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.     

Fulminant type 1 diabetes mellitus with anti‐programmed cell death‐1 therapy

Anti‐programmed cell death‐1 (PD‐1) antibodies are regarded as a risk factor for insulin‐dependent diabetes mellitus as a side‐effect. While a small number of cases have been reported, evidence remains limited. This is the first report of an Asian patient developing insulin‐dependent diabetes during anti‐PD‐1 therapy. A 55‐year‐old euglycemic woman receiving nivolumab for malignant melanoma showed abrupt onset of ketonuria, and elevated levels of plasma glucose (580 mg/dL) and hemoglobin A1c (7.0%). Over the next 2 weeks, serum C‐peptide levels fell below the limit of detection. Islet autoantibodies were negative, and the patient showed a human leukocyte antigen haplotype associated with type 1 diabetes. Anti‐PD‐1 therapy can cause rapid onset of insulin‐dependent diabetes, possibly because of inappropriate activation of T cells. Human leukocyte antigen haplotypes might be related to the onset of this disease. Physicians should be aware of this serious adverse event and carry out routine blood glucose testing during anti‐PD‐1 therapy.     

Case of fulminant type 1 diabetes induced by the anti‐programmed death‐ligand 1 antibody,avelumab

With the expansive use of immune checkpoint inhibitors, the frequency of immune‐related adverse events, including autoimmune type 1 diabetes, has been exponentially increased. The anti‐programmed death‐ligand 1 antibody, avelumab, has recently been approved for metastatic Merkel cell carcinoma therapy. Here, we report a patient that developed fulminant type 1 diabetes during avelumab treatment. An 81‐year‐old woman with no history of diabetes received avelumab for metastatic Merkel cell carcinoma. Elevated plasma glucose level (483 mg/dL), hemoglobin A1c level (7.5%) and ketosis were observed after 10 courses of avelumab without any symptoms related to hyperglycemia. As the laboratory tests showed insulin depletion, we diagnosed her with fulminant type 1 diabetes induced by avelumab. This is the first reported case of avelumab‐induced type 1 diabetes, illustrating the necessity for close monitoring of glycemic control during avelumab therapy, as well as other immune checkpoint inhibitors.     

Case of ketoacidosis by a sodium‐glucose cotransporter 2 inhibitor in a diabetic patient with a low‐carbohydrate diet

We present a case of a 32‐year‐old diabetic woman with Prader–Willi syndrome who developed severe ketoacidosis caused by a sodium‐glucose cotransporter 2 (SGLT2) inhibitor, a novel class of antihyperglycemic agents, during a strict low‐carbohydrate diet. At admission, a serum glucose level of 191 mg/dL was relatively low, though laboratory evaluations showed severe ketoacidosis. This is the first report of ketoacidosis caused by a SGLT2 inhibitor. It is necessary to not only pay attention when using a SGLT2 inhibitor in patients following a low‐carbohydrate diet, but also to start a low‐carbohydrate diet in patients treated with a SGLT2 inhibitor because of a high risk for developing ketoacidosis.     

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.