Diabetology International

Excess glucagon activity in diabetes increases hepatic glucose production via gluconeogenic gene induction, thus exacerbating hyperglycemia. Glucagon receptor-activated cAMP-dependent protein kinase A (PKA) induces proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) expression via the cAMP response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) pathway. Transcriptional coactivator PGC-1α subsequently coactivates transcription factors, such as forkhead box O1 (FoxO1) and hepatocyte nuclear factor 4 alpha (HNF4α), to induce gluconeogenic genes. The current review first summarizes the mechanism by which transcriptional cofactor CBP and p300-activated transactivator with glutamic acid and aspartic acid-rich COOH-terminal domain 2 (CITED2) activates gluconeogenesis via the regulation of PGC-1α and general control of amino acid synthesis protein 5-like 2 (GCN5). Type 2 diabetes is closely linked with non-alcoholic fatty liver disease (NAFLD). Between 10 and 20% of NAFLD progresses to non-alcoholic steatohepatitis (NASH), which can cause liver cirrhosis and can also lead to hepatocellular carcinoma. Liver macrophages are considered to be related to inflammation and fibrosis observed in NASH. This review outlines liver-derived signals underlying the differentiation of liver macrophages and the mechanism of myeloid cell diversification in NASH.

Serum lipid management is important for patients with diabetes; however, it has not been examined in our specialized diabetes clinic. The aim of the study was to assess the percentage of patients who did not achieve management targets (MT) for low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG), and explore factors related to failure to achieve lipid MT in Japanese patients with type 1 (T1D) and type 2 diabetes (T2D). This cross-sectional study included 795 patients (35% men) with T1D and 4018 patients (60% men) with T2D attending our diabetes center. MTs for serum lipids were in accordance with the guidelines of the Japan Atherosclerosis Society. Logistic regression analysis was performed to identify factors related to failure to achieve MTs for serum lipids. The percentages of men/women who did not achieve MT for LDL-C were 34.1/31.8% in T1D and 40.5/52.7% in T2D. The corresponding values for TG were 35.1/14.0% in T1D and 50.1/47.9% in T2D, and for HDL-C were 2.5/0% in T1D and 8.6/2.9% in T2D. Increase in body mass index (BMI) and glycated hemoglobin (HbA1c) were significantly and independently associated with failure to achieve lipid MT in patients with T1D and T2D for both sexes. The percentages of our patients who did not achieve serum lipid MT were relatively high in T1D and T2D, and higher HbA1c and BMI were associated with failure to achieve serum lipid MTs. More attention should be paid to lipid management in patients with diabetes especially who have higher HbA1c and BMI in our facility.

The aims of this study are to evaluate any differences in the Quality of life among Continuous Subcutaneous Insulin Infusion (CSII) and Multiple Dose Injection (MDI) insulin delivery, applying the Diabetes Quality of life Brief Clinical Inventory (DQoL-BCI) questionnaire, and assess the diabetes management strategies between the two groups. One hundred and ten adult participants (male/female ratio 1:2.7) with type 1 diabetes were recruited in this online survey. Forty-eight of them were using CSII and the rest 62 (were using) MDI insulin delivery. A 23-item socio-demographic/diabetes management strategies questionnaire and the 15-item DQoL-BCI were administered. CSII users scored statistically, significantly better at the satisfaction treatment subscale (p = 0.032) of the DQoL-BCI and emerged that they were implemented more management strategies such as dietician guidance services (p = 0.002), carbohydrate education seminars (p = 0.03). Predictive factors were also detected regarding the HbA1c < 7% (53 mmol/mol) and β-coefficients in relation to DQoL-BCI questionnaire with the subscales of a negative impact and satisfaction treatment. Diabetes self-management education plays a key role to a better compliance with the treatment. Client-centered multidisciplinary centers in T1DM education are essential so that they be applicable for all T1DM patients irrespective of the type of insulin delivery they used.

Periodontal disease often develops in patients with diabetes, and further exacerbated with diabetic complications. It would be clinically important to clarify the relationship between diabetic microvascular diseases and periodontal disease. This study aimed to evaluate the association between periodontal disease and diabetic complications in patients with type 2 diabetes with poor glycemic control. A total of 447 patients with type 2 diabetes hospitalized at Rakuwakai Otowa Hospital, Japan, were initially recruited in this study. After excluding 134 patients who lacked clinical data or were edentulous, 312 were included in our study. The severity of periodontal disease was evaluated based on the average bone resorption rate. Patients with diabetic nephropathy developed severe periodontal disease (multivariate-adjusted odds ratio, 3.00 [95% CI 1.41–5.19]). Diabetic neuropathy was positively associated with the severity of periodontal disease; the multivariate-adjusted odds ratio (95% CI) was 1.62 (0.87‒2.99) for moderate and 4.26 (2.21‒8.20) for severe periodontal disease. In contrast, diabetic retinopathy was linked with moderate periodontal disease (multivariate-adjusted odds ratio 2.23 [95% CI 1.10–4.10]), but not with severe conditions (multivariate-adjusted odds ratio 0.92 [95% CI 0.67–3.07]). In conclusion, periodontal disease, evaluated by average bone resorption rate, was associated with diabetic nephropathy and neuropathy.

In order to achieve good glycemic control, the prevention and management of insulin balls is important for diabetic patients during insulin therapy. However, insulin balls still occur within the clinical setting. This review evaluated the effectiveness of programs designed to manage insulin balls. A scoping review was conducted based on the Japanese and English literature available from a systematic literature search conducted from January 1964 to March 2022. Three databases were searched: PubMed, CINAHL, and Ichushi-Web. A total of 33 articles met the inclusion criteria, which consisted of 3 for prevention management of insulin balls and 30 for management after the occurrence of insulin balls. Findings for prevention management suggested that the insulin injection technique education (avoidance of repeated injections to the same site) and providing knowledge (about insulin balls) prevented the appearance of insulin balls. As for post-occurrence management, insulin injection technique education (avoidance of injections to the insulin ball, avoidance of repeated injections to the same site, and switching the injection site) improved blood glucose control. Hypoglycemia was observed in all studies that included an assessment of hypoglycemia. None of the studies evaluated long-term effects of either preventive or post-occurrence management. Providing insulin injection technique education is an effective management protocol for insulin balls. Moreover, education about hypoglycemia is important for patients with insulin balls. Further studies to investigate the long-term effects in the management of insulin balls are needed.

Resistin, secreted from adipocytes, causes insulin resistance in mice. We previously reported that the G/G genotype of a single-nucleotide polymorphism (SNP)-420 (rs1862513) in the human resistin gene (RETN) resulted in an increase in circulating resistin and susceptibility to type 2 diabetes (T2D). Whereas PPARG Pro12Ala Pro/Pro and RETN SNP-420 G/G genotypes were synergistically associated with plasma resistin, no other trans-acting SNPs associated with circulating resistin have been reported. We cross-sectionally analyzed the association between plasma resistin and SNPs recently reported to be associated with T2D in 2,038 community-dwelling Japanese individuals. These SNPs are located around the TCF7L2, KCNJ11, IGF2BP2, CDKN2A/B, SLC30A8, CDKAL1, GCKR, HHEX, KCNQ1, WFS1, TCF2, TSPAN8, CDC123, ADAMTS9, THADA, JAZF1, PANK1, IRS1, HK1, and MTNR1B genes. The SNPs were analyzed by TaqMan assays, and plasma resistin was determined by ensyme-linked immunosorbent assay (ELISA). Plasma resistin was significantly associated with rs7578597 in THADA [C/C 6.81, C/T 8.64 ± 5.26, T/T 11.54 ± 6.54 ng/ml; P = 0.0159, analysis of variance (ANOVA)]. Plasma resistin appeared to be higher in individuals with the THADA T/T and RETN SNP-420 G/G genotypes. A multiple regression analysis revealed that plasma resistin was also associated with THADA after adjustment for age, gender, body mass index, and SNP-420 (β = 1.89, P = 0.036). A nominal association between plasma resistin and rs4607103 in ADAMTS9 disappeared after multivariate adjustment. Circulating resistin was associated with rs7578597 in THADA in the general Japanese population. In addition to the cis-acting effect of SNP-420 in the RETN promoter, circulating resistin could be affected by other trans-acting SNPs.

We aimed to estimate the causes of death and their incidence rates and risk factors for all-cause mortality in Japanese people with type 2 diabetes using baseline data from the Japan Diabetes Complication and its Prevention (JDCP) prospective study. We analyzed a multicenter prospective cohort of 5944 Japanese people with diabetes aged 40–74 years. Causes of death were categorized as cardiac or cerebrovascular disease, malignancy, infectious disease, accident or suicide, sudden death of unknown cause, and other unknown causes. The Cox proportional hazards model was used to estimate the hazard ratio of all-cause mortality risk factors. The mean age was 61.4 years, and 39.9% of the population was female. Overall, the mortality ratio per 100,000 person-years (95% confidence interval [CI]) was 515.3 (95% CI 445.1–596.9). Malignancies are the most common cause of death among people with type 2 diabetes, accounting for 46.9% of all deaths, followed by cardiac and cerebrovascular diseases at 11.7% and infectious diseases at 3.9%. Higher mortality risk was significantly associated with older age, lower body-mass index, alcohol intake, history of hypertension, and acute myocardial infarction (AMI). The frequency of causes of death in people with type 2 diabetes identified in this study was similar to that from a recent survey on causes of death conducted by the Japan Diabetes Society. A lower body-mass index, alcohol intake, history of hypertension, and AMI were found to be associated with an increased total risk of type 2 diabetes.

Lipoatrophy (LA) is one of the complications of insulin treatment. It has become rare thanks to insulin analogues but it can still be observed in patients with diabetes type 1(T1DM). No effective treatment exists. Herein, we report for the first time two children with T1DM and LA successfully treated with laser treatment. A 6-year-old child with T1DM presented with LA 4 months post-diagnosis. He was on continuous subcutaneous insulin infusion (CSII). LA presented on body sites where insulin catheter was never inserted. He underwent different treatment options with no positive effect. Laser treatment was tried with impressive improvement. The second 9-year-old child presented with LA 5 years postdiagnosis. He changed the insulin type, the site of insulin injection, and tried topical use of sodium chromoglycate cream with partial improvement. Laser treatment was finally used with remarkable outcome. Insulin-induced LA is now a rare skin complication with no effective treatment up to now. Laser treatment seems to be an effective treatment option.