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.     

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.     

Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels

Aims To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25‐hydroxyvitamin D levels. Methods Double‐blind, parallel group, placebo‐controlled randomized trial. A single dose of 100 000 IU vitamin D2 or placebo was administered to patients with Type 2 diabetes over the winter, when levels of circulating 25‐hydroxyvitamin D were likely to be lowest. Patients were enrolled if their baseline 25‐hydroxyvitamin D level was < 50 nmol/l. Endothelial function and blood pressure were measured and fasting blood samples were taken at baseline and 8 weeks after administration of vitamin D. Results Forty‐nine per cent of subjects screened had 25‐hydroxyvitamin D levels < 50 nmol/l. Thirty‐four subjects completed the study, with a mean age of 64 years and a baseline 25‐hydroxyvitamin D level of 38.3 nmol/l. Vitamin D supplementation increased 25‐hydroxyvitamin D levels by 15.3 nmol/l relative to placebo and significantly improved flow mediated vasodilatation (FMD) of the brachial artery by 2.3%. The improvement in FMD remained significant after adjusting for changes in blood pressure. Vitamin D supplementation significantly decreased systolic blood pressure by 14 mmHg compared with placebo; this did not correlate with change in FMD. Conclusions Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotland. A single large dose of oral vitamin D2 improves endothelial function in patients with Type 2 diabetes and vitamin D insufficiency.     

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.     

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.     

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.     

Comparing treatment intensification and clinical outcomes of metformin and dipeptidyl peptidase‐4 inhibitors in treatment‐naïve patients with type 2 diabetes in Japan

Japan's guidelines emphasize tailored therapy, but do not guide physicians on the use of a specific regimen in drug‐naive patients. The role of long‐term initial therapy could be important in key elements of diabetes treatment, such as continuation of the initially prescribed drug. We investigated the frequency of occurrence to treatment intensification after the initiation of metformin or dipeptidyl peptidase‐4 inhibitor treatment. In multivariable‐adjusted Cox proportional hazards models, initiation of dipeptidyl peptidase‐4 inhibitor was associated with a low hazard of intensification. The findings of this survey showed that dipeptidyl peptidase‐4 inhibitors were the preferred first‐line treatment in Japan because of the high continuation rate of the treatment and hemoglobin A1c‐lowering effect. This information would provide guidance in selecting initial hypoglycemic drugs to optimize the treatment of type 2 diabetes mellitus patients in Japan and Asia.