Insulin degludec compared with insulin glargine in insulin‐naïve patients with type 2 diabetes: A 26‐week,randomized, controlled,Pan‐Asian,treat‐to‐target trial

Introduction

Insulin degludec (IDeg) is an ultra‐long‐acting basal insulin with a consistent action profile of >42 h. This trial compared the efficacy and safety of IDeg with insulin glargine (IGlar) in insulin‐naïve Asian patients with type 2 diabetes.

Materials and Methods

In this multinational, 26‐week, open‐label, treat‐to‐target trial, 435 participants (202 females, 233 males; mean age 58.6 years; mean body mass index 25 kg/m²; mean glycated hemoglobin [HbA_1c] 8.5%) were randomized (2:1) to IDeg or IGlar, each administered once daily with ≥1 oral antidiabetic drug(s) (OAD).

Results

After 26 weeks, HbA_1c had decreased by 1.24 and 1.35% in the IDeg and IGlar groups, respectively (treatment difference [IDeg – IGlar] 0.11%, 95% confidence interval [CI] −0.03 to 0.24), confirming non‐inferiority. Rates of overall confirmed hypoglycemia were similar for IDeg and IGlar during the full trial period (3.0 vs 3.7 episodes/patient‐year of exposure [PYE]; rate ratio [RR] 0.82, 95% CI 0.60 to 1.11, P = 0.20), but significantly lower (by 37%) for IDeg during the maintenance period (from week 16 onward; RR 0.63, 95% CI 0.42 to 0.94, P = 0.02). No significant difference in the rate of nocturnal confirmed hypoglycemia was found between IDeg and IGlar in the full trial period (0.8 vs 1.2 episodes/PYE; RR 0.62, 95% CI 0.38 to 1.04, P = 0.07) or maintenance period (RR 0.52, 95% CI 0.27 to 1.00, P = 0.05). Adverse event rates were similar between treatments.

Conclusions

Initiating insulin therapy with IDeg in Asian patients with type 2 diabetes, inadequately controlled with OADs, provides similar improvements in long‐term glycemic control to IGlar, but at a significantly lower rate of overall confirmed hypoglycemia once stable glycemic control and insulin dosing are achieved. This trial was registered with www.clinicaltrials.gov (no. NCT01059799).     

Impact of cigarette smoking on impaired insulin secretion and insulin resistance in Japanese men: The Saku Study

Aims/Introduction

To assess the impact of smoking on impaired insulin secretion and insulin resistance in Japanese men.

Materials and Methods

This study included 1,199 men aged 30–79 years without diabetes, impaired insulin secretion and insulin resistance at baseline who underwent a comprehensive medical check‐up between April 2006 and March 2007 at Saku Central Hospital. Smoking status was categorized as current, ex‐smoker and never‐smoker. Insulinogenic index and homeostasis model assessment‐insulin resistance were determined using a standard 75‐g oral glucose tolerance test. The Japan Diabetes Society criteria were used to define impaired insulin secretion and insulin resistance. Participants were followed up until March 2011.

Results

A total of 449 and 99 men developed impaired insulin secretion and insulin resistance during 3,403 and 4,092 person‐years follow up, respectively. The multivariable‐adjusted hazard ratios (HRs) for impaired insulin secretion were 1.06 (95% confidence interval [CI] 0.84–1.33) in ex‐smokers and 1.95 (95% CI 1.44–2.63) in current smokers compared with never‐smokers after adjustment for age, familial history of diabetes, alcohol consumption, exercise, systolic blood pressure, triglyceride, γ‐glutamyltransferase, waist circumference, leukocyte count, changes in smoking status and changes in waist circumference. The number of pack‐years was positively associated with the risk for impaired insulin secretion in a dose‐dependent manner (P‐values for trend <0.001). The multivariable‐adjusted HRs for insulin resistance were 0.95 (95% CI 0.56–1.61) in ex‐smokers and 1.11 (95% CI 0.67–1.79) in current smokers compared with never‐smokers.

Conclusions

Cigarette smoking is a modifiable risk factor for impaired insulin secretion. The findings might also be important for other Asian populations, which have low insulin secreting ability.     

Replication study for the association of rs391300 in SRR and rs17584499 in PTPRD with susceptibility to type 2 diabetes in a Japanese population

Aims/Introduction

Genetic risk variants for type 2 diabetes; rs391300‐G in SRR and rs17584499‐T in PTPRD, have been identified by a genome‐wide association study using Han Chinese individuals living in Taiwan. In an attempt to know the effects of these two variants in conferring susceptibility to type 2 diabetes in the Japanese, we carried out a replication study for the association of the two single nucleotide polymorphisms (SNPs) with type 2 diabetes in a Japanese population.

Materials and Methods

We genotyped 11,530 Japanese individuals (8,552 type 2 diabetes patients and 2,978 controls) for rs391300 and rs17584499, and analyzed the association of these two SNPs with type 2 diabetes by logistic regression analysis.

Results

Neither of the variants was associated with susceptibility to type 2 diabetes in the Japanese population (rs391300‐G: odds ratio [OR] = 0.97; 95% confidence interval [CI] 0.91–1.04; P = 0.44; rs17584499‐T: OR = 1.04; 95% CI 0.96–1.14; P = 0.34). Adjustment or stratified analysis for age, sex and body mass index (BMI) did not affect the association of these variants with the disease. We did not observe a significant association of the SNPs with any metabolic traits, BMI, fasting plasma glucose, homeostasis model assessment of β‐cell function (HOMA‐β) and HOMA of insulin resistance (HOMA‐IR) (P > 0.05).

Conclusions

Neither rs391300 nor rs17584499 had a significant effect on conferring susceptibility to type 2 diabetes in the Japanese population.     

Difference between old and young adults in contribution of β‐cell function and sarcopenia in developing diabetes mellitus

Aims/Introduction

To investigate the difference in contributing factors in developing diabetes between old and young adults.

Materials and Methods

Subjects with recent‐onset diabetes were selected from a nationwide survey data and classified according to age: elderly (age ≥75 years), middle‐age (age 45–64 years) and young (age 25–39 years). The homeostasis model assessment of insulin resistance and β‐cell function were calculated. Sarcopenia was assessed using dual‐energy X‐ray absorptiometry.

Results

The prevalence of recent‐onset diabetes was 13.5%, 8.0%, and 1.4% in patients aged ≥75 years (unweighted n = 1,082), 45–64 years (unweighted n = 6,532), and 25–39 years (unweighted n = 5,178), respectively. Homeostasis model assessment of β‐cell function along with homeostasis model assessment of insulin resistance showed increasing trends as onset age increased in recent‐onset diabetes (P for trend < 0.001 in both). Elderly‐onset diabetic patients had significantly higher homeostasis model assessment of β‐cell function and homeostasis model assessment of insulin resistance compared with the middle‐age‐onset group (P < 0.001 and 0.014, respectively). Multivariate analysis showed that sarcopenia was significantly associated with recent‐onset diabetes only in patients aged ≥75 years (odds ratio [OR] 2.478, 95% confidence interval [CI] 1.379–4.452) but not in patients aged 45–64 years. In the middle‐age group, abdominal obesity (OR 2.933, 95% CI 2.086–4.122), hypertriglyceridemia (OR 1.529, 95% CI 1.078–2.169]) and low high‐density lipoprotein cholesterolemia (OR 1.930, 95% CI 1.383–2.695) were associated with recent‐onset diabetes.

Conclusions

Elderly‐onset diabetic patients had higher insulin resistance and relatively preserved β‐cell function compared with middle‐age‐onset patients. Sarcopenia might play a more important role in developing diabetes in the elderly population.     

Association between diabetes or antidiabetic therapy and lung cancer: A meta‐analysis

Aims/Introduction

Diabetes can increase the risk of cancers at several sites, but the association between diabetes and lung cancer remains unclear. We aimed to provide the quantitative estimates for the association between diabetes or antidiabetic treatment and lung cancer risk in the present meta‐analysis.

Materials and Methods

Cohort studies were identified by searching the PubMed database (January 1960 through October 2012) and manually assessing the cited references in the retrieved articles. Study‐specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random‐effects model. Study quality was assessed using the Newcastle–Ottawa scale.

Results

A total of 19 cohort studies were included in the present meta‐analysis. Of these, 14 studies focused on the association between diabetes and lung cancer incidence, and seven studies focused on the association between antidiabetic treatment and lung cancer incidence. Compared with non‐diabetic individuals, diabetic patients do not have an increased risk of lung cancer (RR = 1.04, 95% CI 0.87–1.24). The association between diabetes and lung cancer remained not statistically significant in subgroup analysis stratified by study characteristics, study quality, diabetes ascertainment or important confounders. A null association between insulin or biguanides therapy and lung cancer risk was found. However, the diabetic patients receiving thiazolidinedione (TZD) treatment had a 20% reduced risk of lung cancer than those without TZD treatment.

Conclusions

No association between diabetes and lung cancer risk was found. However, TZD treatment might reduce lung cancer risk in diabetic patients.     

Higher intake of fruits,vegetables or their fiber reduces the risk of type 2 diabetes: A meta‐analysis

Aims/Introduction

Some previous studies reported no significant association of consuming fruit or vegetables, or fruit and vegetables combined, with type 2 diabetes. Others reported that only a greater intake of green leafy vegetables reduced the risk of type 2 diabetes. To further investigate the relationship between them, we carried out a meta‐analysis to estimate the independent effects of the intake of fruit, vegetables and fiber on the risk of type 2 diabetes.

Materials and Methods

Searches of MEDLINE and EMBASE for reports of prospective cohort studies published from 1 January 1966 to 21 July 2014 were carried out, checking reference lists, hand‐searching journals and contacting experts.

Results

The primary analysis included a total of 23 (11 + 12) articles. The pooled maximum‐adjusted relative risk of type 2 diabetes for the highest intake vs the lowest intake were 0.91 (95% confidence interval [CI] 0.87–0.96) for total fruits, 0.75 (95% CI 0.66–0.84) for blueberries, 0.87 (95% CI 0.81–0.93) for green leafy vegetables, 0.72 (95% CI 0.57–0.90) for yellow vegetables, 0.82 (95% CI 0.67–0.99) for cruciferous vegetables and 0.93 (95% CI 0.88–0.99) for fruit fiber in these high‐quality studies in which scores were seven or greater, and 0.87 (95% CI 0.80–0.94) for vegetable fiber in studies with a follow‐up period of 10 years or more.

Conclusions

A higher intake of fruit, especially berries, and green leafy vegetables, yellow vegetables, cruciferous vegetables or their fiber is associated with a lower risk of type 2 diabetes.     

Risk of hospitalization for diabetic macrovascular complications and in‐hospital mortality with irregular physician visits using propensity score matching

Aims/Introduction

The objective of the present study was to evaluate the risk of diabetic macrovascular complications and in‐hospital mortality among diabetic patients with irregular physician visits.

Materials and Methods

We carried out a health insurance‐based retrospective cohort study using claims data from diabetic patients who were newly hospitalized between April 2010 and September 2010 among beneficiaries of the Fukuoka National Health Insurance Organization. Regular visits were defined as physician visits for diabetes mellitus at least every 3 months between April 2009 and March 2010, whereas other visits or no visits were defined as irregular visits. We assigned 5,940 patients to the regular visit or the irregular visit groups using propensity score matching. We compared in‐hospital mortality and hospitalization for diabetic macrovascular complications between the two groups by multiple logistic regression models.

Results

The irregular visit group had a significantly higher risk of hospitalization for acute myocardial infarction (AMI), ischemic heart diseases (IHDs) except AMI, all IHDs, all strokes and diabetic macrovascular complications than did the regular visit group. Adjusted odds ratios for AMI, IHDs except AMI, all IHDs, all strokes, and diabetic macrovascular complications were 3.52 (95% confidence interval [CI] 1.79–6.96), 1.25 (95% CI 1.02–1.54), 1.37 (95% CI 1.12–1.66), 1.29 (95% CI 1.04–1.60), and 1.28 (95% CI 1.10–1.48), respectively.

Conclusions

The present study shows that the irregular visit group had significantly higher risks of hospitalization for IHD and stroke among diabetic patients. Insurers need to motivate diabetic beneficiaries to make regular visits to physicians.     

Association of chemokine ligand 5/chemokine receptor 5 gene promoter polymorphisms with diabetic microvascular complications: A meta‐analysis

Aims/Introduction

Chemokine ligand 5 (CCL5) is a member of the CC‐chemokine family expressed in various organs. It contributes to the migration of monocytes/macrophages into injured vascular walls by binding with its receptor chemokine receptor 5 (CCR5). Many studies have accessed the association between CCL5/CCR5 gene promoter polymorphisms and diabetic microvascular complications (DMI). However, the results are conflicting and inconclusive. The aim of the present study was to evaluate the association more precisely.

Materials and Methods

Trials were retrieved through PubMed, Embase, Medline, China National Knowledge Infrastructure, Web of Science and Cochrane database without restrictions on language. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to describe the strength of association with DMI.

Results

Data were obtained from 11 case–control studies that included 2,737 DMI patients and 2,435 diabetic control subjects. In the overall analysis, the CCL5‐403 G/A and CCL5‐28 C/G gene polymorphisms were not significantly associated with the risk of DMI. However, CCR5‐59029 G/A was an independent risk factor of DMI in a dominant model (OR 1.77, 95% CI 1.06–2.97). Subgroup analysis showed that the risk of the CCR5 59029A‐positive genotype was significant in Asians (OR 2.08, 95% CI 1.68–2.57). In addition, the CCR5 59029A‐positive genotype was associated with increased risk of albuminuria.

Conclusions

There were no associations of CCL5 gene promoter polymorphism with the risk of DMI. However, the 59029A polymorphism in CCR5 might affect individual susceptibility for DMI.     

Morningness–eveningness questionnaire score correlates with glycated hemoglobin in middle‐aged male workers with type 2 diabetes mellitus

Aims/Introduction

‘Morningness’ and ‘eveningness’ represent the sleep–wake patterns of the circadian rhythm might also affect glycemic control in patients with type 2 diabetes. The aim of this study was to examine the relationship between the morningness–eveningness trait and metabolic parameters.

Materials and Methods

The study participants comprised 101 Japanese male workers with type 2 diabetes treated in an outpatient clinic. Blood samples were obtained, and a morningness–eveningness questionnaire (MEQ), where a high score represents morningness; and the Pittsburg Sleep Quality Index (PSQI), where the higher the score the worse the sleep quality, were carried out.

Results

MEQ correlated positively with age, and high‐density lipoprotein cholesterol (HDL‐C), and negatively with glycated hemoglobin (HbA_1c) and PSQI. Multivariate regression analysis showed that MEQ was significantly associated with HbA_1c and HDL‐C. In addition, we classified the study patients into three groups: ‘morning type’, ‘neither type’ and ‘evening type’ according to the sum of the MEQ score, and analyzed the difference between morning type (n = 32) and evening type (n = 11). We found that HbA_1c, low‐density lipoprotein cholesterol and PSQI of the morning type group were significantly lower than those of the evening type group.

Conclusions

The present study suggests that ‘eveningness’ type male Japanese workers with type 2 diabetes suffer inadequate glycemic control.     

Changes of blood glucose and gastrointestinal hormones 4 months after Roux‐en‐Y gastric bypass surgery in Chinese obese type 2 diabetes patients with lower body mass index

Aims/Introduction

The goal of this study was to evaluate the effect of Roux‐en‐Y gastric bypass (RYGB) on hyperglycemia and gastrointestinal hormones in Chinese obese type 2 diabetic patients with body mass index (BMI) between 28 and 35 kg/m².

Materials and Methods

A total of eight obese type 2 diabetes patients with BMI 28–35 kg/m² who underwent RYGB and 10 obese normal glucose tolerance (NGT) patients with no surgery were identified. BMI and blood glucose on baseline, and 2–4 months postoperative, changes of glucagon‐like peptide‐1 (GLP‐1), glucose‐dependent insulinotropic polypeptide (GIP), peptide YY (PYY), and oxyntomodulin (OXM) were recorded. Efficacy of RYGB was defined by the percentage of excess weight loss (%EWL) and amelioration of type 2 diabetes.

Results

The %EWL was 53.00 ± 26.25% in 2 month and 63.65 ± 33.71% in 4 month. Glycated hemoglobin changed from 7.2 ± 1.0% preoperative to 6.2 ± 0.9% in 2 month and 6.3 ± 1.2% in 4 month postoperative. The improvement rate of type 2 diabetes 4 months after RYGB was 83.3%. After surgery, area under the curve (AUC) GLP‐1 120 increased with no significance. AUC PYY 120 changed from 10.37 ± 5.45 pmol/L/min preoperative to 22.19 ± 10.61 pmol/L/min in 2 month and 22.04 ± 7.73 pmol/L/min in 4 month postoperative. Postoperative AUC OXM 120 was also higher than that of the preoperative level. AUC GIP 120 decreased from 13.06 ± 8.45 pg/mL/min preoperative to 8.71 ± 3.28 pg/ml/min in 2 month and 6.88 ± 2.33 pg/mL/min in 4 month postoperative.

Conclusions

Roux‐en‐Y gastric bypass has a beneficial effect on weight loss and glucose metabolism in obese type 2 diabetes patients with lower BMI. Postoperative concentrations of GLP‐1, PYY and OXM increased, whereas GIP decreased.     

Low high‐density lipoprotein cholesterol level is a significant risk factor for development of type 2 diabetes: Data from the Hawaii–Los Angeles–Hiroshima study

Aims/Introduction

A low level of high‐density lipoprotein cholesterol (HDLC) is a common feature of metabolic syndrome. We have reported that Japanese–Americans who share a virtually identical genetic makeup with native Japanese, but who have lived Westernized lifestyles for decades, have lower HDLC levels and a high prevalence of type 2 diabetes compared with native Japanese. However, the impact of low HDLC level on type 2 diabetes is unclear. The aims of the present study were to evaluate whether serum HDLC level was associated with development of type 2 diabetes and if the effect might be modified by lifestyle.

Materials and Methods

We examined 1,133 non‐diabetic Japanese–Americans and 1,072 non‐diabetic Japanese, who underwent the 75‐g oral glucose tolerance test (OGTT) and were followed for an average of 8.8 and 7.0 years, respectively. We analyzed whether serum HDLC level is a risk factor for development of type 2 diabetes based on the Cox proportional hazards model.

Results

After adjustment for age and sex, hazard ratios for development of type 2 diabetes per unit of serum HDLC level (mmol/L) were 0.292 (95% confidence interval [CI] 0.186–0.458, P < 0.0001) among Japanese–Americans and 0.551 (95% CI 0.375–0.88, P = 0.0023) among native Japanese. Comparable hazard ratios after further adjustment for category of OGTT and body mass index were 0.981 (95% CI 0.970–0.993, P = 0.0018) and 0.991 (95% CI 0.980–1.002, P = 0.112), respectively.

Conclusions

HDLC level was associated with development of type 2 diabetes in both Japanese–Americans and native Japanese. However, these results suggest that the impact of high‐density lipoprotein on glucose metabolism might be affected by lifestyle.     

Dipeptidyl peptidase‐4 inhibitors are effective in Japanese type 2 diabetic patients with sustained endogenous insulin‐secreting capacity,a higher body mass index and insulin resistance

Aims/Introduction

Recently, dipeptidyl peptidase‐4 (DPP‐4) inhibitors have become available in Japan. It has not yet been clarified what clinical parameters could discriminate DPP‐4 inhibitor‐effective patients from DPP‐4 inhibitor‐ineffective patients.

Materials and Methods

We reviewed 33 consecutive patients with type 2 diabetes admitted to Osaka University Hospital for glycemic control. All of the patients were treated with medical nutrition therapy plus insulin therapy to improve fasting plasma glucose (FPG) and postprandial glucose below 150 and 200 mg/dL, respectively. After insulin secretion and insulin resistance were evaluated, insulin was replaced by DPP‐4 inhibitors. The efficacy of DPP‐4 inhibitors was determined according to whether glycemic control was maintained at the target levels.

Results

Dipeptidyl peptidase‐4 inhibitors were effective in 16 of 33 patients. DPP‐4 inhibitor‐effective patients were younger than DPP‐4 inhibitor‐ineffective patients. Body mass index (BMI) was significantly higher in DPP‐4 inhibitor‐effective patients. Endogeneous insulin‐secreting capacity, including insulinogenic index (II), fasting plasma C‐peptide (F‐CPR) and C‐peptide index (CPI), was more sustained in DPP‐4 inhibitor‐effective patients than DPP‐4 inhibitor‐ineffective patients. Insulin resistance evaluated by homeostasis model assessment of insulin resistance (HOMA‐IR) was significantly higher in DPP‐4 inhibitor‐effective patients than DPP‐4 inhibitor‐ineffective patients. In receiver operating characteristic analyses, the cut‐off values for predicting the efficacy of DPP‐4 inhibitors were 0.07 for II, 1.5 ng/mL for F‐CPR, 1.0 for CPI, 23.0 kg/m² for BMI, 1.3 for HOMA‐IR and 67.5 years for age.

Conclusions

Dipeptidyl peptidase‐4 inhibitors were effective in Japanese type 2 diabetic patients with sustained endogenous insulin‐secreting capacity, a higher BMI and insulin resistance.     

Changes in oral antidiabetic prescriptions and improved glycemic control during the years 2002–2011 in Japan (JDDM32)

Aims/Introduction

Six kinds of oral antidiabetic drugs (OADs), including the new dipeptidyl peptidase 4 (DPP‐4) inhibitors, are available. The present study aimed to define trends within the prescribing patterns of OADs, as well as changes in glycemic control in Japan over a 10‐year period from 2002 to 2011.

Materials and Methods

We carried out a cross‐sectional study using data of type 2 diabetes mellitus patients from 24 clinics for 2002, 2005, 2008 and 2011. OAD use was analyzed combined with clinical data.

Results

Sulfonylureas (SUs) were the most commonly used OAD, but their use for monotherapy markedly decreased over the study period. Biguanides (BGs) were the second most commonly used OAD, and their prescribing rate increased both for mono‐ and combination therapy. DPP‐4 inhibitors (DPP‐4I), released in 2009, were the third most commonly prescribed OAD in 2011 both for mono‐ and combination therapy. Among combination therapies, two OADs were mostly prescribed, but the use of three OADs and four OADs in 2011 was two‐ and 14.8‐fold those in 2002. These trends were accompanied by an improvement in average glycated hemoglobin from 7.5 ± 1.2% in 2002 to 7.1 ± 0.9% in 2011.

Conclusions

The OAD prescribing trend has moved away from monotherapy with SUs and toward combination therapies to achieve better glycemic control. Increased use of BGs and DPP‐4I was predominant in 2011. These trends were accompanied by an improvement of the glycated hemoglobin level.     

Usefulness of the insulin tolerance test in patients with type 2 diabetes receiving insulin therapy

Aims/Introduction

To establish the validity of the plasma glucose disappearance rate (KITT), derived from an insulin‐tolerance test (ITT), for evaluating the insulin sensitivity of patients with type 2 diabetes after insulin therapy.

Materials and Methods

In the first arm of the study, 19 patients with poorly controlled diabetes were treated with insulin and underwent an ITT and a euglycemic clamp test (clamp‐IR). The relationship between the insulin resistance index, as assessed by both the clamp‐IR and KITT tests, was examined. In the second arm of the study, the relationships between KITT values and various clinical parameters were investigated in 135 patients with poorly controlled diabetes, after achieving glycemic control with insulin.

Results

In study 1, a close correlation between KITT and the average glucose infusion rate during the last 30 min of the standard clamp‐IR test (M‐value) was noted (P < 0.001). In study 2, body mass index (P = 0.0011), waist circumference (P = 0.0004), visceral fat area (P = 0.0011) and the log‐transformed homeostasis model assessment of insulin resistance value (P = 0.0003) were negatively correlated with the log‐transformed KITT. High‐density lipoprotein cholesterol (P = 0.0183), low‐density lipoprotein cholesterol (P = 0.0121) and adiponectin (P = 0.0384) levels were positively correlated with the log‐transformed KITT.

Conclusions

The ITT is a valid and useful test for evaluating the insulin sensitivity of patients with diabetes, even after treatment with insulin.     

Albuminuria: Prevalence,associated risk factors and relationship with cardiovascular disease

Aims/Introduction

To investigate the prevalence and associated risk factors of microalbuminuria, and to explore the relationship between albuminuria and cardiovascular disease (CVD).

Materials and Methods

A nationally representative sample of 38,203 Chinese participants was categorized by different levels of urinary albumin‐to‐creatinine ratio (ACR; 0 –10 mg/g, 10 –20 mg/g, 20 –30 mg/g, 30 –300 mg/g). The prevalence of albuminuria was compared by using a single urinary ACR cut‐off point and by sex‐specific ACR cut‐off points. Factors associated with the presence of albuminuria, and the relationship between albuminuria and CVD were analyzed by logistic regression.

Results

Prevalence of albuminuria as measured by a single ACR cut‐point was significantly lower for men compared with women (13.9% vs 19.1% in the normal glucose tolerance group; 20.8% vs 26.8% in the impaired glucose tolerance group, P < 0.01). The prevalence of albuminuria, as measured by sex‐specific ACR cut‐points, was higher for men than women (31.4% vs 29.6% in the normal glucose tolerance group; 42.2% vs 39.3% in the impaired glucose tolerance group, P < 0.01). The independent risk factors for the presence of albuminuria were aging, female sex, hypertension, hyperglycemia, obesity, dyslipidemia, insulin resistance and metabolic syndrome. The subdivided normal ACR group did not show a linear or statistically significant relationship with CVD after adjusting for conventional CVD risk factors (P > 0.05).

Conclusions

The prevalence of albuminuria was high in the general Chinese population. Aging, female sex, hypertension, hyperglycemia, dyslipidemia, insulin resistance, obesity and metabolic syndrome were all independent risk factors for albuminuria. The causal relationship between ACR and CVD might require further follow‐up investigation.     

Effect of endurance training on retinol‐binding protein 4 gene expression and its protein level in adipose tissue and the liver in diabetic rats induced by a high‐fat diet and streptozotocin

Aims/Introduction

The present study was designed to investigate from which tissues the decrease in retinol‐binding protein 4 (RBP4) expression could contribute to the improvement of serum RBP4 and insulin resistance (IR) after endurance training.

Materials and Methods

Male 7‐week‐old Wistar rats were randomly assigned into four groups including control (C), trained (T), diabetic control (DC) and trained diabetic (TD). At 8 weeks‐of‐age, diabetes was induced by a high‐fat diet and intraperitoneal injection of low‐dose streptozotocin (STZ; 35 mg/kg). Rats in the T and TD groups carried out a 7‐week exercise program on a motorized treadmill (15–20 m/min for 20 min/day for 5 weeks), whereas the C and DC remained sedentary in their cages. Tissues gene expression and protein levels of RBP4 were assessed by using real‐time polymerase chain reaction and western blot, respectively, while serum RBP4 was measured using an enzyme‐linked immunosorbent assay kit.

Results

Exercise significantly improved IR and reduced serum concentration of RBP4 in the TD group. This reduction of serum RBP4 was accompanied by decreased RBP4 protein expression in visceral fat tissue. In contrast, exercise had no significant effect on RBP4 expression in liver and subcutaneous fat tissue in the TD group. Exercise also significantly decreased RBP4 gene expression in visceral fat tissue and muscle, whereas the effect of exercise on liver RBP4 messenger ribonucleic acid expression was not significant.

Conclusions

The present study showed that the mechanism for RBP4 reducing the effect of endurance training could involve decreased RBP4 messenger ribonucleic acid expression and its protein level in adipose tissue in STZ‐induced diabetic rats.     

Effects of soybean product intake on fasting and postload hyperglycemia and type 2 diabetes in Japanese men with high body mass index: The Saku Study

Aims/Introduction

The inverse association between soybean intake and type 2 diabetes mellitus has been reported. We investigated the effects of soybean product intake on the incidence of type 2 diabetes mellitus considering fasting and postload hyperglycemia.

Materials and Methods

The present 4‐year, cohort study included 1,738 men and 1,301 women, aged 30–69 years, without diabetes mellitus at baseline who underwent comprehensive medical check‐ups between April 2006 and March 2007 at Saku Central Hospital. Participants were stratified by sex and body mass index (BMI), and further classified into three groups based on soybean product intake: group 1 (0–1 time/week), group 2 (2–3 times/week) and group 3 (four or more times per week). Participants underwent annual standard 75‐g oral glucose tolerance testing during follow‐up periods until March 2011. Main outcomes were incidence of fasting hyperglycemia, postload hyperglycemia and type 2 diabetes mellitus.

Results

During 10,503 person‐years of follow up, 204 participants developed type 2 diabetes mellitus, including 61 who developed fasting hyperglycemia and 147 who developed postload hyperglycemia. Among men with a high BMI, group 3 had significantly lower risk for the incidence of type 2 diabetes mellitus, fasting hyperglycemia and postload hyperglycemia than group 1, and multivariable‐adjusted hazard ratios and 95% confidence intervals were 0.44 (0.22–0.89), 0.36 (0.15–0.96) and 0.40 (0.18–0.92), respectively. Similar results were not observed among men with low BMI or women.

Conclusions

Soybean product intake prevented fasting and postload hyperglycemia and type 2 diabetes mellitus in men with a high BMI. Further long‐term observation is necessary.     

Association of hypertension status and cardiovascular risks with sympathovagal imbalance in first degree relatives of type 2 diabetics

Aims/Introduction

As reports show cardiovascular (CV) risks in first‐degree relatives (FDR) of type 2 diabetics, and autonomic imbalance predisposing to CV risks, in the present study we have assessed the contribution of sympathovagal imbalance (SVI) to CV risks in these subjects.

Materials and Methods

Body mass index (BMI), waist‐to‐hip ratio (WHR), basal heart rate (BHR), blood pressure (BP), rate pressure product (RPP), and spectral indices of heart rate variability (HRV) were reordered and analyzed in FDR of type 2 diabetics (study group, n = 293) and in subjects with no family history of diabetes (control group, n = 405).

Results

The ratio of low‐frequency (LF) to high‐frequency (HF) power of HRV (LF–HF), a sensitive marker of SVI, was significantly increased (P < 0.001) in the study group compared with the control group. The SVI in the study group was due to concomitant sympathetic activation (increased LF) and vagal inhibition (decreased HF). In the study group, the LF–HF ratio was significantly correlated with BMI, WHR, BHR, BP and RPP. Multiple regression analysis showed an independent contribution of LF–HF to hypertension status (P = 0.000), and bivariate logistic regression showed significant prediction (odds ratio 2.16, confidence interval 1.130–5.115) of LF–HF to increased RPP, the marker of CV risk, in the study group.

Conclusions

Sympathovagal imbalance in the form of increased sympathetic and decreased parasympathetic activity is present in FDR of type 2 diabetics. Increased resting heart rate, elevated hypertension status, decreased HRV and increased RPP in these subjects make them vulnerable to CV risks. SVI in these subjects contributes to CV risks independent of the degree of adiposity.     

Evaluation of insulin regimens as an effective option for glycemic control in patients with type 2 diabetes: A propensity score‐matched cohort study across Japan (JDDM31)

Aims/Introduction

We evaluated the long‐term efficacy of insulin regimens in patients with type 2 diabetes mellitus and poor glycemic control despite oral antidiabetic drugs (OAD).

Materials and Methods

We carried out a propensity score‐matched cohort study using the CoDiC^® database of the Japan Diabetes Data Management Study Group across 54 institutions in Japan from 2005 to 2010. A total of 10,854 patients on OAD in 2005 were studied, and 1,253 patients (11.5%) were treated with insulin until 2010. The changes in insulin regimens and glycated hemoglobin (HbA1c) levels were analyzed over this study period.

Results

Propensity score matching showed no differences in the baseline patient characteristics. A total of 96 patients transferred to insulin, and HbA1c gradually and significantly decreased in the patients on a twice‐daily premixed preparation of rapid‐acting human‐insulin analogs (twice‐daily MIX) and basal–bolus therapy with rapid‐acting human‐insulin analogs (RA) plus long‐acting insulin analog (LA; P < 0.001). A total of 418 patients had insulin added to OAD treatment, and HbA1c decreased in the patients with a twice‐daily MIX (P < 0.001), but HbA1c did not differ from the baseline values in the patients on basal LA (P = 0.497). The mean decline in HbA1c at the end of the study was therefore larger in the patients receiving twice‐daily MIX than in the patients receiving basal LA (P < 0.05).

Conclusion

The present study could suggest the potential loss of opportunity for many patients treated using basal LA to have received alternative insulin regimens and to achieve better glycemic control.     

Comparison of the efficacy of sitagliptin and glimepiride dose‐up in Japanese patients with type 2 diabetes poorly controlled by sitagliptin and glimepiride in combination

Aims/Introduction

The goal of the study was to examine the effects of sitagliptin dose‐up or glimepiride dose‐up in Japanese patients with type 2 diabetes who were controlled inadequately by sitagliptin and glimepiride in combination.

Materials and Methods

A multicenter, prospective, randomized, open‐label study was carried out in 50 patients with type 2 diabetes treated with sitagliptin and low‐dose glimepiride. The patients were randomly assigned to receive the addition of 50 mg/day sitagliptin or 0.5 mg/day glimepiride. The primary end‐point was the percentage change in glycated hemoglobin (HbA1c).

Results

During a follow‐up period, the difference in the percentage changes in HbA1c between the two groups was not significant (P = 0.13). However, HbA1c was significantly decreased by glimepiride dose‐up (P < 0.01 vs baseline), but not by sitagliptin dose‐up (P = 0.74). Univariate linear regression analyses showed that the percentage change in HbA1c was significantly associated with the serum level of arachidonic acid (AA) in both groups.

Conclusions

There was no significant difference in the HbA1c‐lowering effects between the two groups. However, a significant HbA1c‐lowering effect from baseline of glimepiride dose‐up was found, and the AA level showed a negative correlation with the decrease in HbA1c in the sitagliptin dose‐up group, but a positive correlation in the glimepiride dose‐up group. These findings suggest that the AA level is associated with HbA1c reduction in response to dose‐up with these drugs in patients with type 2 diabetes in a combination therapy with sitagliptin and glimepiride. This trial was registered with UMIN (no. 000009544).