Diabetology International最新文献

Slowly progressive type 1 diabetes mellitus (SPIDDM), solely positive for zinc transporter 8 autoantibody (ZnT8A) is rare, and the factors involved in the single positivity remain largely unknown. Thus, this case report aimed to infer the factors based on a literature review. A 40-year-old female was hospitalized for hyperglycemia. She was diagnosed with sensorineural hearing loss and steroid-induced diabetes at 29 and 30 years of age, respectively. She started insulin therapy at 36 years of age, following oral hypoglycemic medication. Blood test results at admission showed fasting serum C-peptide level of 0.29 ng/mL; single positivity for ZnT8A; mitochondrial DNA 3243 mutation; and human leukocyte antigen-DRB1*09:01-DQB1*03:03 associated with Japanese type 1 diabetes. She was diagnosed with ZnT8A-single-positive SPIDDM accompanying mitochondrial diabetes. Most islet cell antibody (ICA)-positive SPIDDM cases with mitochondrial DNA 3243 mutations are negative for glutamic acid decarboxylase autoantibodies, suggesting ZnT8A-single-positive SPIDDM cases among such cases. Therefore, mitochondrial DNA 3243 mutation may be associated with ZnT8A single positivity in SPIDDM.

We report a beneficial effect of a sodium glucose co-transporter 2 (SGLT2) inhibitor in the management of insulin resistant diabetes mellitus (IRDM) in a Japanese girl with mild Rabson-Mendenhall syndrome (RMS). At 10 2/12 years of age, she was referred to us because of glucosuria, and was found to have marked acanthosis nigricans and RMS-like facial features such as proptosis, large ears, full lips, and gingival hypertrophy, but not other clinical features frequently found in RMS. At 11 9/12 years of age, her blood HbA1c level, though it remained ~ 6.5% until then, increased to 7.9% with pubertal development. She was treated with an SGLT2 inhibitor and metformin, which ameliorated overt hyperglycemia in the afternoon and the evening (postprandial time) as well as obvious hypoglycemia in the early morning (before breakfast), and reduced her blood HbA1c to 5.5%. Whole exome sequencing revealed probably disease-causing c.2465 T > C:p.(Leu822Pro) of paternal origin and c.3038C > T:p.(Pro1013Leu) of maternal origin in INSR. These findings imply the usefulness of SGLT2 inhibitor in the treatment of IRDM. It is likely that SGLT2 inhibitor mitigated hyperglycemia by increasing the urine glucose excretion and prevented severe hypoglycemia probably because of attenuated hyperinsulinemia in the absence of overt hyperglycemia.

Insulin treatment should be introduced in patients with slowly progressive type 1 diabetes (SPIDDM; definite), according to the revised diagnostic criteria of SPIDDM (2023). In contrast, SPIDDM (probable) patients are in a non-insulin-dependent state; therefore, a more flexible treatment can be considered, although sulfonylurea agents should be avoided. Insulin treatment has been shown to maintain endogenous insulin secretion capacity in SPIDDM (probable); however, this does not mean that all SPIDDM (probable) patients should use insulin from the early phase. Dipeptidyl peptidase-4 inhibitors and biguanides might be the treatment of choice for SPIDDM (probable), but no evidence exists for other hypoglycemic agents. In any case, careful monitoring of the endogenous insulin secretion capacity should be carried out, and if a decrease in insulin secretion capacity is suspected, a change in treatment should be considered to prevent progression to an insulin-dependent state.

A 73-year-old Japanese woman was admitted to our hospital with anorexia, weight loss, and fever. A few weeks prior to admission, she became aware of anorexia. She was leukopenic, complement-depleted, and positive for antinuclear antibodies and anti-double stranded DNA antibodies. She was also found to have chronic airway inflammation on computed tomography. At the time of admission, she had multiple erythematous plaques on face and neck. She had blood glucose 343 mg/dL, HbA1c 12.7%, serum C-peptide 0.74 ng/mL, urinary C-peptide 17 μg/day, and urinary ketone 3+; and was positive for anti-glutamic acid decarboxylase antibodies and anti-zinc transporter 8 antibodies. Her human leukocyte antigen type was DRB1* 09:01-DQB1* 03:03, which is a susceptibility haplotype for acute-onset type 1 diabetes (T1D). Therefore, she was diagnosed as having concomitant T1D and SLE. Initial treatment with insulin and prednisolone alleviated her symptoms. However, sputum culture revealed Mycobacterium tuberculosis 23 days later, and she was treated with a multidrug regimen. The timing of onset of the SLE and T1D was estimated to be 4-7 weeks prior to admission. No imaging findings were available prior to 3 weeks of admission, making it difficult to determine the timing of onset of pulmonary tuberculosis (TB). In summary, SLE and T1D are both autoimmune diseases, but rarely occur together. Environmental and genetic factors are involved in the development of T1D and SLE, but TB is rarely thought of as a causative environmental factor. In the present case, SLE, T1D, and TB may have interacted during their respective onsets.

Aim: Patients with diabetes are frequently complicated with diabetic foot ulcers (DFUs) which are vulnerable to recurrence after healing. We retrospectively surveyed the recurrence of foot ulcer and related factors in Japanese patients with DFUs.

Subjects and methods: Forty-two feet of 39 patients were initially recruited in this study. During the follow-up period, the recurrence of foot ulcers was observed in nine feet. Peak planter pressure (PPP) distribution on the affected side was measured at three pressure levels. Photographs of the plantar scar were superimposed on the high-pressure plantar area, and the concordance of both lesions was counted.

Results: The recurrence of foot ulcer was significantly related to higher body weight, a history of discontinued or unused insole, the existence of scar at the sole concomitant with load, and longer observation period. The existence of scar was further selected as a significant predictive variable in multiple logistic regression analysis. Furthermore, the recurrence rate significantly increased in parallel with the increment of the concordance rate at 250 kPa or more level of pressure (P = 0.0199, odds ratio = 22.054).

Conclusions: For the prevention of the recurrence of foot ulcers, education on the continuous use of insole and adequate treatments of scar at the sole, concomitant with load especially in patients with higher body weight and longer observation period, is required. It is plausible that the concordance of PPP and scar lesions properly predicts the recurrences of foot ulcers, which may help to avoid unnecessary amputations in the future in Japanese patients with diabetes.

In Japan, most HbA1c measurements by enzymatic assays or immunoassays represent the HbA1c levels in the blood cell fraction obtained after centrifugation of the blood samples. The present study investigated that the blood cell enzymatic HbA1c assay (EA-HbA1c) was compared with whole blood HbA1c in patients with iron deficiency anemia (IDA). Study 1: EA-HbA1c levels using blood cell samples (blood cell EA-HbA1c) and high-performance liquid chromatography (HPLC)-HbA1c levels using whole blood samples (whole blood HPLC-HbA1c) were measured in 15 IDA patients with Hb < 8 g/dL and transferrin saturation (TSAT) < 20%, and the correlations between the blood cell EA-HbA1c/whole blood HPLC-HbA1c ratio (%) and various IDA indicators [mean corpuscular hemoglobin concentration (MCHC), TSAT, and logarithmically transformed ferritin (log-FER)] were examined. Study 2: Blood cell EA-HbA1c levels were compared with EA-HbA1c levels using whole blood samples (whole blood EA-HbA1c) and whole blood HPLC-HbA1c levels in 10 of the above IDA patients. In Study 1, blood cell EA-HbA1c levels were significantly higher than whole blood HPLC-HbA1c levels, and the blood cell EA-HbA1c/whole blood HPLC-HbA1c ratio (%) showed significant negative correlations with MCHC, TSAT, and log-FER in the IDA patients. In Study 2, blood cell EA-HbA1c levels were significantly higher than whole blood EA-HbA1c and whole blood HPLC-HbA1c levels in IDA patients. The present study showed for the first time that blood cell EA-HbA1c are higher than whole blood HbA1c in IDA patients. In IDA patients with marked anemia, EA-HbA1c levels using blood cells show different results from those using whole blood.

This study aimed to the investigate prevalence and factors associated with reduced skeletal muscle mass in non-elderly adults with type 1 diabetes (T1D). Ninety-nine patients (65 women, mean age: 43 ± 11 years, range 20-65 years) with acute-onset T1D who underwent body component analysis between October 2016 and April 2018 were studied. Bioelectrical impedance analysis was used to calculate the skeletal muscle mass index (SMI) of the limbs. A multivariate logistic regression analysis was employed to identify factors related to SMI reduction. Seventeen participants (17.1%) exhibited decreased SMI. There were no significant differences in sex, age, or HbA1c between the low and normal SMI groups. The prevalence of diabetic retinopathy was 58.8% in the low SMI group, which was significantly higher than that in the normal SMI group (15.9%; p < 0.05). The duration of T1D was significantly longer in the low SMI group (25.6 ± 11.3 years) than that in the normal SMI group (20.0 ± 10.0 years, p < 0.04). Multivariate logistic regression analysis revealed that retinopathy, male sex, and body mass index were independent risk factors for low SMI (all p < 0.05). Thus, the factors associated with decreased skeletal muscle mass in non-elderly adult patients with T1D were identified.

A 58-year-old woman with a body mass index of 26.4 kg/m² was referred because of high glycated hemoglobin (HbA1c) at a medical checkup. Her anti-glutamic acid decarboxylase antibody (GADA) titer was positive (16.0 U/mL; normal < 5.0 U/mL). Her HbA1c was controlled at 6.4%-7.5% using metformin, ipragliflozin, and sitagliptin. Two-and-a-half years later, she was diagnosed with endometrial cancer with pelvic lymph node metastasis and underwent surgery followed by chemotherapy with carboplatin and paclitaxel, then carboplatin and docetaxel. However, owing to enlargement of the metastatic nodules, combination therapy with pembrolizumab and lenvatinib (pem + len) was initiated (DAY 1). On DAY 36, her plasma glucose (PG) concentration was high; therefore, insulin degludec was administered once daily and self-monitoring of blood glucose commenced. On DAY 50, her PG and HbA1c were 509 mg/dL and 10.2%, respectively, and her insulin therapy was changed to a basal-bolus. Urinary ketones were negative. Treatment with pem + len was continued without interruption. Her GADA was negative 3 months before starting pem + len (DAY - 119), but was high (234 U/mL) on DAY 50, and then negative on DAYs 345 and 670. Her serum C-peptide concentration gradually decreased, but it did not disappear (DAYs - 119, 50, 156, 345, 607 and 670: 2.49, 1.80, 0.90, 0.21, 0.85 and 0.65 ng/mL, respectively). Human leukocyte antigen analysis revealed two susceptibility haplotypes (DRB1^*04:05-DQB1^*04:01-DPB1^*02:01 and DRB1^*04:05-DQB1^*04:01-DPB1^*05:01) for type 1 diabetes (T1D). This case is notable in that pembrolizumab-related T1D progressed more slowly than previously reported, and lenvatinib may have contributed to this delay.

Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now widely used for treating type 2 diabetes mellitus (T2DM) and obesity. We examined their association with acetonemic vomiting, especially when given to patients with low body weight, in hopes of achieving early recognition of this complication which is potentially life-threatening if not dealt with appropriately.

Methods: Cases identified incidentally are described and discussed referring to prior reports.

Results: We managed two episodes of acetonemic vomiting, associated with GLP-1 RA use, affecting type 2 diabetes patients with low body weight. The absence of significant abnormalities in regularly tested laboratory data or imaging workup findings in these patients made it difficult to diagnose and recognize the emergent nature of the problem.

Conclusion: GLP1-RAs have the potential to induce acetonemic vomiting when prescribed to patients with diabetes, especially those with low body weight. Although it is a potentially life-threatening disorder, acetonemic vomiting is not common in adults, making accurate diagnosis challenging. It is important that clinicians not hesitate to administer a dextrose-containing intravenous bolus, with insulin if necessary, to maintain normal glucose levels and thereby prevent progression to severe outcomes including death.

Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), is becoming more common in the treatment of heart failure and hypertension. Neprilysin is highly expressed in the renal tubules, and reports have shown increases in urinary C-peptide reactivity (CPR) levels after administration of ARNI. However, the effect of ARNI on serum CPR levels, a critical marker of insulin secretion in diabetes, remains underexplored. We evaluated the effect of ARNI on serum CPR levels in patients with type 2 diabetes and its impact on the assessment of endogenous insulin secretion. We retrospectively investigated the medical records of patients with type 2 diabetes at two hospitals, where fasting plasma glucose and serum CPR levels were measured before and after administration of ARNI. All eleven patients (five males, six females) who met the criteria showed an increase in median fasting serum CPR levels following ARNI administration. The levels rose from a median of 1.78 ng/mL (IQR: 1.26-2.02) to 3.19 ng/mL (IQR: 2.71-5.12), accompanied by significant increases in the C-peptide index. Immunoreactive insulin levels barely changed after ARNI administration, but the ratio of immunoreactive insulin to CPR decreased significantly, from 3.3 (IQR: 2.5-3.9) to 1.6 (IQR: 1.3-1.9). The increase in serum CPR levels is attributed to inhibition of CPR degradation rather than an increase in endogenous insulin secretion, as fasting blood glucose levels remained unchanged. These findings suggest the need for caution when using serum CPR levels to evaluate endogenous insulin secretion in patients treated with an ARNI, which are increasingly being prescribed for heart failure and hypertension.