Analysis of pancreatic volume in acute‐onset,slowly‐progressive and fulminant type 1 diabetes in a Japanese population

Aims/Introduction

A decrease in the size of the pancreas is observed in islet autoantibody‐positive non‐diabetic donors and acute‐onset type 1 diabetes irrespective of the diabetes duration. Little is known, however, about the relationship between the size of the pancreas and type 1 diabetes subtypes, including fulminant type 1 diabetes.

Materials and Methods

We examined the pancreatic volume (PV) in 44 adult patients with type 1 diabetes (16 acute‐onset type 1 diabetes, 18 slowly progressive type 1 diabetes and 10 fulminant type 1 diabetes) and 39 age‐ and body mass index‐matched non‐diabetic controls. PV was measured by computed tomography. The ability to secrete insulin was assessed by stimulated C‐peptide after intravenous glucagon administration.

Results

PV was significantly correlated with bodyweight in both control participants and type 1 diabetes patients. The PV index (PVI; PV/bodyweight) was decreased by 39% in type 1 diabetes compared with that in controls. PVI was significantly decreased in acute‐onset type 1 diabetes patients and slowly progressive type 1 diabetes patients (both P < 0.0001), but not in fulminant type 1 diabetes patients (P = 0.10), compared with control participants. In cases patients with recent‐onset type 1 diabetes (0–7 days post‐diagnosis), PVI was significantly decreased in acute‐onset type 1 diabetes patients (n = 8, P = 0.0005), but not in fulminant type 1 diabetes patients (n = 7, P = 0.44), compared with controls. PVI showed no correlations with the diabetes duration, C‐peptide levels, glycated hemoglobin, glutamic acid decarboxylase autoantibody levels, serum amylase or daily total insulin dose in type 1 diabetes subtypes.

Conclusions

The present results show that patients with acute‐onset type 1 diabetes and slowly progressive type 1 diabetes have small pancreases irrespective of the diabetes duration or C‐peptide levels. In contrast to earlier findings on acute‐onset type 1 diabetes, we found no reduction of PVI at the onset of fulminant type 1 diabetes.     

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.     

Effect of serum 25‐hydroxyvitamin D3 on insulin resistance and β‐cell function in newly diagnosed type 2 diabetes patients

Aims/Introduction

To evaluate serum 25‐hydroxyvitamin D₃ (25(OH)D₃) in newly diagnosed type 2 diabetes patients and to explore the associations of 25(OH)D₃ with insulin resistance and β‐cell function.

Materials and Methods

A total of 97 newly diagnosed type 2 diabetes patients and 69 healthy controls were recruited. Serum 25(OH)D₃ was determined using high‐pressure liquid chromatography. Insulin resistance was measured using a homeostasis model assessment of insulin resistance (HOMA‐IR). β‐Cell function was determined using the HOMA β‐cell function index (HOMA‐β), early‐phase insulin secretion index (ΔI30/ΔG30) and area under the insulin curve (AUCins). Correlation analysis was carried out using Pearson''s correlation and multiple stepwise regression analysis.

Results

Serum 25(OH)D₃ was much lower in patients with newly diagnosed type 2 diabetes (t = −13.00, P < 0.01), and the prevalence of hypovitaminosis 25(OH)D₃ was 62.9% (61/97) in diabetic patients. Among the diabetic patients, patients with hypovitaminosis 25(OH)D₃ showed higher glycosylated hemoglobin and AUCglu (P < 0.01) as well as lower HOMA‐β, ΔI30/ΔG30 and AUCins. Serum 25(OH)D₃ was independently positively correlated with ΔI30/ΔG30 and AUCins (P < 0.05), but was not significantly correlated with either HOMA‐IR or HOMA‐β. Only triglycerides, glycosylated hemoglobin and ΔI30/ΔG30 emerged as independent factors associated with serum 25(OH)D₃ in both diabetes patients and the health control group.

Conclusions

The present results further showed a low serum 25(OH)D₃ concentration in patients with newly diagnosed type 2 diabetes. 25(OH)D₃ deficiency is associated with disturbances in glucose metabolism and lipid metabolism. Serum 25(OH)D₃ is not correlated with basal insulin resistance or β‐cell function, but is significantly positively correlated with glucose‐stimulated insulin secretion and β‐cell function.     

Simultaneous development of Graves’ disease and type 1 diabetes during anti‐programmed cell death‐1 therapy: A case report

We present the first case of simultaneous development of Graves’ disease and type 1 diabetes during anti‐programmed cell death 1 therapy. A 48‐year‐old man with parotid gland adenocarcinoma and lung metastasis had received five courses of nivolumab. Fourteen days after administration of the sixth course, his casual plasma glucose and hemoglobin A1c levels were 379 mg/dL and 7.2%, respectively. Furthermore, thyrotoxicosis was detected with a blood test. Serum total ketone body and thyroid‐stimulating hormone receptor antibody levels increased, and serum C‐peptide level decreased to 0.01 ng/mL thereafter. Thus, we concluded that he simultaneously developed anti‐programmed cell death 1 therapy‐associated type 1 diabetes and Graves’ disease. Among Japanese patients with autoimmune polyglandular syndrome type III, the frequency of human leukocyte antigen‐DRB1*04:05 is higher in those with both type 1 diabetes and Graves’ disease. Our case had human leukocyte antigen‐DRB1*04:05, which might be associated with the simultaneous development of the two diseases.     

Studies on cocktails of 31‐kDa, 36‐kDa and 51‐kDa antigens of Leishmania donovani along with saponin against murine visceral leishmaniasis

A substantial number of antigens of Leishmania donovani have been described in the past. However, identifying candidate antigens is not enough. Appropriate antigen delivery to induce the right type of immune response against leishmaniasis (i.e. induction of a strong antigen‐specific Th1 type of immune response) is another crucial component of an effective vaccine. Therefore, ‘cocktail’ vaccines are proposed based on the assumption that such cocktails will show enhanced efficacy. Studies have been carried out on LD31 and LD51 polypeptides from L. donovani promastigotes, which have proven to be potential vaccine candidates. This study was designed to check the protective efficacy of various cocktails of low molecular weight antigens alone and along with saponin as adjuvant. Mice were sacrificed on different post‐challenge days for evaluation of parasite load and other immunological parameters. Protective efficacy of different vaccine formulations was revealed by significant decline in parasite burden and increased DTH Delayed Type Hypersenstivity responses. The antibody response was of IgG type with elevated IgG2a and decreased production of IgG1, whereas cytokine levels pointed towards the generation of protective Th1 type of immune response. Among all vaccine formulations, cocktail of 31+51+saponin was found to be highly immunogenic and imparted maximum protection.     

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.     

High‐normal levels of albuminuria predict the development of micro‐ and macroalbuminuria and increased mortality in Brazilian Type 2 diabetic patients: an 8‐year follow‐up study

Aim To analyse the risk factors for the development of micro‐ and macroalbuminuria and mortality rates in a cohort of normoalbuminuric Type 2 diabetes mellitus (DM) patients. Methods In this prospective study, 193 Type 2 DM patients with urinary albumin excretion (UAE) < 20 µg/min, 96 men (50%), aged 56.5 ± 9 years, were followed for a mean period of 8 ± 3 years. UAE and estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease) were measured. The outcomes were development of persistent micro‐ and macroalbuminuria and mortality. Results Twenty patients were lost to follow‐up. Of the 173 remaining patients, 33 (19%) died. The Cox analysis [hazard ratio (HR), 95% confidence interval] revealed that the baseline significant predictors of mortality were higher UAE [above median (5 µg/min); HR 2.7, 1.2–6.1; P = 0.02], male sex (HR  3.9, 1.7–9.2; P = 0.002), age (HR 1.6, 1.3–1.9; P = 0.0001), and fasting plasma glucose (HR 1.2, 1.1–1.3; P = 0.004). Smoking and eGFR were not significant in this model. Follow‐up renal data were available for 158 patients: 34 (22%) progressed to microalbuminuria and seven (4%) to macroalbuminuria, and the baseline predictors were a higher UAE (> 5 µg/min, HR 2.5, 1.2–5.1; P = 0.02), presence of diabetic retinopathy (HR 2.5, 1.3–5.0; P = 0.009), fasting glucose (HR 1.1, 1.0–1.2; P = 0.015), and male sex (HR 2.2, 1.1–4.7; P = 0.04), independently of smoking and hypertension. Lower GFR (HR 0.98, 0.97–1.00; P = 0.07) was of borderline significance. Conclusions In normoalbuminuric Type 2 DM patients, the development of micro‐ or macroalbuminuria and mortality rates was independently and positively associated with higher levels of albuminuria, although still in the traditionally established normal range.     

Ketoacidosis occurs in both Type 1 and Type 2 diabetes— a population‐based study from Northern Sweden

Aims To determine the occurrence of diabetic ketoacidosis (DKA) in adult Type 2 and Type 1 diabetic patients in Northern Sweden and to determine whether DKA presents with a different clinical picture in Type 2 compared with Type 1 diabetic subjects. Methods All adult patients from a hospital catchment area in Northern Sweden with diagnosed DKA episodes during 1997–2000 were included in a retrospective study. Medical records and laboratory reports were analysed. Results During the years 1997 to 2000, the average annual incidence rate for DKA was 5.9 per 100 000 adult inhabitants. Twenty‐five patients developed DKA, eight (32%) had Type 2 diabetes, while 17 (68%) had Type 1 diabetes. Type 2 diabetic patients with DKA were older and had higher levels of C‐peptide than Type 1 diabetic patients. On admission because of DKA, a similar degree of hyperglycaemia was present in Type 1 and Type 2 patients. Metabolic acidosis was more severe in Type 1 compared with Type 2 diabetic patients. In 50% of the Type 2 diabetic patients, diabetes was diagnosed at the episode of DKA. Conclusions DKA occurs in Caucasian Type 2 diabetic patients within a Swedish population. Although the frequency of DKA is much higher in Type 1 diabetic patients, Type 2 diabetes may account for as much as one‐third of the overall DKA cases.     

Effects of sulfonylurea as initial treatment on testosterone of middle‐aged men with type 2 diabetes: A 16‐week,pilot study

Aims/Introduction

To evaluate the effect of sulfonylurea (glimepiride)-based oral antidiabetic agents on testosterone levels in middle-aged men with type 2 diabetes.

Materials and Methods

As a substudy, 15 participants from the phase IV clinical trial of glimepiride (GREAT study) of middle-aged men with type 2 diabetes were included in the current study. After enrolment, the initial dose of oral glimepiride was 1 mg/day. The dose was titrated according to blood glucose levels and the participants were treated for 16 weeks. Meanwhile, another 15 healthy age- and body mass index-matched male subjects were randomly selected as the healthy control group.

Results

Compared with the healthy control group, the middle-aged men with type 2 diabetes had significantly decreased total testosterone levels and a lower testosterone secretion index. Blood glucose and lipid profile levels were significantly improved after 16 weeks of treatment with no significant differences in bodyweight and waist circumference compared with baseline values. Recorded changes in luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin levels were not statistically significant. However, total testosterone levels were significantly increased and testosterone secretion index values were significant higher than those of the baseline.

Conclusions

It is highly possible that sulfonylurea as an initial treatment can recover the decreased total serum testosterone levels and testosterone secretion index values in middle-aged men with type 2 diabetes.