Matrix metallopeptidase 9 contributes to the beginning of plaque and is a potential biomarker for the early identification of atherosclerosis in asymptomatic patients with diabetes.

Aims: To determine the roles of matrix metallopeptidase-9 (MMP9) on human coronary artery smooth muscle cells (HCASMCs) , early beginning of atherosclerosis in diabetic mice, and drug naïve patients with diabetes.

Methods: Active human MMP9 (act-hMMP9) was added to HCASMCs and the expressions of MCP-1, ICAM-1, and VCAM-1 were measured. Act-hMMP9 (n=16) or placebo (n=15) was administered to diabetic KK.

Response of blood glucose and GLP-1 to different food temperature in normal subject and patients with type 2 diabetes.

Background: Eating behavior is a major factor in type 2 diabetes. We investigated the different responses of glucose-regulating hormones to cold and hot glucose solutions in normal subjects and patients with type 2 diabetes.

Methods: In this crossover, self-controlled study, normal subjects (N = 19) and patients with type 2 diabetes (N = 22) were recruited and randomly assigned to a hot (50 °C) or a cold (8 °C) oral glucose-tolerance test (OGTT).

Charting the next century of insulin replacement with cell and gene therapies.

The discovery of insulin a century ago changed the lives of millions of individuals suffering from diabetes, paving the way for long-term survival. While the availability of recombinant insulin for hormone replacement therapy has served extremely well to help control blood glucose in diabetes, there remains significant room for further improvements for an ultimate "cure" for diabetes patients. In this review, we celebrate the 100th anniversary of the discovery of insulin and consolidate the key milestones and advances in the development of recombinant human insulin.

Metformin treatment is associated with an increase in bone mineral density in type 2 diabetes mellitus patients in China: A retrospective single center study.

Aims: To investigate the association between metformin and bone mineral density (BMD) in a large cohort of Chinese patients with type 2 diabetes mellitus (T2DM).

Methods: A total of 11,458 T2DM patients aged ≥40 years were included. Information on demographic, anthropometric and clinical characteristics was collected from medical records.

First use of gene therapy to treat growth hormone resistant dwarfism in a mouse model.

The only treatment tested for growth hormone receptor (GHR) defective Laron Syndrome (LS) is injections of recombinant insulin-like-growth factor 1 (rhIGF1). The response is suboptimal and associated with progressive obesity. In this study, we treated 4-5-week-old Laron dwarf mice (GHR-/-) with an adeno-associated virus expressing murine GHR (AAV-GHR) injection at a dose of 4 × 10 vector genome per mouse.

Progressive endoplasmic reticulum stress over time due to human insulin gene mutation contributes to pancreatic beta cell dysfunction.

Aims/hypothesis: We studied the effects of heterozygous human INS gene mutations on insulin secretion, endoplasmic reticulum (ER) stress and other mechanisms in both MIN6 and human induced pluripotent stem cells (hiPSC)-derived beta-like cells, as well as the effects of prolonged overexpression of mutant human INS in MIN6 cells.

Methods: We modelled the structure of mutant C109Y and G32V proinsulin computationally to examine the in silico effects. We then overexpressed either wild-type (WT), mutant (C109Y or G32V), or both WT and mutant human preproinsulin in MIN6 cells, both transiently and stably over several weeks.

Association of decreased sperm motility and increased seminal plasma IGF-I, IGF-II, IGFBP-2, and PSA levels in infertile men.

Purpose: Previous studies have suggested the involvement of serum insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in the regulation of the female reproductive system. Little is known of these peptides in the seminal plasma (SP) of men and their potential effects on fertility. We assessed SP levels of these peptides in infertile men with low sperm motility (asthenozoospermic; AZ) and low sperm counts (oligozoospermic; OZ), its effects on in vivo sperm motility, and whether there is a correlation with aging.

Rapid Changes in Serum Testosterone in Men With Newly Diagnosed Type 2 Diabetes With Intensive Insulin and Metformin.

Objective: To investigate the effect of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM).

Research Design And Methods: Seventy men with newly diagnosed drug-naive T2DM and HbA >9.0% (75 mmol/mol) were treated with intensive insulin pump therapy for 5 days to achieve glucose normalization.

Modification of a Constitutive to Glucose-Responsive Liver-Specific Promoter Resulted in Increased Efficacy of Adeno-Associated Virus Serotype 8-Insulin Gene Therapy of Diabetic Mice.

We have previously used a hepatotropic adeno-associated viral (AAV) vector with a modified human insulin gene to treat diabetic mice. The HLP (hybrid liver-specific promoter) used was constitutively active and non-responsive to glucose. In this study, we examined the effects of addition of glucose responsive elements (R3G) and incorporation of a 3' albumin enhancer (3'iALB) on insulin expression.

Flash Glucose Monitoring Improves Glucose Control in People with Type 2 Diabetes Mellitus Receiving Anti-diabetic Drug Medication.

Objective: To investigate the effects of Flash Glucose Monitoring (FGM) on glucose profile in people with Type 2 Diabetes Mellitus (T2DM) receiving anti-diabetic drug medication.

Methods: This is a prospective non-randomized uncontrolled study. 111 people with T2DM were enrolled and received FGM for 14 days.

Contributions of Fasting and Postprandial Glucose Concentrations to Haemoglobin A1c in Drug-Naïve Mal-Glucose Metabolism in Chinese Population Using Continuous Glucose Monitoring System.

Aim: To clarify the contributions of fasting glucose (FG) and postprandial glucose (PG) to HbA1c in drug-naïve patients with type 2 diabetes (T2D) and impaired glucose tolerate (IGT)/impaired fasting glucose (IFG).

Methods: Continuous glucose monitoring (CGM) was performed in 305 drug-naïve Chinese patients with T2D or IGT/IFG. The incremental area under the curve (AUC) above a glucose value of 6.

New insights into human beta cell biology using human pluripotent stem cells.

Pancreatic β-cells are responsible for maintaining glucose homeostasis. Therefore, their dysregulation leads to diabetes. Pancreas or islet transplants can be used to treat diabetes but these human tissues remain in short supply.

The characteristics of blood glucose fluctuations in patients with fulminant type 1 diabetes mellitus in the stable stage.

Objective: The aim was to characterize blood glucose fluctuations in patients with fulminant type 1 diabetes (FT1DM) at the stable stage using continuous blood glucose monitoring systems (CGMSs).

Subjects And Methods: Ten patients with FT1DM and 20 patients with classic type 1 diabetes mellitus (T1DM) (the control group) were monitored using CGMSs for 72 hours.

Results: The CGMS data showed that the mean blood glucose (MBG), the standard deviation of the blood glucose (SDBG), the mean amplitude glycemic excursions (MAGE), the blood glucose areas and the percentages of blood glucose levels below 13.

Development of a liver-specific Tet-off AAV8 vector for improved safety of insulin gene therapy for diabetes.

Background: Diabetes mellitus is caused by a partial or complete lack of insulin production in the body. We have previously shown that a single injection of an adeno-associated virus serotype 8 (AAV8) vector carrying a modified and codon optimized human insulin gene induced hepatic production of insulin and corrected streptozotocin (STZ)-induced diabetes in mice for more than 1 year. Insulin production was constitutive, analogous to long-acting insulin therapy.

Efficacy and safety of pulsed intravenous methylprednisolone in early active thyroid eye disease.

: The mainstay of therapy for active inflammatory phase of thyroid eye disease (TED) is immunosuppression. Patients in our centre with early active TED are treated with pulsed intravenous methylprednisolone (IVMP). Two different protocols are offered in our centre: High dose (1g/day for 3 days, monthly for 6 months), or EUGOGO protocol (500 mg weekly for six weeks, followed by 250 mg weekly for the next 6 weeks).

Relationship between Thyroid Function and Kidney Function in Patients with Type 2 Diabetes.

Purpose: To determine if the TSH is related to estimated glomerular filtration rate (eGFR) in T2D patients without overt thyroid dysfunction.

Methods: A cohort study of 5936 T2D patients was assessed for thyroid and kidney functions, in whom 248 with subclinical hyperthyroidism and 362 with subclinical hypothyroidism. Serum creatinine and 24-hour urine albumin excretion (UAE) were collected.

Immunosuppression overcomes insulin- and vector-specific immune responses that limit efficacy of AAV2/8-mediated insulin gene therapy in NOD mice.

We report the restoration of euglycaemia in chemically induced diabetic C57BL/6 mice and spontaneously diabetic Non Obese Diabetic (NOD) mice by intravenous systemic administration of a single-stranded adeno-associated virus (ssAAV2/8) codon optimised (co) vector encoding furin cleavable human proinsulin under a liver-specific promoter. There were no immunological barriers to efficacy of insulin gene therapy in chemically induced C57BL/6 mice, which enjoyed long-lasting correction of hyperglycaemia after therapy, up to 250 days. Euglycaemia was also restored in spontaneously diabetic NOD mice, although these mice required a 7-10-fold higher dose of vector to achieve similar efficacy as the C57BL/6 mice and the immunodeficient NOD mice.

Bioavailability of Orally Administered Des-Aspartate-Angiotensin I in Human Subjects.

In an earlier single-dose escalation study to evaluate the safety and pharmacokinetics of orally administered des-aspartate-angiotensin I (DAA-I) in healthy subjects, the plasma level of DAA-I could not be determined because DAA-I is rapidly degraded in the circulation. The present study investigated the oral bioavailability of DAA-I by measuring the prostaglandin E metabolite (PGEM) in the plasma samples of the same trial. PGEM is a stable derivative of PGE, which has been shown to be a biomarker of DAA-I.

Comparison of Diabetic and Non-diabetic Human Leukocytic Responses to Different Capsule Types of Responsible for Causing Pyogenic Liver Abscess.

The major risk factor for Klebsiella liver abscess (KLA) is type 2 diabetes mellitus (DM), but the immunological mechanisms involved in the increased susceptibility are poorly defined. We investigated the responses of neutrophils and peripheral blood mononuclear cells (PBMCs) to hypervirulent (hvKP), the causative agent of KLA. DNA and myeloperoxidase levels were elevated in the plasma of KLA patients compared to uninfected individuals indicating neutrophil activation, but diabetic status had no effect on these neutrophil extracellular trap (NET) biomarkers in both subject groups.

Anti-Cancer Drug HMBA Acts as an Adjuvant during Intracellular Bacterial Infections by Inducing Type I IFN through STING.

The anti-proliferative agent hexamethylene bisacetamide (HMBA) belongs to a class of hybrid bipolar compounds developed more than 30 y ago for their ability to induce terminal differentiation of transformed cells. Recently, HMBA has also been shown to trigger HIV transcription from latently infected cells, via a CDK9/HMBA inducible protein-1 dependent process. However, the effect of HMBA on the immune response has not been explored.

Use of cabergoline for the management of persistent Cushing's disease in pregnancy.

Cushing's disease (CD) is rare during pregnancy and is associated with significant maternal and fetal complications. It is important to control hypercortisolism during pregnancy, either surgically or medically, for a successful maternal and fetal outcome. We report a patient with recurrent CD who was treated with low-dose cabergoline (CAB) for persistent hypercortisolism throughout pregnancy.

Continuous Glucose Monitoring in Newly Diagnosed Type 2 Diabetes Patients Reveals a Potential Risk of Hypoglycemia in Older Men.

We performed continuous glucose monitoring (CGM) to define the features of patients with newly diagnosed type 2 diabetes (T2D) before and after Continuous Subcutaneous Insulin Infusion (CSII) therapy. This was a retrospective analysis. Newly diagnosed T2D patients (106) were admitted from eight centers in China.

PGE1 improves diabetic peripheral neuropathy in patients with type 2 diabetes.

Background: Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes. We aim to investigate the efficacy of Prostaglandin E1 (PGE1) treatment in addition to intensive insulin therapy on DPN in patients with type 2 diabetes.

Methods: Seventy-seven patients with DPN received daily intravenous injection of Prostaglandin E1 (PGE1) in lipid microspheres (Lipo-PGE1) for 10days as an additional therapy to standard glucose control therapy (PGE1 group).