Progression, of Diabetic Nephropathy Among Japanese Type 2 Diabetic Patients: A Prospective Cohort Study (Diabetes Distress and Care Registry at Tenri [DDCRT7])

OBJECTIVE To assess the prospective association between baseline serum hs-CRP concentration and the subsequent risk of development or progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS Longitudinal data were obtained from 2,518 patients with type 2 diabetes registered in a Japanese diabetes registry. To assess the independent correlations between serum baseline hs-CRP and either the development or progression of diabetic nephropathy 1 year later, the Cox proportional hazards model was used and adjusted for potential confounders. RESULTS The mean patient age, BMI, and HbA1c level were 66.1 years, 24.6 kg/m2, and 7.5% (57.6 mmol/mol), respectively. Baseline serum hs-CRP levels were significantly associated with the urinary albumin-to-creatinine ratio at baseline (P < 0.001). Multivariable adjusted hazard ratio for the development from normoalbuminuria to microalbuminuria was 1.31 (95% CI 0.80–2.17; P = 0.286), 1.55 (1.16–2.08; P = 0.003), and 1.57 (1.22–2.03; P = 0.001), respectively, for the second, third, and fourth quartiles of serum hs-CRP levels, showing a statistically significant linear trend across categories (P < 0.001). We did not observe a significant association between hs-CRP levels and the subsequent risk of diabetic nephropathy progression (P for trend = 0.575). CONCLUSIONS Serum hs-CRP levels, independent of possible confounders, were associated with a subsequent risk of developing, not progressing, diabetic nephropathy in type 2 diabetic patients. Serum hs-CRP may be useful for predicting the future risk of developing diabetic nephropathy.

High Frequency of Non-nocturnal Hypoglycemia was Associated with Poor Sleep Quality Measure by Pittsburg Sleep Quality Index in Patients with Diabetes Receiving Insulin Therapy: Diabetes Distress and Care Registry at Tenri (DDCRT 4)

To investigate the temporal association between frequency of non-nocturnal hypoglycemia and sleep quality among patients with diabetes receiving insulin therapy.We used data from 1 513 patients with diabetes receiving insulin therapy. We estimated the relative risks (RR) of the frequency of non-nocturnal hypoglycemia for poor sleep quality measured by the Pittsburgh Sleep Quality Index.The average age and HbA1c value of the patients were 63.7 years and 7.8%, respectively. Compared with poor sleep quality in patients without any type of non-nocturnal disabling hypoglycemia (NNDH), the multivariable-adjusted RR values for poor sleep quality were 1.30 (95% confidence interval [CI], 1.06-1.61) and 1.37 (95% CI, 0.96-1.95) in patients who experienced 1-4 and ≥5 episodes of NNDH, respectively (p=0.004). Experiencing non-nocturnal severe hypoglycemia (NNSH) once in the past 90 days significantly increased the risk of poor sleep quality by 1.54 episodes (95% CI, 1.16-2.05; p=0.003). By adding the presence of depression as a variable to the multivariable-adjusted model, these associations were attenuated because we did not observe any significant association between NNDH and poor sleep quality (p=0.178). However, a significant association between NNSH and poor sleep quality was observed (RR=1.43; 95% CI, 1.09-1.90; p=0.011).A high frequency of non-nocturnal hypoglycemia was associated with poor sleep quality in patients with diabetes receiving insulin therapy. Our data also suggested that the association of NNDH, and not NNSH, was mediated by comorbid depression.

Effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance related to beta‐3 adrenergic receptor gene polymorphism Trp64Arg(C/T): Results from the Japan Diabetes Prevention Program

The beta‐3 adrenergic receptor (ADRB3), primarily expressed in adipose tissue, is involved in the regulation of energy metabolism. The present study hypothesized that ADRB3 (Trp64Arg, rs4994) polymorphisms modulate the effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance. Data were analyzed from 112 patients with impaired glucose tolerance in the Japan Diabetes Prevention Program, a lifestyle intervention trial, randomized to either an intensive lifestyle intervention group or usual care group. Changes in weight and metabolic parameters were measured after the 6‐month intervention. The ADRB3 polymorphisms were determined using the polymerase chain reaction restriction fragment length polymorphism method. Non‐carriers showed a greater weight reduction compared with the carriers in both the lifestyle intervention group and usual care group, and a greater increase of high‐density lipoprotein cholesterol levels than the carriers only in the lifestyle intervention group. ADRB3 polymorphisms could influence the effects of lifestyle interventions on weight and lipid parameters in impaired glucose tolerance patients.