Association between insulin-like growth factor 1 and pancreatic volume in type 1 and type 2 diabetes: cross-sectional study of a Japanese population.

AIMS/HYPOTHESIS: Although IGF-1 is known to promote organ growth, including exocrine pancreas, the association between plasma IGF-1 levels and pancreatic size remains unclear in diabetic patients. METHODS: This cross-sectional study was designed to investigate the correlations among pancreatic volume (PV) based on computed tomography, IGF-1 levels, age- and sex-adjusted IGF-1 levels (IGF-1 Z-score), and C-peptide levels in patients with type 1 diabetes (T1D) (n = 51) and type 2 diabetes (T2D) (n = 104) in a Japanese population. RESULTS: PV was significantly correlated with body weight (BW) in both types of diabetes. PV adjusted for BW (PV/BW), IGF-1 Z-score and C-peptide levels were significantly lower in patients with T1D than T2D. There was a significant positive correlation between C-peptide levels and PV/BW in both subtypes of diabetes. IGF-1 Z-scores were significantly correlated with PV/BW in patients with T1D (r = 0.37, P = 0.007), but not T2D. Although IGF-1 Z-scores were not correlated with age, age of disease onset, disease duration, HbA1c, or C-peptide levels in both types of diabetes, a multivariable liner regression analysis revealed that IGF-1 Z-score and C-peptide levels were independent correlates of PV/BW in T1D patients, while C-peptide levels were a sole correlate in T2D. CONCLUSIONS/INTERPRETATION: Decreased IGF-1 levels might be one causal factor for smaller pancreas in patients with T1D.

Glucose Variability is Independently Correlated with Serum Level of Pigment Epithelium-Derived Factor in Type 2 Diabetes.

INTRODUCTION: Pigment epithelium-derived factor (PEDF) may play a role in cardiometabolic disorders. The aim of this study was to investigate which biochemical and clinical parameters are independently associated with serum PEDF levels in patients with type 2 diabetes mellitus (T2DM). METHODS: We performed a cross-sectional analysis of 124 patients with T2DM who underwent continuous glucose monitoring (CGM) and blood chemistry analysis, including the diacron-reactive oxygen metabolites (d-ROMs) test and serum PEDF measurement (study 1). Then we investigated whether the changes in the studied biochemical and clinical parameters after 24 weeks of treatment (Δparameters) with anti-hyperglycemic agents, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and/or insulin and anti-hypertensive drugs and statins, were independently correlated with change in PEDF (ΔPEDF) in 52 of the patients with T2DM for whom there was sufficient serum samples to perform the post-treatment analysis (study 2). Serum levels of PEDF were measured with an enzyme-linked immunosorbent assay. CGM metrics were calculated on days 2 and 3. Oxidative stress was evaluated using the d-ROMs test. RESULTS: Body mass index (BMI), triglycerides, fasting C-peptide, mean amplitude of glycemic excursions (MAGE), urinary albumin-to-creatinine ratio (UACR), and d-ROMs were positively associated with serum PEDF level, and high-density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) were inversely associated with serum PEDF level. Because these parameters were correlated with each other, multivariate stepwise analysis was performed: eGFR, HDL-C, BMI, MAGE, and UACR remained significant (R2 = 0.452). Furthermore, ΔMAGE and Δd-ROMs were positively correlated with ΔPEDF in study 2. CONCLUSIONS: The results of this study suggest that MAGE may be independently correlated with elevations in serum PEDF level in patients with T2DM.

Pancreatic fat accumulation evaluated by multidetector computed tomography in patients with type 2 diabetes.

AIMS: To clarify the clinical impact of pancreatic fat volume on beta cell function in type 2 diabetes patients. MATERIALS AND METHODS: One hundred thirty two consecutive type 2 diabetic patients (mean age, 63.7 years) were enrolled in this cross-sectional study. Total pancreatic volume (TPV), pancreatic fat volume (PFV), and pancreatic parenchymal volume (PPV), and visceral fat volume were examined quantitatively with multidetector computed tomography using SYNAPSE VINCENT image analysis system (Fujifilm Inc., Tokyo, Japan). Pancreatic fat was identified using Hounsfield Units of less than zero. The capacity of insulin secretion was assessed by C-peptide immunoreactivity (CPR) index (100 × fasting CPR/fasting plasma glucose). Insulin sensitivity was evaluated using CPR-insulin resistance (20/fasting CPR × fasting plasma glucose). RESULTS: TPV, PFV, PPV, and visceral fat volume were significantly correlated with body weight (BW). PPV/BW, but not PFV/BW, significantly decreased with increasing duration of diabetes and aging. PFV/BW was positively associated with body mass index and visceral fat volume/BW. PFV/BW was significantly correlated with CPR index, while inversely associated with insulin sensitivity. CPR index, but not CPRinsulin resistance was progressively decreased in patients with a longer duration of diabetes. When patients were divided into two groups according to a median PFV/BW value, CPR index in high PFV/BW group with diabetes duration >5 years was significantly lower than those ≤5 years. However, duration-dependent decrease in CPR index was not observed in low PFV/BW group. CONCLUSIONS: Our present study suggests that PFV might predict the progression of beta cell dysfunction in patients with type 2 diabetes.

Association of Hemoglobin A1c, 1,5-Anhydro-D-Glucitol and Glycated Albumin with Oxidative Stress in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study.

INTRODUCTION: Oxidative stress plays a central role in the development and progression of vascular complications in patients with type 2 diabetes mellitus (T2DM). We have previously shown that markers of glucose variability evaluated by continuous glucose monitoring (CGM) are positively associated with oxidative stress in patients with T2DM. However, the evaluation of the glycemic variability by CGM remains a time- and money-consuming procedure. Therefore, this study investigated the independent correlates of oxidative stress among various other clinical markers routinely measured in primary care. METHODS: This was a retrospective cross-sectional study with 234 T2DM patients to examine which clinical variables, including 1,5-anhydro-D-glucitol (1,5-AG) and glycated albumin (GA), were independently associated with oxidative stress. Oxidative stress was measured using the diacron-reactive oxygen metabolites (d-ROMs) test. The relationships between d-ROMs and clinical factors, such as blood glucose, glycated hemoglobin (HbA1c), 1,5-AG, GA, lipid parameters, and blood pressure, were examined. RESULTS: Multiple stepwise regression analysis revealed that 1,5-AG (inversely), GA, triglycerides, use of metformin and being female were independently associated with d-ROMs. When patients with T2DM were stratified into two groups with HbA1c < 8.0% and HbA1c ≥ 8.0%, 1,5-AG (inversely), HbA1c, use of metformin and being female were independently associated with d-ROMs in diabetes patients with HbA1c < 8.0%, whereas GA, fasting plasma glucose and being female were independently associated with d-ROMs in patients with HbA1c ≥ 8.0%. CONCLUSION: Our present study suggests that 1,5-AG and GA are the strongest correlates of oxidative stress in patients with well and poorly controlled T2DM, respectively.

Circulating anti-glutamic acid decarboxylase-65 antibody titers are positively associated with the capacity of insulin secretion in acute-onset type 1 diabetes with short duration in a Japanese population.

AIMS/INTRODUCTION: To elucidate the relationship between titers of islet autoantibodies, the C-X-C motif chemokine 10 - a circulating chemokine that activates T-helper 1 cells leading to ß-cell destruction - and ß-cell function in type 1 diabetes. MATERIALS AND METHODS: In total, 58 type 1 diabetes patients positive for glutamic decarboxylase-65 autoantibodies (GADA)-radioimmunoassay (mean age 54.1 years; 27 acute-onset cases and 31 slowly progressive cases) were enrolled; serum C-X-C motif chemokine 10 (n = 50), zinc transporter 8 autoantibodies (n = 50) and GADA (n = 58) by an enzyme-linked immunosorbent assay, and insulinoma-associated antigen-2 autoantibodies by radioimmunoassay (n = 50) were measured. The ratio of 100 × random C-peptide (ng/mL)-to-plasma glucose levels (mg/dL; C-peptide index [CPI]) was measured. RESULTS: The CPI significantly decreased in both groups with the progression of disease duration. GADA titers by radioimmunoassay and enzyme-linked immunosorbent assay were strongly correlated with the CPI in acute-onset type 1 diabetes patients with a shorter disease duration (≤10 years), but not in those with a longer duration or slowly progressive type 1 diabetes. Neither insulinoma-associated antigen-2 nor zinc transporter 8 autoantibodies titers were correlated with the CPI. Serum C-X-C motif chemokine 10 levels in both groups were significantly higher than in non-diabetic controls, and persisted at high levels even in those with chronic duration. CONCLUSIONS: Among islet autoantibodies, the intensity of the humoral immune response, as defined by GADA titers, reflected the degree of residual ß-cell function in acute-onset type 1 diabetes patients with short duration. Prolonged disease activity might accelerate ß-cell impairment in both subtypes of type 1 diabetes.

Pheochromocytoma presenting with severe hyperglycemia and metabolic acidosis following intra-articular glucocorticoid administration: a case report.

BACKGROUND: There are several reports of pheochromocytoma crisis triggered by systemic glucocorticoid administration. However, pheochromocytoma crisis after intra-articular glucocorticoid administration has been rarely reported. CASE PRESENTATION: A 45-year-old Japanese man presented to our hospital with a sudden, severe headache. He had no history of diabetes. He had received an intra-articular injection of betamethasone (2 mg) for joint pain, 2 days prior to his admission. On examination, his blood pressure was 240/126 mmHg and pulse was 120 beats/minute. The possibility of cerebrovascular events was ruled out by imaging studies and lumbar puncture. Blood tests revealed severe hyperglycemia (523 mg/dL) and metabolic acidosis (pH 7.21, anion gap 26.2 mEq/L, lactate 11.75 mmol/L) with a glycosylated hemoglobin level of 5.7%. Although a urine sample could not be obtained, fulminant type 1 diabetes mellitus and diabetic ketoacidosis were suspected based on these findings. However, after the initial treatment for diabetic ketoacidosis, his insulin secretion was found to be normal and the plasma levels of ketones were not elevated. This excluded the possibility of fulminant type 1 diabetes mellitus and diabetic ketoacidosis. Subsequently, a left adrenal gland tumor and elevated levels of serum catecholamine and urinary catecholamine metabolites were detected, while his other hormone levels were normal. Serum catecholamine levels did not decrease following the clonidine test, and a functional scintigraphy using iodine-131 metaiodobenzylguanidine showed strong uptake in the region of the left adrenal gland. Although no signs of pheochromocytoma crisis, such as paroxysmal hyperglycemia and hypertension, had been observed since admission, a pheochromocytoma was diagnosed based on the investigations. After controlling his blood pressure, a left adrenalectomy was performed. CONCLUSIONS: This case illustrates that intra-articular glucocorticoid administration can induce a pheochromocytoma crisis and an increase in hyperglycemia, and that pheochromocytoma crisis can resemble the clinical picture of fulminant type 1 diabetes mellitus owing to severe hyperglycemia with metabolic acidosis and normal glycosylated hemoglobin levels, especially under the influence of glucocorticoid.

Improvements of ambient hyperglycemia and glycemic variability are associated with reduction in oxidative stress for patients with type 2 diabetes.

AIMS: We aimed to evaluate which parameters of improvement in glucose metabolism reduce oxidative stress for patients with Type 2 diabetes mellitus (T2DM). METHODS: Sixty-seven outpatients with T2DM underwent 72 h of continuous glucose monitoring (CGM) and were measured for oxidative stress before and after a 24-week intervention with the following targets: fasting plasma glucose (FPG), <130 mg/dl; postprandial plasma glucose (PPG), <180 mg/dl; and glycated hemoglobin (HbA1c), <7% (53 mmol/mol). The mean glucose level (MGL), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), percentage coefficient of variation for glucose (%CV) and area under the postprandial plasma glucose curve (AUCPP) were calculated from the CGM data. Oxidative stress was estimated using the diacron-reactive oxygen metabolites (d-ROMs) test. Finally, the association between the improvements in glucose metabolism and oxidative stress was evaluated. RESULTS: FPG, MGL, HbA1c, MAGE, MODD, %CV, AUCPP, and d-ROMs significantly improved after 24 weeks of intervention. The change in d-ROMs was significantly correlated with that in FPG (r = 0.414), MGL (r = 0.402), HbA1c (r = 0.271), MAGE (r = 0.457), MODD (r = 0.371), and AUCPP (r = 0.352). The correlation of the change in d-ROMs with that in FPG, MAGE, and MODD and the use of glucose-like peptide 1 receptor agonists and statins remained significant after adjustment for other markers of diabetes control (multiple R2 = 0.406). CONCLUSIONS: Improvements in glucose metabolism, including FPG and daily and day-to-day glucose variability, were all correlated with reduced oxidative stress for patients with T2DM.

Comparison of liraglutide plus basal insulin and basal-bolus insulin therapy (BBIT) for glycemic control, body weight stability, and treatment satisfaction in patients treated using BBIT for type 2 diabetes without severe insulin deficiency: A randomized prospective pilot study.

AIMS: We examined whether 0.9 mg/day liraglutide plus basal insulin (Lira-basal) is superior to basal-bolus insulin therapy (BBIT) for type 2 diabetes (T2DM) without severe insulin deficiency as determined by glucagon stimulation. METHODS: Fifty patients receiving BBIT were enrolled in this 24-week, prospective, randomized, open-labeled study. After excluding subjects with fasting C-peptide immunoreactivity (CPR) < 1.0 ng/mL and CPR increase < 1.0 ng/mL at 6 min post glucagon injection, 25 were randomly allocated to receive Lira-basal (n = 12) or continued BBIT (n = 13). Primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight (BW), 7-point self-monitored blood glucose (SMBG), and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores. RESULT: The Lira-basal group demonstrated reduced HbA1c, whereas the BBIT group showed no change. BW was reduced in the Lira-basal group but increased in the BBIT group. The Lira-basal group also exhibited significantly reduced pre-breakfast and pre-lunch SMBG. DTSQs scores improved in the Lira-basal group but not the BBIT group. Plasma lipids, liver function, and kidney function were not significantly changed in either group. CONCLUSIONS: Lira-basal therapy is superior to BBIT for T2DM without severe insulin deficiency. This study was registered with UMIN Clinical Trials Registry (UMIN000028313).