Effect of periodontal treatment on glycemic control of patients with diabetes: A systematic review and meta‐analysis

Aims/Introduction

The aim of the present study was to investigate whether non‐surgical periodontal treatment reduces glycated hemoglobin (HbA_1c) and fasting plasma glucose (FPG) levels in diabetic patients.

Materials and Methods

An electronic search was carried out on MEDLINE (through PubMed interface), EMBASE and the Cochrane Central Register of Controlled Trials. Randomized controlled trials with a minimum of 3 months follow up were included. The risk of bias was assessed for each study. A meta‐analysis was carried out to evaluate the effect of non‐surgical periodontal treatment on HbA_1c and FPG levels. The effect of the adjunctive use of antimicrobials was also assessed.

Results

A total of 15 studies were included. A reduction of −0.38% (95% confidence interval [CI] −0.23 to −0.53) after 3–4 months (P < 0.001) and of −0.31% (95% CI 0.11 to −0.74) after 6 months (P = 0.15) of follow‐up was found for HbA_1c, favoring the treatment group. Similarly, in treated patients, a significantly greater decrease in FPG was observed in respect to control participants. Such difference amounted to −9.01 mg/dL (95% CI −2.24 to −15.78) after 3–4 months (P = 0.009) and −13.62 mg/dL (95% CI 0.45 to −27.69) after 6 months (P = 0.06) from treatment, respectively. In participants treated with adjunctive antimicrobials, a non‐significant increase of HbA_1c was observed 3 months after treatment, whereas FPG decreased by 0.27 mg/dL (95% CI 39.56 to −40.11; P = 0.99).

Conclusions

The meta‐analysis showed that non‐surgical periodontal treatment improves metabolic control in patients with both periodontitis and diabetes.     

Increased arterial stiffness is closely associated with hyperglycemia and improved by glycemic control in diabetic patients

Aims/Introduction

Although arteriosclerotic diseases have been reported to be frequently complicated by diabetes mellitus (DM), a detailed relationship between hyperglycemia and arterial stiffness has not been fully clarified. We investigated the influence of hyperglycemia on arterial stiffness using the cardio‐ankle vascular index (CAVI), which is a new method for estimating arterial stiffness.

Materials and Methods

CAVI values of 52 early‐staged DM patients (duration <5 years, no microangiopathies) were compared with those of 43 age‐matched non‐diabetic (NDM) subjects. The association between CAVI and clinical background factors was evaluated. The effect of glycemic improvement on CAVI was examined in 36 DM patients who were hospitalized for 2 weeks to treat hyperglycemia. CAVI and clinical parameters were measured twice during hospitalization and again after 8 weeks. Additionally, we measured CAVI before and 2 h after breakfast in five DM and five NDM subjects.

Results

The CAVI of DM patients was significantly higher than that of NDM subjects. Multiple regression analysis showed that neither hypertension, obesity nor dyslipidemia, but aging and hemoglobin A1c (HbA_1c) were significantly related to CAVI elevation. The CAVI, HbA_1c and total cholesterol (TC) had significantly improved. Improvement of CAVI was significantly associated with HbA_1c improvement. In contrast, no significant association was observed between the improvements of TC and CAVI. CAVI values before and after breakfast did not change significantly.

Conclusions

CAVI elevation seems to be a sensitive arteriosclerotic marker, which is closely associated with hyperglycemia and improved by glycemic control.     

Randomized,placebo‐controlled,double‐blind glycemic control trial of novel sodium‐dependent glucose cotransporter 2 inhibitor ipragliflozin in Japanese patients with type 2 diabetes mellitus

Aims/Introduction

In the present dose–response study, we evaluated the efficacy and safety of ipragliflozin (ASP1941), a novel and selective inhibitor of sodium‐dependent glucose cotransporter 2, in Japanese patients with type 2 diabetes mellitus.

Materials and Methods

A total of 361 patients from 39 Japanese centers were randomized to receive either once‐daily oral ipragliflozin (12.5, 25, 50 or 100 mg) or a placebo for 12 weeks.

Results

All ipragliflozin‐treated groups had clinically significant, dose‐dependent decreases in glycated hemoglobin (HbA1c) and fasting plasma glucose levels compared with placebo‐treated groups. The adjusted mean difference in HbA1c change from baseline to the end of treatment between the placebo and 12.5, 25, 50, and 100 mg ipragliflozin groups were −0.61%, −0.97%, −1.29%, and −1.31%, respectively (P < 0.001). Reductions in HbA1c levels were similar between obese and non‐obese patients, and were larger in patients with baseline HbA1c ≥8.4% than in those with HbA1c <8.4%. Furthermore, bodyweight significantly (P < 0.001) and dose‐dependently decreased among ipragliflozin‐treated groups compared with the placebo group. The incidence of adverse events was similar across all groups. However, mild increases in hematocrit and blood urea nitrogen were found in ipragliflozin treated groups.

Conclusions

Once‐daily administration of ipragliflozin was dose‐dependently effective in glycemic control without major adverse effects. Ipragliflozin was equally effective between obese and non‐obese patients, and led to weight loss in both groups. Ipragliflozin was safe and well‐tolerated in Japanese patients with type 2 diabetes mellitus. This trial was registered with ClinicalTrials.gov (no. NCT00621868).     

Subject‐driven titration of biphasic insulin aspart 30 twice daily is non‐inferior to investigator‐driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized,open‐label,parallel‐group,multicenter trial

Aims/Introduction

The present study was to compare the efficacy and safety of subject‐driven and investigator‐driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID).

Materials and Methods

In this 20‐week, randomized, open‐label, two‐group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self‐mixed human insulin were randomized 1:1 to subject‐driven or investigator‐driven titration of BIAsp 30 BID, in combination with metformin and/or α‐glucosidase inhibitors. Dose adjustment was decided by patients in the subject‐driven group after training, and by investigators in the investigator‐driven group.

Results

Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA_1c) reduction was 14.5 mmol/mol (1.33%) in the subject‐driven group and 14.3 mmol/mol (1.31%) in the investigator‐driven group. Non‐inferiority of subject‐titration vs investigator‐titration in reducing HbA_1c was confirmed, with estimated treatment difference −0.26 mmol/mol (95% confidence interval −2.05, 1.53) (–0.02%, 95% confidence interval –0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self‐measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient‐year) was reported in the subject‐driven (1.10) and investigator‐driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA_1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA_1c target without confirmed hypoglycemia throughout the trial in the subject‐driven and investigator‐driven groups, respectively.

Conclusions

Subject‐titration of BIAsp 30 BID was as efficacious and well‐tolerated as investigator‐titration. The present study supported patients to self‐titrate BIAsp 30 BID under physicians’ supervision.     

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.     

Influence of atherosclerosis‐related risk factors on serum high‐sensitivity C‐reactive protein levels in patients with type 2 diabetes: Comparison of their influence in obese and non‐obese patients

Aims/Introduction

Increased levels of high‐sensitivity C‐reactive protein (hs‐CRP) likely leads to the development of atherosclerosis. Therefore, it is very important to know which factors largely influence hs‐CRP levels. In the present study, we examined the influence of various atherosclerosis‐related factors on hs‐CRP levels in patients with type 2 diabetes.

Materials and Methods

A total of 275 patients (176 men, 99 women) were enrolled in this study. We tested the relationship between the number of risk factors reaching a desired value and hs‐CRP levels. The Mann–Whitney U‐test was used to compare two groups. The Kruskal–Wallis test was used to carry out overall group comparisons, and the Steel–Dwass test was used to carry out between‐group comparisons. Spearman''s rank correlation was carried out to study the correlation between hs‐CRP levels and clinical parameters. Multivariate regression method was used to analyze the factors independently contributing to hs‐CRP levels.

Results

Hs‐CRP levels were lower in patients with a larger number of risk factors reaching a desired value. In particular, triglyceride and body mass index (BMI) were independent risk factors determining hs‐CRP levels in a multivariate regression analysis. Furthermore, we compared the influence of various factors on hs‐CRP levels in both obese (BMI ≥25 kg/m²) and non‐obese patients with type 2 diabetes (BMI <25 kg/m²). In obese groups, BMI and urinary albumin were independent risk factors determining hs‐CRP levels, whereas triglyceride and statin were independent risk factors in non‐obese patients.

Conclusions

There is some difference in the factors responsible for hs‐CRP levels in obese and non‐obese patients with type 2 diabetes.     

Effect of combination therapy with repaglinide and metformin hydrochloride on glycemic control in Japanese patients with type 2 diabetes mellitus

Aims/Introduction

We investigated the efficacy and safety of repaglinide as an add‐on therapy for Japanese patients with type 2 diabetes mellitus receiving metformin monotherapy (at a dose of 1,500 mg/day, mainly) in addition to diet and exercise.

Materials and methods

In the 16‐week multicenter, placebo‐controlled, randomized, double‐blind, parallel‐group trial (the phase III study), patients with type 2 diabetes mellitus with metformin monotherapy were randomly assigned to the repaglinide or placebo group. Thereafter, a 36‐week, multicenter, uncontrolled, dose‐titration method study was extended to a total duration of 52 weeks (the long‐term study). The primary end‐point of each study was a change in glycated hemoglobin (HbA_1c) from baseline.

Results

After 16 weeks, mean reductions in HbA_1c were significantly greater for the repaglinide group than for the placebo group (–0.98 ± 0.72% vs 0.13 ± 0.63%, P < 0.001). In the long‐term study, the mean change in HbA_1c was −0.76 ± 0.83%. The rate of adverse events was 60.6 and 50.0% in the repaglinide and placebo groups, respectively, in the phase III study, and 78.3% in the long‐term study. Hypoglycemia was reported in 11.7, 0 and 13.3% of patients in the repaglinide group, placebo group and long‐term study, respectively.

Conclusions

Combination therapy with repaglinide and metformin resulted in an approximately 1% reduction in HbA_1c at week 16 and in a significant long‐term improvement in HbA_1c at the end of the study. No safety problems were noted during the concomitant use of repaglinide and metformin. These studies were registered with JapicCTI (nos. JapicCTI‐101202 and JapicCTI‐101203).     

Prevalences of diabetic retinopathy and nephropathy are lower in Korean type 2 diabetic patients with non‐alcoholic fatty liver disease

Aims/Introduction

The associations between non‐alcoholic fatty liver disease (NAFLD) and chronic vascular complications of type 2 diabetes remain uncertain. We assessed the relationships between NAFLD and chronic vascular complications in patients with type 2 diabetes.

Materials and Methods

Patients with type 2 diabetes (n = 929) attending a diabetes clinic of a university hospital were studied retrospectively. Patients who had any clinical evidence of cirrhosis or other causes of chronic liver disease were excluded. Prevalences of chronic microvascular and macrovascular complications were assessed. NAFLD was ascertained by ultrasonography.

Results

The prevalence of NAFLD in patients with type 2 diabetes was 63.3%. The prevalences of diabetic retinopathy and nephropathy were significantly lower in patients with NAFLD than those without NAFLD (33.0 vs 70.2%, P < 0.001; 29.3 vs 37.1%, P = 0.007, respectively), whereas no difference was found in the prevalence of diabetic neuropathy. The prevalence of diabetic macrovascular complications was lower in type 2 diabetic patients with NAFLD than those without NAFLD (9.2 vs 14.7%, P = 0.008). After adjustment for confounding factors, such as age, sex, glycated hemoglobin, fasting serum C‐peptide, diabetic duration, body mass index and hypertension, NAFLD remained significantly associated with a lower odds ratio (OR) of diabetic retinopathy (OR 0.440, 95% confidence interval 0.255–0.757, P = 0.003) and nephropathy, (OR 0.541, 95% confidence interval 0.358–0.817, P = 0.003). In contrast, NAFLD was not significantly associated with macrovascular complications after adjustment for confounding factors.

Conclusions

These results suggest that NAFLD is inversely associated with prevalences of diabetic retinopathy and nephropathy in Korean patients with type 2 diabetes.     

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).     

Postprandial serum C‐peptide value is the optimal index to identify patients with non‐obese type 2 diabetes who require multiple daily insulin injection: Analysis of C‐peptide values before and after short‐term intensive insulin therapy

Aims/Introduction

Type 2 diabetes is a progressive disease characterized by a yearly decline in insulin secretion; however, no definitive evidence exists showing the relationship between decreased insulin secretion and the need for insulin treatment. To determine the optimal insulin secretory index for identifying patients with non‐obese type 2 diabetes who require multiple daily insulin injection (MDI), we evaluated various serum C‐peptide immunoreactivity (CPR) values.

Materials and Methods

We near‐normalized blood glucose with intensive insulin therapy (IIT) over a 2‐week period in 291 patients with non‐obese type 2 diabetes, based on our treatment protocol. After improving hyperglycemia, we challenged with oral hypoglycemic agent (OHA), and according to the responsiveness to OHA, patients were classified into three therapy groups: OHA alone (n = 103), basal insulin plus OHA (basal insulin‐supported oral therapy [BOT]; n = 56) and MDI (n = 132). Glucagon‐loading CPR increment (ΔCPR), fasting CPR (FCPR), CPR 2 h after breakfast (CPR2h), the ratio of FCPR to FPG (CPI), CPI 2 h after breakfast (CPI2h) and secretory unit of islets in transplantation (SUIT) were submitted for the analyses. Receiver operating characteristic (ROC) and multiple logistic analyses for these CPR indices were carried out.

Results

Many CPR values were significantly lower in the MDI group compared with the OHA alone or BOT groups. ROC and multiple logistic analyses disclosed that post‐prandial CPR indices (CPR2h and CPI2h) were the most reliable CPR markers to identify patients requiring MDI.

Conclusions

Postprandial CPR level after breakfast is the most useful index for identifying patients with non‐obese type 2 diabetes who require MDI therapy.     

Circulating cell‐free mitochondrial deoxyribonucleic acid is increased in coronary heart disease patients with diabetes mellitus

Aims/Introduction

Circulating cell‐free mitochondrial deoxyribonucleic acid (ccf‐mtDNA) is presumably derived from injured tissues or cells in the body and has been suggested to be potential biomarker in several diseases. The present study explored whether mtDNA could be used as a biomarker to evaluate disease in coronary heart disease (CHD) patients with or without diabetes mellitus (DM).

Materials and Methods

A total of 50 CHD patients with type 2 diabetes, 50 CHD patients without type 2 diabetes, and 50 age‐ and sex‐matched patients without CHD and DM (non‐CHD‐DM) were recruited. Ccf‐mtDNA levels were assessed by measuring the nicotinamide adenine dinucleotide dehydrogenase 1 gene using quantitative real‐time polymerase chain reaction. Receiver operating characteristic curve analysis of plasma mtDNA in CHD with or without DM was also determined. Multivariate logistic regression analyses were carried out to determine the correlation between the mtDNA levels and traditional CHD risk factors.

Results

The plasma ccf‐mtDNA levels were significantly elevated in CHD patients with DM compared with those without and non‐CHD‐DM. The area under the receiver operating characteristic curves of mtDNA in CHD patients with DM vs non‐CHD‐DM was 0.907%. Correlation analyses of the mtDNA levels and traditional CHD risk factors showed that the mtDNA levels were significantly correlated with fasting blood glucose in CHD patients with DM.

Conclusions

Ccf‐mtDNA levels can be used as a biomarker in CHD patients with DM.     

Retrospective analysis of safety and efficacy of insulin‐to‐liraglutide switch in Japanese type 2 diabetes: A caution against inappropriate use in patients with reduced β‐cell function

Aims/Introduction

The safety and efficacy of insulin‐to‐liraglutide switch in type 2 diabetes has not been studied adequately. Here, we retrospectively characterize clinical parameters that might predict insulin‐to‐liraglutide treatment switch without termination due to hyperglycemia, and examine the effects of switching the therapies on glycated hemoglobin (HbA_1c) and bodyweight in Japanese type 2 diabetes.

Materials and Methods

Japanese type 2 diabetes patients who underwent the switch of therapy were evaluated for their clinical data including β‐cell function‐related indices, such as increment of serum C‐peptide during glucagon stimulation test (GST‐ΔCPR). HbA_1c and bodyweight were analyzed in patients continuing with liraglutide after switching from insulin for 12 weeks.

Results

Of 147 patients, 28 failed in the switch due to hyperglycemia, nine failed because of other reasons and 110 continued with liraglutide for the 12‐week period. Patients failing in the switch due to hyperglycemia showed longer duration and higher daily insulin dose, as well as lower GST‐ΔCPR. Receiver–operating characteristic analysis showed that GST‐ΔCPR of 1.34 ng/mL is a cut‐off point for insulin‐to‐liraglutide switch without termination due to hyperglycemia. In patients continuing liraglutide for 12 weeks, the switch significantly reduced HbA_1c and bodyweight with no severe hypoglycemia, irrespective of sulfonylurea co‐administration, body mass index, duration and total daily insulin dose. The switch also significantly reduced the percentage of body fat and visceral fat areas.

Conclusions

Insulin‐to‐liraglutide switch can improve glycemic control and reduce bodyweight in Japanese type 2 diabetes patients. However, caution must be taken with the switch in patients with reduced insulin secretory capacity as predicted by GST‐ΔCPR.     

Efficacy and safety of exenatide once‐weekly vs exenatide twice‐daily in Asian patients with type 2 diabetes mellitus

Aims/Introduction

To compare safety and efficacy of the extended‐release formulation exenatide once weekly (EQW) vs exenatide twice daily (EBID) for 26 weeks in type 2 diabetes patients from China, India, Japan, South Korea and Taiwan.

Materials and Methods

A randomized, comparator‐controlled, open‐label study included 681 patients with type 2 diabetes inadequately controlled (hemoglobin A1c [HbA_1c] ≥7 and ≤11%) with oral antihyperglycemic medications (OAMs). Patients added 2 mg EQW or 10 μg EBID to current OAMs. Safety was re‐evaluated 10 weeks after last treatment.

Results

EQW was superior to EBID on HbA_1c measures at week 26 (Least‐squares mean treatment difference: −0.31% [95% confidence interval −0.49, −0.14%]). More EQW‐treated patients achieved target HbA_1c ≤7.0% (P = 0.003), ≤6.5% (P < 0.001), or ≤6.0% (P = 0.003). Fasting serum glucose reductions were greater among EQW‐treated patients (P < 0.001). Blood glucose profiles improved in both treatment groups (P < 0.001). Weight loss occurred with both treatments, but was greater with EBID. Adverse events (≥10%, either group) were nausea, injection‐site induration, dyslipidemia and vomiting. Injection‐site induration was more frequent with EQW, whereas nausea, vomiting and hypoglycemia were less frequent. One episode each of major hypoglycemia (EBID) and pancreatitis (EQW) were reported.

Conclusion

In this population, EQW and EBID showed efficacious glucose and weight control; safety and tolerability were consistent with observations in non‐Asian patients. This trial was registered with ClinicalTrials.gov (no. NCT00917267).     

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.     

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.     

Fasting serum insulin levels and insulin resistance are associated with colorectal adenoma in Koreans

Aims/Introduction

Insulin has been associated with the risk of colorectal cancer (CRC). However, few studies have evaluated the association between insulin and colorectal adenoma. We investigated the relationship between fasting serum insulin levels or homeostasis model assessment of insulin resistance (HOMA‐IR) and colorectal adenoma.

Materials and Methods

We retrospectively enrolled 15,427 participants who underwent both fasting serum insulin measurement and colonoscopy for a routine health examination at Asan Medical Center from January 2007 to December 2008. Participants with a history of any cancer, previous colectomy or polypectomy, those taking antidiabetic medications, and inflammatory bowel disease, non‐specific colitis, non‐adenomatous polyps only or CRC on colonoscopic findings were excluded. Finally, 3,606 participants with histologically confirmed colorectal adenoma and 6,019 controls with no abnormal findings on colonoscopy were included. Participants were categorized into quartiles (Q) based on fasting serum insulin levels and HOMA‐IR.

Results

Fasting serum insulin and HOMA‐IR were significantly higher in participants with colorectal adenomas compared with controls. Multivariate regression analysis adjusting for age, sex, smoking habits, drinking habits and family history of CRC showed that participants with higher quartiles of fasting serum insulin levels (odd ratio [OR] 1.17 for 2nd Q, 1.19 for 3rd Q, and 1.42 for 4th Q, P < 0.05) or HOMA‐IR (OR 1.18 for 2nd Q and 1.45 for 4th Q, P < 0.05) showed significantly increased ORs of colorectal adenoma compared with the lowest quartiles.

Conclusions

These findings showed that increased serum insulin levels and insulin resistance were significantly associated with the presence of colorectal adenoma.     

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.     

Effect of glycemic control on periodontitis in type 2 diabetic patients with periodontal disease

Aims/Introduction

Diabetes mellitus and periodontitis are closely related. A huge number of reports has addressed the effect of periodontal intervention therapy on glycemic control, but no reports have addressed the effect of glycemic intervention therapy on periodontal disease in type 2 diabetic patients. The aim of this study was to examine the effect of improved glycemic control by glycemic intervention therapy on periodontitis in type 2 diabetic patients.

Materials and Methods

A total of 35 patients underwent intervention therapy to improve glycemic control without periodontal treatment. Glycohemoglobin (HbA_1c), high‐sensitivity C‐reactive protein (hs‐CRP), bleeding on probing (BOP), probing pocket depth (PPD) and intraoral community periodontal index (CPI) codes of the World health Organization (WHO) were examined at baseline, and 2 and 6 months after the intervention therapy to improve glycemic control.

Results

After the improvement of glycemic control, BOP lesions improved, but deep PPD lesions and WHO CPI codes did not improve. Subanalyses showed that effective glycemic control (average HbA_1c reduction 1.8%) improved BOP lesions, but did not affect deep PPD lesions and WHO CPI codes. In addition, high BOP lesions at baseline responded more effectively to glycemic intervention. Further analysis of CPI codes in all individual periodontal sites independent of WHO CPI codes in 35 patients showed that only gingival inflammation without a deep periodontal pocket improved after glycemic intervention.

Conclusions

Effective glycemic control improves BOP lesions in type 2 diabetic patients with periodontitis through ameliorating inflammation at the gingival sites of periodontal tissue. This trial was registered with the University Hospital Medical Information Network (no. UMIN000007670).     

Postprandial C‐peptide to glucose ratio as a predictor of β‐cell function and its usefulness for staged management of type 2 diabetes

Aims/Introduction

Type 2 diabetes is characterized by progressive deterioration of β‐cell function. Recently, it was suggested that the C‐peptide‐to‐glucose ratio after oral glucose ingestion is a better predictor of β‐cell mass than that during fasting. We investigated whether postprandial C‐peptide‐to‐glucose ratio (PCGR) reflects β‐cell function, and its clinical application for management of type 2 diabetes.

Materials and Methods

We carried out a two‐step retrospective study of 919 Korean participants with type 2 diabetes. In the first step, we evaluated the correlation of PCGR level with various markers for β‐cell function in newly diagnosed and drug‐naïve patients after a mixed meal test. In the second step, participants with well‐controlled diabetes (glycated hemoglobin <7%) were divided into four groups according to treatment modality (group I: insulin, group II: sulfonylurea and/or dipeptityl peptidase IV inhibitor, group III: metformin and/or thiazolidinedione and group IV: diet and exercise group).

Results

In the first step, PCGR was significantly correlated with various insulin secretory indices. Furthermore, PCGR showed better correlation with glycemic indices than homeostatic model assessment of β‐cell function (HOMA‐β). In the second step, the PCGR value significantly increased according to the following order: group I, II, III, and IV after adjusting for age, sex, body mass index and duration of diabetes. The cut‐off values of PCGR for separating each group were 1.457, 2.870 and 3.790, respectively (P < 0.001).

Conclusions

We suggest that PCGR might be a useful marker for β‐cell function and an ancillary parameter in the choice of antidiabetic medication in type 2 diabetes.     

Liraglutide administration in type 2 diabetic patients who either received no previous treatment or were treated with an oral hypoglycemic agent showed greater efficacy than that in patients switching from insulin

Aims/Introduction

Liraglutide, a glucagon‐like peptide‐1 receptor agonist, is expected to provide a new treatment option for diabetes. However, the suitable timing of liraglutide administration in type 2 diabetic patients has not yet been clarified.

Materials and Methods

We reviewed type 2 diabetic patients (n = 155) who visited the Osaka Red Cross Hospital for glycemic control, with administration of liraglutide at a dose of 0.6 mg (average glycated hemoglobin [HbA_1c] level, 8.7 ± 0.1%). The effect of liraglutide based on the pretreatment status was compared. We also analyzed the background factors of both a successful and failed group of patients who switched to liraglutide from insulin.

Results

An improvement in blood glucose levels was confirmed in 122 of 155 patients. During the 4‐month observation period, the improvement in HbA_1c levels was significantly greater in the group of drug‐naïve/previous oral hypoglycemic agent (9.1 ± 0.2 to 7.2 ± 0.2%) than that in the group switching from insulin (8.6 ± 0.2 to 7.8 ± 0.2%). In addition, C‐peptide immunoreactivity levels (fasting > 2.2 ng/mL; delta >1.6 ng/mL; urine > 70 μg/day), younger age and a smaller number of insulin units used per day were considered important when deciding on switching to liraglutide from insulin.

Conclusions

Liraglutide was more effective in patients who had not been treated previously or received oral hypoglycemic agents than in patients switching from insulin. With respect to switching to liraglutide from insulin, the most important factors to be considered were C‐peptide immunoreactivity levels, age, and the number of insulin units used per day.